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Uranium-zirconium alloy is an important nuclear fuel in Integral Fast Reactor, which is of great significance to study its basic physical properties at high temperature by using advanced calculation methods. This work used deep potential molecular dynamics method, which combines the high accuracy of the first principles with the high efficiency of the classical molecular dynamics, to perform an evaluation of the static and thermophysical properties of body-centered cubic phase zirconium, uranium, and uranium-zirconium alloy. Firstly, the deep potential(DP) models of body-centered cubic zirconium(Zr-BCC), body-centered cubic uranium(U-BCC), and body-centered cubic uranium-zirconium alloy(U-Zr（BCC）) were trained by using deep neural network machine learning. Secondly, the DP models were used to predict equilibrium state equation, lattice constant, elastic properties, and phonon spectrum of the three systems, and the predicted results can reach the accuracy of the first principles. Then, the variation of heat capacity and density at constant pressure of Zr-BCC, U-BCC, and U-Zr（BCC） with temperature were predicted by using DP models, and the results are in good agreement with the experimental values. The research results show that the machine learning method provides an important path for successfully exploring more complex nuclear fuel properties.

Traditional physical methods for measuring solubility were often affected by viscosity, density, and surface tension. In this study, we selected appropriate electrolytes to determine the solubility of impurities in the lead-bismuth circuit at reactor operating temperatures using electrochemical methods. Taking the measurement of the solubility of impurity Ce in liquid Bi as an example, we demonstrated that electrochemical methods can accurately determine its solubility in the LiCl-KCl molten salt. Furthermore, the successful measurement of other impurities such as La, Ce, U, and Mn in lead-bismuth eutectic (LBE) using the designed system has confirmed the universality of this method.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).This article has been retracted at the request of the authors. The manuscript was submitted before a final round of revision by the authors. As a result, not all authors had the opportunity to review the final manuscript and approve it, and there are a series of errors that should have been rectified prior to publication. These are: • Some figures do not contain the reference to the original source (permissions was obtained to reproduce the figures but this has not been properly represented). • Some sentences in the Introduction were taken verbatim from other sources while no reference was included to the original source. • The authors need to further supplement some data and discussion to improve the paper.The authors apologise for this error.

This article has been retracted: Please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the authors. The manuscript was submitted before a final round of revision by the authors. As a result, not all authors had the opportunity to review the final manuscript and approve it, and there are a series of errors that should have been rectified prior to publication. These are:• Some figures do not contain the reference to the original source (permissions was obtained to reproduce the figures but this has not been properly represented).• Some sentences in the Introduction were taken verbatim from other sources while no reference was included to the original source.• The authors need to further supplement some data and discussion to improve the paper.The authors apologise for this error.

The thermodynamic and transport properties of high-temperature chloride molten salt systems are of great significance for spent fuel reprocessing in the field of nuclear energy engineering. Here, by using machine learning based deep potential (DP) method, we train a high-precision force field model for the LiCl-KCl-LiF system. During force field training, adding new dataset through multiple iterations improves the accuracy of the force field model and its applicability to more configurations. The comparison of density functional theory (DFT) and DP results for the test dataset indicates that our trained DP model has the same accuracy as DFT. Then, we comprehensively investigate the local structure, thermophysical properties, and transport properties of the LiCl-KCl and LiCl-KCl-LiF molten salt systems using the trained DP model. The effects of temperature and LiF concentration on the above properties are analyzed. This work provides guidance for the training of machine learning force fields in molten salt systems and the study of basic physical properties of high-temperature chloride molten salt systems.

Abstract Currently, many types of non-linear topological structure polymers, such as brush-shaped, star, branched and dendritic structures, have captured much attention in the field of gene delivery and nanomedicine. Compared with linear polymers, non-linear topological structural polymers offer many advantages, including multiple terminal groups, broad and complicated spatial architecture and multi-functionality sites to enhance gene delivery efficiency and targeting capabilities. Nevertheless, the complexity of their synthesis process severely hampers the development and applications of nonlinear topological polymers. This review aims to highlight various synthetic approaches of non-linear topological architecture polymers, including reversible-deactivation radical polymerization (RDRP) including atom-transfer radical polymerization (ATRP), nitroxide-mediated polymerization (NMP), reversible addition-fragmentation chain transfer (RAFT) polymerization, click chemistry reactions and Michael addition, and thoroughly discuss their advantages and disadvantages, as well as analyze their further application potential. Finally, we comprehensively discuss and summarize different non-linear topological structure polymers for genetic materials delivering performance both in vitro and in vivo, which indicated that topological effects and nonlinear topologies play a crucial role in enhancing the transfection performance of polymeric vectors. This review offered a promising guideline for the design and development of novel nonlinear polymers and facilitated the development of a new generation of polymer-based gene vectors.

The exploration of microbial genetic resources for the production of fFen-flavor Baijiu has not only enriched the microbial library for baijiu production but has also laid the foundation for process improvement and strain optimization in baijiu brewing. In this study, a total of 177 fungal isolates were screened, including Saccharomyces cerevisiae, non-Saccharomyces cerevisiae, molds, and some pathogenic bacteria. Among them, Saccharomyces cerevisiae was the most abundant with 119 isolates, playing a major role in the fermentation of baijiu production. A total of 148 bacterial isolates were obtained from the fermentation mash samples, showing greater diversity compared to fungi. Bacillus species were the most abundant, with 94 isolates. Bacillus licheniformis, in particular, can produce a rich enzymatic system and flavor precursors, making it an important contributor to the sensory quality of baijiu. Lactic acid bacteria were the second most abundant, with 16 isolates. Additionally, five pathogenic fungal species were identified, including Candida pelliculosa, Candida lusitaniae, Fusarium oxysporum, Fusarium solani and Talaromyces marneffei. Six pathogenic bacterial species were also isolated, namely Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus xylosus, Moraxella osloensis, Actinomyces meyeri and Stenotrophomonas maltophilia. Finally, two strains of high acetate ethyl ester-producing yeast and lactate-degrading bacteria with good tolerance to temperature, pH, and ethanol concentration were identified as Saccharomyces cerevisiae and Bacillus licheniformis, respectively.

