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Daily briefing: Brain–immune crosstalk worsens the damage of heart attacks
This AI has chemical expertise — and helps synthesize 35 new compounds
Effects of silybin on triptorelin-induced bone metabolic abnormalities in prostate cancer revealed based on TMT-based proteomics
Aims The aim of this study was to investigate the mechanism of action of SB on TRP-induced abnormalities of bone metabolism in LNCaP cells. Methods The effects of different concentrations of SB and TRP alone and in combination on the proliferation of LNCaP cells were examined by CCK-8 assay, and the half maximal inhibitory concentration were screened for the subsequent experiments. Transwell migration and invasion assays were used to further investigate the effects of SB and TRP alone and in combination on the migration and invasion ability of LNCaP cells. Based on Tandem Mass Tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, the differentially expressed proteins (DEPs) of LNCaP cells in the control group, SB group, TRP group and combination group were quantified. Bioinformatics technology was used to analyze the DEPs of LNCaP cells in each group. At last, the achieved key targets were verified by western blot. Results The inhibitory effects of different concentrations of SB and TRP alone and in combination on the proliferation, migration and invasion of LNCaP cells showed both time-dependent and concentration-dependent effects, and the inhibitory effects of the combination of drugs on LNCaP cells were more significant. The proteomics results showed that a total of 153 DEPs were identified in the SB group and the control group, 100 DEPs were identified in the TRP group and the control group, and 524 DEPs were identified in the combination group and the control group. Bioinformatics analysis showed that a higher number of DEPs were enriched in the IL-17 signaling pathway in the SB and combined treatment groups compared to the control group. These findings suggest a potential role of SB and the combined treatment in modulating the IL-17 signaling pathway. In contrast, the same DEPs were found to be enriched in both the Circadian entrainment and Apelin signaling pathways in the TRP versus control and combined treatment versus control comparisons. Conclusions SB may regulate TRP-induced bone metabolism abnormalities in LNCaP cells through the IL-17 signaling pathway as well as five DEPs: p-ERK2, RELA, HSP90B1, GNAI1and GNAI3.
Multiple contexts and frequencies aggregation network for deepfake detection
Deepfake detection faces increasing challenges since the fast growth of generative models in developing massive and diverse Deepfake technologies. Recent advances rely on introducing heuristic features from spatial or frequency domains rather than modeling general forgery features within backbones. To address this issue, we turn to the backbone design with two intuitive priors from spatial and frequency detectors, i.e., learning robust spatial attributes and frequency distributions that are discriminative for real and fake samples. To this end, we propose an efficient network for face forgery detection named MkfaNet, which consists of two core modules. For spatial contexts, we design a Multi-Kernel Aggregator that adaptively selects organ features extracted by multiple convolutions for modeling subtle facial differences between real and fake faces. For the frequency components, we propose a Multi-Frequency Aggregator to process different bands of frequency components by adaptively reweighing high-frequency and low-frequency features. Comprehensive experiments on seven popular Deepfake detection benchmarks demonstrate that MkfaNet achieves an AUC of 0.9591 in within-domain evaluations and 0.7963 in cross-domain evaluations, outperforming several state-of-the-art methods while maintaining high computational efficiency. Results confirm that MkfaNet is effective and efficient in detecting forgery, offering enhanced robustness against diverse Deepfake manipulations. Our code is available at https://github.com/GGshawn/MkfaNet .
Critical social-media posts linked to retractions of scientific papers
Producer perspectives on the constraints to aquaculture development in the US Great Lakes region
Despite significant federal interest and the vast resource potential of the region, the land-based food fish aquaculture industry remains relatively stagnant in the U.S. Great Lakes states. In this study, we use the Theory of Planned Behavior to explore the factors influencing aquaculture producers’ intentions to expand or diversify their operations. We conducted semi-structured interviews with 34 food fish producers across the eight Great Lakes states. Our thematic analysis revealed that while most producers expressed positive intentions to grow, these intentions were often constrained by low perceived behavioral control. Major barriers included limited access to capital, regulatory complexity, inadequate institutional support, and challenges in public perception. Attitudes toward expansion were shaped by both mission-driven motivations, such as supporting local food systems, and pragmatic concerns about cost, risk, and labor. Subjective norms were overwhelmingly favorable, reflecting a strong sense of community and peer support within the industry. Past experiences with expansion further influenced current intentions, as well, reinforcing cautious, incremental growth strategies. These findings suggest that policy reforms and structural support, particularly in financing, regulation, and outreach, are critical to unlocking the growth potential of aquaculture in the Great Lakes region. By centering the voices of producers, this study provides actionable insight into the systemic barriers that must be addressed for meaningful industry advancement.
