HIMS-Net: Horizontal-vertical interaction and multiple side-outputs network for cyst segmentation in jaw images.

Jaw cysts are mainly caused by abnormal tooth development, chronic oral inflammation, or jaw damage, which may lead to facial swelling, deformity, tooth loss, and other symptoms. Due to the diversity and complexity of cyst images, deep-learning algorithms still face many difficulties and challenges. In response to these problems, we present a horizontal-vertical interaction and multiple side-outputs network for cyst segmentation in jaw images. First, the horizontal-vertical interaction mechanism facilitates complex communication paths in the vertical and horizontal dimensions, and it has the ability to capture a wide range of context dependencies. Second, the feature-fused unit is introduced to adjust the network's receptive field, which enhances the ability of acquiring multi-scale context information. Third, the multiple side-outputs strategy intelligently combines feature maps to generate more accurate and detailed change maps. Finally, experiments were carried out on the self-established jaw cyst dataset and compared with different specialist physicians to evaluate its clinical usability. The research results indicate that the Matthews correlation coefficient (Mcc), Dice, and Jaccard of HIMS-Net were 93.61, 93.66 and 88.10% respectively, which may contribute to rapid and accurate diagnosis in clinical practice.

A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses.

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

PDC-Net: parallel dilated convolutional network with channel attention mechanism for pituitary adenoma segmentation.

Accurate segmentation of the medical image is the basis and premise of intelligent diagnosis and treatment, which has a wide range of clinical application value. However, the robustness and effectiveness of medical image segmentation algorithms remains a challenging subject due to the unbalanced categories, blurred boundaries, highly variable anatomical structures and lack of training samples. For this reason, we present a parallel dilated convolutional network (PDC-Net) to address the pituitary adenoma segmentation in magnetic resonance imaging images. Firstly, the standard convolution block in U-Net is replaced by a basic convolution operation and a parallel dilated convolutional module (PDCM), to extract the multi-level feature information of different dilations. Furthermore, the channel attention mechanism (CAM) is integrated to enhance the ability of the network to distinguish between lesions and non-lesions in pituitary adenoma. Then, we introduce residual connections at each layer of the encoder-decoder, which can solve the problem of gradient disappearance and network performance degradation caused by network deepening. Finally, we employ the dice loss to deal with the class imbalance problem in samples. By testing on the self-established patient dataset from Quzhou People's Hospital, the experiment achieves 90.92% of Sensitivity, 99.68% of Specificity, 88.45% of Dice value and 79.43% of Intersection over Union (IoU).

Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption.

OBJECTIVES: To investigate the value of CCKBRfl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH). METHODS: In the first part, 2-month-old CCKBRfl/fl villin-Cre mice (CKO) and control CCKBRfl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo. RESULTS: The CCKBRfl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBRfl/fl villin-Cre mice, but no significant histopathological changes were observed. CONCLUSIONS: These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBRfl/fl villin-Cre mice. The CCKBRfl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.

BiDFDC-Net: a dense connection network based on bi-directional feedback for skin image segmentation.

Accurate segmentation of skin lesions in dermoscopic images plays an important role in improving the survival rate of patients. However, due to the blurred boundaries of pigment regions, the diversity of lesion features, and the mutations and metastases of diseased cells, the effectiveness and robustness of skin image segmentation algorithms are still a challenging subject. For this reason, we proposed a bi-directional feedback dense connection network framework (called BiDFDC-Net), which can perform skin lesions accurately. Firstly, under the framework of U-Net, we integrated the edge modules into each layer of the encoder which can solve the problem of gradient vanishing and network information loss caused by network deepening. Then, each layer of our model takes input from the previous layer and passes its feature map to the densely connected network of subsequent layers to achieve information interaction and enhance feature propagation and reuse. Finally, in the decoder stage, a two-branch module was used to feed the dense feedback branch and the ordinary feedback branch back to the same layer of coding, to realize the fusion of multi-scale features and multi-level context information. By testing on the two datasets of ISIC-2018 and PH2, the accuracy on the two datasets was given by 93.51% and 94.58%, respectively.

