Light controls mesophyll-specific post-transcriptional splicing of photoregulatory genes by AtPRMT5.

Light plays a central role in plant growth and development, providing an energy source and governing various aspects of plant morphology. Previous study showed that many polyadenylated full-length RNA molecules within the nucleus contain unspliced introns (post-transcriptionally spliced introns, PTS introns), which may play a role in rapidly responding to changes in environmental signals. However, the mechanism underlying post-transcriptional regulation during initial light exposure of young, etiolated seedlings remains elusive. In this study, we used FLEP-seq2, a Nanopore-based sequencing technique, to analyze nuclear RNAs in Arabidopsis (Arabidopsis thaliana) seedlings under different light conditions and found numerous light-responsive PTS introns. We also used single-nucleus RNA sequencing (snRNA-seq) to profile transcripts in single nucleus and investigate the distribution of light-responsive PTS introns across distinct cell types. We established that light-induced PTS introns are predominant in mesophyll cells during seedling de-etiolation following exposure of etiolated seedlings to light. We further demonstrated the involvement of the splicing-related factor A. thaliana PROTEIN ARGININE METHYLTRANSFERASE 5 (AtPRMT5), working in concert with the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a critical repressor of light signaling pathways. We showed that these two proteins orchestrate light-induced PTS events in mesophyll cells and facilitate chloroplast development, photosynthesis, and morphogenesis in response to ever-changing light conditions. These findings provide crucial insights into the intricate mechanisms underlying plant acclimation to light at the cell-type level.

Self-Assembly of Strain-Adaptable Surface-Enhanced Raman Scattering Substrate on Polydimethylsiloxane Nanowrinkles.

Flexible surface-enhanced Raman scattering (SERS) substrates adaptable to strains enable effective sampling from irregular surfaces, but the preparation of highly stable and sensitive flexible SERS substrates is still challenging. This paper reports a method to fabricate a high-performance strain-adaptable SERS substrate by self-assembly of Au nanoparticles (AuNPs) on polydimethylsiloxane (PDMS) nanowrinkles. Nanowrinkles are created on prestrained PDMS slabs by plasma-induced oxidation followed by the release of the prestrain, and self-assembled AuNPs are transferred onto the nanowrinkles to construct the high-performance SERS substrate. The results show that the nanowrinkled structure can improve the surface roughness and enhance the SERS signals by ∼4 times compared to that of the SERS substrate prepared on flat PDMS substrates. The proposed SERS substrate also shows good adaptability to dynamic bending up to ∼|0.4| 1/cm with excellent testing reproducibility. Phenolic pollutants, including aniline and catechol, were quantitatively tested by the SERS substrate. The self-assembled flexible SERS substrate proposed here provides a powerful tool for chemical analysis in the fields of environmental monitoring and food safety inspection.

Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of ß-catenin.

BACKGROUND: Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive. METHODS: The expression and subcellular localization of CDH4 were determined through immunohistochemistry, immunofluorescence, and western blot analyses. The impact of CDH4 on cell migration, invasion, angiogenesis, and metastasis was assessed using transwell assays, tube formation assays, and animal experiments. Immunoprecipitation assay and mass spectrometry were employed to examine protein associations. The influence of CDH4 on the subcellular expression of ß-catenin and active ß-catenin was investigated via western blotting and immunofluorescence. Protein stability and ubiquitination assay were employed to verify the impact of CDH4 on ß-catenin degradation. Rescue experiments were performed to ensure the significance of CDH4 in regulating nuclear ß-catenin signaling. RESULTS: CDH4 was found to be significantly overexpressed in PTC tissues and predominantly localized in the cytoplasm. Furthermore, the overexpression of CDH4 in tumor tissues is associated with lymph node metastasis in PTC patients. Cytosolic CDH4 promoted the migration, invasion, and lung metastasis of PTC cells and stimulated the angiogenesis and tumorigenesis of PTC; however, this effect could be reversed by Tegavivint, an antagonist of ß-catenin. Mechanistically, cytosolic CDH4 disrupted the interaction between ß-catenin and ß-TrCP1, consequently impeding the ubiquitination process of ß-catenin and activating the nuclear ß-catenin signaling. CONCLUSIONS: CDH4 induces PTC angiogenesis and metastasis via the inhibition of ß-TrCP1-dependent ubiquitination of ß-Catenin.