The neuromuscular system of Chironomus vitellinus (Diptera: Chironomidae)
Chironomids are important laboratory model organisms used to assess toxicity in freshwater environments. Cell and tissue features are not commonly used as chironomid markers to detect toxicity, but they could be extremely helpful in identifying acute and chronic effects of pollutants. The nervous system is an excellent cellular candidate since it is reactive to toxic substances. However, a detailed description of the chironomid nervous system is required prior to considering it as a candidate for a cellular toxicity marker. The present study describes the central ganglia, nerves, axons, and the neuromuscular system of Chironomus vitellinus (Freeman, 1961) to facilitate its use as a model organism in environmental studies. We find that the structure of the C. vitellinus central nervous system is identical to that observed in other Chironomus larvae. We then focused our study on the first abdominal segment and labeled the 31 hemi-segmental muscles according to a nomenclature based on their position and orientation. We also characterized their innervation and assigned the nerves a nomenclature based on their terminals’ location in the muscle tissue. Finally, we investigated the neuromuscular junctions (NMJs) throughout this segment and defined four types of NMJs illustrating their great variability in size and shape. We selected a model NMJ, VEL 2, and quantified its mean bouton number and muscle size. Together with documenting a neurobiological system that could be informative to insects’ comparative biology, these results could help establish the Chironomus NMJ as an aquatic toxicity marker.
Protocol for investigating the warping of spatial experience across the blind spot to contrast predictions of the Integrated Information Theory and Predictive Processing accounts of consciousness
We investigate the subjective experience of space around the visual blind spot area, the cortical representation of which is missing feedforward connectivity from one eye. We performed these experiments as part of an adversarial collaboration to test contrasting theories of consciousness; Integrated Information Theory (IIT), Predictive Processing Active Inference (AI), and Predictive Processing Neurorepresentationalism (NREP) accounts. According to the Integrated Information Theory of consciousness, non-activatable retinotopic cortical regions, such as the blind spot region for the ipsilateral eye, create a different cause-effect structure and therefore should contribute differently to the perceived quality of space of activatable retinotopic regions. The two Predictive Processing accounts, in contrast, posit that internal models will accommodate structural deviations around the blind spot based on the available sensory evidence (particulars of this accommodation differ between the two accounts). We present a series of paradigms in which participants evaluate distances and areas that either include the blind spot or not (without stimulating it directly), as well as illusory motion that is either adjacent to the blind spot or not. We model psychometric functions relating perceived and objective space. These models vary in terms of bias and precision according to the experimental conditions (blind spot involved vs. not involved, ipsilateral vs. contralateral eye), making it possible to quantify the potential disruption of subjective spatial extendedness induced by the blind spot. We present simulated results for each experiment corresponding to the predictions of each account and conclude by discussing challenges and plans for dissemination.
