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The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR–Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR–Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.

Calcium ion batteries (CIBs) are a promising energy storage device due to the low redox potential of the Ca metal and the abundant reserves of the Ca element. However, the large radius and divalent nature of Ca2+lead to its slow ion diffusion kinetics and the lack of suitable electrode materials for Ca storage. Here, a layered structure of Na2Ti3O7(NTO) is presented as an anode material for nonaqueous CIBs. This NTO anode demonstrates a high discharge capacity of 165 mA h g–1at 100 mA g–1and a remarkable capacity retention rate of 80%, even after 2000 cycles at 500 mA g–1, surpassing the performance of all reported intercalation-type anode materials for CIBs. The NTO transfers to layered CaVIINaIXTi3O7(CNTO) with intercalation of Ca2+and extraction of Na+during the first discharge process. Then, the CNTO undergoes the reversible insertion/extraction of Ca2+during subsequent cycling. Additionally, density functional theory calculations reveal that NTO possesses a rapid two-dimensional diffusion pathway for Ca2+. Moreover, the full CIBs based on NTO as the anode further underscore its potential for CIBs. This work presents promising anode materials for CIBs, offering opportunities to promote the development of high-performance CIBs.

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundiiand Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederikseniiand Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacaeand Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

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On the basis of the [Fe3(μ3-O)(COO)6] cluster and 3,3′,5,5′-diphenyltetracarboxylic acid (H4BPTC), three novel metal–organic frameworks (MOFs), NJU-Bai25, NJU-Bai26, and NJU-Bai27 (NJU-Bai for Bai’s group at Nanjing University ) with different (4,4,4,6)-, (4,4,4,4,4,6)-, and (4,4,6)-connected nets were obtained in different solvent systems, in which due to the steric hindrance of the coordinated solvents the conformations of BPTC gradually change from the planar to the torsional; thus, the pore sizes of those MOFs were also gradually narrowed. Interestingly, the MOFs show high thermal/chemical stabilities and selective CO2adsorption: NJU-Bai27 exhibits larger CO2uptake (5.0 and 13.8 wt %) at 298 K under 0.15 and 1 bar, whereas NJU-Bai26 has a higher selectivity for CO2/N2(366).

A pure-supramolecular-linker (PSL) approach for the formation of metal–organic frameworks (MOFs) was initially given, which was demonstrated by syntheses of two highly connected and isostructural MOFs, {Fe3O(TPBTM6–)(Cl)(H2O)2}∞(TPBTM = N,N′,N″-tris(isophthalyl)-1,3,5-benzenetricarboxamide) (NJU-Bai52, NJU-Bai for Nanjing University Bai group) and {Sc3O(TPBTM6–)(OH)(H2O)2}∞(NJU-Bai53). Very interestingly, they exhibit exceptional thermal stability, water stability, and highly selective CO2capture properties. In particular, NJU-Bai53 with higher uptakes (2.74 wt % at 0.4 mbar and 298 K, 7.67 wt % at 298 K and 0.15 bar) and higher selectivity may be an excellent candidate for CO2capture.

Verticillium wilt caused by the soil-borne fungus Verticillium dahliaeis a devastating disease of cotton, leading to serious loss of lint yield in China. It is important to characterize the prevailing populations of V. dahliaefor understanding disease development. In this study, the representative 74 V. dahliaeisolates from 28 different cotton regions in three major cotton-production areas in China were identified for their pathotypes, races, vegetative compatibility groups (VCGs) and genetic diversity by specific PCR, amplified fragment length polymorphism (AFLP) and inter simple sequence repeat (ISSR) analysis. Of 74 isolates, 60 isolates (81%) were defoliating (D) pathotype strains, especially in Yellow River/Yantze River Valley region. Seventy isolates belonged to race 2, whereas no race 1 specific fragment was amplified. These isolates were grouped into five VCGs: VCG1A (48), VCG2A/VCG4B (3), VCG2B824(6), VCG6 (5). The D pathotype and VCG1A isolates have become the dominant strains, moderately and highly virulent isolates were widely distributed in three major cotton-growing areas in China. High level of polymorphic markers was obtained by AFLP and ISSR analyses. Through comparison of the obtained dendrograms by unweighted paired group method with arithmetic averages cluster analysis (UPGMA), the V. dahliaeisolates were divided into two major groups and five subgroups. The obvious correlations with the geographic origin of the isolates between AFLP and ISSR were revealed, with significant diversity among V. dahliaeisolates. In addition, AFLP dendrogram showed relationships with pathotypes. The results offered a better understanding of the epidemiology of Verticillium wilt in China.