Abstract Extensive efforts have been dedicated to enhancing the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in cancer cells for the development of effective cancer treatments. However, highly safe and efficient delivery of TRAIL gene remains a significant challenge, especially using cationic polymers. Here, a series of highly branched-linear poly(β-amino ester)s (H-LPAEs) are developed through a unique oligomer branching strategy. H-LPAEs exhibit a more uniform distribution of linear segments and branching units, leading to excellent DNA condensation and favorable physicochemical properties of H-LPAE/DNA polyplexes. In SW1353 and BMSC cells, the optimized H-LPAEs, H-LPAEB4−S5−TMPTA, achieves superior gene transfection efficiency of 58.0% and 33.4%, which were 2.5-fold and 2.0-fold higher than that of the leading commercial gene transfection reagent, Lipofectamine 3000. Excitingly, H-LPAEB4−S5−TMPTA mediated 56.7% and 28.1% cell apoptosis in HepG2 cells and HeLa cells highlighting its potential application in cancer gene therapy. In addition, locally administered H-LPAEB4−S5−TMPTA delivered TRAIL DNA to HepG2 xenograft tumors and inhibited tumor growth in vivo. This study not only proposes a novel strategy for synthesizing poly(β-amino ester)s with a unique branched-linear topology but also identifies a promising candidate for highly efficient TRAIL gene transfection.

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The fermentation process of Chinese Baijiu’s fermented grains involves the intricate succession and metabolism of microbial communities, collectively shaping the Baijiu’s quality. Understanding the composition and succession of these living microbial communities within fermented grains is crucial for comprehending fermentation and flavor formation mechanisms. However, conducting high-throughput analysis of living microbial communities within the complex microbial system of fermented grains poses significant challenges. Thus, this study addressed this challenge by devising a high-throughput analysis framework using light-flavor Baijiu as a model. This framework combined propidium monoazide (PMA) pretreatment technology with amplicon sequencing techniques. Optimal PMA treatment parameters, including a concentration of 50 μM and incubation in darkness for 5 min followed by an exposure incubation period of 5 min, were identified. Utilizing this protocol, viable microorganism biomass ranging from 8.71 × 106 to 1.47 × 108 copies/μL was successfully detected in fermented grain samples. Subsequent amplicon sequencing analysis revealed distinct microbial community structures between untreated and PMA-treated groups, with notable differences in relative abundance compositions, particularly in dominant species such as Lactobacillus, Bacillus, Pediococcus, Saccharomycopsis, Issatchenkia and Pichia, as identified by LEfSe analysis. The results of this study confirmed the efficacy of PMA-amplicon sequencing technology for analyzing living microbial communities in fermented grains and furnished a methodological framework for investigating living microbial communities in diverse traditional fermented foods. This technical framework holds considerable significance for advancing our understanding of the fermentation mechanisms intrinsic to traditional fermented foods.

Abstract Gene therapy holds great promise for treating a multitude of inherited and acquired diseases by delivering functional genes, comprising DNA or RNA, into targeted cells or tissues to elicit manipulation of gene expression. However, the clinical implementation of gene therapy remains substantially impeded by the lack of safe and efficient gene delivery vehicles. This review comprehensively outlines the novel fastest-growing and efficient non-viral gene delivery vectors, which include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). Particularly, we discuss the research progress, potential development directions, and remaining challenges. Additionally, we provide a comprehensive overview of the currently approved non-viral gene therapeutics, as well as ongoing clinical trials. With advances in biomedicine, molecular biology, materials science, non-viral gene vectors play an ever-expanding and noteworthy role in clinical gene therapy.

A first-principle approach within the framework of density functional theory was employed to study the effect of vacancy defects and fission products (FPs) doping on the mechanical, electronic, and thermodynamic properties of uranium monocarbide (UC). Firstly, the calculated vacancy formation energies confirm that the C vacancy is more stable than the U vacancy. The solution energies indicate that FPs prefer to occupying in U site rather than in C site. Zr, Mo, Th, and Pu atoms tend to directly replace U atom and dissolve into the UC lattice. Besides, the results of the mechanical properties show that U vacancy reduces the compressive and deformation resistance of UC while C vacancy has little effect. The doping of all FPs except He has a repairing effect on the mechanical properties of U1-xC. In addition, significant modifications are observed in the phonon dispersion curves and partial phonon density of states (PhDOS) of UC1-x, ZrxU1-xC, MoxU1-xC, and RhxU1-xC, including narrow frequency gaps and overlapping phonon modes, which increase the phonon scattering and lead to deterioration of thermal expansion coefficient (αV) and heat capacity (Cp) of UC predicted by the quasi harmonic approximation (QHA) method.

Abstract Purpose Microbial resources are abundant in fermented grains of the Chinese Fen-flavor Baijiu, which is closely related to the quality of Baijiu. The purpose of this study was to investigate the microbial community structure and function in Daqu and fermented grains. Methods We systematically compared two technical approaches, amplicon sequencing, and metagenomic sequencing, to analyze the microbial communities during Baijiu fermentation. Result The results showed that lactic acid bacteria (LAB) and yeasts were the main microorganisms in the fermentation process. Firmicutes (Lactobacillus, Pediococcus, and Weissella) were the dominant bacteria, and Ascomycota (Issatchenkia or Pichia) was the dominant fungus in fermented grains. Moreover, Pichia kudriavzevii, Lichtheimia ramosa, and Companilactobacillus paralimentarius were the dominant species at the initial stage of fermentation by metagenomic sequencing. Latilactobacillus curvatus, Loigolactobacillus coryniformis subsp. coryniformis, and Lentilactobacillus parabuchneri became dominant during the middle stage of fermentation. Lentilactobacillus parabuchneri and Lactobacillus acetotolerans were the dominant species in the final stage of fermentation. Spearman correlation analysis showed that LAB inhibited the growth of yeasts. Conclusion Combining the two sequencing methods provided valuable insights into the dynamic succession of microorganisms during the fermentation of Baijiu. It had had a particular significance for mining microbial species resources in fermented grains.

