Activation of astrocytic NMDA receptors counteracted Aß-induced reduction of BDNF and elevation of GFAP and complement 3 in the hippocampal astrocytes.

N-methyl-D-aspartate receptors (NMDARs) play a crucial role in mediating Amyloid-ß (Aß) synaptotoxicity. Our previous studies have demonstrated an opposite (neuroprotection and neurotoxicity) effect of activating astrocytic and neuronal NMDARs with higher dose (10 µM) of NMDA, an agonist of NMDARs. By contrast, activating neuronal or astrocyitc NMDARs with lower dose (1 µM) of NMDA both exerts neuroprotective effect in Aß-induced neurotoxicity. However, the underlying mechanism of activating astrocytic NMDARs with lower dose of NMDA to protect against Aß neurotoxicity remains unclear. Based on our previous related work, in this study, using a co-cultured cell model of primary hippocampal neurons and astrocytes, we further investigated the possible factors involved in 1 µM of NMDA activating astrocytic NMDARs to oppose Aß-induced synaptotoxicity. Our results showed that activation of astrocytic NMDARs by 1 µM NMDA rescued Aß-induced reduction of brain-derived neurotrophic factor (BDNF), and inhibited Aß-induced increase of GFAP, complement 3 (C3) and activation of NF-κB. Furthermore, blockade of astrocytic GluN2A with TCN201 abrogated the ability of 1 µM NMDA to counteract the effects of Aß decreasing BDNF, and increasing GFAP, C3 and activation of NF-κB. These findings suggest that activation of astrocytic NMDARs protect against Aß-induced synaptotoxicity probably through elevating BDNF and suppressing GFAP and C3. Our present research provides valuable insights for elucidating the underlying mechanism of astrocytic NMDARs activation resisting the toxic effects of Aß.

Prompt-and-Transfer: Dynamic Class-aware Enhancement for Few-shot Segmentation.

For more efficient generalization to unseen domains (classes), most Few-shot Segmentation (FSS) would directly exploit pre-trained encoders and only fine-tune the decoder, especially in the current era of large models. However, such fixed feature encoders tend to be class-agnostic, inevitably activating objects that are irrelevant to the target class. In contrast, humans can effortlessly focus on specific objects in the line of sight. This paper mimics the visual perception pattern of human beings and proposes a novel and powerful prompt-driven scheme, called "Prompt and Transfer" (PAT), which constructs a dynamic class-aware prompting paradigm to tune the encoder for focusing on the interested object (target class) in the current task. Three key points are elaborated to enhance the prompting: 1) Cross-modal linguistic information is introduced to initialize prompts for each task. 2) Semantic Prompt Transfer (SPT) that precisely transfers the class-specific semantics within the images to prompts. 3) Part Mask Generator (PMG) that works in conjunction with SPT to adaptively generate different but complementary part prompts for different individuals. Surprisingly, PAT achieves competitive performance on 4 different tasks including standard FSS, Cross-domain FSS (e.g., CV, medical, and remote sensing domains), Weak-label FSS, and Zero-shot Segmentation, setting new state-of-the-arts on 11 benchmarks.

Identification of Blood Biomarkers Related to Energy Metabolism and Construction of Diagnostic Prediction Model Based on Three Independent Alzheimer's Disease Cohorts.

Background: Blood biomarkers are crucial for the diagnosis and therapy of Alzheimer's disease (AD). Energy metabolism disturbances are closely related to AD. However, research on blood biomarkers related to energy metabolism is still insufficient. Objective: This study aims to explore the diagnostic and therapeutic significance of energy metabolism-related genes in AD. Methods: AD cohorts were obtained from GEO database and single center. Machine learning algorithms were used to identify key genes. GSEA was used for functional analysis. Six algorithms were utilized to establish and evaluate diagnostic models. Key gene-related drugs were screened through network pharmacology. Results: We identified 4 energy metabolism genes, NDUFA1, MECOM, RPL26, and RPS27. These genes have been confirmed to be closely related to multiple energy metabolic pathways and different types of T cell immune infiltration. Additionally, the transcription factors INSM2 and 4 lncRNAs were involved in regulating 4 genes. Further analysis showed that all biomarkers were downregulated in the AD cohorts and not affected by aging and gender. More importantly, we constructed a diagnostic prediction model of 4 biomarkers, which has been validated by various algorithms for its diagnostic performance. Furthermore, we found that valproic acid mainly interacted with these biomarkers through hydrogen bonding, salt bonding, and hydrophobic interaction. Conclusions: We constructed a predictive model based on 4 energy metabolism genes, which may be helpful for the diagnosis of AD. The 4 validated genes could serve as promising blood biomarkers for AD. Their interaction with valproic acid may play a crucial role in the therapy of AD.

