Mix-Key: graph mixup with key structures for molecular property prediction.

Molecular property prediction faces the challenge of limited labeled data as it necessitates a series of specialized experiments to annotate target molecules. Data augmentation techniques can effectively address the issue of data scarcity. In recent years, Mixup has achieved significant success in traditional domains such as image processing. However, its application in molecular property prediction is relatively limited due to the irregular, non-Euclidean nature of graphs and the fact that minor variations in molecular structures can lead to alterations in their properties. To address these challenges, we propose a novel data augmentation method called Mix-Key tailored for molecular property prediction. Mix-Key aims to capture crucial features of molecular graphs, focusing separately on the molecular scaffolds and functional groups. By generating isomers that are relatively invariant to the scaffolds or functional groups, we effectively preserve the core information of molecules. Additionally, to capture interactive information between the scaffolds and functional groups while ensuring correlation between the original and augmented graphs, we introduce molecular fingerprint similarity and node similarity. Through these steps, Mix-Key determines the mixup ratio between the original graph and two isomers, thus generating more informative augmented molecular graphs. We extensively validate our approach on molecular datasets of different scales with several Graph Neural Network architectures. The results demonstrate that Mix-Key consistently outperforms other data augmentation methods in enhancing molecular property prediction on several datasets.

A Sparse Recovery Algorithm for Suppressing Multiple Linear Frequency Modulation Interference in the Synthetic Aperture Radar Image Domain.

In synthetic aperture radar (SAR) signal processing, compared with the raw data of level-0, level-1 SAR images are more readily accessible and available in larger quantities. However, an amount of level-1 images are affected by radio frequency interference (RFI), which typically originates from Linear Frequency Modulation (LFM) signals emitted by ground-based radars. Existing research on interference suppression in level-1 data has primarily focused on two methods: transforming SAR images into simulated echo data for interference suppression, or focusing interference in the frequency domain and applying notching filters to reduce interference energy. However, these methods overlook the effective utilization of the interference parameters or are confined to suppressing only one type of LFM interference at a time. In certain SAR images, multiple types of LFM interference manifest bright radiation artifacts that exhibit varying lengths along the range direction while remaining constant in the azimuth direction. It is necessary to suppress multiple LFM interference on SAR images when original echo data are unavailable. This article proposes a joint sparse recovery algorithm for interference suppression in the SAR image domain. In the SAR image domain, two-dimensional LFM interference typically exhibits differences in parameters such as frequency modulation rate and pulse width in the range direction, while maintaining consistency in the azimuth direction. Based on this observation, this article constructs a series of focusing operators for LFM interference in SAR images. These operators enable the sparse representation of dispersed LFM interference. Subsequently, an optimization model is developed that can effectively suppress multi-LFM interference and reduce image loss with the assistance of a regularization term in the image domain. Simulation experiments conducted in various scenarios validate the superior performance of the proposed method.

Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model.

Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 µM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 µM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 µM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.

Towards Inductive and Efficient Explanations for Graph Neural Networks.

Despite recent progress in Graph Neural Networks (GNNs), explaining predictions made by GNNs remains a challenging and nascent problem. The leading method mainly considers the local explanations, i.e., important subgraph structure and node features, to interpret why a GNN model makes the prediction for a single instance, e.g. a node or a graph. As a result, the explanation generated is painstakingly customized at the instance level. The unique explanation interpreting each instance independently is not sufficient to provide a global understanding of the learned GNN model, leading to the lack of generalizability and hindering it from being used in the inductive setting. Besides, training the explanation model explaining for each instance is time-consuming for large-scale real-life datasets. In this study, we address these key challenges and propose PGExplainer, a parameterized explainer for GNNs. PGExplainer adopts a deep neural network to parameterize the generation process of explanations, which renders PGExplainer a natural approach to multi-instance explanations. Compared to the existing work, PGExplainer has better generalization ability and can be utilized in an inductive setting without training the model for new instances. Thus, PGExplainer is much more efficient than the leading method with significant speed-up. In addition, the explanation networks can also be utilized as a regularizer to improve the generalization power of existing GNNs when jointly trained with downstream tasks. Experiments on both synthetic and real-life datasets show highly competitive performance with up to 24.7% relative improvement in AUC on explaining graph classification over the leading baseline.

