Identification and Structural Characterization of Twisted Atomically Thin Bilayer Materials by Deep Learning.

Two-dimensional materials are expected to play an important role in next-generation electronics and optoelectronic devices. Recently, twisted bilayer graphene and transition metal dichalcogenides have attracted significant attention due to their unique physical properties and potential applications. In this study, we describe the use of optical microscopy to collect the color space of chemical vapor deposition (CVD) of molybdenum disulfide (MoS2) and the application of a semantic segmentation convolutional neural network (CNN) to accurately and rapidly identify thicknesses of MoS2 flakes. A second CNN model is trained to provide precise predictions on the twist angle of CVD-grown bilayer flakes. This model harnessed a data set comprising over 10,000 synthetic images, encompassing geometries spanning from hexagonal to triangular shapes. Subsequent validation of the deep learning predictions on twist angles was executed through the second harmonic generation and Raman spectroscopy. Our results introduce a scalable methodology for automated inspection of twisted atomically thin CVD-grown bilayers.

Kelp forest food webs as hot spots for the accumulation of microplastic and polybrominated diphenyl ether pollutants.

Kelp forests (KFs) are one of the most significant marine ecosystems in the planet. They serve as a refuge for a wide variety of marine species of ecological and economic importance. Additionally, they aid with carbon sequestration, safeguard the coastline, and maintain water quality. Microplastic (MP) and polybrominated diphenyl ethers (PBDEs) concentrations were analyzed across trophic levels in KFs around Todos Santos Bay. Spatial variation patterns were compared at three sites in 2021 and temporal change at Todos Santos Island (TSI) in 2021 and 2022. We analyzed these MPs and PBDEs in water, primary producers (Macrocystis pyrifera), grazers (Strongylocentrotus purpuratus), predators (Semicossyphus pulcher), and kelp detritus. MPs were identified in all samples (11 synthetic and 1 semisynthetic polymer) and confirmed using Fourier-transform infrared microspectroscopy-attenuated total reflectance (µ-FTIR-ATR). The most abundant type of MP is polyester fibers. Statistically significant variations in MP concentration were found only in kelps, with the greatest average concentrations in medium-depth kelps from TSI in 2022 (0.73 ± 0.58 MP g-1 ww) and in the kelp detritus from TSI in 2021 (0.96 ± 0.64 MP g-1 ww). Similarly, PBDEs were found in all samples, with the largest concentration found in sea urchins from Punta San Miguel (0.93 ± 0.24 ng g-1 ww). The similarity of the polymers can indicate a trophic transfer of MPs. This study shows the extensive presence of MP and PBDE subtropical trophic web of a KF, but correlating these compounds in environmental samples is highly complex, influenced by numerous factors that could affect their presence and behavior. However, this suggests that there is a potential risk to the systems and the services that KFs offer.

Changes in the expression of genes encoding xanthophyl acyltransferases during the postharvest ripening of avocado (Persea americana) fruit.

BACKGROUND: Avocado fruit is rich in xanthophylls, which have been related to positive effects on human health. Xanthophyl acetyltransferases (XATs) are enzymes catalyzing the esterification of carboxylic acids to the hydroxyl group of the xanthophyll molecule. This esterification is thought to increase the lipophilic nature of the xanthophyll and its stability in a lipophilic environment. Studies on XATs in fruits are very scarce, and no studies had been carried out in avocado fruit during postharvest. The objective of this work was to investigate the changes in the expression of genes encoding XAT, during avocado fruit ripening. RESULTS: Avocado fruits were obtained from a local market and stored at 15 °C for 8 days. The fruit respiration rate, ethylene production, and fruit peel's color space parameters (L*, a*, b*) were measured during storage. Fruit mesocarp samples were taken after 1, 3, 5, and 7 days of storage and frozen with liquid nitrogen. Total RNA was extracted from fruit mesocarp, and the quantification of the two genes designated as COGE_ID: 936743791 and COGE_ID: 936800185 encoding XATs was performed with real-time quantitative reverse transcription polymerase chain reaction using actin as a reference gene. The presence of a climacteric peak and large changes in color were recorded during postharvest. The two genes studied showed a large expression after 3 days of fruit storage. CONCLUSIONS: We conclude that during the last stages of ripening in avocado fruit there was an active esterification of xanthophylls with carboxylic acids, which suggests the presence of esterified xanthophylls in the fruit mesocarp. © 2024 Society of Chemical Industry.

