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Abstract Posttraumatic stress disorder (PTSD) is associated with glutamatergic neuron hyperactivation in the basolateral amygdala (BLA) brain area, while GABAergic interneurons in the BLA modulate glutamatergic neuron excitability. Studies have shown that propofol exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid. The neuronal mechanism by which propofol anesthesia modulates fear memory is currently unknown. Here, we used optogenetics and chemogenetics to suppress glutamatergic neurons or activate GABAergic interneurons in the BLA to assess alterations in neuronal excitation-inhibition balance and investigate fear memory. The excitability of glutamatergic neurons in the BLA was significantly reduced by the suppression of glutamatergic neurons or activation of GABAergic interneurons, while propofol-mediated enhancement of fear memory was attenuated. We suggest that propofol anesthesia could reduce the excitability of GABAergic neurons through activation of GABAA receptors, subsequently increasing the excitability of glutamatergic neurons in the mice BLA; the effect of propofol on enhancing mice fear memory might be mediated by strengthening glutamatergic neuronal excitability and decreasing the excitability of GABAergic neurons in the BLA; neuronal excitation-inhibition imbalance in the BLA might be important in mediating the enhancement of fear memory induced by propofol.

Abstract The genomic signature of an organism captures the characteristics of repeated oligonucleotide patterns in its genome 1, such as oligomer frequencies, GC content, and differences in codon usage. Viruses, however, are obligate intracellular parasites that are dependent on their host cells for replication, and information about genomic signatures in viruses has hitherto been sparse. Here, we investigate the presence and specificity of genomic signatures in 2,768 eukaryotic viral species from 105 viral families, aiming to illuminate dependencies and selective pressures in viral genome evolution. We demonstrate that most viruses have highly specific genomic signatures that often also differ significantly between species within the same family. The species-specificity is most prominent among dsDNA viruses and viruses with large genomes. We also reveal consistent dissimilarities between viral genomic signatures and those of their host cells, although some viruses present slight similarities, which may be explained by genetic adaptation to their native hosts. Our results suggest that significant evolutionary selection pressures act upon viral genomes to shape and preserve their genomic signatures, which may have implications for the field of synthetic biology in the construction of live attenuated vaccines and viral vectors.

Abstract Cryo-EM particle identification from micrographs (“picking”) is challenging due to the low signal-to-noise ratio and lack of ground truth for particle locations. State-of-the-art computational algorithms (“pickers”) identify different particle sets, complicating the selection of the best-suited picker for a protein of interest. Here, we present REliable PIcking by Consensus (REPIC), a computational approach to identifying particles common to the output of multiple pickers. We frame consensus particle picking as a graph problem, which REPIC solves using integer linear programming. REPIC picks high-quality particles even when the best picker is not known a priori or a protein is difficult-to-pick (e.g., NOMPC ion channel). Reconstructions using consensus particles without particle filtering achieve resolutions comparable to those from particles picked by experts. Our results show that REPIC requires minimal (often no) manual intervention, and considerably reduces the burden on cryo-EM users for picker selection and particle picking. Availability: https://github.com/ccameron/REPIC .

Abstract Background Mitochondria-endoplasmic reticulum membrane contact (MERC) is an important mode of intercellular organelle communication and plays a crucial role in adipose tissue metabolism. Functionality of Hoxa5 is an important transcription factor involved in adipose tissue fate determination and metabolic regulation, but the relationship between Hoxa5 and MERC is not well understood. Results In our study, we established an obesity model mouse by high-fat diet (HFD), induced the alteration of Hoxa5 expression by adenoviral transfection, and explored the effect of Hoxa5 on MERC dysfunction and metabolic distortions of adipose tissue with the help of transmission electron microscopy, calcium ion probe staining, and other detection means. The results showed Hoxa5 was able to reduce MERC production, alleviate endoplasmic reticulum stress (ERS) and calcium over-transport, and affect cGAS-STING-mediated innate immune response affecting adipose tissue energy metabolism, as well as affect the AKT-IP3R pathway to alleviate insulin resistance and ameliorate metabolic distortions in adipose tissue of mice. Conclusions Our results suggest that Hoxa5 can ameliorate high-fat diet-induced MERC overproduction and related functional abnormalities, in which finding is expected to provide new ideas for the improvement of obesity-related metabolic distortions.

Abstract Background The Leishmania genome harbors formerly active short interspersed degenerated retroposons (SIDERs) representing the largest family of repetitive elements among trypanosomatids. Their substantial expansion in Leishmania is a strong predictor of important biological functions. In this study, we combined multilevel bioinformatic predictions with high-throughput genomic and transcriptomic analyses to gain novel insights into the diversified roles retroposons of the SIDER2 subfamily play in Leishmania genome evolution and expression. Results We show that SIDER2 retroposons form various evolutionary divergent clusters, each harboring homologous SIDER2 sequences usually located nearby in the linear sequence of chromosomes. This intriguing genomic organization underscores the importance of SIDER2 proximity in shaping chromosome dynamics and co-regulation. Accordingly, we show that transcripts belonging to the same SIDER2 cluster can display similar levels of expression. SIDER2 retroposons are mostly transcribed as part of 3'UTRs and account for 13% of the Leishmania transcriptome. Genome-wide expression profiling studies underscore SIDER2 association generally with low mRNA expression. The remarkable link of SIDER2 retroposons with downregulation of gene expression supports their co-option as major regulators of mRNA abundance. SIDER2 sequences also add to the diversification of the Leishmania gene expression repertoire since ~ 35% of SIDER2-containing transcripts can be differentially regulated throughout the parasite development, with a few encoding key virulence factors. In addition, we provide evidence for a functional bias of SIDER2-containing transcripts with protein kinase and transmembrane transporter activities being most represented. Conclusions Altogether, these findings provide important conceptual advances into evolutionary innovations of transcribed extinct retroposons acting as major RNA cis-regulators.

Abstract Background Climate change is driving increased extreme weather events that can impact ecology by moderating host–pathogen interactions. To date, few studies have explored how cold snaps affect disease prevalence and proliferation. Using the Daphnia magna–Ordospora colligata host-parasite system, a popular model system for environmentally transmitted diseases, the amplitude and duration of cold snaps were manipulated at four baseline temperatures, 10 days post-exposure, with O. colligata fitness recorded at the individual level. Results Cold snaps induced a fivefold increase or a threefold decrease in parasite burden relative to baseline temperature, with complex nuances and varied outcomes resulting from different treatment combinations. Both amplitude and duration can interact with the baseline temperature highlighting the complexity and baseline dependence of cold snaps. Furthermore, parasite fitness, i.e., infection prevalence and burden, were simultaneously altered in opposite directions in the same cold snap treatment. Conclusions We found that cold snaps can yield complicated outcomes that are unique from other types of temperature variation (for example, heatwaves). These results underpin the challenges and complexity in understanding and predicting how climate and extreme weather may alter disease under global change.