Veronica linariifolia subsp. dilatata ameliorates LPS-induced acute lung injury by attenuating endothelial cell barrier dysfunction via EGFR/Akt/ZO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried aerial parts of Veronica linariifolia subsp. dilatata (Nakai & Kitag.) D.Y.Hong named Shui Man Jing (SMJ) is a traditional Chinese medicine with a long history of clinical use in the treatment of chronic bronchitis and coughing up blood, however, its role on acute lung injury (ALI) has not been revealed yet. AIM OF THE STUDY: To assess the efficiency of SMJ on ALI and to investigate whether it inhibited endothelial barrier dysfunction by regulating the EGFR/Akt/ZO-1 pathway to alleviate ALI in vivo and in vitro based on the result of network pharmacology. MATERIALS AND METHODS: An in vivo model of ALI was established using inhalation of atomized lipopolysaccharide (LPS), and the effects of SMJ on ALI were evaluated through histopathological examination and inflammatory cytokines, lung histology and edema, vascular and alveolar barrier disruption. Network pharmacology was applied to predict the mechanism of SMJ in the treatment of ALI. The crucial targets were validated by RT-PCR, Western Blotting, molecular docking, immunohistochemistry and immunofluorescence methods in vivo and in virto. RESULTS: Administration of SMJ protected mice against LPS-induced ALI, including ameliorating the histological alterations in the lung tissues, and decreasing lung edema, protein content of bronchoalveolar lavage fluid, infiltration of inflammatory cell and secretion of cytokines. SMJ exerted protective effects in ALI by inhibiting endothelial barrier dysfunction in mice and bEnd.3 cell. SMJ relieved endothelial barrier dysfunction induced by LPS through upregulating the EGFR expression. SMJ also increased the phosphorylation of Akt, and ZO-1 expression both in vivo and in vitro. CONCLUSION: SMJ attenuates vascular endothelial barrier dysfunction for LPS-induced ALI via EGFR/Akt/ZO-1 pathway, and is a promising novel therapeutic candidate for ALI.

Evidence for marine sedimentary rocks in Utopia Planitia: Zhurong rover observations.

Decades of research using remotely sensed data have extracted evidence for the presence of an ocean in the northern lowlands of Mars in the Hesperian (∼3.3 Ga), but these claims have remained controversial due to the lack of in situ analysis of the associated geologic unit, the Vastitas Borealis Formation (VBF). The Tianwen-1/Zhurong rover was targeted to land within the VBF near its southern margin and has traversed almost 2 km southward toward the interpreted shoreline. We report here on the first in situ analysis of the VBF that reveals sedimentary structures and features in surface rocks that suggest that the VBF was deposited in a marine environment, providing direct support for the existence of an ancient (Hesperian) ocean on Mars.

Comprehensive Comparison of Effects of Antioxidant (Astaxanthin) Supplementation from Different Sources in Haliotis discus hannai Diet.

Dietary antioxidant supplementation, especially astaxanthin, has shown great results on reproductive aspects, egg quality, growth, survival, immunity, stress tolerance, and disease resistance in aquatic animals. However, the effects of dietary astaxanthin supplementation from different sources are still unknown. A comprehensive comparison of survival, growth, immune response, antioxidant activity, thermal resistance, disease resistance, and intestinal microbial structure was conducted in dietary antioxidant supplementation from the sources of Gracilaria lemaneiformis (GL), industrial synthetic astaxanthin (80 mg/kg astaxanthin actual weight, named as group 'SA80'), Phaffia rhodozyma (80 mg/kg astaxanthin actual weight, named as group 'PR80') and Haematococcus pluvialis (120 mg/kg astaxanthin actual weight, named as group 'HP120') at their optimal supplementation amounts. Furthermore, the SA80, PR80, and HP120 groups performed better in all aspects, including survival, growth, immune response, antioxidant activity, thermal resistance, and disease resistance, compared with the GL group. The PR80 and HP120 group also had a better growth performance than the SA80 group. In terms of heat stress and bacterial challenge, abalone in the PR80 group showed the strongest resistance. Overall, 80 mg/kg astaxanthin supplementation from Phaffia rhodozyma was recommended to obtain a more effective and comprehensive outcome. This study contributes to the discovery of the optimum dietary astaxanthin supplementation source for abalone, which is helpful to improve the production efficiency and economic benefits of abalone. Future research can further explore the action mechanism and the method of application of astaxanthin to better exploit its antioxidant role.

