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[Display omitted] • N -doped C-coated Cu0/NC3-600 catalyst was prepared by pyrolysis of modified Cu-MOF. • Cu0/NC3-600 can fulfill effective degradation of NOR in the range of pH 3–11. • At pH 9, the removal of 20 mg/L NOR by 1 g/L Cu0/NC3-600 reached 98.34 % after 60 min. • In Cu0/NC3-600/air system, •O 2 – is the main active specie in acidic conditions. • Cu3+ and •O 2 – act together under alkaline conditions to destroy NOR. The Fenton-like activated molecular oxygen technology demonstrates significant potential in the treatment of refractory organic pollutants in wastewater, offering promising development prospects. We prepared a N -doped C -coated copper-based catalyst Cu0/NC3-600 through the pyrolysis of Mel-modified Cu-based metal–organic framework (MOF). The results indicate that the degradation of 20 mg/L norfloxacin (NOR) was achieved using 1.0 g/L Cu0/NC3-600 across a wide pH range, with a removal rate exceeding 95 % and total organic carbon (TOC) removals approaching 70 % after 60 min at pH 5–11. The nitrogen doping enhances the electronic structure of the carbon material, facilitating the adsorption of molecular oxygen. Additionally, the formed carbon layer effectively prevent copper leaching,contributing to increased stability to a certain extent. Subsequently, we propose the catalytic reaction mechanism for the Cu0/NC/air system. Under acidic conditions, Cu0/NC3-600 activates molecular oxygen to produce the •O 2 –, which serves as the primary active species for NOR degradation. While in alkaline conditions, the high-valent copper species Cu3+ is generated in conjunction with •O 2 –, both working simultaneously for NOR degradation. Furthermore, based on the LC-MS results, we deduced four possible degradation pathways. This work offers a novel perspective on expanding the pH range of copper-based catalysts with excellent ability to activate molecular oxygen for environmental water treatment. [ABSTRACT FROM AUTHOR]

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions–Severity of Illness scale (CGI-SI) and Clinical Global Impressions–Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96–11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders. In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Eukaryotic genes contain introns that are removed by the spliceosomal machinery during mRNA maturation. Introns impose a huge energetic burden on a cell; therefore, they must play an essential role in maintaining genome stability and/or regulating gene expression. Many genes (> 50%) in Plasmodium parasites contain predicted introns, including introns in 5′ and 3′ untranslated regions (UTR). However, the roles of UTR introns in the gene expression of malaria parasites remain unknown. Methods: In this study, an episomal dual-luciferase assay was developed to evaluate gene expression driven by promoters with or without a 5′UTR intron from four Plasmodium yoelii genes. To investigate the effect of the 5′UTR intron on endogenous gene expression, the pytctp gene was tagged with 3xHA at the N-terminal of the coding region, and parasites with or without the 5′UTR intron were generated using the CRISPR/Cas9 system. Results: We showed that promoters with 5′UTR introns had higher activities in driving gene expression than those without 5′UTR introns. The results were confirmed in recombinant parasites expressing an HA-tagged gene (pytctp) driven by promoter with or without 5′UTR intron. The enhancement of gene expression was intron size dependent, but not the DNA sequence, e.g. the longer the intron, the higher levels of expression. Similar results were observed when a promoter from one strain of P. yoelii was introduced into different parasite strains. Finally, the 5′UTR introns were alternatively spliced in different parasite development stages, suggesting an active mechanism employed by the parasites to regulate gene expression in various developmental stages. Conclusions: Plasmodium 5′UTR introns enhance gene expression in a size-dependent manner; the presence of alternatively spliced mRNAs in different parasite developmental stages suggests that alternative slicing of 5′UTR introns is one of the key mechanisms in regulating parasite gene expression and differentiation. [ABSTRACT FROM AUTHOR]

