Apolipoprotein A-IV polymorphisms Q360H and T347S attenuate its endogenous inhibition of thrombosis.

Platelets are small anucleate cells that play a key role in thrombosis and hemostasis. Our group previously identified apolipoprotein A-IV (apoA-IV) as an endogenous inhibitor of thrombosis by competitive blockade of the αIIbß3 integrin on platelets. ApoA-IV inhibition of platelets was dependent on the N-terminal D5/D13 residues, and enhanced with absence of the C-terminus, suggesting it sterically hinders its N-terminal platelet binding site. The C-terminus is also the site of common apoA-IV polymorphisms apoA-IV-1a (T347S) and apoA-IV-2 (Q360H). Interestingly, both are linked with an increased risk of cardiovascular disease, however, the underlying mechanism remains unclear. Here, we generated recombinant apoA-IV and found that the Q360H or T347S polymorphisms dampened its inhibition of platelet aggregation in human platelet-rich plasma and gel-filtered platelets, reduced its inhibition of platelet spreading, and its inhibition of P-selectin on activated platelets. Using an ex vivo thrombosis assay, we found that Q360H and T347S attenuated its inhibition of thrombosis at both high (1800s-1) and low (300s-1) shear rates. We then demonstrate a conserved monomer-dimer distribution among apoA-IV WT, Q360H, and T347S and use protein structure modelling software to show Q360H and T347S enhance C-terminal steric hindrance over the N-terminal platelet-binding site. These data provide critical insight into increased cardiovascular risk for individuals with Q360H or T347S polymorphisms.

A meta-analysis of melanoma risk in idiopathic inflammatory myopathy patients.

BACKGROUND: Idiopathic inflammatory myopathy (IIM) is a group of chronic acquired autoimmune diseases. The association between IIM and malignancies has been observed for decades. No meta-analysis has been conducted to summarize the relationship between IIM and melanoma. Herein, we specifically wanted to investigate whether IIM is associated with a higher incidence of melanoma. METHODS: We searched both Chinese and English databases (CNKI, VIP, Wanfang, PubMed, Embase, Web of Science) for studies on IIM related to melanoma published up to October 2023. Two independent authors reviewed all literature to identify studies according to predefined selection criteria. Fixed effects models were applied to pool the risk. Publication bias was also evaluated and sensitivity analysis performed. RESULTS: A total of 1660 articles were initially identified but only four cohort studies met the criteria. Thus, 4239 IIM patients were followed up. The pooled overall risk ratio/hazard ratio was 3.08 (95% confidence interval [CI] 0.79-5.37) and the standardized incidence ratio was 6.30 (95% CI 1.59-11.02). CONCLUSION: The present meta-analysis suggests that IIM patients are at a significantly higher risk of developing melanoma.

Optical system design of double-sided telecentric microscope with high numerical aperture and long working distance.

The working distance of the high numerical aperture visible video microscope is extremely short, which greatly limits its application scenarios. To solve this problem, this paper proposes an unobstructed design method of double-sided telecentric microscope with high numerical aperture and long working distance. First, aiming at the obstruction problem of the image-side telecentric catadioptric microscope objective, the structure of the catadioptric optical system is improved. Then, the aspheric design method based on the best aberration compensation is analyzed theoretically to better correct the primary aberration of the high-numerical aperture microscope objective. Finally, a double-sided telecentric microscope optical system with a numerical aperture (NA) of 0.8 and a working distance of 10.0 mm was designed, which is composed of a spherical reflector, a beam splitter plate, a collimating lens group, and an image-side telecentric eyepiece optical system. The design results show that the imaging resolution of this high numerical aperture video microscope is as high as 0.42 µm, and the microscope has a magnification of about 220× for the image with 1080P (1920 × 1080 pixels) resolution. This double-sided telecentric microscope has the advantages of a large field of view, compact structure, good stray light suppression ability, and manufacturability, and has high practical value in the field of high-precision measurement and detection.

