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Amplification-free, OR-gated CRISPR-Cascade reaction for pathogen detection in blood samples

Rapid and accurate detection of DNA from disease-causing pathogens is essential for controlling the spread of infections and administering timely treatments. While traditional molecular diagnostics techniques like PCR are highly sensitive, they include nucleic acid amplification and many need to be performed in centralized laboratories, limiting their utility in point-of-care settings. Recent advances in CRISPR-based diagnostics (CRISPR-Dx) have demonstrated the potential for highly specific molecular detection, but the sensitivity is often constrained by the slow trans-cleavage activity of Cas enzymes, necessitating preamplification of target nucleic acids. In this study, we present a CRISPR-Cascade assay that overcomes these limitations by integrating a positive feedback loop that enables nucleic acid amplification-free detection of pathogenic DNA at atto-molar levels and achieves a signal-to-noise ratio greater than 1.3 within just 10 min. The versatility of the assay is demonstrated through the detection of bloodstream infection pathogens, including Methicillin-Sensitive Staphylococcus aureus (MSSA), Methicillin-Resistant Staphylococcus aureus (MRSA), Escherichia coli , and Hepatitis B Virus (HBV) spiked in whole blood samples. Additionally, we introduce a multiplexing OR-function logic gate, further enhancing the potential of the CRISPR-Cascade assay for rapid and accurate diagnostics in clinical settings. Our findings highlight the ability of the CRISPR-Cascade assay to provide highly sensitive and specific molecular detection, paving the way for advanced applications in point-of-care diagnostics and beyond.

Using machine learning to predict depression among middle-aged and elderly population in China and conducting empirical analysis

Objective To develop a predictive model for evaluating depression among middle-aged and elderly individuals in China. Methods Participants aged ≥ 45 from the 2020 China Health and Retirement Survey (CHARLS) cross-sectional study were enrolled. Depressive mood was defined as a score of 10 or higher on the CESD-10 scale, which has a maximum score of 30. A predictive model was developed using five selected machine learning algorithms. The model was trained and validated on the 2020 database cohort and externally validated through a questionnaire survey of middle-aged and elderly individuals in Shaanxi Province, China, following the same criteria. SHapley Additive Interpretation (SHAP) was employed to assess the importance of predictive factors. Results The stacked ensemble model demonstrated an AUC of 0.8021 in the test set of the training cohort for predicting depressive symptoms; the corresponding AUC in the external validation cohort was 0.7448, outperforming all base models. Conclusion The stacked ensemble approach serves as an effective tool for identifying depression in a large population of middle-aged and elderly individuals in China. For depression prediction, factors such as life satisfaction, self-reported health, pain, sleep duration, and cognitive function are identified as highly significant predictive factors.

Development of a UVC application machine for managing plant diseases in soilless greenhouse crop production

The <i>Arabidopsis</i> demethylase REF6 physically interacts with phyB to promote hypocotyl elongation under red light

The plant photoreceptor phytochrome B (phyB) mediates the responses of plants to red (R) light. Trimethylation of histone H3 at Lys27 (H3K27me3) plays a crucial role in governing gene expression and controlling the response of plants to environmental changes. However, how dynamic H3K27me3 mediates plant response to R light is poorly understood. Here, we report that RELATIVE OF EARLY FLOWERING 6 (REF6), an H3K27me3 demethylase, promotes hypocotyl elongation under R light in Arabidopsis . Upon exposure to R light, REF6 preferentially interacts with the active Pfr form of phyB. Consequently, phyB enhances REF6 accumulation and its binding ability, which are necessary for inducing cell-elongation-related genes from open chromatin, ensuring normal plant growth under prolonged light exposure. Moreover, REF6 acts together with the phyB-PIF4 module to mediate light regulation of hypocotyl growth. These findings provide insights into the understanding of how phytochromes, epigenetic factors, and transcription factors coordinately control plant growth in response to changing light environment.

