Proteomic profile of tissue-derived extracellular vesicles from benign odontogenic lesions.

BACKGROUND: Benign odontogenic lesions (BOLs) can cause severe jaw bone defects and compromise the quality of life of patients. Extracellular vesicles (EVs) are well-established and versatile players in mediating pathophysiological events. EVs in the interstitial space (tissue-derived EVs or Ti-EVs) possess higher specificity and sensitivity in disease-related biomarker discovery. However, the role of Ti-EV-loaded proteins in mediating the development of BOLs has remained untapped. Herein, we aim to explore the contribution of Ti-EV-loaded proteins to the development of BOLs. METHODS: Samples were obtained from 3 with dental follicle, 3 with dentigerous cyst (DC), 7 with odontogenic keratocyst (OKC), and 3 patients with ameloblastoma (AM). Tissue-derived EVs were then extracted, purified, and validated using ultracentrifugation, transmission electron microscopy, and western blotting. Proteins from Ti-EVs were analyzed using LC-ESI tandem mass spectroscopy and differentially expressed proteins were screened, which was then validated by immunohistochemistry and immunofluorescence assays. RESULTS: The protein profile of Ti-EVs in each group was mapped by LC-MS analysis. The top 10 abundant proteins in BOL-derived Ti-EVs were COL6A3, COL6A1, ALB, HIST1H4A, HBB, ACTB, HIST1H2BD, ANXA2, COL6A2 and FBN1. Additionally, unique proteins in the Ti-EVs from various lesions were identified. Moreover, focal adhesion kinase (FAK) and myeloid differentiation primary response 88 (MyD88) showed higher expressions in Ti-EVs derived from OKC and AM, which were confirmed by immunohistochemistry and immunofluorescence staining. CONCLUSIONS: Ti-EVs containing FAK and MyD88 might be related to the development of OKC and AM, which can be potential therapeutic targets.

Effect of LRRC15 on autophagy in A549 cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and irreversible interstitial lung disease with unknown cause. To explore the role and regulatory mechanism of leucine-rich repeat-containing protein 15 (LRRC15) in IPF, bleomycin (BLM)-induced pulmonary fibrosis in mouse and A549 cells were constructed, and the expression of LRRC15 were detected. Then, MTT, GFP-RFP-LC3 dual fluorescent labeling system and Western blotting were used to investigate the effects of LRRC15 on cell activity and autophagy after transfection of siLRRC15, respectively. The results indicated that the expression of LRRC15 was significantly increased after the BLM treatment in mouse lung tissue and A549 cells. The designed and synthesized siLRRC15 followed by transfection into A549 cells resulted in a dramatic reduction in LRRC15 expression and partially restored the cell damage induced by BLM. Moreover, the expression of LC3-II and P62 were up-regulated, the amount of autophagosome were increased by GFP-RFP-LC3 dual fluorescent labeling assay after BLM treatment. Meanwhile, this study also showed that the key autophagy proteins LC3-II, ATG5 and ATG7 were up-regulated, P62 was down-regulated and autophagic flux were enhanced after further treatment of A549 cells with siLRRC15. The above findings suggest that LRRC15 is an indicator of epithelial cell damage and may participate in the regulation of fibrosis through autophagy mechanism in IPF. This study provides necessary theoretical basis for further elucidating the mechanism of IPF.

A Review of AIoT-based Human Activity Recognition: From Application to Technique.

This scoping review paper redefines the Artificial Intelligence-based Internet of Things (AIoT) driven Human Activity Recognition (HAR) field by systematically extrapolating from various application domains to deduce potential techniques and algorithms. We distill a general model with adaptive learning and optimization mechanisms by conducting a detailed analysis of human activity types and utilizing contact or non-contact devices. It presents various system integration mathematical paradigms driven by multimodal data fusion, covering predictions of complex behaviors and redefining valuable methods, devices, and systems for HAR. Additionally, this paper establishes benchmarks for behavior recognition across different application requirements, from simple localized actions to group activities. It summarizes open research directions, including data diversity and volume, computational limitations, interoperability, real-time recognition, data security, and privacy concerns. Finally, we aim to serve as a comprehensive and foundational resource for researchers delving into the complex and burgeoning realm of AIoT-enhanced HAR, providing insights and guidance for future innovations and developments.

Deep mutational scanning of influenza A virus NEP reveals pleiotropic mutations in its N-terminal domain.