Functional abdominal pain disorders in children in southern Anhui Province, China are related to academic stress rather than academic performance.

BACKGROUND: Functional abdominal pain disorders (FAPDs) are one of the most common gastrointestinal disorders in children. The aim of this study was to investigate the prevalence of FAPDs in children in southern Anhui Province, China and their association with academic stress. METHODS: In this cross-sectional survey, we randomly selected children aged 6-17 years from 11 public schools in southern Anhui Province. FAPDs were diagnosed according to the Rome IV criteria, and a custom-designed questionnaire was used to investigate the association between academic stress and FAPDs in children. RESULTS: A total of 2,344 children aged 6-17 years were enrolled. The mean age was 12.4 ± 3.0 years. Of these children, 335 (14.3%) were diagnosed with FAPDs according to the Rome IV criteria. Among the children with FAPDs, 156 (46.6%) were boys, and 179 (53.4%) were girls. The prevalence was higher in girls than in boys. The most common disorder was irritable bowel syndrome (IBS) (n = 182 (7.8%)). Other types of FAPDs included functional abdominal pain-not otherwise specified (FAPNOS) (n = 70 (3.0%)), functional dyspepsia (FD) (n = 55 (2.3%)), and abdominal migraine (AM) (n = 28 (1.2%)). Academic stress, not meeting parental expectations, poor relationships with parents, and sleep disturbances were independent risk factors for FAPDs in children; academic performance was not associated with the development of FAPDs. CONCLUSION: There was a high prevalence of FAPDs among children in southern Anhui Province, China, and IBS was the most common subtype of functional abdominal pain. Academic stress, rather than academic performance, was associated with FAPDs in children.

Global analysis of the biosynthetic chemical space of marine prokaryotes.

BACKGROUND: Marine prokaryotes are a rich source of novel bioactive secondary metabolites for drug discovery. Recent genome mining studies have revealed their great potential to bio-synthesize novel secondary metabolites. However, the exact biosynthetic chemical space encoded by the marine prokaryotes has yet to be systematically evaluated. RESULTS: We first investigated the secondary metabolic potential of marine prokaryotes by analyzing the diversity and novelty of the biosynthetic gene clusters (BGCs) in 7541 prokaryotic genomes from cultivated and single cells, along with 26,363 newly assembled medium-to-high-quality genomes from marine environmental samples. To quantitatively evaluate the unexplored biosynthetic chemical space of marine prokaryotes, the clustering thresholds for constructing the biosynthetic gene cluster and molecular networks were optimized to reach a similar level of the chemical similarity between the gene cluster family (GCF)-encoded metabolites and molecular family (MF) scaffolds using the MIBiG database. The global genome mining analysis demonstrated that the predicted 70,011 BGCs were organized into 24,536 mostly new (99.5%) GCFs, while the reported marine prokaryotic natural products were only classified into 778 MFs at the optimized clustering thresholds. The number of MF scaffolds is only 3.2% of the number of GCF-encoded scaffolds, suggesting that at least 96.8% of the secondary metabolic potential in marine prokaryotes is untapped. The unexplored biosynthetic chemical space of marine prokaryotes was illustrated by the 88 potential novel antimicrobial peptides encoded by ribosomally synthesized and post-translationally modified peptide BGCs. Furthermore, a sea-water-derived Aquimarina strain was selected to illustrate the diverse biosynthetic chemical space through untargeted metabolomics and genomics approaches, which identified the potential biosynthetic pathways of a group of novel polyketides and two known compounds (didemnilactone B and macrolactin A 15-ketone). CONCLUSIONS: The present bioinformatics and cheminformatics analyses highlight the promising potential to explore the biosynthetic chemical diversity of marine prokaryotes and provide valuable knowledge for the targeted discovery and biosynthesis of novel marine prokaryotic natural products. Video Abstract.

Optimal number of charging station and pricing strategy for the electric vehicle with component commonality considering consumer range anxiety.

