Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.

Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes regulate proliferation, with most performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in somatic copy number changes (SCNAs) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue-type-specific genetic network architectures underlie SCNA and driver selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive insights about the genetic network architecture of aneuploidy in tumors.

WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

Brain local stability and network flexibility of table tennis players: a 7T MRI study.

Table tennis players have adaptive visual and sensorimotor networks, which are the key brain regions to acquire environmental information and generate motor output. This study examined 20 table tennis players and 21 control subjects through ultrahigh field 7 Tesla magnetic resonance imaging. First, we measured percentage amplitude of fluctuation across five different frequency bands and found that table tennis players had significantly lower percentage amplitude of fluctuation values than control subjects in 18 brain regions, suggesting enhanced stability of spontaneous brain fluctuation amplitudes in visual and sensorimotor networks. Functional connectional analyses revealed increased static functional connectivity between two sensorimotor nodes and other frontal-parietal regions among table tennis players. Additionally, these players displayed enhanced dynamic functional connectivity coupled with reduced static connectivity between five nodes processing visual and sensory information input, and other large-scale cross-regional areas. These findings highlight that table tennis players undergo neural adaptability through a dual mechanism, characterized by global stability in spontaneous brain fluctuation amplitudes and heightened flexibility in visual sensory networks. Our study offers novel insights into the mechanisms of neural adaptability in athletes, providing a foundation for future efforts to enhance cognitive functions in diverse populations, such as athletes, older adults, and individuals with cognitive impairments.

Spatially Confined in Situ Formed Sodiophilic-Conductive Network for High-Performance Sodium Metal Batteries.

The sodium (Na) metal anode encounters issues such as volume expansion and dendrite growth during cycling. Herein, a novel three-dimensional flexible composite Na metal anode was constructed through the conversion-alloying reaction between Na and ultrafine Sb2S3 nanoparticles encapsulated within the electrospun carbon nanofibers (Sb2S3@CNFs). The formed sodiophilic Na3Sb sites and the high Na+-conducting Na2S matrix, coupled with CNFs, establish a spatially confined "sodiophilic-conductive" network, which effectively reduces the Na nucleation barrier, improves the Na+ diffusion kinetics, and suppresses the volume expansion, thereby inhibiting the Na dendrite growth. Consequently, the Na/Sb2S3@CNFs electrode exhibits a high Coulombic efficiency (99.94%), exceptional lifespan (up to 2800 h) at high current densities (up to 5 mA cm-2), and high areal capacities (up to 5 mAh cm-2) in symmetric cells. The coin-type full cells assembled with a Na3V2(PO4)3/C cathode demonstrate significant enhancement in electrochemical performance. The flexible pouch cell achieves an excellent energy density of 301 Wh kg-1.

Stretchable Tissue-Like Gold Nanowire Composites with Long-Term Stability for Neural Interfaces.

Soft and stretchable nanocomposites can match the mechanical properties of neural tissue, thereby minimizing foreign body reactions to provide optimal stimulation and recording specificity. Soft materials for neural interfaces should simultaneously fulfill a wide range of requirements, including low Young's modulus (<<1 MPa), stretchability (≥30%), high conductivity (>> 1000 S cm-1), biocompatibility, and chronic stability (>> 1 year). Current nanocomposites do not fulfill the above requirements, in particular not the combination of softness and high conductivity. Here, this challenge is addressed by developing a scalable and robust synthesis route based on polymeric reducing agents for smooth, high-aspect ratio gold nanowires (AuNWs) of controllable dimensions with excellent biocompatibility. AuNW-silicone composites show outstanding performance with nerve-like softness (250 kPa), high conductivity (16 000 S cm-1), and reversible stretchability. Soft multielectrode cuffs based on the composite achieve selective functional stimulation, recordings of sensory stimuli in rat sciatic nerves, and show an accelerated lifetime stability of >3 years. The scalable synthesis method provides a chemically stable alternative to the widely used AgNWs, thereby enabling new applications within electronics, biomedical devices, and electrochemistry.

