On-Surface Synthesis of Organolanthanide Sandwich Complexes.

The synthesis of lanthanide-based organometallic sandwich compounds is very appealing regarding their potential for single-molecule magnetism. Here, it is exploited by on-surface synthesis to design unprecedented lanthanide-directed organometallic sandwich complexes on Au(111). The reported compounds consist of Dy or Er atoms sandwiched between partially deprotonated hexahydroxybenzene molecules, thus introducing a distinct family of homoleptic organometallic sandwiches based on six-membered ring ligands. Their structural, electronic, and magnetic properties are investigated by scanning tunneling microscopy and spectroscopy, X-ray absorption spectroscopy, X-ray linear and circular magnetic dichroism, and X-ray photoelectron spectroscopy, complemented by density functional theory-based calculations. Both lanthanide complexes self-assemble in close-packed islands featuring a hexagonal lattice. It is unveiled that, despite exhibiting analogous self-assembly, the erbium-based species is magnetically isotropic, whereas the dysprosium-based compound features an in-plane magnetization.

Demographics aspects of brain and spine metastatic melanoma. Retrospective analysis in a single third-level center.

Background: Melanoma metastases to the CNS rank third in frequency, just after lung and breast metastases. There is controversy regarding the factors predisposing to developing CNS metastases in patients with cutaneous melanoma and their survival with conventional treatments. Methods: We carried out a retrospective analysis in a third-level hospital in Mexico to determine epidemiological aspects of melanoma metastases to the central nervous system, factors related to its appearance, clinical presentation, and survival in three treatment groups: surgery, radiotherapy, and conservative management. Results: We found that the nodular variant has the most significant association with CNS metastases. In addition, the superficial spreading variant has the highest risk of presenting a more substantial number of lesions, up to seven for each case and predominantly in the infratentorial space. On the other hand, we found more remarkable survival in patients treated only with surgery than those treated with radiotherapy or conservatively. Conclusions: This study lays the foundations for future prospective survival analysis of the different current treatment modalities for metastatic melanoma in the brain and spine. It also highlights the clinical risk factors for metastatic brain and spine tumors of melanoma.

Characterisation of experimental flowable composites containing fluoride-doped calcium phosphates as promising remineralising materials.

OBJECTIVE: Remineralising composites with antibacterial properties may seal the cavity and prevent secondary caries. This study aimed at developing experimental flowable composites containing different concentrations of fluoride-doped calcium phosphate fillers and evaluating their remineralising and antibacterial properties. METHODS: Experimental resin-based composites containing different concentrations (0-20 %) of fluoride-doped calcium phosphate fillers (VS10/VS20) were formulated. The release of calcium (Ca), phosphate (PO) and fluoride (F) ions was assessed for 30 days. Remineralisation properties were evaluated through ATR-FTIR and SEM/EDX after storage in simulated body fluid (SBF). The metabolic activity and viability of Streptococcus gordonii was also evaluated through ATP, CFU and live/dead confocal microscopy. The evaluation of specific monomer elution from the experimental composites was conducted using high-performance liquid chromatography (HPLC). RESULTS: The composites containing VS10 showed the highest release of Ca, those containing VS20 released more F over time (p < 0.05), while there was no significant difference in terms of PO ions release between the groups (p > 0.05). A quick 7-day mineral precipitation was observed in the tested composites containing VS10 or VS20 at 10 %; these materials also showed the greatest antibacterial activity (p < 0.05). Moreover, the tested composites containing VS10 presented the lowest elution of monomers (p < 0.05). CONCLUSIONS: Innovative composites were developed with low monomers elution, evident antibacterial activity against S. gordonii and important remineralisation properties due to specific ions release. CLINICAL SIGNIFICANCE: Novel composites containing fluoride-doped calcium phosphates may be promising to modulate bacteria growth, promote remineralisation and reduce the risk of cytotoxicity related to monomers' elution.

Assessment of hemostasis in hyperthyroid and euthyroid cats using two viscoelastic assays and platelet aggregometry.