A new amide-functionalized metal–organic framework (AFMOF) with the combined feature of highly selective CO2adsorption and high thermal and chemical stability, [Sc3(μ3-O)(L)1.5(H2O)3Cl]n[NJU-Bai49; NJU-Bai for Nanjing University Bai’s group, H4L = 5-(3,5-dicarboxybenzamido)isophthalic acid], was synthesized that exhibits 4.5 wt % CO2uptake at 298 K and 0.15 bar and the highest selectivity for CO2/N2(166.7) among all AFMOFs. Grand canonical Monte Carlo simulations further indicate that both the decorated amide group and the open metal site act as CO2binding sites, which may contribute to its highly selective CO2uptake.

Here, we describe single-tube long fragment read (stLFR), a technology that enables sequencing of data from long DNA molecules using economical second-generation sequencing technology. It is based on adding the same barcode sequence to subfragments of the original long DNA molecule (DNA cobarcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Using a combinatorial process, up to 3.6 billion unique barcode sequences were generated on beads, enabling practically nonredundant cobarcoding with 50 million barcodes per sample. Using stLFR, we demonstrate efficient unique cobarcoding of more than 8 million 20- to 300-kb genomic DNA fragments. Analysis of the human genome NA12878 with stLFR demonstrated high-quality variant calling and phase block lengths up to N50 34 Mb. We also demonstrate detection of complex structural variants and complete diploid de novo assembly of NA12878. These analyses were all performed using single stLFR libraries, and their construction did not significantly add to the time or cost of whole-genome sequencing (WGS) library preparation. stLFR represents an easily automatable solution that enables high-quality sequencing, phasing, SV detection, scaffolding, cost-effective diploid de novo genome assembly, and other long DNA sequencing applications.

A new approach of finely tuning multinuclear clusters of metal–organic frameworks (MOFs) through symmetry-upgradingly isoreticular transformation was first presented and a bcu-type MOF, {[Cu4(μ4-O)Cl2(IN)4][CuCl2]}∞(NJU-Bai35; NJU-Bai for Nanjing University Bai group), with cluster [Cu4(μ4-O)Cl2(COO)4N4] of higher symmetry compared to the pristine MOF, was successfully synthesized. The symmetry upgrading implemented on the inorganic part triggers the adjustment of channels in NJU-Bai35 to fit CO2molecules, leading to a high CO2adsorption capacity (7.20 wt % at ∼0.15 bar and 298 K) and high selectivity of CO2over N2and CH4(275.8 for CO2/N2and 11.6 for CO2/CH4) in NJU-Bai35. Breakthrough experiments further confirmed that NJU-Bai35 might be an excellent candidate for CO2capture and natural gas purification.