Agreement between the perception of colon cleansing reported by patients and colon cleansing assessed by a validated colon cleansing scale.

AIMS: Patients' perception of their cleansing quality can guide strategies to improve cleansing during colonoscopy. There are no studies assessing the agreement between the quality of cleansing perceived by patients and cleansing quality assessed during colonoscopy using validated bowel preparation scales. The main aim of this study was to compare the cleansing quality reported by patients with the quality during colonoscopy using the Boston Bowel Preparation Scale (BBPS). PATIENTS AND METHODS: Consecutive patients referred to an outpatient colonoscopy were included. Four drawings representing different degrees of cleansing were designed. Patients chose the drawing that most resembled the last stool. The predictive ability of the patient's perception and agreement between the patient's perception and the BBPS were calculated. A BBPS score of <2 points in any segment was considered inadequate. RESULTS: Six hundred and thirty-three patients were included (age: 62.8±13.7 years, male: 53.4%). Overall, 107 patients (16.9%) had inadequate cleansing during colonoscopy, and in 12.2% of cases, the patient's perception was poor. The patient's perception compared to the quality of cleanliness during colonoscopy presented a positive and negative predictive value of 54.6% and 88.3%, respectively. The agreement between patient perception and the BBPS was significant (P<0.001), although fair (k=0.37). The results were similar in a validation cohort of 378 patients (k=0.41). CONCLUSIONS: The cleanliness perceived by the patient and the quality of cleanliness using a validated scale were correlated, although fair. However, this measure satisfactorily identified patients with adequate preparation. Cleansing rescue strategies may target patients who self-report improper cleaning. Registration number of the trial: NCT03830489.

Protective effect of microbiota-derived short chain fatty acids on vascular dysfunction in mice with systemic lupus erythematosus induced by toll like receptor 7 activation.

Our objective was to investigate whether short-chain fatty acids (SCFAs), specifically acetate and butyrate, could prevent vascular dysfunction and elevated blood pressure (BP) in mice with systemic lupus erythematosus (SLE) induced by TLR7 activation using imiquimod (IMQ). Treatment with both SCFAs and dietary fibers rich in resistant starch (RS) or inulin-type fructans (ITF) effectively prevented the development of hypertension and cardiac hypertrophy. Additionally, these treatments improved aortic relaxation induced by acetylcholine and mitigated vascular oxidative stress. Acetate and butyrate treatments also contributed to the maintenance of colonic integrity, reduced endotoxemia, and decreased the proportion of helper T (Th)17 cells in mesenteric lymph nodes (MLNs), blood, and aorta in TLR7-induced SLE mice. The observed changes in MLNs were correlated with increased levels of GPR43 mRNA in mice treated with acetate and increased GPR41 levels along with decreased histone deacetylase (HDAC)- 3 levels in mice treated with butyrate. Notably, the effects attributed to acetate, but not butyrate, were nullified when co-administered with the GPR43 antagonist GLPG-0974. T cell priming and differentiation into Th17 cells in MLNs, as well as increased Th17 cell infiltration, were linked to aortic endothelial dysfunction and hypertension subsequent to the transfer of faecal microbiota from IMQ-treated mice to germ-free (GF) mice. These effects were counteracted in GF mice through treatment with either acetate or butyrate. To conclude, these findings underscore the potential of SCFA consumption in averting hypertension by restoring balance to the interplay between the gut, immune system, and vascular wall in SLE induced by TLR7 activation.

High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery.

The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter.

In vitro evaluation of the antagonistic activity of native strains of Trichoderma spp. against Fusarium spp.

