Ag-doped non-imperfection-enabled uniform memristive neuromorphic device based on van der Waals indium phosphorus sulfide.

Memristors are considered promising energy-efficient artificial intelligence hardware, which can eliminate the von Neumann bottleneck by parallel in-memory computing. The common imperfection-enabled memristors are plagued with critical variability issues impeding their commercialization. Reported approaches to reduce the variability usually sacrifice other performances, e.g., small on/off ratios and high operation currents. Here, we demonstrate an unconventional Ag-doped nonimperfection diffusion channel-enabled memristor in van der Waals indium phosphorus sulfide, which can combine ultralow variabilities with desirable metrics. We achieve operation voltage, resistance, and on/off ratio variations down to 3.8, 2.3, and 6.9% at their extreme values of 0.2 V, 1011 ohms, and 108, respectively. Meanwhile, the operation current can be pushed from 1 nA to 1 pA at the scalability limit of 6 nm after Ag doping. Fourteen Boolean logic functions and convolutional image processing are successfully implemented by the memristors, manifesting the potential for logic-in-memory devices and efficient non-von Neumann accelerators.

MWCNTs-GNPs Reinforced TPU Composites with Thermal and Electrical Conductivity: Low-Temperature Controlled DIW Forming.

As an effective technique for fabricating conductive and thermally conductive polymer composites, a multi-filler system incorporates different types and sizes of multiple fillers to form interconnected networks with improved electrical, thermal, and processing properties. In this study, DIW forming of bifunctional composites was achieved by controlling the temperature of the printing platform. The study was based on enhancing the thermal and electrical transport properties of hybrid ternary polymer nanocomposites with multi-walled carbon nanotubes (MWCNTs) and graphene nanoplates (GNPs). With thermoplastic polyurethane (TPU) used as the matrix, the addition of MWCNTs, GNPs and both mixtures further improved the thermal conductivity of the elastomers. By adjusting the weight fraction of the functional fillers (MWCNTs and GNPs), the thermal and electrical properties were gradually explored. Here, the thermal conductivity of the polymer composites increased nearly sevenfold (from 0.36 W·m-1·k-1 to 2.87 W·m-1·k-1) and the electrical conductivity increased up to 5.49 × 10-2 S·m-1. It is expected to be used in the field of electronic packaging and environmental thermal dissipation, especially for modern electronic industrial equipment.

Interface-Modulated Resistive Switching in Mo-Irradiated ReS2 for Neuromorphic Computing.

Coupling charge impurity scattering effects and charge-carrier modulation by doping can offer intriguing opportunities for atomic-level control of resistive switching (RS). Nonetheless, such effects have remained unexplored for memristive applications based on 2D materials. Here a facile approach is reported to transform an RS-inactive rhenium disulfide (ReS2 ) into an effective switching material through interfacial modulation induced by molybdenum-irradiation (Mo-i) doping. Using ReS2 as a model system, this study unveils a unique RS mechanism based on the formation/dissolution of metallic ß-ReO2 filament across the defective ReS2 interface during the set/reset process. Through simple interfacial modulation, ReS2 of various thicknesses are switchable by modulating the Mo-irradiation period. Besides, the Mo-irradiated ReS2 (Mo-ReS2 ) memristor further exhibits a bipolar non-volatile switching ratio of nearly two orders of magnitude, programmable multilevel resistance states, and long-term synaptic plasticity. Additionally, the fabricated device can achieve a high MNIST learning accuracy of 91% under a non-identical pulse train. The study's findings demonstrate the potential for modulating RS in RS-inactive 2D materials via the unique doping-induced charged impurity scattering property.

In-Memory Computing using Memristor Arrays with Ultrathin 2D PdSeOx /PdSe2 Heterostructure.

In-memory computing based on memristor arrays holds promise to address the speed and energy issues of the classical von Neumann computing system. However, the stochasticity of ions' transport in conventional oxide-based memristors imposes severe intrinsic variability, which compromises learning accuracy and hinders the implementation of neural network hardware accelerators. Here, these challenges are addressed using a low-voltage memristor array based on an ultrathin PdSeOx /PdSe2 heterostructure switching medium realized by a controllable ultraviolet (UV)-ozone treatment. A distinctively different ions' transport mechanism is revealed in the heterostructure that can confine the formation of conductive filaments, leading to a remarkable uniform switching with low set and reset voltage variability values of 4.8% and -3.6%, respectively. Moreover, convolutional image processing is further implemented using various crossbar kernels that achieve a high recognition accuracy of ≈93.4% due to the highly linear and symmetric analog weight update as well as multiple conductance states, manifesting its potential beyond von Neumann computing.

