Regulation of the Drosophila transcriptome by Pumilio and the CCR4-NOT deadenylase complex.

The sequence-specific RNA-binding protein Pumilio (Pum) controls Drosophila development; however, the network of mRNAs that it regulates remains incompletely characterized. In this study, we use knockdown and knockout approaches coupled with RNA-seq to measure the impact of Pum on the transcriptome of Drosophila cells in culture. We also use an improved RNA coimmunoprecipitation method to identify Pum-bound mRNAs in Drosophila embryos. Integration of these data sets with the locations of Pum-binding motifs across the transcriptome reveals novel direct Pum target genes involved in neural, muscle, wing, and germ cell development and in cellular proliferation. These genes include components of Wnt, TGF-ß, MAPK/ERK, and Notch signaling pathways, DNA replication, and lipid metabolism. We identify the mRNAs regulated by the CCR4-NOT deadenylase complex, a key factor in Pum-mediated repression, and observe concordant regulation of Pum:CCR4-NOT target mRNAs. Computational modeling reveals that Pum binding, binding site number, clustering, and sequence context are important determinants of regulation. In contrast, we show that the responses of direct mRNA targets to Pum-mediated repression are not influenced by the content of optimal synonymous codons. Moreover, contrary to a prevailing model, we do not detect a role for CCR4-NOT in the degradation of mRNAs with low codon optimality. Together, the results of this work provide new insights into the Pum regulatory network and mechanisms and the parameters that influence the efficacy of Pum-mediated regulation.

Transcriptome and metabolome analyses reveal chlorogenic acid accumulation in pigmented potatoes at different altitudes.

Pigmented potato tubers are abundant in chlorogenic acids (CGAs), a metabolite with pharmacological activity. This article comprehensively analyzed the transcriptome and metabolome of pigmented potato Huaxingyangyu and Jianchuanhong at four altitudes of 1800 m, 2300 m, 2800 m, and 3300 m. A total of 20 CGAs and intermediate CGA compounds were identified, including 3-o-caffeoylquinic acid, 4-o-caffeoylquinic acid, and 5-o-caffeoylquinic acid. CGA contents in Huaxinyangyu and Jianchuanhong reached its maximum at an altitude of 2800 m and slightly decreased at 3300 m. 48 candidate genes related to the biosynthesis pathway of CGAs were screened through transcriptome analysis. Weighted gene co-expression network analysis (WGCNA) identified that the structural genes of phenylalanine deaminase (PAL), coumarate-3 hydroxylase (C3H), cinnamic acid 4-hydroxylase (C4H) and the transcription factors of MYB and bHLH co-regulate CGA biosynthesis. The results of this study provide valuable information to reveal the changes in CGA components in pigmented potato at different altitudes.

In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation.

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.

Metabolic Regulation-Mediated Reversion of the Tumor Immunosuppressive Microenvironment for Potentiating Cooperative Metabolic Therapy and Immunotherapy.

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

MiR-494-3p regulates skin fibroblast activities by mediating fibromodulin production.

Skin wound healing is a well-coordinated process in which various cells and factors participate, during which fibroblast exhibits a critical role by exerting its multiple activities, including proliferation, migration, invasion, and differentiation. Previous studies have identified that fibromodulin (FMOD) could enhance dermal wound healing by promoting skin fibroblast activities, but little is known about its upstream regulator. We occasionally found that FMOD expression was downregulated in skin fibroblast by transforming growth factor-ß1 treatment. It was hypothesized that microRNAs (miRNA) in skin fibroblast could downregulate FMOD production and blocking them would increase FMOD expression, as well as promote skin wound healing. Here, by utilizing combined analysis of miRNA microarray from the Gene Expression Omnibus database and miRNA targets prediction, we successfully identified a miRNA, termed miR-494-3p, could regulate FMOD production in human skin fibroblast (BJ fibroblast). The functional analysis revealed that miR-494-3p mimics could inhibit BJ fibroblast migration and invasion but not proliferation and differentiation, while miR-494-3p inhibition markedly promotes migration, invasion, and differentiation of BJ fibroblast. Moreover, we established FMOD overexpression (OE) and knockout BJ fibroblast. We found that FMOD OE could rescue the inhibitory effects of miR-494-3p mimics on the migration and invasion of BJ fibroblast. In contrast, the miR-494-3p inhibitor transfection could not enhance migration, invasion, and differentiation of FMOD KO BJ fibroblast. Together, our results suggest that miR-494-3p may be a potential target for skin wound management via regulating FMOD production.

