A positive association between RDW and coronary heart disease in the rheumatoid arthritis population: A cross-sectional study from NHANES.

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036-1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55-66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.

Phosphorylation of KAT-2B by WKS1/Yr36 redirects the lipid flux to jasmonates to enhance resistance against wheat stripe rust.

Wheat (Triticum aestivum) is one of the most essential human energy and protein sources. However, wheat production is threatened by devastating fungal diseases such as stripe rust, caused by Puccinia striiformis Westend. f. sp. tritici (Pst). Here, we reveal that the alternations in chloroplast lipid profiles and the accumulation of jasmonate (JA) in the necrosis region activate JA signaling and trigger the host defense. The collapse of chloroplasts in the necrosis region results in accumulations of polyunsaturated membrane lipids and the lipid-derived phytohormone JA in transgenic lines of Yr36 that encodes Wheat Kinase START 1 (WKS1), a high-temperature-dependent adult plant resistance protein. WKS1.1, a protein encoded by a full-length splicing variant of WKS1, phosphorylates and enhances the activity of keto-acyl thiolase (KAT-2B), a critical enzyme catalyzing the ß-oxidation reaction in JA biosynthesis. The premature stop mutant, kat-2b, accumulates less JA and shows defects in the host defense against Pst. Conversely, overexpression of KAT-2B results in a higher level of JA and limits the growth of Pst. Moreover, JA inhibits the growth and reduces pustule densities of Pst. This study illustrates the WKS1.1‒KAT-2B‒JA pathway for enhancing wheat defense against fungal pathogens to attenuate yield loss.

Suppressing ASPARTIC PROTEASE 1 prolongs photosynthesis and increases wheat grain weight.

The elongation of photosynthesis, or functional staygreen, represents a feasible strategy to propel metabolite flux towards cereal kernels. However, achieving this goal remains a challenge in food crops. Here we report the cloning of wheat CO2 assimilation and kernel enhanced 2 (cake2), the mechanism underlying the photosynthesis advantages and natural alleles amenable to breeding elite varieties. A premature stop mutation in the A-genome copy of the ASPARTIC PROTEASE 1 (APP-A1) gene increased the photosynthesis rate and yield. APP1 bound and degraded PsbO, the protective extrinsic member of photosystem II critical for increasing photosynthesis and yield. Furthermore, a natural polymorphism of the APP-A1 gene in common wheat reduced APP-A1's activity and promoted photosynthesis and grain size and weight. This work demonstrates that the modification of APP1 increases photosynthesis, grain size and yield potentials. The genetic resources could propel photosynthesis and high-yield potentials in elite varieties of tetraploid and hexaploid wheat.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Suppression of ZEAXANTHIN EPOXIDASE 1 restricts stripe rust growth in wheat.

Reducing losses caused by pathogens is an effective strategy for stabilizing crop yields. Daunting challenges remain in cloning and characterizing genes that inhibit stripe rust, a devastating disease of wheat (Triticum aestivum) caused by Puccinia striiformis f. sp. tritici (Pst). We found that suppression of wheat zeaxanthin epoxidase 1 (ZEP1) increased wheat defense against Pst. We isolated the yellow rust slower 1 (yrs1) mutant of tetraploid wheat in which a premature stop mutation in ZEP1-B underpins the phenotype. Genetic analyses revealed increased H2O2 accumulation in zep1 mutants and demonstrated a correlation between ZEP1 dysfunction and slower Pst growth in wheat. Moreover, wheat kinase START 1.1 (WKS1.1, Yr36) bound, phosphorylated, and suppressed the biochemical activity of ZEP1. A rare natural allele in the hexaploid wheat ZEP1-B promoter reduced its transcription and Pst growth. Our study thus identified a novel suppressor of Pst, characterized its mechanism of action, and revealed beneficial variants for wheat disease control. This work opens the door to stacking wheat ZEP1 variants with other known Pst resistance genes in future breeding programs to enhance wheat tolerance to pathogens.

HSP90.2 modulates 2Q2-mediated wheat resistance against powdery mildew.

