Associations between the multitrajectory neuroplasticity of neuronavigated rTMS-mediated angular gyrus networks and brain gene expression in AD spectrum patients with sleep disorders.

INTRODUCTION: The multifactorial influence of repetitive transcranial magnetic stimulation (rTMS) on neuroplasticity in neural networks is associated with improvements in cognitive dysfunction and sleep disorders. The mechanisms of rTMS and the transcriptional-neuronal correlation in Alzheimer's disease (AD) patients with sleep disorders have not been fully elucidated. METHODS: Forty-six elderly participants with cognitive impairment (23 patients with low sleep quality and 23 patients with high sleep quality) underwent 4-week periods of neuronavigated rTMS of the angular gyrus and neuroimaging tests, and gene expression data for six post mortem brains were collected from another database. Transcription-neuroimaging association analysis was used to evaluate the effects on cognitive dysfunction and the underlying biological mechanisms involved. RESULTS: Distinct variable neuroplasticity in the anterior and posterior angular gyrus networks was detected in the low sleep quality group. These interactions were associated with multiple gene pathways, and the comprehensive effects were associated with improvements in episodic memory. DISCUSSION: Multitrajectory neuroplasticity is associated with complex biological mechanisms in AD-spectrum patients with sleep disorders. HIGHLIGHTS: This was the first transcription-neuroimaging study to demonstrate that multitrajectory neuroplasticity in neural circuits was induced via neuronavigated rTMS, which was associated with complex gene expression in AD-spectrum patients with sleep disorders. The interactions between sleep quality and neuronavigated rTMS were coupled with multiple gene pathways and improvements in episodic memory. The present strategy for integrating neuroimaging, rTMS intervention, and genetic data provide a new approach to comprehending the biological mechanisms involved in AD.

Molecular simulation of the slurrying mechanism in microplastic semi-coke water slurry.

CONTEXT: This study explores the interaction between particles in microplastic semi-coke water slurry at the molecular level using molecular simulation methods, specifically DFT calculations and MD simulations. In addition, the experiment of slurry preparation was carried out to study the viscosity and stability of the slurry. The electrostatic potential analysis shows that the interaction between microplastics and dispersant molecules occurs on atoms with large electronegativity or oxygen-containing functional groups, and the energy gap of frontier molecular orbitals indicated that PVC interacts most easily with the dispersant (0.39 eV), followed by PS (1.08 eV) and PET (3.65 eV). In addition, it is also noted that due to the steric hindrance effect, the adsorption energy was opposite to the DFT calculation results: PET was - 213.338 kcal/mol (NNO) which was highest, followed by PS (- 107.603 kcal/mol, NNO), and PVC (NNO) was lowest which was - 94.808 kcal/mol. And RDF shows similar results, which the probability of water molecules in the PET system was the highest, followed by PS, and finally, PVC. The MD results are consistent with the viscosity and stability characterization results of the slurry which PET has the lowest viscosity of 87.3 mPa·s. Finally, this study provides new ideas for the treatment of microplastics and the improvement of the performance of semi-coke water slurry and reveals the interaction mechanism between microplastics and semi-coke water slurry. METHODS: All calculations were performed using Materials Studio (MS) version 2020 software, BIOVIA Corporation. The DFT calculation was carried out through the DMol3 module. The DFT calculations include electron density, electrostatics, orbitals, and population analysis. In DMol3 module, the GGA-PBE function was selected to consider gradient changes in density in the simulated calculation. The DFT-D correction was selected, and all electrons were calculated by DNP for accurate core potentials and the DNP file was 4.4. MD simulation was performed through the Forcite module. MD simulation mainly focuses on relative concentration distribution analysis, radial distribution function, and adsorption energy calculation. All molecular geometry optimizations are performed in the Forcite module. In the molecular dynamic part, all simulations used PCFF forcefield. The NVT ensemble was adopted and using the Nosé thermostat.

Neurexin-3 in the paraventricular nucleus of the hypothalamus regulates body weight and glucose homeostasis independently of food intake.

Neurexin-3 (Nrxn3) has been genetically associated with obesity, but the underlying neural mechanisms remain poorly understood. This study aimed to investigate the role of Nrxn3 in the paraventricular nucleus of the hypothalamus (PVN) in regulating energy balance and glucose homeostasis. We found that Nrxn3 expression in the PVN was upregulated in response to metabolic stressors, including cold exposure and fasting. Using Cre-loxP technology, we selectively ablated Nrxn3 in CaMKIIα-expressing neurons of the PVN in male mice. This genetic manipulation resulted in marked weight gain attributable to increased adiposity and impaired glucose tolerance, without affecting food intake. Our findings identify PVN CaMKIIα-expressing neurons as a critical locus where Nrxn3 modulates energy balance by regulating adipogenesis and glucose metabolism, independently of appetite. These results reveal a novel neural mechanism potentially linking Nrxn3 dysfunction to obesity pathogenesis, suggesting that targeting PVN Nrxn3-dependent neural pathways may inform new therapeutic approaches for obesity prevention and treatment.

