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ABSTRACT To safely and effectively explore the natural methane hydrate, it is crucial to examine the mechanical behavior of methane hydrate‐bearing sediments (MHBSs). Natural methane hydrate unevenly distributes in pores or bonds with soil particles in MHBS, changing the mechanical behavior of MHBS including stiffness, shear strength, and dilatancy. This paper presents an anisotropic critical state model for MHBS considering hydrate pore‐filling and cementing effects. Based on the unified critical state model for both clay and sand, an equivalent hydrate ratio is defined to address pore‐filling effect. Cohesive strength and its hardening law are introduced to characterize hydrate cementation. To describe the anisotropic behavior, the inherent anisotropy of soil particles and hydrates are modeled separately, and rotation hardening is introduced to describe the stress‐induced anisotropy. Comparisons with existing triaxial tests of both synthetic and natural MHBS demonstrate that the proposed model comprehensively describes the mechanical behavior of MHBS. Detailed predictions indicate that hydrate pore‐filling affects the hydrate‐dependent stiffness and dilatancy of MHBS, which become more pronounced with increasing hydrate saturation. Cementing effect increases the initial stiffness and peak strength of MHBS. The pronounced influence of inherent anisotropic parameters on pre‐peak stress–strain relation of MHBS is noted, and increasing hydrate saturation enhances the effect of hydrate anisotropy. These predictions contribute to a better understanding of the relation between hydrate morphologies and MHBS mechanical properties. [ABSTRACT FROM AUTHOR]

Developing high‐efficiency alkaline water splitting technology holds great promise in potentially revolutionizing the traditional petrochemical industry to a more sustainable hydrogen economy. Importantly, the oxygen evolution reaction (OER) accompanied at the anode is considered as a critical bottleneck in terms of both complicated mechanism and sluggish kinetics, requiring rational design of OER electrocatalysts to elucidate the structure‐performance relationship and reduce the applied overpotential. As a benchmarked non‐precious metal candidate, NiFe‐based electrocatalysts have gained enormous attention due to low‐cost, earth‐abundance, and remarkable intrinsic OER activity, which are expected to be implemented in industrial alkaline water splitting. In this contribution, a comprehensive overview of NiFe‐based OER electrocatalysts is provided, starting with fundamental mechanisms, evaluation metrics, and synthetic protocols. Subsequently, basic principles with corresponding regulatory strategies are summarized following the sequence of substrate‐catalyst‐electrolyte design of efficient and robust NiFe‐based electrocatalysts toward industrial‐scale deployment. Perspectives on remaining challenges and instructive opportunities in this booming field are finally discussed. [ABSTRACT FROM AUTHOR]

Alternate layers of Al2O3 and ZrO2 nanocomposite films were prepared on silicon wafers and glass substrates at room temperature using the electrostatic self-assembly monolayer (ESAM) process. The versatile approach of the ESAM process provides the possibility of integrating diverse inorganic colloids on the nanosize level in a layer-by-layer or block-by-block fashion. Further, it allows the combination of inorganic colloids and organic molecules, making it possible to fabricate thick films with large pores and good stress relaxation. Highly ordered, micron-thick films have been formed, sintered, and characterized by scanning electron microscopy and ellipsometry. There is no significant visible crack formation for Al2O3–ZrO2 composite films after heat treatment at 1200°C for 2 h, although significant thickness reduction occurs. The hardness and Young's modulus of these films before and after sintering were measured using nanoindentation techniques. [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]

Introduction. Alcohol dependence (AD) and sleep disturbance (SD) independently affect gut microbiota, potentially disrupting the circadian rhythm of the microbiota and the host. However, the impact of SD on the composition and rhythmicity of gut flora in AD patients remains poorly understood. Gap Statement. Characteristics of gut flora and diurnal oscillations in AD patients experiencing SD are unknown. Aim. This study aims to explore alterations in gut flora and diurnal oscillations in AD patients experiencing SD. Methodology. Thirty-two AD patients and 20 healthy subjects participated, providing faecal samples at 7 : 00 AM, 11 : 00 AM, 3 : 00 PM and 7 : 00 PM for gut microbiota analysis using 16S rDNA sequencing. AD patients were further categorized into those with poor sleep (ADwPS) and those with good sleep (ADwGS) for further analyses. Results. The ADwPS group demonstrated elevated levels of anxiety, depression and withdrawal severity compared to the ADwGS group (all P <0.05). The β-diversity of gut microbiota in the ADwPS group differed from that in the ADwGS group ( P <0.05). Bacterial abundances at various taxonomic levels, including Cyanobacteria and Pseudomonadales, differed between the ADwPS and ADwGS groups (all P <0.05). Utilizing unweighted UniFrac analysis, the β-diversity of gut microbiota in the ADwPS group demonstrated robust diurnal oscillation ( P <0.05), whereas this pattern was statistically insignificant in the ADwGS group. Notably, the abundance of pathogenic bacteria like Pseudomonadales and Pseudomonadaceae exhibited marked diurnal fluctuation in the ADwPS group (all P <0.05). Conclusion. SD in AD patients extends beyond alcohol-induced alterations, impacting gut microbiota composition, function and diurnal oscillation patterns. This highlights its add-on influence, supplementing AD-related changes.