Five samples of agricultural soil and five samples of Aloe barbadensis (P. Mill., 1768) plants with symptoms of wilt and root necrosis were collected in five localities of the state of Tamaulipas, México. The aims of this study were the morphological identification, molecular identification and in vitro evaluation of the antagonistic activity of Trichoderma spp. on Fusarium spp. Four strains of Trichoderma asperellum, one strain of Trichoderma harzianum and five strains of Fusarium oxysporum were identified by morphological and molecular methods. The evaluation of the antagonistic activity of T. harzianum isolate (TP) showed the highest inhibition in Fusarium spp. (78.80%). The evaluation of the antagonistic activity of Trichoderma spp. extracts in Fusarium spp. did not show significant differences between treatments (P ≤ 0.05), with Trichoderma growth percentages that oscillated between 81.08 and 94.38%. The native isolate of T. harzianum (TP) showed significant competitive capability against the mycelial growth of F. oxysporum. Trichoderma species are promising agents of biological control in the central area of the State Tamaulipas, Mexico.

The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown. METHODS: We carried out a translational approach to study the relationship between the FGF23-Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels. RESULTS: Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K+) current (Itof), caused by the downregulation of K+ channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced Itof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes. CONCLUSION: The FGF23-Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD.

Can ectopic right coronary from the left sinus have a different course than intramural? A case of ectopic right with retroaortic course.

Retrocardiac course of an ectopic right coronary artery is newly described. The alternative (usual) course of an anomalous right coronary from the left sinus of Valsalva is pre-aortic and intramural, with stenosis. In the present exceptional case, there was no stenosis.

New Insight on Phenolic Composition and Evaluation of the Vitamin C and Nutritional Value of Smoothies Sold on the Spanish Market.

Fruits and vegetables are a source of a wide range of nutrients, including bioactive compounds. These compounds have great biological activity and have been linked to the prevention of chronic non-communicable diseases. Currently, the food industry is developing new products to introduce these compounds, whereby smoothies are becoming more popular among consumers. The aim of this study was to evaluate the nutritional quality and the polyphenol and vitamin C content of smoothies available on the Spanish market. An evaluation of the nutritional information and ingredients was carried out. The phenolic compounds were determined by HPLC-ESI-TOF-MS; the vitamin C content was quantified using HPLC-UV/VIS; and the antioxidant activity was analyzed by DPPH and FRAP. Among all of the ingredients of the smoothies, coconut and banana have shown a negative impact on the polyphenol content of the smoothies. In contrast, ingredients such as orange, mango, and passion fruit had a positive correlation with the vitamin C content. Moreover, apple and red fruits showed the highest positive correlations with most of the phenolic acids, flavonoids, total phenolic compounds, and antioxidant activities. In addition, a clustering analysis was performed, and four groups were clearly defined according to the bioactive composition determined here. This research is a precious step for the formulation of new smoothies and to increase their polyphenol quality.

Use of activated carbon and camphor carbon as cathode and clay cup as proton exchange membrane in a microbial fuel cell for the bioenergy production from crude glycerol biodegradation.

This work characterizes two alternative materials to substitute the most expensive microbial fuel cells (MFCs) components: proton exchange membrane (PEM) and cathode. Crude glycerol biodegradation was studied in MFCs using a clay cup as a PEM and activated carbon and camphor carbon mixture (CAC) as a cathode. The cathode performance was compared with Platinum on carbon cloth. Two clay cup single-chamber MFCs were operated with each cathode and fed with 2000 mg/L of crude glycerol. Electrochemical properties were characterized by linear sweep voltammetry, electrochemical impedance spectroscopy, and chronoamperometry. Biodegradation efficiencies were estimated with the chemical oxygen demand (COD) removal percentage. MFCs with CAC showed a maximum power density of 100 mW/m2. This result was a 43.47% power response regarding MFCs with Platinum. COD removal efficiencies of 94% were achieved in 37 days for both cells. The Columbic efficiencies were 24.04% and 22.78% for the MFCs with Platinum and CAC. The economic analysis showed a cost of USD 9.97 for MFCs with CAC. This cost is five times lower than when using Platinum. MFCs utilizing clay cups and CAC showed an acceptable performance for the bioenergy production from crude glycerol biodegradation above all economic advantage in the cell cost.

In vitro biocontrol of Fusarium oxysporum with antagonistic microorganisms and In vivo effect on Solanum lycopersicum L.

