Biosensors based on peptide exposure show single molecule conformations in live cells.

We describe an approach to study the conformation of individual proteins during single particle tracking (SPT) in living cells. "Binder/tag" is based on incorporation of a 7-mer peptide (the tag) into a protein where its solvent exposure is controlled by protein conformation. Only upon exposure can the peptide specifically interact with a reporter protein (the binder). Thus, simple fluorescence localization reflects protein conformation. Through direct excitation of bright dyes, the trajectory and conformation of individual proteins can be followed. Simple protein engineering provides highly specific biosensors suitable for SPT and FRET. We describe tagSrc, tagFyn, tagSyk, tagFAK, and an orthogonal binder/tag pair. SPT showed slowly diffusing islands of activated Src within Src clusters and dynamics of activation in adhesions. Quantitative analysis and stochastic modeling revealed in vivo Src kinetics. The simplicity of binder/tag can provide access to diverse proteins.

Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Effect of Early Treatment with Ivermectin among Patients with Covid-19.

BACKGROUND: The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear. METHODS: We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 µg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization. RESULTS: A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events. CONCLUSIONS: Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).

In Situ and Operando Characterizations of Metal Halide Perovskite and Solar Cells: Insights from Lab-Sized Devices to Upscaling Processes.

The performance and stability of metal halide perovskite solar cells strongly depend on precursor materials and deposition methods adopted during the perovskite layer preparation. There are often a number of different formation pathways available when preparing perovskite films. Since the precise pathway and intermediary mechanisms affect the resulting properties of the cells, in situ studies have been conducted to unravel the mechanisms involved in the formation and evolution of perovskite phases. These studies contributed to the development of procedures to improve the structural, morphological, and optoelectronic properties of the films and to move beyond spin-coating, with the use of scalable techniques. To explore the performance and degradation of devices, operando studies have been conducted on solar cells subjected to normal operating conditions, or stressed with humidity, high temperatures, and light radiation. This review presents an update of studies conducted in situ using a wide range of structural, imaging, and spectroscopic techniques, involving the formation/degradation of halide perovskites. Operando studies are also addressed, emphasizing the latest degradation results for perovskite solar cells. These works demonstrate the importance of in situ and operando studies to achieve the level of stability required for scale-up and consequent commercial deployment of these cells.

Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial.

BACKGROUND: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. OBJECTIVE: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. DESIGN: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424). SETTING: 12 clinical sites in Brazil. PARTICIPANTS: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. INTERVENTION: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. MEASUREMENTS: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions. RESULTS: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected. LIMITATION: Low event rate overall, consistent with contemporary trials in vaccinated populations. CONCLUSION: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care. PRIMARY FUNDING SOURCE: Latona Foundation, FastGrants, and Rainwater Charitable Foundation.

Unlocking the Potential: Increasing Muscle Strength in Lower Limbs of Youth Soccer Players over Five Weeks through Mat Pilates Training-A Pilot Study.

The interest in soccer generally starts during childhood, with children and young people often looking for opportunities in sports. New exercise techniques can be effective in improving training. The aim of this study was to compare the effects on the strength and physical posture of a group practicing Pilates with another not practicing Pilates, both undergoing continuous football training. In this controlled randomized clinical trial, the participants were 15 soccer club members, who had a training frequency of least three times weekly. The sample was divided into a control group (n = 7) of players who did not undergo any therapeutic intervention (only the usual training) and a Pilates group (n = 8) of players who participated in the mat Pilates program. The intervention consisted of fifteen sessions. Postural evaluations were performed using biophotogrammetry and force analysis. Significant improvements were obtained in terms of increased muscle strength (p = 0.001) for the Pilates group, but there were no significant postural alterations when comparing the two groups. Five weeks of mat Pilates was sufficient to increase lower limb muscle strength in young football players. This pilot study indicates that Mat Pilates as a method that could be planned to be included in training.

