Decoding the potential role of regulatory T cells in sepsis-induced immunosuppression.

Sepsis, a multiorgan dysfunction with high incidence and mortality, is caused by an imbalanced host-to-infection immune response. Organ-support therapy improves the early survival rate of sepsis patients. In the long term, those who survive the "cytokine storm" and its secondary damage usually show higher susceptibility to secondary infections and sepsis-induced immunosuppression, in which regulatory T cells (Tregs) are evidenced to play an essential role. However, the potential role and mechanism of Tregs in sepsis-induced immunosuppression remains elusive. In this review, we elucidate the role of different functional subpopulations of Tregs during sepsis and then review the mechanism of sepsis-induced immunosuppression from the aspects of regulatory characteristics, epigenetic modification, and immunometabolism of Tregs. Thoroughly understanding how Tregs impact the immune system during sepsis may shed light on preclinical research and help improve the translational value of sepsis immunotherapy.

Immune features revealed by single-cell RNA and single-cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID-19 booster vaccination.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.

Development and validation of a major adverse limb events prediction model for peripheral arterial disease with frailty.

OBJECTIVE: To investigate the risk factors for major limb adverse events (MALE) in peripheral arterial disease (PAD) combined with frailty and to develop and validate a risk prediction model of MALE. METHODS: This prospective study was performed in the vascular surgery department of patients in six hospitals in southwest China. Prospective collection of patients with PAD combined with frailty from February 1 to December 20, 2021, with MALE as the primary outcome, and followed for 1 year. The cohort was divided into a development cohort and a validation cohort. In the development cohort, a multivariate risk prediction model was developed to predict MALE using random forests for variable selection and multivariable Cox regression analysis. The model is represented by a visualized nomogram and a web-based calculator. The model performance was tested with the validation cohort and assessed using the C-statistic and calibration plots. RESULTS: A total of 1179 patients were prospectively enrolled from February 1 to December 20, 2021. Among 816 patients with PAD who were included in the analysis, the median follow-up period for this study was 9 ± 4.07 months, the mean age was 74.64 ± 9.43 years, and 249 (30.5%) were women. Within 1 year, 222 patients (27.2%) developed MALE. Target lesion revascularizations were performed in 99 patients (12.1%), and amputations were performed in 131 patients (16.1%). The mortality rate within the whole cohort was 108 patients (13.2%). After controlling for competing risk events (death), the cumulative risk of developing MALE was not statistically different. Prealbumin (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.41-0.89; P = .010), percutaneous coronary intervention (HR, 2.31; 95% CI, 1.26-4.21; P = .006), Rutherford classification (HR, 1.77; 95% CI, 1.36-2.31; P < .001), white blood cell (HR, 1.85; 95% CI, 1.20-2.87; P = .005), high altitude area (HR, 3.1; 95% CI, 1.43-6.75; P = .004), endovascular treatment (HR, 10.2; 95% CI, 1.44-72.50; P = .020), and length of stay (HR, 1.01; 95% CI, 1.00-1.03; P = .012) were risk factors for MALE. The MALE prediction model had a C-statistic of 0.76 (95% CI, 0.70-0.79). The C-statistic was 0.68 for internal validation and 0.66 for external validation for the MALE prediction model. The MALE prediction model for PAD presented an interactive nomogram and a web-based network calculator. CONCLUSIONS: In this study, the MALE prediction model has a discriminative ability to predict MALE among patients with PAD in frailty. The MALE model can optimize clinical decision-making for patients with PAD in frailty.

Individual Predictors of Response to A Behavioral Activation-Based Digital Smoking Cessation Intervention: A Machine Learning Approach.

Background: Depression is prevalent among individuals who smoke cigarettes and increases risk for relapse. A previous clinical trial suggests that Goal2Quit, a behavioral activation-based smoking cessation mobile app, effectively increases smoking abstinence and reduces depressive symptoms. Objective: Secondary analyses were conducted on these trial data to identify predictors of success in depression-specific digitalized cessation interventions. Methods: Adult who smoked cigarettes (age = 38.4 ± 10.3, 53% women) were randomized to either use Goal2Quit for 12 weeks (N = 103), paired with a 2-week sample of nicotine replacement therapy (patch and lozenge) or to a Treatment-As-Usual (TAU) control (N = 47). The least absolute shrinkage and selection operator was utilized to identify a subset of baseline variables predicting either smoking or depression intervention outcomes. The retained predictors were then fitted via linear regression models to determine relations to each intervention outcome. Results: Relative to TAU, only individuals who spent significant time using Goal2Quit (56 ± 46 min) were more likely to reduce cigarette use by at least 50% after 12 weeks, whereas those who spent minimal time using Goal2Quit (10 ± 2 min) did not exhibit significant changes. An interaction between educational attainment and treatment group revealed that, as compared to TAU, only app users with an educational degree beyond high school exhibited significant reductions in depression. Conclusions: The findings highlight the importance of tailoring depression-specific digital cessation interventions to individuals' unique engagement needs and educational level. This study provides a potential methodological template for future research aimed at personalizing technology-based treatments for cigarette users with depressive symptoms.

