Postnatal neuronal Bace1 deletion impairs neuroblast and oligodendrocyte maturation.

Beta amyloid cleaving enzyme 1 (BACE1) is largely expressed by neurons and is the sole ß-secretase for initiating the production of neuronal ß-amyloid peptides (Aß). To fully understand the physiological functions of neuronal BACE1, we used mouse genetic approach coupled with unbiased single nucleus RNA sequencing (snRNAseq) to investigate how targeted deletion of Bace1 in neurons, driven by Thy-1-Cre recombinase, would affect functions in the nervous system. Our transcriptome results revealed that BACE1 is essential for maturation of neural precursor cells and oligodendrocytes in mice. RNA velocity analysis confirmed deficit in the trajectory of neuroblasts in reaching the immature granule neuron state in young Bace1fl/fl; Thy1-cre mice. Further analysis of differential gene expression indicated changes in genes important for SNARE signaling, tight junction signaling, synaptogenesis and insulin secretion pathways. Morphological studies revealed a hypomyelination in Bace1fl/fl;Thy1-cre sciatic nerves, but no detectable myelination changes in the corpus callosum, despite clear reduction in myelination proteins in the brain. Functional studies showed reduction in long-term potential, defects in synaptogenesis and learning behavioral. Altogether, our results show that neuronal BACE1 is critical for optimal development of central and peripheral nervous system, and inhibition of neuronal BACE1 will result in deficits in synaptic functions and cognitive behaviors.

Bace1 Deletion in the Adult Reverses Epileptiform Activity and Sleep-wake Disturbances in AD Mice.

Alzheimer's disease (AD) increases the risk for seizures and sleep disorders. We show here that germline deletion of ß-site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) in neurons, but not in astrocytes, increased epileptiform activity. However, Bace1 deletion at adult ages did not alter the normal EEG waveform, indicating less concern for BACE1 inhibition in patients. Moreover, we showed that deletion of Bace1 in the adult was able to reverse epileptiform activity in 5xFAD mice. Intriguingly, treating 5xFAD and APPNL-G-F/NL-G-F (APP KI) mice of either sex with one BACE1 inhibitor Lanabecestat (AZD3293) dramatically increased epileptiform spiking, likely resulting from an off-target effect. We also monitored sleep-wake pathologies in these mice and showed increased wakefulness, decreased non-rapid eye movement sleep, and rapid eye movement sleep in both 5xFAD and APP KI mice; BACE1 inhibition in the adult 5xFAD mice reversed plaque load and sleep disturbances, but this was not seen in APP KI mice. Further studies with and without BACE1 inhibitor treatment showed different levels of plaque-associated microgliosis and activated microglial proteins in 5xFAD mice compared with APP KI mice. Together, BACE1 inhibition should be developed to avoid off-target effect for achieving benefits in reducing epileptic activity and sleep disturbance in Alzheimer's patients.SIGNIFICANCE STATEMENT BACE1 is widely recognized as a therapeutic target for treating Alzheimer's disease patients. However, BACE1 inhibitors failed in clinical trials because of inability to show cognitive improvement in patients. Here we show that BACE1 inhibition actually reduces sleep disturbances and epileptic seizures; both are seen in AD patients. We further showed that one of clinically tested BACE1 inhibitors does have off-target effects, and development of safer BACE1 inhibitors will be beneficial to AD patients. Results from this study will provide useful guidance for additional drug development.

Self-Assembly of Two Tubular Metalloligand-Based Palladium-Organic Cages as Hosts for Polycyclic Aromatic Hydrocarbons.

Herein we report two tubular metal-organic cages (MOCs), synthesized by the self-assembly of bidentate metalloligands with different lengths and PdII. These two MOCs feature Pd4L8-type square tubular and Pd3L6-type triangular cage structures, respectively. Both MOCs have been fully characterized by NMR spectroscopy, mass spectrometry, and theoretical calculation. Both cages can be employed for encapsulating polycyclic aromatic hydrocarbons and show high binding affinity toward coronene.

The Influence of Informal Caregivers' Preparedness on Psychological Symptoms and Quality of Life Among Patients With Heart Failure And Insufficient Self-care.

