Three-dimensional analysis of the positional relationship between the dentition and basal bone region in patients with skeletal Class I and Class II malocclusion with mandibular retrusion.

Objective: This study aimed to determine the maxillary and mandibular basal bone regions and explore the three-dimensional positional relationship between the dentition and basal bone regions in patients with skeletal Class I and Class II malocclusions with mandibular retrusion. Methods: Eighty patients (40 each with Class I and Class II malocclusion) were enrolled. Maxillary and mandibular basal bone regions were determined using cone-beam computed tomography images. To measure the relationship between the dentition and basal bone region, the root position and root inclination were calculated using the coordinates of specific fixed points by a computer program written in Python. Results: In the Class II group, the mandibular anterior teeth inclined more labially (P < 0.05), with their apices positioned closer to the external boundary. The apex of the maxillary anterior root was positioned closer to the external boundary in both groups. Considering the molar region, the maxillary first molars tended to be more lingually inclined in females (P = 0.037), whereas the mandibular first molars were significantly more labially inclined in the Class II group (P < 0.05). Conclusions: Mandibular anterior teeth in Class II malocclusion exhibit a compensatory labial inclination trend with the crown and apex relative to the basal bone region when mandibular retrusion occurs. Moreover, as the root apices of the maxillary anterior teeth are much closer to the labial side in Class I and Class II malocclusion, the range of movement at the root apex should be limited to avoid extensive labial movement.

Acetaldehyde Dehydrogenase 2 Deficiency Aggravates Lung Fibrosis through Mitochondrial Dysfunction and Aging in Fibroblasts.

Idiopathic pulmonary fibrosis, a fatal interstitial lung disease, is characterized by fibroblast activation and aberrant extracellular matrix accumulation. Effective therapeutic development is limited because of incomplete understanding of the mechanisms by which fibroblasts become aberrantly activated. Here, we show acetaldehyde dehydrogenase 2 (ALDH2) in fibroblasts as a potential therapeutic target for pulmonary fibrosis. A decrease in ALDH2 expression was observed in patients with idiopathic pulmonary fibrosis and bleomycin-treated mice. ALDH2 deficiency spontaneously induces collagen accumulation in the lungs of aged mice. Furthermore, young ALDH2 knockout mice exhibited exacerbated bleomycin-induced pulmonary fibrosis and increased mortality compared with that in control mice. Mechanistic studies revealed that transforming growth factor (TGF)-ß1 induction and ALDH2 depletion constitute a positive feedback loop that exacerbates fibroblast activation. TGF-ß1 down-regulated ALDH2 through a TGF-ß receptor 1/Smad3-dependent mechanism. The subsequent deficiency in ALDH2 resulted in fibroblast dysfunction that manifested as impaired mitochondrial autophagy and senescence, leading to fibroblast activation and extracellular matrix production. ALDH2 overexpression markedly suppressed fibroblast activation, and this effect was abrogated by PTEN-induced putative kinase 1 (PINK1) knockdown, indicating that the profibrotic effects of ALDH2 are PINK1- dependent. Furthermore, Alda-1-induced ALDH2 activation reversed the established pulmonary fibrosis in both young and aged mice. In conclusion, ALDH2 expression inhibits the pathogenesis of pulmonary fibrosis. Strategies to up-regulate or activate ALDH2 expression could be potential therapies for pulmonary fibrosis.

Metal-Organic Framework PCN-224 Combined Cobalt Oxide Nanoparticles for Hypoxia Relief and Synergistic Photodynamic/Chemodynamic Therapy.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@Co3O4-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified Co3O4 nanoparticles decorated metal-organic framework PCN-224. Co3O4 can catalyze the decomposition of highly expressed H2O2 in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@Co3O4-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@Co3O4-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@Co3O4-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.

Removal of dyes from wastewater using Eucalyptus wood fiber loaded nanoscale zero-valent iron: Characterization and removal mechanism.