Temperature drives elevational diversity patterns of different types of organisms in Qinghai-Tibetan Plateau wetlands.

The spatial pattern and driving mechanism of biodiversity along elevational gradients are key topics in ecology. However, it is still unclear whether the multidimensional diversity of different types of organisms shows a similar response to elevation changes. Here, we measured the species and phylogenetic diversity of plants, bacteria, fungi, and microbial functional groups (nitrifiers, denitrifiers, methanogens, and methanotrophs) in 36 wetland sites on the Qinghai-Tibetan Plateau. The results showed that both species and phylogenetic diversity of plants, bacteria, and fungi exhibited a significant elevational gradient, in direct contrast to no significant diversity changes observed for denitrifiers, methanogens, and methanotrophs along the same altitude gradient. Our findings suggest that elevation and temperature were more likely to associate with the diversity of plants, bacteria, and fungi than the diversity of microbial functional groups, with important implications for assessing the effect of ongoing climate warming on biodiversity in Qinghai-Tibetan alpine wetlands.

Group theoretic particle swarm optimization for gray-level medical image enhancement.

As a principal category in the promising field of medical image processing, medical image enhancement has a powerful influence on the intermedia features and final results of the computer aided diagnosis (CAD) system by increasing the capacity to transfer the image information in the optimal form. The enhanced region of interest (ROI) would contribute to the early diagnosis and the survival rate of patients. Meanwhile, the enhancement schema can be treated as the optimization approach of image grayscale values, and metaheuristics are adopted popularly as the mainstream technologies for medical image enhancement. In this study, we propose an innovative metaheuristic algorithm named group theoretic particle swarm optimization (GT-PSO) to tackle the optimization problem of image enhancement. Based on the mathematical foundation of symmetric group theory, GT-PSO comprises particle encoding, solution landscape, neighborhood movement and swarm topology. The corresponding search paradigm takes place simultaneously under the guidance of hierarchical operations and random components, and it could optimize the hybrid fitness function of multiple measurements of medical images and improve the contrast of intensity distribution. The numerical results generated from the comparative experiments show that the proposed GT-PSO has outperformed most other methods on the real-world dataset. The implication also indicates that it would balance both global and local intensity transformations during the enhancement process.

Group theoretic particle swarm optimization for multi-level threshold lung cancer image segmentation.

Background: Image segmentation is an important step during the processing of medical images. For example, for the computer aid diagnostic systems for lung cancer image analysis, the segmented regions of tumors would help doctors in early diagnosis to determine timely and appropriate treatment possibilities and thereby improve the survival rate of the patients. However, general clinical routines of manual segmentation for large number of medical images are very difficult and time consuming, which is the challenge we aim to tackle using our proposed method. Methods: A novel image segmentation method with evolutionary learning technique named Group Theoretic Particle Swarm Optimization is proposed. It can tackle multi-level thresholding optimization problem during the segmentation process and rebuild the search paradigm according to the solid mathematical foundation of symmetric group from four designable aspects, which are particle encoding, solution landscape, neighborhood movement and swarm topology, respectively. The Kapur's entropy of multi-level thresholds is assessed as the objective function. Results: In contrast to those conventional metaheuristics methods for lung cancer image segmentation, this newly presented method generates the best performance result among them. Experimental results show that its Kapur's entropy has the value of 9.07, which is 16% higher than the worst case. Computational time is acceptable at the cost of 173.730 seconds, average level of evaluation metrics [Kappa, Precision, Recall, F1-measure, intersection over union (IoU) and receiver operating characteristic (ROC)] is over 90%, and search process of multi-level threshold combination would finally converge in the later phase of iterations after 700. The ablation study indicates that all components are significant to the contributions of our proposed method. Conclusions: Group Theoretic Particle Swarm Optimization for multi-level threshold segmentation is an efficient way to split a medical image into distinct regions and extract tumor tissues regions from the background. It maintains the balanced relationship between diversification and intensification during the search process and helps clinicians to make the diagnosis more accurately. Our proposed method processes potential medical value and clinical meanings.