The objective was to evaluate the effects of In vitro biocontrol of Trichoderma spp. and Bacillus spp. against Fusarium oxysporum and its in vivo effect on Solanum lycopersicum plants. The antagonistic effect in vitro of microcapsules of Trichoderma spp. and Bacillus spp. against F. oxysporum, was evaluated by inhibition and antagonism classification, in the in vivo part growth variables in plant and fruit were measured. Trichoderma asperellum showed inhibition of 84.7% and class 1 and Bacillus spp., obtained an inhibition of 83.7% with a positive classification. The canonical correspondence analysis of the fruit, the T1 treatment indicates that the variables that highlight the effect of the treatment are the firmness of the fruit and the Brix. The canonical correspondence analysis of the plant, the height presents a significant difference (P < 0.05), highlighting B. subtilis, Bacillus liquefasciens, T. harzianum and T. asperellum + Bacillus amiloliquefasciens, with 1.05 and 1.1 m compared to the control of 74 cm, also highlighted the number of total fruits in the T. harzianum treatment with an average of 22.6 fruits and root weight in B. subtilis with 37.12 g. Strains of Trichoderma spp. and Bacillus spp. successfully inhibited F. oxysporum also induced growth in the tomato plant.

Probiotic Bifidobacterium breve prevents DOCA-salt hypertension.

Many probiotics that affect gut microbial ecology have been shown to produce beneficial effects on renin-angiotensin-dependent rodent models and human hypertension. We hypothesized that Bifidobacterium breve CECT7263 (BFM) would attenuate hypertension in deoxycorticosterone acetate (DOCA)-salt rats, a renin-independent model of hypertension. Rats were randomly divided into five groups: control, DOCA-salt, treated DOCA-salt-BFM, treated DOCA-salt-butyrate, and treated DOCA-salt-acetate, for 5 weeks. BFM prevented the increase in systolic blood pressure, cardiac weight, and renal damage induced by DOCA-salt. BFM increased acetate-producing bacterial population and gut acetate levels, improved colonic integrity, normalized endotoxemia, plasma trimethylamine (TMA) levels, and restored the Th17 and Treg content in mesenteric lymph nodes and aorta. Furthermore, BFM improved nitric oxide-dependent vasorelaxation induced by acetylcholine in aortic rings and reduced NADPH oxidase activity in DOCA-salt animals. These protective effects were mimicked by acetate, but not by butyrate supplementation. These data demonstrate that BFM induces changes in gut microbiota linked with attenuation of endothelial dysfunction and increase in blood pressure in this low-renin form of hypertension. These beneficial effects seem to be mediated by increased acetate and reduced TMA production by gut microbiota, thus, improving gut integrity and restoring Th17/Tregs polarization and endotoxemia.

Endonasal Endoscopic and Hybrid Surgery Techniques for Blunt Trauma Fractures of the Skull Base With Cerebrospinal Fluid Leaks.

ABSTRACT: Cerebrospinal fluid (CSF) leakage caused by skull base fracture represents high risks of bacterial meningitis, and a rate of mortality of 8.9%. Endoscopic endonasal repair of CSF leaks is quite safe and effective procedure with high rates of success. The aim of this study is to describe our technique for management of skull base CSF leaks secondary to craniofacial trauma based on the anatomic location of the leak. This is a retrospective case series of 17 patients with diagnosis of craniofacial trauma, surgically treated with sole endonasal endoscopic and combined endonasal/transcranial approaches with diagnosis of CSF leak secondary to skull base fractures. Seventeen patients met inclusion criteria for this study. Mean age was 46 years old. Most common etiology was motor vehicle. Early surgery was performed in 8 patients, and late surgery in 9 patients. The most common site of CSF leak was at ethmoid cells or at the fronto-ethmoid junction in 9 patients. Thirteen patients (76.4%) were treated only with endonasal endoscopic technique, and 4 (23.5%) with hybrid surgery, combining endonasal endoscopic and cranial bicoronal approaches with nasal and pericranial vascularized flaps, and nasal mucosal free flaps. Mean hospital stay was 23.7 days.The mean follow-up time was 25.6 months. When surgical reconstruction is indicated for CSF leaks secondary to skull base fractures, endonasal endoscopic techniques should be part of the surgical management either as a sole procedure, or in combination with classical transcranial approaches with high rates of success and low morbidity.