BACKGROUND: Most patients with heart failure find self-care difficult to perform and rely on family caregivers for support. Informal caregivers, however, often face insufficient psychological preparation and challenges in providing long-term care. Insufficient caregiver preparedness not only results in psychological burden for the informal caregivers but may also lead to a decline in caregiver contributions to patient self-care that affects patient outcomes. OBJECTIVE: Our objective was to test (1) the association of baseline informal caregivers' preparedness with psychological symptoms (anxiety and depression) and quality of life 3 months after baseline among patients with insufficient self-care and (2) the mediating effects of caregivers' contributions to self-care of heart failure (CC-SCHF) on the relationship of caregivers' preparedness with patients' outcomes at 3 months. METHODS: A longitudinal design was used to collect data between September 2020 and January 2022 in China. Data analyses were conducted using descriptive statistics, correlations, and linear mixed models. We used model 4 of the PROCESS program in SPSS with bootstrap testing to evaluate the mediating effect of CC-SCHF of informal caregivers' preparedness at baseline with psychological symptoms or quality of life among patients with HF 3 months later. RESULTS: Caregiver preparedness was positively associated with CC-SCHF maintenance ( r = 0.685, P < .01), CC-SCHF management ( r = 0.403, P < .01), and CC-SCHF confidence ( r = 0.600, P < .01). Good caregiver preparedness directly predicted lower psychological symptoms (anxiety and depression) and higher quality of life for patients with insufficient self-care. The associations of caregiver preparedness with short-term quality of life and depression of patients with HF with insufficient self-care were mediated by CC-SCHF management. CONCLUSIONS: Enhancing the preparedness of informal caregivers may improve psychological symptoms and quality of life of heart failure patients with insufficient self-care.

Self-Assembly of a Pd4Cu8L8 Cage for Epoxidation of Styrene and Its Derivatives.

Herein we report a discrete heterometallic Pd4Cu8L8 cage with a tubular structure, which was synthesized by the assembly of copper metalloligands and PdII ions in a stepwise manner. The Pd4Cu8L8 cage has been unequivocally characterized by single-crystal X-ray diffraction, electrospray ionization-mass spectroscopy, and energy dispersive spectroscopy. The cage showed excellent catalytic activity in the epoxidation of styrene and its derivatives under conditions without using additional solvent, providing potential material for catalyzing the oxidation reactions.

CT23 knockdown attenuating malignant behaviors of hepatocellular carcinoma cell is associated with upregulation of metallothionein 1.

The cancer-testis antigen 23 (CT23) gene has been reported in association with the pathogenesis and progress of hepatocellular carcinoma (HCC). However, the alterations of gene expression profiling induced by CT23 knockdown in HCC cells remains largely unknown. In this study, the RNA interfering (RNAi) method was used to silence CT23 expression in BEL-7404 cells. Microarray analysis was performed on mRNA extracted from the CT23 knockdown cells and the control cells to determine the alterations of gene expression profiles. The result showed a total of 1051 genes expressed differentially (two-fold change), including 470 genes upregulated and 581 gene downregulated in the CT23 knockdown cells. A bioinformatic analysis showed that the functional differentially expressed genes (DEGs) were linked to cell proliferation, migration, and apoptosis, and metallothionein 1 (MT1) attained the maximum enrichment scores in functional annotation, classification, and pathway analysis of DEGs. Furthermore, Western blot analysis and cell behaviors assays verified that CT23 modulates cell proliferation, migration, and apoptosis by regulating MT1 expression in HCC cells and non-neoplastic hepatocytes. In summary, downregulated CT23 gene in BEL-7404 cells might change the expressions of carcinogenesis and progression related genes in HCC by upregulating MT1 expression, which would provide insight into searching for a novel therapeutic target for HCC.

Nanochemoprevention with therapeutic benefits: An updated review focused on epigallocatechin gallate delivery.

