Impact of Oxygen Stoichiometry on the Thermoelectric Properties of Bi2Sr2Co2Oy Thin Films.

In this study, we present a comprehensive analysis of the thermoelectric (TE) properties of highly c-axis-oriented thin films of layered misfit cobaltates Bi2Sr2Co2Oy. The films exhibit a high c-axis orientation, facilitating precise measurements of electronic transport and TE properties along the a-b crystallographic plane. Our findings reveal that the presence of nearly stoichiometric oxygen content results in high thermopower with metallic conductivity, while the annealing of the films in a reduced oxygen atmosphere eliminates their metallic behavior. According to the well-established Heike's limit, the thermopower tends to become temperature independent when the thermal energy significantly exceeds the bandwidth, which provides a rough estimation of charge carrier density by using the Heike's formula. This observation suggests that the dominant contribution to the thermopower comes from the narrow Co-t2g bands near the Fermi energy. Our study demonstrates that the calculated thermopower value using Heike's formula, based on the Hall electron density of the Bi2Sr2Co2Oy thin films at 300 K, aligns well with the experimental results, shedding light on the intriguing TE properties of this family of layered cobaltate oxide films.

Enhanced Thermal Conductivity of Free-Standing Double-Walled Carbon Nanotube Networks.

Nanomaterials are driving advances in technology due to their oftentimes superior properties over bulk materials. In particular, their thermal properties become increasingly important as efficient heat dissipation is required to realize high-performance electronic devices, reduce energy consumption, and prevent thermal damage. One application where nanomaterials can play a crucial role is extreme ultraviolet (EUV) lithography, where pellicles that protect the photomask from particle contamination have to be transparent to EUV light, mechanically strong, and thermally conductive in order to withstand the heat associated with high-power EUV radiation. Free-standing carbon nanotube (CNT) films have emerged as candidates due to their high EUV transparency and ability to withstand heat. However, the thermal transport properties of these films are not well understood beyond bulk emissivity measurements. Here, we measure the thermal conductivity of free-standing CNT films using all-optical Raman thermometry at temperatures between 300 and 700 K. We find thermal conductivities up to 50 W m-1 K-1 for films composed of double-walled CNTs, which rises to 257 W m-1 K-1 when considering the CNT network alone. These values are remarkably high for randomly oriented CNT networks, roughly seven times that of single-walled CNT films. The enhanced thermal conduction is due to the additional wall, which likely gives rise to additional heat-carrying phonon modes and provides a certain resilience to defects. Our results demonstrate that free-standing double-walled CNT films efficiently dissipate heat, enhancing our understanding of these promising films and how they are suited to applications in EUV lithography.

Functionalizing Dendrimers for Targeted Delivery of Bioactive Molecules to Macrophages: A Potential Treatment for Mycobacterium tuberculosis Infection-A Review.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.

Reduction in the Cocoa Spontaneous and Starter Culture Fermentation Time Based on the Antioxidant Profile Characterization.

In current systems, the fermentation spontaneous process produces fermented beans of heterogeneous quality due to the fermentation time. This study demonstrated that the fermentation time should be reduced. For this purpose, the physicochemical parameters, antioxidant profile, and volatile compounds were characterized in two types of fermentation (spontaneous and starter culture) for 168 h in cocoa from three altitude levels. Multivariate analysis (cluster and PCA) was used to discriminate the fermentation stages. We found three stages in all fermentations, where the first two stages (0 h to 96 h) were characterized by a higher antioxidant potential of the cocoa bean and the presence of desirable volatile compounds such as acids, alcohols, aldehydes, ketones, and esters, which are precursors of cocoa aroma; however, prolonged fermentation times affected the antioxidant profile of the bean. In addition, the use of a starter culture facilitates the release of compounds in a shorter time (especially alcohols and esters). It is concluded that it is necessary to reduce the fermentation time under these conditions in the region of Amazonas.

Engineering Heat Transport Across Epitaxial Lattice-Mismatched van der Waals Heterointerfaces.

