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Senescence impairs liver physiology, mitochondrial function and circadian regulation, resulting in systemic metabolic dysregulation. Given the limited research on the effects of combined exercise on an ageing liver, this study aimed to evaluate its impact on liver metabolism, circadian rhythms and mitochondrial function in senescence‐accelerated mouse‐prone 8 (SAMP8) and senescence‐accelerated mouse‐resistant 1 (SAMR1) mice. Histological, reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and immunoblotting analyses were conducted, supplemented by transcriptomic data sets and AML12 hepatocyte studies. Sedentary SAMP8 mice exhibited decreased muscle strength, reduced mitochondrial complex I levels and increased lipid droplet accumulation. In contrast, combined exercise mitigated muscle strength loss, upregulated proteins involved in mitochondrial complexes (CIII, CIV, CV) and increased Bmal1 messenger RNA (mRNA) expression in the liver. These molecular adaptations are associated with healthier liver phenotypes and may influence metabolic function and cellular longevity. Notably, elevated lipid content in aged mice was reduced post‐exercise, indicating liver benefits even after a relatively short intervention. The combined exercise regimen did not improve aerobic capacity, likely due to the low volume and brief duration of running. Moreover, no significant effects were observed in SAMR1 mice, possibly because the training intensity was insufficient for younger, healthier animals. These findings underscore the potential of combined strength and endurance exercise to attenuate age‐related liver dysfunction, particularly in ageing populations. [ABSTRACT FROM AUTHOR]

Data from the Internet of Things (IoT) enables the design of new business models and services that improve user experience and satisfaction. These data serve as important information sources for many domains, including disaster management, biosurveillance, smart cities, and smart health, among others. However, this scenario involves the collection of personal data, raising new challenges related to data privacy protection. Therefore, we aim to provide state-of-the-art information regarding privacy issues in the context of IoT, with a particular focus on findings that utilize the Personal Data Store (PDS) as a viable solution for these concerns. To achieve this, we conduct a systematic mapping review to identify, evaluate, and interpret the relevant literature on privacy issues and PDS-based solutions in the IoT context. Our analysis is guided by three well-defined research questions, and we systematically selected 49 studies published until 2023 from an initial pool of 176 papers. We analyze and discuss the most common privacy issues highlighted by the authors and position the role of PDS technologies as a solution to privacy issues in the IoT context. As a result, our findings reveal that only a small number of works (approximately 20%) were dedicated to presenting solutions for privacy issues. Most works (almost 82%) were published between 2018 and 2023, demonstrating an increased interest in the theme in recent years. Additionally, only two works used PDS-based solutions to deal with privacy issues in the IoT context. [ABSTRACT FROM AUTHOR]

• Post-COVID-19 cases present global cognition, memory, and executive function deficits. • Increased persistent inflammation correlated with diffusion brain abnormalities. • Cognitive deficits were mediated by widespread microstructural brain changes. • Global cognitive deficits were associated with severity of depressive symptoms. Post-COVID-19 Condition (PCC) refers to a multisystemic syndrome that persists for months after SARS-CoV-2 infection. Cognitive deficits, fatigue, depression, and anxiety are common manifestations of the condition, but the underlying mechanisms driving these long-lasting neuropsychiatric features are still unclear. We conducted a prospective multi-method investigation of post-hospitalization COVID-19 patients in Rio de Janeiro, Brazil. Months after hospital admission (mean = 168.45 ± 90.31 days; range = 75.00–365.00 days), COVID-19 survivors (n = 72) presented significant difficulties in tests tapping global cognition, episodic memory, working memory and inhibitory control relative to controls and to validated normative scores. A considerable proportion of participants suffered from fatigue (36.1 %), anxiety (27.8 %), and depressive symptoms (43.1 %). Elevated blood levels of TNF-α, during hospitalization, and TNF-α and IL-1β, at follow-up, correlated with changes in brain microstructural diffusion indices (β = 0.144, p = 0.005). These neuroimaging markers were associated with decreased episodic memory (β = -0.221, p = 0.027), working memory (β = -0.209, p = 0.034) and inhibitory control (β = -0.183, p = 0.010) at follow-up. Severity of depressive symptoms correlated with deficits in global cognition in post-COVID-19 cases (β = -0.366, p = 0.038). Our study provides preliminary evidence that long-term cognitive dysfunction following COVID-19 may be mediated by brain microstructural damage, triggered by persistent neuroinflammation. In addition, depressive symptoms may contribute to prolongated global cognitive impairments in those cases. [ABSTRACT FROM AUTHOR]

Background: The results of vital pulp treatments in permanent teeth have been encouraging. Currently, pulpotomy treatment for permanent teeth primarily utilizes mineral trioxide aggregate (MTA) as the dressing material, followed by calcium hydroxide. While other calcium‐silicate‐based cements have been suggested for pulpotomy, there is a limited number of studies evaluating their long‐term effectiveness. Objectives: The objective of this systematic review and meta‐analysis was to evaluate the success rate of pulpotomies performed on permanent teeth, comparing the use of ProRoot MTA with that of calcium hydroxide and other bioceramic materials. Methods: A comprehensive search was conducted in several electronic databases, including PubMed, Cochrane Library, Scopus, Web of Science, Embase and Science Direct until December 2022. The search was guided by PICOS criteria, including only randomized clinical trials (RCTs) that evaluated the success rate of pulpotomy treatments in permanent teeth using ProRoot MTA in comparison to calcium hydroxide and other bioceramic materials. The quality of the included studies was assessed using the RoB‐2 tool to evaluate the risk of bias, and relevant data were extracted and analysed in RevMan software 5.3 using fixed‐effect models. The GRADE tool was used to determine the overall quality of evidence. Results: The initial search retrieved 1072 studies and, after eliminating duplicates, 677 studies were screened and 28 studies were considered for eligibility. In the final selection process, 16 studies were included in the systematic review, with 10 being determined as having a high risk of bias. Pulpotomy showed an overall mean success rate of 92% after 1 year. The meta‐analysis indicated a significantly higher success rate for pulpotomies utilizing MTA in comparison with calcium hydroxide, while no significant difference was seen between MTA and calcium‐enriched mixture (CEM) or Biodentine. The GRADE assessment revealed an overall low level of evidence for the included studies. Discussion: Most randomized controlled trials exhibited a significant absence of control over confounding factors. Conclusions: This systematic review and meta‐analysis demonstrate that pulpotomy is a highly effective treatment for managing permanent teeth. The results indicate that the success rate of pulpotomy using ProRoot MTA is significantly higher than when using calcium hydroxide. However, the certainty of evidence supporting these findings is low, and there is a need for well‐designed RCTs to assess the long‐term outcomes of pulpotomy using newer bioceramic materials. Registration: This systematic review was registered in the PROSPERO database (registration number CRD42023393970). [ABSTRACT FROM AUTHOR]

