Combining Machine Learning and Molecular Dynamics to Predict Mechanical Properties and Microstructural Evolution of FeNiCrCoCu High-Entropy Alloys.

Compared with traditional alloys, high-entropy alloys have better mechanical properties and corrosion resistance. However, their mechanical properties and microstructural evolution behavior are unclear due to their complex composition. Machine learning has powerful data processing and analysis capabilities, that provides technical advantages for in-depth study of the mechanical properties of high-entropy alloys. Thus, we combined machine learning and molecular dynamics to predict the mechanical properties of FeNiCrCoCu high-entropy alloys. The optimal multiple linear regression machine learning algorithm predicts that the optimal composition is Fe33Ni32Cr11Co11Cu13 high-entropy alloy, with a tensile strength of 28.25 GPa. Furthermore, molecular dynamics is used to verify the predicted mechanical properties of high-entropy alloys, and it is found that the error between the tensile strength predicted by machine learning and the tensile strength obtained by molecular dynamics simulation is within 0.5%. Moreover, the tensile-compression asymmetry of Fe33Ni32Cr11Co11Cu13 high-entropy alloy increased with the increase of temperature and Cu content and the decrease of Fe content. This is due to the increase in stress caused by twinning during compression and the decrease in stress due to dislocation slip during stretching. Interestingly, high-entropy alloy coatings reduce the tensile-compression asymmetry of nickel; this is attributed to the reduced influence of dislocations and twinning at the interface between the high-entropy alloy and the nickel matrix.

Sevoflurane preconditioning improves neuroinflammation in cerebral ischemia/reperfusion induced rats through ROS-NLRP3 pathway.

AIM: We aimed to study the influence of sevoflurane on the nucleotide-binding domain and Leucine-rich repeat protein 3 (NLRP3) pathways in rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Sixty Sprague-Dawley rats were equally divided into five groups randomly: sham-operated, cerebral I/R, sevoflurane (Sevo), NLRP3 inhibitor-treated (MCC950), and sevoflurane and NLRP3 inducer-treated groups. Rats' neurological functions were assessed using Longa scoring after 24 h of reperfusion, after which they were sacrificed, and cerebral infarction area was determined by triphenyl tetrazolium chloride staining. Pathological changes in damaged portions were assessed using hematoxylin-eosin and Nissl staining, and cell apoptosis was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Interleukin 1 beta (IL-1ß), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18), malondialdehyde (MDA), and superoxide dismutase (SOD) levels in brain tissues were determined using enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) levels were analyzed using a ROS assay kit. Protein levels of NLRP3, caspase-1, and IL-1ß were determined by western blot. RESULTS: Neurological function scores, cerebral infarction areas, and neuronal apoptosis index were decreased in the Sevo and MCC950 groups than in the I/R group. IL-1ß, TNF-α, IL-6, IL-18, NLRP3, caspase-1, and IL-1ß levels decreased in the Sevo and MCC950 groups (p < 0.05). ROS and MDA levels increased, but SOD levels increased in the Sevo and MCC950 groups than in the I/R group. NLPR3-inducer nigericin eliminated the protective effects of sevoflurane on cerebral I/R injury in rats. CONCLUSION: Sevoflurane could alleviate cerebral I/R-induced brain damage by inhibiting the ROS-NLRP3 pathway.

Thermal batteries based on inverse barocaloric effects.

To harvest and reuse low-temperature waste heat, we propose and realize an emergent concept-barocaloric thermal batteries based on the large inverse barocaloric effect of ammonium thiocyanate (NH4SCN). Thermal charging is initialized upon pressurization through an order-to-disorder phase transition, and the discharging of 43 J g-1 takes place at depressurization, which is 11 times more than the input mechanical energy. The thermodynamic equilibrium nature of the pressure-restrained heat-carrying phase guarantees stable long-duration storage. The barocaloric thermal batteries reinforced by their solid microscopic mechanism are expected to substantially advance the ability to take advantage of waste heat.

Attenuation of the Bauschinger effect and enhancement of tension-compression asymmetry in single crystal aluminum by temperature.

