Depth- and curvature-based quantitative susceptibility mapping analyses of cortical iron in Alzheimer's disease.

In addition to amyloid beta plaques and neurofibrillary tangles, Alzheimer's disease (AD) has been associated with elevated iron in deep gray matter nuclei using quantitative susceptibility mapping (QSM). However, only a few studies have examined cortical iron, using more macroscopic approaches that cannot assess layer-specific differences. Here, we conducted column-based QSM analyses to assess whether AD-related increases in cortical iron vary in relation to layer-specific differences in the type and density of neurons. We obtained global and regional measures of positive (iron) and negative (myelin, protein aggregation) susceptibility from 22 adults with AD and 22 demographically matched healthy controls. Depth-wise analyses indicated that global susceptibility increased from the pial surface to the gray/white matter boundary, with a larger slope for positive susceptibility in the left hemisphere for adults with AD than controls. Curvature-based analyses indicated larger global susceptibility for adults with AD versus controls; the right hemisphere versus left; and gyri versus sulci. Region-of-interest analyses identified similar depth- and curvature-specific group differences, especially for temporo-parietal regions. Finding that iron accumulates in a topographically heterogenous manner across the cortical mantle may help explain the profound cognitive deterioration that differentiates AD from the slowing of general motor processes in healthy aging.

Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.

Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFß and TNFα/NFκB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells - reflecting this disease's unique inflammatory T-cell driven nature - as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.

ATM-mediated double-strand break repair is required for meiotic genome stability at high temperature.

In eukaryotes, meiotic recombination maintains genome stability and creates genetic diversity. The conserved Ataxia-Telangiectasia Mutated (ATM) kinase regulates multiple processes in meiotic homologous recombination, including DNA double-strand break (DSB) formation and repair, synaptonemal complex organization, and crossover formation and distribution. However, its function in plant meiotic recombination under stressful environmental conditions remains poorly understood. In this study, we demonstrate that ATM is required for the maintenance of meiotic genome stability under heat stress in Arabidopsis thaliana. Using cytogenetic approaches we determined that ATM does not mediate reduced DSB formation but does ensure successful DSB repair, and thus meiotic chromosome integrity, under heat stress. Further genetic analysis suggested that ATM mediates DSB repair at high temperature by acting downstream of the MRE11-RAD50-NBS1 (MRN) complex, and acts in a RAD51-independent but chromosome axis-dependent manner. This study extends our understanding on the role of ATM in DSB repair and the protection of genome stability in plants under high temperature stress.

Extracellular Vesicle-Derived Non-Coding RNAs: Key Mediators in Remodelling Heart Failure.

Heart failure (HF), a syndrome of persistent development of cardiac insufficiency due to various heart diseases, is a serious and lethal disease for which specific curative therapies are lacking and poses a severe burden on all aspects of global public health. Extracellular vesicles (EVs) are essential mediators of intercellular and interorgan communication, and are enclosed nanoscale vesicles carrying biomolecules such as RNA, DNA, and proteins. Recent studies have showed, among other things, that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long ncRNAs (lncRNA), and circular RNAs (circRNAs) can be selectively sorted into EVs and modulate the pathophysiological processes of HF in recipient cells, acting on both healthy and diseased hearts, which makes them promising targets for the diagnosis and therapy of HF. This review aims to explore the mechanism of action of EV-ncRNAs in heart failure, with emphasis on the potential use of differentially expressed miRNAs and circRNAs as biomarkers of cardiovascular disease, and recent research advances in the diagnosis and treatment of heart failure. Finally, we focus on summarising the latest advances and challenges in engineering EVs for HF, providing novel concepts for the diagnosis and treatment of heart failure.

Phase Engineering-Mediated D-Band Center of Ru Sites Promote the Hydrogen Evolution Reaction Under Universal pH Condition.

