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1.
Fish Shellfish Immunol ; 150: 109605, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38704111

ABSTRACT

Crucian carp (Carassius carassius) is an important aquatic economic animal, and the immune barrier function of its intestine has been a focus of research into oral vaccines and drugs. However, the histological structures of the intestinal barrier and its adjacent areas have not been clearly established, and little subcellular evidence is available to elucidate the spatial distribution of intracellular biological processes. In this study, the spatial distribution of autophagy and endosome formation in the intestinal epithelial cells (IECs) of crucian carp were analyzed. These two biological activities are closely related to intestinal homeostasis, immunity, and cell communication. Periodic acid-Schiff (PAS) and Masson's trichrome staining were employed to elucidate the distinctive histological framework of the Crucian carp's myoid cell network, which resides within the subepithelial layer and is characterized by gap junctions. Transmission electron microscopy (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) were used to detect the structural and functional aspects of the IEC in different intestinal segments. TEM and immunohistochemical analyses captured the biogenesis and maturation of early and late endosomes as well as multivesicular bodies (MVBs), as well as the initiation and progression of autophagy, including macroautophagy and mitophagy. The endosome and MVBs-specific marker CD63 and autophagy-related protein LC3 were highly expressed in IECs and were correlated with autophagy and endosome biosynthesis in the apical and basal regions of individual cells, and differed between different intestinal segments. In summary, this study elucidated the ubiquity and morphological characteristics of autophagy and endosome formation across different intestinal segments of crucian carp. A unique myoid cell network beneath the intestinal epithelium in crucian carp was also identified, expanding the histological understanding of this animal's intestinal tract.


Subject(s)
Autophagy , Carps , Endosomes , Animals , Carps/immunology , Endosomes/immunology , Endosomes/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/cytology , Intestines/immunology , Intestines/cytology , Epithelial Cells/immunology
2.
J Am Soc Mass Spectrom ; 35(5): 992-998, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38634762

ABSTRACT

This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples space- and velocity-focusing to precisely analyze the flight-time distribution of ions and predict optimal experimental parameters for the highest mass resolving power. Experimental validation was conducted using a laboratory-made instrument to analyze CsI3 and angiotensin I ions in low to medium m/z range. The results indicate that the predicted optimal extraction voltage and delay were reasonably accurate and effective. In the low m/z range, the peak width obtained using optimal parameters reached the sub nanosecond range, corresponding to a mass resolving power of 10 000-17 000, or 20 000-34 000 if shot-to-shot random fluctuations were minimized by the dynamic data correction method. The observed optimal mass resolving power in the current experiment is 4.8-7.8 times that of commercial instruments. Practical limitations resulting in the gap between the observed and theoretical ultimate mass resolving power are discussed.

3.
Insect Mol Biol ; 33(3): 259-269, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38335442

ABSTRACT

The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR-6498-5p was down-regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 (BmPLPP2) was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR-6498-5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR-6498-5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4-deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR-6498-5p has a potential anti-BmNPV role by down-regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR-6498-5p down-regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori-BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.


Subject(s)
Bombyx , MicroRNAs , Nucleopolyhedroviruses , Animals , Bombyx/virology , Bombyx/genetics , Bombyx/metabolism , Down-Regulation , Insect Proteins/metabolism , Insect Proteins/genetics , Larva/metabolism , Larva/virology , Larva/genetics , Larva/growth & development , MicroRNAs/metabolism , MicroRNAs/genetics , Nucleopolyhedroviruses/physiology , Pyridoxal Phosphate/metabolism , Virus Replication
4.
Neural Regen Res ; 19(5): 1126-1133, 2024 May.
Article in English | MEDLINE | ID: mdl-37862218