Design method of dual-band synchronous zoom microscope optical system based on coaxial Kohler illumination.

The intrinsic properties of the observed object are closely related to its spectral information, to extend the imaging spectral range of a continuous zoom microscope to obtain more detailed intrinsic properties of the object, this paper proposes a design method of dual-band simultaneous zoom microscope optical system based on the coaxial Koehler uniform illumination. First, the imaging principle of the dual-band simultaneous zoom microscope optical system is theoretically analyzed, and we propose to split the front fixed group of the zoom system into a collimation lens group and a converging lens group to realize the compact design of the system. Then, two different rear fixed groups are used to correct the residual aberration, and a method for solving the initial structure of the dual-band simultaneous zoom microscope optical system is proposed. Finally, a dual-band synchronous zoom microscope optical system is designed using the method proposed in this paper. The design results show that the imaging magnification of the visible (VIS) band is -0.4 to -4.0, the simultaneous imaging magnification ranges are -0.4 to -0.8 in the VIS and short-wave infrared (SWIR) bands, and the magnification difference of its simultaneous zoom imaging is less than 1.25%. In addition, the system has the advantages of good imaging quality, clever design of coaxial illumination, and compact structure, thus verifying the feasibility of the design method.

Design of the dual-band shared-aperture asynchronous zoom optical system using focus tunable lenses.

To meet the increasing demand of the current market and the diversity of application scenarios, combine the zoom system and the multi-band shared-aperture system, and fully harness their respective advantages, this paper proposes a dual-band shared-aperture asynchronous zoom optical system using focus tunable lenses (FTLs). To address the lack of available patents for such systems, we designed a sub-system simultaneous iterative optimization algorithm to calculate the initial structure parameters. This synchronous iterative optimization approach can strengthen the connection between sub-systems and compensate for the shortcomings of current mainstream design methods. The initial structure constructed in this way has a good performance in terms of structural stability and optimization potential. Based on these methods, we successfully designed an optical system that can work in both VIS and NIR bands, and the two sub-systems can zoom independently. The design results possess good performance in terms of distortion control, aberration correction, and volume control.

Automatic aberration compensation for digital holographic microscopy based on bicubic downsampling and improved minimization of global phase gradients.

In digital holographic microscopy, aberrations caused by imperfect optical system settings can greatly affect the quantitative measurement of the target phase, so the compensation of aberrations in the distorted phase has become a key point of research in digital holographic microscopy. Here, we propose a fully automatic numerical phase aberration compensation method with fast computational speed and high robustness. The method uses bicubic downsampling to smooth the sample phase for reducing its disturbance to the background aberration fit, while reducing the computational effort of aberration compensation. Polynomial coefficients of the aberration fitting are iteratively optimized in the process of minimizing the global phase gradient by improving the phase gradient operator and constructing the loss function to achieve accurate fitting of the phase aberration. Simulation and experimental results show that the proposed method can achieve high aberration compensation accuracy without prior knowledge of the hologram recording settings or manual selection of the background area free of samples, and it is suitable for samples with moderate and relatively flat background area, which can be widely used in the quantitative analysis of biological tissues and micro and nano structures.

Geometric error modeling and compensation for high precision composite optical measurement systems.

Composite optical measurement systems are widely used in the field of precision measurement due to their combination of inspection with high accuracy, speed, wide range, real-time, and other advantages. Whereas errors are prevalent in measurements, in order to improve detection accuracy, the systems must be compensated for geometric errors in three-dimensional space. Aiming at the complex situation of multi-probes and multi-zooms in the composite optical measurement system, the current error modelling methods are difficult to be directly applied, so this paper establishes a unified three-dimensional volumetric error model based on the theory of multi-body system and combined with the principle of geometric optics, performs the error verification through the direct measurement method, and finally realises the compensation of geometric error in the continuous space of the whole measurement range. Eventually, the accuracy of the proposed error model and the effectiveness of the error compensation method were verified by a laser interferometer and standard objects to be measured, and the integrated geometric error of the system was decreased by 76.55%, which effectively improved the accuracy of the system. The error modelling and compensation method proposed in this paper provides a new idea for the error compensation of the zoom measurement system, and at the same time, it is universal for the measurement systems of different structures and motion forms, which can be widely used in the field of precision measurement.

