Browse Articles

Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice

Theory of frequency fluctuation of intramolecular vibration in solution phase: Application to C–N stretching mode of organic compounds

We formulate frequency fluctuations of intramolecular vibrations of a solute by exploring the fluctuation of the electrostatic potential by solvents. We present a numerical methodology for estimating the frequency fluctuations; the methodology is based on the reference interaction site model self-consistent field with a constrained spatial electron density distribution, a theoretical model of solvation fields based on classical statistic mechanics. By applying the present theory to the C–N stretching vibrations of several nitrile compounds, our estimated frequency fluctuation scale and bandwidth shift by changing solvent kinds reproduced the experimental data. Furthermore, we regard the standard deviation of the electrostatic potential as the multiple random variables for analyzing the frequency fluctuations. Our results reveal that the dominant fluctuation of the electrostatic field is almost parallel to the vibrational axis. In addition, the fluctuations of electrostatic potential become spatially nonuniform as the solvents form stronger hydrogen bonds with the solute. The development of the solvation field confirms that the nonuniformity of the electrostatic field is crucial to the frequency fluctuations.

Polaritonic Fourier crystal

USP7 V517F mutation as a mechanism of inhibitor resistance

FKBP51 in glutamatergic forebrain neurons promotes early life stress inoculation in female mice

Abstract Early life stress (ELS) can increase vulnerability to psychiatric disorders, but also trigger resilience. FKBP51 has been associated with an increased risk for developing psychiatric disorders, specifically in interaction with ELS exposure. Here, the contribution of FKBP51 in glutamatergic forebrain neurons to the long-term consequences of ELS was investigated in both sexes. In female wild-type Fkbp5 lox/lox mice, ELS exposure led to an anxiolytic phenotype and improved memory performance in a stressful context, however this ELS effect was absent in Fkbp5 Nex mice. These interactive FKBP51 x ELS effects in female mice were also reflected in reduced brain region volumes, and on structural and electrophysiological properties of CA1 pyramidal neurons of the dorsal hippocampus. In contrast, the behavioral, structural and functional effects in male ELS mice were less pronounced and independent of FKBP51. RNA sequencing of the hippocampus revealed the transcription factor 4 (TCF4) as a potential regulator of the female interactive effects. Cre-dependent viral overexpression of TCF4 in female Nex-Cre mice led to similar beneficial effects on behavior as the ELS exposure. This study demonstrates a sex-specific role for FKBP51 in mediating the adaptive effects of ELS on emotional regulation, cognition, and neuronal function, implicating TCF4 as a downstream effector.

ER O-glycosylation in synovial fibroblasts drives cartilage degradation

Abstract How arthritic synovial fibroblasts (SFs) activate cartilage ECM degradation remains unclear. GALNT enzymes initiate O-glycosylation in the Golgi; when relocated to the ER, their activity stimulates ECM degradation. Here, we show that in human rheumatoid and osteoarthritic synovial SFs, GALNTs are relocated to the ER. In an RA mouse model, GALNTs relocation occurs shortly before arthritis symptoms and abates as the animal recovers. An ER GALNTs inhibitor prevents cartilage ECM degradation in vitro and expression of this chimeric protein in SFs results in the protection of cartilage. One of the ER targets of GALNTs is the resident protein Calnexin, which is exported to the cell surface of arthritic SFs. Calnexin participates in matrix degradation by reducing ECM disulfide bonds. Anti-Calnexin antibodies block ECM degradation and protect animals from RA. In sum, ER O-glycosylation is a key switch in arthritic SFs and glycosylated surface Calnexin could be a therapeutic target.

