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Insecticide resistance in the bed bug Cimex lectularius is poorly understood due to the lack of genome sequences for resistant strains. In Japan, we identified a resistant strain of C. lectularius that exhibits a higher pyrethroid resistance ratio compared to many previously discovered strains. We sequenced the genomes of the pyrethroid-resistant and susceptible strains using long-read sequencing, resulting in the construction of highly contiguous genomes (N50 of the resistant strain: 2.1 Mb and N50 of the susceptible strain: 1.5 Mb). Gene prediction was performed by BRAKER3, and the functional annotation was performed by the Fanflow4insects workflow. Next, we compared their amino acid sequences to identify gene mutations, identifying 729 mutated transcripts that were specific to the resistant strain. Among them, those defined previously as resistance genes were included. Additionally, enrichment analysis implicated DNA damage response, cell cycle regulation, insulin metabolism, and lysosomes in the development of pyrethroid resistance. Genome editing of these genes can provide insights into the evolution and mechanisms of insecticide resistance. This study expanded the target genes to monitor allele distribution and frequency changes, which will likely contribute to the assessment of resistance levels. These findings highlight the potential of genome-wide approaches to understand insecticide resistance in bed bugs.

The urban areas of Mediterranean Europe, and particularly Italy, have experienced considerable expansion since the late 19th century in terms of settlements, structures, and infrastructure, especially in large population centers. In such areas, the geohydrological risk is high not only for inhabited areas but also along roadways exposed to flooding. This scenario is worrying, especially in road underpass sections, where drivers are unlikely to perceive a real risk due to the high degree of confidence that comes from the habit of driving. Underpasses have been widely used to obviate the need to find shorter alternative routes and manage vehicular traffic in urban settings impeded by previous anthropogenic and natural constraints. To assess the numerical consistency, frequency, and areal distribution of flood risk around road underpasses, several hundred pieces of data were selected (mostly from international, national and local newspapers, CNR IRPI archive and local archives) and cataloged in a thematic database, referring mainly to the Italian territory. The behavioral aspects in the face of risk were also examined in order to provide a better understanding and raise awareness for preventive purposes. The results of this specific CNR research, which lasted about two years, confirm the exposure of underpasses to extreme risk events, affecting road users. In Italy alone, between 1942 and 2023, 698 underpasses were identified as having experienced a flooding event at least once. The database shows that 680 vehicles were involved in Italy, with a total of at least 812 individuals, of whom 19 died. Despite incomplete and uneven information, the findings of the analysis regarding the increment in underpasses flooding and the drivers action in front of a flooded underpass may be useful for undertaking the appropriate mitigation strategies.

Non-human primates (NHPs) host a variety of helminth and protist parasites that are able to cause infection in humans. Gastrointestinal parasites in NHPs living in two zoological gardens of Northern Italy were studied. An total of 96 faecal pools were collected from 26 groups of NHPs. The mini-Flotac method was applied to fecal samples to detect gastrointestinal helminthiases, while the detection of the protists Cryptosporidium spp., Blastocystis sp. and Giardia duodenalis was performed by targeting SSU rRNA through nested PCR and real-time PCR; they were further studied by sequencing the same gene for Blastocystis and βgiardine and triosephosphate isomerase (TPI) genes for Giardia. Twenty-two out of the 96 examined fecal pools (22.9%) were positive for one or more helminth species, including Hymenolepis diminuta, Trichurid, Capillariid and Strongylid eggs. All samples were negative for Cryptosporidium spp., while 16/26 (61.5%) animals were positive for G. duodenalis in the real-time PCR; the sequences obtained assigned them all to sub-assemblage BIV. Blastocystis sp. was detected in 22/26 of the NHPs (84.6%); molecular analyses attributed the isolates to ST 4, allele 92. Analyses of the feces of sympatric rats revealed the presence of the same allele, as well as of Hymenolepis diminuta eggs, raising concern about their role as parasite reservoirs in the facilities.

Gliomas present a complex challenge in neuro-oncology, often accompanied by the debilitating complication of epilepsy. Understanding the biological interaction and common pathways between gliomagenesis and epileptogenesis is crucial for improving the current understanding of tumorigenesis and also for developing effective management strategies. Shared genetic and molecular mechanisms, such as IDH mutations and dysregulated glutamate signaling, contribute to both tumor progression and seizure development. Targeting these pathways, such as through direct inhibition of mutant IDH enzymes or modulation of glutamate receptors, holds promise for improving patient outcomes. Additionally, advancements in surgical techniques, like supratotal resection guided by connectomics, offer opportunities for maximally safe tumor resection and enhanced seizure control. Advanced imaging modalities further aid in identifying epileptogenic foci and tailoring treatment approaches based on the tumor’s metabolic characteristics. This review aims to explore the complex interplay between gliomagenesis, epileptogenesis, and neural circuit remodeling, offering insights into shared molecular pathways and innovative treatment strategies to improve outcomes for patients with gliomas and associated epilepsy.

Traditional frame-based cameras, despite their effectiveness and usage in computer vision, exhibit limitations such as high latency, low dynamic range, high power consumption, and motion blur. For two decades, researchers have explored neuromorphic cameras, which operate differently from traditional frame-based types, mimicking biological vision systems for enhanced data acquisition and spatio-temporal resolution. Each pixel asynchronously captures intensity changes in the scene above certain user-defined thresholds, and streams of events are captured. However, the distinct characteristics of these sensors mean that traditional computer vision methods are not directly applicable, necessitating the investigation of new approaches before being applied in real applications. This work aims to fill existing gaps in the literature by providing a survey and a discussion centered on the different application domains, differentiating between computer vision problems and whether solutions are better suited for or have been applied to a specific field. Moreover, an extensive discussion highlights the major achievements and challenges, in addition to the unique characteristics, of each application field.