High-precision calibration to zoom lens of optical measurement machine based on FNN.

We proposed a calibration method for high-precision zoom lenses of optical measurement machines based on Fully Connected Neural Network (FNN), using a 5-layer neural network instead of a camera calibration model, to achieve continuous calibration of zoom lenses at any zoom setting by calibrating typical zooms. From the experimental verification, the average calibration error of this method is 9.83×10-4mm and the average measurement error at any zoom setting is 0.01317mm. The overall calibration precision is better than that of Zhang's calibration method and can meet the application requirements of a high-precision optical measurement machine. The method proposed in this paper provided a new solution and a new idea for the calibration of zoom lenses, which can be widely used in the fields of precision parts inspection and machine-vision measurement.

40× zoom optical system design based on stable imaging principle of four groups.

Based on stable imaging principle of four groups and combined with optical design software, a method for initial structure calculation of zoom optical system and optical system optimization design is proposed to solve the problems of difficult initial structure calculation, large volume, and inflection point of zoom curves of a high zoom ratio optical system. First, this paper theoretically derives the four-group stable imaging principle of the zoom optical system. Then, using the derived equations and optical design software, the initial structural parameters of the four-group zoom optical system are solved to ensure that there is no inflection point in the zoom curves. Finally, a lightweight and small 40× continuous zoom optical system is designed to verify the feasibility and effectiveness of the design method proposed in this paper. The zoom optical system has the advantages of good imaging quality, lightweight, small size, smooth zoom, and no inflection point.

Leishmania Regulated MTDH Expression to Suppress Dendritic Cells.

This study aimed to investigate the correlation between Leishmania infection and dendritic cell infiltration and explore the underlying molecular mechanism how Leishmania infection regulates dendritic cell infiltration. Three datasets, GSE63931, GSE80008 and GSE77528 were combined and their batch effects were removed by Combat function in sva R package. Immune cell infiltrations were estimated using the Microenvironment Cell Populations-counter (MCP-counter) R package. Statistical results were verified by Student's t test. The differential expression of metadherin (MTDH) was identified by Limma R package. The correlation between MTDH expression and dendritic cell infiltration was estimated by Pearson's product moment correlation coefficient. GDS5086 was used to explore MTDH expression pattern in dendritic cells infected with Leishmania. Compared with normal samples, 5 types of immune cells showed differential infiltration in leishmaniasis samples, including T cells, CD8+ T cells, dendritic cells, cytotoxic lymphocytes and B lineage cells. Among these, only DCs were significantly suppressed in leishmaniasis samples. Notably, MTDH expression was differential between leishmaniasis and normal samples. There was a significant correlation between MTDH expression and dendritic cell infiltration. In conclusion, these results demonstrate that Leishmania infection leads to the downregulation of MTDH expression and the suppression of dendritic cell infiltration.

A Method Based on Curvature and Hierarchical Strategy for Dynamic Point Cloud Compression in Augmented and Virtual Reality System.

As a kind of information-intensive 3D representation, point cloud rapidly develops in immersive applications, which has also sparked new attention in point cloud compression. The most popular dynamic methods ignore the characteristics of point clouds and use an exhaustive neighborhood search, which seriously impacts the encoder's runtime. Therefore, we propose an improved compression means for dynamic point cloud based on curvature estimation and hierarchical strategy to meet the demands in real-world scenarios. This method includes initial segmentation derived from the similarity between normals, curvature-based hierarchical refining process for iterating, and image generation and video compression technology based on de-redundancy without performance loss. The curvature-based hierarchical refining module divides the voxel point cloud into high-curvature points and low-curvature points and optimizes the initial clusters hierarchically. The experimental results show that our method achieved improved compression performance and faster runtime than traditional video-based dynamic point cloud compression.

