Regulation of interstitial fluid flow in adventitia along vasculature by heartbeat and respiration.

Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

LA-Net: layer attention network for 3D-to-2D retinal vessel segmentation in OCTA images.

Objective.Retinal vessel segmentation from optical coherence tomography angiography (OCTA) volumes is significant in analyzing blood supply structures and the diagnosing ophthalmic diseases. However, accurate retinal vessel segmentation in 3D OCTA remains challenging due to the interference of choroidal blood flow signals and the variations in retinal vessel structure.Approach.This paper proposes a layer attention network (LA-Net) for 3D-to-2D retinal vessel segmentation. The network comprises a 3D projection path and a 2D segmentation path. The key component in the 3D path is the proposed multi-scale layer attention module, which effectively learns the layer features of OCT and OCTA to attend to the retinal vessel layer while suppressing the choroidal vessel layer. This module also efficiently captures 3D multi-scale information for improved semantic understanding during projection. In the 2D path, a reverse boundary attention module is introduced to explore and preserve boundary and shape features of retinal vessels by focusing on non-salient regions in deep features.Main results.Experimental results in two subsets of the OCTA-500 dataset showed that our method achieves advanced segmentation performance with Dice similarity coefficients of 93.04% and 89.74%, respectively.Significance.The proposed network provides reliable 3D-to-2D segmentation of retinal vessels, with potential for application in various segmentation tasks that involve projecting the input image. Implementation code:https://github.com/y8421036/LA-Net.

Contour attention network for cerebrovascular segmentation from TOF-MRA volumetric images.

BACKGROUND: Cerebrovascular segmentation is a crucial step in the computer-assisted diagnosis of cerebrovascular pathologies. However, accurate extraction of cerebral vessels from time-of-flight magnetic resonance angiography (TOF-MRA) data is still challenging due to the complex topology and slender shape. PURPOSE: The existing deep learning-based approaches pay more attention to the skeleton and ignore the contour, which limits the segmentation performance of the cerebrovascular structure. We aim to weight the contour of brain vessels in shallow features when concatenating with deep features. It helps to obtain more accurate cerebrovascular details and narrows the semantic gap between multilevel features. METHODS: This work proposes a novel framework for priority extraction of contours in cerebrovascular structures. We first design a neighborhood-based algorithm to generate the ground truth of the cerebrovascular contour from original annotations, which can introduce useful shape information for the segmentation network. Moreover, We propose an encoder-dual decoder-based contour attention network (CA-Net), which consists of the dilated asymmetry convolution block (DACB) and the Contour Attention Module (CAM). The ancillary decoder uses the DACB to obtain cerebrovascular contour features under the supervision of contour annotations. The CAM transforms these features into a spatial attention map to increase the weight of the contour voxels in main decoder to better restored the vessel contour details. RESULTS: The CA-Net is thoroughly validated using two publicly available datasets, and the experimental results demonstrate that our network outperforms the competitors for cerebrovascular segmentation. We achieved the average dice similarity coefficient ( D S C $DSC$ ) of 68.15 and 99.92% in natural and synthetic datasets. Our method segments cerebrovascular structures with better completeness. CONCLUSIONS: We propose a new framework containing contour annotation generation and cerebrovascular segmentation network that better captures the tiny vessels and improve vessel connectivity.

Gasotransmitter-Mediated Cysteinome Oxidative Posttranslational Modifications: Formation, Biological Effects, and Detection.

Significance: Gasotransmitters, including nitric oxide (NO), hydrogen sulfide (H2S) and sulfur dioxide (SO2), participate in various cellular processes via corresponding oxidative posttranslational modifications (oxiPTMs) of specific cysteines. Recent Advances: Accumulating evidence has clarified the mechanisms underlying the formation of oxiPTMs derived from gasotransmitters and their biological functions in multiple signal pathways. Because of the specific existence and functional importance, determining the sites of oxiPTMs in cysteine is crucial in biology. Recent advances in the development of selective probes, together with upgraded mass spectrometry (MS)-based proteomics, have enabled the quantitative analysis of cysteinome. To date, several cysteine residues have been identified as gasotransmitter targets. Critical Issues: To clearly understand the underlying mechanisms for gasotransmitter-mediated biological processes, it is important to identify modified targets. In this review, we summarize the chemical formation and biological effects of gasotransmitter-dependent oxiPTMs and highlight the state-of-the-art detection methods. Future Directions: Future studies in this field should aim to develop the next generation of probes for in situ labeling to improve spatial resolution and determine the dynamic change of oxiPTMs, which can lay the foundation for research on the molecular mechanisms and clinical translation of gasotransmitters. Antioxid. Redox Signal. 40, 145-167.

