Comparison of Budesonide/formoterol versus Fluticasone furoate/vilanterol as maintenance and reliever therapy for asthma control: a real-world observational study.

BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group. CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.

Heme oxygenase-1 inhibits DENV-induced endothelial hyperpermeability and serves as a potential target against dengue hemorrhagic fever.

Dengue virus (DENV) is a cause of vascular endothelial dysfunction and vascular leakage, which are characterized as hallmarks of dengue hemorrhagic fever or dengue shock syndrome, which become a severe global health emergency with substantial morbidity and mortality. Currently, there are still no promising therapeutics to alleviate the dengue-associated vascular hemorrhage in a clinical setting. In the present study, we first observed that heme oxygenase-1 (HO-1) expression level was highly suppressed in severe DENV-infected patients. In contrast, the overexpression of HO-1 could attenuate DENV-induced pathogenesis, including plasma leakage and thrombocytopenia, in an AG129 mouse model. Our data indicate that overexpression of HO-1 or its metabolite biliverdin can maintain endothelial integrity upon DENV infection in vitro and in vivo. We further characterized the positive regulatory effect of HO-1 on the endothelial adhesion factor vascular endothelial-cadherin to decrease DENV-induced endothelial hyperpermeability. Subsequently, we confirmed that two medicinal plant-derived compounds, andrographolide, and celastrol, widely used as a nutritional or medicinal supplement are useful to attenuate DENV-induced plasma leakage through induction of the HO-1 expression in DENV-infected AG129 mice. In conclusion, our findings reveal that induction of the HO-1 signal pathway is a promising option for the treatment of DENV-induced vascular pathologies.

Application of impulse oscillometry to detect interstitial lung disease and airway disease in adults with rheumatoid arthritis.

BACKGROUND: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. METHODS: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.

The Role of Paxillin Aberrant Expression in Cancer and Its Potential as a Target for Cancer Therapy.

Paxillin is a multi-domain adaptor protein. As an important member of focal adhesion (FA) and a participant in regulating cell movement, paxillin plays an important role in physiological processes such as nervous system development, embryonic development, and vascular development. However, increasing evidence suggests that paxillin is aberrantly expressed in many cancers. Many scholars have also recognized that the abnormal expression of paxillin is related to the prognosis, metastases, invasion, survival, angiogenesis, and other aspects of malignant tumors, suggesting that paxillin may be a potential cancer therapeutic target. Therefore, the study of how aberrant paxillin expression affects the process of tumorigenesis and metastasis will help to develop more efficacious antitumor drugs. Herein, we review the structure of paxillin and its function and expression in tumors, paying special attention to the multifaceted effects of paxillin on tumors, the mechanism of tumorigenesis and progression, and its potential role in tumor therapy. We also hope to provide a reference for the clinical prognosis and development of new tumor therapeutic targets.

Peritoneal Fluid Analysis of Advanced Ovarian Cancers after Hyperthermic Intraperitoneal Chemotherapy.

This study investigated miRNA and cytokine expression changes in peritoneal fluid samples of patients with advanced ovarian cancer (OVCA) after receiving hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS). We collected samples prior to HIPEC, immediately after HIPEC, and 24/48/72 h after CRS from a total of 6 patients. Cytokine levels were assessed using a multiplex cytokine array, and a miRNA PanelChip Analysis System was used for miRNA detection. Following HIPEC, miR-320a-3p, and miR-663-a were found to be immediately down-regulated but increased after 24 h. Further, significant upregulation post-HIPEC and sustained increases in expression were detected in six other miRNAs, including miR-1290, miR-1972, miR-1254, miR-483-5p, miR-574-3p, and miR-574-5p. We also found significantly increased expression of cytokines, including MCP-1, IL-6, IL-6sR, TIMP-1, RANTES, and G-CSF. The changing expression pattern throughout the study duration included a negative correlation in miR-320a-3p and miR-663-a to cytokines including RANTES, TIMP-1, and IL-6 but a positive correlation in miRNAs to cytokines including MCP-1, IL-6sR, and G-CSF. Our study found miRNAs and cytokines in the peritoneal fluid of OVCA patients demonstrated different expression characteristics following CRS and HIPEC. Both changes in expression demonstrated correlations, but the role of HIPEC remains unknown, prompting the need for research in the future.