This research presents a new, eco-friendly, and swift method combining solid-phase extraction and hydrophobic deep eutectic solvents (DES) with high-performance liquid chromatography (SPE-DES-HPLC) for extracting and quantifying catechin and epicatechin in Shanxi aged vinegar (SAV). The parameters, such as the elution solvent type, the XAD-2 macroporous resin dosage, the DES ratio, the DES volume, the adsorption time, and the desorption time, were optimized via a one-way experiment. A central composite design using the Box–Behnken methodology was employed to investigate the effects of various factors, including 17 experimental runs and the construction of three-dimensional response surface plots to identify the optimal conditions. The results show that the optimal conditions were an HDES (tetraethylammonium chloride and octanoic acid) ratio of 1:3, an XAD-2 macroporous resin dosage of 188 mg, and an adsorption time of 11 min. Under these optimal conditions, the coefficients of determination of the method were greater than or equal to 0.9917, the precision was less than 5%, and the recoveries ranged from 98.8% to 118.8%. The environmentally friendly nature of the analytical process and sample preparation was assessed via the Analytical Eco-Scale and AGREE, demonstrating that this method is a practical and eco-friendly alternative to conventional determination techniques. In summary, this innovative approach offers a solid foundation for the assessment of flavanol compounds present in SAV samples.

Landslide No.3 in Fei'e Mountain is located in the Shunde District of Foshan City, Guangdong Province, and its' lithology is mainly composed of pre-Cretaceous Baizushan Formation (K1b) argillaceous siltstone. In this study, engineering geological drilling, geophysical exploration, geological mapping, and indoor testing were used to determine that it is a medium-scale bedding rocky landslide with a typical double-layer deep sliding surface. The maximum length of the landslide body is approximately 220 m in the longitudinal (south-west) direction and approximately 230 m in the horizontal (north-west) direction; the maximum thickness is approximately 32m, and the attitude of sliding surface is 230°∠12°-17°. Landslide body tensile cracks, including nine large-scale tensile cracks, are very well-developed. The longest crack is approximately 120 m long and has a crack opening width of 0-13 cm, with a height difference between the two sides of the crack (rupture wall) of 0-0.2 m. The ground of the leading edge of the landslide was uplifted and cracked, with a maximum uplift height of approximately 1.7 m. The landslide shear outlet was clearly visible and exhibited well-developed scratches. The scratch direction was the same as the main slide direction of the underlying landslide. Landslide deformation severely cracked the building structure and obstructed the drainage channel. There was a loose residual soil layer on the surface of the slope of Landslide No.3, and many fractures and joints were present in the lower bedrock. During rainfall, rainwater penetrated the deep part of the slope along the rock layer surface, joints, and fractures, which greatly increased the bulk density of the rock and soil mass, and softened the argillaceous siltstones, which greatly decreased their shear strength. The excavation of the slope formed a steep surface, which reduced the load at the foot of the slope and thus reduced the anti-sliding force. During long-term seepage, the rock and soil mass near the landslide face was softened to form a weak zone mixed with joints and stratigraphic phases. During long periods of heavy rain, the weak zone became soaked, soft, and plastic, which reduced its shear strength. When downward force increased, the effective anti-sliding force of the weak zone was greatly reduced, resulting in a landslide. During this process, Landslide No.3 developed two slip surfaces. The maximum buried depths of slip surfaces 1 and 2 (corresponding to landslides 1 and 2) were 32 and 15.5 m, respectively, which means that landslide 2 overlaid landslide 1 and slip surface 1 creeping occurred before that of slip surface 2. The trailing edge of slip surface 1 developed a fissure, the characteristics of which are described above. As the fracture surface was not fresh, its' development time is unknown. As in the sliding process, landslide 2 first formed a continuous sliding surface, and its' sliding rate was slightly greater than that of landslide 1, landslide 2 was the first to cut out from the steep ridge of the landslide's front edge. As a result of the shearing action of landslide 2, landslide 1 developed multiple vertical cracks. Rainwater seeping down these cracks further lubricated slip surface 1, which resulted in drum mounds and cracks in the leading edge of the landslide. Slip surface 1 subsequently formed a continuous sliding surface, and Landslide No.3 entered the uniform deformation stage. Timely emergency measures prevented landslide deformation damage and halted landslide progression before entering the accelerated deformation stage. Considering its double-layer slip surface structure, a comprehensive combination of slope cutting, an anchor (cable), lattice beam, double-row prestressed anchor-pulling anti-slip pile, three-dimensional mesh grass greening, interception, drainage, and a hairy stone retaining wall was used to prevent and control the landslide. Long-term monitoring results showed that these methods had a high rectification effect and successfully controlled landslide deformation and displacement.

Abstract Fluid and bicarbonate secretion is a principal function of cholangiocytes, and impaired secretion results in cholestasis. Cholangiocyte secretion depends on peri‐apical expression of the type 3 inositol trisphosphate receptor (ITPR3), and loss of this intracellular Ca2+ release channel is a final common event in most cholangiopathies. Here we investigated the mechanism by which ITPR3 localizes to the apical region to regulate secretion. Isolated bile duct units, primary mouse cholangiocytes, and polarized Madin‐Darby canine kidney (MDCK) cells were examined using a combination of biochemical and fluorescence microscopy techniques to investigate the mechanism of ITPR3 targeting to the apical region. Apical localization of ITPR3 depended on the presence of intact lipid rafts as well as interactions with both caveolin 1 (CAV1) and myosin heavy chain 9 (MYH9). Chemical disruption of lipid rafts or knockdown of CAV1 or MYH9 redistributed ITPR3 away from the apical region. MYH9 interacted with the five c‐terminal amino acids of the ITPR3 peptide. Disruption of lipid rafts impaired Ca2+ signaling, and absence of CAV1 impaired both Ca2+ signaling and fluid secretion. Conclusion: A cooperative mechanism involving MYH9, CAV1, and apical lipid rafts localize ITPR3 to the apical region to regulate Ca2+ signaling and secretion in cholangiocytes.

Histones and DNA associate to form the nucleosomes of eukaryotic chromatin. Chromatin assembly factor 1 (CAF-1) complex and histone regulatory protein A (HIRA) complex mediate replication-couple (RC) and replication-independent (RI) nucleosome assembly, respectively. CHAF1B and HIRA share a similar domain but play different roles in nucleosome assembly by binding to the different interactors. At present, there is limited understanding for the similarities and differences in their respective functions. Tetrahymena thermophila contains transcriptionally active polyploid macronuclei (MAC) and transcriptionally silent diploid micronuclei (MIC). Here, the distribution patterns of Caf1b and Hir1 exhibited both similarities and distinctions. Both proteins localized to the MAC and MIC during growth, and to the MIC during conjugation. However, Hir1 exhibited additional signaling on parental MAC and new MAC during sexual reproduction and displayed a punctate signal on developing anlagen. Caf1b and Hir1 only co-localized in the MIC with Pcna1 during conjugation. Knockdown of CAF1B impeded cellular growth and arrested sexual reproductive development. Loss of HIR1 led to MIC chromosome defects and aborted sexual development. Co-interference of CAF1B and HIR1 led to a more severe phenotype. Moreover, CAF1B knockdown led to the up-regulation of HIR1 expression, while knockdown of HIR1 also led to an increase in CAF1B expression. Furthermore, Caf1b and Hir1 interacted with different interactors. These results showed that CAF-1 and Hir1 have independent and complementary functions for chromatin assembly in T. thermophila.