The rational design of pH-universal electrocatalyst with high-efficiency, low-cost and large current output suitable for industrial hydrogen evolution reaction (HER) is crucial for hydrogen production via water splitting. Herein, phase engineering of ruthenium (Ru) electrocatalyst comprised of metastable unconventional face-centered cubic (fcc) and conventional hexagonal close-packed (hcp) crystalline phase supported on nitrogen-doped carbon matrix (fcc/hcp-Ru/NC) is successfully synthesized through a facile pyrolysis approach. Fascinatingly, the fcc/hcp-Ru/NC displayed excellent electrocatalytic HER performance under a universal pH range. To deliver a current density of 10 mA cm-2, the fcc/hcp-Ru/NC required overpotentials of 16.8, 23.8 and 22.3 mV in 1 M KOH, 0.5 M H2SO4 and 1 M phosphate buffered solution (PBS), respectively. Even to drive an industrial-level current density of 500 and 1000 mA cm-2, the corresponding overpotentials are 189.8 and 284 mV in alkaline, 202 and 287 mV in acidic media, respectively. Experimental and theoretical calculation result unveiled that the charge migration from fcc-Ru to hcp-Ru induced by work function discrepancy within fcc/hcp-Ru/NC regulate the d-band center of Ru sites, which facilitated the water adsorption and dissociation, thus boosting the electrocatalytic HER performance. The present work paves the way for construction of novel and efficient electrocatalysts for energy conversion and storage.

Ultraviolet attenuates centromere-mediated meiotic genome stability and alters gametophytic ploidy consistency in flowering plants.

Ultraviolet (UV) radiation influences development and genome stability in organisms; however, its impact on meiosis, a special cell division essential for the delivery of genetic information across generations in eukaryotes, has not yet been elucidated. In this study, by performing cytogenetic studies, we reported that UV radiation does not damage meiotic chromosome integrity but attenuates centromere-mediated chromosome stability and induces unreduced gametes in Arabidopsis thaliana. We showed that functional centromere-specific histone 3 (CENH3) is required for obligate crossover formation and plays a role in the protection of sister chromatid cohesion under UV stress. Moreover, we found that UV specifically alters the orientation and organization of spindles and phragmoplasts at meiosis II, resulting in meiotic restitution and unreduced gametes. We determined that UV-induced meiotic restitution does not rely on the UV Resistance Locus8-mediated UV perception and the Tapetal Development and Function1- and Aborted Microspores-dependent tapetum development, but possibly occurs via altered JASON function and downregulated Parallel Spindle1. This study provides evidence that UV radiation influences meiotic genome stability and gametophytic ploidy consistency in flowering plants.

Comamonas endophytica sp. nov., a novel indole acetic acid producing endophyte isolated from bamboo in China.

Two novel indole acetic acid-producing strains, 5MLIRT and D4N7, were isolated from Indosasa shibataeoides in Yongzhou, Hunan province, and Phyllostachys edulis in Hangzhou, Zhejiang province, respectively. Based on their 16S rRNA sequences, strains 5MLIRT and D4N7 were closely related to Comamonas antarcticus 16-35-5T (98.4 % sequence similarity), and the results of 92-core gene phylogenetic trees showed that strains 5MLIRT and D4N7 formed a phylogenetic lineage within the clade comprising Comamonas species. The complete genome size of strain 5MLIRT was 4.49 Mb including two plasmids, and the DNA G+C content was 66.5 mol%. The draft genome of strain D4N7 was 4.26 Mb with 66.7 mol% G+C content. The average nucleotide identity and digital DNA-DNA hybridization values among strain 5MLIRT and species in the genus Comamonas were all below the species delineation threshold. The colonies of strain 5MLIRT and D4N7 were circular with regular margins, convex, pale yellow and 1.0-2.0 mm in diameter when incubated at 30 °C for 3 days. Strains 5MLIRT and D4N7 grew optimally at 30 °C, pH 7.0 and 1.0 % NaCl. The respiratory isoprenoid quinone was ubiquinone-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Polyphasic analyses indicated that strains 5MLIRT and D4N7 could be distinguished from related validly named Comamonas species and represent a novel species of the genus Comamonas, for which the name Comamonas endophytica sp. nov. is proposed. The type strain is 5MLIRT (=ACCC 62069T=GDMCC 1.2958T=JCM 35331T).

Characterization of Tfgal-9: A galectin in innate immune system of Trachidermus fasciatus - Insights into its sequence analysis, expression patterns, and in vitro bioactivities.

