Search Results (532)

A high-fat diet (HFD) can lead to obesity and skeletal muscle atrophy. Sleeve gastrectomy (SG) improves obesity and increases skeletal muscle mass. This study examined whether SG prevented skeletal muscle atrophy in a diet-induced rat obesity rat model. First, 8-week-old male Sprague-Dawley rats underwent surgical (sham-operated or SG) and dietary (standard, high-fat diet, or same pair feeding as SG [PF]) interventions without exercise. In the second experiment, treadmill exercise was added for 4 weeks post-SG (SG + Ex). In the third experiment, rats received an adiponectin receptor agonist (AdipoRon) injection. The HFD induced weight gain and decreased muscle fiber area. SG + Ex reversed these levels, followed by increases in adiponectin in the blood and skeletal muscle and myoblast determination protein 1 (MyoD) and decreased peri-muscular adipose tissue (PMAT) mass, but SG alone did not. No similar changes were observed in the PF group, with or without exercise. Injection of AdipoRon had a similar effect on skeletal muscle and PMAT as SG + Ex. The combination of SG and exercise, but not calorie restriction alone, had better impacts on skeletal muscle and PMAT than SG or exercise alone. Full article

Malaria remains a significant public health challenge, particularly in endemic regions. The extensive genetic diversity of Plasmodium falciparum (Pf) complicates outbreak prediction and transmission control. One of its most polymorphic markers, merozoite surface protein 2 (MSP2), presents a potential target for molecular surveillance. This cross-sectional study, conducted at King Faisal Hospital Rwanda (KFHR) from October 2021 to June 2023, assessed MSP2’s utility in malaria prediction. PfMSP2 was sequenced, and selected amplicons were cloned, expressed in bacteria, and purified. These antigens were tested against sera from malaria patients and geographically diverse healthy individuals, with complementary surveys contextualizing serological findings. Of the 75 processed monoallelic clinical isolates, 3D7 strains predominated over FC27. Three MSP2-derived biomarkers were produced, eliciting significantly low IgG responses in malaria patients and Belgian controls, but a complex pattern emerged in healthy individuals, with significant differences between Rwandan and Cameroonian samples. IgG3 was the predominant subclass in individuals with high IgG responses. Notably, Rwandan individuals with weak humoral responses to the tested antigens but also other with high responses experienced malaria episodes in the subsequent year. These findings highlight MSP2 polymorphism as a valuable tool for malaria surveillance and outbreak prediction. Integrating genotyping and serology could enable precise, community-specific malaria risk assessments, strengthening control strategies. Full article

Oil seals are vital components in industrial production, necessitating high-precision 3D reconstruction for automated geometric measurement and quality inspection. High-quality point cloud completion is integral to this process. However, existing methods heavily rely on large datasets and often yield sub-optimal outcomes—such as distorted geometry and uneven point distributions—under limited sample conditions, constraining their industrial applicability. To address this, we propose a point cloud completion network that integrates a dynamic weighted fusion of multi-scale features with Transformer enhancements. Our approach incorporates three key innovations: a multi-layer perceptron fused with EdgeConv to enhance local feature extraction for small-sample oil seal rings, a dynamic weighted fusion strategy to adaptively optimize global feature integration across varying missing rates of oil seal rings, and a Transformer-enhanced multi-layer perceptron to ensure geometric consistency by linking global and local features. These innovations collectively enable high-quality point cloud completion for small-sample oil seal rings, achieving significant improvements at a 25% missing rate, reducing CD by 46%, EMD by 49%, and MMD by 74% compared to PF-Net. Experiments on the ShapeNet-Part dataset further validate the model’s strong generalizability across diverse categories. Experimental results on the industrial oil seal ring dataset and the small-sample ShapeNet sub-dataset show that our approach exhibits highly competitive performance compared to existing models. Full article