The protein, essential amino acid, and fatty acid composition of European pilchard (Sardina pilchardus), European hake (Merluccius merluccius), surmullet (Mullus surmuletus), red mullet (Mullus barbatus), and deep water rose shrimp (Parapenaeus longirostris) from the central Mediterranean Sea were investigated. All the species showed an essential amino acid content of about 50% of total amino acids, while the protein and total fatty acids content varied from 19.9 to 24.8% and from 1.4 to 5.1%, respectively. The fatty acid profile mainly followed the order SFA (39.1–52.6%) > PUFA (21.0–39.3%) > MUFA (15.6–24.3%). Palmitic and stearic acids were predominant among saturated fatty acids (38–52% and 21–25%, respectively), while palmitoleic and oleic acids were the most represented of the total monounsaturated acids (10–21% and 55–68%, respectively). All the species, as expected, showed a more significant proportion of n-3 PUFA (EPA + DHA) of about 81–93% of the total PUFA, with the highest values was found in European pilchard. Also, several fat quality index values, such as n-6/n-3 ratio, PUFA/SFA, the index of atherogenicity (IA), the index of thrombogenicity (IT), the hypocholesterolemic/hypercholesterolemic ratio (HH), and fish lipid quality/flesh lipid quality (FLQ) were calculated to assess the nutritional quality. All the obtained results, along with the fat quality indexes, indicated the excellent nutritional values of the selected species.

Coniolo and Brusaschetto, are two small towns located in the Monferrato area of the Alessandria Province, northern Italy. These communities have similar histories related to development and subsequent abandonment of marl quarry activity that began more than a century ago and continued until recently. Quarrying occurred until soil conditions, water infiltration, and excessive depth made cost of extracting and7 lifting material prohibitive. Quarries consisted of tunnels located directly beneath the towns at about 150 m below ground surface. Collapse of the tunnels led to surface subsidence and destruction of overlying homes and much of the municipal infrastructure. In the early Twentieth Century, regulations pertaining to mine and quarry safety were typically deficient, entirely absent, or not followed. Extractive activities of non-energy mineral resources from quarries and mines were and continue to be widespread in Italy, which currently ranks fifth among what are now countries of the European Union (EU). Mining sites are present in all regions of Italy, particularly in the northern part of the country and along coasts, often in areas of geohydrogeological risk. Consequences of anthropogenic pressures that alter the natural environment, such as the physical size of aquifer drawdowns, are linked to issues for a number of extractive sites across the country. This report analyzes historical and technical documents, conducts a geomorphological analysis of hilly slopes surrounding these communities, and examines urban planning and geophysical surveys to determine the impact of subsurface quarrying activities on the overlying ground surface. The study highlights significant problems that are applicable to other localities globally. This research demonstrates: (a) the importance of geological considerations to development and abandonment of mining activity in inhabited areas; (b) the importance of establishing and following safety protocols; and (c) the manner in which economic interests can take precedence over the well-being and lives of those employed to extract resources.

Domesticated animals have undergone significant changes in their behavior, morphology, and physiological functions during domestication. To identify the changes in gene expression associated with domestication, we collected the RNA-seq data of pigs, chickens, wild boars, and red junglefowl from public databases and performed a meta-analysis. Gene expression was quantified, and the expression ratio between domesticated animals and their wild ancestors (DW-ratio) was calculated. Genes were classified as “upregulated”, “downregulated”, or “unchanged” based on their DW-ratio, and the DW-score was calculated for each gene. Gene set enrichment analysis revealed that genes upregulated in pigs were related to defense from viral infection, whereas those upregulated in chickens were associated with aminoglycan and carbohydrate derivative catabolic processes. Genes commonly upregulated in pigs and chickens are involved in the immune response, olfactory learning, epigenetic regulation, cell division, and extracellular matrix. In contrast, genes upregulated in wild boar and red junglefowl are related to stress response, cell proliferation, cardiovascular function, neural regulation, and energy metabolism. These findings provide valuable insights into the genetic basis of the domestication process and highlight potential candidate genes for breeding applications.

Aurones, particular polyphenolic compounds belonging to the class of minor flavonoids and overlooked for a long time, have gained significative attention in medicinal chemistry in recent years. Indeed, considering their unique and outstanding biological properties, they stand out as an intriguing reservoir of new potential lead compounds in the drug discovery context. Nevertheless, several physicochemical, pharmacokinetic, and pharmacodynamic (P3) issues hinder their progression in more advanced phases of the drug discovery pipeline, making lead optimization campaigns necessary. In this context, scaffold hopping has proven to be a valuable approach in the optimization of natural products. This review provides a comprehensive and updated picture of the scaffold-hopping approaches directed at the optimization of natural and synthetic aurones. In the literature analysis, a particular focus is given to nitrogen and sulfur analogues. For each class presented, general synthetic procedures are summarized, highlighting the key advantages and potential issues. Furthermore, the biological activities of the most representative scaffold-hopped compounds are presented, emphasizing the improvements achieved and the potential for further optimization compared to the aurone class.

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes.

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of “NanoExplore Project” [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations—Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers—TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance.

Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25–57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.

Chronic ethanol exposure often triggers neuroinflammation in the brain’s reward system, potentially promoting the drive for ethanol consumption. A main marker of neuroinflammation is the microglia-derived monocyte chemoattractant protein 1 (MCP1) in animal models of alcohol use disorder in which ethanol is forcefully given. However, there are conflicting findings on whether MCP1 is elevated when ethanol is taken voluntarily, which challenges its key role in promoting motivation for ethanol consumption. Here, we studied MCP1 mRNA levels in areas implicated in consumption motivation—specifically, the prefrontal cortex, hippocampus, and striatum—as well as in the cerebellum, a brain area highly sensitive to ethanol, of C57BL/6 mice subjected to intermittent and voluntary ethanol consumption for two months. We found a significant increase in MCP1 mRNA levels in the cerebellum of mice that consumed ethanol compared to controls, whereas no significant changes were observed in the prefrontal cortex, hippocampus, or striatum or in microglia isolated from the hippocampus and striatum. To further characterize cerebellar neuroinflammation, we measured the expression changes in other proinflammatory markers and chemokines, revealing a significant increase in the proinflammatory microRNA miR-155. Notably, other classical proinflammatory markers, such as TNFα, IL6, and IL-1β, remained unaltered, suggesting mild neuroinflammation. These results suggest that the onset of neuroinflammation in motivation-related areas is not required for high voluntary consumption in C57BL/6 mice. In addition, cerebellar susceptibility to neuroinflammation may be a trigger to the cerebellar degeneration that occurs after chronic ethanol consumption in humans.

