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What Trump’s flurry of executive orders means for science

Octopuses changing colour rapidly incur a high metabolic cost

All together now: chimps engage in contagious peeing

Rubbish under the floorboards exposes secret snacking in colonial Australia

Obesity drugs: huge study identifies new health risks

Distinguishing classes of neuroactive drugs based on computational physicochemical properties and experimental phenotypic profiling in planarians

Mental illnesses put a tremendous burden on afflicted individuals and society. Identification of novel drugs to treat such conditions is intrinsically challenging due to the complexity of neuropsychiatric diseases and the need for a systems-level understanding that goes beyond single molecule-target interactions. Thus far, drug discovery approaches focused on target-based in silico or in vitro high-throughput screening (HTS) have had limited success because they cannot capture pathway interactions or predict how a compound will affect the whole organism. Organismal behavioral testing is needed to fill the gap, but mammalian studies are too time-consuming and cost-prohibitive for the early stages of drug discovery. Behavioral medium-throughput screening (MTS) in small organisms promises to address this need and complement in silico and in vitro HTS to improve the discovery of novel neuroactive compounds. Here, we used cheminformatics and MTS in the freshwater planarian Dugesia japonica –an invertebrate system used for neurotoxicant testing–to evaluate the extent to which complementary insight could be gained from the two data streams. In this pilot study, our goal was to classify 19 neuroactive compounds into their functional categories: antipsychotics, anxiolytics, and antidepressants. Drug classification was performed with the same computational methods, using either physicochemical descriptors or planarian behavioral profiling. As it was not obvious a priori which classification method was most suited to this task, we compared the performance of four classification approaches. We used principal coordinate analysis or uniform manifold approximation and projection, each coupled with linear discriminant analysis, and two types of machine learning models–artificial neural net ensembles and support vector machines. Classification based on physicochemical properties had comparable accuracy to classification based on planarian profiling, especially with the machine learning models that all had accuracies of 90–100%. Planarian behavioral MTS correctly identified drugs with multiple therapeutic uses, thus yielding additional information compared to cheminformatics. Given that planarian behavioral MTS is an inexpensive true 3R (refine, reduce, replace) alternative to vertebrate testing and requires zero a priori knowledge about a chemical, it is a promising experimental system to complement in silico cheminformatics to identify new drug candidates.

MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban

Objective To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression. Methods The MIRI mouse model was created and mice were divided into sham, MIRI, MIRI+ 221, and MIRI+ scr groups, with miRNA 221 overexpression induced in the myocardium of MIRI mice by targeted myocardial injection. Quantitative RT-PCR analysis was performed to observe the variation in miRNA 221, PLB, SERCA2, RYR2, NCX1, Cyt C and caspase 3 mRNA levels in myocardium, while Western blot assessed the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), SERCA2, RYR2, NCX1, Cyt C and caspase 3 proteins. Changes in the structural integrity of the mouse heart were identified with HE and MASSON staining, while TUNEL staining was used to evaluate the TUNEL-positive cells of cardiomyocytes. Changes in myocardium calcium concentration were detected with reagent kits and the targeting interaction between miRNA 221 and PLB was evaluated using a luciferase reporter assay. Results In the myocardium of MIRI mice, miRNA 221 level was significantly reduced, while the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), and apoptosis-related genes caspase 3, and Cyt C were increased markedly, as well as calcium levels in myocardium. Following the overexpression of miRNA 221 in myocardium, there was a marked alleviation of myocardial injury and cardiomyocyte apoptosis and necrosis, significant enhancement of left ventricular systolic function, and marked decrease in the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), caspase 3 and Cyt C, as well as a significant decrease in total calcium levels in myocardium. Conclusions miRNA 221 can alleviate myocardial injury in mouse myocardial ischemia/reperfusion by suppressing the expression of PLB, thus reducing calcium overload in myocardium.