Characteristics of B lymphocyte infiltration in HPV+ head and neck squamous cell carcinoma.

Human papillomavirus (HPV) is an important etiological factor of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients usually have a better prognosis, which probably results from the higher infiltration of B lymphocytes. This study was purposed to detect the infiltration of B lymphocyte subsets and the correlation between B lymphocyte subsets and the prognosis in HPV-related HNSCC. In this study, 124 HPV+ and 513 HPV- HNSCC samples were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database for transcriptomic analysis. Infiltration of B lymphocytes subsets was detected with 7 HPV+ HNSCC and 13 HPV- HNSCC tissues through immunohistochemistry and immunofluorescence. One HPV- HNSCC sample was detected with single-cell sequencing for chemokine analysis. In the results, the infiltration of plasma cells (CD19+ CD38+ ) and memory B cells (MS4A1+ CD27+ ) was higher in HPV+ HNSCC samples. High infiltration of plasma cells and memory B cells was related to a better prognosis. High density of B lymphocytes was positively correlated with high CXCL13 production mainly from CD4+ T lymphocytes in HNSCC. These results indicated that a high density of plasma cells and memory B cells could predict excellent prognosis. CD4+ T lymphocytes might affect B lymphocytes and their subsets through the CXCL13/CXCR5 axis in HNSCC.

Long noncoding RNA and atrial fibrillation. / é•¿é“¾éžç¼–ç RNA与心房纤颤.

Atrial fibrillation (AF), a common arrhythmia that usually occurs in patients with heart disease, is one of the leading causes for mortality and disability worldwide. Current drug therapy for AF patients lacks sufficient efficacy and has side effects. Radiofrequency ablation is more effective than traditional drug therapy, but this invasive procedure is associated with potential risks and postoperative recurrence, limiting the clinical benefits for AF patients. Therefore, it is necessary to expand our understanding about the underlying molecular mechanism of AF and to explore the new therapeutic strategies. Long noncoding RNA (lncRNA) is a set of noncoding RNA longer than 200 nucleotides. Growing evidence indicates that lncRNA is involved in numerous pathophysiological processes of AF, such as structural remodeling, electrical remodeling, renin-angiotensin system, abnormal calcium regulation, etc. In addition, lncRNA involved in structural remodeling and electrical remodeling has the potential to be a novel target for the diagnosis and treatment of AF, and lncRNA involved in autonomic nerve remodeling may bring new enlightenment for the prognosis and recurrence of AF.

Cellular heterogeneity landscape in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a highly malignant tumor originated from respiratory system. Although there have been many improvements in therapy until now, reducing the high mortality remains difficult. Understanding the cellular heterogeneity of LSCC could contribute to improve this problem. Single-cell RNA sequencing was applied to dissect the cell composition and molecular characteristics of LSCC tissues. Immunohistochemistry staining of the LSCC tissues was performed to identify the spatial location of tumor cells. Survival analysis of marker genes was executed in The Cancer Genome Atlas to verify the correlation between each cell clusters and patients' prognosis. The LSCC tissue cells were finely grouped into various clusters, including tumor cells, immune cells, epithelial cells, fibroblasts and endothelial cells. Notably, in tumor cells, keratinocyte-like cells were in the core of tumor while malignant proliferating cells were located at the tumor edge. The malignant proliferating cells were correlated with poor prognosis. In summary, this is the first study to delineate a landscape of the LSCC intratumor heterogeneity. Our work might help researchers have a better understanding for tumor progression.

Ultrasound Elastic Parameters Predict Central Lymph Node Metastasis of Papillary Thyroid Carcinoma.

