Blood Oxygen Level-Dependent MR Imaging of Lower Extremities in Peripheral Artery Disease and Its Correlation With Walking Performance.

BACKGROUND: A noninvasive and reliable approach to quantitatively measure muscle perfusion of lower extremity is needed to aid the diagnosis and treatment of peripheral artery disease (PAD). PURPOSE: To verify the reproductivity of using blood oxygen level-dependent (BOLD) imaging to evaluate perfusion in lower extremities, and explore its correlation with walking performance in patients with PAD. STUDY TYPE: Prospective observational study. SUBJECTS: Seventeen patients with lower extremity PAD (mean age: 67 ± 6 years, 15 males) and eight older adults (controls). FIELD STRENGTH/SEQUENCE: Dynamic multi-echo gradient echo T2* weighted imaging at 3T. ASSESSMENT: Perfusion was analyzed in regions of interest according to muscle groups. Perfusion parameters were measured, such as minimum ischemia value (MIV), time to peak (TTP), and gradient during reactive hyperemia (Grad) by two independent users. Walking performance experiments including short physical performance battery (SPPB) and 6-minute walk were tested in patients. STATISTICAL TESTS: BOLD parameters were compared using Mann-Whitney U test and Kruskal-Wallis test. Relations between parameters and walking performance were assessed by Mann-Whitney U test and Spearman's correlation coefficient. RESULTS: Good to perfect agreement was demonstrated for all perfusion parameters of interuser reproducibility, and the interscan reproducibility of MIV, TTP, and Grad was good. The TTP of the patients was longer than that of the controls (87.85 ± 38.85 s vs. 36.54 ± 7.27 s), while the Grad of patients was smaller (0.16 ± 0.12 msec/s vs. 0.24 ± 0.11 msec/s). Among PAD patients, the MIV was significantly lower in the low SPPB subgroup (score 6-8) than in the high SPPB group (score 9-12), and the TTP was negatively correlated with 6-minute walk distance (ρ = -0.549). DATA CONCLUSION: BOLD imaging method had overall good reproducibility for the perfusion assessment of calf muscles. The perfusion parameters were different between PAD patients and controls, and were correlated with lower extremity function. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Midterm Results of a Surgeon-Modified Device to Preserve the Flow of the Internal Iliac Artery During Endovascular Repair of Aneurysm: Single-Center Experiences.

BACKGROUND: During endovascular aneurysm repair (EVAR), commercial iliac branch devices (IBDs) have become an inescapable alternative for preserving antegrade internal iliac artery (IIA) blood flow. Due to the different morphological features of aneurysms, commercial IBDs may not be suitable for all patients. Reported experience with the implantation of the new surgeon-modified IBD (sm IBD) is limited. This investigation describes the indications, efficacy, and safety of the sm IBD. METHODS: Data from consecutive elective implantations of IBDs in patients between March 2011 and May 2021 in a single center were incorporated. The sm IBDs were indicated in patients with common iliac artery aneurysms (CIAAs) and with a challenging anatomy and in those patients with or without abdominal aortic aneurysm (AAA). RESULTS: Fifteen patients (15 male, mean age 67.6 ± 7.9 years) were included. Fifteen sm IBDs were implanted in 1 procedure (100%). Fourteen (93.3%) patients had simultaneous endovascular aneurysm repair (EVAR) and 1 (6.7%) patient previously had a bilateral CIAAs repair by EVAR. The mean common iliac artery (CIA) diameter was 36.6 ± 12.5 mm. Technical success was obtained in all patients (100%). The median operation time was 189.7 ± 78.6 min, with a median fluoroscopy time of 45.3 ± 15.9 min. Axillary artery access was used in 11 (73.3%) procedures. The mean total hospital stay was 5.6 ± 2.8 days, and the postoperative follow-up was 35.4 months (range 2-120). The estimated IIA bridge stent patency at 1 year after operation was 100% and 85.7% ± 13.2% 5 years postoperatively. One (6.7%) IIA branch was occluded, and this patient remained asymptomatic. One patient (6.7%) needed reintervention, and another (6.7%) patient had type II leakage, which is currently under close surveillance. CONCLUSIONS: Using an IBD to maintain the pelvic blood flow is an effective and feasible intravascular technique, especially for patients with an abnormal iliac artery anatomy. This novel technique has similar midterm procedural success rate compared to the use of commercial IBDs. Therefore, these devices are more suitable for patients with certain anatomic challenges and can be used as an alternative treatment.