MetBil as a novel molecular regulator in ischemia-induced cardiac fibrosis via METTL3-mediated m6A modification.

Cardiac fibrosis is a common pathological manifestation in multiple cardiovascular diseases and often results in myocardial stiffness and cardiac dysfunctions. LncRNA (long noncoding RNA) participates in a number of pathophysiological processes. However, its role in cardiac fibrosis remains unclear. The purpose of this study was to investigate the role and molecular mechanism of MetBil in regulating cardiac fibrosis. Our data showed that METTL3 binding lncRNA (MetBil) was significantly increased both in fibrotic tissue following myocardial infarction (MI) in mice and in cardiac fibroblasts (CFs) exposed to TGF-ß1 (20 ng/mL) or 20% FBS. Overexpression of MetBil augmented collagen deposition, CF proliferation and activation while silencing MetBil exhibited the opposite effects. Importantly, heterozygous knockout of MetBil alleviated cardiac fibrosis and improved cardiac function after MI. RNA pull-down and RNA-binding protein immunoprecipitation assay showed that METTL3 is a direct downstream target of MetBil; consistently, MetBil and METTL3 were co-localized in both the nucleus and cytoplasm of CFs. Interestingly, MetBil regulated METTL3 expression at protein level, but not mRNA level, in ubiquitin-proteasome pathway. Enforced expression of METTL3 canceled the antifibrotic effects of silencing MetBil reflected by increased collagen production, CF proliferation and activation. Most notably, the m6A-modified fibrosis-regulated genes mediated by METTL3 are profoundly involved in the regulation of MetBil in the cardiac fibrosis following MI. Our study reveals that MetBil as a novel regulator of fibrosis promotes cardiac fibrosis via interacting with METTL3 and regulating the expression of the methylated fibrosis-associated genes, providing a new intervening target for fibrosis-associated cardiac diseases.

The Significant Role of New Particle Composition and Morphology on the HNO3-Driven Growth of Particles down to Sub-10 nm.

New particle formation and growth greatly influence air quality and the global climate. Recent CERN Cosmics Leaving OUtdoor Droplets (CLOUD) chamber experiments proposed that in cold urban atmospheres with highly supersaturated HNO3 and NH3, newly formed sub-10 nm nanoparticles can grow rapidly (up to 1000 nm h-1). Here, we present direct observational evidence that in winter Beijing with persistent highly supersaturated HNO3 and NH3, nitrate contributed less than ∼14% of the 8-40 nm nanoparticle composition, and overall growth rates were only ∼0.8-5 nm h-1. To explain the observed growth rates and particulate nitrate fraction, the effective mass accommodation coefficient of HNO3 (αHNO3) on the nanoparticles in urban Beijing needs to be 2-4 orders of magnitude lower than those in the CLOUD chamber. We propose that the inefficient uptake of HNO3 on nanoparticles is mainly due to the much higher particulate organic fraction and lower relative humidity in urban Beijing. To quantitatively reproduce the observed growth, we show that an inhomogeneous "inorganic core-organic shell" nanoparticle morphology might exist for nanoparticles in Beijing. This study emphasized that growth for nanoparticles down to sub-10 nm was largely influenced by their composition, which was previously ignored and should be considered in future studies on nanoparticle growth.

Modeling the Formation of Organic Compounds across Full Volatility Ranges and Their Contribution to Nanoparticle Growth in a Polluted Atmosphere.