Screening and functional analysis of StMYB transcription factors in pigmented potato under low-temperature treatment.

MYB transcription factors play an extremely important regulatory role in plant responses to stress and anthocyanin synthesis. Cloning of potato StMYB-related genes can provide a theoretical basis for the genetic improvement of pigmented potatoes. In this study, two MYB transcription factors, StMYB113 and StMYB308, possibly related to anthocyanin synthesis, were screened under low-temperature conditions based on the low-temperature-responsive potato StMYB genes family analysis obtained by transcriptome sequencing. By analyzed the protein properties and promoters of StMYB113 and StMYB308 and their relative expression levels at different low-temperature treatment periods, it is speculated that StMYB113 and StMYB308 can be expressed in response to low temperature and can promote anthocyanin synthesis. The overexpression vectors of StMYB113 and StMYB308 were constructed for transient transformation tobacco. Color changes were observed, and the expression levels of the structural genes of tobacco anthocyanin synthesis were determined. The results showed that StMYB113 lacking the complete MYB domain could not promote the accumulation of tobacco anthocyanins, while StMYB308 could significantly promote the accumulation involved in tobacco anthocyanins. This study provides a theoretical reference for further study of the mechanism of StMYB113 and StMYB308 transcription factors in potato anthocyanin synthesis.

Effects of appropriate low-temperature treatment on the yield and quality of pigmented potato (Solanum tuberosum L.) tubers.

Temperature is one of the important environmental factors affecting plant growth, yield and quality. Moreover, appropriately low temperature is also beneficial for tuber coloration. The red potato variety Jianchuanhong, whose tuber color is susceptible to temperature, and the purple potato variety Huaxinyangyu, whose tuber color is stable, were used as experimental materials and subjected to 20 °C (control check), 15 °C and 10 °C treatments during the whole growth period. The effects of temperature treatment on the phenotype, the expression levels of structural genes related to anthocyanins and the correlations of each indicator were analyzed. The results showed that treatment at 10 °C significantly inhibited the potato plant height, and the chlorophyll content and photosynthetic parameters in the leaves were reduced, and the enzyme activities of SOD and POD were significantly increased, all indicating that the leaves were damaged. Treatment at 10 °C also affected the tuberization of Huaxinyangyu and reduced the tuberization and coloring of Jianchuanhong, while treatment at 15 °C significantly increased the stem diameter, root-to-shoot ratio, yield and content of secondary metabolites, especially anthocyanins. Similarly, the expression of structural genes were enhanced in two pigmented potatoes under low-temperature treatment conditions. In short, proper low temperature can not only increase yield but also enhance secondary metabolites production. Previous studies have not focused on the effects of appropriate low-temperature treatment during the whole growth period of potato on the changes in metabolites during tuber growth and development, these results can provide a theoretical basis and technical guidance for the selection of pigmented potatoes with better nutritional quality planting environment and the formulation of cultivation measures.

Comparisons of different extraction methods and solvents for saliva samples.

INTRODUCTION: Changes in the categories and concentrations of salivary metabolites may be closely related to oral, intestinal or systemic diseases. To study salivary metabolites, the first analytical step is to extract them from saliva samples as much as possible, while reducing interferences to a minimum. Frequently used extraction methods are protein precipitation (PPT), liquid-liquid extraction (LLE) and solid-phase extraction (SPE), with various organic solvents. The types and quantities of metabolites extracted with different methods may vary greatly, but few studies have systematically evaluated them. OBJECTIVES: This study aimed to select the most suitable methods and solvents for the extraction of saliva according to different analytical targets. METHODS: An untargeted metabolomics approach based on liquid chromatography-mass spectrometry was applied to obtain the raw data. The numbers of metabolites, repeatability of the data and intensities of mass spectrometry signals were used as evaluation criteria. RESULTS: PPT resulted in the highest coverage. Among the PPT solvents, acetonitrile displayed the best repeatability and the highest coverage, while acetone resulted in the best signal intensities for the extracted compounds. LLE with the mixture of chloroform and methanol was the most suitable for the extraction of small hydrophobic compounds. CONCLUSION: PPT with acetonitrile or acetone was recommended for untargeted analysis, while LLE with the mixture of chloroform and methanol was recommended for small hydrophobic compounds.

