Search Results (383)

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality, with therapeutic resistance posing the primary barrier to durable outcomes. Beyond genetic and epigenetic alterations, amino acid transporter-driven metabolic reprogramming—mediated by LAT1 (SLC7A5), ASCT2 (SLC1A5), and xCT (SLC7A11)—supports tumor proliferation, redox homeostasis, and immune escape. Their preferential expression in NSCLC highlights their potential as therapeutic targets and predictive biomarkers. In parallel, α-particle therapy has gained attention for its capacity to eradicate resistant clones through densely clustered, irreparable DNA double-strand breaks. Astatine-211 (²¹¹At) combines a clinically relevant half-life, high linear energy transfer, and predictable decay scheme, positioning it as a unique candidate among α-emitters. Preclinical studies of ²¹¹At-labeled transporter ligands, particularly LAT1-targeted conjugates, demonstrate potent tumor suppression and synergy with targeted therapy, chemotherapy, radiotherapy, immunotherapy, and ferroptosis inducers. Advances in radiochemistry, delivery systems (antibodies, peptides, and nanocarriers), and PET tracers such as [¹⁸F]FAMT and [¹⁸F]FSPG collectively support a theranostic framework for patient stratification and adaptive dosing. By linking transporter biology with α-particle delivery, ²¹¹At-based theranostics offer a mechanistically orthogonal strategy to overcome resistance and heterogeneity in NSCLC. Successful translation will depend on precise dosimetry, scaffold stabilization, and biomarker-guided trial design, enabling progression toward first-in-human studies and future integration into multimodal NSCLC therapy. Full article

The flow and heat transfer inside the mold play an important role in the quality of the casting billet during continuous casting. In this work, a three-dimensional coupled model of flow and heat transfer was established, and the flow field and temperature distribution characteristics of molten steel were explored in depth. The results indicated that the narrow impact position is 315 mm away from the meniscus. The maximum turbulence kinetic energy of the centerline reached 0.00284 m²∙s⁻², 108 mm from the narrow surface. The temperature of the steel liquid on the path of the two splitting strands located in the upper and lower circulation zones was above 1781 K. The temperature range from the center of the billet to the narrow 1/4 section, which was enclosed by the upper annular flow zone and 400 mm below the liquid level, was relatively low and lower than the liquidus temperature. The model can provide guidance for improving and optimizing the quality of continuous casting billets. Full article

The number of known mitochondrial genomes in Buprestidae is limited, especially in Chrysochroinae, which seriously hinders the phylogenetic study of this family. The mitogenomes of Capnodis miliaris, Lamprodila cupreosplendens, Sphenoptera insidiosa and Philocteanus rubroaureus were sequenced, assembled and annotated in this study. The mitogenomes of these four species are typical circular double-stranded DNA molecules, containing 13 protein-coding genes (PCGS), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and a control region (CR). The total lengths of these four mitogenomes are moderate, ranging from 15,778 bp to 16,230 bp. Additionally, their A + T content ranges from 68.76% to 73.47%, showing positive AT-skew values ranging from 0.098 to 0.181. Relative Synonymous Codon Usage (RSCU) analysis indicated that TTT (Phe), ATT (Ile), TCT (Ser2), and TTA (Leu2) are the most frequently used codons. The gene arrangement of four mitogenomes is consistent with the previously reported Buprestidae mitogenomes. Most of the PCGs use ATN as the start codon, with TAA as the stop codon or an incomplete stop codon T-. Phylogenetic trees were constructed based on the PCGs and rRNAs using both maximum-likelihood and Bayesian inference methods. The phylogenetic results showed that Julodinae, Polycestinae, Buprestinae and Agrilinae are monophyletic groups, and Chrysochroinae is a paraphyletic group. As the number of Buprestidae mitogenomes used for polyogenetic analysis increases, the topology of phylogenetic tree shows differences compared to previous studies. Full article