Enhancing rice ecological production: synergistic effects of wheat-straw decomposition and microbial agents on soil health and yield.

Aims: This study evaluated the impact of wheat straw return and microbial agent application on rice field environments. Methods: Using Rice variety Chuankangyou 2115 and a microbial mix of Bacillus subtilis and Trichoderma harzianum. Five treatments were tested: T1 (no straw return), T2 (straw return), T3, T4, and T5 (straw return with varying ratios of Bacillus subtilis and Trichoderma harzianum). Results: Results indicated significant improvements in rice root length, surface area, dry weight, soil nutrients, and enzyme activity across T2-T5 compared to T1, enhancing yield by 3.81-26.63%. T3 (50:50 microbial ratio) was optimal, further increasing root dry weight, soil enzyme activity, effective panicle and spikelet numbers, and yield. Dominant bacteria in T3 included MBNT15, Defluviicoccus, Rokubacteriales, and Latescibacterota. Higher Trichoderma harzianum proportions (75% in T5) increased straw decomposition but slightly inhibited root growth. Correlation analysis revealed a significant positive relationship between yield and soil microorganisms like Gemmatimonadota and Firmicutes at the heading stage. Factors like dry root weight, straw decomposition rate post-jointing stage, and elevated soil enzyme activity and nutrient content from tiller to jointing stage contributed to increased panicle and spikelet numbers, boosting yield. Conclusion: The optimal Bacillus subtilis and Trichoderma harzianum ratio for straw return was 50:50, effectively improving soil health and synergizing high rice yield with efficient straw utilization.

High efficiency of biosurfactants in stabilizing oil micro-droplets within the aging time scale of milliseconds: a microfluidic study.

Rapid adsorption of surfactants onto a freshly formed interface is vital for emulsification because emulsification is a competitive process occurring between the very short time span of interface formation and surfactant mass transport. The biosurfactant surfactin has been previously reported to reach adsorption equilibrium at the hydrophobic/hydrophilic interface within hundreds of milliseconds and rapidly reduce the interfacial tension compared to chemically synthesized surfactants. According to a prior study, surfactin is expected to exhibit good performance in stabilizing micro-droplets of oil within the aging time scale of milliseconds. Herein, the stabilities of micro-droplets of n-hexadecane in the presence of a biosurfactant, surfactin (C15-SFT), and a chemically synthesized surfactant, sodium cetyl benzene sulfonate (8-SCBS), were investigated using a microfluidic method. The coalescence frequency of micro-droplets, the evolution of micro-droplet size, and the coalescence time of micro-droplets were evaluated. The results indicated that C15-SFT exhibited superiority over 8-SCBS in stabilizing the micro-droplets of n-hexadecane. Biosurfactant C15-SFT effectively reduced the fusion probability between oil droplets and elongated the coalescence time compared to 8-SCBS, and these phenomena were obvious at a shorter aging time (150 ms) and lower surfactant concentration (0.1 × critical micelle concentration). The stabilities of micro-droplets increased with aging time and the bulk concentration of surfactants. Stable micro-droplets of n-hexadecane were formed in 1 × 10-4 mol L-1 C15-SFT solution at 600 ms aging time, and the bulk concentration was 1 × 10-3 mol L-1 in the case of 8-SCBS. The micro-droplets rarely coalesced in the presence of 1 × 10-4 mol L-1 C15-SFT after 600 ms aging time, but the micro-droplets in 1 × 10-4 mol L-1 8-SCBS coalesced frequently in the midstream and downstream of the coalescence chamber, and big droplets were dominant in the emulsion. The coalescence time of micro-droplets stabilized by C15-SFT was obviously longer than that of those stabilized by 8-SCBS under the same condition, indicating that the interfacial film formed by C15-SFT has much strength to resist coalescence during collisions. This work is helpful for understanding the activity of lipopeptides in the very short early stage of the emulsification process, laying the foundation for biosurfactant research in the fields of enhanced oil recovery, bioremediation of contaminated water or soil, etc.

Efficient utilization of coral waste for internal curing material to prepare eco-friendly marine geopolymer concrete.

