Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer's continuum.

BACKGROUND: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer's disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. METHODS: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aß42, Aß40, Aß42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman's correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aß42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. RESULTS: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aß42 and Aß40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aß42 and Aß40 levels with MMSE scores (19.08% and 36.57%), and Aß42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aß42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aß42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05). CONCLUSIONS: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.

Mitigation of gestational diabetes-induced endothelial dysfunction through FGF21-NRF2 pathway activation involving L-Cystine.

Gestational diabetes mellitus (GDM) disrupts glucolipid metabolism, endangering maternal and fetal health. Despite limited research on its pathogenesis and treatments, we conducted a study using serum samples from GDM-diagnosed pregnant women. We performed metabolic sequencing to identify key small molecule metabolites and explored their molecular interactions with FGF21. We also investigated FGF21's impact on GDM using blood samples from affected women. Our analysis revealed a novel finding: elevated levels of L-Cystine in GDM patients. Furthermore, we observed a positive correlation between L-Cystine and FGF21 levels, and found that L-Cystine induces NRF2 expression via FGF21 for a period of 96 h. Under high glucose (HG) conditions, FGF21 upregulates NRF2 and downstream genes NQO1 and EPHX1 via AKT phosphorylation induced by activation of IRS1, enhancing endothelial function. Additionally, we confirmed that levels of FGF21, L-Cystine, and endothelial function at the third trimester were effectively enhanced through appropriate exercise and diet during pregnancy in GDM patients (GDM + ED). These findings suggest FGF21 as a potential therapeutic agent for GDM, particularly in protecting endothelial cells. Moreover, elevated L-Cystine via appropriate exercise and diet might be a potential strategy to enhance FGF21's efficacy.

Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer.

Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become evident in recent years. Although targeted therapies have shown in treating certain subsets of non-small cell lung cancers (NSCLC), a significant proportion of patients still face suboptimal therapeutic outcomes. Neuregulin-1 (NRG1), a critical member of the NRG gene family, initially drew interest due to its distribution within the nascent ventricular endocardium, showcasing an exclusive presence in the endocardium and myocardial microvessels. Recent research has highlighted NRG1's pivotal role in the genesis and progression across a spectrum of tumors, influencing molecular perturbations across various tumor-associated signaling pathways. This review provides a concise overview of NRG1, including its expression patterns, configuration, and fusion partners. Additionally, we explore the unique features and potential therapeutic strategies for NRG1 fusion-positive occurrences within the context of NSCLC.

Spatiotemporal Regulation of Cell Fate in Living Systems Using Photoactivatable Artificial DNA Membraneless Organelles.

Coacervates formed by liquid-liquid phase separation emerge as important biomimetic models for studying the dynamic behaviors of membraneless organelles and synchronously motivating the creation of smart architectures with the regulation of cell fate. Despite continuous progress, it remains challenging to balance the trade-offs among structural stability, versatility, and molecular communication for regulation of cell fate and systemic investigation in a complex physiological system. Herein, we present a self-stabilizing and fastener-bound gain-of-function methodology to create a new type of synthetic DNA membraneless organelle (MO) with high stability and controlled bioactivity on the basis of DNA coacervates. Specifically, long single-strand DNA generated by rolling circle amplification (RCA) is selected as the scaffold that assembles into membraneless coacervates via phase separation. Intriguingly, the as-formed DNA MO can recruit RCA byproducts and other components to achieve self-stabilization, nanoscale condensation, and function encoding. As a proof of concept, photoactivatable DNA MO is constructed and successfully employed for time-dependent accumulation and spatiotemporal management of cancer in a mouse model. This study offers new, important insights into synthetic membraneless organelles for the basic understanding and manipulation of important life processes.

Association between spectrum of mycotoxins and semen quality: A cross-sectional study in Beijing, China.