Due to their high porosity, large specific surface area, and structural similarity with the extracellular matrix (ECM), electrospun nanofiber membranes are often endowed with the antibacterial properties for biomedical applications. The purpose of this study was to synthesize nano-structured Sc2O3-MgO by doping Sc3+, calcining at 600 °C, and then loading it onto the PCL/PVP substrates with electrospinning technology with the aim of developing new efficient antibacterial nanofiber membranes for tissue engineering. A scanning electron microscope (SEM) and energy dispersive X-ray spectrometer (EDS) were used to study the morphology of all formulations and analyze the types and contents of the elements, and an X-ray diffraction (XRD), thermogravimetric analysis (TGA), and Fourier transform attenuated total reflection infrared spectroscopy (ATR-FTIR) were used for further analysis. The experimental results showed that the PCL/PVP (SMCV-2.0) nanofibers loaded with 2.0 wt% Sc2O3-MgO were smooth and homogeneous with an average diameter of 252.6 nm; the antibacterial test indicated that a low load concentration of 2.0 wt% Sc2O3-MgO in PCL/PVP (SMCV-2.0) showed a 100% antibacterial rate against Escherichia coli (E. coli). [ABSTRACT FROM AUTHOR]

In order to obtain the inorganic efficient antibacterial agents, the means of ion doping and morphology construction in this research are used to enhance the antibacterial property of nano-MgO, which is according to the "oxidative damage mechanism" and "contact mechanism". In this work, the nano-textured Sc2O3-MgO are synthesized by doping Sc3+ in nano-MgO lattice through calcining at 600 °C. When the Sc3+ content reaches 10%, the nanotextures on the powders surface are pretty clearly visible and uniform, and the specific surface area and the oxygen vacancy are ideal, so that the 10% Sc3+-doped powders (SM-10) has the excellent antibacterial property against E. coli and S. aureus (MBC = 0.03 mg/mL). The efficient antibacterial agents in this research have a better antibacterial effect than the 0% Sc3+-doped powders (SM-0, MBC = 0.20 mg/mL) and the commercial nano-MgO (CM, MBC = 0.40 mg/mL), which have application prospects in the field of antibacterial. [ABSTRACT FROM AUTHOR]

The multifunctional polyethylene terephthalate (PET) fabrics were successfully prepared through a dip-coating technology to endow the flame retardant and antibacterial properties of PET fabrics, which are extensively used in many fields. The flame retardant and antibacterial agent was synthesized by a double drop-reverse precipitation method and surface-modified by the mixtures of titanate coupling agents and stearic acid to result in a good compatibility of the hydrophilic nano-Mg(OH)2 and the hydrophobic PET fabrics. The results indicated that the suitable synthesis conditions of nano-Mg(OH)2 are: Mg2+ concentration 1.5 mg/mL, reaction temperature 50 °C and reaction time 50 min, and the optimal modification conditions of nano-Mg(OH)2 are: modifier ratio 5/5, modification temperature 70 °C and modification time 40 min. The flame retardant test and the antibacterial test showed that the multifunctional PET fabrics had excellent flame retardant and antibacterial properties. [ABSTRACT FROM AUTHOR]

