Brain topology improved spiking neural network for efficient reinforcement learning of continuous control.

The brain topology highly reflects the complex cognitive functions of the biological brain after million-years of evolution. Learning from these biological topologies is a smarter and easier way to achieve brain-like intelligence with features of efficiency, robustness, and flexibility. Here we proposed a brain topology-improved spiking neural network (BT-SNN) for efficient reinforcement learning. First, hundreds of biological topologies are generated and selected as subsets of the Allen mouse brain topology with the help of the Tanimoto hierarchical clustering algorithm, which has been widely used in analyzing key features of the brain connectome. Second, a few biological constraints are used to filter out three key topology candidates, including but not limited to the proportion of node functions (e.g., sensation, memory, and motor types) and network sparsity. Third, the network topology is integrated with the hybrid numerical solver-improved leaky-integrated and fire neurons. Fourth, the algorithm is then tuned with an evolutionary algorithm named adaptive random search instead of backpropagation to guide synaptic modifications without affecting raw key features of the topology. Fifth, under the test of four animal-survival-like RL tasks (i.e., dynamic controlling in Mujoco), the BT-SNN can achieve higher scores than not only counterpart SNN using random topology but also some classical ANNs (i.e., long-short-term memory and multi-layer perception). This result indicates that the research effort of incorporating biological topology and evolutionary learning rules has much in store for the future.

Karst fissures mitigate the negative effects of drought on plant growth and photosynthetic physiology.

Hard limestone substrates, which are extensively distributed, are believed to exacerbate drought and increase the difficulty of restoration in vulnerable karst regions. Fissures in such substrates may alleviate the negative effect of drought on plants, but the underlying mechanisms remain poorly understood. In a two-way factorial block design, the growth and photosynthesis of 2-year-old Phoebe zhennan seedlings were investigated in two water availabilities (high versus low) and three stimulated fissure habitat groups (soil, soil-filled fissure and non-soil-filled fissure). Moreover, the fissure treatments included both small and big fissures. Compared to the soil group, the non-soil-filled fissure group had decreased the total biomass, root biomass, total root length, and the root length of fine roots in the soil layer at both water availabilities, but increased net photosynthetic rate (Pn) and retained stable water use efficiency (WUE) at low water availability. However, there were no significant differences between the soil-filled fissure group and soil group in the biomass accumulation and allocation as well as Pn. Nevertheless, the SF group decreased the root distribution in total and in the soil layer, and also increased WUE at low water availability. Across all treatments, fissure size had no effect on plant growth or photosynthesis. Karst fissures filled with soil can alleviate drought impacts on plant root growth, which involves adjusting root distribution strategies and increasing water use efficiency. These results suggest that rock fissures can be involved in long-term plant responses to drought stress and vegetation restoration in rocky mountain environments under global climate change.

DFT Study of Functional Reduction of CO2 with BH3NMe3: The Real Role of Organic Catalyst TBD.

The detailed mechanism of transition metal-free-catalyzed monomethylation of 2-naphthyl acetonitrile (1a) with CO2 in the presence of triazabicyclodecene (TBD) and BH3NMe3 was investigated using density functional theory. The C-methylation process proved to generate formaldehyde followed by the formation of the product via an alcohol rather than a methoxyborane intermediate. During the reaction, CO2 is activated to form the TBD-CO2 adduct and BH3NMe3 is changed into TBD-BH2 (IM2) in the presence of TBD. IM2 plays a real reducing role within the system due to the unique coordination capability of the B atom. In addition to enhancing the nucleophilicity of 1a through deprotonation by tBuOK, our research also indicates that the generated tBuOH not only assists in proton transfer to generate an alcohol intermediate but also promotes the regeneration of TBD.

Far-red light modulates grapevine growth by increasing leaf photosynthesis efficiency and triggering organ-specific transcriptome remodelling : Author.