Abstract Background Accurate prediction of compound-protein interaction (CPI) plays a crucial role in drug discovery. Existing data-driven methods aim to learn from the chemical structures of compounds and proteins yet ignore the conceptual knowledge that is the interrelationships among the fundamental elements in the biomedical knowledge graph (KG). Knowledge graphs provide a comprehensive view of entities and relationships beyond individual compounds and proteins. They encompass a wealth of information like pathways, diseases, and biological processes, offering a richer context for CPI prediction. This contextual information can be used to identify indirect interactions, infer potential relationships, and improve prediction accuracy. In real-world applications, the prevalence of knowledge-missing compounds and proteins is a critical barrier for injecting knowledge into data-driven models. Results Here, we propose BEACON, a data and knowledge dual-driven framework that bridges chemical structure and conceptual knowledge for CPI prediction. The proposed BEACON learns the consistent representations by maximizing the mutual information between chemical structure and conceptual knowledge and predicts the missing representations by minimizing their conditional entropy. BEACON achieves state-of-the-art performance on multiple datasets compared to competing methods, notably with 5.1% and 6.6% performance gain on the BIOSNAP and DrugBank datasets, respectively. Moreover, BEACON is the only approach capable of effectively predicting knowledge representations for knowledge-lacking compounds and proteins. Conclusions Overall, our work provides a general approach for directly injecting conceptual knowledge to enhance the performance of CPI prediction.

Abstract This open-label, single-arm, phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab combined with anlotinib and chemotherapy, followed by adjuvant sintilimab, for resectable NSCLC. Forty-five patients received anlotinib (10 mg, QD, PO, days 1–14), sintilimab (200 mg, day 1), and platinum-based chemotherapy of each three-week cycle for 3 cycles, followed by surgery within 4–6 weeks. Adjuvant sintilimab (200 mg) was administered every 3 weeks. The primary endpoint was achieving a pathological complete response (pCR). From June 10, 2021 through October 10, 2023, 45 patients were enrolled and composed the intention-to-treat population. Twenty-six patients (57.8%) achieved pCR, and 30 (66.7%) achieved major pathological response (MPR). Forty-one patients underwent surgery. In the per-protocol set (PP set), 63.4% (26/41) achieved pCR, and 73.2% achieved MPR. The median event-free survival was not attained (95% CI, 25.1-NE). During the neoadjuvant treatment phase, grade 3 or 4 treatment-related adverse events were observed in 25 patients (55.6%), while immune-related adverse events were reported in 7 patients (15.6%). We assessed vascular normalization and infiltration of immune-related cells by detecting the expression of relevant cell markers in NSCLC tissues with mIHC. Significant tumor microenvironment changes were observed in pCR patients, including reduced VEGF+ cells and CD4+Foxp3+ Treg cells, and increased perivascular CD4+ T cells, CD39+CD8+ T cells, and M1 macrophages. In conclusion, perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment (ClinicalTrials.gov NCT05400070).

Abstract UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.

Abstract Background Deep learning-based drug-target affinity (DTA) prediction methods have shown impressive performance, despite a high number of training parameters relative to the available data. Previous studies have highlighted the presence of dataset bias by suggesting that models trained solely on protein or ligand structures may perform similarly to those trained on complex structures. However, these studies did not propose solutions and focused solely on analyzing complex structure-based models. Even when ligands are excluded, protein-only models trained on complex structures still incorporate some ligand information at the binding sites. Therefore, it is unclear whether binding affinity can be accurately predicted using only compound or protein features due to potential dataset bias. In this study, we expanded our analysis to comprehensive databases and investigated dataset bias through compound and protein feature-based methods using multilayer perceptron models. We assessed the impact of this bias on current prediction models and proposed the binding affinity similarity explorer (BASE) web service, which provides bias-reduced datasets. Results By analyzing eight binding affinity databases using multilayer perceptron models, we confirmed a bias where the compound-protein binding affinity can be accurately predicted using compound features alone. This bias arises because most compounds show consistent binding affinities due to high sequence or functional similarity among their target proteins. Our Uniform Manifold Approximation and Projection analysis based on compound fingerprints further revealed that low and high variation compounds do not exhibit significant structural differences. This suggests that the primary factor driving the consistent binding affinities is protein similarity rather than compound structure. We addressed this bias by creating datasets with progressively reduced protein similarity between the training and test sets, observing significant changes in model performance. We developed the BASE web service to allow researchers to download and utilize these datasets. Feature importance analysis revealed that previous models heavily relied on protein features. However, using bias-reduced datasets increased the importance of compound and interaction features, enabling a more balanced extraction of key features. Conclusions We propose the BASE web service, providing both the affinity prediction results of existing models and bias-reduced datasets. These resources contribute to the development of generalized and robust predictive models, enhancing the accuracy and reliability of DTA predictions in the drug discovery process. BASE is freely available online at https://synbi2024.kaist.ac.kr/base .

Abstract Time-synchronised data streams from bio-loggers are becoming increasingly important for analysing and interpreting intricate animal behaviour including split-second decision making, group dynamics, and collective responses to environmental conditions. With the increased use of AI-based approaches for behaviour classification, time synchronisation between recording systems is becoming an essential challenge. Current solutions in bio-logging rely on manually removing time errors during post processing, which is complex and typically does not achieve sub-second timing accuracies. We first introduce an error model to quantify time errors, then optimise three wireless methods for automated onboard time (re)synchronisation on bio-loggers (GPS, WiFi, proximity messages). The methods can be combined as required and, when coupled with a state-of-the-art real time clock, facilitate accurate time annotations for all types of bio-logging data without need for post processing. We analyse time accuracy of our optimised methods in stationary tests and in a case study on 99 Egyptian fruit bats (Rousettus aegyptiacus). Based on the results, we offer recommendations for projects that require high time synchrony. During stationary tests, our low power synchronisation methods achieved median time accuracies of 2.72 / 0.43 ms (GPS / WiFi), compared to UTC time, and relative median time accuracies of 5 ms between tags (wireless proximity messages). In our case study with bats, we achieved a median relative time accuracy of 40 ms between tags throughout the entire 10-day duration of tag deployment. Using only one automated resynchronisation per day, permanent UTC time accuracies of ≤ 185 ms can be guaranteed in 95% of cases over a wide temperature range between 0 and 50 °C. Accurate timekeeping required a minimal battery capacity, operating in the nano- to microwatt range. Time measurements on bio-loggers, similar to other forms of sensor-derived data, are prone to errors and so far received little scientific attention. Our combinable methods offer a means to quantify time errors and autonomously correct them at the source (i.e., on bio-loggers). This approach facilitates sub-second comparisons of simultaneously recorded time series data across multiple individuals and off-animal devices such as cameras or weather stations. Through automated resynchronisations on bio-loggers, long-term sub-second accurate timestamps become feasible, even for life-time studies on animals. We contend that our methods have potential to greatly enhance the quality of ecological data, thereby improving scientific conclusions.