Soil carbon content prediction using multi-source data feature fusion of deep learning based on spectral and hyperspectral images.

Visible near-infrared reflectance spectroscopy (VNIR) and hyperspectral images (HSI) have their respective advantages in soil carbon content prediction, and the effective fusion of VNIR and HSI is of great significance for improving the prediction accuracy. But the contribution difference analysis of multiple features in the multi-source data is inadequate, and there is a lack of in-depth research on the contribution difference analysis of artificial feature and deep learning feature. In order to solve the problem, soil carbon content prediction methods based on VNIR and HSI multi-source data feature fusion are proposed. The multi-source data fusion network under the attention mechanism and the multi-source data fusion network with artificial feature are designed. For the multi-source data fusion network based on the attention mechanism, the information are fused through the attention mechanism according to the contribution difference of each feature. For the other network, artificial feature are introduced to fuse multi-source data. The results show that multi-source data fusion network based on the attention mechanism can improve the prediction accuracy of soil carbon content, and multi-source data fusion network combined with artificial feature has better prediction effect. Compared with two single-source data from the VNIR and HSI, the relative percent deviation of Neilu, Aoshan Bay and Jiaozhou Bay based on multi-source data fusion network combined with artificial feature are increased by 56.81% and 149.18%, 24.28% and 43.96%, 31.16% and 28.73% respectively. This study can effectively solve the problem of the deep fusion of multiple features in the soil carbon content prediction by VNIR and HSI, so as to improve the accuracy and stability of soil carbon content prediction, promote the application and development of soil carbon content prediction in spectral and hyperspectral image, and provide technical support for the study of carbon cycle and the carbon sink.

Configurational patterns for COVID-19 related social media rumor refutation effectiveness enhancement based on machine learning and fsQCA.

Infodemics are intertwined with the COVID-19 pandemic, affecting people's perception and social order. To curb the spread of COVID-19 related false rumors, fuzzy-set qualitative comparative analysis (fsQCA) is used to find configurational pathways to enhance rumor refutation effectiveness. In this paper, a total of 1,903 COVID-19 related false rumor refutation microblogs on Sina Weibo are collected by a web crawler from January 1, 2022 to April 20, 2022, and 10 main conditions affecting rumor refutation effectiveness index (REI) are identified based on "three rules of epidemics". To reduce data redundancy, five ensemble machine learning models are established and tuned, among which Light Gradient Boosting Machine (LGBM) regression model has the best performance. Then five core conditions are extracted by feature importance ranking of LGBM. Based on fsQCA with the five core conditions, REI enhancement can be achieved through three different pathway elements configurations solutions: "Highly influential microblogger * high followers' stickiness microblogger", "high followers' stickiness microblogger * highly active microblogger * concise information description" and "high followers' stickiness microblogger * the sentiment tendency of the topic * concise information description". Finally, decision-making suggestions for false rumor refutation platforms and new ideas for improving false rumor refutation effectiveness are proposed. The innovation of this paper reflects in exploring the REI enhancement strategy from the perspective of configuration for the first time.

Toughening and Hardening Limited Zone of High-Strength Steel through Geometrically Necessary Dislocation When Exposed to Electropulsing.