The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. Besides, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function. Here, we systematically measured the replication fitness effects of >1,800 mutations of NEP. Our results show that the N-terminal domain has high mutational tolerance. Additional experiments demonstrate that N-terminal domain mutations pleiotropically affect viral transcription and replication dynamics, host cellular responses, and mammalian adaptation of avian influenza virus. Overall, our study not only advances the functional understanding of NEP, but also provides insights into its evolutionary constraints.

Bacterial Biohybrids for Invasion of Tumor Cells Promote Antigen Cross-Presentation Through Gap Junction.

Due to inherent differences in cellular composition and metabolic behavior with host cells, tumor-harbored bacteria can discriminatorily affect tumor immune landscape. However, the mechanisms by which intracellular bacteria affect antigen presentation process between tumor cells and antigen-presenting cells (APCs) are largely unknown. The invasion behavior of attenuated Salmonella VNP20009 (VNP) into tumor cells is investigated and an attempt is made to modulate this behavior by modifying positively charged polymers on the surface of VNP. It is found that non-toxic chitosan oligosaccharide (COS) modified VNP (VNP@COS) bolsters the formation of gap junction between tumor cells and APCs by enhancing the ability of VNP to infect tumor cells. On this basis, a bacterial biohybrid is designed to promote in situ antigen cross-presentation through intracellular bacteria induced gap junction. This bacterial biohybrid also enhances the expression of major histocompatibility complex class I molecules on the surface of tumor cells through the incorporation of Mdivi-1 coupled with VNP@COS. This strategic integration serves to heighten the immunogenic exposure of tumor antigens; while, preserving the cytotoxic potency of T cells. A strategy is proposed to precisely controlling the function and local effects of microorganisms within tumors.

Altered microbiome of serum exosomes in patients with acute and chronic cholecystitis.

BACKGROUND: This study aimed to investigate the differences in the microbiota composition of serum exosomes from patients with acute and chronic cholecystitis. METHOD: Exosomes were isolated from the serum of cholecystitis patients through centrifugation and identified and characterized using transmission electron microscopy and nano-flow cytometry. Microbiota analysis was performed using 16S rRNA sequencing. RESULTS: Compared to patients with chronic cholecystitis, those with acute cholecystitis exhibited lower richness and diversity. Beta diversity analysis revealed significant differences in the microbiota composition between patients with acute and chronic cholecystitis. The relative abundance of Proteobacteria was significantly higher in exosomes from patients with acute cholecystitis, whereas Actinobacteria, Bacteroidetes, and Firmicutes were significantly more abundant in exosomes from patients with chronic cholecystitis. Furthermore, functional predictions of microbial communities using Tax4Fun analysis revealed significant differences in metabolic pathways such as amino acid metabolism, carbohydrate metabolism, and membrane transport between the two patient groups. CONCLUSIONS: This study confirmed the differences in the microbiota composition within serum exosomes of patients with acute and chronic cholecystitis. Serum exosomes could serve as diagnostic indicators for distinguishing acute and chronic cholecystitis.

Utility of paired plasma and drainage fluid mNGS in diagnosing acute intra-abdominal infections with sepsis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs). METHODS: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed. RESULTS: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study. CONCLUSIONS: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use.

Modularization of Regional Electronic Structure over Defect-Rich CeO2 Rods for Enhancing Photogenerated Charge Transfer and CO2 Activation.

Oxygen vacancy (OV) engineering has been widely applied in different types of metal oxide-based photocatalytic reactions. Our study has shown that the redistributed OVs resulting from voids in CeO2 rods lead to significant differences in the band structure in space. The flat energy band within the highly crystallized bulk region hinders the recombination of photogenerated carrier pairs during the transfer process. The downward curved energy band in the surface region enhances the activation of the absorbents. Therefore, the localization of the band structure through crystal structure regionalization renders V-CeO2 capable of achieving efficient utilization of photogenerated carriers. Practically, the V-CeO2 rod shows a remarkable turnover number of 190.58 µmol g-1 h-1 in CO2 photoreduction, which is ∼9.4 times higher than that of D-CeO2 (20.46 µmol g-1 h-1). The designed modularization structure in our work is expected to provide important inspiration and guidance in coordinating the kinetic behavior of carriers in OV defect-rich photocatalysts.

Potassium affects the association between dietary intake of vitamin C and NAFLD among adults in the United States.

