Knowledge, Attitude and Practice of Radiologists Regarding Artificial Intelligence in Medical Imaging.

Purpose: This study aimed to investigate the knowledge, attitudes, and practice (KAP) of radiologists regarding artificial intelligence (AI) in medical imaging in the southeast of China. Methods: This cross-sectional study was conducted among radiologists in the Jiangsu, Zhejiang, and Fujian regions from October to December 2022. A self-administered questionnaire was used to collect demographic data and assess the KAP of participants towards AI in medical imaging. A structural equation model (SEM) was used to analyze the relationships between KAP. Results: The study included 452 valid questionnaires. The mean knowledge score was 9.01±4.87, the attitude score was 48.96±4.90, and 75.22% of participants actively engaged in AI-related practices. Having a master's degree or above (OR=1.877, P=0.024), 5-10 years of radiology experience (OR=3.481, P=0.010), AI diagnosis-related training (OR=2.915, P<0.001), and engaging in AI diagnosis-related research (OR=3.178, P<0.001) were associated with sufficient knowledge. Participants with a junior college degree (OR=2.139, P=0.028), 5-10 years of radiology experience (OR=2.462, P=0.047), and AI diagnosis-related training (OR=2.264, P<0.001) were associated with a positive attitude. Higher knowledge scores (OR=5.240, P<0.001), an associate senior professional title (OR=4.267, P=0.026), 5-10 years of radiology experience (OR=0.344, P=0.044), utilizing AI diagnosis (OR=3.643, P=0.001), and engaging in AI diagnosis-related research (OR=6.382, P<0.001) were associated with proactive practice. The SEM showed that knowledge had a direct effect on attitude (ß=0.481, P<0.001) and practice (ß=0.412, P<0.001), and attitude had a direct effect on practice (ß=0.135, P<0.001). Conclusion: Radiologists in southeastern China hold a favorable outlook on AI-assisted medical imaging, showing solid understanding and enthusiasm for its adoption, despite half lacking relevant training. There is a need for more AI diagnosis-related training, an efficient standardized AI database for medical imaging, and active promotion of AI-assisted imaging in clinical practice. Further research with larger sample sizes and more regions is necessary.

Useful or not? The discussion of traditional Chinese medicine to treat COVID-19 on a Chinese social networking site.

The use of traditional medicine is a global phenomenon, and the WHO advocated its appropriate integration into modern healthcare systems. However, there is a hot debate about the legitimacy of traditional medicine among the general public. Here, we investigated the debate in the Chinese digital context by analysing 1954 responses related to 100 questions about traditional Chinese medicine (TCM) treatment against COVID-19 on the Zhihu platform. Attitude function theory was applied to understand the reasons underlying public attitudes.Results showed that Zhihu users generally held a supportive attitude toward TCM. Their attitudes mainly came from their own experience and traditional media. The general users were more negative while medical professionals were more positive toward TCM. Ego defence (eg, derogating evidence sources) was used the most to support attitudes, followed by value expression (eg, believing in science). Supporters showed fewer expressions of faith (eg, the use of TCM is a kind of faith), politics (eg, supporting TCM is about politics) and science value (eg, TCM is a field of science), fewer ego defence, more patriotism and cultural confidence expressions (eg, TCM is a cultural pride) and more knowledge explanation (eg, TCM accelerates the metabolism of phlegm) than expected. Opposers showed fewer utilitarian and knowledge functions, fewer expressions of patriotism and more expressions of faith, politics and economics, but more ego defence functions than expected. Opposing posts were more likely to attract engagement than supporting and neutral posts. Posts that mentioned attitude functions generally attracted more engagement.Our findings indicate that TCM debate in modern China is not only relevant to medical science and health, but also rooted deeply in cultural ideology, politics and economics. The findings can provide global insights into the development of proactive policies and action plans that will help the integration of traditional medicine into modern healthcare systems.

An Environmental Uncertainty Perception Framework for Misinformation Detection and Spread Prediction in the COVID-19 Pandemic: Artificial Intelligence Approach.