ABSTRACT

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

5.
Fish Shellfish Immunol ; 141: 109024, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37619762

ABSTRACT

The allogeneic crucian carp is an important fish farm animal with a very different digestive system structure from that of mammals. The lamina propria of the fish intestine is also considered to be an important site of intestinal immunity in fish, but functional histological studies of the lamina propria of the allogeneic crucian carp intestine are still lacking. In this study, Identification of the ubiquitous lamina propria mucus cells in the lamina propria of the intestine by hematoxylin-eosin staining, and determination of the mucocytic properties, class, and distribution of these cells in each intestinal segment by Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining. The results show that type III mucus cells were abundant in the lamina propria of the foregut and midgut, while type II and type IV mucus cells predominate in the hindgut, possibly reflecting the distinct functions of these intestinal segments. Transmission electron microscopy dissected the differentiation of mucus cells in the lamina propria of the intestine at the ultrastructural level and investigated their morphology and distribution patterns in different intestinal segments, the findings revealed that lamina propria mucus cells perform rudimentary functions such as mucous secretion, phagocytosis, and degradation functions. Moreover, immunohistochemistry labeling with CD68 and LAMP1 revealed that numerous cells in the anterior, middle, and posterior intestines were positive for both proteins. Immunofluorescence double-labeling demonstrated that these cells highly co-expressed CD68 and LAMP1. Besides, the distribution and morphology of CD68+ and LAMP1+ cells were similar to those of AB-PAS positive cells and they accounted for the majority of parenchyma cells. Considering the above results, there were abundant cells with both mucous secretion and phagocytosis in the intestinal lamina propria of allogeneic crucian carp, which are a essential component of the intestinal immune process of allogeneic crucian carp.


Subject(s)
Carps , Hematopoietic Stem Cell Transplantation , Animals , Intestinal Mucosa , Mucus , Cell Differentiation , Mammals
6.
J Comput Aided Mol Des ; 37(11): 507-517, 2023 11.
Article in English | MEDLINE | ID: mdl-37550462

ABSTRACT

Generative approaches to molecular design are an area of intense study in recent years as a method to generate new pharmaceuticals with desired properties. Often though, these types of efforts are constrained by limited experimental activity data, resulting in either models that generate molecules with poor performance or models that are overfit and produce close analogs of known molecules. In this paper, we reduce this data dependency for the generation of new chemotypes by incorporating docking scores of known and de novo molecules to expand the applicability domain of the reward function and diversify the compounds generated during reinforcement learning. Our approach employs a deep generative model initially trained using a combination of limited known drug activity and an approximate docking score provided by a second machine learned Bayes regression model, with final evaluation of high scoring compounds by a full docking simulation. This strategy results in molecules with docking scores improved by 10-20% compared to molecules of similar size, while being 130 × faster than a docking only approach on a typical GPU workstation. We also show that the increased docking scores correlate with (1) docking poses with interactions similar to known inhibitors and (2) result in higher MM-GBSA binding energies comparable to the energies of known DDR1 inhibitors, demonstrating that the Bayesian model contains sufficient information for the network to learn to efficiently interact with the binding pocket during reinforcement learning. This outcome shows that the combination of the learned latent molecular representation along with the feature-based docking regression is sufficient for reinforcement learning to infer the relationship between the molecules and the receptor binding site, which suggest that our method can be a powerful tool for the discovery of new chemotypes with potential therapeutic applications.


Subject(s)
Deep Learning , Drug Discovery , Bayes Theorem , Computer Simulation , Machine Learning , Drug Design
7.
Anal Chim Acta ; 1264: 341307, 2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37230717