Background: Nutritional biomarkers are essential for assessing the impact of dietary interventions on health. Amino Acids (AA) serve as potential biomarkers due to their role in metabolic pathways, although the influence of combining macronutrients on AA metabolism remains unclear. Objective: This study aims to evaluate the effects of combining macronutrients (fat, protein, and fiber) on AA metabolism. Methods: A dietary intervention was conducted with 41 participants who were assigned to two groups: the Protein Fat (PF) group and the Protein Fat and Fiber (PFF) group. AA concentration was measured using LC-MS/MS. Results: Our findings indicated that combining macronutrients reduced plasma levels of AA with statistically significant differences between the two diets (p < 0.05 for EAA and BCAA; p < 0,01 for NEAA and AAA). Metabolic profile analysis showed differences between the groups, especially at 55 days (55 D) (R2X: 0.749; R2Y: 0.589; Q2: 0.582, p < 0.001) and 98 days (98 D) (R2X: 0.886; R2Y: 0.7; Q2: 0.605, p < 0.001). Five metabolites (leucine, asparagine, alanine, cysteine, and creatine) were the most influential factors in group differentiation (VIP score), with values ranging between 1.04 and 1.75. Conclusions: The combination of macronutrients led to a significant reduction in plasma amino acids and amines in the PFF group, with recovery post-intervention. These findings highlight the possibility that these metabolites are related to different health statuses. Full article

Cunninghamia lanceolata, contributing 25% to China’s commercial timber production, faces severe drought threats. However, provenance-specific photosynthetic adaptations remain poorly understood. Here, we compared gas exchange, prompt/delayed fluorescence (PF/DF), and modulated 820-nm reflection (MR) responses of two provenances (JXJJ and FJSM) under different drought treatment times. JXJJ maintained a higher net photosynthetic rate (Pn) and stomatal conductance (Gs) than FJSM under drought stress. The declining rates of F_V/F_M, φE_O, Ψ_O, δR_O, PI_ABS, TR_O/CS_M, and ET_O/CS_M were much more rapid in the FJSM than in the JXJJ. An MR kinetics analysis revealed significantly greater PSI impairment in FJSM, evidenced by a 60.2% reduction in P700⁺ re-reduction rate (V_red) compared to only 44.4% in JXJJ (p < 0.05) at 20 d drought treatment. Similarly, DF measurements demonstrated more pronounced PSII energy transfer disruption in FJSM, with the I₂/I₁ ratio increasing by 51.3% vs. 43.0% in JXJJ at 20 d drought treatment. These results demonstrate JXJJ’s superior drought resilience through coordinated stomatal and non-stomatal regulation. Our findings provide actionable criteria for selecting drought-tolerant C. lanceolata provenances, which is essential for sustainable forestry as the climate changes. This study underscores the significance of photosynthetic activity in how C. lanceolata responds to drought and gives insights into boosting drought tolerance in forest species through genetic improvements. Full article

A mononuclear complex [Dy(phenN₆)(HL′)₂]PF₆·CH₂Cl₂ (H₂L′ = R/S-1,1′-binaphthyl-2,2′-diphenol) with local D_6h symmetry was synthesized. Structural determination shows that Dy³⁺ was encapsulated within the coordination cavity of the neutral hexaaza macrocyclic ligand phenN₆, forming a non-planar coordination environment. The axial positions are occupied by two phenoxy groups of binaphthol in the trans form. The local geometry of Dy³⁺ closely resembles a regular hexagonal bipyramid D_6h configuration. The axial Dy-O_phenoxy distances are 2.189(5) and 2.145(5) Å, respectively, while the Dy-N bond lengths in the equatorial plane are in the range of 2.524(7)–2.717(5) Å. The axial O_phthalmoxy-Dy-O_phthalmoxy bond angle is 162.91(17)°, which deviates from the ideal linearity. Under the excitation at 320 nm, the complex exhibits a characteristic emission peak at 360 nm, corresponding to the naphthalene ring. The AC susceptibility measurements under an applied DC field of 1800 Oe show distinct temperature-dependent and frequency-dependent AC magnetic susceptibility, typical of single-molecule magnetic behavior. The Cole–Cole plot in the temperature range of 6.0–28.0 K was fitted using a model incorporating Orbach and Raman relaxation mechanisms, giving an effective energy barrier of U_eff = 300.2 K. Theoretical calculations on complex 1 reveal that the magnetization relaxation proceeds through the first excited Kramers doublets with a calculated magnetization blocking barrier of 404.1 cm⁻¹ (581.4 K). Full article

