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Abstract Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by COL18A1, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between COL18A1/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure–volume loops in patients with PAH to assess RV–pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV–pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased COL18A1/ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1/ES increases early in disease development in the RV and implicates COL18A1/ES in pathologic RV dysfunction in PAH.

  Achieving adequate integration and success at school in the post-compulsory stages involving situations where there is a risk of social exclusion is a real identity challenge for adolescents. In this research, we used a convenience sampling and selected two high schools located in Areas in Need of Social Transformation in Seville (southern Spain). We studied the learner identity of all their students in the first and second grade of secondary post-compulsory education ( N  = 70). These students present a trajectory of resilience, as they remained in the education system despite facing many difficulties. In this exploratory research, their identity as learners was analysed through an interview applied in a focus group format ( N  = 12), where their supports, strengths and psycho-social obstacles that facilitate/hinder their stay in the education system in the post-compulsory stage were also identified. Results show that adolescents have a good attitude towards academic training, based on the conviction that, in the future, they will be able to achieve a higher quality of life and a rapid insertion in skilled jobs. The image students have of themselves combines a negative perception of their lack of work habits, the difficulty of self-regulation and the little effort made, with a more positive view of their agency in the process, highlighting their intellectual and academic capacity and their effort when they set out to do so. Family, teachers and peers play a role in the resilience and identity construction of the adolescents, through protecting them, developing positive perceptions and expectations, stimulating control and effort and attributing successes and failures to students. Programmes based on the participation of the target group are essential for the design and improvement of psychosocial intervention programmes in these contexts.

The development of newfangled bioprocess strategies for the capture of C1-gases (CO and CO 2 ) and their bioconversion into valuable products is currently one of the main focuses of research in order to achieve a more resilient world. This work analyses the viability of the co-culture C. carboxidivorans and C. beijerinkii to produce bioproducts (bioalcohols and organic acids) in mixotrophic conditions. In this way, the bioconversion of C1 gases (CO and CO 2 ), in the presence of Fe 0 , using mixotrophic co-culture fermentation by C. carboxidivorans and C. beijerinkii , was evaluated, analyzing the influence of the ratio between both microorganisms, the pH, and the presence of Fe 0 . As a result, up to 7 g/L of butanol were achieved at pH 7, 12.5 g/L Fe 0 , and using a 1:1 ratio of C. carboxidivorans : C. beijerinkii , also improving the production of ethanol, acetic acid, and butyric acid as compared to individual culture fermentations. Finally, the operation in a bioreactor, comparing discontinuous and continuous gas feeding operation modes, was also studied, with better C1-gases utilization and overall fermentation efficiency (7 vs 4.6 g/L butanol) in continuous gas operation mode. Highlights Mixotrophic co-cultures by C. carboxidivorans and C. beijerinkii in presence of Fe 0 Influence of microorganisms ratio, pH, and Fe 0 presence in mixotrophic co-cultures 7 g/L butanol (pH 7, 12.5 g/L Fe 0 ) by C. carboxidivorans : C. beijerinkii (1:1) Acceptable C1-gases use in biorreactor co-culture with continuous gas feeding Graphical Abstract

Renal cell carcinoma (RCC) is a heterogeneous malignancy influenced by genetic and environmental factors. Previous genome-wide association studies (GWAS) have identified risk single nucleotide polymorphisms (SNPs) associated with RCC susceptibility, particularly within genes such as , , , , and . These SNPs are in regions implicated in key cellular processes like calcium signaling, chromatin remodeling, hypoxia response and oncogenesis. These pathways are highly relevant to RCC pathogenesis, although the functional significance of these genetic variations in sporadic RCC remains insufficiently characterized. This study analyzed five GWAS-identified SNPs-rs1049380 and rs10771279 ( ), rs4903064 ( ), rs7579899 ( ), and rs35252396 ( )-in a Spanish case-control cohort comprising 168 RCC patients and 259 healthy controls. Genotyping was performed from buccal swabs, and gene expression levels were assessed in 33 paired formalin-fixed paraffin-embedded (FFPE) tumor and adjacent normal kidney tissue samples. Associations between SNPs, overall survival, and expression of quantitative trait loci (eQTLs) were evaluated in relation to RCC risk and RCC progression in the case of survival curves. The C/C genotype of rs10771279 was nominally associated with a protective effect (OR: 0.41), with higher expression observed in healthy tissues than in RCC. The C/C genotype of rs4903064 was nominally correlated with increased RCC risk (OR: 2.21) and higher expression, potentially linked to hypoxia-inducible pathways. Similarly, rs7579899 A/A genotype was nominally associated with RCC risk (OR: 1.78) While rs35252396 did not show susceptibility relation, both genes showed upregulated expression in RCC tissue. In survival analyses, the G allele of rs1049380 ( ) was significantly associated with reduced 5-year survival in metastic and non-metastatic patients. Additionally, the AC genotype of rs35252396 showed nominal associations with highest risk in 5-year survival models. This study provides independent evidence supporting the biological relevance of GWAS-identified loci in RCC. While several variants showed nominal associations with disease risk, rs1049380 emerged as a variant of potential prognostic relevance for five-year overall survival. Overall, these findings highlight the differential contribution of genetic variants to RCC susceptibility and progression and should be considered hypothesis-generating, warranting validation in larger, independent cohorts.