Abstract Cardiovascular disease is the leading cause of mortality in women worldwide. Yet cardiovascular disease in women remains underdiagnosed and undertreated, especially among vulnerable populations such as older women, low-income populations, and ethnic minorities. Resultantly, reduction in cardiovascular mortality among women has stagnated. To examine, consolidate current research findings and policies to identify gaps in women’s heart health practice, this review screened 21476 records and synthesized results from 124 English language publications worldwide. Using a life course approach, we assessed the connection between clinical recommendations and policy, and documented global recommendations and policies addressing prevention of cardiovascular disease in women. Key recommendations include fostering environments that encourage sustainable health behaviors for young women, advocating for national surveillance systems and guidelines for monitoring and increasing the understanding of cardiovascular health in high-risk pregnancy/postpartum groups, developing community prevention programs for midlife/menopause, and implementing direct population health management initiatives for elderly women, with an emphasis on higher risk groups. Inequalities still exist among women with varying socioeconomic status and race between countries, and even within countries.

The Parque Estadual do Forno Grande is a fully protected area in the southern Espírito Santo State, Brazil. It belongs to the Atlantic Forest domain, with predominantly dense, ombrophilous, seasonal semi-deciduous forests and herbaceous/shrubby vegetation on rock outcrops. The area is recognised as highly important for conservation, designated as a priority biological area for protecting the Atlantic Forest's biodiversity. Although the importance of Protected Areas in conserving the Atlantic Forest biodiversity is unquestionable, it is crucial to understand the floristic patterns within these regions to develop effective conservation strategies. We utilised national online databases to compile species lists containing relevant information about their biodiversity. The updated list of vascular plants recorded in the Parque Estadual do Forno Grande is available in the “Catálogo de Plantas das Unidades de Conservação do Brasil” and it is presented here with further information on richness, endemism and conservation status.The Parque Estadual do Forno Grande harbours 958 species of vascular plants, of which 79.2% are angiosperms, 18.4% are ferns and 2.4% are lycophytes. Amongst these species, 44% are endemic to the Atlantic Forest. There are 58 threatened species, of which six are Critically Endangered, 39 are Endangered and 13 are Vulnerable. Amongst the threatened species, 51 are endemic to the Atlantic Forest. The number of records and the species richness in this area are notably high for Atlantic Forest standards. Our findings suggest that floristic inventories of Brazilian Protected Areas are a key contribution to the general perception of how much we still do not know about our flora. It also highlights the necessity of supporting floristic surveys in poorly-known areas, especially those remaining as forest remnants.

Invasive alien species are an important component of global change, threatening biodiversity, ecosystem functioning, economy, and human health. The number of alien species that attain the invasive status has experienced an exponential increase in recent years, leading some government agencies and stakeholders to allocate substantial resources to early detection, control, mitigation, and eradication programs. To develop effective nature conservation strategies, it is crucial to understand the invasive status of alien species and to identify priority species for management at spatial scales with a biogeographical basis. Despite significant progress in producing lists of alien species at the country level, a standard methodology for species assessment within ecological regions (i.e., regions with similar environmental or biogeographical characteristics) is still lacking. Here, we develop a systematic approach to determine invasion status and to prioritize invasive alien plant species within an ecoregion. We apply this approach in the Cantabrian Mixed Forests ecoregion, which encompasses biogeographically related areas from N Portugal, NW Spain, and SW France, and is strongly affected by plant invasions. By combining scientific evidence with expert opinion on the ecological characteristics of alien plants, we identified 175 invasive plant species in the study ecoregion, of which 37 cause massive environmental and/or socio-economic impacts. For each species, we provide comprehensive information and recommendations for scientists, land managers, policy makers, and other stakeholders under a biogeographical basis. This information includes species characteristics, invasion status/level, population trends, geographic locations and range size, local abundance, environmental and socio-economic impacts, and invaded habitats. We also accounted for administrative divisions within the ecoregion to facilitate the use of such evaluations in local-scale management and conservation plans. Our framework may be applied to any ecoregion worldwide, enhancing the assessment and management of invasive species pools within biogeographically meaningful regions.

A new species of the genus Rhopalopsole (Plecoptera, Leuctridae) from Yunnan Province, China, Rhopalopsole dulongjianga sp. nov., is described and illustrated.This new species is compared to the similar species, Rhopalopsole bispina (Wu, 1949). Additionally, we provide a supplemental description and colour plates of R. bispina. A key to Rhopalopsole species from Yunnan Province, China, is also provided in this paper.

Invasive alien plants cause severe global problems; therefore, determining the factors that lead to the success or failure of invasion is a critical question in the field of invasion ecology. In this study, we aimed to determine the factors underlying differences in the distribution range of alien plants in Japan by investigating why Lolium multiflorum thrives in a wide range of habitats while L. rigidum is mainly distributed on sandy beaches. We initially evaluated environmental niche suitability through species distribution modelling and subsequently examined whether species traits influence the differences in range expansion between the two species. We used MaxEnt modelling to identify potential environmental niches for both species. The analysis revealed that L. rigidum was considerably less suited to the Japanese climate compared to L. multiflorum, with high summer precipitation in Japan identified as one of the climatic factors limiting the distribution of L. rigidum. Given that these winter annual plants remain dormant as seeds during summer, in subsequent experiments, we buried seeds in paddy field soil and sandy beach sand during summer and evaluated their survival rate in autumn. The survival rate of L. rigidum seeds was significantly lower than that of L. multiflorum, particularly in paddy soil. Factors contributing to seed mortality may include the decay or early germination of L. rigidum seeds under Japan’s high rainfall conditions. This study emphasises the importance of considering local environmental factors alongside climate niche modelling in the risk assessment of invasive species. Moreover, the integration of species distribution modelling for large-scale evaluations and manipulation experiments for fine-scale assessments proved effective in identifying climatic conditions and species traits influencing the success or failure of alien species invasion.

As many new evolutionary lineages are being discovered and formally named, sequencing topotypes when holotypes are not available becomes essential for taxonomy. This study uses a DNA-taxonomy approach to sequence new populations of the Ischnocnema verrucosa species complex (Brazilian Wart Frogs) from different locations, including, for the first time, individuals from the type localities. Phylogenetic analysis of the mitochondrial 16S gene recovered a monophyletic Ischnocnema verrucosa species series composed of three main clades. The most recent common ancestor was estimated to be 33.76 million years ago, and diversification within the three main clades occurred primarily during the Miocene. We delimited eight species-level lineages with high levels of sequence divergence (7% to 16%). Our study highlights the importance of DNA taxonomy and the necessity of protecting and sequencing topotypes in taxonomic studies. Our study also contributes to the conservation and understanding of the genus Ischnocnema and the biodiversity of the Brazilian Atlantic Forest region.

The leafminer Phytomyza rufipes Meigen, 1830 (Diptera, Agromyzidae) is an oligophagous pest of plants of the family Cruciferae. These include Canola, Brassica napus L. We report the record of P. rufipes in Uruguay, which is confirmed through molecular characterization using DNA barcoding. Characteristic dam-age symptoms and immature stages of the pest were first confirmed on a Canola crop in Flores, Uruguay.

Procellaria cinerea Gmelin, 1789 and Pachyptila vittata (Forster, 1977) are considered vagrants in Brazil, with very few documented records in the country. Here, we present the first documented records of these species from the state of São Paulo, southeastern Brazil. Morphometrics, post-mortem examinations, and a genetic analysis allowed us to identify the species, reproductive status, cause of death, and sex of the specimens.