Shiga toxin-producing Escherichia coli are zoonotic pathogens that cause food-borne human disease. Among these, the O157:H7 serotype has evolved from an enteropathogenic O55:H7 ancestor through the displacement of the somatic gene cluster and recurrent toxigenic conversion by Shiga toxin-converting bacteriophages. However, atypical strains that lack the Shiga toxin, the characteristic virulence hallmark, are circulating in this lineage. For this study, we analyzed the pathogenome and virulence inventories of the stx+ strain, TT12A, isolated from a patient with hemorrhagic colitis, and its respective co-isolated stx− strain, TT12B. Sequencing the genomes to closure proved critical to the cataloguing of subtle strain differentiating sequence and structural polymorphisms at a high-level of phylogenetic accuracy and resolution. Phylogenomic profiling revealed SNP and MLST profiles similar to the near clonal outbreak isolates. Their prophage inventories, however, were notably different. The attenuated atypical non-shigatoxigenic status of TT12B is explained by the absence of both the ΦStx1a- and ΦStx2a-prophages carried by TT12A, and we also recorded further alterations in the non-Stx prophage complement. Phenotypic characterization indicated that culture growth was directly impacted by the strains’ distinct lytic phage complement. Altogether, our phylogenomic and phenotypic analyses show that these intimately related isogenic strains are on divergent Stx(+/stx−) evolutionary paths.

Background: The aim of the study is to identify the advantages, if any, of post-operative MRIs performed at 48 h compared to MRIs performed after 48 h in glioblastoma surgery. Materials and Methods: To assess the presence of a residual tumor, the T1-weighted Contrast Enhancement (CE), Apparent Diffusion Coefficient (ADC), and Cerebral Blood Volume (rCBV) in the proximity of the surgical cavity were considered. The rCBV ratio was calculated by comparing the rCBV with the contralateral normal white matter. After the blind image examinations by the two radiologists, the patients were divided into two groups according to time window after surgery: ≤48 h (group 1) and >48 h (group 2). Results: A total of 145 patients were enrolled; at the 6-month follow-up MRI, disease recurrence was 89.9% (125/139), with a mean patient survival of 8.5 months (SD 7.8). The mean ADC and rCBV ratio values presented statistical differences between the two groups (p < 0.05). Of these 40 patients in whom an ADC value was not obtained, the rCBV values could not be calculated in 52.5% (21/40) due to artifacts (p < 0.05). Conclusion: The study showed differences in CE, rCBV, and ADC values between the groups of patients undergoing MRIs before and after 48 h. An MRI performed within 48 h may increase the ability of detecting GBM by the perfusion technique with the calculation of the rCBV ratio.

Acute-on-chronic liver failure (ACLF) is a syndrome marked by sudden liver function decline and multiorgan failure, predominantly acute kidney injury (AKY), in patients with chronic liver disease. Unregulated inflammation is a hallmark of ACLF; however, the key drivers of ACLF are not fully understood. This study explores the therapeutic properties of human mesenchymal stem cell (MSC) secretome, particularly focusing on its enhanced anti-inflammatory and pro-regenerative properties after the in vitro preconditioning of the cells. We evaluated the efficacy of the systemic administration of MSC secretome in preventing liver failure and AKI in a rat ACLF model where chronic liver disease was induced using by the administration of porcine serum, followed by D-galN/LPS administration to induce acute failure. After ACLF induction, animals were treated with saline (ACLF group) or MSC-derived secretome (ACLF-secretome group). The study revealed that MSC-secretome administration strongly reduced liver histological damage in the ACLF group, which was correlated with higher hepatocyte proliferation, increased hepatic and systemic anti-inflammatory molecule levels, and reduced neutrophil and macrophage infiltration. Additionally, renal examination revealed that MSC-secretome treatment mitigated tubular injuries, reduced apoptosis, and downregulated injury markers. These improvements were linked to increased survival rates in the ACLF-secretome group, endorsing MSC secretomes as a promising therapy for multiorgan failure in ACLF.

Although botulinum toxin is widely considered an effective and safe treatment for a variety of neurological conditions (such as disabling spasticity), local or systemic adverse effects have often been reported. This study describes three cases of patients with severe acquired brain injury who were receiving speech therapy for recovering dysphagia and dysarthria but showed worsening of these symptoms after receiving BoNT treatment for motor spasticity. To increase clinicians’ knowledge of these adverse effects, we present our cases and explore their significance to avoid major complications such as aspiration pneumonia.

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12–16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment.

Escherichia albertii is an emerging foodborne pathogen. To better understand the pathogenesis and health risk of this pathogen, comparative genomics and phenotypic characterization were applied to assess the pathogenicity potential of E. albertii strains isolated from wild birds in a major agricultural region in California. Shiga toxin genes stx2f were present in all avian strains. Pangenome analyses of 20 complete genomes revealed a total of 11,249 genes, of which nearly 80% were accessory genes. Both core gene-based phylogenetic and accessory gene-based relatedness analyses consistently grouped the three stx2f-positive clinical strains with the five avian strains carrying ST7971. Among the three Stx2f-converting prophage integration sites identified, ssrA was the most common one. Besides the locus of enterocyte effacement and type three secretion system, the high pathogenicity island, OI-122, and type six secretion systems were identified. Substantial strain variation in virulence gene repertoire, Shiga toxin production, and cytotoxicity were revealed. Six avian strains exhibited significantly higher cytotoxicity than that of stx2f-positive E. coli, and three of them exhibited a comparable level of cytotoxicity with that of enterohemorrhagic E. coli outbreak strains, suggesting that wild birds could serve as a reservoir of E. albertii strains with great potential to cause severe diseases in humans.

Numerous riverbeds and floodplains in the Western Mediterranean Area (WMA) have been affected by anthropogenic modifications during the last centuries. In recent decades, an increase in floods in the coastal WMA has been observed. Variations in the rainfall regime and anthropisation have influenced the relevant geomorphological processes. The coastal floodplains analysed include those in Italy, France, and Spain. Geomorphological and land use changes that occurred in the last two centuries were examined using historical and recent maps, historical data, and European big data since the 1800s for 65 basins, for which over 670 flood events and more than 1300 victims were identified. Anthropogenic activities have changed the patterns of floodplains. In most cases, narrowing of the riverbeds, especially in the lower river sections, has been observed. The riverbeds have also changed from braided- to single-channel morphologies. GIS analysis shows reductions in the coastal watercourse widths ranging from 10% to 95%, with an average of 55%. Other changes are related to the deviation in the watercourses, with trends that did not respect the natural river flow. In some cases, the watercourses were covered and have vanished from recent maps. This aspect has reduced or eliminated the perception of the risk not only for the residents but also for land planners.

