Development and validation of a nomogram for predicting critical respiratory events during early anesthesia recovery in elderly patients.

BACKGROUND: Elderly patients undergoing recovery from general anesthesia face a heightened risk of critical respiratory events (CREs). Despite this, there is a notable absence of effective predictive tools tailored to this specific demographic. This study aims to develop and validate a predictive model (nomogram) to address this gap. CREs pose significant risks to elderly patients during the recovery phase from general anesthesia, making it an important issue in perioperative care. With the increasing aging population and the complexity of surgical procedures, it is crucial to develop effective predictive tools to improve patient outcomes and ensure patient safety during post-anesthesia care unit (PACU) recovery. METHODS: A total of 324 elderly patients who underwent elective general anesthesia in a grade A tertiary hospital from January 2023 to June 2023 were enrolled. Risk factors were identified using least absolute shrinkage and selection operator (LASSO) regression. A multivariate logistic regression model was constructed and represented as a nomogram. Internal validation of the model was performed using Bootstrapping. This study followed the TRIPOD checklist for reporting. RESULTS: The indicators included in the nomogram were frailty, snoring, patient-controlled intravenous analgesia (PCIA), emergency delirium and cough intensity at extubation. The diagnostic performance of the nomogram model was satisfactory, with AUC values of 0.990 and 0.981 for the training set and internal validation set, respectively. The optimal cutoff value was determined to be 0.22, based on a Youden index of 0.911. The F1-score was 0.927, and the MCC was 0.896. The calibration curve, Brier score (0.046), and HL test demonstrated acceptable consistency between the predicted and actual results. DCA revealed high net benefits of the nomogram prediction across all threshold probabilities. CONCLUSIONS: This study developed and validated a nomogram to identify elderly patients in the PACU who are at higher risk of CREs. The identified predictive factors included frailty condition, snoring syndrome, PCIA, emergency delirium, and cough intensity at extubation. By identifying patients at higher risk of CREs early on, medical professionals can implement targeted strategies to mitigate the occurrence of complications and provide better postoperative care for elderly patients recovering from general anesthesia.

Early positive tactile stimulation reverses the increase of anxiety and decrease of sociality induced by early chronic mechanical pain in mandarin voles.

Animals may experience early negative (mechanical pain: being retrieved using an incisor by parents or attacked) or positive stimulation (being licked and groomed) that may affect emotional and social behaviors in adulthood. Whether positive tactile stimulation can reverse adverse consequences on emotional and social behaviors in adulthood resulting from chronic mechanical pain and underlying mechanisms remain unclear. This study used a tail-pinching model during development to simulate mechanical pain experienced by pups in high-social mandarin voles (Microtus mandarinus). Subsequently, brush-like positive tactile stimuli were applied to the backs of the mandarin voles. Various behavioral tests were used to measure levels of anxiety, depression, and sociability. The results showed that early tail-pinching delayed the eye opening of pups, increased levels of anxiety, reduced levels of sociality in male mandarin voles, and impaired social cognition in females during adulthood. Brushing on the back reversed some of these effects. While mandarin voles that were exposed to tail-pinching during development were exposed to sub-threshold variable stress as adults, they were more likely to show a stress-induced increase of anxiety-like behavior, reduction of sociability, and impairment of social cognition, displaying heightened susceptibility to stress, particularly in males. However, back-brushing reversed some of these effects, implying that these adults display enhanced stress resilience. In addition, tail-pinching reduced levels of serum oxytocin and increased corticosterone levels in serum, but back-brushing reversed these effects. Overall, it was found that positive tactile stimulation reversed increases in anxiety and impairments of social behavior induced by negative stimulation in male mandarin voles via alteration of oxytocin and corticosterone levels.

Copper-Catalyzed Oxidative α-Double Bond Construction in α-Amino Carbonyl Compounds via Homocoupling with Arylamine Release.