ABSTRACT

Informative dissociation of carbohydrates using an infrared (IR) irradiation system is demonstrated under ambient conditions without the instrumentation of a mass spectrometer. Structural identification of carbohydrates and associated conjugates is essential for understanding their biological functions, but identification remains challenging. Herein, an easy and rugged method is reported for the structural identification of model carbohydrates, including Globo-H, three trisaccharide isomers (nigerotriose/laminaritriose/cellotriose), and two hexasaccharide isomers (laminarihexaose/isomaltohexaose). For Globo-H, the numbers of cross-ring cleavages increased by factors of 4.4 and 3.4 upon ambient IR exposure, compared to an untreated control and a collision-induced dissociation (CID) sample. Moreover, 25-82% enhancement in the numbers of glycosidic bond cleavages upon ambient IR exposure was also obtained compared to untreated and CID samples. Unique features of first-generation fragments produced by ambient IR facilitated the differentiation of three trisaccharide isomers. Semi-quantitative analysis was achieved (coefficient of determination (R2) of 0.982) in a mixture of two hexasaccharide isomers via unique features generated upon ambient IR. Photothermal and radical migration effects induced by ambient IR were postulated as responsible for promoting carbohydrate fragmentation. This easy and rugged method could be a universally applicable protocol and complementary to other techniques for detailed structural characterization of carbohydrates.


Subject(s)
Carbohydrates , Trisaccharides , Carbohydrates/chemistry , Mass Spectrometry/methods
8.
Mass Spectrom Rev ; 42(6): 2426-2445, 2023.
Article in English | MEDLINE | ID: mdl-35686331

ABSTRACT

A major challenge in modern mass spectrometry (MS) is achieving high mass resolving power and accuracy for precision analyses in high mass-to-charge (m/z) regions. To advance the capability of MS for increasingly demanding applications, understanding limitations of state-of-the-art techniques and their status in applied sciences is essential. This review summarizes important instruments in high-resolution mass spectrometry (HRMS) and related advances to extend their working range to high m/z regions. It starts with an overview of HRMS techniques that provide adequate performance for macromolecular analysis, including Fourier-transform, time-of-flight (TOF), quadrupole-TOF, and related data-processing techniques. Methodologies and applications of HRMS for characterizing macromolecules in biochemistry and material sciences are summarized, such as top-down proteomics, native MS, drug discovery, structural virology, and polymer analyses.

10.
J Ovarian Res ; 15(1): 134, 2022 Dec 23.
Article in English | MEDLINE | ID: mdl-36564848

ABSTRACT

BACKGROUND: Peritoneal dissemination is the predominant feature of malignant progression in ovarian cancer and is a major cause of poor surgical outcomes and clinical prognoses. Abnormal glycosylation of carbohydrate antigen 125 (CA125) may be involved in peritoneal implantation and metastasis. Here, we evaluated the clinical relevance of CA125-Tn glycoform in the assessment of high-grade serous ovarian cancer (HGSOC). METHODS: A total of 72 patients diagnosed with HGSOC were included. Pre-treatment serum CA125-Tn levels were measured using an antibody-lectin enzyme-linked immunosorbent assay. The association of CA125-Tn with clinical factors was analyzed in all cases, whereas its association with peritoneal dissemination, residual disease, and progression-free survival was analyzed in stage III-IV cases. RESULTS: Pre-treatment serum CA125-Tn levels were significantly higher in advanced-stage HGSOC patients than in early-stage patients (P = 0.029). In advanced-stage patients, the pre-treatment CA125-Tn level increased with an increase in Fagotti's score (P = 0.004) and with the extension of peritoneal dissemination (P = 0.011). The pre-treatment CA125-Tn level increased with the volume of residual disease (P = 0.005). The association between CA125-Tn level and suboptimal surgery remained significant even after adjustment for treatment type and stage. Pre-treatment CA125-Tn levels were also related to disease recurrence. CONCLUSION: Serum CA125-Tn level could be a novel biomarker for peritoneal dissemination and a promising predictor of surgical completeness in ovarian cancer. Patients with lower CA125-Tn levels were more likely to have no residual disease. CA125-Tn could help surgeons to adopt optimized treatment strategies for patients with advanced ovarian cancer as a pre-treatment evaluator.