Effect of Endovascular Treatment on Urinary Obstruction Caused by Iliac Artery Aneurysm: A Case Series and Review of the Literature.

BACKGROUND: Endovascular aneurysm repair is superior to open surgical repair (OSR) in multiple aspects and is the mainstay for noninflammatory iliac artery aneurysm (IAA) treatment. However, for noninflammatory IAAs with neighboring structures compressed, the experience of endovascular treatment is limited. This case series study aimed to describe the experience of endovascular aneurysm repair of noninflammatory IAAs with urinary obstruction and to review the limited reports in the literature. METHODS: From December 2012 to July 2020, we reported 7 cases of noninflammatory IAAs combined with urinary obstruction that was treated successfully with endovascular treatment. The literature on noninflammatory IAAs combined with urinary obstruction was reviewed using the online databases PubMed, Embase, and the Cochrane Library. RESULTS: Thirty nine articles were found in the literature. OSR accounted for 80% of the treatment options in previous publications, while only 20% of patients accepted endovascular treatment. Hydronephrosis remission was observed in all patients treated by OSR, while the endovascular treatment group lacked long-term follow-up. In our retrospective study containing 7 cases, no complications, reintervention, or mortality was observed, all stents were patent, and all symptoms were relieved after the operation. Diameter reduction of the aneurysms was observed in 6/7 cases and the average aneurysm reduction was -24.1 ± 15.8 mm (P = 0.0097). Urinary obstruction faded in 5/7 cases where aneurysm shrinking was found simultaneously. CONCLUSIONS: This case series and literature review on noninflammatory IAAs combined with urinary obstruction suggests that the diameter of the responsible aneurysm may be reduced after endovascular treatment, which may also alleviate symptoms of urinary obstruction caused by noninflammatory IAAs.

A Review on Gold Nanotriangles: Synthesis, Self-Assembly and Their Applications.

Gold nanoparticles (AuNPs) with interesting optical properties have attracted much attention in recent years. The synthesis and plasmonic properties of AuNPs with a controllable size and shape have been extensively investigated. Among these AuNPs, gold nanotriangles (AuNTs) exhibited unique optical and plasmonic properties due to their special triangular anisotropy. Indeed, AuNTs showed promising applications in optoelectronics, optical sensing, imaging and other fields. However, only few reviews about these applications have been reported. Herein, we comprehensively reviewed the synthesis and self-assembly of AuNTs and their applications in recent years. The preparation protocols of AuNTs are mainly categorized into chemical synthesis, biosynthesis and physical-stimulus-induced synthesis. The comparison between the advantages and disadvantages of various synthetic strategies are discussed. Furthermore, the specific surface modification of AuNTs and their self-assembly into different dimensional nano- or microstructures by various interparticle interactions are introduced. Based on the unique physical properties of AuNTs and their assemblies, the applications towards chemical biology and sensing were developed. Finally, the future development of AuNTs is prospected.