Herein, we present a copper-catalyzed method for oxidative α-double bond formation in α-amino ketone compounds using DTBP as the oxidant. This process, involving homocoupling of α-amino radicals and arylamine release, efficiently produces a series of enaminone skeletons. The strategy has a broad substrate scope and functional group tolerance. In particular, arylamines bearing electron-rich substituents exhibit a pronounced reactivity. This approach facilitates the synthesis of diverse enaminones, enabling the efficient construction of nitrogen-containing heterocycles.

Toxoplasma gondii infection is associated with schizophrenia from the perspectives of seroepidemiology and serum metabolomics in Hunan Province, China.

Toxoplasma gondii (T.gondii) can influence the host's neurotransmission, central immune responses, and brain structure, potentially impacting the onset and development of various psychiatric disorders such as schizophrenia. We employed Electrochemiluminescence Immunoassay (ECLIA) to measure anti-Toxoplasma antibodies in 451 schizophrenic patients and 478 individuals from the general population in Hunan, China. The incidence rate of T.gondii infection in schizophrenic patients (8.87 %) was higher than that in the general population (3.77 %). A significant difference was observed among females, but not in males. Age-stratified analysis revealed significant differences in the 21-40 and 41-60 age groups. The two populations had no significant difference in the antibody titer for T. gondii infection. Additionally, the profile of circulating metabolites in the serum of schizophrenic patients with or without T. gondii infection was examined using non-targeted metabolomics assay. A total of 68 metabolites were differentially expressed between Toxoplasma-positive and Toxoplasma-negative groups, potentially mediating the connection between T. gondii infection and schizophrenia. Our research suggests that schizophrenic patients are susceptible to T. gondii infection with distinct metabolic program.

Metabolomic and Transcriptomic Analyses Revealed Lipid Differentiation Mechanisms in Agaricus bisporus at Ambient Conditions.

Agaricus bisporus is one of the most popular mushroom species in the world; however, mushrooms are highly susceptible to browning due to the absence of a protective cuticle layer and high respiration rate. The molecular mechanism underlying the process of mushroom browning needs to be explored. Here, we analyzed the transcriptomic and metabolomic data from A. bisporus at ambient temperature. Specifically, a total of 263 significantly changed metabolites and 4492 differentially expressed genes were identified. Lipid metabolites associated with cell membrane degradation were predominantly up-regulated during ambient storage. Transcriptomic data further revealed the alterations of the expression of membrane lipid metabolism-related enzymes. Additionally, energy metabolic processes and products such as glycolysis and linoleic acid changed significantly during ambient storage, indicating their potential roles in the quality deterioration of A. bisporus. These findings provide new insights into the underlying lipid metabolic mechanisms of A. bisporus during postharvest ambient storage and will provide values for mushroom preservation techniques.

Prediction models for amputation after diabetic foot: systematic review and critical appraisal.

BACKGROUND: Numerous studies have developed or validated prediction models aimed at estimating the likelihood of amputation in diabetic foot (DF) patients. However, the quality and applicability of these models in clinical practice and future research remain uncertain. This study conducts a systematic review and assessment of the risk of bias and applicability of amputation prediction models among individuals with DF. METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, EBSCO CINAHL Plus, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedical Literature Database (CBM), and Weipu (VIP) from their inception to December 24, 2023. Two investigators independently screened the literature and extracted data using the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies. The Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist was employed to evaluate both the risk of bias and applicability. RESULTS: A total of 20 studies were included in this analysis, comprising 17 development studies and three validation studies, encompassing 20 prediction models and 11 classification systems. The incidence of amputation in patients with DF ranged from 5.9 to 58.5%. Machine learning-based methods were employed in more than half of the studies. The reported area under the curve (AUC) varied from 0.560 to 0.939. Independent predictors consistently identified by multivariate models included age, gender, HbA1c, hemoglobin, white blood cell count, low-density lipoprotein cholesterol, diabetes duration, and Wagner's Classification. All studies were found to exhibit a high risk of bias, primarily attributed to inadequate handling of outcome events and missing data, lack of model performance assessment, and overfitting. CONCLUSIONS: The assessment using PROBAST revealed a notable risk of bias in the existing prediction models for amputation in patients with DF. It is imperative for future studies to concentrate on enhancing the robustness of current prediction models or constructing new models with stringent methodologies.