Nanoparticle growth influences atmospheric particles' climatic effects, and it is largely driven by low-volatility organic vapors. However, the magnitude and mechanism of organics' contribution to nanoparticle growth in polluted environments remain unclear because current observations and models cannot capture organics across full volatility ranges or track their formation chemistry. Here, we develop a mechanistic model that characterizes the full volatility spectrum of organic vapors and their contributions to nanoparticle growth by coupling advanced organic oxidation modeling and kinetic gas-particle partitioning. The model is applied to Nanjing, a typical polluted city, and it effectively captures the volatility distribution of low-volatility organics (with saturation vapor concentrations <0.3 µg/m3), thus accurately reproducing growth rates (GRs), with a 4.91% normalized mean bias. Simulations indicate that as particles grow from 4 to 40 nm, the relative fractions of GRs attributable to organics increase from 59 to 86%, with the remaining contribution from H2SO4 and its clusters. Aromatics contribute much to condensable organic vapors (∼37%), especially low-volatility vapors (∼61%), thus contributing the most to GRs (32-46%) as 4-40 nm particles grow. Alkanes also contribute 19-35% of GRs, while biogenic volatile organic compounds contribute minimally (<13%). Our model helps assess the climatic impacts of particles and predict future changes.

Effect of WeChat-Based Medication Guidance on Symptoms and Serological Parameters in Children with Mycoplasma Pneumoniae.

Objective: The aim of this study was to assess the effect of microsoft-based medication guidance on the level of symptoms and serological indicators in children receiving budesonide nebulisation combined with terbutaline for the treatment of Mycoplasma pneumoniae pneumoniae (MPP). Methods: A total of 109 children with MPP treated in The First Affiliated Hospital of Ningbo University of China between October 2022 and April 2023 were divided into the conventional group (n=54, with medication guidance by telephone follow-up) and the WeChat group (n=55, with medication guidance based on the WeChat platform) using a randomized number table. The time to resolution of symptoms, serological index levels, incidence of adverse drug events, medication adherence scores and satisfaction rate of family guidance were compared between the two groups. Results: The disappearance time of symptoms such as wheezing and cough in the WeChat group was shorter than that in the conventional group (P < .05). After treatment, the C-reactive protein (CRP), interleukin-6 (IL-6) and calcitoninogen (PCT) levels and the incidence of adverse drug events were lower in the WeChat group than in the conventional group (P < .05). After treatment, the levels of forceful spirometry (FVC), 1st-second expiratory volume (FEV1), peak expiratory flow rate (PEF), medication compliance score and family guidance satisfaction rate were higher in the WeChat group than in the conventional group (P < .05). Conclusion: WeChat-based medication guidance can optimize the therapeutic effect of MPP, improve children's medication compliance and satisfaction rate of family guidance, and reduce the occurrence of adverse drug events.

Lightweight Ghost Enhanced Feature Attention Network: An Efficient Intelligent Fault Diagnosis Method under Various Working Conditions.

Recent advancements in applications of deep neural network for bearing fault diagnosis under variable operating conditions have shown promising outcomes. However, these approaches are limited in practical applications due to the complexity of neural networks, which require substantial computational resources, thereby hindering the advancement of automated diagnostic tools. To overcome these limitations, this study introduces a new fault diagnosis framework that incorporates a tri-channel preprocessing module for multidimensional feature extraction, coupled with an innovative diagnostic architecture known as the Lightweight Ghost Enhanced Feature Attention Network (GEFA-Net). This system is adept at identifying rolling bearing faults across diverse operational conditions. The FFE module utilizes advanced techniques such as Fast Fourier Transform (FFT), Frequency Weighted Energy Operator (FWEO), and Signal Envelope Analysis to refine signal processing in complex environments. Concurrently, GEFA-Net employs the Ghost Module and the Efficient Pyramid Squared Attention (EPSA) mechanism, which enhances feature representation and generates additional feature maps through linear operations, thereby reducing computational demands. This methodology not only significantly lowers the parameter count of the model, promoting a more streamlined architectural framework, but also improves diagnostic speed. Additionally, the model exhibits enhanced diagnostic accuracy in challenging conditions through the effective synthesis of local and global data contexts. Experimental validation using datasets from the University of Ottawa and our dataset confirms that the framework not only achieves superior diagnostic accuracy but also reduces computational complexity and accelerates detection processes. These findings highlight the robustness of the framework for bearing fault diagnosis under varying operational conditions, showcasing its broad applicational potential in industrial settings. The parameter count was decreased by 63.74% compared to MobileVit, and the recorded diagnostic accuracies were 98.53% and 99.98% for the respective datasets.

