ABSTRACT
Real-time 3D reconstruction has been applied in many fields, calling for many ongoing efforts to improve the speed and accuracy of the used algorithms. Phase shifting profilometry based on the Lucas-Kanade optical flow method is a fast and highly precise method to construct and display the three-dimensional shape of objects. However, in this method, a dense optical flow calculation is required for the modulation image corresponding to the acquired deformed fringe pattern, which consumes a lot of time and affects the real-time performance of 3D reconstruction and display. Therefore, this paper proposes a dynamic 3D phase shifting profilometry based on a corner optical flow algorithm to mitigate this issue. Therein, the Harris corner algorithm is utilized to locate the feature points of the measured object, so that the optical flow needs to calculate for only the feature points which, greatly reduces the amount of calculation time. Both our experiments and simulations show that our method improves the efficiency of pixel matching by four times and 3D reconstruction by two times.
ABSTRACT
BACKGROUND: The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA) was developed to predict the survival of patients with spinal metastasis. The algorithm was successfully tested in five international institutions using 1101 patients from different continents. The incorporation of 18 prognostic factors strengthens its predictive ability but limits its clinical utility because some prognostic factors might not be clinically available when a clinician wishes to make a prediction. QUESTIONS/PURPOSES: We performed this study to (1) evaluate the SORG-MLA's performance with data and (2) develop an internet-based application to impute the missing data. METHODS: A total of 2768 patients were included in this study. The data of 617 patients who were treated surgically were intentionally erased, and the data of the other 2151 patients who were treated with radiotherapy and medical treatment were used to impute the artificially missing data. Compared with those who were treated nonsurgically, patients undergoing surgery were younger (median 59 years [IQR 51 to 67 years] versus median 62 years [IQR 53 to 71 years]) and had a higher proportion of patients with at least three spinal metastatic levels (77% [474 of 617] versus 72% [1547 of 2151]), more neurologic deficit (normal American Spinal Injury Association [E] 68% [301 of 443] versus 79% [1227 of 1561]), higher BMI (23 kg/m2 [IQR 20 to 25 kg/m2] versus 22 kg/m2 [IQR 20 to 25 kg/m2]), higher platelet count (240 × 103/µL [IQR 173 to 327 × 103/µL] versus 227 × 103/µL [IQR 165 to 302 × 103/µL], higher lymphocyte count (15 × 103/µL [IQR 9 to 21× 103/µL] versus 14 × 103/µL [IQR 8 to 21 × 103/µL]), lower serum creatinine level (0.7 mg/dL [IQR 0.6 to 0.9 mg/dL] versus 0.8 mg/dL [IQR 0.6 to 1.0 mg/dL]), less previous systemic therapy (19% [115 of 617] versus 24% [526 of 2151]), fewer Charlson comorbidities other than cancer (28% [170 of 617] versus 36% [770 of 2151]), and longer median survival. The two patient groups did not differ in other regards. These findings aligned with our institutional philosophy of selecting patients for surgical intervention based on their level of favorable prognostic factors such as BMI or lymphocyte counts and lower levels of unfavorable prognostic factors such as white blood cell counts or serum creatinine level, as well as the degree of spinal instability and severity of neurologic deficits. This approach aims to identify patients with better survival outcomes and prioritize their surgical intervention accordingly. Seven factors (serum albumin and alkaline phosphatase levels, international normalized ratio, lymphocyte and neutrophil counts, and the presence of visceral or brain metastases) were considered possible missing items based on five previous validation studies and clinical experience. Artificially missing data were imputed using the missForest imputation technique, which was previously applied and successfully tested to fit the SORG-MLA in validation studies. Discrimination, calibration, overall performance, and decision curve analysis were applied to evaluate the SORG-MLA's performance. The discrimination ability was measured with an area under the receiver operating characteristic curve. It ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An area under the curve of 0.7 is considered clinically acceptable discrimination. Calibration refers to the agreement between the predicted outcomes and actual outcomes. An ideal calibration model will yield predicted survival rates that are congruent with the observed survival rates. The Brier score measures the squared difference between the actual outcome and predicted probability, which captures calibration and discrimination ability simultaneously. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. A decision curve analysis was performed for the 6-week, 90-day, and 1-year prediction models to evaluate their net benefit across different threshold probabilities. Using the results from our analysis, we developed an internet-based application that facilitates real-time data imputation for clinical decision-making at the point of care. This tool allows healthcare professionals to efficiently and effectively address missing data, ensuring that patient care remains optimal at all times. RESULTS: Generally, the SORG-MLA demonstrated good discriminatory ability, with areas under the curve greater than 0.7 in most cases, and good overall performance, with up to 25% improvement in Brier scores in the presence of one to three missing items. The only exceptions were albumin level and lymphocyte count, because the SORG-MLA's performance was reduced when these two items were missing, indicating that the SORG-MLA might be unreliable without these values. The model tended to underestimate the patient survival rate. As the number of missing items increased, the model's discriminatory ability was progressively impaired, and a marked underestimation of patient survival rates was observed. Specifically, when three items were missing, the number of actual survivors was up to 1.3 times greater than the number of expected survivors, while only 10% discrepancy was observed when only one item was missing. When either two or three items were omitted, the decision curves exhibited substantial overlap, indicating a lack of consistent disparities in performance. This finding suggests that the SORG-MLA consistently generates accurate predictions, regardless of the two or three items that are omitted. We developed an internet application (https://sorg-spine-mets-missing-data-imputation.azurewebsites.net/) that allows the use of SORG-MLA with up to three missing items. CONCLUSION: The SORG-MLA generally performed well in the presence of one to three missing items, except for serum albumin level and lymphocyte count (which are essential for adequate predictions, even using our modified version of the SORG-MLA). We recommend that future studies should develop prediction models that allow for their use when there are missing data, or provide a means to impute those missing data, because some data are not available at the time a clinical decision must be made. CLINICAL RELEVANCE: The results suggested the algorithm could be helpful when a radiologic evaluation owing to a lengthy waiting period cannot be performed in time, especially in situations when an early operation could be beneficial. It could help orthopaedic surgeons to decide whether to intervene palliatively or extensively, even when the surgical indication is clear.
ABSTRACT
Circular RNAs (circRNAs) are a group of RNAs featured by a covalently closed continuous loop structure. This study aimed to uncover the function and mechanism of circ-ubiquitin specific peptidase 36 (USP36) in endothelial cells treated with oxidized low-density lipoprotein (ox-LDL). The levels of circ-USP36, microRNA-98-5p (miR-98-5p) and vascular cell adhesion molecule 1 (VCAM1) were examined by a quantitative real-time polymerase chain reaction (qRT-PCR). The viability, apoptosis and inflammation were detected by (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Western blot assay was performed to detect the expression of apoptosis and proliferation-related markers and VCAM1 protein level. The targets of circ-USP36 and miR-98-5p were searched using starBase website, and dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the above predictions. Ox-LDL exposure induced the upregulation of circ-USP36 in HUVEC cells. Circ-USP36 accelerated ox-LDL-induced apoptosis, inflammatory and viability inhibition of HUVEC cells. MiR-98-5p was a direct downstream gene of circ-USP36. Circ-USP36 promoted the injury of ox-LDL-induced HUVEC cells through targeting miR-98-5p. VCAM1 could bind to miR-98-5p, and the protective effects of miR-98-5p accumulation on ox-LDL-induced HUVEC cells were reversed by the transfection of VCAM1. VCAM1 was regulated by circ-USP36/miR-98-5p signaling in HUVEC cells. Ox-LDL promoted the apoptosis and inflammation but suppressed the viability of HUVEC cells through upregulating circ-USP36, thus elevating the expression of VCAM1 via miR-98-5p.
Subject(s)
Endothelium, Vascular/pathology , Inflammation/pathology , Lipoproteins, LDL/adverse effects , MicroRNAs/genetics , RNA, Circular/genetics , Ubiquitin Thiolesterase/genetics , Vascular Cell Adhesion Molecule-1/metabolism , Apoptosis , Cell Proliferation , Endothelium, Vascular/drug effects , Endothelium, Vascular/injuries , Endothelium, Vascular/metabolism , Gene Expression Regulation , Human Umbilical Vein Endothelial Cells , Humans , Inflammation/chemically induced , Inflammation/genetics , Inflammation/metabolism , Signal Transduction , Vascular Cell Adhesion Molecule-1/geneticsABSTRACT
High resolution, real-time three-dimensional (3D) measurement plays an important role in many fields. In this paper, a multi-directional dynamic real-time phase measurement profilometry based on improved optical flow is proposed. In a five-step phase shifting dynamic measurement, pixel matching is needed to make the pixels one-to-one corresponding in five patterns. However, in the frequently-used pixel matching method at present, it is necessary to calculate the correlation and traverse the whole deformed pattern for the motion information of the measured object. The huge amount of computation caused by correlation computation takes up most of the time in the process of the entire 3D reconstruction, so it can not meet the requirement of real-time dynamic measurement. In order to solve the problem, the improved optical flow algorithm is introduced to replace correlation calculation in pixel matching. In one measurement, five captured patterns need to be dealt with, and the optical flow between each two adjacent frames is calculated. Then four two-dimensional vector matrices can be obtained. The vector matrices contain the complete motion information of the measured object. Experiments and simulations prove that this method can improve the efficiency of pixel matching by 42 times and 3D reconstruction by 32 times on the premise of ensuring the accuracy.
