Search Results (1,082)

Aim: To compare diabetic polyneuropathy (DPN) and cardiac autonomic neuropathy (CAN) between T1DM and T2DM patients. Methods: This study enrolled 66 T1DM and 79 T2DM patients. DPN was evaluated using three different methods: clinical examination, using neuropathy symptom score (NSS) and neuropathy disability score (NDS), current perception threshold (CPT) using Neurometer, and nerve conduction studies (NCSs). CAN was assessed by cardiovascular autonomic reflex tests (CARTs). Results: The prevalence of DPN did not differ between T1DM and T2DM (p > 0.05 for all), however, the proportion of DPN depended on the method used and was highest with CPT (53.0% vs. 46.8%), followed by NCSs (44.1% vs. 41.2%) and clinical examination (25.8% vs. 31.6%). T2DM vs. T1DM patients were more often diagnosed with painful DPN (51.9% vs. 27.3%, p = 0.004), reduced perception of vibration (72.2% vs. 48.5%, p = 0.006), and autonomic neuropathy (59.5% vs. 32.3%, p = 0.001), while NCSs revealed more prevalent motor nerve dysfunction in T1DM compared to T2DM (41.2% vs. 19.6%). Multivariate regression analysis showed increased DPN risk with age and CAN risk with worsening of eGFR in T1DM. No significant associations remained after multivariate adjustment for T2DM. Conclusions: The prevalence of DPN is highly varied and depends on the diagnostic method used. T2DM patients more often had symptoms and signs of diabetic neuropathy. However, stronger associations with risk factors were observed in T1DM. Full article

Olive mill wastewaters (OMWWs) are an environmental problem in the Mediterranean region, and it is crucial to explore strategies for their treatment and repurposing. The chemical precipitation technique (CPT) has been presented as a cost-effective wastewater treatment solution that might be applied to OMWW. The CPT-resulting precipitant subproducts (sludge) may be reprocessed (e.g., agricultural fertilizer and/or soil amendment), while the treated wastewater may be repurposed or reused (e.g., irrigation, aquaponic, or industrial processes). This study aimed to evaluate the efficacy of CPT in treating wastewater from the olive oil industry from an ecotoxicological perspective. Additionally, to assess the safe use of the obtained sludge in CPT treatment, its effects on soil biota were assessed. For this, a set of ecotoxicological assays using freshwater (Raphidocelis subcapitata, Daphnia magna and Danio rerio), terrestrial invertebrates (Folsomia candida and Enchytraeus crypticus), and plants (Brassica oleracea and Lolium perenne) were used as model organisms. Results demonstrated that CPT reduced OMWW toxicity to freshwater organisms, offering a favorable outlook on CPT’s potential as a wastewater treatment method. Increasing application rates of sludge in soil reduced the shoot biomass and the hydric content of both plants compared to the control. Survival of F. candida and E. crypticus was not affected by sludge in soil at any tested application rate, yet sludge application negatively affected the reproduction of both species, even at relevant sludge application rates (2%) of sludge in soils. Overall, the applicability of this sludge obtained by the CPT treatment in soils should be carefully evaluated due to the observed adverse effects on soil biota. Although the results of CPT were promising in reducing the toxicity of OMWW for these aquatic species, some adjustments/improvements should be performed to improve this technique and use all the obtained resources (treated water and sludge) in a fully circular perspective. Full article