Industrial water electrolysis typically operates at high current densities, the efficiency and stability of catalysts are greatly influenced by mass transport processes and adhesion with substrates. The core scientific issues revolve around reducing transport overpotential losses and enhancing catalyst-substrate binding to ensure long-term performance. Herein, vertical Ni-Co-P is synthesized and employed plasma treatment for dual modification of its surface and interface with the substrate. The (N)Ni-Co-P/Ni 3 N cathode exhibits an ultra-low overpotential of 421 mV at 4000 mA cm -2 , and the non-noble metal system only requires a voltage of 1.85 V to reach 1000 mA cm -2 . When integrated into an anion exchange membrane (AEM) electrolyzer, it can operate stably for >300 h at 500 mA cm -2 . Under natural light, the solar-driven AEM electrolyzer operates at a current density up to 1585 mA cm -2 with a solar-to-hydrogen efficiency (SHT) of 9.08%. Density functional theory (DFT) calculations reveal that plasma modification leads to an "atomic-scale soldering" effect, where the Ni 3 N strong coupling with the Co increases free charge density, simultaneously enhancing stability and conductivity. This research offers a promising avenue for optimizing ampere-level current density water splitting, paving the way for efficient and sustainable industrial hydrogen production., (© 2024 Wiley‐VCH GmbH.)

This study explores the impact of government subsidies on the production dynamics within the medical product supply chain, particularly focusing on the remanufacturing of medical goods. Amidst the backdrop of the COVID-19 pandemic, which has underscored the critical shortages in medical supplies, our research delves into the adoption of remanufacturing practices by medical product manufacturers as a strategic response to these shortages and environmental concerns. We investigate how government subsidies influence the production volumes of original manufacturers and remanufacturers and examine the competitive interplay between newly manufactured and remanufactured medical products. Through the development of three production game models-Scenario B (manufacturers produce both new and refurbished products), Scenario N (separate production of new and refurbished products by manufacturers and remanufacturers, respectively), and Scenario C (similar to Scenario N but includes a certification fee paid by remanufacturers to original manufacturers)-we analyze the strategies that could mitigate supply deficiencies during medical crises. Our findings indicate that the certification strategy (Scenario C) not only yields the highest total production of medical products but also offers a viable solution to enhance the sustainability of the entire medical production system by alleviating supply chain disruptions. Furthermore, we discuss the managerial implications of our results, emphasizing the potential of a joint remanufacturing strategy to stabilize the supply chain and foster environmental conservation. Lastly, we highlight our study's limitations and suggest future research directions, particularly concerning the variability in product quality and the reliance on government subsidies. This research contributes to a nuanced understanding of green remanufacturing within the pharmaceutical supply chain, offering insights for manufacturers, remanufacturers, and policymakers aiming for sustainable industry practices., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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 Cu 0 /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 Cu 0 /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 Cu 0 /NC/air system. Under acidic conditions, Cu 0 /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 Cu 3+ 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024. The Author(s).)