The functions of triple gene block proteins and coat protein of apple stem pitting virus in viral cell-to-cell movement.

Apple stem pitting virus is a species in the genus Foveavirus in the family Betaflexiviridae. Apple stem pitting virus (ASPV) commonly infects apple and pear plants grown worldwide. In this study, by integrating bimolecular fluorescence complementation, split-ubiquitin-based membrane yeast two-hybrid, and Agrobacterium-mediated expression assays, the interaction relationships and the subcellular locations of ASPV proteins TGBp1-3 and CP in Nicotiana benthamiana leaf cells were determined. Proteins CP, TGBp1, TGBp2, and TGBp3 were self-interactable, and TGBp2 played a role in the formation of perinuclear viroplasm and enhanced the colocalization of TGBp3 with CP and TGBp1. We found that the plant microfilament and endoplasmic reticulum structures were involved in the production of TGBp3 and TGBp2 vesicles, and their disruption decreased the virus accumulation level in the systemic leaves. The TGBp3 motile vesicles functioned in delivering the viral ribonucleoprotein complexes to the plasma membrane. Two cysteine residues at sites 35 and 49 of the TGBp3 sorting signal were necessary for the diffusion of TGBp3-marked vesicles. Furthermore, our results revealed that TGBp1, TGBp2, and CP could increase plasmodesmal permeability and move to the adjacent cells. This study demonstrates an interaction network and a subcellular location map of four ASPV proteins and for the first time provides insight into the functions of these proteins in the movement of a foveavirus.

Pediatric adenovirus pneumonia: clinical practice and current treatment.

Adenovirus pneumonia is common in pediatric upper respiratory tract infection, which is comparatively easy to develop into severe cases and has a high mortality rate with many influential sequelae. As for pathogenesis, adenoviruses can directly damage target cells and activate the immune response to varying degrees. Early clinical recognition depends on patients' symptoms and laboratory tests, including those under 2 years old, dyspnea with systemic toxic symptoms, atelectasis or emphysema in CT image, decreased leukocytes, and significantly increased C-reaction protein (CRP) and procalcitonin (PCT), indicating the possibility of severe cases. Until now, there is no specific drug for adenovirus pneumonia, so in clinical practice, current treatment comprises antiviral drugs, respiratory support and bronchoscopy, immunomodulatory therapy, and blood purification. Additionally, post-infectious bronchiolitis obliterans (PIBO), hemophagocytic syndrome, and death should be carefully noted. Independent risk factors associated with the development of PIBO are invasive mechanical ventilation, intravenous steroid use, duration of fever, and male gender. Meanwhile, hypoxemia, hypercapnia, invasive mechanical ventilation, and low serum albumin levels are related to death. Among these, viral load and serological identification are not only "gold standard" for adenovirus pneumonia, but are also related to the severity and prognosis. Here, we discuss the progress of pathogenesis, early recognition, therapy, and risk factors for poor outcomes regarding severe pediatric adenovirus pneumonia.

Preparation of biochar-based surface molecularly imprinted polymers and evaluation of their selective adsorption and removal of carbaryl from rice and corn.

The residue of carbaryl in food is a threat to human health. In this study, activated soybean shell biochar (A-SBC) was used as a carrier, methacrylic acid (MAA) was used as a functional monomer, and carbaryl was used as a template molecule to synthesize the activated biochar surface molecularly imprinted polymer (A-SBC@MIP). The synthesized A-SBC@MIP was characterized by SEM, FT-IR, XRD and XPS techniques, and then applied as adsorbent for carbaryl removal. The adsorption capacity of A-SBC@MIP for carbaryl was 8.6 mg‧g-1 and the imprinting factor was 1.49 at the optimum ionic strength and pH. The kinetic and isothermal data indicated that it had fast mass transfer rate and high binding capacity(Qmax=47.9 mg‧g-1). A-SBC@MIP showed good regenerative properties and the adsorption of carbaryl was excellent in its structural analogues. A solid-phase extraction (SPE) column composed of A-SBC@MIP was developed for the detection of rice and corn under optimized conditions, with recoveries of 93-101% for the spiked carbaryl. The limit of detection (LOD) of the method was 3.6 µg‧kg-1 with good linearity (R2=0.994) in the range of 0.01-5.00 mg‧L-1. The results show that the developed MIPs-SPE can enrich carbaryl from food samples as a specific and cost-effective method.

