Browse Articles
Discover research articles across all indexed journals
Dynamic multiday seizure cycles and evolving rhythms in a tetanus toxin rat model of epilepsy
Chronic stress–induced cholesterol metabolism abnormalities promote ESCC tumorigenesis and predict neoadjuvant therapy response
Recent studies have demonstrated that chronic stress can enhance the development of multiple human diseases, including cancer. However, the role of chronic stress in esophageal carcinogenesis and its underlying molecular mechanisms remain unclear. This study uncovered that dysregulated cholesterol metabolism significantly promotes esophageal carcinogenesis under chronic stress conditions. Our findings indicate that the persistent elevation of glucocorticoids induced by chronic stress stimulates cholesterol uptake, contributing to esophageal carcinogenesis. The activated glucocorticoid receptor (GCR) enrichment at the promoter region of High Mobility Group Box 2 (HMGB2) facilitates its transcription. As a transcription coactivator, HMGB2 enhances Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) transcription and regulates cholesterol metabolism through LDL particle uptake into cells via Low Density Lipoprotein Receptor (LDLR). These results emphasize the significant impact of chronic stress on esophageal carcinogenesis and establish cholesterol metabolism disorder as a crucial link between chronic stress and the development of ESCC. The implications suggest that effectively managing chronic stress may serve as a viable strategy for preventing and treating ESCC.
CRIP1 inhibits cutaneous melanoma progression through TFAM-mediated mitochondrial biogenesis
New evidence for early Indian Ocean trade routes into the South African interior
The rise and spread of ancient Indian Ocean Rim (IOR) trade networks profoundly impacted southern Africa. Control over this trade played a critical role in the rise and maintenance of complex societies of the second millennium CE such as Mapungubwe and Great Zimbabwe. While the African origins of this trade lie in the first millennium CE, understanding its earliest phases and subsequent development in the far south has been hampered by a general paucity of research. The recovery of Persian Gulf ceramic sherds and Asian glass beads from the Letaba region of northeastern South Africa demonstrates that communities up to 400 km inland were already part of IOR trade by the 10th century. Although glass beads have been found at several late first millennium CE sites throughout the region, glazed wares are much rarer by comparison. In southern Africa, archaeological sites with Persian Gulf ceramics largely date to between the 9th and 10th centuries with a distribution limited to the Limpopo River’s main tributaries. This distribution poses new questions about early IOR trade routes into the southern African interior and suggests Xai-Xai in southern Mozambique as a possible entry point for early IOR trade.
Panoramic radiographic features for machine learning based detection of mandibular third molar root and inferior alveolar canal contact
How should the advancement of large language models affect the practice of science?
Large language models (LLMs) are being increasingly incorporated into scientific workflows. However, we have yet to fully grasp the implications of this integration. How should the advancement of large language models affect the practice of science? For this opinion piece, we have invited four diverse groups of scientists to reflect on this query, sharing their perspectives and engaging in debate. Schulz et al. make the argument that working with LLMs is not fundamentally different from working with human collaborators, while Bender et al. argue that LLMs are often misused and overhyped, and that their limitations warrant a focus on more specialized, easily interpretable tools. Marelli et al. emphasize the importance of transparent attribution and responsible use of LLMs. Finally, Botvinick and Gershman advocate that humans should retain responsibility for determining the scientific roadmap. To facilitate the discussion, the four perspectives are complemented with a response from each group. By putting these different perspectives in conversation, we aim to bring attention to important considerations within the academic community regarding the adoption of LLMs and their impact on both current and future scientific practices.
Identification of a comprehensive set of transcriptional regulators involved in the long-term survivability of Escherichia coli in soil
14-3-3 promotes sarcolemmal expression of cardiac Ca <sub>V</sub> 1.2 and nucleates isoproterenol-triggered channel superclustering
The L-type Ca 2+ channel (Ca V 1.2) is essential for cardiac excitation–contraction coupling. To contribute to the inward Ca 2+ flux that drives Ca 2+ -induced-Ca 2+ -release, Ca V 1.2 channels must be expressed on the sarcolemma; thus the regulatory mechanisms that tune Ca V 1.2 expression to meet contractile demand are an emerging area of research. A ubiquitously expressed protein called 14-3-3 has been proposed to affect Ca 2+ channel trafficking in nonmyocytes; however, whether 14-3-3 has similar effects on Ca V 1.2 in cardiomyocytes is unknown. 14-3-3 preferentially binds phospho-serine/threonine residues to affect many cellular processes and is known to regulate cardiac ion channels including Na V 1.5 and the human ether-à-go-go–related gene (hERG) potassium channel. Altered 14-3-3 expression and function have been implicated in cardiac pathologies including hypertrophy. Accordingly, we tested the hypothesis that 14-3-3 interacts with Ca V 1.2 in a phosphorylation-dependent manner and regulates cardiac Ca V 1.2 trafficking and recycling. Confocal imaging, proximity ligation assays, superresolution imaging, and coimmunoprecipitation revealed a population of 14-3-3 colocalized and closely associated with Ca V 1.2. The degree of 14-3-3/Ca V 1.2 colocalization increased upon stimulation of β -adrenergic receptors with isoproterenol. Notably, only the 14-3-3-associated Ca V 1.2 population displayed increased cluster size with isoproterenol, revealing a role for 14-3-3 as a nucleation factor that directs Ca V 1.2 superclustering. Isoproterenol-stimulated augmentation of sarcolemmal Ca V 1.2 expression, Ca 2+ currents, and Ca 2+ transients in ventricular myocytes were strengthened by 14-3-3 overexpression and attenuated by 14-3-3 inhibition. These data support a model where 14-3-3 interacts with Ca V 1.2 in a phosphorylation-dependent manner to promote enhanced trafficking/recycling, clustering, and activity during β -adrenergic stimulation.