Epigallocatechin gallate (EGCG) is a natural phenolic compound found in many plants, especially in green tea, which is a popular and restorative beverage with many claimed health benefits such as antioxidant, anti-cancer, anti-microbial, anti-diabetic, and anti-obesity activities. Despite its great curative potential, the poor bioavailability of EGCG restricts its clinical applcation. However, nanoformulations of EGCG are emerging as new alternatives to traditional formulations. This review focuses on the nanochemopreventive applications of various EGCG nanoparticles such as lipid-based, polymer-based, carbohydrate-based, protein-based, and metal-based nanoparticles. EGCG hybridized with these nanocarriers is capable of achieving advanced functions such as targeted release, active targeting, and enhanced penetration, ultimately increasing the bioavailability of EGCG. In addition, this review also summarizes the challenges for the use of EGCG in therapeutic applications, and suggests future directions for progress.

Characterization of the metabolite of AdipoRon in rat and human liver microsomes by ultra-high-performance liquid chromatography combined with Q-Exactive Orbitrap tandem mass spectrometry.

AdipoRon is an orally active adiponectin receptor agonist. The aim of this study was to characterize the metabolites of AdipoRon in rat and human liver microsomes using ultra-high performance liquid chromatography combined with Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive-Orbitrap-MS) together with data processing techniques including extracted ion chromatograms and a mass defect filter. AdipoRon (10 µm) was incubated with liver microsomes in the presence of NADPH and this resulted in a total of 11 metabolites being detected. The identities of these metabolites were characterized by comparing their accurate masses and fragment ions as well as their retention times with those of AdipoRon using MetWorks software. Metabolites M1-M3, M6, and M8-M11 were identified for the first time. Metabolite M4, the major metabolite both in rat and human liver microsomes, was further confirmed using the reference standard. Our results revealed that the metabolic pathways of AdipoRon in liver microsomes were N-dealkylation (M2), hydroxylation (M, M5-M9), carbonyl reduction (M4) and the formation of amide (M10 and M11). Our results provide valuable information about the in vitro metabolism of AdipoRon, which would be helpful for us to understand the mechanism of the elimination of AdipoRon and, in turn, its effectiveness and toxicity.

Polyphenols in Common Beans (Phaseolus vulgaris L.): Chemistry, Analysis, and Factors Affecting Composition.

Common bean (Phaseolus vulgaris L.) is one of the most important grain legumes worldwide. Polyphenols are the predominant bioactive components with multifold bioactivities in diverse common bean cultivars. Phenolic acids, flavonoids, and proanthocyanidins are the main polyphenols in common beans, and colorful common beans are overall rich in polyphenols, mainly in their pigmented seed coats. In addition, factors of influence, such as genotype, environmental conditions, storage, and processing methods, play a critical role in the content and composition of common bean polyphenols. Besides, analytical methods, including extraction, separation, and identification, are of importance for precise and comparable evaluation of polyphenols in common beans. Therefore, in order to provide a comprehensive and updated understanding of polyphenols in common beans, this review first summarizes the content and different compositions of polyphenols in common beans, and next discusses the factors affecting these compositions, followed by introducing the analytical methods for common bean polyphenols, and finally highlights the antioxidant activity of polyphenols in common beans. Considering the recent surge in interest in the use of grain legumes, we hope this review will further stimulate work in this field by providing a blueprint for further analytical studies to better utilize common bean polyphenols in food products to improve human nutrition.

BACE1 regulates the proliferation and cellular functions of Schwann cells.

BACE1 is an indispensable enzyme for generating ß-amyloid peptides, which are excessively accumulated in brains of Alzheimer's patients. However, BACE1 is also required for proper myelination of peripheral nerves, as BACE1-null mice display hypomyelination. To determine the precise effects of BACE1 on myelination, here we have uncovered a role of BACE1 in the control of Schwann cell proliferation during development. We demonstrate that BACE1 regulates the cleavage of Jagged-1 and Delta-1, two membrane-bound ligands of Notch. BACE1 deficiency induces elevated Jag-Notch signaling activity, which in turn facilitates proliferation of Schwann cells. This increase in proliferation leads to shortened internodes and decreased Schmidt-Lanterman incisures. Functionally, evoked compound action potentials in BACE1-null nerves were significantly smaller and slower, with a clear decrease in excitability. BACE1-null nerves failed to effectively use lactate as an alternative energy source under conditions of increased physiological activity. Correlatively, BACE1-null mice showed reduced performance on rotarod tests. Collectively, our data suggest that BACE1 deficiency enhances proliferation of Schwann cell due to the elevated Jag1/Delta1-Notch signaling, but fails to myelinate axons efficiently due to impaired the neuregulin1-ErbB signaling, which has been documented.

