MicroRNA Expression Profiling Screen miR-3557/324-targeted CaMK/mTOR in the Rat Striatum of Parkinson\u27s Disease in Regular Aerobic Exercise

This study aimed to screen the target miRNAs and to investigate the differential miR-3557/324-targeted signal mechanisms in the rats’ model of Parkinson’s disease (PD) with regular aerobic exercise. Rats were divided into sedentary control PD group (SED-PD, n = 18) and aerobic exercise PD group (EX-PD, n = 22). After 8 weeks of regular aerobic exercise, a 6-hydroxydopamine- (6-OHDA-) induced PD lesion model was constructed. Preregular aerobic exercises enhanced the injury resistance of rats with 6-OHDA-induced PD. The rotational behavior after injection of apomorphine hydrochloride was alleviated. Under the scanning electron microscopy, we found the neurons, axons, and villi of the striatum were clearly and tightly arranged, and neurons and axons significantly becoming larger. Tyrosine hydroxylase (TH) was increased significantly and α-synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group. Screening from miRNA microarray chip, we further found upregulation of miR-3557 and downregulation of miR-324 were closely related to the calcium-modulating signaling pathway, remitting the progress of Parkinson’s disease on aerobic exercise. Compared to the SED-PD group, Ca2+/calmodulin dependent protein kinase II (CaMK2α) was upregulated, but CaMKV and voltage-dependent anion-selective channel protein 1 (Vdac1) were significantly downregulated in the EX-PD group. Additionally, phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) expression were activated, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) expression was upregulated in the EX-PD group. Conclusions: the adaptive mechanism of regular aerobic exercise delaying neurodegenerative diseases and lesions was that miR-3557/324 was activated to regulate one of its targets CaMKs signaling pathways. CaMKs, coordinated with mTOR pathway-related gene expression, improved UCH-L1 level to favor for delaying neurodegeneration or improving the pathogenesis of PD lesions

Relationship Between Lipoprotein(a), Renal Function Indicators, and Chronic Kidney Disease: Evidence From a Large Prospective Cohort Study

BACKGROUND: Chronic kidney disease (CKD) poses a significant global public health challenge. While lipoprotein(a) (Lp[a]) has been established as a significant factor in cardiovascular disease, its connection to CKD risk remains a topic of debate. Existing evidence indicates diverse risks of kidney disease among individuals with various renal function indicators, even when within the normal range. OBJECTIVE: This study aims to investigate the joint associations between different renal function indicators and Lp(a) regarding the risks of incident CKD in the general population. METHODS: The analysis involved a cohort of 329,415 participants without prior CKD who were enrolled in the UK Biobank between 2006 and 2010. The participants, with an average age of 56 (SD 8.1) years, included 154,298/329,415 (46.84%) males. At baseline, Lp(a) levels were measured using an immunoturbidimetric assay and classified into 2 groups: low (&lt;75 nmol/L) and high (≥75 nmol/L). To assess participants' baseline renal function, we used the baseline urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The relationship between Lp(a), renal function indicators, and the risk of CKD was evaluated using multivariable Cox regression models. These models were adjusted for various factors, including sociodemographic variables, lifestyle factors, comorbidities, and laboratory measures. RESULTS: A total of 6003 incident CKD events were documented over a median follow-up period of 12.5 years. The association between elevated Lp(a) levels and CKD risk did not achieve statistical significance among all participants, with a hazard ratio (HR) of 1.05 and a 95% CI ranging from 0.98 to 1.13 (P=.16). However, a notable interaction was identified between Lp(a) and UACR in relation to CKD risk (P for interaction=.04), whereas no significant interaction was observed between Lp(a) and eGFR (P for interaction=.96). When compared with the reference group with low Lp(a) and low-normal UACR (&lt;10 mg/g), the group with high Lp(a) and low-normal UACR exhibited a nonsignificant association with CKD risk (HR 0.98, 95% CI 0.90-1.08; P=.74). By contrast, both the low Lp(a) and high-normal UACR (≥10 mg/g) group (HR 1.16, 95% CI 1.08-1.24; P&lt;.001) and the high Lp(a) and high-normal UACR group (HR 1.32, 95% CI 1.19-1.46; P&lt;.001) demonstrated significant associations with increased CKD risks. In individuals with high-normal UACR, elevated Lp(a) was linked to a significant increase in CKD risk, with an HR of 1.14 and a 95% CI ranging from 1.03 to 1.26 (P=.01). Subgroup analyses and sensitivity analyses consistently produced results that were largely in line with the main findings. CONCLUSIONS: The analysis revealed a significant interaction between Lp(a) and UACR in relation to CKD risk. This implies that Lp(a) may act as a risk factor for CKD even when considering UACR. Our findings have the potential to provide valuable insights into the assessment and prevention of CKD, emphasizing the combined impact of Lp(a) and UACR from a public health perspective within the general population. This could contribute to enhancing public awareness regarding the management of Lp(a) for the prevention of CKD.</p

