ABSTRACT
BACKGROUND: Understanding the tooth anatomy is crucial for ensuring effective endodontic treatment. This study investigated the root canal morphology of the second mesiobuccal (MB2) canal in maxillary first molars (MFMs) in a Chinese population using cone-beam computed tomography (CBCT). METHODS: This study evaluated 486 MFMs with MB2 canals from 285 participants undergoing CBCT examination and determined the Vertucci's classification and position of the MB2 canal orifice. The prevalence of the MB2 canal was correlated with the sex, age, and tooth side. The correlations between the prevalence of the MB2 canal and sex and tooth side were assessed using the Fisher's exact test. The chi-square test was used for evaluating the correlation between the prevalence of the MB2 canal and age. RESULTS: The number of type II, III, IV, V, VI, VII, and other root canals in the MFMs was 30.9%, 0.6%, 65.0%, 1.2%, 1.2%, 0.4%, and 0.6%, respectively. Among the 201 cases with bilateral inclusion, 87.6% showed consistent canal configuration. Results of the first clear apparent position (FCAP) of the MB2 canals showed that 434, 44, and 3 teeth had FCAP at the upper, middle, and bottom one-third of the root, respectively. The FCAPs of the MB2 canal in the MFMs with types II, IV, and VI, as well as types III and V canals showed significant differences (p<0.05). The horizontal distance between the MB1 and MB2 canal orifices in the type II canals of MFMs was significantly lesser than those in the type IV canals of MFMs (p < 0.01). The longitudinal distance between the pulp chamber floor plane and MB2 canal orifice significantly correlated with age (p < 0.05). CONCLUSIONS: The morphology of the mesiobuccal root canal in the MFMs is complex. Complete understanding of the anatomical morphology of the root canal combined with the CBCT and dental operating microscope is necessary for the accurate detection of the MB2 canal and consequently improved success rate of root canal treatment. Our study findings can help endodontists improve endodontic treatment outcomes.
Subject(s)
Cone-Beam Computed Tomography , Dental Pulp Cavity , Maxilla , Molar , Humans , Cone-Beam Computed Tomography/methods , Molar/anatomy & histology , Molar/diagnostic imaging , Male , Female , Adult , Dental Pulp Cavity/diagnostic imaging , Dental Pulp Cavity/anatomy & histology , Middle Aged , Maxilla/diagnostic imaging , Maxilla/anatomy & histology , China , Adolescent , Aged , Young Adult , East Asian PeopleABSTRACT
Anemia commonly aggravates the severity of respiratory diseases, whereas thus far, few studies have elucidated the impact of anemia on coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the clinical characteristics of patients with anemia, and to further explore the relationship between anemia and the severity of COVID-19. In this single-center, retrospective, observational study, a total of 222 confirmed patients admitted to Wuhan Ninth Hospital from 1 December 2019 to 20 March 2020 were recruited, including 79 patients with anemia and 143 patients without anemia. Clinical characteristics, laboratory findings, disease progression and prognosis were collected and analyzed. Risk factors associated with the severe illness in COVID-19 were established by univariable and multivariable logistic regression models. In our cohort, compared to patients without anemia, patients with anemia were more likely to have one or more comorbidities and severe COVID-19 illness. More patients demonstrated elevated levels of C-reactive protein (CRP), procalcitonin (PCT) and creatinine in anemia group. Levels of erythrocyte sedimentation rate, D-dimer, myoglobin, T-pro brain natriuretic peptide (T-pro-BNP) and urea nitrogen in patients with anemia were significantly higher than those without. In addition, the proportion of patients with dyspnea, elevated CRP, and PCT was positively associated with the severity of anemia. The odd ratio of anemia related to the severe condition of COVID-19 was 3.47 (95% confidence interval [CI]: 1.02-11.75; P = .046) and 3.77 (95% CI: 1.33-10.71; P = .013) after adjustment for baseline date and laboratory indices, respectively. Anemia is an independent risk factor associated with the severe illness of COVID-19, and healthcare professionals should be more sensitive to the hemoglobin levels of COVID-19 patients on admission. Awareness of anemia as a risk factor for COVID-19 was of great significance.
