Directed Greybox Fuzzing with Stepwise Constraint Focusing

Dynamic data flow analysis has been widely used to guide greybox fuzzing. However, traditional dynamic data flow analysis tends to go astray in the massive path tracking and requires to process a large volume of data, resulting in low efficiency in reaching the target location. In this paper, we propose a directed greybox fuzzer based on dynamic constraint filtering and focusing (CONFF). First, all path constraints are tracked, and those with high priority are filtered as the next solution targets. Next, focusing on a single path constraint to be satisfied, we obtain its data condition and probe the mapping relationship between it and the input bytes through multi-byte mapping and single-byte mapping. Finally, various mutation strategies are utilized to solve the path constraint currently focused on, and the target location of the program is gradually approached through path selection. The CONFF fuzzer can reach a specific location faster in the target program, thus efficiently triggering the crash. We designed and implemented a prototype of the CONFF fuzzer and evaluated it with the LAVA-1 dataset and some real-world vulnerabilities. The results show that the CONFF fuzzer can reproduce crashes on the LAVA-1 dataset and most of the real-world vulnerabilities. For most vulnerabilities, the CONFF fuzzer reproduced the crashes with significantly reduced time compared to state-of-the-art fuzzers. On average, the CONFF fuzzer was 23.7x faster than the state-of-the-art code coverage-based fuzzer Angora and 27.3x faster than the classical directed greybox fuzzer AFLGo

Submarine erosional troughs in the northern South China Sea: Evidence for Early Miocene deepwater circulation and paleoceanographic change

The paleoceanography of the South China Sea (SCS) is poorly understood, although recent cruises and an ODP expedition (Leg 184) have provided a useful general framework. Here we report previously unrecognized multi-km scale sedimentary structures consisting of coupled ridges and troughs within the Early Miocene strata, using high-resolution 3D seismic data from the northern SCS margin. The troughs are interpreted as linear and/or arcuate erosional features which truncate the underlying strata. They range in orientation from E-W in the southern part of the study area to nearly NE-SW in the northwestern part of the study area. The spacing of erosional troughs varies from less than 0.1 km in the southern part to more than 3 km in the northern part, and they are about 50 to 1500 m in width, with a relief of 10 to 90 m. The erosional troughs are parallel to the regional strike of the Early Miocene slope of the northern SCS. From their internal geometry, context, regional distribution and most importantly their orientation relative to the paleo-slope gradient at the time of their formation, it is argued that they formed due to the action of bottom currents linked to the broader paleo-circulation regime in the basin. We infer that the paleo-bottom currents intruding from the Pacific flowed along the northern SCS slope, resulting in the occurrence of localized erosional troughs as deep water masses impinged on and interacted with the sea floor topography. This study provides new insights into the Early Miocene paleoceanography of the SCS and demonstrates the utility of 3D seismic data to enhance our understanding of paleo-bottom current circulation regimes

The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model

Background and Objective. TWIK-related acid-sensitive potassium channel 1 (TASK-1) is closely related to respiratory central control and neuronal injury. We investigated the effect of MV on TASK-1’s functions and explored the mechanism using a rat model. Methods. Male Sprague-Dawley rats were randomized to three groups: (1) high tidal volume (HVt): MV for four hours with Vt at 10 mL/kg; (2) low Vt (LVt): MV for four hours with Vt at 5 mL/kg; (3) basal (BAS): anesthetized and unventilated animals. We measured lung histology and plasma and brain levels of proteins (IL-6, TNF-α, and S-100B) and determined TASK-1 levels in rat brainstems as a marker of respiratory centre activity. Results. The LISs (lung injury scores) were significantly higher in the HVt group. Brain inflammatory cytokines levels were different to those in serum. TASK-1 levels were significantly lower in the MV groups (P=0.002) and the HVt group tended to have a lower level of TASK-1 than the LVt group. Conclusion. MV causes not only lung injury, but also brain injury. MV affects the regulation of the respiratory centre, perhaps causing damage to it. Inflammation is probably not the main mechanism of ventilator-related brain injury

Effects of Non-invasive Positive Pressure Ventilation on Sleep of Patients in Respiratory Intensive Care Unit Assessed by Overnight Polysomnography