CDK-1 and PARP-1 play crucial roles in breast cancer progression. Compounds acting as CDK-1 and/or PARP-1 inhibitors can induct cell death in breast cancer with a selective synthetic lethality mechanism. A mixed treatment by means of CDK-1 and PARP-1 inhibitors resulted in radical breast cancer cell growth reduction. Inhibitors with a dual target mechanism of action could arrest cancer progression by simultaneously blocking the DNA repair mechanism and cell cycle, resulting in advantageous monotherapy. To this aim, in the present work, we identified compound 645656 with a significant affinity for both CDK-1 and PARP-1 by a mixed ligand- and structure-based virtual screening protocol. The Biotarget Predictor Tool was used at first in a Multitarget mode to filter the large National Cancer Institute (NCI) database. Then, hierarchical docking studies were performed to further screen the compounds and evaluate the ligands binding mode, whose putative dual-target mechanism of action was investigated through the correlation between the antiproliferative activity data and the target proteins’ (CDK-1 and PARP-1) expression pattern. Finally, a Molecular Dynamics Simulation confirmed the high stability of the most effective selected compound 645656 in complex with both PARP-1 and CDK-1.

Climate change has significantly increased the frequency of our exposure to heat, adversely affecting human health and industries. Heat stress is an environmental stress defined as the exposure of organisms and cells to abnormally high temperatures. To comprehensively explain the mechanisms underlying an organism’s response to heat stress, it is essential to investigate and analyze genes that have been under-represented or less well-known in previous studies. In this study, we analyzed heat stress-responsive genes using a meta-analysis of numerous gene expression datasets from the public database. We obtained 322 human and 242 mouse pairs as the heat exposure and control data. The meta-analysis of these data identified 76 upregulated and 37 downregulated genes common to both humans and mice. We performed enrichment, protein–protein interaction network, and transcription factor target gene analyses for these genes. Furthermore, we conducted an integrated analysis of these genes using publicly available chromatin immunoprecipitation sequencing (ChIP-seq) data for HSF1, HSF2, and PPARGC1A (PGC-1α) as well as gene2pubmed data from the existing literature. The results identified previously overlooked genes, such as ABHD3, ZFAND2A, and USPL1, as commonly upregulated genes. Further functional analysis of these genes can contribute to coping with climate change and potentially lead to technological advancements.

Urbanization in flood-prone areas is a critical issue worldwide. The historical floods, the urban expansion in terms of building footprint, the extent and construction period of inundated buildings with reference to two representative floods (5–6 November 1994 and 24–25 November 2016), and the ground effects and dynamics of these events were investigated in the cities of Garessio, Ceva, and Clavesana, along the Tanaro River (NW Italy). An integrated approach based on historical data analysis, photograph interpretation, field surveys, and GIS investigations was adopted, and novel metrics for quantitative analysis of urbanization and flood exposure at the individual-building scale were introduced. The considered cities were hit by damaging floods several times over the last centuries and experienced an increase in built-up surface after the mid-19th century, especially between the 1930s and 1994. The 1994 and 2016 high-magnitude floods highlighted that urban expansion largely occurred in flood-prone areas, and anthropogenic structures conditioned flood propagation. One of the rare Italian cases of the relocation of elements exposed to floods is documented. This research aims to emphasize the relevance of information on past floods and urbanization processes for land planning and land management and the need for land use planning for flood control to forbid new urban expansion in potentially floodable areas. The outcomes represent an essential knowledge base to define effective and sustainable management measures to mitigate hydrogeomorphic risk.

During pregnancy, reactive oxygen species (ROS) may physiologically increase due to changes and growth of mother and fetal tissues. Consequently, oxidative stress (OS) may occur and be involved in the onset of pregnancy and newborn complications. Among exogenous antioxidant sources, diet is a cost-effective prevention strategy supporting the health of mothers and newborns; however, there is still a lack of nutritional education during pregnancy interviews. This review aims to systematically summarize the knowledge on the association between OS and diet during pregnancy. Four electronic databases (PubMed Central, EMBASE, Web of Science, and Food Science and Technology Abstracts) were searched on 22 December 2022. Among 4162 records, 13 original articles were finally included. Overall, 80% of the studies considered dietary patterns as exposure and 60% of them assessed the association with malondialdehyde levels in blood and urine. Three studies analyzed the influence of daily intakes of fruit and vegetables on different OS biomarkers (malondialdehyde, nitric oxide and 8-hydroxy-2′-deoxyguanosine). Among studies exploring dietary fat intakes (39%), 80% focused on polyunsaturated fatty acids, finding a positive association with glutathione peroxidase, biopirryn and isoprostane levels, respectively. Four studies analyzed vitamin intakes and 50% of them in association with 8-hydroxy-2′-deoxyguanosine.

Green synthesis is a promising strategy for producing eco-friendly, non-toxic, and less expensive metallic nanoparticles from plants and microorganisms. This research synthesized silver nanoparticles (AgNPs) from fermented leaf extract of bush tea (Athrixia phylicoides DC). The physicochemical characterization of AgNPs was conducted by UV-vis spectroscopy, Fourier Transform Infrared Spectrometry (FTIR), and Differential Scanning Calorimetry (DSC). In addition, the total phenolic and flavonoid contents, antioxidant and antimicrobial activities of AgNPs were evaluated. The results indicated the successful formation of AgNPs by a visual change of color in fermented bush tea leaf extract from black to brown and in unfermented bush tea leaf crude extract from dark brown to light brown. The UV-vis spectrum of the reaction of the mixture of synthesized AgNPs with unfermented and fermented bush tea showed maximum absorbance at 457 nm and 450 nm, which confirmed the formation of AgNPs. FTIR revealed the functional groups of a leaf extract from bush tea that contributed to the reduction and capping process. The thermal properties suggest that low thermal stable compounds contributed to the reduction of Ag+ to Ag° in the phyto compounds found in the extract. The total phenolic content was higher in fermented AgNPs (290.44 mg/g GAE) compared to unfermented AgNPs (171.34 mg/g GAE). On the other hand, the total flavonoid content was higher in unfermented AgNPs (17.87 mg/g CE) than in fermented AgNPs (9.98 mg/g CE). Regarding antioxidant activity values, unfermented AgNPs had the highest FRAP (535.30 TE/mL) and 47.58% for DPPH. Fermented AgNPs had more antimicrobial activity than unfermented AgNPs. The results show that bush tea leaf extract can be used in different industries such as food, cosmetics, and biomedical.