Background/Objective: This study examines the composite influence of frailty, malnutrition, and anemia on postoperative outcomes for patients with adult spinal deformity (ASD). Methods: In this retrospective cohort study using the 2011–2022 NSQIP database, we utilized CPT and ICD codes to identify ASD patients who underwent PSF. Subjects were stratified based on frailty status. Frail patients were then classified according to malnutrition and anemia status. Frailty was determined using the revised risk analysis index (RAI-rev). Our primary outcomes were extended length of stay (LOS), non-routine discharge (NRD), 30-day adverse events (AE), and 30-day mortality. For each outcome, we fitted four nested multivariable logistic regression models (RAI-rev + anemia + malnutrition, RAI-rev + anemia, RAI-rev + malnutrition, and RAI-rev alone) and compared the incremental discrimination of each model using receiver operating characteristic (ROC) analysis. Results: Of 3639 patients, 460 were frail alone, 266 were frail + anemic, 37 were frail + malnourished, 121 were frail + anemic + malnourished, and 2755 were not frail. RAI-rev (aOR: 1.84, 95% CI: 1.45–2.35), anemia (aOR: 1.84, 95% CI: 1.45–2.35), and malnourishment (aOR: 2.34, 95% CI: 1.69–3.24) were independent predictors of extended LOS. RAI-rev (aOR: 1.07, 95% CI: 1.04–1.11) and anemia (aOR: 2.09, 95% CI: 1.66–2.61) were associated with an increased risk of 30-day AEs. RAI-rev and malnutrition were independent predictors of NRD (RAI-rev: aOR: 1.11, 95% CI: 1.06–1.16; Malnutrition: aOR: 1.57, 95% CI: 1.08–2.29) and 30-day mortality (RAI-rev: aOR: 1.10, 95% CI: 1.04–1.17; Malnutrition: aOR: 3.79, 95% CI: 1.24–11.60). Based on ROC analysis, RAI-rev + anemic + malnourished was a superior predictor of LOS and 30-day AEs (both p < 0.001). Compared to RAI-rev, RAI-rev + anemic superiorly predicted LOS and 30-day AEs, and RAI-rev + malnutrition superiorly predicted LOS (all p < 0.001). Conclusions: Our results reveal RAI-rev combined with malnutrition and anemia superiorly predicts 30-day AEs and LOS in postoperative ASD patients. Future studies should investigate the feasibility and efficacy of these models for perioperative risk stratification and optimized recovery planning to improve outcomes for ASD patients. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

The development of functional endothelial monolayers on synthetic vascular grafts remains challenging, particularly for small-diameter vessels (<6 mm) prone to thrombosis. Here, we present a pharmacological strategy combining 8-(4-chlorophenylthio) adenosine 3′,5′-cyclic monophosphate sodium salt (pCPT-cAMP, a tight junction promoter) with nitric oxide/cGMP pathway agonists 3-morpholinosydnonimine (SIN-1), captopril, and sildenafil) to enhance endothelialization. In human umbilical vein endothelial cells (HUVECs), this four-agent cocktail induced a flat, extended phenotype with a 3-fold increased cell area and 57.5% fewer cells required for surface coverage compared to controls. Immunofluorescence analysis revealed enhanced ZO-1 expression and continuous tight junction formation, while sustained nitric oxide (NO) production (3.9-fold increase) and restored prostacyclin (PGI₂) secretion demonstrated preserved endothelial functionality. Anticoagulation assays confirmed a significant reduction in thrombus formation (p < 0.01) via dual inhibition of platelet activation and thrombin binding. These findings establish a synergistic drug combination that promotes rapid endothelialization while maintaining antithrombogenic activity, offering a promising solution for small-diameter vascular grafts. Further studies should validate long-term stability and translational potential in preclinical models. Full article

Background/Objectives: Astaxanthin, a xanthophyll carotenoid, has garnered significant interest due to its benefits with regard to dyslipidemia. This multifaceted functional food ingredient modulates several key enzymes associated with lipid regulation, including HMG-CoA reductase, CPT1, ACCβ, and acyl-CoA oxidase. It influences key antioxidant molecular pathways like the Nrf2, limiting dyslipidemia occurrence and regulating liver cholesterol uptake through the modulation of liver lipid receptors. Due to the current lack of systematic reviews and meta-analyses assessing moderate to high dosages (6–24 mg/d) of astaxanthin supplementation on lipid dysregulation, the present manuscript aims to fill this gap in the literature. Methods: Following the PRISMA guidelines, we included eight studies comprising eleven results from the PubMed, Springer Link, Science Direct, Cochrane, and Google Scholar databases. The Jamovi (Version 2.6.26, Solid) software was utilized for statistics. Our primary objective was to assess in detail the effects of astaxanthin on LDL-C, HDL-C, triglyceride, and total cholesterol levels. Results: The meta-analysis concludes positive effects of astaxanthin (6–20 mg/d) on HDL-C (0.4200; 95% CI: 0.1081 to 0.7319) and triglyceride (−0.3058; 95% CI: −0.5138 to −0.0978) levels. Unfortunately, astaxanthin (6–20 mg/d) does not appear to significantly influence LDL-C (−0.0725; 95% CI: −0.3070 to 0.1620) and total cholesterol (−0.0448; 95% CI: −0.3369 to 0.2473) levels. Regarding HDL-C, improvements were observed from 55 ± 8 mg/dL (pre-intervention) to 63 ± 8 mg/dL (post-intervention) (p < 0.01) in the 12 mg/d of astaxanthin groups. In the assessment of triglyceride levels, results show a decrease from 151 ± 26 mg/dL (pre-intervention) to 112 ± 40 mg/dL (post-intervention) (p < 0.01) for 18 mg/d astaxanthin supplementation. Conclusions: Further research is necessary to fully harness the potential of astaxanthin, which includes assessing astaxanthin in different subsets of patients, using a GWAS, and in combination with other nutraceuticals to understand the compound’s effectiveness with regard to varying health conditions, genetic and epigenetic factors, and synergistic effects with other compounds. Full article