The enhancement of both low-temperature impact toughness and the hardness of a high strength steel heat-affected zone (HAZ) is investigated by using high-density electropulsing (EP). The athermal and thermal effects of EP on HAZ microstructure and resultant mechanical properties were examined based on physical metallurgy by electron backscattered diffraction and on tests of hardness and impact toughness at -60 °C, respectively. EP parameters were carefully determined to avoid electro-contraction and excessive pollution of the base metal by using numerical simulation. The EP results show that the mean impact toughness and hardness of HAZ are 2.1 times and 1.4 times improved, respectively. In addition to the contribution of microstructure evolution, geometrically necessary dislocation (GND) is also a contributor with an increase of 1.5 times, against the slight decrease in dislocation line density and dislocation density. The mechanisms behind this selective evolution of dislocation components were correlated with the localized thermal cycle EP, i.e., the competition among thermo- and electro-plasticity, and work-hardening due to local thermal expansion. The selective evolution enables the local thermal cycle EP tailor the martensitic substructure that is most favorable for toughness and less for hardness. This selective span was limited within 4 mm for a 5 mm thick sample. The local thermal cycle EP is confirmed to be capable of enhancing in both toughness and hardness within a millimeter-scale region.

Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics.

Click chemistry─specifically the copper-catalyzed azide-alkyne cycloaddition─has enabled the development of a wide range of chemical probes to analyze subsets of the functional proteome. The "clickable" proteome can be selectively enriched by using diverse cleavable biotin tags, but the direct identification of probe/tag-modified peptides (or peptide-centric analysis) remains challenging. Here, we evaluated the performance of five commercially available cleavable biotin tags in three most common chemoproteomic workflows, resulting in a comparative analysis of 15 methods. An acid-cleavable biotin tag with a dialkoxydiphenylsilane moiety, in combination with the protein "click", peptide "capture" workflow, outperforms all other methods in terms of enrichment efficiency, identification yield, and reproducibility, although its performance may be slightly compromised by the formation of an unwanted formate product revealed by blind search. Despite being inferior, photocleavable, and reduction-cleavable, biotin tags can also find their applicable sceneries, especially when dealing with acid-sensitive probes or probe-derived modifications. Furthermore, the systematic comparison of LC-MS/MS characteristics of tag-modified peptides provides valuable information for the future development of cleavable biotin reagents. Taken together, our data provides a much-needed practical guidance for researchers interested in developing and/or applying an ideal cleavable biotin tag to peptide-centric chemoproteomics.

Eliminating the Brittleness Constituent to Enhance Toughness of the High-Strength Steel Weld Heat-Affected Zone Using Electropulsing.

The evolution of the martensite-austenite (MA) constituent in the heat-affected zone (HAZ) of high-strength steel FH690 welds when subjected to electropulsing (EP) treatment was investigated herein, with the aim of eliminating brittle MA to enhance toughness. The features induced by EPT were correlated with the microstructure and fractography through scanning electron microscopy and electron backscatter diffraction analyses, together constituting an impact property evaluation. The Charpy V-notch impact results showed EPT could improve toughness of the HAZ from 34.1 J to 51.8 J (the calibrated value was 46 J). Examinations of EP-treated microstructure showed a preferred Joule heating: at the site of the MA constituent, the cleavage fractography introduced by the MA constituent was substituted with ductile dimples with various sizes. Decreases in grain size of 40% and 47% for the matrix and the retained austenite, respectively, were achieved; while for regions without the MA constituent, microstructural modification was negligible. The temperature rise at sample surface was less than 60 °C. The mechanism behind this favorable Joule heating for the MA constituent was correlated with the electrical properties of the MA constituent in contrast with martensite matrix. The toughness enhancement of the HAZ was thus attributed to the elimination of the coarse MA constituent. The present investigation suggested that electropulsing, characterized as a narrow-duration current, is a promising method for preferred elimination of brittle factors and thus improving the toughness of HAZ of high-strength steel within a limited region with a width less than 2 mm.

Clinical observation of transcatheter arterial chemoembolization in super-aged patients with advanced gastric cancer.