The type 3 effector NopL of Sinorhizobium sp. strain NGR234 is a mitogen-activated protein kinase substrate.

Pathogenic bacteria utilize type 3 secretion systems to inject type 3 effectors (T3Es) into host cells, thereby subverting host defense reactions. Similarly, T3Es of symbiotic nitrogen-fixing rhizobia can affect nodule formation on roots of legumes. Previous work showed that NopL (nodulation outer protein L) of Sinorhizobium(Ensifer) sp. strain NGR234 is multiply phosphorylated in eukaryotic cells and that this T3E suppresses responses mediated by mitogen-activated protein (MAP) kinase signaling in yeast (mating pheromone signaling) and plant cells (expression of pathogenesis-related defense proteins). Here, we show that NopL is a MAP kinase substrate. Microscopic observations of fluorescent fusion proteins and bimolecular fluorescence complementation analysis in onion cells indicated that NopL is targeted to the nucleus and forms a complex with SIPK (salicylic acid-induced protein kinase), a MAP kinase of tobacco. In vitro experiments demonstrated that NopL is phosphorylatyed by SIPK. At least nine distinct spots were observed after two-dimensional gel electrophoresis, indicating that NopL can be hyperphosphorylated by MAP kinases. Senescence symptoms in nodules of beans (Phaseolus vulgaris cv. Tendergreen) were analyzed to determine the symbiotic effector activity of different NopL variants with serine to alanine substitutions at identified and predicted phosphorylation sites (serine-proline motif). NopL variants with six or eight serine to alanine substitutions were partially active, whereas NopL forms with 10 or 12 substituted serine residues were inactive. In conclusion, our findings provide evidence that NopL interacts with MAP kinases and reveals the importance of serine-proline motifs for effector activity during symbiosis.

Impact of RTN3 deficiency on expression of BACE1 and amyloid deposition.

Reticulon 3 (RTN3) has previously been shown to interact with BACE1 and negatively regulate BACE1 activity. To what extent RTN3 deficiency affects BACE1 activity is an intriguing question. In this study, we aimed to address this by generating RTN3-null mice. Mice with complete deficiency of RTN3 grow normally and have no obviously discernible phenotypes. Morphological analyses of RTN3-null mice showed no significant alterations in cellular structure, although RTN3 is recognized as a protein contributing to the shaping of tubular endoplasmic reticulum. Biochemical analysis revealed that RTN3 deficiency increased protein levels of BACE1. This elevation of BACE1 levels correlated with enhanced processing of amyloid precursor protein at the ß-secretase site. We also demonstrated that RTN3 deficiency in Alzheimer's mouse models facilitates amyloid deposition, further supporting an in vivo role of RTN3 in the regulation of BACE1 activity. Since it has been shown that RTN3 monomer is reduced in brains of Alzheimer's patients, our results suggest that long-lasting reduction of RTN3 levels has adverse effects on BACE1 activity and may contribute to Alzheimer's pathogenesis.

Bibliometric Analysis of Development Trends and Research Hotspots in the Study of Data Mining in Nursing Based on CiteSpace.

Backgrounds: With the advent of the big data era, hospital information systems and mobile care systems, among others, generate massive amounts of medical data. Data mining, as a powerful information processing technology, can discover non-obvious information by processing large-scale data and analyzing them in multiple dimensions. How to find the effective information hidden in the database and apply it to nursing clinical practice has received more and more attention from nursing researchers. Aim: To look over the articles on data mining in nursing, compiled research status, identified hotspots, highlighted research trends, and offer recommendations for how data mining technology might be used in the nursing area going forward. Methods: Data mining in nursing publications published between 2002 and 2023 were taken from the Web of Science Core Collection. CiteSpace was utilized for reviewing the number of articles, countries/regions, institutions, journals, authors, and keywords. Results: According to the findings, the pace of data mining in nursing progress is not encouraging. Nursing data mining research is dominated by the United States and China. However, no consistent core group of writers or organizations has emerged in the field of nursing data mining. Studies on data mining in nursing have been increasingly gradually conducted in the 21st century, but the overall number is not large. Institution of Columbia University, journal of Cin-computers Informatics Nursing, author Diana J Wilkie, Muhammad Kamran Lodhi, Yingwei Yao are most influential in nursing data mining research. Nursing data mining researchers are currently focusing on electronic health records, text mining, machine learning, and natural language processing. Future research themes in data mining in nursing most include nursing informatics and clinical care quality enhancement. Conclusion: Research data shows that data mining gives more perspectives for the growth of the nursing discipline and encourages the discipline's development, but it also introduces a slew of new issues that need researchers to address.

