Prognostic predictive modeling of non-small cell lung cancer associated with cadmium-related pathogenic genes.

Persistent exposure to low-dose of cadmium is strongly linked to both the development and prognosis of non-small cell lung cancer (NSCLC), yet the precise molecular mechanism behind this relationship remains uncertain. In this study, cadmium-related pathogenic genes (CRPGs) in NSCLC were identified via differential expression analysis. NSCLC patient clusters related to CRPGs were constructed through univariate Cox and K-means clustering algorithms. Multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were employed to determine the prognosis. Sixteen CRPGs showed a significant association with NSCLC. We found biological and prognostic differences between patients in clusters A and B. A predictive prognostic risk model for NSCLC revealed that FAM83H, MSMO1, and SNAI1 are central. Hence, the 3 hub genes were named. To further elucidate the role of CRPGs in NSCLC, A549 cells were exposed to CdCl2. The mRNA and protein expression levels of the 3 hub genes and cell invasion were detected. Moreover, 10 µM CdCl2 may increase the protein expression of 3 hub genes and enhance the invasive ability of A549 cells. This risk model may have established a theoretical foundation for investigating the mechanisms, treatment, and prognosis of NSCLC.

Guild-level signature of gut microbiome for diabetic kidney disease.

Current microbiome signatures for chronic diseases such as diabetic kidney disease (DKD) are mainly based on low-resolution taxa such as genus or phyla and are often inconsistent among studies. In microbial ecosystems, bacterial functions are strain specific, and taxonomically different bacteria tend to form co-abundance functional groups called guilds. Here, we identified guild-level signatures for DKD by performing in-depth metagenomic sequencing and conducting genome-centric and guild-based analysis on fecal samples from 116 DKD patients and 91 healthy subjects. Redundancy analysis on 1,543 high-quality metagenome-assembled genomes (HQMAGs) identified 54 HQMAGs that were differentially distributed among the young healthy control group, elderly healthy control group, early-stage DKD patients (EDG), and late-stage DKD patients (LDG). Co-abundance network analysis classified the 54 HQMAGs into two guilds. Compared to guild 2, guild 1 contained more short-chain fatty acid biosynthesis genes and fewer genes encoding uremic toxin indole biosynthesis, antibiotic resistance, and virulence factors. Guild indices, derived from the total abundance of guild members and their diversity, delineated DKD patients from healthy subjects and between different severities of DKD. Age-adjusted partial Spearman correlation analysis showed that the guild indices were correlated with DKD disease progression and with risk indicators of poor prognosis. We further validated that the random forest classification model established with the 54 HQMAGs was also applicable for classifying patients with end-stage renal disease and healthy subjects in an independent data set. Therefore, this genome-level, guild-based microbial analysis strategy may identify DKD patients with different severity at an earlier stage to guide clinical interventions. IMPORTANCE: Traditionally, microbiome research has been constrained by the reliance on taxonomic classifications that may not reflect the functional dynamics or the ecological interactions within microbial communities. By transcending these limitations with a genome-centric and guild-based analysis, our study sheds light on the intricate and specific interactions between microbial strains and diabetic kidney disease (DKD). We have unveiled two distinct microbial guilds with opposite influences on host health, which may redefine our understanding of microbial contributions to disease progression. The implications of our findings extend beyond mere association, providing potential pathways for intervention and opening new avenues for patient stratification in clinical settings. This work paves the way for a paradigm shift in microbiome research in DKD and potentially other chronic kidney diseases, from a focus on taxonomy to a more nuanced view of microbial ecology and function that is more closely aligned with clinical outcomes.

Alcohol inducing macrophage M2b polarization in colitis by modulating the TRPV1-MAPK/NF-κB pathways.