Wafer-Scale 2D Hafnium Diselenide Based Memristor Crossbar Array for Energy-Efficient Neural Network Hardware.

Memristor crossbar with programmable conductance could overcome the energy consumption and speed limitations of neural networks when executing core computing tasks in image processing. However, the implementation of crossbar array (CBA) based on ultrathin 2D materials is hindered by challenges associated with large-scale material synthesis and device integration. Here, a memristor CBA is demonstrated using wafer-scale (2-inch) polycrystalline hafnium diselenide (HfSe2 ) grown by molecular beam epitaxy, and a metal-assisted van der Waals transfer technique. The memristor exhibits small switching voltage (0.6 V), low switching energy (0.82 pJ), and simultaneously achieves emulation of synaptic weight plasticity. Furthermore, the CBA enables artificial neural network with a high recognition accuracy of 93.34%. Hardware multiply-and-accumulate (MAC) operation with a narrow error distribution of 0.29% is also demonstrated, and a high power efficiency of greater than 8-trillion operations per second per Watt is achieved. Based on the MAC results, hardware convolution image processing can be performed using programmable kernels (i.e., soft, horizontal, and vertical edge enhancement), which constitutes a vital function for neural network hardware.

Preliminary clinical study of the safety of hepatectomy predicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced T1 mapping magnetic resonance imaging.

BACKGROUND AND AIM: Studies have found that gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced T1 mapping magnetic resonance imaging (MRI) could assess liver fibrosis, cirrhosis, and function with high effectiveness. The aim of this study is to explore the efficacy of MRI in predicting the safety of hepatectomy. METHODS: Forty-nine patients who underwent liver resection were recruited. Gd-EOB-DTPA-enhanced MRI examination was performed 1 week before surgery, and the rate of T1 relaxation time reduction (ΔT120min%) of liver parenchyma was calculated. Posthepatectomy liver failure (PHLF) was defined by the "50-50 criteria" and International Study Group of Liver Surgery (ISGLS) classification, respectively, and posthepatectomy complications (PHC) were defined by the Clavien-Dindo grading system. The effectiveness of ΔT120min% in predicting the occurrence of PHLF and PHC was analyzed. RESULTS: The area under the curve (AUC) for ΔT120min% predicting PHLF meeting "50-50 criteria" was 0.957, with a cutoff value of 0.497, sensitivity of 100%, and specificity of 89.1%. The AUC for predicting ISGLS grade B/C (severe) PHLF was 0.84, with a cutoff value of 0.5232, sensitivity of 63.6%, and specificity of 92.6%. The AUC for predicting PHC of Clavien-Dindo grades 3-5 (severe) was 0.882, with a cutoff value of 0.5646, sensitivity of 87.5%, and specificity of 75.8%. Univariate and multivariate analyses showed that ΔT120min% < 0.4970 (P < 0.01) was an independent risk factor for the development of PHLF (50-50 criteria). Univariate and multivariate analyses showed that liver stiffness measurement and ΔT120min% were risk factors for severe PHLF and severe PHC. CONCLUSIONS: Gd-EOB-DTPA-enhanced T1 mapping MRI accurately predicts the safety of hepatectomy.

Elbaite catalyze peroxymonosulfate for advanced oxidation of organic pollutants: Hydroxyl groups induced generation of reactive oxygen species.