BackgroundSleep disorders are commonin RICU patients, with mechanical ventilation as one of the important factors leading to sleep disorders in RICU patients. Previous studies have mainly focused on the effect of invasive positive pressure ventilation (IPPV) on sleep in RICU patients, but there is no study on the effect of polysomnography on sleep in RICU patients with non-invasive positive pressure ventilation (NIPPV) .ObjectiveTo evaluate patients' sleep disorders and the effect of NIPPV on sleep in patients in respiratory intensive care unitsby overnight polysomnography.MethodsThe clinical data of 31 patients who underwent overnight polysomnography in the Department of Respiratory and Critical Care Medicine of Peking University First Hospital from May 2012 to August 2021 were retrospectively analyzed. The clinical data〔sex, age, height, body mass index, APACHEⅡscore, underlying diseases, main diagnosis, white blood cell count, hemoglobin, serum albumin, high-sensitivity C-reactive protein (hs-CRP) , arterial blood gas analysis, respiratory failure classification, total length of hospital stay, length of stay in RICU, RICU stay in the past 6 months, death during hospitalization〕, sleep characteristics 〔respiratory events: apnea-hypopnea index (AHI) , respiratory disturbance index (RDI) , total detection time, total sleep time, sleep latency, sleep efficiency, sleep stage: time, latency and proportion of REM and NREM, pulse oxygen: minimum pulse oxygen, average pulse oxygen during sleep, heart rate: minimum heart rate, maximum heart rate〕 of patients were collected. The patients were divided into NIPPV group and control group (non-NIPPV group) according to whether NIPPV treatment was performed during overnight polysomnography, and the clinical data and sleep characteristics of the two groups were compared.ResultsThere were 15 cases in the NIPPV group and 16 cases in the control group. Compared with the control group, the total sleep time (P=0.028) , REM sleep time (P=0.034) , NREM time (P=0.003) and N2 sleep time (P=0.003) were shortened in the NIPPV group, while the sleep efficiency (P=0.038) decreased, and the average heart rate increased (P=0.028) .ConclusionSleep disturbance is a common problem in RICU patients, and NIPPV patients are more likely to lead to decreased total sleep time, decreased REM sleep, and decreased sleep efficiency. It is recommended that RICU patients be routinely assessed with overnight polysomnography and given appropriate intervention to conduct appropriate interventions

Treg/Th17 Cells in Chronic Lung Inflammation Models Exposed to PM2.5 in Beijing China

CPCI-S(ISTP)4407A-407A14

CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2

Background/Aims: Pancreatic cancer cells (PCC) is one of the most risky cancers and gemcitabine (GEM) is the standard first-line drug for treating PCC. The PCC will develop drug resistance to GEM after a period of treatment. However, the detailed molecular mechanism of pathogenesis and drug resistance remains unresolved. Methods: we employed qRT-PCR and western blot to examine the expression level of CXCR4, let-7a and HMGA2. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness. The expression level of epithelial marker E-cadherin and mesenthymal marker N-cadherin was detected by western blot. The apoptosis was determined using annexin V-FITC/PI apoptosis detection kit by flow cytometry. Results: we first proved that CXCR4 negatively regulated let-7a in PCC. Next, let-7a was confirmed to play crucial role in tumorigenesis, metastasis and drug resistance of pancreatic cancer cells Bxpc-3 and Panc-1 in vitro and in vivo. Finally, we identified HMGA2 as important downsteam target of let-7a in PCC and overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of GEM inhibited by let-7a. Conlusion: Taken together, we show an important signaling pathway involved in pathogenesis and drug resistance of PCC, thereby providing deeper insight into molecular mechanism by which CXCR4/let-7a regulates tumorigenesis and drug resistance of PCC. These findings will help us develop new strategies for diagnosis and treatment of PCC

Impact of interstitial lung disease on mortality in ANCA-associated vasculitis: A systematic literature review and meta-analysis

Several retrospectivee described the association of interstitial lung disease (ILD) and ANCA-associated vasculitis (AAV). However, the relationship between the ILD and mortality in AAV patients have not been established so far. This study aims to estimate the relevance of AAV-associated-ILD (AAV-ILD) and mortality risk by conducting a systematic review and meta-analysis.A comprehensive systematic review was conducted in accordance with the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses). PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies. Summary estimates were derived with a random-effects model and reported as risk ratio (RR), tested for publication bias and heterogeneity. Ten retrospective cohort studies were included, comprising 526 AAV-ILD patients enrolled from 1974 to 2018. Meta-analysis yielded a pooled RR of 2.90 (95% confidence interval 1.77–4.74) for death among those with AAV-ILD compared to control group. UIP pattern was associated with an even poorer prognosis in comparison to non-UIP pattern (RR 4.36, 95% confidence interval 1.14–16.78). Sensitivity analysis suggested that the meta-RR result was not skewed by a single dominant study. ILD might be associated with a higher mortality risk in AAV patients.</jats:p