A novel classification method for balance differences in elite versus expert athletes based on composite multiscale complexity index and ranking forests

Balance is crucial for various athletic tasks, and accurately assessing balance ability among elite athletes using simple and accessible measurement methods is a significant challenge in sports science. A common approach to balance assessment involves recording center of pressure (CoP) displacements using force platforms, with various indicators proposed to distinguish subtle balance differences. However, these indicators have not reached a consensus, and it remains unclear whether these analyses alone can fully explain the complex interactions of postural control. In this study, we investigated four parameters related to balance control—anterior-posterior (AP) displacement, medial-lateral (ML) displacement, length, and tilt angle—in 13 elite athletes and 12 freestyle skiing aerial expert athletes. Data were recorded during 30-second trials on both soft and hard support surfaces, with eyes open and closed. We calculated the CMCI and used four machine learning algorithms—Logistic Regression, Support Vector Machine(SVM), Naive Bayes, and Ranking Forest—to combine these features and assess each participant’s balance ability. A classic train-test split method was applied, and the performance of different classifiers was evaluated using Receiver Operating Characteristic(ROC) analysis. The ROC results showed that traditional time-domain features were insufficient for accurately distinguishing athletes’ balance abilities, whereas CMCI performed the best overall. Among all classifiers, the combination of CMCI and Ranking Forest yielded the best performance, with a sensitivity of 0.95 and specificity of 0.35. This nonlinear, multidimensional approach appears to be highly suitable for assessing the complexity of postural control.

Breast and cervical cancer screening among women at reproductive age in Cambodia: A secondary analysis of Cambodia Demographic and Health Survey 2022

Breast and cervical cancers are the most prevalent diagnosed in women worldwide, significantly contributing to maternal morbidity and mortality. We examined socio-demographic and behavioral factors associated with breast and cervical cancer screening among Cambodian women aged 15–49 years old. We analyzed women’s data from the 2022 Cambodia Demographic and Health Survey (CDHS). In total, 19,496 women were interviewed. Multiple logistic regression was performed using STATA V17 to examine factors associated with breast and cervical cancer screening. The proportion of breast and cervical cancer screenings was 10.6% and 15.3%, respectively. After being adjusted, factors independently associated with breast cancer screening included age group 20–29 years [AOR = 2.51; 95% CI: 1.55–4.06], 30–39 years [AOR = 4.34; 95% CI: 2.66–7.09], and 40–49 years [AOR = 4.66; 95% CI: 2.81–7.71], higher education [AOR = 1.92; 95% CI: 1.26–2.93], exposure media [AOR = 1.66; 95% CI: 1.32–2.10], and rich wealth quintile [AOR = 1.50; 95% CI: 1.25–1.80]. Similarly, the odds of having cervical cancer screening were age group 20–29 years [AOR = 2.88; 95% CI: 1.76–4.71], 30–39 years [AOR = 5.94; 95% CI: 3.58–9.83], and 40–49 years [AOR = 7.61; 95% CI: 4.55–12.73], higher education [AOR = 1.55; 95% CI: 1.55–2.73], exposure media [AOR = 1.62; 95% CI: 1.35,1.95], and rich wealth quintile [AOR = 2.14; 95% CI: 1.78–2.5f8]. In conclusion, this study shows the low screening proportion for both breast and cervical cancers, and it also highlights that socio-economic factors are significantly important in determining the health care seeking for these two main cancer screening services among women aged 15–49 years in Cambodia. Therefore, increase of exposure media with health education focusing on these cancer screenings should be made better accessible to women, particularly those of low socio-economic status.