Pain characterization in patients with Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) often report chronic pain, which is one of the most complex non-motor symptoms. Therefore, this study aims to review the literature on the characteristics of pain in patients with PD. METHODS: A systematic literature review was conducted following MOOSE recommendations. Observational studies reporting pain in patients with PD were included. No time restrictions were applied, but studies in Portuguese, Spanish, and English were considered. The search was performed in PubMed®, LILACS, and SciELO databases. RESULTS: Twenty-six articles of observational studies were identified, reporting an average pain prevalence of 67.36%, emphasizing the significance of this symptom in the PD population. Pain was reported in various body regions, including lower limbs, upper limbs, lumbar spine, cervical spine, and other joints. Pain classification varied, encompassing musculoskeletal pain, PD-related pain, neuropathic pain, and dystonic pain, among others. DISCUSSION: Pain in patients with PD is a prevalent and multifactorial condition, significantly impacting patients' quality of life. CONCLUSION: Heterogeneity in data across included studies was observed, highlighting the need for additional research to elucidate the underlying mechanisms of pain in patients with PD and develop effective therapeutic strategies to address this symptom and improve the quality of life for individuals living with the disease.

The Associations Between Physician-Patient Communication and Adjustment Outcomes of Patients and Physicians: A Systematic Review and Meta-Analysis of Correlations.

Physician-Patient communication (PPC) has been linked to patient adjustment outcomes. However, conflicting results have been reported and previous systematic reviews showed some methodological weaknesses. It has also been suggested that PPC is related to physicians' own adjustment outcomes. This systematic review aims to explore and synthesize the associations between PPC and both patient and physician adjustment outcomes. A systematic search was conducted primarily in five databases and 11.488 non-duplicated articles were identified. Forty-five studies met the eligibility criteria and data extraction was performed for sample characteristics, PPC measurement, adjustment outcomes under examination and main outcomes. The observed results showed that the majority of the included studies were cross-sectional, assessed PPC by proxy-report and reported an overall positive association with patients' adjustment outcomes. None of the studies examined the association between PPC and physicians' adjustment outcomes. Thirty-three studies were meta-analyzed and showed a positive and significant association between PPC and patients' adjustment outcomes (r = .16). Due to the small number of studies included in the meta-analysis, the heterogeneity was high. Subgroup analysis could not identify sources for heterogeneity. Research on the associations between PPC and physicians' own adjustment outcomes is warranted. Future studies should be rigorous in defining clear PPC definitions, directionality of communication processes, and study design.

University students' opinion on gamete donor identification regimes.

PURPOSE: This study aims to evaluate the opinion of university students about the identification or nonidentification of gamete donation and the probability of donation according to the different regimes. METHODS: This was a cross-sectional observational study based on an online anonymous survey including questions about sociodemographic data, reasons for considering donations, information about the donation process and legislation, and their opinions about the different regimes and how they would influence donations. RESULTS: In total, 1393 valid responses were obtained, with a mean age of 24.0 years (SD = 4.8), most of the respondents being female (68.5%), living in a relationship (56.7%), and without children (88.4%). The main reasons for considering donation would be altruism and monetary compensation. Overall, it was found that participants were poorly informed about the donation procedure and legislation. Students revealed preference for nonidentified donation, and they were less likely to donate in an open identity regime. CONCLUSION: Most university students consider themselves poorly informed about gamete donation, express a preference for nonidentified gamete donation, and would less likely donate on an open identity basis. Thus, an identified regime may be less attractive to potential donors and lead to a decrease in the availability of gamete donors.

Genetic diversity and correlation between morphological traits of pequi fruits (Caryocar brasiliense Camb.) with and without thorns at the endocarp.

Morphological characteristics of pequi fruits (Caryocar brasiliense) allows us to obtain information for the conservation, breeding, and detect genetic variability. Thus, the aims of this research were to characterize the genetic diversity of Caryocar brasiliense that produce fruits with and without thorn at the endocarp; determine the important characters in the study of genetic diversity, and to estimate phenotypic and genotypic correlations. 80 fruits with thorns and 90 fruits without thorns were evaluated. Data were used for analysis: Euclidian distance as a measure of dissimilarity and the Tocher method for delimitation of groups; Principal Component Analysis, and genotypic and phenotypic correlations. Genetic dissimilarity of C. brasiliense ranged from 0.066 (B6-D6) to 0.908 (A14-B3). Tocher method allowed dividing the matrices into three groups, the dendrogram into five groups, and the principal components allowed the distribution in 8 groups. We observed 15 significant correlations for characters of fruit with thorns and 31 correlations for characters of fruit without thorns. The weight of the fruit (with thorns) and the pyrene yield (without thorns) are relevant correlations for production. The groupings generated allowed the classification of the matrices into distinct sets. Allowed the identification of potential producers plants that could be used in breeding programs.