The diversity of CRISPR systems, coupled with scientific ingenuity, has led to an explosion of applications; however, to test newly described innovations in their model systems, researchers typically embark on cumbersome, one-off cloning projects to generate custom reagents that are optimized for their biological questions. Here, we leverage Golden Gate cloning to create the Fragmid toolkit, a modular set of CRISPR cassettes and delivery technologies, along with a web portal, resulting in a combinatorial platform that enables scalable vector assembly within days. We further demonstrate that multiple CRISPR technologies can be assessed in parallel in a pooled screening format using this resource, enabling the rapid optimization of both novel technologies and cellular models. These results establish Fragmid as a robust system for the rapid design of CRISPR vectors, and we anticipate that this assembly approach will be broadly useful for systematic development, comparison, and dissemination of CRISPR technologies., Competing Interests: Declaration of interests E.J.S. is a co-founder, scientific advisor, and equity holder of Intellia Therapeutics and a member of the scientific advisory board of Tessera Therapeutics. J.G.D. consults for Microsoft Research, BioNTech, Servier, and Pfizer. J.G.D. consults for and has equity in Tango Therapeutics. J.G.D. serves as a paid scientific advisor to the Laboratory for Genomics Research, funded in part by GSK, and the Innovative Genomics Institute, funded in part by Apple Tree Partners. J.G.D. receives funding support from the Functional Genomics Consortium: Abbvie, Bristol Myers Squibb, Janssen, and Merck. J.G.D.’s interests are reviewed and managed by the Broad Institute in accordance with its conflict of interest policies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest We declare no conflict of interest between us., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Jingfeng Tong and Chengchen Huang are affiliated with Shanghai Conlight Medical Co., Ltd. The authors declare no other conflicts of interest in this work., (© 2024 Qin et al.)

Cas12a CRISPR technology, unlike Cas9, allows for facile multiplexing of guide RNAs from a single transcript, simplifying combinatorial perturbations. While Cas12a has been implemented for multiplexed knockout genetic screens, it has yet to be optimized for CRISPR activation (CRISPRa) screens in human cells. Here, we develop a new Cas12a-based transactivation domain (TAD) recruitment system using the ALFA nanobody and demonstrate simultaneous activation of up to four genes. We screen a genome-wide library to identify modulators of growth and MEK inhibition, and we compare these results with those obtained with open reading frame (ORF) overexpression and Cas9-based CRISPRa. We find that the activity of multiplexed arrays is largely predictable from the best-performing guide and provide criteria for selecting active guides. We anticipate that these results will greatly accelerate the exploration of gene function and combinatorial phenotypes at scale., Competing Interests: J.G.D. consults for Microsoft Research, Abata Therapeutics, Maze Therapeutics, BioNTech, Sangamo, and Pfizer. J.G.D. consults for and has equity in Tango Therapeutics. J.G.D. serves as a paid scientific advisor to the Laboratory for Genomics Research, funded in part by GSK, and the Innovative Genomics Institute, funded in part by Apple Tree Partners. J.G.D. receives funding support from the Functional Genomics Consortium: Abbvie, Bristol Myers Squibb, Janssen, Merck, and Vir Biotechnology. J.G.D.’s interests are reviewed and managed by the Broad Institute in accordance with its conflict-of-interest policies., (© 2023 The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier GmbH. All rights reserved.)

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 Sc 3+ , 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% Sc 2 O 3 -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 ).

The toxicity of Mg(OH) 2 nanoparticles (NPs) as antibacterial agents to a normal biological system is unclear, so it is necessary to evaluate their potential toxic effect for safe use. In this work, the administration of these antibacterial agents did not induce pulmonary interstitial fibrosis as no significant effect on the proliferation of HELF cells was observed in vitro. Additionally, Mg(OH) 2 NPs caused no inhibition of the proliferation of PC-12 cells, indicating that the brain's nervous system was not affected by Mg(OH) 2 NPs. The acute oral toxicity test showed that the Mg(OH) 2 NPs at 10,000 mg/kg induced no mortality during the administration period, and there was little toxicity in vital organs according to a histological analysis. In addition, the in vivo acute eye irritation test results showed little acute irritation of the eye caused by Mg(OH) 2 NPs. Thus, Mg(OH) 2 NPs exhibited great biosafety to a normal biological system, which was critical for human health and environmental protection.

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 Sc 2 O 3 -MgO are synthesized by doping Sc 3+ in nano-MgO lattice through calcining at 600 °C. When the Sc 3+ 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% Sc 3+ -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% Sc 3+ -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., (© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

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., Competing Interests: The authors declare that they have no conflict of competing financial interests in this paper.