Superior Unidirectional Water Transport and Mechanically Stable 3D Orthogonal Woven Fabric for Human Body Moisture and Thermal Management.

Unidirectional water transport performance is vital for maintaining human thermal and wet comfort in the field of garment materials. In this work, a 3D orthogonal woven fabric (3DOWF) with excellent one-way transport capacity and mechanical properties is developed via 3D weaving and plasma treatment. The 3DOWF consists of polyester yarns (first layer), cotton yarns (second layer), and viscose yarns (third layer) with successively enhanced water absorption capacity. This allows droplets to penetrate spontaneously from the hydrophobic layer to the hydrophilic layer but not vice versa. Moreover, the Coolmax yarn with the core suction effect in the Z-direction and the plasma-treated polyester of the 3DOWF are shown to efficiently speed up the water transport process. In particular, the water penetration rate of the 3DOWF reaches 25 µl s-1 . In turn, the surface temperature after water absorption is increased by 2.6 °C compared with the cotton fabric, while the tensile strengths in the weft and warp directions of the 3DOWF are 49.62 and 18 MPa, respectively. These values represent the best insulation and mechanical characteristics thus far reported among unidirectional water transport fabrics. Therefore, the 3DOWF has great potential for use in watchbands, backpack belts, insoles, and other functional textiles.

Identification of environmental microorganism using optimally fine-tuned convolutional neural network.

To not only optimize the hyper-parameters of the classification layer of dense convolutional network with 201 convolutional layers (DenseNet-201) but also use data augmentation processes could enhance the performance of DenseNet-201, and DenseNet-201 is rarely applied to the identifications of the environmental microorganism (EM) images. Hence, this study was to propose the optimally fine-tuned DenseNet-201 (OFTD) with data augmentation to better classify the EM images on Environmental Microorganism Dataset (EMDS). The training dataset was composed of 70% Environmental Microorganism Dataset (EMDS) images and so was mainly used to fit the parameters of convolutional layers of optimally fine-tuned DenseNet-201 (OFTD). Meanwhile, the other EMDS images were considered as the testing dataset and used to qualify the performance of the OFTD. Also, gradient-weighted class activation mapping method (Grad-CAM) was adopted to visually illustrate the dominant features of the EM images. Based on the results, the OFTD model with data augmentation achieved the highest classification accuracy of 98.4%. In this case, so its stability and accuracy were guaranteed. Besides, the optimally fine-tuned classification layer is considered a more efficient method than the data augmentation technique adopted in this study when it comes to the improvement of the performance in DenseNet-201 implemented on EMDS. Grad-CAM highlighted the coarse EM features identified effectively by the OFTD; for example, foot and stalk were considered as the dominated features of Rotifera and Vorticella, respectively. In summary, the proposed OFTD with data augmentation could provide an efficient solution for the EM detection in digital microscope.

Quality assurance of integrative big data for medical research within a multihospital system.

BACKGROUND: The need is growing to create medical big data based on the electronic health records collected from different hospitals. Errors for sure occur and how to correct them should be explored. METHODS: Electronic health records of 9,197,817 patients and 53,081,148 visits, totaling about 500 million records for 2006-2016, were transmitted from eight hospitals into an integrated database. We randomly selected 10% of patients, accumulated the primary keys for their tabulated data, and compared the key numbers in the transmitted data with those of the raw data. Errors were identified based on statistical testing and clinical reasoning. RESULTS: Data were recorded in 1573 tables. Among these, 58 (3.7%) had different key numbers, with the maximum of 16.34/1000. Statistical differences (P < 0.05) were found in 34 (58.6%), of which 15 were caused by changes in diagnostic codes, wrong accounts, or modified orders. For the rest, the differences were related to accumulation of hospital visits over time. In the remaining 24 tables (41.4%) without significant differences, three were revised because of incorrect computer programming or wrong accounts. For the rest, the programming was correct and absolute differences were negligible. The applicability was confirmed using the data of 2,730,883 patients and 15,647,468 patient-visits transmitted during 2017-2018, in which 10 (3.5%) tables were corrected. CONCLUSION: Significant magnitude of inconsistent data does exist during the transmission of big data from diverse sources. Systematic validation is essential. Comparing the number of data tabulated using the primary keys allow us to rapidly identify and correct these scattered errors.