BACKGROUND: Amidst the COVID-19 pandemic, misinformation on social media has posed significant threats to public health. Detecting and predicting the spread of misinformation are crucial for mitigating its adverse effects. However, prevailing frameworks for these tasks have predominantly focused on post-level signals of misinformation, neglecting features of the broader information environment where misinformation originates and proliferates. OBJECTIVE: This study aims to create a novel framework that integrates the uncertainty of the information environment into misinformation features, with the goal of enhancing the model's accuracy in tasks such as misinformation detection and predicting the scale of dissemination. The objective is to provide better support for online governance efforts during health crises. METHODS: In this study, we embraced uncertainty features within the information environment and introduced a novel Environmental Uncertainty Perception (EUP) framework for the detection of misinformation and the prediction of its spread on social media. The framework encompasses uncertainty at 4 scales of the information environment: physical environment, macro-media environment, micro-communicative environment, and message framing. We assessed the effectiveness of the EUP using real-world COVID-19 misinformation data sets. RESULTS: The experimental results demonstrated that the EUP alone achieved notably good performance, with detection accuracy at 0.753 and prediction accuracy at 0.71. These results were comparable to state-of-the-art baseline models such as bidirectional long short-term memory (BiLSTM; detection accuracy 0.733 and prediction accuracy 0.707) and bidirectional encoder representations from transformers (BERT; detection accuracy 0.755 and prediction accuracy 0.728). Additionally, when the baseline models collaborated with the EUP, they exhibited improved accuracy by an average of 1.98% for the misinformation detection and 2.4% for spread-prediction tasks. On unbalanced data sets, the EUP yielded relative improvements of 21.5% and 5.7% in macro-F1-score and area under the curve, respectively. CONCLUSIONS: This study makes a significant contribution to the literature by recognizing uncertainty features within information environments as a crucial factor for improving misinformation detection and spread-prediction algorithms during the pandemic. The research elaborates on the complexities of uncertain information environments for misinformation across 4 distinct scales, including the physical environment, macro-media environment, micro-communicative environment, and message framing. The findings underscore the effectiveness of incorporating uncertainty into misinformation detection and spread prediction, providing an interdisciplinary and easily implementable framework for the field.

Silicon dioxide nanoparticles induce anxiety-like behavior in a size-specific manner via the microbiota-gut-brain axis.

The impacts of silicon dioxide nanoparticles (SiO2-NPs) on human health have attracted increasing interest due to their widespread utilization in medicine and food additives. However, the size-dependent effects of SiO2-NPs on brain health remain sparse. Herein we investigated alterations in behavioral patterns, the gut microbiota, inflammation and oxidative stress of mice after a 12-week exposure to SiO2-NPs with either small size (NP-S) or large size (NP-L). A more pronounced deleterious effect of NP-S was found on anxiety-like behavior in mice relative to NP-L. We also found that SiO2-NPs exposure induced inflammation and oxidative stress in the colon, hippocampus and cortex of mice in a size-specific manner. Correlation network analysis revealed potential links between anxiety-like behavior and SiO2-NPs-induced shifts in the gut microbiota including Parvibacter, Faecalibaculum, Gordonibacter and Ileibacterium. Furthermore, anxiety-like behavior caused by SiO2-NPs exposure exhibited correlations with decreased levels of hippocampal IL-10 and cortex Nqo1 as well as increased levels of intestinal Acox1 and hippocampal TNF-α. Therefore, our findings suggest that exposure to SiO2-NPs promoted anxiety-like behavior through the mediation of interplay between the gut and the brain, and SiO2-NPs of smaller size may generate a more adverse effect on brain health.

Comparative analysis of immunological changes following realgar and arsenic trioxide treatments in a murine model of myelodysplastic syndrome.