Artificially engineered 2D materials offer unique physical properties for thermal management, surpassing naturally occurring materials. Here, using van der Waals epitaxy, we demonstrate the ability to engineer extremely insulating thermal metamaterials based on atomically thin lattice-mismatched Bi2Se3/MoSe2 superlattices and graphene/PdSe2 heterostructures with exceptional thermal resistances (70-202 m2 K/GW) and ultralow cross-plane thermal conductivities (0.012-0.07 W/mK) at room temperature, comparable to those of amorphous materials. Experimental data obtained using frequency-domain thermoreflectance and low-frequency Raman spectroscopy, supported by tight-binding phonon calculations, reveal the impact of lattice mismatch, phonon-interface scattering, size effects, temperature, and interface thermal resistance on cross-plane heat dissipation, uncovering different thermal transport regimes and the dominant role of long-wavelength phonons. Our findings provide essential insights into emerging synthesis and thermal characterization methods and valuable guidance for the development of large-area heteroepitaxial van der Waals films of dissimilar materials with tailored thermal transport characteristics.

Profiling the Physical Performance of Young Boxers with Unsupervised Machine Learning: A Cross-Sectional Study.

Mexico City is the location with the largest number of boxers in Mexico; in fact, it is the first city in the country to open a Technological Baccalaureate in Education and Sports Promotion with a pugilism orientation. This cross-sectional study aimed to determine the physical-functional profile of applicants for admission to the baccalaureate in sports. A total of 227 young athletes (44F; 183M; 15.65 (1.79) years; 63.66 (14.98) kg; >3 years of boxing experience) participated in this study. Body mass (BM), maximal isometric handgrip (HG) strength, the height of the countermovement jump (CMJ), the velocity of straight boxing punches (PV), and the rear hand punch impact force (PIF) were measured. The young boxers were profiled using unsupervised machine learning algorithms, and the probability of superiority (ρ) was calculated as the effect size of the differences. K-Medoids clustering resulted in two sex-independent significantly different groups: Profile 1 (n = 118) and Profile 2 (n = 109). Except for BM, Profile 2 was statistically higher (p < 0.001) with a clear distinction in terms of superiority on PIF (ρ = 0.118), the PIF-to-BM ratio (ρ = 0.017), the PIF-to-HG ratio (ρ = 0.079) and the PIF-to-BM+HG ratio (ρ = 0.008). In general, strength levels explained most of the data variation; therefore, it is reasonable to recommend the implementation of tests aimed at assessing the levels of isometric and applied strength in boxing gestures. The identification of these physical-functional profiles might help to differentiate training programs during sports specialization of young boxing athletes.

Enhanced Thermoelectric Properties of Misfit Bi2Sr2-xCaxCo2Oy: Isovalent Substitutions and Selective Phonon Scattering.

Layered Bi-misfit cobaltates, such as Bi2Sr2Co2Oy, are the natural superlattice of an electrically insulating rocksalt (RS) type Bi2Sr2O4 layer and electrically conducting CoO2 layer, stacked along the crystallographic c-axis. RS and CoO2 layers are related through charge compensation reactions (or charge transfer). Therefore, thermoelectric transport properties are affected when doping or substitution is carried out in the RS layer. In this work, we have shown improved thermoelectric properties of spark plasma sintered Bi2Sr2-xCaxCo2Oy alloys (x = 0, 0.3 and 0.5). The substitution of Ca atoms affects the thermal properties by introducing point-defect phonon scattering, while the electronic conductivity and thermopower remain unaltered.

Application of Synchrotron Radiation-Based Fourier-Transform Infrared Microspectroscopy for Thermal Imaging of Polymer Thin Films.