Optimization and Application of the QuEChERS-UHPLC-QTOF-MS Method for the Determination of Broflanilide Residues in Agricultural Soils.

In this study, the separation conditions of UHPLC-QTOF-MS and the extraction conditions of QuEChERS were optimized. The analytical process for determining Broflanilide residues in different soil types was successfully established and applied to its adsorption, desorption, and leaching in soil. Broflanilide was extracted from soil with acetonitrile and purified using PSA and MgSO4. The modified UHPLC-QTOF-MS method was used for quantification. The average recovery of Broflanilide was between 87.7% and 94.38%, with the RSD lower than 7.6%. In the analysis of adsorption, desorption, and leaching quantities in four soil types, the RSD was less than 9.2%, showing good stability of the method, which can be applied to determine the residue of Broflanilide in different soils.

Blood perfusion status is important in the prognosis of ventricular aneurysm complicated by ventricular septal rupture.

AIMS: Due to its low incidence, poor prognosis, and high mortality in the acute phase, the long-term prognosis of the left ventricular aneurysm (LVA) complicated by ventricular septal rupture (VSR) has received little attention. This study focus on the long-term prognosis of patients with LVA complicated by relatively stable VSR. METHODS AND RESULTS: Over a decade of retrospection, 68 patients with both LVA and VSR were compared with 136 patients with LVA alone after propensity score matching. Patients with both LVA and VSR were further divided into two groups depending on whether pre-operative intra-aortic balloon pump (IABP) was used (23 pre-operative IABP vs. 45 non-pre-operative IABP). The primary endpoint was defined as major adverse cardiovascular and cerebrovascular events, a composite endpoint including mortality, myocardial infarction, revascularization, stroke, and heart failure. Patients with both LVA and VSR were generally in a worse condition upon admission compared with those with LVA alone [percentage of patients in New York Heart Association IV: 42.6% (29/68) vs. 11.0% (15/136), P < 0.001]. Both pre-operative and post-operative IABP use rates were significantly higher in patients with both LVA and VSR than in patients with LVA alone [pre-operative IABP use rates: 33.8% (23/68) vs. 0.74% (1/136), P < 0.001 and post-operative IABP use rates: 33.8% (23/68) vs. 10.3% (14/136), P < 0.001]. No significant difference was observed in the primary endpoint between patients with both LVA and VSR and those with LVA alone (log-rank test, P = 0.63, median follow-up time 63 months). We further investigated the effect of pre-operative IABP on the long-term prognosis of patients with both LVA and VSR. Patients who applied pre-operative IABP had a worse long-term prognosis than those who did not (log-rank test, P = 0.0011). CONCLUSIONS: The long-term prognosis of LVA combined with VSR was not inferior than LVA alone after surgery, but poor blood perfusion status was associated with a worse prognosis.

Capturing ion trapping and detrapping dynamics in electrochromic thin films.

Ion trapping has been found to be responsible for the performance degradation in electrochromic oxide thin films, and a detrapping procedure was proved to be effective to rejuvenate the degraded films. Despite of the studies on ion trapping and detrapping, its dynamics remain largely unknown. Moreover, coloration mechanisms of electrochromic oxides are also far from clear, limiting the development of superior devices. Here, we visualize ion trapping and detrapping dynamics in a model electrochromic material, amorphous WO3. Specifically, formation of orthorhombic Li2WO4 during long-term cycling accounts for the origin of shallow traps. Deep traps are multiple-step-determined, composed of mixed W4+-Li2WO4, amorphous Li2WO4 and W4+-Li2O. The non-decomposable W4+-Li2WO4 couple is the origin of the irreversible traps. Furthermore, we demonstrate that, besides the typical small polaron hopping between W5+ ↔ W6+ sites, bipolaron hopping between W4+ ↔ W6+ sites gives rise to optical absorption in the short-wavelength region. Overall, we provide a general picture of electrochromism based on polaron hopping. Ion trapping and detrapping were demonstrated to also prevail in other cathodic electrochromic oxides. This work not only provides the ion trapping and detrapping dynamics of WO3, but also open avenues to study other cathodic electrochromic oxides and develop superior electrochromic devices with great durability.