BACKGROUND: Myelodysplastic syndrome (MDS) is a prevalent hematological neoplastic disorder in clinics and its immunopathogenesis has garnered growing interest. Oral and intravenous arsenic agents have long been used to treat hematological malignancies. The main component of oral arsenic is realgar (arsenic disulfide), while arsenic trioxide is the main component of intravenous arsenic. METHODS: This study aimed to assess the effects of ATO and Realgar on the enhancement of peripheral blood, drug safety, and T cell immune status in the NUP98-HOXD13 (NHD13) mice model of MDS, specifically in the peripheral blood, spleen, and liver. RESULTS: The study findings indicate that realgar and arsenic trioxide (ATO) can improve peripheral hemogram in mice, whereas realgar promotes higher peripheral blood cell production than ATO. Furthermore, the clinical administration method and dose did not cause significant toxicity or side effects and thus can be considered safe. Coexistence and interconversion of hyperimmune function and immunosuppression in mice were also observed in this study. In addition, there were interactions between immune cells in the peripheral blood, spleen, and liver to regulate the immune balance of the body and activate immunity via T-cell activation. CONCLUSION: In summary, oral and intravenous arsenic agents are beneficial in improving peripheral hemogram and immunity in mice.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's dis-ease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disas-sembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find as-sembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by the disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

Label-free Colorimetric Detection of Viral RNA Based on Clustered Regularly Interspaced Short Palindromic Repeats and Gold Nanoparticles with a Portable Device.

Viral infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are some of the most dangerous threats to humans. SARS-CoV-2 has caused a global pandemic, highlighting the unprecedented demand for rapid and portable diagnostic methods. To meet these requirements, we designed a label-free colorimetric platform that combines the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated proteins (Cas) 12a system for naked-eye detection (named LFP). This method utilizes reverse transcription loop-mediated isothermal amplification (RT-LAMP) and the trans-cleavage activity of the CRISPR/Cas12a system to increase the sensitivity and specificity of the reaction. This platform can detect as few as 4 copies/µL of RNA and produces no false positive results when tested against the influenza virus. To better meet the requirements of point-of-care (POC) detection, we developed a portable device that can be applied in resource-poor and densely populated regions. The LFP assay holds great potential for application in resource-limited settings, and the label-free gold nanoparticle (AuNPs) probe can reduce costs, making it suitable for large-scale screening. We expect that the LFP assay will be promising for the POC screening of COVID-19.

Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.

Research of biomimetic corrugation on the blade flutter suppression in large-scale wind turbine systems.

Aiming at the blade flutter of large horizontal-axis wind turbines, a method by utilizing biomimetic corrugation to suppress blade flutter is first proposed. By extracting the dragonfly wing corrugation, the biomimetic corrugation airfoil is constructed, finding that mapping corrugation to the airfoil pressure side has better aerodynamic performance. The influence of corrugation type, amplitudeλ, and intensity on airfoil flutter is analyzed using orthogonal experiment, which determines that theλhas the greatest influence on airfoil flutter. Based on the fluctuation range of the moment coefficient ΔCm, the optimal airfoil flutter suppression effect is obtained when the type is III,λ= 0.6, and intensity is denser (n= 13). The effective corrugation layout area in the chord direction is determined to be the leading edge, and the ΔCmof corrugation airfoil is reduced by 7.405%, compared to the original airfoil. The application of this corrugation to NREL 15 MW wind turbine 3D blades is studied, and the influence of corrugation layout length in the blade span direction on the suppressive effect is analyzed by fluid-structure interaction. It is found that when the layout length is 0.85 R, the safety marginSfreaches a maximum value of 0.3431 Hz, which is increased 2.940%. The results show that the biomimetic corrugated structure proposed in this paper can not only improve the aerodynamic performance by changing the local flow field on the surface of the blade, but also increase the structural stiffness of the blade itself, and achieve the effect of flutter suppression.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disassembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find assembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

Integrative physiology and transcriptome reveal salt-tolerance differences between two licorice species: Ion transport, Casparian strip formation and flavonoids biosynthesis.