Evaluation of the high-quality development of China's media industry.

Accelerating the in-depth integration of media to achieve high-quality development in the media industry has become important for China's cultural media. We built a high-quality development index system for China's media sector and used financial data from A-share media industry listed companies from 2017 to 2020 to measure the high-quality development index of China's media business using the Global Malmquist-Luenberger production function method with the framework of the SBM model degree. We used the generalised method of moments model and the single-threshold model to estimate the threshold value of the media convergence degree and its factor distortions. Deep media integration can promote high-quality development in the media sector. However, insufficient and unbalanced development of media integration is the main hindrance to China's high-quality development of its media.

Development and Psychometric Properties of a Scale Measuring Barriers to Perioperative Hypothermia Prevention for Anesthesiologists and Nurses.

PURPOSE: To develop a scale that measures barriers to perioperative hypothermia prevention (BPHP) as perceived by anesthesiologists and nurses. DESIGN: A methodological and prospective psychometric study. METHODS: Based on the theoretical domains framework, the item pool was created through a literature review, qualitative interviews, and expert consultation. The scale was pretested with a sample of 154 key stakeholders in perioperative temperature management and then field tested with 416 anesthesiologists and nurses working at three hospitals in Southeast China. Item analysis, and reliability and validity analysis were performed. FINDINGS: The average content validity index was 0.94. According to exploratory factor analysis, seven factors were obtained that could explain 70.283% of the total variance. Confirmatory factor analysis showed excellent or acceptable goodness-of-fit indices. The reliability analysis demonstrated that the scale had high internal consistency and temporal stability, with Cronbach's α, split-half coefficient and test-retest values of 0.926, 0.878 and 0.835, respectively. CONCLUSIONS: The BPHP scale meets the psychometric criteria for reliability and validity and promises to be a useful quality measure for IPH management during the perioperative period. Further investigations on educational or resource needs and the development of an optimal perioperative hypothermia prevention protocol to narrow the gap between research evidence and clinical practice should be performed.

Construction of a Molecularly Imprinted Sensor Modified with Tea Branch Biochar and Its Rapid Detection of Norfloxacin Residues in Animal-Derived Foods.

Norfloxacin (NOR) is a common antibiotic used in humans and animals, and its high levels can cause intolerance or poisoning. Therefore, NOR levels in animal-derived foods must be monitored due to potential side effects and illegal use phenomena. This research centered on the development of an environmentally friendly electrochemical sensor for NOR detection. Potassium carbonate activated tea branch biochar (K-TBC) as an efficient use of waste was coated on the surface of glassy carbon electrode (GCE), and a molecular-imprinted polymer (MIP) layer was subsequently electropolymerized onto the modified electrode. NOR was used as template molecule and o-phenylenediamine (o-PD) and o-aminophenol (o-AP) were used as bifunctional monomers. The electrochemical sensor was built and its electrochemical behavior on NOR was investigated. The sensor demonstrated an excellent linear current response to NOR concentrations in the ranges of 0.1-0.5 nM and 0.5-100 nM under ideal experimental circumstances, with a detection limit of 0.028 nM (S/N = 3). With recoveries ranging from 85.90% to 101.71%, the designed sensor was effectively used to detect NOR in actual samples of milk, honey, and pork. Besides, the fabricated sensor had low price, short detection time, good selectivity and stability, which can provide a theoretical and practical basis for the actual monitoring of NOR residues.

Exploring the Coordination and Spatial-Temporal Characteristics of the Tourism-Economy-Environment Development in the Pearl River Delta Urban Agglomeration, China.