In this study, crucial genes and microRNAs (miRNAs) associated with the progression, staging, and prognosis of papillary thyroid cancer (PTC) were identified. Four PTC datasets, including our own mRNA-sequencing (mRNA-seq) dataset and three public datasets downloaded from Gene Expression Omnibus and The Cancer Genome Atlas, were used to analyze differentially expressed genes (DEGs) and miRNAs (DEMs) between PTC tumor tissues and paired normal tissues (control). Gene ontology (GO) terms and pathways associated with these DEGs were identified, and protein–protein interactions (PPIs) were analyzed. Additionally, an miRNA-mRNA regulatory network was constructed and the functions of DEMs were explored. Finally, miRNAs/mRNAs associated with tumor staging and prognosis were identified. The expression levels of several key genes and miRNAs were validated by qRT-PCR. Numerous DEGs and DEMs were identified between tumor and control groups in four datasets. The DEGs were significantly enriched in cell adhesion and cancer-related GO terms and pathways. In the constructed PPI network, ITGA2, FN1, ICAM1, TIMP1 and CDH2 were hub proteins. In the miRNA-mRNA negative regulatory networks, miR-204-5p regulated the largest number of target genes, such as TNFRSF12A. miR-146b, miR-204, miR-7-2, and FN1were associated with tumor stage in PTC, and TNFRSF12Aand CLDN1were related to prognosis. Our results suggested the important roles of ITGA2, FN1, ICAM1, TIMP1and CDH2in the progression of PTC. miR-204-5p, miR-7-2, and miR-146b are potential biomarkers for PTC staging and FN1, CLDN1, and TNFRSF12Amay serve as markers of prognosis in PTC.

Sequencing of hypervariable regions as well as internal transcribed spacer regions of ribosomal RNA genes (rDNA) is broadly used to identify bacteria and fungi, but taxonomic and phylogenetic resolution is hampered by insufficient sequencing length using high throughput, cost-efficient second-generation sequencing. We developed a method to obtain nearly full-length rDNA by assembling single DNA molecules combining DNA co-barcoding with single-tube long fragment read technology and second-generation sequencing. Benchmarking was performed using mock bacterial and fungal communities as well as two forest soil samples. All mock species rDNA were successfully recovered with identities above 99.5% compared to the reference sequences. From the soil samples we obtained good coverage with identification of more than 20,000 unknown species, as well as high abundance correlation between replicates. This approach provides a cost-effective method for obtaining extensive and accurate information on complex environmental microbial communities.

Recent technological advances in multi-omics and bioinformatics provide an opportunity to develop precision health assessments, which require big data and relevant bioinformatic methods. Here we collect multi-omics data from 4,277 individuals. We calculate the correlations between pairwise features from cross-sectional data and then generate 11 biological functional modules (BFMs) in males and 12 BFMs in females using a community detection algorithm. Using the features in the BFM associated with cardiometabolic health, carotid plaques can be predicted accurately in an independent dataset. We developed a model by comparing individual data with the health baseline in BFMsto assess health status (BFM-ash). Then we apply the model to chronic patients and modify the BFM-ash model to assess the effects of consuming grape seed extract as a dietary supplement. Finally, anomalous BFMs are identified for each subject. Our BFMs and BFM-ash model have huge prospects for application in precision health assessment.

Introduction:The autonomic nervous system plays a major role in development of atrial fibrillation (AF), with evidence of marked autonomic remodeling in a canine rapid atrial pacing (RAP) model of AF. Nerve growth factor (NGF), a neurotrophin essential for peripheral neuron growth, was upregulated in fibrillating atria, particularly in the left atrial appendage (LAA).Hypothesis:Inhibiting NGF signaling in the entire atria or the LAA alone can prevent the development of AF.Methods:NGF shRNA was injected in both atria or in the LAA of dogs followed by electroporation to facilitate gene delivery. Animals were subjected to RAP for up to 12 weeks. Duration of AF was recorded. At terminal EP study, residual AF electrograms were recorded in the posterior left atrium, left atrial free wall and LAA for analysis of AF characteristics. Tissue of each region was used for IHC with markers for parasympathetic (acetylcholinesterase) or sympathetic nerves (dopamine beta-hydroxylase).Results:Controls (n=10) developed persistent AF (>8 hours) after a median of 14 days. In contrast, pan-atrial NGF shRNA animals (n=4) never developed this burden of AF. Residual AF was less fractionated (longer fractionation interval), more organized (higher organization index and lower Shannon's entropy) and more homogeneous (coefficient of variation of dominant frequency). RAP-induced nerve bundle hypertrophy and atrial myocardium hyperinnervation was significantly attenuated in pan-atrial NGF shRNA dogs. Importantly, these findings were reproduced when NGF shRNA injection was limited to the LAA alone (n=4), with prevention of development of persistent AF, and global attenuation of left atrial hyperinnervation.Conclusion:Targeted inhibition of atrial autonomic remodeling by NGF shRNA prevents development of persistent AF. NGF Inhibition in the LAA alone is sufficient to attenuate global atrial autonomic remodeling. This approach may lead to a novel, mechanism-guided therapy for AF.