Wood fiber as a natural and renewable material has low cost and plenty of functional groups, which owns the ability to adsorb dyes. In order to improve the application performance of wood fiber in dye-pollution wastewater, Eucalyptus wood fiber loaded nanoscale zero-valent iron (EWF-nZVI) was developed to give EWF magnetism and the ability to degrade dyes. EWF-nZVI was characterized via FTIR, XRD, zeta potential, VSM, SEM-EDS and XPS. Results showed that EWF-nZVI owned a strong magnetism of 96.51 emu/g. The dye removal process of EWF-nZVI was more in line with the pseudo-second-order kinetics model. In addition, the Langmuir isotherm model fitting results showed that the maximum removal capacities of Congo red and Rhodamine B by EWF-nZVI were 714.29 mg/g and 68.49 mg/g at 328 K, respectively. After five adsorption-desorption cycles, the regeneration efficiencies of Congo red and Rhodamine B were 74 % and 42 % in turn. The dye removal mechanisms of EWF-nZVI included redox degradation (Congo red and Rhodamine B) and electrostatic adsorption (Congo red). In summary, EWF-nZVI is a promising biomass-based material with high dye removal capacities. This work is beneficial to promote the large-scale application of wood fiber in water treatment.

The accuracy of electromagnetic navigation bronchoscopy compared to fluoroscopy in navigation of transbronchial lung cryobiopsy in patients with interstitial lung disease.

BACKGROUND: Safely implementing transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) requires accurate navigation. Traditional fluoroscopy falls short in reducing the risk of post-procedure pneumothorax. The potential of electromagnetic navigation bronchoscopy (ENB) as a more precise navigation method warrants further exploration. METHODS: A prospective cohort study was conducted on ILD patients undergoing TBLC. Patients were assigned either fluoroscopy or ENB for cryoprobe positioning. Navigation accuracy was evaluated using cone beam computed tomography (CBCT) images as the standard. Safety and diagnostic yield were also observed. RESULTS: Seventeen patients underwent TBLC, with 10 guided by fluoroscopy and seven by ENB. Fluoroscopy-guided cryoprobe navigation required more adjustments [9/15 (60%) v.s. 1/9 (11%), p = 0.018] for subsequent TBLC compared to ENB, as confirmed by CBCT images. Clinical characteristics, post-procedure complications, and biopsy specimen size showed no significant differences between the groups. Fourteen patients obtained a pathological diagnosis, and 15 received a multidisciplinary discussion (MDD) diagnosis. In the fluoroscopy group, three patients failed to obtain a pathological diagnosis, and two failed to obtain an MDD diagnosis. CONCLUSIONS: ENB demonstrates significantly superior accuracy in TBLC navigation compared to traditional fluoroscopy when CBCT images are used as a reference. Further studies are necessary to determine the value of ENB in TBLC navigation for ILD patients.

Mfn2/Hsc70 Complex Mediates the Formation of Mitochondria-Lipid Droplets Membrane Contact and Regulates Myocardial Lipid Metabolism.

The heart primarily derives its energy through lipid oxidation. In cardiomyocytes, lipids are stored in lipid droplets (LDs) and are utilized in mitochondria, although the structural and functional connections between these two organelles remain largely unknown. In this study, visible evidence have presented indicating that a complex is formed at the mitochondria-LD membrane contact (MLC) site, involving mitochondrion-localized Mfn2 and LD-localized Hsc70. This complex serves to tether mitochondria to LDs, facilitating the transfer of fatty acids (FAs) from LDs to mitochondria for ß-oxidation. Reduction of Mfn2 induced by lipid overload inhibits MLC, hinders FA transfer, and results in lipid accumulation. Restoring Mfn2 reinstates MLC, alleviating myocardial lipotoxicity under lipid overload conditions both in-vivo and in-vitro. Additionally, prolonged lipid overload induces Mfn2 degradation through the ubiquitin-proteasome pathway, following Mfn2 acetylation at the K243 site. This leads to the transition from adaptive lipid utilization to maladaptive lipotoxicity. The experimental findings are supported by clinical data from patients with obesity and age-matched non-obese individuals. These translational results make a significant contribution to the molecular understanding of MLC in the heart, and offer new insights into its role in myocardial lipotoxicity.

Feasibility of spheno-occipital synchondrosis fusion stages as an indicator for the assessment of maxillomandibular growth: A mixed longitudinal study.