In this work, the abundant, low-cost, innocuous, and chemically stable elbaite (a type of tourmaline) was employed to catalyze peroxymonosulfate (PMS) for wastewater purification by using methylene blue (MB) as one of the target pollutants. The results revealed that PMS could be catalyzed by elbaite within broad pH range (i.e., 2.9-10.7) and with low activation energy (i.e., 18.6 kJ/mol). Complete MB degradation was obtained within 15 min under the optimized conditions: [elbaite]0 = 1.00 g/L, [PMS]0 = 0.50 g/L, initial solution pH = 2.9. MB degradation (%) sustained 99.9 % after five successive catalytic reactions, indicating good durability and long-term stability. In addition, the complete degradation of doxycycline hydrochloride (DOX) and bisphenol A (BPA) further confirmed the degradation activity of the PMS/elbaite system. PMS interacted with elbaite via replacing the surface-bonded and structural OH groups of elbaite with its OH groups to bond with YLiYAlYR and YLiZAlZR cations (R = Al, Li, Fe, Mg, Mn, Cr, V), which offered channels for electron transfer from negatively charged elbaite to PMS, leading to the activation of PMS. Thus, elbaite is found to be promising for catalyzing PMS to treat organic wastewater.

Synthesis and enhanced photocatalytic performance of 0D/2D CuO/tourmaline composite photocatalysts.

Photocatalysis is considered to be a green and promising technology for transforming organic contaminants into nontoxic products. In this work, a CuO/tourmaline composite with zero-dimensional/two-dimensional (0D/2D) CuO architecture was successfully obtained via a facile hydrothermal process, and its photocatalytic activity was evaluated by the degradation of methylene blue (MB). Surface element valence state and molecular vibration characterization revealed that CuO chemically interacted with tourmaline via Si-O-Cu bonds. The specific surface area of the CuO/tourmaline composite (23.60 m2 g-1) was larger than that of the pristine CuO sample (3.41 m2 g-1). The CuO/tourmaline composite exhibited excellent photocatalytic activity for the degradation of MB, which was ascribed to the increase in the quantity of the adsorption-photoreactive sites and the efficient utilization of the photoinduced charge carriers. This study provides a facile strategy for the construction of 0D/2D CuO structures and the design of tourmaline-based functional composite photocatalysts for the treatment of organic contaminants in water.

Carbon-Nanomaterial-Based Flexible Batteries for Wearable Electronics.

Wearable electronics have received considerable attention in recent years. These devices have penetrated every aspect of our daily lives and stimulated interest in futuristic electronics. Thus, flexible batteries that can be bent or folded are desperately needed, and their electrochemical functions should be maintained stably under the deformation states, given the increasing demands for wearable electronics. Carbon nanomaterials, such as carbon nanotubes, graphene, and/or their composites, as flexible materials exhibit excellent properties that make them suitable for use in flexible batteries. Herein, the most recent progress on flexible batteries using carbon nanomaterials is discussed from the viewpoint of materials fabrication, structure design, and property optimization. Based on the current progress, the existing advantages, challenges, and prospects are outlined and highlighted.

Long Stress Induced Non-Coding Transcripts 5 (LSINCT5) Promotes Hepatocellular Carcinoma Progression Through Interaction with High-Mobility Group AT-hook 2 and MiR-4516.

BACKGROUND Long non-coding RNAs (lncRNAs) have been implicated in various human cancer types. However, the underlying mechanisms involved in hepatocellular carcinoma (HCC) progression remain poorly understood. MATERIAL AND METHODS In this study, lncRNA array was used to identify HCC related lncRNAs. RNA immunoprecipitation (RIP) followed mass spectrometry was used to explore lncRNA binding proteins. Western blot, quantitative PCR, tumor sphere formation, migration and viability assay were performed to evaluate the oncogenic role of lncRNAs. RESULTS We identified a novel lncRNA named long stress induced non-coding transcripts 5 (LSINCT5) which facilitates HCC progression. LSINCT5 was significantly upregulated in both HCC specimens and cell lines and correlates with poor survival. In vitro experiments showed that LSINCT5 promoted migration and viability of HepG2 and Huh7 cells. The in vivo xenograft mouse model also confirmed an oncogenic role for LSINCT5. RIP in combination with mass spectrometry identified HMGA2 as the LSINCT5 binding partner. LSINCT5 could bind to HMGA2 and decrease proteasome-mediated HMGA2 degradation leading to EMT activation. LSINCT5 also served as a competing endogenous RNA (ceRNA) for miR-4516, resulting in increased STAT3/BclxL expression and attenuated apoptosis. CONCLUSIONS Our data have collectively established a lncRNA LSINCT5 mediated process during HCC carcinogenesis and might have provided novel insight into therapeutic targeting.

Protective effect of electro-acupuncture on liver ischemia-reperfusion injury in rats.