To address shortages in construction materials for island engineering, tackle the accumulation of solid waste, and inhibit the shrinkage of geopolymers, coral waste was utilized as the internal curing material to prepare high-performance marine geopolymer concrete (MGC) with seawater, sea-sand, and normal limestone aggregate (LsA). The coral coarse aggregate (CorA) used in this investigation has a total porosity ranging from 50% to 58.3% with internal pore diameters spanning 50-400 µm. The water desorption of CorA followed a two-stage pattern within a relative humidity (RH) range of 75%-85%, becoming nonlinear above 90% RH, which released about 85% of its moisture within 200 h at 97% RH, demonstrating potential for internal curing. Adding a small amount of CorA to MGC increased slump and setting time by providing internal curing water. However, as CorA content exceeded 30%, the slump significantly decreased due to reduced mixing water and elevated activator concentration, while the initial setting time slightly decreased. Furthermore, the inclusion of saturated CorA in MGC significantly reduced autogenous shrinkage, with higher CorA contents (exceeding 30%) leading to slight expansion in the early stages and nearly eliminating shrinkage at contents above 40%. The greater drying shrinkage in geopolymer systems compared to ordinary Portland cement is due to capillary pressure compressing the product framework, converting larger gel pores into smaller ones. Additionally, the layered calcium aluminosilicate hydrate (C-A-S-H) gel exhibits more pronounced creep characteristics under low internal humidity conditions. The higher CorA content in MGC promoted the formation of hybrid C, N-A-S-H gel and hydrotalcite-like phases, and reduced carbonation issues. The interfacial transition zone (ITZ) between CorA and the geopolymer matrix formed a robust mechanical interlock, enhancing tensile strength and minimizing shrinkage-induced cracks. Based on overall performance and marine material utilization, an optimal substitution rate of CorA between 40% and 50% is recommended.

Preparation and Application of Co-Doped Zinc Oxide: A Review.

Due to a wide band gap and large exciton binding energy, zinc oxide (ZnO) is currently receiving much attention in various areas, and can be prepared in various forms including nanorods, nanowires, nanoflowers, and so on. The reliability of ZnO produced by a single dopant is unstable, which in turn promotes the development of co-doping techniques. Co-doping is a very promising technique to effectively modulate the optical, electrical, magnetic, and photocatalytic properties of ZnO, as well as the ability to form various structures. In this paper, the important advances in co-doped ZnO nanomaterials are summarized, as well as the preparation of co-doped ZnO nanomaterials by using different methods, including hydrothermal, solvothermal, sol-gel, and acoustic chemistry. In addition, the wide range of applications of co-doped ZnO nanomaterials in photocatalysis, solar cells, gas sensors, and biomedicine are discussed. Finally, the challenges and future prospects in the field of co-doped ZnO nanomaterials are also elucidated.

Distinguishable neural circuit mechanisms associated with the clinical efficacy of rTMS in aMCI patients.

Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer's disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4 weeks, 20 Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.

View-Driven Multi-View Clustering via Contrastive Double-Learning.

Multi-view clustering requires simultaneous attention to both consistency and the diversity of information between views. Deep learning techniques have shown impressive abilities to learn complex features when working with extensive datasets; however, existing deep multi-view clustering methods often focus only on either consistency information or diversity information, making it difficult to balance both aspects. Therefore, this paper proposes a view-driven multi-view clustering using the contrastive double-learning method (VMC-CD), aiming to generate better clustering results. This method first adopts a view-driven approach to consider information from other views to encourage diversity, thus guiding feature learning. Additionally, it presents the idea of dual contrastive learning to enhance the alignment of views at both the clustering and feature levels. The VMC-CD method's superiority over various cutting-edge methods is substantiated by experimental findings across three datasets, affirming its effectiveness.

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.

Protein function annotation and virulence factor identification of Klebsiella pneumoniae genome by multiple machine learning models.

Klebsiella pneumoniae is a type of Gram-negative bacterium which can cause a range of infections in human. In recent years, an increasing number of strains of K. pneumoniae resistant to multiple antibiotics have emerged, posing a significant threat to public health. The protein function of this bacterium is not well known, thus a systematic investigation of K. pneumoniae proteome is in urgent need. In this study, the protein functions of this bacteria were re-annotated, and their function groups were analyzed. Moreover, three machine learning models were built to identify novel virulence factors. Results showed that the functions of 16 uncharacterized proteins were first annotated by sequence alignment. In addition, K. pneumoniae proteins share a high proportion of homology with Haemophilus influenzae and a low homology proportion with Chlamydia pneumoniae. By sequence analysis, 10 proteins were identified as potential drug targets for this bacterium. Our model achieved a high accuracy of 0.901 in the benchmark dataset. By applying our models to K. pneumoniae, we identified 39 virulence factors in this pathogen. Our findings could provide novel clues for the treatment of K. pneumoniae infection.