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we aimed to summarize the recent data on the oncogenic role of concurrent genomic alterations, by specifically evaluating the characteristics, the pathological significance, and their potential impact on the treatment approach.

As the world’s population grows, so does the need for more and more animal feed. In 2006, the EU banned the use of antibiotics and other chemicals in order to reduce chemical residues in food consumed by humans. It is well known that oxidative stress and inflammatory processes must be combated to achieve higher productivity. The adverse effects of the use of pharmaceuticals and other synthetic compounds on animal health and product quality and safety have increased interest in phytocompounds. With the use of plant polyphenols in animal nutrition, they are gaining more attention as a supplement to animal feed. Livestock feeding based on a sustainable, environmentally friendly approach (clean, safe, and green agriculture) would also be a win–win for farmers and society. There is an increasing interest in producing healthier products of animal origin with a higher ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids by modulating animal nutrition. Secondary plant metabolites (polyphenols) are essential chemical compounds for plant physiology as they are involved in various functions such as growth, pigmentation, and resistance to pathogenic organisms. Polyphenols are exogenous antioxidants that act as one of the first lines of cell defense. Therefore, the discoveries on the intracellular antioxidant activity of polyphenols as a plant supplement have contributed significantly to the improvement of antioxidant activity, as polyphenols prevent oxidative stress damage and eliminate excessively produced free radicals. To achieve animal welfare, reduce stress and the need for medicines, and increase the quality of food of animal origin, the addition of polyphenols to research and breeding can be practised in part with a free-choice approach to animal nutrition.

In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy of an individualized technique of subcutaneous injection of botulinum toxin type A (BoNT-A) targeted (SjBoT) to the occipital or trigeminal skin area in non-responder patients with chronic migraine (CM). Patients who had not previously responded to at least two treatments of intramuscular injections of BoNT-A were randomly assigned (2:1) to receive two subcutaneous administrations of BoNT-A (up to 200 units) with the SjBoT injection paradigm or placebo. Following the skin area where the maximum pain began, treatment was given in the trigeminal or occipital region bilaterally. The primary endpoint changed in monthly headache days from baseline to the last 4 weeks. Among 139 randomized patients, 90 received BoNT-A and 49 received placebo, and 128 completed the double-blind phase. BoNT-A significantly reduced monthly headache days versus placebo (−13.2 versus −1.2; p < 0.0001) in the majority of patients who had cutaneous allodynia. Other secondary endpoints, including measures for disability (Migraine Disability Assessment questionnaire from baseline 21.96 to 7.59 after treatment, p = 0.028), also differed. Thus, in non-responder patients with CM, BoNT-A significantly reduced migraine days when administered according to the “follow the origin of maximum pain” approach using SjBoT injection paradigm.

The application of intelligent systems for structural health monitoring is investigated. A change in the nominal configuration can be related to a structural defect that has to be monitored before it reaches a critical condition. Evidently, the ability to automatically detect changes in a structure is a very attractive feature. When there is no prior knowledge on the system, deep learning models could effectively detect a change and enhance the capability of determining the damage location. However, the acquisition of data related to damaged structures is not always practical. In this paper, two deep learning approaches, a physics-informed autoencoder and a simple data-driven autoencoder, are applied to a test rig consisting of a small four-storey building model. Modifications to the system are simulated by changing the stiffness of the springs. Both the machine learning algorithms outperform the traditional approach based on an experimental modal analysis. Moreover, the increased potential of the physics-informed neural networks to detect and locate damage is confirmed.

Eusociality in insects has evolved independently many times. One of the most notable characteristics of eusociality is the reproductive division of labor. In social insects, the reproductive division of labor is accomplished by queens and workers. Transcriptome analyses of queens and workers have been conducted for various eusocial species. However, the genes that regulate the reproductive division of labor across all or multiple eusocial species have not yet been fully elucidated. Therefore, we conducted a meta-analysis using publicly available RNA-sequencing data from four major groups of social insects. In this meta-analysis, we collected 258 pairs (queen vs. worker) of RNA-sequencing data from 34 eusocial species. The meta-analysis identified a total of 20 genes that were differentially expressed in queens or workers. Out of these, 12 genes have not previously been reported to be involved in the reproductive division of labor. Functional annotation of these 20 genes in other organisms revealed that they could be regulators of behaviors and physiological states related to the reproductive division of labor. These 20 genes, revealed using massive datasets of numerous eusocial insects, may be key regulators of the reproductive division of labor.

The viral main protease is one of the most attractive targets among all key enzymes involved in the life cycle of SARS-CoV-2. Considering its mechanism of action, both the catalytic and dimerization regions could represent crucial sites for modulating its activity. Dual-binding the SARS-CoV-2 main protease inhibitors could arrest the replication process of the virus by simultaneously preventing dimerization and proteolytic activity. To this aim, in the present work, we identified two series’ of small molecules with a significant affinity for SARS-CoV-2 MPRO, by a hybrid virtual screening protocol, combining ligand- and structure-based approaches with multivariate statistical analysis. The Biotarget Predictor Tool was used to filter a large in-house structural database and select a set of benzo[b]thiophene and benzo[b]furan derivatives. ADME properties were investigated, and induced fit docking studies were performed to confirm the DRUDIT prediction. Principal component analysis and docking protocol at the SARS-CoV-2 MPRO dimerization site enable the identification of compounds 1b,c,i,l and 2i,l as promising drug molecules, showing favorable dual binding site affinity on SARS-CoV-2 MPRO.

Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visuospatial processing but spared verbal competencies. Neurocognitive markers may provide confirmatory evidence for characterizing NVLD as a separate neurodevelopmental disorder. Visuospatial performance and high-density electroencephalography (EEG) were measured in 16 NLVD and in 16 typically developing (TD) children. Cortical source modeling was applied to assess resting-state functional connectivity (rs-FC) in spatial attention networks (dorsal (DAN) and ventral attention networks (VAN)) implicated in visuospatial abilities. A machine-learning approach was applied to investigate whether group membership could be predicted from rs-FC maps and if these connectivity patterns were predictive of visuospatial performance. Graph theoretical measures were applied to nodes inside each network. EEG rs-FC maps in the gamma and beta band differentiated children with and without NVLD, with increased but more diffuse and less efficient functional connections bilaterally in the NVLD group. While rs-FC of the left DAN in the gamma range predicted visuospatial scores for TD children, in the NVLD group rs-FC of the right DAN in the delta range predicted impaired visuospatial performance, confirming that NVLD is a disorder with a predominant dysfunction in right hemisphere connectivity patterns.