Retraction: SE-stacking: Improving user purchase behavior prediction by information fusion and ensemble learning

Relations between suggestibility, working memory and response inhibition in middle childhood

eDNA confirms lower trophic interactions help to modulate population outbreaks of the notorious crown-of-thorns sea star

Variability in predator–prey interactions can modulate population dynamics with impacts scalable to entire ecosystems. As notorious corallivores, crown-of-thorns sea stars (CoTS; Acanthaster spp.) have caused extensive losses of coral habitat during unexplained population outbreaks across the Indo-Pacific. While predation of adult CoTS may help to suppress their outbreaks, it does not sufficiently explain their profound boom-bust dynamics and so remains equivocal. Factors influencing early postsettlement mortality are generally more impactful on population size, thus lower trophic interactions involving juvenile CoTS may better contribute to outbreak prevention. We evaluated the impact of key predatory decapods that interact with juvenile CoTS in their coral rubble nursery before they emerge as destructive corallivores. Decapod density was influenced by habitat complexity and varied regionally, inverse to spatial trends in CoTS outbreaks on the Great Barrier Reef. Using eDNA gut content analysis, we confirmed seven species (~12% of individuals) of wild-caught decapod, collected from two reefs separated by &gt;1,000 km, as CoTS predators. Owing to spatial variation in predator abundance and community structure, we estimated potential (previous aquarium experiments) and realized (eDNA results here) rates of CoTS consumption were ~3-fold and ~1.6-fold lower, respectively, in outbreak hotspots. Through combination of field and molecular techniques, we demonstrated the appreciable impact of cryptic predators on early population success of this nuisance species, which expands our knowledge of CoTS outbreaks, pest species management, and reef conservation. Resolving predator–prey interactions at lower levels of the ecosystem can be crucial to understanding broader ecological outcomes.

Retraction: Mechanisms of hybrid oligomer formation in the pathogenesis of combined Alzheimer’s and Parkinson’s diseases

Data driven design of ultra high performance concrete prospects and application

G-quadruplexes and their unexpected ability to fold proteins

Bipolar vs. unipolar scaling in dynamic network analyses of Ecological Momentary Assessment data

This study examined the statistical and clinical benefits of using bipolar versus unipolar scaling in dynamic network analysis of Ecological Momentary Assessment (EMA) data. Methods: Forty-seven students completed EMA reports three times daily for five weeks via either unipolar (n = 24) or bipolar (n = 23) scales. The data were analyzed to construct idiographic network models. Results: The bipolar scaling group presented significantly lower zero inflation (2.37% vs. 10.31%, U = 2407756, r = 0.75, p &lt; .05) and greater response variability. Network analysis revealed more participants with significant network edges in the bipolar group (69.57% vs. 41.67%, χ²(1) = 12.06, p = .0007). Additionally, the bipolar group had lower odds of zero responses than the unipolar group did (p = .038). Conclusion: Bipolar scaling enhances EMA data quality by reducing zero inflation and increasing variability, resulting in richer dynamic network models. Further research is needed to confirm these findings in clinical populations.

Altered auditory brainstem responses are post-acute sequela of SARS-CoV-2 (PASC)

DR5 is a restriction factor for human herpesviruses

Restriction factors are dominant proteins that target different essential steps of the viral life cycle; thus, these proteins provide an early line of defense against viruses. Here, we found that the internalization of DR5, an important receptor of the extrinsic apoptotic pathway, initiates apoptosis to inhibit Kaposi sarcoma–associated herpesvirus (KSHV) lytic replication. An evolutionary analysis of the DR5 sequence demonstrated that three amino acids underwent positive selection in primates. Notably, one of these positive selection sites, A62, is essential for the antiviral function of DR5 and is important for the binding of DR5 to its ligand, TNF-related apoptosis-inducing ligand. Moreover, DR5 exhibits broad antiviral activity against and inhibits various herpesviruses, including Epstein–Barr virus, herpes simplex virus type 1, and herpes simplex virus type 2. As a countermeasure, the KSHV K5 protein interacts with DR5 and promotes DR5 degradation through the lysosomal and proteasomal degradation pathways; lysine 245 of DR5 is essential for K5-induced DR5 degradation. These findings demonstrate that DR5 is a restriction factor for human herpesviruses.