Emerging roles of circular RNAs in osteoporosis.

Osteoporosis is one bone disease characterized with skeletal impairment, bone strength reduced and fracture risk enhanced. The regulation processes of bone metabolism are associated with several factors such as mechanical stimulation, epigenetic regulation and hormones. However, the mechanism of osteoporosis remains unsatisfactory. Increasing high-throughput RNA sequencing and circular RNAs (circRNAs) microarray studies indicated that circRNAs are differentially expressed in osteoporosis. Growing functional studies further pinpointed specific deregulated expressed circRNAs (e.g., circ_28313, circ_0016624, circ_0006393, circ_0076906 and circ_0048211) for their functions involved in bone metabolism, including bone marrow stromal cells (BMSCs) differentiation, proliferation and apoptosis. Moreover, CircRNAs (circ_0002060, Circ_0001275 and Circ_0001445) may be acted as diagnostic biomarkers for osteoporosis. This review discussed recent progresses in the circRNAs expression profiling analyses and their potential functions in regulating BMSCs differentiation, proliferation and apoptosis.

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.

Identification of Specific Endobronchial Ultrasound Features to Differentiate Sarcoidosis From Other Causes of Lymphadenopathy.

OBJECTIVES: We hypothesized that specific endobronchial ultrasound (EBUS) features may differentiate sarcoidosis from other causes of lymphadenopathy. METHODS: We conducted this retrospective observational study from January 2014 to January 2019 to analyze patients with intrathoracic lymphadenopathy who underwent EBUS-guided transbronchial needle aspiration. Ultrasound features, including nodal size, margin, echogenicity, the presence or absence of calcification, a central hilar structure, the coagulation necrosis sign, nodal conglomeration, and the septal vessel sign in the color Doppler mode were recorded and compared between 3 groups. RESULTS: Of the 90 included patients, 15 had a diagnosis of tuberculosis; 56 had a diagnosis of sarcoidosis; and 19 had a diagnosis of malignant lymph nodes by EBUS-guided transbronchial needle aspiration. The presence of nodal conglomeration (94.6% versus 60.0% versus 5.3%; P < .001), the septal vessel sign in the color Doppler mode (55.4% versus 13.3% versus 15.8%; P = .002), and a distinct margin (73.2% versus 13.3% versus 47.4%; P < .001) were significantly higher in the sarcoidosis group than in the tuberculosis lymphadenopathy and malignant lymph node groups. The presence of the coagulation necrosis sign (8.9% versus 93.3% versus 31.6%; P < .001) was significantly lower in the sarcoidosis group than in tuberculosis lymphadenopathy and malignant lymph node groups. A multivariate analysis showed that the presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode were independent predictive factors for the diagnosis of sarcoidosis. CONCLUSIONS: The presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode in lymph nodes on EBUS are predictive of sarcoidosis.

Utility of Activated Carbon Nanoparticle (CNP) During total Thyroidectomy for Clinically Nodal Positive Papillary Thyroid Carcinoma (PTC).