Teratocytes are specialized cells released by parasitoid wasps into their hosts. They are known for producing regulatory molecules that aid the development of immature parasitoids. We have recently reported the primary structures of cystine‐rich peptides, including some containing inhibitor cystine knot (ICK) motifs, produced by teratocytes of the parasitoid Cotesia flavipes (Hymenoptera: Braconidae). ICKs are known for their stability and diverse biological functions. In this study, we produced four putative ICK peptides from the teratocytes of C. flavipes using solid‐phase peptide synthesis or recombinant expression in E. coli, and investigated their functions on host immune modulation as well their potential to impair the development of two lepidopterans after ingestion of the peptides. In addition, the peptides were assayed against pathogens and human cells. The peptides did not influence total hemocyte count but suppressed cellular immunity, detectable as a reduction of hemocyte encapsulation (CftICK‐I, CftICK‐II, CftICK‐III) and spread indexes (CftICK‐IV) in the host. None of the peptides influenced the activities of prophenoloxidase and phenoloxidase in the hemolymph of larval Diatraea saccharalis (Lepidoptera: Crambidae). CftICK‐I and CftICK‐II with previously unknown function showed antifungal activity against Candida albicans but were non‐toxic to human cells. CftICK‐I, CftICK‐II, and CftICK‐III increased larval mortality and reduced leaf consumption of D. saccharalis, a permissive host for C. flavipes. The CftICK‐III also increased larval mortality and reduced leaf consumption of Spodoptera frugiperda (Lepidoptera: Noctuidae), a non‐permissive host for C. flavipes. This study highlights biological functions and biotechnological potential of ICK peptides from the teratocytes of C. flavipes. [ABSTRACT FROM AUTHOR]

A twodimensional axisymmetric model, which is computationally inexpensive, has been proposed to predict the property changes that occur in a seasonal rock‐pit energy storage (RPES) system. The geometry of the rock‐pit has been simplified into a shape that can be extended for any seasonal storage system with a three‐dimensional conical geometry. The computational domain has been solved using both linear thermal equilibrium (LTE) and linear thermal non‐equilibrium (LTNE) models, and the former has been found to be computationally quick and accurate. The model has predicted a 95% energy saving at the highest flow conditions required in the mine. Further analysis has suggested that the increase in storage capacity by decreasing the porosity of rocks in the rock‐pit is insignificant compared to the corresponding increase in fan power. Furthermore, the investigation done on natural rocks has indicated an increased ability to store heat in the rock‐pit when rocks with higher thermal mass have been used. The use of RPES has shown a significant potential to reduce the carbon footprint. Finally, an economic analysis done on the system has shown a return on investment of just under 12 years. [ABSTRACT FROM AUTHOR]

Many conditions, such as inflammation and physical exercise, can induce endoplasmic reticulum (ER) stress. Toll‐like Receptor 4 (TLR4) can trigger inflammation and ER stress events. However, there are still no data in the literature regarding the role of TLR4 in ER stress during exercise in skeletal muscle. Therefore, the current investigation aimed to verify the responses of ER stress markers in wild‐type (WT) and Tlr4 global knockout (KO) mice after acute and chronic physical exercise protocols. Eight‐week‐old male WT and KO mice were submitted to acute (moderate or high intensity) and chronic (4‐week protocol) treadmill exercises. Under basal conditions, KO mice showed lower performance in the rotarod test. Acute high‐intensity exercise increased eIF2α protein in the WT group. After the acute high‐intensity exercise, there was an increase in Casp3 and Ddit3 mRNA for the KO mice. Acute moderate exercise increased the cleaved Caspase‐3/Caspase‐3 in the KO group. In response to chronic exercise, the KO group showed no improvement in any performance evaluation. The 4‐week chronic protocol did not generate changes in ATF6, CHOP, p‐IRE1α, p‐eIF2α/eIF2α, and cleaved Caspase‐3/Caspase‐3 ratio but reduced BiP protein compared with the KO‐Sedentary group. These results demonstrate the global deletion of Tlr4 seems to have the same effects on UPR markers of WT animals after acute and chronic exercise protocols but decreased performance. The cleaved Caspase‐3/Caspase‐3 ratio may be activated by another pathway other than ER stress in Tlr4 KO animals. Key points: While acute high‐intensity exercise increased the Casp3 and Ddit3 mRNA in KO mice, acute moderate‐intensity exercise increased the cleaved Caspase‐3/Caspase‐3 in the same group.Under basal conditions, Tlr4 KO mice showed lower performance in the rotarod test. In response to chronic exercise, the Tlr4 KO group showed no improvement in any performance evaluation.The global deletion of Tlr4 seems to have the same effects on UPR markers of WT animals after acute and chronic exercise protocols but decreased performance and seems to activate the apoptosis pathway. Significance statement The endoplasmic reticulum (ER) is responsible for translating and folding most proteins in our body. Protein homeostasis imbalance leads to malformed proteins in the ER lumen, and their accumulation leads to ER stress. Toll‐like Receptor 4 (TLR4) can trigger inflammation, and TLR4 global knockout (KO) mice are protected against ER stress. Furthermore, physical exercise can reduce the TLR4 in the cell. As inflammation seems to affect physical exercise‐related ER stress, the present study investigated the relationship between TLR4 and ER stress after physical exercise in skeletal muscle. [ABSTRACT FROM AUTHOR]

Recently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3′ massive analysis of cDNA ends (3′MACE). We found >30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-β-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/β-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of malaria and provides a laboratory view. It describes the case of a woman from Guinea Bissau who presented with fever, nausea, vomiting, and malaise. It discusses the diagnostic methods, laboratory findings, and pathogenic mechanisms of malaria, emphasizing the importance of accurate diagnosis and appropriate treatment for the preventable and treatable infectious disease.

The transcriptional repressor REV-ERB-α, encoded by Nuclear Receptor Subfamily 1 Group D Member 1 (Nr1d1), has been considered to play an essential role in the skeletal muscle oxidative capacity adaptation and muscle mass control. Also, this molecule regulates autophagy via the repression of autophagy-related genes both in skeletal muscle and brain regions. Classically, training programs based on endurance or strength characteristics enhance skeletal muscle mass content and/or oxidative capacity, leading to autophagy activation in several tissues. Thus, it seems that REV-ERB-α regulates similar responses induced by exercise. However, how this molecule responds to different exercise models/intensities in different tissues is still unclear. Therefore, the main aim was to characterize the responses of REV-ERB-α and autophagy-related genes to different exercise protocols (endurance/interval run/strength) in distinct tissues (gastrocnemius, soleus and hippocampus). Since REV-ERB-α presents a circadian rhythm, the analyses were performed in a time-course manner. The endurance and strength groups attenuated REV-ERB-α transcriptional response during the time course in gastrocnemius and soleus. Conversely, the interval group enhanced the Nr1d1 expression in the hippocampus. All protocols downregulated the REV-ERB-α protein levels in gastrocnemius following the exercise session with concomitant nuclear exclusion. The major autophagy-related genes presented downregulation after the exercise session in all analyzed tissues. Altogether, these results highlight that REV-ERB-α is extremely sensitive to physical exercise stimuli, including different models and intensities in skeletal muscle and the hippocampus. [ABSTRACT FROM AUTHOR]

The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules approved by authorities for commercial use, there is a demand for faster methods to repurpose such drugs. Here we present a review on virtual screening web tools, such as publicly available databases of molecular targets and libraries of ligands, with the aim to facilitate the discovery of potential anticancer drugs based on microbial products. We provide an entry-level step-by-step description of the workflow for virtual screening of microbial metabolites with known protein targets, as well as two practical examples using freely available web tools. The first case presents a virtual screening study of drugs developed from microbial products using Caver Web, a web tool that performs docking along a tunnel. The second case comprises a comparative analysis between a wild type isocitrate dehydrogenase 1 and a mutant that results in cancer, using the recently developed web tool PredictSNPOnco. In summary, this review provides the basic and essential background information necessary for virtual screening experiments, which may accelerate the discovery of novel anticancer drugs. [ABSTRACT FROM AUTHOR]