Temperature has a great influence on the mechanical properties of nano-materials. The molecular dynamics method was used to study the effect of temperature on the tension-compression asymmetry and Bauschinger effect of nano single crystal aluminum (NSCA). The strain-hardening behavior of NSCA in the tensile plastic stage is significantly enhanced when the temperature is higher than 400 K. The plastic deformation mechanism of tensile loading shifts from slip blocking of dislocations in grains to dislocation nucleation. The degradation of the mechanical properties of NSCA under compressive loading increases gradually with the increase of temperature. Dislocation emission is limited under compressive loading. Nonetheless, plastic deformation may still be regulated by dislocation slip during severe plastic deformation stages and at elevated temperatures. Temperature enhancement can effectively promote the movement of pre-dislocations and eliminate residual stresses. A new microscopic insight into the temperature attenuated Bauschinger effect is provided. This study provides important theoretical guidance for a comprehensive and in-depth understanding of the high-temperature mechanical properties and microstructure evolution mechanism of NSCA.

Corrigendum: Propofol Protects Myocardium From Ischemia/Reperfusion Injury by Inhibiting Ferroptosis Through the AKT/p53 Signaling Pathway.

[This corrects the article DOI: 10.3389/fphar.2022.841410.].

Propofol Protects Myocardium From Ischemia/Reperfusion Injury by Inhibiting Ferroptosis Through the AKT/p53 Signaling Pathway.

The molecular mechanism underlying the protective role of propofol against myocardial ischemia/reperfusion (I/R) injury remains poorly understood. Previous studies have shown that ferroptosis is an imperative pathological process in myocardial I/R injury. We hypothesized that propofol prevents myocardial I/R injury by inhibiting ferroptosis via the AKT/p53 signaling pathway. The ferroptosis-inducing agent erastin (E) and AKT inhibitor MK2206 (MK) were used to investigate the role of propofol in myocardial I/R injury. H9C2 cells treated without any reagents, erastin for 24 h, propofol for 1 h before adding erastin were assigned as the control (C), E, and E + P group, respectively. Cell viability, reactive oxygen species (ROS), and the expression of antioxidant enzymes, including ferritin heavy chain 1 (FTH1), cysteine/glutamate transporter (XCT), and glutathione peroxidase 4 (GPX4) in H9C2 cells. Rat hearts from the I/R + P or I/R groups were treated with or without propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min. Rat hearts from the I/R + P + MK or I/R + MK groups were treated with or without propofol for 20 min, with a 10-min treatment of MK2206 before stopping perfusion. Myocardial histopathology, mitochondrial structure, iron levels, and antioxidant enzymes expression were assessed. Our results demonstrated that erastin increased H9C2 cell mortality and reduced the expression of antioxidant enzymes. I/R, which reduced the expression of antioxidant enzymes and increased iron or p53 (p < 0.05), boosted myocardium pathological and mitochondrion damage. Propofol inhibited these changes; however, the effects of propofol on I/R injury were antagonized by MK (p < 0.05). In addition, AKT siRNA inhibited the propofol-induced expression of antioxidant enzymes (p < 0.05). Our findings confirm that propofol protects myocardium from I/R injury by inhibiting ferroptosis via the AKT/p53 signal pathway.

Hybridly double-crosslinked carbon nanotube networks with combined strength and toughness via cooperative energy dissipation.

Although chemical crosslinking has been extensively explored to enhance the mechanical properties of network-type materials for structural and energy (electrochemical, thermal, etc.) applications, loading-induced energy dissipations usually occur through a single channel that either leads to network brittleness or low strength/stiffness. In this work, we apply coarse-grained molecular dynamics simulations to explore the potential of hybridly double-crosslinked carbon nanotube (CNT) networks as a light weight functional material with combined strength and toughness. While increasing the crosslinking density or strong crosslink composition may, in general, enhance the strength and toughness, further increasing the two parameters would surprisingly lead to deteriorated strength and toughness. We find that double-crosslinked networks can nicely achieve cooperative energy dissipation with minimal structural damage. In particular, the weak crosslinks serve as "sacrificial bonds" to dissipate elastic energies from external loading, while the strong crosslinks act as "structure holders" and break at a much later stage during the tensile test. Therefore, the combination of more than one type of crosslinking with hybrid potential energy landscapes and breaking time scales can prevent premature simultaneous breaking of multiple strong crosslinks. By deploying intermediate amounts of weak and strong crosslinks, we observe an outstanding density-normalized strength of 227-2130 kPa m3 kg-1 as compared to many structural materials and advanced nanocomposites. The crosslinking strategies developed here would pave new avenues for the rational design of functional network materials beyond CNTs, such as hydrogels, nanofibers, and nanocomposites.