INTRODUCTION: Although the association between nonalcoholic fatty liver disease (NAFLD) and vitamin C has been well studied, the effects of dietary potassium intake on this relationship are still unclear. Thus, this study aimed to determine the effects of dietary potassium intake on the association between vitamin C and NAFLD. METHODS: We performed a cross-sectional learn about with 9443 contributors the usage of 2007-2018 NHANES data. Multiple logistic regression evaluation has been utilized to check out the affiliation of dietary vitamin C intake with NAFLD and advanced hepatic fibrosis (AHF). Subsequently, we plotted a smoothed match curve to visualize the association. Especially, the analysis of AHF was conducted among the NAFLD population. In addition, stratified evaluation used to be developed primarily based on demographic variables to verify the steadiness of the results. Effect amendment by way of dietary potassium intake used to be assessed via interplay checks between vitamin C and NAFLD in the multivariable linear regression. RESULTS: In this cross-sectional study, we found that vitamin C was negatively related to NAFLD and AHF. The relationship between vitamin C and NAFLD was different in the low, middle and high potassium intake groups. Furthermore, potassium intake significantly modified the negative relationship between vitamin C and NAFLD in most of the models. CONCLUSION: Our research showed that potassium and vitamin C have an interactive effect in reducing NAFLD, which may have great importance for clinical medication.

Robotics Perception and Control: Key Technologies and Applications.

The integration of advanced sensor technologies has significantly propelled the dynamic development of robotics, thus inaugurating a new era in automation and artificial intelligence. Given the rapid advancements in robotics technology, its core area-robot control technology-has attracted increasing attention. Notably, sensors and sensor fusion technologies, which are considered essential for enhancing robot control technologies, have been widely and successfully applied in the field of robotics. Therefore, the integration of sensors and sensor fusion techniques with robot control technologies, which enables adaptation to various tasks in new situations, is emerging as a promising approach. This review seeks to delineate how sensors and sensor fusion technologies are combined with robot control technologies. It presents nine types of sensors used in robot control, discusses representative control methods, and summarizes their applications across various domains. Finally, this survey discusses existing challenges and potential future directions.

[Age-dependent expression of HSP90 in the hippocampus of APP/PS1 mice].

The present study aims to observe the change in expression of heat shock protein 90 (HSP90) along with amyloid-ß (Aß) and phosphorylated Tau (p-Tau) protein levels in the hippocampus tissue of Alzheimer's disease (AD) transgenic animal model with age. APP/PS1 transgenic mice at age of 6-, 9- and 12-month and C57BL/6J mice of the same age were used. The cognitive abilities of these animals were evaluated using a Morris water maze. Western blot or immunohistochemistry was used to detect the expressions of HSP90 and Aß1-42, as well as the phosphorylation levels of Tau protein in the hippocampus. The hsp90 mRNA levels and the morphology and number of cells in the hippocampus were detected with real-time quantitative polymerase chain reaction (qRT-PCR) and Nissl staining, respectively. The results showed that compared with C57BL/6J mice of the same age, HSP90 and hsp90 mRNA expression were decreased (P < 0.05 or P < 0.01), while Aß1-42 and p-Tau protein levels were increased (P < 0.05 or P < 0.01) in the hippocampal tissue of APP/PS1 transgenic mice. Meanwhile, the decrease in HSP90 and hsp90 mRNA expression (P < 0.05 or P < 0.01), the increase in Aß1-42 and p-Tau levels (P < 0.01 or P < 0.05) in hippocampal tissue and the reduction in behavioral ability showed a progressive development with the advancing of age in the APP/PS1 transgenic mice. In conclusion, in the hippocampal tissue of APP/PS1 mice, the decrease in HSP90 expression and the increase in Aß1-42 and p-Tau levels together with the decline of their cognitive ability are age-dependent.

Application of PRI-E-a combined learning method in oral and maxillofacial oncology education.

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.

Identification critical host factors for Japanese encephalitis virus replication via CRISPR screening of human sgRNA library.

Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

Efficacy and safety of different chemotherapy regimens combined with thalidomide in the treatment of diagnosed HIV-associated diffuse large B-cell lymphoma.