Impact of COVID-19 confinement on eating behaviours across 16 European countries: The COVIDiet cross-national study.

We aimed to evaluate the changes in eating behaviours of the adult population across 16 European countries due to the COVID-19 confinement and to evaluate whether these changes were somehow related to the severity of the containment measures applied in each country. An anonymous online self-reported questionnaire on socio-demographic characteristics, validated 14-items Mediterranean diet (MedDiet) Adherence Screener (MEDAS) as a reference of a healthy diet, eating and lifestyle behaviours prior to and during the COVID-19 confinement was used to collect data. The study included an adult population residing in 16 European countries at the time of the survey. Aggregated Stringency Index (SI) score, based on data from the Oxford COVID-19 Government Response Tracker, was calculated for each country at the time the questionnaire was distributed (range: 0-100). A total of 36,185 participants completed the questionnaire (77.6% female, 75.2% with high educational level and 42.7% aged between 21 and 35 years). In comparison to pre-confinement, a significantly higher adherence to the MedDiet during the confinement was observed across all countries (overall MEDAS score prior to- and during confinement: 5.23 ± 2.06 vs. 6.15 ± 2.06; p < 0.001), with the largest increase seen in Greece and North Macedonia. The highest adherence to MedDiet during confinement was found in Spain and Portugal (7.18 ± 1.84 and 7.34 ± 1.95, respectively). Stricter contingency restrictions seemed to lead to a significantly higher increase in the adherence to the MedDiet. The findings from this cross-sectional study could be used to inform current diet-related public health guidelines to ensure optimal nutrition is followed among the population, which in turn would help to alleviate the current public health crisis.

Insecticidal capacity of polyphenolic seed compounds from neem (Azadirachta indica) on Spodoptera frugiperda (J. E. Smith) larvae.

The objective of this study was to evaluate the insecticidal activity of the polyphenolic compounds found in neem on S. frugiperda larvae. Three neem extracts (1:12 (m/v) with 70% ethanol, 1:12 (m/v) with 0% ethanol (only water), and 1:4 (m/v) with 0% ethanol) were employed. Subsequently, the extraction of phytochemical compounds of each extract was performed using ultrasound and microwave technologies simultaneously. The compound characterization was performed by HPLC-mass. In addition, the insecticidal evaluation of the neem extract was performed against S. frugiperda of the second-stage larvae. The extracts were applied by spraying the larvae according to each bioassay. Results showed that the extract obtained with a 1:12 (m/v) relationship and 70% ethanol was effective for the control of S. frugiperda larvae. In this extract, the predominant organic compound families were: methoxyflavones, flavonols, hydroxycoumarins, anthocyanins, methoxycinnamic acid, and alkylflavones. Phytochemical compounds obtained from neem seeds with environmentally friendly solvents and alternative technologies (ultrasound and microwave) have potent insecticidal activity against S. frugiperda larvae.

Mechanistic Analysis of Solid-State Colorimetric Switching: Monoalkoxynaphthalene-Naphthalimide Donor-Acceptor Dyads.

There is growing interest in creating solids that are responsive to various stimuli. Herein we report the first molecular-level mechanistic picture of the thermochromic polymorphic transition in a series of MAN-NI dyad crystals that turn from orange to yellow upon heating with minimal changes to the microscopic morphology following the transition. Detailed structural analyses revealed that the dyads assemble to create an alternating bilayer type structure, with horizontal alternating alkyl and stacked aromatic layers in both the orange and yellow forms. The observed dynamic behavior in the solid state moves as a yellow wavefront through the orange crystal. The overall process is critically dependent on a complex interplay between the layered structure of the starting crystal, the thermodynamics of the two differently colored forms, and similar densities of the two polymorphs. Upon heating, the orange form alkyl chain layers become disordered, allowing for some lateral diffusion of dyads within their own layer. Moving to either adjacent stack in the same layer allows a dyad to exchange a head-to-head stacking geometry (orange) for a head-to-tail stacking geometry (yellow). This transition is unique in that it involves a nucleation and growth mechanism that converts to a faster cooperative wavefront mechanism during the transition. The fastest moving of the wavefronts have an approximately 38° angle with respect to the long axis of the crystal, corresponding to a nonconventional C-H···O hydrogen bond network of dyad molecules in adjacent stacks that enables a transition with cooperative character to proceed within layers of orange crystals. The orange-to-yellow transition is triggered at a temperature that is very close to the temperature at which the orange and yellow forms exchange as the more stable, while being lower than the melting temperature of the original orange, or final yellow, solids.