Across the annals of time, organic molecules sourced from nature have found innumerable uses within the realms of healthcare, pharmaceuticals, and the study of living organisms. This abundant source of natural compounds has exhibited immense promise in the cure of diverse ailments, mainly neurodegenerative diseases owing to their minimum toxic and adverse effects. However, different challenges exist with phytocompounds from plants such as poor permeation, poor solubility (water/lipid), unsteadiness under extremely acidic pH conditions, and lack of targeting specificity. Furthermore, as a result of the existence of blood-brain barrier membrane and inconvenient pharmacokinetics characteristics of phytocompounds, their passage into the brain is constrained. In order to address this issue and augment the transportation of medications into the brain at a therapeutically effective level, it is imperative to formulate an innovative and pragmatic strategy. Many papers have shown that nanoformulations containing phytocompounds (resveratrol, quercetin, ferulic acid, curcumin, berberine, etc.) effectively improved many neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s diseases. This study provides an overview of phytocompounds that are used in nanosized lipid drug delivery systems. These systems are categorized according to lipid types and preparation techniques used in the formulation. Some studies regarding these systems and phytocompounds are also summarized.

Objective: To estimate the bone protective effect of alpinumisoflavone, a natural prenylated isoflavonoid, against glucocorticoid-induced osteoporosis in rats. Methods: Male Wistar rats received intramuscular administration of dexamethasone (4 mg/mL) at a dose level of 7 mg/kg for 5 weeks, and then alpinumisoflavone (5, 10, and 15 mg/kg) and alendronate (2 mg/kg) from 2 weeks. The body weight and organ weight (femoral, vagina, and uterus) were estimated. MicroCT analysis, bone turnover markers, bone parameters, oxidative stress parameters, and inflammatory cytokines were estimated. mRNA expressions of related genes were also estimated. Results: Alpinumisoflavone remarkably boosted body weight and organ weight (ureters and vagina), improved microCT analysis parameters, and boosted levels of bone markers. Besides, alpinumisoflavone considerably (P

Objective: To explore the effect of geraniol on cyclophosphamide- induced cardiotoxicity. Methods: Mice were divided into five groups: the control group, the cyclophosphamide group (200 mg/kg cyclophosphamide, i.p. on day 7), the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14, along with a single dose of cyclophosphamide on day 7, and the geraniol alone group (200 mg/kg geraniol from day 1 to day 14). At the end of the study, animals were sacrificed, and blood and heart were collected and analyzed for biochemical, histopathological, and immunohistochemical changes. Results: Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers, malondialdehyde, and inflammatory and apoptotic markers, while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity. Moreover, it remarkably alleviated histopathological aberrations in cardiac tissue. Conclusions: Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant, anti-inflammatory, and antiapoptotic effects.

Objective: To evaluate the anticancer potential of Cymbopogon citratus extract. Methods: GC-MS analysis was used to identify phytocomponents in the methanolic extract of Cymbopogon citratus. A fractionation method was employed to isolate and assess the bioactivity of different fractions and their cytotoxic activities against cancer cell lines HCT116, LoVo, Caco-2, and HT-29 were investigated. A dual staining method with acridine orange and ethidium bromide was used to assess the effect of the extract on cell apoptosis. Additionally, the expression levels of Bax and TP53 were quantified using realtime PCR in Caco-2 cells treated with the ethyl acetate fraction of Cymbopogon citratus extract. A protein array was employed to profile key pro- and anti-apoptotic proteins in Caco-2 cells. Moreover, molecular docking studies were conducted to investigate the interactions between key compounds of Cymbopogon citratus extract and specific apoptosis-related protein domains (PDB IDs: 7wql and 4bkx). Results: A significant growth inhibition was observed in Caco-2 cells treated with Cymbopogon citratus extract. Among the seven fractions of the plant extract, the ethyl acetate fraction showed the highest cytotoxicity against Caco-2 cells with an IC50 value of (6.16 ± 0.01) μg/mL. The immunofluorescence assay showed that the ethyl acetate fraction could induce apoptosis of Caco-2 cells. Moreover, the fraction upregulated the gene expressions of Bax and TP53 in a dose-dependent manner. The docking analysis demonstrated the interaction of five compounds isolated from the ethyl acetate fraction with key proteins in Caco-2 cells, indicating their anticancer properties. Conclusions: Cymbopogon citratus extract shows anticancer activity against Caco-2 cells by inducing apoptosis. It may be a promising candidate for the treatment of colon cancer, which needs further investigation.

The paper presents novel findings of little-known species of rodents, the blind tree mice Typhlomys in Son La Province, Vietnam, with the first morphological and genetic characterisation and taxonomical description of the new species, T. taxuansis. The study also summarises all the data available on this genus species distribution, museum collections and notes on its taxonomy, which are important to establish the proper conservation status of the species. An exhaustive map of the findings is provided, along with a refined taxonomic key for all six currently morphologically characterised species of the genus. It is shown that, based on the data available to date, the genus is still far from complete. Most species, apparently, do not need a special conservation measure; their status may be established as Least Concerns and Near Threatened (B1a+2a) and the current population trend is stable (IUCN).The paper introduced innovative findings regarding lesser-known rodents, the blind tree mice Typhlomys in Son La Province, Vietnam, along with the primary morphological and genetic identification and taxonomic explanation of the novel species T. taxuansis.

The Chimanimani Mountains of Mozambique and Zimbabwe harbour diverse and unique flora and fauna. Because of these unique floral characteristics, this region has received considerable attention by botanists. In contrast, the vertebrates occurring here have received little attention. The aim of this paper was to synthesise data collected on multiple recent surveys into the first annotated checklist of the mammals of the Mozambican side of the Chimanimani Mountains. We identified medium-sized and large mammals by exterior appearance, mostly as captured on camera traps. We combined morphological and molecular methods to identify small mammals, and we report on echolocation calls of some of the poorly known bat species. In total, we recorded 69 species, including 23 species of bats (Chiroptera), 15 species of rodents (Rodentia), 11 species of carnivores (Carnivora), nine species of ungulates (Cetartiodactyla), and the rest comprising Primates, Eulipotyphla, Lagomorpha, Proboscidea, and Pholidota. Of these, five species are listed as threatened, demonstrating the importance of the Chimanimani Mountains for mammalian biodiversity conservation in South Eastern Africa.

Siamcyclops isanus sp. nov. has been found from a cave in northeastern Thailand. It differs from the other member of its genus by having: 1) smooth free margin of anal operculum, 2) a different armature on the second endopod of the first and fourth legs, 3) the armature of the second endopod of the male third leg, and 4) the shape of spermatophore. The discovery of the second species from the genus Siamcyclops thus leads to the proposal for the generic diagnosis. The morphological differences between the genus Siamcyclops and other closely related genera is added.

Pterygoplichthys ambrosettii (Holmberg, 1893) is indigenous to the middle/lower Paraná basin and has been intentionally introduced to several continents, including North America, Asia and Europe. In Brazil, the presence of allochthonous P. ambrosettii has been documented in the Upper portion of Paraná River, São Francisco River, and Doce River. This study aims to report the first documented occurrence of P. ambrosettii in the Mucuri river basin, located in the municipality of Mucuri, Bahia, Brazil.