Oral microbiota dysbiosis alters chronic restraint stress-induced depression-like behaviors by modulating host metabolism.

Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.

Augmented type 2 inflammatory response in allergic rhinitis patients experiencing systemic reactions to house dust mite subcutaneous immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. METHODS: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. RESULTS: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 µg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). CONCLUSION: The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.

Photocatalytic Nitrogen Fixation Coupled with the Generation of Value-Added Chemicals from N2 and Cellulose over MoO3 Nanosheets.

Photocatalytic nitrogen fixation from N2 provides an alternative strategy for ammonia (NH3) production, but it was limited by the consumption of a sacrificial electron donor for the currently reported half-reaction system. Here, we use naturally abundant and renewable cellulose as the sacrificial reagent for photocatalytic nitrogen fixation over oxygen-vacancy-modified MoO3 nanosheets as the photocatalyst. In this smartly designed photocatalytic system, the photooxidation of cellulose not only generates value-added chemicals but also provides electrons for the N2 reduction reaction and results in the production of NH3 with a maximum rate of 68 µmol·h-1·g-1. Also, the oxygen vacancies provide efficient active sites for both cellulose oxygenolysis and nitrogen fixation reactions. This work represents useful inspiration for realizing nitrogen fixation coupled with the generation of value-added chemicals from N2 and cellulose through a photocatalysis strategy.

Accelerated Charge Transfer through Interface Chemical Bonds in MoS2/TiO2 for Photocatalytic Conversion of Lignocellulosic Biomass to H2.

Solar photocatalytic H2 production from lignocellulosic biomass has attracted great interest, but it suffers from low photocatalytic efficiency owing to the absence of highly efficient photocatalysts. Herein, we designed and constructed ultrathin MoS2-modified porous TiO2 microspheres (MT) with abundant interface Ti-S bonds as photocatalysts for photocatalytic H2 generation from lignocellulosic biomass. Owing to the accelerated charge transfer related to Ti-S bonds, as well as the abundant active sites for both H2 and ●OH generation, respectively, related to the high exposed edge of MoS2 and the large specific surface area of TiO2, MT photocatalysts demonstrate good performance in the photocatalytic conversion of α-cellulose and lignocellulosic biomass to H2. The highest H2 generation rate of 849 µmol·g-1·h-1 and apparent quantum yield of 4.45% at 380 nm was achieved in α-cellulose aqueous solution for the optimized MT photocatalyst. More importantly, lignocellulosic biomass of corncob, rice hull, bamboo, polar wood chip, and wheat straw were successfully converted to H2 over MT photocatalysts with H2 generation rate of 10, 19, 36, 29, and 8 µmol·g-1·h-1, respectively. This work provides a guiding design approach to develop highly active photocatalysts via interface engineering for solar H2 production from lignocellulosic biomass.

Measuring job stress of dental workers in China during the COVID-19 pandemic: reliability and validity of the hospital consultants' job stress questionnaire.