Implementation of universal antiretroviral treatment (ART) in pregnancy has improved maternal health and reduced vertical transmission. However, women living with HIV (WLHIV) still experience worse perinatal outcomes. This retrospective study compared demographic, virological factors, ART regimens and perinatal outcomes in pregnant WLHIV between 2000–2010 (n = 318) and 2011–2021 (n = 140) at a tertiary center in Barcelona. Significant demographic shifts included changes in ethnic distribution, substance use, educational attainment, and maternal BMI. Significant progress in infection control was observed, with increased ART coverage up to 97%, improved viral suppression (80% to 91.3%, p = 0.002), and enhanced immunological status. ART regimens shifted significantly, with an increase in integrase strand transfer inhibitors (INSTI)-based regimens (0.7% to 39.2%, p < 0.001). Obstetric management evolved, with a rise in vaginal deliveries (24.8% to 44.3%, p < 0.001) and a decline in intrapartum zidovudine (93.7% to 54.7%, p < 0.001). Notably, preterm birth rates sharply declined, yet small-for-gestational-age (SGA) infants (26.4% vs. 20%, p = 0.323) and preeclampsia rates remained unchanged and higher than in the general population. All statistical analyses were performed in IBM SPSS statistics 23. In conclusion, although maternal and perinatal outcomes in pregnant WLHIV have improved over the past two decades, a high rate of adverse perinatal outcomes related to placental dysfunction (SGA, preeclampsia) persist. Our findings highlight the need for optimized prenatal care and further research to develop targeted interventions for WLHIV. Full article

Background/Objectives: Excessive weight gain is a growing concern among people living with HIV (PWH) receiving integrase strand transfer inhibitor (INSTI)-based regimens as first-line antiretroviral therapy (ART), as it may contribute to multimorbidity. The mechanisms driving weight gain in INSTI users are not fully understood but are thought to be multifactorial. This study examines the plasma metabolome associated with weight gain in PWH on INSTI-based regimens. Methods: We conducted a nested case–control study within the randomized clinical trial MICTLAN (NCT06629480). Sixty-six participants were randomized to receive INSTI-based regimens, either bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) or dolutegravir/abacavir/lamivudine (DTG/ABC/3TC), and followed for 18 months. Weight gain >10% relative to baseline was considered a primary endpoint and used as a criterium to categorize cases (n = 28) and controls (n = 38). Anthropometric and clinical measurements, plasma insulin, and metabolomic profiles were assessed at baseline and 18 months post-ART. Plasma untargeted metabolomics was performed using liquid chromatography–mass spectrometry (LC-MS/MS) to identify metabolomic changes linked to weight gain. Bioinformatic tools, including Partial Least Squares Discriminant Analysis (PLS-DA), volcano plots, and KEGG pathway enrichment analysis, were used to analyze plasma metabolomes and identify significant differential metabolites. Results: Weight gain at 18 months in PWH on INSTI-based ART was associated with insulin resistance, as measured by HOMA-IR (OR 3.23; 95% CI 1.14–9.10; p = 0.023), and visceral adipose tissue thickness > 4 cm (OR 4.50; 95% CI 1.60–13.03; 9.10; p = 0.004), and hypertriglyceridemia (OR 3.9; 95% CI 1.38–10.94; p = 0.008). Baseline HIV RNA viral load >50,000 copies/mL (OR 8.05; 95% CI 2.65–24.43; p = 0.0002) was identified as a baseline predictor of weight gain (aOR 6.58 (1.83–23.58); p = 0.004). In addition, accumulation of circulating medium-chain acylcarnitines, indicative of mitochondrial dysfunction, and insulin resistance were linked to weight gain in PWH on INSTI-based regimens after 18 months of therapy. Conclusions: This metabolomic study identified metabolites reflecting mitochondrial dysfunction, dysregulated lipid metabolism, and altered amino acid metabolism as key mechanisms underlying insulin resistance and weight gain in PWH on INSTI-based ART. Full article

Background/Objectives: The butterfish Stromateus stellatus is undervalued and usually discarded as bycatch, leading to an inefficient and unsustainable use of marine biomass. Overall, although Stromateus is the type genus of the family Stromateidae, its species are less studied than more economically important fishes. Methods: In this study, we determined and analyzed the complete mitochondrial genome sequence of S. stellatus. Furthermore, we performed maximum likelihood and Bayesian inference analyses to infer the phylogenetic relationships among 21 species of the order Scombriformes. Results: Using next-generation sequencing (NGS) and de novo assembly, a circular mitochondrial genome of 16,509 bp was obtained, exhibiting the typical vertebrate mitochondrial structure comprising 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes. Three intergenic regions were identified, including the control region and the origin of light-strand replication, along with several gene overlaps. The heavy strand nucleotide composition was determined to be 28.79% A, 27.84% C, 16.32% G, and 27.05% T, with a GC content of 44.16%. The three Peprilus and five Pampus species formed a clade together with S. stellatus, supported by high bootstrap and posterior probability values, confirming the monophyly of Stromateidae. Conclusions: The gene order and content are consistent with those reported for other Stromateidae species and correspond to the typical arrangement observed in most bony fishes. This mitochondrial genome represents the first one reported for the genus Stromateus, providing valuable insights into the genetic makeup of S. stellatus, contributing to a better understanding of marine biodiversity. Additionally, these data will support future research on pelagic fish evolution and assist in sustainable fisheries management. Full article