Exposure to mycotoxins is unavoidable in daily life through ingestion, dermal, and inhalation routes. Toxicological studies found that exposure to mycotoxins might affect male reproductive function. However, there is still a lack of population evidence. We aimed to assess the association of individual and joint exposure to spectrum of mycotoxins with semen quality. The present study included 192 participants in Beijing, China. We measured conventional semen parameters and assessed semen quality. Sixty-seven traditional or emerging mycotoxins were determined to describe the spectrum of mycotoxins. The participants were widely exposed to multiple mycotoxins, and nearly half were simultaneously exposed to more than six mycotoxins. After adjusting potential confounders, logistic regression indicated that the number and concentration of plasma mycotoxin were correlated to the risk of low semen quality. Plasma beauvericin and citrinin concentrations were associated with lower semen quality. The least absolute shrinkage and selection operator regression showed similar results to logistic regression. Quantile-based g-computation and Bayesian kernel machine regression models found that the mixture of mycotoxins was harmful to semen quality, especially in sperm motility. In conclusion, both individual and mixture of mycotoxin exposure were correlated with lower semen quality. More regulations and measures should be taken to reduce mycotoxin contamination.

Dilute Electrolytes with Fluorine-free Ether Solvents for 4.5 V Lithium Metal Batteries.

The limited oxidation stability of ether solvents has posed significant challenges for their applications in high-voltage lithium metal batteries (LMBs). To tackle this issue, the prevailing strategy either adopts a high concentration of fluorinated salts or relies on highly fluorinated solvents, which will significantly increase the manufacturing cost and create severe environmental hazards. Herein, an alternative and sustainable salt engineering approach is proposed to enable the utilization of dilute electrolytes consisting of fluorine (F)-free ethers in high-voltage LMBs. The proposed 0.8 M electrolyte supports stable lithium plating-stripping with a high Coulombic efficiency of 99.47% and effectively mitigates the metal dissolution, phase transition, and gas release issues of the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode upon charging to high voltages. Consequently, the 4.5 V high-loading Li||NCM 811 cell shows a capacity retention of 75.2% after 300 cycles. Multimodal experimental characterizations coupled with theoretical investigations demonstrate that the boron-containing salt plays a pivotal role in forming the passivation layers on both anode and cathode. The present simple and cost-effective electrolyte design strategy offers a promising and alternative avenue for using commercially mature, environmentally benign, and low-cost F-free ethers in high-voltage LMBs.

Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

Environmental exposure patterns to 94 current-use pesticides in women of reproductive age who are preparing for pregnancy.

Current-use pesticides (CUPs), including insecticides, fungicides, and herbicides, are extensively employed in agriculture to manage pests, diseases, and weeds. Nonetheless, their widespread application raises significant concerns regarding potential impacts on human health, particularly with reproductive health. This study focuses on exploring the landscape of CUP exposure among pre-pregnancy women. Based on a cohort study comprising 354 pre-pregnancy women of reproductive age in Beijing, China, we measured the concentrations of 94 CUPs in serum and conducted an in-depth analysis of exposure profiles, health risks, and contributing factors. The results revealed that the serum of pre-pregnancy women was contaminated with CUPs, of which the median concentrations ranged from 0.114 (fenamiphos-sulfone) to 61.2 ng/L (mefenacet). Among the 94 CUPs, 54 exhibited detection rates higher than 50 %, including 26 insecticides, 14 fungicides, and 14 herbicides. The exposure concentration profile highlighted that the insecticides contributed 56 % to the total CUP concentration percentages, with organophosphate insecticides being the primary contributors within this category (63.0 %). The average daily intake (ADI) of CUPs ranged from 2.23 to 16,432.28 ng/kg, while diflubenzuron had the highest ADI. Health risk assessments showed that exposure to a combination of total insecticides or herbicides poses a moderate risk for 15.8 % and 30.2 % of women, with mefenacet being the most significant, which showed moderate hazard in 29.4 % of participants. The overlap analysis showed that methiocarb-sulfone, diflubenzuron, and mefenacet were the dominant pesticides. In addition, maternal age, annual income level, smoking, and vitamin B12 supplementation were associated with serum CUP concentrations. Our study contributes a novel and comprehensive exposure profile of CUPs in pre-pregnancy women in northern China, providing valuable insights for evaluating the potential consequences of pre-pregnancy exposure on reproductive health. SYNOPSIS: We provided a comprehensive exposure landscape, health effects, and influential factors of 94 current-use pesticides among pre-pregnancy women in China.