Sound Classification and Processing of Urban Environments: A Systematic Literature Review.

Audio recognition can be used in smart cities for security, surveillance, manufacturing, autonomous vehicles, and noise mitigation, just to name a few. However, urban sounds are everyday audio events that occur daily, presenting unstructured characteristics containing different genres of noise and sounds unrelated to the sound event under study, making it a challenging problem. Therefore, the main objective of this literature review is to summarize the most recent works on this subject to understand the current approaches and identify their limitations. Based on the reviewed articles, it can be realized that Deep Learning (DL) architectures, attention mechanisms, data augmentation techniques, and pretraining are the most crucial factors to consider while creating an efficient sound classification model. The best-found results were obtained by Mushtaq and Su, in 2020, using a DenseNet-161 with pretrained weights from ImageNet, and NA-1 and NA-2 as augmentation techniques, which were of 97.98%, 98.52%, and 99.22% for UrbanSound8K, ESC-50, and ESC-10 datasets, respectively. Nonetheless, the use of these models in real-world scenarios has not been properly addressed, so their effectiveness is still questionable in such situations.

Transformers for Urban Sound Classification-A Comprehensive Performance Evaluation.

Many relevant sound events occur in urban scenarios, and robust classification models are required to identify abnormal and relevant events correctly. These models need to identify such events within valuable time, being effective and prompt. It is also essential to determine for how much time these events prevail. This article presents an extensive analysis developed to identify the best-performing model to successfully classify a broad set of sound events occurring in urban scenarios. Analysis and modelling of Transformer models were performed using available public datasets with different sets of sound classes. The Transformer models' performance was compared to the one achieved by the baseline model and end-to-end convolutional models. Furthermore, the benefits of using pre-training from image and sound domains and data augmentation techniques were identified. Additionally, complementary methods that have been used to improve the models' performance and good practices to obtain robust sound classification models were investigated. After an extensive evaluation, it was found that the most promising results were obtained by employing a Transformer model using a novel Adam optimizer with weight decay and transfer learning from the audio domain by reusing the weights from AudioSet, which led to an accuracy score of 89.8% for the UrbanSound8K dataset, 95.8% for the ESC-50 dataset, and 99% for the ESC-10 dataset, respectively.

Are Chronic Pain Syndromes the Reason for Statin-associated Muscle Symptoms?

BACKGROUND: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia. OBJECTIVES: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not. METHODS: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population. RESULTS: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia. CONCLUSIONS: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.

Factors Related to Delayed Diagnosis of Cutaneous Melanoma in the Brazilian Public Health System.

In Brazil, 75% of the population uses the Sistema Único de Saúde (SUS), public health system, where the general practitioner (GP) is responsible for melanoma diagnosis. Identify the factors related to the delay in diagnosing melanoma patients assisted by SUS. A prospective observational study based on a questionnaire and medical records review assessed the sociodemographic features, melanoma signs and symptoms, previous knowledge of the disease, and factors related to delays in seeking medical care. One hundred sixty-six patients were included. Healthcare professionals suspected a lesion in only 23.5% of cases. The average time between lesion suspicion by patient/relative and first medical appointment with GP was over 6 months (31%). The time between the first GP exam and biopsy conducted by a specialist ranged from less than 1 month (34.9%) to more than 1 year (18.7%). Half of the patients (49.4%) experienced delays in histopathological diagnosis due to SUS bureaucracy/slowness. Most (80%) patients did not know what melanoma was before diagnosis. Delay in melanoma diagnosis was related to a lack of knowledge about the disease's signs and symptoms for both the study population and the primary physicians, indicating that both players must receive proper education about melanoma. Also, the infrastructure and work processed at SUS impeded the patient flow, contributing to the diagnosis of the lesions at more advanced stages.

Inter-sectoral prioritization of climate technologies: insights from a Technology Needs Assessment for mitigation in Brazil.