Liver ischemia-reperfusion injury is an important clinical complication in which excessive inflammation is a key factor; however, few studies have provided effective means of its regulation. As previous studies suggested that electro-acupuncture (EA) is able control excessive inflammation, the present study aimed to explore its effects on liver ischemia-reperfusion injury in experimental rats. The animals were randomly divided into surgery and sham groups, which were further divided into four sub-groups, including a non-treatment (NT), a non-point acupuncture (NPA), the non-selective nicotinic acetylcholine receptor (AChR) agonist 1,1-dimethyl-4-phenyl L-pioperazinium iodide (DMPPI) and an EA group. The alanine aminotransferase (ALT), serum cytokine and myeloperoxidase (MP) levels and the tissue pathology were evaluated after 90 min of ischemia followed by a 4, 8 or 24 h reperfusion. The results demonstrated that EA and DMPPI suppressed serum ALT elevation at 4 and 8 h reperfusion, whereas NPA did not. I/R induced hepatocellular necrosis, and cytoplasmic vacuolization and sinusoidal congestion was ameliorated by EA treatment after an 8 and 24 h reperfusion. In addition, EA also inhibited liver neutrophil accumulation, evidenced by a decreased MPO level at 8 h reperfusion. EA also suppressed the release of serum inflammatory factors TNF-α and IL-6 for the duration of reperfusion. However, little influence on IL-10 was observed. Mechanistically, vagus block by subphrenic vagotomy or mecamylamine hydrochloride abolished EA effect on liver damage, neutrophil accumulation and inflammatory factor release. In conclusion, it was demonstrated that EA protects the liver against I/R induced injury by inhibiting the inflammatory response, which is associated with the vagus.

Nonsteroidal anti-inflammatory drugs, especially aspirin, are linked to lower risk and better survival of hepatocellular carcinoma: a meta-analysis.

OBJECTIVE: The roles of nonsteroidal anti-inflammatory drugs (NSAIDs) in the occurrence and prognosis of hepatocellular carcinoma (HCC) remain controversial. This analysis aimed to summarize the relationships between NSAIDs and HCC development. METHODS: Studies published prior to October 1, 2017, in the PubMed, Embase, Ovid, Web of Science, and Cochrane Library databases were systematically searched and analyzed. RESULTS: Eleven studies were included in this analysis. A meta-analysis of five studies revealed that aspirin use could significantly decrease the risk of HCC occurrence (hazards ratio [HR] = 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.014). No significant difference was found for the use of NSAIDs (six studies) and non-aspirin NSAIDs (three studies) in HCC occurrence (HR = 0.74, 95%CI = 0.53-1.02, P = 0.064 and HR = 0.98, 95%CI = 0.87-1.12, P = 0.81, respectively). However, subgroup analysis of cohort studies demonstrated that NSAIDs significantly decreased the risk of HCC occurrence (HR = 0.58, 95%CI = 0.43-0.78, P < 0.001). HCC patients who received NSAIDs achieved better disease-free survival and overall survival compared with the non-NSAID users (HR = 0.79, 95%CI = 0.74-0.84, P<0.001 and HR = 0.60, 95%CI = 0.50-0.72, P<0.001, respectively). Additionally, a meta-analysis of two studies showed that aspirin treatment in HCC patients could significantly decrease the 2-year and 4-year mortalities (rate ratio [RR] = 0.50, 95%CI = 0.36-0.69, P < 0.001 and RR = 0.67, 95%CI = 0.45-0.998, P = 0.049, respectively). A meta-analysis of two studies showed that aspirin use was not associated with a higher risk of bleeding in HCC patients (HR = 0.71, 95%CI = 0.41-1.23, P = 0.223). CONCLUSION: The use of NSAIDs, especially aspirin, is linked to a lower risk of HCC development and better survival in HCC populations. High-quality, well-designed trials should be conducted to reevaluate the relationships between NSAIDs and HCC.

Metabolic syndrome relates to high risk in hepatocellular carcinoma: a meta-analysis.