BACKGROUND: The Hospital Consultants' Job Stress Questionnaire (HCJSQ) has been widely used to assess sources and levels of job stress. However, its reliability and validity among Chinese dental workers have not been extensively studied. The objective of this study was to assess the reliability and validity of the HCJSQ specifically in Chinese dental workers. METHODS: The HCJSQ was used to explore the sources and the global ratings of job stress among Chinese dental workers. To assess the reliability and validity of the HCJSQ, various statistical measures were employed, including Cronbach's alpha coefficient, Spearman-Brown coefficient, Spearman correlation coefficient, exploratory factor analysis, confirmatory factor analysis, convergent validity, and discriminant validity. RESULTS: Of the participants, 526 (17.4%) reported high levels of stress, while 1,246 (41.3%) and 1,248 (41.3%) reported moderate and low levels of stress, respectively. The Cronbach's alpha coefficient for the modified HCJSQ was 0.903, and the Spearman-Brown coefficient was 0.904. Spearman correlation coefficient between individuals' items and the total score ranged from 0.438 to 0.785 (p < 0.05). Exploratory factor analysis revealed that three factors accounted for 60.243% of the total variance. Confirmatory factor analysis demonstrated factor loadings between 0.624 and 0.834 on the specified items. The fit indices of the confirmatory factor analysis indicated good model fit, with a Root Mean Square Error of Approximation of 0.064, Normative Fit Index of 0.937, Comparative Fit Index of 0.952, Incremental Fit Index of 0.952, Tucker-Lewis index of 0.941, and Goodness of Fit Index of 0.944. Additionally, the convergent validity and discriminant validity showed a good fit for the three-factor model. CONCLUSION: The results of this study confirm that Chinese dental workers experience high levels of stress, and the three-factor model of the HCJSQ proves to be a suitable instrument for evaluating the sources and levels of job stress among Chinese dental workers. Therefore, it is imperative that relevant entities such as hospitals, medical associations, and government take appropriate measures to address the existing situation.

Long intergenic non-coding RNA 01126 activates IL-6/JAK2/STAT3 pathway to promote periodontitis pathogenesis.

OBJECTIVES: Periodontitis seriously affects oral-related quality of life and overall health. Long intergenic non-coding RNA 01126 (LINC01126) is aberrantly expressed in periodontitis tissues. This study aimed to explore the possible pathogenesis of LINC01126 in periodontitis. METHODS: Inflammatory model of human gingival fibroblasts (HGFs) was established. Cell Counting Kit-8 (CCK-8), wound healing assay, and flow cytometry were utilized to detect biological roles of LINC01126. Binding site of miR-655-3p to LINC01126 and IL-6 was predicted. Then, subcellular localization of LINC01126 and the binding ability of miR-655-3p to LINC01126 and IL-6 in HGFs were verified. Hematoxylin-Eosin (H&E) staining and immunohistochemistry (IHC) staining were utilized to detect tissue morphology and proteins expression of clinical samples. RESULTS: LINC01126 silencing can alleviate cell inflammation induced by lipopolysaccharide derived from Porphyromonas gingivalis, reduce cell apoptosis, and promote cell migration. As a "sponge" for miR-655-3p, LINC01126 inhibits its binding to mRNA of IL-6, thereby promoting inflammation progression and JAK2/STAT3 pathway activation. Quantitative real-time PCR, Western Blot, and IHC results of clinical tissue samples further confirmed that miR-655-3p expression was down-regulated and IL-6/JAK2/STAT3 was abnormally activated in periodontitis tissues. CONCLUSIONS: In summary, serving as an endogenous competitive RNA of miR-655-3p, LINC01126 promotes IL-6/JAK2/STAT3 pathway activation, thereby promoting periodontitis pathogenesis.

Salivary microbiota and metabolic phenotype of patients with recurrent aphthous ulcers.

OBJECTIVES: Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disease, affecting around 20% of the global population. It can greatly impair the quality of life for affected individuals. However, the exact etiology of RAU remains unknown. SUBJECTS AND METHODS: 16S rRNA sequencing (16S rRNA-seq) and non-targeted liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the salivary microbiota and metabolic phenotype between RAU patients (N = 61) and healthy controls (HCs) (N = 105). RESULTS: Findings from 16S rRNA -seq indicated reduced oral microbial diversity in RAU patients compared to HCs, but increased interactions. Clinical variables did not show any significant association with the overall diversity of oral microbiota in RAU patients. However, significant correlations were observed between specific microorganisms and clinical variables. LC-MS results revealed dysregulation of amino acid, lipid, nucleotide, and caffeine metabolism in RAU patients. Furthermore, correlation analysis of 16S rRNA-seq and LC-MS data revealed a significant association between salivary microbiota and metabolites in RAU patients. CONCLUSIONS: Our study revealed notable differences in salivary microbiota and metabolic profiles between RAU patients and HCs, indicating a strong link between oral microbiota dysbiosis, metabolic disturbances, and the onset and progression of RAU.