Tracking cropland transitions: A comparative analysis of U.S. land cover change data

There are a growing number of land cover data available for the conterminous United States, supporting various applications ranging from biofuel regulatory decisions to habitat conservation assessments. These datasets vary in their source information, frequency of data collection and reporting, land class definitions, categorical detail, and spatial scale and time intervals of representation. These differences limit direct comparison, contribute to disagreements among studies, confuse stakeholders, and hamper our ability to confidently report key land cover trends in the U.S. Here we assess changes in cropland derived from the Land Change Monitoring, Assessment, and Projection (LCMAP) dataset from the U.S. Geological Survey and compare them with analyses of three established land cover datasets across the coterminous U.S. from 2008-2017: (1) the National Resources Inventory (NRI), (2) a dataset Lark et al. 2020 derived from the Cropland Data Layer (CDL), and (3) a dataset from Potapov et al. 2022. LCMAP reports more stable cropland and less stable noncropland in all comparisons, likely due to its more expansive definition of cropland which includes managed grasslands (pasture and hay). Despite these differences, net cropland expansion from all four datasets was comparable (5.18-6.33 million acres), although the geographic extent and type of conversion differed. LCMAP projected the largest cropland expansion in the southern Great Plains, whereas other datasets projected the largest expansion in the northwestern and central Midwest. Most of the pixel-level disagreements (86%) between LCMAP and Lark et al. 2020 were due to definitional differences among datasets, whereas the remainder (14%) were from a variety of causes. Cropland expansion in the LCMAP likely reflects conversions of more natural areas, whereas cropland expansion in other data sources also captures conversion of managed pasture to cropland. The particular research question considered (e.g., habitat versus soil carbon) should influence which data source is more appropriate.

Towards simultaneous imaging of ultrafast nuclear and electronic dynamics in small molecules

Abstract When a chemical bond is broken, the molecular structure undergoes a transformation. An ideal experiment should probe the change in the electronic and nuclear structure simultaneously. Here, we present a method for the simultaneous time-resolved imaging of nuclear and electron dynamics by combining Coulomb explosion imaging with strong-field photoelectron momentum imaging. We study the dissociative photoionization of H2 and N2O using time-resolved photoion-photoelectron coincidence spectroscopy. The measured delay-dependent kinetic energy release clearly reveals the ultrafast nuclear dynamics. The transient changes in the electronic structure of the dissociating $$\hbox {H}_2^+$$ molecular ion are studied by solving the three-dimensional Schrödinger equation in the fixed-nuclei approximation. A detailed comparison of the numerical results to those from a simple imaging model is conducted. The numerical results reflect the evolution in the electron density in the molecular ion as its bond is first stretched and then breaks apart. While these details remain unresolved in the H2 experiment, we demonstrate the sensitivity of the photoelectron signal to the site of electron localization following bond cleavage for the case of N2O. Our work shows opportunities and challenges on the track towards capturing simple gas-phase chemical dynamics in complete molecular movies.

Behold the scale of global zoogeomorphic activity

The effect of exposure to the COVID-19 pandemic on nutritional status and cognitive, motor, and behavioural development among children aged 20 months in rural Bangladesh: A repeated cross-section study between 2020 and 2022