ABSTRACT
This paper presents a dynamic phase measurement profilometry (PMP) method based on the simulated annealing algorithm. In dynamic PMP for rigid objects, pixel matching is an effective method to make one-to-one pixel correspondence in each captured pattern. However, pixel matching by the global traversing algorithm takes up most of the time in the whole reconstruction process. For the purpose of optimizing pixel matching and enhancing performance in dynamic PMP, the simulated annealing algorithm is introduced. By generating a random path based on the simulated annealing algorithm, it is sufficient to locate the approximate area of the measured object. Then the accurate position can be calculated by combining it with a partial traversing algorithm. The proposed method can reduce pixel matching time by 63% and increase reconstruction efficiency by 58%. Simulations and experiments prove feasibility and precision.
ABSTRACT
In this paper, a convex micro-glass lens array fabrication process that utilizes ${{\rm CO}_2}$CO2 laser thermal reflow in the Bessel picosecond laser inscribing and hydrofluoric acid processed micro-glass pillars array is presented. The Bessel picosecond laser permits high tolerance and precise micro-pillar fabrication. In the thermal reshape process, the ${{\rm CO}_2}$CO2 laser power, relative defocus length, and scanning velocity are three crucial parameters to the microlens array's focal length. By using this method, microlens arrays with focal length ranging from several tens of micrometers to several hundred micrometers can be created. This research provides another way to fabricate convex micro-glass lens arrays with several hundred micrometers focal length in good utility.
ABSTRACT
There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.
Subject(s)
Drug Resistance, Multiple, Bacterial/drug effects , Drug Synergism , Enterococcus faecium/drug effects , Escherichia coli/drug effects , Pore Forming Cytotoxic Proteins/pharmacology , Staphylococcus aureus/drug effects , Vancomycin/pharmacology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity TestsABSTRACT
In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi's resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.
Subject(s)
Antifungal Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Candida albicans/drug effects , Drug Resistance, Fungal/drug effects , Amino Acid Sequence , Antifungal Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Candida albicans/ultrastructure , Dose-Response Relationship, Drug , Histatins/chemistry , Humans , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Proteolysis , Time FactorsABSTRACT
A strategy was described to design antimicrobial peptides (AMPs) with enhanced salt resistance and antiendotoxin activities by linking two helical AMPs with the Ala-Gly-Pro (AGP) hinge. Among the designed peptides, KR12AGPWR6 demonstrated the best antimicrobial activities even in high salt conditions (NaCl ~300 mM) and possessed the strongest antiendotoxin activities. These activities may be related to hydrophobicity, membrane-permeability, and α-helical content of the peptide. Amino acids of the C-terminal helices were found to affect the peptide-induced permeabilization of LUVs, the α-helicity of the designed peptides under various LUVs, and the LPS aggregation and size alternation. A possible model was proposed to explain the mechanism of LPS neutralization by the designed peptides. These findings could provide a new approach for designing AMPs with enhanced salt resistance and antiendotoxin activities for potential therapeutic applications.