The efficacy of furmonertinib in untreated advanced NSCLC patients with sensitive EGFR mutations in a real-world setting: a single institutional experience.

Background: Furmonertinib is the standard treatment option in the first-line setting for advanced non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations in China. However, there are limited real-world data available. Methods: We conducted a retrospective study at a single center, analyzing a cohort of 73 NSCLC patients who tested positive for EGFR mutations and were treated with furmonertinib as their initial therapy between August 2022 and December 2023. The primary endpoint was progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), overall survival (OS), and safety profile. Results: The median observation period was 9 months (95% confidence interval [CI], 8.0-20.0). The median PFS was 19.5 months (95% CI, 14.6-24.4). OS data were not yet mature. Univariate analysis showed no significant correlation between PFS and factors such as Eastern Cooperative Oncology Group performance status (ECOG PS) score, presence of brain or liver metastases, sex, age, EGFR mutation status, or number of metastatic sites. However, multivariate analysis indicated a potential trend toward extended PFS in patients younger than 65 years (p = 0.053, 95% CI, 0.10-1.02), although the p-value was only marginally significant. The most common adverse events were diarrhea (24%), anemia (36%), and liver injury (32%); however, only four cases experienced severe adverse events. Conclusion: In a real-world setting, furmonertinib appears to be a favorable treatment option for EGFR-mutated patients. The manageable nature of adverse events further supports its use in clinical practice.

Corrigendum: The efficacy of furmonertinib in untreated advanced NSCLC patients with sensitive EGFR mutations in a real-world setting: a single institutional experience.

[This corrects the article DOI: 10.3389/fonc.2024.1331128.].

Directly selecting cell-type marker genes for single-cell clustering analyses.

In single-cell RNA sequencing (scRNA-seq) studies, cell types and their marker genes are often identified by clustering and differentially expressed gene (DEG) analysis. A common practice is to select genes using surrogate criteria such as variance and deviance, then cluster them using selected genes and detect markers by DEG analysis assuming known cell types. The surrogate criteria can miss important genes or select unimportant genes, while DEG analysis has the selection-bias problem. We present Festem, a statistical method for the direct selection of cell-type markers for downstream clustering. Festem distinguishes marker genes with heterogeneous distribution across cells that are cluster informative. Simulation and scRNA-seq applications demonstrate that Festem can sensitively select markers with high precision and enables the identification of cell types often missed by other methods. In a large intrahepatic cholangiocarcinoma dataset, we identify diverse CD8+ T cell types and potential prognostic marker genes.

APbI3-A2AgBiI6 Double-Layer Perovskite Film for a Self-Powered and High-Stability X-ray Detector.

The development of lead halide perovskite X-ray detectors has promising applications in medical imaging and security inspection but is hindered by poor long-term stability and drift of the dark current and photocurrent. Herein, we design a (Cs0.05MA0.65FA0.3)PbI3-(Cs0.1MA1.3FA0.6)AgBiI6 double-layer perovskite film to assemble a self-powered flat-panel X-ray detector. The demonstrated X-ray detector achieves an outstanding self-powered sensitivity of 80 µC Gyair-1 cm-2 under a 0 V bias. More importantly, owing to the inhibition of the phase transition process and ion migration of (Cs0.05MA0.65FA0.3)PbI3 by the (Cs0.1MA1.3FA0.6)AgBiI6 layer, the device exhibits excellent continuous operating stability with a retention rate of 99% dark current and photocurrent over X-ray pulses of up to 4000 s and excellent long-term stability without a loss of the original response current after 150 days in an air environment. The strategy of double-layer perovskites improves the stability and sensitivity of devices, which paves a path for the industrial application of lead halide perovskite X-ray detectors.

Enhancing Carrier Mobility in Monolayer MoS2 Transistors with Process-Induced Strain.