Regulating pathway for bacterial diversities toward improved ecological benefits of thiencarbazone-methyl·isoxaflutole application: A field experiment.

Herbicide abuse has a significantly negative impact on soil microflora and further influences the ecological benefit. The regulating measures and corresponding mechanisms mitigating the decreased bacterial diversity due to herbicide use have rarely been studied. A field experiment containing the application gradient of an efficient maize herbicide thiencarbazone-methyl·isoxaflutole was performed. The relationship between soil bacterial community and thiencarbazone-methyl·isoxaflutole use was revealed. Modified attapulgite was added to explore its impacts on soil microflora under the thiencarbazone-methyl·isoxaflutole application. Based on the analytic network process-entropy weighting method-TOPSIS method model, the ecological benefit focusing on microbial responses was quantitatively estimated along with technical effectiveness and economic benefit. The results showed that the diversity indices of soil microflora, especially the Inv_Simpson index, were reduced at the recommended, 5 and 10 times the recommended dosages of thiencarbazone-methyl·isoxaflutole use. The Flavisolibacter bacteria was negatively correlated with the residues in soils based on the random forest model and correlation analysis, indicating a potential degrader of thiencarbazone-methyl·isoxaflutole residues. The structural equation model further confirmed that the high soil water content and soil pH promoted the function of Flavisolibacter bacteria, facilitated the dissipation of thiencarbazone-methyl·isoxaflutole residues and further improved the diversity of soil microflora. In addition, the presence of modified attapulgite was found to increase the soil pH, which may improve bacterial diversity through the regulating pathway. This explained the high ecological benefits of the treatment where the thiencarbazone-methyl·isoxaflutole was applied at the recommended dosage rates in conjunction with modified attapulgite addition. Therefore, the comprehensive benefits of thiencarbazone-methyl·isoxaflutole application with a focus on ecological benefits can be improved by regulating the soil pH with modified attapulgite.

Elevating Discharge Voltage of Li2CO3-routine Li-CO2 Battery over 2.9 V at an Ultra-wide Temperature Window.

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ/mol) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh/g and robust cyclability over 1600 hours (1000 mAh/g cut-off) at a current density of 100 mA/g , the batteries show high temperature adaptability (-30~80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

Electrochemiluminescence Sensor with Controlled-Release Triggering Electrostatic Attraction Elimination Mechanism for Trenbolone Trace Detection.

A controlled-release strategy can meet the needs of sensitive environmental monitoring for pollutants through a self-on/off mode. In this work, an electrochemiluminescence (ECL) biosensor with controlled-release triggering electrostatic attraction elimination and biomolecular stimulated response strategies was constructed to detect environmental steroid hormones sensitively. The blocked pores on the aminated mesoporous silica nanocontainers were opened by specific binding between the trenbolone (TB) antigen and the antibody. The released l-cysteine counteracted the negative charge on the MnO2 NF surface through the redox reaction between -SH and MnO2, making the electrostatic interaction between the MnO2 NFs and the Ru(dcbpy)32+ disappear. Ru(dcbpy)32+ released an ECL signal on the electrode, thus completing the controlled-release triggering electrostatic attraction elimination strategy. In addition, with the TB antibody as the target and the competition strategy between the TB antigen and the standard substance, the constructed controlled-release ECL biosensor was used to detect the TB standard substance. Moreover, MnO2 NFs as the substrate of the ECL biosensor increased the active specific surface area of the electrode, effectively catalyzing the production of OH• and O2•-, thus endowing the ECL biosensor with coreactant-catalytic enhancement characteristic and further improving its ECL performance. This sensitive signal response brought about a low limit of detection of 2.53 fg/mL for the constructed ECL biosensor, which contributed a feasible idea for efficient trace analysis of pollutants in the environment.