Biomimetic NO Scavenging Hyaluronic Acid Nanoparticles Enable Targeted Delivery of MTX and Integrated Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage, and bone damage. In the RA microenvironment, RA-involved cells, overproduced nitric oxide (NO), and pro-inflammatory cytokines are highly interplayed and mutually reinforced, which form a vicious circle and play crucial roles in the formation and progression of RA. To comprehensively break the vicious circle and obtain the maximum benefits, we have developed neutrophil membrane-camouflaged NO scavenging nanoparticles based on an NO-responsive hyaluronic acid derivative for delivery of MTX. These multifunctional nanoparticles (NNO-NPs/MTX), by inheriting the membrane functions of the source cells, possess prolonged circulation and specific localization at the inflamed sites when administrated in the body. Remarkably, NNO-NPs/MTX can neutralize the pro-inflammatory cytokines via the outer membrane receptors, scavenge NO, and be responsively disassociated to release MTX for RA-involved cell regulation and HA for lubrication in the RA sites. In a collagen-induced arthritis mouse model, NNO-NPs/MTX exhibits a significant anti-inflammation effect and effectively alleviates the characteristic RA symptoms such as synovial hyperplasia and cartilage destruction, realizing the synergistic and boosted therapeutic outcome against intractable RA. Thus, NNO-NPs/MTX provides a promising and potent platform to integrately treat RA.

Investigating the spatial distribution of volatile organic compounds in aircraft cabins from various emission sources.

Volatile organic compounds (VOCs) significantly affect the air quality in aircraft cabins, consequently affecting passenger health and comfort. Although VOC emission sources and their contributions have been studied extensively, the distribution characteristics of VOCs originating from diverse sources within cabins have received limited attention, and the correlation between VOC sources and concentrations in passenger breathing zones remains largely unexplored. To fill this knowledge gap, the concentration field of VOCs was investigated using a computational fluid dynamics model, and the results were experimentally validated in a typical single-aisle aircraft cabin with seven seat rows. The diffusion characteristics of different VOCs emitted by four typical sources in aircraft cabins (floors, human surfaces, seats, and respiratory sources) were analyzed and compared. The distribution of VOCs emitted by different sources was nonuniform and could be classified into two distinct categories. When the emission intensities of all sources were equal, the average concentration of VOCs emitted from the floor source were considerably lower in the passenger breathing zone (4.01 µg/m³) than those emitted from the human surface, seat, and respiratory sources, which exhibited approximately equal concentrations (6.82, 6.90, and 7.29 µg/m³, respectively). The analysis highlighted that the simplified lumped-parameter method could not accurately estimate the exposure concentrations within an aircraft cabin. To address this issue, we propose a correction method based on the emission intensity of each VOC source. This study provides critical insights into the diffusion characteristics of VOCs within aircraft cabins and VOC emissions from various sources.

Rapid prediction for the transient dispersion of leaked airborne pollutant in urban environment based on graph neural networks.

Rapidly predicting airborne pollutant dispersion in urban is vital for ventilation design and evacuation planning. Computational fluid dynamics (CFD) simulations are commonly used to provide accurate predictions, but the computational cost is too high. Although graph neural networks (GNNs) provide fast predictions of flow fields by manipulating unstructured mesh on GPU, they suffer from high memory usage and accuracy decreases when applied to large-scale urban scenes. Moreover, it is difficult for GNNs to learn the coupled relationship between wind field and pollutant concentration field. We propose a multi-objective GNN model as CFD surrogate to rapidly predict the transient dispersion of airborne pollutant under the influence of complex wind field patterns in urban environment. Based on random urban layouts generated by a 2D bin packing algorithm, we employ a validated CFD model to construct a sample dataset of wind fields and concentration fields. We leverage graph pooling and multi-scale feature fusion to improve prediction accuracy, and subgraph partitioning of both wind field and concentration field to reduce GPU memory usage. The results show that our GNN model at its best runs 1-2 orders of magnitude faster than CFD simulation with accuracy evaluation metrics R2=0.92, and achieves 70 % GPU memory reduction.