In silico screening and in vivo experimental validation of 15-PGDH inhibitors from traditional Chinese medicine promoting liver regeneration.

The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which acts as a negative regulator of prostaglandin E2 (PGE2) levels and activity, represents a promising pharmacological target for promoting liver regeneration. In this study, we collected data on 15-PGDH homologous family proteins, their inhibitors, and traditional Chinese medicine (TCM) compounds. Leveraging machine learning and molecular docking techniques, we constructed a prediction model for virtual screening of 15-PGDH inhibitors from TCM compound library and successfully screened genistein as a potential 15-PGDH inhibitor. Through further validation, it was discovered that genistein considerably enhances liver regeneration by inhibiting 15-PGDH, resulting in a significant increase in the PGE2 level. Genistein's effectiveness suggests its potential as a novel therapeutic agent for liver diseases, highlighting this study's contribution to expanding the clinical applications of TCM.

The potential value of cancer-testis antigens in ovarian cancer: Prognostic markers and targets for immunotherapy.

BACKGROUND: Tumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response. AIMS: This review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy. METHODS: We analyzed publications and outlined a comprehensive of overview the regulatory mechanism, immunogenicity, clinical expression significance, tumorigenesis, and application prospects of CTA in ovarian cancer, with a particular focus on recent progress in CTA-based immunotherapy. RESULTS: The expression of CTA affects the occurrence, development, and prognosis of ovarian cancer and is closely related to tumor immunity. CONCLUSION: CTA can be used as a biomarker for the diagnosis and prognosis evaluation of ovarian cancer and is an ideal target for antitumor immunotherapy. These findings provide novel insights on CTA in the improvement of diagnosis and treatment for ovarian cancer. The successes, current challenges and future prospects were also discussed to portray its significant potential.

Retinal vessel segmentation based on multi-scale feature and style transfer.

Retinal vessel segmentation is very important for diagnosing and treating certain eye diseases. Recently, many deep learning-based retinal vessel segmentation methods have been proposed; however, there are still many shortcomings (e.g., they cannot obtain satisfactory results when dealing with cross-domain data or segmenting small blood vessels). To alleviate these problems and avoid overly complex models, we propose a novel network based on a multi-scale feature and style transfer (MSFST-NET) for retinal vessel segmentation. Specifically, we first construct a lightweight segmentation module named MSF-Net, which introduces the selective kernel (SK) module to increase the multi-scale feature extraction ability of the model to achieve improved small blood vessel segmentation. Then, to alleviate the problem of model performance degradation when segmenting cross-domain datasets, we propose a style transfer module and a pseudo-label learning strategy. The style transfer module is used to reduce the style difference between the source domain image and the target domain image to improve the segmentation performance for the target domain image. The pseudo-label learning strategy is designed to be combined with the style transfer module to further boost the generalization ability of the model. Moreover, we trained and tested our proposed MSFST-NET in experiments on the DRIVE and CHASE_DB1 datasets. The experimental results demonstrate that MSFST-NET can effectively improve the generalization ability of the model on cross-domain datasets and achieve improved retinal vessel segmentation results than other state-of-the-art methods.

Viral communities locked in high elevation permafrost up to 100 m in depth on the Tibetan Plateau.