Treatment for relapsed/refractory multiple myeloma (RRMM) is complex, with several classes of drugs that can be combined into doublet, triplet, or quadruplet regimens. Real-world studies can help to determine the optimal treatment sequences and dosing through observed usage of drugs outside of clinical trials. Previous clinical trials have demonstrated high rates of durable responses in the treatment of patients with triple-class-exposed RRMM with regimens containing selinexor, a first-in-class, orally available selective exportin 1 inhibitor. This study analyzed real-world treatment patterns and survival outcomes using a nationwide electronic health record-derived, deidentified database of patients with RRMM treated with an eligible selinexor-containing, triplet-based regimen, including combinations with dexamethasone and pomalidomide, bortezomib, carfilzomib, or daratumumab. Patients had a real-world overall survival (rwOS) of 14.7 months (95% CI: 10.6, 20.9) and a derived progression-free survival (dPFS) of 4.7 months (95% CI: 3.4, 6.7). Patients with previous exposure to anti-CD38 monoclonal antibodies (mAbs) in the most recent regimen prior to the selinexor treatment had numerically higher survival outcomes (rwOS, 20.9; dPFS, 8.7 months). These data suggest that, in the real-world setting, the use of selinexor triplet regimens is effective in patients with RRMM, especially those with prior exposure to an anti-CD38 mAb in the immediate prior line of therapy. Full article

Background: The purpose of this study was to evaluate the long-term outcomes of patients with locally advanced gastric adenocarcinoma (LAGC) intended to receive induction chemotherapy, chemoradiation and surgery and to develop an algorithm to estimate the individual risk of relapse in a population-based setting. Methods: Patients with LAGC (cT3-4 and/or N+) were retrospectively evaluated. A pathological response was graded according to the Becker criteria. The nodal regression grade was assessed by a 4-point scale (A–D). A comprehensive analysis of 155 individual patient variables was performed, and logistic regression (LR) was utilized to develop a predictive model for relapse risk. Results: From 2010 to 2024, 48 patients were analyzed. After a median follow-up of 49 months (range, 12–212), the 5-year actuarial PFS and OS rates were 44% and 48%, respectively. Four variables were identified as the most relevant features for training the LR model. Scores for the model accuracy, sensitivity and specificity (mean +/− sd) were 0.79 +/− 0.12, 0.74 +/− 0.221 and 0.88 +/− 0.14, respectively. For a validation dataset, the figures were 0.78, 0.88 and 0.73, respectively. Conclusions: This neoadjuvant strategy seems to correlate with a favorable long-term outcome in a subset of intestinal-type LAGA patients who achieve ypN0 features. Full article

Background: In patients with COVID-19 pneumonia, the estimation of PaO₂ represents the method of choice for monitoring a patient’s oxygenation status and assessing disease severity. The aim of this study is, therefore, to investigate the correlation between SpO₂/FiO₂ and PaO₂/FiO₂, as well as radiological and laboratory biomarkers of severity. Methods: In this monocentric observational, analytical, retrospective large cohort study, consecutive patients with a confirmed diagnosis of pneumonia from SARS-CoV-2, hospitalized at the Cotugno Hospital—AORN dei Colli—of Naples, between 1 September 2020 and 28 February 2022 were considered for study inclusion. Patients with missing data were excluded. Results: We included 585 patients (median age 63 [22–95]). Mean PaO₂/FiO₂ was 203 [66–433], whilst mean SpO₂/FiO₂ was 240 [81–471]. We found that P/F ratio could be predicted from S/F ratio, as described by the linear regression equation (P/F = 13.273 + 0.790 × S/F). In addition, we found that SpO₂/FiO₂ ratio significantly correlated with HRCT score and laboratory markers of severity, including IL-6, D-Dimer, and NLR. Conclusions: SpO₂/FiO₂ ratio represents a highly useful resource as a valid surrogate of P/F ratio in patients with COVID pneumonia, also correlating with other biomarkers of severity, such as HRCT score and key laboratory markers. Full article

FAM46C is a tumor suppressor initially identified in multiple myeloma (MM) but increasingly recognized for its role also in other cancers. Despite its significance, studies exploring the therapeutic potential of FAM46C in combination with targeted treatments remain limited. Sphingosine kinases (SphK1 and SphK2) are key regulators of sphingolipid signaling, a pathway essential for maintaining cell structure and function but frequently deregulated in tumors, making them promising targets for cancer therapy. Preliminary work from our laboratory showed that FAM46C expression synergizes with administration of SKI-I, a pan-inhibitor of sphingosine kinases. In this study, we focused specifically on SphK1, the sphingosine kinase predominantly implicated in cancer and investigated the combinatorial effect of forced FAM46C expression and treatment with PF-543, a selective SphK1 inhibitor. We found that FAM46C overexpression enhances, whereas its downregulation reduces, the cytotoxic efficacy of PF-543 in MM cell lines. Using an in vivo xenograft model, we further validated these findings, showing that FAM46C-expressing MM tumors are indeed sensitive to PF-543 while tumors harboring the D90G loss-of-function variant of FAM46C are not. Overall, our results uncover a novel synergistic interaction between FAM46C expression and SphK1 inhibition, highlighting a promising therapeutic strategy for MM treatment. Full article