Wheat (Triticum aestivum L.) is a critical food crop feeding the world, but pathogens threaten its production. Wheat Heat Shock Protein 90.2 (HSP90.2) is a pathogen-inducible molecular chaperone folding nascent preproteins. Here, we used wheat HSP90.2 to isolate clients regulated at the posttranslational level. Tetraploid wheat hsp90.2 knockout mutant was susceptible to powdery mildew, while the HSP90.2 overexpression line was resistant, suggesting that HSP90.2 was essential for wheat resistance against powdery mildew. We next isolated 1500 clients of HSP90.2, which contained a wide variety of clients with different biological classifications. We utilized 2Q2, a nucleotide-binding leucine repeat-rich protein, as a model to investigate the potential of HSP90.2 interactome in fungal resistance. The transgenic line co-suppressing 2Q2 was more susceptible to powdery mildew, suggesting 2Q2 as a novel Pm-resistant gene. The 2Q2 protein resided in chloroplasts, and HSP90.2 played a critical role in the accumulation of 2Q2 in thylakoids. Our data provided over 1500 HSP90.2 clients with a potential regulation at the protein folding process and contributed a nontypical approach to isolate pathogenesis-related proteins.

Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases.

Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 µM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1ß secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.

Catalytic oxidation of polystyrene to aromatic oxygenates over a graphitic carbon nitride catalyst.

The continuous increase in manufacturing coupled with the difficulty of recycling of plastic products has generated huge amounts of waste plastics. Most of the existing chemical recycling and upcycling methods suffer from harsh conditions and poor product selectivity. Here we demonstrate a photocatalytic method to oxidize polystyrene to aromatic oxygenates under visible light irradiation using heterogeneous graphitic carbon nitride catalysts. Benzoic acid, acetophenone, and benzaldehyde are the dominant products in the liquid phase when the conversion of polystyrene reaches >90% at 150 °C. For the transformation of 0.5 g polystyrene plastic waste, 0.36 g of the aromatic oxygenates is obtained. The reaction mechanism is also investigated with various characterization methods and procedes via polystyrene activation to form hydroxyl and carbonyl groups over its backbone via C-H bond oxidation which is followed by oxidative bond breakage via C-C activation and further oxidation processes to aromatic oxygenates.

Methane Activation by (MoO3 )5 O- Cluster Anions: The Importance of Orbital Orientation.

The reactivity of the molybdenum oxide cluster anion (MoO3 )5 O- , bearing an unpaired electron at a bridging oxygen atom (Ob .- ), towards methane under thermal collision conditions has been studied by mass spectrometry and density functional theory calculations. This reaction follows the mechanism of hydrogen atom transfer (HAT) and is facilitated by the Ob .- radical center. The reactivity of (MoO3 )5 O- can be traced back to the appropriate orientation of the lowest unoccupied molecular orbitals (LUMO) that is essentially the 2p orbital of the Ob .- atom. This study not only makes up the blank of thermal methane activation by the Ob .- radical on negatively charged clusters but also yields new insights into methane activation by the atomic oxygen radical anions.

An Eight-Atom Iridium-Aluminum Oxide Cluster IrAlO6+ Catalytically Oxidizes Six CO Molecules.

Fundamental understanding regarding oxygen storage capacity involving how and why an active site can buffer a large number of oxygen atoms in redox processes is vital to the design of advanced oxygen storage materials, while it is challenging because of the complexity of heterogeneous catalysis. Herein, we identified that an eight-atom iridium-aluminum oxide cluster IrAlO6+ can transfer all the oxygen atoms to catalytically oxidize six CO molecules. This finding represents a breakthrough in cluster catalysis where at most three oxygen atoms from a heteronuclear metal oxide cluster can be catalytically involved in CO oxidation. We found that oxygen prefers to be stored on aluminum to form an O3-• radical in the energetically unfavorable IrAlO6+ isomer and generate the low-coordinated iridium that is pivotal to capturing CO and triggering the catalysis. The powerful electron cycling capability of iridium and the cooperative iridium-aluminum interplay are emphasized to drive the oxygen atom-transfer behavior.

C-N Coupling in N2 Fixation by the Ditantalum Carbide Cluster Anions Ta2C4.