An in-depth understanding of the immune system of endangered species is crucial for successful conservation efforts. Galectins, as members of the lectin family, play a crucial role in the fish innate immune system. Galectin-9 (Tfgal-9) was cloned from endangered species Trachidermus fasciatus, revealing a cDNA sequence of 1453 bp with an open reading frame of 900 bp encoding a protein of 299 amino acids. Tfgal-9 protein features two repeated carbohydrate-binding domains, each characterized by two conserved galactose-binding sites (H-NPR and WG-EER), and it possesses neither a signal peptide nor a transmembrane domain. The qRT-PCR analysis revealed that Tfgal-9 was widely expressed across all examined tissues, with the highest expression in the intestine, followed by the blood, heart and brain. Expression was notably up-regulated in the blood, skin, liver, stomach, and heart when challenged with LPS. Following induction by the heavy metal solution containing Cu, Pb, Cd, and Hg, the expression Tfgal-9 was dramatically induced to 32 times higher than that of the control group in the brain. The recombinant Tfgal-9 protein exhibits calcium-independent binding and agglutination of selected bacteria and yeast. Antimicrobial activity of recombinant Tfgal-9 protein against Gram positive bacteria Staphylococcus aureus was confirmed using the cylinder-plate method. In vitro antioxidant experiments showed that radical scavenging activity of DPPH was 50.38 % when Tfgal-9 concentration reached 200 µg/mL. These results indicate that Tfgal-9 may play important roles in the immune response against microbial infections and the maintaining of redox homeostasis.

Differentiated management of ROS level in tumor and kidney to alleviate Cis-platinum induced acute kidney injury with improved efficacy.

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy.

Soil and stone terraces offset the negative impacts of sloping cultivation on soil microbial diversity and functioning by protecting soil carbon.

Cultivation of sloping land is a main cause for soil erosion. Conservation practices, such as soil and stone terraces, may reduce the impacts of erosion but their impacts on soil microbial diversity and functioning related to carbon (C) and nutrient metabolisms remain unclear. This study was conducted to evaluate the effects of slope gradients (5°, 8°, 15°, 25°) and conservation practices (cultivated, uncultivated, soil terrace, and stone terrace) on bacterial and fungal diversities, metagenomic and metabolomic functioning associated with basic soil properties. Our results showed that steep slopes at 25° significantly decreased soil pH, silt percentage, and bacterial and fungal abundances, but that soil and stone terraces increased soil organic C (SOC), silt and clay contents, and fungal abundance compared to sloping cultivated lands. In addition, soil and stone terraces increased both bacterial and fungal alpha diversities, and relative abundances of Crenarchaeota, Nitrospirota, and Latescibacterota, but reduced the proportions of Actinobacteriota and Patescibacteria, thus shifting microbial beta diversities, which were significantly associated with increased SOC and silt content. For metagenomics, soil and stone terraces greatly increased the relative abundance of functional genes related to Respiration, Virulence, disease and defense, Stress response, and nitrogen and potassium metabolisms, such as Denitrification and Potassium homeostasis. For soil metabolomics, a total of 22 soil metabolites was enriched by soil and stone terraces, such as Lipids and lipid-like molecules (Arachidonic acid, Gamma-Linolenic acid, and Pentadecanoic acid), and Organoheterocyclic compounds (Adenine, Laudanosine, Methylpyrazine, and Nicotinic acid). To sum up, soil and stone terraces could reduce some of the negative impacts of steep slope cultivation on soil microbial diversity as well as their metagenomic and metabolomic functioning related to C and nutrient metabolism useful for soil health improvement, potentially bolstering the impact of sustainable practices in erosion hotspots around the world.

[Colon polyp detection based on multi-scale and multi-level feature fusion and lightweight convolutional neural network].