Fusarium pseudograminearum biomass and toxin accumulation in wheat tissues with and without Fusarium crown rot symptoms.

Fusarium crown rot (FCR) is an important and devastating disease of wheat (Triticum aestivum) caused by the fungus Fusarium pseudograminearum and related pathogens. Using two distinct susceptible cultivars, we investigated the isolation frequencies of F. pseudograminearum and quantified its biomass accumulation and the levels of the associated toxins deoxynivalenol (DON) and DON-3-glucoside (D3G) in inoculated field-grown wheat plants. We detected F. pseudograminearum in stem, peduncle, rachis, and husk tissues, but not in grains, whereas DON and D3G accumulated in stem, rachis, husk, and grain tissues. Disease severity was positively correlated with the frequency of pathogen isolation, F. pseudograminearum biomass, and mycotoxin levels. The amount of F. pseudograminearum biomass and mycotoxin contents in asymptomatic tissue of diseased plants were associated with the distance of the tissue from the diseased internode and the disease severity of the plant. Thus, apparently healthy tissue may harbor F. pseudograminearum and contain associated mycotoxins. This research helps clarify the relationship between F. pseudograminearum occurrence, F. pseudograminearum biomass, and mycotoxin accumulation in tissues of susceptible wheat cultivars with or without disease symptoms, providing information that can lead to more effective control measures.

Study on Calculation Method of Bending Performance of Concrete Sandwich Composite Slab.

In order to explore the flexural behavior of a concrete sandwich panel under concentrated boundary conditions, based on Kirachhoff's elastic thin plate theory in this paper, the geometric deformation, physical conditions, and equilibrium relationship of a sandwich panel are deduced by constructing the layered analysis model of the sandwich panel, the basic differential equation of the flexural deformation of the concrete sandwich thin plate is obtained, and the mathematical expression of the internal force and displacement under the boundary condition of concentrated support is given. Combined with an engineering example, the proposed calculation method is verified. The results show that, in the arrangement of reliable connectors for concrete sandwich panels, the concrete wythes bear the load while the contribution of the core layer to the bending capacity of the structure can be ignored. When subjected to a laterally distributed load, the sandwich panel mainly experiences out-of-plane bending deformation, and the bending normal stress in the concrete panel layer shows a linear non-uniform distribution along the thickness direction of the panel. The bending deformation performance and bearing efficiency of a concrete sandwich slab with the change in concentrated support position have significant effects, and the load transfer efficiency can be improved by optimizing the arrangement of supports. Except for small local areas near the supports, the bending stress distribution and deformation behavior of the concrete sandwich panel can be accurately analyzed by the calculation method established in this paper.

Whole-genome Sequencing Reveals Autooctoploidy in Chinese Sturgeon and Its Evolutionary Trajectories.

The order Acipenseriformes, which includes sturgeons and paddlefishes, represents "living fossils" with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.

Comparative proteomics reveals that fatty acid metabolism is involved in myocardial adaptation to chronic hypoxic injury.

Congenital heart disease (CHD) is the most serious form of heart disease, and chronic hypoxia is the basic physiological process underlying CHD. Some patients with CHD do not undergo surgery, and thus, they remain susceptible to chronic hypoxia, suggesting that some protective mechanism might exist in CHD patients. However, the mechanism underlying myocardial adaptation to chronic hypoxia remains unclear. Proteomics was used to identify the differentially expressed proteins in cardiomyocytes cultured under hypoxia for different durations. Western blotting assays were used to verify protein expression. A Real-Time Cell Analyzer (RTCA) was used to analyze cell growth. In this study, 3881 proteins were identified by proteomics. Subsequent bioinformatics analysis revealed that proteins were enriched in regulating oxidoreductase activity. Functional similarity cluster analyses showed that chronic hypoxia resulted in proteins enrichment in the mitochondrial metabolic pathway. Further KEGG analyses found that the proteins involved in fatty acid metabolism, the TCA cycle and oxidative phosphorylation were markedly upregulated. Moreover, knockdown of CPT1A or ECI1, which is critical for fatty acid degradation, suppressed the growth of cardiomyocytes under chronic hypoxia. The results of our study revealed that chronic hypoxia activates fatty acid metabolism to maintain the growth of cardiomyocytes.