Background/Objectives: Dyslipidemia is one of the major problems of long-term management in people living with human immunodeficiency virus (HIV) (PLH) as a risk factor for cardiovascular diseases. Lipoprotein lipase (LPL) is anchored on the surface of the capillary endothelial cells and plays a pivotal role in triglyceride metabolism by catabolizing dietary chylomicrons and very low-density lipoprotein synthesized in the liver. However, the details of the mechanisms in the era of integrase strand transfer inhibitor-based antiretroviral therapy have not yet been clarified. Methods: This study was a cross-sectional, single-center, non-interventional study evaluating the underlying factors associated with dyslipidemia, insulin resistance or secretion, and changes in the body composition of PLH. Results: Among PLH (n = 48), lower LPL (<60.8 ng/mL) and older age independently predicted antilipemic drug (ALD) necessity. A comparison of ALD-naïve PLH (n = 33) and age- and sex-matched non-HIV controls (n = 33) showed that PLH were significantly associated with lower high-density lipoprotein cholesterol (HDL-C) and higher HOMA-β. LPL was also the independent predictor of HDL-C < 40 mg/dL in PLH (adjusted odds ratio = 0.901, p = 0.044). Furthermore, LPL < 65.3 ng/mL predicted HDL-C < 40 mg/dL with 100% sensitivity and 60.9% specificity. Low levels of HIV-RNA were detected in the high HOMA-β group. Conclusions: In Japanese individuals, compared to non-HIV controls, PLH has low HDL-C and LPL. The measurement of LPL may confer the risk assessment and decision-making with relevance to ALD in PLH. Additionally, the effectiveness of HIV antiviral therapy and glucose tolerance may interact with each other. Full article

The HIV-1 epidemic continues to challenge global public health, especially in sub-Saharan Africa. The rise in drug-resistant viruses, particularly pan-resistant strains, threatens treatment effectiveness, hindering progress toward UNAIDS viral suppression goals. This is critical in low-to-middle income countries (LMICs) like Zimbabwe, where treatment options and access to drug resistance testing are limited. This cross-sectional study analyzed 102 genotypes from patients with HIV-1 RNA ≥ 1000 copies/mL after at least 6 months on a dolutegravir (DTG)-based ART. HIV-1 genotyping and drug resistance interpretation were performed using the Stanford HIV Drug Resistance Database. Overall, 62% of genotypes harbored at least one drug resistance mutation, with 27% showing integrase strand transfer inhibitor (INSTI)-associated mutations. High-level resistance to DTG and cabotegravir was found in 14% and 23% of integrase sequences, respectively, primarily driven by G118R and E138K/T mutations. Pan-resistance was observed in 18% of complete genotypes, with one case of four class resistance. These results highlight the emergence of INSTI resistance in LMICs. The study underscores the urgent need for enhanced HIV drug resistance testing, continuous surveillance, and strategic optimization of ART regimens in resource-constrained settings to ensure effective HIV management. Full article

White-lipped tree frogs, Polypedates braueri, are currently included in the list of terrestrial wildlife with important ecological, scientific, and social value in China. Understanding the structure and characteristics of the mitochondrial genome provides essential information for resource conservation and phylogenetic analyses of P. braueri. While the complete mitochondrial genomes serve as important molecular markers for phylogenetic and genetic studies, the mitochondrial genome of P. braueri has received little attention. In this paper, we analyzed the characterization of the mitochondrial genome of P. braueri and investigated the phylogenetic relationships of Rhacophoridae. The complete mitochondrial genome of P. braueri was 20,254 bp in length, containing thirty-six genes (twelve protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), twenty-two transfer RNA genes (tRNAs)), three non-coding regions for the origin of light strand (O_L), and two control regions (CR). There were six overlapping regions and seventeen intergenic spacer regions in the mitogenome. The mitogenome also showed a bias towards A + T content (61.87%) and had negative AT-skew (−0.039) and GC-skew (−0.209). All the PCGs employed the ATG, ATA, or ATT as the start codon and TAA, TAG, AGG, or single T as the stop codon. Additionally, all of the tRNAs displayed a typical cloverleaf secondary structure, except trnS1, which lacked the D arm. The phylogenetic analysis, based on the maximum likelihood (ML) and Bayesian inference (BI) methods, revealed that Rhacophoridae could be classified into four monophyletic genera. The phylogenetic status of P. braueri was closely related to that of Polypedates megacephalus and Polypedates leucomystax. Additionally, selective pressure analysis suggested that COX1 and ND1 were highly efficient for discriminating closely related species in the genus Polypedates, while ND4L was the most appropriate marker for population-level genetic analyses. The diversification of the Polypedates commenced during the Late Oligocene and extended into the Miocene. The present study provides valuable genomic information on P. braueri and new insights into the phylogenetic relationships of Rhacophoridae. Full article