Subject(s)
Anemia/complications , COVID-19/complications , COVID-19/physiopathology , Adult , Aged , C-Reactive Protein/analysis , COVID-19/diagnosis , Comorbidity , Disease Progression , Humans , Inflammation , Middle Aged , Procalcitonin/blood , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness IndexABSTRACT
INTRODUCTION: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. METHODS: Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. RESULTS: Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84-0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R2 = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients. CONCLUSIONS: We validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.
Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , COVID-19/complications , Severity of Illness Index , Acute Kidney Injury/mortality , Adult , Aged , COVID-19/mortality , China/epidemiology , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Regression Analysis , Retrospective Studies , Risk Factors , SARS-CoV-2ABSTRACT
BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.
Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Hypophosphatemia/complications , Pneumonia, Viral/complications , Acute Kidney Injury/epidemiology , COVID-19/epidemiology , China/epidemiology , Female , Hospitalization , Humans , Hypophosphatemia/epidemiology , Incidence , Intensive Care Units , Kidney Function Tests , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Retrospective Studies , Risk Factors , SARS-CoV-2ABSTRACT
BACKGROUND: The objective of this report was to highlight the importance of using a dental operating microscope (DOM) to locate supernumerary canals and diagnose variations in root canals using cone-beam computed tomographic (CBCT) images. CASE PRESENTATION: A 35-year-old Chinese female had repeated swelling in the upper right posterior maxilla for 3 months and was referred to evaluate symptomatic apical periodontitis and mesotaurodonts for upper right first permanent molar and upper right second permanent molar. Root canal therapy was proposed and conducted with the use of DOM and CBCT. CONCLUSIONS: Proper diagnosis and careful clinicoradiological examination are necessary, and it is essential to reinforce the knowledge of the rare morphology of root canals for clinicians.
Subject(s)
Dental Pulp Cavity , Tooth Root , Adult , Cone-Beam Computed Tomography , Dental Pulp Cavity/diagnostic imaging , Female , Humans , Maxilla/diagnostic imaging , Molar/diagnostic imagingABSTRACT
Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system and the level of GFAP normally rises with brain injury and astroglial tumors. So, serum GFAP is used as a marker for diagnosing various types of brain damage and astroglial tumors. In this study, a new sensor based on carbon dots (CDs) linked with antibodies to specifically detect GFAP in human serum was developed. Anti-GFAP (Ab1) linked with protein A/G agarose resin (PA/G) as a capture antibody (PA/G-Ab1) and anti-GFAP (Ab2) labeled with CDs as a detection antibody (CDs-Ab2) were prepared firstly. Then the CD-linked antibody immunosorbent assay (CLAISA) method was constructed based on the sandwich conjunction reaction among PA/G-Ab1, GFAP, and CDs-Ab2. CLAISA, using the fluorescence of PA/G-Ab1-GFAP-Ab2-CDs as the direct signal, enabled the proposed immunosensor to detect GFAP sensitively with a linear range of 0.10-8.00 ng ml-1 and a detection limit of 25 pg ml-1. This method was applied to the determination of GFAP in human serum by the standard addition method, and the results showed high accuracy and precision. Considering the easy synthetic process and excellent performance of CLAISA, this method has great potential to be used to monitor GFAP in the clinic.