BACKGROUND: Hyperthyroidism in humans is associated with a hypercoagulable state and an increased risk of thromboembolism. OBJECTIVE: To evaluate hemostatic variables in hyperthyroid and euthyroid cats with the hypothesis that hyperthyroid cats will have evidence of altered hemostasis consistent with a potential hypercoagulable state. ANIMALS: Client-owned hyperthyroid (n = 16) and euthyroid (n = 15) cats over 8 years of age. METHODS: Prospective observational study. Hyperthyroid and euthyroid cats were enrolled. Rotational thromboelastometry (ROTEM), whole-blood platelet impedance aggregometry (WBPIA) and a point-of-care viscoelastic coagulation monitor (VCM-Vet) were performed immediately after minimally traumatic venipuncture under sedation. RESULTS: Hyperthyroid cats had significantly higher values for variables as assessed by VCM-Vet: A10 (34 [17-47] vs 25 [17-38], P = .003); A20 (39.5 [23-55] vs 31 [21-45], P = .003); and MCF (41 [24-58] vs 35 [22-49], P = .03). Hyperthyroid cats had significantly different values versus the euthyroid cohort as assessed by different ROTEM channels: increased A10, INTEM (61.5 [39-75] vs 54 [23-66], P = .007) and FIBTEM (18 [10-35] vs 13 [2-27], P = .01); increased A20, INTEM (68 [45-78] vs 61 [30-70], P = .006) and FIBTEM (17 [10-34] vs 11 [2-25], P = .002); increased MCF, EXTEM (72 [65-81] vs 69 [34-78], P = .04), INTEM (70 [45-85] vs 62 [35-71], P = .01) and FIBTEM (18 [13-37] vs 14 [3-27], P = .02); increased alpha angle, EXTEM (80 [68-85] vs 76 [41-84], P = .01); shortened CT, EXTEM (52.5 [29-73] vs 60 [52-92], P = .003) and FIBTEM (52.5 [16-75] vs 65 [53-165], P = .001); and decreased ML, FIBTEM (20 [1-36] vs 33 [19-59], P <.001). No significant differences were found with WBPIA. CONCLUSIONS AND CLINICAL IMPORTANCE: The hyperthyroid cats in this study had evidence of altered hemostasis as assessed by 2 viscoelastic methodologies, and characterized by increased clot amplitude, firmness, and faster coagulation times vs euthyroid controls.

Survival Impact of Combined Biguanide and Temozolomide in Glioblastoma Preclinical Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Glioblastoma (GBM) is an aggressive tumor known for its poor prognosis. Despite extensive research into its molecular and clinical aspects, the current management strategies have shown limited efficacy in improving survival rate. Despite some preclinical studies exploring the combination of temozolomide (TMZ) with biguanides such as metformin (MET) and others, the potential benefits of this combination remain uncertain. The aim of this study is to evaluate the overall survival (OS) in GBM murine-models treated with a combination of TMZ + biguanide compared to those treated with TMZ alone. METHODS: We systematically searched Medline, Embase, and Lilacs databases for studies comparing TMZ + biguanide versus TMZ alone in GBM models and reporting OS data. The mean difference (MD) with 95% confidence interval and random-effects model was adopted. RESULTS: Nine studies were included in this systematic review. The meta-analysis comprised 6 studies involving 85 rat-models, with 45 subjects undergoing combined-treatment. GBM-murine models treated with TMZ + biguanide exhibited notably superior OS rates compared to those who received TMZ alone, showing an MD of 21.0 days (6.9-35.0). Within the subgroup of orthotopic models, the OS was also significantly better in combination-therapy with an MD of 23.7 days (6.5-40.9). Similarly, in the subgroup where MET was used as biguanide therapy, TMZ + MET demonstrated a significant increase in OS, with an MD of 27.4 days (6.0-48.8). In immunocompromised models, the combination-therapy also exhibited higher survival rates, with an MD of 13 days (9.4-16.6). CONCLUSIONS: This systematic review and meta-analysis provide compelling evidence regarding the beneficial effects of TMZ + biguanide in GBM models compared with TMZ alone, resulting in a significant improvement in OS.

Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.

The metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown. Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneoplastic detection, and challenging endoscopic resection make the identification of their metabolic requirements a priority. Here, we demonstrate that the phosphorylation of SCAP by the atypical PKC (aPKC), PKCλ/ι promotes its degradation and inhibits the processing and activation of SREBP2, the master regulator of cholesterol biosynthesis. We show that the upregulation of SREBP2 and cholesterol by reduced aPKC levels is essential for controlling metaplasia and generating the most aggressive cell subpopulation in serrated tumors in mice and humans. Since these alterations are also detected prior to neoplastic transformation, together with the sensitivity of these tumors to cholesterol metabolism inhibitors, our data indicate that targeting cholesterol biosynthesis is a potential mechanism for serrated chemoprevention.

Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

2D Co-Directed Metal-Organic Networks Featuring Strong Antiferromagnetism and Perpendicular Anisotropy.

Antiferromagnetic spintronics is a rapidly emerging field with the potential to revolutionize the way information is stored and processed. One of the key challenges in this field is the development of novel 2D antiferromagnetic materials. In this paper, the first on-surface synthesis of a Co-directed metal-organic network is reported in which the Co atoms are strongly antiferromagnetically coupled, while featuring a perpendicular magnetic anisotropy. This material is a promising candidate for future antiferromagnetic spintronic devices, as it combines the advantages of 2D and metal-organic chemistry with strong antiferromagnetic order and perpendicular magnetic anisotropy.

Information in feedback ratchets.

Feedback control uses the state information of the system to actuate on it. The information used implies an effective entropy reduction of the controlled system, potentially increasing its performance. How to compute this entropy reduction has been formally shown for a general system and has been explicitly computed for spatially discrete systems. Here, we address a relevant example of how to compute the entropy reduction by information in a spatially continuous feedback-controlled system. Specifically, we consider a feedback flashing ratchet, which constitutes a paradigmatic example for the role of information and feedback in the dynamics and thermodynamics of transport induced by the rectification of Brownian motion. A Brownian particle moves in a periodic potential that is switched on and off by a controller. The controller measures the position of the particle at regular intervals and performs the switching depending on the result of the measurement. This system reaches a long-time dynamical regime with a nonzero mean particle velocity, even for a symmetric potential. Here, we calculate the efficiency at maximum power in this long-time regime, computing all the required contributions. We show how the entropy reduction can be evaluated from the entropy of the non-Markovian sequence of control actions, and we also discuss the required sampling effort for its accurate computation. Moreover, the output power developed by the particle against an external force is investigated, which-for some values of the system parameters-is shown to become larger than the input power provided by the switching of the potential. The apparent efficiency of the ratchet thus becomes higher than one, if the entropy reduction contribution is not considered. This result highlights the relevance of including the entropy reduction by information in the thermodynamic balance of feedback-controlled devices, specifically when writing the second principle. The inclusion of the entropy reduction by information leads to a well-behaved efficiency over all the range of parameters investigated.

High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population.

Purpose: Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%-90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics. Methods: A total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively. Results: WNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants. Conclusion: We observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.

[Depression and anxiety among medical students in virtual education during COVID-19 pandemic]. / Depresión y ansiedad en estudiantes de medicina en la educación virtual durante la pandemia por COVID-19.