The battery driving mileage on a single charge and convenience of the charging stations affect Electric Vehicle's (EV) demand. This paper studies the optimal number of charging stations and EV's price strategy considering different component commonality configurations. Assume the EV manufacturer provides two types of EV and the two EVs have the same battery configuration (battery as a common part) or the same naked vehicle-EV without batteries (naked vehicle as a common part). And the common part could be configured with low or high quality. We discuss four scenarios with different common parts and different quality levels. For each scenario, we present the optimal number of the charging stations and EV prices. Then we compare the optimal solutions and manufacturer's profits in above four scenarios with numerical simulation and give some managerial insights. Our analysis reveals that (1) consumers' range anxiety towards battery will affect manufacturer's product configuration strategy, EVs' prices and demands. (2) large consumers' sensitivity towards charging station will corresponding to more charging station, high EV prices and demands. If consumers are very concerned about the charging convenience, high-end electric vehicles need to be launched first, then as customers' anxiety about charging decreases, the low quality EV could be developed and diffused. (3) the unit product cost reduction caused by the commonality may increase or decrease the EVs' prices, which depends on the relationship between the demand increment incurred by one more charging station and the cost coefficient of building the charging station. (4) The low quality naked vehicle as common component will increase both the number of the charging stations and the demand and the manufacturer is more likely to obtain high profits. (5) the cost saving coefficient of battery common parts has greater influence on the selection of commonality. When consumers' range anxiety towards battery is very high, manufacturers should choose low-quality naked vehicles or high-quality battery as common components.

An extensive assessment of seasonal rainfall on intracellular and extracellular antibiotic resistance genes in Urban River systems.

Rainfall events are responsible for the accelerated transfer of antibiotic-resistant contaminants to receiving environments. However, the specific profiles of various ARG types, including intra- and extracellular ARGs (iARGs and eARGs) responding to season rainfall needed more comprehensive assessments. Particularly, the key factors driving the distribution and transport of iARGs and eARGs have not been well characterized. Results revealed that the absolute abundance of eARGs was observed to be more than one order of magnitude greater than that of iARGs during the dry season in the reservoir. However, the absolute abundance of iARGs significantly increased after rainfall (p < 0.01). Meanwhile, seasonal rainfall significantly decreased the diversity of eARGs and the number of shared genes between iARGs and eARGs (p < 0.01). Results of structural equation models (SEM) and network analysis showed the rank and co-occurrence of influencing factors (e.g., microbial community, MGEs, environmental variables, and dissolved organic matter (DOM)) concerning the changes in iARGs and eARGs. DOM contributed majorly to eARGs in the reservoir and pathogens was responsible for eARGs in the river during the wet season. Network analysis revealed that the tnp-04 and IS613 genes-related MGEs co-occurred with eARGs in the dry and wet seasons, which were regarded as potential molecular indicators to shape eARGs profiles in urban rivers. Besides, the results demonstrated close relationships between DOM fluorescence signatures and two-typed ARGs. Specifically, humic acid was significantly and positively correlated with the eARGs in the reservoir during the wet season, while fulvic acid-like substances exhibited strong correlations of iARGs and eARGs in the river during the dry season (p < 0.01). This work provides extensive insights into the potential effect of seasonal rainfall on the dynamic distribution of iARGs and eARGs and the dominance of DOM in driving the fate of two-typed ARGs in urban river systems.

Identification and validation of hub genes and pathways associated with mitochondrial dysfunction in hypertrophy of ligamentum flavum.

Background: Lumbar spinal stenosis which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy of ligamentum flavum (HLF). Recent studies have indicated that mitochondrial dysfunction may contribute to the development of HLF. However, the underlying mechanism is still unclear. Methods: The dataset GSE113212 was obtained from the Gene Expression Omnibus database, and the differentially expressed genes were identified. The intersection of DEGs and mitochondrial dysfunction-related genes were identified as mitochondrial dysfunction-related DEGs. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis were performed. Protein-protein interaction network was constructed, and miRNAs and transcriptional factors of the hub genes were predicted via the miRNet database. Small molecule drugs targeted to these hub genes were predicted via PubChem. Immune infiltration analysis was performed to evaluate the infiltration level of immune cells and their correlation with the hub genes. In final, we measured the mitochondrial function and oxidative stress in vitro and verified the expression of hub genes by qPCR experiments. Results: In total, 43 genes were identified as MDRDEGs. These genes were mainly involved in cellular oxidation, catabolic processes, and the integrity of mitochondrial structure and function. The top hub genes were screened, including LONP1, TK2, SCO2, DBT, TFAM, MFN2. The most significant enriched pathways include cytokine-cytokine receptor interaction, focal adhesion, etc. Besides, SP1, PPARGC1A, YY1, MYC, PPARG, and STAT1 were predicted transcriptional factors of these hub genes. Additionally, increased immune infiltration was demonstrated in HLF, with a close correlation between hub genes and immune cells found. The mitochondrial dysfunction and the expression of hub genes were validated by evaluation of mitochondrial DNA, oxidative stress markers and quantitative real-time PCR. Conclusion: This study applied the integrative bioinformatics analysis and revealed the mitochondrial dysfunction-related key genes, regulatory pathways, TFs, miRNAs, and small molecules underlying the development of HLF, which improved the understanding of molecular mechanisms and the development of novel therapeutic targets for HLF.

Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study.

BACKGROUND: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases and is the leading cause of pain and disability in the aged population. However, the underlying biological mechanism has not been fully understood. This study aims to reveal the causal effect of circulation metabolites on OA susceptibility. METHODS: A two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of GDMs on OA. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas 8 different OA phenotypes, including any-site OA (All OA), knee and/or hip OA (knee/hip OA), knee OA, hip OA, spine OA, finger and/or thumb OA (hand OA), finger OA, thumb OA, were set the outcomes. Inverse-variance weighted (IVW) was used for calculating causal estimates. Methods including weight mode, weight median, MR-egger, and MR-PRESSO were used for the sensitive analysis. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0. All statistical analyses were performed in R software. RESULTS: In this MR analysis, a total of 235 causative associations between metabolites and different OA phenotypes were observed. After false discovery rate (FDR) correction and sensitive analysis, 9 robust causative associations between 7 metabolites (e.g., arginine, kynurenine, and isovalerylcarnitine) and 5 OA phenotypes were finally identified. Additionally, eleven significant metabolic pathways in 4 OA phenotypes were identified by metabolic pathway analysis. CONCLUSION: The finding of our study suggested that identified metabolites and metabolic pathways can be considered useful circulating metabolic biomarkers for OA screening and prevention in clinical practice, and can also serve as candidate molecules for future mechanism exploration and drug target selection.

Smurf1 Facilitates Oxidative Stress and Fibrosis of Ligamentum Flavum by Promoting Nrf2 Ubiquitination and Degradation.

Lumbar spinal stenosis (LSS), which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy and fibrosis in the ligamentum flavum (LF). However, the underlying mechanism is still unclear. In the current study, the effect of Smurf1, a kind of E3 ubiquitin ligase, in promoting the fibrosis and oxidative stress of LF was investigated, and its underlying mechanism was explored. The expression of oxidative stress and fibrosis-related markers was assessed in the tissue of lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Next, the expression of the top 10 E3 ubiquitin ligases, obtained from Gene Expression Omnibus (GEO) dataset GSE113212, was assessed in LDH and LSS, and confirmed that Smurf1 expression was markedly upregulated in the LSS group. Furthermore, Smurf1 overexpression promotes the fibrosis and oxidative stress of LF cells. Subsequently, NRF2, an important transcription factor for oxidative stress and fibrosis, was predicted to be a target of Smurf1. Mechanistically, Smurf1 directly interacts with Nrf2 and accelerates Nrf2 ubiquitination and degradation. In conclusion, the current study suggests that Smurf1 facilitated the fibrosis and oxidative stress of LF and induced the development of LSS by promoting Nrf2 ubiquitination and degradation.

Secondary Metabolic Potential of Kutzneria.

Kutzneria is a rare genus of Actinobacteria that harbors a variety of secondary metabolite gene clusters and produces several interesting types of bioactive secondary metabolites. Recent efforts have partially elucidated the biosynthetic pathways of some of these bioactive natural products, suggesting the diversity and specificity of secondary metabolism within this genus. Here, we summarized the chemical structures, biosynthetic pathways, and key metabolic enzymes of the secondary metabolites isolated from Kutzneria strains. In-depth comparative genomic analysis of all six available high-quality Kutzneria genomes revealed that the majority (77%) of the biosynthetic gene cluster families of Kutzneria were untapped and identified homologues of key metabolic enzymes in the putative gene clusters, including cytochrome P450s, halogenases, and flavin-dependent N-hydroxylases. The present study suggests that Kutzneria exhibits great potential to synthesize novel secondary metabolites, encodes a variety of valuable metabolic enzymes, and also provides valuable information for the targeted discovery and biosynthesis of novel natural products from Kutzneria.