Subject(s)
Endotoxemia/drug therapy , Lipopolysaccharides/antagonists & inhibitors , Pore Forming Cytotoxic Proteins/pharmacology , Salt Tolerance/drug effects , Sodium Chloride/pharmacology , Amino Acid Sequence , Animals , Colony Count, Microbial , Drug Evaluation, Preclinical , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Hydrophobic and Hydrophilic Interactions , Limulus Test , Lipopolysaccharides/toxicity , Male , Mice , Mice, Inbred C57BL , Pore Forming Cytotoxic Proteins/chemical synthesis , Pore Forming Cytotoxic Proteins/therapeutic use , Protein Conformation, alpha-Helical , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/blood , Unilamellar LiposomesABSTRACT
Saikosaponins-a (Ssa) is a major bioactive extract of Radix Bupleuri which is a traditional Chinese medicine. The roles of inflammatory response and lipid transportation in the process of atherosclerosis have drawn increasing attention. We explored the regulation of lipid transportation and immune-inflammatory role of Ssa in early atherosclerosis. The antiatherogenic actions and possible molecular mechanisms of Ssa were texted in THP-1 cells. We examined the effect of Ssa on oxidized low-density lipoprotein (ox-LDL)-induced lipid uptake, cholesterol efflux, immune-inflammatory response. THP-1 macrophages were treated with Ssa followed by ox-LDL for 24 hours. Results from western blot showed that Ssa obviously reduced lipoprotein uptake to block foam cell formation and the expression of Density Lipoprotein Receptor-1 and CD36. Ssa also significantly boosted cholesterol efflux and the expression of ATP binding cassettetransporter A1 and peroxisome proliferator-activated receptor γ. The results also indicated that Ssa inhibited ox-LDL-induced activation of AKT and nuclear factor-κB, assembly of NLRP3 inflammasome and production of proinflammatory cytokines. It is suggested that the ability against immune inflammatory response of Ssa is due to modulation of the PI3K/AKT/NF-κB/NLRP3 pathway. In conclusion, this study provides new insight into Ssa's molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.
Subject(s)
Atherosclerosis/physiopathology , Cholesterol/metabolism , Lipoproteins, LDL/drug effects , Macrophages/drug effects , Oleanolic Acid/analogs & derivatives , Saponins/pharmacology , ATP Binding Cassette Transporter 1/biosynthesis , CD36 Antigens/metabolism , Cell Culture Techniques , Cytokines/metabolism , Humans , Lipoproteins/metabolism , NF-kappa B/biosynthesis , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oleanolic Acid/pharmacology , PPAR gamma/biosynthesis , Receptors, Lipoprotein/metabolismABSTRACT
We decided to assess the prognostic value of NLRP3 inflammasome level in acute coronary syndrome (ACS) patients and whether it was related to coronary atherosclerotic severity. Study population included one-hundred and twenty-three (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with clinical presentation, angiographic characteristics and its scoring systems as well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased with increasing number of vessels, the number of lesions present and the presence bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3 to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and receiver operating characteristic curves for NLRP3 showed good predictive value for MACE. There is a positive correlation of NLRP3 level with severity of coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is efficient in event prediction for MACE.
Subject(s)
Acute Coronary Syndrome/complications , Acute Coronary Syndrome/mortality , Coronary Artery Disease/blood , Creatinine/blood , Lipids/blood , NLR Family, Pyrin Domain-Containing 3 Protein/blood , Aged , Case-Control Studies , Coronary Angiography , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , ROC Curve , Risk Assessment , Risk Factors , Severity of Illness IndexABSTRACT
Currently, most transducers in photoacoustic endoscopy (PAE) are ceramic based, which are complicated to fabricate and are expensive. In this work, we have for the first time presented a hollow structured epoxy lens-focused transducer that was based on a 52 µm thick polyvinylidine fluoride (PVDF) film for the purpose of PAE imaging. Intensive field characteristic tests were performed on transducers with different lens curvatures, and results show that with the 6 mm fixed aperture, a lateral resolution less than 0.5 mm can be obtained with a focal length around 19 mm, which is close to the theoretical calculations. The PAE application of the built transducer was also demonstrated with phantom experiments. Compared with the commonly used ceramic-based transducers, the proposed method has greatly reduced the design and fabrication cost of the hollow structured focused transducer as required in PAE, and facilitated the development of the PAE system in lab conditions. The built transducer may play an important role in the PAE imaging of some relatively large human structures and organs, such as the gastrointestinal tract and the cervical canal.
