Enhanced mast cell activation in mice deficient in the A2b adenosine receptor

Antigen-mediated cross-linking of IgE bound to mast cells via the high affinity receptor for IgE triggers a signaling cascade that results in the release of intracellular calcium stores, followed by an influx of extracellular calcium. The collective increase in intracellular calcium is critical to the release of the granular contents of the mast cell, which include the mediators of acute anaphylaxis. We show that the sensitivity of the mast cell to antigen-mediated degranulation through this pathway can be dramatically influenced by the A2b adenosine receptor. Loss of this Gs-coupled receptor on mouse bone marrow–derived mast cells results in decreased basal levels of cyclic AMP and an excessive influx of extracellular calcium through store-operated calcium channels following antigen activation. Mice lacking the A2b receptor display increased sensitivity to IgE-mediated anaphylaxis. Collectively, these findings show that the A2b adenosine receptor functions as a critical regulator of signaling pathways within the mast cell, which act in concert to limit the magnitude of mast cell responsiveness when antigen is encountered

Meet-in-the-Middle Preimage Attacks on Sponge-based Hashing

The Meet-in-the-Middle (MitM) attack has been widely applied to preimage attacks on Merkle-Damg{\aa}rd (MD) hashing. In this paper, we introduce a generic framework of the MitM attack on sponge-based hashing. We find certain bit conditions can significantly reduce the diffusion of the unknown bits and lead to longer MitM characteristics. To find good or optimal configurations of MitM attacks, e.g., the bit conditions, the neutral sets, and the matching points, we introduce the bit-level MILP-based automatic tools on Keccak, Ascon and Xoodyak. To reduce the scale of bit-level models and make them solvable in reasonable time, a series of properties of the targeted hashing are considered in the modelling, such as the linear structure and CP-kernel for Keccak, the Boolean expression of Sbox for Ascon. Finally, we give an improved 4-round preimage attack on Keccak-512/SHA3, and break a nearly 10 years’ cryptanalysis record. We also give the first preimage attacks on 3-/4-round Ascon-XOF and 3-round Xoodyak-XOF

Mind the TWEAKEY Schedule: Cryptanalysis on SKINNYe-64-256

Designing symmetric ciphers for particular applications becomes a hot topic. At EUROCRYPT 2020, Naito, Sasaki and Sugawara invented the threshold implementation friendly cipher SKINNYe-64-256 to meet the requirement of the authenticated encryption PFB_Plus. Soon, Thomas Peyrin pointed out that SKINNYe-64-256 may lose the security expectation due the new tweakey schedule. Although the security issue of SKINNYe-64-256 is still unclear, Naito et al. decided to introduce SKINNYe-64-256 v2 as a response. In this paper, we give a formal cryptanalysis on the new tweakey schedule of SKINNYe-64-256 and discover unexpected differential cancellations in the tweakey schedule. For example, we find the number of cancellations can be up to 8 within 30 consecutive rounds, which is significantly larger than the expected 3 cancellations. Moreover, we take our new discoveries into rectangle, MITM and impossible differential attacks, and adapt the corresponding automatic tools with new constraints from our discoveries. Finally, we find a 41-round related-tweakey rectangle attack on SKINNYe-64-256 and leave a security margin of 3 rounds only. As STK accepts arbitrary tweakey size, but SKINNY and SKINNYe-64-256 v2 only support up to 4n tweakey size. We introduce a new design of tweakey schedule for SKINNY-64 to further extend the supported tweakey size. We give a formal proof that our new tweakey schedule inherits the security requirement of STK and SKINNY. We also discuss possible ways to extend the tweakey size for SKINNY-128

Tree plantations displacing native forests: The nature and drivers of apparent forest recovery on former croplands in Southwestern China from 2000 to 2015

China is credited with undertaking some of the world's most ambitious policies to protect and restore forests, which could serve as a role model for other countries. However, the actual environmental consequences of these policies are poorly known. Here, we combine remote-sensing analysis with household interviews to assess the nature and drivers of land-cover change in southwestern China between 2000–2015, after China's major forest protection and reforestation policies came into effect. We found that while the region's gross tree cover grew by 32%, this increase was entirely due to the conversion of croplands to tree plantations, particularly monocultures. Native forests, in turn, suffered a net loss of 6.6%. Thus, instead of truly recovering forested landscapes and generating concomitant environmental benefits, the region's apparent forest recovery has effectively displaced native forests, including those that could have naturally regenerated on land freed up from agriculture. The pursuit of profit from agricultural or forestry production along with governmental encouragement and mobilization for certain land uses – including tree planting – were the dominant drivers of the observed land-cover change. An additional driver was the desire of many households to conform with the land-use decisions of their neighbors. We also found that households' lack of labor or financial resources, rather than any policy safeguards, was the primary constraint on further conversion of native forests. We conclude that to achieve genuine forest recovery along with the resulting environmental benefits, China's policies must more strongly protect existing native forests and facilitate native forest restoration. Natural regeneration, which thus far has been grossly neglected in China's forest policies, should be recognized as a legitimate means of forest restoration. In addition, social factors operating at the household level, notably the pursuit of profit and conformation to social norms, should be harnessed to promote better land-cover, biodiversity, and environmental outcomes. More generally, for China and other countries to succeed in recovering forests, policies must clearly distinguish between native forests and tree plantations