Subject(s)
Antibodies, Monoclonal/chemistry , Carbon/chemistry , Glial Fibrillary Acidic Protein/blood , Immunosorbent Techniques , Quantum Dots/chemistry , Animals , Antibodies, Monoclonal/isolation & purification , Bacterial Proteins/chemistry , Bacterial Proteins/immunology , Fluorescence , Humans , Immunization , Limit of Detection , Quantum Dots/ultrastructure , Rabbits , Reproducibility of Results , Staphylococcal Protein A/chemistry , Staphylococcal Protein A/immunologyABSTRACT
The authors describe a fluorometric aptamer based assay for adenosine triphosphate (ATP). It is based on the use of carbon dots (CDs) and graphene oxide (GO). The resultant CD-aptamer is adsorbed on the surface of GO via π-stacking and hydrophobic interaction, and the fluorescence of CD-aptamer is quenched via fluorescence resonance energy transfer (FRET) between CDs and GO. If ATP is present, it will bind to the aptamer and the CD-aptamer will be desorbed from GO. This will suppress FRET and the fluorescence of the CDs is restored. Under the optimal conditions and at typical excitation/emission wavelengths of 358/455 nm, the assay has a 80 pM detection limit and a linear range that extends from 0.10 to 5.0 nM concentrations of ATP. The method was successfully applied to the determination of ATP in yogurt samples. This method can also be conceivably applied to the detection of other analytes for which appropriate aptamers are available. Graphical abstract Schematic of a novel fluorometric ATP assay based on the fluorescence resonance energy transfer (FRET) between aptamer modified carbon dots (CD-aptamer) and graphene oxide (GO). CD-aptamer was used as the energy donor and molecular recognition probe, and GO acted as energy acceptor. This assay exhibits high sensitivity and selectivity with a detection limit as low as 80 pM.
ABSTRACT
The authors describe an aptamer-based fluorescent assay for adenosine (Ade). It is based on the interaction between silver nanoparticles (AgNPs) and CdTe quantum dots (QDs). The beacon comprises a pair of aptamers, one conjugated to Fe3O4 magnetic nanoparticles, the other to AgNPs. In the presence of Ade, structural folding and sandwich association of the two attachments takes place. After magnetic separation, the associated sandwich structures are exposed to the QDs. The AgNPs in sandwich structures act as the signaling label of Ade by quenching the fluorescence of QDs (at excitation/emission wavelengths of 370/565 nm) via inner filter effect, electron transfer and trapping processes. As a result, the fluorescence of QDs drops with increasing Ade concentration. The assay has a linear response in the 0.1 nM to 30 nM Ade concentration range and a 60 pM limit of detection. The assay only takes 40 min which is the shortest among the aptamer-based methods ever reported. The method was successfully applied to the detection of Ade in spiked biological samples and satisfactory recoveries were obtained. Graphical abstract Schematic of a highly efficient and convenient adenosine (Ade) fluorometric assay. It is based on the interaction between Ag nanoparticles (NPs) and CdTe quantum dots (QDs). Ade aptamers (ABA1 and ABA2) are used as recognition unit and Fe3O4 magnetic nanoparticles act as magnetic separator. The assay exhibits superior sensitivity and speediness.
ABSTRACT
The authors describe a fluorometric aptamer based assay for detecting ß-lactoglobulin by using carbon dots (C-dots) as a signal indicator. The aptamer was immoblized on magnetite (Fe3O4) nanoparticles (MNPs), and the C-dots served as a label for the complementary oligonucleotide (cDNA). The assay is based on the hybridization that takes place between aptamer and cDNA. In the presence of ß-lactoglobulin (ß-LG), the aptamer preferentially binds to ß-LG, and this leads to a partial release of the C-dots-cDNA into the solution. After magnetic separation, the supernatant of the solution contains the released C-dots-cDNA which are quantified by fluorometry, best under excitation/emission wavelengths of 354/447 nm. Under the optimal conditions, the fluorescence intensity is proportional to the logarithm of the ß-LG concentration in the 0.25 to 50 ng mL-1 range, with a 37 pg mL-1 detection limit. The method was successfully applied to the determination of ß-LG in hypoallergenic formulations, and the results demonstrated that this assay is a promising tool in food quality control. Conceivably, it also provides the opportunity for detection of other analytes. Graphical abstract Schematic of a novel aptamer based fluorometric ß-lactoglobulin assay based on the use of magnetite (Fe3O4) nanoparticles (MNPs) and carbon dots (C-dots). C-dots were used as a signal indicator and Fe3O4 MNPs acted as a magnetic separator. This assay exhibits high sensitivity and selectivity with a detection limit as low as 37 pg mL-1.