Subject(s)
Biomarkers, Tumor , Ovarian Neoplasms , Humans , Female , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , CA-125 Antigen , Ovarian Neoplasms/pathology , Prognosis , Carcinoma, Ovarian Epithelial/pathology
11.
Environ Res ; 214(Pt 4): 113934, 2022 11.
Article in English | MEDLINE | ID: mdl-36027962

ABSTRACT

The overuse of N fertilizers has caused serious environmental problems (e.g., soil acidification, excessive N2O in the air, and groundwater contamination) and poses a serious threat to human health. Improving N fertilizer utilization efficiency and plant uptake is an alternative for N fertilizers overuses. Enterobacter cloacae is an opportunistic pathogen, also used as plant growth-promoting rhizobacteria (PGPR), has been widely presented in the fields of bioremediation and bioprotection. Here we developed a new N fixation-release model by combining biochar with E. cloacae. The efficiency of the model was evaluated using a greenhouse pot experiment with maize (Zea mays L.) as the test crop. The results showed that biochar combined with E. cloacae significantly increased the N content. The application of biochar combined with E. cloacae increased total N in soil by 33% compared with that of N fertilizers application. The N-uptake and utilization efficiency (NUE) in plant was increased 17.03% and 14.18%, respectively. The activities of urease, dehydrogenase and fluorescein diacetate hydrolase (FDA) was improved, the catalase (CAT) activity decreased. Analysis of the microbial community diversity revealed the abundance of Proteobacteria, Actinobacteria, Firmicutes, and Gemmatimonadetes were significantly improved. The mechanism under the model is that E. cloacae acted as N-fixation by capturing N2 from air. Biochar served as carrier, supporting better living environment for E. cloacae, also as adsorbent adsorbing N from fertilizer and from fixed N by E. cloacae, the adsorption in turn slower the N release. Altogether, the model promotes N utilization by plants, improves the soil environment, and reduces N pollution.


Subject(s)
Fertilizers , Nitrogen , Agriculture/methods , Bacteria , Environmental Pollution , Fertilizers/analysis , Humans , Nitrogen/analysis , Soil , Zea mays
12.
J Chromatogr A ; 1680: 463445, 2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36041250

ABSTRACT

Polysaccharides are biopolymers known to possess various bioactivities. Because of their molecular complexity, the structural characterization of polysaccharides remains challenging, and difficult to be completed with a single analytical method. In this study, a novel approach for the characterization of linkages and anomeric configuration of polysaccharides was proposed. Based on ion mobility-mass spectrometry (IM-MS), a database containing 5 glucotriose standards was set up. Information about the arrival time distribution and fragmentation patterns of these standards were included. The method was validated by three commercially available purified polysaccharides, namely laminarin, dextrin, and dextran, each having distinct connectivity and configuration of the glycosidic bonds. Lastly, the method was successfully applied to analyze polysaccharides prepared from three medicinal mushrooms, namely Xylaria nigripes, Grifola frondosa, and Laetiporus sulphureus. The results showed that water-soluble non-digestible polysaccharides of X. nigripes and G. frondosa were mainly composed of (1→3)-ß-glucan, while that of L. sulphureus was composed of (1→3)-ɑ-glucan. The present method has the advantages of being simple in sample preparation and short analysis time.


Subject(s)
Agaricales , Grifola , beta-Glucans , Agaricales/chemistry , Grifola/chemistry , Mass Spectrometry , Polysaccharides/chemistry , beta-Glucans/chemistry
13.
Analyst ; 147(18): 4116-4123, 2022 Sep 12.
Article in English | MEDLINE | ID: mdl-35971964

ABSTRACT

A miniature matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometer suitable for the high mass-to-charge (m/z) region is described. The instrument size is roughly 1/50th that of regular instruments, and detailed dimensions and experimental parameters were optimized based on the comprehensive calculation method to provide satisfactory mass resolving power. Observations showed that the performance is limited in the low m/z range and becomes comparable with that of regular instruments in the mid m/z range. In the high m/z range, the miniature instrument provides better mass resolving power and sensitivity than regular instruments, showing superior performance for microbial, protein conjugate, and polymer analyses.