DNA mismatch repair (MMR) improves replication accuracy by up to three orders of magnitude. The MutS protein in E. coli or its eukaryotic homolog, the MutSα (Msh2-Msh6) complex, recognizes base mismatches and initiates the mismatch repair mechanism. Msh6 is an essential protein for assembling the heterodimeric complex. However, the function of the Msh6 subunit remains elusive. Tetrahymena undergoes multiple DNA replication and nuclear division processes, including mitosis, amitosis, and meiosis. Here, we found that Msh6Tt localized in the macronucleus (MAC) and the micronucleus (MIC) during the vegetative growth stage and starvation. During the conjugation stage, Msh6Tt only localized in MICs and newly developing MACs. MSH6Tt knockout led to aberrant nuclear division during vegetative growth. The MSH6TtKO mutants were resistant to treatment with the DNA alkylating agent methyl methanesulfonate (MMS) compared to wild type cells. MSH6Tt knockout affected micronuclear meiosis and gametogenesis during the conjugation stage. Furthermore, Msh6Tt interacted with Msh2Tt and MMR-independent factors. Downregulation of MSH2Tt expression affected the stability of Msh6Tt. In addition, MSH6Tt knockout led to the upregulated expression of several MSH6Tt homologs at different developmental stages. Msh6Tt is involved in macronuclear amitosis, micronuclear mitosis, micronuclear meiosis, and gametogenesis in Tetrahymena.

The flavonoids from Perilla leaves were extracted using flash extraction assisted by ultrasonic extraction with ethanol. Subsequently, macroporous resin was employed for the isolation and purification of these flavonoids, followed by an investigation into their antioxidant activity. The process conditions for the extraction of flavonoids from Perilla leaves were designed and optimized using a one-way experiment combined with a response surface methodology. The optimal extraction conditions were determined as follows: the liquid–solid ratio was 20:1, ethanol volume fraction of 60%, ultrasound temperature of 60 °C, ultrasound time of 10 min and flash evaporation time of 60 s. The optimal extraction rate of flavonoids is 9.8 mg/g. In terms of separation and purification, a high-performance macroporous resin (HPD450 resin) with high purification efficiency was selected through static analysis and adsorption experiments. The optimal enrichment conditions were as follows: loading concentration of 0.06 mg/mL, optimal loading concentration of 20 mL, elution concentration of 70% and 76 mL, providing a reference for the further development and utilization of Perilla leaf flavonoids.

This study aimed to explore key physicochemical characteristics and evolutionary patterns of microbial community structure during the fermentation of aged vinegar. The correlation between microorganisms and physicochemical characteristics during fermentation was examined. The results revealed significant differences in genera at different stages of fermentation. The dominant bacteria in R1 were Bacillus, Lactobacillus, Aspergillus, and Issatchenkia. During the R2 fermentation stage, Lactobacillus, Acetobacter, and Saccharomyces exhibited an upward trend and finally became the dominant bacteria. Aspergillus was the main bacterial genus at the end of overall fermentation. The correlation analysis showed that the bacterial genera significantly positively and negatively correlated with reducing sugars and amino acid nitrogen were the same in Cuqu. Similarly, the bacterial genera significantly positively and negatively correlated with pH and saccharification power were the same. pH, reducing sugar, and saccharification ability were mainly positively correlated with bacterial genera during fermentation. Further, studies found that the overall correlation between fungal communities and physicochemical characteristics was weaker than the correlation with bacteria during fermentation.

In order to investigate the antioxidant activity of Elaeagnus umbellata polysaccharides, the physicochemical characteristics of purified Elaeagnus umbellata polysaccharides (EUP, consisting of two fractions, EUP1 and EUP2) were investigated using UV spectrophotometry, high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), and Fourier transform infrared spectroscopy (FT-IR). This revealed that EUP1 and EUP2 were acidic polysaccharides with an average molecular weight (MW) of 63 and 38 kDa, respectively. EUP1 mainly consisted of L-rhamnose and D-galactose in a molar ratio of 2.05:1, and EUP2 consisted of D-mannose, L-rhamnose, D-galactose, and D-arabinose in a molar ratio of 2.06:1:2.78:1. Furthermore, EUP exhibited considerable antioxidant potential for scavenging hydroxyl, superoxide anion, DPPH, and ABTS radicals. Therefore, EUP can be developed as a potential antioxidant for the functional food or pharmaceutical field.

Xiaoer-Feire-Kechuan (XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation. The complicated composition rendered its chemical analysis and effective-component elucidation. In this study, we combined quantitative analysis and bioactivity test to reveal the anti-inflammatory constituents of XFK. First, UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes (covering 9 out of 11 herbs) in different XFK formulations. Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity. Then, anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay. Finally, major analytes forsythosides H, I, A (8–10), and baicalin (15) (total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities (inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK. The present study provided an effective strategy to discover effective constituents of multi-herb formulas.