Stress granules (SGs) are highly dynamic micromolecular membraneless condensates that generate in cells subjected to stress. Formed from pools of untranslating messenger ribonucleoproteins (RNP), SGs dynamics constitute vital processes essential for cell survival. Here, we investigate whether established cytotoxic agents, such as the platinum-based chemotherapeutic agent cisplatin and the aminoglycoside antibiotic gentamicin, elicit SG formation in the House Ear Institute-Organ of Corti-1 (HEI-OC1) auditory cell line, H4 human neuroglioma cells and HEK-293T human embryonic kidney cells. Cells were treated with cisplatin or gentamicin for specific durations at designated concentrations. SG formation was assessed using immunocytochemistry and live cell imaging. Levels of essential proteins involved in SG assembly were evaluated using immunoblotting. We observed cisplatin-associated SG assembly in HEI-OC1 and H4 cells via confocal microscopy through antibody colabeling of G3BP1 with PABP or Caprin1. While maintaining an unchanged pattern of expression of main constituent SG proteins, cisplatin-related SGs in H4 cells persisted for at least 12 h after drug removal. Cells subjected to gentamicin exposure did not exhibit SGs. Our findings offer insights into subcellular mechanisms related to cisplatin-associated cytotoxicity, highlighting the need for future studies to further investigate this stress-response mechanism.

Losses in crop yield due to invasive insects, weeds, pathogens, and herbivores cost trillions of dollars per year globally. To prevent further spread of invasive agricultural pest species, continuous monitoring and prevention are crucial. Once introduced, however, assessing the impact of an invasive pest on agricultural production and testing management strategies are essential. The green iguana (Iguana iguana), a globally widespread invasive herbivore, is considered a possible agricultural pest although no quantitative data on its impact are available. In this study, we evaluated the impact of the invasive green iguana on cucumber (Cucumis sativus, var. Dasher II) and lettuce (Lactuca sativa, var. Black-seeded Simpson) yield by testing the efficacy of two management strategies – Neem-based pesticide and mesh fencing – compared to open field cultivation in Puerto Rico. Mesh fencing led to 20% more growth and doubled cucumber yield compared to open field cultivation, while spraying Neem led to an 18% increase in plant growth but no effect on cucumber yield. We found no difference in lettuce growth or yield among treatment and control plots. This study supports categorizing the green iguana as an invasive agricultural pest species and demonstrates the reptile’s potential to reduce crop yield. It also shows that Neem application at the manufacturer’s suggested concentration is not an effective mitigation technique for reducing crop loss due to green iguana herbivory. Government agencies in regions where the green iguana has the potential to be introduced should consider the species a threat to food production when developing monitoring programs and drafting regulations.

Herbicide control of invasive plant species is generally efficient. However, there is a likelihood of the excessive application of non-selective herbicides that kill co-occurring native species and cause environmental toxicity. We present a case study on the control of the invasive exotic Solidago canadensis with photosynthetically active leaves in winter by applying glyphosate. This approach improves herbicide control efficiency, while preventing harm to most co-occurring native plants. We quantified the winter leaf phenology and photosynthetic capacity of S. canadensis and two commonly co-occurring native species. We tested the effects of glyphosate and competition on S. canadensis and native Imperata cylindrica with contrasting winter leaf phenology in both pot and field experiments. Finally, we surveyed the life forms and winter leaf phenology of most co-occurring plant species in eastern China to determine whether most co-occurring species and S. canadensis differ in winter leaf phenology. Old leaves withered much later and new leaves developed much earlier in S. canadensis than in the two co-occurring species. Both the old and new leaves of S. canadensis had high photosynthetic capacity in winter. In summer, glyphosate suppressed the growth of S. canadensis by 20.1–59.5% and growth of I. cylindrica to a greater extent (by 57.6–91.7%), whereas winter application of glyphosate at a certain concentration suppressed the growth of S. canadensis by 91.4–95.6% (the efficiency was higher than summer application), but had no impact on I. cylindrica. Glyphosate application in winter alleviated competition stress from S. canadensis on I. cylindrica. We conclude that winter glyphosate application can increase the selectivity and efficiency of chemical control of invasive S. canadensis, which may shift the competition balance towards native species and favour native vegetation recovery in sites invaded by S. canadensis. The principles of this approach can be applied to any scenario where invasive species and co-occurring species have distinct phenological niche separation.

A new species of the genus Colydium Fabricius, 1792 (Coleoptera, Zopheridae, Colydiinae), Colydium noblecourti sp. nov. is described. An illustrated and updated key for the identification of the Western Palearctic species of Colydium is presented. Distribution maps for the three species are provided.

Elytrimitatrix (Grossifemora) pubescens Santos-Silva & Hovore, 2008 (Disteniidae) is redescribed based on three males, morphological and chromatic variation in the species is reported. The unknown female of Neocompsa flavoquadripunctata Botero & Santos-Silva, 2022 is shortly described and a new Mexican state record is provided. The absence of the paratype of Nealcidion bruchi (Melzer, 1934) in the MZSP collection (see acronym below) is reported, and the date of description of the species is commented. Alphinellus Bates, 1881 is transferred from Acanthocinini to Desmiphorini. Alphinellus minimus Bates, 1881 is recorded for the first time from the Mexican state of Campeche and from Guatemala. Three new species are described: Psyrassa peninsularis sp. nov. (Cerambycidae, Cerambycinae, Elaphidiini) from Mexico (Quintana Roo); Pseudastylopsis skillmani sp. nov. (Cerambycidae, Lamiinae, Acanthocinini), from Guatemala; and Eranina amaura sp. nov. (Cerambycidae, Lamiinae, Hemilophini), from Guatemala.

In recent years, pre-service teacher education programs have recognized the importance of equipping future educators with the necessary skills such as argumentation skills and metacognitive awareness. However, the extent to these skills in ore-service biology teachers remains relatively unexplored. This study aimed to explore the effect of argument-driven inquiry on pre-service biology teachers’ argumentation skills and metacognitive awareness. This study also investigated the correlation between argumentation skills and metacognitive awareness in pre-service biology teachers. This research was conducted as quasi experiment using nonrandomized control group pretest–post-test design with two classes. One class as experiment group (N=44) which participated in series of activities in laboratory work using argument-driven inquiry, and control group (N=44) which participated in the regular laboratory activities. The laboratory work focused on the topic of mendelian genetic. This research was conducted on the second year of pre-service biology teachers in the Department of Biology Education. Data were generated by administrating pre-test and post-test on argumentation skill using open-ended question and metacognitive awareness using Metacognitive Awareness Inventory (MAI). Result showed a significant difference between experimental group and control group in argumentation skills (p value= .016) as well as in metacognitive awareness (p value = .005). However, the correlation between argumentation skills and metacognitive awareness were relatively low (r= -.119). This research findings can be used as suggestions for policy makers and educational institute to integrate argumentation skills and metacognitive awareness in designed for professional development program in teacher training program.