The rise of mass tourism has encouraged rapid economic growth; meanwhile, the eco-environmental system has come under increasing pressure. To achieve sustainable development, it is critical to deeply explore the relationship and evolution characteristics between three subsystems: tourism, the economy, and the eco-environment. This study aims to develop a more comprehensive indicator system for evaluating the coupling coordination degree (CCD) of the tourism-economy-environment (TEE) system using statistical data from nine cities in the Pearl River Delta (PRD) urban agglomeration from 2010 to 2019. We investigated the spatial-temporal evolution characteristics and driving forces of the TEE system in the PRD using the CCD model and the geo-detector model. The research results show the following: (1) The comprehensive benefits of the TEE system have increased steadily over the past 10 years, whereas the benefits of the eco-environment subsystem have fluctuated and been relatively unstable. (2) Spatially, in terms of tourism development, the eastern regions of the PRD are more developed than the western regions, and the regions with the greatest tourism benefits have gradually shifted to the northeastern regions of the PRD. Economic development presented an imbalanced but relatively stable spatial pattern. Guangzhou and Shenzhen have been the two most economically developed cities over the past 10 years. The eco-environment development has fluctuated over time, revealing a spatial pattern of cities with low environmental benefits in the center and cities with high eco-environmental benefits in the surrounding regions. (3) The PRD's TEE system has become more integrated, moving from moderate disorder to a model of high-quality coordinated development, demonstrating a spatial pattern in which the cities of high development coordination are located near the Pearl River Estuary, and the coordination decreases the further away they are from the estuary. (4) The major driving factors of heterogeneous TEE coordination development include eco-environment protection, opening-up policies, education investment, technological innovation level, and the regional economic development level. The results are expected to effectively promote economic, tourism, and environmental improvement in the PRD, as well as to provide policy recommendations for coordinated TEE development in other similar urban agglomerations.

Oct4 reduction contributes to testicular injury of unilateral testicular torsion in mice model and apoptotic death of Sertoli cells through mediating CIP2A expression.

This study explored the mechanism of ipsilateral testis injury after ipsilateral testicular torsion detorsion (T/D) and the potential testis-protective part of the octamer-binding transcription factor 4 (Oct4)-cancerous inhibitors of protein phosphatase 2A (CIP2A) axis in a T/D animal model and in ischemia-reperfusion (IR)-treated testicular Sertoli TM4 cells. Quantitative Polymerase chain reaction (PCR) and western blot (WB) confirmed the downregulation of both CIP2A and Oct4 expression in the testicular tissue from T/D mice compared with sham-operated mice. T/D model was then established in mice with upregulated Oct4 expression in the testis. Oct4 elevation restored CIP2A expression in testes after T/D treatment. Furthermore, we observed that an increase in Oct4 ameliorated the testicular damage caused by torsion in the testis. Biochemical analysis indicated that T/D treatment increased serum anti-sperm antibody levels, but reduced testosterone levels. Meanwhile, in testicular tissue, reactive oxygen species (ROS), malondialdehyde (MDA), and activity of testicular myeloperoxidase (MPO) enzymes were promoted, while glutathione peroxidase activity (GPx) was decreased by T/D injury. Notably, testicular Oct4 restoration partially counteracted the effect of T/D treatment on these biochemical indices. Hypoxia/reoxygenation (HR) treatment was applied to TM4 cells to mimic TT injury in vitro. A gain-of-function study showed that Oct4 overexpression partly counteracted the promoting role of HR in cell damage, apoptosis, and oxidative stress in TM4 cells. These observations provide novel insights into the possible biochemical mechanism underlying the mediation of the Oct4-CIP2A axis in T/D injury.