This research presents a novel, eco-friendly, vortex-assisted liquid–liquid microextraction (VALLME) approach, integrating hydrophobic deep eutectic solvents (DESs) with HPLC for the identification and quantification of nine specific flavonoids in Shanxi aged vinegar (SAV). The parameters of DES-VALLME, including the ratio of trioctylmethylammonium chloride to 1,4-butanediol (1:6), DES volume (150 μL), vortex duration (5 min), the concentration of NaCl (0.40 g), and centrifugation time (10 min), were optimized to achieve the maximum extraction efficiency of target substances. Under these optimal conditions, quantitative analyses performed via HPLC demonstrated a broad linear range of 0.20–50.00 μg/mL and correlation coefficients (r2) greater than 0.9944 for all nine calibration curves. The limits of detection (LOD) and limits of quantitation (LOQ) were 0.09–0.18 μg/mL and 0.30–0.60 μg/mL, respectively, ensuring high sensitivity. The relative standard deviations for intra-day and inter-day variability were within the acceptable range, 2.34–3.77% and 3.04–4.96%, respectively, demonstrating the method’s reliability. The recovery rates ranged from 85.97% to 108.11%, underscoring the method’s precision. This technique exhibited a significant enrichment effect (enrichment factor: 43 to 296) on SAV flavonoids. Notably, the eco-friendliness of this procedure was evaluated using the Analytical Eco-Scale, Green Analytical Procedure Index, and Analytical Greenness Metric. The results suggested that this technique is a viable green alternative to traditional flavonoid determination methods in SAV. In summary, this novel method provides a theoretical basis for assessing flavonoid content in SAV samples and tracing SAV products. This contribution has significant implications for enhancing analytical techniques in food chemistry and environmental science and the sustainable development of the food industry.

Mismatch repair (MMR) is a conserved mechanism that is primarily responsible for the repair of DNA mismatches during DNA replication. Msh2 forms MutS heterodimer complexes that initiate the MMR in eukaryotes. The function of Msh2 is less clear under different chromatin structures. Tetrahymena thermophila contains a transcriptionally active macronucleus (MAC) and a transcriptionally silent micronucleus (MIC) in the same cytoplasm. Msh2 is localized in the MAC and MIC during vegetative growth. Msh2 is localized in the perinuclear region around the MIC and forms a spindle-like structure as the MIC divides. During the early conjugation stage, Msh2 is localized in the MIC and disappears from the parental MAC. Msh2 is localized in the new MAC and new MIC during the late conjugation stage. Msh2 also forms a spindle-like structure with a meiotic MIC and mitotic gametic nucleus. MSH2 knockdown inhibits the division of MAC and MIC during vegetative growth and affects cellular proliferation. MSH2 knockdown mutants are sensitive to cisplatin treatment. MSH2 knockdown also affects micronuclear meiosis and gametogenesis during sexual development. Furthermore, Msh2 interacts with MMR-dependent and MMR-independent factors. Therefore, Msh2 is necessary for macronuclear stability, as well as micronuclear mitosis and meiosis in Tetrahymena.

Abstract Histone chaperones facilitate DNA replication and repair by promoting chromatin assembly, disassembly and histone exchange. Following histones synthesis and nucleosome assembly, the histones undergo posttranslational modification by different enzymes and are deposited onto chromatins by various histone chaperones. In Tetrahymena thermophila, histones from macronucleus (MAC) and micronucleus (MIC) have been comprehensively investigated, but the function of histone chaperones remains unclear. Histone chaperone Nrp1 in Tetrahymena contains four conserved tetratricopepeptide repeat (TPR) domains and one C-terminal nuclear localization signal. TPR2 is typically interrupted by a large acidic motif. Immunofluorescence staining showed that Nrp1 is located in the MAC and MICs, but disappeared in the apoptotic parental MAC and the degraded MICs during the conjugation stage. Nrp1 was also colocalized with α-tubulin around the spindle structure. NRP1 knockdown inhibited cellular proliferation and led to the loss of chromosome, abnormal macronuclear amitosis, and disorganized micronuclear mitosis during the vegetative growth stage. During sexual developmental stage, the gametic nuclei failed to be selected and abnormally degraded in NRP1 knockdown mutants. Affinity purification combined with mass spectrometry analysis indicated that Nrp1 is co-purified with core histones, heat shock proteins, histone chaperones, and DNA damage repair proteins. The physical direct interaction of Nrp1 and Asf1 was also confirmed by pull-down analysis in vitro. The results show that histone chaperone Nrp1 is involved in micronuclear mitosis and macronuclear amitosis in the vegetative growth stage and maintains gametic nuclei formation during the sexual developmental stage. Nrp1 is required for chromatin stability and nuclear division in Tetrahymena thermophila.

We summarized two cases of congenital factor V deficiency (FVD) associated with a novel F5 mutation, and analyzed the relationship of the clinical features and genetic characteristics in congenital FVD. Case 1 was a female newborn infant with remarkable bleeding who died of severe intracranial hemorrhage on day 42 after birth. She had significant prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT). The percentage activity of FV (PFV) was lower than 3% in case 1. The mother of case 1 showed no tendency to bleed. She had mild prolongation of PT and APTT. The PFV was only 43%. Both cases were found to have the same novel mutation in F5, which was c.5419G>A (p.Ala1807Thr) in exon 16. The variant in case 1 was inherited from the mother of case 1. Whole-exome sequencing (WES) also found a splice site mutation: a 103 Mb maternal uniparental disomy (UPD) of 1q21.1-qter in case 1, in which the F5 gene is located in this segment. So case 1 was homozygote and the mother of case 1 was heterozygote. The novel mutation of F5 was predicted to be harmful by bioinformatics software including Sorting Intolerant From Tolerant (SIFT), Polyphen2, LRT, and Mutation Taster. In summary, c.5419G>A (p.Ala1807Thr) in exon 16 of F5 is a pathogenic mutation, which causes severe congenital FVD in homozygote patients.

As a means of resource reserve and economic compensation，earthquake catastrophe insurance can effectively reduce the burden of the government and provide economic compensation for the victims. After an earthquake，the economic damage of a megacity is worse than that in other cities. Therefore，it is particularly important to promote earthquake catastrophe insurance in megacities. In this paper，we compare and sort out the current situation of earthquake catastrophe insurance from aspects of policy，regulation，model construction and practical application. We analyze the difficulties in carrying out earthquake insurance in megacities of China. Finally，taking Beijing as an example，we put forward some suggestions on the development of megacity earthquake catastrophe insurance，and provide reference for policy-making and decision-making of relevant government departments in Beijing.