The surprisingly big health benefits of just a little exercise
Correction: Reaching those at risk: Active case detection of leprosy and contact tracing at Kokosa, a hot spot district in Ethiopia
Low-power integrated optical amplification through second-harmonic resonance
Exploring the role of meaning in non-Māori speakers’ ‘proto-lexicon’
Previous work has demonstrated that New Zealanders who do not speak Māori but are regularly exposed to the language develop implicit knowledge of it. The core of this knowledge, it has been argued, is the ‘proto-lexicon’—a set of stored word-forms, without associated meaning, which yields subsequent Māori phonotactic and morphological knowledge. Previous research shows that having a proto-lexicon gives learners a head start in learning Māori word meanings in formal education. We investigate experimentally whether the proto-lexicon confers an advantage for attaching meanings to words. In Experiment 1, non-Māori-speaking New Zealanders were tested on their ability to identify meanings of Māori words in a forced-choice definition task, and they did this relatively well. Then, words with low accuracy were selected for Experiment 2, where non-Māori-speaking New Zealanders and non-New Zealanders were asked to learn meanings for Māori words and nonwords. New Zealanders performed better, indicating that familiarity with Māori word shapes confers an advantage. However, they showed no greater advantage for real words over nonwords. If these words are definitely in the proto-lexicon, then this would suggest that knowledge of individual word-forms does not, in fact, confer an advantage. In Experiment 3, we therefore explore whether the words in Experiment 2 are actually robustly in the participants’ proto-lexicon, by running a word identification task with the same participants. These words were not robustly distinguished from nonwords. By selecting words for their lack of semantic knowledge, we also inadvertently selected words that do not appear to be in the proto-lexicon. Together, our results indicate that different levels of semantic knowledge exist for different words, even when we consider only words that cannot confidently be said to be in a full lexicon. The results suggest that the claim of previous studies that the proto-lexicon is ‘without semantics’ may be oversimplified.
Six highlights from lung-health research
A randomised pilot trial of perioperative propranolol combined with celecoxib versus standard of care in stage III melanoma: The ProCel study protocol
In cutaneous melanoma patients, the presence of lymph node or in transit metastasis can be associated with poor survival. Adjuvant treatment with BRAF-MEK inhibitors or immunotherapy is costly and can cause side effects, so there remains a need for safe and inexpensive adjuvant treatments. Beta-blockers can control the pro-inflammatory stress response associated with surgery, and their use may attenuate the risk of melanoma progression. COX-2 may promote melanoma progression by increasing prostaglandin production, so COX-2 inhibition may be beneficial. This randomised controlled trial will be conducted at Royal Prince Alfred Hospital and Melanoma Institute Australia, and will include forty participants aged 18–85 years with nodal and/or in transit metastatic melanoma. Participants will be randomly allocated to receive propranolol combined with celecoxib perioperatively, or surgical management only. The primary objective is to determine the effect of propranolol combined with celecoxib on intra-tumoral immune cell populations and tumour proliferative markers, assessed using imaging mass cytometry. The secondary objectives are to evaluate the safety and tolerability of the combination, as well as its effects on: 1) serum inflammatory markers; 2) quality of life; and 3) recurrence/progression rates. The trial is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12624001353583). Protocol version 1 was submitted to PLOS One in February 2025. The trial is supported by Sydney Cancer Partners with funding from Cancer Institute NSW (Grant ID 2021/CBG0002). The sponsors are Sydney Local Health District and Melanoma Institute Australia.
Association analysis of Mycoplasma pneumoniae 23S rRNA gene mutation with refractory Mycoplasma pneumoniae pneumonia in children
Objective This study investigates the current status of macrolide resistance in Mycoplasma pneumoniae (MP) and analyzes the relationship between mutations at the 23S rRNA A2063G and/or A2064G loci and refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods A retrospective analysis was conducted on 205 hospitalized children diagnosed with MPP at the Third Ward of the department of paediatrics, Jingzhou Central Hospital, from October 2023 to October 2024. Diagnosis was confirmed by pharyngeal MP nucleic acid testing and MP antibody titers ( MP -Ab ≥ 1:160). All patients were screened for macrolide-resistant gene mutations (A2063G/A2064G). Patients were categorized based on the presence of macrolide-resistant gene mutations and RMPP diagnosis. Clinical features, laboratory results, and treatments were compared between groups. Multiple logistic regression was used to identify independent risk factors for RMPP. Results Among 205 children with MPP, 157 (76.6%) harbored A2063G/A2064G mutations. Of the 77 children with RMPP, 71 (92.2%) carried these mutations, showing a significant association ( P < 0.05). Compared to the non-resistant group, children with resistant mutations had prolonged fever duration, delayed defervescence after azithromycin, and required more bronchoscopic alveolar lavage ( P < 0.05). The RMPP group exhibited more severe symptoms, longer fever and hospital stays, higher inflammatory markers (CRP, LDH, D-dimer, ESR, PCT; P < 0.001), and more frequent pulmonary consolidation, pleural effusion, plastic bronchitis, and extrapulmonary involvement. Multivariate analysis identified macrolide-resistant mutations, fever duration, and D-dimer level as independent risk factors for RMPP. Conclusion The widespread macrolide resistance in M. pneumoniae (76.6% in this cohort) was associated with point mutations at the A2063G and/or A2064G loci in the 23S rRNA gene. The development of RMPP is linked to macrolide-resistant mutations, duration of fever and D-dimer levels. D-dimer emerged as the most predictive risk factor.