The interactions of ZDHHC5/GOLGA7 with SARS-CoV-2 spike (S) protein and their effects on S protein's subcellular localization, palmitoylation and pseudovirus entry.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein determines virus entry and the palmitoylation of S protein affects virus infection. An acyltransferase complex ZDHHC5/GOGAL7 that interacts with S protein was detected by affinity purification mass spectrometry (AP-MS). However, the palmitoylated cysteine residues of S protein, the effects of ZDHHC5 or GOLGA7 knockout on S protein's subcellular localization, palmitoylation, pseudovirus entry and the enzyme for depalmitoylation of S protein are not clear. METHODS: The palmitoylated cysteine residues of S protein were identified by acyl-biotin exchange (ABE) assays. The interactions between S protein and host proteins were analyzed by co-immunoprecipitation (co-IP) assays. Subcellular localizations of S protein and host proteins were analyzed by fluorescence microscopy. ZDHHC5 or GOGAL7 gene was edited by CRISPR-Cas9. The entry efficiencies of SARS-CoV-2 pseudovirus into A549 and Hela cells were analyzed by measuring the activity of Renilla luciferase. RESULTS: In this investigation, all ten cysteine residues in the endodomain of S protein were palmitoylated. The interaction of S protein with ZDHHC5 or GOLGA7 was confirmed. The interaction and colocalization of S protein with ZDHHC5 or GOLGA7 were independent of the ten cysteine residues in the endodomain of S protein. The interaction between S protein and ZDHHC5 was independent of the enzymatic activity and the PDZ-binding domain of ZDHHC5. Three cell lines HEK293T, A549 and Hela lacking ZDHHC5 or GOLGA7 were constructed. Furthermore, S proteins still interacted with one host protein in HEK293T cells lacking the other. ZDHHC5 or GOLGA7 knockout had no significant effect on S protein's subcellular localization or palmitoylation, but significantly decreased the entry efficiencies of SARS-CoV-2 pseudovirus into A549 and Hela cells, while varying degrees of entry efficiencies may be linked to the cell types. Additionally, the S protein interacted with the depalmitoylase APT2. CONCLUSIONS: ZDHHC5 and GOLGA7 played important roles in SARS-CoV-2 pseudovirus entry, but the reason why the two host proteins affected pseudovirus entry remains to be further explored. This study extends the knowledge about the interactions between SARS-CoV-2 S protein and host proteins and probably provides a reference for the corresponding antiviral methods.

Infrapopliteal endovascular intervention and the angiosome concept: intraoperative real-time assessment of foot regions' blood volume guides and improves direct revascularization.

OBJECTIVE: There is no consensus for determining which vessel should be revascularized in patients with multiple diseased infrapopliteal arteries. The angiosome concept may guide a more efficient targeted direct revascularization. Therefore, we conducted a study to assess whether the regional evaluation of foot blood volume may guide direct revascularization (DR) and if it will lead to better perfusion improvement than indirect revascularization (IR). METHODS: We performed a prospective single-center observational cohort study in patients treated in the Department of Vascular Surgery of Peking Union Medical College Hospital from November 2016 to April 2019. Twenty-seven patients treated with endovascular intervention were included. The intraoperative parenchymal blood volume of different foot regions was obtained for each patient using C-arm CT before and after intervention. RESULTS: The intervention procedure significantly increased the overall blood volume (48.95 versus 81.97 ml/1000 ml, p = 0.002). Patients with direct revascularization had a 197% blood volume increase while patients with indirect revascularization had a 39% increase (p = 0.028). The preoperative blood volume was higher in patients with mild symptoms than in patients with severe symptoms (58.20 versus 30.45 ml/1000 ml, p = 0.039). However, in regard to postoperative blood volume, no significant difference was discovered between these two groups (75.05 versus 95.01 ml/1000 ml, p = 0.275). CONCLUSION: Based on quantitative measurements, we conclude that overall blood volume can rise significantly after the intervention. Revascularizing the supplying vessel of the ischemic area directly will result in better perfusion improvement than restoring blood supply through the collateral circulation. Preoperative blood volume is associated with preoperative symptoms. KEY POINTS: • Flat panel detector CT can obtain intraoperative perfusion status and guide treatment in endovascular intervention. • Revascularizing the supplying vessel of the ischemic area directly will result in better perfusion improvement than restoring the blood supply through the collateral circulation. • Patients with severer clinical manifestations have lower blood volumes.

Techniques to characterize dynamics in biomaterials microenvironments: XPCS and microrheology of alginate/PEO-PPO-PEO hydrogels.