Deep representation learning for clustering longitudinal survival data from electronic health records

Abstract Precision medicine requires accurate identification of clinically relevant patient subgroups. Electronic health records provide major opportunities for leveraging machine learning approaches to uncover novel patient subgroups. However, many existing approaches fail to adequately capture complex interactions between diagnosis trajectories and disease-relevant risk events, leading to subgroups that can still display great heterogeneity in event risk and underlying molecular mechanisms. To address this challenge, we implemented VaDeSC-EHR, a transformer-based variational autoencoder for clustering longitudinal survival data as extracted from electronic health records. We show that VaDeSC-EHR outperforms baseline methods on both synthetic and real-world benchmark datasets with known ground-truth cluster labels. In an application to Crohn’s disease, VaDeSC-EHR successfully identifies four distinct subgroups with divergent diagnosis trajectories and risk profiles, revealing clinically and genetically relevant factors in Crohn’s disease. Our results show that VaDeSC-EHR can be a powerful tool for discovering novel patient subgroups in the development of precision medicine approaches.

Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization

Abstract The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.

High-fidelity remote entanglement of trapped atoms mediated by time-bin photons

Abstract Photonic interconnects between quantum processing nodes are likely the only way to achieve large-scale quantum computers and networks. The bottleneck in such an architecture is the interface between well-isolated quantum memories and flying photons. We establish high-fidelity entanglement between remotely separated trapped atomic qubit memories, mediated by photonic qubits stored in the timing of their pulses. Such time-bin encoding removes sensitivity to polarization errors, enables long-distance quantum communication, and is extensible to quantum memories with more than two states. Using a measurement-based error detection process and suppressing a fundamental source of error due to atomic recoil, we achieve an entanglement fidelity of 97% and show that fundamental limits due to atomic recoil still allow fidelities in excess of 99.9%.

Deep learning prioritizes cancer mutations that alter protein nucleocytoplasmic shuttling to drive tumorigenesis

Chiral europium halides with high-performance magnetic field tunable red circularly polarized luminescence at room temperature

Solar-powered light-modulated microwave programmable metasurface for sustainable wireless communications

Groundwater quality evolution across China

Amplified multipartite entanglement witnessed in a quantum critical metal

Traffic signal active control method for short-distance intersections

Aiming at the existing problems about the overflow prevention goal and the overall traffic efficiency guarantee being difficult to optimize at the same time in the signal control process of short-distance intersections scenario, this paper proposes a traffic signal active control method based on key state prediction. In order to construct the key state evolution trend of short-distance intersection scenarios, this paper proposes the concept of overflow index for short-distance road sections and designs the prediction method of overflow index. In order to perform fast computation and solution for the active control scheme, this paper builds a solution algorithm based on deep reinforcement learning and optimizes the problem of reward sparsity in the algorithm, which improves the ability of active control in terms of state space and reward function. The experimental results show that this method can not only ensure the overall traffic efficiency of short-distance intersections and reduce the travel delay but also can actively sense the change of overflow state, improve the overflow prevention and control ability of the target scenario, and reduce the overflow risk.

Methods for the health technology assessment of complex interventions: A scoping review