BACKGROUND: Growing evidence demonstrates that the synergistic interaction of far-red light with shorter wavelength lights could evidently improve the photosynthesis efficiency of multiple species. However, whether/how far-red light affects sink organs and consequently modulates the source‒sink relationships are largely unknown. RESULTS: Here, equal intensities of white and far-red lights were added to natural light for grape plantlets to investigate the effects of far-red light supplementation on grapevine growth and carbon assimilate allocation, as well as to reveal the underlying mechanisms, through physiological and transcriptomic analysis. The results showed that additional far-red light increased stem length and carbohydrate contents in multiple organs and decreased leaf area, specific leaf weight and dry weight of leaves in comparison with their counterparts grown under white light. Compared to white light, the maximum net photosynthetic rate of the leaves was increased by 31.72% by far-red light supplementation, indicating that far-red light indeed elevated the photosynthesis efficiency of grapes. Transcriptome analysis revealed that leaves were most responsive to far-red light, followed by sink organs, including stems and roots. Genes related to light signaling and carbon metabolites were tightly correlated with variations in the aforementioned physiological traits. In particular, VvLHCB1 is involved in light harvesting and restoring the balance of photosystem I and photosystem II excitation, and VvCOP1 and VvPIF3, which regulate light signal transduction, were upregulated under far-red conditions. In addition, the transcript abundances of the sugar transporter-encoding genes VvSWEET1 and VvSWEET3 and the carbon metabolite-encoding genes VvG6PD, VvSUS7 and VvPGAM varied in line with the change in sugar content. CONCLUSIONS: This study showed that far-red light synergistically functioning with white light has a beneficial effect on grape photosystem activity and is able to differentially affect the growth of sink organs, providing evidence for the possible addition of far-red light to the wavelength range of photosynthetically active radiation (PAR).

Effects of higher femoral tunnels on clinical outcomes, MRI, and second-look findings in double-bundle anterior cruciate ligament reconstruction with a minimal 5-year follow-up.

BACKGROUND: To perform anatomical anterior cruciate ligament reconstruction (ACLR), tunnels should be placed relatively higher in the femoral anterior cruciate ligament (ACL) footprint based on the findings of direct and indirect femoral insertion. But the clinical results of higher femoral tunnels (HFT) in double-bundle ACLR (DB-ACLR) remain unclear. The purpose was to investigate the clinical results of HFT and lower femoral tunnels (LFT) in DB-ACLR. METHODS: From September 2014 to February 2016, 83 patients who underwent DB-ACLR and met the inclusion and exclusion criteria were divided into HFT-ACLR (group 1, n = 37) and LFT-ACLR (group 2, n = 46) according to the position of femoral tunnels. Preoperatively and at the final follow-up, clinical scores were evaluated with International Knee Documentation Committee (IKDC), Tegner activity, and Lysholm score. The stability of the knee was evaluated with KT-2000, Lachman test, and pivot-shift test. Cartilage degeneration grades of the International Cartilage Repair Society (ICRS) were evaluated on magnetic resonance imaging (MRI). Graft tension, continuity, and synovialization were evaluated by second-look arthroscopy. Return-to-sports was assessed at the final follow-up. RESULTS: Significantly better improvement were found for KT-2000, Lachman test, and pivot-shift test postoperatively in group 1 ( P >0.05). Posterolateral bundles (PL) showed significantly better results in second-look arthroscopy regarding graft tension, continuity, and synovialization ( P <0.05), but not in anteromedial bundles in group 1. At the final follow-up, cartilage worsening was observed in groups 1 and 2, but it did not reach a stastistically significant difference ( P >0.05). No statistically significant differences were found in IKDC subjective score, Tegner activity, and Lysholm score between the two groups. Higher return-to-sports rate was found in group 1 with 86.8% (32/37) vs. 65.2% (30/46) in group 2 ( P = 0.027). CONCLUSION: The HFT-ACLR group showed better stability results, better PL, and higher return-to-sports rate compared to the LFT-ACLR group.

SecBERT: Privacy-preserving pre-training based neural network inference system.

Pre-trained models such as BERT have made great achievements in natural language processing tasks in recent years. In this paper, we investigate the privacy-preserving pre-training based neural network inference in a two-server framework based on additive secret sharing technique. Our protocol allows a resource-restrained client to request two powerful servers to cooperatively process the natural processing tasks without revealing any useful information about its data. We first design a series of secure sub-protocols for non-linear functions used in BERT model. These sub-protocols are expected to have broad applications and of independent interest. Based on the building sub-protocols, we propose SecBERT, a privacy-preserving pre-training based neural network inference protocol. SecBERT is the first cryptographically secure privacy-preserving pre-training based neural network inference protocol. We show security, efficiency and accuracy of SecBERT protocol through comprehensive theoretical analysis and experiments.

Terminal crystalline solid solutions, solubility enhancements and T-X phase diagram of salicylic acid - 4-hydroxybenzoic acid.