BACKGROUND: Glycyrrhiza inflata Bat. and Glycyrrhiza uralensis Fisch. are both original plants of 'Gan Cao' in the Chinese Pharmacopoeia, and G. uralensis is currently the mainstream variety of licorice and has a long history of use in traditional Chinese medicine. Both of these species have shown some degree of tolerance to salinity, G. inflata exhibits higher salt tolerance than G. uralensis and can grow on saline meadow soils and crusty saline soils. However, the regulatory mechanism responsible for the differences in salt tolerance between different licorice species is unclear. Due to land area-related limitations, the excavation and cultivation of licorice varieties in saline-alkaline areas that both exhibit tolerance to salt and contain highly efficient active substances are needed. The systematic identification of the key genes and pathways associated with the differences in salt tolerance between these two licorice species will be beneficial for cultivating high-quality salt-tolerant licorice G. uralensis plant varieties and for the long-term development of the licorice industry. In this research, the differences in growth response indicators, ion accumulation, and transcription expression between the two licorice species were analyzed. RESULTS: This research included a comprehensive comparison of growth response indicators, including biomass, malondialdehyde (MDA) levels, and total flavonoids content, between two distinct licorice species and an analysis of their ion content and transcriptome expression. In contrast to the result found for G. uralensis, the salt treatment of G. inflata ensured the stable accumulation of biomass and total flavonoids at 0.5 d, 15 d, and 30 d and the restriction of Na+ to the roots while allowing for more K+ and Ca2+ accumulation. Notably, despite the increase in the Na+ concentration in the roots, the MDA concentration remained low. Transcriptome analysis revealed that the regulatory effects of growth and ion transport on the two licorice species were strongly correlated with the following pathways and relevant DEGs: the TCA cycle, the pentose phosphate pathway, and the photosynthetic carbon fixation pathway involved in carbon metabolism; Casparian strip formation (lignin oxidation and translocation, suberin formation) in response to Na+; K+ and Ca2+ translocation, organic solute synthesis (arginine, polyamines, GABA) in response to osmotic stresses; and the biosynthesis of the nonenzymatic antioxidants carotenoids and flavonoids in response to antioxidant stress. Furthermore, the differential expression of the DEGs related to ABA signaling in hormone transduction and the regulation of transcription factors such as the HSF and GRAS families may be associated with the remarkable salt tolerance of G. inflata. CONCLUSION: Compared with G. uralensis, G. inflata exhibits greater salt tolerance, which is primarily attributable to factors related to carbon metabolism, endodermal barrier formation and development, K+ and Ca2+ transport, biosynthesis of carotenoids and flavonoids, and regulation of signal transduction pathways and salt-responsive transcription factors. The formation of the Casparian strip, especially the transport and oxidation of lignin precursors, is likely the primary reason for the markedly higher amount of Na+ in the roots of G. inflata than in those of G. uralensis. The tendency of G. inflata to maintain low MDA levels in its roots under such conditions is closely related to the biosynthesis of flavonoids and carotenoids and the maintenance of the osmotic balance in roots by the absorption of more K+ and Ca2+ to meet growth needs. These findings may provide new insights for developing and cultivating G. uralensis plant species selected for cultivation in saline environments or soils managed through agronomic practices that involve the use of water with a high salt content.

Deep learning of pretreatment multiphase CT images for predicting response to lenvatinib and immune checkpoint inhibitors in unresectable hepatocellular carcinoma.

Objectives: Combination therapy of lenvatinib and immune checkpoint inhibitors (CLICI) has emerged as a promising approach for managing unresectable hepatocellular carcinoma (HCC). However, the response to such treatment is observed in only a subset of patients, underscoring the pressing need for reliable methods to identify potential responders. Materials & methods: This was a retrospective analysis involving 120 patients with unresectable HCC. They were divided into training (n = 72) and validation (n = 48) cohorts. We developed an interpretable deep learning model using multiphase computed tomography (CT) images to predict whether patients will respond or not to CLICI treatment, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). We evaluated the models' performance and analyzed the impact of each CT phase. Critical regions influencing predictions were identified and visualized through heatmaps. Results: The multiphase model outperformed the best biphase and uniphase models, achieving an area under the curve (AUC) of 0.802 (95% CI = 0.780-0.824). The portal phase images were found to significantly enhance the model's predictive accuracy. Heatmaps identified six critical features influencing treatment response, offering valuable insights to clinicians. Additionally, we have made this model accessible via a web server at http://uhccnet.com/ for ease of use. Conclusions: The integration of multiphase CT images with deep learning-generated heatmaps for predicting treatment response provides a robust and practical tool for guiding CLICI therapy in patients with unresectable HCC.