Abstract Background Cadmium (Cd) is a nonessential heavy metal with potentially deleterious effects on different organisms. The organisms have evolved sophisticated defense system to alleviate heavy metal toxicity. Hydrogen sulfide (H2S) effectively alleviates heavy metal toxicity in plants and reduces oxidative stress in mammals. However, the function of H2S for alleviating heavy metal toxicity in aquatic organisms remains less clear. Tetrahymena thermophila is an important model organism to evaluate toxic contaminants in an aquatic environment. In this study, the molecular roles of exogenously H2S application were explored by RNA sequencing under Cd stress in T. thermophila. Results The exposure of 30 μM Cd resulted in T. thermophila growth inhibition, cell nigrescence, and malondialdehyde (MDA) content considerably increase. However, exogenous NaHS (donor of H2S, 70 μM) significantly alleviated the Cd-induced toxicity by inhibiting Cd absorbtion, promoting CdS nanoparticles formation and improving antioxidant system. Comparative transcriptome analysis showed that the expression levels of 9152 genes changed under Cd stress (4658 upregulated and 4494 downregulated). However, only 1359 genes were differentially expressed with NaHS treatment under Cd stress (1087 upregulated and 272 downregulated). The functional categories of the differentially expressed genes (DEGs) by gene ontology (GO) revealed that the transcripts involved in the oxidation–reduction process, oxidoreductase activity, glutathione peroxidase activity, and cell redox homeostasis were the considerable enrichments between Cd stress and NaHS treatment under Cd stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the carbon metabolism, glutathione metabolism, metabolism of xenobiotics by cytochrome P450, and ABC transporters were significantly differentially expressed components between Cd stress and NaHS treatment under Cd stress in T. thermophila. The relative expression levels of six DEGs were further confirmed through quantitative real-time polymerase chain reaction (qRT-PCR). Conclusion NaHS alleviated Cd stress mainly through inhibiting Cd absorbtion, promoting CdS nanoparticles formation, increasing oxidation resistance, and regulation of transport in free-living unicellular T. thermophila. These findings will expand our understanding for H2S functions in the freshwater protozoa.

ObjectiveSome studies have demonstrated a bidirectional association between obesity and depression, whereas others have not. This discordance might be due to the metabolic health status. We aimed to determine whether the relationship between obesity and depression is dependent on metabolic health status.MethodsIn total, 9,022,089 participants were enrolled and classified as one of four obesity phenotypes: metabolically healthy nonobesity (MHNO), metabolically unhealthy nonobesity (MUNO), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). We then divided the population into eight phenotypes based on obesity and the number of metabolic risk factors. Furthermore, the associations of eight phenotypes, based on obesity and specific metabolic risk factors, with depression were assessed.ResultAmong all participants, a higher risk of depression was observed for MUNO, MHO and MUO than for MHNO. The risk was highest for MUO (OR = 1.442; 95% CI = 1.432, 1.451). However, the association between MHO and depression was different for men and women (OR = 0.941, men; OR = 1.132, women). The risk of depression increased as the number of metabolic risk factors increased. Dyslipidemia was the strongest metabolic risk factor. These relationships were consistent among patients ≥ 45 years of age.ConclusionsThe increased risk of obesity-related depression appears to partly depend on metabolic health status. The results highlight the importance of a favorable metabolic status, and even nonobese populations should be screened for metabolic disorders.

Abstract Background Neonatal thrombocytopenia is common in preterm and term neonates admitted to neonatal intensive care units. The etiology behind neonatal thrombocytopenia is complex. Inherited thrombocytopenia is rare and usually results from genetic mutations. Case presentation Here we report a case of twins with severe inherited thrombocytopenia presented in the neonatal period who were shown to be compound heterozygotes for 2 UDP-N-acetylglucosamine 2-epimerase (GNE) gene mutations, c.1351C > T and c.1330G > T, of which c.1330G > T is a novel mutation. Conclusion These two GNE mutations may help in the diagnosis and management of thrombocytopenia diagnosed in neonates.

Abstract Background COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. Methods A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. Results Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). Conclusions Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. Trial registration Chinese Clinical Trial Registry ( chictr.org.cn ) identifier: ChiCTR2000030464.

Gas emission from the goaf is one of the important sources of gas in the working face and a reasonable goaf drainage scheme can effectively solve the problem of gas overrun in working face.Combined with numerical simulation and field application, the gas intubation extraction system in the gob of the fully mechanized caving face in 42-top coal seam of Buertai Coal Mine is optimized in this paper.Firstly, the FLUENT fluid simulation software is utilized to simulate the characteristics of gas migration in the stope, considering the desorption of the remaining coal in the goaf and the gas emission from the upper adjacent layer.The distribution laws of gas concentration in the goaf are revealed, and the influence of the distance between the extraction outlet and the air-return corner, drainage negative pressure and air supply ratio on the extraction effect are analyzed, the optimized scheme of extractionis proposed accordingly.Then the optimization scheme is applied on the spot, focusing on the distance between the extraction outlet and the air-return corner and negative pressure.It is concluded that when the intubation distance is 70 m and negative pressure is 12~18 kPa, the extraction effect is better.The research results have theoretical and practical significance for the optimization of gas drainage scheme in goaf of high yield, high efficiency and low gas mines.

Given the high and increasing prevalence of obesity and associated disorders, such as type-2 diabetes, it is important to understand the mechanisms that regulate lipid storage and the differentiation of fat cells, a process termed adipogenesis. Using the well-established mouse 3T3-L1 in vitro model of adipogenesis, we refine how the induction of two key adipogenic transcription factors, CCAAT/enhancer-binding proteins (C/EBPs) β and δ are regulated during early adipogenesis. We identify, in the gene promoters of Cebpb and Cebpd, the DNA response elements responsible for binding transcription factors that are activated by cAMP or glucocorticoids. We also show that mitogen-activated protein kinase (MAPK)-interacting kinase 2 (MNK2; Mknk2), which plays a distinct role in diet-induced obesity, is induced during early adipogenesis and identify the functional DNA response elements responsible for regulating its expression. Mknk2 expression is maintained in differentiated 3T3-L1 adipocytes and is expressed at high levels across a range of mouse adipose tissue depots. Together, these new insights help to clarify the transcriptional programme of early adipogenesis and identify Mknk2 as one of potentially many genes up-regulated during adipogenesis.