Early diagnosis and treatment of colorectal polyps are crucial for preventing colorectal cancer. This paper proposes a lightweight convolutional neural network for the automatic detection and auxiliary diagnosis of colorectal polyps. Initially, a 53-layer convolutional backbone network is used, incorporating a spatial pyramid pooling module to achieve feature extraction with different receptive field sizes. Subsequently, a feature pyramid network is employed to perform cross-scale fusion of feature maps from the backbone network. A spatial attention module is utilized to enhance the perception of polyp image boundaries and details. Further, a positional pattern attention module is used to automatically mine and integrate key features across different levels of feature maps, achieving rapid, efficient, and accurate automatic detection of colorectal polyps. The proposed model is evaluated on a clinical dataset, achieving an accuracy of 0.9982, recall of 0.9988, F1 score of 0.9984, and mean average precision (mAP) of 0.9953 at an intersection over union (IOU) threshold of 0.5, with a frame rate of 74 frames per second and a parameter count of 9.08 M. Compared to existing mainstream methods, the proposed method is lightweight, has low operating configuration requirements, high detection speed, and high accuracy, making it a feasible technical method and important tool for the early detection and diagnosis of colorectal cancer.

iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) technology has enabled assessment of transcriptome-wide changes at single-cell resolution. Due to the heterogeneity in environmental exposure and genetic background across subjects, subject effect contributes to the major source of variation in scRNA-seq data with multiple subjects, which severely confounds cell type specific differential expression (DE) analysis. Moreover, dropout events are prevalent in scRNA-seq data, leading to excessive number of zeroes in the data, which further aggravates the challenge in DE analysis. RESULTS: We developed iDESC to detect cell type specific DE genes between two groups of subjects in scRNA-seq data. iDESC uses a zero-inflated negative binomial mixed model to consider both subject effect and dropouts. The prevalence of dropout events (dropout rate) was demonstrated to be dependent on gene expression level, which is modeled by pooling information across genes. Subject effect is modeled as a random effect in the log-mean of the negative binomial component. We evaluated and compared the performance of iDESC with eleven existing DE analysis methods. Using simulated data, we demonstrated that iDESC had well-controlled type I error and higher power compared to the existing methods. Applications of those methods with well-controlled type I error to three real scRNA-seq datasets from the same tissue and disease showed that the results of iDESC achieved the best consistency between datasets and the best disease relevance. CONCLUSIONS: iDESC was able to achieve more accurate and robust DE analysis results by separating subject effect from disease effect with consideration of dropouts to identify DE genes, suggesting the importance of considering subject effect and dropouts in the DE analysis of scRNA-seq data with multiple subjects.

High-resolution multi-shot diffusion imaging of structural networks in healthy neurocognitive aging.

Healthy neurocognitive aging has been associated with the microstructural degradation of white matter pathways that connect distributed gray matter regions, assessed by diffusion-weighted imaging (DWI). However, the relatively low spatial resolution of standard DWI has limited the examination of age-related differences in the properties of smaller, tightly curved white matter fibers, as well as the relatively more complex microstructure of gray matter. Here, we capitalize on high-resolution multi-shot DWI, which allows spatial resolutions < 1 mm3 to be achieved on clinical 3T MRI scanners. We assessed whether traditional diffusion tensor-based measures of gray matter microstructure and graph theoretical measures of white matter structural connectivity assessed by standard (1.5 mm3 voxels, 3.375 µl volume) and high-resolution (1 mm3 voxels, 1µl volume) DWI were differentially related to age and cognitive performance in 61 healthy adults 18-78 years of age. Cognitive performance was assessed using an extensive battery comprising 12 separate tests of fluid (speed-dependent) cognition. Results indicated that the high-resolution data had larger correlations between age and gray matter mean diffusivity, but smaller correlations between age and structural connectivity. Moreover, parallel mediation models including both standard and high-resolution measures revealed that only the high-resolution measures mediated age-related differences in fluid cognition. These results lay the groundwork for future studies planning to apply high-resolution DWI methodology to further assess the mechanisms of both healthy aging and cognitive impairment.

PEC-SERS Dual-Mode Detection of Foodborne Pathogens Based on Binding-Induced DNA Walker and C3N4/MXene-Au NPs Accelerator.

