Building Confidential and Efficient Query Services in the Cloud with RASP Data Perturbation

With the wide deployment of public cloud computing infrastructures, using clouds to host data query services has become an appealing solution for the advantages on scalability and cost-saving. However, some data might be sensitive that the data owner does not want to move to the cloud unless the data confidentiality and query privacy are guaranteed. On the other hand, a secured query service should still provide efficient query processing and significantly reduce the in-house workload to fully realize the benefits of cloud computing. We propose the RASP data perturbation method to provide secure and efficient range query and kNN query services for protected data in the cloud. The RASP data perturbation method combines order preserving encryption, dimensionality expansion, random noise injection, and random projection, to provide strong resilience to attacks on the perturbed data and queries. It also preserves multidimensional ranges, which allows existing indexing techniques to be applied to speedup range query processing. The kNN-R algorithm is designed to work with the RASP range query algorithm to process the kNN queries. We have carefully analyzed the attacks on data and queries under a precisely defined threat model and realistic security assumptions. Extensive experiments have been conducted to show the advantages of this approach on efficiency and security.Comment: 18 pages, to appear in IEEE TKDE, accepted in December 201

Virtual screening–based discovery of AI-2 quorum sensing inhibitors that interact with an allosteric hydrophobic site of LsrK and their functional evaluation

Introduction: Quorum sensing (QS) is a bacterial intracellular and intercellular communication system that regulates virulence factor production, biofilm formation, and antibiotic sensitivity. Quorum-sensing inhibitors (QSIs) are a novel class of antibiotics that can effectively combat antibiotic resistance. Autoinducer-2 (AI-2) is a universal signaling molecule that mediates inter- and intraspecies QS systems among different bacteria. Furthermore, LsrK plays an important role in regulating the activity and stability of the intracellular AI-2 signaling pathway. Thus, LsrK is considered an important target for the development of QSIs.Methods: We designed a workflow integrating molecular dynamic (MD) simulations, virtual screening, LsrK inhibition assays, cell-based AI-2-mediated QS interference assays, and surface plasmon resonance (SPR)-based protein affinity assays to screen for potential LsrK kinase inhibitors.Results: MD simulation results of the LsrK/ATP complex revealed hydrogen bonds and salt bridge formation among four key residues, namely, Lys 431, Tyr 341, Arg 319, and Arg 322, which are critical for the binding of ATP to LsrK. Furthermore, MD simulation results indicated that the ATP-binding site has an allosteric pocket that can become larger and be occupied by small molecule compounds. Based on these MD simulation results, a constraint of forming at least one hydrogen bond with Arg 319, Arg 322, Lys 431, or Tyr 341 residues was introduced when performing virtual screening using Glide’s virtual screening workflow (VSW). In the meantime, compounds with hydrophobic group likely to interact with the allosteric hydrophobic pocket are preferred when performing visual inspection. Seventy-four compounds were selected for the wet laboratory assays based on virtual screening and the absorption, distribution, metabolism, and excretion (ADME) properties of these compounds. LsrK inhibition assays revealed 12 compounds inhibiting LsrK by more than 60% at a 200 μM concentration; four of these (Y205-6768, D135-0149, 3284–1358, and N025-0038) had IC50 values below 50 μM and were confirmed as ATP-competitive inhibitors. Six of these 12 LsrK inhibitors exhibited high AI-2 QS inhibition, of which, Y205-6768 had the highest activity with IC50 = 11.28 ± 0.70 μM. The SPR assay verified that compounds Y205-6768 and N025-0038 specifically bound to LsrK. MD simulation analysis of the docking complexes of the four active compounds with LsrK further confirmed the importance of forming hydrogen bonds and salt bridges with key basic amino acid residues including Lys 431, Tyr 341, Arg 319, and Arg 322 and filling the allosteric hydrophobic pocket next to the purine-binding site of LsrK.Discussion: Our study clarified for the first time that there is an allosteric site near the ATP-binding site of Lsrk and that it enriches the structure–activity relationship information of Lsrk inhibitors. The four identified compounds showed novel structures, low molecular weights, high activities, and novel LsrK binding modes, rendering them suitable for further optimization for effective AI-2 QSIs. Our work provides a valuable reference for the discovery of QSIs that do not inhibit bacterial growth, thereby avoiding the emergence of drug resistance

Association between maternal blood lipids levels during pregnancy and risk of small-for-gestational-age infants.