Effect of cytotoxic CD8+ T-cells secretory proteins on hypoxic pancreatic cancer cells

Background Hypoxia in tumor cells is linked to increased drug resistance and more aggressive behavior. In pancreatic cancer, the tumor microenvironment is notably hypoxic and exhibits strong immunosuppressive properties. Given that immunotherapy is now approved for pancreatic cancer treatment, further understanding of how pancreatic tumor cell hypoxia influences T-cell cytotoxicityis essential. Objective This study examined how hypoxia affects the interaction between pancreatic tumor cells (PANC-1) and cytotoxic CD8+ T-cells. Methods Pancreatic tumor cells (PANC-1) were exposed to 20 cycles of chronic hypoxic conditions, each for 72 hours, followed by a re-oxygenation period for 24 hours. On cycles 10 and 20, PANC-1 conditioned media (CM) was harvested, and the hypoxic PANC-1 cells were co-cultured with either the activated cytotoxic CD8+ T-cells or with CD8+ T-cells CM. CD8+ T-cells CM was collected after five days of cell activation using anti-CD3/CD28 antibodies and interleukin-2 (IL-2). CD8+ T-cells were activated for 72 hours and then cultured with the hypoxic PANC-1 CM. Results Hypoxic PANC-1 cells showed significant resistance to the lytic effect of either CD8+ T-cells co-culture or CD8+ T-cells CM treatment compared to normoxic PANC-1 cells. A significant decrease in TNF-α and IFN-γ levels was also detected. Additionally, a significant increase in IL-6, p53 and TNF-α gene expression levels was observed in PANC-1 cells treated with CD8+ T-cells CM. Moreover, IL-6 gene expression level showed a significant difference between hypoxic and normoxic PANC-1 cells. CD8+ T-cell proliferation and cytokines production were significantly higher in cells co-cultured with PANC-1 CM. However, no significant differences were observed after treatment with either hypoxic or normoxic PANC-1 CM. Conclusion Hypoxia decreases PANC-1 cells’ sensitivity to cytotoxic CD8+ T-cells. Reduced tumor cell susceptibility to CD8+ T-cells was associated with increased IL-6 expression and reduced TNF-α and IFN-γ levels. Thus, cytokine dysregulation might contribute to the hypoxia-mediated resistance of pancreatic tumor cells to CD8+ T-cells.

Possible influence of sex on the relationship between dual-task gait costs and cognitive decline in older adults

The impact of cognitive decline in older adults can be evaluated with dual-task gait (DTG) testing in which a cognitive task is performed during walking, leading to increased costs of gait. Previous research demonstrated that higher DTG costs correlate with increasing cognitive deficits and with age. The present study was conducted to explore whether the relationship between the DTG costs and cognitive abilities in older individuals is influenced by sex differences. To address this objective, we conducted a study with 216 elderly participants (age range: 60 to 75 years, 127 females). These underwent Cognitive Functional Dementia (CFD) testing to determine their cognitive abilities and DTG testing to evaluate their gait parameters (gait speed, cadence, stride length, stride variance, and stance phase duration) while performing a backward serial number counting task. We carried out a correlation analysis between the CFD scores and the DTG costs. The DTG costs were calculated as the percentage difference between the gait parameters in single- and in dual-task testing, and the effects were compared considering the factors of sex and age. A significant negative correlation between the CFD scores and the dual-task costs of gait parameters was found only in males. The DTG costs did not differ between the sexes, while women obtained superior scores in the CFD test. The higher DTG costs significantly correlated with older age in men. In summary, our study provides evidence that, unlike in women, the DTG costs during the backward serial number counting task significantly increase in older men, correlating with declines in cognitive performance and increasing age. These findings suggest that the assessment of DT gait characteristics in relation to cognitive decline in older adults may manifest differently between sexes.