Antibacterial and active packaging materials have gained significant research attention in response to the growing interest in food packaging. In this investigation, we developed hydrogel packaging materials with antibacterial and antioxidant properties by incorporating chitooligosaccharide (COS) and fish skin gelatin (FSG) nanofiber membranes, which readily absorbed water and exhibited swelling characteristics. The nanofiber membranes were fabricated by electrospinning technology, embedding COS within FSG, and subsequently crosslinked through the Maillard reaction facilitated by the addition of glucose. The behavior of conductivity, viscosity, and surface tension in the spinning solutions was analyzed to understand their variation patterns. Scanning electron microscopy (SEM) results revealed that the crosslinked COS/FSG nanofiber membranes possessed a uniform yet disordered fiber structure, with the diameter of the nanofibers increasing as the COS content increased. Remarkably, when the COS content reached 25 %, the COS/FSG nanofiber membranes (CF-C-25) exhibited a suitable fiber diameter of 437.16 ± 63.20 nm. Furthermore, the thermal crosslinking process involving glucose supplementation enhanced the hydrophobicity of CF-C-25. Upon hydration, the CF-H-25 hydrogel displayed a distinctive porous structure, exhibiting a remarkable swelling rate of 954 %. Notably, the inclusion of COS significantly augmented the antibacterial and antioxidant properties of the hydrogel-based nanofiber membranes. CF-H-25 demonstrated an impressive growth inhibition of 90.56 ± 5.91 % against E. coli , coupled with excellent antioxidant capabilities. In continuation, we performed a comprehensive analysis of the total colony count, pH, TVB-N, and TBA of crucian carp. The CF-H-25 hydrogel proved highly effective in extending the shelf life of crucian carp by 2–4 days, suggesting its potential application as an edible membrane for aquatic product packaging. [Display omitted] • Nanofibers composed of COS/FSG were synthetized via the electrospinning technique. • Hydrogel was prepared by water absorption swelling of nanofibers after Maillard reaction. • COS/FSG nanofiber-based hydrogel was fabricated for food packaging. • COS/FSG nanofiber-based hydrogel have significant antibacterial and antioxidant properties. [ABSTRACT FROM AUTHOR]

Microwave plasma chemical vapor deposition (MPCVD) has received tremendous research interest in fabrication of carbon nanotubes (CNTs) due to its unique advantages of high reactivity, rapid heating, no pollution, good controllability, etc. It would be meaningful to summarize the efforts that have been devoted in this area. Up to now, no such review has been seen in the literature. In this review, a summarization and discussion of the MPCVD devices applied in CNTs fabrication are firstly given, followed by the discussion on effect and affecting mechanisms of H2 plasma pretreatment, nitrogen atoms in the reacting gases and microwave power. Notably, the parameters of as-synthesized CNTs products and the corresponding synthesizing MPCVD conditions are listed out. Finally, the capabilities of MPCVD in facilitating atmospheric-pressure, low-temperature and in situ growth of CNTs are reviewed. This review can give a comprehensive grasp of current progress and understanding of MPCVD in preparation of CNTs and may provide a useful guidance for readers to design their fabricating systems to obtained required CNTs using MPCVD. [ABSTRACT FROM AUTHOR]

This article utilizes two ingestible substrates, pullulan and pectin, to fabricate nanofiber membranes by means of electrospinning technology, and assessed their digestion characteristics in simulated gastrointestinal fluids. The physicochemical properties of pullulan/pectin spinning solution and the effects of electrospinning process parameters on the diameter and morphology of pullulan/pectin nanofibers were investigated. Scanning electron microscope indicates that the best electrospinning process parameters were obtained as spinning voltage: 20 kV, needle-collector distance: 15 cm, propulsion speed: 0.6 mL/h and needle inner diameter: 0.41 mm. Moreover, at a pullulan/pectin volume ratio of 8:2, the nanofiber morphology exhibited optimal characteristics, featuring an average fiber diameter of 369.45 ± 42.41 nm. Fourier transform infrared spectroscopy, X-ray diffraction, and thermal analysis indicates the formation of strong hydrogen bonds between pullulan and pectin. The mechanical performance tests demonstrated that, with a volume ratio of 8:2 for pullulan and pectin, the nanofiber exhibited a tensile strength of 1196.86 ± 51.87 cN and an elongation at break of 80.26 ± 3.6%, indicating favorable capacity for elongation and deformation. Furthermore, the in vitro degradability test indicates that pullulan/pectin nanofibers with a volume ratio of 8:2 were decomposed by specific enzymes in intestinal fluid. Therefore, ingestible pullulan/pectin nanofiber substrates have shown certain development potential in the field of targeted drug or bioactive delivery. • Smooth and uniform PUL/PEC fiber substrates were prepared by electrospinning. • Nanofibers were designed using blend of pullulan and pectin with a mass ratio of 8: 2. • Colon-specific decomposition property was evaluated by an in vitro degradability test. • PUL/PEC nanofibers showed potential as colon delivery systems. [ABSTRACT FROM AUTHOR]