Background and Clinical Significance: Mycotic aortic aneurysm is a rare but life-threatening vascular condition characterized by infection-induced dilation or pseudoaneurysm formation in the aorta. The condition carries a high risk of rupture and mortality, especially in individuals with underlying cardiovascular disease, who have undergone recent vascular procedures, or with immunocompromising comorbidities such as diabetes. Its diagnosis is challenging due to its non-specific symptoms and often requires a high index of suspicion, especially in patients presenting with persistent fever and negative initial imaging. Early recognition and intervention are critical, as delayed treatment significantly worsens outcomes. Case Presentation: A 68-year-old male with a history of coronary artery disease, recent stent placement, and hypertension presented with two days of fever, chills, rigors, and a mild nonproductive cough. The laboratory findings were only significant for leukocytosis. The initial chest X-ray and non-contrast CT scans were unremarkable. He was admitted for presumed pneumonia and started on intravenous antibiotics. Persistent fever prompted further investigation with contrast-enhanced CT, which revealed a distal-aortic-arch pseudoaneurysm and mild mediastinal stranding. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Transthoracic echocardiogram was negative for endocarditis. The patient was transferred to a tertiary center, where repeat imaging confirmed a 1.5 cm pseudoaneurysm and a 4 mm penetrating atherosclerotic ulcer. After multidisciplinary assessment, he underwent thoracic endovascular aortic repair (TEVAR) and completed four weeks of intravenous cefazolin. Follow-up imaging showed successful aneurysm repair with no complications. Conclusions: Thoracic mycotic aneurysm is a rapidly fatal entity despite intervention. High clinical suspicion is necessary given its non-specific presentation. It is diagnosed most practically using CTA. In addition to antibiotics, TEVAR is gaining traction as a feasible and a safe alternative to open surgical repair (OSR). Full article

A simple Lagrangian travelling slice model has been successfully used to predict the relations between the process parameters and the strand temperatures in the continuous casting of steel. The present paper aims to include a simple macrosegregation, grain structure and mechanical stress and deformation model on top of the thermal slice framework. The basis of all the mentioned models is the slice heat-conduction model that considers the complex heat extraction mechanisms in the mould, with the sprays, rolls, and through radiation. Its main advantage is the fast calculation time, which is suitable for the online control of the caster. The macroscopic thermal and species transfer models are based on the continuum mixture theory. The macrosegregation model is based on the lever rule microsegregation model. The thermal conductivity and species diffusivity of the liquid phase are artificially enhanced to consider the convection of the melt. The grain structure model is based on cellular automata and phase-field concepts. The calculated thermal field is used to estimate the thermal contraction of the solid shell, which, in combination with the metallostatic pressure, drives the elastic-viscoplastic solid-mechanics models. The solution procedure of all the models is based on the meshless radial basis function generated finite difference method on the macroscopic scale and the meshless point automata concept on the grain structure scale. Simulation results point out the areas susceptible to hot tearing. Full article

With the increasing demand for green materials, natural fiber-reinforced composites have garnered significant attention due to their environmental benefits and cost-effectiveness. However, the weak interfacial bonding between flax fibers and resin matrices limits their broader application. This study systematically investigates the interfacial properties of single-ply and double-ply flax yarn-reinforced epoxy resin composites, focusing on interfacial shear strength (IFSS) and its influencing factors. Pull-out tests were conducted to evaluate the mechanical behavior of yarns under varying embedded lengths, while scanning electron microscopy (SEM) was employed to characterize interfacial failure modes. Critical embedded lengths were determined as 1.49 mm for single-ply and 2.71 mm for double-ply configurations. Results demonstrate that the tensile strength and elastic modulus of flax yarns decrease significantly with increasing gauge length. Single-ply yarns exhibit higher IFSS (30.90–32.03 MPa) compared to double-ply yarns (20.61–25.21 MPa), attributed to their tightly aligned fibers and larger interfacial contact area. Single-ply composites predominantly fail through interfacial debonding, whereas double-ply composites exhibit a hybrid failure mechanism involving interfacial separation, fiber slippage, and matrix fracture, caused by stress inhomogeneity from their multi-strand twisted structure. The study reveals that interfacial failure originates from the incompatibility between hydrophilic fibers and hydrophobic resin, coupled with stress concentration effects induced by the yarn’s multi-level hierarchical structure. These findings provide theoretical guidance for optimizing interfacial design in flax fiber composites to enhance load-transfer efficiency, advancing their application in lightweight, eco-friendly materials. Full article