The construction of C-N bonds by the direct incorporation of dinitrogen (N2) instead of ammonia (NH3) into active species is particularly desirable but has been rarely reported. Herein, a ditantalum carbide cluster anion (Ta2C4-) capable of cleaving the N≡N bond and constructing a C-N bond under mild conditions has been identified using mass spectrometry, photoelectron imaging spectroscopy, and quantum-chemical calculations. The photoelectron spectrum of Ta2C4N2- is remarkably different from that of Ta2C4- and matches the simulated spectrum of the Ta2C4N2- species with an end-on-bonded CN unit. The formation of the C-N bond has also been supported by the CN- fragment observed in the collision-induced dissociation of Ta2C4N2-. The exceptional reactivity of Ta2C4- is ascribed to the low-valent metal center serving as an electron reservoir. This study provides a non-NH3 route to construct C-N bonds by incorporating N2 into carbide compounds to produce nitrogenous species.

The effects of physical activity on executive function in children with attention-deficit/hyperactivity disorder: A systematic review and meta-analysis protocol.

BACKGROUND: The effects of physical activity on executive function are well documented, but whether physical activity contributes to the executive function of attention deficit hyperactivity disorder (ADHD) children are still inconclusive. METHODS: The study is guided by the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will search the following databases PubMed, EMBASES, the Cochrane Library, CNKI, and Wanfang-Data to identify the Randomized Controlled Trials evaluating the effects of physical activity on executive function among ADHD children. The language of literature restricted in Chinese and English, which published from inception to January 2019. Two reviewers will screen the studies independently, while risk of bias assessment, data extraction, and inconsistent results will be discussed by the third reviewer. Revman 5.3 and Stata 12 software will be used to complete data analysis and synthesis. CONCLUSION: This study will be based on findings of previous studies, thus the ethics approval is not required. The final results will be presented at an international conference and submitted to a peer-reviewed journal of relative field for consideration of publication. PROSPERO REGISTRATION NUMBER: CRD42019118622.

Size-Dependent Reactivity of Nano-Sized Neutral Manganese Oxide Clusters toward Ethylene.

Neutral manganese oxide clusters with the general composition Mn2 N O3 N+x (N=2-22; x=-1, 0, 1) with dimensions up to a nanosize were prepared by laser ablation and reacted with C2 H4 in a fast flow reactor. The size-dependent reactivity of C2 H4 adsorption on these clusters was experimentally identified and the adsorption reactivity decreases generally with an increase of the cluster size. Density functional theory calculations were performed to study the geometrical and electronic structures of the Mn2 N O3 N (N=1-6) clusters. The calculated results indicated that the coordination number and the charge distribution of the metal centers are responsible for the experimentally observed size-dependent reactivity. The highly charged Mn atoms with low coordination are preferential to adsorb C2 H4 . In contrast, the neutral manganese oxide clusters are completely inert toward the saturated hydrocarbon molecule C2 H6 . This work provides new perspectives to design related materials in the separation of hydrocarbon molecules.

Does Each Atom Count in the Reactivity of Vanadia Nanoclusters?

Vanadium oxide cluster anions (V2O5)nVxOy- (n = 1-31; x = 0, 1; and x + y ≤ 5) with different oxygen deficiencies (Δ = 2y-1-5x = 0, ± 1, and ±2) have been prepared by laser ablation and reacted to abstract hydrogen atoms from alkane molecules (n-butane) in a fast flow reactor. When the cluster size n is less than 25, the Δ = 1 series [(V2O5)nO- clusters] that can contain atomic oxygen radical anions (O•-) generally have much higher reactivity than the other four cluster series (Δ = -2, -1, 0, and 2), indicating that each atom counts in the hydrogen-atom abstraction (HAA) reactivity. Unexpectedly, all of the five cluster series have similar HAA reactivity when the cluster size is greater than 25. The critical dimension of vanadia particles separating the cluster behavior (each atom counts) from the bulk behavior (each atom contributes a little part) is thus about 1.6 nm (∼V50O125). The strong electron-phonon coupling of the vanadia particles has been proposed to create the O•- radicals (V5+ = O2-+ heat → V4+-O•-) for the n > 25 clusters with Δ = -2, -1, 0, and 2. Such a mechanism is supported by a comparative study with the scandium system [(Sc2O3)nScxOy- (n = 1-29; x = 0, 1; and x + y ≤ 4)] for which the Δ = 1 series [(Sc2O3)nO- clusters] always have much higher HAA reactivity than the other cluster series.

Gas-Phase Reactions of Atomic Gold Cations with Linear Alkanes (C2-C9).