Subject(s)
Aptamers, Nucleotide/chemistry , Carbon/chemistry , Fluorescent Dyes/chemistry , Lactoglobulins/analysis , Magnetite Nanoparticles/chemistry , Quantum Dots/chemistry , Biological Assay , Limit of Detection , Particle Size , Sensitivity and Specificity , Spectrometry, Fluorescence , Surface PropertiesABSTRACT
BACKGROUND: MicroRNA-663a expression is downregulated in several tumors. However, its functions and mechanisms in human non-small cell lung (NSCLC) cancer remain obscure. The present study aimed to identify the expression pattern, biological roles and potential mechanisms by which miR-663a dysregulation is associated with NSCLC. METHODS: We examined expression level of miR-663a in 62 cases of NSCLC tissues and 5 NSCLC cell lines by reverse transcription PCR. In vitro, gain-of-function and loss-of-function experiments were performed to examine the impact of miR-663a on proliferation, cell cycle progression and invasion of NSCLC cells. Using fluorescence reporter assays, we also explored the potential targets and possible mechanisms of miR-663a in NSCLC cells. RESULTS: Downregulation of miR-663a was observed in 42 of 62 of lung cancer tissues compared with paired normal tissues (mean cancer/normal value = 0.745) and its downregulation correlated with nodal metastasis. Transfection of miR-663a mimic suppressed cell proliferation, cell cycle progression and invasion, with downregulation of cyclin D1, cyclin E and MMP9 in both H460 and H1299 cell lines. Transfection of miR-663a inhibitor in both H460 and H1299 cell lines exhibited the opposite effects. In addition, we confirmed that miR-663a could inhibit AP-1 activity and AP-1 component JunD was a direct target of miR-663a in lung cancer cells. Transfection of miR-663a mimic downregulated JunD expression. In addition, JunD siRNA treatment abrogated miR-663a inhibitor-induced expression of cyclin D1, cyclin E and MMP9. Above all, both miRNA mimic and inhibitor in two different NSCLC cell lines demonstrated that miR-663a inhibits proliferation and invasion by targeting AP-1 transcription factor JunD. CONCLUSIONS: This study indicates that miR-663a downregulation might be associated with NSCLC progression. MiR-663a suppresses proliferation and invasion by targeting AP-1 component JunD in NSCLC cells.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , MicroRNAs/physiology , Proto-Oncogene Proteins c-jun/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/metabolism , Male , Middle Aged , Neoplasm Invasiveness , Proto-Oncogene Proteins c-jun/metabolism , RNA InterferenceABSTRACT
Our previous study reported that waltonitone treatment inhibited proliferation and induced apoptosis of lung cancer cells. However, the mechanism of waltonitone-induced toxicity remains unclear. In the present study, we treated H460 and H3255 lung cancer cells using different concentration of waltonitone (0, 10, 20, 30 µmol/L). We observed that waltonitone inhibited cell viability and induced apoptosis in a concentration dependent manner, with upregulation of caspase-3 cleavage. We also observed upregulation of miR-663, a potential tumor suppressor, after waltonitone treatment. Suppression of miR-663 function using miR-663 inhibitor partly alleviated cell toxicity induced by waltonitone. In addition, both waltonitone treatment and transfection of miR-663 mimic upregulated Bcl-2 mRNA and protein expression. Bcl-2 transfection alleviated waltonitone-induced toxicity. Furthermore, transfection of miR-663 inhibitor upregulated Bcl-2 levels in both cell lines. In summary, the present study demonstrated that waltonitone induced apoptosis of lung cancer cells through, at least partly, miR-663-induced Bcl-2 downregulation.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , MicroRNAs/biosynthesis , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Triterpenes/administration & dosage , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , MicroRNAs/genetics , Proto-Oncogene Proteins c-bcl-2/geneticsABSTRACT