BACKGROUND: Macrophages exhibit different phenotypes in inflammatory bowel disease (IBD) and promote inflammation or tissue repair depending on their polarization state. Alcohol is a widely used solvent in pharmaceutical formulations, and its consumption is associated with an increased risk of colitis; however, its effects on macrophages in IBD remain poorly understood. PURPOSE: This study aimed to investigate the effect of alcohol on macrophages in dextran sodium sulfate (DSS)-induced colitis and understand the underlying mechanisms. METHODS: DSS-treated C57BL/6 mice were exposed to varying concentrations of alcohol, transient receptor potential vanilloid 1 (TRPV1) antagonist, and 5-aminosalicylic acid. The distal colon was resected, fixed, stained, and histologically analyzed, through hematoxylin and eosin (H&E) staining and immunofluorescence staining. Ratio [Ca2+]i measurements, western blotting, quantitative polymerase chain reaction, cytokine measurements, and RNA sequencing analyses were also performed. Peritoneal macrophages and RAW264.7 cells were used for in vitro experiments, and various assays were performed to evaluate cellular responses, gene expression, and signaling pathways. RESULTS: Alcohol exacerbated DSS-treated mice colitis and promoted the secretion of various inflammatory cytokines from colonic macrophages. Alcohol enhances the calcium ion influx induced by lipopolysaccharide (LPS) in peritoneal macrophages, while the TRPV1 antagonist capsazepine (CPZ) inhibits LPS- and/or alcohol- induced calcium influx in macrophages. Alcohol and LPS activate the MAPK/P38, MAPK/ERK, and NF-κB signaling pathways and induce the macrophage M2b polarization, resulting in the increased expression level of inflammatory cytokines such as Tnf, Il1b, and Il10. Additionally, CPZ can inhibit the facilitatory effects of alcohol or LPS on the abovementioned pathways and inflammatory factors, reversing macrophage M2b polarization and promoting alcohol-induced colitis. The inhibition of nucleotide binding oligomerization domain containing 2 (NOD2) partially suppressed the alcohol and LPS effects on macrophages. CONCLUSION: Alcohol exacerbates experimental colitis and induces M2b polarization of macrophage via TRPV1-MAPK/NF-κB. Our study provides new insights into the potential therapeutic targets for IBD treatment by elucidating the role of TRPV1 in alcohol-exacerbated colitis, using CPZ as a potential therapeutic option. The identification of transient receptor potential ankyrin subtype 1 (TRPA1) as a therapeutic target expands the scope of future research.

HtrA3 paves the way for MSC migration and promotes osteogenesis.

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin ß1 expression. Subsequently, integrin ß1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

Structural effects of provincial digital economy on carbon emissions within China: A multi-region input-output based structural decomposition analysis.

The digital economy, serving as a new engine to boost China's economic growth, inevitably affects carbon emissions given both its green features and its potential demands for energy inputs. To investigate the province-level impacts of the digital economy on carbon emissions, this study splits the digital industry from the multi-regional input-output table, and adopts a downscale structural decomposition analysis to reveal the technological, structural, and scale effects of the digital economy on carbon emissions. The results show that: (1) the expansion of digital economy increased 186.3 Mt of carbon emissions at the aggregate level during the investigated period (2012-2017) and that, therefore, the direct structural effects of the digital economy played a leading role in emission reduction (-156 Mt); (2) in terms of heterogeneity, most provinces presented a U distribution with the structural mitigation effect at the bottom and highly-developed provinces generated significant negative spillover effects; (3) from a regional coordination perspective, digital production achieved greater carbon emission reductions in the eastern and western areas of the country, while the northeastern and central regions gained environmental benefits via digital applications. The main conclusions thus enhance existent understanding of China's digital economy and low-carbon development, and the paper also proffers corresponding policy recommendations, e.g., accelerating the convergence of digital economy and traditional industries to promote carbon emissions reduction.

Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study.