Air disinfection performance of upper-room ultraviolet germicidal irradiation (UR-UVGI) system in a multi-compartment dental clinic.

Multi-compartment dental clinics present significant airborne cross-infection risks. Upper-room ultraviolet germicidal irradiation (UR-UVGI) system have shown promise in preventing airborne pathogens, but its available application data are insufficient in multi-compartment dental clinics. Therefore, the UR-UVGI system's performance in a multi-compartment dental clinic was comprehensively evaluated in this study. The accuracy of the turbulence and drift flux models was verified by experimental data from ultrasonic scaling. The effects of the ventilation rate, irradiation zone volume, and irradiation flux on UR-UVGI performance were analyzed using computational fluid dynamics coupled with a UV inactivation model. Different patient numbers were considered. The results showed that UR-UVGI significantly reduced virus concentrations and outperformed increased ventilation rates alone. At a ventilation rate of six air changes per hour (ACH), UR-UVGI with an irradiation zone volume of 20% and irradiation flux of 5 µW/cm2 achieved a 70.44% average virus reduction in the whole room (WR), outperforming the impact of doubling the ventilation rate from 6 to 12 ACH without UR-UVGI. The highest disinfection efficiency of UR-UVGI decreased for WRs with more patients. The compartment treating patients exhibited significantly lower disinfection efficiency than others. Moreover, optimal UR-UVGI performance occurs at lower ventilation rates, achieving over 80% virus disinfection in WR. Additionally, exceeding an irradiation zone volume of 20% or an irradiation flux of 5 µW/cm2 notably reduces the improvement rates of UR-UVGI performance. These findings provide a scientific reference for strategically applying UR-UVGI in multi-compartment dental clinics.

Susceptibility and exposure risk to airborne aerosols in intra-urban microclimate: Evidence from subway system of mega-cities.

The health of intra-urban population in modern megacities relies largely on the biosafety within the microclimate of subway system, which can be vulnerable to epidemical challenges brought by virus-laden bioaerosols under varying factors. The literature has yet to address the association between the exposure risks to infectious pathogens and the dynamic changes of boundary conditions in this densely populated microclimate. This study aims at characterizing the bioaerosol dispersion, evaluating the exposure risks under various train arrival scenarios and hazard releasing positions in a real-world double-decker subway station. The results provide the evidence for the dominating airflow pattern, bioaerosols dispersion behaviors, exposure risk, and evacuation guidance in a representative microclimate of mega-cities. The tunnel effects of nearby pedestrian passageways are found to be dominating the airflow pattern, leading to the discharging of airborne bioaerosols. At least 60 % increasing of discharging rate of bioaerosol is attributed to the arrival of one or two trains at the subway platform compared with the scenario with no train arriving. Results from risk assessment with improved Wells-Riley model estimate 57.62 % of maximum infectivity probability with no train arriving. Large areas near the source at the platform floor still cannot be considered safe within 20 min. For the other two scenarios where trains arrive at the platform, the maximum probability of infection is below 5 %. Moreover, the majority of train carriages can be regarded as safe zones, as the ventilation across the screen door are mostly directed towards the platform. Additionally, releasing the bioaerosols at the platform floor poses the most severe threats to human health, and the corresponding evacuation strategies are suggested. These findings offer practical guidance for the design of the intra-urban microclimate, reinforcing the need for exposure reduction device or contingency plans, and providing potential evacuation strategy towards improved health outcomes.

Spatial distribution of bioaerosols and evaluation of four ventilation method on controlling their diffusion in a typical enhanced biosafety level 2 laboratory.

Biosafety laboratories are critical in many fields. However, experimenters associated the infection risk from biological aerosols. In this study, by conducting experiments on the release and collection of bioaerosols within a typical BSL-2 + laboratory, the spatial distribution of bioaerosols was tracked. Numerical calculations were employed to obtain and visualize the airflow patterns and aerosol dispersion paths of four ventilation methods. The results indicated that equipment and tables led to uneven airflow distribution within the laboratory. The comparison results of the four evaluation indicators showed that the air age distribution of UU (Upward supply and upward return) mode and CD (Cross-supply and downward return) mode was superior, with air change efficiency values of 0.595 and 0.603, respectively. Additionally, the contaminant removal index of CD mode was 1.48, significantly higher than the other ventilation methods. The statistical results of the contaminant dispersion index also indicated that CD mode was most conducive to diluting aerosols in the spatial environment. The LD (lateral supply and downward return) mode may lead to airflow short-circuiting. The UD (upward supply and downward return) mode can provide balanced protection for laboratory. Overall, CD mode performed the best among the four ventilation methods, followed by UU mode.