Developing methodologies to accurately characterise the energy conditions of existing building stock is a fundamental aspect of energy consumption reduction strategies. To that end, a case study using a thermal information modelling method for existing buildings (as-is T-BIM) is reported. This proposed new method is based on the automatic processing of 3D thermal clouds of interior zones of a building that generates a semantic proprietary model that contains time series of surface temperatures assigned to its surface elements. The proprietary as-is T-BIM automatically generates an as-is BEM model with gbXML standards for energy simulation. This is a multi-zone energy model of the building. In addition, the surface temperature data series of the as-is T-BIM model elements permit the calculation of their thermal transmittances, increasing the calibration options of the obtained as-is BEM model. To test the as-is TBIM method, a case study compares the as-is BEM model obtained by as-is T-BIM methods with the one obtained by standard methods for the same building. The results demonstrate differences in geometry, transmittance, and infiltration values, as well as insignificant differences in annual air conditioning energy consumption or the comfort parameters tested. This seems to indicate shorter modelling times and greater accuracy of the as-is T-BIM model.

Structural health monitoring of civil infrastructure, such as bridges and buildings, has become a trending topic in the last few years. The key factor is the technological push given by new technologies that permit the acquisition, storage, processing and visualisation of data in real time, thus assessing a structure’s health condition. However, data related to anomaly conditions are difficult to retrieve, and, by the time those conditions are met, in general, it is too late. For this reason, the problem becomes unsupervised, since no labelled data are available, and anomaly detection algorithms are usually adopted in this context. This research proposes a novel algorithm that transforms the intrinsically unsupervised problem into a supervised one for condition monitoring purposes. Considering a bridge equipped with N sensors, which measure static structural quantities (rotations of the piers) and environmental parameters, exploiting the relationships between different physical variables and determining how these relationships change over time can indicate the bridge’s health status. In particular, this algorithm involves the training of N models, each of them able to estimate the quantity measured via a sensor by using the others’ N−1 measurements. Hence, the system can be represented by the ensemble of the N models. In this way, for each sensor, it is possible to compare the real measurement with the predicted one and evaluate the residual between the two; this difference can be addressed as a symptom of changes in the structure with respect to the condition regarded as nominal. This approach is applied to a real test case, i.e., Candia Bridge in Italy, and it is compared with a state-of-the-art anomaly detector (namely an autoencoder) in order to validate its robustness.

Gratitude interventions can provide cost-effective support for mental health to under-resourced schools. This study aims to better understand the effects of a promising intervention Bono et al. evaluated in 2020. Using a quasi-experimental design (where classes were assigned to a thanking app, gratitude curriculum, app + curriculum, or control condition), that evaluation found that the full (combined) intervention impacted students’ self-reported trait gratitude, anxiety, and subjective well-being (SWB) over six weeks, compared against only the control condition. However, here, we evaluated the individual intervention components’ effectiveness on students (N = 326) using multilevel modeling. As hypothesized, the full intervention impacted students’ gratitude, anxiety, and SWB, compared to the control condition, but impacted SWB more than the app-only condition, suggesting that teaching gratitude science makes thanking more meaningful. Then, we examined if stress mediated these effects. Perceived stress partially mediated the relationships of gratitude with depression and SWB and fully mediated the relationship of gratitude with anxiety. Additionally, changes in perceived stress and SWB differed by gender. Finally, we qualitatively analyzed thanks exchanges during the intervention using informal content analysis and found themes of psychological safety—a critical feature neglected in other interventions. We conclude with recommendations for optimizing school gratitude interventions.

The heteromer composed of dopamine D1 and D3 receptors (D1R–D3R) has been defined as a structure able to trigger Erk1/2 and Akt signaling in a G protein-independent, beta-arrestin 1-dependent way that is physiologically expressed in the ventral striatum and is likely involved in the control of locomotor activity. Indeed, abnormal levels of D1R-D3R heteromer in the dorsal striatum have been correlated with the development of L-DOPA-induced dyskinesia (LID) in Parkinson’s disease patients, a motor complication associated with striatal D1R signaling, thus requiring Gs protein and PKA activity to activate Erk1/2. Therefore, to clarify the role of the D1R/D3R heteromer in LID, we investigated the signaling pathway induced by the heteromer using transfected cells and primary mouse striatal neurons. Collectively, we found that in both the cell models, D1R/D3R heteromer-induced activation of Erk1/2 exclusively required the D1R molecular effectors, such as Gs protein and PKA, with the contribution of the phosphatase Shp-2 and beta-arrestins, indicating that heterodimerization with the D3R abolishes the specific D3R-mediated signaling but strongly allows D1R signals. Therefore, while in physiological conditions the D1R/D3R heteromer could represent a mechanism that strengthens the D1R activity, its pathological expression may contribute to the abnormal PKA-Shp-2-Erk1/2 pathway connected with LID.

The leading mechanisms through which air pollutants exert their damaging effects are the promotion of oxidative stress, the induction of an inflammatory response, and the deregulation of the immune system by reducing its ability to limit infectious agents’ spreading. This influence starts in the prenatal age and continues during childhood, the most susceptible period of life, due to a lower efficiency of oxidative damage detoxification, a higher metabolic and breathing rate, and enhanced oxygen consumption per unit of body mass. Air pollution is involved in acute disorders like asthma exacerbations and upper and lower respiratory infections, including bronchiolitis, tuberculosis, and pneumoniae. Pollutants can also contribute to the onset of chronic asthma, and they can lead to a deficit in lung function and growth, long-term respiratory damage, and eventually chronic respiratory illness. Air pollution abatement policies, applied in the last decades, are contributing to mitigating air quality issues, but more efforts should be encouraged to improve acute childhood respiratory disease with possible positive long-term effects on lung function. This narrative review aims to summarize the most recent studies on the links between air pollution and childhood respiratory illness.