OBJECTIVES: This study aimed to assess the relative growth rates (RGRs) of the maxilla and mandible at varying fusion stages of the spheno-occipital synchondrosis (SOS), thereby elucidating the potential of SOS stages in predicting maxillomandibular growth. MATERIALS AND METHODS: A total of 320 subjects (171 boys and 149 girls), aged 6 to 18 years, were retrospectively included. Each subject had a minimum of two longitudinal cone-beam computed tomography (CBCT) images, with no more than one interval of SOS fusion stage change between the two scans. Subjects were categorized based on their SOS fusion stages and genders. The RGRs of the maxilla and mandible at various SOS fusion stages were measured and compared using longitudinal CBCT images. RESULTS: Significant statistical differences were observed in maxillomandibular RGRs across various SOS fusion stages. In girls, the sagittal growth of the maxilla remained stable and active until SOS 3, subsequently exhibited deceleration in SOS 4-5 (compared to SOS 3-4, P < .05) and continued to decrease in SOS 5-6. Whereas in boys, the sagittal growth of the maxilla remained stable until SOS 4, and a deceleration trend emerged starting from SOS 5 to 6 (P < .01 compared to SOS 4-5). Mandibular growth patterns in both genders exhibited a progression of increasing-accelerating-decelerating rates from SOS 2 to 6. The highest RGRs for total mandibular length were observed in SOS 3-4 and SOS 4-5. CONCLUSION: Spheno-occipital synchondrosis fusion stages can serve as a valid indicator of maxillomandibular growth maturation.

Assessment of lung deformation in patients with idiopathic pulmonary fibrosis with elastic registration technique on pulmonary three-dimensional ultrashort echo time MRI.

OBJECTIVE: To assess lung deformation in patients with idiopathic pulmonary fibrosis (IPF) using with elastic registration algorithm applied to three-dimensional ultrashort echo time (3D-UTE) MRI and analyze relationship of lung deformation with the severity of IPF. METHODS: Seventy-six patients with IPF (mean age: 62 ± 6 years) and 62 age- and gender-matched healthy controls (mean age: 58 ± 4 years) were prospectively enrolled. End-inspiration and end-expiration images acquired with a single breath-hold 3D-UTE sequence were registered using elastic registration algorithm. Jacobian determinants were calculated from deformation fields and represented on color maps. Jac-mean (absolute value of the log means of Jacobian determinants) and the Dice similarity coefficient (Dice) were compared between different groups. RESULTS: Compared with healthy controls, the Jac-mean of IPF patients significantly decreased (0.21 ± 0.08 vs. 0.27 ± 0. 07, p < 0.001). Furthermore, the Jac-mean and Dice correlated with the metrics of pulmonary function tests and the composite physiological index. The lung deformation in IPF patients with dyspnea Medical Research Council (MRC) ≥ 3 (Jac-mean: 0.16 ± 0.03; Dice: 0.06 ± 0.02) was significantly lower than MRC1 (Jac-mean: 0. 25 ± 0.03, p < 0.001; Dice: 0.10 ± 0.01, p < 0.001) and MRC 2 (Jac-mean: 0.22 ± 0.11, p = 0.001; Dice: 0.08 ± 0.03, p = 0.006). Meanwhile, Jac-mean and Dice correlated with health-related quality of life, 6 min-walk distance, and the extent of pulmonary fibrosis. Jac-mean correlated with pulmonary vascular-related indexes on high-resolution CT. CONCLUSION: The decreased lung deformation in IPF patients correlated with the clinical severity of IPF patients. Elastic registration of inspiratory-to-expiratory 3D UTE MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. CRITICAL RELEVANCE STATEMENT: This prospective study demonstrated that lung deformation decreased in idiopathic pulmonary fibrosis (IPF) patients and correlated with the severity of IPF. Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. KEY POINTS: • Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI could evaluate lung deformation. • Lung deformation significantly decreased in idiopathic pulmonary fibrosis (IPF) patients, compared with the healthy controls. • Reduced lung deformation of IPF patients correlated with worsened pulmonary function and the composite physiological index (CPI).