Introduction Health Technology Assessment (HTA) methods have been developed to support evidence-informed policy-making by assessing the comparative value and costs of health interventions and programs. However, the complexity of many health interventions presents challenges to the use of conventional HTA methods. This scoping review collated and synthesised international approaches to the HTA of complex interventions including identifying assessment criteria, types of evidence and the domains of value that are most favoured. Materials and methods A systematic scoping review was conducted using JBI guidelines, Arksey and O’Malley’s six-stage framework and recent advances in scoping review methodology. Seven electronic databases, grey literature sources, three leading HTA journals and backward citation searching were used to search complex intervention HTA records written in English from January 2000 to December 2023. Supplementary searches were also conducted to identify actual HTA reports produced by certain countries. The Population (or Participants), Concept and Context framework guided the literature selection process, with a two-phase screening process and subsequent narrative synthesis. The PRISMA-ScR checklist guided reporting. Independent screening by two reviewers ensured accuracy of study selection, and data extraction followed a customised form grounded in the HTA-core model. Results A total of 10684 references yielded 35 records from twelve countries. The review identified two clusters of research on HTA of complex interventions: methodological orientation and conceptual models (n = 19) and actual HTAs conducted on complex interventions (n = 16). Several evaluation criteria and domains were used or recommended for use that extended beyond the core HTA domains. Three distinct HTA approaches emerged: the integrative approach, highlighted in methodological guides and theoretical frameworks; and either sequential or concurrent approaches, emphasised in practical HTAs. In the theoretical literature, equal weight is given to various HTA domains for complex intervention assessment, but in practice, the scope and specificity of domains vary across reports, with countries exhibiting differing priorities. Cost-effectiveness, clinical effectiveness and organisational aspects predominated in complex intervention evaluation, albeit with gradually increasing emphasis on a technology’s description, intended use, safety and patient and social aspects over the past decade. There was less focus on ethical and legal considerations. This trend is consistent with the evaluation of non-complex interventions in HTA. HTAs undertaken on complex interventions introduced unique domains like politics, implementation, early stakeholder engagement, outcome uncertainty, adaptive methods and real-world data, with expert opinion recommended when data were insufficient. Conclusion A shift towards considering broader contextual and implementation factors in the HTA of complex interventions was evident in this scoping review, extending beyond traditional HTA domains. However, discrepancies persist between theoretical and methodological guidance suggesting one approach and practical HTAs often adopting another. The implications of the shift towards contextual and implementation factors require exploration in future research. This could help to establish consensus on metrics and evidentiary elements, optimising HTA for complex health interventions.

Family caregivers’ contributions to self-care behaviors among heart failure patients in Oman

Background Family caregiver’s role can be involving patients with heart failure (HF) in each behavior of self-care such as treatment adherence, and healthy eating, which will \ultimately lead to disease control. This study aimed to investigate family caregivers’ contributions to self-care behaviors among patients with heart failure in Oman. Methods A descriptive cross-sectional design was used. A convenience sample of 136 family caregivers of patients with HF has completed the family caregivers’ demographics characteristics sheet and the Caregiver Contribution to Self-Care of HF Index2 (CC-SCHFI 2). Results Caregivers demonstrated low levels of contribution to patients’ self-care. The mean and (standard deviation) of caregivers’ contribution to maintenance tasks, patients’ ability to perceive symptoms, and to patients’ ability to manage self-care tasks scored 64.12 (SD = 15.70), 66.78 (SD = 14.72).and 52.26 (SD = 15.98) respectively. Education, exercise, and quality of social support were found to have a statistically significant association with caregivers’ contribution to self-care maintenance at a p–value of 0.004, 0.004, 0.004 respectively. While gender, education, marital status, exercise, and quality of social support had statistically significant association with caregivers’ contribution to self-care perception at a p-value of 0.003, 0.002, 0.006, < 0.01, and 0.004 respectively. Moreover, gender, education, marital status, exercise, and health compared to 1 year ago had significant association with caregivers’ contribution to self-care management at a p-value of 0.009, 0.006, 0.005, <  0.01, 0.007 respectively. Conclusion Giving attention and support to caregivers can indirectly impact the self-care behaviors of patients with HF and consequently enhance patients’ outcomes.

Unveiling the social and environmental benefits of digital transformation in corporations

In the context of the “dual-carbon” goal and the digital economy, exploring the impact of digital transformation on enterprises’ social and environmental responsibility is a key issue for achieving sustainable enterprise development and promoting high-quality economic development. This study empirically examines the impact of digital transformation on enterprises’ social and environmental responsibility and its mechanism. We achieved this through using instrumental variables and DID (Differences-in-Differences)models and selecting the data of Chinese A-share listed enterprises from 2008 to 2021. The study concludes that an enterprise’s digital transformation positively contributes to the fulfilment of corporate social responsibility. However, the digital transformation of the enterprise has a dampening effect on the fulfilment of the enterprise’s environmental responsibility. Additionally, this effect holds after a series of robustness tests. Further investigation shows that financial constraints have a positive moderating effect on enterprise digital transformation and corporate social responsibility(CSR) and a negative moderating effect on enterprise environmental responsibility. In addition, we found that the impact of enterprise digital transformation on CSR and environmental responsibility varies by firm type. The above studies provide valuable practical experiences for enterprises to achieve green and low-carbon development, reduce environmental pollution, and realize high-quality economic development as well as insight for enterprises and policy implementers.