Effects of Land Use Change on Terrestrial Ecosystem Service Value and Carbon Storage

[Objective] Ecosystem services value (ESV) is one of the important measures used to evaluate whether regional land use change is scientific. ESV is related to regional sustainable development. ESV and terrestrial carbon storage (TCS) changes in coastal cities were evaluated in order to provide a basis for economic development and ESV regulation in Dalian City, Liaoning Province. [Methods] Five periods of land use data and related data from 2000 to 2020 were analyzed in this study. Land dynamics, the equivalent factor method, a land transfer matrix, ESV contribution rate, TCS, and principal component analysis were used to calculate the land use change dynamics in Dalian City and their impacts on ESV, TCS, and terrestrial carbon storage value (TCSV). [Results] ① Construction land in Dalian City mainly encroached on farmland and forest land in the southwestern coastal area. ② During the four time periods from 2000 to 2020, ESV in Dalian City initially decreased and then increased, and the decline continued to intensify. The decrease in arable land area and the increase in construction land area had a direct impact on the maintenance of ecosystem service functions. ③ During the four time periods from 2000 to 2020, TCS and TCSV in Dalian City initially increased and then decreased, and the decline continued to intensify. The reduction of forest area directly affected the maintenance of TCS function. ④ In the land use transfer matrix for Dalian City from 2000 to 2020, farmland, forest land, and grassland were mainly transferred out, while construction land was mainly transferred in. The contribution of ecosystem services varied among different land use types, with contributions ranging from cultivated land, forest land, wetlands, water bodies, grasslands, and unused land. ⑤ The changes in ESV and TCS in Dalian City from 2000 to 2020 were mainly influenced by economic growth, adjustments to the three major industrial structures, and the development of urbanization level. [Conclusion] From the perspective of economic development, ESV improvement, TCS capacity improvement, and sustainable development in Dalian City, it is necessary to focus on the conflict between the expansion of coastal construction land and ecological and agricultural land, strengthen the protection of northern forest and grass ecological land, accelerate the ecological environment restoration work in coastal areas, enhance the carbon sequestration capacity of ecological land, and avoid unrestricted blind expansion of construction land

Blebbistatin as a novel antiviral agent targeting equid herpesvirus type 8

IntroductionEquid herpesvirus type 8 (EqHV-8) poses a significant threat to equine health, leading to miscarriages and respiratory diseases in horses and donkeys, and results in substantial economic losses in the donkey industry. Currently, there are no effective drugs or vaccines available for EqHV-8 infection control.MethodsIn this study, we investigated the in vitro and in vivo antiviral efficacy of Blebbistatin, a myosin II ATPase inhibitor, against EqHV-8.ResultsOur results demonstrated that Blebbistatin significantly inhibited EqHV-8 infection in Rabbit kidney (RK-13) and Madin-Darby Bovine Kidney (MDBK) cells in a concentration-dependent manner. Notably, Blebbistatin was found to disrupt EqHV-8 infection at the entry stage by modulating myosin II ATPase activity. Moreover, in vivo experiments revealed that Blebbistatin effectively reduced EqHV-8 replication and mitigated lung pathology in a mouse model.ConclusionCollectively, these findings suggest that Blebbistatin holds considerable potential as an antiviral agent for the control of EqHV-8 infection, presenting a novel approach to addressing this veterinary challenge

Gut microbiome regulation in equine animals: current understanding and future perspectives