Association Between the Cervical Extensor Musculature and the Demographic Features, Symptoms, and Sagittal Balance in Patients with Multilevel Cervical Spondylotic Myelopathy.

OBJECTIVE: To obtain the quantitative measurements of the muscle morphology of cervical extensors in patients with multilevel cervical spondylotic myelopathy, and determine whether the morphological parameter of each muscle correlates with the patients' demographic features, symptoms, and cervical sagittal balance. METHODS: We retrospectively evaluated 100 hospitalized patients scheduled to undergo surgery for multilevel cervical spondylotic myelopathy. Demographic data, including age, sex, and body mass index, were recorded, and symptoms were evaluated using the visual analog scale (VAS), neck disability index (NDI), and modified Japanese Orthopedic Association scale scores. The cross-sectional area (CSA) of the multifidus, semispinalis capitis, semispinalis cervicis, splenius capitis and splenius cervicis were measured on magnetic resonance imaging. The CSA of the total extensor muscles, deep extensor muscles (DEM, consisting of multifidus and semispinalis capitis), and superficial extensor muscles (consisting of semispinalis cervicis, splenius capitis and splenius cervicis) were calculated. The adjusted CSA (aCSA) was calculated as the CSA of the muscle/CSA of the corresponding vertebral body. The fat infiltration ratio (FIR) of the posterior extensor muscles was assessed using a pseudocoloring technique. Sagittal parameters, including cervical lordosis (CL), C2-7 cervical sagittal vertical axis (SVA), T1-slope, mismatch between T1-slope and CL (T1S-CL), and range of motion, were measured. The measured parameters were compared between the males and the females, between the patients with higher muscle aCSA and the patients with lower muscle aCSA, and between the patients with and without sagittal balance. A Pearson correlation analysis was conducted to determine the correlations between the paraspinal muscle measurements, and the clinical and radiographic parameters. RESULTS: There were 67 males and 33 females in this study, and the mean age was 59.22 ± 9.54 years. Compared with females, male patients showed higher CSA and aCSA of extensor muscles. Patients with lower muscle aCSA were significantly older and had worse NDI scores, with significantly greater C2-7 SVA and T1S-CL. Patients with sagittal imbalance showed significantly lower aCSA of total extensor muscles and DEM, as well as a significantly higher FIR. Age was significantly correlated with the aCSA of each measured muscle and the FIR. The aCSA of the DEM was correlated with the NDI score, the visual analog scale score, the SVA, the T1-slope, and the T1S-CL. CONCLUSIONS: In patients with multilevel CSM, age and sex were demographic factors that were highly correlated with muscle morphology changes. Extensor muscles, especially DEM, play important roles in maintaining cervical sagittal balance and are associated with the severity of neck symptoms.

Mo-Based Heterogeneous Interface and Sulfur Vacancy Synergistic Effect Enhances the Fenton-like Catalytic Performance for Organic Pollutant Degradation.

Heterogeneous Fenton-like reactions (HFLRs) based on the in situ electrochemical generation of hydrogen peroxide (H2O2) are one of the green methods to remediate organic pollutants in wastewater. However, the design of Fenton-like catalysts with specific active sites and high pollutant degradation rate is still challenging. Here, MoS2-MoC and MoS2-Mo2N catalytic cathodes with heterojunctions were successfully prepared, and the mechanism by which hydroxyl radicals and singlet oxygen (1O2) were generated cleanly without adding chemical additives other than oxygen was clarified. The composite catalysts contained more sulfur vacancies, and the catalytic cathode achieved a high paracetamol pollutant degradation efficiency with 0.17 kWh g-1 TOC specific energy consumption. And almost 5 times higher activity was achieved compared to a pure MoS2 catalytic cathode. Experimental studies confirmed that the production of 1O2 was based on the transformation of superoxide radicals by Mo6+, and 1O2 accounted for approximately 66% of the total degradation and enhanced the nonradical behavior in the reaction. This work provides a sustainable strategy for pollutant utilization, which is valuable for solving the difficult problems of HFLRs and developing new environmental remediation technologies.