Subject(s)
Proteins , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
14.
J Agric Food Chem ; 70(31): 9625-9636, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35915870

ABSTRACT

Herbicides are critical resources for meeting agricultural demand. While similar in structure and function to pharmaceuticals, the development of new herbicidal mechanisms of action and new scaffolds against known mechanisms of action has been much slower than in pharmaceutical sciences. We hypothesized that this may be due in part to a relative undersampling of possible herbicidal chemistries and set out to test whether this difference in sampling existed and whether increasing the diversity of possible herbicidal chemistries would be likely to result in more efficacious herbicides. To conduct this work, we first identified databases of commercially available herbicides and clinically approved pharmaceuticals. Using these databases, we created a two-dimensional embedding of the chemical, which provides a qualitative visualization of the degree to which each chemotype is distributed within the combined chemical space and shows a moderate degree of overlap between the two sets. Next, we trained several machine learning models to classify herbicides versus drugs based on physicochemical characteristics. The most accurate of these models has an accuracy of 93% with the key differentiating characteristics being the number of polar hydrogens, number of amide bonds, LogP, and polar surface area. We then used several types of scaffold decomposition to quantitatively evaluate the chemical diversity of each molecular family and showed herbicides to have considerably fewer unique structural fragments. Finally, we used molecular docking as an in silico evaluation of further structural diversification in herbicide development. To this end, we identified herbicides with well-characterized binding sites and modified those scaffolds based on similar structural subunits from the drug dataset not present in any commercial herbicide while using the machine-learned model to ensure that required herbicide properties were maintained. Redocking the original and modified scaffolds of several herbicides showed that even this simple design strategy is capable of yielding new molecules with higher predicted affinity for the target enzymes. Overall, we show that herbicides are distinct from drugs based on physicochemical properties but less diverse in their chemistry in a way not governed by these properties. We also demonstrate in silico that increasing the diversity of herbicide scaffolds has the potential to increase potency, potentially reducing the amount needed in agricultural practice.


Subject(s)
Herbicides , Cheminformatics , Herbicides/chemistry , Herbicides/pharmacology , Molecular Docking Simulation , Pharmaceutical Preparations
15.
Biochem Biophys Res Commun ; 619: 166-172, 2022 09 03.
Article in English | MEDLINE | ID: mdl-35803057

ABSTRACT

RNA N6-methyladenosine (m6A) level is closely associated with neurodevelopment and central nervous system dysfunctions including spinal cord injury (SCI). M6A level can be dynamically regulated by m6A methyltransferases and demethylases. In this text, the roles of m6A demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) in SCI development along with its m6A-dependent regulatory mechanisms were investigated in hypoxia-induced PC12 cell injury model. The results showed that FTO was low expressed in spinal cord tissues of rats after contusive SCI and hypoxia-treated PC12 cells. FTO knockdown alleviated hypoxia-induced PC12 cell injury. FTO loss increased GADD45B expression and m6A level in PC12 cells. GADD45B knockdown weakened the protective effects of FTO depletion on hypoxia-treated PC12 cells. FTO regulated GADD45B expression in an IGF2BP2-dependent manner. In conclusion, FTO knockdown mitigated the injury of hypoxia-induced PC12 cells by up-regulating GADD45B in an IGF2BP2-dependent manner.


Subject(s)
Adenosine , Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Ketoglutarate Dehydrogenase Complex/metabolism , Adenosine/metabolism , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Animals , Antigens, Differentiation , Hypoxia , Methyltransferases/metabolism , PC12 Cells , RNA-Binding Proteins/metabolism , Rats
16.
Clin Hemorheol Microcirc ; 82(2): 169-182, 2022.
Article in English | MEDLINE | ID: mdl-35662113