Single-molecule detection assisted by the target-triggered signal amplification strategy for ultrasensitive quantitative analysis of intracellular telomerase activity.

We developed a multiplex single-molecule quantitative assay of intracellular telomerase that used target-triggered signal amplification to enhance sensitivity, substrate reaction to increase signal stability, and quantum dots to enhance signal-to-noise ratio, obtaining an LOD of 5 × 10-14 IU for intracellular telomerase and LOD of 3 cells for multiple cancer cells.

PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway.

BACKGROUND: Cardiac hypertrophy is studied in relation to energy metabolism, autophagy, and ferroptosis, which are associated with cardiovascular adverse events and chronic heart failure. Protein kinase D (PKD) has been shown to play a degenerative role in cardiac hypertrophy. However, the role of ferroptosis in PKD-involved cardiac hypertrophy remains unclear. METHODS: A cardiac hypertrophy model was induced by a subcutaneous injection of angiotensin II (Ang II) for 4 weeks. Adeno-associated virus serotype 9 (AAV9)-PKD or AAV9-Negative control were injected through the caudal vein 2 weeks prior to the injection of Ang II. The degree of cardiac hypertrophy was assessed using echocardiography and by observing cardiomyocyte morphology. Levels of ferroptosis and protein expression in the Jun N-terminal kinase (JNK)/P53 signaling pathway were measured both in vivo and in vitro. RESULTS: The results indicated that PKD knockdown reduces Ang II-induced cardiac hypertrophy, enhances cardiac function and inhibits ferroptosis. The involvement of the JNK/P53 pathway in this process was further confirmed by in vivo and in vitro experiments. CONCLUSION: In conclusion, our findings suggest that PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway.

Recent Progress in the Development and Clinical Application of New Drugs for Transthyretin Cardiac Amyloidosis.

ABSTRACT: Transthyretincardiac amyloidosis is a rare disease that has gained significant attention in recent years because of misfolding of transthyretin fibrils produced by the liver, leading to their deposition in the myocardium. The disease has an insidious onset, nonspecific clinical manifestations, and historically lacked effective drugs, making early diagnosis and treatment challenging. The survival time of patients largely depends on the extent of heart involvement at the time of diagnosis, and conventional treatments for cardiovascular disease do not provide significant benefits. Effective management of the disease requires treatment of its underlying cause. Orthotopic liver transplantation and combined hepato-heart transplantation have been clinically effective means of treating transthyretin cardiac amyloidosis mutants for many years. However, transplantation has many limitations in clinical practice. In recent years, the development of new drugs has brought new hope to patients. This review presents the latest advances in drug development and clinical application to provide a reference for clinicians managing transthyretin cardiac amyloidosis.

Elastic Registration Algorithm Based on Three-dimensional Pulmonary MRI in Quantitative Assessment of Severity of Idiopathic Pulmonary Fibrosis.