Chronic restraint stress promotes oral squamous cell carcinoma development by inhibiting ALDH3A1 via stress response hormone.

BACKGROUND: Chronic restraint stress (CRS) has iteratively been reported to be possibly implicated in the development of numerous cancer types. However, its role in oral squamous cell carcinoma (OSCC) has not been well elucidated. Here we intended to evaluate the role and mechanism. METHODS: The effects of CRS were investigated in xenograft models of OSCC by using transcriptome sequencing, LC-MS, ELISA and RT-PCR. Moreover, the role of CRS and ALDH3A1 on OSCC cells was researched by using Trans-well, flow cytometry, western blotting, immunofluorescence, ATP activity and OCR assay. Furthermore, immunohistochemical staining was employed to observe the cell proliferation and invasion of OSCC in xenotransplantation models. RESULTS: CRS promoted the progression of OSCC in xenograft models, stimulated the secretion of norepinephrine and the expression of ADRB2, but decreased the expression of ALDH3A1. Moreover, CRS changed energy metabolism and increased mitochondrial metabolism markers. However, ALDH3A1 overexpression suppressed proliferation, EMT and mitochondrial metabolism of OSCC cells. CONCLUSION: Inhibition of ALDH3A1 expression plays a pivotal role in CRS promoting tumorigenic potential of OSCC cells, and the regulatory of ALDH3A1 on mitochondrial metabolism may be involved in this process.

Do patients with cN0 oral squamous cell carcinoma benefit from elective neck dissection? A large-scale population-based study.

BACKGROUND: The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. METHODS: Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. RESULTS: A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P < 0.001 for OS) and T2 (P = 0.001 for DSS and < 0.001 for OS) tongue squamous cell carcinoma (TSCC) but not for other primary tumor sites. CONCLUSION: This large-scale retrospective population-based cohort study suggests that not all patients with cN0 OSCC could benefit from END. Patients with cN0 TSCC are recommended to undergo END, especially with early-stage tumors.

[Epidemiology and hospitalization costs analysis of female inpatients with acute exacerbation of chronic obstructive pulmonary disease in Beijing from 2013 to 2020].

OBJECTIVE: To study epidemiological characteristics and hospitalization costs of female inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing. METHODS: A retrospective study was conducted to analyze electronic hospitalization summary reports of female inpatients with AECOPD in Beijing from 2013 to 2020. Clinical characteristics (age distribution and comorbidities), epidemiological characteristics (temporal and spatial distribution characteristics), hospi-talization times and costs of patients were described. RESULTS: A total of 57 911 subjects in 166 hospitals were included in this study, with a mean age of (78.84±8.59) years and the highest number of patients aged 80-89 years (49.06%), followed by patients aged 70-79 years (31.08%), and the lowest number of patients under 50 years (0.41%). The proportions of patients with coronary heart disease, hypertension and heart failure were 30.60%, 30.52% and 26.54% respectively. The median number of daily hospitalizations during the study period was 18 (IQR: 16). The number of daily hospitalizations for AECOPD showed an overall growth trend over the eight years from 2013 to 2020, starting to increase significantly in 2015 and continuing to increase until 2019, then followed by a decline in 2020. The proportion of inpatient admissions was higher in winter and spring (54.09%) than that in summer and autumn (45.91%). The top three districts in terms of the proportion of total inpatient admissions were Xicheng district (14.18%), Chaoyang district (14.12%) and Fengtai district (13.47%). The density of inpatients was relatively high in the western regions, central urban areas and northeastern regions of the city, while the density of inpatients was relatively low in the near suburbs. The median number of hospital days for female patients with AECOPD was 12 days, and the median hospital costs was CNY 20 648.37. Patients from urban areas had longer hospitalization times and higher hospitalization costs than those from suburban areas (P < 0.001). Western medicine expenses accounted for the largest proportion of total hospital expenses (33.32%). During the study period, hospitalization costs exhibited an overall pattern of initial growth, followed by subsequent decline, eventually stabilizing. The differences in hospitalization costs among the patients with different comorbidities were significant. CONCLUSION: Female hospitalized patients with AECOPD in Beijing were older than 70 years, often complicated by cardiovascular disease. AECOPD occurred mainly in winter and spring, with regional differences. The hospitalization costs were closely associated with the patients' age, comorbidities, and the geographicical region.