Background:While vagal contribution to paroxysmal atrial fibrillation (AF) is well demonstrated, a role for parasympathetic signaling in persistent AF is less clear. We have shown marked atrial parasympathetic hyperinnervation in a canine rapid atrial pacing (RAP) model of AF. However, the role of these new nerves in AF development is unknown.Hypothesis:RAP-induced parasympathetic hyperinnervation contributes to the onset and maintenance of AF, and a gene therapy approach inhibiting muscarinic M2 signaling (Gαiand Gαo- GiGo) in the atria can prevent persistent AF.Methods:Plasmids expressing GiGo inhibitory peptides (GiGo_ct) were injected in the atria of 7 dogs followed by electroporation to facilitate gene delivery. RAP was performed for up to 12 weeks. At terminal EP study, residual AF was recorded in the posterior left atrium (PLA), left atrial free wall (LAFW) and left atrial appendage (LAA). Regional atrial ERP was measured.Results:Controls developed ≥30 minutes of AF after a median of 4 days, and persistent AF (≥8 hours) after a median of 14 days. GiGo_ct delayed onset of AF of ≥30 minutes, and attenuated development of persistent AF. ERP was markedly shortened in the PLA and LAA of controls, and this was attenuated by GiGo_ct (p<0.001). Residual AF was slower (lower dominant frequency; PLA 9.4±0.6Hz Vs 11.0±0.7Hz; LAFW 7.8±0.3Hz Vs 10.4±0.7Hz; LAA 8.9±0.6Hz Vs 9.9±0.5Hz p<0.01), less fractionated (longer fractionation interval; PLA 70.0.4±5.2ms Vs 68.1±5.2ms; LAFW 98.8±4.1ms Vs 70.9±3.1ms; LAA 88.9±7.8ms Vs 80.3±2.0ms p<0.01) and more organized (lower Shannon's entropy; p<0.05).Conclusion:Newly sprouted atrial parasympathetic nerves play a functional role in development of persistent AF. Gene-based, selective M2 signaling inhibition by GiGo_ct attenuates electrical remodeling and prevents initiation and maintenance AF. Future optimization of gene therapy targeting autonomic remodeling may lead to novel, mechanism-guided treatments for AF.

Metabolism is a highly integrated process that is coordinately regulated between tissues and within individual cells. FoxO proteins are major targets of insulin action and contribute to the regulation of gluconeogenesis, glycolysis, and lipogenesis in the liver. However, the mechanisms by which FoxO proteins exert these diverse effects in an integrated fashion remain poorly understood. We report that FoxO proteins also exert important effects on intrahepatic lipolysis and fatty acid oxidation via the regulation of adipose triacylglycerol lipase (ATGL), which mediates the first step in lipolysis, and its inhibitor, the G0/S1 switch 2 gene (G0S2). We also find that ATGL-dependent lipolysis plays a critical role in mediating diverse effects of FoxO proteins in the liver, including effects on gluconeogenic, glycolytic, and lipogenic gene expression and metabolism. These results indicate that intrahepatic lipolysis plays a critical role in mediating and integrating the regulation of glucose and lipid metabolism downstream of FoxO proteins.

Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

Gene expression microarray has been the primary biomarker platform ubiquitously applied in biomedical research, resulting in enormous data, predictive models, and biomarkers accrued. Recently, RNA-seq has looked likely to replace microarrays, but there will be a period where both technologies co-exist. This raises two important questions: Can microarray-based models and biomarkers be directly applied to RNA-seq data? Can future RNA-seq-based predictive models and biomarkers be applied to microarray data to leverage past investment? We systematically evaluated the transferability of predictive models and signature genes between microarray and RNA-seq using two large clinical data sets. The complexity of cross-platform sequence correspondence was considered in the analysis and examined using three human and two rat data sets, and three levels of mapping complexity were revealed. Three algorithms representing different modeling complexity were applied to the three levels of mappings for each of the eight binary endpoints and Cox regression was used to model survival times with expression data. In total, 240,096 predictive models were examined. Signature genes of predictive models are reciprocally transferable between microarray and RNA-seq data for model development, and microarray-based models can accurately predict RNA-seq-profiled samples; while RNA-seq-based models are less accurate in predicting microarray-profiled samples and are affected both by the choice of modeling algorithm and the gene mapping complexity. The results suggest continued usefulness of legacy microarray data and established microarray biomarkers and predictive models in the forthcoming RNA-seq era.

A modified steady-state thermal conductivity measurement method that adds a thermal compensation device (TCD) is proposed. Calibration experiments verify that the heat loss rate of the test apparatus is less than 5.0%. The thermal conductivities of the spirally wound cylindrical Li/SOCl2 batteries are measured at different discharge currents (1.0 A, 1.2 A, and 2.0 A) and at different depths of discharge (DOD) (0% DOD, 50% DOD, and 100% DOD). The measured values exhibit a dependence on the DOD and independence from the discharge current. To validate the test method, a model combining a statistical averaging method with a hybrid computing strategy is established to simplify the calculation model; the model considered influencing factors, such as physical uncertainty and the shape irregularity of the Li/SOCl2 battery. The tendency for thermal conductivity to decrease when DOD increases demonstrates that the measurement and simulation are consistent. The analysis results indicate that the consumption coefficient (f) is an important factor for the thermal conductivity of a Li/SOCl2 battery. At a constant DOD, the overall axial thermal conductivities decrease significantly when the consumption coefficient increases. Therefore, when designing batteries, the change in the thermal conductivities relative to the consumption coefficient and DOD should be monitored.

In this differential RNA-seq study, Wu et al. identified 29 small RNAs expressed by the pig pathogen Streptococcus suis. The authors then went on to show that S. suisstrains lacking some of these small RNAs were attenuated in a zebrafish infection model or were more sensitive to killing by pig blood. The study thus provides further evidence that small, regulatory RNAs play roles in bacterial virulence.

A convenient convective type dimensionless lumped-capacitance (DLC) method for battery heat generation measurement is proposed. The effective heat transfer coefficient and heat generation can be obtained simultaneously, and no prior calibration of the equipment is needed. The new dimensionless method is verified by reference sample, and the experimental results agree with the theoretical line. The heat generated by a lithium thionyl chloride (Li/SOCl2) battery is measured at the ambient temperature range of 38degC to 50degC. Results reveal that the heat generation is not influenced by ambient temperature at a small discharge current, and the heat generation increases at higher ambient temperature under a higher discharge current condition. The heat generation is approximately proportional to the discharge current in the range of 1.0 A to 5.0 A. The heat generation measurement method can be extended to obtain the heat generated by other types of battery.

The specific heat capacity of lithium thionyl chloride batteries is measured with precise specific heat capacity test apparatus. The experiment instrument is calibrated with standard sample brass with the same geometry of battery. Different heating end temperatures during the measurement do not affect the heat capacity measurements. Experiment analysis reveals that the heat loss part which is not proportional to the calorimeter liquid temperature change cannot be neglected. The heat capacity is independent on the discharge current. At 100% depth of discharge, the battery loses 17.1% of the initial heat capacity 904 J kg[?]1 K[?]1. Both experimental and computational results show that the heat capacity reduces as battery discharges at certain currents, and this is different from available published results. Heat capacity loss increases the difficulty of battery module thermal design especially at the end of discharge when both the ambient temperature and the interior battery temperature are high.