Holistic higher-order thinking (H-HOT) is needed by someone who lives in the 21st century to solve environmental problems. This study aims to determine the ability of H-HOT to solve environmental problems in undergraduate students of biology and biology education programs in Indonesia. The research used a survey method. The sample was taken using a purposive sampling technique, namely only undergraduate students from the biology and biology education program who had graduated from environmental theme lectures. The research instrument in the form of a H-HOT ability test in solving environmental problems is 10 numbers that have been validated by material and construction experts, and empirically validated given to 205 respondents online. Data in the form of H-HOT ability values ​​in solving environmental problems were analyzed descriptively and quantitatively. The results showed that the ability of H-HOT to solve environmental problems in undergraduate students of the biology study program obtained an average score of 24.81, biology education study program is 27.48, and overall average score of all undergraduate students from both the Biology study program and the Biology Education study program are 26.23. The conclusion of this study is that the ability of H-HOT in solving environmental problems in undergraduate students of biology and biology education programs is in a very low category so that efforts need to be made to improve. The study implies a need for improved educational approaches to enhance students' higher-order thinking skills for effectively solving environmental problems.

Kampus Mengajar is a program intended for university students in Indonesia to establish partnerships with schools and prepare themselves as future professional educators. Student participation in the Kampus Mengajar program requires mastery of pedagogical competencies, one of which is the development of teaching modules as a learning design that will be implemented. The purpose of this study was to describe the ability of Biology Education students of FKIP UNTAN to develop teaching modules, specifically, students who participated in the Kampus Mengajar Batch 6 (KM6). This research is descriptive qualitative research conducted by observing the completeness of the components of the 14 teaching modules developed. Based on the analysis conducted, it is known that the average percentage of general information is 98.81% with a very good category, the main components are 97.62% with a very good category, and the appendices are 78.57% with a good category. Overall, the average of all components is 92.44%, so it can be concluded that the ability of Biology Education students at FKIP UNTAN to develop teaching modules can be categorized as very good. The results obtained show that there are still flaws in the 14 teaching modules analyzed. Students need to develop their pedagogical professionalism so that their knowledge and skills in developing teaching modules increase.

The lack of scientific documentation on the ethnobotany of Dayak medicinal plants makes this knowledge vulnerable to disappearing. Ethnobotany as a learning resource is one very effective step to make students more familiar with and love the knowledge of their ancestors. The purpose of this study was to determine the kinds of drugs and plants used by the community in Kayu Ara village and also the potential of ethnobotany of Dayak medicinal plants as a learning resource. This research uses a qualitative method where researchers divide 2 stages of research from collecting medicinal plant data by interview and observation. Interviews were conducted using snowball sampling technique. Further data collection is in the form of questionnaire results of potential biology learning resources. The results of the study found 21 types of medicinal plants which are divided into 16 families. The most widely used part is the leaves 45% and the least part of the fruit is only 3%. Potential learning resources obtained Clarity of Potential 88.89%, Suitability with Purpose 100%, Clarity of Target 91.67%, Clarity of Information Revealed 88.89%, Clarity of Exploration Guidelines 100%, Clarity of Expected Gain 100%. These results indicate that the ethnobotany of Dayak medicinal plants in kayu ara village, jelimpo sub-district, landak district is very effective in being used as a biology learning resource, especially in class X on biodiversity subject matter.

E-worksheets are needed to support learning of SDG-13 material on climate change material, but analysis related to this has not attracted much attention from researchers. The purpose of this study was to determine the needs of students related to digital-based teaching materials that they want to apply in the classroom in biology learning, especially on climate change material to show the phenomenon of global warming with the application of the Merdeka Curriculum. The use of digital-based media is still very suboptimal in utilization, especially in the material of climate change in biology subjects. This quantitative research was conducted using questionnaire techniques, namely giving questionnaires to X-grade students in two schools, namely SMAN in Yogyakarta and SMAN in South Sulawesi Regency, and descriptive techniques were used for analysis tools. The results of student respondents show that 100% want to use electronic worksheets as a learning medium on climate change material. The implication of this research is expected to increase the potential use of digital-based teaching materials and realize the 21st-century era that relies on technology.

Ochratoxin A (OTA) is a toxic secondary metabolite produced by the Aspergillus species which can contaminate various food products. This study analysed the transcriptome of the Aspergillus westerdijkiae fc-1 strain under NaCl concentrations of 0, 20, and 100 g/L using RNA-Seq technology to examine gene transcriptional changes linked to osmotic stress and OTA production. Significant changes were observed in metabolic-pathways associated with carbohydrates, cellular communication, and hydrolase activity under 20 g/L NaCl. The HOG1 gene, associated with osmotic pressure regulation was down-regulated by 78.06%. In contrast, OTA biosynthesis genes otaA, otaB, and otaC were up-regulated by 3.26 fold, 1.99 fold, and 2.06 fold, respectively. Conversely, the otaD gene was down-regulated by 43.50%. At 100 g/L NaCl, pathways related to ion transport, peptide metabolism, ribosomal function, and transmembrane transporter protein activities were significantly up-regulated. The HOG1 gene was up-regulated by 28.32% and OTA biosynthesis genes otaA, otaB, otaC, and otaD showed up-regulation of 27.06%, 36.80%, 19.59%, and 5.72 fold, respectively. The study highlights the role of metabolic pathways in osmotic stress regulation and the correlations between HOG1 expression and OTA biosynthesis genes, providing insights for developing strategies to prevent OTA contamination in food.

Abstract Objectives To enhance the identification of individuals at risk of developing clinically significant kidney stones. Methods In this study, data from the Fasa Adults Cohort Study were analyzed to explore factors linked to symptomatic and clinically significant kidney stone disease. After cleaning, 10,128 participants with 103 variables were studied. One outcome variable (presence of symptomatic kidney stones) and 102 predictor variables from surveys and tests were assessed. Five Machine learning (ML) algorithms (SVM, RF, KNN, GBM, XGB) were applied to examine kidney stone factors, with performance comparisons made. Data balancing was done using SMOTE, and metrics like accuracy, precision, sensitivity, specificity, F1 score, and AUC were evaluated for each algorithm. Results The XGB model outperformed others with AUC of 0.60, while RF, GBM, SVC, and KNN had AUC values of 0.58, 0.57, 0.54, and 0.52. RF, GBM, and XGB showed good accuracy at 0.81, 0.81, and 0.77. Top predictors for kidney stones were serum creatinine, salt intake, hospitalization history, sleep duration, and BUN levels. Conclusions ML models show promise in evaluating an individual’s risk of developing painful kidney stones and recommending early lifestyle changes to reduce this risk. Further research can enhance predictive accuracy and tailor interventions for better prevention/management.