Many recent studies have highlighted the timescale for stress relaxation of biomaterials on the microscale as an important factor in regulating a number of cell-material interactions, including cell spreading, proliferation, and differentiation. Relevant timescales on the order of 0.1-100 s have been suggested by several studies. While such timescales are accessible through conventional mechanical rheology, several biomaterials have heterogeneous structures, and stress relaxation mechanisms of the bulk material may not correspond to that experienced in the cellular microenvironment. Here we employ X-ray photon correlation spectroscopy (XPCS) to explore the temperature-dependent dynamics, relaxation time, and microrheology of multicomponent hydrogels comprising of commercial poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer F127 and alginate. Previous studies on this system have shown thermoreversible behavior in the bulk oscillatory shear rheology. At physiological temperatures, bulk rheology of these samples shows behavior characteristic of a soft solid, with G' > G'' and no crossover between G' and G'' over the measurable frequency range, indicating a relaxation time >125 s. By contrast, XPCS-based microrheology shows viscoelastic behavior at low frequencies, and XPCS-derived correlation functions show relaxation times ranging from 10-45 s on smaller length scales. Thus, we are able to use XPCS to effectively probe the viscoelasticity and relaxation behavior within the material microenvironments.

One-year outcomes of drug-coated balloon treatment for long femoropopliteal lesions: a multicentre cohort and real-world study.

BACKGROUND: Drug-coated balloons (DCBs) have shown superiority in the endovascular treatment of short femoropopliteal artery disease. Few studies have focused on outcomes in long lesions. This study aimed to evaluate the safety and effectiveness of Orchid® DCBs in long lesions over 1 year of follow-up. METHODS: This study is a multicentre cohort and real-world study. The patients had lesions longer than or equal to 150 mm of the femoropopliteal artery and were revascularized with DCBs. The primary endpoints were primary patency, freedom from clinically driven target lesion revascularization (TLR) at 12 months and major adverse events (all-cause death and major target limb amputation). The secondary endpoints were the changes in Rutherford classification and the ankle brachial index (ABI). RESULTS: One hundred fifteen lesions in 109 patients (mean age 67 ± 11 years, male proportion 71.6%) were included in this study. The mean lesion length was 252.3 ± 55.4 mm, and 78.3% of the lesions were chronic total occlusion (CTO). Primary patency by Kaplan-Meier estimation was 98.1% at 6 months and 82.1% at 12 months. The rate of freedom from TLR by Kaplan-Meier estimation was 88.4% through 12 months. There were no procedure- or device-related deaths through 12 months. The rate of all-cause death was 2.8%. Cox regression analysis suggested that renal failure and critical limb ischaemia (CLI) were statistically significant predictors of the primary patency endpoint. CONCLUSION: In our real-world study, DCBs were safe and effective when used in long femoropopliteal lesions, and the primary patency rate at 12 months by Kaplan-Meier estimation was 82.1%.

[Latest Progresses in Surgical Treatment of Median Arcuate Ligament Syndrome].

Median arcuate ligament syndrome(MALS)is compression of the celiac trunk by the median arcuate ligament.Median arcuate ligament release is the corner stone for the surgical treatment of MALS.Open surgery,laparoscopic surgery,and robot-assisted surgery have been developed,among which laparoscopic surgery has been proposed as the preferred approach in view of its minimal trauma and short hospital stay.Auxiliary celiac plexus neurolysis could further alleviate the patient's discomfort.Moreover,vascular reconstitution is of vital importance in the case of persistent stenosis in the celiac artery despite of median arcuate ligament decompression.Vascular reconstruction has satisfactory long-term patency rate,while endovascular treatment is less invasive.This article aims to summarize the consensuses and advances and shed light on the surgical treatment of MALS.