Identification and Exploration of Serine Peptidase Inhibitor Kazal Type I (SPINK1) as a Potential Biomarker Correlated with the Progression of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Although significant advances have been achieved in the treatment of NSCLC during the past two decades, the 5-year survival rate of patients with NSCLC remains <20%. Thus, there is an urgent requirement to further understand the molecular mechanisms that promote NSCLC development and to identify novel therapeutic targets. In the present study, the gene expression profiles of patients with NSCLC from The Cancer Genome Atlas database were carefully analyzed and SPINK1 was identified as a tumor-inducing factor. SPINK1 expression level was found to be increased in both NSCLC tissues and cell lines. Moreover, SPINK1 promoted cell proliferation in A549 and H1299 cells. Knockdown of SPINK1 could activate cell autophagy and apoptosis. Mechanistically, SPINK1 was demonstrated to induce the proliferation of NSCLC via activating the MEK/ERK signaling pathway. In conclusion, these findings suggested that SPINK1 may serve as a potential biomarker in NSCLC.

Periodontitis induced by orthodontic wire ligature drives oral microflora dysbiosis and aggravates alveolar bone loss in an improved murine model.

Aim: To assess the contribution of polymicrobial disruption of host homeostasis to periodontitis progression in orthodontic wire ligation murine model. Methods: Orthodontic wire rings were inserted between the first and second molars of mice for 18 days for the orthodontic wire ligation mouse model, and Pg injection model and Pg-LPS injection model were used as controls. Alveolar bone loss and periodontal inflammation were analyzed by micro-CT, histological staining and qRT-PCR. Further, pyrosequencing of 16S rRNA gene amplicon was used to analyze the development of oral microorganism dysbiosis in the mice. Results: Micro-CT, TRAP staining and qRT-PCR showed that orthodontic wire ligation model led to more severe alveolar bone loss than Pg and Pg-LPS models.H&E staining and qRT-PCR demonstrated that stronger inflammatory response was induced by the orthodontic wire treatment compared to the other models. In addition, pyrosequencing of 16S rRNA gene amplicons revealed that the composition of oral microbiota presented a transition as the disease progressed and significant differences emerged in oral microbiota communities between orthodontic ligature mice and healthy controls. Furthermore, antibiotic treatment decreased both inflammation and alveolar bone loss in response to microbial community dysbiosis. However, no significant difference in bacterial community composition was observed in Pg and Pg-LPS models. Conclusions: Orthodontic wire ligation drove oral microbial community transitions that mimicked polymicrobial communities characterized by polymicrobial synergy and dysbiosis. Our improved model is suitable for further study of pathogenesis of periodontitis and exploration of corresponding treatment strategies.

Facile Synthesis of N, S-Doped Carbon Quantum Dots from Food Waste as Fluorescent Probe for Sensitive Detection of Thiamphenicol and Its Analogues in Real Food Samples along with an Application in Bioimaging.

Herein, N, S co-doped carbon quantum dots (N, S-CDs) with high absolute quantitative yield (Abs-QY) of 50.2% were produced by hydrothermal treatment of food residue crayfish shells. A new detection method of thiamphenicol (TAP) and its analogues was established by discovering the obvious fluorescence response between TAP and N, S-CDs, which achieved a wide linear range of 20-300 µg·L-1 with a detection limit (LOD) of 11.12 µg·L-1. This novel probe exhibited strong sensitivity and shows rapid response in complex food matrices (overall detection time is less than 45 min) mainly induced by static quenching. Spiked food sample recovery ranged from 97.3 to 99.34%. Further, the cell experiments of N, S-CDs were conducted, and the cell viability remained 91.76% under high concentration of N, S-CDs due to the environmentally friendly materials. The low cytotoxicity and good cytocompatibility make these N, S-CDs compatible for cell bioimaging and intracellular detection of TAP.

Development of a sensitive real-time quantitative RT-PCR assay for the detection of pear chlorotic leaf spot-associated virus.

Pear chlorotic leaf spot associated virus (PCLSaV) belongs to the genus Emaravirus and possesses a genome composed of five negative-sense single-stranded RNA (-ssRNA) segments. This study developed a SYBR green-based reverse transcription quantitative PCR (RT-qPCR) assay for the detection of PCLSaV infecting pear trees. A set of two primers q5-F2/q5-R2 designed based on the viral RNA5 sequences showed high specificity and feasibility for PCLSaV detection. The standard curve was established. RT-qPCR assays showed that PCLSaV content was greatly higher in diseased branch and symptomatic leaf samples than that in un-diseased branch and asymptomatic leaf samples. The RT-qPCR was reliability in the detection of the virus in field and in-vitro cultured pear samples. This technique would be useful for the supervision of the viral disease and the certification of pear planting materials.

