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Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor–stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases. Mechanisms regulating the formation of pre-metastatic niches remain poorly understood. Here, the authors show that ITGBL1-containing extracellular vesicles derived from primary colorectal cancer cells activate the production of inflammatory cytokines by resident fibroblasts in distant organs, promoting metastatic cancer growth.

School-based interventions are crucial for enhancing physical activity (PA) and sport participation among children and adolescents. While numerous studies have examined these interventions, their efficacy in fostering motivation requires synthesis. This umbrella review evaluated systematic reviews and meta-analyses on school-based interventions targeting students' motivation for PA and sport. Comprehensive literature searches were conducted in Web of Science, ERIC, Scopus, PubMed, and SPORTDiscus for reviews published between 2010 and 2024. Twenty reviews met the inclusion criteria. The primary outcomes were motivational constructs (e.g., intrinsic motivation, basic psychological needs), and secondary outcomes were PA levels and sport participation. Findings revealed that interventions grounded in Self-Determination Theory (SDT), particularly the Sport Education Model (SEM), were most effective in fostering intrinsic motivation, autonomy, and competence. Teacher training in autonomy-supportive strategies was a critical component for success. However, evidence on the long-term impact of these interventions on sustained PA behavior remains limited. This synthesis provides robust evidence for educators and policymakers, highlighting the importance of theory-driven, student-centered approaches in school-based PA and sport programs.

The COVID-19 pandemic gave rise to countless user-facing mobile apps to help fight the pandemic (\"COVID-19 mitigation apps\"). These apps have been at the center of data privacy discussions because they collect, use, and even retain sensitive personal data from their users (eg, medical records and location data). The US government ended its COVID-19 emergency declaration in May 2023, marking a unique time to comprehensively investigate how data privacy impacted people's acceptance of various COVID-19 mitigation apps deployed throughout the pandemic. This research aims to provide insights into health data privacy regarding COVID-19 mitigation apps and policy recommendations for future deployment of public health mobile apps through the lens of data privacy. This research explores people's contextual acceptance of different types of COVID-19 mitigation apps by applying the privacy framework of contextual integrity. Specifically, this research seeks to identify the factors that impact people's acceptance of data sharing and data retention practices in various social contexts. A mixed methods web-based survey study was conducted by recruiting a simple US representative sample (N=674) on Prolific in February 2023. The survey includes a total of 60 vignette scenarios representing realistic social contexts that COVID-19 mitigation apps could be used. Each survey respondent answered questions about their acceptance of 10 randomly selected scenarios. Three contextual integrity parameters (attribute, recipient, and transmission principle) and respondents' basic demographics are controlled as independent variables. Regression analysis was performed to determine the factors impacting people's acceptance of initial data sharing and data retention practices via these apps. Qualitative data from the survey were analyzed to support the statistical results. Many contextual integrity parameter values, pairwise combinations of contextual integrity parameter values, and some demographic features of respondents have a significant impact on their acceptance of using COVID-19 mitigation apps in various social contexts. Respondents' acceptance of data retention practices diverged from their acceptance of initial data sharing practices in some scenarios. This study showed that people's acceptance of using various COVID-19 mitigation apps depends on specific social contexts, including the type of data (attribute), the recipients of the data (recipient), and the purpose of data use (transmission principle). Such acceptance may differ between the initial data sharing and data retention practices, even in the same context. Study findings generated rich implications for future pandemic mitigation apps and the broader public health mobile apps regarding data privacy and deployment considerations.