The thermal imaging of surfaces with microscale spatial resolution over micro-sized areas remains a challenging and time-consuming task. Surface thermal imaging is a very important characterization tool in mechanical engineering, microelectronics, chemical process engineering, optics, microfluidics, and biochemistry processing, among others. Within the realm of electronic circuits, this technique has significant potential for investigating hot spots, power densities, and monitoring heat distributions in complementary metal-oxide-semiconductor (CMOS) platforms. We present a new technique for remote non-invasive, contactless thermal field mapping using synchrotron radiation-based Fourier-transform infrared microspectroscopy. We demonstrate a spatial resolution better than 10 um over areas on the order of 12,000 um2 measured in a polymeric thin film on top of CaF2 substrates. Thermal images were obtained from infrared spectra of poly(methyl methacrylate) thin films heated with a wire. The temperature dependence of the collected infrared spectra was analyzed via linear regression and machine learning algorithms, namely random forest and k-nearest neighbor algorithms. This approach speeds up signal analysis and allows for the generation of hyperspectral temperature maps. The results here highlight the potential of infrared absorbance to serve as a remote method for the quantitative determination of heat distribution, thermal properties, and the existence of hot spots, with implications in CMOS technologies and other electronic devices.

Risk stratification, prognosis, and survival in a pulmonary arterial hypertension cohort in Latin America. A multicenter study.

BACKGROUND: Pulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort. METHODS: 92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study. Patients were stratified at baseline and at early follow-up, within the first year, using three non-invasive variables (WHO functional class, 6-minute walking distance, BNP/NT-proBNP) from the ESC/ERS 2015 risk assessment instrument. Median (IQR) follow-up was 3.11 years (3.01 years). RESULTS: At baseline assessment, 25% of patients were at low risk, 61.9% at intermediate-risk, and 13% at high-risk. At early follow-up (median 9.5 months), 56.5% of patients were at low-risk, 40.2% at intermediate-risk, and 3.2% at high-risk (p<0.001 vs. baseline). According to risk stratification at early follow-up, one, three and five-year overall survival was 100% in the low-risk group (no deaths at five-year follow-up), and 100%, 84% (95% CI: 72-98%), and 66% (95% CI: 48-90%) respectively in the intermediate-risk group, p = 0.0003. Mortality in the high-risk patients at early follow-up was 1/3 (33.3%). One, three, and five-year event-free survival (death or transplant or first hospitalization due to worsening PAH) based on early follow-up risk assessment was higher in the low-risk group, p = 0.0003. CONCLUSION: Our study validates a risk assessment strategy based on three non-invasive variables and confirms that early achievement of a low-risk profile should be the treatment goal.

Excitation and detection of acoustic phonons in nanoscale systems.

Phonons play a key role in the physical properties of materials, and have long been a topic of study in physics. While the effects of phonons had historically been considered to be a hindrance, modern research has shown that phonons can be exploited due to their ability to couple to other excitations and consequently affect the thermal, dielectric, and electronic properties of solid state systems, greatly motivating the engineering of phononic structures. Advances in nanofabrication have allowed for structuring and phonon confinement even down to the nanoscale, drastically changing material properties. Despite developments in fabricating such nanoscale devices, the proper manipulation and characterization of phonons continues to be challenging. However, a fundamental understanding of these processes could enable the realization of key applications in diverse fields such as topological phononics, information technologies, sensing, and quantum electrodynamics, especially when integrated with existing electronic and photonic devices. Here, we highlight seven of the available methods for the excitation and detection of acoustic phonons and vibrations in solid materials, as well as advantages, disadvantages, and additional considerations related to their application. We then provide perspectives towards open challenges in nanophononics and how the additional understanding granted by these techniques could serve to enable the next generation of phononic technological applications.

Spectroscopic and Thermal Characterization of Extra Virgin Olive Oil Adulterated with Edible Oils.

The substitution of extra virgin olive oil with other edible oils is the primary method for fraud in the olive-oil industry. Developing inexpensive analytical methods for confirming the quality and authenticity of olive oils is a major strategy towards combatting food fraud. Current methods used to detect such adulterations require complicated time- and resource-intensive preparation steps. In this work, a comparative study incorporating Raman and infrared spectroscopies, photoluminescence, and thermal-conductivity measurements of different sets of adulterated olive oils is presented. The potential of each characterization technique to detect traces of adulteration in extra virgin olive oils is evaluated. Concentrations of adulterant on the order of 5% can be detected in the Raman, infrared, and photoluminescence spectra. Small changes in thermal conductivity were also found for varying amounts of adulterants. While each of these techniques may individually be unable to identify impurity adulterants, the combination of these techniques together provides a holistic approach to validate the purity and authenticity of olive oils.