The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules approved by authorities for commercial use, there is a demand for faster methods to repurpose such drugs. Here we present a review on virtual screening web tools, such as publicly available databases of molecular targets and libraries of ligands, with the aim to facilitate the discovery of potential anticancer drugs based on microbial products. We provide an entry-level step-by-step description of the workflow for virtual screening of microbial metabolites with known protein targets, as well as two practical examples using freely available web tools. The first case presents a virtual screening study of drugs developed from microbial products using Caver Web, a web tool that performs docking along a tunnel. The second case comprises a comparative analysis between a wild type isocitrate dehydrogenase 1 and a mutant that results in cancer, using the recently developed web tool PredictSNPOnco. In summary, this review provides the basic and essential background information necessary for virtual screening experiments, which may accelerate the discovery of novel anticancer drugs. [ABSTRACT FROM AUTHOR]

Regular endurance exercise is a non‐pharmacological strategy to protect the liver against diseases. Conversely, exercise may be harmful when excessive, the so‐called overtraining. As expected, mice who underwent an overtraining protocol presented higher levels of proinflammatory cytokines in the serum and liver. Based on the relationship among overtraining, inflammation and mammalian target of rapamycin complex 1 (mTORC1) upregulation, the present study verified if animals submitted to an overtraining protocol, but with inhibition of the mTOR pathway via rapamycin injections could mitigate the liver and serum inflammation. Once autophagy can be linked to the improvement of hepatic dysfunction, we also investigated if the inhibition of mTORC1 by rapamycin can improve hepatic autophagy. The animals were randomized into four groups: control (CT; sedentary mice), overtraining by downhill running (OT; mice submitted to the downhill running‐based overtraining protocol), overtraining by downhill running with chronic administration of rapamycin (OT/Rapa; mice submitted to the downhill running‐based overtraining protocol with intraperitoneal injections of rapamycin) and aerobic (AER; submitted to aerobic training protocol). The serum and liver of the animals were used for biochemical analysis, reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and immunoblotting. The main results are (a) OT and OT/Rapa protocols decreased the performance; (b) the protein levels of interleukin 6 (IL‐6) were higher for the OT group; the OT/Rapa group reduced the autophagic genes, increased the microtubule‐associated protein light chain 3 II/I (LC3II/LC3I) protein ratio and decreased the sequestosome 1 (SQSTM1) protein. In conclusion, rapamycin appears efficiently to increase the autophagy proteins and decrease IL‐6 protein in the liver of overtraining mice. [ABSTRACT FROM AUTHOR]

The search for lightweight structures increases the demand for non-metallic materials, such as polymers, composites, and hybrid structures. This work presents the dissimilar joining through direct laser joining between polymethylmethacrylate (PMMA) and S235 galvanised steel using a pulsed Nd:YAG laser. The main goal is to determine the influence of processing parameters on joint strength and quality. In addition, the impact of surface conditions on the joint quality was also analysed. Overall, the optimum ranges of process parameters were found, and some are worth highlighting, such as the laser beam diameter and pulse duration, which significantly influenced the joint strength. Failure of the welded samples occurred in PMMA component, demonstrating good joint efficiency. Additionally, a maximum increase of 5.1% of the tensile shear strength was achieved thanks to the mechanical pre-treatment. It is possible to conclude that the joining between PMMA and the S235 galvanised steel can be performed by optimising the process parameters. Additionally, it can be enhanced through surface pre-treatments by exploring the mechanical interlock between both materials. [ABSTRACT FROM AUTHOR]

The intensity, duration, type of contraction, and muscle damage influence interleukin‐6 (IL‐6) response to acute exercise. However, in response to an exhaustive exercise session, the upregulation of IL‐6 in the serum and heart is associated with an inflammatory condition and can inhibit autophagy. This study aimed to investigate the role of IL‐6 in autophagy pathway responses and mitochondrial function in the heart of mice submitted to acute exhaustive physical exercise. The mice were allocated into three groups, five animals per group, for the wild type (WT) and the IL‐6 knockout (IL‐6 KO): Basal (sedentary; Basal), 1 h (after 1 h of the acute exercise; 1 h), and 3 h (after 3 h of the acute exercise; 3 h). After the specific time for each group, the blood was collected, each mouse heart was removed, and the left ventricle (LV) was isolated. In summary, under basal conditions, without the influence of the acute exercise, the IL‐6 KO group showed lower number of nuclei in the cardiac tissue, but higher collagen deposition; lower messenger RNA (mRNA) levels of Prkaa1 and Mtco1, but higher mRNA levels of Ulk1; and higher protein levels of the ratio p‐AMPK/AMPK in the heart when compared to WT at the same time point. After the acute exercise (1 and 3 h), the IL‐6 KO group had lower mRNA levels of Tfam, Mtnd1, Mtco1, and Nampt in the heart when compared to WT after exercise; higher serum levels of creatine kinase (CK), CK‐MB, and lactate dehydrogenase for the IL‐6 group when compared to the WT group after the exercise. Specifically, the heat‐shock protein 60 protein levels in the heart increased 3 h after exhaustive exercise in the WT group, but not in the IL‐6 KO group. The study emphasizes that IL‐6 may offer cardioprotective effects, including mitochondrial adaptations in response to acute exhaustive exercise. Significance statement: The characterization of cytokines, like interleukin‐6 (IL‐6), which has pro‐ and anti‐inflammatory effects in the physiological and cardiac responses to physical exercise, is necessary for the context of metabolic health. In response to physical exercise, IL‐6 can promote anti‐inflammatory effects; however, after an exhaustive exercise session, the upregulation of IL‐6 in the serum is related to a pro‐inflammatory state. This study demonstrated that IL‐6 might exert cardioprotective effects and mitochondrial adaptations in response to acute exhaustive exercise. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is an organelle responsible for the post‐translational folding and modification of proteins. Under stress conditions, such as physical exercise, there is accumulation of misfolded proteins. The increased load of proteins in the ER results in ER stress, which activates the unfolded protein response (UPR). UPR is comprised of three parallel pathways, responsible for ensuring the quality of secreted proteins. Scientific studies show that resistance or endurance acute physical exercise can induce ER stress and activate the UPR pathways. On the other hand, regular moderate‐intensity exercise can attenuate the responses of genes and proteins related to ER stress. However, these positive adaptations do not occur when exercise intensity and volume increase without adequate rest periods, which is observed in overtraining. The current review discusses the frontier‐of‐knowledge findings on the effects of different acute and chronic physical exercise protocols on skeletal muscle ER stress and its metabolic consequences. [ABSTRACT FROM AUTHOR]