• The dynamic characteristic of wet clutch actuating system is analyzed. • Three types of speed deviations occurring in clutch filling process are analyzed. • An adaptive iterative control strategy for the wet-clutch filling process is proposed. • A double-input-and-double-output fuzzy logic controller (DIDO-FLC) is designed. • The vehicle test is performed to validate the proposed control strategy. In the gear shifting processes of an automatic transmission (AT), fast and smooth transitions between different gears without drivetrain jerking are always expected, which leads to a desire for high-quality clutch-to-clutch shifts. The accurate and effective filling control of clutches is the base for achieving desirable clutch-to-clutch shifts. This study focuses on developing an adaptive fuzzy iterative control strategy for the filling process of wet clutches in ATs. Firstly, a specific structure and dynamic characteristics of the wet clutch actuating system is analyzed to assist in the designing of control strategies. Afterwards, three types of deviations that usually occur in the filling process, named as speed drop, clutch tie-up and engine flare respectively, are defined and analyzed according to their different characteristics. The adaptive control strategy is then developed to realize the reduction of the deviations. The concrete adjustment performed by the control strategy is based on the features of the previous deviations during the adaptive iteration. Moreover, a double-input-and-double-output fuzzy logic controller (DIDO-FLC) is designed and introduced in the control strategy, which can adjust the fast filling time and the maximum fast filling pressure of the clutch simultaneously. In order to validate the proposed strategy, the results of vehicle test are presented, which demonstrate that the deviations are effectively diminished and the shifting quality is obviously improved. [ABSTRACT FROM AUTHOR]

Presents information on a study which described a method for the preparation of multilayer thin films alternately composed of platinum nanoclusters and polymer dye molecules by a novel ionic self-assembled monolayer (ISAM) process. Experimentation; Results and discussion; Conclusions.

• Plasmodium yoelii can repair CRISPR/Cas9-generated DNA breaks by microhomology-mediated end joining. • Size mutants of the central repeat in circumsporozoite surface protein (CSP) were successfully generated. • A minimum size of the CSP central repeat region is required for mosquito stage development. CRISPR/Cas9 is a powerful genome editing method that has greatly facilitated functional studies in many eukaryotic organisms including malaria parasites. Due to the lack of genes encoding enzymes necessary for the non-homologous end joining DNA repair pathway, genetic manipulation of malaria parasite genomes is generally accomplished through homologous recombination requiring the presence of DNA templates. Recently, an alternative double-strand break repair pathway, microhomology-mediated end joining, was found in the Plasmodium falciparum parasite. Taking advantage of the MMEJ pathway, we developed a MMEJ-based CRISPR/Cas9 (mCRISPR) strategy to efficiently generate multiple mutant parasites simultaneously in genes with repetitive sequences. As a proof of principle, we successfully produced various size mutants in the central repeat region of the Plasmodium yoelii circumsporozoite surface protein without the use of template DNA. Monitoring mixed parasite populations and individual parasites with different sizes of CSP-CRR showed that the CSP-CRR plays a role in the development of mosquito stages, with severe developmental defects in parasites with large deletions in the repeat region. However, the majority of the csp mutant parasite clones grew similarly to the wild type P. yoelii 17XL parasite in mice. This study develops a useful technique to efficiently generate mutant parasites with deletions or insertions, and shows that the CSP-CRR plays a role in parasite development in mosquito. [ABSTRACT FROM AUTHOR]