Our understanding of the molecular mechanisms undergirding artemisinin (ART) resistance in Plasmodium falciparum is currently based on two organizing principles: reduced hemoglobin trafficking into the digestive food vacuole, resulting in lower levels of activated ART, and increased tolerance to ART-induced oxidative stress in the infected erythrocyte. We had previously proposed an extracellular vesicle (EV) export model of ART resistance in P. falciparum. This model predicts that EV abundance will be altered by ART exposure and that the peptide cargo of EVs from the ART-exposed condition will be enriched with aggregation-prone peptides. We tested the predictions of the EV export hypothesis in this study using in vitro culture assays of an ART-resistant transgenic line engineered on a 3D7 background (R561H) and a 3D7 knock-out line (PfVps60KO) with deficient EV production phenotype. EV enrichment was obtained from in vitro parasite culture supernatants via a series of ultracentrifugation and filtration steps, followed by size exclusion chromatography. A quality check on EVs was performed using dynamic light scattering. Liquid chromatography with tandem mass spectrometry was used to determine the proteome cargo from extracted EVs, and parasite peptides were queried for aggregation-prone tendency using open-access software. We report that dihydroartemisinin (DHA) exposure was positively correlated with EV abundance (coefficient estimate = 1038.58, confidence interval of 194.86–1882.30, and p-value = 0.018) and suggests that EV biogenesis is part of the parasite’s response to DHA/ART. Furthermore, our findings suggest the expression of a non-constitutive DHA-induced alternate EV biogenesis pathway as the PfVps60KO was observed to produce the highest number of EVs under DHA exposure. Finally, we show that EVs from both ART-susceptible and resistant parasites under DHA exposure carry a cargo of Chorein N-terminal domain-containing protein (PF3D7_1021700) with a high aggregation-prone index (prion-like domain [PrLD] score = 26.5) out of nine identified parasite peptides. The former of these findings is in concordance with the EV export hypothesis, which posits that the removal of DHA/ART-induced aggregated and/or misfolded peptides is critical to the parasite’s survival under DHA/ART exposure. This observation further implicates EVs in the development of the ART-resistant phenotype. However, the finding of one aggregation-prone peptide out of the nine parasite proteins in the EV cargo does not sufficiently support the EV export hypothesis. Future replicates of this study and further interrogations of the EV export hypothesis are needed. Full article

Background and Objectives: Glioblastoma presents a significant challenge in oncology due to its aggressive nature and poor prognosis, despite advancements in treatment. This study aims to comprehensively evaluate the prognostic significance of coagulation biomarkers, including the novel albumin/D-dimer ratio, in adult glioblastoma patients. Material and Methods: This retrospective study included 74 adult glioblastoma patients who underwent Stupp protocol treatment. Blood samples were collected before radiotherapy to measure biomarkers, including prothrombin time (PT), activated partial thromboplastin time (aPTT), albumin, D-dimer, and the albumin/D-dimer ratio. The prognostic significance of these biomarkers for progression-free survival (PFS) and overall survival (OS) was assessed using both univariate and multivariate Cox regression analyses. Results: The median follow-up time was 12.2 months (range, 1–77.4 months). Univariate analysis revealed that ECOG performance status (p = 0.001), D-dimer (p = 0.03), and albumin (p = 0.001) were significant prognostic factors for PFS. Multivariate analysis identified albumin (p = 0.02) as an independent prognostic biomarker for PFS. For OS, univariate analysis showed that age (p = 0.004), ECOG performance status (p = 0.001), tumor volume (p = 0.007), extent of resection (p = 0.01), radiotherapy dose (p = 0.001), D-dimer (p = 0.02), albumin (p = 0.001), albumin/D-dimer ratio (p = 0.02), and PT (p = 0.002) were significant prognostic factors. Multivariate analysis revealed age (p = 0.04), extent of resection (p = 0.02), and PT (p = 0.04) as independent prognostic factors for OS. Conclusions: Our findings highlight the prognostic significance of coagulation biomarkers, particularly PT, D-dimer, albumin, and the albumin/D-dimer ratio, in glioblastoma. These biomarkers may serve as valuable tools for prognostic assessment and personalized treatment strategies, warranting further exploration in larger prospective studies. Full article