PURPOSE: To retrospectively analyze the safety and efficacy of transcatheter arterial chemoembolization (TACE) in super-aged patients with advanced gastric cancer (AGC), as well as the effects of TACE on quality of life (QOL) and anxiety state. METHODS: In this study, 32 AGC patients aged over 80 years old were enrolled and treated with TACE. Complications of TACE and total effective rate of symptom relief after TACE were observed. Changes of the maximum diameter of solid tumors before and after TACE were compared by reexamination of abdominal computerized tomography. QOL, Eastern Cooperative Oncology Group (ECOG), and Hamilton anxiety scale (HAMA) scores of tumor patients were performed before TACE and 3d, 28d, and 90d after TACE. RESULTS: No serious complications occurred during or after TACE in any patient. The total effective rate of symptom relief was 56.25% at 28d after TACE and 71.88% at 90d after TACE. Compared with before TACE, the maximum diameter of tumor was significantly decreased after TACE; ECOG was increased at 3d after TACE, while was decreased at 28d and 90d after TACE (P < 0.05); QOL and HAMA had no significant change at 3d after TACE, while increased significantly at 28d and 90d after TACE (all P < 0.05). CONCLUSION: TACE was safe and effective, could shrink tumors, and improve the QOL and anxiety for super-aged patients with AGC.

Multi-stage Internet public opinion risk grading analysis of public health emergencies: An empirical study on Microblog in COVID-19.

In the period of Corona Virus Disease 2019 (COVID-19), millions of people participate in the discussion of COVID-19 on the Internet, which can easily trigger public opinion and threaten social stability. This paper creatively proposes a multi-stage risk grading model of Internet public opinion for public health emergencies. On the basis of general public opinion risk grading analysis, the model continuously pays attention to the risk level of Internet public opinion based on the time scale of regular or major information updates. This model combines Analytic Hierarchy Process Sort II (AHPSort II) and Swing Weighting (SW) methods and proposes a new Multi-Criteria Decision Making (MCDM) method - AHPSort II-SW. Intuitionistic fuzzy number and linguistic fuzzy number are introduced into the model to evaluate the criteria that cannot be quantified. The multi-stage model is tested using more than 2,000 textual data about COVID-19 collected from Microblog, a leading social media platform in China. Seven public opinion risk assessments were conducted from January 23 to April 8, 2020. The empirical results show that in the early COVID-19 outbreak, the risk of public opinion is more serious on macroscopic view. In details, the risk of public opinion decreases slowly with time, but the emergence of important events may still increase the risk of public opinion. The analysis results are in line with the actual situation and verify the effectiveness of the method. Comparative analysis indicates the improved method is proved to be superior and effective, sensitivity analysis confirms its stability. Finally, management suggestions was provided, this study contributes to the literature on public opinion risk assessment and provides implications for practice.

Rice GLUTATHIONE PEROXIDASE1-mediated oxidation of bZIP68 positively regulates ABA-independent osmotic stress signaling.

Osmotic stress caused by drought and high salinity is a significant environmental threat that limits plant growth and agricultural yield. Redox regulation plays an important role in plant stress responses, but the mechanisms by which plants perceive and transduce redox signals are still underexplored. Here, we report a critical function for the thiol peroxidase GPX1 in osmotic stress response in rice, where it serves as a redox sensor and transducer. GPX1 is quickly oxidized upon exposure to osmotic stress and forms an intramolecular disulfide bond, which is required for the activation of bZIP68, a VRE-like basic leucine zipper (bZIP) transcription factor involved in the ABA-independent osmotic stress response pathway. The disulfide exchange between GPX1 and bZIP68 induces homo-tetramerization of bZIP68 and thus positively regulates osmotic stress response by regulating osmotic-responsive gene expression. Furthermore, we discovered that the nuclear translocation of GPX1 is regulated by its acetylation under osmotic stress. Taken together, our findings not only uncover the redox regulation of the GPX1-bZIP68 module during osmotic stress but also highlight the coordination of protein acetylation and redox signaling in plant osmotic stress responses.

Regional water resources security grading evaluation considering both visible and virtual water: a case study on Hubei province, China.