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BACKGROUND: Salt-sensitive hypertension is often more prone to induce damage to target organs such as the heart and kidneys. Abundant recent studies have demonstrated a close association between ferroptosis and cardiovascular diseases.Therefore, we hypothesize that ferroptosis may be closely associated with organ damage in salt-sensitive hypertension. This study aimed to investigate whether ferroptosis is involved in the occurrence and development of myocardial fibrosis and renal fibrosis in salt-sensitive hypertensive rats. METHODS: Ten 7-week-old male Dahl salt-sensitive (Dahl-SS) rats were adaptively fed for 1 week, then randomly divided into two groups and fed either a normal diet (0.3% NaCl, NDS group) or a high-salt diet (8% NaCl, HDS group) for 8 weeks. Blood pressure of the rats was observed, and analysis of the hearts and kidneys of Dahl-SS rats was conducted via HE-staining, Masson-staining, Prussian-blue-staining, TEM, tissue iron content detection, MDA content detection, immunofluorescence, and Western blot. RESULTS: Compared to the NDS group, rats in the HDS group increases in systolic blood pressure(SBP) and diastolic blood pressure(DBP)(P<0.05);collagen fiber accumulation was observed in the heart and kidney tissues (P<0.01), accompanied by alterations in mitochondrial ultrastructure,reduced mitochondrial volume, and increased density of the mitochondrial double membrane. Additionally,there were significant increases in both iron content and MDA levels(P<0.05). Immunofluorescence and Western blot results both indicated significant downregulation (P<0.05) of xCT and GPX4 proteins associated with ferroptosis in the HDS group. CONCLUSION: Ferroptosis is involved in the damage and fibrosis of the heart and kidney tissues in salt-sensitive hypertensive rats.
ABSTRACT
BACKGROUND: Both diabetic and hypertensive nephropathy eventually progress to glomerulosclerosis. Previous studies revealed a potential role of endothelial-to-mesenchymal transition (EndMT) in the pathophysiology of glomerulosclerosis in diabetic rats. Therefore, we hypothesized that EndMT was also involved in the development of glomerulosclerosis in salt-sensitive hypertension. We aimed to explore the effects of high-salt diet on endothelial-to-mesenchymal transition (EndMT) in glomerulosclerosis in Dahl salt-sensitive (Dahl-SS) rats. METHODS: Eight-week-old male rats were fed high-salt (8%NaCl; DSH group) or normal salt (0.3%NaCl; DSN group) for eight weeks, with systolic blood pressure (SBP), serum creatinine, urea, 24-hour urinary protein/sodium, renal interlobar artery blood flow, and pathological examination measured. We also examined endothelial-(CD31) and fibrosis-related protein(α-SMA) expressions in glomeruli. RESULTS: High-salt diet increased SBP (DSH vs. DSN, 205.2â ±â 8.9 vs. 135.4â ±â 7.9 mm Hg, Pâ <â 0.01), 24-hour urinary protein (132.55â ±â 11.75 vs. 23.52â ±â 5.94 mg/day, Pâ <â 0.05), urine sodium excretions (14.09â ±â 1.49 vs. 0.47â ±â 0.06 mmol/day, Pâ <â 0.05), and renal interlobar artery resistance. Glomerulosclerosis increased (26.1â ±â 4.6 vs. 7.3â ±â 1.6%, Pâ <â 0.05), glomerular CD31 expressions decreased while α-SMA expression increased in DSH group. Immunofluorescence staining showed that CD31 and α-SMA co-expressed in glomeruli of the DSH group. The degree of glomerulosclerosis negatively correlated with CD31 expressions (râ =â -0.823, Pâ <â 0.01) but positively correlated with α-SMA expressions (râ =â 0.936, Pâ <â 0.01). CONCLUSIONS: We demonstrated that a high-salt diet led to glomerulosclerosis involving the EndMT process, which played an essential role in glomerulosclerosis in hypertensive Dahl-SS rats.
Subject(s)
Diabetes Mellitus, Experimental , Hypertension, Renal , Hypertension , Male , Rats , Animals , Rats, Inbred Dahl , Sodium Chloride , Diabetes Mellitus, Experimental/metabolism , Kidney/metabolism , Hypertension/metabolism , Blood Pressure , Hypertension, Renal/metabolism , Sodium Chloride, Dietary/metabolism , Sodium/metabolism , Diet , FibrosisABSTRACT
There is an urgent and imminent need to develop new agents to fight against cancer. In addition to the antimicrobial and anti-inflammatory activities, many antimicrobial peptides can bind to and lyse cancer cells. P-113, a 12-amino acid clinically active histatin-rich peptide, was found to possess anti-Candida activities but showed poor anticancer activity. Herein, anticancer activities and induced immunogenic cancer cell death of phenylalanine-(Phe-P-113), ß-naphthylalanine-(Nal-P-113), ß-diphenylalanine-(Dip-P-113), and ß-(4,4'-biphenyl)alanine-(Bip-P-113) substituted P-113 were studied. Among these peptides, Nal-P-113 demonstrated the best anticancer activity and caused cancer cells to release potent danger-associated molecular patterns (DAMPs), such as reactive oxygen species (ROS), cytochrome c, ATP, and high-mobility group box 1 (HMGB1). These results could help in developing antimicrobial peptides with better anticancer activity and induced immunogenic cell death in therapeutic applications.