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) often co-occur and present significant treatment challenges. Cognitive Processing Therapy (CPT) is a widely used, efficacious treatment for PTSD, but the application of CPT among individuals with co-occurring PTSD/AUD has been limited. To address this gap, we developed a novel, 12-session trauma-focused treatment that combines CPT with Relapse Prevention (RP) for AUD (CPT+RP). This paper describes CPT+RP and presents preliminary outcomes from the first six participants enrolled in a larger, ongoing multisite clinical trial of CPT+RP. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD Checklist for DSM-5 (PCL-5). The Timeline Follow-Back (TLFB) assessed frequency (percent days drinking; PDD) and quantity (drinks per drinking day; DDD) of alcohol use, and craving was measured using the Penn Alcohol Craving Scale (PACS). The Client Satisfaction Questionnaire measured acceptability. Pre- to post-treatment reductions were observed in PTSD symptoms (ΔMCAPS-5 = 14.00; ΔMPCL-5 = 20.50), frequency and quantity of alcohol use (ΔMPDD = 38.65; ΔMDDD = 6.24), and craving (ΔPACS = 6.17). Most participants achieved clinically significant improvement in their PTSD symptoms and acceptability was high. Although preliminary, the findings suggest the new CPT+RP intervention is feasible, acceptable, and a promising treatment innovation for co-occurring PTSD and AUD. Full article

Extended reality (XR)-based rehabilitation is an emerging therapeutic approach that combines real and virtual environments to enhance patient engagement and promote motor and cognitive recovery. Its clinical utility in children with cerebral palsy (CP), particularly regarding gross motor skills, balance, and psychosocial well-being, remains underexplored. This preliminary study aimed to evaluate the potential effects of XR-based rehabilitation on gross motor function, balance, parental stress, and quality of life in children with cerebral palsy. Thirty children with cerebral palsy were randomly assigned to an extended reality training group (XRT, n = 15) or a conventional physical therapy group (CPT, n = 15). Both groups received 30 min sessions, three times per week for 6 weeks. Outcome measures included the Gross Motor Function Measure-88 (GMFM-88), Pediatric Balance Scale (PBS), Functional Independence Measure (FIM), Parenting Stress Index (PSI), and Pediatric Quality of Life Inventory (PedsQL), assessed pre- and post-intervention. A 2 (group) × 2 (time) mixed ANOVA was conducted. The XR group demonstrated improvements in GMFM-88, PBS, and FIM scores, with decreased PSI and increased PedsQL scores. Although most interaction effects were not statistically significant (GMFM-88: η² = 0.035, p = 0.329; PBS: η² = 0.043, p = 0.274), a marginal interaction effect was observed for PSI (p = 0.065, η² = 0.059), suggesting a potential benefit of XR-based rehabilitation in reducing parental stress. This preliminary study indicates that XR-based rehabilitation may provide beneficial trends in motor function and psychosocial health in children with CP, particularly in reducing parental stress. Further studies with larger sample sizes are needed to confirm these findings. Full article