Identification of tissue-specific and cold-responsive lncRNAs in Medicago truncatula by high-throughput RNA sequencing.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in the regulation of plant responses to environmental stress by acting as essential regulators of gene expression. However, whether and how lncRNAs are involved in cold acclimation-dependent freezing tolerance in plants remains largely unknown. Medicago truncatula is a prominent model for studies of legume genomics, and distinguished by its cold-acclimation characteristics. To determine the roles of lncRNAs in plant cold stress response, we conducted genome-wide high-throughput sequencing in the legume model plant M. truncatula. RESULTS: RNA-seq data were generated from twelve samples for the four treatments, i.e., non-cold treated leaves and roots, cold-treated leaves and roots of M. truncatula Jemalong A17 seedlings. A total of 1204 million raw reads were generated. Of them, 1150 million filtered reads after quality control (QC) were subjected to downstream analysis. A large number of 24,368 unique lncRNAs were identified from the twelve samples. Among these lncRNAs, 983 and 1288 were responsive to cold treatment in the leaves and roots, respectively. We further found that the intronic-lncRNAs were most sensitive to the cold treatment. The cold-responsive lncRNAs were unevenly distributed across the eight chromosomes in M. truncatula seedlings with obvious preferences for locations. Further analyses revealed that the cold-responsive lncRNAs differed between leaves and roots. The putative target genes of the lncRNAs were predicted to mainly involve the processes of protein translation, transport, metabolism and nucleic acid transcription. Furthermore, the networks of a tandem array of CBF/DREB1 genes that were reported to be located in a major freezing tolerance QTL region on chromosome 6 and their related lncRNAs were dissected based on their gene expression and chromosome location. CONCLUSIONS: We identified a comprehensive set of lncRNAs that were responsive to cold treatment in M. truncatula seedlings, and discovered tissue-specific cold-responsive lncRNAs in leaves and roots. We further dissected potential regulatory networks of CBF Intergenic RNA (MtCIR1) and MtCBFs that play critical roles in response and adaptation of M. truncatula to cold stress.

Targeting Multiple Binding Sites on Cholera Toxin B with Glycomimetic Polymers Promotes the Formation of Protein-Polymer Aggregates.

The canonical binding site on the B subunit of cholera toxin (CTB) binds to GM1 gangliosides on host cells. However, the recently discovered noncanonical binding site on CTB with affinity for fucosylated molecules has raised the possibility that both sites can be involved in initiating intoxication. Previously, we showed that blocking CTB binding to human and murine small intestine epithelial cells can be increased by simultaneously targeting both binding sites with multivalent norbornene-based glycopolymers [ACS Infect. Dis. 2020, 6, 5, 1192-1203]. However, the mechanistic origin of the increased blocking efficacy was unclear. Herein, we observed that mixing CTB pentamers and glycopolymers that display fucose and galactose sugars results in the formation of large aggregates, which further inhibits binding of CTB to human granulocytes. Dynamic light scattering analysis, small-angle X-ray scattering analysis, transmission electron microscopy, and turbidimetric assays revealed that the facial directionality of CTB promotes interchain cross-linking, which in turn leads to self-assembly of protein-polymer networks. This cross-linking-induced self-assembly occurs only when the glycopolymer system contains both galactose and fucose. In an assay of the glycopolymer's ability to block CTB binding to human granulocytes, we observed a direct correlation between IC50 and self-assembly size. The aggregation mechanism of inhibition proposed herein has potential utility for the development of low-cost macromolecular clinical therapeutics for cholera that do not have exotic architectures and do not require complex synthetic sequences.

One-year results of drug-coated balloons for long and occlusive Femoropopliteal artery disease: a single-arm trial.