ABSTRACT
Cecropins are a family of antimicrobial peptides (AMPs) that are widely found in the innate immune system of Cecropia moths. Cecropins exhibit a broad spectrum of antimicrobial and anticancer activities. The structures of Cecropins are composed of 34-39 amino acids with an N-terminal amphipathic α-helix, an AGP hinge and a hydrophobic C-terminal α-helix. KR12AGPWR6 was designed based on the Cecropin-like structural feature. In addition to its antimicrobial activities, KR12AGPWR6 also possesses enhanced salt resistance, antiendotoxin and anticancer properties. Herein, we have developed a strategy to produce recombinant KR12AGPWR6 through a salt-sensitive, pH and temperature dependent intein self-cleavage system. The His6-Intein-KR12AGPWR6 was expressed by E. coli and KR12AGPWR6 was released by the self-cleavage of intein under optimized ionic strength, pH and temperature conditions. The molecular weight and structural feature of the recombinant KR12AGPWR6 was determined by MALDI-TOF mass, CD, and NMR spectroscopy. The recombinant KR12AGPWR6 exhibited similar antimicrobial activities compared to the chemically synthesized KR12AGPWR6. Our results provide a potential strategy to obtain large quantities of AMPs and this method is feasible and easy to scale up for commercial production.
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BACKGROUND CONTEXT: Preoperative prediction of prolonged postoperative opioid prescription helps identify patients for increased surveillance after surgery. The SORG machine learning model has been developed and successfully tested using 5,413 patients from the United States (US) to predict the risk of prolonged opioid prescription after surgery for lumbar disc herniation. However, external validation is an often-overlooked element in the process of incorporating prediction models in current clinical practice. This cannot be stressed enough in prediction models where medicolegal and cultural differences may play a major role. PURPOSE: The authors aimed to investigate the generalizability of the US citizens prediction model SORG to a Taiwanese patient cohort. STUDY DESIGN: Retrospective study at a large academic medical center in Taiwan. PATIENT SAMPLE: Of 1,316 patients who were 20 years or older undergoing initial operative management for lumbar disc herniation between 2010 and 2018. OUTCOME MEASURES: The primary outcome of interest was prolonged opioid prescription defined as continuing opioid prescription to at least 90 to 180 days after the first surgery for lumbar disc herniation at our institution. METHODS: Baseline characteristics were compared between the external validation cohort and the original developmental cohorts. Discrimination (area under the receiver operating characteristic curve and the area under the precision-recall curve), calibration, overall performance (Brier score), and decision curve analysis were used to assess the performance of the SORG ML algorithm in the validation cohort. This study had no funding source or conflict of interests. RESULTS: Overall, 1,316 patients were identified with sustained postoperative opioid prescription in 41 (3.1%) patients. The validation cohort differed from the development cohort on several variables including 93% of Taiwanese patients receiving NSAIDS preoperatively compared with 22% of US citizens patients, while 30% of Taiwanese patients received opioids versus 25% in the US. Despite these differences, the SORG prediction model retained good discrimination (area under the receiver operating characteristic curve of 0.76 and the area under the precision-recall curve of 0.33) and good overall performance (Brier score of 0.028 compared with null model Brier score of 0.030) while somewhat overestimating the chance of prolonged opioid use (calibration slope of 1.07 and calibration intercept of -0.87). Decision-curve analysis showed the SORG model was suitable for clinical use. CONCLUSIONS: Despite differences at baseline and a very strict opioid policy, the SORG algorithm for prolonged opioid use after surgery for lumbar disc herniation has good discriminative abilities and good overall performance in a Han Chinese patient group in Taiwan. This freely available digital application can be used to identify high-risk patients and tailor prevention policies for these patients that may mitigate the long-term adverse consequence of opioid dependence: https://sorg-apps.shinyapps.io/lumbardiscopioid/.