Improved U-Net based on cross-layer connection for pituitary adenoma MRI image segmentation.

Pituitary adenoma is a common neuroendocrine neoplasm, and most of its MR images are characterized by blurred edges, high noise and similar to surrounding normal tissues. Therefore, it is extremely difficult to accurately locate and outline the lesion of pituitary adenoma. To sovle these limitations, we design a novel deep learning framework for pituitary adenoma MRI image segmentation. Under the framework of U-Net, a newly cross-layer connection is introduced to capture richer multi-scale features and contextual information. At the same time, full-scale skip structure can reasonably utilize the above information obtained by different layers. In addition, an improved inception-dense block is designed to replace the classical convolution layer, which can enlarge the effectiveness of the receiving field and increase the depth of our network. Finally, a novel loss function based on binary cross-entropy and Jaccard losses is utilized to eliminate the problem of small samples and unbalanced data. The sample data were collected from 30 patients in Quzhou People's Hospital, with a total of 500 lesion images. Experimental results show that although the amount of patient sample is small, the proposed method has better performance in pituitary adenoma image compared with existing algorithms, and its Dice, Intersection over Union (IoU), Matthews correlation coefficient (Mcc) and precision reach 88.87, 80.67, 88.91 and 97.63%, respectively.

Modified UNet++ with atrous spatial pyramid pooling for blood cell image segmentation.

Blood cell image segmentation is an important part of the field of computer-aided diagnosis. However, due to the low contrast, large differences in cell morphology and the scarcity of labeled images, the segmentation performance of cells cannot meet the requirements of an actual diagnosis. To address the above limitations, we present a deep learning-based approach to study cell segmentation on pathological images. Specifically, the algorithm selects UNet++ as the backbone network to extract multi-scale features. Then, the skip connection is redesigned to improve the degradation problem and reduce the computational complexity. In addition, the atrous spatial pyramid pooling (ASSP) is introduced to obtain cell image information features from each layer through different receptive domains. Finally, the multi-sided output fusion (MSOF) strategy is utilized to fuse the features of different semantic levels, so as to improve the accuracy of target segmentation. Experimental results on blood cell images for segmentation and classification (BCISC) dataset show that the proposed method has significant improvement in Matthew's correlation coefficient (Mcc), Dice and Jaccard values, which are better than the classical semantic segmentation network.

Fabrication and Experimental Validation of a Sensitive and Robust Tactile Sensing Array with a Micro-Structured Porous Dielectric Layer.

The development of pressure sensors of high sensitivity and stable robustness over a broad range is indispensable for the future progress of electronic skin applicable to the detection of normal and shear pressures of various dynamic human motions. Herein, we present a flexible capacitive tactile sensing array that incorporates a porous dielectric layer with micro-patterned structures on the surface to enable the sensitive detection of normal and shear pressures. The proposed sensing array showed great pressure-sensing performance in the experiments, with a broad sensing range from several kPa to 150 kPa of normal pressure and 20 kPa of shear pressure. Sensitivities of 0.54%/kPa at 10 kPa and below, 0.45%/kPa between 10 kPa and 80 kPa, and 0.12%/kPa at 80 kPa and above were achieved for normal pressures. Meanwhile, for shear pressures, sensitivities up to 1.14%/kPa and 1.08%/kPa in x and y directions, respectively, and below 10 kPa, 0.73%/kPa, and 0.75%/kPa under shear pressure over 10 kPa were also validated. The performance of the finger-attached sensing array was also demonstrated, demonstrating which was a potential electronic skin to use in all kinds of wearable devices, including prosthetic hands, surgical robots, and other pressure monitoring systems.

Furosemide improves the stone clearance rate of extracorporeal shockwave lithotripsy for kidney stones but not ureteral stones: a systematic review and meta-analysis.

