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Electrolytic water splitting using renewable energy sources, such as solar power, provides a green and sustainable approach for hydrogen production. Anion exchange membrane (AEM) electrolyzers present substantial commercial prospects; however, the rate of hydrogen evolution reaction (HER) in alkaline electrolytes is limited by the water dissociation step. In this work, we fabricated an N-doped Ni substrate for loading ultrafine Pt nanoparticles, realizing spatial decoupling of the reaction process to break the limitation of water dissociation, where the N-doped Ni substrate and Pt nanoparticles facilitate the supply of ample H* and H2 release, respectively. The prepared Pt–N–Ni/NC with extremely low Pt loading (1.0 wt%) requires only 15 and 149 mV overpotentials to reach current densities of 10 and 1000 mA cm−2, respectively. When assembled into an AEM electrolyzer, the system requires a cell voltage of only 1.75 V to achieve a current density of 1000 mA cm−2. Notably, the solar-driven AEM electrolyzer demonstrates a current density of 1390 mA cm−2 with a solar-to-hydrogen efficiency (STH) of 8.27%. This study proposes a strategy to achieve efficient utilization and performance improvement of precious metals, promoting the development of efficient green hydrogen production. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase (CDK), the pivotal controller of cell cycle progression, is involved in stress resistance and plant growth. Moso bamboo (Phyllostachys edulis) with surprisingly rapid growth depends on continuous cell division, but the CDK gene family information is still lacking. Here, we performed the systematic identification and analysis of the CDK genes in moso bamboo. 40 PeCDK genes were identified and divided into eight subgroups via phylogeny. The same subgroup possessed extremely conserved sequences and similar gene structure. In addition, evolutionary analysis suggested that the PeCDK gene family may have experienced extensive duplication events primarily 6.85–13.71 million years ago (MYA), with segmental duplication dominating. Furthermore, the multiple promoter cis-elements determined in PeCDK genes indicated their potential functions. The expression patterns revealed that most PeCDK genes participated in responses to drought, salt, ABA and SA signals, cell wall synthesis, organ developmental processes and callus growth. The insights gained provide beneficial reference for clarifying the functions of PeCDKs as well as exploring the growth mechanism in bamboo. [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]

Mirabilis himalaica is a traditional Tibetan medicinal plant in China. However, it has become a class I endangered medicinal plant. Therefore, the utilization of M. himalaica callus to propagate germplasm resources is of great significance. Numerous active compounds have been found in M. himalaica, most of which have been isolated from phenolic acids. In this study, UV-B radiation enhanced the accumulation of phenolic acids effectively in M. himalaica callus. The multi-omics profiles were used to reveal the co-expression regulated patterns of genes related to phenolic acid synthesis in UV-B treated M. himalaica callus. In this way, 8 medicinal metabolites were identified, including rosmarinic acid, sinapic acid, coniferin, salicylic acid, tyrosol, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C. The transcriptome data were divided into 26 modules based on similar expression pattern by using the weighted gene correlation network analysis (WGCNA). It revealed that MEturquoise module correlated with above eight target metabolites. Eventually, 11 structural genes and 31 transcription factors related to phenolic acid biosynthesis were screened. Subsequently, co-expression network was constructed between these genes, transcription factors and metabolites, among which PAL, CAD and CYP73A had strong co-expression relationship with above eight target metabolites. Transcription factors such as MYB, bHLH, bZIP, PLATZ, AP2/ERF-ERF73, WRKY33 and WRKY42 had strong co-expression relationship with eight target metabolites. Consequently, these findings indicated that UV-B treated callus is a cost-efficient alternative to wild M. himalaica, which is valuable for the use of this endangered plant.Key message: Phenolic acid content in Mirabilis himalaica callus was increased by UV-B treatment and the biosynthesis of phenolic acid is initiated by phenylpropanoid pathway and tyrosine-derived pathway. [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]

Community forestry is a strategy in which communities are, to some degree, responsible for managing the forests, using a more participatory approach to replace the traditional top-down model. Various forms of policies and governance have been developed to balance goals to ensure the community's socioeconomic resilience and the landscape's biological sustainability. The reinvestment of community forest (CF) income back into forest regeneration is not well documented, and there is a lack of research comparing forest income to the costs associated with forest regeneration. This research examines how changes in timber income and forest-regeneration costs affected CF social and ecological viability. We conducted expert elicitation interviews for CFs (n = 33) under three zones of management in Chitwan, Nepal (Zone 1: buffer zone, Zone 2: forest corridor, and Zone 3: community forest). To examine how CFs differ financially, we asked questions regarding timber income and forest-regeneration expenditures and then posed 22 questions regarding socioeconomic and biological aspects of the CF. Finally, a Kruskal–Wallis rank-sum test was performed to determine whether there were statistically significant differences in perceptions between groups, including zone, timber income (high, medium, low), and forest-regeneration expenditures (high, medium, low). The amount of income from timber had a substantial impact on the communities' biological benefits and financial stability. Lower timber-income areas were thought to be less economically stable, lack the resources to enforce rules and regulations necessary to meet the CF's socioeconomic or biological goals, and place more significant restrictions on the amount of wood members can harvest from the forest. Communities that spent less money on forest regeneration reported poorer levels of forest regeneration, economic sustainability, and community rights. Our research shows that community-forest user groups in the Chitwan district have a significant income and expenditure gap between their forests' biological and socioeconomic advantages and resilience. [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 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. [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]