Background: Patients with alcohol dependence (AD) can exhibit gut dysbacteria. Dysbacteria may co-occur with disruptions of circadian rhythmicity of the gut flora, which can aggravate AD. Herein, this study aimed to investigate diurnal oscillations of the gut microbiota in AD patients., Methods: Thirty-two patients with AD, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 20 healthy subjects were enrolled in this study. Demographic and clinical data were collected by self-report questionnaires. Fecal samples at 7:00 AM, 11:00 AM, 3:00 PM, and 7:00 PM were collected from each subject. 16S rDNA sequencing was conducted. Wilcoxon and Kruskal-Wallis tests were performed to characterize alterations and oscillations of the gut microbiota., Results: We found that β-diversity of the gut microbiota in AD patients oscillated diurnally compared with healthy subjects (p = 0.01). Additionally, 0.66% of operational taxonomic units oscillated diurnally in AD patients versus 1.68% in healthy subjects. At different taxonomic levels, bacterial abundance oscillated diurnally in both groups, such as Pseudomonas and Prevotella pallens (all p < 0.05). β-diversity of the gut microbiota in AD patients with high daily alcohol consumption, high-level cravings, short AD durations, and mild withdrawal symptoms oscillated diurnally compared with other AD patients (all p < 0.05)., Conclusion: The gut microbiota in AD patients exhibits disruptions of diurnal oscillation, which may provide novel insights into mechanisms of AD and the development of therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Ni, Qin, Zhu, Yu, Ma, Chen, Sun, Wang, Liu, Zhao, Peng, Hu, Shi, Lu and Sun.)

Aims: Alanine aminotransferase (ALT) is positively related to diabetes risk in observational studies, whereas Mendelian randomization supports a linear causal association. In contrast, the relationship between ALT and diabetic nephropathy, and diabetic retinopathy is counter-intuitive in observational studies. Furthermore, no MR study has examined their causal association. The study aimed to investigate whether genetically determined ALT has a causal effect on diabetic nephropathy and diabetic retinopathy., Methods: Genetic instruments associated with ALT ( P < 5×10 -8 ) were obtained from a recent genome-wide association study (GWAS) that included 437,267 individuals of European ancestry. Summary data of diabetic microvascular complications were derived from the FinnGen study (3,283 cases and 181,704 controls for diabetic nephropathy, and 14,584 cases and 176,010 controls for diabetic retinopathy, both were of European ancestry). Effect estimation and pleiotropy testing were performed using inverse variance weighted (IVW), MR-Egger regression, weighted median, and mode-based estimator methods. We additionally performed sensitivity analysis excluding proxy single nucleotide polymorphisms (SNPs) or lowering the GWAS significance threshold ( P < 5×10 -7 ) to test the robustness of the results., Results: Based on IVW, a 2-fold increase in genetically determined ALT level was positively associated with diabetic nephropathy (odd ratio, [95% confidence interval], 1.73 [1.26-2.37], P = 0.001) and diabetic retinopathy (1.29 [1.08-1.54], P = 0.005), but a null causal association in three pleiotropy robust methods, namely, MR-Egger, weighted median and mode-based estimator. We obtained similar results in the sensitivity analysis of excluding proxy SNPs or lowering the GWAS significance threshold., Conclusions: With caution, we concluded that ALT plays no linear causal role in developing both diabetic nephropathy and diabetic retinopathy. Further investigations are required to test the hypothesis of a non-linear causal association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could constructed as a potential conflict of interest., (Copyright © 2023 Bi, Liu, Wang, Tian and Sun.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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: Mg 2+ 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.

Background: Image-guided computer-aided navigation system is an indispensable part of computer assisted orthopaedic surgery. However, the location and number of fiducial markers, the time required to localise fiducial markers in existing systems affect their effectiveness., Method: The study proposed that spatial surface registration between the point cloud on the surface of the fusion model based on preoperative knee MRI and CT images and the point cloud on the cartilage surface captured by intraoperative laser scanner could solve the above limitations., Results: The experimental results show that the registration error of the method is less than 2 mm, but the total time from scanning the point cloud on patient's cartilage surface to registering it with the point cloud in preoperative image space is less than 2 min., Conclusion: The method achieves the registration accuracy similar to existing methods without selecting anatomical corresponding points, which is of great help to the clinic., (© 2022 John Wiley & Sons Ltd.)