In this paper, a photoelectrochemical (PEC)-surface-enhanced Raman scattering (SERS) dual-mode biosensor is constructed coupled with a dual-recognition binding-induced DNA walker with a carbon nitride nanosheet (C3N4)/MXene-gold nanoparticles (C/M-Au NPs) accelerator, which is reliable and capable for sensitive and accurate detection of Staphylococcus aureus (S. aureus). Initially, a photoactive heterostructure is formed by combining C3N4 and MXene via a simple electrostatic self-assembly as they possess well-matched band-edge energy levels. Subsequently, in situ growth of gold nanoparticles on the formed surface results in better PEC performance and SERS activity, because of the synergistic effects of surface plasmon resonance and Schottky barrier. Furthermore, a three-dimensional, bipedal, and dual-recognition binding-induced DNA walker is introduced with the formation of Pb2+-dependent DNAzyme. In the presence of S. aureus, a significant quantity of intermediate DNA (I-DNA) is generated, which can open the hairpin structure of Methylene Blue-tagged hairpin DNA (H-MB) on the electrode surface, thereby enabling the switch of signals for the quantitative determination of S. aureus. The constructed PEC-SERS dual-mode biosensor that can be mutually verified under one reaction effectively addresses the problem of the low detection accuracy of traditional sensors. Experimental results revealed that the effective combination of PEC and SERS is achieved for amplification detection of S. aureus with a detection range of 5-108 CFU/mL (PEC) and 10-108 CFU/mL (SERS), and a detection of limit of 0.70 CFU/mL (PEC) and 1.35 CFU/mL (SERS), respectively. Therefore, this study offers a novel and effective dual-mode sensing strategy, which has important implications for bioanalysis and health monitoring.

PSMC5 regulates microglial polarization and activation in LPS-induced cognitive deficits and motor impairments by interacting with TLR4.

Luteolin is a flavonoid found in high concentrations in celery and green pepper, and acts as a neuroprotectant. PSMC5 (proteasome 26S subunit, ATPase 5) protein levels were reduced after luteolin stimulation in activated microglia. We aimed to determine whether regulating PSMC5 expression could inhibit neuroinflammation, and investigate the underlying mechanisms.BV2 microglia were transfected with siRNA PSMC5 before the addition of LPS (lipopolysaccharide, 1.0 µg/ml) for 24 h in serum free DMEM. A mouse model of LPS-induced cognitive and motor impairment was established to evaluate the neuroprotective effects of shRNA PSMC5. Intracerebroventricular administration of shRNA PSMC5 was commenced 7 days prior to i.p. injection of LPS (750 µg/kg). Treatments and behavioral experiments were performed once daily for 7 consecutive days. Behavioral tests and pathological/biochemical assays were performed to evaluate LPS-induced hippocampal damage. Molecular dynamics simulation was used to confirm the interaction between PSMC5 and TLR4 (Toll-like receptor 4) in LPS-stimulated BV2 microglia. SiRNA PSMC5 inhibited BV2 microglial activation, and suppressed the release of inflammatory factors (IL-1ß, COX-2, PGE2, TNF-α, and iNOS) upon after LPS stimulation in BV2 microglia. LPS increased IκB-α and p65 phosphorylation, which was attenuated by siRNA PSMC5. Behavioral tests and pathological/biochemical assays showed that shRNA PSMC5 attenuated LPS-induced cognitive and motor impairments, and restored synaptic ultrastructure and protein levels in mice. ShRNA PSMC5 reduced pro-inflammatory cytokine (TNF-α, IL-1ß, PGE2, and NO) levels in the serum and brain, and relevant protein factors (iNOS and COX-2) in the brain. Furthermore, shRNA PSMC5 upregulated the anti-inflammatory mediators interleukin IL-4 and IL-10 in the serum and brain, and promoted a pro-inflammation-to-anti-inflammation phenotype shift in microglial polarization. Mechanistically, shRNA PSMC5 significantly alleviated LPS-induced TLR4 expression. The polarization of LPS-induced microglial pro-inflammation phenotype was abolished by TLR4 inhibitor and in the TLR-4-/- mouse, as in shRNA PSMC5 treatment. PSMC5 interacted with TLR4 via the amino sites Glu284, Met139, Leu127, and Phe283. PSMC5 site mutations attenuated neuroinflammation and reduced pro-inflammatory factors by reducing TLR4-related effects, thereby reducing TLR4-mediated MyD88 (myeloid differentiation factor 88)-dependent activation of NF-κB. PSMC5 could be an important therapeutic target for treatment of neurodegenerative diseases involving neuroinflammation-associated cognitive deficits and motor impairments induced by microglial activation.