Introduction: We conducted a meta-analysis (MA) to investigate the effects of furosemide on the prognosis of extracorporeal shockwave lithotripsy (SWL) therapy to remove renal (RS) and ureteric stones (US). Methods: We screened scientific databases including PubMed, Clinicalkey, Google Scholar, Medline, Embase, and Cochrane, from the date of establishment until March 2022, to search for randomized controlled trials evaluating SWL, in combination with furosemide (experimental group) or with SWL alone (control group), in treating RS or US. Our search terms included furosemide, extracorporeal SWL, and urolithiasis. For this MA, we employed the Cochrane Collaboration's RevMan version 5.3.0. Results: Six trials, involving 1344 participants, with RS (n = 1097) and/or US (n = 247), met our predefined criteria. This included 137 proximal ureteral stones (PUSs), 35 mid-ureteral stones (MUS), and 75 distal ureteral stones (DUS). In case of RS, the experimental group exhibited significantly enhanced clearance, relative to controls (risk ratio [RR] = 1.16, 95% confidence interval [CI] = 1.07-1.25, p = 0.0002), yet there was no obvious difference in the PUS, MUS, and DUS (RR = 1.14, 95% CI = 0.97-1.33, p = 0.10; odds ratio [OR] = 1.26, 95% CI = 1.40-3.95, p = 0.69; RR = 1.21, 95% CI = 0.99-1.49, p = 0.06). There was also no marked difference between fragmentations in either group. Only reports of SWL treatment of RS provided adequate data on shocks, sessions, and complications for our analysis. Unfortunately, there was no significant alteration between the two groups. Conclusion: According to our analysis, furosemide strongly accelerates the clearance rate of SWL-treated RS. However, it does not enhance the fragmentation rate. Given this evidence, we propose that furosemide does not significantly improve the efficacy of SWL therapy in removing US. Registration: Our work is registered with PROSPERO (CRD42020204780).

SEACU-Net: Attentive ConvLSTM U-Net with squeeze-and-excitation layer for skin lesion segmentation.

BACKGROUND AND OBJECTIVE: Accurate segmentation of skin lesions is a pivotal step in dermoscopy image classification, which provides a powerful means for dermatologists to diagnose skin diseases. However, due to blurred boundaries, low contrast between the lesion and its surrounding skin, and changes in color and shape, most existing segmentation methods still face great challenges in obtaining receptive fields and extracting image feature information. To settle the above issues, we construct a new framework, named SEACU-Net, to analyze and segment skin lesion images. METHODS: Inspired by the U-Net, we utilize dense convolution blocks to obtain more discriminative information. Then, at each encoding and decoding stage, a channel and spatial squeeze & excitation layer are designed after each convolution, to adaptively enhance useful information features and suppress low-value ones from different feature channels. In addition, the attention mechanism is integrated into the convolutional long short-term memory (ConvLSTM) structure, which improves sensitivity and prediction accuracy. Furthermore, this network introduces a novel loss based on binary cross-entropy and Jaccard losses, which can ensure more balanced segmentation. RESULTS: The proposed method is applied to the ISIC 2017 and 2018 publicly image databases, then obtains a better performance in Dice, Jaccard, and Accuracy, with 89.11% and 87.58% Dice value, 80.50% and 78.12% Jaccard value, 95.01%, and 93.60% Accuracy value, respectively. CONCLUSION: The results of quantitative and qualitative experiments show that our method reaches high-performance skin lesion segmentation, and can help radiologists make radiotherapy treatment plans in clinical practice.

Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na+/H+ Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway.