An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells

Aflatoxin B1 (AFB1) is a class 1 carcinogen and mycotoxin known to contribute to the development of hepatocellular carcinoma (HCC), growth impairment, altered immune system modulation, and malnutrition. AFB1 is synthesized by Aspergillus flavus and is known to widely contaminate foodstuffs, particularly maize, wheat, and groundnuts. The mechanism in which AFB1 causes genetic mutations has been well studied, however its metabolomic effects remained largely unknown. A better understanding of how AFB1 disrupts metabolism would provide insight into how this mycotoxin leads to carcinogenesis, growth impairment, and/or immunomodulation, and may reveal potential targets for pharmacological or nutritional interventions to protect against these effects. The current study evaluated the metabolomic effects of various doses (2.5 μM, 5 μM, 10uM) of AFB1 treatment to HepG2 (liver), MDA-MB-231 (breast), and A549 (lung) cells. Treated and control cells’ metabolomic profiles were evaluated via ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Univariate and multivariate analyses revealed significant alterations in metabolite concentrations from each dose of AFB1 treatment in each cell type. Pathway analysis was then used to understand broader biochemical functions affected by AFB1 treatment in each cell type. HepG2 cell pathway analyses revealed significant pathway perturbations in lipid metabolism, carnitine synthesis, catecholamine biosynthesis, purine metabolism, and spermidine and spermine biosynthesis. Analysis of A549 cells found a greater emphasis of perturbations on various amino acids along with lipid synthesis-related pathways, and catecholamine biosynthesis. Finally, analysis of treated MDA-MB-231 cells found spermidine and spermine biosynthesis, carnitine synthesis, plasma membrane-related pathways (phosphatidylcholine synthesis and alpha linolenic acid and linoleic acid metabolism), and various amino acid metabolism pathways to be most affected. These highlighted pathways should be targeted in future investigations to evaluate their potential in mitigating or preventing the development of negative health effects associated with AFB1 exposure.

Correction: Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: Study protocol for a double-blind single dummy randomized controlled trial

Stochastic simulation of soil moisture dynamics in farmland in the eastern region of the Songnen Plain

Soil moisture is the core of the hydrological cycle in agroecosystems, and most of the studies on soil moisture dynamics modeling adopt deterministic research methods, which are not well suited to study the hydrological processes in agricultural fields under changing conditions. Therefore, the present study adopts a stochastic approach to reveal the distribution characteristics of soil moisture in agroecosystems under the effects of soil, climate, vegetation, and other influencing factors. Using soil moisture and precipitation data and based on a stochastic model of soil moisture dynamics, the point-scale soil moisture dynamic characteristics and soil moisture probability density function of farmland systems in the Songnen Plain region were investigated. The soil moisture of maize in the study area showed a certain degree of stochasticity, and the curve characteristics of the probability density function of soil moisture p(s) obtained from the simulation were very close to those of the measured p(s). It shows that the stochastic model can effectively simulate the probability density function of soil moisture in the study area, which can provide a theoretical basis and scientific method for efficiently using soil and water resources in the area.

Martin Karplus obituary: theoretical chemist who first simulated proteins using molecular dynamics

Habitat suitability mapping and landscape connectivity analysis to predict African swine fever spread in wild boar populations: A focus on Northern Italy

African swine fever (ASF) is a highly contagious disease affecting wild and domestic pigs, characterised by severe haemorrhagic symptoms and high mortality rates. Originally confined to Sub-Saharan Africa, ASF virus genotype II has spread to Europe since 2014, mainly affecting Eastern Europe, and progressing through wild boar migrations and human action. In January 2022, the first case of ASF, due to genotype II, was reported in North-western Italy, in a wild boar carcass. Thereafter, numerous positive wild boars were identified, indicating an expanding wild epidemic, severely threatening Italian pig farming and trade. This study focused on the mapping of the suitable habitats for wild boars and their potential dispersal corridors in Northern Italy, using species distribution models and landscape connectivity analysis. The resulting maps identified areas with higher likelihood of wild boar presence, highlighting their preferential pathways crossing Northern Italy. The distribution of ASF positive wild boars along the major corridors predicted by the model suggests the obtained maps as valuable support to decision-makers to improve ASF surveillance and carcass early detection, aiming for eradication. The applied framework can be easily replicated in other regions and countries.