Coupling Coordination Degree between the Socioeconomic and Eco-Environmental Benefits of Koktokay Global Geopark in China.

The rapid economic growth of geoparks has put pressure on their ecological environments. Therefore, to ensure the sustainable development of geoparks, we must explore the coupling relationship between their socioeconomic benefits (SEBs) and eco-environmental benefits (EEBs). Based on coupling coordination theory and using statistical data from 2005 to 2018, in this study, we aimed to establish an indicator system for evaluating the coupling coordination degree (CCD) between the SEBs and EEBs of the Koktokay Global Geopark in China, which is both theoretically and practically relevant for research on the sustainable development of geoparks. As a result, we found the following: First, the comprehensive development level of the SEBs of the Koktokay Global Geopark showed a fluctuating upward trend during the study period. Second, the comprehensive development level of the EEBs of the geopark remained stable but fluctuated slightly: it declined from 2009 to 2012, affected by the deterioration of the eco-environment, and fell to its lowest point in 2012. By strengthening the protection of the eco-environment of geoparks, the EEBs gradually improved and became stable. Finally, we found that the CCD between the SEBs and EEBs of the Koktokay Global Geopark improved from mildly disordered to basically coordinated, indicating that the CCD is developing toward an increasingly higher level. The purpose of this study was to promote the reasonable development of geotourism while focusing on a sound eco-environment and to provide recommendations for the sustainable development of the Koktokay Global Geopark and a reference for the development of other similar geoparks.

MZB1 targeted by miR-185-5p inhibits the migration of human periodontal ligament cells through NF-κB signaling and promotes alveolar bone loss.

OBJECTIVE: To explore the role of Marginal Zone B and B-1 Cell-Specific Protein (MZB1), a novel molecule associated with periodontitis, in migration of human periodontal ligament cells (hPDLCs) and alveolar bone orchestration. BACKGROUND: MZB1 is an ER-localized protein and its upregulation has been found to be associated with a variety of human diseases. However, few studies have investigated the effect and mechanism of MZB1 on hPDLCs in periodontitis. METHODS: Gene expression profiles in human gingival tissues were acquired from the Gene Expression Omnibus (GEO) database, and candidate molecules were then selected through bioinformatic analysis. Subsequently, we identified the localization and expression of MZB1 in human gingival tissues, mice, and hPDLCs by immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was applied to assess the binding of miR-185-5p to MZB1. Furthermore, the effects of MZB1 on cell migration, proliferation, and apoptosis in vitro were investigated by wound-healing assay, transwell assay, CCK-8 assay, and flow cytometry analysis. Finally, Micro-CT analysis and H&E staining were performed to examine the effects of MZB1 on alveolar bone loss in vivo. RESULTS: Bioinformatic analysis discovered that MZB1 was one of the most significantly increased genes in periodontitis patients. MZB1 was markedly increased in the gingival tissues of periodontitis patients, in the mouse models, and in the hPDLCs treated with lipopolysaccharide of Porphyromonas gingivalis (LPS-PG). Furthermore, in vitro experiments showed that MZB1, as a target gene of miR-185-5p, inhibited migration of hPDLCs. Overexpression of MZB1 specifically upregulated the phosphorylation of p65, while pretreatment of MZB1-overexpressed hPDLCs with PDTC (NF-κB inhibitor) notably reduced the p-p65 level and promoted cell migration. In addition, the mRNA expression levels of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2) were inhibited in MZB1-overexpressed hPDLCs and miR-185-5p inhibitor treated hPDLCs, respectively. In vivo experiments showed that knockdown of MZB1 alleviated the loss of alveolar bone. CONCLUSION: As a target gene of miR-185-5p, MZB1 plays a crucial role in inhibiting the migration of hPDLCs through NF-κB signaling pathway and deteriorating alveolar bone loss.