Background: With the development of the novel coronavirus disease 2019 (COVID-19), China implemented measures in an attempt to control the infection rate. We conducted a single-center, cross-sectional study to ascertain the impact of the COVID-19 pandemic on the equitable availability of medical resources for children diagnosed with malignant solid tumors in China. Methods: Data on the demographics, clinical characteristics, and medical expenses of 876 patients diagnosed with neuroblastoma, rhabdomyosarcoma (RMS), Wilms tumor, hepatoblastoma (HB), Ewing sarcoma (ES), and central nervous system (CNS) tumors from 2019 to 2021, during the COVID-19 pandemic, were retrospectively collected from the National Center for Children's Health. The Pearson χ2 test and Mann-Whitney test were performed to analyze the differences among variables. Results: Except for the regional origin of children with tumors during the epidemic, no significant differences were found in the demographic or clinical characteristics of patients at initial diagnosis. The number of patients from northern China and northeastern China who attended Beijing Children's Hospital (BCH) increased after the outbreak of COVID-19 (P=0.001). There was no significant alteration observed in the frequency of hospitalizations per individual per annum (P=0.641) or the mean expense incurred per individual per hospitalization (P=0.361). In addition, the medical insurance coverage rate of real-time settlement increased year by year. Conclusions: After the COVID-19 outbreak, the origin of patients with solid tumor who visited BCH was concentrated in the northern region of China. COVID-19 had no impact on the other demographic factors, clinical characteristics, or economic burden of patients with pediatric malignant solid tumors.

Matrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis.

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increases Piezo1 expression, as well as leads to subsequent activation of the mechanotransduction signalling effector YAP, thus favouring M1 polarisation whilst suppressing M2 polarisation. Moreover, upon treatment with YAP inhibitor, we successfully induce macrophage re-polarisation to the M2 state within the implant site microenvironment, which in turn promotes implant osseointegration. Collectively, our present study thus characterises the critical role of the Piezo1-YAP signalling axis in macrophage mechanosensing and stiffness-mediated macrophage polarisation and provides cues for the design of immuno-modulatory biomaterials that can regulate the macrophage phenotype.

Metagenomics revealing biomolecular insights into the enhanced toluene removal and electricity generation in PANI@CNT bioanode.

Microbial fuel cells (MFCs) have significant potential for environmental remediation and energy recycling directly from refractory aromatic hydrocarbons. To boost the capacities of toluene removal and the electricity production in MFCs, this study constructed a polyaniline@carbon nanotube (PANI@CNT) bioanode with a three-dimensional framework structure. Compared with the control bioanode based on graphite sheet, the PANI@CNT bioanode increased the output voltage and toluene degradation kinetics by 2.27-fold and 1.40-fold to 0.399 V and 0.60 h-1, respectively. Metagenomic analysis revealed that the PANI@CNT bioanode promoted the selective enrichment of Pseudomonas, with the dual functions of degrading toluene and generating exogenous electrons. Additionally, compelling genomic evidence elucidating the relationship between functional genes and microorganisms was found. It was interesting that the genes derived from Pseudomonas related to extracellular electron transfer, tricarboxylic acid cycle, and toluene degradation were upregulated due to the existence of PANI@CNT. This study provided biomolecular insights into key genes and related microorganisms that effectively facilitated the organic pollutant degradation and energy recovery in MFCs, offering a novel alternative for high-performance bioanode.