The security of water resources is of great importance to long-term sustainability. In order to better ensure the security of water resources, a significant link is to conduct water resources security evaluation, which should be considered from many perspectives as it involves natural reserves, social production, the efficiency of use, and environmental protection. In this paper, a fuzzy analytic hierarchy process sort (AHPSort) II-entropy weight (EW) method for regional water resources security evaluation is proposed based on the security of visible water and virtual water. Firstly, this paper takes into account the criterion of efficiency of water use in addition to two other criteria of quantity of water resources, pressure on water resources to establish a comprehensive water resources security evaluation system. Secondly, a combination method of hesitant fuzzy language judgment and entropy weight is employed to obtain the weight of each indicator. Thirdly, AHPSort II is used to classify the security levels of the evaluated regions, in which the security levels of regional water resources are divided into five levels. Furthermore, a case study on the cities of Hubei province, China, is conducted to show the applicability of the proposed method, the effectiveness, and reliability of the method are then verified by being compared with a subjective method and an objective method as well as sensitivity analysis. Finally, according to the comprehensive evaluation results, specific management suggestions for improving the water resources security in the case are put forward.

Diagnosis and functional prediction of microbial markers in tumor tissues of sporadic colorectal cancer patients associated with the MLH1 protein phenotype.

Objective: Most patients with sporadic colorectal cancer (SCRC) develop microsatellite instability because of defects in mismatch repair (MMR). Moreover, the gut microbiome plays a vital role in the pathogenesis of SCRC. In this study, we assessed the microbial composition and diversity of SCRC tumors with varying MutL protein homolog 1 (MLH1) status, and the effects of functional genes related to bacterial markers and clinical diagnostic prediction. Methods: The tumor microbial diversity and composition were profiled using high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene V4 region. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) software and BugBase tool were used to predict the functional roles of the microbiome. We aimed to construct a high-accuracy model to detect and evaluate the area under the receiver operating characteristic curve with candidate biomarkers. Results: The study included 23 patients with negative/defective MLH1 (DM group) and 22 patients with positive/intact MLH1 (IM group). Estimation of alpha diversity indices showed that the Shannon index (p = 0.049) was significantly higher in the DM group than in the controls, while the Simpson index (p = 0.025) was significantly lower. At the genus level, we observed a significant difference in beta diversity in the DM group versus the IM group. Moreover, the abundance of Lachnoclostridium spp. and Coprococcus spp. was significantly more enriched in the DM group than in the IM group (q < 0.01 vs. q < 0.001). When predicting metagenomes, there were 18 Kyoto Encyclopedia of Genes and Genomes pathways and one BugBase function difference in both groups (all q < 0.05). On the basis of the model of diagnostic prediction, we built a simplified optimal model through stepwise selection, consisting of the top two bacterial candidate markers (area under the curve = 0.93). Conclusion: In conclusion, the genera Lachnoclostridium and Coprococcus as key species may be crucial biomarkers for non-invasive diagnostic prediction of DM in patients with SCRC in the future.

A bi-level multi-objective location-routing model for municipal waste management with obnoxious effects.

Municipal waste management is a complex problem. This paper develops a bi-level multi-objective location-routing model for municipal waste management that considers the interests of both the government and the sanitation companies. The government as the leader decides on the location and scale of the waste recycling centers to reduce the obnoxious effects and ensure cost effectiveness, and the sanitation company as the follower decides on the waste collection routing plans based on the government-approved locations to minimize the logistics cost. An improved hybrid NSGA-II is then developed to solve the proposed model. Two initial solution methods are employed: clustering for the leader and a Clarke and Wright method for the follower. Non-dominated sorting and best-cost route crossover operator are used to improve the effectiveness of NSGA-II. Based on Prins (24 instances) and Barreto (13 instances) benchmarks, the experimental results indicated that the improved operator had strong competitiveness and a better performance than previous methods, with the improved algorithm achieving the best average gaps of 0.18% and 0.24% and improving the best-known solutions in some instances. The model and solution methodology are illustrated using a waste collection problem in Tianjin, from which practical insights are derived.

Hydrogen sulfide-linked persulfidation of ABI4 controls ABA responses through the transactivation of MAPKKK18 in Arabidopsis.