Fruit prickles are widely distributed on the pericarp and exhibit polymorphic traits at different developmental stages. Although they are multicellular appendages that are well-known for helping plants defend against biotic and abiotic stresses, their origination and molecular mechanism are still less known. Here, we studied the origination and molecular mechanism of fruit prickles in Rosa roxburghii . Using morphological and histological observations, we found that the fruit prickle primordium of R. roxburghii originated from the ground meristem that underwent cell division to form flagelliform prickles, continued to enlarge, and finally lignified to form mature fruit prickles. We amplified a homolog of candidate gene TRANSPARENT TESTA GLABRA1 ( TTG1 ) from R. roxburghii , named RrTTG1 . RrTTG1 harbored four conserved WD-repeat domains and was exclusively nuclear-localized. Using qRT-PCR and in situ hybridization, we found that RrTTG1 was constitutively expressed and highly expressed during the initiation and cell expansion phases of fruit prickles. Ectopic expression analysis in Arabidopsis proved that RrTTG1 substantially enhanced the number of trichome and pigmentation production and inhibited root hair formation. Besides, RrTTG1 complemented the phenotypes of the ttg1 mutant in Arabidopsis , thus indicating that RrTTG1 played pleiotropic roles akin to AtTTG1 . We demonstrated that the RrTTG1 only interacted with RrEGL3, a homolog of ENHANCER OF GLABRA3 (EGL3), via yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Briefly, RrTTG1 might positively regulate the initiation of fruit prickle primordium and cell enlargement by forming the RrTTG1-RrEGL3-RrGL1 complex in R. roxburghii . Therefore, our results help characterize the RrTTG1 in R. roxburghii and also elucidate the establishment of the prickles regulatory system in the Rosaceae plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Yi, Liu, Li, Jiang, Yi and Yan.)

Aim: The association between gamma-glutamyl transferase (GGT) and type 2 diabetes mellitus (T2DM) is controversial. In this study, we investigated the association between GGT and the risk of T2DM using real-world data, Mendelian randomization (MR) analysis, and literature mining., Methods: A cross-sectional study enrolled 3,048 participants (>40 years) from a community in Northeastern China was conducted. A generalized additive model was used to examine the relation between GGT and T2DM. A two-sample MR was performed to investigate the causal effect of GGT (61,089 individuals, mostly of European ancestry) on T2DM (29,193 cases and 182,573 controls of European ancestry)., Results: GGT was related to glucose metabolism indicators, such as fasting plasma glucose and glycosylated hemoglobin ( P < 0.05). The odds ratios (ORs) [95% confidence interval (95% CI), P ] for T2DM across the GGT categories (14-16, 17-20, 21-25, 26-35, ≥36) were 1.14 [(0.88-1.47), P = 0.330], 1.55 [(1.22-1.98), P < 0.001], 1.87 [(1.47-2.28), P < 0.001], 1.97 [(1.55-2.52), P < 0.001], and 2.29 [(1.78-2.94), P < 0.001] versus GGT ≤ 13 category after adjusting for potential confounding factors. A generalized additive model identified a non-linear correlation between GGT and T2DM and indicated that the risk of T2DM almost levelled out when GGT exceeded 34 IU/L. The MR analysis showed that the odds of having T2DM for a one-time increase in genetically determined GGT was 0.998 [(0.995-1.002), P = 0.34]., Conclusions: Our analysis of observational study suggested that GGT, its increment, within a certain range, is indicative of the development of T2DM. However, MR analysis provided no evidence that GGT is a linear causal factor of T2DM. Further investigation is required to determine if GGT exerts a non-linear causal effect on T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest., (Copyright © 2022 Bi, Yang, Liu, Cao, Gao, Liu, Li, Tian and Sun.)

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.)., (Copyright © 2022 Massachusetts Medical Society.)

The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls; the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza., (© 2021. The Author(s).)

Oncofetal protein SALL4 is critical for cancer cell survival. Targeting SALL4, however, is only applicable in a fraction of cancer patients who are positive for this gene. To overcome this limitation, we propose to induce a cancer vulnerability by engineering a partial dependency upon SALL4. Following exogenous expression of SALL4, SALL4-negative cancer cells became partially dependent on SALL4. Treatment of SALL4-negative cells with the FDA-approved hypomethylating agent 5-aza-2'-deoxycytidine (DAC) resulted in transient upregulation of SALL4. DAC pretreatment sensitized SALL4-negative cancer cells to entinostat, which negatively affected SALL4 expression through a microRNA, miRNA-205, both in culture and in vivo . Moreover, SALL4 was essential for the efficiency of sequential treatment of DAC and entinostat. Overall, this proof-of-concept study provides a framework whereby the targeting pathways such as SALL4-centered therapy can be expanded, sensitizing cancer cells to treatment by transient target induction and engineering a dependency. SIGNIFICANCE: These findings provide a therapeutic approach for patients harboring no suitable target by induction of a SALL4-mediated vulnerability., (©2021 American Association for Cancer Research.)