Two-dimensional electronic materials are a promising candidate for beyond-silicon electronics due to their favorable size scaling of electronic performance. However, a major challenge is the heterogeneous integration of 2D materials with CMOS processes while maintaining their excellent properties. In particular, there is a knowledge gap in how thin film deposition and processes interact with 2D materials to alter their strain and doping, both of which have a drastic impact on device properties. In this study, we demonstrate how to utilize process-induced strain, a common technique extensively applied in the semiconductor industry, to enhance the carrier mobility in 2D material transistors. We systematically varied the tensile strain in monolayer MoS2 transistors by iteratively depositing thin layers of high-stress MgOx stressor. At each thickness, we combined Raman spectroscopy and transport measurements to unravel and correlate the changes in strain and doping within each transistor with their performance. The transistors displayed uniform strain distributions across their channels for tensile strains of up to 0.48 ± 0.05%, at 150 nm of stressor thickness. At higher thicknesses, mechanical instability occurred, leading to nonuniform strains. The transport characteristics systematically varied with strain, with enhancement in electron mobility at a rate of 130 ± 40% per % strain and enhancement of the channel saturation current density of 52 ± 20%. This work showcases how established CMOS technologies can be leveraged to tailor the transport in 2D transistors, accelerating the integration of 2D electronics into a future computing infrastructure.

Robotic Nanomanipulation Based on Spatiotemporal Modulation of Optical Gradients.

Robotic nanomanipulation emerges as a cutting-edge technique pivotal for in situ nanofabrication, advanced sensing, and comprehensive material characterization. In this study, we develop an optical robotic platform (ORP) for the dynamic manipulation of colloidal nanoparticles (NPs). The ORP incorporates a human-in-the-loop control mechanism enhanced by real-time visual feedback. This feature enables the generation of custom optical landscapes with adjustable intensity and phase configurations. Based on the ORP, we achieve the parallel and reconfigurable manipulation of multiple NPs. Through the application of spatiotemporal phase gradient-reversals, our platform demonstrates capabilities in trapping, binding, rotating, and transporting NPs across custom trajectories. This presents a previously unidentified paradigm in the realm of in situ nanomanipulation. Additionally, the ORP facilities a "capture-and-print" assembly process, utilizing a strategic interplay of phase and intensity gradients. This process operates under a constant laser power setting, streamlining the assembly of NPs into any targeted configuration. With its precise positioning and manipulation capabilities, underpinned by the spatiotemporal modulation of optical gradients, the ORP will facilitate the development of colloid-based sensors and on-demand fabrication of nanodevices.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis.

Background: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.

Case report: The effect of second-line vebreltinib treatment on a patient with advanced NSCLC harboring the MET exon 14 skipping mutation after tepotinib treatment.

Background: Highly selective type Ib mesenchymal-epithelial transition gene (MET) tyrosine kinase inhibitors (TKIs) are the standard-of-care (SOC) therapy for previously untreated non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations. However, there are rare reports describing effective regimens for patients who fail SOC without identifying resistant mutations or tissue transformation. Case report: We report the first case of a 74-year-old woman with lung adenocarcinoma (cT1cNxM0) harboring METex14 splice region mutation, which was identified by a next-generation sequencing (NGS)-based assay. The patient was administered two treatments, including first-line tepotinib and second-line vebreltinib. The patient achieved progression-free survival (PFS) of 7.6 months, and then disease progression of tepotinib was observed. A re-biopsy was performed for NGS, which revealed the same mutations as before, with no new gene mutations detected. The woman received subsequent vebreltinib therapy and experienced durable clinical benefits. In the first 6.8 months, chest computed tomography demonstrated stable disease. Then, she achieved partial response (PR). The durable PR lasted for more than 13 months, and the PFS is currently over 20 months, exceeding the prior treatment. Conclusion: This case highlights the importance of considering re-biopsy and reanalysis of genetic profiles in NSCLC patients harboring METex14 skipping mutations after progressive disease in MET TKI treatment. This raises the possibility that vebreltinib may have long-term survival benefits for patients without mutations conferring resistance (funded by Beijing Pearl Biotechnology Co., Ltd; ClinicalTrials.gov number, NCT04258033).