Vision matters for shape representation: Evidence from sculpturing and drawing in the blind.

Shape is a property that could be perceived by vision and touch, and is classically considered to be supramodal. While there is mounting evidence for the shared cognitive and neural representation space between visual and tactile shape, previous research tended to rely on dissimilarity structures between objects and had not examined the detailed properties of shape representation in the absence of vision. To address this gap, we conducted three explicit object shape knowledge production experiments with congenitally blind and sighted participants, who were asked to produce verbal features, 3D clay models, and 2D drawings of familiar objects with varying levels of tactile exposure, including tools, large nonmanipulable objects, and animals. We found that the absence of visual experience (i.e., in the blind group) led to stronger differences in animals than in tools and large objects, suggesting that direct tactile experience of objects is essential for shape representation when vision is unavailable. For tools with rich tactile/manipulation experiences, the blind produced overall good shapes comparable to the sighted, yet also showed intriguing differences. The blind group had more variations and a systematic bias in the geometric property of tools (making them stubbier than the sighted), indicating that visual experience contributes to aligning internal representations and calibrating overall object configurations, at least for tools. Taken together, the object shape representation reflects the intricate orchestration of vision, touch and language.

Synergistic antitumor effects of Peiminine and Doxorubicin on breast cancer through enhancing DNA damage via ZEB1.

Peiminine, the primary biologically active compound from Fritillaria thunbergii Miq., has demonstrated significant pharmacological activities. Doxorubicin is one of the most potent chemotherapeutic agents for breast cancer (BC). This study was designed to investigate the efficacy and underlying mechanisms of Peiminine combined with Doxorubicin in treating BC. Our results demonstrated that the combination of Peiminine and 1 mg/kg Doxorubicin exhibited more significant suppression of tumor growth compared with the monotherapy in MDA-MB-231 xenograft nude mice model, which is comparable to the effect of 3 mg/kg Doxorubicin in vivo. Notably, the 3 mg/kg Doxorubicin monotherapy resulted in organ toxicity, specifically in the liver and heart, whereas no toxicity was observed in the combination group. In vitro, this combined treatment exhibited a synergistic reduction on the viability of BC cells. Peiminine enhanced the cell cycle arrest and DNA damage induced by Doxorubicin. Furthermore, the combination treatment effectively blocked DNA repair by inhibiting the MAPKs signaling pathways. And ZEB1 knockdown attenuated the combined effect of Peiminine and Doxorubicin on cell viability and DNA damage. In conclusion, our study found that the combination of Peiminine and Doxorubicin showed synergistic inhibitory effects on BC both in vivo and in vitro through enhancing Doxorubicin-induced DNA damage. These findings support that their combination is a novel and promising therapeutic strategy for treating BC.

Removal of N-nitrosopyrrolidine from GAC by a three-dimensional electrochemical reactor: degradation mechanism and degradation path.

Nitrogen-containing disinfection by-products (N-DBPs) produced in the process of drinking water disinfection are widely concerning due to the high cytotoxicity and genotoxicity. It is due to the difficulty of natural degradation of N-DBPs in water and the fact that conventional treatment systems do not effectively treat N-DBPs in drinking water. In this study, N-nitrosopyrrolidine (NPYR) in water was electrocatalytically degraded by a three-dimensional electrode reactor (3DER). This system applied graphite plates as anode and cathode. The granular activated carbon (GAC) was used as third electrode. The degradation of NPYR using a continuous flow three-dimensional electrode reactor was investigated by examining the effects of flow rate, current density, electrolyte concentration, and pollutant concentration on the degradation efficiency, energy consumption, and reaction kinetics of GAC particle electrodes. The results showed that the optimal operating conditions were flow rate = 0.45 mL/min, current density = 6 mA/cm2, Na2SO4 concentration = 0.28 mol/L, and NPYR concentration = 20 mg/L. Under optimal conditions, the degradation of NPYR exceeded 58.84%. The main contributor of indirect oxidation was deduced from free radical quenching experiments. NPYR concentration was measured by GC-MS with DB-5 capillary column, operating in full scan monitoring mode for appropriate quantification of NPYR and intermediates. Based on the identification of reaction intermediates, a possible pathway for the electrochemical oxidation of NPYR on GAC particle electrodes was proposed.