Abstract Background Dietary patterns are important factors associated with cardiovascular diseases (CVDs). We examined the association between dietary patterns derived from factor analysis and CVD risk factors. Methods In the present cross-sectional study, a total of 3,687 adults (aged 40 to 70 years) with one or more types of CVDs were enrolled as participants. A validated semi-quantitative food-frequency questionnaire was utilized to assess food intakes, and then dietary patterns were extracted by factor analysis. Fasting blood sugar (FBS), lipid profile, anthropometric indices, and blood pressure (BP) were measured. Multivariable-adjusted logistic regression analysis was employed to ascertain the odds ratio (OR) of CVD risk factors associated with posteriori dietary patterns. In this study, healthy and unhealthy dietary patterns were identified. Results Adherence to a healthy dietary pattern was associated with a decrease in systolic BP (SBP) (OR = 0.78; 95% confidence interval (CI): 0.62–0.99) and high-density lipoprotein cholesterol (HDL-C) levels (OR = 1.32; 95% CI: 1.06–1.64). Additionally, greater adherence to the unhealthy dietary pattern was positively associated with SBP (OR = 1.43; 95% CI: 1.13–1.80) and diastolic BP (DBP) (OR = 1.33; 95% CI: 1.01–1.76). Conclusions We concluded that greater adherence to an unhealthy dietary pattern was associated with an increase in SBP and DBP. On the other hand, greater adherence to a healthy dietary pattern could be effective in reducing SBP. Further investigation is recommended to validate these findings.

Abstract Background Candida africana is an emergent variant that has been listed as a new species or variety within the Candida albicans complex since 2001. It has a worldwide intra-albicans complex pooled prevalence of 1.67% and varies between 0 and 8% depending on geographical region. We present the results of a pilot study on its prevalence in Uganda. Methodology We conducted a cross-sectional study between March and June 2023. We recruited 4 pregnant women from Mulago Specialized Women and Neonatal Hospital, 102 from Kawempe National Referral Hospital, and 48 from Sebbi Hospital. Vaginal swabs were tested using microscopy, culture and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). Results The prevalence of C. africana was zero. Out of the 103 isolates, the majority (81.553%) were identified as Candida albicans, followed by Nakeseomyces glabrata (13.592%) and Pichia kudriavzevii (1.942%). Cyberlindnera jadinii, Candida tropicalis, and Candida parapsilosis each accounted for 0.971% of the isolates. Conclusion The prevalence of C. africana in Uganda is zero. However, large-scale cross-sectional studies, including studies involving the collection of vaginal samples from both urban and rural settings in Uganda and the use of both MALDI-TOF- and PCR-based laboratory methods, are needed to fully describe the public health burden of C. africana infections.

Abstract Objective The objective of the present study was to examine the effect of calorie restricted diet (CRD) plus inulin supplementation on serum levels of tryptophan (Trp), kynurenine (Kyn) and Trp/Kyn ratio in obese women with major depressive disorder (MDD). Results In this double-blind placebo-controlled randomized clinical trial, 51 obese women (BMI = 30–40 kg/m2) with mild MDD were assessed for depression level using Hamilton depression rating scale (HDRS). The patients were randomly allocated into either “Prebiotic group” (received 10 g/day inulin) or “Placebo group” (received 10 g/day maltodextrin). All participants also received individualized CRD. Fasting serum levels of Trp, Kyn, and Trp/Kyn ratio were assessed at baseline and after 8 weeks. Results showed slightly greater increases in serum levels of Trp and Trp/Kyn ratio as well as reductions in serum level of Kyn and HDRS score in prebiotic group than placebo group. However, between group differences in these parameters as well as HDRS score were not statistically significant after adjusting for baseline variables at the end of the trial. Results indicates that CRD accompanied by inulin supplementation (10 g/day) did not influence serum levels of Trp, Kyn and Trp/Kyn ratio as well as HDRS score after 8 weeks. Trial registration: The trial was registered in the Iranian registry of clinical trials at 2018-08-02 ( https://www.irct.ir/ ; registration number: IRCT20100209003320N15).

Abstract Head lice infestations are the most prominent ectoparasitic infection in the world, including Iran, particularly among school children. Recently, numerous cases of infestation have been reported in various provinces of the country. This study aimed to investigate the prevalence of head louse infestations and analyze kdr gene sequences in terms of resistance mutations in the Torbat-e Heydarieh, Mahvelat, and Zaveh cities of Khorasan Razavi Province, Northeast Iran. The data related to the epidemiological and demographic history of head lice populations were extracted from their medical records and analyzed in Excel software. After extracting the genomic DNA, the kdr fragment was amplified using specific primers. The sequences were also analyzed using bioinformatics software. The prevalence of head louse infestations was 1.59% and 1.7% during 2016 and 2017, respectively. Sequence analysis revealed the frequency distribution of two kdr haplotypes, I and V, in the study areas. The increase in head louse infestations in recent years and the simultaneous presence of kdr mutations indicate the need for new treatments and monitoring/controlling resistance to head louse insecticides.

Abstract Objective To obtain physicians’ “real-world” perspectives on early experiences with triamcinolone acetonide suprachoroidal injection (SCS-TA) for treatment of patients with uveitic macular edema (UME). Results Twelve retina/uveitis specialists in the United States were surveyed about SCS-TA injection procedure and patient outcomes. Survey participants administered ≥ 291 SCS-TA injections to 243 patients with UME with various disease characteristics (etiologies, chronicity, and anatomical subtypes). Commonly reported reasons for SCS-TA adoption included potential for lowering the risk of steroid-associated intraocular pressure elevations versus intravitreal injections or implants (100%), potential for longer duration of action versus intravitreal steroid injections or implants (92%), and desire to use a new delivery modality (83%). Nearly all participants (92%) found injection procedure relatively easy post-training, with most (75%) procedurally comfortable after completing 2–5 injections. 58% of participants indicated that their patients gained 2–3 lines of vision by first follow-up visit, and 92% reported having patients who experienced 100–150 μm or greater reduction in central subfield thickness. Overall, 92% of participants were satisfied with SCS-TA treatment outcomes. Findings from this survey of early adopters of SCS-TA indicate that the suprachoroidal injection technique was easy to learn and resulted in favorable patient outcomes consistent with clinical trial data.

Abstract Objective Sarcopenia is linked to escalating health costs, heightened risk of physical disability, diminished quality of life and an increased demand for care services. This study aimed to assess the economic impact of sarcopenia-related disability in Iran. A prevalence-based economic burden study was conducted utilizing the Population Attributable Risk (PAR) method, based on 2022 price index. Prevalence data for sarcopenia, categorized by gender and disease severity, were extracted from recent comprehensive studies. The relative risk of sarcopenia disability was determined from the most robust available evidence. Subsequently, direct medical costs, direct non-medical costs, and indirect costs for each individual with sarcopenia were computed and adjusted to 2022 values to estimate disability costs. Results Taking into account the prevalence of sarcopenia and the Iranian population across various age groups, 2,192,168 adults aged ≥ 60 years with sarcopenia in Iran were included. The total PAR of sarcopenia for men and women was estimated at 49% and 28%, respectively. The cumulative direct medical costs, direct non-medical costs, and indirect costs amounted to $215.1 million, $7.76 million, and $34.1 million, respectively. Additionally, the average total economic burden of sarcopenia-related disability in Iranian population aged ≥ 60 years was estimated at $257.1 million.