Factores psicológicos asociados al riesgo suicida en estudiantes universitarios de Honduras / Factors Related to Suicide Risk in University Students from Honduras / Fatores psicológicos associados ao risco de suicídio em estudantes universitários em Honduras

El riesgo suicida es definido como la posibilidad de que una persona atente deliberadamente contra su vida y se considera una conducta autodestructiva de causas multifactoriales. El propósito de esta investigación fue determinar los factores psicológicos aso-ciados al riesgo suicida en estudiantes universitarios. Esto se realizó por medio de un enfoque cuantitativo no experimental. La muestra estuvo conformada por 1696 estudiantes de pregrado, 54.7 % correspondiente al sexo femenino y 43.6 % al masculino. Se aplicaron escalas para evaluar sentido de la vida, depresión, esperanza, soledad, apoyo interpersonal y riesgo suicida. Los resultados indicaron que el 50 % de la muestra reportó nunca haber tenido pensamientos suicidas. Sin embargo, el 26.8 % tuvo un pensamiento pasajero al respecto; el 9.9 % planeó quitarse la vida, pero no lo intentó; el 5.8 % realizó un intento suicida sin intención real de concretar el acto, el 5 % hizo planes para quitarse la vida con intención real de concretar el acto; y el 2.4 % efectuó intentos suicidas con deseos de morir. Se evidenció que existe una relación inversa significativa entre el riesgo suicida y la esperanza, presencia y búsqueda de sentido de la vida y apoyo interpersonal. No obstante, los individuos con mayor riesgo suicida poseen puntajes más altos en soledad y depresión. Estos resultados se discuten desde sus implicaciones en el ejercicio clínico

Suicide risk is defined as the possibility of a person deliberately taking his/her own life; this is considered a self-destructive behavior with multifactorial causes. This research aimed to determine the psychological fac-tors associated with suicide risk in university students. This was done through a quantitative, non-experimental approach. The sample consisted of 1.696 undergraduate students, 54.7 % female and 43.6 % male students. Ques-tionnaires were applied to evaluate meaning in life, depression, hope, loneliness, interpersonal support, and suicide risk. The results indicated that 50 % of the parti-cipants reported never having suicidal thoughts. However, 26.8 % had had a passing thought about committing suicide, 9.9 % had thought of a specific (but unexecuted) plan to commit suicide, 5.8 % reported a previous suicide attempt without the intention of actually committing suicide, 5 % had made plans to take their own life with a real intention to commit the act, and 2.4 % had made at least one suicide attempt with a desire to die. Results indicate that there is a significant inverse relation be-tween suicide risk and hope, the presence and search for a meaning in life, and interpersonal support. However, a higher suicide risk is positively correlated with loneliness and depression. These results are discussed according to their implications in clinical practice

O risco de suicídio é definido como a possibilidade de uma pessoa deliberadamente atentar contra sua vida, considerando-o como um comportamento autodestrutivo com causas multifatoriais. O objetivo desta pesquisa foi determinar os fatores psicológicos associados ao risco de suicídio em estudantes universitários. Isso foi feito por meio de uma abordagem quantitativa, não experimental. A amostra foi composta por 1696 alunos de graduação, sendo 54.7 % do sexo feminino e 43.6 % do sexo mascu-lino. Foram aplicadas escalas para avaliar o sentido de vida, depressão, esperança, solidão, apoio interpessoal e risco de suicídio. Os resultados indicaram que 50 % da amostra relatou nunca ter tido pensamentos suicidas. No entanto, 26.8 % tiveram um pensamento passageiro sobre isso, 9.9 % planejaram se matar, mas não tentaram; 5.8 % fizeram uma tentativa de suicídio sem real intenção de realizar o ato, 5 % fizeram planos para tirar a própria vida com real intenção de realizar o ato e 2.4 % fizeram ten-tativas de suicídio com desejo de morrer. Evidenciou-se que existe uma relação inversa significativa entre risco de suicídio e esperança, presença e busca de sentido na vida e apoio interpessoal. No entanto, indivíduos com maior risco de suicídio apresentam pontuações mais altas em solidão e depressão. Esses resultados são discutidos a partir de suas implicações na prática clínica

Cry1Ac Protoxin Confers Antitumor Adjuvant Effect in a Triple-Negative Breast Cancer Mouse Model by Improving Tumor Immunity.