PURPOSE: To quantitatively analyze lung elasticity in idiopathic pulmonary fibrosis (IPF) using elastic registration based on 3-dimensional pulmonary magnetic resonance imaging (3D-PMRI) and to assess its' correlations with the severity of IPF patients. MATERIAL AND METHODS: Thirty male patients with IPF (mean age: 62±6 y) and 30 age-matched male healthy controls (mean age: 62±6 y) were prospectively enrolled. 3D-PMRI was acquired with a 3-dimensional ultrashort echo time sequence in end-inspiration and end-expiration. MR images were registered from end-inspiration to end-expiration with the elastic registration algorithm. Jacobian determinants were calculated from deformation fields on color maps. The log means of the Jacobian determinants (Jac-mean) and Dice similarity coefficient were used to describe lung elasticity between 2 groups. Then, the correlation of lung elasticity with dyspnea Medical Research Council (MRC) score, exercise tolerance, health-related quality of life, lung function, and the extent of pulmonary fibrosis on chest computed tomography were analyzed. RESULTS: The Jac-mean of IPF patients (-0.19, [IQR: -0.22, -0.15]) decreased (absolute value), compared with healthy controls (-0.28, [IQR: -0.31, -0.24], P<0.001). The lung elasticity in IPF patients with dyspnea MRC≥3 (Jac-mean: -0.15; Dice: 0.06) was significantly lower than MRC 1 (Jac-mean: -0.22, P=0.001; Dice: 0.10, P=0.001) and MRC 2 (Jac-mean: -0.21, P=0.007; Dice: 0.09, P<0.001). In addition, the Jac-mean negatively correlated with forced vital capacity % (r=-0.487, P<0.001), forced expiratory volume 1% (r=-0.413, P=0.004), TLC% (r=-0.488, P<0.001), diffusing capacity of the lungs for carbon monoxide % predicted (r=-0.555, P<0.001), 6-minute walk distance (r=-0.441, P=0.030) and positively correlated with respiratory symptoms (r=0.430, P=0.042). Meanwhile, the Dice similarity coefficient positively correlated with forced vital capacity % (r=0.577, P=0.004), forced expiratory volume 1% (r=0.526, P=0.012), diffusing capacity of the lungs for carbon monoxide % predicted (r=0.435, P=0.048), 6-minute walk distance (r=0.473, P=0.016), final peripheral oxygen saturation (r=0.534, P=0.004), the extent of fibrosis on chest computed tomography (r=-0.421, P=0.021) and negatively correlated with activity (r=-0.431, P=0.048). CONCLUSION: Lung elasticity decreased in IPF patients and correlated with dyspnea, exercise tolerance, health-related quality of life, lung function, and the extent of pulmonary fibrosis. The lung elasticity based on elastic registration of 3D-PMRI may be a new nonradiation imaging biomarker for quantitative evaluation of the severity of IPF.

Personalized Teaching Questioning Strategies Study Based on Learners' Cognitive Structure Diagnosis.

Personalized education has been a widely shared goal pursued by Chinese and foreign educators. As the primary method of teacher-student interaction, the importance of personalized questioning is self-evident. Due to a lack of technical support, teachers rely on their teaching experience to ask questions without considering the learning situation of learners. This results in teaching questioning being unable to support learners' learning. These questions are relatively shallow and cannot promote the construction and transfer of learners' knowledge. Cognitive diagnostic technology could diagnose learners' cognitive states and provide services for personalized teaching. Therefore, a personalized teaching questioning strategy based on learners' cognitive structure diagnosis was proposed in this study. Firstly, we diagnosed learners' cognitive structure through usability, distinguishability, and stability. Secondly, we discussed the types of questions that teachers should raise when facing learners in different situations. We also discussed the application of personalized teaching questioning strategies. The experiment took place at M Primary School in Ningxia, China, with the participation of one teacher and ninety-seven fourth-grade students. Seven lessons were observed and videotaped across a range of topics. The study revealed that personalized teaching questioning strategies could improve learners' academic performance and subject literacy. They can also increase the number of teacher questioning, change the depth of teacher questioning content, and expand the scope of questioning subjects.

Synthesis and modification mechanism of vanadium oxide coated LiFePO4cathode materials with excellent electrochemical performance.

In an era of rapid industrial development, such that the demand for energy is increasing daily, lithium-ion batteries are playing a dominant role in energy storage devices due to their high safety and low cost. However, it is still a challenge for the preparation of advanced cathodes, which can determine the battery performance, with stable structures and fast diffusion of Li+. This is especially the case for lithium iron phosphate (LFP), a cathode material with severe limitations due to its low conductive efficiency. To improve its conductivity, LFP was compounded with defect-modified V2O5to prepare LFP/V/C materials with excellent electrochemical properties, which exhibited an initial capacity of 138.85 mAh g-1and 95% retention after 500 charge/discharge cycles at a current density of 5 C. Also, the effect of defects on ionic diffusion was discussed in detail by means of density function theor (DFT) calculations, confirming that the improvement of electrochemical performance is closely related to the introduction of hybrid conductive layers of surface cladding.

A Positive Feedback Loop of lncRNA HOXD-AS2 and SMYD3 Facilitates Hepatocellular Carcinoma Progression via the MEK/ERK Pathway.