The rise of baobab trees in Madagascar.

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.

Mitophagy in Alzheimer's Disease: A Bibliometric Analysis from 2007 to 2022.

Background: The investigation of mitophagy in Alzheimer's disease (AD) remains relatively underexplored in bibliometric analysis. Objective: To delve into the progress of mitophagy, offering a comprehensive overview of research trends and frontiers for researchers. Methods: Basic bibliometric information, targets, and target-drug-clinical trial-disease extracted from publications identified in the Web of Science Core Collection from 2007 to 2022 were assessed using bibliometric software. Results: The study encompassed 5,146 publications, displaying a consistent 16-year upward trajectory. The United States emerged as the foremost contributor in publications, with the Journal of Alzheimer's Disease being the most prolific journal. P. Hemachandra Reddy, George Perry, and Xiongwei Zhu are the top 3 most prolific authors. PINK1 and Parkin exhibited an upward trend in the last 6 years. Keywords (e.g., insulin, aging, epilepsy, tauopathy, and mitochondrial quality control) have recently emerged as focal points of interest within the past 3 years. "Mitochondrial dysfunction" is among the top terms in disease clustering. The top 10 drugs/molecules (e.g., curcumin, insulin, and melatonin) were summarized, accompanied by their clinical trials and related targets. Conclusions: This study presents a comprehensive overview of the mitophagy research landscape in AD over the past 16 years, underscoring mitophagy as an emerging molecular mechanism and a crucial focal point for potential drug in AD. This study pioneers the inclusion of targets and their correlations with drugs, clinical trials, and diseases in bibliometric analysis, providing valuable insights and inspiration for scholars and readers of JADR interested in understanding the potential mechanisms and clinical trials in AD.

Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers.

As the genome is organized into a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, most epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the horizontal dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to resolve the genome conformation by capturing the epigenetic information in single-molecular resolution while simultaneously resolving the genome conformation. Using SCA-seq, we are able to examine the spatial interaction of chromatin accessibility (e.g. enhancer-promoter contacts), CpG island methylation, and spatial insulating functions of the CCCTC-binding factor. We demonstrate that SCA-seq paves the way to explore the mechanism of epigenetic interactions and extends our knowledge in 3D packaging of DNA in the nucleus.

Lateralized brunt of sleep deprivation on white matter injury in a rat model of Alzheimer's disease.

Sleep disturbance is a recognized risk factor for Alzheimer's disease (AD), but the underlying micro-pathological evidence remains limited. To bridge this gap, we established an amyloid-ß oligomers (AßO)-induced rat model of AD and subjected it to intermittent sleep deprivation (SD). Diffusion tensor imaging (DTI) and transmission electron microscopy were employed to assess white matter (WM) integrity and ultrastructural changes in myelin sheaths. Our findings demonstrated that SD exacerbated AßO-induced cognitive decline. Furthermore, we found SD aggravated AßO-induced asymmetrical impairments in WM, presenting with reductions in tract integrity observed in commissural fibers and association fasciculi, particularly the right anterior commissure, right corpus callosum, and left cingulum. Ultrastructural changes in myelin sheaths within the hippocampus and corpus callosum further confirmed a lateralized effect. Moreover, SD worsened AßO-induced lateralized disruption of the brain structural network, with impairments in critical nodes of the left hemisphere strongly correlated with cognitive dysfunction. This work represents the first identification of a lateralized impact of SD on the mesoscopic network and cognitive deficits in an AD rat model. These findings could deepen our understanding of the complex interplay between sleep disturbance and AD pathology, providing valuable insights into the early progression of the disease, as well as the development of neuroimaging biomarkers for screening early AD patients with self-reported sleep disturbances. Enhanced understanding of these mechanisms may pave the way for targeted interventions to alleviate cognitive decline and improve the quality of life for individuals at risk of or affected by AD.

Study on the accelerated biodegradation of PAHs in subsurface soil via coupled low-temperature thermally treatment and electron acceptor stimulation based on metagenomic sequencing.