The Cry1Ac protoxin from Bacillus thuringiensis is a systemic and mucosal adjuvant, able to confer protective immunity in different infection murine models and induce both Th1 and TCD8+ cytotoxic lymphocyte responses, which are required to induce antitumor immunity. The Cry1Ac toxin, despite having not being characterized as an adjuvant, has also proved to be immunogenic and able to activate macrophages. Here, we investigated the potential antitumor adjuvant effect conferred by the Cry1Ac protoxin and Cry1Ac toxin in a triple negative breast cancer (TNBC) murine model. First, we evaluated the ability of Cry1Ac proteins to improve dendritic cell (DC) activation and cellular response through intraperitoneal (i.p.) coadministration with the 4T1 cellular lysate. Mice coadministered with the Cry1Ac protoxin showed an increase in the number and activation of CD11c+MHCII- and CD11c+MHCII+low in the peritoneal cavity and an increase in DC activation (CD11c+MHCII+) in the spleen. Cry1Ac protoxin increased the proliferation of TCD4+ and TCD8+ lymphocytes in the spleen and mesenteric lymph nodes (MLN), while the Cry1Ac toxin only increased the proliferation of TCD4+ and TCD8+ in the MLN. Remarkably, when tested in the in vivo TNBC mouse model, prophylactic immunizations with 4T1 lysates plus the Cry1Ac protoxin protected mice from developing tumors. The antitumor effect conferred by the Cry1Ac protoxin also increased specific cytotoxic T cell responses, and prevented the typical tumor-related decrease of T cells (TCD3+ and TCD4+) as well the increase of myeloid-derived suppressor cells (MDSC) in spleen. Also in the tumor microenvironment of mice coadministered twice with Cry1Ac protoxin immunological improvements were found such as reductions in immunosupressive populations (T regulatory lymphocytes and MDSC) along with increases in macrophages upregulating CD86. These results show a differential antitumor adjuvant capability of Cry1Ac proteins, highlighting the ability of Cry1Ac protoxin to enhance local and systemic tumor immunity in TNBC. Finally, using a therapeutic approach, we evaluated the coadministration of Cry1Ac protoxin with doxorubicin. A significant reduction in tumor volume and lung metastasis was found, with increased intratumoral levels of tumor necrosis factor-α and IL-6 with respect to the vehicle group, further supporting its antitumor applicability.

Unraveling Heat Transport and Dissipation in Suspended MoSe2 from Bulk to Monolayer.

Understanding heat flow in layered transition metal dichalcogenide (TMD) crystals is crucial for applications exploiting these materials. Despite significant efforts, several basic thermal transport properties of TMDs are currently not well understood, in particular how transport is affected by material thickness and the material's environment. This combined experimental-theoretical study establishes a unifying physical picture of the intrinsic lattice thermal conductivity of the representative TMD MoSe2 . Thermal conductivity measurements using Raman thermometry on a large set of clean, crystalline, suspended crystals with systematically varied thickness are combined with ab initio simulations with phonons at finite temperature. The results show that phonon dispersions and lifetimes change strongly with thickness, yet the thinnest TMD films exhibit an in-plane thermal conductivity that is only marginally smaller than that of bulk crystals. This is the result of compensating phonon contributions, in particular heat-carrying modes around ≈0.1 THz in (sub)nanometer thin films, with a surprisingly long mean free path of several micrometers. This behavior arises directly from the layered nature of the material. Furthermore, out-of-plane heat dissipation to air molecules is remarkably efficient, in particular for the thinnest crystals, increasing the apparent thermal conductivity of monolayer MoSe2 by an order of magnitude. These results are crucial for the design of (flexible) TMD-based (opto-)electronic applications.