Recent years have seen an explosion of interest in understanding the physicochemical parameters that shape enzyme evolution, as well as substantial advances in computational enzyme design. This review discusses three areas where evolutionary information can be used as part of the design process: (i) using ancestral sequence reconstruction (ASR) to generate new starting points for enzyme design efforts; (ii) learning from how nature uses conformational dynamics in enzyme evolution to mimic this process in silico ; and (iii) modular design of enzymes from smaller fragments, again mimicking the process by which nature appears to create new protein folds. Using showcase examples, we highlight the importance of incorporating evolutionary information to continue to push forward the boundaries of enzyme design studies. We can learn from nature's tricks by reconstructing evolutionary trajectories to design improved enzymes. Ancestral sequence reconstruction (ASR) provides a compelling tool to obtain enzymes with customized catalytic properties. Conformational dynamics in enzyme design is crucial in increasing the sampling of states with new catalytic functions as well as reducing the sampling of non-productive conformations. A catalog of fragments characterized by specific biophysical features may provide an invaluable resource for the design of custom-made enzymes. [ABSTRACT FROM AUTHOR]

Whole-genome transcriptional analyses performed on microorganisms are traditionally based on a small number of samples. To map transient expression variations, and thoroughly characterize gene expression throughout the growth curve of the widely used model organism Lactococcus lactis MG1363, gene expression data were collected with unprecedented time resolution. The resulting gene expression patterns were globally analyzed in several different ways to demonstrate the richness of the data and the ease with which novel phenomena can be discovered. When the culture moves from one growth phase to another, gene expression patterns change to such an extent that we suggest that those patterns can be used to unequivocally distinguish growth phases from each other. Also, within the classically defined growth phases, subgrowth phases were distinguishable with a distinct expression signature. Apart from the global expression pattern shifts seen throughout the growth curve, several cases of short-lived transient gene expression patterns were clearly observed. These could help explain the gene expression variations frequently observed in biological replicates. A method was devised to estimate a measure of unnormalized/absolute gene expression levels and used to determine how global transcription patterns are influenced by nutrient starvation or acidification of the medium. Notably, we inferred that L. lactis MG1363 produces proteins with on average lower pIs and lower molecular weights as the medium acidifies and nutrients get scarcer. [ABSTRACT FROM AUTHOR]

The role of platinum basis set (PTBS) and relativistic effects for predicting the vibrational frequencies and intramolecular force constants for cisplatin are discussed. Nonrelativistic and relativistic computational protocols were built at B3LYP/PTBS/jorge-DZP/C-PCM and B3LYP-DKH2/PTBS/jorge-DZP-DKH/C-PCM levels, respectively, where 19 distinct PTBS were tested. As expected, the structural parameters were not very sensitive to the PTBS, however, the inclusion of relativistic effects improves the description of the cisplatin structure. When it comes to the vibrational frequencies, the results show that the PTBS, and mainly the relativistic effects, are both important. Moreover, the PBE0 functional led to better results than B3LYP in the protocols PBE0/LANL2TZ(f)/jorge-DZP/C-PCM (P20) and PBE0-DKH2/Sapporo-DKH3-DZP-2012/jorge-DZP-DKH/C-PCM (P22), which provided a mean absolute deviation (MAD) of only 10.8 cm−1 and 9.5 cm−1, respectively, for vibrational frequencies, which are excellent choices to study Pt complexes. Finally, a discussion of the intramolecular force constants for cisplatin is carried out, with the calculated bond and angles force constants with P20 and P22 protocols being recommended for the parameterization of the force field of cisplatin. [ABSTRACT FROM AUTHOR]

Background: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage.Methodology: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage.Discussion: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is an onco-hematologic disease with distinct levels of peripheral blood cytopenias, dysplasias in cell differentiation and various forms of chromosomal and cytogenomic alterations. In this study, the Chromosomal Microarray Analysis (CMA) was performed in patients with primary MDS without numerical and/or structural chromosomal alterations in karyotypes. A total of 17 patients was evaluated by GTG banding and eight patients showed no numerical and/or structural alterations. Then, the CMA was carried out and identified gains and losses CNVs and long continuous stretches of homozygosity (LCSHs). They were mapped on chromosomes 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 14, 16, 17, 18, 19, 20, 21, X, and Y. Ninety-one genes that have already been implicated in molecular pathways important for cell viability were selected and in-silico expression analyses demonstrated 28 genes differentially expressed in mesenchymal stromal cells of patients. Alterations in these genes may be related to the inactivation of suppressor genes or the activation of oncogenes contributing to the evolution and malignization of MDS. CMA provided additional information in patients without visible changes in the karyotype and our findings could contribute with additional information to improve the prognostic and personalized stratification for patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate whether variations in 163 C > A CYP1A2 genotypes (rs 762 551) (AA, AC, and CC) modify the ergogenic effects of caffeine (CAF) on strength, power, muscular endurance, agility, and endurance in adolescent athletes. Methods: One hundred adolescents (age = 15 ± 2 years) were recruited. Participants ingested CAF (6 mg.kg−1) or placebo (PLA, 300 mg of cellulose) 1 hour before performing a sequence of physical tests: handgrip strength, vertical jumps, agility test, sit‐ups, push‐ups, and the Yo‐Yo intermittent recovery test level 1 (Yo‐Yo IR1). Results: Compared to PLA, CAF enhanced (P <.05) sit‐up (CAF = 37 ± 9; PLA = 35 ± 8 repetitions) and push‐up repetitions (CAF = 26 ± 11; PLA = 24 ± 11 repetitions), and increased distance covered in Yo‐Yo IR1 test (CAF = 1010.4 ± 378.9; PLA = 903.2 ± 325.7 m). There was no influence of CAF on handgrip strength (CAF = 35.1 ± 8.9; PLA = 33.7 ± 8.7 kgf), countermovement jump height (CAF = 49.3 ± 12.6; PLA = 47.9 ± 13.8 cm), spike jump height (CAF = 54.2 ± 13.6; PLA = 52.9 ± 14.5 cm), and time in agility test (CAF = 15.8 ± 1.1; PLA = 15.9 ± 1.3 s, P >.05). When present, the ergogenic effect of CAF was not dependent of genotype. Conclusion: CAF improves muscular endurance and aerobic performance in adolescent athletes, regardless of their 163 C > A CYP1A2 genotype. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of alcohol and nicotine, when used alone or simultaneously, in the development of apical periodontitis induced in rats, using a correlative analytic approach with micro‐CT, histological and immunohistochemical analysis. Methodology: Twenty‐eight male Wistar rats were arranged into four groups: Control, Nicotine, Alcohol and Alcohol + Nicotine. The alcohol groups were exposed to self‐administration of a 25% alcohol solution, whilst the other groups drunk only filtered water. The nicotine groups received daily intraperitoneal injections of a solution with 0.19 μL of nicotine per mL, whilst the other groups received saline solution. The pulps of the left mandibular first molars were exposed for 28 days to induce periapical lesions. Throughout the experiment, drug administration was maintained, and the animals had their weight and solid and liquid consumption measured. After euthanasia, the mandibles were removed and the area, volume and major diameter of the periapical lesions were measured using micro‐computed tomography images. The samples were submitted to histopathological evaluation and immunohistochemistry for RANKL and PTHrP. Statistical analysis was undertaken with a significance level of 5%. Nonparametric data were analysed using the Kruskal–Wallis test followed by Dunn's test, whilst one‐way anova followed by Tukey's test was performed for parametric data. Results: The alcohol groups had lower solid and liquid consumption and gained less weight when compared to the nonalcohol groups (P < 0.05). The Alcohol + Nicotine group had lesions with significantly larger volume and area when compared to the other groups (P < 0.05), whilst the Alcohol or Nicotine groups had significantly larger lesions than the control group (P < 0.05). There was no significant difference in the largest diameter of the lesions amongst groups (P > 0.05). The experimental groups had greater inflammatory response scores than the control group (P < 0.05), and the representative samples had more pronounced immunoreaction against RANKL and PTHrP antibodies. Conclusions: Alcohol and nicotine consumption exacerbated the inflammatory response and the development of periradicular lesions in rats. The association of both substances enhanced their harmful effects. [ABSTRACT FROM AUTHOR]