In situ anoxic bioremediation is a sustainable technology to remediate PAHs contaminated soils. However, the limited degradation rate of PAHs under anoxic conditions has become the primary bottleneck hindering the application of this technology. In this study, coupled low-temperature thermally treatment (<50 °C) and EA biostimulation was used to enhance PAH removal. Anoxic biodegradation of PAHs in soil was explored in microcosms in the absence and presence of added EAs at 3 temperatures (15 °C, 30 °C, and 45 °C). The influence of temperature, EA, and their interaction on the removal of PAHs were identified. A PAH degradation model based on PLSR analysis identified the importance and the positive/negative role of parameters on PAH removal. Soil archaeal and bacterial communities showed similar succession patterns, the impact of temperature was greater than that of EA. Soil microbial community and function were more influenced by temperature than EAs. Close and frequent interactions were observed among soil bacteria, archaea, PAH-degrading genes and methanogenic genes. A total of 15 bacterial OTUs, 1 PAH-degrading gene and 2 methanogenic genes were identified as keystones in the network. Coupled low-temperature thermally treatment and EA stimulation resulted in higher PAH removal efficiencies than EA stimulation alone and low-temperature thermally treatment alone.

Efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure: a meta-analysis.

Objective: The objective of this study is to investigate the efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure. Methods: A systematic search was conducted on PubMed, Cochrane Library, and EMbase databases from inception to April 2023 to identify randomized controlled trials that compared the efficacy and safety of early ultrafiltration and conventional diuretics in patients with acute decompensated heart failure. Two investigators independently screened all eligible studies and extracted relevant data. The primary outcomes of interest were changes in body weight and creatinine levels, as well as the rate of readmission and mortality within 30 days. Meta-analysis was conducted using RevMan 5.4 software. Results: This meta-analysis included eight studies and found that early ultrafiltration was effective in reducing body weight in patients with acute decompensated heart failure (RR = 1.45, 95% CI: 0.54-2.35, P = 0.002), but it also increased serum creatinine (RR = 0.1, 95% CI: 0.03-0.17, P = 0.003). However, it did not reduce the 30-day rehospitalization rate or mortality rate (30-day rehospitalization rate: RR = 0.84, 95% CI: 0.62-1.14, P = 0.28; Mortality: RR = 0.90, 95% CI: 0.57-1.44, P = 0.67). Conclusion: Although early ultrafiltration is more effective in reducing body weight in patients with acute decompensated heart failure, it is associated with an increase in serum creatinine levels and does not reduce the rate of readmission or mortality within 30 days. Systematic Review Registration: identifier: CRD42023416152.

A case report of acute myocardial infarction with extremely severe thrombocytopenia after percutaneous coronary intervention.

INTRODUCTION: The case report's purpose is to remind doctors a rare complication named thrombocytopenia of antithrombotic drugs. As a result, severe bleeding or even life-threatening situations may be avoided. PATIENT CONCERNS: A specific case of a patient with acute myocardial infarction, a significant decrease in platelet count was observed after percutaneous coronary intervention. DIAGNOSIS: After ruling out other potential causes, the medical team considered tirofiban-induced thrombocytopenia as a possible explanation. INTERVENTIONS AND OUTCOMES: Through careful monitoring and adjustment of medication, the patient's platelet count eventually returned to normal. CONCLUSION: To ensure patient safety, it is advised to regularly monitor platelet counts at intervals of 2 to 6 hours before and after administering tirofiban.

Gap-free genome assembly of Salangid icefish Neosalanx taihuensis.

Neosalanx taihuensis is widely distributed in freshwater and brackish water areas in China. Due to its high commercial value, it has been artificially introduced into many lakes and reservoirs, showing strong ecological adaptability. Here, a gap-free chromosome-level reference genome was constructed by combining short reads, PacBio HiFi long reads, Nanopore ultralong reads and Hi-C data. The reference genome of N. taihuensis was 397.29 Mb with a contig N50 of 15.61 Mb. The assembled sequences were anchored to 28 chromosomes. Furthermore, 20,024 protein-coding genes and 98.16% of the predicted genes were annotated in publicly available biological databases. This high-quality gap-free assembled genome will provide an essential reference for studying the evolution and ecological adaptability of N. taihuensis.

Improving the RNA velocity approach with single-cell RNA lifecycle (nascent, mature and degrading RNAs) sequencing technologies.

We presented an experimental method called FLOUR-seq, which combines BD Rhapsody and nanopore sequencing to detect the RNA lifecycle (including nascent, mature, and degrading RNAs) in cells. Additionally, we updated our HIT-scISOseq V2 to discover a more accurate RNA lifecycle using 10x Chromium and Pacbio sequencing. Most importantly, to explore how single-cell full-length RNA sequencing technologies could help improve the RNA velocity approach, we introduced a new algorithm called 'Region Velocity' to more accurately configure cellular RNA velocity. We applied this algorithm to study spermiogenesis and compared the performance of FLOUR-seq with Pacbio-based HIT-scISOseq V2. Our findings demonstrated that 'Region Velocity' is more suitable for analyzing single-cell full-length RNA data than traditional RNA velocity approaches. These novel methods could be useful for researchers looking to discover full-length RNAs in single cells and comprehensively monitor RNA lifecycle in cells.