Production of novel theranostic nano-vector based on superparamagnetic iron oxide nanoparticles/miR-497 targeting colorectal cancer
Abstract Colorectal cancer (CRC) is a serious public health concern worldwide. Immune checkpoint inhibition medication is likely to remain a crucial part of CRC clinical management. This study aims to create new super paramagnetic iron oxide nano-carrier (SPION) that can effectively transport miRNA to specific CRC cell lines. In addition, evaluate the efficiency of this nano-formulation as a therapeutic candidate for CRC. Bioinformatics tools were used to select a promising tumor suppressor miRNA (mir-497-5p). Green route, using Fusarium oxyporium fungal species, manipulated for the synthesis of SPION@Ag@Cs nanocomposite as a carrier of miR-497-5p. That specifically targets the suppression of PD1/PDL1 and CTLA4pathways for colorectal therapy. UV/visible and FTIR spectroscopy, Zeta potential and MTT were used to confirm the allocation of the miR-497 on SPION@Ag@Cs and its cytotoxicity against CRC cell lines. Immunofluorescence was employed to confirm transfection of cells with miR-497@NPs, and the down- regulation of CTLA4 in HT29, and Caco2 cell lines. On the other hand, PDL1 showed a significant increase in colorectal cell lines (HT-29 and Caco-2) in response to mir497-5p@Nano treatment. The data suggest that the mir-497 -loaded SPION@Ag@Cs nano-formulation could be a good candidate for the suppression of CTLA4in CRC human cell lines. Consequently, the targeting miR-497/CTLA4 axis is a potential immunotherapy treatment strategy for CRC.
Is Ockham’s razor losing its edge? New perspectives on the principle of model parsimony
The preference for simple explanations, known as the parsimony principle, has long guided the development of scientific theories, hypotheses, and models. Yet recent years have seen a number of successes in employing highly complex models for scientific inquiry (e.g., for 3D protein folding or climate forecasting). In this paper, we reexamine the parsimony principle in light of these scientific and technological advancements. We review recent developments, including the surprising benefits of modeling with more parameters than data, the increasing appreciation of the context-sensitivity of data and misspecification of scientific models, and the development of new modeling tools. By integrating these insights, we reassess the utility of parsimony as a proxy for desirable model traits, such as predictive accuracy, interpretability, effectiveness in guiding new research, and resource efficiency. We conclude that more complex models are sometimes essential for scientific progress, and discuss the ways in which parsimony and complexity can play complementary roles in scientific modeling practice.
The unskilled-and-unaware problem and performance feedback in monotonous, easily accustomed, and repetitive work
Abstract The current research examined whether people predict their performance on monotonous, easily accustomed, and repetitive (MEAR) tasks accurately and confirm the effects of performance feedback on their MEAR work predictions. Considering typing on the keyboard as an MEAR task in modern society, 128 university students were asked to type a 12-digit number displayed on each monitor within 5 minutes, explaining that there would be 75 typing problems and participants would receive 20 yen per correct answer. Additionally, participants were informed that they could earn money by reaching a self-determined performance target, with the condition that if they did not reach their self-set goal, they would not receive any earnings. The main findings were as follows: Regardless of the performance levels of typing on keyboards, only 23% of the participants reached the goal, indicating that the absence of performance feedback led to individuals’ overestimation of performance. In contrast, providing feedback significantly improved performance predictions: 76% of the participants reached the goal with feedback on their own performance, 70% with feedback on others’ performance, and 88% with feedback on both their own and others’ performance information. Specifically, the effects between one’s own and others’ performance feedback did not vary at statistically significant levels.
Fatty acid metabolism and the oxidative stress response support bacterial predation
Despite growing awareness of their importance in soil ecology, the genetic and physiological traits of bacterial predators are still relatively poorly understood. In the course of a Myxococcus xanthus predator evolution experiment, we identified a class of genotypes leading to enhanced predation against diverse species. RNA-seq analysis demonstrated that this phenotype is linked to the constitutive activation of a predation-specific program. Functional analysis of the mutations accumulated across the evolutionary time in a two-component system and Acyl-CoA-manipulating enzymes revealed the critical roles of fatty acid metabolism and antioxidant gene induction. The former likely adapts the predator to metabolites derived from the prey while the latter protects predatory cells from reactive oxygen species generated by prey cells under stress and released upon lysis during predation. These findings reveal interesting parallels between bacterial predator–prey dynamics and pathogen–host cell interactions.
Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation
The present and future of peer review: Ideas, interventions, and evidence
What is wrong with the peer review system? Is peer review sustainable? Useful? What other models exist? These are central yet contentious questions in today’s academic discourse. This perspective critically discusses alternative models and revisions to the peer review system. The authors highlight possible changes to the peer review system, with the goal of fostering further dialog among the main stakeholders, including producers and consumers of scientific research. Neither our list of identified issues with the peer review system nor our discussed resolutions are complete. A point of agreement is that fair assessment and efficient change would require more comprehensive and rigorous data on the various aspects of the peer review system.
Study of evolution for 3D structured surface with nano-balls and walls-like features with thickness variation for WO3 thin films made by spray deposition
Dialogues about the practice of science
Integrating radiological and clinical data for clinically significant prostate cancer detection with machine learning techniques
Discourse on measurement
Measurement literacy is required for strong scientific reasoning, effective experimental design, conceptual and empirical validation of measurement quantities, and the intelligible interpretation of error in theory construction. This discourse examines how issues in measurement are posed and resolved and addresses potential misunderstandings. Examples drawn from across the sciences are used to show that measurement literacy promotes the goals of scientific discourse and provides the necessary foundation for carving out perspectives and carrying out interventions in science.