ARID1A (AT-rich interactive domain 1A) is a key member of the SWI/SNF chromatin-modeling complex, and the gene has emerged as a tumor suppressor in various human cancers. In the present study, we investigated the expression and clinical significance of ARID1A in non-small cell lung cancer (NSCLC). We found that ARID1A expression was decreased in NSCLC tissues compared with normal bronchial epithelium and was significantly correlated with nodal metastasis, tumor, node, metastasis (TNM) stage, and poor differentiation. ARID1A expression was lower in lung cancer cell lines than normal bronchial epithelial HBE cell line. We also explored the involvement of ARID1A in biological behavior of lung cancer cell lines. ARID1A depletion by small interfering RNA (siRNA) in H460 and H1299 cell lines promoted proliferation, colony formation ability, and inhibited paclitaxel-induced apoptosis. Furthermore, we identified that ARID1A regulated several cell cycle and apoptosis-related targets such as cyclin D1 and Bcl-2. In addition, the activity of Akt phosphorylation was also enhanced after ARID1A depletion. In conclusion, our data suggested that ARID1A may serve as an important tumor suppressor in NSCLC.
Subject(s)
Apoptosis , Carcinoma, Non-Small-Cell Lung/pathology , Cell Proliferation , Lung Neoplasms/pathology , Nuclear Proteins/physiology , Transcription Factors/physiology , Tumor Suppressor Proteins/physiology , Adult , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Cyclin D1/metabolism , DNA-Binding Proteins , Down-Regulation , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Nuclear Proteins/analysis , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Transcription Factors/analysisABSTRACT
Objectives: To analyze the clinical significance of seven autoantibodies (P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE, and CAGE) in patients with non-small cell lung cancer (NSCLC) and the factors that influence false-negative results. Methods: Seven autoantibodies were measured in the serum of 502 patients with non-small cell lung cancer (NSCLC) using ELISA, and their correlations with age, sex, smoking history, pathological type, clinical stage, and PD-L1 gene expression were analyzed. The clinicopathological data of the false-negative and positive groups for the seven autoantibodies were compared to determine the influencing factors. Results: P53 antibody expression level was correlated with lobulation sign, PGP9.5 antibody expression level with sex and vascular convergence; SOX2 antibody expression level with pathological type, clinical stage, and enlarged lymph nodes; and MAGE antibody expression level with the pathological type (P<0.05). False-negative autoantibodies are prone to occur in lung cancer patients with ground-glass nodules, no enlarged lymph nodes, no vascular convergence, and PD-L1 gene expression <1% (P <0.05). Conclusion: Detection of seven autoantibodies was clinically significant in patients with NSCLC. However, poor sensitivity should be considered in clinical diagnoses to prevent missed diagnoses.
ABSTRACT
Background: Pulmonary embolism (PE) is a popular area of research in the field of respiratory medicine. We performed a bibliometric analysis based on PubMed database to characterize the distribution pattern of literature and knowledge structures related to PE. Methods: Literature pertaining to PE from January 1, 2017, to December 31, 2021, was retrieved from the PubMed database. Bibliographic information was generated using the Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). The visualization matrix was established using gCLUTO software. Strategic diagram analysis was performed using GraphPad Prism 9 software. Social network analysis (SNA) was generated using Ucinet6.0 and NetDraw 2.084 software. Results: Out of all the retrieved MeSH terms and subheadings, 52 MeSH terms/MeSH subheadings with a high frequency were found, and hot subjects were sorted into 6 clusters. The strategy diagram showed that the epidemiology, etiology, and drug therapy of PE were well advanced. In contrast, studies on diagnostic imaging, pathology, and complications of PE were still immature and offered potential research space. Social network analysis showed that marginal topics such as surgical treatment of pulmonary hypertension, prevention and control of postoperative complications, and metabolism and analysis of fibrin/fibrinogen degradation products were emerging research hotspots. Conclusion: Objective analysis of the research developments in the field of PE can provide intuitive knowledge structure for researchers and clinicians. Analysis of the research hotspots related to PE is helpful for researchers and clinicians by highlighting future research directions.