To develop proper ionization methods for alkanes, the reactivity of bare or ligated transition metal ions toward alkanes has attracted increasing interests. In this study, the reactions of the gold cations with linear alkanes from ethane up to nonane (CnH2n+2, n = 2-9) under mild conditions have been characterized by mass spectrometry and density functional theory calculations. When reacting with Au(+), small alkanes (n = 2-6) were confirmed to follow specific reaction channels of dehydrogenation for ethane and hydride transfer for others to generate product ions characteristic of the original alkanes, which indicates that Au(+) can act as a reagent ion to ionize alkanes from ethane to n-hexane. Strong dependence of the chain length of alkanes was observed for the rate constants and reaction efficiencies. Extensive fragmentation took place for larger alkanes (n > 6). Theoretical results show that the fragmentation induced by the hydride transfer occurs after the release of AuH. Moreover, the fragmentation of n-heptane was successfully avoided when the reaction took place in a high-pressure reactor. This implies that Au(+) is a potential reagent ion to ionize linear and even the branched alkanes.

Reactions of metal cluster anions with inorganic and organic molecules in the gas phase.

The study of gas phase ion-molecule reactions by state-of-the-art mass spectrometric experiments in conjunction with quantum chemistry calculations offers an opportunity to clarify the elementary steps and mechanistic details of bond activation and conversion processes. In the past few decades, a considerable number of publications have been devoted to the ion-molecule reactions of metal clusters, the experimentally and theoretically tractable models for the active phase of condensed phase systems. The focus of this perspective concerns progress on activation and transformation of important inorganic and organic molecules by negatively charged metal clusters. The metal cluster anions cover bare metal clusters as well as ligated systems with oxygen, carbon, and nitrogen, among others. The following important issues have been summarized and discussed: (i) dependence of chemical reactivity and selectivity on cluster structures and sizes, metals and metal oxidation states, odd-even electron numbers, etc. and (ii) effects of doping, ligation, and pre-adsorption on the reactivity of metal clusters toward rather inert molecules.

Janus kinase/signal transducer and activator of transcription inhibitors enhance the protective effect mediated by tanshinone IIA from hypoxic/ischemic injury in cardiac myocytes.

Tanshinone IIA is a lipophilic abietane diterpene compound, which exhibits protective effects against ischaemia/reperfusion injury; however, the pathways responsible for the myocardial protective activities of tanshinone IIA remain to be elucidated. The aim of the present study was to investigate the effect of tanshinone IIA on the Janus­activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which is associated with cardiac dysfunction during ischemia/reperfusion. The results demonstrated that tanshinone IIA protected myocardial cells from hypoxia/ischemia­induced injury in vitro and recovered decreased cell viability due to activation of the JAK2/STAT3 pathway, with 10 µM tanshinone IIA exhibiting the most potent protective effects. Flow cytometric analysis revealed that tanshinone IIA reversed the apoptotic aggravation induced by JAK2/STAT3 inhibitors following hypoxic ischemia. However, JAK2 inhibitors promoted the myocardial protective effect of tanshinone IIA from hypoxic­ischemic injury. Furthermore, tanshinone IIA and JAK2/STAT3 inhibitors in combination augmented the protection of myocardial cells from apoptosis induced by ischemia/reperfusion preconditioning in vivo. In conclusion, the results of the present study indicated that JAK2/STAT3 inhibitors may enhance the protective effect of tanshinone IIA on cardiac myocytes from hypoxic ischemia-induced injury, therefore suggesting that JAK2/STAT3 inhibitors may have a potential application in combination therapies with tanshinone IIA.

[Temporal and Spatial Distribution Characteristics of Dissolved Organic Matter and Influencing Factors in Lake Chaohu].