Genome-wide SNPs reveal novel genetic relationships among Atlantic cod (Gadus morhua) from the south coast of Newfoundland, Canada (subdivision 3Ps), Northern cod stock complex, and Gulf of St Lawrence

The south coast of Newfoundland, Canada (Northwest Atlantic Fisheries Organization (NAFO) Subdivision 3Ps) is known to be a mixing zone for Atlantic cod (Gadus morhua). Tagging and genetic studies have shown cod from the Northern and Southern Gulf of St. Lawrence (NAFO Divisions 3Pn, 4RST), Southern Grand Banks (3NO), and the Northern cod stock complex (2J3KL) frequent the waters of 3Ps at various times throughout the year, but the extent of genetic mixing is unknown. However, 3Ps has not been the central focus of previous large-scale genomic analyses of population structure, a knowledge gap that we address using single nucleotide polymorphisms. Using 38,111 neutral markers from reduced representation next-generation sequencing data, we determined the provenance of 3Ps cod relative to the Northern stock complex, Gulf of St. Lawrence, Bay of Fundy, and Gulf of Maine. We present evidence for genetic similarity between 3Ps and the Northern stock complex, particularly NAFO Division 3L. Additionally, genetic clustering analyses suggest 3Ps to be a mixed stock, containing individuals from the Northern stock complex and Gulf of St. Lawrence. Genetic clustering also suggests that there are two subtle subclusters of Northern stock complex and 3Ps cod, indicating there may be subtle population structure within the Northern stock complex and surrounding zones. This new information on population structure gives insight into connectivity and may be useful in future management for rebuilding cod populations.

Optimization design and experiment of key components of mountain pendulum-lever cam type hole seeders based on DEM-MBD coupling simulation

In response to issues such as high miss-seeding rates and uneven seed grain distribution during the operation of the pendulum-lever camshaft hole seeders under the compound planting mode of corn and soybeans in hilly mountainous areas, a method for optimizing the hole seeders by adjusting movable pendulum-lever angle and the number of cam roller groups is proposed. By analyzing the motion process and mechanism of hole formation of the hole-forming device, it was possible to elucidate the influence of the movable pendulum-lever angle and cam roller group number on the improvement of seeding quality. Based on the DEM-MBD coupled simulation, single-factor simulation experiments were conducted using the hole seeders shaft speed, movable pendulum- lever angle, and cam roller group number as test factors, with the seed grain qualification rate, reseeding rate, and miss-seeding rate as test indicators. A three-factor, three-level orthogonal rotation combination simulation experiment was designed to derive a mathematical model of the relationship between test factors and indicators. Data analysis was performed using Design-Expert 13 soft-ware to optimize the regression model for multiple objectives and obtain the optimal parameter combination. The simulation test results indicate that when the hole seeder shaft speeds were 47.43 r/min and 48.09 r/min, the movable pendulum- lever angles were 100.23° and 101.70°, and the number of rollers in the cam group were 2.81 and 2.95,the qualified rates of corn and soybean seeding were 95.19% and 96.07%. The reseeding rates were 3.58% and 2.35%, while the missed seeding rates were 1.23% and 1.58%. The field test results indicate that under the optimal parameter combination, the relative errors of the qualification rate, the reseeding rate, and the missed seeding rate between the simulation tests and the field tests were 0.4% and 0.13%, 1.17% and 0.36%, and 1.57% and 0.23%. This serves to validate the accuracy of the coupled simulation model, and the research findings can provide theoretical support and a point of reference for the design and performance optimization of pendulum- lever cam-type hole seeders in hilly and mountainous areas.