Hydrogen sulfide (H2S) is a signaling molecule that regulates plant hormone and stress responses. The phytohormone abscisic acid (ABA) plays an important role in plant adaptation to unfavorable environmental conditions and induces the persulfidation of L-CYSTEINE DESULFHYDRASE1 (DES1) and the production of H2S in guard cells. However, it remains largely unclear how H2S and protein persulfidation participate in the relay of ABA signals. In this study, we discovered that ABSCISIC ACID INSENSITIVE 4 (ABI4) acts downstream of DES1 in the control of ABA responses in Arabidopsis. ABI4 undergoes persulfidation at Cys250 that is triggered in a time-dependent manner by ABA, and loss of DES1 function impairs this process. Cys250 and its persulfidation are essential for ABI4 function in the regulation of plant responses to ABA and the H2S donor NaHS during germination, seedling establishment, and stomatal closure, which are abolished in the ABI4Cys250Ala mutated variant. Introduction of the ABI4Cys250Ala variant into the abi4 des1 mutant did not rescue its hyposensitivity to ABA. Cys250 is critical for the binding of ABI4 to its cognate motif in the promoter of Mitogen-Activated Protein Kinase Kinase Kinase 18 (MAPKKK18), which propagates the MAPK signaling cascade induced by ABA. Furthermore, the DES1-mediated persulfidation of ABI4 enhances the transactivation activity of ABI4 toward MAPKKK18, and ABI4 can bind the DES1 promoter, forming a regulatory loop. Taken together, these findings advance our understanding of a post-translational regulatory mechanism and suggest that ABI4 functions as an integrator of ABA and MAPK signals through a process in which DES1-produced H2S persulfidates ABI4 at Cys250.

Endogenous SO2-dependent Smad3 redox modification controls vascular remodeling.

Sulfur dioxide (SO2) has emerged as a physiological relevant signaling molecule that plays a prominent role in regulating vascular functions. However, molecular mechanisms whereby SO2 influences its upper-stream targets have been elusive. Here we show that SO2 may mediate conversion of hydrogen peroxide (H2O2) to a more potent oxidant, peroxymonosulfite, providing a pathway for activation of H2O2 to convert the thiol group of protein cysteine residues to a sulfenic acid group, aka cysteine sulfenylation. By using site-centric chemoproteomics, we quantified >1000 sulfenylation events in vascular smooth muscle cells in response to exogenous SO2. Notably, ~42% of these sulfenylated cysteines are dynamically regulated by SO2, among which is cysteine-64 of Smad3 (Mothers against decapentaplegic homolog 3), a key transcriptional modulator of transforming growth factor ß signaling. Sulfenylation of Smad3 at cysteine-64 inhibits its DNA binding activity, while mutation of this site attenuates the protective effects of SO2 on angiotensin II-induced vascular remodeling and hypertension. Taken together, our findings highlight the important role of SO2 in vascular pathophysiology through a redox-dependent mechanism.

A quantitative thiol reactivity profiling platform to analyze redox and electrophile reactive cysteine proteomes.

Cysteine is unique among all protein-coding amino acids, owing to its intrinsically high nucleophilicity. The cysteinyl thiol group can be covalently modified by a broad range of redox mechanisms or by various electrophiles derived from exogenous or endogenous sources. Measuring the response of protein cysteines to redox perturbation or electrophiles is critical for understanding the underlying mechanisms involved. Activity-based protein profiling based on thiol-reactive probes has been the method of choice for such analyses. We therefore adapted this approach and developed a new chemoproteomic platform, termed 'QTRP' (quantitative thiol reactivity profiling), that relies on the ability of a commercially available thiol-reactive probe IPM (2-iodo-N-(prop-2-yn-1-yl)acetamide) to covalently label, enrich and quantify the reactive cysteinome in cells and tissues. Here, we provide a detailed and updated workflow of QTRP that includes procedures for (i) labeling of the reactive cysteinome from cell or tissue samples (e.g., control versus treatment) with IPM, (ii) processing the protein samples into tryptic peptides and tagging the probe-modified peptides with isotopically labeled azido-biotin reagents containing a photo-cleavable linker via click chemistry reaction, (iii) capturing biotin-conjugated peptides with streptavidin beads, (iv) identifying and quantifying the photo-released peptides by mass spectrometry (MS)-based shotgun proteomics and (v) interpreting MS data by a streamlined informatic pipeline using a proteomics software, pFind 3, and an automatic post-processing algorithm. We also exemplified here how to use QTRP for mining H2O2-sensitive cysteines and for determining the intrinsic reactivity of cysteines in a complex proteome. We anticipate that this protocol should find broad applications in redox biology, chemical biology and the pharmaceutical industry. The protocol for sample preparation takes 3 d, whereas MS measurements and data analyses require 75 min and <30 min, respectively, per sample.