The binary T-X phase diagram of salicylic acid (SA) and 4-hydroxybenzoic acid (4HBA) has been constructed from 20 °C to melting, revealing a partially miscible system with an eutectic composition of 27.3 mol% 4HBA in SA. Terminal crystalline solid solutions were obtained at the extremes of the phase diagram with solid-state miscibility limits below 0.4% at 20 °C. The limited phase boundaries could be captured experimentally by both DSC analyses at around melting temperature and solid-liquid equilibria studies at 20 °C in two solvent systems. The NRTL model was applied to regress phase boundaries and generate the final binary T-X phase diagram. The NRTL model was also used to regress solubility data, and reproduce the ternary SA/4HBA/solvent phase diagram at 20 °C and 1 atm. 4HBA was obtained as two crystal forms, viz. anhydrate and monohydrate. It is shown how the monohydrate of 4HBA is less miscible with SA in the solid state than the anhydrous form of 4HBA. As compared to pure SA and 4HBA, the crystalline solid solutions exhibited significant changes in physical properties that are relevant for organic and pharmaceutical materials in the context of impurity effects. A lattice incorporation of just 0.2 mol% 4HBA in SA caused a 10% reduction in melting enthalpy and a 66% solubility increase in 40 wt% MeOH in H2O. The reasons for this thermodynamic effect are discussed.

Soil nutrient limitation and natural enemies promote the establishment of alien species in native communities.

The invasion of alien plant species threatens the composition and diversity of native communities. However, the invasiveness of alien plants and the resilience of native communities are dependent on the interactions between biotic and abiotic factors, such as natural enemies and nutrient availability. In our study, we simulated the invasion of nine invasive plant species into native plant communities using two levels of nutrient availability and suppression of natural enemies. We evaluated the effect of biotic and abiotic factors on the response of alien target species and the resistance of native communities to invasion. The results showed that the presence of enemies (enemy release) increased the biomass proportion of alien plants while decreasing that of native communities in the absence of nutrient addition. Furthermore, we also found that the negative effect of enemy suppression on the evenness of the native community and the root-to-shoot ratio of alien target species was greatest under nutrient addition. Therefore, nutrient-poor and natural enemies might promote the invasive success of alien species in native communities, whereas nutrient addition and enemy suppression can better enhance the resistance of native plant communities to invasion.

SCD1 is the critical signaling hub to mediate metabolic diseases: Mechanism and the development of its inhibitors.

Metabolic diseases, featured with dysregulated energy homeostasis, have become major global health challenges. Patients with metabolic diseases have high probability to manifest multiple complications in lipid metabolism, e.g. obesity, insulin resistance and fatty liver. Therefore, targeting the hub genes in lipid metabolism may systemically ameliorate the metabolic diseases, along with the complications. Stearoyl-CoA desaturase 1(SCD1) is a key enzyme that desaturates the saturated fatty acids (SFAs) derived from de novo lipogenesis or diet to generate monounsaturated fatty acids (MUFAs). SCD1 maintains the metabolic and tissue homeostasis by responding to, and integrating the multiple layers of endogenous stimuli, which is mediated by the synthesized MUFAs. It critically regulates a myriad of physiological processes, including energy homeostasis, development, autophagy, tumorigenesis and inflammation. Aberrant transcriptional and epigenetic activation of SCD1 regulates AMPK/ACC, SIRT1/PGC1α, NcDase/Wnt, etc, and causes aberrant lipid accumulation, thereby promoting the progression of obesity, non-alcoholic fatty liver, diabetes and cancer. This review critically assesses the integrative mechanisms of the (patho)physiological functions of SCD1 in metabolic homeostasis, inflammation and autophagy. For translational perspective, potent SCD1 inhibitors have been developed to treat various types of cancer. We thus discuss the multidisciplinary advances that greatly accelerate the development of SCD1 new inhibitors. In conclusion, besides cancer treatment, SCD1 may serve as the promising target to combat multiple metabolic complications simultaneously.

Carbon tax and low-carbon credit: Which policy is more beneficial to the capital-constrained manufacturer's remanufacturing activities?