Prevalence and outcomes of atrial fibrillation in patients suffering prostate cancer: a national analysis in the United States.

Purpose: Although the adverse effects of atrial fibrillation (AF) on cancers have been well reported, the relationship between the AF and the adverse outcomes in prostate cancer (PC) remains inconclusive. This study aimed to explore the prevalence of AF and evaluate the relationship between AF and clinical outcomes in PC patients. Methods: Patients diagnosed with PC between 2008 and 2017 were identified from the National Inpatient Sample database. The trends in AF prevalence were compared among PC patients and their subgroups. Multivariable regression models were used to assess the associations between AF and in-hospital mortality, length of hospital stay, total cost, and other clinical outcomes. Results: 256,239 PC hospitalizations were identified; 41,356 (83.8%) had no AF and 214,883 (16.2%) had AF. AF prevalence increased from 14.0% in 2008 to 20.1% in 2017 (P < .001). In-hospital mortality in PC inpatients with AF increased from 5.1% in 2008 to 8.1% in 2017 (P < .001). AF was associated with adverse clinical outcomes, such as in-hospital mortality, congestive heart failure, pulmonary circulation disorders, renal failure, fluid and electrolyte disorders, cardiogenic shock, higher total cost, and longer length of hospital stay. Conclusions: The prevalence of AF among inpatients with PC increased from 2008 to 2017. AF was associated with poor prognosis and higher health resource utilization. Better management strategies for patients with comorbid PC and AF, particularly in older individuals, are required.

Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1.

BACKGROUND: The current study aimed to investigate the molecular mechanism of long non-coding RNA (lncRNA) MEG3 in the development of breast cancer. METHODS: The regulating relationships among lncRNA MEG3, miRNA-330 and CNN1 were predicted by bioinformatics analysis of breast cancer samples in the Cancer Genome Atlas database. The differential expression of lncRNA MEG3, miRNA-330 and CNN1 was first validated in breast cancer tissues and cells. The effects of lncRNA MEG3 on breast cancer malignant properties were evaluated by manipulating its expression in MCF-7 and BT-474 cells. Rescue experiments, dual-luciferase assays, and RNA immunoprecipitation (RIP) experiments were further used to validate the relationships among lncRNA MEG3, miRNA-330 and CNN1. RESULTS: Bioinformatics analysis showed that lncRNA MEGs and CNN1 were significantly downregulated in breast cancer tissues, while miR-330 was upregulated. These differential expressions were further validated in our cohort of breast cancer samples. High expression levels of lncRNA MEG3 and CNN1 as well as low expression of miR-330 were significantly associated with favorable overall survival. Overexpression of lncRNA MEG3 significantly inhibited cell viability, migration and invasion, decreased cells in S stage and promoted cell apoptosis. Dual-luciferase reporter gene assay and RIP experiments showed that lncRNA MEG3 could directly bind to miR-330. Moreover, miR-330 mimics on the basis of lncRNA MEG3 overexpression ameliorated the tumor-suppressing effects of lncRNA MEG3 in breast cancer malignant properties by decreasing CNN1 expression. CONCLUSION: Our study indicated lncRNA MEG3 is a breast cancer suppressor by regulating miR-330/CNN1 axis.

Comprehensive performance evaluation of six bioaerosol samplers based on an aerosol wind tunnel.