The equine intestinal microbiome represents a complex and dynamic ecosystem that fundamentally influences host health and physiological function. This microbial community exhibits distinct compositional and functional variations across different anatomical segments of the intestinal tract, with diversity and abundance patterns shaped by host genetics, dietary inputs, and environmental conditions. The resident microbiota performs essential functions in feed fermentation, nutrient metabolism, pathogen exclusion, and immunological programming. This review synthesizes current knowledge regarding the core taxonomic and functional attributes of the equine intestinal microbiome, examining interspecies variation and conservation patterns. We evaluate key determinants of microbial community assembly and regulation, while examining mechanistic links between microbiota composition and host health outcomes. Through critical analysis of existing literature, this work provides an integrated framework for understanding the equine gut microbiome, with implications for clinical intervention strategies and evidence-based approaches to promote intestinal health in equine

Is there sufficient evidence to support the health benefits of including donkey milk in the diet?

Donkey milk has attracted attention due to its distinctive nutritional composition and potential health advantages, particularly because of its whey protein content, which includes lysozyme, α-lactalbumin, lactoferrin, and β-lactoglobulin and vitamin C, among other components. These elements contribute to immunoregulatory, antimicrobial, antioxidant, and anti-inflammatory properties, positioning donkey milk as a possible therapeutic option. In addition, due to the low levels of caseins, the casein-to-whey protein ratio, and the β-lactoglobulin content in donkey milk, it presents an optimal alternative for infant formula for individuals with cow’s milk allergies. Moreover, research into donkey milk’s potential for cancer prevention, diabetes management, and as a treatment for various diseases is ongoing, thanks to its bioactive peptides and components. Nevertheless, challenges such as its low production yield and the not fully understood mechanisms behind its potential therapeutic role necessitate more thorough investigation. This review consolidates the existing knowledge on the therapeutic possibilities of donkey milk, emphasizing its importance for human health and the need for more detailed studies to confirm its health benefits

Plant immunity suppression by an exo-β-1,3-glucanase and an elongation factor 1α of the rice blast fungus

Fungal cell walls undergo continual remodeling that generates β-1,3-glucan fragments as products of endo-glycosyl hydrolases (GHs), which can be recognized as pathogen-associated molecular patterns (PAMPs) and trigger plant immune responses. How fungal pathogens suppress those responses is often poorly understood. Here, we study mechanisms underlying the suppression of β-1,3-glucan-triggered plant immunity by the blast fungus Magnaporthe oryzae. We show that an exo-β-1,3-glucanase of the GH17 family, named Ebg1, is important for fungal cell wall integrity and virulence of M. oryzae. Ebg1 can hydrolyze β-1,3-glucan and laminarin into glucose, thus suppressing β-1,3-glucan-triggered plant immunity. However, in addition, Ebg1 seems to act as a PAMP, independent of its hydrolase activity. This Ebg1-induced immunity appears to be dampened by the secretion of an elongation factor 1 alpha protein (EF1α), which interacts and co-localizes with Ebg1 in the apoplast. Future work is needed to understand the mechanisms behind Ebg1-induced immunity and its suppression by EF1α

Systematic discovery of mutation-directed neo-protein-protein interactions in cancer

Comprehensive sequencing of patient tumors reveals genomic mutations across tumor types that enable tumorigenesis and progression. A subset of oncogenic driver mutations results in neomorphic activity where the mutant protein mediates functions not engaged by the parental molecule. Here, we identify prevalent variant-enabled neomorph-protein-protein interactions (neoPPI) with a quantitative high-throughput differential screening (qHT-dS) platform. The coupling of highly sensitive BRET biosensors with miniaturized coexpression in an ultra-HTS format allows large-scale monitoring of the interactions of wild-type and mutant variant counterparts with a library of cancer-associated proteins in live cells. The screening of 17,792 interactions with 2,172,864 data points revealed a landscape of gain of interactions encompassing both oncogenic and tumor suppressor mutations. For example, the recurrent BRAF V600E lesion mediates KEAP1 neoPPI, rewiring a BRAFV600E/KEAP1 signaling axis and creating collateral vulnerability to NQO1 substrates, offering a combination therapeutic strategy. Thus, cancer genomic alterations can create neo-interactions, informing variant-directed therapeutic approaches for precision medicine. © 2022 Elsevier Inc