Remanufacturing has attracted much attention for its enormous potential in resource recycling and low-carbon emission reduction. To investigate the effects of different government intervention policies on remanufacturing and carbon emissions, two profit maximization models of the capital-constrained manufacturer under carbon tax and low-carbon credit policies are constructed respectively. Then, through theoretical and numerical analyses, some significant findings are drawn: (1) Both carbon tax and low-carbon credit policies can encourage capital-constrained manufacturers to produce more remanufactured products, but which intervention policy is more advantageous also depends on the carbon emission cost of new products or financing cost of the remanufactured products. (2) Although carbon tax policy can effectively control carbon emissions, it is always at the expense of both capital-constrained manufacturers and consumers; while low-carbon credit policy can help capital-constrained manufacturers achieve the goal of win-win economic and environmental benefits when the remanufacturing carbon savings advantages are more apparent. (3) From the perspective of consumer benefits, carbon tax is more advantageous when the consumer willingness to pay for remanufactured products is higher; otherwise, low-carbon credit policy should be implemented. (4) The higher the environmental damage coefficient is, the more it can highlight the advantages of the two intervention policies in social welfare enhancement, especially the carbon tax policy; and when the environmental damage coefficient is given, the stronger the consumers' willingness to pay for remanufactured products is, the more it is conducive to reducing the negative effects caused by the carbon tax or low-carbon credit policy in social welfare enhancement, or increasing the corresponding positive effects. Based on above findings, some managerial insights and policy implications are provided to capital-constrained manufacturers and policy-makers.

Sample preparation, analytical characterization, monitoring, risk assessment and treatment of naphthenic acids in industrial wastewater and surrounding water impacted by unconventional petroleum production.

Industrial extraction of unconventional petroleum results in notable volumes of oil sands process water (OSPW), containing elevated concentrations of naphthenic acids (NAs). The presence of NAs represents an intricate amalgamation of dissolved organic constituents, thereby presenting a notable hurdle for the domain of environmental analytical chemistry. There is growing concern about monitoring the potential seepage of OSPW NAs into nearby groundwater and river water. This review summarizes recent studies on sample preparation, characterization, monitoring, risk assessment, and treatment of NAs in industrial wastewater and surrounding water. Sample preparation approaches, such as liquid-liquid extraction, solid phase microextraction, and solid phase extraction, are crucial in isolating chemical standards, performing molecular level analysis, assessing aquatic toxicity, monitoring, and treating OSPW. Instrument techniques for NAs analysis were reviewed to cover different injection modes, ionization sources, and mass analyzers. Recent studies of transfer and transformation of NAs provide insights to differentiate between anthropogenic and natural bitumen-derived sources of NAs. In addition, related risk assessment and treatment studies were also present for elucidation of environmental implication and reclamation strategies. The synthesis of the current state of scientific knowledge presented in this review targets government regulators, academic researchers, and industrial scientists with interests spanning analytical chemistry, toxicology, and wastewater management.

Transforming Dye Molecules into Electrochemical Allies: Direct Red 80 as a Dual-Functional Electrolyte Additive for Dendrite-Free Aqueous Zinc-Ion Batteries.

Despite the numerous advantages of abundant zinc resources, low redox potential, and affordability, aqueous zinc-ion batteries (AZIBs) currently face limitations due to dendritic growth and side reactions. This study explores the use of low-cost and efficient anionic dyes, specifically Direct Red 80 (DR80) as dual-functional electrolyte additives to enhance the electrochemical performance of AZIBs and facilitate the reuse of dye wastewater. Experimental and theory calculation results all demonstrate that the DR80 molecules readily adsorb onto the surface of the zinc anode, creating a stable and robust solid electrolyte interphase layer. This layer acts as a protective barrier, effectively mitigating H+ attacks and reducing both hydrogen evolution and corrosion reactions. Additionally, it covers any initial protrusions on the zinc anode, preventing the occurrence of the "tip-effect" phenomenon and limiting access of water to the zinc anode, thereby minimizing water decomposition. Moreover, the sulfonic acid groups of DR80 molecules displace some water molecules in [Zn(H2O)6]2+, disrupting the original solvent sheath and reducing water decomposition. Especially, using the DR80 additive, the Zn/Zn cell reaches an impressive cycle life of 1500 h at 2 mA cm-2@1 mAh cm-2. Given the low cost and widespread availability, this additive shows great potential in the future practical implementation of AZIBs.

Exact New Mobility Edges between Critical and Localized States.