Metabolic syndrome (MetS) has been linked to the development of cancer. The relationship between MetS and hepatocellular carcinoma (HCC) remains controversial. Studies up to September 2017 of MetS and HCC were systematically identified and meta-analyzed. Ten studies (nine cohorts and one case-control) were included in this meta-analysis. It was found that MetS patients are significantly more likely to develop HCC (RR = 1.60, 95%CI = 1.12-2.28, P = 0.01). Additionally, when only cohort studies were included, MetS is a potential risk factor for HCC occurrence (RR = 1.52, 95%CI = 1.01-2.30, P = 0.05). Interestingly, subgroup analysis showed that male patients with MetS are more likely to develop HCC compared with female patients (RR = 1.91, 95%CI = 1.38-2.65, P < 0.0001 in male and RR = 2.1, 95%CI = 0.69-6.37, P = 0.19 in female). Additionally, MetS could significantly increase the risk of HCC in the Euro-US population (RR = 1.71, 95%CI = 1.09-2.67, P = 0.02). In conclusion, metabolic syndrome might be associated with a high risk of HCC occurrence, especially in male and the Euro-US population. However, no statistical significances were found between MetS and HCC clinicopathological features including capsule, vascular invasion, and moderate-poor differentiation, and between MetS and HCC survivals. Prospectively, well-designed trials with large numbers of samples should be conducted to evaluate the links between MetS and HCC.

Effect and safety of dual anti-human epidermal growth factor receptor 2 therapy compared to monotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer: a systematic review.

BACKGROUND: Dual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. We undertook a systematic review to compare treatment outcomes for patients who received single or combined anti-HER2 therapies. METHODS: We identified randomized control trials that compared dual anti-HER2 therapy and anti-HER2 monotherapy in patients with HER2-positive breast cancer. Outcomes included pathologic complete response (pCR), overall survival (OS), progression-free survival (PFS), and adverse events. Included in the analysis were seven trials that recruited 2,609 patients. RESULTS: In the neoadjuvant setting, the pooled pCR rate in the dual anti-HER2 therapy and monotherapy groups in combination with chemotherapy was 54.8% and 36%, respectively. This difference was statistically significant (relative risk, 1.56; 95% confidence interval (CI), 1.23-1.97; p < 0.001). In the metastatic setting, dual anti-HER2 therapy demonstrated significant benefits in both PFS (hazard ratio (HR), 0.71; 95% CI, 0.62-0.81; p < 0.001) and OS (HR, 0.68; 95% CI, 0.57-0.82; p < 0.001). Subgroup analyses indicated that the addition of chemotherapy to dual anti-HER2 therapy could greatly improve pCR in the neoadjuvant settings. However, in the metastatic setting, similar PFS and OS were found in patients receiving dual anti-HER2 therapy with or without chemotherapy. Dual anti-HER2 therapy was associated with more frequent adverse events than monotherapy, but no statistical differences were observed in cardiac toxicity. CONCLUSIONS: This systematic review provides a summary of all the data currently available, and confirms the benefits and risks of dual anti-HER2 therapy for HER2-positive breast cancer.

Risk of treatment-related mortality with sorafenib in patients with cancer.

BACKGROUND: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. METHODS: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. RESULTS: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). CONCLUSIONS: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

Bevacizumab attenuates hepatic fibrosis in rats by inhibiting activation of hepatic stellate cells.

Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-ß1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.

Combined EGFR and VEGFR versus single EGFR signaling pathways inhibition therapy for NSCLC: a systematic review and meta-analysis.

BACKGROUND: Lung cancer is a heterogeneous disease with multiple signaling pathways influencing tumor cell survival and proliferation, and it is likely that blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Whether combined inhibition therapy has greater anti-tumor activity than single inhibition therapy is a matter of debate. Hence, a meta-analysis comparing therapy inhibiting both VEGFR and EGFR signaling pathways with that inhibiting EGFR signaling pathway alone was performed. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EMBASE database and the proceedings of major conferences for relevant clinical trials. Outcomes analyzed were objective tumor response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Besides, subgroup analyses were performed to investigate whether the combined inhibition therapy is best performed using combination of selective agents or a single agent with multiple targets. Six trials recruiting 3,302 patients were included in the analysis. Combined inhibition therapy was associated with a 3% improvement in OS as compared with single-targeted therapy, but this difference was not statistically significant (HR, 0.97; 95% CI, 0.89-1.05; P=0.472). Patients receiving combined inhibition therapy had significant longer PFS than the group with single-targeted therapy (HR, 0.80; 95% CI, 0.67-0.95; P=0.011). There was no difference in the ORR between the groups (OR, 1.44; 95% CI, 0.95-2.18; P=0.085). Subgroup analysis revealed that combined inhibition therapy using combination regimens was associated with statistically significant improvement in both ORR and PFS. Toxicity was greater in combined inhibition therapy. CONCLUSIONS: There is no evidence to support the use of combined inhibition therapy in unselected patients with advanced NSCLC. However, given the significant advantage in ORR and PFS, combined inhibition therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.