On the thermoelectric properties of Nb-doped SrTiO3 epitaxial thin films.

The exploration for thermoelectric thin films of complex oxides such as SrTiO3-based oxides is driven by the need for miniaturized harvesting devices for powering the Internet of Things (IoT). However, there is still not a clear consensus in the literature for the underlying influence of film thickness on thermoelectric properties. Here, we report the fabrication of epitaxial thin films of 6% Nb-doped SrTiO3 on (001) (LaAlO3)0.3(Sr2AlTaO6)0.7 (LSAT) single crystal using pulsed laser deposition (PLD) where the film thickness was varied from 2 nm to 68 nm. The thickness dependence shows a subtle increase of tetragonality of the thin film lattice and a gradual drop of the electrical conductivity, the density of charge carriers, and the thermoelectric Seebeck coefficient as the film thickness decreases. DFT-based calculations show that ∼2.8% increase in tetragonality results in an increased splitting between t2g and eg orbitals to ∼42.3 meV. However, experimentally observed tetragonality for films between 68 to 13 nm is only 0.06%. Hence, the effect of thickness on tetragonality is neglected. We have discussed the decrease of conductivity and the Seebeck coefficient based on the decrease of carriers and change in the scattering mechanism, respectively.

Review on Sol-Gel Synthesis of Perovskite and Oxide Nanomaterials.

Sol-Gel is a low cost, well-established and flexible synthetic route to produce a wide range of micro- and nanostructures. Small variations in pH, temperature, precursors, time, pressure, atmosphere, among others, can lead to a wide family of compounds that share the same molecular structures. In this work, we present a general review of the synthesis of LaMnO3, SrTiO3, BaTiO3 perovskites and zinc vanadium oxides nanostructures based on Sol-Gel method. We discuss how small changes in the parameters of the synthesis can modify the morphology, shape, size, homogeneity, aggregation, among others, of the products. We also discuss the different precursors, solvents, working temperature, reaction times used throughout the synthesis. In the last section, we present novel uses of Sol-Gel with organic materials with emphasis on carbon-based compounds. All with a perspective to improve the method for future applications in different technological fields.

Anisotropic Thermal Conductivity of Crystalline Layered SnSe2.

The degree of thermal anisotropy affects critically key device-relevant properties of layered two-dimensional materials. Here, we systematically study the in-plane and cross-plane thermal conductivity of crystalline SnSe2 films of varying thickness (16-190 nm) and uncover a thickness-independent thermal conductivity anisotropy ratio of about ∼8.4. Experimental data obtained using Raman thermometry and frequency domain thermoreflectance showed that the in-plane and cross-plane thermal conductivities monotonically decrease by a factor of 2.5 with decreasing film thickness compared to the bulk values. Moreover, we find that the temperature-dependence of the in-plane component gradually decreases as the film becomes thinner, and in the range from 300 to 473 K it drops by more than a factor of 2. Using the mean free path reconstruction method, we found that phonons with MFP ranging from ∼1 to 53 and from 1 to 30 nm contribute to 50% of the total in-plane and cross-plane thermal conductivity, respectively.

B19-VLPs as an effective delivery system for tumour antigens to induce humoral and cellular immune responses against triple negative breast cancer.