Background: Controversial findings exist in the literature regarding the association between tobacco smoking and development of apical periodontitis or need for root canal treatment, with some studies reporting an increase in the prevalence of these outcomes in smokers, whilst others reporting no association. Aim: To evaluate if there is scientific evidence to support an association between tobacco smoking and a greater prevalence of apical periodontitis and/or root canal treatments. Data Sources: A systematic search was performed using MeSH terms and free terms in the PubMed, Scopus, Virtual Health Library (VHL), Cochrane library and Open Gray databases. Study Eligibility Criteria, Participants and Interventions: Observational studies that evaluated the association between smoking and the development or healing of periapical lesion and/or the prevalence of root canal treatment in humans were included. Study Appraisal and Synthesis Methods: A quality assessment of included studies was performed, and the relevant information and findings were evaluated. A meta‐analysis using nine included studies was performed through RevMan software, and the certainty of evidence was evaluated through GRADE. Results: Fifteen studies were included, of which 10 were classified as low risk of bias, 4 were considered as moderate risk of bias and 1 as high risk of bias. Ten studies reported that smoking was associated with a greater prevalence of periapical periodontitis and/or root canal treatment. Five studies reported no association. Nine studies were included in the pooled meta‐analysis, comprising two subgroups: apical periodontitis and root canal treatment. From these nine studies, eight studies were included in the apical periodontitis subgroup meta‐analysis and demonstrated that this condition was significantly more prevalent in smokers when compared to the nonsmokers (odds ratio = 2.78[CI: 1.60, 4.85], P < 0.001; I2 = 79%; no adjusted odds ratio). Three studies were included in the root canal treatment subgroup meta‐analysis and demonstrated an increased prevalence in smokers when compared to the nonsmokers (odds ratio = 2.73 [CI: 1.06, 2.83], P < 0.001; I2 = 72%; no adjusted odds ratio). The pooled meta‐analysis demonstrated that smokers had twice the chance of having apical periodontitis and/or root canal treatment when compared to nonsmokers (odds ratio of 2.42 [CI: 1.59, 3.68], P < 0.01; I2 = 85%). The GRADE analysis demonstrated moderate certainty of evidence. Limitations: Several confounding factors were identified such as misinformation regarding the period of time subjects had smoked, as well as the frequency of smoking and the number of cigarettes consumed. No adjustment in odds ratio data for confounding was performed. Conclusions and Implications of Key Findings: This systematic review and meta‐analysis indicate that tobacco smokers have an increased prevalence of periapical periodontitis and root canal treatments with moderate certainty of evidence. [ABSTRACT FROM AUTHOR]

Background Adherence to anti-tuberculosis treatment (ATT) in Brazil remains a challenge in achieving the goals set by the World Health Organization (WHO). Patients who are lost to follow-up during treatment pose a significant public health problem. This study aimed to investigate the factors associated with unfavorable ATT outcomes among those undergoing retreatment in Brazil. Methods We conducted an observational study of patients aged ≥18 years with tuberculosis (TB) reported to the Brazilian National Notifiable Disease Information System between 2015 and 2022. Clinical and epidemiologic variables were compared between the study groups (new cases and retreatment). Regression models identified variables associated with unfavorable outcomes. Results Among 743 823 reported TB cases in the study period, 555 632 cases were eligible, consisting of 462 061 new cases and 93 571 undergoing retreatments (44 642 recurrent and 48 929 retreatments after loss to follow-up [RLTFU]). RLTFU (odds ratio [OR], 3.96 [95% confidence interval {CI}, 3.83–4.1]) was a significant risk factor for any type of unfavorable ATT. Furthermore, RLTFU (OR, 4.93 [95% CI, 4.76–5.11]) was the main risk factor for subsequent LTFU. For death, aside from advanced age, living with HIV (OR, 6.28 [95% CI, 6.03–6.54]) was the top risk factor. Conclusions Retreatment is a substantial risk factor for unfavorable ATT outcomes, especially after LTFU. The rates of treatment success in RLTFU are distant from the WHO End TB Strategy targets throughout Brazil. These findings underscore the need for targeted interventions to improve treatment adherence and outcomes in persons who experience RLTFU. [ABSTRACT FROM AUTHOR]

In the current designed study, we explore the dielectric and energy storage performance of silver nanoparticle decorated graphene oxide nanocomposites incorporated into chitosan blended with poly (1-vinylpyrrolidone-co-vinyl acetate) in comparison with only graphene oxide nanocomposite doped into the same blend matrix. A sustainable and eco-friendly green route approach was used to form the silver nanoparticle decorated graphene oxide nanocomposites. The nanocomposite films so fabricated using the solvent evaporation method, were subjected to various characterisation techniques such as X-ray diffraction analysis, Fourier transform infrared spectroscopy, thermal analysis, surface morphology and impedance spectroscopy. Slight decrease in crystallinity (44.3 %), difference in the positioning of infrared bands, thermal stability (up to ∼77 °C) and evenly distributed morphology depict the advantage of silver coating over graphene oxide nanoparticles in the blended nanocomposite films. A boost in the dielectric properties and energy storage ability was displayed by the silver encapsulated graphene oxide reinforced nanocomposite blend films. The dielectric properties were examined by using a Nyquist plot (Bulk resistance - 1.01 × 104 Ω). An ionic conductivity of 1.044 × 10−4 S/cm and a DC conductivity of 1.196 × 10‐−4 S/cm was observed. Of note, it can be inferred that silver nanoparticle decorated graphene oxide nanocomposites impart tremendous electrical properties to the chitosan/poly (1-vinylpyrrolidone-co-vinylacetate) films, enabling them to be used in energy storage applications. [Display omitted] • CH/PVPcoVA films were enhanced with GO and Ag-GO nanoparticles. • The films showed good compatibility among the blended components. • The AgNP coating over GO nanoparticles boosted the dielectric properties of the CH/PVPcoVA films. • The films depicted an increase in ionic as well as DC conductivity with addition of Ag-GO. [ABSTRACT FROM AUTHOR]

A comparison among VMIX, VMAX and the adapted step-down Sullivan et al. (SE) tests for covariance matrix under bivariate normal assumption is presented. The type I error and power estimates were obtained by using Monte Carlo simulation under different scenarios with respect to covariance and correlation structures. In general, VMIX was more powerful than VMAX being SE more powerful than both, with few exceptions. SE test is more general since it can be used for normal and non-normal data, with no restriction with respect to the pattern of the covariance matrix shifts, and for larger dimension than the bivariate case. [ABSTRACT FROM AUTHOR]