Virtual and Interprofessional Objective Structured Clinical Examination in Dentistry and Dental Technology: Development and User Evaluations.

BACKGROUND: Interprofessional education (IPE) facilitates interprofessional collaborative practice (IPCP) to encourage teamwork among dental care professionals and is increasingly becoming a part of training programs for dental and dental technology students. However, the focus of previous IPE and IPCP studies has largely been on subjective student and instructor perceptions without including objective assessments of collaborative practice as an outcome measure. OBJECTIVE: The purposes of this study were to develop the framework for a novel virtual and interprofessional objective structured clinical examination (viOSCE) applicable to dental and dental technology students, to assess the effectiveness of the framework as a tool for measuring the outcomes of IPE, and to promote IPCP among dental and dental technology students. METHODS: The framework of the proposed novel viOSCE was developed using the modified Delphi method and then piloted. The lead researcher and a group of experts determined the content and scoring system. Subjective data were collected using the Readiness for Interprofessional Learning Scale and a self-made scale, and objective data were collected using examiner ratings. Data were analyzed using nonparametric tests. RESULTS: We successfully developed a viOSCE framework applicable to dental and dental technology students. Of 50 students, 32 (64%) participated in the pilot study and completed the questionnaires. On the basis of the Readiness for Interprofessional Learning Scale, the subjective evaluation indicated that teamwork skills were improved, and the only statistically significant difference in participant motivation between the 2 professional groups was in the mutual evaluation scale (P=.004). For the viOSCE evaluation scale, the difference between the professional groups in removable prosthodontics was statistically significant, and a trend for negative correlation between subjective and objective scores was noted, but it was not statistically significant. CONCLUSIONS: The results confirm that viOSCE can be used as an objective evaluation tool to assess the outcomes of IPE and IPCP. This study also revealed an interesting relationship between mutual evaluation and IPCP results, further demonstrating that the IPE and IPCP results urgently need to be supplemented with objective evaluation tools. Therefore, the implementation of viOSCE as part of a large and more complete objective structured clinical examination to test the ability of students to meet undergraduate graduation requirements will be the focus of our future studies.

Identification of a novel Providencia species showing multi-drug-resistant in three patients with hospital-acquired infection.

Providencia species are important opportunistic pathogens for humans and are associated with several infectious diseases. In this study, we found three clinical strains belonging to a novel Providencia species, namely Providencia huashanensis, including strains CRE-3FA-0001T, CRE-138-0026, and CRE-138-0111. These strains were recovered from three patients, and all of them were associated with nosocomial infections, including incision infection, urinary tract infection, and intracranial infection. The three strains showed high-level resistance to many types of antimicrobials, including amikacin, aztreonam, ceftazidime, cefepime, ciprofloxacin, colistin, polymyxin B, imipenem, meropenem, ceftazidime-avibactam, imipenem-relebactam. Investigation of the resistance mechanism revealed that acquired resistance genes such as blaKPC, blaNDM, blaPER, blaOXA, aac, ant, and qnrD, played an important role in the multi-drug-resistant phenotype for the three strains. The phylogenetic trees were reconstructed based on the 16S rRNA gene sequences, multi-locus sequence analysis, and core single nucleotide polymorphisms. The genome sequence of the strains had a range of 83.5%-85.8% average nucleotide identity and 21%-25.5% in silico DNA-DNA hybridization scores with other Providencia type strains. The average nucleotide identity and in silico DNA-DNA hybridization values and the phylogenetic trees indicated that the strains CRE-3FA-0001T, CRE-138-0026, and CRE-138-0111 strains should be considered as a novel species of the genus Providencia, for which the name P. huashanensis sp. nov. is proposed. The type strain is CRE-3FA-0001T = China Center for Type Culture Collection AB 2023186T = Korean Collection for Type Cultures 8373T.