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.

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.

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.

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.

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.

Sleep deprivation aggravated amyloid ß oligomers-induced damage to the cerebellum of rats: Evidence from magnetic resonance imaging.

For quite a long time, researches on Alzheimer's disease (AD) primarily focused on the cortex and hippocampus, while the cerebellum has been ignored because of its abnormalities considered to appear in the late stage of AD. In recent years, increasing evidence suggest that the cerebellar pathological changes possibly occur in the preclinical phase of AD, which is also associated with sleep disorder. Sleep disturbance is a high risk factor of AD. However, the changes and roles of cerebellum has rarely been reported under conditions of AD accompanied with sleep disorders. In this study, using an amyloid-ß oligomers (AßO)-induced rat model of AD subjected to sleep deprivation, combining with a 7.0 T animals structural magnetic resonance imaging (MRI), we assessed structural changes of cerebellum in MRI. Our results showed that sleep deprivation combined with AßO led to an increased FA value in the anterior lobe of cerebellum, decreased ADC value in the cerebellar lobes and cerebellar nuclei, and increased cerebellum volume. Besides that, sleep deprivation exacerbated the damage of AßO to the cerebellar structural network. This study demonstrated that sleep deprivation could aggravate the damage to cerebellum induced by AßO. The present findings provide supporting evidence for the involvement of cerebellum in the early pathology of AD and sleep loss. Our data would contribute to advancing the understanding of the mysterious role of cerebellum in AD and sleep disorders, as well as would be helpful for developing non-invasive MRI biomarkers for screening early AD patients with self-reported sleep disturbances.

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.

Transcriptomic and Metabolomic Analyses of the Response of Resistant Peanut Seeds to Aspergillus flavus Infection.

Peanut seeds are susceptible to Aspergillus flavus infection, which has a severe impact on the peanut industry and human health. However, the molecular mechanism underlying this defense remains poorly understood. The aim of this study was to analyze the changes in differentially expressed genes (DEGs) and differential metabolites during A. flavus infection between Zhonghua 6 and Yuanza 9102 by transcriptomic and metabolomic analysis. A total of 5768 DEGs were detected in the transcriptomic study. Further functional analysis showed that some DEGs were significantly enriched in pectinase catabolism, hydrogen peroxide decomposition and cell wall tissues of resistant varieties at the early stage of infection, while these genes were differentially enriched in the middle and late stages of infection in the nonresponsive variety Yuanza 9102. Some DEGs, such as those encoding transcription factors, disease course-related proteins, peroxidase (POD), chitinase and phenylalanine ammonialyase (PAL), were highly expressed in the infection stage. Metabolomic analysis yielded 349 differential metabolites. Resveratrol, cinnamic acid, coumaric acid, ferulic acid in phenylalanine metabolism and 13S-HPODE in the linolenic acid metabolism pathway play major and active roles in peanut resistance to A. flavus. Combined analysis of the differential metabolites and DEGs showed that they were mainly enriched in phenylpropane metabolism and the linolenic acid metabolism pathway. Transcriptomic and metabolomic analyses further confirmed that peanuts infected with A. flavus activates various defense mechanisms, and the response to A. flavus is more rapid in resistant materials. These results can be used to further elucidate the molecular mechanism of peanut resistance to A. flavus infection and provide directions for early detection of infection and for breeding peanut varieties resistant to aflatoxin contamination.

Gap-free genome assembly of anadromous Coilia nasus.

The Chinese tapertail anchovy, Coilia nasus, is a socioeconomically important anadromous fish that migrates from near ocean waters to freshwater to spawn every spring. The analysis of genomic architecture and information of C. nasus were hindered by the previously released versions of reference genomes with gaps. Here, we report the assembly of a chromosome-level gap-free genome of C. nasus by incorporating high-coverage and accurate long-read sequence data with multiple assembly strategies. All 24 chromosomes were assembled without gaps, representing the highest completeness and assembly quality. We assembled the genome with a size of 851.67 Mb and used BUSCO to estimate the completeness of the assembly as 92.5%. Using a combination of de novo prediction, protein homology and RNA-seq annotation, 21,900 genes were functionally annotated, representing 99.68% of the total predicted protein-coding genes. The availability of gap-free reference genomes for C. nasus will provide the opportunity for understanding genome structure and function, and will also lay a solid foundation for further management and conservation of this important species.

Astrocytic AT1R deficiency ameliorates Aß-induced cognitive deficits and synaptotoxicity through ß-arrestin2 signaling.