flgL mutation reduces pathogenicity of Aeromonas hydrophila by negatively regulating swimming ability, biofilm forming ability, adherence and virulence gene expression.

Aeromonas hydrophila is a serious human and animal co-pathogenic bacterium. Flagellum, a key virulence factor, is vital for bacterium tissue colonization and invasion. flgL is a crucial gene involved in the composition of flagellum. However, the impact of flgL on virulence is not yet clear. In this study, we constructed a stable mutant strain (△flgL-AH) using homologous recombination. The results of the attack experiments indicated a significant decrease in the virulence of △flgL-AH. The biological properties analysis revealed a significant decline in swimming ability and biofilm formation capacity in △flgL-AH and the transmission electron microscope results showed that the ∆flgL-AH strain did not have a flagellar structure. Moreover, a significant decrease in the adhesion capacity of ∆flgL-AH was found using absolute fluorescence quantitative polymerase chain reaction (PCR). The quantitative real-time PCR results showed that the expression of omp and the eight flagellum-related genes were down-regulated. In summary, flgL mutation leads to a reduction in pathogenicity possibly via decreasing the swimming ability, biofilm formation capacity and adhesion capacity, these changes might result from the down expression of omp and flagellar-related genes.

Nlrc3 signaling is indispensable for hematopoietic stem cell emergence via Notch signaling in vertebrates.

Hematopoietic stem and progenitor cells generate all the lineages of blood cells throughout the lifespan of vertebrates. The emergence of hematopoietic stem and progenitor cells is finely tuned by a variety of signaling pathways. Previous studies have revealed the roles of pattern-recognition receptors such as Toll-like receptors and RIG-I-like receptors in hematopoiesis. In this study, we find that Nlrc3, a nucleotide-binding domain leucine-rich repeat containing family gene, is highly expressed in hematopoietic differentiation stages in vivo and vitro and is required in hematopoiesis in zebrafish. Mechanistically, nlrc3 activates the Notch pathway and the downstream gene of Notch hey1. Furthermore, NF-kB signaling acts upstream of nlrc3 to enhance its transcriptional activity. Finally, we find that Nlrc3 signaling is conserved in the regulation of murine embryonic hematopoiesis. Taken together, our findings uncover an indispensable role of Nlrc3 signaling in hematopoietic stem and progenitor cell emergence and provide insights into inflammation-related hematopoietic ontogeny and the in vitro expansion of hematopoietic stem and progenitor cells.

Cryo-EM structures of the D290V mutant of the hnRNPA2 low-complexity domain suggests how D290V affects phase separation and aggregation.

Heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2) is a human ribonucleoprotein that transports RNA to designated locations for translation via its ability to phase separate. Its mutated form, D290V, is implicated in multisystem proteinopathy known to afflict two families, mainly with myopathy and Paget's disease of bone. Here, we investigate this mutant form of hnRNPA2 by determining cryo-EM structures of the recombinant D290V low complexity domain. We find that the mutant form of hnRNPA2 differs from the WT fibrils in four ways. In contrast to the WT fibrils, the PY-nuclear localization signals in the fibril cores of all three mutant polymorphs are less accessible to chaperones. Also, the mutant fibrils are more stable than WT fibrils as judged by phase separation, thermal stability, and energetic calculations. Similar to other pathogenic amyloids, the mutant fibrils are polymorphic. Thus, these structures offer evidence to explain how a D-to-V missense mutation diverts the assembly of reversible, functional amyloid-like fibrils into the assembly of pathogenic amyloid, and may shed light on analogous conversions occurring in other ribonucleoproteins that lead to neurological diseases such as amyotrophic lateral sclerosis and frontotemporal dementia.