A novel composite patch osteosynthesis technique (CPT) has demonstrated promising ex vivo biomechanical performance in small tubular bones. To bridge the gap toward clinical evaluations, this study compared the stability of the CPT to a stainless-steel locking plate (LP) in an experimental in vivo ovine bilateral proximal phalanx fracture model. Eight sheep underwent a midline osteotomy with a 4.5 mm circular unicortical defect in the lateral proximal phalanx of both front limbs, treated with the CPT (n = 8) or the LP (n = 8). A half-limb walking cast, or a custom off-loading hoof shoe, was used for postoperative protection. Implant stability was assessed by post-surgery X-ray evaluations and post-euthanasia (16 weeks) dual-energy X-ray absorptiometry (DXA). At week one, all CPT implants demonstrated mechanical failure, while all LPs remained overall intact. Mean BMD was 0.45 g/cm² for CPT and 0.60 g/cm² for LP in the fracture area (p = 0.078), and 0.37 g/cm² vs. 0.41 g/cm² in the distal epiphysis (p = 0.016), respectively. In conclusion, the CPT demonstrated indications of inferior stability compared to the LP in this fracture model, which may limit its clinical applicability in weight-bearing or high-load scenarios and in non-compliant patients. Full article

This paper presents the results of an investigation into the catalytic activity and selectivity of rhodium-based catalysts supported on natural zeolite clinoptilolite from the Shankanai field (Kazakhstan) in the dehydrogenation of light alkanes from associated petroleum gas (APG). Three modifications of the catalyst have been studied: basic 1%Rh/HCpt, modified with tin 1%Rh/10%SnO/HCpt, and combined with additives of tin and potassium 1%Rh/10%SnO/5%K₂O/HCpt. It has been shown that the addition of tin contributes to increased thermal stability and a decreased coking rate, while the addition of potassium suppresses side reactions (cracking and isomerization), increasing the selectivity for olefins. The highest yield of olefins (~30%) is achieved with the 1%Rh/10%SnO/5%K₂O/HCpt catalyst in the presence of water vapor. Using scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM), improved distribution of active components and reduced catalyst deactivation have been confirmed. The obtained data demonstrate the potential of the developed systems for the efficient processing of APG and the selective synthesis of olefins. Full article

Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150–300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1–18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases. Full article

Background/Objectives: The treatment of multiple myeloma (MM) remains a challenge, as almost all patients will eventually relapse. Proteasome inhibitors are a cornerstone in the management of MM. Unfortunately, validated biomarkers predicting drug response are largely missing. Therefore, we aimed to identify genes associated with drug resistance or sensitization to proteasome inhibitors. Methods: We performed genome-wide CRISPR-Cas9 knockout (KO) screens in human KMS-28-BM myeloma cells to identify genetic determinants associated with resistance or sensitization to proteasome inhibitors. Results: We show that KO of KLF13 and PSMC4 induces drug resistance, while NUDCD2, OSER1 and HERC1 KO cause drug sensitization. Subsequently, we focused on top sensitization hit, NUDCD2, which acts as a co-chaperone of Hsp90 to regulate the LIS1/dynein complex. RNA sequencing showed downregulation of genes involved in the ERAD pathway and in ER-associated ubiquitin-dependent protein catabolic processes in both untreated and carfilzomib-treated NUDCD2 KO cells, suggesting that NUDCD2 depletion alters protein degradation. Furthermore, bortezomib-treated NUDCD2 KO cells showed a decreased expression of genes that have a function in oxidative phosphorylation and the mitochondrial membrane, such as Carnitine Palmitoyltransferase 1A (CPT1A). CPT1A catalyzes the uptake of long chain fatty acids into mitochondria. Mitochondrial lipid metabolism has recently been reported as a possible therapeutic target for MM drug sensitivity. Conclusions: These results contribute to the search for therapeutic targets that can sensitize MM patients to proteasome inhibitors. Full article