Subject(s)
Intervertebral Disc Displacement , Opioid-Related Disorders , Algorithms , Analgesics, Opioid/adverse effects , Humans , Intervertebral Disc Displacement/drug therapy , Intervertebral Disc Displacement/surgery , Machine Learning , Prescriptions , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate the effect of evidence-based nursing on anxiety and depression, sleep quality and life quality of patients with acute coronary syndrome during perioperative period of percutaneous coronary intervention. METHOD: 113 patients with acute coronary syndrome treated with percutaneous coronary intervention in our hospital from November 2016 to June 2019 were collected and randomly divided into group A and group B. Among them, 58 cases in group A were given routine nursing care, another 55 cases in group B were given evidence-based nursing on the basis of group A. The left ventricular ejection fraction (EF) and left ventricular end diastolic diameter (LVEDD), VAS pain score index, anxiety and depression after nursing intervention were observed in groups A and B. The improvement of sleep quality (Pittsburgh Sleep Quality Index (PSQI)), the incidence of adverse reactions, nursing satisfaction (with the total score of 10 points for each item, the higher score indicates the higher satisfaction), coronary self-management scale (CSMS) were recorded so as to evaluate self-management ability and quality of life after nursing. RESULTS: After nursing, the indicators of heart function, VAS score, anxiety, depression, sleep quality, incidence of adverse reactions, nursing satisfaction, self-management score and quality of life in Group B showed better results compared with Group A (P < 0.05). CONCLUSION: Evidence-based nursing can alleviate anxiety and depression of patients with acute coronary syndrome during perioperative period of percutaneous coronary intervention and improve the quality of life.
ABSTRACT
The global spread of antibiotic-resistant infections has meant that there is an urgent need to develop new antimicrobial alternatives. In this study, we developed a strategy to boost and/or synergize the activity of conventional antibiotics by combination with antimicrobial peptides tagged with the bulky non-natural amino acid ß-naphthylalanine (Nal) to their N- or C-terminus. A checkerboard method was used to evaluate synergistic effects of the parent peptide and the Nal-tagged peptides. Moreover, boron-dipyrro-methene labeled vancomycin was used to characterize the synergistic mechanism of action between the peptides and vancomycin on the bacterial strains. These Nal-tagged antimicrobial peptides also reduced the antibiotic-induced release of lipopolysaccharide from Gram-negative bacteria by more than 99.95%. Our results demonstrate that Nal-tagged peptides could help in developing antimicrobial peptides that not only have enhanced antibacterial activities but also increase the synergistic effects with conventional antibiotics against antibiotic-resistant bacteria.
ABSTRACT
Circular RNA (circRNA) is an important factor for regulating the progression of many cardiovascular diseases, including acute myocardial infarction (AMI). However, the role of circ_0124644 in AMI progression remains unclear. Hypoxia was used to induce cardiomyocytes injury. The expression of circ_0124644, microRNA (miR)-590-3p, and SRY-box transcription factor 4 (SOX4) mRNA was measured by qRT-PCR. Cell counting kit 8 (CCK8) assay and flow cytometry were utilized to detect cell viability, cell cycle progression, and apoptosis. The protein levels of apoptosis markers and SOX4 were determined by western blot (WB) analysis, and the levels of oxidative stress markers were assessed using commercial Assay Kits. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were employed to confirm the interaction between miR-590-3p and circ_0124644 or SOX4. Circ_0124644 was upregulated in AMI patients and hypoxia-induced cardiomyocytes. Hypoxia could inhibit cardiomyocytes viability, cell cycle process, and promote apoptosis and oxidative stress, while silencing circ_0124644 could alleviate hypoxia-induced cardiomyocytes injury. In terms of mechanism, circ_0124644 could target miR-590-3p. MiR-590-3p overexpression could relieve hypoxia-induced cardiomyocytes injury. Also, the suppressive effect of circ_0124644 knockdown on hypoxia-induced cardiomyocytes injury could be reversed by miR-590-3p inhibitor. Moreover, SOX4 was found to be a target of miR-590-3p, and its overexpression also could reverse the regulation of miR-590-3p on hypoxia-induced cardiomyocytes injury. Circ_0124644 silencing could alleviate hypoxia-induced cardiomyocytes injury by regulating the miR-590-3p/SOX4 axis, suggesting that it might be a target for alleviating AMI.