To study the temporal and spatial distribution of dissolved organic matter (DOM) and the related influencing factors of Lake Chaohu, surface water samples were collected at seventeen sites in three different regions of the Lake from April 2013 to April 2014. The concentration of dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) were then analyzed. A significance difference in DON concentration was observed among the sampling sites (P <0. 01, n = 13), which was caused by the terrestrial input from the western rivers and the bioavailability of DON. The ratio of total nitrogen to total phosphorus, total dissolved nitrogen to total dissolved phosphorus, and dissolved inorganic nitrogen to soluble reactive phosphorus (DIN/SRP) declined gradually during the phytoplankton bloom period, especially the ratio of DIN/SRP dropped to 5 ± 7 in August 2013, indicating the nitrogen was limited in lake water. Moreover, the concentration of DON was decreased and a significant negative correlation was observed between DON and Chl-a (r = - 0. 265, P < 0. 05, n = 91), suggesting that DON is bioavailable, and can be utilized by phytoplankton directly or indirectly during nitrogen limitation. No significant difference in DOC concentration was observed and water temperature was the major factor related to the variation of DOC. Chl-a and nitrate concentrations can also affect the dynamics of DOC. In addition, the ratio of DOC/DON was considerably varied, the concentration of DON contributed to the variation of DOC/DON, and DON was the major component contributed to the bioavailability of DOM.

Sodium tanshinone IIA sulfonate protects rat myocardium against ischemia-reperfusion injury via activation of PI3K/Akt/FOXO3A/Bim pathway.

AIM: To investigate the mechanisms underlying the protective effects of sodium tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat myocardial injury model. METHODS: Male SD rats were iv injected with STS, STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining, DNA laddering and measuring caspase-3 activity. In addition, isolated cardiomyocytes of neonatal rats were pretreated with the above drugs, then exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with immunoblotting. RESULTS: Compared to NS group, administration of STS (20 mg/kg) significantly reduced myocardial infarct size (40.28%±5.36% in STS group vs 59.52%±7.28% in NS group), and improved the myocardial function as demonstrated by the increased values of dp/dtmax, LVDP and coronary flow at different reperfusion time stages. Furthermore, STS significantly decreased the rate of apoptotic cells (15.11%±3.71% in STS group vs 38.21%±7.83% in NS group), and reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS significantly increased the phosphorylation of Akt and its downstream target FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects induced by STS treatment. In isolated cardiomyocytes, STS exerted similar protective effects as shown in the ex vivo I/R model. CONCLUSION: STS pretreatment reduces infarct size and improves cardiac function in an I/R-induced rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal pathway.

Glycyrrhizin protects rat heart against ischemia-reperfusion injury through blockade of HMGB1-dependent phospho-JNK/Bax pathway.

AIM: Glycyrrhizin (GL) has been found to inhibit extracellular HMGB1 cytokine's activity, and protect spinal cord, liver and brain against I/R-induced injury in experimental animals. The purpose of this study was to investigate the protective effect of GL in rat myocardial I/R-induced injury and to elucidate the underlying mechanisms. METHODS: Male adult Sprague-Dawley rats underwent a 30-min left coronary artery occlusion followed by a 24-h reperfusion. The rats were treated with glycyrrhizin or glycyrrhizin plus recombinant HMGB1 after 30 min of ischemia and before reperfusion. Serum HMGB1, TNF-α and IL-6 levels, and hemodynamic parameters were measured at the onset and different time points of reperfusion. At the end of the experiment, the heart was excised, and the infarct size and histological changes were examined. The levels of Bcl2, Bax and cytochrome c, as well as phospho-ERK1/2, phospho-JNK and phospho-P38 in the heart tissue were evaluated using Western blot analysis, and myocardial caspase-3 activity was measured colorimetrically using BD pharmingen caspase 3 assay kit. RESULTS: Intravenous administration of GL (10 mg/kg) significantly reduced the infarct size, but did not change the hemodynamic parameters at different time points during reperfusion. GL significantly decreased the levels of serum HMGB1, TNF-α and IL-6. GL changed the distribution of Bax and cytochrome c expression between the mitochondrial and cytosolic fractions in the heart tissue, resulting in inhibition of myocardial apoptosis. Moreover, expression of phospho-JNK, but not ERK1/2 and P38 was decreased by GL in the heart tissue. All of the effects produced by GL treatment were reversed by co-administration with the recombinant HMGB1 (100 µg). Intravenous administration of SP600125, a selective phospho-JNK inhibitor (0.5 mg/kg), attenuated HMGB1-dependent Bax translocation and the subsequent apoptosis. CONCLUSION: These results demonstrate that GL alleviates rat myocardial I/R-induced injury via directly inhibiting extracellular HMGB1 cytokine activity and blocking the phospho-JNK/Bax pathway.