The poll gland, a specialized tissue of male Bactrian camels, undergoes seasonal enlargement and marked metabolic activation during the rutting season. However, the metabolic mechanisms of the poll gland and its role in rutting activities and inducing estrus are still not fully understood. This study aimed to investigate the contribution of fatty acid metabolic pathways, specifically those mediated by carnitine palmitoyltransferase 1A (CPT1A), in poll gland activity during the breeding season; poll gland tissue, neck mane, and urine samples were systematically collected from healthy male Bactrian camels stratified into breeding and non-breeding season groups for integrated proteomic, metabolomic, and biochemical assays. Histological and immunohistochemical analyses revealed reduced adipocytes but elevated ATP production in rutting camels, suggesting increased mitochondrial activity and enhanced oxidative phosphorylation. Proteomic analyses identified 119 differentially expressed proteins (DEPs) linked to fatty acid metabolism, with CPT1A, a key regulator of mitochondrial fatty acid oxidation, emerging as a central hub. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further confirmed enrichment in fatty acid biosynthesis, degradation, and PPAR/AMPK signaling. The metabolomic analysis identified 14 metabolites, including acetylcarnitine and glycine, that were closely correlated with CPT1A expression, suggesting their potential involvement in regulating fatty acid metabolism during the breeding season. Quantitative expression analyses revealed that CPT1A in glandular acini was significantly upregulated in the breeding group compared to the non-breeding group across all assays: qPCR (2.53-fold, p < 0.05), Western blot (3.5-fold, p < 0.05), and immunohistochemistry (1.5-fold, p < 0.05). This demonstrated that CPT1A-mediated fatty acid metabolism plays a pivotal role in energy provision for reproductive activities. The results suggested that CPT1A-mediated fatty acid oxidation sustains poll gland function and reproductive behaviors in male Bactrian camels. This study provided a theoretical basis for understanding the role of CPT1A-mediated fatty acid oxidation in maintaining poll gland function and supporting reproductive activities in male Bactrian camels. Full article

To address the dynamic decision-making and control problem in unmanned aerial vehicle (UAV) swarms, this paper proposes a cumulative prospect theory-driven pigeon-inspired optimization (CPT-PIO) algorithm. Gray relational analysis and information entropy theory are integrated into cumulative prospect theory (CPT), constructing a prospect value model for Pareto solutions by setting reference points, defining value functions, and determining attribute weights. This prospect value is used to evaluate the quality of each Pareto solution and serves as the fitness function in the pigeon-inspired optimization (PIO) algorithm to guide its evolutionary process. Furthermore, incorporating individual and swarm situation assessment methods, the situation assessment model is constructed and the information entropy theory is employed to ascertain the weight of each assessment index. Finally, the reverse search mechanism and competitive learning mechanism are introduced into the standard PIO to prevent premature convergence and enhance the population’s exploration capability. Simulation results demonstrate that the proposed CPT-PIO algorithm significantly outperforms two novel multi-objective optimization algorithms in terms of search performance and solution quality, yielding higher-quality Pareto solutions for dynamic UAV swarm decision-making. Full article

This study systematically investigated the effects of dietary tea polyphenols (TPs, major bioactive polyphenols from Camellia sinensis with potent antioxidant and anti-inflammatory properties) on the growth performance and intestinal health of hybrid crucian carp HCC2 under chronic crowding stress. A low-density control group (44.4 fish/m³, basal diet without TPs) and four high-density crowding stress groups (222.2 fish/m³) were established, one fed the basal diet without TPs (CS) and three fed basal diets supplemented with 100 (CSLTP), 200 (CSMTP), or 400 (CSHTP) mg/kg TPs. We analyzed the impacts of TPs on growth performance, serum biochemical parameters, antioxidant capacity, expression of lipid metabolism-related genes, and intestinal microbiota composition. The results demonstrated that chronic crowding stress significantly suppressed the final body weight, weight gain rate, and specific growth rate of HCC2, while increasing serum lactate LDH, TG, and ALB and decreasing GLU, LDL-C, ALT, AST, and ALP levels. Dietary TPs supplementation enhanced antioxidant capacity (T-AOC, SOD, CAT, and GSH) and alleviated lipid metabolic disorders by activating the Nrf2/Keap1 and PPARα signaling pathways, thereby upregulating the expression of liver antioxidant genes (CAT and SOD) and fatty acid oxidation genes (CPT1 and acox1). Furthermore, intestinal microbiota analysis revealed that chronic crowding stress significantly increased the abundance of Proteobacteria and decreased the proportion of Firmicutes compared to the low-density control. Dietary TPs intervention, particularly at higher doses, partially restored the Firmicutes abundance and reduced the enrichment of potential pathogenic bacteria associated with stress. This study is the first to comprehensively elucidate the mechanism by which TPs alleviate crowding stress through enhanced antioxidant capacity, metabolic regulation, and microbiota remodeling, providing robust theoretical support for the application of plant-based additives in aquaculture. Full article