Background Nitrogen (N) is a crucial element for increasing photosynthesis and crop yields. The study aims to evaluate the photosynthetic regulation and yield formation mechanisms of different nodulating peanut varieties with N fertilizer application. Method The present work explored the effect of N fertilizer application rates (N0, N45, N105, and N165) on the photosynthetic characteristics, chlorophyll fluorescence characteristics, dry matter, N accumulation, and yield of four peanut varieties. Results The results showed that N application increased the photosynthetic capacity, dry matter, N accumulation, and yield of peanuts. The measurement of chlorophyll a fluorescence revealed that the K-phase, J-phase, and I-phase from the OJIP curve decreased under N105 treatment compared with N0, and W OI , ET 0 /CS M , RE 0 /CS M , ET 0 /RC, RE 0 /RC, φPo, φEo, φRo, and Ψ0 increased, whereas V J , V I , W K , ABS/RC, TR 0 /RC, DI 0 /RC, and φDo decreased. Meanwhile, the photosystem activity and electron transfer efficiency of nodulating peanut varieties decreased with an increase in N (N165). However, the photosynthetic capacity and yield of the non-nodulating peanut variety, which highly depended on N fertilizer, increased with an increase in N. Conclusion Optimized N application (N105) increased the activity of the photosystem II (PSII) reaction center, improved the electron and energy transfer performance in the photosynthetic electron transport chain, and reduced the energy dissipation of leaves in nodulating peanut varieties, which is conducive to improving the yield. Nevertheless, high N (N165) had a positive effect on the photosystem and yield of non-nodulating peanut. The results provide highly valuable guidance for optimizing peanut N management and cultivation measures.

The Cahn–Hilliard equation is a classic model of phase separation in binary mixtures that exhibits spontaneous coarsening of the phases. We study the Cahn–Hilliard equation with an imposed advection term in order to model the stirring and eventual mixing of the phases. The main result is that if the imposed advection is sufficiently mixing, then no phase separation occurs, and the solution instead converges exponentially to a homogeneous mixed state. The mixing effectiveness of the imposed drift is quantified in terms of the dissipation time of the associated advection–hyperdiffusion equation, and we produce examples of velocity fields with a small dissipation time. We also study the relationship between this quantity and the dissipation time of the standard advection–diffusion equation.

Xinjiang is the largest arid and saline agricultural region in China. The common irrigation methods in this area are traditional flood irrigation and drip irrigation. In this study, we investigated the effects of these two irrigation methods on the fungal diversity, community structures, and functions in alfalfa rhizosphere soil as well as the associated environmental factors in northern Tianshan Mountain (Xinjiang, China). Soil enzyme activities (urease and neutral phosphatase) were significantly higher in the drip-irrigated alfalfa rhizosphere soil than in the flood-irrigated alfalfa rhizosphere soil, whereas the fungal alpha diversity in the drip-irrigated alfalfa rhizosphere soil was significantly lower than that in the flood-irrigated alfalfa rhizosphere soil. Six dominant fungal phyla were identified (>0.1%), with Ascomycota being the most abundant in all soils, followed by Basidiomycota (5.47%), Mortierellomycota (1.07%), Glomeromycota (0.55%), Rozellomycota (0.27%), and Chytridiomycota (0.14%). Ascomycota and Glomeromycota species were significantly less abundant in drip-irrigated alfalfa rhizosphere soil than in flood-irrigated alfalfa rhizosphere soil. A LEFSe analysis identified Cladosporiaceae (20.8%) species as the most abundant marker fungi in drip-irrigated alfalfa rhizosphere soil. Of the 13 fungal functional groups identified on the basis of the functional annotation using the FUNGuild database, Ectomycorrhizal (22.29%) was the primary functional group. Compared with flood irrigation, drip irrigation significantly decreased the relative abundance of Ectomycorrhizal and Arbuscular_Mycorrhizal, while increasing the relative abundance of Plant_Pathogen, although not significantly (P = 0.19). Available potassium was revealed to be the main environmental factor influencing soil enzyme activities, fungal alpha diversity, fungal community structures, and fungal functions in response to the different irrigation methods. In conclusion, drip irrigation may be more appropriate than flood irrigation in the Tianshan dryland agricultural area for enhancing soil enzyme activities, but it may also increase the abundance of plant pathogenic fungi in the soil.

[This corrects the article DOI: 10.1371/journal.pone.0268175.].

CRISPR-Cas systems revolutionize life science. Metagenomes contain millions of unknown Cas proteins. Traditional mining relies on protein sequence alignments. In this work, we employ an evolutionary scale language model (ESM) to learn the information beyond sequences. Trained with CRISPR-Cas data, ESM accurately identifies Cas proteins without alignment. Limited experimental data restricts feature prediction, but integrating with machine learning enables trans -cleavage activity prediction of uncharacterized Cas12a. We discover 7 undocumented Cas12a subtypes with unique CRISPR loci. Structural analyses reveal 8 subtypes of Cas1, Cas2, and Cas4. Cas12a subtypes display distinct 3D-folds. CryoEM analyses unveil unique RNA interactions with the uncharacterized Cas12a. These proteins show distinct double-strand and single-strand DNA cleavage preferences and broad PAM recognition. Finally, we establish a specific detection strategy for the oncogene SNP without traditional Cas12a PAM. This study highlights the potential of language models in exploring undocumented Cas protein function via gene cluster classification. Novel Cas protein discovery is vital in CRISPR-Cas technology. Here, authors develop AIL-Scan, an AI-assisted Cas detection strategy using the ESM model, and discover seven unreported Cas12a subtypes with distinct DNA cleavage and PAM recognition, enabling SNP detection and precise gene editing.