Global pandemics such as COVID-19 have resulted in significant global social and economic disruption. Although polymerase chain reaction (PCR) is recommended as the standard test for identifying the SARS-CoV-2, conventional assays are time-consuming. In parallel, although artificial intelligence (AI) has been employed to contain the disease, the implementation of AI in PCR analytics, which may enhance the cognition of diagnostics, is quite rare. The information that the amplification curve reveals can reflect the dynamics of reactions. Here, we present a novel AI-aided on-chip approach by integrating deep learning with microfluidic paper-based analytical devices (µPADs) to detect synthetic RNA templates of the SARS-CoV-2 ORF1ab gene. The µPADs feature a multilayer structure by which the devices are compatible with conventional PCR instruments. During analysis, real-time PCR data were synchronously fed to three unsupervised learning models with deep neural networks, including RNN, LSTM, and GRU. Of these, the GRU is found to be most effective and accurate. Based on the experimentally obtained datasets, qualitative forecasting can be made as early as 13 cycles, which significantly enhances the efficiency of the PCR tests by 67.5% (∼40 min). Also, an accurate prediction of the end-point value of PCR curves can be obtained by GRU around 20 cycles. To further improve PCR testing efficiency, we also propose AI-aided dynamic evaluation criteria for determining critical cycle numbers, which enables real-time quantitative analysis of PCR tests. The presented approach is the first to integrate AI for on-chip PCR data analysis. It is capable of forecasting the final output and the trend of qPCR in addition to the conventional end-point Cq calculation. It is also capable of fully exploring the dynamics and intrinsic features of each reaction. This work leverages methodologies from diverse disciplines to provide perspectives and insights beyond the scope of a single scientific field. It is universally applicable and can be extended to multiple areas of fundamental research.

This study investigated the antifungal activity and possible mode of action of Bacillus pumilusHN-10 antifungal peptide P-1 against Trichothecium roseum. The results showed that the antifungal peptide P-1 at a concentration of 1.0 μg mL-1had strong antifungal activity against T. roseum. P-1 inhibited the tricarboxylic acid cycle (TCA) pathway and the transporter pathway of NADH to coenzyme Q on the electron transport chain. P-1 significantly reduced succinate dehydrogenase (SDH), malate dehydrogenase (MDH), ATPase, mitochondrial complex enzymes I, II and IV enzyme activities on the electron transport chain, and 5'-triphosphate (ATP), 5'-diphosphate (ADP), 5'-monophosphate (AMP) content, and energy charge (EC); significantly increased 6-phosphofructokinase (PFK) enzyme activity. The release of Ca2+(OD680) from the inner mitochondrial membrane and the openness of the mitochondrial permeability transition pore (MPTP) were analysed, and microscopy was performed following staining of mitochondria with JC-1. The results indicated that P-1 significantly increased the release of Ca2+and the openness of MPTP, decreased the mitochondrial membrane potential, and produced green fluorescence; transcriptomics data analysis showed that there were 39 differentially expressed genes (DEGs) related to energy metabolism enzymes. The results verified by qRT-PCR were basically consistent with the transcriptome sequencing results. Thus, P-1 achieved its inhibitory effect mainly by regulating genes related to energy metabolism.