In this study, lactic acid bacteria (LAB) strains were isolated from fermented grains of traditional Chinese Baijiu, and their probiotic properties were characterized. Eleven out of 29 LAB strains showed good tolerance to the gastrointestinal tract and bile salts. The surface characteristics (auto-aggregation, co-aggregation, hydrophobicity), safety (hemolytic and antibiotic sensitivity), antibacterial activity against three foodborne pathogens, and antioxidant and hypoglycemic properties of the 11 LAB strains were investigated. Principal component analysis (PCA) was used to comprehensively evaluate LAB strains and their probiotic properties. It was found that Weissella cibaria (OP288150), Pediococcus acidilactici (OP288151), Pediococcus pentosaceus (OP288154), Pediococcus pentosaceus (OP288156) and Levilactobacillus brevis (OP288158) showed high probiotic properties, with potential for commercial development. The results also demonstrated that fermented grains of Chinese Baijiu can be used as a source of high-quality probiotics.

Diabetes is a type of metabolic disease associated with changes in the intestinal flora. In this study, the regulatory effect of millet bran on intestinal microbiota in a model of type 2 diabetes (T2DM) was investigated in an effort to develop new approaches to prevent and treat diabetes and its complications in patients. The effect of purified millet bran polysaccharide (MBP) with three different intragastric doses (400 mg/kg, 200 mg/kg, and 100 mg/kg) combined with a high-fat diet was determined in a streptozotocin (STZ)-induced model of T2DM. By analyzing the changes in indicators, weight, fasting blood sugar, and other bio-physiological parameters, the changes in gut microbiota were analyzed via high-throughput sequencing to establish the effect of MBP on the intestinal flora. The results showed that MBP alleviated symptoms of high-fat diet-induced T2DM. A high dosage of MBP enhanced the hypoglycemic effects compared with low and medium dosages. During gavage, the fasting blood glucose (FBG) levels of rats in the MBP group were significantly reduced (p < 0.05). The glucose tolerance of rats in the MBP group was significantly improved (p < 0.05). In diabetic mice, MBP significantly increased the activities of CAT, SOD, and GSH-Px. The inflammatory symptoms of liver cells and islet cells in the MBP group were alleviated, and the anti-inflammatory effect was partially correlated with the dose of MBP. After 4 weeks of treatment with MBP, the indices of blood lipid in the MBP group were significantly improved compared with those of the DM group (p < 0.05). Treatment with MBP (400 mg/kg) increases the levels of beneficial bacteria and decreases harmful bacteria in the intestinal tract of rats, thus altering the intestinal microbial community and antidiabetic effect on mice with T2DM by modulating gut microbiota. The findings suggest that MBP is a potential pharmaceutical supplement for preventing and treating diabetes.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a chronic and progressive liver disease with an increased risk of morbidity and mortality. However, so far no specific pharmacotherapy has been approved. Gynostemma pentaphylla (Thunb.) Makino (GP) is a traditional Chinese medicine that is widely used against hyperlipemia as well as hyperglycemia. This study aims to evaluate the effect of GP on NAFLD and explore the possible mechanism. Methods High-fat-diet induced NAFLD mice model were orally administrated with GP at dose of 11.7 g/kg or equivalent volume of distilled water once a day for 16 weeks. Body weight, food intake and energy expenditure were assessed to evaluate the general condition of mice. The triglycerides, total cholesterol content in the liver and liver histopathology, serum lipid profile and serum insulin level, fecal microbiome, hepatic microRNAs and relative target genes were analyzed. Results Mice in GP treatment group displayed improved hepatic triglycerides content with lower lipid droplet in hepatocyte and NAFLD activity score. Besides, GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components that are implicated in metabolic disorders, especially phylum Firmicutes (Eubacterium, Blautia, Clostridium and Lactobacillus). Several hepatic microRNAs were downregulated by GP treatment such as miR-130a, miR-34a, miR-29a, miR-199a, among which the expression miR-34a was altered by more than four-fold compared to that of HFD group (3:14). The correlation analysis showed that miR-34a was strongly related to the change of gut microbiota especially phylum Firmicutes (R = 0.796). Additionally, the target genes of miR-34a (HNF4α, PPARα and PPARα) were restored by GP both in mRNA and protein levels. Conclusion Our results suggested that GP modulated the gut microbiota and suppressed hepatic miR-34a, which was associated with the amelioration of hepatic steatosis.

Objectives: Diet-driven obesity is increasingly widespread. Its consequences pose major challenges to human health and health care systems. There are MAP kinase-interacting kinases (MNKs) in mice, MNK1 and MNK2. Studies have demonstrated that mice lacking either MNK1 or MNK2 were partially protected against high-fat diet (HFD)-induced weight gain and insulin resistance. The aims of this study were to evaluate the phenotype of mice lacking both MNKs when given an HFD, to assess whether pharmacological inhibition of MNK function also protects against diet-induced obesity (DIO) and its consequences and to probe the mechanisms underlying such protection. Methods: Male wild-type (WT) C57Bl6 mice or mice lacking both MNK1 and MNK2 (double knockout, DKO) were fed an HFD or control diet (CD) for up to 16 weeks.In a separate study, WT mice were also given an HFD for 6 weeks, after which half were treated with the recently-developed MNK inhibitor ETC-206 daily for 10 more weeks while continuing an HFD. Metabolites and other parameters were measured, and the expression of selected mRNAs and proteins was assessed. Results: MNK-DKO mice were almost completely protected from HFD-induced obesity. Higher energy expenditure (EE) in MNK-DKO mice was observed, which probably reflects the changes in a number of genes or proteins linked to lipolysis, mitochondrial function/biogenesis, oxidative metabolism, and/or ATP consumption. The MNK inhibitor ETC-206 also prevented HFD-induced weight gain, confirming that the activity of the MNKs facilitates weight gain due to excessive caloric consumption. Conclusions: Disabling MNKs in mice, either genetically or pharmacologically, strongly prevents weight gain on a calorie-rich diet. This finding likely results from increased energy utilisation, involving greater ATP consumption, mitochondrial oxidative metabolism, and other processes.