Anterior-temporal hippocampal network mechanisms of left angular gyrus-navigated rTMS for memory improvement in aMCI: A sham-controlled study.

INTRODUCTION: Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although abnormalities in two hippocampal networks, the anterior-temporal (AT) and posterior-medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI. METHODS: Sixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response. RESULTS: Compared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group. CONCLUSIONS: Neuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.

Identification of novel single nucleotide variants in the drug resistance mechanism of Mycobacterium tuberculosis isolates by whole-genome analysis.

BACKGROUND: Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium. METHODS: In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool. RESULTS: We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins. CONCLUSION: This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.

Effects of urea topdressing time on yield, nitrogen utilization, and quality of mechanical direct-seeding hybrid indica rice under slow-mixed fertilizer base application.

Introduction: The use of controlled-release nitrogen (N) fertilizers has been shown to improve yield and N-use efficiency (NUE) in mechanical transplanted rice. However, the fertilizer requirements for mechanical direct-seeding rice differ from those for mechanical transplanted rice. The effects of controlled-release fertilizers on yield, NUE, and quality in mechanical direct-seeding rice are still unknown. Methods: Hybrid indica rice varieties Yixiangyou 2115 and Fyou 498 were used as test materials, and slow-mixed N fertilizer (120 kg hm-2) as a base (N1), N1+urea-N (30 kg hm-2) once as a base (N2), N1+urea-N (30 kg hm-2) topdressing at the tillering stage (N3), N1+urea-N (30 kg hm-2) topdressing at the booting stage (N4) four N fertilizer management to study their impact on the yield, NUE and quality of mechanical direct-seeding rice. Results and discussion: Compared with Yixiangyou 2115, Fyou 498 significantly increased photosynthetic potential, population growth rate, root vigor, and N transport rate by 3.34-23.88%. This increase further resulted in a significant improvement in the yield and NUE of urea-N topdressing by 1.73-5.95 kg kg-1. However, Fyou 498 showed a significant decrease in the head rice rate and taste value by 3.34-7.67%. All varieties were treated with N4 that significantly increase photosynthetic potential and population growth rate by 15.41-62.72%, reduce the decay rate of root vigor by 5.01-21.39%, promote the N transport amount in stem-sheaths (leaves) by 13.54-59.96%, and then significantly increase the yields by 4.45-20.98% and NUE of urea-N topdressing by 5.20-45.56 kg kg-1. Moreover, the rice processing and taste values were optimized using this model. Correlation analysis revealed to achieve synergistic enhancement of high-yield, high-quality, and high-NUE in rice, it is crucial to focus on increasing photosynthetic potential, population growth rate, and promoting leaf N transport. Specifically, increasing the contribution rate of N transport in stem-sheaths is the most important. These findings offer an effective N management strategy for 4R nutrient stewardship (right source, right method, right rate and right timing) of mechanical direct-seeding hybrid indica rice.

Single-nucleus RNA and ATAC sequencing analyses provide molecular insights into early pod development of peanut fruit.

Peanut (Arachis hypogaea L.) is an important leguminous oil and economic crop that produces flowers aboveground and fruits belowground. Subterranean fruit-pod development, which significantly affects peanut production, involves complex molecular mechanisms that likely require the coordinated regulation of multiple genes in different tissues. To investigate the molecular mechanisms that underlie peanut fruit-pod development, we characterized the anatomical features of early fruit-pod development and integrated single-nucleus RNA-sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) data at the single-cell level. We identified distinct cell types, such as meristem, embryo, vascular tissue, cuticular layer, and stele cells within the shell wall. These specific cell types were used to examine potential molecular changes unique to each cell type during pivotal stages of fruit-pod development. snRNA-seq analyses of differentially expressed genes revealed cell-type-specific insights that were not previously obtainable from transcriptome analyses of bulk RNA. For instance, we identified MADS-box genes that contributes to the formation of parenchyma cells and gravity-related genes that are present in the vascular cells, indicating an essential role for the vascular cells in peg gravitropism. Overall, our single-nucleus analysis provides comprehensive and novel information on specific cell types, gene expression, and chromatin accessibility during the early stages of fruit-pod development. This information will enhance our understanding of the mechanisms that underlie fruit-pod development in peanut and contribute to efforts aimed at improving peanut production.

The Effect of Laser Remelting during SLM on Microstructure and Mechanical Properties of CoCrFeNiNb0.25.