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The Yellow River basin is an important area for China to implement ecological protection policies. Studying the habitat quality of the Yellow River floodplain area is of great significance to the ecological security and sustainable development of the entire basin. This study primarily investigated the spatial pattern of habitat quality in the Yellow River floodplain area from 2000 to 2020, then, we also simulated changes of habitat quality in 2025-2035 and analyzed the influencing factors by coupling the PLUS (Patch-generating Land Use Simulation) model, InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) model and RF (Random Forest) model. The results showed that:(1) From 2000 to 2020, cultivated land and build-up land constituted an important part of the Yellow River floodplain area, and the growth rate of build-up land was fast. (2) We also found that the ecological land (forest land, grassland, waterbody) had a higher contribution value to the habitat quality, while the build-up land had a lower contribution value to the habitat quality. (3) Overall, the habitat quality of the floodplain area showed a degradation trend from 2000 to 2020. In addition, the regions with low habitat quality accounted for the major proportion. (4) Based on the calculation results of the Random Forest (RF) model, we found that topographical relief (TR) and land use intensity (LUI) were the two most important factors affecting habitat quality of the floodplain area. (5) According to the four scenarios from 2025 to 2035, it is found that the habitat quality level would be the highest under the ecological protection scenario, while under the urban development scenario its level would be the lowest. This study attempts to combine the RF model with PLUS model to improve the objectivity and accuracy of the future prediction scenario of habitat quality, which can provide scientific reference for ecological governance and policy formulation in the Yellow River floodplain area.
ABSTRACT
Comprehensively regulating the TME is now regarded as a promising approach for cancer treatment. Herein, a novel "three-in-one" effect is presented for simultaneously killing tumor cells, inhibiting the EMT of CAFs, and improving immune responses. In this study, bortezomib (BTZ) is selected for the treatment of breast cancer; it has multiple pharmacological mechanisms for killing tumor cells through the NF-κB signaling pathway, inhibiting the activity of CAFs by activating caspase-3, and enhancing the function of CD8+ T cells by regulating the expression of immune-stimulating factors. To improve the druggability of BTZ in solid tumors, BTZ-loaded lipid/glycocholic acid mixed micelles (BTZ-LGs) were prepared to verify the "three-in-one" effect in killing tumor cells, inhibiting CAFs, and improving immune responses. In the present work, BTZ-LGs were verified to show enhanced in vitro cytotoxicity in both 4T1 cells and 4T1/NIH3T3 co-cultured cells, as well as a superior in vivo treatment effect in different tumor-bearing mouse models. Additionally, BTZ-LGs could regulate the expression of α-SMA, caspase-3, E-cadherin, and N-cadherin, indicating their good inhibiting ability on both tumor cells and CAFs. More importantly, immunological analysis revealed that BTZ-LGs promoted the expression of the immunostimulatory factor IL-2 in tumor tissues, activated anti-tumor T cells, and overcame tumor-induced CD8+ T cell dysfunction. All these findings suggest that BTZ-LGs can achieve a "three-in-one" effect in terms of killing tumor cells, suppressing CAFs, and improving immune responses. This simple and multi-effective therapeutic strategy offers a promising approach for cancer therapy.