Thyroxine metabolism is an important topic of pathogenesis research and treatment schedule of subclinical hypothyroidism (SCH). L-Thyroxine replacement therapy (LRT) is usually recommended for severe SCH patients only. Our previous studies reported that disordered serum lipid of mild SCH people could also benefit from LRT. However, the benefits were different among individuals, as shown by the variations in drug dosage that required to maintain thyroid-stimulating hormone (TSH) stability. Alternative pathways, such as sulfation and glucuronidation of iodothyronine, may play a role in thyroid hormones metabolism in peripheral tissues aside from thyroid. Conjugated thyroxine can be hydrolyzed and reused in tissues including gastrointestinal tract, in which gut microbiota are one of the most attractive physiological components. On this site, the roles of gut microbiota in thyroidal metabolism should be valued. In this study, a cross-sectional study was performed by analyzing 16S rDNA of gut microbiota in mild SCH patients treated with L-thyroxine or not. Subjects were divided by serum lipid level, L-thyroxine treatment, or L-thyroxine dosage, respectively. Relationship between gut microbiome and serum profile, L-thyroxine treatment, and dose were discussed. Other metabolic disorders such as type 2 diabetes and hypertension were also taken into consideration. It turned out that microbiome varied among individuals divided by dose and the increment of L-thyroxine but not by serum lipid profile. Relative abundance of certain species that were associated with thyroxine metabolism were found varied among different L-thyroxine doses although in relatively low abundance. Moreover, serum cholesterol may perform relevance effects with L-thyroxine in shaping microbiome. Our findings suggested that the differences in L-thyroxine dosage required to maintain TSH level stability, as well as the SCH development, which was displayed by the increased L-thyroxine doses in subsequent follow-up, had relationship with gut microbial composition. The reason may due to the differences in thyroxine metabolic capacity in gut. In addition, the metabolic similarity of iodothyronines and bile acid in gut also provides possibilities for the correlation between host's thyroxine and cholesterol levels.This study was registered with ClinicalTrials.gov as number NCT01848171.

Objective: This study aimed to investigate the clinical efficacy and safety of different non-invasive respiratory support methods in preterm infants with respiratory distress syndrome (RDS) after extubation.Methods: From Oct 2017 to 2018, 120 preterm infants were recruited from the NICUs of three hospitals. They were diagnosed with RDS and required mechanical ventilation. After extubation from mechanical ventilation, these infants were divided into NCPAP group, SNIPPV group and SNIPPV + NCPAP group. The time of non-invasive ventilation, reintubation rate within 72 h, success rate of non-invasive ventilation within 1 week, duration of oxygen therapy, hospital stay and incidence of complications were recorded and compared.Results: Compared with the NCPAP group, the SNIPPV group and the SNIPPV + NCPAP group had significantly higher rate of successful extubation and removal from non-invasive ventilation within 1 week (P < 0.05). There were no significant differences among three groups in the time of non-invasive ventilation, time of oxygen therapy, hospital stay or incidence of complications (P > 0.05).Conclusion: SNIPPV + NCPAP after mechanical ventilation is a relatively safe and effective ventilation strategy for preterm infants with severe RDS. The use of NCPAP facilitates the turnover of SNIPPV ventilators in developing countries.

Objectives. Nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia (HL) are common metabolic disorders due to overnutrition and obesity. NAFLD is often associated with hyperlipidemia. The aim of this study was to identify and compare the erythrocyte membrane lipids profile in NAFLD patients with or without HL. Methods. A total of 112 subjects (with similar age and body mass index) were divided into four groups: (1) normal controls, (2) NAFLD alone, (3) HL alone, and (4) NAFLD combined with HL (NAFLD + HL). Lipid was extracted from the erythrocyte membrane, and lipid profiles of subjects were analyzed by liquid chromatography mass spectrometry (LC-MS). Results. Data sets from 103 subjects were adopted for lipidomic analysis. Significant changes of lipid species were observed in patient groups, especially in the HL group and NAFLD + HL group. The HL group showed increased level of most lipid species, and decreased level of most lipid species was observed in the NAFLD + HL group. The weight percent of myristic acid, stearic acid, erucic acid, and docosahexaenoic acid also showed distinct variation between different groups. Conclusions. NAFLD, HL, and NAFLD + HL all had an impact on lipid profiling of the erythrocyte membrane. The influence of NAFLD alone is less important compared with HL. Some lipids should be highlighted because of their specific role in cell function and systemic metabolism.

Histone modification and nucleosome assembly are mainly regulated by various histone-modifying enzymes and chaperones. The roles of histone-modification enzymes have been well analyzed, but the molecular mechanism of histone chaperones in histone modification and nucleosome assembly is incompletely understood. We previously found that the histone chaperone Nrp1 is localized in the micronucleus (MIC) and the macronucleus (MAC) and involved in the chromatin stability and nuclear division of Tetrahymena thermophila. In the present work, we found that truncated C-terminal mutant HA-Nrp1TrC abnormally localizes in the cytoplasm. The truncated-signal-peptide mutants HA-Nrp1TrNLS1 and HA-Nrp1TrNLS2 are localized in the MIC and MAC. Overexpression of Nrp1TrNLS1 inhibited cellular proliferation and disrupted micronuclear mitosis during the vegetative growth stage. During sexual development, Nrp1TrNLS1 overexpression led to abnormal bouquet structures and meiosis arrest. Furthermore, Histone H3 was not transported into the nucleus; instead, it formed an abnormal speckled cytoplastic distribution in the Nrp1TrNLS1 mutants. The acetylation level of H3K56 in the mutants also decreased, leading to significant changes in the transcription of the genome of the Nrp1TrNLS1 mutants. The histone chaperone Nrp1 regulates the H3 nuclear import and acetylation modification of H3K56 and affects chromatin stability and genome transcription in Tetrahymena.

Nuclear autophagy is an important selective autophagy process. The selective autophagy of sexual development micronuclei (MICs) and the programmed nuclear degradation of parental macronucleus (paMAC) occur during sexual reproduction in Tetrahymena thermophila. The molecular regulatory mechanism of nuclear selective autophagy is unclear. In this study, the autophagy-related protein Atg5 was identified from T. thermophila. Atg5 was localized in the cytoplasm in the early sexual-development stage and was localized in the paMAC in the late sexual-development stage. During this stage, the degradation of meiotic products of MIC was delayed in atg5i mutants. Furthermore, paMAC was abnormally enlarged and delayed or failed to degrade. The expression level and lipidation of Atg8.2 significantly decreased in the mutants. All these results indicated that Atg5 was involved in the regulation of the selective autophagy of paMAC by regulating Atg8.2 in Tetrahymena.

MicroRNAs (miRNAs) are small noncoding RNAs approximately 20–25 nt in length, which play crucial roles through directly binding to corresponding 3′ UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations. Keywords: miR-134, human cancer, microRNA

Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient’s intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.