Background: LBDs, as the plant-specific gene family, play essential roles in lateral organ development, plant regeneration, as well as abiotic stress and pathogen response. However, the number and characteristic of LBD genes in Pyscomitrella patens were still obscure., Objective: This study was performed to identify the LBD family gene in moss and to determine the expression profiles of LBDs under the abiotic and pathogen stress., Methods: Complete genome sequences and transcriptomes of P. patens were downloaded from the Ensembl plant database. The hidden Markov model-based profile of the conserved LOB domain was submitted as a query to identify all potential LOB domain sequences with HMMER software. Expression profiles of PpLBDs were obtained based on the GEO public database and qRT-PCR analysis., Results: In this study, a total of 31 LBDs were identified in the P. patens genome, divided into two classes based on the presence of the leucine zipper-like coiled-coil motif. A phylogenetic relationship was obtained between 31 proteins from P. patens and 43 proteins from the Arabidopsis thaliana genome, providing insights into their conserved and potential functions. Furthermore, the exon-intron organization of each PpLBD were analyzed. All PpLBD contain the conserved DNA binding motif (CX2CX6CX3C zinc finger-like motif), and were predicted to be located in cell nuclear. The 31 PpLBD genes were unevenly assigned to 18 out of 27 chromosomes based on the physical positions. Among these genes, PpLBD27 was not only remarkably highest expressed in desiccation, but also a susceptible gene to pathogens through jasmonic acid-mediated signaling pathway. Most of PpLBDs were up-regulated with the treatment of mannitol. These results showed they were differentially induced and their potential functions in the environmental stimulus of the early terrestrial colonizers., Conclusion: Despite significant differences in the life cycle in P. patens and flowering plants, their functions involved in abiotic and biotic stress-regulated by LBDs have been identified and appear to be conserved in the two lineages. These results provided a comprehensive analysis of PpLBDs and paved insights into studies aimed at a better understanding of PpLBDs.

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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Establishment of a rapid, highly specific, and accurate method for diagnosis of Toxoplasma gondii infection is essential to control and prevent zoonotic toxoplasmosis. In this study, a novel diagnostic strategy using magnetic bead-based serum peptide profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was developed. The serum peptides (samples I, II, and III) from T. gondii RH strain-infected mice at days 3, 6, and 9 post-infection (p.i.), and healthy mice were enriched by the optimized magnetic bead-based hydrophobic interaction (MB-HIC8). The mass spectrograms were acquired by MALDI-TOF MS, and analyzed by ClinProTools bioinformatics software from Bruker Daltonics. The diagnostic models from T. gondii RH-infected serum peptide profiling of samples I, II, and III were produced by genetic algorithms, and verified by cross-validation. The sample II model could correctly recognize T. gondii RH strain infection in mice at days 3, 6, and 9 p.i. with a sensitivity of 91.1% and a specificity of 96.7%., and also detect T. gondii ME49 strain-infected serum samples at days 3, 6, 9, and 12 p.i. with a sensitivity of 91.7%. The results of the present study suggest that serum peptide profiling by MALDI-TOF MS is a novel potential tool for the clinical diagnosis of acute T. gondii infection.

Toxoplasmosis is an important food-borne parasitic disease. In the present study, the seroprevalence of Toxoplasma gondii infection in slaughtered pigs and cattle was surveyed in Liaoning Province, northeastern China in May and June 2011. In total, 1,164 porcine serum samples and 646 bovine serum samples were collected from 5 counties and examined for T. gondii antibodies by an indirect hemagglutination test. Antibodies to T. gondii were found in 12.0% (140/1,164) of pigs, with some regional differences. The highest prevalence of 14.4% (47/326) was found in Fuxin followed by 12.5% (62/497) in Jinzhou; overall, 6.0% (39/646) was observed in cattle but with no regional difference (P > 0.05). Prevalence of T. gondii infection in pigs was also significantly higher compared to cattle (P < 0.05). The results of the present study indicate that infection with T. gondii in pigs and cattle is widely spread in China including Liaoning Province, northeastern China, and is, therefore, of public health concern.