Objective: To investigate the short-term efficacy and safety of different chemotherapy regimens combined with thalidomide, in the treatment of low-income patients with newly diagnosed HIV-associated diffuse large B-cell lymphoma. Methods: A retrospective analysis was performed on 42 patients with HIV-DLBCL who were admitted to the Infectious Diseases Department of Yunnan Provincial Infectious Diseases Hospital from January 2018 to December 2020. 14 cases (including 1 case in stage II and 13 cases in stage III/IV) were treated with R-CHOP, 24 cases (including 1 case in stage II and 23 cases in stage III/IV) were treated with R-DAEPOCH, and 4 cases (including 1 case in stage II and 3 cases in stage III/IV) were treated with EPOCH. All patients were treated with thalidomide. The ART regimen was adjusted. At least 1 and up to 6 intrathecal injections were given during chemotherapy, and cotrimoxazole was taken orally to prevent infection. The clinical efficacy was evaluated after 4 cycles of chemotherapy, and adverse events were evaluated at each cycle of chemotherapy. Results: All patients received 1-8 cycles of chemotherapy. CR (64.2 %) was achieved in 9 patients in R-CHOP group, and 5 patients died. In the R-DAEPOCH group, 17 patients achieved CR (70.8 %) and 7 died. In the EPOCH group, 2 patients reached CR (50 %) and 2 died. The main adverse reactions were grade II and above myelosuppression. Conclusion: Combined treatment with thalidomide can improve the prognosis of low-income patients with newly diagnosed HIV-DLBCL.

BRAF V600E mutation mediates invasive and growth features in ameloblastoma.

OBJECTIVES: Ameloblastoma (AM), a locally aggressive tumor with extensive growth capacity, causes significant damage to the jaw and affects facial appearance. Although the high prevalence of BRAF V600E mutation in AM is known, its specific impacts on patients with AM remain unclear. Thus, the present study investigated the role of BRAF V600E mutation, thereby focusing on its impact on AM invasion and growth. MATERIALS AND METHODS: Immunohistochemical analysis was used to compare BRAF V600E, MMP2, MMP9, and Ki-67 expressions in AM (n = 49), normal oral mucosa (NOM) (n = 10), and odontogenic keratocyst (OKC) (n = 15) tissues. AM was further classified according to the presence or absence of BRAF V600E. The relationship between BRAF V600E and invasion as well as growth was evaluated. In addition, correlation analysis was performed using immunohistochemistry and confirmed via double-labeling immunofluorescence. Finally, comparative analyses using mass spectrometry, immunohistochemistry, and immunofluorescence were performed to explore and identify underlying mechanisms. RESULTS: AM exhibited a higher incidence of BRAF V600E mutation than NOM and OKC. BRAF V600E expression was positively correlated with the invasion-associated proteins MMP2 and MMP9 and the growth-related protein Ki-67. Proteomic data revealed that BRAF V600E primarily activates the MAPK signaling pathway in AM, particularly driving the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). CONCLUSIONS: In summary, the findings suggested that the BRAF V600E mutation enhances the invasion and growth abilities of AM via the MAPK/ERK signaling pathway. Thus, targeting BRAF V600E or the MAPK/ERK pathway may be a potential AM therapy.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

DEHP induces apoptosis and autophagy of the thyroid via Rap1 signaling pathway: In vivo and in vitro study.

OBJECTIVE: DEHP has thyroid toxicity and affects thyroid function. However, the mechanism is unclear. METHODS: The offspring of SD rats were gavaged with different doses of DEHP from in utero to 8 or 12 weeks old. We observed the thyroid morphology with HE and autophagosomes with TEM. The THs levels were tested with ELISA. The apoptosis level was tested by flow cytometry. The levels of apoptosis-related genes, autophagy-related genes and Rap1 pathway genes, were measured with qRT-PCR and Western blot. We established an MEHP-treated Nthy-ori 3-1 cell model and inhibited the Rap1 to verify the mechanism. RESULTS: DEHP could cause pathological damage and ultrastructure damage of thyroids in offspring rats. After DEHP exposure, the THs levels were altered, the apoptosis levels increased, and autophagosomes appeared. DEHP significantly affected the levels of apoptosis-related genes and autophagy-related genes. DEHP also affected the levels of Rap1 pathway, which was correlated with the levels of apoptosis and autophagy. After inhibiting Rap1 in Nthy-ori 3-1 cells, the THs levels were altered. Rap1 pathway was inhibited and the levels of apoptosis and autophagy were down-regulated. CONCLUSION: DEHP could induce the apoptosis and autophagy of the thyroid, and Rap1 signaling pathway may play a significant role.