BACKGROUND: The performance of drug-coated balloons (DCBs) in femoropopliteal interventions has been proven through randomized trials in short lesions and lesions with relatively low proportion of occlusions. There is limited evidence of DCBs in long or occlusive lesions. This study is to investigate the efficacy of the paclitaxel-coated balloon for treatment of long and occlusive femoropopliteal arterial lesions. METHODS: A single-arm trial including 44 femoropopliteal lesions (chronic total occlusion (CTO) plus > 10 cm) treated with DCBs was performed to collect data of average 1-year follow-up. Endpoints contain primary patency, target lesion revascularization (TLR), amelioration of the Rutherford classification, change of ankle brachial index (ABI) and major adverse events. RESULTS: Technical success is 97.7% while device success is 100%. Mean lesion length was 186 ± 86.3 cm. Stent implantation was performed in 13.6%. Cumulative probability of primary patency was 78.8% ± 6.8% at 1 year while that of freedom from TLR was 91.4% ± 4.9%. Rutherford classification improved from average 3.3 ± 1.0 to 2.1 ± 1.4 (p < 0.001) at follow-up with a 72.7% amelioration rate. Ankle-branchial index changed from 0.33 ± 0.40 to 0.67 ± 0.37 (p = 0.002). No major adverse event was observed. CONCLUSION: These results suggest that it is safe and effective to treat long and totally occlusive femoropopliteal artery disease with DCBs. Further studies are demanded to confirm these results.

Long-term outcomes of conservative treatment and endovascular treatment in patients with symptomatic spontaneous isolated superior mesenteric artery dissection: a single-center experience.

BACKGROUND: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder, and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD. METHODS: Forty-two consecutive SISMAD patients who were admitted to a single center between October 2009 and May 2018 were enrolled in this study. Based on their symptoms, 15 had conservative treatment, and 27 had endovascular treatment. The baseline characteristics, treatments, and follow-up results of the conservative group and endovascular group were analysed. RESULTS: The rates of symptom relief were 93.3% in the conservative group and 96.3% in the endovascular group. The procedure-related complications in the endovascular group included one case of pseudoaneurysm formation in the left brachial artery. During the follow-up period (median 28.5 months), a higher proportion of patients in the conservative group had symptom recurrence (42.9% in the conservative group versus 4.8% in the endovascular group, p < 0.001). Four patients in the conservative group and one patient in the endovascular group had additional endovascular intervention during follow-up. Compared with the conservative group, patients in the endovascular group had statistically significantly longer symptom-free survival (p = 0.014) and a higher rate of superior mesenteric artery (SMA) remodeling (p < 0.001). CONCLUSIONS: For symptomatic SISMAD, endovascularly treated patients had a lower rate of symptom recurrence and a higher rate of SMA remodeling in the long term. Prospective, multi-center studies are needed to confirm the long-term outcomes of both treatments.

Emulsions Stabilized by Inorganic Nanoclays and Surfactants: Stability, Viscosity, and Implications for Applications.

Pickering emulsions, or emulsions with solid particles at the interface, have attracted significant interest in Enhanced Oil Recovery (EOR) processes, cosmetics, and drug delivery systems due to their ability to resist coalescence. Here, a synthetic clay nanoparticle, laponite®, is utilized to create oil-in-water (o/w) emulsions, and the addition of small-molecule surfactants induces a more stable emulsion. In this study, the stability of laponite® Pickering emulsions with and without the surfactants (dodecyltrimethylammonium bromide (DTAB), Pluronic F68 (F68), and sodium dodecyl sulfate (SDS) is investigated using dynamic light scattering (DLS), ζ-potential, optical microscopy, and rheology. With laponite® and no added surfactants, the DLS and ζ-potential results show formation of emulsion droplets with a diameter of 3 µm and a ζ-potential of -90 mV. With the addition of surfactants, both the droplet diameter and ζ-potential increase, suggesting adsorption of surfactants on the surface of laponite® particle. Optical microscopy suggests that the Pickering emulsion without surfactant undergoes flocculation, while the emulsion becomes stable to coalescence and creaming with addition of surfactants due to formation of a network structure. Regardless of the formation of network structure, the laponite®-F68 emulsion rheologically behaves as a Newtonian fluid, while the laponite®-SDS and laponite®-DTAB emulsions display shear thinning behavior. The difference in the rheological behavior can be attributed to the weak adsorption of F68 on laponite® and electrostatic interactions between laponite® and charged surfactants at oil-water interface.