Meet-in-the-Middle Attacks Revisited: Key-recovery, Collision, and Preimage Attacks

At EUROCRYPT 2021, Bao et al. proposed an automatic method for systematically exploring the configuration space of meet-in-the-middle (MITM) preimage attacks. We further extend it into a constraint-based framework for finding exploitable MITM characteristics in the context of key-recovery and collision attacks by taking the subtle peculiarities of both scenarios into account. Moreover, to perform attacks based on MITM characteristics with nonlinear constrained neutral words, which have not been seen before, we present a procedure for deriving the solution spaces of neutral words without solving the corresponding nonlinear equations or increasing the overall time complexities of the attack. We apply our method to concrete symmetric-key primitives, including SKINNY, ForkSkinny, Romulus, Saturnin, Grostl, Whirlpool, and hashing modes with AES-256. As a result, we identify the first 23-round key-recovery attack on SKINNY-$n$-$3n$ and the first 24-round key-recovery attack on ForkSkinny-$n$-$3n$ in the single-key model. Moreover, improved (pseudo) preimage or collision attacks on round-reduced Whirlpool, Grostl, and hashing modes with AES-256 are obtained. In particular, employing the new representation of the AES key schedule due to Leurent and Pernot (EUROCRYPT 2021), we identify the first preimage attack on 10-round AES-256 hashing

Primary Clinical Evaluation of Photodynamic Therapy With Oral Leukoplakia in Chinese Patients

Background: Photodynamic therapy (PDT) has demonstrated promising results in the treatment of oral leukoplakia. This study evaluated the clinical efficacy and side effects of PDT in the treatment of Chinese patients with oral leukoplakia.Methods: Twenty-nine patients with oral leukoplakia were enrolled in this study, including patients with both homogenous and non-homogenous lesions and various dysplastic tissues. All patients received PDT using a 632 nm laser at 500 mW/cm2 power density at a dosage of 90–180 J/cm2 and with aminolevulinic acid (ALA) used as a photosensitizer. A fixing and restricting complex as well as high laser power density for PDT in oral cavity was applied.Results: An overall response rate of 86.2% was achieved in this study, including 55.2% complete remission and 31.0% partial remission. The only adverse events observed in subjects were transient local ulcer and pain. It is observed the PDT utilizing ALA showed strong effectiveness in patients with moderate to severe dysplasia, as less treatment time per cm2 of lesion is required.Conclusion: Topic ALA-PDT is effective to treat oral leukoplakia, especially for that with the presence of dysplasia. A fixing and restricting complex as well as high laser power density for PDT in oral cavity should be considered as an optimal choice

Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection

Abstract Background Viral infections and exposure to oxidant air pollutants are two of the most important inducers of asthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial cells in vitro and in mice in vivo. Therefore, we examined whether in the setting of allergic asthma, exposure to oxidant air pollutants enhances the susceptibility to respiratory virus infections, which in turn leads to increased virus-induced exacerbation of asthma. Ovalbumin-sensitized (OVA) male C57BL/6 mice were instilled with diesel exhaust particles (DEP) or saline and 24 hours later infected with influenza A/PR/8. Animals were sacrificed 24 hours post-infection and analyzed for markers of lung injury, allergic inflammation, and pro-inflammatory cytokine production. Results Exposure to DEP or infection with influenza alone had no significant effects on markers of injury or allergic inflammation. However, OVA-sensitized mice that were exposed to DEP and subsequently infected with influenza showed increased levels of eosinophils in lung lavage and tissue. In addition Th2-type cytokines, such as IL-4 and IL-13, and markers of eosinophil chemotaxis, such as CCL11 and CCR3, were increased in OVA-sensitized mice exposed to DEP prior to infection with influenza. These mice also showed increased levels of IL-1α, but not IL-10, RANTES, and MCP-1 in lung homogenates. Conclusion These data suggest that in the setting of allergic asthma, exposure to diesel exhaust could enhance virus-induced exacerbation of allergic inflammation

Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells

The mechanisms responsible for the development of airway hyperresponsiveness in asthma are poorly understood. Adenosine levels are high in the lungs of patients with asthma, but a role for adenosine in the development of this cardinal feature of asthma has not been previously reported