Introduction:It is currently not possible to measure and therapeutically target oxidative injury (OI) in the intact fibrillating atrium.Hypothesis:We postulated that measurement of AF electrogram characteristics after acute administration of a reactive oxygen species (ROS) scavenger can help ‘uncover’ regions of high OI in the fibrillating human atrium.Methods:We mapped in both atria pre/post NAC (intravenous, 100mg/kg) in 15 persistent AF dogs (3-14 weeks rapid atrial pacing) using a high-density epicardial mapping-plaque (6 atrial regions in both atria, 130 electrodes, electrode-distance 2.5mm) and in 4 patients using the HD-grid catheter. We quantified the OS-levels as ratio of oxidatively damaged nuclei (Figure A) against the total number in 8-OHdG staining (N=36) and the degree of dense fibro-fatty tissue in Masson’s trichrome stained tissue (N=24) using Qupath. We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-region sizes with >10% change pre vs. post NAC.Results:Oxidative stress (OS) levels, highest in the left atrial free wall, lowest in the appendages increased with increasing degree of fibro-fatty tissue (R=0.6,P<0.05) and with decreasing cycle length (R=0.5, P<0.05) in all regions (Figure C). NAC selectively reduced AF characteristics in ‘hot spot’-sub-regions (Figure D). OS level correlated with delta CL, delta DF, and delta Organization Index in delta maps (NAC - baseline) (R=0.5, P<0.05, all comparisons) (Figure E). In patients, NAC (Figure G)reduced AF characteristics in subregions (Figure H)and increased cycle length from 210±50ms to 252±18ms (P<0.05) in the left atrium (Figure I).Conclusions:OS-level correlated with the degree of dense fibro-fatty tissue and with electrogram measures in both atria. Acute scavenging of ROS reduced AF characteristics in the left atrium in dogs and patients. We might have found a new way to target regions of high OS in the atrium in the individual patient.

Atrial fibrillation (AF), the most common progressive tachyarrhythmia, results in structural remodeling that impairs electrical activation of the atria. Studies have shown that mitochondrial dysfunction underlies cardiomyocyte remodeling. Here, we report a 50% reduction in total mitochondrial DNA in the atria tissue of RAP dogs as compared to control dogs, as assessed by qPCR the levels of mitochondrial DNA including mt-NT-1, mt-NT-4, mt-NT 5, mt-NT 6. This reduction in mitochondrial DNA suggests reduced mitochondria number in RAP dogs. Autophagic flux (LC3 II protein levels) was markedly increased in the atria tissue of the AF dog model (vs control dog).Furthermore, we examined autophagy flux in isolated cardiomyocytes. Results showed that LC3II was remarkably activated when subject to electrical stimulation for 6 hours under 3 Hertz condition, suggesting the direct effect of electrical stimulation on increasing autophagy. There was no change in the mRNA levels of autophagosome genes including Belin 1, ATG8, LC3, Lamp1 in the RAP dog tissue as compared to control, however, ATG7 increased by 2 fold and GNG2 increased by 5 fold. In conclusion, our study suggests that electrical stimulation-induced autophagy, and reduced mitochondria number and function, may underlie cardiomyocyte remodeling in AF. Targeting the autophagy pathway may present new therapeutic targets for AF. Ongoing AAV-mediated knockdown experiments in isolated cardiomyocytes will further elucidate the mechanism of electrical stimulation-induced autophagy.

Tiller angle is an important component of plant architecture in rice even though little is known of its mode of inheritance. A quantitative trait loci (QTL) analysis based on a set of recombinant inbred lines extracted from an indica× japonicacross identified a major effect locus (designated qTA‐9a) on chromosome 9, which was expressed in two independent environments. The qTA‐9aallele derived from the indicaparent IR24 increased tiller angle. This QTL was validated in a set of chromosome segment substitution lines involving the same two parental lines. A high resolution genetic map was constructed from a large secondary F2population and anchored to the genomic sequence of rice. The QTL was narrowed to a 65‐kb physical region, inclusive of eight putative genes. We have provided the basis for positional cloning of qTA‐9aand have developed markers for a major tiller angle QTL.

Transposon mutagenesis was applied to generate mutants in Fusarium graminearum. The mimp1/impalasystem originally identified in F. oxysporumproved very promising for mutagenesis as the transposon and reinserted at high frequency in (the vicinity) of genes. A collection of mutants was screened for growth, for pathogenicity and for perithecia production. Several mutants blocked in one or more functions were obtained. The wild-type phenotype of one such mutant could be restored by complementation with a non-disrupted copy of the gene. In addition reinsertions occurred on each of the four chromosomes of F. graminearum, making this system a powerful tool in the functional analyses of the > 10,000 genes predicted in the F. graminearumgenome.