Regulatory mechanism of vulnerability disclosure behavior considering security crowd-testing: An evolutionary game analysis.

The security crowd-testing regulatory mechanism is a vital means to promote collaborative vulnerability disclosure. However, existing regulatory mechanisms have not considered multi-agent responsibility boundaries and stakeholders' conflicts of interest, leading to their dysfunction. Distinguishing from previous research on the motivations and constraints of ethical hacks' vulnerability disclosure behaviors from a legal perspective, this paper constructs an evolutionary game model of SRCs, security researchers, and the government from a managerial perspective to propose regulatory mechanisms promoting tripartite collaborative vulnerability disclosure. The results show that the higher the initial willingness of the three parties to choose the collaborative strategy, the faster the system evolves into a stable state. Regarding the government's incentive mechanism, establishing reward and punishment mechanisms based on effective thresholds is essential. However, it is worth noting that the government has an incentive to adopt such mechanisms only if it receives sufficient regulatory benefits. To further facilitate collaborative disclosure, Security Response Centers (SRC) should establish incentive mechanisms including punishment and trust mechanisms. Additionally, publicity and training mechanisms for security researchers should be introduced to reduce their revenue from illegal participation, which promotes the healthy development of security crowd-testing. These findings contribute to improving SRCs' service quality, guiding security researchers' legal participation, enhancing the government's regulatory effectiveness, and ultimately establishing a multi-party collaborative vulnerability disclosure system.

New insights into the controlling factors of nitrate spatiotemporal characteristics in groundwater of Dagu aquifer in Qingdao, China.

Identifying spatiotemporal variation of groundwater NO3-N and its primary controlling factors are vital for groundwater protection. This study, under the data scarce conditions and based on time series monitoring data in Dagu aquifer, applied methods including hydrochemical ion ratio, multiple linear regression, support vector regression and grey relational analysis and dedicated to revealing primary controlling factors of temporal variation patterns of groundwater NO3-N. The results showed that agricultural and manure fertilizer are the main sources of NO3-N in north and central area (vegetable farming area), and that domestic sewage discharge and manure fertilizer are the main sources of NO3-N in south area (residential and grain planting area). In addition, results identified the dominant influencing factors of variation of NO3-N in different regions, with human wastewater discharge, nitrogen load amount and water-table depth being the dominant factors of variations of NO3-N in north area, human wastewater discharge being the main factor of variations of NO3-N in central area, and irrigation water and human wastewater being the leading factors of variations of NO3-N in south area. Moreover, types of controlling factors can influence the seasonal variations of NO3-N. NO3-N in vegetable farming area that dominantly affected by fertilization generally shows higher concentration and larger variation range of concentration during summer and autumn than that during spring. NO3-N which mainly affected by human wastewater discharge and manure inputs shows minimal seasonal variation of mean concentration. NO3-N in grain area influenced by irrigation could show more significant variations during spring and autumn than that during summer. The conclusions can enhance understandings of major influencing factors on NO3-N variation in local aquifer. Importantly, the dominant roles of water-table depth and irrigation in NO3-N variation of N2 site (vegetable planting area) and S5 site (grain planting area), respectively, were highlighted.

The impact of regulatory mechanisms on vulnerability disclosure behavior during crowdsourcing cybersecurity testing.

There are various regulatory mechanisms to coordinate vulnerability disclosure behaviors during crowdsourcing cybersecurity testing. However, in the case of unclear regulatory effectiveness, enterprises cannot obtain sufficient vulnerability information, third-party crowdsourcing cybersecurity testing platforms fail to provide trusted services, and the government lacks strong credibility. We have constructed a tripartite evolutionary game model to analyze the evolutionary process of the equilibrium of {legal disclosure, active operation, strict regulation}, and the paper reveals the impact of three regulatory mechanisms. We find that these participants' positive behaviors are in a stable state. Higher initial willingness accelerates the speed of reaching the evolutionary stability of the system, and this equilibrium is satisfied only if the governmental regulatory benefits are sufficiently high. Regarding the punishment mechanism, increased punishment for enterprises causes them to adopt positive behaviors faster, while the opposite occurs for platforms; increased punishment for platforms drives both participants to adopt positive behaviors faster. Concerning the subsidy mechanism, increased subsidy to enterprises causes them to adopt legal disclosure behaviors faster, while platforms remain unresponsive; increased subsidy to platforms motivates both players to choose their own positive behaviors. In terms of the collaborative disclosure mechanism, excessive collaborative costs reduce the platforms' willingness to operate actively, which decreases the enterprises' incentives to disclose vulnerability legally. These findings guide the government to establish suitable mechanisms to regulate the participants' behavior and promote the healthy development of the cybersecurity crowdsourcing industry.