Alzheimer's disease (AD) seriously influences human health, and there is no effective treatment to prevent or cure AD. Recent studies have shown that angiotensin II type 1 receptor (AT1R) blockers significantly reduce the prevalence of AD, while the precise role and mechanism of AT1R in AD remain obscure. In this study, for the first time, we identified that astrocytic but not neuronal AT1R levels were significantly increased in AD model rats and found that astrocyte-specific knockout of AT1R significantly ameliorated amyloid ß (Aß)-induced cognitive deficits and synaptotoxicity. Pretreating astrocytes with an AT1R blocker also alleviated Aß-induced synaptotoxicity in the coculture system of hippocampal neurons and astrocytes. Moreover, AT1R could directly bind to Aß1-42 and activate the astrocytic ß-arrestin2 pathway in a biased manner, and biased inhibition of the astrocytic AT1R/ß-arrestin2 pathway relieved Aß-induced neurotoxicity. Furthermore, we demonstrated that astrocytic AT1R/ß-arrestin2 pathway-mediated synaptotoxicity was associated with the aggregation of autophagosomes, which triggered the disordered degradation of Aß. Our findings reveal a novel molecular mechanism of astrocytic AT1R in Aß-induced neurodegeneration and might contribute to establishing new targets for AD prevention and therapy.

A theoretical base for non-invasive prenatal paternity testing.

There is an increasing demand for prenatal paternity testing in the forensic applications, which identify biological fathers before the birth of children. Currently, one of the most effective and safe Non-Invasive Prenatal Paternity Testing (NIPPT) methods is high-throughput Next-Generation Sequencing (NGS)-based SNP genotyping of cell-free DNA in maternal peripheral blood. To the best of our knowledge, nearly all methods being used in such applications are based on traditional postnatal paternity tests and/or statistical models of conventional polymorphism sites. These methods have shown unsatisfactory performance due to the uncertainty of fetal genotype. In this study, we propose a cutting-edge methodology called the Prenatal paternity Test Analysis System (PTAS) for cell-free fetal DNA-based NIPPT using NGS-based SNP genotyping. With the implementation of our proposed PTAS methodology, 63 out of 64 early-pregnancy (i.e., less than seven weeks) samples can be precisely identified to determine paternity, except for one sample that does not meet quality control requirements. Although the fetal fraction of the non-identified sample is extremely low (0.51%), its paternity can still be detected by our proposed PTAS methodology through unique molecular identifier tagging. Paternity of the total 313 samples for mid-to-late pregnancy (i.e., more than seven weeks) can be accurately identified. Extensive experiments indicate that our methodology makes a significant breakthrough in the NIPPT theory and will bring substantial benefits to forensic applications.

BIND&MODIFY: a long-range method for single-molecule mapping of chromatin modifications in eukaryotes.

Epigenetic modifications of histones are associated with development and pathogenesis of disease. Existing approaches cannot provide insights into long-range interactions and represent the average chromatin state. Here we describe BIND&MODIFY, a method using long-read sequencing for profiling histone modifications and transcription factors on individual DNA fibers. We use recombinant fused protein A-M.EcoGII to tether methyltransferase M.EcoGII to protein binding sites to label neighboring regions by methylation. Aggregated BIND&MODIFY signal matches bulk ChIP-seq and CUT&TAG. BIND&MODIFY can simultaneously measure histone modification status, transcription factor binding, and CpG 5mC methylation at single-molecule resolution and also quantifies correlation between local and distal elements.

Lithium-ion spontaneous exchange and synergistic transport in ceramic-liquid hybrid electrolytes for highly efficient lithium-ion transfer.

Ceramic electrolytes are important in ceramic-liquid hybrid electrolytes (CLHEs), which can effectively solve the interfacial issues between the electrolyte and electrodes in solid-state batteries and provide a highly efficient Li-ion transfer for solid-liquid Li metal batteries. Understanding the ionic transport mechanisms in CLHEs and the corresponding role of ceramic electrolytes is crucial for a rational design strategy. Herein, the Li-ion transfer in the ceramic electrolytes of CLHEs was confirmed by tracking the 6Li and 7Li substitution behavior through solid-state nuclear magnetic resonance spectroscopy. The ceramic and liquid electrolytes simultaneously participate in Li-ion transport to achieve highly efficient Li-ion transfer in CLHEs. A spontaneous Li-ion exchange was also observed between ceramic and liquid electrolytes, which serves as a bridge that connects the ceramic and liquid electrolytes, thereby greatly strengthening the continuity of Li-ion pathways in CLHEs and improving the kinetics of Li-ion transfer. The importance of an abundant solid-liquid interface for CLHEs was further verified by the enhanced electrochemical performance in LiFePO4/Li and LiNi0.8Co0.1Mn0.1O2/Li batteries from the generated interface. This work provides a clear understanding of the Li-ion transport pathway in CLHEs that serves as a basis to build a universal Li-ion transport model of CLHEs.