STK3 kinase activation inhibits tumor proliferation through FOXO1-TP53INP1/P21 pathway in esophageal squamous cell carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is an aggressive disease with a poor prognosis, caused by the inactivation of critical cell growth regulators that lead to uncontrolled proliferation and increased malignancy. Although Serine/Threonine Kinase 3 (STK3), also known as Mammalian STE20-like protein kinase 2 (MST2), is a highly conserved kinase of the Hippo pathway, plays a critical role in immunomodulation, organ development, cellular differentiation, and cancer suppression, its phenotype and function in ESCC require further investigation. In this study, we report for the first time on the role of STK3 kinase and its activation condition in ESCC, as well as the mechanism and mediators of kinase activation. METHODS: In this study, we investigated the expression and clinical significance of STK3 in ESCC. We first used bioinformatics databases and immunohistochemistry to analyze STK3 expression in the ESCC patient cohort and conducted survival analysis. In vivo, we conducted a tumorigenicity assay using nude mouse models to demonstrate the phenotypes of STK3 kinase. In vitro, we conducted Western blot analysis, qPCR analysis, CO-IP, and immunofluorescence (IF) staining analysis to detect molecule expression, interaction, and distribution. We measured proliferation, migration, and apoptosis abilities in ESCC cells in the experimental groups using CCK-8 and transwell assays, flow cytometry, and EdU staining. We used RNA-seq to identify genes that were differentially expressed in ESCC cells with silenced STK3 or FOXO1. We demonstrated the regulatory relationship of the TP53INP1/P21 gene medicated by the STK3-FOXO1 axis using Western blotting and ChIP in vitro. RESULTS: We demonstrate high STK3 expression in ESCC tissue and cell lines compared to esophageal epithelium. Cellular ROS induces STK3 autophosphorylation in ESCC cells, resulting in upregulated p-STK3/4. STK3 activation inhibits ESCC cell proliferation and migration by triggering apoptosis and suppressing the cell cycle. STK3 kinase activation phosphorylates FOXO1Ser212, promoting nuclear translocation, enhancing transcriptional activity, and upregulating TP53INP1 and P21. We also investigated TP53INP1 and P21's phenotypic effects in ESCC, finding that their knockdown significantly increases tumor proliferation, highlighting their crucial role in ESCC tumorigenesis. CONCLUSION: STK3 kinase has a high expression level in ESCC and can be activated by cellular ROS, inhibiting cell proliferation and migration. Additionally, STK3 activation-mediated FOXO1 regulates ESCC cell apoptosis and cell cycle arrest by targeting TP53INP1/P21. Our research underscores the anti-tumor function of STK3 in ESCC and elucidates the mechanism underlying its anti-tumor effect on ESCC.

Role of cell rearrangement and related signaling pathways in the dynamic process of tip cell selection.

Angiogenesis is a complex, highly-coordinated and multi-step process of new blood vessel formation from pre-existing blood vessels. When initiated, the sprouting process is spearheaded by the specialized endothelial cells (ECs) known as tip cells, which guide the organization of accompanying stalk cells and determine the function and morphology of the finally-formed blood vessels. Recent studies indicate that the orchestration and coordination of angiogenesis involve dynamic tip cell selection, which is the competitive selection of cells to lead the angiogenic sprouts. Therefore, this review attempt to summarize the underlying mechanisms involved in tip cell specification in a dynamic manner to enable readers to gain a systemic and overall understanding of tip cell formation, involving cooperative interaction of cell rearrangement with Notch and YAP/TAZ signaling. Various mechanical and chemical signaling cues are integrated to ensure the right number of cells at the right place during angiogenesis, thereby precisely orchestrating morphogenic functions that ensure correct patterning of blood vessels. Video Abstract.

TRPM8 inhibits substance P release from primary sensory neurons via PKA/GSK-3beta to protect colonic epithelium in colitis.

Transient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a pro-inflammatory neuropeptide secreted by the neurons, and it aggravates colitis. However, the regulatory role of TRPM8 in SP release is still unclear. Our study aimed to investigate TRPM8's role in SP release from primary sensory neurons during colitis and clarify the effect of SP on colonic epithelium. We analyzed inflammatory bowel disease patients' data from the Gene Expression Omnibus dataset. Dextran sulfate sodium (DSS, 2.5%)-induced colitis in mice, mouse dorsal root ganglion (DRG) neurons, ND7/23 cell line, and mouse or human colonic organoids were used for this experiment. Our study found that TRPM8, TAC1 and WNT3A expression were significantly correlated with the severity of ulcerative colitis in patients and DSS-induced colitis in mice. The TRPM8 agonist (menthol) and the SP receptor antagonist (Aprepitant) can attenuate colitis in mice, but the effects were not additive. Menthol promoted calcium ion influx in mouse DRG neurons and inhibited the combination and phosphorylation of PKAca from the cAMP signaling pathway and GSK-3ß from the Wnt/ß-catenin signaling pathway, thereby inhibiting the effect of Wnt3a-driven ß-catenin on promoting SP release in ND7/23 cells. Long-term stimulation with SP inhibited proliferation and enhanced apoptosis in both mouse and human colonic organoids. Conclusively, TRPM8 inhibits SP release from primary sensory neurons by inhibiting the interaction between PKAca and GSK-3ß, thereby inhibiting the role of SP in promoting colonic epithelial apoptosis and relieving colitis.