ABSTRACT

BACKGROUND: Circular RNA (circRNA) is considered to be an important regulator of human diseases, including atherosclerosis (AS). However, the role of circ_ARHGAP32 in AS formation needs further confirmation. OBJECTIVE: To explore the role of circ_ARHGAP32 in AS formation. METHODS: Oxidized low density lipoprotein (ox-LDL) was used to treat vascular smooth muscle cells (VSMCs) to mimic AS cell models in vitro. The expression of circ_ARHGAP32, microRNA (miR)-665, and fibroblast growth factor 2 (FGF2) was analyzed by quantitative real-time PCR. VSMCs function was measured by EdU assay, cell counting kit 8 assay and transwell assay. Protein expression was determined using western blot analysis. Dual-luciferase reporter assay and RNA pull-down assay were performed to verify RNA interaction. RESULTS: Circ_ARHGAP32 was highly expressed in AS patients and ox-LDL-induced VSMCs. Knockdown of circ_ARHGAP32 repressed ox-LDL-induced proliferation and migration in VSMCs. Circ_ARHGAP32 sponged miR-665 to positively regulate FGF2. MiR-665 inhibitor reversed the regulation of sh-circ_ARHGAP32 on ox-LDL-induced VSMCs proliferation and migration. MiR-665 also had a suppressive effect on the proliferation and migration of ox-LDL-induced VSMCs, and this effect could be reversed by FGF2 overexpression. CONCLUSIONS: Circ_ARHGAP32 might be a potential target for AS treatment, which promoted ox-LDL-induced VSMCs proliferation and migration by regulating miR-665/FGF2 network.


Subject(s)
Atherosclerosis , Fibroblast Growth Factor 2 , MicroRNAs , Myocytes, Smooth Muscle , RNA, Circular , Humans , Apoptosis , Atherosclerosis/genetics , Cell Movement , Cell Proliferation , Cells, Cultured , Fibroblast Growth Factor 2/genetics , Lipoproteins, LDL/pharmacology , MicroRNAs/genetics , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/cytology , RNA, Circular/genetics
17.
Vaccines (Basel) ; 10(2)2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35214622

ABSTRACT

Immune checkpoint inhibitors such as monoclonal antibodies (mAbs) are amongst the most important breakthroughs in cancer therapeutics. However, high cost and short acting time limits its affordability and clinical application. Therefore, an economical and durable alternative is urgently needed. Previously, we identified an IL-17RB targeting mAb which intercepts IL-17B/IL-17RB signal transduction and suppresses tumorigenesis in many types of cancer. We reason that active immunity against the antigenic epitope of IL-17RB can reproduce the anti-cancer effect of mAbs with better sustainability. Here, we present a cancer vaccine composed of multiple synthesized epitope peptides chemically conjugated onto CRM197, a highly immunogenic carrier protein. Combining mass spectrometry with immunoassay, we standardized hapten density determination and optimized vaccine design. Furthermore, orthotopically transplanted syngeneic mouse tumor 4T1 showed that administration of this vaccine therapeutically mitigates primary cancer growth as well as distance metastasis. In conclusion, we demonstrate preparation, characterization and pre-clinical application of a novel peptide cancer vaccine.

18.
Article in English | MEDLINE | ID: mdl-35162624

ABSTRACT

Over one-third of energy is generated from coal consumption in Taiwan. In order to estimate the health impact assessment attributable to PM2.5 concentrations emitted from coal consumption in Taiwan. We applied a Gaussian trajectory transfer-coefficient model to obtain county-wide PM2.5 exposures from coal consumption, which includes coal-fired power plants and combined heat and power plants. Next, we calculated the mortality burden attributable to PM2.5 emitted by coal consumption using the comparative risk assessment framework developed by the Global Burden of Disease study. Based on county-level data, the average PM2.5 emissions from coal-fired plants in Taiwan was estimated at 2.03 ± 1.29 (range: 0.32-5.64) µg/m3. With PM2.5 increments greater than 0.1 µg/m3, there were as many as 16 counties and 66 air quality monitoring stations affected by coal-fired plants and 6 counties and 18 monitoring stations affected by combined heat and power plants. The maximum distances affected by coal-fired and combined heat and power plants were 272 km and 157 km, respectively. Our findings show that more counties were affected by coal-fired plants than by combined heat and power plants with significant increments of PM2.5 emissions. We estimated that 359.6 (95% CI: 334.8-384.9) annual adult deaths and 124.4 (95% CI: 116.4-132.3) annual premature deaths were attributable to PM2.5 emitted by coal-fired plants in Taiwan. Even in six counties without power plants, there were 75.8 (95% CI: 60.1-91.5) deaths and 25.8 (95%CI: 20.7-30.9) premature deaths annually attributable to PM2.5 emitted from neighboring coal-fired plants. This study presents a precise and effective integrated approach for assessing air pollution and the health impacts of coal-fired and combined heat and power plants.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , Air Pollution/statistics & numerical data , Coal , Particulate Matter/analysis , Particulate Matter/toxicity , Power Plants , Taiwan/epidemiology
19.
Int J Surg ; 98: 106218, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34995806