An ion-pair complex [FBzPyNH2][Ni(mnt)2] {[FBzPyNH2]⁺ = [1-(4'-fluorobenzyl)-4-amino]pyridinium and mnt²⁻ = maleonitriledithiolate} has been obtained by I2 oxidation of the corresponding dianion complex. It forms a wellsegregated stacking column structure in the solid state, and exhibits antiferromagnetic ordering below 2.5 K. It is the first complex in this series of complexes containing a maleonitriledithiolate dianion that exhibits metamagnetism. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

[BrFPy]2[Ni(dto)2] (1) and [BrPy]2[Ni(dto)2] (2) complexes have been prepared by reaction of Na2[Ni(S2C2O2)2] and the corresponding 1-(Rbenzyl)pyridinium bromide salt (R1= 4′-bromo-2′-fluoro, R2= 4′-bromo). The crystallographic data for 1: monoclinic P21/c, a= 14.2192(1) Å, b= 14.2533(4) Å, c= 15.6535(3) Å, β= 96.463(1)°, V= 3152.34(11) Å3, Z= 4. Two cations, [Br1F1Py]+and [Br2F2Py]+, both adopt a conformation where both the aromatic rings are twisted to the corresponding N(1)–C(10)–C(11) or N(2)–C(22)–C(23) reference plane. Data for 2: triclinic $$P\bar 1$$ , a= 9.4042(3) Å, b= 9.6814(4) Å, c= 10.3357(4) Å, α = 80.155(1)°, β= 65.245(1)°, γ = 64.259(1)°, V= 769.68(5) Å3, Z= 1. The [Ni(dto)2]2−anion exhibits a quasi-planar structure in both complexes. An extensive hydrogen bond network of C–H ⋅ ⋅ ⋅ O is clearly observed in 1and 2, and two complexes show similar crystal packing.

Ion-pair complexes consisting of the [Fe(mnt)2]−anion and [RBzPy]+cations [R = NO2(1)or Cl (2)] have been prepared and characterized by elemental analysis and i.r. spectroscopy. The single crystal structure of (1)shows that the [Fe(mnt)2]−anions are dimeric, and that the coordination geometry of each Fe atom is square pyramidal. The most significant structural feature of (1)is that anions and cations form completely separate columns and π–πinteractions occur within the cation columns. Thermal variations of χmTfor the complexes indicated antiferromagnetic coupling within the dimer.

New racemic complexes of titanium with Schiff bases derived from condensation of salicylaldehyde with dl-alanine (H2Sal-dl-Ala) and dl-valine (H2Sal-dl-Val) have been prepared. The crystal structure of [(Sal-dl-Val)2Ti·CH2Cl2bis(N-salicylidenevalinato)titanate(IV) CH2Cl2] has been solved by single-crystal X-ray diffraction methods; the crystal is a racemate consisting of a pair of enantiomers (Sal-d-Val)2Ti and (Sal-l-Val)2Ti. The Schiff-base ligand acts as a double negatively-charged tridentate ONO chelate, coordinated to the titanium atom. The geometry around titanium is a distorted octahedron. The i.r. and u.v.–vis. spectra of the complexes have been evaluated.

An algorithm for optimizing a bipolar interconnection weight matrix with the Hopfield network is proposed. The effectiveness of this algorithm is demonstrated by computer simulation and optical implementation. In the optical implementation of the neural network the interconnection weights are biased to yield a nonnegative weight matrix. Moreover, a threshold subchannel is added so that the system can realize, in real time, the bipolar weighted summation in a single channel. Preliminary experimental results obtained from the applications in associative memories and multitarget classification with rotation invariance are shown.