Acute lymphoblastic leukemia (ALL) represents the most common type of cancer in the pediatric population. The (1;19)(q23;p13) translocation is a primary chromosomal abnormality present in 3–12% of ALL cases. The current study aims to develop a label-free innovative nanodevice for the ultrasensitive diagnosis of the TCF3-PBX1 chimeric oncogene, featuring simplified operation and rapid analysis using minimal sample volumes, which positions it as a superior alternative for clinical diagnostics and early leukemia identification. The biosensor system was engineered on a nanostructured platform composed of polypyrrole (PPy) and a novel chemically functionalized hybrid nanocomposite of platinum nanospheres and titanium dioxide nanoparticles (TiO₂@Pt). Single-stranded oligonucleotide sequences were chemically immobilized on the nanoengineered transducer to enable biospecific detection. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), ultraviolet-visible spectroscopy (UV-Vis), and atomic force microscopy (AFM) were used to characterize each stage of the biotechnological device fabrication process. The analytical properties of the sensing tool were explored using recombinant plasmids containing the TCF3-PBX1 oncogenic sequence and clinical specimens from pediatric patients with B-cell ALL. After exposing the molecular monitoring system to the genetic target, significant variations were observed in the voltammetric oxidation current (∆I = 33.08% ± 0.28 to 124.91% ± 17.08) and in the resistance to charge transfer (ΔR_CT = 19.73% ± 0.96 to 83.51% ± 0.84). Data analysis revealed high reproducibility, with a relative standard deviation of 3.66%, a response range from 3.58 aM to 357.67 fM, a detection limit of 19.31 aM, and a limit of quantification of 64.39 aM. Therefore, a novel nanosensor for multiparametric electrochemical screening of the TCF3-PBX1 chimeric oncogene was described for the first time, potentially improving the quality of life for leukemic patients. Full article

HIV mother-to-child transmission (MTCT) continues to pose a significant public health challenge, especially in regions with limited resources, although the worldwide distribution of antiretroviral therapy (ART) has drastically lowered the risk of vertical transmission to even below 1% in some regions. There are still uncertainties regarding the safety of some ART regimens during pregnancy and their longer-term effects on infants who are perinatally exposed to HIV but remain uninfected. This review explores current evidence regarding the interplay between maternal HIV infection, ART during pregnancy, and both maternal and pediatric outcomes. Particular attention is given to the risk/benefit ratio surrounding different drug classes, with integrase inhibitors seeming promising choices in MTCT due to their rapid viral suppression and favorable safety profiles. Meanwhile, regimens containing protease inhibitors or nucleoside reverse transcriptase inhibitors have been linked to some adverse outcomes such as low birth weight, growth restriction, and potential mitochondrial or metabolic disturbances. Although ART remains central in preventing MTCT, a deeper understanding of its effects on fetal development and postnatal health is needed, and it should be thoroughly monitored through future research and longitudinal surveillance. Full article

Since the initial use of biological ion channels to detect single-stranded genomic base pair differences, label-free and highly sensitive resistive pulse sensing (RPS) with nanopores has made remarkable progress in single-molecule analysis. By monitoring transient ionic current disruptions caused by molecules translocating through a nanopore, this technology offers detailed insights into the structure, charge, and dynamics of the analytes. In this work, the RPS platforms based on biological, solid-state, and other sensing pores, detailing their latest research progress and applications, are reviewed. Their core capability is the high-precision characterization of tiny particles, ions, and nucleotides, which are widely used in biomedicine, clinical diagnosis, and environmental monitoring. However, current RPS methods involve bottlenecks, including limited sensitivity (weak signals from sub-nanometer targets with low SNR), complex sample interference (high false positives from ionic strength, etc.), and field consistency (solid-state channel drift, short-lived bio-pores failing POCT needs). To overcome this, bio-solid-state fusion channels, in-well reactors, deep learning models, and transfer learning provide various options. Evolving into an intelligent sensing ecosystem, RPS is expected to become a universal platform linking basic research, precision medicine, and on-site rapid detection. Full article