Elastic MSM: A Fast, Elastic and Modular Preprocessing Technique for Multi-Scalar Multiplication Algorithm on GPUs

Zero-knowledge proof (ZKP) is a cryptographic primitive that enable a prover to convince a verifier that a statement is true without revealing any other information beyond the correctness of the statement itself. Due to its powerful capabilities, its most practical type, called zero-knowledge Succinct Non-interactive ARgument of Knowledge (zkSNARK), has been widely deployed in various privacy-preserving applications such as cryptocurrencies and verifiable computation. Although state-of-the-art zkSNARKs are highly efficient for the verifier, the computational overhead for the prover is still orders of magnitude too high to warrant use in many applications. This overhead is due to several time-consuming operations, including large-scale matrix-vector multiplication (MUL), number-theoretic transform (NTT), and especially the multi-scalar multiplication (MSM) with the highest proportion. Thus, further efficiency improvements are needed. In this paper we focus on comprehensive optimization of running time and storage space needed by the MSM algorithm on GPUs. Specifically, we propose a new modular and adaptive parameter configuration technique—elastic MSM to enable us to change the scale of MSM according to our own wishes by performing a corresponding amount of preprocessing. This technique enable us to fully unleash the potential of various efficient parallel MSM algorithms. From another perspective, our technique could also be regarded as a preprocessing technique over the well-known Pippenger algorithm, which is modular and could be used to accelerate almost all the most advanced parallel Pippenger algorithms on GPUs. Meanwhile, our technique provides an adaptive trade-off between the running time and the extra storage space needed by parallel Pippenger algorithms on GPUs. We implemented and tested elastic MSM over two prevailing parallel Pippenger algorithms on GPUs. Given a range of practical parameters, across various preprocessing space limitations (across various MSM scales), our construction achieves up to about 28× and 45× (25× and 40×) speedup versus two state-of-the-art preprocessing parallel Pippenger algorithms on GPUs, respectively

Faster NTRU-based Bootstrapping in less than 4 ms

Bootstrapping is a critical technique in constructing fully homomorphic encryption (FHE), which serves to refresh the noise in FHE ciphertexts, enabling an arbitrary number of homomorphic operations. Among published results, the TFHE-rs library [Zam22] offers the fastest bootstrapping implementation on CPU platforms by taking advantage of AVX-512 instructions. In this paper, we improve the efficiency of the bootstrapping algorithm based on the NTRU problem. First, we introduce the approximate gadget decomposition method tailored for NTRU ciphertext, reducing the number of NTT operations required for external products. Second, by integrating the approximate decomposition and key unrolling techniques, we improve the performance of CMux-based blind rotation. Third, for the automorphism-based blind rotation method, we present a hybrid window size technique that reduces the number of automorphisms by 34% compared to recent work [XZD+23](in Crypto23). Subsequently, we implement the proposed bootstrapping algorithm on the CPU platform with AVX instructions. Experimental results demonstrate that our method only takes 3.8ms, which achieves a 1.8× speedup compared to the TFHE-rs library. Finally, we propose an efficient FPGA accelerator based on the CMux method, which not only achieves the best performance but also exhibits high throughput advantages. Our accelerator can improve performance by 2x compared to state-of-the-art FPGA implementations (e.g., FPT)

High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on αIIbβ3 and platelet secretion

Fucosylated glycosaminoglycan (FG) from sea cucumbers has been reported to have anticoagulant effects via targeting intrinsic tenase. However, FG from natural source also potentially poses risks due to its FXIIa activation and platelet aggregating effects. Here, we found that the effect of FG on human platelet aggregation depended on both the sulfation pattern and chain length. FGs with higher content of Fuc2S4S and larger molecular weight (≥14 kD) had stronger activity. Both platelet aggregation and P-selectin expression induced by TaFG (an FG from Thelenota ananas) were decreased as the molecular weight reduced. Ticagrelor, aspirin and wortmannin completely blocked the secretion (ADP) but only partially blocked the aggregation induced by TaFG. Tirofiban an αIIbβ3 antagonist however potently inhibited both the secretion and aggregation, with IC50 of 6.01 ± 1.1.97 nM. Furthermore, TaFG could bind to human αIIbβ3 with high affinity, and the affinities of two FGs were paralleled with their activity in platelet aggregation or activation. These results indicated that αIIbβ3 played an important role in TaFG-induced platelet aggregation which was mediated by PI3K, and that platelet secretion was required for the amplification of aggregation

Physicochemical Characteristics and Anticoagulant Activities of the Polysaccharides from Sea Cucumber <i>Pattalus mollis</i>