An improved asymmetric susceptibility tensor imaging model with frequency offset correction.

PURPOSE: To improve susceptibility tensor imaging (STI) reconstruction using the asymmetric STI model with the correction of non-bulk-magnetic-susceptibility (NBMS) effects. METHOD: A frequency offset term was introduced into the asymmetric STI model to account for the bias between measured MRI frequency signals and conventional susceptibility tensor models because of NBMS contributions. Experiments were conducted to compare the proposed model with conventional STI, conventional STI with the proposed frequency offset correction, and asymmetric STI on simulation, ex vivo mouse brain, and in vivo human brain data. RESULTS: In the simulation where NBMS contributions are head rotation-invariant, the proposed method achieves the lowest errors in mean magnetic susceptibility (MMS) and magnetic susceptibility anisotropy (MSA) and is more robust to noise in the estimation of principal eigenvector (PEV). When considering the head orientation dependency of NBMS contributions, the proposed method shows advantages in estimating MSA and PEV. On the mouse and human brain data, the proposed method produces more reliable MSA maps and more consistent white matter fiber directions when referring to those from DTI than the compared STI methods. CONCLUSION: The proposed method can reduce the effects of NBMS-related frequency shifts on the susceptibility tensors in the brain white matter. This study inspires STI reconstruction from the perspective of better modeling the sources of frequency shifts.

Interfered chromosome pairing at high temperature promotes meiotic instability in autotetraploid Arabidopsis.

Changes in environmental temperature affect multiple meiotic processes in flowering plants. Polyploid plants derived from whole-genome duplication (WGD) have enhanced genetic plasticity and tolerance to environmental stress but face challenges in organizing and segregating doubled chromosome sets. In this study, we investigated the impact of increased environmental temperature on male meiosis in autotetraploid Arabidopsis (Arabidopsis thaliana). Under low to mildly increased temperatures (5°C-28°C), irregular chromosome segregation universally occurred in synthetic autotetraploid Columbia-0 (Col-0). Similar meiotic lesions occurred in autotetraploid rice (Oryza sativa L.) and allotetraploid canola (Brassica napus cv Westar), but not in evolutionarily derived hexaploid wheat (Triticum aestivum). At extremely high temperatures, chromosome separation and tetrad formation became severely disordered due to univalent formation caused by the suppression of crossing-over. We found a strong correlation between tetravalent formation and successful chromosome pairing, both of which were negatively correlated with temperature elevation, suggesting that increased temperature interferes with crossing-over predominantly by impacting homolog pairing. We also showed that loading irregularities of axis proteins ASY1 and ASY4 co-localize on the chromosomes of the syn1 mutant and the heat-stressed diploid and autotetraploid Col-0, revealing that heat stress affects the lateral region of synaptonemal complex (SC) by impacting the stability of the chromosome axis. Moreover, we showed that chromosome axis and SC in autotetraploid Col-0 are more sensitive to increased temperature than those in diploid Arabidopsis. Taken together, our data provide evidence suggesting that WGD negatively affects the stability and thermal tolerance of meiotic recombination in newly synthetic autotetraploid Arabidopsis.

Enhanced grey wolf algorithm for automatic tuning of an ensemble neural network in predicting PCF optical properties.

The structural characteristics of photonic crystal fibers (PCFs) determine their optical properties. This paper introduces an enhanced Grey Wolf Optimization algorithm termed ACD-GWO, which proposes adaptive strategies, chaotic mapping and dimension-based approaches and integrates them into the Grey Wolf Optimization framework. The aim is to achieve efficient automatic adjustment of hyperparameters and architecture for ensemble neural networks. The resulting ensemble neural network demonstrates accurate and rapid prediction of optical properties in PCFs, including effective refractive index, effective mode area, dispersion, and confinement loss, based on the PCF's structural characteristics. Compared to random forest and feedforward neural network models, the ensemble neural network achieves higher accuracy with a mean squared error of 3.78 × 10-6. Additionally, the computational time is significantly reduced, with only 2.27 minutes required for training and 0.08 seconds for prediction, which is much faster than numerical simulation software. This will provide new possibilities for optical device design and performance optimization, driving cutting-edge research and practical applications in the field of optics.