Divergent Carry-Over Effects of Hypoxia during the Early Development of Abalone.

After being exposed to environmental stimuli during early developmental stages, some organisms may gain or weaken physiological regulating abilities, which would have long-lasting effects on their performance. Environmental hypoxia events can have significant effects on marine organisms, but for breeding programs and other practical applications, it is important to further explore the long-term physiological effects of early hypoxia exposure in economically significant species. In this study, the Pacific abalone Haliotis discus hannai was exposed to moderate hypoxia (∼4 mg/L) from zygote to trochophora, and the assessments of hypoxia tolerance were conducted on the grow-out stage. The results revealed that juvenile abalones exposed to hypoxia at the early development stages were more hypoxia-tolerant but with slower weight growth, a phenomenon called the trade-off between growth and survival. These phenotypic effects driven by the hypoxia exposure were explained by strong selection of genes involved in signal transduction, autophagy, apoptosis, and hormone regulation. Moreover, long non-coding RNA regulation plays an important role modulating carry-over effects by controlling DNA replication and repair, signal transduction, myocardial activity, and hormone regulation. This study revealed that the ability to create favorable phenotypic differentiation through genetic selection and/or epigenetic regulation is important for the survival and development of aquatic animals in the face of rapidly changing environmental conditions.

Non-ribosomal peptide biosynthetic potential of the nematode symbiont Photorhabdus.

Photorhabdus, the symbiotic bacteria of Heterorhabditis nematodes, has been reported to possess many non-ribosomal peptide synthetase (NRPS) biosynthesis gene clusters (BGCs). To provide an in-depth assessment of the non-ribosomal peptide biosynthetic potential of Photorhabdus, we compared the distribution of BGCs in 81 Photorhabdus strains, confirming the predominant presence (44.80%) of NRPS BGCs in Photorhabdus. All 990 NRPS BGCs were clustered into 275 gene cluster families (GCFs) and only 13 GCFs could be annotated with known BGCs, suggesting their great diversity and novelty. These NRPS BGCs encoded 351 novel peptides containing more than four amino acids, and 173 of them showed high sequence similarity to known BGCs encoding bioactive peptides, implying the promising potential of Photorhabdus to produce valuable peptides. Sequence similarity networking of adenylation (A-) domains suggested that the substrate specificity of A-domains was not directly correlated with the sequence similarity. The molecular similarity network of predicted metabolite scaffolds of NRPS BGCs and reported peptides from Photorhabdus and a relevant database demonstrated that the non-ribosomal peptide biosynthetic potential of Photorhabdus was largely untapped and revealed the core peptides deserving intensive studies. Our present study provides valuable information for the targeted discovery of novel non-ribosomal peptides from Photorhabdus.

Genomic selection applications can improve the environmental performance of aquatics: A case study on the heat tolerance of abalone.

Aquaculture is one of the world's fastest-growing and most traded food industries, but it is under the threat of climate-related risks represented by global warming, marine heatwave (MHW) events, ocean acidification, and deoxygenation. For the sustainable development of aquaculture, selective breeding may be a viable method to obtain aquatic economic species with greater tolerance to environmental stressors. In this study, we estimated the heritability of heat tolerance trait of Pacific abalone Haliotis discus hannai, performed genome-wide association studies (GWAS) analysis for heat tolerance to detect single nucleotide polymorphisms (SNPs) and candidate genes, and assessed the potential of genomic selection (GS) in the breeding of abalone industry. A total of 1120 individuals were phenotyped for their heat tolerance and genotyped with 64,788 quality-controlled SNPs. The heritability of heat tolerance was moderate (0.35-0.42) and the predictive accuracy estimated using BayesB (0.55 ± 0.05) was higher than that using GBLUP (0.40 ± 0.01). A total of 11 genome-wide significant SNPs and 2 suggestive SNPs were associated with heat tolerance of abalone, and 13 candidate genes were identified, including got2,znfx1,l(2)efl, and lrp5. Based on GWAS results, the prediction accuracy using the top 5K SNPs was higher than that using randomly selected SNPs and higher than that using all SNPs. These results suggest that GS is an efficient approach for improving the heat tolerance of abalone and pave the way for abalone selecting breeding programs in rapidly changing oceans.