BACKGROUND: The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension. METHODS: Adult intestine-specific Cckbr-knockout mice (Cckbrfl/fl villin-Cre) and Dahl salt-sensitive rats were studied on the effect of high salt intake (8% NaCl, 6-7 weeks) on intestinal Na+/H+ exchanger 3 expression, urine sodium concentration, and blood pressure. High-salt diet increased urine sodium concentration and systolic blood pressure to a greater extent in Cckbrfl/fl villin-Cre mice and Dahl salt-sensitive rats than their respective controls, Cckbrfl/fl villin mice and SS13BN rats. We constructed gastrin-SiO2 microspheres to enable gastrin to stimulate specifically and selectively intestinal CCKBR without its absorption into the circulation. RESULTS: Gastrin-SiO2 microspheres treatment prevented the high salt-induced hypertension and increase in urine Na concentration by inhibiting intestinal Na+/H+ exchanger 3 trafficking and activity, increasing stool sodium without inducing diarrhea. Gastrin-mediated inhibition of intestinal Na+/H+ exchanger 3 activity, related to a PKC (protein kinase C)-mediated activation of NHERF1 and NHERF2. CONCLUSIONS: These results support a crucial role of intestinal gastrin/CCKBR in decreasing intestinal sodium absorption and keeping the blood pressure in the normal range. The gastrointestinal administration of gastrin-SiO2 microspheres is a promising and safe strategy to treat salt-sensitive hypertension without side effects.

The Effects of ATIR Blocker on the Severity of COVID-19 in Hypertensive Inpatients and Virulence of SARS-CoV-2 in Hypertensive hACE2 Transgenic Mice.

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.

P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt.

PURPOSE: P-selectin glycoprotein ligand-1 (PSGL-1) acts as a crucial regulator for the inflammatory cells infiltration by mediating the adhesion of leukocytes. However, the role of PSGL-1 in aortic aneurysm remains elusive. Here, we investigated the role of PSGL-1 in aortic aneurysm (AA) development. METHODS: We first detected PSGL-1 expression in samples from aortic aneurysm patients and mouse AA models via western blotting, immunofluorescence, and flow cytometry, and then we used global PSGL-1 knockout mice and their wild type controls to establish an aortic aneurysm model induced by deoxycorticosterone acetate (DOCA) plus high salt (HS). The incidence, fatality rates, and the pathological changes of aortic aneurysm were analyzed in each group. The inflammation, adhesion molecules expression, and PSGL-1 mediated leukocyte-endothelial adhesion and their underlying mechanisms were explored further. RESULTS: Increased PSGL-1 levels were observed in human and mouse aortic aneurysm, and on leukocytes of mice treated with DOCA+HS. PSGL-1 deficiency reduced the incidence and severity of aortic aneurysm significantly, as well as decreased elastin fragmentation, collagen accumulation, and smooth muscle cells degeneration. Mechanistically, the protective effect of PSGL-1 inhibition was mediated by the reduced adhesion molecules, and the subsequently reduced leukocyte-endothelial adhesion through the NF-κB pathway, which finally led to reduced inflammatory cells infiltration and decreased inflammatory factors expression. CONCLUSION: PSGL-1 deficiency is protective against inflammatory cells migration and recruitment in the condition of AA through attenuation of leukocyte-endothelial adhesion. Inhibition of PSGL-1 may be a potential therapeutic target for the prevention and treatment of human AA.

Comparison of ureteroscopy (URS) complementary treatment after extracorporeal shock wave lithotripsy failure with primary URS lithotripsy with holmium laser treatment for proximal ureteral stones larger than10mm.