BACKGROUND: Activated carbon nanoparticle (CNP) is a novel tracer that may facilitate nodal dissection in clinically nodal positive (cN1) papillary thyroid carcinoma (PTC). The present study compared the nodal yield and surgical outcomes between surgery with CNP and without CNP. METHODS: Patients who underwent total thyroidectomy with therapeutic nodal dissection for cN1 PTC were given the option of intraoperative CNP injection. Among those who received CNP, 0.2 mL CNP suspension was injected in both thyroid lobes before dissection. Study endpoints included number of total and metastatic lymph nodes, inadvertently removed parathyroid glands (PGs), postoperative parathyroid hormone, calcium, and post-6-month thyroglobulin (Tg). Biochemical complete response (BCR) was defined as Tg ≤ 1 ng/mL and/or stimulated Tg ≤ 2 ng/mL. RESULTS: One-hundred and twenty patients (58.3%) received CNP, while 86 (41.7%) had surgery without CNP. Demographics, tumor characteristics, and operative time were comparable between the two groups. However, total mean number of normal and metastatic lymph nodes retrieved were significantly greater in CNP group (10.0 vs. 8.1, p = 0.032 and 4.5 vs. 2.7, p = 0.002, respectively). Rate of inadvertently removed PG was significantly less in CNP group (13.3% vs. 23.3%, p = 0.042). Postoperative Tg level and BCR were significantly lower in CNP group (9.9 ng/mL vs. 14.7 ng/mL, p = 0.297 and 82.4% vs. 72.9%, p = 0.002, respectively). However, large-sized ( ≥ 3 cm) PTCs had a significantly lower nodal staining rate than smaller-sized PTCs (10.3% vs. 69.4%, p < 0.001). CONCLUSIONS: CNP injection can facilitate therapeutic central nodal dissection by increasing the nodal yield rates and reducing inadvertent PG removal. To enhance its utility, a greater volume of CNP might be necessary in larger-sized (> 3 cm) PTCs.

MicroRNA-let-7c suppresses hepatitis C virus replication by targeting Bach1 for induction of haem oxygenase-1 expression.

MicroRNAs are small noncoding RNAs that are central factors between hepatitis C virus (HCV) and host cellular factors for viral replication and liver disease progression, including liver fibrosis, cirrhosis and hepatocellular carcinoma. In the present study, we found that overexpressing miR-let-7c markedly reduced HCV replication because it induced haem oxygenase-1 (HO-1) expression by targeting HO-1 transcriptional repressor Bach1, ultimately leading to stimulating an antiviral interferon response and blockade of HCV viral protease activity. In contrast, the antiviral actions of miR-let-7c were attenuated by miR-let-7c inhibitor treatment, exogenously expressing Bach1 or suppressing HO-1 activity and expression. A proposed model indicates a key role for miR-let-7c targeting Bach1 to transactivate HO-1-mediated antiviral actions against HCV. miR-let-7c may serve as an attractive target for antiviral development.

Outcome and prognostic factors of patients treated in the intensive care unit for carbon monoxide poisoning.

BACKGROUND: Carbon monoxide (CO), a colorless and odorless gas, is one of the common causes of poisoning-related deaths worldwide. CO poisoning can result in hypoxic brain damage and death, but intensive care can improve the likely outcome for critically ill patients. However, there is a paucity of clinical data regarding the prognostic factors and association between organ dysfunction and clinical outcome of patients treated for CO poisoning in the intensive care unit (ICU). METHODS: We performed a retrospective study of patients admitted to a university affiliated hospital ICU between July 2001 and December 2010 following CO poisoning. Outcomes were survival to ICU discharge and to hospital discharge. RESULTS: Seven hundred and eighty-seven patients were admitted to the university hospital following CO poisoning, of which 140 (17.8%) were admitted to the hospital ICU. The overall mortality rate of the patients admitted to the ICU was 14.3% (20/140). Univariate analysis indicated that non-surviving patients with CO poisoning were more likely to have initial blood carboxyhemoglobin (COHb) level > 30%, shock, acute respiratory failure, Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 25, Glasgow coma scale (GCS) score of 3, acute renal failure, dysfunction or failure of more than 3 organs, low blood pH, low HCO3- level, high potassium level, and high glucose level. They were also more likely to have not received hyperbaric oxygen (HBO) intervention. Multivariate logistical regression analysis indicated that the mortality rate of patients treated in the ICU for CO poisoning was higher if their initial APACHE II score was ≥25, GCS was 3, and more than 3 organs were dysfunctional. Moreover, HBO intervention in ICU significantly decreased patients' risk of mortality due to CO poisoning. CONCLUSION: In conclusion, we observed that APACHE II score >25, GCS 3, and dysfunction of more than 3 organ systems on admission to emergency department was associated with a significant mortality risk in patients treated in the ICU for CO poisoning. Moreover, HBO therapy could reduce the risk of mortality in patients with CO poisoning in ICU.

Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism.

Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 µg/mL, activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.

Construction of diagnosis system and gene regulatory networks based on microarray analysis.

A microarray analysis generally contains expression data of thousands of genes, but most of them are irrelevant to the disease of interest, making analyzing the genes concerning specific diseases complicated. Therefore, filtering out a few essential genes as well as their regulatory networks is critical, and a disease can be easily diagnosed just depending on the expression profiles of a few critical genes. In this study, a target gene screening (TGS) system, which is a microarray-based information system that integrates F-statistics, pattern recognition matching, a two-layer K-means classifier, a Parameter Detection Genetic Algorithm (PDGA), a genetic-based gene selector (GBG selector) and the association rule, was developed to screen out a small subset of genes that can discriminate malignant stages of cancers. During the first stage, F-statistic, pattern recognition matching, and a two-layer K-means classifier were applied in the system to filter out the 20 critical genes most relevant to ovarian cancer from 9600 genes, and the PDGA was used to decide the fittest values of the parameters for these critical genes. Among the 20 critical genes, 15 are associated with cancer progression. In the second stage, we further employed a GBG selector and the association rule to screen out seven target gene sets, each with only four to six genes, and each of which can precisely identify the malignancy stage of ovarian cancer based on their expression profiles. We further deduced the gene regulatory networks of the 20 critical genes by applying the Pearson correlation coefficient to evaluate the correlationship between the expression of each gene at the same stages and at different stages. Correlationships between gene pairs were calculated, and then, three regulatory networks were deduced. Their correlationships were further confirmed by the Ingenuity pathway analysis. The prognostic significances of the genes identified via regulatory networks were examined using online tools, and most represented biomarker candidates. In summary, our proposed system provides a new strategy to identify critical genes or biomarkers, as well as their regulatory networks, from microarray data.

One-Pot Two-Nanoprobe Assay Uncovers Targeted Glycoprotein Biosignature.

We report a one-pot two-nanoprobe approach coupled to mass spectrometry for simultaneous quantification and post-translational modification (PTM) profiling of targeted protein in biofluid. Using N-glycoprotein as model, the assay employs two nanoprobes, antibody-conjugated SiO2 nanoparticles and lectin-conjugated magnetic Fe3O4 nanoparticles, to achieve target glycoprotein isolation from biofluid and subsequent glycopeptide enrichment in a single tube. As demonstrated on α-fetoprotein (AFP), a serum biomarker for hepatocellular carcinoma (HCC), the assay has high purification specificity (20 glycopeptides) with 2-fold and 10-fold superior total glycopeptide intensity compared to non-one-pot method (9 glycopeptides) or without enrichment (6 glycopeptides), respectively. By multiple reaction monitoring mass spectrometry (MRM-MS) analysis of the nonglycopeptides, the assay can quantify low abundant AFP expression (0.5 ng) with good correlation with conventional ELISA method (Pearson's r = 0.987). Furthermore, we present the first study revealing AFP glycopeptide signatures of individual HCC patients, comprised of 23 heterogeneous glycoforms of bi- and triantennary, core and terminal fucosylation, and mono- to trisialylation. In addition to 12 novel AFP glycoforms, our quantification result uncovers five abundant glycoforms in HCC, including 3 core-fucosylated (CF) forms. These identified CF forms may be evaluated in future studies as potential targets in a glycopeptide biomarker panel to further improve accuracy of conventional AFP-L3 tests. Through this one-pot assay, a comprehensive target protein profile comprised of protein expression and glycosylation pattern was achieved in simple protocol with high sensitivity, reduced analysis time, and minute starting material. This assay can be extended to other PTM biosignatures by conjugation of other affinity ligands on the nanoprobe.