Clinical applications of telemedicine services using a regional telemedicine platform for cancer treatment: a cross-sectional study.

BACKGROUND: Telemedicine is beneficial for improving treatment efficiency and reducing medical expenses of cancer patients. This study focuses on cancer patients participating in teleconsultations through a regional telemedicine platform in China, analyzes the consultation process, and provides references for the clinical application of telemedicine. METHODS: We collected information on teleconsultations of cancer patients conducted from 2015 to 2022 through the regional telemedicine platform. Utilizing SPSS 23.0 software, we conducted descriptive analysis to summarize the distribution of patient gender, age, region, and disease types. The ordinal logistic regression analysis was adopted to analyze the factors influencing the waiting time and consultation duration for teleconsultations. RESULTS: From 2015 to 2022, a total of 23,060 teleconsultations were conducted for cancer patients via regional telemedicine platform, with an average growth rate of 11.09%. The main types of consultations were for lung cancer, liver cancer, and breast cancer, accounting for 18.14%, 10.49%, and 9.46% respectively. 57.05% of teleconsultations had a waiting time of less than 24 h, while patient age, consultation expert level, and disease type were the main factors influencing the waiting time. 50.06% of teleconsultations had a duration of more than 20 min, and the inviting hospital level and the title of invited consultant were the main factors influencing the consultation duration. CONCLUSIONS: In China, telemedicine has been widely employed in the clinical diagnosis and treatment of cancers, covering various types of oncological diseases. However, the waiting time for teleconsultations was generally more than 12 h, indicating the need to enhance consultation scheduling and allocate more expert resources to further optimize the efficiency of teleconsultations. Additionally, further exploration is required for remote health management of outpatients with cancers outside the hospital.

Overexpression of Wild Soybean Expansin Gene GsEXLB14 Enhanced the Tolerance of Transgenic Soybean Hairy Roots to Salt and Drought Stresses.

As a type of cell-wall-relaxing protein that is widely present in plants, expansins have been shown to actively participate in the regulation of plant growth and responses to environmental stress. Wild soybeans have long existed in the wild environment and possess abundant resistance gene resources, which hold significant value for the improvement of cultivated soybean germplasm. In our previous study, we found that the wild soybean expansin gene GsEXLB14 is specifically transcribed in roots, and its transcription level significantly increases under salt and drought stress. To further identify the function of GsEXLB14, in this study, we cloned the CDS sequence of this gene. The transcription pattern of GsEXLB14 in the roots of wild soybean under salt and drought stress was analyzed by qRT-PCR. Using an Agrobacterium rhizogenes-mediated genetic transformation, we obtained soybean hairy roots overexpressing GsEXLB14. Under 150 mM NaCl- and 100 mM mannitol-simulated drought stress, the relative growth values of the number, length, and weight of transgenic soybean hairy roots were significantly higher than those of the control group. We obtained the transcriptomes of transgenic and wild-type soybean hairy roots under normal growth conditions and under salt and drought stress through RNA sequencing. A transcriptomic analysis showed that the transcription of genes encoding expansins (EXPB family), peroxidase, H+-transporting ATPase, and other genes was significantly upregulated in transgenic hairy roots under salt stress. Under drought stress, the transcription of expansin (EXPB/LB family) genes increased in transgenic hairy roots. In addition, the transcription of genes encoding peroxidases, calcium/calmodulin-dependent protein kinases, and dehydration-responsive proteins increased significantly. The results of qRT-PCR also confirmed that the transcription pattern of the above genes was consistent with the transcriptome. The differences in the transcript levels of the above genes may be the potential reason for the strong tolerance of soybean hairy roots overexpressing the GsEXLB14 gene under salt and drought stress. In conclusion, the expansin GsEXLB14 can be used as a valuable candidate gene for the molecular breeding of soybeans.

Repairing Exposed Tendon Wounds with Absorbable Gelatin Sponges and Autologous Split-Thickness Skin Grafts: A Case Series.