Iron (Fe) is commonly found in aluminum (Al), but its contents are usually kept as low as possible, because the formation of intermetallic phases may induce fracture. In this study, high-pressure torsion (HPT) was used to control the microstructure in an Al-2 %Fe alloy in conjunction with wire drawing and an aging treatment, in order to improve not only their mechanical properties but also the electrical conductivity. It is shown that HPT processing of ring-shaped samples produced ultrafine grains with a size of ~150 nm in the matrix, while intermetallic phases were fragmented to nanosizes with some Fe fraction dissolved in the matrix. Semi-rings were extracted from the HPT-processed samples and swaged to a round section with 0.4-mm diameter. The HPT-processed sample was successfully drawn to a final diameter of 0.08 mm (25:1 ratio, 96 % reduction in area), whereas the sample without HPT processing failed after drawing to 0.117-mm diameter (12:1 ratio, 91 % reduction in area). The electrical conductivity increased to ~65 IACS % in the HPT-processed rings and to ~54 IACS % in the wires by aging for 1 h after the drawing.

A cast Al-2 wt pct Fe alloy was processed by high-pressure torsion (HPT) at room temperature and then subjected to artificial aging at temperatures of 373 K and 473 K (100 °C and 200 °C). The aging behavior was studied by Vickers microhardness measurements and by microstructural analyses using transmission electron microscopy and X-ray diffraction. The initial intermetallic structures, composed of a mixture of Al + Al 6 Fe and Al + Al 3 Fe eutectics phases, were partially dissolved in the matrix up to a supersaturation of ~1 wt pct Fe. The microstructure was refined by HPT to an ultrafine-grained level with a minimum grain size of ~120 nm in the matrix and a dispersion of particles less than 400 nm. Age hardening was achieved within 0.25 hours at 473 K (200 °C), to a maximum UTS of ~700 MPa as a result of nano-sized precipitation within the ultrafine grains. The uniform elongation exceeded ~12 pct even at intermediate levels of imposed strain by HPT, while it decreased to ~6 pct with the subsequent aging treatment. The thermal stability of the ultrafine-grained structure was verified to exceed 16 days at 373 K (100 °C) and 12 hours at 473 K (200 °C).

Mg2Ni is a highly promising candidate for solid-state hydrogen storage due to its high storage capacity. However, its synthesis is challenging due to the high melting point of Ni (1455 °C) and the boiling point of Mg (1090 °C). In this study, elemental powder mixtures of Mg and 30 at% Ni were processed by high-pressure torsion (HPT) to synthesize the Mg2Ni intermetallic compound through mechanical methods. The formation of 11 wt% of Mg2Ni after 50 turns of HPT was confirmed by X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS), reaching a maximum of 59 wt% after 100 turns. Rietveld refinement confirmed a nanocrystalline size for the Mg2Ni phase synthesized via HPT. Hydrogenation tests showed that the Mg-Ni synthesized by HPT can absorb hydrogen at 350 °C even after several weeks of air exposure. Furthermore, a maximum absorption capacity of 3.8 wt% was reached after 20 h of hydrogen exposure for the sample with 100 turns. This capacity is close to the theoretical capacity of 3.9 wt% for this composition. The results confirm that combining HPT with subsequent heat treatment is an efficient strategy to increase the Mg2Ni fraction after HPT processing.

Al-Fe alloys in the form of thin disks 10 mm in diameter, with Fe nominal weight fractions of 0.5, 1, 2, and 5 pct, were extracted from bulk-extruded rods and processed by high-pressure torsion (HPT). A group of these bulk samples was processed in an as-received state, whereas another group was annealed at 773 K (500 °C) for a period of 1 hour, prior to the application of HPT. An additional set of samples was prepared by mixing high-purity powders with similar Fe contents and consolidated directly in the HPT facility. The samples were processed up to 10 revolutions. Vickers microhardness, tensile strength, and elongation to failure were evaluated for all cases along with observations of the Al matrix by transmission electron microscopy (TEM). Basic characterization of the microstructures was carried out by X-ray diffraction (XRD) and optical microscopy (OM). Significant strengthening with ductility retained was achieved in the bulk samples as a consequence of grain refinement and dispersion of intermetallic phases. Powder samples had a more gradual increase in strength but increased ductility as a result of the imposed strain.

This study is a comparison of the efficiency of three technologies used for Y chromosome capture and the next-generation sequencing (NGS) technologies applied for determining its whole sequence. Our main findings disclose that streptavidin–biotin magnetic particle-based capture methodology offers better and a deeper sequence coverage for Y chromosome capture, compared to chromosome sorting and microdissection procedures. Moreover, this methodology is less time consuming and the most selective for capturing only Y chromosomal material, in contrast with other methodologies that result in considerable background material from other, non-targeted chromosomes. NGS results compared between two platforms, NextSeq 500 and SOLID 5500xl, produce the same coverage results. This is the first study to explore a methodological comparison of Y chromosome capture and genetic analysis. Our results indicate an improved strategy for Y chromosome research with applications in several scientific fields where this chromosome plays an important role, such as forensics, medical sciences, molecular anthropology and cancer sciences.

Background: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly ( XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly ( PARP1 and major vault protein ( MVP )) involved in non-homologous end joining were examined in 494 Spanish PCa patients. Methods: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. Results: ( XRCC6 ) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26–3.29, P= 0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19–3.78, P= 0.011), higher Gleason score (OR=1.65, 95% CI 1.01–2.68, P= 0.044) and D’Amico higher risk tumors (OR=2.38, 95% CI 1.24–4.58, P= 0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the ( MVP ) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40–16.07, P= 0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D’Amico higher risk tumors (OR=3.33, 95% CI 1.56–7.17, P= 0.002). Conclusions: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.