To assess the prevalence of macular abnormalities not suspected by the biomicroscopic fundus examination and identified only by macular optical coherence tomography (OCT) in the preoperative evaluation for cataract surgery in a large series of Brazilian patients. Private practice, Recife, Brazil. Retrospective case series. All eyes that had cataract surgery by the same physician between August 2014 and July 2016 were eligible. Excluded were eyes with a previous diagnosis of macular abnormalities, with a suspicious biomicroscopic fundus examination, and without OCT results. Based on the preoperative macular OCT, patients were divided into the following 2 groups: those with a normal OCT and those with an abnormal OCT. Nine hundred fifty-two eyes (614 patients) were included in the study. Macular OCT identified abnormalities in 47 eyes (4.9%) of 44 patients (7.2%). Thirty-one eyes (3.3%) had epiretinal membrane, 7 (0.7%) had age-related macular degeneration, 4 (0.4%) had intraretinal cysts, 4 (0.4%) had a lamellar hole, and 1 (0.1%) had a macular hole. Patients with an abnormal OCT had a statistically significant higher mean age (P =.004). In the preoperative evaluation for cataract surgery in Brazilian patients, 7.2% of those with a normal biomicroscopic fundus examination had macular abnormalities that were identified only by OCT. [ABSTRACT FROM AUTHOR]

• Excessive training leads to negative outcomes in multiple tissues. • Recent data about excessive training did not support the cytokine hypothesis. • Cytokines did not play a central role in performance decrement. Chronic moderate-intensity exercise is an efficient non-pharmacological strategy to prevent and treat several diseases such as type 2 diabetes mellitus, cardiovascular and chronic obstructive pulmonary diseases, cancers, and Parkinson's disease. On the other hand, improving an athlete's performance requires completing high-intensity and volume exercise sessions. When the delicate balance between high-load exercise sessions and adequate recovery periods is disrupted, excessive training (known as overtraining) can lead to performance decline. The cytokine hypothesis considers that an imbalance involving excessive exercise and inadequate recovery induces musculoskeletal trauma, increasing the production and release of proinflammatory cytokines, mainly interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1beta), which interact with different organic systems, initiating most of the signs and symptoms linked to performance decrement. This leading article used recent data to discuss the scientific basis of Smith's cytokine theory and highlighted that the adverse effects of excessive exercise go beyond performance decline, proposing a multi-organ approach for this issue. These recent insights will allow coaches and exercise physiologists to develop strategies to avoid chronic excessive exercise-induced adverse outcomes. [ABSTRACT FROM AUTHOR]

Motivation With the development of droplet based systems, massive single cell transcriptome data has become available, which enables analysis of cellular and molecular processes at single cell resolution and is instrumental to understanding many biological processes. While state-of-the-art clustering methods have been applied to the data, they face challenges in the following aspects: (i) the clustering quality still needs to be improved; (ii) most models need prior knowledge on number of clusters, which is not always available; (iii) there is a demand for faster computational speed. Results We propose to tackle these challenges with Para llelized Split Merge Sampling on D irichlet P rocess M ixture M odel (the Para-DPMM model). Unlike classic DPMM methods that perform sampling on each single data point, the split merge mechanism samples on the cluster level, which significantly improves convergence and optimality of the result. The model is highly parallelized and can utilize the computing power of high performance computing (HPC) clusters, enabling massive inference on huge datasets. Experiment results show the model outperforms current widely used models in both clustering quality and computational speed. Availability and implementation Source code is publicly available on https://github.com/tiehangd/Para%5fDPMM/tree/master/Para%5fDPMM%5fpackage. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

The non‐linearity and fear hypothesis predicts that certain non‐linear sounds are one way to evoke antipredator responses in both birds and mammals. This hypothesis, however, has not been studied in non‐vocal species or in reptiles. Such a study would be important because if non‐linear sounds are evocative even in a species that does not produce sounds, then there may be generally salient cues of risk in these sounds. We asked whether non‐vocal lizards, white‐bellied copper‐striped skinks (Emoia cyanura), respond to experimentally broadcast non‐linearities. This species is ideal to ask the question in because prior research has shown that they respond to predator sounds and alarm calls of other species even though they are not vocal. We conducted playback experiments with three computer‐generated simulated non‐linearities to assess whether or not skinks increased antipredator behavior after hearing them. We controlled for novelty by broadcasting a 3‐kHz, 500‐ms pure tone and tropical kingbird (Tyrannus melancholicus) song. Our treatments consisted of a 3‐kHz, 400‐ms pure tone followed by a frequency shift up to 5‐kHz for 100‐ms, a 3‐kHz, 400‐ms pure tone to frequency shift down to 1‐kHz for 100‐ms, and a pure tone followed by 100‐ms of white noise. Following a total of 222 playbacks, we categorized responses into looking, locomotion, and high locomotion, focusing on how skinks changed their rates of time allocation from baseline. We examined 95% confidence intervals to identify whether skinks responded to playbacks and fitted general linear models followed by pairwise comparisons to ask whether skinks discriminated between broadcast stimuli. We found that skinks were especially responsive to frequency downshifts: They significantly increased looking and locomotion, consistent with our predictions based on the non‐linearity and fear hypothesis. Surprisingly, they decreased rates of looking behavior after hearing frequency upshifts, possibly suggesting an increase in relaxed behavior. While skinks responded to noise by increasing their rate of locomotion, this response was not significantly different from controls. We conclude that skinks increase antipredator behavior after hearing downshifts more than any other type of non‐linearity. This provides some support for the non‐linearity and fear hypothesis; even non‐vocal species may respond fearfully to specific types of non‐linear sounds. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) stress and inflammation relations hip occurs at different levels and is essential for the adequate homeostatic function of cellular systems, becoming harmful when chronically engaged. Intense physical exercise enhances serum levels of interleukin 6 (IL-6). In response to a chronic exhaustive physical exercise protocol, our research group verified an increase of the IL-6 co ncentration and ER stress proteins in extensor digitorium longus (EDL) and soleus. Based on these results, we hypothesized that IL-6-knockout mice would demonstrate a lower modulation in the ER stress proteins compared to the wild-type mice. To clarify the relationship between exercise-induced IL-6 increased and ER stress, we studied the e ffects of an acute exhaustive physical exercise protocol on the levels of ER stress proteins in the skeletal muscles of IL-6-knockout (KO) mice. The WT group displayed a higher exhaustion time compared to the IL-6 KO group. After 1 h of the acute exercise protocol, the serum levels of IL-6 and IL-10 were enhanced in the WT group. Independent of the experimental group, the CHOP and cleaved caspase 12/total caspase 12 ratio in EDL as well as ATF6 and CHOP in soleus were sensitive to the acute exercise protocol. Compared to the WT group, the oscillation patterns over time of BiP in EDL and soleus as well as of peIF2-alpha/eIF2-alpha ratio in soleus were attenuated for the IL-6 KO group. In conclusion, IL-6 seems to be related with the ER stress homeostasis, once knockout mice presented attenuation of BiP in EDL and soleus as well as of pEiF2-alpha/EiF2-alpha ratio in soleus after the acute exhaustive physical exercise protocol. [ABSTRACT FROM AUTHOR]