Kidney transplantation in the extremely elderly from extremely aged deceased donors: a kidney for each age.

BACKGROUND: Advances in life expectancy have led to an increase in the number of elderly people with end-stage renal disease (ESRD). Scarce information is available on the outcomes of kidney transplantation (KT) in extremely elderly patients based on an allocation policy prioritizing donor-recipient age matching. METHODS: We included recipients ≥75 years that underwent KT from similarly aged deceased donors at our institution between 2002 and 2015. Determinants of death-censored graft and patient survival were assessed by Cox regression. RESULTS: We included 138 recipients with a median follow-up of 38.8 months. Median (interquartile range) age of recipients and donors was 77.5 (76.3-79.7) and 77.0 years (74.7-79.0), with 22.5% of donors ≥80 years. Primary graft non-function occurred in 8.0% (11/138) of patients. Cumulative incidence rates for post-transplant infection and biopsy-proven acute rejection (BPAR) were 70.3% (97/138) and 15.2% (21/138), respectively. One- and 5-year patient survival were 82.1 and 60.1%, respectively, whereas the corresponding rates for death-censored graft survival were 95.6 and 93.1%. Infection was the leading cause of death (46.0% of fatal cases). The occurrence of BPAR was associated with lower 1-year patient survival [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.64-10.82; P = 0.003]. Diabetic nephropathy was the only factor predicting 5-year death-censored graft survival (HR = 4.82, 95% CI 1.08-21.56; P = 0.040). CONCLUSIONS: ESRD patients ≥75 years can access KT and remain dialysis free for their remaining lifespan by using grafts from extremely aged deceased donors, yielding encouraging results in terms of recipient and graft survival.

Amino-Functionalized Mesoporous Silica Nanoparticle-Encapsulated Octahedral Organoruthenium Complex as an Efficient Platform for Combatting Cancer.

In the process of synthesis of a new drug, as important as the drug itself is the formulation used, because the same compound can present a very different efficacy depending on how it is administered. In this work, we demonstrate how the antitumor capacity of a new octahedral organoruthenium complex, [Ru(ppy-CHO)(phen)2][PF6] is affected by its encapsulation in different types of mesoporous silica nanoparticles. The interactions between the Ru complex and the silica matrix and how these interactions are affected at two different pHs (7.4 and 5.4, mimicking physiological and endolysosomal acidic conditions, respectively) have been studied. The encapsulation has also been shown to affect the induction of apoptosis and necrosis and progression of the cell cycle compared to the free drug. The encapsulation of the Ru complex in nanoparticles functionalized with amino groups produced very high anticancer activity in cancer cells in vitro, especially against U87 glioblastoma cells, favoring cellular internalization and significantly increasing the anticancer capacity of the initial non-encapsulated Ru complex.

Cancer nanomedicine meets immunotherapy: opportunities and challenges.

Cancer nanomedicines have shown promise in combination immunotherapy, thus far mostly preclinically but also already in clinical trials. Combining nanomedicines with immunotherapy aims to reinforce the cancer-immunity cycle, via potentiating key steps in the immune reaction cascade, namely antigen release, antigen processing, antigen presentation, and immune cell-mediated killing. Combination nano-immunotherapy can be realized via three targeting strategies, i.e., by targeting cancer cells, targeting the tumor immune microenvironment, and targeting the peripheral immune system. The clinical potential of nano-immunotherapy has recently been demonstrated in a phase III trial in which nano-albumin paclitaxel (Abraxane®) was combined with atezolizumab (Tecentriq®) for the treatment of patients suffering from advanced triple-negative breast cancer. In the present paper, besides strategies and initial (pre)clinical success stories, we also discuss several key challenges in nano-immunotherapy. Taken together, nanomedicines combined with immunotherapy are gaining significant attention, and it is anticipated that they will play an increasingly important role in clinical cancer therapy.