Purpose: HOX cluster-embedded long noncoding RNAs (HOX-lncRNAs) have been shown to be tightly related to hepatocellular carcinoma (HCC). However, the potential biological roles and underlying molecular mechanism of HOX-lncRNAs in HCC largely remains to be elucidated. Methods: The expression signature of eighteen HOX-lncRNAs in HCC cell lines were measured by qRT-PCR. HOXD-AS2 expression and its clinical significance in HCC was investigated by bioinformatics analysis utilizing the TCGA data. Subcellular localization of HOXD-AS2 in HCC cells was observed by RNA-FISH. Loss­of­function experiments in vitro and in vivo were conducted to probe the roles of HOXD-AS2 in HCC. Potential HOXD-AS2-controlled genes and signaling pathways were revealed by RNA-seq. Rescue experiments were performed to validate that SMYD3 mediates HOXD-AS2 promoting HCC progression. The positive feedback loop of HOXD-AS2 and SMYD3 was identified by luciferase reporter assay and ChIP-qPCR. Results: HOXD-AS2 was dramatically elevated in HCC, and its up-regulation exhibited a positive association with aggressive clinical features (T stage, pathologic stage, histologic grade, AFP level, and vascular invasion) and unfavorable prognosis of HCC patients. HOXD-AS2 was distributed both in the nucleus and the cytoplasm of HCC cells. Knockdown of HOXD-AS2 restrained the proliferation, migration, invasion of HCC cells in vitro, as well as tumor growth in subcutaneous mouse model. Transcriptome analysis demonstrated that SMYD3 expression and activity of MEK/ERK pathway were impaired by silencing HOXD-AS2 in HCC cells. Rescue experiments revealed that SMYD3 as downstream target mediated oncogenic functions of HOXD-AS2 in HCC cells through altering the expression of cyclin B1, cyclin E1, MMP2 as well as the activity of MEK/ERK pathway. Additionally, HOXD-AS2 was uncovered to be positively regulated at transcriptional level by its downstream gene of SMYD3. Conclusion: HOXD-AS2, a novel oncogenic HOX-lncRNA, facilitates HCC progression by forming a positive feedback loop with SMYD3 and activating the MEK/ERK pathway.

Evaluation of the Clinical Value of KL-6 and Tumor Markers in Primary Sjögren's Syndrome Complicated with Interstitial Lung Disease.

OBJECTIVE: primary Sjögren's syndrome (pSS) is an autoimmune disease, of which the most common complication is interstitial lung disease (ILD). This study aimed to analyze the clinical value of Krebs von den Lungen-6 (KL-6), carcinoembryonic antigen (CEA), and carbohydrate antigen 153(CA153) in patients with pSS complicated with ILD (pSS-ILD), given that only few studies have evaluated this. METHODS: This is a cross-sectional study. Serum KL-6 levels (U/mL) were measured using chemiluminescence immunoassay, and concentrations of serum tumor markers were determined using the immunofluorescence method in 64 cases of pSS-ILD (pSS-ILD group), 23 cases without ILD (non-ILD group), and 45 healthy controls. The correlation between KL-6 and tumor markers as well as lung function was analyzed, and the factors that were associated with pSS-ILD were screened. RESULTS: The serum KL-6 was more abnormally increased in patients with pSS-ILD, and the serum KL-6, CEA, carbohydrate antigen 125 (CA125), and CA153 levels were significantly higher in the pSS-ILD group than in the non-ILD and healthy control groups (p < 0.05). KL-6, CEA, and CA153 were negatively correlated with forced vital capacity (FVC%), forced expiratory volume in 1 s (FEV1%), total lung capacity (TLC%), and diffusing capacity for carbon monoxide (DLCO%) (all p < 0.05). Multivariate logistic analysis showed that KL-6 was an independent factor associated with pSS-ILD. CONCLUSIONS: In conclusion, we evaluated the association between clinical values of KL-6, tumor markers, and pSS-ILD, and found that KL-6 and tumor markers such as CEA, CA153, and CA125 in patients with pSS-ILD were higher than in patients with non-ILD, and KL-6 was more abnormally increased and significantly associated with ILD development in patients with pSS.

Clinical characteristics of hypersensitivity pneumonitis: non-fibrotic and fibrotic subtypes.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS: Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.