Choosing a suitable bioaerosol sampler for atmospheric microbial monitoring has been a challenge to researchers interested in environmental microbiology, especially during a pandemic. However, a comprehensive and integrated evaluation method to fully assess bioaerosol sampler performance is still lacking. Herein, we constructed a customized wind tunnel operated at 2-20 km/h wind speed to systematically and efficiently evaluate the performance of six frequently used samplers, where various aerosols, including Arizona test dust, bacterial spores, gram-positive and gram-negative bacteria, phages, and viruses, were generated. After 10 or 60 min of sampling, the physical and biological sampling efficiency and short or long-term sampling capabilities were determined by performing aerodynamic particle size analysis, live microbial culturing, and a qPCR assay. The results showed that AGI-30 and BioSampler impingers have good physical and biological sampling efficiencies for short-term sampling. However, their ability to capture aerosols at low concentrations is restricted. SASS 2300 and BSA-350 wet-wall cyclones had excellent enrichment ratios and high microbial cultivability in both short-term and long-term sampling; however, they were not suitable for quantitative studies of aerosols. Polycarbonate filter samplers showed outstanding performance in physical and long-term sampling but lacked the ability to maintain microbial activity, which can be improved by gelatin filter samplers. However, limitations remain for some fragile microorganisms, such as E. coli phage PhiX174 and coronavirus GX_P2V. In addition, the effects of wind speed and direction should be considered when sampling particles larger than 4 µm. This study provides an improved strategy and guidance for the characterization and selection of a bioaerosol sampler for better measurement and interpretation of collected ambient bioaerosols.

Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets.

BACKGROUND: Recent clinical studies have shown that transfusions of adult platelets increase morbidity and mortality in preterm infants. Neonatal platelets are hyporesponsive to agonist stimulation, and emerging evidence suggests developmental differences in platelet immune functions. OBJECTIVES: This study was designed to compare the proteome and phosphoproteome of resting adult and neonatal platelets. METHODS: We isolated resting umbilical cord blood-derived platelets from healthy full-term neonates (n = 8) and resting blood platelets from healthy adults (n = 6) and compared protein and phosphoprotein contents using data-independent acquisition mass spectrometry. RESULTS: We identified 4770 platelet proteins with high confidence across all samples. Adult and neonatal platelets were clustered separately by principal component analysis. Adult platelets were significantly enriched in immunomodulatory proteins, including ß2 microglobulin and CXCL12, whereas neonatal platelets were enriched in ribosomal components and proteins involved in metabolic activities. Adult platelets were enriched in phosphorylated GTPase regulatory enzymes and proteins participating in trafficking, which may help prime them for activation and degranulation. Neonatal platelets were enriched in phosphorylated proteins involved in insulin growth factor signaling. CONCLUSION: Using label-free data-independent acquisition mass spectrometry, our findings expanded the known neonatal platelet proteome and identified important differences in protein content and phosphorylation between neonatal and adult platelets. These developmental differences suggested enhanced immune functions for adult platelets and presence of molecular machinery related to platelet activation. These findings are important to understanding mechanisms underlying key platelet functions as well as the harmful effects of adult platelet transfusions given to preterm infants.

Interpenetrating LiB/Li3BN2 phases enabling stable composite lithium metal anode.

Host-less lithium metal anode generally suffers from large volume changes and serious dendrite growth during cycling, which poses challenges for its practical application. Interpenetrating phase composites with continuous architectures offer a solution to enhance mechanical properties of materials. Herein, a robust composite Li anode (LBN) material is fabricated through the metallurgical reaction between Li and hexagonal boron nitride (h-BN) with the formation of interpenetrating LiB/Li3BN2 phases. As LiB fibers are anchored by Li3BN2 granules, the collapse and slippage of LiB fibers are suppressed whilst the mechanical strength and structural stability of LBN are reinforced. By rolling, ultrathin (15 µm), freestanding, and electrochemically stable LBN foil can be obtained. The LBN anode exhibits a high average Coulombic efficiency of 99.69% (1 mA cm-2, 3 mAh cm-2) and a long lifespan of 2500 h (1 mA cm-2, 1 mAh cm-2). Notably, the LiCoO2 (with double-sided load 40 mg cm-2)|LBN pouch cell can operate over 450 cycles with a capacity retention of 90.1%. The exceptional cycling stability of LBN can be ascribed to the interpenetrating reinforcement architectures and synergistic electronic/ionic conductivity of the LiB/Li3BN2 dual-lithiophilic-phases. This work provides a new methodology for thin Li strip processing and reinforced-architecture design, with implications beyond battery applications.