Multifunctional PtCuTe Nanosheets with Strong ROS Scavenging and ROS-Independent Antibacterial Properties Promote Diabetic Wound Healing.

Nanozymes, as one of the most efficient reactive oxygen species (ROS)-scavenging biomaterials, are receiving wide attention in promoting diabetic wound healing. Despite recent attempts at improving the catalytic efficiency of Pt-based nanozymes (e.g., PtCu, one of the best systems), they still display quite limited ROS scavenging capacity and ROS-dependent antibacterial effects on bacteria or immunocytes, which leads to uncontrolled and poor diabetic wound healing. Hence, a new class of multifunctional PtCuTe nanosheets with excellent catalytic, ROS-independent antibacterial, proangiogenic, anti-inflammatory, and immuno-modulatory properties for boosting the diabetic wound healing, is reported. The PtCuTe nanosheets show stronger ROS scavenging capacity and better antibacterial effects than PtCu. It is also revealed that the PtCuTe can enhance vascular tube formation, stimulate macrophage polarization toward the M2 phenotype and improve fibroblast mobility, outperforming conventional PtCu. Moreover, PtCuTe promotes crosstalk between different cell types to form a positive feedback loop. Consequently, PtCuTe stimulates a proregenerative environment with relevant cell populations to ensure normal tissue repair. Utilizing a diabetic mouse model, it is demonstrated that PtCuTe significantly facilitated the regeneration of highly vascularized skin, with the percentage of wound closure being over 90% on the 8th day, which is the best among the reported comparable multifunctional biomaterials.

Pore-Matched Sponge for Microorganisms Pushes Electron Extraction Limit in Microbial Fuel Cells.

Microbial fuel cells (MFCs) are of great potential for wastewater remediation and chemical energy recovery. Nevertheless, limited by inefficient electron transfer between microorganisms and electrode, the remediation capacity and output power density of MFCs are still far away from the demand of practical application. Herein, a pore-matching strategy is reported to develop uniform electroactive biofilms by inoculating microorganisms inside a pore-matched sponge, which is assembled of core-shell polyaniline@carbon nanotube (PANI@CNT). The maximum power density achieved by the PANI@CNT bioanode is 7549.4 ± 27.6 mW m-2 , which is higher than the excellent MFCs with proton exchange membrane reported to date, while the coulombic efficiency also attains a considerable 91.7 ± 1.2%. The PANI@CNT sponge enriches the exoelectrogen Geobacter significantly, and is proved to play the role of conductive pili in direct electron transfer as it down-regulates the gene encoding pilA. This work exemplifies a practicable strategy to develop excellent bioanode to boost electron extraction in MFCs and provides in-depth insights into the enhancement mechanism.

Hepatoblastoma with neonatal necrotizing enterocolitis: Two case reports.

We report two children with hepatoblastoma (HB) with a history of neonatal necrotizing enterocolitis (NEC). Case 1 was diagnosed with HB at 5 months of age. Liver enlargement was found during the NEC operation at 3 months of age and then was clinically diagnosed by imaging. After six chemotherapy courses, a partial hepatectomy was performed. Three months after ceasing the chemotherapy, a chest computed tomography scan suggested that distant metastasis of the tumor should be considered, and the lesion was removed. However, 9 months after the operation, alpha-fetoprotein concentrations were increased, and abdominal imaging showed a recurrence of the tumor in situ, resulting in a hepatectomy. Case 2 was diagnosed with NEC shortly after birth and underwent an intestinal resection and anastomosis 1 month later. He was diagnosed with HB at 3 years of age. Hepatectomy was performed after five courses of chemotherapy. Chemotherapy was stopped after 10 courses, and alpha-fetoprotein concentrations were normal. At present, both children have survived and are in a healthy condition. Physicians should be aware of the possibility of HB and a history of NEC in children. Premature birth and low birth weight are common factors leading to the pathogenesis of HB and NEC. The association between these two diseases requires further study.