BACKGROUND: To compare ureteroscopy (URS) complementary treatment following extracorporeal shock wave lithotripsy (SWL) failure with primary URS lithotripsy for proximal ureteral stones > 10 mm, and try to find out acceptable number of SWL sessions followed by safe URS. METHODS: This was a retrospective study following approval from Medical Ethics Committee of People's Hospital of Chongqing Banan District. Patients (n = 340) who received URS in our hospital for stones > 10 mm from Jan 2015 to June 2020 were divided into two groups according to their previous SWL history. Group 1 consisted of 160 patients that underwent unsuccessful SWL before URS. Group 2 encompassed 180 patients without SWL before URS. Patient's operative outcomes were compared. A logistic regression and receiver operator characteristics (ROC) were used to identify the acceptable number of SWL sessions prior to URS, regarding the intra-operative complications of URS. RESULTS: The group 1 required more surgery time (41.38 ± 11.39 min vs. 36.43 ± 13.36 min, p = 0.01). At the same time, more intra-operative (68.1% VS 22.8%, p < 0.05) and post-operative (35% VS 18.0%, p = 0.001) complications occurred in group 1. Need more hospital stay in group 1 (2.7 ± 1.2 days vs 1.6 ± 1.1 days, p < 0.05). More patients in group 1 need further URS (16.3% VS 8.9%, p = 0.029). After second URS, the SFR of URS in two groups was insignificant differences (82.5% VS 88.9%, p > 0.05). The median (25-75%) of SWL sessions before URS was 2 (1-3) in group 1. According to the results of logistic regression analysis, patients suffered more SWL failure have an increased risk of complications during URS (OR = 1.995, 95% CI: 1.636-2.434). ROC showed that the optimal number of SWL session followed by URS were 0.5, with a sensitivity of 67.7% and specificity of 71.5%. Intra-operative complication rates of URS treatment were higher in patients who suffered > 1 SWL failure (72.6% vs 57.4%, p = 0.047). CONCLUSION: There was no acceptable number of SWL sessions that could be followed by URS with fewer intra-operative complications. Patients who underwent previous SWL were likely to suffer more intra-operative complications, the average operating time, hospitalization time, and needing further treatment, during URS treatment for proximal ureteral stones larger than 10 mm.

The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis.

BACKGROUND AND AIMS: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and plaque vulnerability. Macrophage apoptosis mediated by endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of HHcy-aggravated atherosclerosis. Endoplasmic reticulum oxidoreductase 1α (Ero1α) is critical for ER stress-induced apoptosis. We hypothesized that Ero1α may contribute to ER-stress induced macrophage apoptosis and plaque stability in advanced atherosclerotic lesions by HHcy. METHODS: Apoe-/- mice were maintained on drinking water containing homocysteine (Hcy, 1.8 g/L) to establish HHcy atherosclerotic models. The role of Ero1α in atherosclerotic plaque stability, macrophage apoptosis and ER stress were monitored in the plaque of aortic roots in HHcy Apoe-/- mice with or without silence or overexpression of Ero1α through lentivirus. Mouse peritoneal macrophages were used to confirm the regulation of Ero1α on ER stress dependent apoptosis in the presence of HHcy. RESULTS: Atherosclerotic plaque vulnerability and macrophage apoptosis were promoted in Apoe-/- mice by high Hcy diet, accompanied by the upregulation of Ero1α expression and ER stress. Inhibition of Ero1α prevented macrophage apoptosis and atherosclerotic plaque vulnerability, and vice versa. Consistently, in mouse peritoneal macrophages, ER stress and apoptosis were attenuated by Ero1α deficiency, but enhanced by Ero1α overexpression. CONCLUSIONS: Hcy, via upregulation of Ero1α expression, activates ER stress-dependent macrophage apoptosis to promote vulnerable plaque formation in atherosclerosis. Ero1α may be a potential therapeutic target for atherosclerosis induced by Hcy.

Microplastic contamination is ubiquitous in riparian soils and strongly related to elevation, precipitation and population density.

Although environmental research has recently begun to focus on the ubiquity of microplastics in terrestrial systems, there is still lack of comprehensive data which describe microplastics levels in soils and the factors influencing the distribution of this contaminant. Here, we show that microplastics contamination (3877 ± 2356 p kg1) is omnipresent in numerous soil samples collected along the Yangtze River. Subsoils (4005 ± 2472 p kg1) showed higher levels of microplastics than topsoils (3748 ± 2301 p kg1), while polyamide (32%) was the most commonly found polymer in the samples. Small microplastics particles (< 200 µm) accounted for approximately 70% of the microplastics detected in subsoils. In terms of shape, microfragments were the most common type of microplastic particle, accounting for 34% of total microplastics, followed by microfibers (30%). Furthermore, microplastics contamination was found to be positively correlated with both the population of the study area and precipitation, yet negatively correlated with the elevation of the sampling site. Our study represents the first large-scale study of microplastic contamination in riparian soils along the Yangtze River, and provides important data regarding the ecotoxicology and ecosystem effects of microplastics in terrestrial environments.