Ultrasensitive Electrochemiluminescence Biosensor with Silver Nanoclusters as a Novel Signal Probe and α-Fe2O3-Pt as an Efficient Co-reaction Accelerator for Procalcitonin Immunoassay.

Herein, a high-efficiency biosensor based on ternary electrochemiluminescence (ECL) system was constructed for procalcitonin (PCT) detection. Specifically, silver nanoclusters (Ag NCs) with stable luminescence properties were prepared with small-molecule lipoic acid (LA) as the ligand, and its ECL emission in persulfate (S2O82-) was first reported. Meanwhile, the prepared Ag NCs possessed ligand-to-metal charge-transfer characteristics, thus transferring energy from LA to Ag+ for luminescence. Based on the small particle size, good biocompatibility, and molecular binding ability, Ag NCs-LA was used as an ideal luminescent probe. In addition, α-Fe2O3-Pt was introduced to facilitate the activation of S2O82-, thereby generating more sulfate radicals to react with the free radicals of Ag NCs to enhance ECL emission. The synergistic effect of the variable valence state of transition metals and high catalytic activity of noble metals endows α-Fe2O3-Pt with excellent catalytic ability for S2O82-. Importantly, the sensing mechanism was systematically demonstrated by UV-vis, fluorescence, and ECL analysis, as well as density functional theory calculations. At last, NKFRGKYKC was designed for specific immobilization of antibodies, thus releasing the antigen binding sites to improve the antigen recognition efficiency. Based on this, the developed biosensor showed high sensitivity for PCT detection, with a wide linear range (10 fg/mL-100 ng/mL) and a low detection limit (3.56 fg/mL), which could be extended to clinical detection of multiple biomarkers.

Rapid Testing of Δ9-Tetrahydrocannabinol and Its Metabolite On-Site Using a Label-Free Ratiometric Fluorescence Assay on a Smartphone.

Excessive consumption of Δ9-tetrahydrocannabinol (THC) severely endangers human health and has raised public safety concerns. However, its quantification by readily rapid tools with simplicity and low cost is still challenging. Herein, we found that a G-rich THC aptamer (THC1.2) can tightly bind to thioflavin T (ThT) with strong fluorescence, which would be specifically quenched in the presence of THC. Based on that, a label-free ratiometric fluorescent sensor for the sensing of THC and its metabolite (THC-COOH) based on THC1.2/ThT as a color emitter and red CdTe quantum dots as reference fluorescence was constructed. Notably, a transition of the fluorescent color of the ratiometric probe from green to red can be instantly observed upon the increased concentration of THC and THC-COOH. Furthermore, a portable smartphone-based fluorescence device integrated with a self-programmed Python program was fabricated and used to accomplish on-site monitoring of THC and THC-COOH within 5 min. Under optimized conditions, this ratiometric fluorescent sensor allowed for an instant response toward THC and its metabolite with considerable limits of detection of 97 and 254 nM, respectively. The established sensor has been successfully applied to urine and saliva samples and exhibited satisfactory recoveries (88-116%). This ratiometric fluorescent sensor can be used for the simultaneous detection of THC and THC-COOH with the advantages of rapidness, low cost, ease of operation, and portability, providing a promising strategy for on-site detection and facilitating law enforcement regulation and roadside control of THC.

Controlled Growth of MoS2 on Dendritic Ferric Oxide to Enhance Electrochemiluminescence of Nitrogen-Doped Carbon Quantum Dots for Sensitive Immunoassay.