Serum Osteopontin, KL-6, and Syndecan-4 as Potential Biomarkers in the Diagnosis of Coal Workers' Pneumoconiosis: A Case-Control Study.

Background: Coal worker's pneumoconiosis (CWP) is a chronic occupational disease mainly caused by coal dust inhalation in miners. This study aimed to investigate the clinical value of Osteopontin (OPN), KL-6, Syndecan-4 and Gremlin-1 as serum biomarkers in CWP. Patients and Methods: We integrated reported lung tissues transcriptome data in pneumoconiosis patients with silica-exposed alveolar macrophage microarray data to identify four CWP-associated serum biomarkers. The serum concentrations of Osteopontin, Krebs von den Lungen-6 (KL-6), Syndecan-4 and Gremlin-1 were measured in 100 healthy controls (HCs), 100 dust-exposed workers (DEWs) and 200 patients of CWP. Receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity, specificity, cut-off value and area under the curve (AUC) value of biomarkers. Results: The pulmonary function parameters decreased sequentially, and the serum OPN, KL-6, Syndecan-4 and Gremlin-1 concentrations were increased sequentially among the HC, DEW and CWP groups. Among all participants, multivariable analysis revealed that these four biomarkers were negatively correlated with the pulmonary function parameters (all p<0.05). Compared with HCs, patients with higher OPN, KL-6, Syndecan-4 and Gremlin-1 had higher risk for CWP. The combination of OPN, KL-6, and Syndecan-4 can improve the diagnostic sensitivity and specificity of CWP patients differentiated from HCs or DEWs. Conclusion: OPN, KL-6 and Syndecan-4 are novel biomarkers that can be used for CWP auxiliary diagnosis. The combination of three biomarkers can improve the diagnostic values of CWP.

A Glucose Metabolic Intervention Nanoplatform for Enhanced Chemodynamic Therapy and Sensitized Photothermal Therapy of Hepatocellular Carcinoma.

Traditional treatments for hepatocellular carcinoma (HCC) still lack effectiveness. Recently, the combined mode of chemodynamic therapy (CDT) and photothermal therapy (PTT) has shown great potential against HCC. However, insufficient Fenton reaction rates and hyperthermia-induced heat shock responses greatly impair their efficiency, hindering their further clinical application. Here, we constructed a cascade-amplified PTT/CDT nanoplatform by coating an IR780-embedded red blood cell membrane on glucose oxidase (GOx)-loaded Fe3O4 nanoparticles for effective HCC treatment. On the one hand, the nanoplatform interfered with glucose metabolism through the action of GOx to reduce the synthesis of ATP, which reduced the expression of heat shock proteins, thereby sensitizing the IR780-mediated PTT. On the other hand, hydrogen peroxide generated during GOx catalysis and the thermal effect of PTT accelerated the Fe3O4-mediated Fenton reaction, realizing enhanced CDT. Consequently, the sensitized PTT and enhanced CDT for HCC management could be simultaneously achieved by interfering with glucose metabolism, providing an alternative strategy for the effective treatment of tumors.

Design, Synthesis, and Bioactivity Investigation of Cyclic Lipopeptide Antibiotics Containing Eight to Nine Amino Acids.

The current global issue of antibiotic resistance is serious, and there is an urgent requirement of developing novel antibiotics. Octapeptins have recently regained interest because of their activities against resistant Gram-negative bacteria. We synthesized four natural octapeptins and 33 derivatives with diverse polarity, amphiphilicity, and acid-base properties by solid-phase synthesis and investigated their in vitro antibacterial activity and renal cytotoxicity. We also assessed the structure-activity relationship and structure-toxicity relationship of the cyclic lipopeptide compounds. Some compounds showed increased activity against Gram-negative and/or Gram-positive bacteria, with improved renal cytotoxicity. C-02 showed remarkable in vitro antibacterial activity and low renal cytotoxicity. We found that C-02 showed high antibacterial activity against Escherichia coli in vivo and manifested its effects preliminarily by increasing outer membrane permeability. Therefore, C-02 might be a new antibiotic lead compound with not only high efficacy but also low renal cytotoxicity.