BACKGROUND: This study aimed to explore the new factors that can predict central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) independently from ultrasound characteristics, elastic parameters, and endocrine indicators. METHODS: A total of 391 patients with PTC undergoing thyroidectomy and prophylactic central lymph node dissection from January 2017 to June 2019 were collected to determine the independent predictors of CLNM by single-factor and multivariate logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed 9 independent predictors of CLNM, age, male, tumors in the middle or lower poles (without tumors in the isthmus), tumors in the isthmus, multiple tumors, and maximum tumor diameter measured by ultrasound, microcalcification, visible surrounding blood flow signal, and the maximum value of elastic modulus (Emax).We used the aforementioned factors to establish a scoring prediction model: predictive score Y(P) = 1/[1 + exp (1.444 + 0.084 ∗ age - 0.834 ∗ men - 0.73 ∗ multifocality - 2.718 ∗ tumors in the isthmus - 0.954 ∗ tumors in the middle or lower poles - 0.086 ∗ tumor maximum diameter - 1.070 ∗ microcalcification - 0.892 ∗ visible surrounding blood flow signal - 0.021 ∗ Emax)]. The area under the curve of the receiver operating characteristic was 0.827. It was found that 0.524 was the highest index of Youden, and the best cutoff value for predicting CLNM. When Y(P)≥0.524, the risk of CLNM in patients with PTC is predicted to be high. Predictive accuracy was 78.5% and 72.4% in the internal validation group and 78.6% in the external validation group. CONCLUSIONS: These data indicate that the scoring prediction model could provide a scientific and quantitative way to predict CLNM in patients with PTC.

DisV-HPV16, versatile and powerful software to detect HPV in RNA sequencing data.

BACKGROUND: The increasing availability of high-throughput sequencing data provides researchers with unprecedented opportunities to investigate viral genetic elements in host genomes that contribute to virus-linked cancers. Almost all of the available computational tools for secondary analysis of sequencing data detect viral infection or genome integration events. However, viral oncogenes expression is likely of importance in carcinoma. We therefore developed a new software, DisV-HPV16, for the evaluation of HPV16 oncogenes expression. RESULTS: HPV16 virus and viral oncogenes expression was detected more rapidly using DisV-HPV16 compared to other software. DisV-HPV16 was proved highly convenient for detecting candidate virus after modification of the reference file. The accuracy of DisV-HPV16 was empirically confirmed in laboratory experiments. DisV-HPV16 exhibited greater reliability than other software. CONCLUSIONS: DisV-HPV16 is a new, dependable software to detect virus and viral oncogenes expression through analysis of RNA sequencing data. Use of DisV-HPV16 can yield deeper, more comprehensive insights into virus infection status and viral and host cell gene expression.

Isoelectric focusing on microfluidic paper-based chips.

Isoelectric focusing (IEF), a powerful technique for protein separation and enrichment, was successfully integrated into microfluidic paper-based analytical devices (µPADs) in this work. The µPADs for isoelectric focusing were fabricated by octadecyltrichlorosilane (OTS) silanization and subsequent region-selective plasma treatment. The system of IEF on µPADs could be easily assembled. And a series of conditions of the system were investigated, including the suitable concentration of ampholyte to create good pH gradient, the effect of polyvinylpyrrolidone (PVP) on electroosmotic flow (EOF) suppression, and focusing voltage applied on the paper channel. After optimization, simultaneous separation and enrichment of protein sample containing myoglobin and cytochrome C was successfully demonstrated. Besides, parallel IEF on multichannels were also achieved for the separation of multiple protein samples on one single chip, and their performance was compared with that of the conventional gel-IEF system. The developed IEF on µPADs exhibits appealing features such as low cost, simplicity, and disposability and are believed to have great application potentials.