Background/Objectives: The interplay between genetics and athletic performance has garnered significant attention, particularly regarding performance-enhancing polymorphisms (PEPs) and their role in determining key traits that are critical for athletic success. Therefore, this study investigates the genetic predispositions related to peroxisome proliferator-activated receptor alpha (PPARα), angiotensin converting enzyme (ACE), and creatine kinase muscle-type (CKM) gene variants and their potential influence on elite point-fighting (PF) athletes. Methods: A total of 24 elite PF athletes (12 women and 12 men; age = 22.1 ± 5.8 years; body mass = 66.1 ± 15.4 kg; and height = 173.0 ± 9.5 cm, BMI = 21.8 ± 3.2 kg·m⁻²) participated in the study. Saliva samples were collected for DNA extraction and genotyping, analyzing the prevalence of key genetic markers, including the D allele and ID genotype for the ACE variant, the G allele and GG genotype for PPARα, and the A allele and AA genotype for CKM. Results: Genotyping revealed a high prevalence of key genetic markers among participants, with the D allele (58.33%) and ID genotype (66.67%) for the ACE variant, the G allele (77.08%) and GG genotype (54.17%) for PPARα, and the A allele (77.08%) with an AA genotype (62.50%) for CKM. The Total Genetic Score (TGS) analysis indicated a mixed-oriented genetic predisposition across the sample. Conclusions: Although PF athletes showed mixed aerobic/anaerobic genetic profiles, their training routines were primarily strength-oriented, suggesting a possible misalignment between genetic predispositions and their current training approach. These findings offer preliminary insights into the genetic characteristics of elite PF athletes and may inform future investigations into the potential role of genetic information in guiding training strategies. Full article

We present in this paper a low-noise, low-power CMOS operational transconductance amplifier designed for the preconditioning stage of implantable neural recording microsystems. The proposed single-stage amplifier utilizes a combination of recently published techniques, including cross-coupled devices in a recycling folded-cascode topology with positive feedback, to achieve high DC voltage gain and unity-gain bandwidth while minimizing power consumption. A mixed N-type and P-type MOSFET input stage enhances input common-mode performance. Designed and implemented in a 0.18-µm CMOS process with a 1.8 V supply, post-layout simulations demonstrate an open-loop voltage gain of 97.23 dB, a 2.91 MHz unity-gain bandwidth (with a 1 pF load), and an input-referred noise of 4.75 μV_rms. The total power dissipation, including bias circuitry, is 5.43 μW, and the amplifier occupies a chip area of 0.0055 mm². Integrated into a conventional neural recording amplifier configuration, the proposed amplifier achieves a simulated input-referred noise of 5.73 µV_rms over a 1 Hz to 10 kHz bandwidth with a power consumption of 5.6 µW. This performance makes it suitable for amplifying both action potential and local field potential signals. The amplifier provides an output voltage swing of 0.976 V_pp with a total harmonic distortion of −62.68 dB at 1 kHz. Full article

Unmanned Aerial Vehicles (UAVs) have progressively gained interest in recent years due to the wide range of related applications, from aerial communications and autonomous flight to agriculture and logistics. However, accurate 3D localization is crucial for enabling these kinds of applications, and commonly used tracking algorithms are often performing unsatisfactorily in critical scenarios like urban canyons and environments, characterized by dense multipath and line of sight obstruction. In this work we derive a novel 3D tracking algorithm which, despite its mathematical simplicity, can efficiently track moving targets handling asynchronous arrival of the anchor measurements or obstructions of line-of-sight links and outperforming commonly used algorithms like the Extended Kalman Filter (EKF) and the Particle Filter (PF). The proposed algorithm tracks the 3D position, velocity, and acceleration of a moving target through the combination of range measurements, between the target and different anchors, which become available in numbers and time instants not necessarily ordered as usually assumed in these applications. We denote this condition as asynchronous measurements, meaning that the ranging measurements are not available from all the anchors and they refer to different positions of the UAV during the tracking. We also show that our estimator is optimal among the linear ones, meaning that within this class, it minimizes the estimation error variance. Finally, we explore the accuracy that can be achieved in simulated scenarios defined by realistic UAV altitudes, velocities, and trajectories, as well as typical ranging errors of wideband localization systems. Full article