Regional Water Resources Security Evaluation Based on a Hybrid Fuzzy BWM-TOPSIS Method.

Nowadays, water resource security is becoming increasingly prominent, and this problem is a primary bottleneck restricting China's future sustainable development. It is difficult to come to a unified conclusion on water resources security, and applications of highly feasible evaluation methods are lacking in practice. In this paper, a novel evaluation methodology is proposed for regional water resources security evaluation. First, water security is divided into two aspects: water quantity security and water quality security. The disposal rate of harmless household garbage, the excellent water resources proportion, and the functional water body loss proportion are creatively considered as indicators of water quality security in the evaluation system. In addition, a Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method is used to evaluate the water security levels in different regions. For distinguishing the importance of different indicators, a Best-Worst Method (BWM) is employed to calculate the indicator weights, as triangular fuzzy linguistic sets can more flexibly describe the preferences of decision makers (DMs) regarding the indicators; therefore, it is embedded in BWM to determine indicator weights. Moreover, the fuzzy BWM-TOPSIS method is applied to evaluate the water security levels of six regions in North China, a comparison analysis with the equal weight TOPSIS method as well as the fuzzy BWM-AHP method, and a sensitivity analysis for indicator weights are presented to illustrate the effectiveness of this proposed method. Finally, some suggestions based on the evaluation results are given for effective and rational utilization of water resources in North China.

Salidroside improves angiogenesis-osteogenesis coupling by regulating the HIF-1α/VEGF signalling pathway in the bone environment.

Angiogenesis is essential for bone formation during skeletal development. HIF-1α and the HIF-responsive gene VEGF (vascular endothelial growth factor) are reported to be a key mechanism for coupling osteogenesis and angiogenesis. Salidroside (SAL), a major biologically active compound of Rhodiola rosea L., possesses diverse pharmacological effects. However, whether SAL can protect against bone loss via the HIF-1α/VEGF pathway, specifically by inducing angiogenesis-osteogenesis coupling in vivo, remains unknown. Therefore, in the present study, we employed primary human umbilical vein endothelial cells (HUVECs) and the permanent EA.hy926 human endothelial cell line to determine the cellular and molecular effects of SAL on vascular endothelial cells and the HIF-1α-VEGF signalling pathway in the coupling of angiogenesis-osteogenesis. The in vitro study revealed that the HUVECs and EA.hy926 cells treated with conditioned medium from osteoblast cells (MG-63 cells) treated with SAL or treated directly with SAL showed enhanced proliferation, migration and capillary structure formation. However, supplementation with an anti-VEGF antibody during the treatment of endothelial cells (ECs) significantly reversed the pro-angiogenic effect of SAL. Moreover, SAL upregulated HIF-1α expression and increased its transcriptional activity, consequently upregulating VEGF expression at the mRNA and protein levels. In addition, our in vivo analysis demonstrated that SAL can stimulate endothelial sprouting from metatarsal bones. Thus, our mechanistic study demonstrated that the pro-angiogenic effects of SAL involve HIF-1α-VEGF signalling by coordinating the coupling of angiogenesis-osteogenesis in the bone environment. Therefore, we have discovered an ideal molecule that simultaneously enhances angiogenesis and osteogenesis and thereby accelerates bone healing.