Microbiota-derived imidazole propionate inhibits type 2 diabetic skin wound healing by targeting SPNS2-mediated S1P transport.

Imidazole propionate (ImP) is a recently discovered metabolite of T2DM-related gut microbiota. The effect of ImP on T2DM wound healing has not been studied yet. In this research, the changes of ImP-producing bacteria on the skin are firstly evaluated. 16sRNA sequencing results showed that the abundance of ImP-producing bacteria-Streptococcus in the intestine and skin of T2DM mice is significantly increased. Animal experiments show that ImP can inhibit the process of wound healing and inhibit the formation of blood vessels in the process of wound healing. Molecular mechanism research results show that ImP can inhibit S1P secretion mediated by SPNS2, and inhibit the activation of Rho signaling pathway, thereby affecting the angiogenesis process of HUVEC cells. This work also provides a potential drug HMPA that promotes T2DM wound healing.

Study on thermal conductivity of improved soil under different freezing temperatures.

Based on the influence of moisture content, dry density and temperature (≦ 0°C) on the thermal conductivity of lime-modified red clay, the thermal conductivity was measured by transient hot wire method. A total of 125 data were obtained and the evolution law of thermal conductivity with influencing factors was analyzed. The fitting formula of thermal conductivity of lime-modified red clay and a variety of intelligent prediction models were established and compared with previous empirical formulas. The results show that the thermal conductivity of lime-modified red clay increases linearly with water content and dry density. The change of thermal conductivity with temperature is divided into three stages. In the first stage, the thermal conductivity increases slowly with the decrease of temperature in the temperature range of-2°Cto 0°C. In the second stage, in the temperature range of-5°Cto (-2)°C, the thermal conductivity increases rapidly with the decrease of temperature. In the third stage, in the range of-10°Cto (-5)°C, the thermal conductivity changes little with the decrease of temperature, and the fitting curve tends to be stable. The fitting formula model and various intelligent prediction models can realize the accurate prediction of the thermal conductivity of lime-improved soil. Using RMSE (Root Mean Square Error) and MAPE (Mean Absolute Percentage Error) to evaluate the model, it is found that the GBDT decision tree model has the best prediction effect, the RMSE value of the predicted value is 0.084, and the MAPE value is 4.1%. The previous empirical models have poor prediction effect on the thermal conductivity of improved red clay. The intelligent prediction models such as GBDT decision tree with strong universality and high prediction accuracy are recommended to predict the thermal conductivity of soil.

Design, synthesis and biological evaluation of novel dihydroquinolin-4(1H)-one derivatives as novel tubulin polymerization inhibitors.

A series of novel dihydroquinolin-4(1H)-one derivatives targeting colchicine binding site on tubulin were designed, synthesized and evaluated as anticancer agents. The most potent compound 6t showed remarkable antiproliferative activities against four cancer cell lines with IC50 values among 0.003-0.024 µM and tubulin polymerization inhibitory activity (IC50 = 3.06 µM). Further mechanism studies revealed that compound 6t could induce K562 cells apoptosis and arrest at the G2/M phase. Meanwhile, 6t significantly inhibited migration and invasion of MDA-MB-231 cells, and disrupted the angiogenesis in human umbilical vein endothelial cells (HUVECs) in vitro. In addition, compound 6t inhibited tumor growth in H22 allograft tumor model with a tumor growth inhibition (TGI) rate of 63.3 % (i.v., 20 mg/kg per day) without obvious toxicity. Collectively, these results indicated that compound 6t was a novel tubulin polymerization inhibitor with potent anticancer properties in vitro and in vivo.

Research Progress in Abrasive Water Jet Processing Technology.

Abrasive water jet machining technology is an unconventional special process technology; its jet stream has high energy, and its machining process is characterized by no thermal deformation, no pollution, high applicability, and high flexibility. It has been widely used for processing different types of materials in different fields. This review elaborates on the basic principles and characteristics of abrasive water jet processing, the mechanism of erosion, the simulation of the processing, the influence of process parameters in machining removal, and the optimization of improvements, as well as introduces the current application status, new technology, and future development direction of abrasive water jet technology. This review can provide an important information reference for researchers studying the machining processing of abrasive water jet technology.