The Synthesis and Assembly Mechanism of Micro/Nano-Sized Polystyrene Spheres and Their Application in Subwavelength Structures.

The following study involved the utilization of dispersion polymerization to synthesize micron/nano-sized polystyrene (PS) spheres, which were then deposited onto a silicon substrate using the floating assembly method to form a long-range monolayer. Subsequently, dry etching techniques were utilized to create subwavelength structures. The adjustment of the stabilizer polyvinylpyrrolidone (PVP), together with changes in the monomer concentration, yielded PS spheres ranging from 500 nm to 5.6 µm in diameter. These PS spheres were suspended in a mixture of alcohol and deionized water before being arranged using the floating assembly method. The resulting tightly packed particle arrangement is attributed to van der Waals forces, Coulomb electrostatic forces between the PS spheres, and surface tension effects. The interplay of these forces was analyzed to comprehend the resulting structure. Dry etching, utilizing the PS spheres as masks, enabled the exploration of the effects of etching parameters on the resultant structures. Unlike traditional dry etching methods controlling RF power and etching gases, in the present study, we focused on adjusting the oxygen flow rate to achieve cylindrical, conical, and parabolic etched structures.

Progerin Inhibits the Proliferation and Migration of Melanoma Cells by Regulating the Expression of Paxillin.

Objective: Progerin, the underlying cause of Hutchinson-Gilford Progeria Syndrome (HGPS), has been extensively studied for its impact on normal cells and premature aging patients. However, there is a lack of research on its specific effects on tumor cells. Melanoma is one of the most common malignant tumors with high morbidity and mortality. This study aimed to elucidate the potential therapeutic role of progerin in melanoma. Materials and Methods: We constructed the melanoma A375 cell line and M14 cell line with stable expression of progerin. The expression of progerin, paxillin, and epithelial-mesenchymal transition (EMT) marker proteins in each cell group was measured using Western blot. The migration, proliferation, and cell cycle of cancer cells were assessed using the transwell assay, wound healing assay, colony formation assay, CCK 8 assay, and flow cytometry. RT-qPCR technology was used to examine the impact of progerin overexpression on microRNA expression. Finally, we transfected paxillin into the progerin overexpression cell group to verify whether progerin regulates the phenotype of tumor cells through paxillin. Results: Our study demonstrated that overexpression of progerin leads to decreased expression of paxillin and inhibits cancer cell migration, proliferation, EMT process and cell cycle progression. Additionally, rescue experiments revealed that the migration, proliferation ability, and EMT marker protein expression in progerin overexpressing cancer cells could be partially restored by transfecting a plasmid containing the paxillin gene. Mechanistic investigations further revealed that progerin achieves this inhibition of paxillin expression by upregulating miR-212. Conclusion: This study reveals that progerin may inhibit the migration and proliferation of melanoma cells through the miR-212/paxillin axis, which provides a new approach for the future treatment of this disease.

Low Driving Voltage Electroluminescence Device for Integrated Visual Strain Sensing.

As a pivotal component in human-machine interactions, display devices have undergone rapid development in modern life. Displays such as alternative current electroluminescence|alternative current electroluminescent (ACEL) devices with high flexibility and long operational lifetimes are essential for wearable electronics. However, ACEL devices are constrained by their inherent high driving voltage and complex fabrication processes. Our work presents an easy blade-coating method for fabricating flexible ACEL display devices based on an all-solution process. By dispersing BaTiO3 and ZnS/Cu powder into waterborne polyurethane, we successfully combined dielectric and fluorescence functionalities within a single layer, significantly reducing the device's driving voltage. Additionally, the ionic conducting hydrogel was chosen as a transparent electrode to achieve good electrical contact and strong interfacial adhesion through in situ polymerization. Owing to the unique method, our ACEL device exhibits high flexibility, low driving voltage (20-100 V), high brightness (300+ cd/m2 at 60 V), and environmental friendliness. Furthermore, by repurposing the hydrogel electrode, we integrated strain visualization capabilities within a single device, highlighting its potential for applications such as wearable healthcare monitoring.