Microbacterium nymphoidis sp. nov. and Microbacterium festucae sp. nov., two novel species with high plant-promoting potential isolated from wetland plants in China.

Two novel plant growth-promoting, rod-shaped, Gram-positive and non-motile rhizobacteria, W1NT and W2RT, were isolated from wetland plants Festuca elata and Nymphoides peltatum, respectively, in China. The results of the 16S rRNA sequence alignment analysis showed that they were related to Microbacterium, with the highest similarity to Microbacterium ketosireducens (98.7 %) and Microbacterium laevaniformans (98.5 %) for strain W1NT, and to Microbacterium terricola (98.1 %) and Microbacterium marinum (98.0 %) for strain W2RT. Phylogenetic analyses based on 16S rRNA gene sequences and 92 conserved concatenated proteins suggested that the two strains belong to the genus Microbacterium and were placed in two separate novel phylogenetic clades. The genome sizes of the two strains were 3.2 and 3.7 Mb, and the G+C contents were 71.7 and 68.5 mol%, respectively. The comparative genome results showed that the average nucleotide identity values between W1NT and W2RT and other species ranged from 73.5 to 83.6 %, and the digital DNA-DNA hybridization values ranged from 19.7 to 26.8 %. These two strains show physiological and biochemical features that differ from those of closely related species. Rhamnose, galactose and glucose were present in the characteristic sugar fractions of strains W1NT and W2RT. The peptidoglycan of strains W1NT and W2RT contained the amino acids ornithine, alanine and aspartic acid. C15 : 0 anteiso, C17 : 0 anteiso and C16 : 0 iso were the predominant cellular fatty acids in W1NT and W2RT. Phosphatidylglycerol and diphosphatidylglycerol are major polar lipid components. Strain W1NT not only formed bacterial biofilms but also had the ability to solubilize phosphorus and produce indole-3-acetic acid. Strain W2RT had siderophore-producing and lignin-degrading properties. Based on their genetic and phenotypic characteristics, strains W1NT and W2RT were classified as novel bacteria in the genus Microbacterium and designated as Microbacterium festucae sp. nov. (type strain W1NT=ACCC 61807T=GDMCC 1.2966T=JCM 35339T) and Microbacterium nymphoidis sp. nov. (type strain W2RT=ACCC 61808T=GDMCC 1.2967T=JCM 35340T).

Hepatotoxicity assessment investigations on PFASs targeting L-FABP using binding affinity data and machine learning-based QSAR model.

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants that have been detected in various environmental media and human serum, but their safety assessment remains challenging. PFASs may accumulate in liver tissues and cause hepatotoxicity by binding to liver fatty acid binding protein (L-FABP). Therefore, evaluating the binding affinity of PFASs to L-FABP is crucial in assessing the potential hepatotoxic effects. In this study, two binding sites of L-FABP were evaluated, results suggested that the outer site possessed high affinity to polyfluoroalkyl sulfates and the inner site preferred perfluoroalkyl sulfonamides, overall, the inner site of L-FABP was more sensitive to PFASs. The binding affinity data of PFASs to L-FABP were used as training set to develop a machine learning model-based quantitative structure-activity relationship (QSAR) for efficient prediction of potentially hazardous PFASs. Further Bayesian Kernel Machine Regression (BKMR) model disclosed flexibility as the determinant molecular property on PFASs-induced hepatotoxicity. It can influence affinity of PFASs to target protein through affecting binding conformations directly (individual effect) as well as integrating with other molecular properties (joint effect). Our present work provided more understanding on hepatotoxicity of PFASs, which could be significative in hepatotoxicity gradation, administration guidance, and safer alternatives development of PFASs.