ABSTRACT: Conventional flap repair surgery has several drawbacks, including operational complexity, donor site damage, and high risk. In this case series, the authors explored an alternative approach for repairing exposed tendon wounds caused by trauma using absorbable gelatin sponges (AGSs) and autologous thigh skin grafts. This report presents two cases of lower-extremity skin necrosis with tendon exposure following wound debridement. The treatment approach involved early debridement, negative-pressure wound therapy, and wound irrigation with 0.9% sodium chloride. Upon achieving controlled wound infection, AGSs were applied to the exposed tendon to prevent degeneration and promote wound healing. Subsequently, areas where granulation tissue failed to cover the tendon were repaired using AGSs and 0.25-mm-thick autologous mesh skin grafts harvested from the thigh. Complete wound healing was achieved in both cases, on the 20th and 12th day after skin grafting, respectively. The proposed method proved successful in repairing exposed tendon wounds, effectively preventing infection and necrosis.

The casein in sheep milk processed by cold plasma technology: Phosphorylation degree, functional properties, oxidation characteristics, and structure.

Cold plasma is a nonthermal process used for modification of proteins. The objective of this study was to investigate the effect of cold plasma technology on the phosphorylation degree, functional and oxidation properties, and structure of casein in sheep milk. Cold plasma treatment for 3-4 min significantly increased the phosphorylation degree and enhanced functional properties, including water-holding capacity, solubility, foaming capacity and stability. Besides, plasma treatment time profoundly influenced protein oxidation, and treatment for 2 and 3 min could be the preferred conditions to minimize protein change. The protein conformation became unstable with the extension of treatment time. Particle size, polymer dispersity index, and microscopy images confirmed alterations in the protein structure following 3 min of processing. Consequently, using cold plasma treatment at 10 kHz 20 kV for 3 min could be suggested for milk protein modification, providing a basis for the application of high-quality caseins in food processing.

Rainbow connections of bioriented graphs.

For a directed graph D, it's deemed rainbow connected if each arc is assigned a different color, so that all paths from the vertex u to the vertex v are rainbow connected. Rainbow connection number refers to how many colors are needed in D to achieve rainbow connectivity. Among ordered vertex pair (u,v) with arc coloring, if both arcs and internal vertices exhibit unique colors, it is referred to as a total colored graph. As the total rainbow connection number indicates, the smallest number of colors are required to total-color D. This paper focuses on investigating the rainbow connection number of the biorientation of a connected graph, as well as the total rainbow connection number.

Multi-view attribute learning and context relationship encoding enhanced segmentation of lung tumors from CT images.

Graph convolutional neural networks (GCN) have shown the promise in medical image segmentation due to the flexibility of representing diverse range of image regions using graph nodes and propagating knowledge via graph edges. However, existing methods did not fully exploit the various attributes of image nodes and the context relationship among their attributes. We propose a new segmentation method with multi-similarity view enhancement and node attribute context learning (MNSeg). First, multiple views were formed by measuring the similarities among the image nodes, and MNSeg has a GCN based multi-view image node attribute learning (MAL) module to integrate various node attributes learnt from multiple similarity views. Each similarity view contains the specific similarities among all the image nodes, and it was integrated with the node attributes from all the channels to form the enhanced attributes of image nodes. Second, the context relationships among the attributes of image nodes are formulated by a transformer-based context relationship encoding (CRE) strategy to propagate these relationships across all the image nodes. During the transformer-based learning, the relationships were estimated based on the self-attention on all the image nodes, and then they were encoded into the learned node features. Finally, we design an attention at attribute category level (ACA) to discriminate and fuse the learnt diverse information from MAL, CRE, and the original node attributes. ACA identifies the more informative attribute categories by adaptively learn their importance. We validate the performance of MNSeg on a public lung tumor CT dataset and an in-house non-small cell lung cancer (NSCLC) dataset collected from the hospital. The segmentation results show that MNSeg outperformed the compared segmentation methods in terms of spatial overlap and the shape similarities. The ablation studies demonstrated the effectiveness of MAL, CRE, and ACA. The generalization ability of MNSeg was proved by the consistent improved segmentation performances using different 3D segmentation backbones.

Comparing the accuracy of four machine learning models in predicting type 2 diabetes onset within the Chinese population: a retrospective study.