Dyslipidemia in pregnancy are associated with risk of adverse outcomes. As an adverse pregnancy outcome, small-for-gestational-age has been extensively studied in Western countries. However, similar studies have rarely been conducted in Asian countries. Data were derived from 5695 pairs of non-diabetic mothers and neonates between 1 Jan 2014 and 31 Dec 2014. 5.6% neonates in our study were SGA. Serum samples were collected during second and third trimesters for evaluation on fasting lipids levels. The present study intended to explore the associations between maternal lipid profile and small-for-gestational-age neonates. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and adjusted via logistic regression analysis. After adjustments for confounders, third-trimester total cholesterol levels were associated with a decreased risk for small-for-gestational-age (aOR = 0.622, 95% CI 0.458-0.848, P = 0.002), and third-trimester high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were associated with an increased risk for small-for-gestational-age (aOR = 1.955, 95% CI 1.465-2.578, P < 0.001; aOR = 1.403, 95% CI 1.014-1.944, P = 0.041).In the highest gestational weight gain strata, especially the third-trimester, the effect of high-density lipoprotein cholesterol levels on the risk for small-for-gestational-age is larger. High high-density lipoprotein cholesterol level during third trimester could be considered as indicators of a high-risk of small-for-gestational-age, regardless of gestational weight gain

Serum perfluoroalkyl substances in residents following long-term drinking water contamination from firefighting foam in Ronneby, Sweden.

BACKGROUND: In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport. OBJECTIVES: To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined. METHODS: Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants. RESULTS: The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005-2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60. DISCUSSION: The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure

Seizing the window of opportunity to mitigate the impact of climate change on the health of Chinese residents

The health threats posed by climate change in China are increasing rapidly. Each province faces different health risks. Without a timely and adequate response, climate change will impact lives and livelihoods at an accelerated rate and even prevent the achievement of the Healthy and Beautiful China initiatives. The 2021 China Report of the Lancet Countdown on Health and Climate Change is the first annual update of China’s Report of the Lancet Countdown. It comprehensively assesses the impact of climate change on the health of Chinese households and the measures China has taken. Invited by the Lancet committee, Tsinghua University led the writing of the report and cooperated with 25 relevant institutions in and outside of China. The report includes 25 indicators within five major areas (climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement) and a policy brief. This 2021 China policy brief contains the most urgent and relevant indicators focusing on provincial data: The increasing health risks of climate change in China; mixed progress in responding to climate change. In 2020, the heatwave exposures per person in China increased by 4.51 d compared with the 1986–2005 average, resulting in an estimated 92% increase in heatwave-related deaths. The resulting economic cost of the estimated 14500 heatwave-related deaths in 2020 is US$176 million. Increased temperatures also caused a potential 31.5 billion h in lost work time in 2020, which is equivalent to 1.3% of the work hours of the total national workforce, with resulting economic losses estimated at 1.4% of China’s annual gross domestic product. For adaptation efforts, there has been steady progress in local adaptation planning and assessment in 2020, urban green space growth in 2020, and health emergency management in 2019. 12 of 30 provinces reported that they have completed, or were developing, provincial health adaptation plans. Urban green space, which is an important heat adaptation measure, has increased in 18 of 31 provinces in the past decade, and the capacity of China’s health emergency management increased in almost all provinces from 2018 to 2019. As a result of China’s persistent efforts to clean its energy structure and control air pollution, the premature deaths due to exposure to ambient particulate matter of 2.5 μm or less (PM2.5) and the resulting costs continue to decline. However, 98% of China’s cities still have annual average PM2.5 concentrations that are more than the WHO guideline standard of 10 μg/m3. It provides policymakers and the public with up-to-date information on China’s response to climate change and improvements in health outcomes and makes the following policy recommendations. (1) Promote systematic thinking in the related departments and strengthen multi-departmental cooperation. Sectors related to climate and development in China should incorporate health perspectives into their policymaking and actions, demonstrating WHO’s and President Xi Jinping’s so-called health-in-all-policies principle. (2) Include clear goals and timelines for climate-related health impact assessments and health adaptation plans at both the national and the regional levels in the National Climate Change Adaptation Strategy for 2035. (3) Strengthen China’s climate mitigation actions and ensure that health is included in China’s pathway to carbon neutrality. By promoting investments in zero-carbon technologies and reducing fossil fuel subsidies, the current rebounding trend in carbon emissions will be reversed and lead to a healthy, low-carbon future. (4) Increase awareness of the linkages between climate change and health at all levels. Health professionals, the academic community, and traditional and new media should raise the awareness of the public and policymakers on the important linkages between climate change and health.</p