Efgartigimod as rescue treatment in acute phase of neuromyelitis optica spectrum disorder: A Case Report.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks except for intravenous methylprednisolone (IVMP). Efgartigimod is a first-in-class novel human immunoglobulin G1 (IgG1) Fc fragment approved for the treatment of generalized myasthenia gravis. Its capacity to rapidly decrease serum IgG levels, including pathogenic autoantibodies, positions it as a potentially effective option for managing the acute phase of NMOSD. Case presentation: We report the case of a 59-year-old female patient with acute NMOSD, presenting with vision loss and numbness in all four limbs. Despite an initial inadequate response to intravenous methylprednisolone (IVMP), the addition of Efgartigimod to her treatment regimen led to rapid improvement, notably including a significant reduction in serum aquaporin-4 antibody titers, total IgG levels, and inflammation cytokine levels. Furthermore, no adverse events were reported during a four-month follow-up period. Conclusion: As an adjunct to glucocorticoid therapy, Efgartigimod has proven effective and safe for this patient. However, to ascertain its potential as a novel therapeutic option for acute NMOSD, larger-scale prospective clinical trials are required.

Identification of eight genes associated with recurrent patellar dislocation.

The inheritance of recurrent patellar dislocation (RPD) is known, but the susceptible gene remains unidentified. Here, we performed the first whole exome sequencing (WES) cohort study to identify the susceptible genes. The results showed eight genes were associated with this disease. Notably, the carboxypeptidase D (CPD) gene showed the highest relevance based on its gene function and tissue expression. Single-cell sequencing results indicate that the CPD gene is involved in the pathophysiological process of RPD through granulocytes. Implicated pathways include nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Wnt/ß-catenin signaling, potentially influencing CPD's role in RPD pathogenesis. This study identified the susceptible gene and investigates the potential pathogenesis of RPD, which provided a new prospect for the understanding of RPD. Besides, it would offer the theoretical basis for disease prevention and genetic counseling.

Unraveling the complex interplay between Mitochondria-Associated Membranes (MAMs) and cardiovascular Inflammation: Molecular mechanisms and therapeutic implications.

Cardiovascular diseases (CVDs) represent a significant public health concern because of their associations with inflammation, oxidative stress, and abnormal remodeling of the heart and blood vessels. In this review, we discuss the intricate interplay between mitochondria-associated membranes (MAMs) and cardiovascular inflammation, highlighting their role in key cellular processes such as calcium homeostasis, lipid metabolism, oxidative stress management, and ERS. We explored how these functions impact the pathogenesis and progression of various CVDs, including myocardial ischemia-reperfusion injury, atherosclerosis, diabetic cardiomyopathy, cardiovascular aging, heart failure, and pulmonary hypertension. Additionally, we examined current therapeutic strategies targeting MAM-related pathways and proteins, emphasizing the potential of MAMs as therapeutic targets. Our review aims to provide new insights into the mechanisms of cardiovascular inflammation and propose novel therapeutic approaches to improve cardiovascular health outcomes.

A Scoring System to Predict Severe Acute Lower Respiratory Infection in Children Caused by Respiratory Syncytial Virus.

There were several factors associated with respiratory syncytial virus (RSV) severe acute lower respiratory infection (RSV-sALRI) in infants and young children. It is vital to develop a convenient scoring system to predict RSV-sALRI in children. Pediatric patients with RSV-ALRI from January 2009 to December 2021 were recruited retrospectively. Two-third of them were randomly grouped into the development set and one-third to the validation set. In the development set, risk factors for RSV-sALRI were transferred into the logistic regression analysis, then their receiver operating characteristic (ROC) curves were built to obtain the area under the ROC curve (AUC), and regression coefficients for each predictor were converted to points. Finally, the value of the scoring system was evaluated in the validation set. A total of 1 066 children with RSV-ALRI were recruited, including 710 in the development set and 356 in the validation set. By logistic regression analysis, six factors (younger than 2 years, gestational age <37 weeks, have siblings, birth weight ≤2500 g, artificial/mix feeding, CHD) showed statistical difference and then were scored with points according to the coefficient value (OR) in the development set. In the validation set, the sensitivity of the scoring system was 70.25%, the specificity 85.53%, the positive predictive value 71.43%, the negative predictive value 84.81%, and coincidence rate 0.80. The Kolmogorov-Smirnov test showed the distribution of AUC 0.765 (SE = 0.027; 95% CI = 0.713-0.818; p < 0.001). A simplified scoring system was developed in the study with high prediction value for RSV-sALRI in children.

Revelation of adhesive proteins affecting cellular contractility through reference-free traction force microscopy.

Over the past few decades, the critical role played by cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-L-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterial design. In this study, reference-free traction force microscopy with a well-organized microdot array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although poly-L-lysine supported cell spreading and elongation, it was inefficient at inducing cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.