Knockdown of lncRNA AK139328 alleviates myocardial ischaemia/reperfusion injury in diabetic mice via modulating miR-204-3p and inhibiting autophagy.

This study was aimed at investigating the effects of lncRNA AK139328 on myocardial ischaemia/reperfusion injury (MIRI) in diabetic mice. Ischaemia/reperfusion (I/R) model was constructed in normal mice (NM) and diabetic mice (DM). Microarray analysis was utilized to identify lncRNA AK139328 overexpressed in DM after myocardial ischaemia/reperfusion (MI/R). RT-qPCR assay was utilized to investigate the expressions of lncRNA AK139328 and miR-204-3p in cardiomyocyte and tissues. Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning shortening (FS) were obtained by transthoracic echocardiography. Haematoxylin-eosin (HE) staining and Masson staining were utilized to detect the damage of myocardial tissues degradation of myocardial fibres and integrity of myocardial collagen fibres. Evans Blue/TTC staining was used to determine the myocardial infarct size. TUNEL staining was utilized to investigate cardiomyocyte apoptosis. The targeted relationship between lncRNA AK139328 and miR-204-3p was confirmed by dual-luciferase reporter gene assay. MTT assay was used for analysis of cardiomyocyte proliferation. Western blot was utilized to investigate the expression of alpha smooth muscle actin (α-SMA), Atg7, Atg5, LC3-II/LC3-I and p62 marking autophagy. Knockdown of lncRNA AK139328 relieved myocardial ischaemia/reperfusion injury in DM and inhibited cardiomyocyte autophagy as well as apoptosis of DM. LncRNA AK139328 modulated miR-204-3p directly. MiR-204-3p and knockdown of lncRNA AK139328 relieved hypoxia/reoxygenation injury via inhibiting cardiomyocyte autophagy. Silencing lncRNA AK139328 significantly increased miR-204-3p expression and inhibited cardiomyocyte autophagy, thereby attenuating MIRI in DM.

Long Noncoding RNAs: New Players in Ischaemia-Reperfusion Injury.

Long noncoding RNAs (lncRNAs) constitute a new class of noncoding RNAs that interfere with gene expression. It has been shown that lncRNAs exert comprehensive effects on biological processes and are associated with numerous diseases such as cancer. However, the possible role of lncRNAs in ischaemia/reperfusion (I/R) injury have received relatively little attention. Accumulating evidence indicates that lncRNAs are also involved in the progression of I/R injury such as myocardial, cerebral, hepatic, renal and mesenteric I/R injury. In this review, we summarise the current knowledge of lncRNAs in I/R injury, attempting to better explain the molecular mechanism of I/R injury and provide new directions for its therapy.

FATAL HONEY POISONING IN SOUTHWEST CHINA: A CASE SERIES OF 31 CASES.

Honey poisoning cases occur in southwestern China. In this case series, we attempted to determine the symptoms and causes of honey poisoning from 2007 to 2012 in southwestern China. We also conducted a quantitative melissopalynological analysis of honey samples. During the study period, 31 honey poisoning cases occurred in the study location, all during July to August. All the cases occurred after consuming at least 100 grams of honey. The most frequent symptoms were nausea and vomiting (100%), abdominal pain (90.3%), diarrhea (74.2%), palpitations (61.3%), dizziness (54.8%), chest congestion (48.4%) and dyspnea (48.4%). Severe cases developed oliguria/anuria, twitch, hematuria, ecchymosis or hematochezia. The median time from ingestion to onset of symptoms was 29 hours. Eight patients died (mortality rate: 25.8%). The pollen of Tripterygium hypoglaucum (a plant with poisonous nectar and pollen) was detected in 22 of 29 honey samples examined (75.9%). The results of pollen analysis were consistent with the clinical findings of previous cases. T. hypoglaucum appears to be the cause of honey poisoning in southwestern China. Honey poisoning should be included in the differential diagnosis of patients who consume honey in this region and develop symptoms of food poisoning.