In order to fabricate antibacterial nanofiber membranes for tissue engineering field, the oxidative damage of magnesium hydroxide nanoparticles (Mg(OH) 2 NPs) against the model system of Escherichia coli (E. coli) was researched by measuring the oxidative stress response, oxidative stress products and glucose metabolism. The toxicity of Mg(OH) 2 NPs to a normal biological system was evaluated in vivo through the acute oral toxicity, blood physiological and serum biochemical markers and acute skin irritation, indicating that the Mg(OH) 2 NPs exhibited great biosafety. The Mg(OH) 2 NPs with antibacterial property and biosafety were loaded on PCL/PVP nanofiber substrates through electrospinning technology to fabricate the Mg(OH) 2 /PCL/PVP nanofiber membranes. The results of characterization and antibacterial test showed that the Mg(OH) 2 /PCL/PVP nanofiber membranes with 8.0 wt% Mg(OH) 2 NPs present excellent antibacterial rate of 100% against E. coli that the Mg(OH) 2 NPs can be physically and evenly loaded on nanofiber substrates. • Oxidative damage of Mg(OH) 2 NPs against E. coli was evaluated. • Biosafety of Mg(OH) 2 NPs was evaluated in vivo. • Mg(OH) 2 /PCL/PVP nanofiber membranes were fabricated for the first time. • Mg(OH) 2 NPs were loaded on nanofiber substrates by electrospinning method. [ABSTRACT FROM AUTHOR]

Welding and the behavior of the weldments are important, since welding of high strength low alloy (HSLA) steels is a conventional method for manufacturing industrial parts. This work conducts a comparative investigation of microstructural characteristics and mechanical properties for joints of 16-mm-thick HSLA Q890 steel produced by multi-layer multi-pass shielded metal arc welding (SMAW) with filler wire and single-layer autogenous laser beam welding (LBW). The mechanical properties of the welded joints were assessed in terms of tensile and impact using butt joints. The results show that tensile failure occurred in the base metal during the tensile tests for most of the trials. The ultimate tensile strength and percent elongation of the LBW welded joint (973.5 MPa and 10%) are higher than those of the SMAW joint (951 MPa and 2.9%) due to the filler filling process of the SMAW process. The Charpy impact energy of the weld metal (16.4 J and 15.1 J) is lower than that of the heat-affected zone (18.5 J and 19.5 J) in the LBW joint and the SMAW joint. [ABSTRACT FROM AUTHOR]

Silicon (Si) has crucial effects on plant development and stress resistance. Silicon transporters regulate Si absorption, transport, and distribution in plants. In this study, we identified and characterized the Si transporter gene family of moso bamboo (Phyllostachys edulis) and cloned seven putative Si transporter genes. Moso bamboo Si transporters contain conserved functional domains that mediate the accumulation of considerable amounts of Si. The analysis of gene duplication patterns and divergence times suggested that the expansion of the moso bamboo Si transporter family was mainly due to segmental duplications. The expression of moso bamboo Si transporter genes, which varied among organs, was significantly modulated by Si treatments. The subcellular localization analysis showed that Si transporters are plasma membrane proteins. The Si content increased in transgenic Arabidopsis overexpressing PeLsi1-1 or PeLsi1-2 , which affected vegetative and reproductive growth. Our single-particle tracking analysis revealed the four diffusion modes of PeLsi1-1 on the plasma membrane. Moreover, the particle velocity, dwell time, and motion range of PeLsi1-1 decreased in response to Si treatments. The results of this study will further clarify the molecular mechanisms underlying Si absorption and accumulation in bamboo plants. • Moso bamboo has the molecular basis of high silicon accumulation. • The excessive accumulation of silicon affected the growth of transgenic Arabidopsis. • The distribution and dynamic changes of PeLsi1-1 were affected by silicon. • A hypothetical model for silicon transport in moso bamboo seedlings was established. [ABSTRACT FROM AUTHOR]