Technological development is key for national strategies to cope with the Paris Agreement's goals. Technology Needs Assessments (TNAs) aim to identify, prioritize, and diffuse climate change mitigation and/or adaptation technologies in developing countries. Their methodology includes a multi-criteria decision analysis (MCDA) framework but, although many countries already conducted a TNA, literature lacks discussions on country-specific processes for a TNA, as it usually follows a one-size-fits-all approach. This paper provides empirical evidence on the importance of country-driven processes that help shaping international programmes into country-specific needs and capabilities. It presents lessons learned from a tailored process for identification, prioritization, and selection of mitigation technologies in the scope of a TNA project for Brazil, an exceptional case of a developing country with strong capacity in integrated assessment modelling (IAM) scenarios for guiding its climate strategies. A previous IAM scenario result allowed pre-selecting technologies in six key economic sectors, while other TNAs prioritized no more than three. This allowed the elaboration of an overall ranking from the MCDA, in contrast to sectoral rankings that are mostly employed in other countries' TNAs. The overall ranking serves not only as a basis for the selection of priority technologies but also provides information on the integrated innovations framework for climate technologies in the country. Further specific findings of the tailored Brazilian TNA approach are discussed in the paper in order to call for the importance that a technology transfer project should not only be country-driven but also conducted through a country-specific process. Supplementary Information: The online version contains supplementary material available at 10.1007/s11027-022-10025-6.

Increased particle size of triacylglycerol-enriched remnant lipoproteins, but not their plasma concentration or lipid content, augments risk prediction of incident type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes prevention requires the accurate identification of those at high risk. Beyond the association of fasting serum triacylglycerols with diabetes, triacylglycerol-enriched remnant lipoproteins (TRLs) more accurately reflect pathophysiological changes that underlie progression to diabetes, such as hepatic insulin resistance, pancreatic steatosis and systemic inflammation. We hypothesised that TRL-related factors could improve risk prediction for incident diabetes. METHODS: We included individuals from the Brazilian Longitudinal Study of Adult Health cohort. We trained a logistic regression model for the risk of incident diabetes in 80% of the cohort using tenfold cross-validation, and tested the model in the remaining 20% of the cohort (test set). Variables included medical history and traits of the metabolic syndrome, followed by TRL-related measurements (plasma concentration, TRL particle diameter, cholesterol and triacylglycerol content). TRL features were measured using NMR spectroscopy. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). RESULTS: Among 4463 at-risk individuals, there were 366 new cases of diabetes after a mean (±SD) of 3.7 (±0.63) years of follow-up. We derived an 18-variable model with a global AUROC of 0.846 (95% CI: 0.829, 0.869). Overall TRL-related markers were not associated with diabetes. However, TRL particle diameter increased the AUROC, particularly in individuals with HbA1c <39 mmol/mol (5.7%) (hold-out test set [n = 659]; training-validation set [n = 2638]), but not in individuals with baseline HbA1c 39-46 mmol/mol (5.7-6.4%) (hold-out test set [n = 233]; training-validation set [n = 933]). In the subgroup with baseline HbA1c <39 mmol/mol (5.7%), AUROC in the test set increased from 0.717 (95% CI 0.603, 0.818) to 0.794 (95% CI 0.731, 0.862), and AUPRC in the test set rose from 0.582 to 0.701 when using the baseline model and the baseline model plus TRL particle diameter, respectively. TRL particle diameter was highly correlated with obesity, insulin resistance and inflammation in those with impaired fasting glucose at baseline, but less so in those with HbA1c <39 mmol/mol (5.7%). CONCLUSIONS/INTERPRETATION: TRL particle diameter improves the prediction of diabetes, but only in individuals with HbA1c <39 mmol/mol (5.7%) at baseline. These data support TRL particle diameter as a risk factor that is changed early in the course of the pathophysiological processes that lead to the development of type 2 diabetes, even before glucose abnormalities are established. Graphical abstract.

A post-invasion role for Chlamydia type III effector TarP in modulating the dynamics and organization of host cell focal adhesions.

The human pathogen Chlamydia trachomatis targets epithelial cells lining the genital mucosa. We observed that infection of various cell types, including fibroblasts and epithelial cells resulted in the formation of unusually stable and mature focal adhesions that resisted disassembly induced by the myosin II inhibitor, blebbistatin. Superresolution microscopy revealed in infected cells the vertical displacement of paxillin and focal adhesion kinase from the signaling layer of focal adhesions, whereas vinculin remained in its normal position within the force transduction layer. The candidate type III effector TarP, which localized to focal adhesions during infection and when expressed ectopically, was sufficient to mimic both the reorganization and blebbistatin-resistant phenotypes. These effects of TarP, including its localization to focal adhesions, required a post-invasion interaction with the host protein vinculin through a specific domain at the C terminus of TarP. This interaction is repurposed from an actin-recruiting and -remodeling complex to one that mediates nanoarchitectural and dynamic changes of focal adhesions. The consequence of Chlamydia-stabilized focal adhesions was restricted cell motility and enhanced attachment to the extracellular matrix. Thus, via a novel mechanism, Chlamydia inserts TarP within focal adhesions to alter their organization and stability.