Background Past studies have documented detrimental effects of the COVID-19 pandemic on the learning and mental health of preschool- and school-age children. Few studies have examined effects on younger children’s development, though this age group is extremely sensitive to economic and health shocks. Methods We assessed the effects of exposure to the pandemic on the cognitive, language, and motor development; behaviour; and growth among toddlers in rural Bangladesh. We estimated average differences between two repeated cross-sectional surveys of children and mothers living in the same villages. The first survey included 20-month-old children in 2019 and 2020 (unexposed group). The second survey took place in a randomly-selected subset of the same villages in 2022 among 20-month-old children, who had experienced pandemic-related lockdowns from approximately mid-gestation through their first year (exposed group). Both surveys used similar inclusion criteria and the same developmental assessments (Bayley’s Scales of Infant and Toddler Development), behaviour observations, and field protocols. Results The exposed group (N = 526) had lower cognitive [Effect size = -0.45 (95% CI = -0.63 to -0.27)] and motor [-0.55 (-0.73 to -0.37)] composite scores, compared to the unexposed group (N = 1344). They were also observed to be less responsive to the examiner [-0.29 (-0.48 to -0.11)], less happy [-0.37 (-0.55 to -0.19)], less vocal [-0.57 (-0.73 to -0.4)] and less cooperative [-0.42 (-0.6 to -0.24)]. The pandemic increased depression among mothers with a primary education or less but not among better educated mothers. Children of less educated mothers also showed larger differences across exposed and unexposed groups in development and behaviour than those with better educated mothers. Conclusion The COVID-19 pandemic detrimentally affected cognitive and motor skills and behaviour of young children in rural Bangladesh. Disadvantaged young children’s development appears to be extremely vulnerable to shocks. Without intervention these deficits will likely lead to later problems in learning and mental health.

Publisher Correction: Development and validation of nomogram models for severe and fatal COVID-19

Identifying the interactions conferring functional mechanical rigidity on RNase-resistant RNA from Zika virus

Some viruses counter host-cell efforts to digest invading viral RNA by using special structures resistant to host RNases, known as exoribonuclease-resistant RNAs (xrRNAs). xrRNAs typically form an unusual fold with the 5′-end threaded through a ring consisting of a multihelix junction closed by a pseudoknot. By using single-molecule force spectroscopy (SMFS), we previously showed that a Zika virus xrRNA is extremely rigid mechanically, withstanding very high forces, and that this mechanical resistance—not simply the knot-like fold topology—is essential for RNase resistance. Here, we have determined which interactions are most important for generating mechanical rigidity in the Zika virus xrRNA, by systematically mutating tertiary contacts. We found that removing any of the tertiary contacts involving the threaded 5′ end was sufficient to abrogate mechanical resistance. In contrast, breaking a single pseudoknot base pair was not sufficient to do so: Two broken pairs were needed. This hierarchy of interaction importance for mechanical rigidity was supported by simulations mapping how mechanical tension was distributed within the xrRNA. For all mutants, RNase resistance varied in lock-step with mechanical resistance, confirming the primary role of mechanical rigidity in xrRNA function. This work reveals which interactions are most important for Zika xrRNA function, with implications for targeting the xrRNA therapeutically.

Are taxes to sugar-sweetened beverages and non-essential energy dense food implemented in Mexico regressive?

Introduction In January 2014, Mexico introduced an excise tax of $1.00 Mexican peso/liter on sugar-sweetened beverages (SSB) and an 8% tax on non-essential energy dense food (NEDF) with at least 275 kilocalories/100 grams. Fiscal policies could be regressive when taxes generate a greater financial burden for low-income households compared to higher-income households. The objective of this study was to analyze whether SSB and NEDF taxes in Mexico were regressive using a nationally representative survey. Materials and methods Information from the National Household Income and Expenditure Survey in Mexico in its 2014, 2016 and 2018 waves were used to estimate changes in expenditures on SSB and NEDF over total expenditures by income quintile and place of residence using own price elasticities, changes in prices after tax implementation and tax pass-through prices. We derived uncompensated own price elasticities using the Linear Approximation of the Almost Ideal Demand System. Results Price elasticities -in absolute values- were higher in urban areas than in rural settings for SSB in 2014 and 2016, while the opposite was observed for NEDF. For SSB, price elasticities -in absolute values- among households in the highest income quintiles were lower than those in the lowest income quintiles. The tax paid for SSB and NEDF over total expenditures was higher among low-income households. However, the reduction in SSB expenditures over total expenditures in low-income households was higher compared to the highest income quintile. For NEDF, weekly expenditures in rural areas were lower than in urban areas for the lowest quintile, while for the highest quintile the reduction was similar. Conclusions Low-income households in urban and rural areas reduced the proportion spent on SSB and NEDF more compared to higher-income residents, counteracting the regressive burden of the taxes.