The disorder systems host three types of fundamental quantum states, known as the extended, localized, and critical states, of which the critical states remain being much less explored. Here we propose a class of exactly solvable models which host a novel type of exact mobility edges (MEs) separating localized states from robust critical states, and propose experimental realization. Here the robustness refers to the stability against both single-particle perturbation and interactions in the few-body regime. The exactly solvable one-dimensional models are featured by a quasiperiodic mosaic type of both hopping terms and on-site potentials. The analytic results enable us to unambiguously obtain the critical states which otherwise require arduous numerical verification including the careful finite size scalings. The critical states and new MEs are shown to be robust, illustrating a generic mechanism unveiled here that the critical states are protected by zeros of quasiperiodic hopping terms in the thermodynamic limit. Further, we propose a novel experimental scheme to realize the exactly solvable model and the new MEs in an incommensurate Rydberg Raman superarray. This Letter may pave a way to precisely explore the critical states and new ME physics with experimental feasibility.

Model-assisted analysis for tuning anthocyanin composition in grape berries.

Anthocyanin composition is responsible for the red colour of grape berries and wines, and contributes to their organoleptic quality. However, anthocyanin biosynthesis is under genetic, developmental and environmental regulation, making its targeted fine-tuning challenging. We constructed a mechanistic model to simulate the dynamics of anthocyanin composition throughout grape ripening in Vitis vinifera, employing a consensus anthocyanin biosynthesis pathway. The model was calibrated and validated using six datasets from eight cultivars and 37 growth conditions. Tuning the transformation and degradation parameters allowed us to accurately simulate the accumulation process of each individual anthocyanin under different environmental conditions. The model parameters were robust across environments for each genotype. The coefficients of determination (R2) for the simulated versus observed values for the six datasets ranged from 0.92 to 0.99, while the relative root mean square errors (RRMSEs) were between 16.8 and 42.1 %. The leave-one-out cross-validation for three datasets showed R2 values of 0.99, 0.96 and 0.91, and RRMSE values of 28.8, 32.9 and 26.4 %, respectively, suggesting a high prediction quality of the model. Model analysis showed that the anthocyanin profiles of diverse genotypes are relatively stable in response to parameter perturbations. Virtual experiments further suggested that targeted anthocyanin profiles may be reached by manipulating a minimum of three parameters, in a genotype-dependent manner. This model presents a promising methodology for characterizing the temporal progression of anthocyanin composition, while also offering a logical foundation for bioengineering endeavours focused on precisely adjusting the anthocyanin composition of grapes.

Nonlinear Transport due to Magnetic-Field-Induced Flat Bands in the Nodal-Line Semimetal ZrTe_{5}.

The Dirac material ZrTe_{5} at very low carrier density was recently found to be a nodal-line semimetal, where ultraflat bands are expected to emerge in magnetic fields parallel to the nodal-line plane. Here, we report that in very low carrier-density samples of ZrTe_{5}, when the current and the magnetic field are both along the crystallographic a axis, the current-voltage characteristics presents a pronounced nonlinearity which tends to saturate in the ultra quantum limit. The magnetic-field dependence of the nonlinear coefficient is well explained by the Boltzmann theory for flat-band transport, and we argue that this nonlinear transport is likely due to the combined effect of flat bands and charge puddles; the latter appear due to very low carrier densities.

Utilization of Fe-Ethylenediamine-N,N'-Disuccinic Acid Complex for Electrochemical Co-Catalytic Activation of Peroxymonosulfate under Neutral Initial pH Conditions.

The ethylenediamine-N,N'-disuccinic acid (EDDS) was utilized to form Fe-EDDS complex to activate peroxymonosulfate (PMS) in the electrochemical (EC) co-catalytic system for effective oxidation of naphthenic acids (NAs) under neutral pH conditions. 1-adamantanecarboxylic acid (ACA) was used as a model compound to represent NAs, which are persistent pollutants that are abundantly present in oil and gas field wastewater. The ACA degradation rate was significantly enhanced in the EC/PMS/Fe(III)-EDDS system (96.6%) compared to that of the EC/PMS/Fe(III) system (65.4%). The addition of EDDS led to the formation of a stable complex of Fe-EDDS under neutral pH conditions, which effectively promoted the redox cycle of Fe(III)-EDDS/Fe(II)-EDDS to activate PMS to generate oxidative species for ACA degradation. The results of quenching and chemical probe experiments, as well as electron paramagnetic resonance (EPR) analysis, identified significant contributions of •OH, 1O2, and SO4•- in the removal of ACA. The ACA degradation pathways were revealed based on the results of high resolution mass spectrometry analysis and calculation of the Fukui index. The presence of anions, such as NO3-, Cl-, and HCO3-, as well as humic acids, induced nonsignificant influence on the ACA degradation, indicating the robustness of the current system for applications in authentic scenarios. Overall results indicated the EC/PMS/Fe(III)-EDDS system is a promising strategy for the practical treatment of NAs in oil and gas field wastewater.