In Situ Analysis Reveals the Role of 2D Perovskite in Preventing Thermal-Induced Degradation in 2D/3D Perovskite Interfaces.

Engineering 2D/3D perovskite interfaces is a common route to realizing efficient and stable perovskite solar cells. Whereas 2D perovskite's main function in trap passivation has been identified and is confirmed here, little is known about its 2D/3D interface properties under thermal stress, despite being one of the main factors that induces device instability. In this work, we monitor the response of two typical 2D/3D interfaces under a thermal cycle by in situ X-ray scattering. We reveal that upon heating, the 2D crystalline structure undergoes a dynamical transformation into a mixed 2D/3D phase, keeping the 3D bulk underneath intact. The observed 3D bulk degradation into lead iodide is blocked, revealing the paramount role of 2D perovskite in engineering stable device interfaces.

Interplay among miR-29 family, mineral metabolism, and gene regulation in Bos indicus muscle.

An interplay between gene expression, mineral concentration, and beef quality traits in Bos indicus muscle has been reported previously under a network approach. However, growing evidence suggested that miRNAs not only modulate gene expression but are also involved with mineral homeostasis. To our knowledge, understanding of the miRNA-gene expression-mineral concentration relationship in mammals is still minimal. Therefore, we carried out a miRNA co-expression and multi-level miRNA-mRNA integration analyses to predict the putative drivers (miRNAs and genes) associated with muscle mineral concentration in Nelore steers. In this study, we identified calcium and iron to be the pivotal minerals associated with miRNAs and gene targets. Furthermore, we identified the miR-29 family (miR-29a, -29b, -29c, -29d-3p, and -29e) as the putative key regulators modulating mineral homeostasis. The miR-29 family targets genes involved with AMPK, insulin, mTOR, and thyroid hormone signaling pathways. Finally, we reported an interplay between miRNAs and minerals acting cooperatively to modulate co-expressed genes and signaling pathways both involved with mineral and energy homeostasis in Nelore muscle. Although we provided some evidence to understand this complex relationship, future work should determine the functional implications of minerals for miRNA levels and their feedback regulation system.\\An interplay between gene expression, mineral concentration, and beef quality traits in Bos indicus muscle has been reported previously under a network approach. However, growing evidence suggested that miRNAs not only modulate gene expression but are also involved with mineral homeostasis. To our knowledge, understanding of the miRNA-gene expression-mineral concentration relationship in mammals is still minimal. Therefore, we carried out a miRNA co-expression and multi-level miRNA-mRNA integration analyses to predict the putative drivers (miRNAs and genes) associated with muscle mineral concentration in Nelore steers. In this study, we identified calcium and iron to be the pivotal minerals associated with miRNAs and gene targets. Furthermore, we identified the miR-29 family (miR-29a, -29b, -29c, -29d-3p, and -29e) as the putative key regulators modulating mineral homeostasis. The miR-29 family targets genes involved with AMPK, insulin, mTOR, and thyroid hormone signaling pathways. Finally, we reported an interplay between miRNAs and minerals acting cooperatively to modulate co-expressed genes and signaling pathways both involved with mineral and energy homeostasis in Nelore muscle. Although we provided some evidence to understand this complex relationship, future work should determine the functional implications of minerals for miRNA levels and their feedback regulation system.

Synthesis and biological effects of small molecule enhancers for improved recombinant protein production in plant cell cultures.

Histone deacetylases are involved in chromatin remodelling and thus play a vital role in the epigenetic regulation of gene expression. HDAC inhibitors alter the acetylation status of histone and non-histone proteins to regulate various cellular events such as transcription. Novel HDAC inhibitors were designed and synthesised to promote higher levels of recombinant protein production in tobacco cell cultures. The effect of these chemical enhancers on the epigenetic profiles in plant cells has been evaluated by molecular docking, in vitro and in vivo studies. The addition of these novel enhancers led to an increase in histone H3 acetylation levels that promoted an increase in the accumulation levels of the recombinant protein in cell culture. These results can pave the way for the application of these enhancers to improve the production of high value products in plant cell based systems.