Sulfated polysaccharides from sea cucumbers possess distinct chemical structure and various biological activities. Herein, three types of polysaccharides were isolated and purified from Pattalus mollis, and their structures and bioactivities were analyzed. The fucosylated glycosaminoglycan (PmFG) had a CS-like backbone composed of the repeating units of {-4-d-GlcA-&#946;-1,3-d-GalNAc4S6S-&#946;-1-}, and branches of a sulfated &#945;-l-Fuc (including Fuc2S4S, Fuc3S4S and Fuc4S with a molar ratio of 2:2.5:1) linked to O-3 of each d-GlcA. The fucan sulfate (PmFS) had a backbone consisting of a repetitively linked unit {-4-l-Fuc2S-&#945;-1-}, and interestingly, every trisaccharide unit in its backbone was branched with a sulfated &#945;-l-Fuc (Fuc4S or Fuc3S with a molar ratio of 4:1). Apart from the sulfated polysaccharides, two neutral glycans (PmNG-1 &amp; -2) differing in molecular weight were also obtained and their structures were similar to animal glycogen. Anticoagulant assays indicated that PmFG and PmFS possessed strong APTT prolonging and intrinsic factor Xase inhibition activities, and the sulfated &#945;-l-Fuc branches might contribute to the anticoagulant and anti-FXase activities of both PmFG and PmFS

From multi-target anticoagulants to DOACs, and intrinsic coagulation factor inhibitors

From the 1940s to 1990s, heparin and warfarin have been the main anticoagulants for the prevention and treatment of thrombotic events. Since then, LMWHs and fondaparinux proved effective in clinical trials, with better pharmacokinetic profiles and no monitoring requirements. Developed in the early 21st century, DOACs have comparable efficacy to LMWHs, but increase bleeding risk, as the anticoagulant targets (FIIa, FXa) are also essential for physiological hemostasis. In contrast, selective inhibition of the intrinsic coagulation pathway may be a promising strategy for safer antithrombotic treatment. FXII, FXI and FIX inhibitors have produced favorable results in preclinical studies. Notably, intrinsic F.Xase is another promising candidate target, yet to be systematically evaluated. Here, we review the development of anticoagulants, including recent research on intrinsic F.Xase inhibitors, and the revision of coagulation models over time. Studies support optimism for future diversification of anticoagulants, which could offer more reliable and patient-specific therapy

Precise Structure and Anticoagulant Activity of Fucosylated Glycosaminoglycan from <i>Apostichopus japonicus</i>: Analysis of Its Depolymerized Fragments

Apostichopus japonicus is one of the most economically important species in sea cucumber aquaculture in China. Fucosylated glycosaminoglycan from A. japonicus (AjFG) has shown multiple pharmacological activities. However, results from studies on the structure of AjFG are still controversial. In this study, the deaminative depolymerization method that is glycosidic bond-selective was used to prepare the depolymerized products from AjFG (dAjFG), and then a series of purified oligosaccharide fragments such as tri-, hexa-, nona-, and dodecasaccharides were obtained from dAjFG by gel permeation chromatography. The 1D/2D NMR and ESI-MS spectrometry analyses showed that these oligosaccharides had the structural formula of l-FucS-&#945;1,3-d-GlcA-&#946;1,3-{d-GalNAc4S6S-&#946;1,4-[l-FucS-&#945;1,3-]d-GlcA-&#946;1,3-}n-d-anTal-diol4S6S (n = 0, 1, 2, 3; FucS represents Fuc2S4S, Fuc3S4S, or Fuc4S). Thus, the unambiguous structure of native AjFG can be rationally deduced: it had the backbone of {-4-d-GlcA-&#946;1,3-d-GalNAc4S6S-&#946;1-}n, which is similar to chondroitin sulfate E, and each d-GlcA residue in the backbone was branched with a l-FucS monosaccharide at O-3. Bioactivity assays confirmed that dAjFG and nonasaccharides and dodecasaccharides from AjFG had potent anticoagulant activity by intrinsic FXase inhibition while avoiding side effects such as FXII activation and platelet aggregation

In Vitro Comparison of the Efficacies of Natamycin and Silver Nitrate against Ocular Fungi▿

The in vitro activity of the silver nitrate was assessed in comparison with that of natamycin against 128 corneal Fusarium isolates and 90 corneal Aspergillus isolates. MIC90s of silver nitrate were 2 μg/ml for Fusarium spp. and 1 μg/ml for Aspergillus spp. MIC90s of natamycin were 8 μg/ml for Fusarium spp. and 32 μg/ml for Aspergillus spp. Silver nitrate exhibited potent antifungal activity against ocular fungi in vitro