Background: The lockdown derived from the declaration of a pandemic due to SARS-CoV-2 in March 2020 by the World Health Organization altered daily activities, including the academic ones, which were adapted to virtuality. In Ecuador, the new modality of study had an increase in the use of electronic devices that triggered new problems. Objective: To stablish the prevalence of depression and anxiety among medical students from the Universidad Central del Ecuador (Central University of Ecuador) in virtual education during the COVID-19 pandemic. Material and methods: Cross-sectional analytic study conducted between June and July of 2021 in students from first to tenth semester during virtual education. All studied subjects were evaluated using an electronic survey, depression and anxiety variables were assessed with the BDI-II and GAD-7 scales, respectively. In addition, sociodemographic data were collected, including the family APGAR. A response rate of 63.3% (1528 students) was obtained. Results: Overall prevalence of depression was 37.8% and the prevalence of anxiety 30.3%. Lower-years students were the most affected by these pathologies. The protective factors found were physical activity and psychological support in religion, whereas the main risk factors found were a dysfunctional family, lack of an exclusive study space and low academic performance. Furthermore, the frequency of depression and anxiety was significantly higher in women. Conclusion: The virtual modality showed a high prevalence of depression and anxiety in medical students.

Introducción: el confinamiento derivado de la declaración de pandemia por SARS-CoV-2 en marzo de 2020 por la Organización Mundial de la Salud alteró las actividades diarias, incluidas las académicas, que se adaptaron a la virtualidad. En Ecuador, la nueva modalidad de estudio tuvo un aumento del uso de dispositivos electrónicos que desencadenó nuevos problemas. Objetivo: determinar la prevalencia de depresión y ansiedad en estudiantes de medicina de la Universidad Central del Ecuador en el ciclo de educación virtual durante la pandemia por COVID-19. Material y métodos: estudio analítico transversal realizado entre junio y julio de 2021 en estudiantes de medicina de primero a décimo semestre durante la educación virtual. Por medio de una encuesta electrónica enviada a todos los sujetos de estudio, se evaluaron las variables depresión y ansiedad mediante las escalas BDI-II y GAD-7 respectivamente. Además, se recopilaron datos sociodemográficos, incluido el APGAR familiar. Se obtuvo una tasa de respuesta del 63.3% (1528 estudiantes). Resultados: la prevalencia de depresión fue de 37.8% y la de ansiedad 30.3%. Los estudiantes de años inferiores fueron los más afectados. Los factores protectores fueron la actividad física y el apoyo psicológico en la religión, mientras que los factores de riesgo fueron tener una familia disfuncional, la ausencia de un espacio exclusivo de estudio y un bajo rendimiento académico. Asimismo, la frecuencia de depresión y ansiedad fue significativamente superior en mujeres. Conclusión: durante la modalidad virtual se observó una alta prevalencia de sintomatología de depresión y ansiedad en estudiantes de medicina.

Short-term dietary intervention improves endothelial dysfunction induced by high-fat feeding in mice through upregulation of the AMPK-CREB signaling pathway.

AIM: In addition to functioning as an energy sensor switch, AMPK plays a key role in the maintenance of cardiovascular homeostasis. However, obesity disrupts AMPK signaling, contributing to endothelial dysfunction and cardiovascular disease. This study aimed to elucidate if a short-term dietary intervention consisting in replacing the high-fat diet with a standard diet for 2 weeks could reverse obesity-induced endothelial dysfunction via AMPK-CREB activation. METHODS: For this, 5-week-old male C57BL6J mice were fed a standard (Chow) or a high-fat (HF) diet for 8 weeks. The HF diet was replaced by the chow diet for the last 2 weeks in half of HF mice, generating 3 groups: Chow, HF and HF-Chow. Vascular reactivity and western-blot assays were performed in the thoracic aorta. RESULTS: Returning to a chow diet significantly reduced body weight and glucose intolerance. Relaxant responses to acetylcholine and the AMPK activator (AICAR) were significantly impaired in HF mice but improved in HF-Chow mice. The protein levels of AMPKα, p-CREB and antioxidant systems (heme oxygenase-1 (HO-1) and catalase) were significantly reduced in HF but normalized in HF-Chow mice. CONCLUSION: Improving dietary intake by replacing a HF diet with a standard diet improves AMPK-mediated responses due to the upregulation of the AMPK/CREB/HO-1 signaling pathway.

Variation in Susceptibility to Downy Mildew Infection in Spanish Minority Vine Varieties.