This paper describes the main results of the JUNO project, a proof of concept developed in the Region of Murcia in Spain, where a smart assistant robot with capabilities for smart navigation and natural human interaction has been developed and deployed, and it is being validated in an elderly institution with real elderly users. The robot is focused on helping people carry out cognitive stimulation exercises and other entertainment activities since it can detect and recognize people, safely navigate through the residence, and acquire information about attention while users are doing the mentioned exercises. All the information could be shared through the Cloud, if needed, and health professionals, caregivers and relatives could access such information by considering the highest standards of privacy required in these environments. Several tests have been performed to validate the system, which combines classic techniques and new Deep Learning-based methods to carry out the requested tasks, including semantic navigation, face detection and recognition, speech to text and text to speech translation, and natural language processing, working both in a local and Cloud-based environment, obtaining an economically affordable system. The paper also discusses the limitations of the platform and proposes several solutions to the detected drawbacks in this kind of complex environment, where the fragility of users should be also considered.

A cytokine storm drives the pathogenesis of severe COVID-19 infection and several biomarkers have been linked to mortality. Chronic kidney disease (CKD) emerged as a risk factor for severe COVID-19. We investigated the association between selected biomarkers and mortality in 77 patients hospitalized for COVID-19, and whether they differ in patients with eGFR higher and lower than 45 mL/min. The association between patients’ characteristics, plasma biomarkers and mortality was conducted by univariate logistic regression models and independent predictors of mortality were then used to create a multivariate prediction model through Cox regression. Patients with lower eGFR had a significant increase of GDF-15, CD-25 and RAGE, with higher plasma levels in non-survivors and in patients who needed ventilation. At univariate analysis, low and mid-low GDF-15 quartiles (4.45 ng/mL) were associated with higher mortality risk. Independent association between GDF-15 quartiles and mortality risk was confirmed in the Cox model and adjusted for eGFR, age, fever and dyspnea (HR 2.28, CI 1.53–3.39, p < 0.0001). The strength of the association between GDF-15 quartiles and mortality risk increased in patients with lower compared to higher eGFR (HR 2.53, CI 1.34–4.79 versus HR 1.99, CI 1.17–3.39). Our findings may suggest a further investigation of the effect of GDF-15 signaling pathway inhibition in CKD.

Lepidopteran insects are an important group of animals, including those used as biochemical and physiological model species in the insect and silk industries as well as others that are major agricultural pests. Therefore, the genome sequences of several lepidopteran insects have been reported. The oriental armyworm, Mythimna separata, is an agricultural pest commonly used to study insect immune reactions and interactions with parasitoid wasps as hosts. To improve our understanding of these research topics, reference genome sequences were constructed in the present study. Using long-read and short-read sequence data, de novo assembly and polishing were performed and haplotigs were purged. Subsequently, gene predictions and functional annotations were performed. To search for orthologs of the Toll and Immune Deficiency (IMD) pathways and for C-type lectins, annotation data analysis, BLASTp, and Hummer scans were performed. The M. separata genome is 682 Mbp; its contig N50 was 2.7 Mbp, with 21,970 genes and 24,452 coding sites predicted. All orthologs of the core components of the Toll and IMD pathways and 105 C-type lectins were identified. These results suggest that the genome data were of sufficient quality for use as reference genome data and could contribute to promoting M. separata and lepidopteran research at the molecular and genome levels.

In this work, a dataset of more than 200 nitroaromatic compounds is used to develop Quantitative Structure–Activity Relationship (QSAR) models for the estimation of in vivo toxicity based on 50% lethal dose to rats (LD50). An initial set of 4885 molecular descriptors was generated and applied to build Support Vector Regression (SVR) models. The best two SVR models, SVR_A and SVR_B, were selected to build an Ensemble Model by means of Multiple Linear Regression (MLR). The obtained Ensemble Model showed improved performance over the base SVR models in the training set (R2 = 0.88), validation set (R2 = 0.95), and true external test set (R2 = 0.92). The models were also internally validated by 5-fold cross-validation and Y-scrambling experiments, showing that the models have high levels of goodness-of-fit, robustness and predictivity. The contribution of descriptors to the toxicity in the models was assessed using the Accumulated Local Effect (ALE) technique. The proposed approach provides an important tool to assess toxicity of nitroaromatic compounds, based on the ensemble QSAR model and the structural relationship to toxicity by analyzed contribution of the involved descriptors.

RNA binding proteins (RBPs) play a fundamental role in the post-transcriptional regulation of gene expression within the germline and nervous system. This is underscored by the prevalence of mutations within RBP-encoding genes being implicated in infertility and neurological disease. We previously described roles for the highly conserved RBP Caper in neurite morphogenesis in the Drosophila larval peripheral system and in locomotor behavior. However, caper function has not been investigated outside the nervous system, although it is widely expressed in many different tissue types during embryogenesis. Here, we describe novel roles for Caper in fertility and mating behavior. We find that Caper is expressed in ovarian follicles throughout oogenesis but is dispensable for proper patterning of the egg chamber. Additionally, reduced caper function, through either a genetic lesion or RNA interference-mediated knockdown of caper in the female germline, results in females laying significantly fewer eggs than their control counterparts. Moreover, this phenotype is exacerbated with age. caper dysfunction also results in partial embryonic and larval lethality. Given that caper is highly conserved across metazoa, these findings may also be relevant to vertebrates.

Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways. Polymorphisms in the Synapsin III (Syn III) gene can associate with ADHD onset and even affect the therapeutic response to the gold standard ADHD medication, methylphenidate (MPH), a monoamine transporter inhibitor whose efficacy appears related with the stimulation of brain-derived neurotrophic factor (BDNF). Interestingly, we previously showed that MPH can bind Syn III, which can regulate neuronal development. These observations suggest that Syn III polymorphism may impinge on ADHD onset and response to therapy by affecting BDNF-dependent dopaminergic neuron development. Here, by studying zebrafish embryos exposed to Syn III gene knock-down (KD), Syn III knock-out (ko) mice and human induced pluripotent stem cells (iPSCs)-derived neurons subjected to Syn III RNA interference, we found that Syn III governs the earliest stages of dopaminergic neurons development and that this function is conserved in vertebrates. We also observed that in mammals Syn III exerts this function acting upstream of brain-derived neurotrophic factor (BDNF)- and cAMP-dependent protein kinase 5 (Cdk5)-stimulated dendrite development. Collectively, these findings own significant implications for deciphering the biological basis of ADHD.