Electroacupuncture improves survival in rats with lethal endotoxemia via the autonomic nervous system.

BACKGROUND: Recent advances have indicated a complex interplay between the autonomic nervous system and the innate immune system. Targeting neural networks for the treatment of sepsis is being developed as a therapeutic strategy. Because electroacupuncture at select acupoints can modulate activities of the autonomic nervous system, we tested the hypothesis that electroacupuncture at specific acupoints could modulate systemic inflammatory responses and improve survival via its impact on the autonomic nervous system in a rat model of sepsis. METHODS: Sprague-Dawley male rats received electroacupuncture for 45 min before and at 1, 2, or 4 h after a lethal dose of intraperitoneal lipopolysaccharide injection (6 mg/kg). Outcomes included survival and systemic cytokine responses. Also, the possible roles of neural circuitry, including the hypothalamic-pituitary-adrenal axis and the autonomic nervous system, were evaluated. RESULTS: Electroacupuncture pretreatment at the Hegu acupoints significantly attenuate systemic inflammatory responses and improve survival rate from 20% to 80% in rats with lethal endotoxemia. Such a site-specific effect requires the activation of muscarinic receptors in the central nervous system, but not increasing central sympathetic tone. In the periphery synergistic, rather than independent, action of the sympathetic and parasympathetic systems is also necessary. CONCLUSIONS: Electroacupuncture pretreatment has a dramatic survival-enhancing effect in rats with lethal endotoxemia, which involves the activation of efferent neural circuits of the autonomic nervous system (e.g., cholinergic antiinflammatory pathway). This approach could be developed as a prophylactic treatment for sepsis or perioperative conditions related to excessive inflammation.

Decreased hepatic peroxisome proliferator-activated receptor-γ contributes to increased sensitivity to endotoxin in obstructive jaundice.

AIM: To investigate the role of hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) in increased susceptibility to endotoxin-induced toxicity in rats with bile duct ligation during endotoxemia. METHODS: Male Sprague-Dawley rats were subjected to bile duct ligation (BDL). Sham-operated animals served as controls. DNA binding were determined by polymerase chain reaction, Western blotting analysis, and electrophoretic mobility shift assay, respectively. BDL and sham-operated rats received a non-lethal dose of intraperitoneal lipopolysaccharide (LPS) injection (3 mg/kg, i.p.). Additionally, the potential beneficial effects of the PPAR-γ agonist rosiglitazone were determined in BDL and sham-operated rats treated with a non-lethal dose of LPS. Survival was assessed in BDL rats treated with a non-lethal dose of LPS and in sham-operated rats treated at a lethal dose of LPS (6 mg/kg, i.p.). RESULTS: PPAR-γ activity in rats undergoing BDL was significantly lower than in the sham-controls. Hepatic PPAR-γ gene expression was downregulated at both the mRNA and protein levels. In a parallel group, serum levels of pro-inflammatory cytokines were nearly undetectable in the sham-operated rats. When challenged with a non-lethal dose of LPS (3 mg/kg), the BDL rats had approximately a 2.4-fold increase in serum IL-6, a 2.7 fold increase in serum TNF-α, 2.2-fold increase in serum IL-1 and 4.2-fold increase in serum ALT. The survival rate was significantly lower as compared with that in sham-operated group. Additionally, rosiglitazone significantly reduced the concentration of TNF-α, IL-1ß, IL-6 and ALT in sham-operated rats, but not in BDL rats, in response to LPS (3 mg/kg). Also, the survival was improved by rosiglitazone in sham-operated rats challenged with a lethal dose of LPS, but not in BDL rats, even with a non-lethal dose of LPS (3 mg/kg). CONCLUSION: Obstructive jaundice downregulates hepatic PPAR-γ expression, which in turn may contribute to hypersensitivity towards endotoxin.