The role and molecular mechanism of flgK gene in biological properties, pathogenicity and virulence genes expression of Aeromonas hydrophila.

Aeromonas hydrophila is a highly pathogenic aquatic resident bacterium that can cause co-morbidity in aquatic animals, waterfowl, poultry, and humans. Flagellum is the motility organ of bacteria important for bacterium tissue colonization and invasion. The flgK gene encodes a flagellar hook protein essential for normal flagellar formation. In order to explore the role of flgK in A. hydrophila, a flgK gene mutant strain of A. hydrophila (∆flgK-AH) was constructed using an efficient suicide plasmid-mediated homologous recombination method, and gene sequencing confirmed successful mutation of the flgK gene. The biological properties, pathogenicity and virulence genes expression were compared. The results showed that there was no significant difference in the growth, hemolytic, and swarming abilities, but the swimming and biofilm formation abilities of ∆flgK-AH were significantly reduced and the transmission electron microscope (TEM) results showed that the ∆flgK-AH strain did not have a flagellar structure. The median lethal dose (LD50) value of the ∆flgK-AH in Carassius auratus was 1.47-fold higher than that of the wild-type strain (WT-AH). The quantitative real-time PCR results showed that only the expression level of the lapA gene was up-regulated by 1.47 times compared with the WT-AH, while the expression levels of other genes were significantly down-regulated. In conclusion, flgK gene mutant led to a decline in the pathogenicity possibly by reducing swimming and biofilm formation abilities, these biological properties might result from the down-regulated expression of flagellate and pilus-related genes.

Clinical markers predict the efficacy of several immune checkpoint inhibitors in patients with non-small cell lung cancer in China.

Objectives: Immune checkpoint inhibitors (ICIs) are one of the most significant oncological treatment modalities as a result of the rapid advancement of immunotherapy. Programmed Cell Death-Ligand 1 (PD-L1) and tumor mutational burden (TMB) have emerged as key markers for predicting the efficacy and prognosis of ICIs in non-small cell lung cancer (NSCLC), and the predictive role of tumor-infiltrating lymphocytes (TILs) has also received significant attention. However, the prognosis of some individuals cannot be determined by these indicators; for instance, some patients with low PD-L1 expression also benefit from longer survival. Therefore, the purpose of this research was to investigate the connection between new haematological and pathological markers and clinical outcomes in NSCLC patients receiving ICIs. Methods: Seventy-six patients with stage III-IV NSCLC treated with ICIs were included in this study. We used the Mann-Whitney test, COX regression and Kaplan-Meier analysis to retrospectively analyze peripheral blood indicators and survival prognostic data of 76 patients in order to investigate the relationship between baseline neutrophil-to-lymphocyte ratio (NLR) and the efficacy of ICIs. To investigate the correlation between CXCL13, CXCR5, CD8 and the efficacy of ICIs, we assessed the expression levels of aforementioned indicators in biopsied tissues of 10 non-small cell lung tumors by immunohistochemistry (IHC) and immunofluorescence (IF) and performed statistical analysis. Results: Disease control rate (DCR) was higher in patients with baseline NLR <3.4 (p=0.016) and neutrophil percentage <71% (P=0.015). Baseline NLR (HR=2.364, P=0.003) and neutrophil percentage (HR=2.824, P=0.013) had the greatest influence on patients' survival prognosis, with baseline NLR exhibiting a stronger predictive value (AUC=0.717), according to univariate and multifactorial COX regression analyses of progression-free survival (PFS) and overall survival (OS). In NSCLC tissues, higher expression of CXCL13 was associated with better clinical outcomes (P=0.032) and higher expression of CD8 was associated with prolonged survival (P=0.022). Conclusion: Low baseline NLR in peripheral blood and high expression of CD8 in tissues are associated with longer PFS and may have a potential predictive value for patients with stage III-IV NSCLC using ICIs.