Subject(s)
Antineoplastic Agents , Neoplasms , Animals , Mice , Bortezomib/pharmacology , Bortezomib/therapeutic use , Micelles , Caspase 3 , NIH 3T3 Cells , Cell Line, Tumor , Apoptosis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapyABSTRACT
Structural variants (SVs), accounting for a larger fraction of the genome than SNPs/InDels, are an important pool of genetic variation, enabling environmental adaptations. Here, we perform long-read sequencing data of 320 Tibetan and Han samples and show that SVs are highly involved in high-altitude adaptation. We expand the landscape of global SVs, apply robust models of selection and population differentiation combining SVs, SNPs and InDels, and use epigenomic analyses to predict enhancers, target genes and biological functions. We reveal diverse Tibetan-specific SVs affecting the regulatory circuitry of biological functions, including the hypoxia response, energy metabolism and pulmonary function. We find a Tibetan-specific deletion disrupts a super-enhancer and downregulates EPAS1 using enhancer reporter, cellular knock-out and DNA pull-down assays. Our study expands the global SV landscape, reveals the role of gene-regulatory circuitry rewiring in human adaptation, and illustrates the diverse functional roles of SVs in human biology.
Subject(s)
Altitude , Genome , Humans , Hypoxia/genetics , Sequence Analysis, DNA , Adaptation, Physiological/geneticsABSTRACT
The development of journalism has a huge impact on mobile communication technology and media ecology. Especially in terms of information dissemination, it not only allows people to better obtain the content they are interested in but also provides media workers with more ways to understand their own needs, meet the needs of audiences, and enhance competitiveness. Therefore, in order to enhance the development space of the journalism major, this article studies the communication development path of this major in colleges and universities in the era of mobile communications. This article mainly uses case analysis method, data method, and investigation method to study the development of journalism education in colleges and universities. The survey results show that 21 people believe that the authenticity of news is an indispensable item in teaching. Therefore, the education and communication development of journalism majors in colleges and universities cannot ignore the principle of authenticity. There are 18 people who think it is necessary to tie their majors with the Internet, indicating that colleges and universities can use the Internet platform to teach journalism.
ABSTRACT
Depression is one of the most common non-motor symptoms in patients with Parkinson's disease (PD). Depression in PD (DPD) increases the disability rate and reduces the quality of life of PD patients and increases the caregiver burden. Although previous studies have explained the relationship between depression and PD through a variety of pathological mechanisms, whether depression is a precursor or an independent risk factor for PD remains unclear. Additionally, increasing evidence shows that conventional anti-PD drug therapy is not ideal for DPD. Chinese Herbal Medicine (CHM) prescriptions exhibit the characteristics of multi-target, multi-pathway, and multi-level treatment of DPD and may simultaneously improve the motor symptoms of PD patients through multiple mechanisms. However, the specific pharmacological mechanisms of these CHM prescriptions remain unelucidated. Here, we investigated the mechanisms of action of the active ingredients of single herbs predominantly used in CHM prescriptions for depression as well as the therapeutic effect of CHM prescriptions on DPD. This review may facilitate the design of new selective and effective treatment strategies for DPD.
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Central nervous system (CNS) disorders, such as ischemic stroke, Alzheimer's disease, Parkinson's disease, spinal cord injury, glioma, and epilepsy, involve oxidative stress and neuronal apoptosis, often leading to long-term disability or death. Emerging studies suggest that oxidative stress may induce epigenetic modifications that contribute to CNS disorders. Non-coding RNAs are epigenetic regulators involved in CNS disorders and have attracted extensive attention. Long non-coding RNAs (lncRNAs) are non-coding RNAs more than 200 nucleotides long and have no protein-coding function. However, these molecules exert regulatory functions at the transcriptional, post-transcriptional, and epigenetic levels. However, the major role of lncRNAs in the pathophysiology of CNS disorders, especially related to oxidative stress, remains unclear. Here, we review the molecular functions of lncRNAs in oxidative stress and highlight lncRNAs that exert positive or negative roles in oxidation/antioxidant systems. This review provides novel insights into the therapeutic potential of lncRNAs that mediate oxidative stress in CNS disorders.