ABSTRACT

PURPOSE: The primary purpose of this systematic review and meta-analysis was to investigate the impact of prior arthroscopy on postoperative revisions, complications, and other clinical outcomes after conversion total lower extremity arthroplasty. METHODS: Two individual researchers conducted the platform searches on the Embase, PubMed, Cochrane Central, and Google Scholar electronic databases from inception to June 02, 2021. We identified cohort trials that compared the outcomes of patients who underwent primary THA or TKA in the prior arthroscopy or control groups. The primary outcome was revision, and secondary outcomes included reoperation, patient-reported outcomes, and postoperative complications. A modified version of the Downs and Black tool was used to assess the methodological quality of the non-randomized cohort studies. RESULTS: Of the 23 included studies with 319946 cases, 18 were matched retrospectively and five were non-matched retrospectively. Methodological quality was high in ten studies and moderate in thirteen studies. Our analysis demonstrated that TKA or THA patients with prior arthroscopy were associated with an increased risk of revision, reoperation, infection, and aseptic loosening. THA patients with prior arthroscopy were also associated with an increased risk of dislocation. Furthermore, there were no significant intergroup differences in periprosthetic fracture, range of motion, Harris Hip Score, or Knee Society Score. CONCLUSION: Arthroscopy performed before total lower extremity arthroplasty substantially increased the revision, reoperation, infection, and aseptic loosening rates. THA patients with prior arthroscopy were also associated with an increased risk of dislocation. Patients should be counseled on the potential increased risks associated with conversion total lower extremity arthroplasty after prior arthroscopy. Further research is needed to better characterize these findings.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroscopy , Arthroplasty, Replacement, Hip/adverse effects , Arthroscopy/adverse effects , Humans , Lower Extremity/surgery , Reoperation , Retrospective Studies , Treatment Outcome
20.
IEEE Trans Biomed Circuits Syst ; 16(1): 138-152, 2022 02.
Article in English | MEDLINE | ID: mdl-35077367

ABSTRACT

Empowered by the rapid advancements of semiconductor techniques, emerging areas such as industry 4.0, precise healthcare, pervasive communications, intelligent robots, and smart buildings are to be realized, which put substantial demands on low-power and high-performance cognitive edge sensors. Capabilities of precise sensing and seamless interactions with human subjects are pivotal to boosting versatile Internet of Everything (IoE) applications. However, it is challenging to attain various kinds of intuitive sensing based on one edge sensor. A novel silicon-based phased-array coherent radar sensing platform is proposed to attain versatile application-driven capabilities by focusing the wideband radar beams accurately at the target's direction to attain precise sensing. The coherent radar platform can support a maximum 60° field-of-view sensing range with smaller than 2° optimum steering step resolution and -70-dBm sensitivity. The silicon-based mixed-signal coherent radar chip platform is fabricated by a 65-nm CMOS process and owns the convenience for massive deployments at the edge. A series of experiments were conducted to validate the integrated radar platform's adaptable capabilities and salient performances on human subject detection, vital signs monitoring, and motion recognition. Notably, the adaptable multifunction integrated radar platform opens up the enticing possibility for next-generation monolithic edge devices supporting seamless health sensing and cognitive interactive functions with human subjects.


Subject(s)
Radar , Silicon , Cognition , Humans , Research Subjects , Signal Processing, Computer-Assisted
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