A sub-eutectic high-entropy alloy composed of CoCrFeNiNb0.25 was prepared using a combination of mechanical powder mixing and selective laser melting (SLM). The mechanical properties of the alloy were enhanced by employing an interlayer laser remelting process. This study demonstrates the feasibility of using mechanical mixing and SLM to form an CoCrFeNiNb0.25 alloy. The interlayer laser remelting process can effectively promote the melting of Nb particles introduced by mechanical mixing, release the stresses near the unfused Nb particles, and reduce their degradation of the specimen properties. The results indicate that the CoCrFeNiNb0.25 alloy, prepared using the interlayer laser remelting process, had an average microhardness of 376 HV, a tensile strength of 974 MPa, and an elongation at break of 10.51%. This process offers a viable approach for rapidly adjusting the composition of high-entropy alloys for SLM forming.

Transcriptomic analysis reveals molecular characterization and immune landscape of PANoptosis-related genes in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis. METHODS: We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein-protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments. RESULTS: PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments. CONCLUSIONS: This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further understanding the pathogenesis and treatment strategies of atherosclerosis.

pathCLIP: Detection of Genes and Gene Relations From Biological Pathway Figures Through Image-Text Contrastive Learning.

In biomedical literature, biological pathways are commonly described through a combination of images and text. These pathways contain valuable information, including genes and their relationships, which provide insight into biological mechanisms and precision medicine. Curating pathway information across the literature enables the integration of this information to build a comprehensive knowledge base. While some studies have extracted pathway information from images and text independently, they often overlook the correspondence between the two modalities. In this paper, we present a pathway figure curation system named pathCLIP for identifying genes and gene relations from pathway figures. Our key innovation is the use of an image-text contrastive learning model to learn coordinated embeddings of image snippets and text descriptions of genes and gene relations, thereby improving curation. Our validation results, using pathway figures from PubMed, showed that our multimodal model outperforms models using only a single modality. Additionally, our system effectively curates genes and gene relations from multiple literature sources. Two case studies on extracting pathway information from literature of non-small cell lung cancer and Alzheimer's disease further demonstrate the usefulness of our curated pathway information in enhancing related pathways in the KEGG database.

Medium optimization and dust suppression performance analysis of microbial-based dust suppressant compound by response surface curve method.

At present, microbial dust suppressants based on microbial communities lack necessary systematic analysis of factors affecting dust suppression performance. Therefore, in this study, the response surface curve method was used to optimize the culture conditions for enrichment of urease-producing microorganisms from activated sludge. The results indicated that when urea = 9.67 g L-1, NH4Cl = 5.21 g L-1, and pH = 9.57, the maximum urease activity of urease-producing microbial community (UPMC) was 8.22 mM min-1. The UPMC under optimized culture conditions reached a mineralization rate of 98.8% on the 1st day of mineralization. Ureolysis is one of the biological mechanisms that trigger microbial mineralization with the consequent effect of dust suppression. The analysis of microbial community structure indicated that the urease-producing bacteria Sporosarcina sp. had the highest abundance at the genus level in the microbial-based dust suppressant compound. Jeotgalicoccus sp. plays an important role in improving and maintaining the stability of urease. In addition, the optimal UPMC had low pathogenicity, which is extremely attractive for the safe application of microbial dust suppressants.

Highly Efficient Hemostatic Cross-Linked Polyacrylate Polymer Dressings for Immediate Hemostasis.

A traumatic hemorrhage is fatal due to the great loss of blood in a short period of time; however, there are a few biomaterials that can stop the bleeding quickly due to the limited water absorption speed. Here, a highly absorbent polymer (HPA), polyacrylate, was prepared as it has the best structure-effectiveness relationship. Within a very short period of time (2 min), HPA continually absorbed water until it swelled up to its 600 times its weight; more importantly, the porous structure comprised the swollen dressing. This instantaneous swelling immediately led to rapid hemostasis in irregular wounds. We optimized the HPA preparation process to obtain a rapidly water-absorbent polymer (i.e., HPA-5). HPA-5 showed favorable adhesion and biocompatibility in vitro. A rat femoral arteriovenous complete shear model and a tail arteriovenous injury model were established. HPA exhibited excellent hemostatic capability with little blood loss and short hemostatic time compared with CeloxTM in both of the models. The hemostatic mechanisms of HPA consist of fast clotting by aggregating blood cells, activating platelets, and accelerating the coagulation pathway via water absorption and electrostatic interaction. HPA is a promising highly water-absorbent hemostatic dressing for rapid and extensive blood clotting after vessel injury.