Downy mildew is one of the most destructive diseases affecting grapevines (Vitis vinifera L.). Caused by the oomycete Plasmopara viticola (Berk. and Curt.) Berl. and de Toni, it can appear anywhere where vines are cultivated. It is habitually controlled by the application of phytosanitary agents (copper-based or systemic) at different stages of the vine growth cycle. This, however, is costly, can lead to reduced yields, has a considerable environmental impact, and its overuse close to harvest can cause fermentation problems. All grapevines are susceptible to this disease, although the degree of susceptibility differs between varieties. Market demands and European legislation on viticulture and the use of phytosanitary agents (art. 14 of Directive 128/2009/EC) now make it important to know the sensitivity of all available varieties, including minority varieties. Such knowledge allows for a more appropriate use of phytosanitary agents, fosters the commercial use of these varieties and thus increases the offer of wines associated with different terroirs, and helps identify material for use in crop improvement programmes via crossing or genetic transformation, etc. Over 2020-2021, the susceptibility to P. viticola of 63 minority vine varieties from different regions of Spain was examined in the laboratory using the leaf disc technique. Some 87% of these varieties were highly susceptible and 11% moderately susceptible; just 2% showed low susceptibility. The least susceptible of all was the variety Morate (Madrid, IMIDRA). Those showing intermediate susceptibility included the varieties Sanguina (Castilla la Mancha, IVICAM), Planta Mula (Comunidad Valenciana, ITVE), Rayada Melonera (Madrid, IMIDRA), Zamarrica (Galicia, EVEGA), Cariñena Roja (Cataluña, INCAVI), Mandrègue (Aragón, DGA) and Bastardo Blanco (Extremadura, CICYTEX). The highly susceptible varieties could be differentiated into three subgroups depending on sporulation severity and density.

Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity.

The angiotensin II type 2 receptor (AT2R) exerts vasorelaxant, anti-inflammatory, and antioxidant properties. In obesity, its activation counterbalances the adverse cardiovascular effects of angiotensin II mediated by the AT1R. Preliminary results indicate that it also promotes brown adipocyte differentiation in vitro. Our hypothesis is that AT2R activation could increase BAT mass and activity in obesity. Five-week-old male C57BL/6J mice were fed a standard or a high-fat (HF) diet for 6 weeks. Half of the animals were treated with compound 21 (C21), a selective AT2R agonist, (1 mg/kg/day) in the drinking water. Electron transport chain (ETC), oxidative phosphorylation, and UCP1 proteins were measured in the interscapular BAT (iBAT) and thoracic perivascular adipose tissue (tPVAT) as well as inflammatory and oxidative parameters. Differentiation and oxygen consumption rate (OCR) in the presence of C21 was tested in brown preadipocytes. In vitro, C21-differentiated brown adipocytes showed an AT2R-dependent increase of differentiation markers (Ucp1, Cidea, Pparg) and increased basal and H+ leak-linked OCR. In vivo, HF-C21 mice showed increased iBAT mass compared to HF animals. Both their iBAT and tPVAT showed higher protein levels of the ETC protein complexes and UCP1, together with a reduction of inflammatory and oxidative markers. The activation of the AT2R increases BAT mass, mitochondrial activity, and reduces markers of tissue inflammation and oxidative stress in obesity. Therefore, insulin reduction and better vascular responses are achieved. Thus, the activation of the protective arm of the renin-angiotensin system arises as a promising tool in the treatment of obesity.

USP15-USP7 Axis and UBE2T Differential Expression May Predict Pathogenesis and Poor Prognosis in De Novo Myelodysplastic Neoplasm.