A learnable sampling method for scalable graph neural networks.

With the development of graph neural networks, how to handle large-scale graph data has become an increasingly important topic. Currently, most graph neural network models which can be extended to large-scale graphs are based on random sampling methods. However, the sampling process in these models is detached from the forward propagation of neural networks. Moreover, quite a few works design sampling based on statistical estimation methods for graph convolutional networks and the weights of message passing in GCNs nodes are fixed, making these sampling methods not scalable to message passing networks with variable weights, such as graph attention networks. Noting the end-to-end learning capability of neural networks, we propose a learnable sampling method. It solves the problem that random sampling operations cannot calculate gradients and samples nodes with an unfixed probability. In this way, the sampling process is dynamically combined with the forward propagation process of the features, allowing for better training of the networks. And it can be generalized to all message passing models. In addition, we apply the learnable sampling method to GNNs and propose two models. Our method can be flexibly combined with different graph neural network models and achieves excellent accuracy on benchmark datasets with large graphs. Meanwhile, loss function converges to smaller values at a faster rate during training than past methods.

Role of the Global Limb Anatomic Staging System in predicting outcomes of chronic limb-threatening ischemia in patients treated by drug-coated balloons.

Background: The Global Limb Anatomic Staging System (GLASS) was proposed to assess the procedural complexity and technical failure rate and stratify the anatomic pattern of chronic limb-threatening ischemia (CLTI). However, more evidence is needed to validate the GLASS in staging outcomes after endovascular therapy in patients with CLTI treated with drug-coated balloons (DCBs). This study aims to evaluate the role of the GLASS in predicting outcomes of CLTI patients treated with DCBs. Methods: This multicenter, retrospective cohort study enrolled patients with CLTI treated with DCBs from July 2016 to June 2019. GLASS stages were assigned for every limb. The limb-based patency (LBP) rate, clinically driven target lesion revascularization (CD-TLR) rate, clinical improvement, and safety endpoints were analyzed and compared across the GLASS stages over 12 months of follow-up. Risk factors for the loss of LBP were identified using Cox regression analysis. Results: A total of 90 limbs were enrolled, with 55 (61.1%) having isolated femoropopliteal lesions and 35 (38.9%) having femoropopliteal and infrapopliteal lesions. Of the limbs, 17 (18.9%), 12 (13.3%), and 61 (67.8%) were assigned to GLASS stages I, II, and III, respectively. The Kaplan-Meier estimate of the 12-month LBP was 65.4%, and no difference was found among the different stages (stage I 81.1%; stage II 85.2%; stage III 54.4%; P=0.080). The LBP was lower in stage III than in stages I and II combined (stage I and II 83.5%; stage III 54.4%; P=0.027). Similar results were found for the freedom from CD-TLR rates among the different stages. The ankle-brachial index values improved from 0.42±0.29 to 0.78±0.35 at follow-up (P<0.001). The rates of mortality, any amputation, and major amputation were similar among the groups. GLASS stage III and coronary heart disease were identified as independent risk factors for the loss of LBP at 12 months. Conclusions: The 1-year LBP and freedom from CD-TLR rates were lower in GLASS stage III than in stages I and II. The GLASS classification could predict the outcomes of CLTI patients with femoropopliteal lesions treated with DCB.