Abstract Purpose The correlation between body weight and health is a significant public health concern. While the adverse effects of obesity on pulmonary function are well-known, the impact of being underweight remains debated due to limited research. This study aimed to investigate the correlation between Body Mass Index (BMI) categories and lung function parameters. Results A study of 3077 participants found significant differences in gender, age, height, and weight across various Body Mass Index (BMI) categories. The study found non-significant variations in forced expiratory flow (FVC) across BMI categories, with underweight individuals showing lower FVC compared to normal and overweight individuals. BMI significantly impacted mean forced expiratory flow during the middle half of FVC. A significant negative correlation was observed between age and FVC, FEV1, FEV1/FVC ratio, and FEF25-75. A significant positive correlation was observed between weight, height, and lung function parameters. Multiple regression analysis revealed a decrease in lung function with advancing age, while height showed significant positive associations. The study concluded that age, sex, smoking, height, and weight collectively explained 41.0% of the variance in FVC, FEV, and FEF25-75.

Abstract Objective Internally displaced persons (IDPs) can have limited access to HIV and hepatitis C Virus (HCV) treatment and prevention. IDPs comprise > 7% of Georgian population but prevalence and levels of HIV and HCV knowledge in this population remain unknown. We tested 100 IDPs in Georgia for HIV and HCV, many of whom had drug injecting experience, and interviewed them about their migration experience, sexual and drug injecting practices, and HIV/HCV transmission knowledge. Results The average age of participants was 37.5 years (range 18–63); 31% were women. Almost half (N = 48) of participants reported ever injecting drugs; 17% of those (N = 8) started injecting drugs within the last year. Anti-HCV and HIV prevalence was 11% and 0%, respectively. Fewer people without drug use experience compared to people who inject drugs correctly answered all questions on the HIV knowledge test (13% vs. 35%, p = 0.015) or knew where to get tested for HIV (67% vs 98%, p

Abstract Background In vitro embryo production is increasingly used for genetic improvement in cattle but bypasses the oviduct environment and exposes the embryos to oxidative stress with deleterious effects on further development. Here we aimed to examine the effect of oviduct epithelial spheroids (OES) on embryo development and quality in terms of morphology and gene expression during two co-culture times (4 days: up to embryonic genome activation at 8–16 cell stage vs. 7 days: up to blastocyst stage) and under two oxygen levels (5% vs. 20%). Methods Bovine presumptive zygotes produced by in vitro fertilization (day 0) using in-vitro matured oocytes were cultured in droplets of synthetic oviductal fluid (SOF) medium with or without (controls) OES for 4 or 7 days under 5% or 20% oxygen (4 treated and 2 control groups). Cleavage rates were evaluated on day 2 and blastocyst rates on days 7–8. Expanded blastocysts on days 7–8 were evaluated for total cell numbers and gene expression analysis by RNA-sequencing. Results Under 20% oxygen, blastocyst rates and total cell numbers were significantly higher in the presence of OES for 4 and 7 days compared to controls (P

Abstract Background Lung cancer constitutes the leading cause of cancer mortality. High levels of endothelin-1 (ET-1), its cognate receptor ETAR and its activating enzyme, the endothelin-converting enzyme-1 (ECE-1), have been reported in several cancer types, including lung cancer. ECE-1 comprises four isoforms, which only differ in their cytoplasmic N-terminus. Protein kinase CK2 phosphorylates the N-terminus of isoform ECE-1c, increasing its stability and leading to enhanced invasiveness in glioblastoma and colorectal cancer cells, which is believed to be mediated by the amino acid residue Lys-6, a conserved putative ubiquitination site neighboring the CK2-phosphorylated residues Ser-18 and Ser-20. Whether Lys-6 is linked to the acquisition of a cancer stem cell (CSC)-like phenotype and aggressiveness in human non–small cell lung cancer (NSCLC) cells has not been studied. Methods In order to establish the role of Lys-6 in the stability of ECE-1c and its involvement in lung cancer aggressiveness, we mutated this residue to a non-ubiquitinable arginine and constitutively expressed the wild-type (ECE-1cWT) and mutant (ECE-1cK6R) proteins in A549 and H1299 human NSCLC cells by lentiviral transduction. We determined the protein stability of these clones alone or in the presence of the CK2 inhibitor silmitasertib, compared to ECE-1cWT and mock-transduced cells. In addition, the concentration of secreted ET-1 in the growth media was determined by ELISA. Expression of stemness genes were determined by Western blot and RT-qPCR. Chemoresistance to cisplatin was studied by MTS viability assay. Migration and invasion were measured through transwell and Matrigel assays, respectively, and the side-population was determined using flow cytometry. Results ECE-1cK6R displayed higher stability in NSCLC cells compared to ECE-1cWT-expressing cells, but ET-1 secreted levels showed no difference up to 48 h. Most importantly, ECE-1cK6R promoted expression of the stemness genes c-Myc, Sox-2, Oct-4, CD44 and CD133, which enhance cellular self-renewal capability. Also, the ECE-1cK6R-expressing cells showed higher cisplatin chemoresistance, correlating with an augmented side-population abundance due to the increased expression of the ABCG2 efflux pump. Finally, the ECE-1cK6R-expressing cells showed enhanced invasiveness, which correlated with the regulated expression of known EMT markers. Conclusions Our findings suggest an important role of ECE-1c in lung cancer. ECE-1c is key in a non-canonical ET-1-independent mechanism which triggers a CSC-like phenotype, leading to enhanced lung cancer aggressiveness. Underlying this mechanism, ECE-1c is stabilized upon phosphorylation by CK2, which is upregulated in many cancers. Thus, phospho-ECE-1c may be considered as a novel prognostic biomarker of recurrence, as well as the CK2 inhibitor silmitasertib as a potential therapy for lung cancer patients.

Abstract Background Determining the postmortem interval (PMI) accurately remains a significant challenge in forensic sciences, especially for intervals greater than 5 years (late PMI). Traditional methods often fail due to the extensive degradation of soft tissues, necessitating reliance on bone material examinations. The precision in estimating PMIs diminishes with time, particularly for intervals between 1 and 5 years, dropping to about 50% accuracy. This study aims to address this issue by identifying key protein biomarkers through proteomics and machine learning, ultimately enhancing the accuracy of PMI estimation for intervals exceeding 15 years. Methods Proteomic analysis was conducted using LC–MS/MS on skeletal remains, specifically focusing on the tibia and ribs. Protein identification was performed using two strategies: a tryptic-specific search and a semitryptic search, the latter being particularly beneficial in cases of natural protein degradation. The Random Forest algorithm was used to model protein abundance data, enabling the prediction of PMI. A thorough screening process, combining importance scores and SHAP values, was employed to identify the most informative proteins for model’s training and accuracy. Results A minimal set of three biomarkers—K1C13, PGS1, and CO3A1—was identified, significantly improving the prediction accuracy between PMIs of 15 and 20 years. The model, based on protein abundance data from semitryptic peptides in tibia samples, achieved sustained 100% accuracy across 100 iterations. In contrast, non-supervised methods like PCA and MCA did not yield comparable results. Additionally, the use of semitryptic peptides outperformed tryptic peptides, particularly in tibia proteomes, suggesting their potential reliability in late PMI prediction. Conclusions Despite limitations such as sample size and PMI range, this study demonstrates the feasibility of combining proteomics and machine learning for accurate late PMI predictions. Future research should focus on broader PMI ranges and various bone types to further refine and standardize forensic proteomic methodologies for PMI estimation.