Purpose: We investigate the association of HTR1A rs10042486 and rs6295 with efficacy and plasma concentrations of atypical antipsychotics in the treatment of male patients with schizophrenia.Patients and Methods: A total of 140 male patients diagnosed with schizophrenia who were treated with any single atypical antipsychotic between May 2020 and May 2022 were retrospectively included. Clinical symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). All SNPs were typed using Agena Bioscience MassARRAY DNA mass spectrometry. Plasma concentrations of antipsychotics at week 3, 6 and 12 after treatment commence were analyzed using mass spectrometry.Results: For efficacy of atypical antipsychotics, we observed no significant difference between HTR1A rs10042486, rs6295 and positive symptom improvement, where the patients with heterozygous mutant at the rs10042486 and rs6295 locus were superior to those with wild-type or homozygous mutant genotypes on negative symptom improvement, especially at 12 weeks of follow-up when the difference between genotypes at the rs6295 locus have statistical significance (P = 0.037). For plasma concentration, we found that quetiapine plasma concentrations were significantly lower in patients with mutation-heterozygous types than in wild-type and homozygous mutation genotypes at week 6. In contrast, higher plasma concentrations were found for mutant heterozygous than wild genotypes in the risperidone monotherapy analysis, and the difference among genotypes at the rs6295 locus was statistically significant at 6 weeks of follow-up.Conclusion: The assessment of the correlation of genetic polymorphisms of HTR1A rs6295 and rs10042486 in male patients with schizophrenia with the monitoring of therapeutic drug concentrations and therapeutic efficacy provides a constructive foundation for the clinical individualization of antipsychotics, such as quetiapine and risperidone, which is important in selecting the dose of the medication and improving the improvement of negative symptoms. [ABSTRACT FROM AUTHOR]

Mirabilis himalaica is an important Tibetan medicinal plant in China. However, it has become a rare and class I endangered Tibetan medicine plant. Therefore, the use of callus to propagate germplasm resources is of great significance. We found that the flavonoid content of M. himalaica callus increased continuously with the extension of UV-B treatment. Multi-omics profiles were used to reveal the co-expression patterns of gene networks of flavonoid metabolism in M. himalaica callus during UV-B radiation. Results showed that five medicinal metabolics, including geranin, eriodictyol, astragalin, isoquercetin, pyrotechnic acid, and one anthocyanin malvide-3-O-glucoside were identified. The transcriptome data were divided into 46 modules according to the expression pattern by WGCNA (weighted gene co-expression network analysis), of which the module Turquoise had the strongest correlation with six target metabolites. We found that seven structural genes and twenty-five transcription factors were related to the metabolism of flavonoid synthesis, among which the structural genes CHI , C4H and UGT79B6 had strong co-expression relationships with the 6 target metabolites. WRKY42, WRKY7, bHLH128 and other transcription factors had strong co-expression relationships with multiple structural genes. Consequently, these findings suggest callus grown under UV-B treatment could be an effective alternative medical resource of M. himalaica , which is valuable for conservation and usage of this wild and endangered plant. • Six key medicinal metabolic were identified in M. himalaica callus by UV-B radiation. • WGCNA was used to analyze the relationship between gene modules and metabolites. • CHI , C4H and UGT79B6 had strong co-expression relationship with 6 target metabolites. • WRKY42, WRKY7, bHLH128 had strong co-expression relationships with structural genes. [ABSTRACT FROM AUTHOR]

Background: Although hypomethylating agents are currently used to treat patients with cancer, whether they can also reactivate and up-regulate oncogenes is not well elucidated.Methods: We examined the effect of hypomethylating agents on SALL4, a known oncogene that plays an important role in myelodysplastic syndrome and other cancers. Paired bone marrow samples that were obtained from two cohorts of patients with myelodysplastic syndrome before and after treatment with a hypomethylating agent were used to explore the relationships among changes in SALL4 expression, treatment response, and clinical outcome. Leukemic cell lines with low or undetectable SALL4 expression were used to study the relationship between SALL4 methylation and expression. A locus-specific demethylation technology, CRISPR-DNMT1-interacting RNA (CRISPR-DiR), was used to identify the CpG island that is critical for SALL4 expression.Results: SALL4 up-regulation after treatment with hypomethylating agents was observed in 10 of 25 patients (40%) in cohort 1 and in 13 of 43 patients (30%) in cohort 2 and was associated with a worse outcome. Using CRISPR-DiR, we discovered that demethylation of a CpG island within the 5' untranslated region was critical for SALL4 expression. In cell lines and patients, we confirmed that treatment with a hypomethylating agent led to demethylation of the same CpG region and up-regulation of SALL4 expression.Conclusions: By combining analysis of patient samples with CRISPR-DiR technology, we found that demethylation and up-regulation of an oncogene after treatment with a hypomethylating agent can indeed occur and should be further studied. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.). [ABSTRACT FROM AUTHOR]