BackgroundA challenge of laparoscopic surgery is learning how to interpret the indirect view of the operative field. Acquiring professional vision—understanding what to see and which information to attend to, is thereby an essential part of laparoscopic training and one in which trainers exert great effort to convey. We designed a virtual pointer (VP) that enables experts to point or draw free-hand sketches over an intraoperative laparoscopic video for a novice to see. This study aimed to investigate the efficacy of the virtual pointer in guiding novices’ gaze patterns.MethodsWe conducted a counter-balanced, within-subject trial to compare the novices’ gaze behaviors in laparoscopic training with the virtual pointer compared to a standard training condition, i.e., verbal instruction with un-mediated gestures. In the study, seven trainees performed four simulated laparoscopic tasks guided by an experienced surgeon as the trainer. A Tobii Pro X3-120 eye-tracker was used to capture the trainees’ eye movements. The measures include fixation rate, i.e., the frequency of trainees’ fixations, saccade amplitude, and fixation concentration, i.e., the closeness of trainees’ fixations.ResultsNo significant difference in fixation rate or saccade amplitude was found between the virtual pointer condition and the standard condition. In the virtual pointer condition, trainees’ fixations were more concentrated (p = 0.039) and longer fixations were more clustered, compared to the Standard condition (p = 0.008).ConclusionsThe virtual pointer effectively improved surgical trainees’ in-the-moment gaze focus during the laparoscopic training by reducing their gaze dispersion and concentrating their attention on the anatomical target. These results suggest that technologies which support gaze training should be expert-driven and intraoperative to efficiently modify novices’ gaze behaviors.

Background Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi are common enteric pathogens in humans and animals. Data on the transmission of these pathogens are scarce from Guangdong, China, which has a subtropical monsoon climate and is the epicenter for many emerging infectious diseases. This study was conducted to better understand the prevalence and identity of the three pathogens in pre-weaned dairy calves in Guangdong. Methods The occurrence and genetic identity of three pathogens were analyzed by polymerase chain reaction. PCR-positive products were sequenced to determine the species and genotypes. A Chi-square test was used to compare the prevalence of pathogens among sampling dates, age groups, or clinical signs. Results The detection rates of Cryptosporidium spp., G. duodenalis and E. bieneusi were 24.0% (93/388), 74.2% (288/388) and 15.7% (61/388), respectively. Three Cryptosporidium species were detected, including C. bovis ( n = 73), C. parvum ( n = 12) and C. ryanae ( n = 7); one animal had concurrence of C. bovis and C. parvum . C. parvum was the dominant species during the first two weeks of life, whereas C. bovis and C. ryanae were mostly seen at 3–9 weeks of age. Sequence analysis identified the C. parvum as subtype IIdA19G1. Assemblage E ( n = 282), assemblage A ( n = 1), and concurrence of A and E ( n = 5) were identified among G. duodenalis -positive animals using multilocus genotyping (MLG). Altogether, 15, 10 and 17 subtypes of assemblage E were observed at the bg , gdh and tpi loci, respectively, forming 49 assemblage E MLGs. The highest detection rate of G. duodenalis was found in winter. Sequence analysis identified genotypes J ( n = 57), D ( n = 3) and one concurrence of J and D among E. bieneusi- positive animals. The detection rate of E. bieneusi was significantly higher in spring (38.0%; 41/108) than in summer (7.2%; 8/111) and winter (7.1%; 12/169). Conclusions These results indicate a common occurrence of C. parvum subtype IIdA19G1, G. duodenalis assemblage E, and E. bieneusi genotype J in pre-weaned dairy calves in Guangdong. More studies are needed to understand the unique genetic characteristics and zoonotic potential of the three enteric pathogens in the province.