Genetic influence on choroidal vascularity index

Purpose To investigate the heritability of genetic influence on macular choroidal vascularity index (CVI). Methods Total choroidal area (TCA), luminal area (LA), and CVI was measured using horizontal scan of spectral-domain optical coherence tomography with enhanced depth imaging in the 373 healthy twin participants. Characteristics of the participants were investigated, including age, sex, axial length, hypertension, diabetes, drinking habits, and smoking status. Univariate and subsequent multivariate regression analyses were performed to evaluate the associations of these factors with TCA, LA, and CVI. Results Patients who were older and had a higher intraocular pressure, higher diastolic blood pressure, and lower pulse pressure showed associations with lower CVI (p<0.001, p = 0.014, p = 0.005, and p = 0.015, respectively). The covariate-adjusted heritability (±standard error) of the CVI was 0.716 ± 0.091, and the heritabilities of the TCA and LA were 0.691 ± 0.089 and 0.634 ± 0.100, respectively. Conclusion The TCA, LA, and CVI are highly heritable.

Correction: Attributable risk factors for asymptomatic malaria and anaemia and their association with cognitive and psychomotor functions in schoolchildren of north-eastern Tanzania

Relationship between secondary metabolites and ecological suitability zones for Eucommia ulmoides

The quality of Chinese medicinal materials is closely related to the types and contents of their secondary metabolites, while ecological adaptability influences the production of secondary metabolites. Therefore, identifying the relationship between ecological adaptability and secondary metabolites is important for enhancing the quality of Chinese medicinal materials. In this study, we collected 10-year-old Cortex Eucommiae (Eucommia ulmoides, EU) samples from 21 plots in eight provinces which are the primary production areas of EU in central China. We used the MaxEnt model to determine the ecological suitability zones for EU at the 21 sampling sites and classified them accordingly. The contents of six pharmacologically active secondary metabolites, including chlorogenic acid, aucubin, geniposidic acid, geniposide, pinoresinol monoglucoside, and pinoresinol diglucoside were measured in the EU bark. The results demonstrated significant variations in the content of the six secondary metabolites in EU bark among different sampling sites. Correlation analysis indicated a close relationship between the content of chlorogenic acid and aucubin in EU bark and the ecological suitability of their respective production areas. The total content of the six secondary metabolites also showed good consistency with the ecological suitability of the production areas. Exploratory factor analysis further revealed a strong consistency between the factor analysis comprehensive scores based on the content of major secondary metabolites and the types of suitability zones at the sample locations. The cluster analysis results demonstrated good consistency between clustering groups and ecological suitability zone groups, with higher consistency as the suitability level of the ecological zone increased. This indicated a significant impact of suitable ecological environments on the content of EU secondary metabolites.

Investigating the miRNA-mRNA interactome of human trabecular meshwork cells treated with TGF-β1 provides insights into the pathogenesis of pseudoexfoliation glaucoma

Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome. Primary human trabecular meshwork cells originating from normal donors were treated with TGF-β1 at 5 ng/mL for 24h; total RNA was extracted followed by RNA-Seq and miRNA-Seq. For both mRNA and miRNA species, differential expression was determined using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts, edgeR (for miRNA) and DESeq2 (for mRNA). Putative mRNA-miRNA interactions between differentially expressed mRNA and miRNA species were determined using interaction databases miRWalk, miRTarBase, TarBase and TargetScan. To classify mRNA species by function and pathway, gene enrichment was performed using Enrichr. The resulting miRNA-mRNA interactome consisted of 1202 interactions. Some highly connected microRNAs were hsa-let-7e-5p, hsa-miR-20a-5p, hsa-miR-122-5p, and hsa-miR-29c-3p. Most differentially expressed genes were indicated to be regulated by miRNAs. The sub-interactomes of genes involved in specific pseudoexfoliation glaucoma related enrichment terms such as oxidative stress, unfolded protein response, signal molecules and ECM remodelling were determined. This is the first study to present a genome-wide microRNA-mRNA regulatory network for human trabecular meshwork cells treated with TGF-β1 and may serve to generate unbiased hypotheses about regulatory functions and mRNA targets of miRNAs in pseudoexfoliation glaucoma and may help to develop miRNA-based therapeutics.