In vitro antiproliferative assays still represent one of the most important tools in the anticancer drug discovery field, especially to gain insights into the mechanisms of action of anticancer small molecules. The NCI-DTP (National Cancer Institute Developmental Therapeutics Program) undoubtedly represents the most famous project aimed at rapidly testing thousands of compounds against multiple tumor cell lines (NCI60). The large amount of biological data stored in the National Cancer Institute (NCI) database and many other databases has led researchers in the fields of computational biology and medicinal chemistry to develop tools to predict the anticancer properties of new agents in advance. In this work, based on the available antiproliferative data collected by the NCI and the manipulation of molecular descriptors, we propose the new in silico Antiproliferative Activity Predictor (AAP) tool to calculate the GI50 values of input structures against the NCI60 panel. This ligand-based protocol, validated by both internal and external sets of structures, has proven to be highly reliable and robust. The obtained GI50 values of a test set of 99 structures present an error of less than ±1 unit. The AAP is more powerful for GI50 calculation in the range of 4–6, showing that the results strictly correlate with the experimental data. The encouraging results were further supported by the examination of an in-house database of curcumin analogues that have already been studied as antiproliferative agents. The AAP tool identified several potentially active compounds, and a subsequent evaluation of a set of molecules selected by the NCI for the one-dose/five-dose antiproliferative assays confirmed the great potential of our protocol for the development of new anticancer small molecules. The integration of the AAP tool in the free web service DRUDIT provides an interesting device for the discovery and/or optimization of anticancer drugs to the medicinal chemistry community. The training set will be updated with new NCI-tested compounds to cover more chemical spaces, activities, and cell lines. Currently, the same protocol is being developed for predicting the TGI (total growth inhibition) and LC50 (median lethal concentration) parameters to estimate toxicity profiles of small molecules.

The Western honeybee (Apis mellifera) is valuable in biological research and agriculture. Its genome sequence was published before those for other insect species. RNA-Seq data for A. mellifera have been applied in several recently published studies. Nevertheless, these data have not been prepared for use in subsequent meta-analyses. To promote A. mellifera transcriptome analysis, we constructed reference transcriptome data using the reference genome sequence and RNA-Seq data curated from about 1,000 runs of public databases. The new reference transcriptome data construct comprised 149,685 transcripts, and 194,174 protein sequences were predicted. Approximately 50–60% of the predicted protein sequences were functionally annotated using the protein sequence data for several model and insect species. Novel candidate immune-related transcripts were searched by meta-analysis using immune-response-related RNA-Seq and reference transcriptome data. Three to twenty candidate transcripts including autophagy-related protein 3 were upregulated or downregulated in response to both viral and bacterial infections. The constructed reference transcriptome data may facilitate future transcriptome analyses of A. mellifera.

To offer point absorber wave energy converters (WECs) as a bankable product on the marine renewable energy market, multiple WECs will be installed together in an array configuration. The wave energy community (research and industrial) has identified the urgent need for available realistic and reliable data on WEC array tests in order to perform a better WEC array optimization approach and in order to validate recently developed (non-linear) numerical models. The ‘WECfarm’ project is initiated to cover this scientific gap on necessary experimental data. The ‘WECfarm’ experimental setup consists of an array of five generic heaving point-absorber WECs. The WECs are equipped with a permanent magnet synchronous motor (PMSM), addressing the need for WEC array tests with an accurate and actively controllable power take-off (PTO). The WEC array control and data acquisition are realized with a Speedgoat Performance real-time target machine, offering the possibility to implement advanced WEC array control strategies in the MATLAB-Simulink environment. The presented article describes the experimental setup, the performed tests and the results of the test campaign using a single, isolated ‘WECfarm’ WEC in April 2021 at the wave basin of Aalborg University (AAU), Denmark. A Coulomb and viscous friction model is determined to partly compensate for the drivetrain (motor, gearbox, rack and pinion) friction. A system identification (SID) approach is adopted considering the WEC system to be composed of two single input single output (SISO) models, the radiation and the excitation model. Radiation tests yield the intrinsic impedance. Excitation tests yield the excitation frequency response function. Adopting an impedance matching approach, the control parameters for the resistive and reactive controller are determined from the complex conjugate of the intrinsic impedance. Both controllers are tested for a selection of regular wave conditions. The performed experimental test campaign using an isolated ‘WECfarm’ WEC allows a full evaluation of the WEC design prior to extending the setup to five WECs. Within the ‘WECfarm’ project, an experimental campaign with a five-WEC array in the Coastal and Ocean Basin (COB) in Ostend, Belgium, is under preparation.

With increasing public data, a statistical analysis approach called meta-analysis, which combines transcriptome results obtained from multiple studies, has succeeded in providing novel insights into targeted biological processes. Locusts and aphids are representative of insect groups that exhibit density-dependent plasticity. Although the physiological mechanisms underlying density-dependent polyphenism have been identified in aphids and locusts, the underlying molecular mechanisms remain largely unknown. In this study, we performed a meta-analysis of public transcriptomes to gain additional insights into the molecular underpinning of density-dependent plasticity. We collected RNA sequencing data of aphids and locusts from public databases and detected differentially expressed genes (DEGs) between crowded and isolated conditions. Gene set enrichment analysis was performed to reveal the characteristics of the DEGs. DNA replication (GO:0006260), DNA metabolic processes (GO:0006259), and mitotic cell cycle (GO:0000278) were enriched in response to crowded conditions. To date, these processes have scarcely been the focus of research. The importance of the oxidative stress response and neurological system modifications under isolated conditions has been highlighted. These biological processes, clarified by meta-analysis, are thought to play key roles in the regulation of density-dependent plasticity.

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR < 30 (n = 23), 30 < eGFR < 60 (n = 33), eGFR > 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases.

Since the Transformer architecture was introduced in 2017, there has been many attempts to bring the self-attention paradigm in the field of computer vision. In this paper, we propose LHC: Local multi-Head Channel self-attention, a novel self-attention module that can be easily integrated into virtually every convolutional neural network, and that is specifically designed for computer vision, with a specific focus on facial expression recognition. LHC is based on two main ideas: first, we think that in computer vision, the best way to leverage the self-attention paradigm is the channel-wise application instead of the more well explored spatial attention. Secondly, a local approach has the potential to better overcome the limitations of convolution than global attention, at least in those scenarios where images have a constant general structure, as in facial expression recognition. LHC-Net achieves a new state-of-the-art in the FER2013 dataset, with a significantly lower complexity and impact on the “host” architecture in terms of computational cost when compared with the previous state-of-the-art.