The aim of this study was to evaluate the expression of USP7, USP15, UBE2O, and UBE2T genes in Myelodysplastic neoplasm (MDS) to identify possible targets of ubiquitination and deubiquitination in MDS pathobiology. To achieve this, eight datasets from the Gene Expression Omnibus (GEO) database were integrated, and the expression relationship of these genes was analyzed in 1092 MDS patients and healthy controls. Our results showed that UBE2O, UBE2T, and USP7 were upregulated in MDS patients compared with healthy individuals, but only in mononucleated cells collected from bone marrow samples (p < 0.001). In contrast, only the USP15 gene showed a downregulated expression compared with healthy individuals (p = 0.03). Additionally, the upregulation of UBE2T expression was identified in MDS patients with chromosomal abnormalities compared with patients with normal karyotypes (p = 0.0321), and the downregulation of UBE2T expression was associated with MDS hypoplastic patients (p = 0.033). Finally, the USP7 and USP15 genes were strongly correlated with MDS (r = 0.82; r2 = 0.67; p < 0.0001). These findings suggest that the differential expression of the USP15-USP7 axis and UBE2T may play an important role in controlling genomic instability and the chromosomal abnormalities that are a striking characteristic of MDS.

Comparison of the Antibacterial Effect of Silver Nanoparticles and a Multifunctional Antimicrobial Peptide on Titanium Surface.

Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) were used to coat titanium surfaces. The modulation of the nanoparticle (≈32.1 ± 9.4 nm) density on titanium could be optimized, and a sequential functionalization with both agents was achieved through a two-step functionalization method by means of surface silanization. The antibacterial character of the coating agents was assessed individually as well as combined. The results have shown that a reduction in bacteria after 4 h of incubation can be achieved on all the coated surfaces. After 24 h of incubation, however, the individual antimicrobial peptide coating was more effective than the silver nanoparticles or their combination against Staphylococcus aureus. All tested coatings were non-cytotoxic for eukaryotic cells.

Lanthanide metal-organic network featuring strong perpendicular magnetic anisotropy.

The coordination of lanthanides atoms in two-dimensional surface-confined metal-organic networks is a promising path to achieve an ordered array of single atom magnets. These networks are highly versatile with plenty of combinations of molecular linkers and metallic atoms. Notably, with an appropriate choice of molecules and lanthanide atoms it should be feasible to tailor the orientation and intensity of the magnetic anisotropy. However, up to now only tilted and almost in-plane easy axis of magnetizations were reported in lanthanide-based architectures. Here we introduce an Er-directed two-dimensional metallosupramolecular network on Cu(111) featuring strong out-of-plane magnetic anisotropy. Our results will contribute to pave avenues for the use of lanthanides in potential applications in nanomagnetism and spintronics.

Discrepancy in transcriptomic profiling between CD34 + stem cells and primary bone marrow cells in myelodysplastic neoplasm.

Differentially expressed genes (DEGs) biomarkers can be used to help diagnose and monitor the disease, as well as to determine which treatments are most effective. So, given the complexity of Myelodysplastic neoplasm (MDS), it is difficult to determine the impact and disparities of DEGs between CD34+ HSC (hematopoietic stem cells) or primary bone marrow cells (PBMC) in MDS pathogenesis, and therefore it remains largely unknown. Here, we performed an in-silico transcriptome analysis on CD34+ HSC and PBMC from 1092 MDS patients analyzing the divergences between differential gene expression patterns in these two cell types as potential pathogenic biomarkers for MDS. Initially, we observed a difference of 7117 expressed transcripts between PBMC (n = 40,165) and CD34 +HSC (n = 33,048). Also, we identified that CD34+ HSC and PBMC samples showed 240 and 2948 DEGs, respectively. In summary, we identified DEGs disparities in CD34+ HSC and PBMC cell types. However, there was a certain similarity of the activated pathways in both cellular samples based on Gene Ontology and KEGG pathways enrichment analyses. Our results provide novel insights into novel DEGs biomarkers to MDS pathogenesis with clinical significance. AVAILABILITY OF DATA AND MATERIALS: All microarray databases were obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). To evaluate the biological function of differentially expressed genes, the DAVID (Database for Annotation, Visualization and Integrated Discovery tool was used) (https://david.ncifcrf.gov/).

