Doubly Efficient Interactive Proofs for General Arithmetic Circuits with Linear Prover Time

We propose a new doubly efficient interactive proof protocol for general arithmetic circuits. The protocol generalizes the doubly efficient interactive proof for layered circuits proposed by Goldwasser, Kalai and Rothblum to arbitrary circuits while preserving the optimal prover complexity that is strictly linear to the size of the circuits. The proof size remains succinct for low depth circuits and the verifier time is sublinear for structured circuits. We then construct a new zero knowledge argument scheme for general arithmetic circuits using our new interactive proof protocol together with polynomial commitments. Not only does our new protocol achieve optimal prover complexity asymptotically, but it is also efficient in practice. Our experiments show that it only takes 1 second to generate the proof for a circuit with 600,000 gates, which is 7 times faster than the original interactive proof protocol on the corresponding layered circuit. The proof size is 229 kilobytes and the verifier time is 0.56 second. Our implementation can take general arithmetic circuits generated by existing tools directly, without transforming them to layered circuits with high overhead on the size of the circuits

Ambient temperature regulates root circumnutation in rice through the ethylene pathway: transcriptome analysis reveals key genes involved

Plant roots are constantly prepared to adjust their growth trajectories to avoid unfavorable environments, and their ability to reorient is particularly crucial for survival. Under laboratory conditions, this continuous reorientation of the root tip is manifested as coiling or waving, which we refer to as root circumnutation. However, the effect of ambient temperature (AT) on root circumnutation remains unexplored. In this study, rice seedlings were employed to assess the impact of varying ATs on root circumnutation. The role of ethylene in mediating root circumnutation under elevated AT was examined using the ethylene biosynthesis inhibitor aminooxyacetic acid (AOA) and the ethylene perception antagonist silver thiosulfate (STS). Furthermore, transcriptome sequencing, weighted gene co-expression network analysis, and real-time quantitative PCR were utilized to analyze gene expressions in rice root tips under four distinct treatments: 25°C, 35°C, 35°C+STS, and 35°C+AOA. As a result, genes associated with ethylene synthesis and signaling (OsACOs and OsERFs), auxin synthesis and transport (OsYUCCA6, OsABCB15, and OsNPFs), cell elongation (OsEXPAs, OsXTHs, OsEGL1, and OsEXORDIUMs), as well as the inhibition of root curling (OsRMC) were identified. Notably, the expression levels of these genes increased with rising temperatures above 25°C. This study is the first to demonstrate that elevated AT can induce root circumnutation in rice via the ethylene pathway and proposes a potential molecular model through the identification of key genes. These findings offer valuable insights into the growth regulation mechanism of plant roots under elevated AT conditions

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.</p

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Antiosteoporosis effect and possible mechanisms of the ingredients of Radix Achyranthis Bidentatae in animal models of osteoporosis: systematic review and meta-analysis of in vivo studies

Abstract Background The effect and mechanisms of the ingredients (IRAB) of Radix Achyranthis Bidentatae (RAB) on treating osteoporosis (OP) remains debated. We aimed to summary the evidence to evaluate the efficacy of IRAB for animal model OP and elucidate the potential mechanism of IRAB in the treatment of OP. Methods In this review and meta-analysis, we searched PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, as well as Chinese VIP databases for targeting articles published from inception to March 2023 in English or Chinese. All randomized controlled animal trials that assessed the efficacy and safety of IRAB for OP were included. We excluded trials according to exclusion criteria. The CAMARADES 10-item quality checklist was utilized to test the risk of potential bias for each including study and modifications were performed accordingly. The primary outcome measures were bone mineral density of the femoral neck (F-BMD), serum calcium (Ca), serum phosphorus (P), serum alkaline phosphatase (ALP), bone gla protein (BGP), bone maximum stress (M-STRESS). The secondary outcome measure was the antiosteoporosis mechanisms of IRAB. Results Data from nine articles were included in the systematic review and meta-analysis, which focused on 196 animals. Egger’s test revealed the presence of publication bias in various studies regarding the primary outcome. Administration of IRAB or RAB could significantly increases the F-BMD (SMD = 2.09; 95% CI = 1.29 to 2.89; P < 0.001, I 2 = 76%), Ca (SMD = 0.86; 95% CI = 0.39to1.34; P = 0.07, I 2 = 49%); P (SMD = 1.01; 95% CI = 0.45–4.57; P = 0.08, I 2 = 50%), BGP (SMD = 2.13; 95% CI = 1.48 to 2.78; I 2 = 46%, P = 0.10), while the ALP (SMD = − 0.85; 95% CI =  − 1.38 to − 0.31; I 2 = 46%, P = 0.10) was remarkably decreased in OP model animals. Moreover, the bone biomechanical indicator M-STRESS (SMD = 2.39; 95% CI = 1.74–3.04; I 2 = 32%, P = 0.21) was significantly improved. Conclusion Collectively, the findings suggest that the RAB or IRAB could be an effective drug or an ingredient in diet for the clinical treatment of OP in future

Efficient Fractionation of Green Bamboo Using an Integrated Hydrothermal–Deep Eutectic Solvent Pretreatment for Its Valorization

Adopting an integrated strategy to realize efficient fractionation of lignocellulose into well-defined components for its valorization is challenging. Combinatorial pretreatments in this study decomposed hemicellulose of green bamboo during hydrothermal pretreatment (HP), and the hydrothermally pretreated bamboo was subsequently subjected to delignification using deep eutectic solvent (DES) consisting of choline chloride and lactic acid, finally facilitating enzymatic hydrolysis of cellulose residue. Upon hydrothermal treatment at 180 °C for 35 min, hemicellulose removal of 88.6% was achieved with xylo-oligosaccharide yield and purity of 50.9% and 81.6%, respectively. After DES treatment at 140 °C for 2 h, lignin removal was determined to be 79.1%. Notably, the regenerated lignin with high purity of 96.8% displayed superior antioxidant activity, and the decrease in the ratio of syringyl units to guaiacyl units led to a slight decrease in radical scavenging activity of lignin after five recycling runs of DES. Moreover, the two-step treated residue had much higher enzymatic digestibility than that of single HP residue and untreated green bamboo. Results show that synergistic pretreatment is a promising strategy to tackle the recalcitrance of lignocellulose towards high value-added utilization

Simultaneous vibrational resonance in the amplitude and phase quadratures of an optical field based on Kerr nonlinearity

Vibrational resonance (VR) is a nonlinear phenomenon in which the system response to a weak signal can be resonantly enhanced by applying a high-frequency modulation signal with an appropriate amplitude. The majority of VR research has focused on amplifying the amplitude or intensity of the system response to a weak signal, whereas the study of the phase information of system responses in VR remains limited. Here, we investigate the VR phenomena in both amplitude and phase quadratures of an optical field in a Kerr nonlinear cavity driven by a near-resonant weak signal and a far-detuned modulation signal. Analytical and numerical results demonstrated that the resonant enhancement in the amplitude and phase quadratures of the system response to a weak signal simultaneously occurs as the amplitude of the modulation signal is varied. There is a linear relation between the amplitude and frequency of the modulation signal for achieving an optimal VR effect. Furthermore, we generalized our study to investigate the quadrature at an arbitrary phase and determined that the VR enhancement sensitively depends on the phase. Our findings not only broaden the scope of VR research by incorporating phase information but also introduces an approach for amplifying an optical field by manipulating another optical field