Montmorillonite clay (MMT) was modified with polyaniline (Pani) and used to produce nanocomposites in a polystyrene (PS) matrix. MMT/Pani particles were evaluated by Infrared Spectroscopy (FT‐IR), where groups of both MMT and Pani were found; and by XRD, where an increase in the interlamellar distance was detected, changes on the resistive electrical behavior of MMT to a diffusive one for MMT/Pani were identified by Electrochemical Impedance Spectroscopy (EIS). Nanocomposites of PS with MMT‐Pani were produced by melt intercalation in the proportions of 1%, 3%, 5%, and 10%. They were characterized by Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), and EIS. Main results showed a decrease in the glass transition temperature and in the onset temperature according to the amount of MMT‐Pani. Analyses by EIS demonstrated a capacitive behavior (polarization) for nanocomposites containing smaller amounts of MMT‐Pani and diffusive behavior for the largest proportions, which were explained by a model of electronic diffusion in the Pani polymeric chain due to the chain intercalation observed by TEM in samples with higher concentration of MMT‐Pani. Therefore, the results suggest that the addition of MMT‐Pani alters some properties of the polystyrene matrix, changing its degradation and transition temperature, and its electrical behavior. POLYM. COMPOS., 40:37–45, 2019. © 2017 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

• Reversed hysteresis is observed for Al 0.5 Si 0.5 O on GaN, possibly due to the presence of K+ and Na+ impurities. • Above 750 °C in PDA, Al 0.5 Si 0.5 O is deteriorated with inhomogeneous Si compositions and a beginning of crystallization. • The interface is impacted with GaO X growth for a PDA above 750 °C. • Hydroxyl groups reduces until 850 °C, while interfacial gallium oxide is reduced at 750 °C. • The optimal PDA temperature for Al 0.5 Si 0.5 O is 750 °C. In this work, we investigate the impact of high-temperature Post-Deposition Annealing (PDA) on Al 0.5 Si 0.5 O x deposited by Atomic Layer Deposition (ALD). Reversed hysteresis is observed and explained by mobile charges originating from K+ and Na+ impurities. The high-temperature annealing does not cure the presence of these mobile charges. We also report the onset of film and interface degradation after annealing above 750 °C under N 2 , with both inhomogeneous aluminium and silicon composition, signs of AlSiO crystallization and interfacial gallium oxide growth. [ABSTRACT FROM AUTHOR]

l -Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff–Wheeler pathway is the primary route for AsA biosynthesis, and understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP- d -mannose 3',5'-epimerase (GME), l -galactose dehydrogenase (l -GalDH), and l -galactono-1,4-lactone dehydrogenase (l -GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The Md GME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Md l -GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Md l -GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications. [ABSTRACT FROM AUTHOR]

Highlights • Inflammation and lymphocyte infiltration are independent determinants of survival in high-grade serous ovarian cancer. • Neutrophil-to-lymphocyte ratio >3, or serum LDH levels >220 mg/dl are associated to poorer overall survival. • CD4+ tumor infiltrating lymphocytes (TILs) are associated to better progression-free and overall survival. Abstract Background High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive histologic type of ovarian cancer. To date, there are no reliable biomarkers to effectively predict patient prognosis. Studies have demonstrated inflammation and tumor infiltrating lymphocytes (TILs) correlate with a bad and good prognosis, respectively. Here, we sought to evaluate systemic inflammation and TILs as early prognostic markers of survival. Methods Neutrophil-to-lymphocyte ratio (NLR) and serum Lactate Dehydrogenase (LDH) were used as indicators of systemic inflammation. NLR, serum LDH, tumor infiltrating lymphocytes (TILs), PDL1 and quality of debulking surgery were evaluated as determinants of progression-free survival (PFS) and overall survival (OS) in a cohort of 128 HGSOC patients. Results Initial univariate analysis showed that systemic inflammation measures (NLR and serum LDH), debulking surgery, and intra-epithelial TILs have a significant impact on both PFS and OS. After adjustment for several variables, multivariate analyses confirmed intraepithelial CD4+ T-cells, systemic inflammation measures, PDL1 and debulking surgery as determinants of better OS and PFS. Conclusions Systemic inflammation and TILs are early determinants of OS in HGSOC. Other variables such as the quality of debulking surgery and PDL1 also improve survival of patients. Regarding TIL sub-populations, intraepithelial CD4+ cells are associated to an increase in both PFS and OS. We also confirmed previous reports that demonstrate intraepithelial CD8+ cells correlate with an increase on PFS in ovarian cancer. A combined score using systemic inflammation and TILs may be of prognostic value for HGSOC patients. [ABSTRACT FROM AUTHOR]

The association between excessive training sessions (i.e., overtraining/OT) and periods of inadequate recovery is linked to the nonfunctional overreaching (NFOR) state, which is defined as an unexplained decrement or stagnation of performance. The cytokine hypothesis of OT considers that pro-inflammatory cytokines are responsible by the NFOR state-induced performance decrement. Investigations using rodent models of OT verified increased levels of pro-inflammatory cytokines in hypothalamus, liver, serum and skeletal muscle samples. Recently, our research group observed that a 2-week total recovery period was not able to re-establish the NFOR state-induced performance decrement. As the responses of anti- and pro-inflammatory cytokines were not measured, we aimed to investigate the effects of 2-week total recovery period on the protein contents of IL-1beta, IL-6, IL-10, IL-15, TNF-alpha and SOCS-3 in serum and skeletal muscle samples of overtrained mice. Also, a bioinformatics analysis was performed to investigate the correlations of IL-1beta, IL-6, IL-10, IL-15, TNF-alpha and SOCS-3 in skeletal muscle with locomotor activity. In summary, the 2-week total recovery period upregulated the anti-inflammatory cytokines and normalized the pro-inflammatory cytokines without a concomitant re-establishment of performance. [ABSTRACT FROM AUTHOR]

The oviduct plays important roles in the early reproductive process. The aim of this study was to evaluate gene transcription and protein expression of progesterone receptor (PGR), estrogen receptors 1 (ESR1) and 2 (ESR2); oxytocin receptor (OXTR); prostaglandin F2α synthase (AKR1C3), and prostaglandin E2 synthase (Ptges) in mare oviduct in different estrous cycle stages. Estradiol (E 2 ), progesterone (P 4 ), oxytocin (OXT), and tumor necrosis factor α (TNF) effect on in vitro PGE 2 and prostaglandin F2α (PGF 2α ) secretion by equine oviduct explants or by oviductal epithelial cells (OECs) were also assessed. During the breeding season, oviduct tissue was obtained post mortem from cyclic mares. Protein of ESR1, ESR2, PGR, AKR1C3, and Ptges was present in OECs, whereas OXTR was shown in oviduct stroma. In follicular phase, protein expression of ESR1, ESR2, PGR, and OXTR increased in oviduct explants ( P < 0.05), whereas no estrous cycle effect was noted for AKR1C3 or Ptges. In follicular phase, mRNA transcription was upregulated for Pgr but downregulated for Oxtr, Ptges , and Akr1c3 ( P < 0.05). Nevertheless, Esr1 an d Esr2 mRNA levels did not change with the estrous cycle. In the ampulla, Esr1, Esr2 , and Oxtr mRNA transcription increased, but not for Pgr or Ptges . In contrast, Akr1c3 mRNA level was upregulated in the infundibulum ( P < 0.05). In follicular phase, E 2 , P 4 , and OXT downregulated PGE 2 production by OEC ( P < 0.05), but no difference was observed in mid-luteal phase. Explants production of PGE 2 rose when treated with OXT in follicular phase; with TNF or OXT in early luteal phase; or with TNF, OXT, or P 4 in mid-luteal phase. PGF 2α production by OEC was downregulated by all treatments in follicular phase but upregulated in mid-luteal phase ( P < 0.05). Oviduct explants PGF 2α production was stimulated by TNF or OXT in all estrous cycle phases. In conclusion, this work has shown that ESR1, ESR2, OXTR, Ptges, and AKRLC3 gene transcription and/or translation is estrous cycle dependent and varies with oviduct portion (infundibulum vs ampulla) and cell type. Ovarian steroid hormones, OXT and TNF stimulation of PGF 2α and/or PGE 2 production is also estrous cycle dependent and varies in the different portions of mare oviduct. Differential transcription level and protein localization in various portions of the oviduct throughout the estrous cycle, as well as PG production, suggest coordinated physiologic actions and mechanisms of steroid hormones, OXT, and TNF in the equine oviduct. [ABSTRACT FROM AUTHOR]