OBJECTIVE: To evaluate the effectiveness of machine learning (ML) models in predicting 5-year type 2 diabetes mellitus (T2DM) risk within the Chinese population by retrospectively analyzing annual health checkup records. METHODS: We included 46,247 patients (32,372 and 13,875 in training and validation sets, respectively) from a national health checkup center database. Univariate and multivariate Cox analyses were performed to identify factors influencing T2DM risk. Extreme Gradient Boosting (XGBoost), support vector machine (SVM), logistic regression (LR), and random forest (RF) models were trained to predict 5-year T2DM risk. Model performances were analyzed using receiver operating characteristic (ROC) curves for discrimination and calibration plots for prediction accuracy. RESULTS: Key variables included fasting plasma glucose, age, and sedentary time. The LR model showed good accuracy with respective areas under the ROC (AUCs) of 0.914 and 0.913 in training and validation sets; the RF model exhibited favorable AUCs of 0.998 and 0.838. In calibration analysis, the LR model displayed good fit for low-risk patients; the RF model exhibited satisfactory fit for low- and high-risk patients. CONCLUSIONS: LR and RF models can effectively predict T2DM risk in the Chinese population. These models may help identify high-risk patients and guide interventions to prevent complications and disabilities.

Unlocking enhanced photocatalytic power: Donor-acceptor synergy in non-metallic g-C3N4 hollow nanospheres.

Selecting safe, non-toxic, and non-metallic semiconductor materials that facilitate the degradation of pollutants in water stands out as an optimal approach to combat environmental pollution. Herein, graphitic carbon nitride (g-C3N4)-based hollow nanospheres nonmetallic photocatalyst modified with covalent organic framework materials named TpMA, based on 1, 3, 5-trimethylchloroglucuronide (Tp) and melamine (MA), was successfully synthesized (abbreviated as CNTP). The ordered electron donor-acceptor structure inherent in TpMA contributed to enhancing the transport efficiency of photogenerated carriers in CNTP. The CNTP photocatalysts exhibited excellent performance in degrading rhodamine B and tetracycline in visible light, with optimal degradation rates reached more than 90% in 60 and 80 min, respectively, which were 5.3 and 3.0 times higher than those of pure CNNS. The increased photocatalytic efficiency observed in CNTP composites could be traced back to the covalently connection between the two molecules, forming a π-conjugated system that facilitated the separative efficiency of photogenerated electron-hole pairs and intensified the utilization of visible light. This study provided a new means to design and fabricate highly efficient and environmentally friendly non-metallic photocatalytic materials.

Ecological restoration for eutrophication mitigation in urban interconnected water bodies: Evaluation, variability and strategy.

Many urban water bodies grapple with low flow flux and weak hydrodynamics. To address these issues, projects have been implemented to form integrated urban water bodies via interconnecting artificial lake or ponds with rivers, but causing pollution accumulation downstream and eutrophication. Despite it is crucial to assess eutrophication, research on this topic in urban interconnected water bodies is limited, particularly regarding variability and feasible strategies for remediation. This study focused on the Loucun river in Shenzhen, comprising an pond, river and artificial lake, evaluating water quality changes pre-(post-)ecological remediation and establishing a new method for evaluating the water quality index (WQI). The underwater forest project, involving basement improvement, vegetation restoration, and aquatic augmentation, in the artificial lake significantly reduced total nitrogen (by 43.58%), total phosphorus (by 79.17%) and algae density (by 36.90%) compared to pre-remediation, effectively controlling algal bloom. Rainfall, acting as a variable factor, exacerbated downstream nutrient accumulation, increasing total phosphorus by 4.56 times and ammonia nitrogen by 1.30 times compared to the dry season, and leading to algal blooms in the non-restoration pond. The improved WQI method effectively assesses water quality status. The interconnected water body exhibits obvious nutrient accumulation in downstream regions. A combined strategy that reducing nutrient and augmenting flux was verified to alleviate accumulation of nutrients downstream. This study provides valuable insights into pollution management strategies for interconnected pond-river-lake water bodies, offering significant reference for nutrient mitigation in such urban water bodies.

Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.

Introduction: Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats. Methods: Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment. Results and discussion: GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.