[Display omitted] • Controllable synthesis of structures and effective modulation of catalytic properties. • Three-dimensional multi-channel structure enhances the catalytic activity. • The 3D NiCo alloy show excellent performance both in HER and OER. The development of high activity and low cost electrocatalysts for enhancing hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is the focus of overall water splitting. It has been found that transition metals have the potential to be highly efficient catalysts. In this paper, NiCo alloy electrode and three-dimensional multi-channel NiCo alloy (3D NiCo alloy) electrode were prepared by chemical coprecipitation-thermal reduction method and impregnation method respectively, which were used for efficient overall water splitting. By adjusting the pH value, alloy electrodes with different morphologies were obtained. The 3D multi-channel structure improved the catalytic activity of the NiCo alloy electrode for HER and OER. In 0.5 M H 2 SO 4 , the 3D NiCo 3 alloy electrode shows excellent catalytic activity for HER and OER. The HER overpotential of the 3D NiCo 3 alloy electrode is 109.6 mV at the current density of −10 mA cm−2, while the corresponding Tafel is 81.23 mV dec−1. The overpotential is as low as 296 mV when the OER current density is 40 mA cm−2, and the corresponding Tafel is 32.58 mV dec−1. This is due to the large specific surface area of the 3D NiCo 3 alloy electrode, and the synergistic effect between Ni-Co alloys and more active sites exposed by the three-dimensional multi-channel structure. It is shown that the morphology and structure have a great influence on the catalytic performance, and the transition metal electrocatalyst has a bright industrial application prospect. [ABSTRACT FROM AUTHOR]

Abstract: The delivery of plasmid DNA to target cells using a simple, defined, non-viral system is an area of intense research in gene therapy. Here, we describe a novel DNA carrier protein termed TG, consisting of the DNA-binding domain of the yeast transcriptional activator GAL4 and human immunodeficiency virus type 1 Tat protein, which can transfer modified naked plasmid DNA into target cells to express foreign genes of interest. The TG protein was expressed in Escherichia coli (E. coli), refolded and purified on an immobilized Ni2+ affinity chromatography column. SDS–PAGE and Western blotting revealed that the fusion protein was highly expressed with a yield of approximately 275mg/L. We also constructed the pIRES-UAS-EGFP DNA vector, consisting of upstream activating sequences (UASs) for the specific binding of the DNA-binding protein and the enhanced green fluorescent protein (EGFP) gene. The TG protein could bind specifically to pIRES-UAS-EGFP, forming a complex which could efficiently transfect target cells and result in detectable EGFP protein expression. Thus, these results provide a basis for development of efficient non-viral DNA transfer vectors for further improvements of gene therapy strategies. [ABSTRACT FROM AUTHOR]

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control. Author summary: Human infection with H7N9 virus has been successfully prevented since the application of an H7N9 vaccine in poultry in September 2017 in China; however, the H7N9 virus has not been eradicated from poultry. In this study, we evaluated the genetic and biologic properties of H7N9 viruses detected in poultry in China from February 2018 to December 2019. We found that the H7N9 viruses gradually lost their binding to human-type receptors and were antigenically different from the H7N9 vaccine strain that was used in China for H7N9 influenza control in poultry. We further uncovered genetic changes that facilitate the escape of the H7N9 viruses from vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control. [ABSTRACT FROM AUTHOR]

The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex?I (type-I NADH dehydrogenase (NDH-1), also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain. The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD+ homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex?I defects, particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex?I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics. Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone- and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQI and UQII) in Ndi1. NADH and UQI can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQI interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQI complex to UQII. Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications. [ABSTRACT FROM AUTHOR]