We evaluated the performance of check-all-that-apply (CATA) questions and intensity scales to describe Minas Frescal cheese and its reformulation based on consumers' perceptions. Ten commercial samples with different formulations (full-fat, low-fat, or low-lactose) were evaluated by 200 consumers divided equally into 2 groups: 1 evaluated samples and described their ideal cheese using intensity scales and 1 did the same using CATA questions. Both methodologies provided similar information about the sensory characteristics of the Minas Frescal cheeses, the description of the ideal product, and directions for product reformulation. The ideal Minas Frescal cheese was characterized by high moisture, intense white color, homogeneous mass, typical Minas Frescal cheese aroma and flavor, softness, and juiciness. For the intensity scales, the recommendation was to increase the typical aroma and flavor, salty taste, and juiciness, and to decrease the bitter flavor; for the CATA questions, only increasing the typical Minas Frescal cheese flavor was important for all classes of cheeses. Even for a heterogeneous product with no defined manufacturing protocol, both methodologies presented satisfactory results that should be considered for use by cheese producers and the dairy industry. [ABSTRACT FROM AUTHOR]

Recently, we demonstrated that an overtraining (OT) protocol for mice based on downhill running sessions increased the hepatic phosphorylation of 70-kDa ribosomal protein S6 kinase 1 (S6K1; Thr389), a downstream target of the mammalian target of rapamycin complex 1 (mTORC1). In liver, the overactivation of the Akt/mTORC1 pathway induces lipogenesis via regulation of the action of sterol regulatory element binding protein-1 (SREBP-1) at multiple steps. Herein, we verified the effects of three running OT models with same external load (i.e., the product between intensity and volume of training), but performed in downhill, uphill and without inclination, on the proteins related to the mTORC1 signaling pathway, the protein content of the SREBP-1, ACC, and FAS, and the morphological characteristics of C57BL/6 mouse livers. In summary, the downhill running-induced OT model up-regulated the levels of major proteins of the mTORC1 signaling pathway, the protein levels of SREBP-1 (p125 precursor) and induced signs of cell swelling accompanied by acute inflammation. The other two OT protocols performed uphill and without inclination did not modulate the most analyzed molecular proteins, but induced hepatic morphological alterations, suggesting an acute pathological adaptation. The three OT models induced hepatic fat accumulation. J. Cell. Physiol. 232: 2094-2103, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Septins are filament-forming GTP-binding proteins involved in many essential cellular events related to cytoskeletal dynamics and maintenance. Septins can self-assemble into heterocomplexes, which polymerize into highly organized, cell membraneinteracting filaments. The number of septin genes varies among organisms, and although their structure and function have been thoroughly studied in opisthokonts (including animals and fungi), no structural studies have been reported for other organisms. This makes the single septin from Chlamydomonas (CrSEPT) a particularly attractive model for investigating whether functional homopolymeric septin filaments also exist. CrSEPT was detected at the base of the flagella in Chlamydomonas, suggesting that CrSEPT is involved in the formation of a membrane-diffusion barrier. Using transmission electron microscopy, we observed that recombinant CrSEPT forms long filaments with dimensions comparable with those of the canonical structure described for opisthokonts. The GTP-binding domain of CrSEPT purified as a nucleotide-free monomer that hydrolyzes GTP and readily binds its analog guanosine 5'-3-O- (thio)triphosphate. We also found that upon nucleotide binding, CrSEPT formed dimers that were stabilized by an interface involving the ligand (G-interface). Across this interface, one monomer supplied a catalytic arginine to the opposing subunit, greatly accelerating the rate of GTP hydrolysis. This is the first report of an arginine finger observed in a septin and suggests that CrSEPT may act as its own GTP-activating protein. The finger is conserved in all algal septin sequences, suggesting a possible correlation between the ability to form homopolymeric filaments and the accelerated rate of hydrolysis that it provides. [ABSTRACT FROM AUTHOR]

The patient was known to have HIV infection and did not comply with therapy. HJBL have been associated with human immunodeficiency virus (HIV)-infected patients, I immunosuppressed i patients and patients on antiviral medications. WHO (2016) clinical stage 4 of HIV disease includes (besides others): HIV wasting syndrome, atypical disseminated leishmaniasis and extrapulmonary cryptococcosis. [Extracted from the article]

Presents information on a study which measured electrical resistivity and the thermoelectric power in the ternary compounds U[sub2]Ni[sub2]In and Nd[sub2]Ni[sub2]Sn. Temperature dependence of the electrical resistivity of U[sub2]Ni[sub2]In and U[sub2]Ni[sub2]Sn; Preparation of the polycrystalline buttons by radio frequency levitation melting then annealing; Electrical resistivity of Nd[sub2]Ni[sub2]Sn in the paramagnetic phase.

Presents information on a study which investigated the magnetothermopower of antiferromagnetically coupled cobalt-rhenium superlattices. Experimental procedure; Results; Discussion.

[Display omitted] • Nanocapsules (NC) of Copaiba essential oil (CO) have been successfully developed. • CO and CO-NC were successfully incorporated into chitosan-based films (CSF). • FTIR and HPLC analysis confirmed the presence of Polycaprolactone and CO in CSF. • CO-NC improves the stability of CO in the chitosan matrix. • The new films provided antibacterial activity against S. aureus and P. aeruginosa. Infections have emerged as a novel target in managing skin and mucosa diseases. Bacterial resistance to antimicrobials and biofilm elimination from surfaces remains a challenge. Because polymeric nanocapsules (NC) can increase antimicrobial activity, this study aimed to produce and characterize NC into chitosan films (CSF). Copaiba essential oil (CO) presents antimicrobial activity and was chosen to load NC. In addition, the antibacterial activity was evaluated to obtain a new biodegradable polymeric platform system with the potential to treat topical diseases associated with bacterial infections. The CO-NC produced by nanoprecipitation presented particle size lower than 250 nm, negative charge, and encapsulation efficiency higher than 70 %. Direct incorporation of CO into CSF (CO-CSF) by casting method worsened the film's characteristics. However, incorporating CO-NC into CSF (CO-NC-CSF) avoided these drawbacks demonstrating improved physical, mechanical, morphological, and topographical properties. FTIR results demonstrated possible intermolecular interactions among the polymers and CO. The CO-NC-CSF and CO-CSF presented antibacterial properties against Staphylococcus aureus, and Pseudomonas aeruginosa , especially the formulation containing 1 % of CO. These results indicated that CO-NC-CSF is a promising candidate for treating skin disorders. [ABSTRACT FROM AUTHOR]