The essential expansion of electrochemiluminescence (ECL) technology into clinical detection relies on sensitive and stable signal and maintenance of the activity of the immune molecules during the analysis. This poses a critical challenge for an ECL biosensor as a luminophore in general requires high potential excitation resulting in a strong ECL signal; nevertheless, it has an irreversible effect on the activity of the antigen or antibody. Herein, a novel electrochemiluminescence (ECL) biosensor utilizing nitrogen-doped carbon quantum dots (N-CQDs) as emitters and molybdenum sulfide/ferric oxide (MoS2@Fe2O3) nanocomposites as a coreaction accelerator was developed for detection of neuron-specific enolase (NSE), a biomarker of small cell lung cancer. The doping of nitrogen allows the CQDs to exhibit ECL signals with low excitation potential, with a more viable activity possible for immune molecules. MoS2@Fe2O3 nanocomposites exhibit superior coreaction acceleration characteristics in hydrogen peroxide than any single component of them, and the highly branched dendrite microstructure provides a large number of binding sites for immune molecular, which is an inevitable factor for trace detection. In addition, ion beam sputtering gold particle technology is introduced into the sensor fabrication via an Au-N bond, which will provide sufficient density orientation for capturing the antibody load via the Au-N bonds. With excellent repeatability, stability, and specificity, the as-purposed sensing platform showed differentiated ECL responses of NSE range from 10.00 fg/mL to 500 ng/mL, and the limit of detection (LOD) was calculated of 6.30 fg/mL (S/N = 3). The proposed biosensor is prospective to provide a new avenue for the analysis of NSE or other biomarkers.

Integrating Tetrathiafulvalene and Nickel-Bis(dithiolene) Units into Donor-Acceptor Covalent Organic Frameworks for Stable and Efficient Photothermal Conversion.

Tetrathiafulvalene (TTF) and Ni-bis(dithiolene) are typical conductive units widely studied in electronics, optics, and photochemistry. However, their applications in near-infrared (NIR) photothermal conversion are often limited by insufficient NIR absorption and low chemical/thermal stability. Herein, we integrate TTF and Ni-bis(dithiolene) into a covalent organic framework (COF) with stable and efficient NIR and solar photothermal conversion performance. Two isostructural COFs, namely Ni-TTF and TTF-TTF, are successfully isolated which are composed of TTF and Ni-bis(dithiolene) units as donor-acceptor (D-A) pairs or TTF units only. Both COFs show high BET surface areas and good chemical/thermal stability. Notably, compared with TTF-TTF, the periodic D-A arrangement in Ni-TTF significantly lowers the bandgap, leading to unprecedented NIR and solar photothermal conversion performance.

High glucose levels contribute to vascular fibrosis via the activation of the endothelial-to-mesenchymal transition in periodontitis.

OBJECTIVE: To determine the changes of Porphyromonas gingivalis (P. gingivalis) growth and metabolism and identify whether the vascular epithelium change could be induced in diabetic periodontitis. BACKGROUND: Maintaining favourable vascular function is a precondition for periodontal regeneration. In diabetic periodontitis, high glucose levels could enhance the metabolism of pathogens, and a complex condition involving inflammation and high glucose levels would disrupt homeostasis of the epithelium and promote fibrosis by endothelial-to-mesenchymal transition (EndMT). METHODS: Porphyromonas gingivalis was cultured with glucose to judge its metabolic activity. Human umbilical vein endothelial cells (HUVECs) were treated with P. gingivalis-lipopolysaccharide (LPS) (10 µg/ml) and/or high glucose concentrations (25 mM), and transforming growth factor (TGF)-ß inhibitor was used to block EndMT. Inflammation level was assessed by flow cytometry. Multiple biological functions including EndMT, angiopoiesis, and cell migration were analysed. Additionally, gene expressions and protein levels were determined with qPCR and western blot, respectively. Finally, blood vessels were cultured ex vivo, and EndMT and fibrosis markers were detected by immunohistochemistry. RESULTS: Glucose could promote P. gingivalis growth and biofilm formation as well as the expression of virulence factor genes including FimA, RgpA, RgpB, and Kgp. P. gingivalis-LPS and glucose could increase intracellular reactive oxygen species (ROS) and promote fibrosis via EndMT in HUVECs, along with attenuating angiopoiesis and cell migration, which could be resumed by blocking EndMT with TGF-ß inhibitor. Vascular fibrosis was observed after the addition of glucose via EndMT regulation. CONCLUSION: Glucose augmented the growth and metabolism of P. gingivalis and promoted fibrosis by the activation of EndMT, as well as the inhibition of angiopoiesis and cell migration.