Grapevine plantlets respond to different monochromatic lights by tuning photosynthesis and carbon allocation.

The quality of planting materials is the foundation for productivity, longevity, and berry quality of perennial grapevines with a long lifespan. Manipulating the nursery light spectrum may speed up the production of healthy and high-quality planting vines but the underlying mechanisms remain elusive. Herein, the effects of different monochromatic lights (green, blue, and red) on grapevine growth, leaf photosynthesis, whole-plant carbon allocation, and transcriptome reprograming were investigated with white light as control. Results showed that blue and red lights were favorable for plantlet growth in comparison with white light. Blue light repressed excessive growth, significantly increased the maximum net photosynthetic rate (Pn) of leaves by 39.58% and leaf specific weight by 38.29%. Red light increased the dry weight of the stem by 53.60%, the starch content of the leaf by 53.63%, and the sucrose content of the stem by 230%. Green light reduced all photosynthetic indexes of the grape plantlet. Photosynthetic photon flux density (PPFD)/Ci-Pn curves indicated that blue light affected photosynthetic rate depending on the light intensity and CO2 concentration. RNA-seq analysis of different organs (leaf, stem, and root) revealed a systematic transcriptome remodeling and VvCOP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1), VvHY5 (ELONGATED HYPOCOTYL5), VvHYH (HY5 HOMOLOG), VvELIP (early light-induced protein) and VvPIF3 (PHYTOCHROME INTERACTING FACTOR 3) may play important roles in this shoot-to-root signaling. Furthermore, the correlation network between differential expression genes and physiological traits indicated that VvpsbS (photosystem II subunit S), Vvpsb28 (photosystem II subunit 28), VvHYH, VvSUS4 (sucrose synthase 4), and VvALDA (fructose-bisphosphate aldolase) were pertinent candidate genes in responses to different light qualities. Our results provide a foundation for optimizing the light recipe of grape plantlets and strengthen the understanding of light signaling and carbon metabolism under different monochromatic lights.

Panaxynol ameliorates cardiac ischemia/reperfusion injury by suppressing NLRP3-induced pyroptosis and apoptosis via HMGB1/TLR4/NF-κB axis.

BACKGROUND AND PURPOSE: Panaxynol (PNN) is a common natural minor component in Umbelliferae plants. Many clinical studies have shown that PNN exhibits nutritional value and anti-inflammatory and other pharmacological activities. However, whether PNN can mediate cardiac ischemia/reperfusion injury (IRI) remains unclear. Here, we aimed to determine the potential effects of PNN on myocardial IRI. METHODS: Myocardial IRI was stimulated in a mouse IRI model, and neonatal rat ventricle myocytes (NRVMs) were exposed to hypoxia/reoxygenation to construct in an vitro model. Myocardial infarction size, myocardial tissue injury, myocardial apoptotic index, hemodynamic monitoring, pyroptosis-related proteins, cardiac enzyme activities and inflammatory responses were examined to assess myocardial injury. RESULTS: It was found that PNN administration markedly reduced myocardial infarct size and apoptosis, suppressed myocardial damage and cell pyroptosis, attenuated pro-inflammatory cytokines and neutrophil infiltration via NLRP3 inhibitor. More importantly, PNN treatment remarkably decreased the expression of TLR4/NF-κB pathway-associated proteins and NLRP3-related pyroptosis proteins by HMGB1 inhibitor. PNN also enhanced cell viability, reduced cardiac enzyme activities, suppressed apoptosis and attenuated inflammation in the isolated NRVMs. Furthermore, vitro studies indicated that MCC950 (a NLRP3 inhibitor) increased the anti-inflammatory and anti-apoptotic effects of PNN on NRVMs via HMGB1/TLR4 pathway. CONCLUSION: To sum up, our results demonstrate that PNN exhibits a cardioprotective effect by modulating heart IRI-induced apoptosis and pyroptosis via HMGB1/TLR4/NF-κB pathway, thereby inhibiting NLRP3 inflammasome stimulation.