Permafrost serves as a natural cold reservoir for viral communities. However, little is known about the viromes in deep permafrost soil, as most studies of permafrost were restricted to shallow areas. Here, permafrost soil samples of up to 100 m in depth were collected from two sites in the Tuotuo River permafrost area on the Tibetan Plateau. We investigated the viral composition in these permafrost soil samples and analyzed the relationship of viral composition and diversity along with depths. Our study revealed that greater permafrost thickness corresponds to higher diversity within the viral community. Bacteriophages were found to be the dominant viral communities, with "kill the winner" dynamics observed within the Siphoviridae and Myoviridae. The abundance and diversity of viral communities may follow a potential pattern along soil layers and depths, influenced by pH, trace elements, and permafrost thickness. Notably, strong correlations were discovered between the content of inorganic elements, including B, Mg, Cr, Bi, Ti, Na, Ni, and Cu, and the viral composition. Moreover, we discovered highly conserved sequences of giant viruses at depth of 10, 20, and 50 m in permafrost, which play a crucial role in evolutionary processes. These findings provide valuable insights into the viral community patterns from shallow to 100-m-depth in high-elevation permafrost, offering crucial data support for the formulation of strategies for permafrost thaw caused by climate change and anthropogenic activities.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

BACKGROUND: Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. METHODS: The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. RESULTS: The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CONCLUSIONS: CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

Dysfunctional Bladder Morphology and Functional Impairments Are Identified in the Alzheimer's Disease APPNL-G-F/NL-G-F Murine Model.

BACKGROUND: While symptoms related to lower urinary tract dysfunction (LUTD) are common in individuals with Alzheimer's disease (AD), pathophysiological links between AD and LUTD remain unclear. OBJECTIVE: This study aimed to investigate whether AD neuropathology would cause autonomic dysfunction along the spinal cord-bladder axis, which could result in alterations in bladder muscle kinetics. METHODS: We utilized APPNL-G-F/NL-G-F knock-in (APP KI) and APPwt/wt (wild-type) mice at two different ages, 4- and 10-month-old, to investigate how AD impacts bladder tissue function by immunohistochemistry, western blotting, and pharmacomyography. RESULTS: We showed that the mucosal layer partially separated from the detrusor in 10-month-old APP KI mouse bladders. Although there was no detectable amyloid deposition in the APP KI bladder, we found amyloid plaques in APP KI lumbar spinal cord. Further immunoblot analysis revealed that tyrosine hydroxylase protein levels were significantly reduced in both 4- and 10-month-old bladder tissues, suggesting reduction of norepinephrine synthesis in APP KI mouse bladders. In contrast, the level of ß2 adrenergic receptor was increased in 4-month-old but not 10-month-old APP KI bladders. In bladder strips, the adrenergic agonist isoproterenol induced increased relaxation in 4- but not 10-month-old APP KI bladders. With 10 Hz electrical field stimulation, 10-month-old APP KI bladder strips were more responsive than wild-type controls, with no differences observed in 4-month-old APP KI bladders. CONCLUSIONS: APP KI mice exhibit LUTD, which is likely arising from amyloid pathology in the spinal cord, and results in maturational declines in presynaptic activity combined with compensatory postsynaptic upregulation.

Viromes of Haemaphysalis longicornis reveal different viral abundance and diversity in free and engorged ticks.

Haemaphysalis longicornis ticks, commonly found in East Asia, can transmit various pathogenic viruses, including the severe fever with thrombocytopenia syndrome virus (SFTSV) that has caused febrile diseases among humans in Hubei Province. However, understanding of the viromes of H. longicornis was limited, and the prevalence of viruses among H. longicornis ticks in Hubei was not well clarified. This study investigates the viromes of both engorged (fed) and free (unfed) H. longicornis ticks across three mountainous regions in Hubei Province from 2019 to 2020. RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging to unclassified viruses and seven RNA viral families, namely Chuviridae, Nairoviridae, Orthomyxoviridae, Parvoviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae. Viral abundance and diversity in these ticks were analysed, and phylogenetic characteristics of the Henan tick virus (HNTV), Dabieshan tick virus (DBSTV), Okutama tick virus (OKTV), and Jingmen tick virus (JMTV) were elucidated based on their full genomic sequences. Prevalence analysis demonstrated that DBSTV was the most common virus found in individual H. longicornis ticks (12.59%), followed by HNTV (0.35%), whereas JMTV and OKTV were not detected. These results improve our understanding of H. longicornis tick viromes in central China and highlight the role of tick feeding status and geography in shaping the viral community. The findings of new viral strains and their potential impact on public health raise the need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.