PD-L1 and MCL-1 markers and the relationship with prognostic characteristics of differentiated thyroid carcinoma.

OBJECTIVES: MCL-1 and PD-L1 proteins are related to carcinogenesis mechanisms in differentiated thyroid carcinoma(DTC). Tumor antigens stimulate the expression of PD-1 in immune cells, which binds to PD-L1 of tumor cells, inducing immune escape from the tumor. MCL-1, an anti-apoptotic member of the BCL-2 family, is necessary for the survival of T and B lymphocytes and has a high oncogenic potential. We aim to evaluate the clinical utility and relevance of MCL-1 and PD-L1 in the long-term prognosis of DTC. METHODS: 120 DTC patients after total thyroidectomy and radioiodine therapy followed for a minimum of 2 years were included. Demographic features, tumor histopathology, persistence/recurrence risk, factors associated with outcome, initial response to therapy, persistence or disease-free at the follow-up were related to MCL-1 and PD-L1 immunohistochemical expression and BRAFV600E mutation. RESULTS: 100(83.3%) were women, 46.64 ± 16.73 years old at diagnosis; 37(30.8%) patients were at high, 45(37.5%) of intermediate and 38(31.7%) of low disease recurrence/persistence risk. At the end of follow-up of 124.86 ± 65.36 months, 48(42.5%) had persistent disease. 103(85.8%) patients had papillary thyroid carcinoma (PTC), 17(14.2%) follicular thyroid carcinoma (FTC). In PTC, moderate/strong PD-L1 and MCL-1 expressions were associated to BRAFV600E (p=0.0467; p=0.0044). PD-L1 was also associated with tall cell subtype (p=0.0274). In FTC, weak PD-L1 expression was associated to the largest nodule diameter (p=0.0100). Strong/moderate PD-L1 expression was associated to T2 and the weak expression with T3 in TNM classification (p=0.0490). Moderate MCL-1 expression was associated to smoking (p=0.0350). CONCLUSIONS: PDL-1, marker of progression of tumor cells and MCL-1, anti-apoptotic marker, were associated with PTC carrying BRAFV600E mutation, while PDL-1 was associated with more aggressive PTC subtype. MCL-1 and PD-L1 could be useful in composing a panel to assess the prognosis of PTC patients. On the other hand, both markers seemed to have lower relevance to FTC patients.

Crop forcing technique and irrigation strategy modified the content and phenolic profile of cv. Tempranillo grape berries grown in a semi-arid climate.

BACKGROUND: Climate change modifies the content and phenolic profiles of grapes and wines. It is known that high temperatures, related to climate change, reduce anthocyanins and procyanidin (catechin and tannin) compounds accumulated in the berries. In recent years, with the aim of improving the phenolic composition of the berries, the technique of crop forcing has been proposed to delay grape ripening to a more favourable period of temperatures. RESULTS: In this study, crop forcing was applied to cv. Tempranillo vines on two different dates, after flowering (F1) and after fruit set (F2), and compared to a treatment control (NF, without forcing). Additionally, as a secondary factor, two irrigation strategies were established in each treatment: irrigation with no water stress, and a pre-veraison deficit irrigation. The study was carried out in three consecutive years (2017-2019). For most of the parameters analysed, no interaction was found. Therefore, for these parameters, the effect of each of these techniques was investigated independently. Regardless of the irrigation strategy, F2 berries achieved higher contents of catechins and anthocyanins than NF berries. Each year, regardless of the irrigation strategy, crop forcing increased the content of monoglucoside forms, and had a positive effect on the total content of malvidin, petunidin, delphinidin, peonidin and malvidin derivatives, but only affected acetyl and coumaryl forms in 2017. However, the effect of irrigation strategy was less significant and consistent, being more dependent on the vintage. CONCLUSION: Regardless of vine water status, crop forcing technique applied after fruit set could be used by vine growers to delay ripening of the grapes and thus achieve an increase in the anthocyanin characteristics of the grapes. © 2023 Society of Chemical Industry.