Methylation-specific, universal, and highly sensitive identification of ctDNA in prostate cancer by multiplex droplet digital PCR
Objective Liquid biopsy for detection of circulating tumor DNA (ctDNA) offers a promising, non-invasive strategy for real-time monitoring of cancer. We aimed to develop a universal and sensitive one-tube droplet digital PCR (ddPCR) multiplex assay able to detect ctDNA in plasma from metastatic prostate cancer (PCa) patients. Methods Publicly available array data are applied to identify methylation signatures specific to both normal and cancerous prostate tissue. The assay is based on the highly sensitive ddPCR technology, and tissue and plasma samples are analyzed using the QX600 ddPCR multiplexing platform from BioRad. Results We identified three novel genomic regions, ACTRT2 , EVX1, and HOXD13 , containing CpG-methylation signatures specific to normal and cancerous prostate tissue. We successfully targeted the three biomarkers in a single-tube methylation-specific multiplex ddPCR (mm-ddPCR) assay along with two previously reported PCa-specific hypermethylated CpG biomarkers, DOCK2 and HAPLN3 , and the ALB reference gene. The mm-ddPCR assay consistently detected ACTRT2 , EVX1, and HOXD13 across all samples originating from prostate-derived tissue. In contrast, the HAPLN3 and DOCK2 biomarkers were predominantly detected in PCa tissue. We also demonstrate that the five ctDNA biomarkers can be detected in plasma samples from metastatic castration-resistant PCa (mCRPC) patients with a 95% CI (85%, 100%) using the mm-ddPCR assay. Conclusion This work demonstrates that the mm-ddPCR assay offers a simple, fast, cost-effective, sensitive, and universal tool for the detection of ctDNA biomarkers in plasma from mCRPC patients. Further studies are required to explore its potential for PCa risk stratification and treatment guidance.
Exposome studies can improve lung health
Cooperative management practices how to influence the productive performance outcomes: Based on the analysis of China’s guangxi 94 farmers professional cooperatives
Objectives Research on the key factors that influence the productive outcomes of farmer professional cooperatives (FPCs) is essential to develop targeted management approaches that promote sustainable growth. This study investigates how cooperative management practices influence productive performance outcomes through an analysis of 94 FPCs in Guangxi, China. Methods Employing cluster analysis, Ordinary Least Squares (OLS) regression, and mediation effect tests, the research categorizes management practices into five typologies (Comprehensive High-Efficiency, Collaboration-Deficient, Monitoring-Deficient, Planning-Deficient, Holistically Deficient) and links these to five distinct performance outcomes (Profitable Outreach High-Efficiency, Loss-Making Insular Low-Efficiency, etc.). Results Results reveal that management practices critically determine performance outcomes types. Regression analysis highlights planning practices significantly influenced profitability, while investment practices positively impacted employment generation. Internal governance practices were strongly associated with institutional compliance, and external collaboration practices had a significant effect on technology dissemination and community reputation.Monitoring practices, while not directly impacting performance outcomes, were found to enhance them through management practices and mechanisms. Key behavioral indicators—revenue planning, capital investment, staff capacity, and role optimization—emerge as primary levers for performance optimization. Conclusion This study underscore the critical role of management practices in shaping the performance of FPCs, suggestions include emphasizing efficient planning, investing in personnel training, and establishing dynamic adjustment mechanisms to ensure sustainable development. These findings provide empirical insights for optimizing rural collective governance and informing evidence-based policy interventions in developing agricultural economies.