Transition metal-free [3 + 3] annulation of cyclopropanols with ß-enamine esters to assemble nicotinate derivatives.

A metal-free and efficient approach for the synthesis of structurally important nicotinates through 4-HO-TEMPO-mediated [3 + 3] annulation of cyclopropanols with ß-enamine esters is presented. This protocol features high atom efficiency, green waste, simple operation and broad substrate scope. Moreover, the experiments of gram-scale synthesis and recovery of oxidants make this strategy more sustainable and practical.

Embedded Mo/Mn Atomic Regulation for Durable Acidity-Reinforced HZSM-5 Catalyst toward Energy-Efficient Amine Regeneration.

Metal-molecular sieve composites with high acidity are promising solid acid catalysts (SACs) for accelerating sluggish CO2 desorption processes and reducing the energy consumption of CO2 chemisorption systems. However, the production of such SACs through conventional approaches such as loading or ion-exchange methods often leads to uncontrolled and unstable metal distribution on the catalysts, which limits their pore structure regulation and catalytic performance. In this study, we demonstrated a feasible strategy for improving the durability, surface chemical activity, and pore structure of metal-doped HZSM-5 through bimetallic Mo/Mn modification. This strategy involves the immobilization of Mo-O-Mn species confined in an MFI structure by regulating MoO42- anions and Mn2+ cations. The embedded Mn/Mo species of low valence can strongly induce electron transfer and increase the density of compensatory H+ on the MoMn@H catalyst, thereby reducing the CO2 desorption temperature by 8.27 °C and energy consumption by 37% in comparison to a blank. The durability enhancement and activity regulation method used in this study is expected to advance the rational synthesis of metal-molecular sieve composites for energy-efficient CO2 capture using amine regeneration technology.

Fire Detection in Ship Engine Rooms Based on Deep Learning.

Ship fires are one of the main factors that endanger the safety of ships; because the ship is far away from land, the fire can be difficult to extinguish and could often cause huge losses. The engine room has many pieces of equipment and is the principal place of fire; however, due to its complex internal environment, it can bring many difficulties to the task of fire detection. The traditional detection methods have their own limitations, but fire detection using deep learning technology has the characteristics of high detection speed and accuracy. In this paper, we improve the YOLOv7-tiny model to enhance its detection performance. Firstly, partial convolution (PConv) and coordinate attention (CA) mechanisms are introduced into the model to improve its detection speed and feature extraction ability. Then, SIoU is used as a loss function to accelerate the model's convergence and improve accuracy. Finally, the experimental results on the dataset of the ship engine room fire made by us shows that the mAP@0.5 of the improved model is increased by 2.6%, and the speed is increased by 10 fps, which can meet the needs of engine room fire detection.

Unveiling a New Perspective on Distinguishing Omicron Breakthrough Cases and Postimmune COVID-19-Naive Individuals: Insights from Antibody Profiles.