COVID-19 rapid antigen tests approved for self-testing in Australia: published diagnostic test accuracy studies and manufacturer-supplied information. A systematic review.

OBJECTIVES: To review evaluations of the diagnostic accuracy of coronavirus disease 2019 (COVID-19) rapid antigen tests (RATs) approved by the Therapeutic Goods Administration (TGA) for self-testing by ambulatory people in Australia; to compare these estimates with values reported by test manufacturers. STUDY DESIGN: Systematic review of publications in any language that reported cross-sectional, case-control, or cohort studies in which the participants were ambulatory people in the community or health care workers in hospitals in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was suspected, and the results of testing self-collected biological samples with a TGA-approved COVID-19 RAT were compared with those of reverse transcription-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Estimates of diagnostic accuracy (sensitivity, specificity) were checked and compared with manufacturer estimates published on the TGA website. DATA SOURCES: Publications (to 1 September 2022) identified in the Cochrane COVID-19 Study Register and the World Health Organization COVID-19 research database. Information on manufacturer diagnostic accuracy evaluations was obtained from the TGA website. DATA SYNTHESIS: Twelve publications that reported a total of eighteen evaluations of eight RATs approved by the TGA for self-testing (manufacturers: All Test, Roche, Flowflex, MP Biomedicals, Clungene, Panbio, V-Chek, Whistling) were identified. Five studies were undertaken in the Netherlands, two each in Germany and the United States, and one each in Denmark, Belgium, and Canada; test sample collection was unsupervised in twelve studies, and supervised by health care workers or researchers in six. Estimated sensitivity with unsupervised sample collection ranged from 20.9% (MP Biomedicals) to 74.3% (Roche), and with supervised collection from 7.7% (V-Chek) to 84.4% (Panbio); the estimates were between 8.2 and 88 percentage points lower than the values reported by the manufacturers. Test specificity was high for all RATs (97.9-100%). CONCLUSIONS: The risk of false negative results when using COVID-19 RATs for self-testing may be considerably higher than apparent in manufacturer reports on the TGA website, with implications for the reliability of these tests for ruling out infection.

Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide-stimulated periodontitis in vitro and in vivo.

OBJECTIVES: Ferroptosis is associated with multiple inflammatory diseases. Periodontitis is an inflammatory disease mainly caused by oral opportunistic pathogens. However, the ferroptosis-periodontitis relationship has not been thoroughly described. We here analyzed whether ferroptosis is involved in periodontitis. MATERIALS AND METHODS: Human gingival fibroblasts (HGFs) were stimulated with P. gingivalis-LPS and ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and changes in mitochondrial morphology, ferroptosis-related factors, and inflammation levels were detected. After the rat experimental periodontitis model was established, changes in ferroptosis-related factors and inflammation levels were re-evaluated in the same manner. RESULTS: Porphyromonas gingivalis-LPS-induced mitochondrial shrinkage, an increase in mitochondrial membrane density, and upregulation of reactive oxygen species in HGFs. The expression of prostaglandin-endoperoxide synthase 2, transferrin receptor 1, and malondialdehyde and inflammation levels were upregulated, whereas the expression of solute carrier family seven member 11, glutathione peroxidase 4, superoxide dismutase, and glutathione were downregulated. Fer-1 attenuated these aforementioned changes and inflammation levels induced by P. gingivalis-LPS. The in vivo experiment results were consistent with the in vitro experiment results. CONCLUSIONS: Ferroptosis is involved in inflammatory processes in HGFs upon P. gingivalis-LPS stimulation. Ferroptosis is observed in the gingival tissue of periodontitis rats.