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]

The investigation was aimed at evaluating the metallurgical and mechanical properties of high-speed fiber laser welded thick Q890 high strength low alloy (HSLA) steel with varying weld geometries instead of multi-layer multi-pass electric arc welding which led to the low machining efficiency and produced multiple sandwich structures in welding joints. 16 mm thick Q890 low alloy high strength steel plate was conducted based 2.5 and 5 mm gap size, respectively. The results showed that the size of hardening and softening zone was reduced by lower heat input laser welding with filling metal. The average width of HAZ was 1.2 mm in 2.5 gap and 1.9 mm in 5 mm gap. The maximum hardness was 485 HV and 482 HV and the minimum was 323 HV and 333 HV, respectively. The average width of softening zone was 0.8 mm and minimum hardness was 323 HV. The tensile properties could meet the standard requirement. The elongation rate was 10.4 and 7.6%, respectively, in 2.5 and 5 mm gap. The Charpy impact energy values of HAZ were 13.48 and 12.97 J, respectively. The weld seam was 21.11 and 16.09 J separately. Comparably, the profile of weld seam was better in 2.5 mm gap size. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The basic helix-loop-helix (bHLH) proteins GL3 (GlABRA 3) and EGL3 (Enhancer of GLABRA 3) are transcription factors that establish physical interactions with GL1 and TTG1 to regulate trichome development in Arabidopsis. In this study, we identified GL3 and EGL3 homologous genes from Rosa roxburghii, named RrGL3 and RrEGL3, respectively. RrGL3 and RrEGL3 were both exclusively localized in the nucleus. Transcriptional profiling and in situ hybridization demonstrated that the expression level of RrEGL3 was significantly higher than RrGL3 in vegetative and reproductive tissues. Moreover, RrEGL3 was remarkably expressed in flower buds and the prickles of young fruits. Notably, overexpression of RrEGL3 produced significantly more trichomes compared with wild type. Besides, RrEGL3 was able to functionally complement the glabrous phenotype of gl3 egl3 and ttg1 mutants. Surprisingly, overexpression of RrGL3 did not influence trichome patterning in Arabidopsis. Finally, while RrEGL3 was found to interact with both TTG1 and GL1 in vitro and in vivo, in contrast, RrGL3 only interacted with GL1. The inability of RrGL3 to interact with TTG1 suggests functional divergence between RrGL3 and RrEGL3. These results illustrated that highly expressed RrEGL3 mediates trichome development in Arabidopsis by forming a GL1-RrEGL3-TTG1 complex, proposing RrEGL3 as a good candidate for controlling prickles in R. roxburghii. This study provides insights into the molecular mechanisms concerning the development of prickles in the Rosaceae family, and provides the theoretical basis for cultivation of prickle-free fruits. Key message: RrEGL3 expressed highly in tissues presenting prickles of Rosa roxburghii could mediated trichome development in Arabidopsis by forming GL1-RrEGL3-TTG1 complex. [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]

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]

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. [ABSTRACT FROM AUTHOR]

Rosa sterilis is an economically and important fruit that is extensively grown in Southwestern China. In this study, we determined the complete chloroplast genome of R. sterilis using high-throughput Illumina sequencing. The chloroplast genome of R. sterilis is 156,561 bp in size, containing a large single-copy region (LSC)(85,701 bp), a small single-copy region (SSC) (18,746 bp), and a pair of inverted repeat (IR) regions (each one of 26,057 bp). The overall GC content of the chloroplast genome is 37.23%, while the corresponding values of GC contents of the LSC, SSC, and IR regions are 35.20%, 31.37%, and 42.70%, respectively. The chloroplast genome of R. sterilis contains 130 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic maximum-likelihood tree revealed that Rosa chinensis or Rosa chinensis var. spontanea is the closest related to R. sterilis in the phylogenetic relationship. This complete chloroplast genome can be further used for genomic studies, evolutionary analyses, and genetic engineering studies of the family Rosaceae. [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.

During 2009, an outbreak of hand, foot, and mouth disease (HFMD) enrolled 490 people in Henan Province, causing the death of two children. In order to investigate the pathogens responsible for this outbreak and characterize their genetic characteristics, a total of 508 clinical specimens (stool, throat swab, and vesicle fluid) were collected from the Center for Disease Control and Prevention of Henan Province. Virological investigations (virus isolation, conventional reverse transcription PCR, and real-time reverse transcription PCR) and phylogenetic analysis were performed. It was found that human enterovirus 71 (EV71) was the main pathogen causing this outbreak, while Coxsackievirus A16 (CoxA16) played only a subsidiary role. Phylogenetic analysis of 24 EV71 isolates collected during the period from March 11 to July 24, 2009 showed that they belonged to subgenotypes C4 and C5. Our study for the first time characterizes the epidemiology of HFMD and EV71 infection in Henan Province in 2009 and provides the first direct evidence of the genotype of EV71 circulating in Henan Province at that time. Our study should facilitate the development of public health measures for the control and prevention of HFMD and EV71 infection in at-risk individuals in China. [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]