Cancer immunotherapy is emerging as a viable treatment option for several types of cancer. Active immunotherapy aims for the induction of specific antitumor immune responses; this goal requires strategies capable of increasing the immunogenicity of tumour antigens. Parvovirus B19 virus-like particles (B19-VLPs) formed of VP2 protein had been shown to be an effective multi-neoepitope delivery system capable of inducing specific cellular responses towards coupled antigens and reducing tumour growth and lung metastases in triple negative breast cancer mouse model. These findings encouraged us to further characterise these VP2 B19-VLPs by testing their capacity to simultaneously induce cellular and humoral responses towards other tumour-associated antigens, as this had not yet been evaluated. Here, we designed and evaluated in the 4T1 breast cancer model the prophylactic and therapeutic effect of VP2 B19-VLPs decorated with cellular (P53) and humoral (MUC1) epitopes. Balb/c mice were immunised with chimaeric VLPs, vehicle, or VLPs plus adjuvant. Tumour establishment and growth, lung metastasis, and cellular and humoral immune responses were evaluated. The prophylactic administration of chimaeric VLPs without adjuvant prevented the establishment of the tumour, while by therapeutic administration, chimaeric VLPs induced smaller tumour growth and decreased the number of metastases in the lung compared to wild-type VLPs. chimaeric VLPs induced high antibody titres towards the MUC1 epitope, as well as specific cellular responses towards P53 epitopes in lymph nodes local to the tumour. Our results reinforce and extend the utility of VP2 B19-VLPs as an encouraging tumour antigen delivery system in cancer immunotherapy able to improve tumour immunity in TNBC by inducing cellular and humoral immune responses.

Reversing the Humidity Response of MoS2- and WS2-Based Sensors Using Transition-Metal Salts.

Two-dimensional materials, such as transition-metal dichalcogenides (TMDs), are attractive candidates for sensing applications due to their high surface-to-volume ratio, chemically active edges, and good electrical properties. However, their electrical response to humidity is still under debate and experimental reports remain inconclusive. For instance, in different studies, the impedance of MoS2-based sensors has been found to either decrease or increase with increasing humidity, compromising the use of MoS2 for humidity sensing. In this work, we focus on understanding the interaction between water and TMDs. We fabricated and studied humidity sensors based on MoS2 and WS2 coated with copper chloride and silver nitrate. The devices exhibited high chemical stability and excellent humidity sensing performance in relative humidity between 4 and 80%, with response and recovery times of 2 and 40 s, respectively. We have systematically investigated the humidity response of the materials as a function of the type and amount of induced metal salt and observed the reverse action of sensing mechanisms. This phenomenon is explained based on a detailed structural analysis of the samples considering the Grotthuss mechanism in the presence of charge trapping, which was represented by an appropriate lumped-element model. Our findings open up a possibility to tune the electrical response in a facile manner and without compromising the high performance of the sensor. They offer an insight into the time-dependent performance and aging of the TMD-based sensing devices.

Understanding the Molecular Basis of 5-HT4 Receptor Partial Agonists through 3D-QSAR Studies.

Alzheimer's disease (AD) is a neurodegenerative disorder whose prevalence has an incidence in senior citizens. Unfortunately, current pharmacotherapy only offers symptom relief for patients with side effects such as bradycardia, nausea, and vomiting. Therefore, there is a present need to provide other therapeutic alternatives for treatments for these disorders. The 5-HT4 receptor is an attractive therapeutic target since it has a potential role in central and peripheral nervous system disorders such as AD, irritable bowel syndrome, and gastroparesis. Quantitative structure-activity relationship analysis of a series of 62 active compounds in the 5-HT4 receptor was carried out in the present work. The structure-activity relationship was estimated using three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques based on these structures' field molecular (force and Gaussian field). The best force-field QSAR models achieve a value for the coefficient of determination of the training set of R2training = 0.821, and for the test set R2test = 0.667, while for Gaussian-field QSAR the training and the test were R2training = 0.898 and R2test = 0.695, respectively. The obtained results were validated using a coefficient of correlation of the leave-one-out cross-validation of Q2LOO = 0.804 and Q2LOO = 0.886 for force- and Gaussian-field QSAR, respectively. Based on these results, novel 5-HT4 partial agonists with potential biological activity (pEC50 8.209-9.417 for force-field QSAR and 9.111-9.856 for Gaussian-field QSAR) were designed. In addition, for the new analogues, their absorption, distribution, metabolism, excretion, and toxicity properties were also analyzed. The results show that these new derivatives also have reasonable pharmacokinetics and drug-like properties. Our findings suggest novel routes for the design and development of new 5-HT4 partial agonists.