In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P < 0.001). Receiver operating characteristic ROC0 curve analysis showed that the area under the curve (AUC) was 0.744 and 0.806 when the cutoff values of IgA and IgG were 1 S/CO and 15 S/CO, respectively. Omicron breakthrough infection can lead to a further increase in IgG and IgA levels relative to those of the immunized population. When nucleic acid real-time PCR was negative, we would use the kinetics of IgG and IgA levels to distinguish the breakthrough cases from the immunized population. IMPORTANCE This study fills a gap in the epidemiological evidence by investigating the value of serological indicators, particularly IgG and IgA levels, in the auxiliary diagnosis of COVID-19 infections when nucleic acid results are undetectable. The findings reveal that among Omicron breakthrough cases, both IgG and IgA antibody levels exhibit significant changes. Serum IgG levels increase during the acute phase and rise further in the recovery phase. Serum IgA can be detected as early as the first week post-symptom onset (PSO), showing a consistent linear increase within 5 weeks PSO. Furthermore, receiver operating characteristic (ROC) curve analysis demonstrates the potential of IgG and IgA cutoff values as diagnostic markers. The study's conclusion underscores the importance of monitoring IgG and IgA kinetics in distinguishing Omicron breakthrough cases from vaccinated individuals. These findings contribute to the development of more accurate diagnostic approaches and help inform public health strategies during the ongoing COVID-19 pandemic.

Perceptions and acceptability of HPV vaccination among parents of female adolescents 9-14 in China: A cross-sectional survey based on the theory of planned behavior.

HPV vaccine uptake remains low in China, especially among girls. Recently, China has initiated a pilot program on HPV immunization for girls 9-14. From November to December 2021, a cross-sectional study was conducted among parents of girls 9-14 in China through a web-based anonymous online questionnaire survey. Descriptive epidemiological analysis was used to analyze parental acceptability. Hierarchical regression analysis and structural equation modeling were to determine associated factors. A total of 5623 participants were included in the analysis. 21.2% girls had received HPV vaccine, and 94.3% parents intended to receive vaccination for their daughters, the Kappa values between them was -0.016. 31.9% of vaccinated mothers had received HPV vaccine for their daughters, vaccination history had a positive impact on behavior (ß = 0.048). Attitude (ß = 0.186), subjective norms (ß = 0.148) and perceived behavioral control (ß = 0.648) had a positive impact on intention. Vaccination intention mediated the relationships between attitude (ß = 0.044), subjective norms (ß = 0.035), and perceived behavioral control (ß = 0.154) with behavior. There is a gap between vaccination intention and behavior in parents of girls 9-14. Perceived behavior control had a strong association on HPV vaccination behavior.

Evaluation of the effect of 3D-bioprinted gingival fibroblast-encapsulated ADM scaffolds on keratinized gingival augmentation.

BACKGROUND AND OBJECTIVES: The keratinized gingiva plays an important role in maintaining healthy periodontal and peri-implant tissue. Acellular dermal matrix (ADM), as a substitute biomaterial, has a porous structure and good biocompatibility. 3D-bioprinting has the potential for tissue engineering because it enables precise loading of cells layer-by-layer. Herein, we bioprinted ADM scaffold encapsulating gingival fibroblasts (GFs) and evaluated its efficacy in keratinized gingiva augmentation in vivo to assess its potential for clinical periodontal tissue regeneration. METHODS: GFs were extracted from the gingiva of beagles and transfected with a green fluorescent protein (GFP). The ADM scaffold (ADM cell-free group) was constructed using ADM, gelatin, and sodium alginate mixed at an appropriate ratio via 3D-bioprinting. The ADM cell scaffold (ADM cell group) was established by adding extra GFs in the same manner. Six beagles were divided into blank control, ADM cell-free, and ADM cell groups; and implant surgery was performed. The keratinized gingiva was clinically and histologically evaluated at baseline and after 2 months. RESULTS: GFs transfected with GFPs expressed green fluorescence and were present in new tissue in the ADM cell group and not observed in the ADM cell-free group. At 2 months after surgery, the keratinized gingival augmentation in the ADM cell group was significantly more than that in the ADM cell-free group. Attached gingival augmentation was also observed more in the ADM cell group than that in the ADM cell-free group. Histological staining showed that the tissue in the ADM cell group displayed a more integrated structure and higher expression of COL I, COL III, and VEGF-A than those in the ADM cell-free group. CONCLUSION: 3D-bioprinted GF-encapsulated ADM scaffolds increased the amount of keratinized gingiva in vivo, suggesting that 3D-bioprinting has great potential for oral soft tissue regeneration.