Interaction of remimazolam benzenesulfonate and human serum albumin: a simulated physiological study.

Here, to elucidate the interaction mechanism and physicochemical properties of remimazolam and human serum albumin interactions, techniques such as fluorescence, circular dichroism (CD) spectroscopy, and isothermal titration calorimetry have been applied for study. The thermodynamic parameters at body temperature (ΔS = -207 J·mol-1 ·K-1 , ΔS = -9.76 × 104 J·mol-1 and ΔG = -3.34 × 104 J·mol-1 ; 310 K) manifests one strong binding site on the protein, which was modulated by van der Waals forces and hydrogen bonds. What is more, the results of CD, synchronous and three-dimensional fluorescence showed that remimazolam altered the microenvironment of the protein amino acid residues. A distance of 2.1 nm between the remimazolam and Trp shows the potential for resonance energy transfer. Furthermore, these results potentially provide information for illustrating the pharmacodynamics and toxicodynamics of remimazolam when it is applied clinically.

Ni/Ni3Al interface-dominated nanoindentation deformation and pop-in events.

Nickel-based single crystal alloys have excellent mechanical properties due to its unique two-phase structure and interface. Therefore, molecular dynamics methods were used to simulate nanoindentation and microstructural evolution. We found the indenter reaction force and hardness of the Ni3Al phase is the largest. The pop-in event in Ni3Al phase is more obvious than that in the Ni phase and Ni/Ni3Al phase. Because lots of dislocations in the Ni3Al phase break through the barrier of the interface and cut into the Ni phase, while dislocations in the Ni phase only slip inside the Ni phase. Moreover, we found that the position of the starting point of the adhesion force recovery is mainly related to the elastic recovery of the material. The stronger the elastic recovery of the phase, the smaller the depth value corresponding to the starting point of the recovery. We further studied the variation of potential energy with indentation depth and found that the change of wave trough of the load-displacement (P-h) curve is related to stacking fault energy. This study has important theoretical guiding significance for the in-depth understanding and engineering application of the mechanical properties of nickel-based single crystal alloys.

Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway.

Both hydrogen peroxide (H2O2, H) and ischemia/reperfusion (I/R) can damage cardiomyocytes, which was inhibited by propofol (P). The present research was designed to examine whether propofol can reduce myocardial I/R injury by activating protein kinase C (PKC)/nuclear factor erythroid-2-related factor 2 (NRF2) pathway in H9C2 cells and rat Langendorff models. H9C2 cells were disposed of no reagents (C), H2O2 for 24 h (H), propofol for 1 h before H2O2 (H+P), and chelerythrine (CHE, PKC inhibitor) for 1 h before propofol and H2O2 (H+P+CHE). N = 3. The PKC gene of H9C2 was knocked down by siRNA and overexpressed by phorbol 12-myristate 13-acetate (PMA, PKC agonist). The cell viability and the expressions of PKC, NRF2, or heme oxygenase-1(HO-1) were evaluated. Propofol significantly reduced H9C2 cell mortality induced by H2O2, and significantly increased NRF2 nuclear location and HO-1 expression, which were restrained by siRNA knockout of PKC and promoted by PMA. Rat hearts were treated with KrebsHenseleit solution for 120 min (C), with (I/R+P) or without (I/R) propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min, and CHE for 10 min before treated with propofol. N = 6. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and creatine kinase-MB (CK-MB) in perfusion fluid and antioxidant enzymes in the myocardium were assessed. I/R, which increased LDH and CK-MB expression and reduced SOD expression, boosted the pathological damage and infarcts of the myocardium after reperfusion. However, propofol restrained all these effects, an activity that was antagonized by CHE. The results suggest that propofol pretreatment protects against I/R injury by activating of PKC/NRF2 pathway.

The Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Catheter-Related Bladder Discomfort in Patients Undergoing Transurethral Resection of the Prostate.

BACKGROUND: Catheter-related bladder discomfort (CRBD), an extremely distressing complication secondary to an indwelling urinary catheterization, is frequently reported in patients with transurethral resection of the prostate (TURP), postoperatively. A prospective, randomized, controlled, double-blind study was designed to assess the efficacy of transcutaneous electrical acupoint stimulation (TEAS) as a treatment for CRBD in patients undergoing TURP. METHODS: Seventy benign prostatic hyperplasia male patients undergoing TURP under general anesthesia requiring intraoperative urinary catheterization were enrolled for the trial. An experienced acupuncturist performed TEAS for 30 minutes before general anesthesia with acupoints RN7, RN6, RN5, RN4, and RN3 and bilateral BL32, BL33, and BL34. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SPO2), body temperature (T), and blood samples were collected during the surgery. A series of assessments included the incidence and severity of CRBD, postoperative pain, nausea and vomiting, and physical and mental state measurements. RESULTS: The incidence of CRBD was significantly lower in TEAS group than in control group at the time T5 [9(26%) vs. 28(80%), P < 0.001], T9 [20(57%) vs. 28(80%), P=0.039], T11 [7(20%) vs. 31(89%), P < 0.001], and T12 [4(11%) vs. 7(20%), P=0.003]. The severity of CRBD was significantly lower in TEAS group than in control group at the time T5 [0 vs. 10 (29%), P < 0.001], T9 [2(6%) vs. 10(29%), P=0.011], and T11 [0 vs .9(26%), P=0.002]. The QoR-40 total score was higher in TEAS group at time T11 [191.7(4.4) vs. 189.1(4.3), P=0.007] and T12 [195.3(1.9) vs. 193.3(3.0), P < 0.001]. The postoperative analgesia requirement was higher in control group [5.0(2.9) vs. 3.8(1.9), P=0.045]. CONCLUSIONS: TEAS could significantly prevent the incidence and severity of CRBD, reduce the postoperative analgesic requirement in the early postoperative period, and promote the quality of early recovery in patients undergoing TURP.

Asymptomatic Patients with Airflow Limitation are at Higher Risk of Postoperative Pulmonary Complications After Lung Surgeries: An Ambispective Cohort Study.

PURPOSE: With the use of pulmonary function tests (PFTs) as a preoperative examination, it is not rare to screen out airflow limitation (AFL) in asymptomatic patients undergoing lung surgeries. This study aims to elucidate whether there is a difference in the prevalence and prognosis of postoperative pulmonary complications (PPCs) between asymptomatic patients with newly diagnosed AFL and the normal population undergoing lung surgeries. PATIENTS AND METHODS: The medical records of asymptomatic patients undergoing lung surgeries who were spirometrically diagnosed with AFL between January and October 2017 were collected in Qilu hospital. These patients were subsequently followed up until February 2021. The diagnosis of PPCs was based on a recommended consensus definition. The incidence of PPCs between the newly diagnosed AFL group and the normal group was compared and a propensity score-matched analysis (PSM) was performed. The survival analysis was performed to investigate the long-term prognosis of the two groups. RESULTS: Overall, 535 asymptomatic subjects were recruited and 126 subjects (11.4%) were spirometrically diagnosed as AFL. The incidence of PPCs was significantly higher in the newly diagnosed AFL group than in the normal population (28.6%VS 14.4%, P < 0.001), especially in the FEV1/FVC≤65% group (P < 0.001), which were all confirmed by PSM analysis. Furthermore, these patients were at a higher risk of ICU admissions (P < 0.001) and 90-day hospital readmissions secondary to PPCs (P < 0.001). No significant differences were found in the overall, in-hospital and 90-day mortality between the AFL group and the normal group (P values >0.05). CONCLUSION: Asymptomatic patients with AFL are at higher risk of PPCs than the general population after lung surgeries, along with an increase in ICU admissions and 90-day hospital readmissions secondary to PPCs. Although these patients tended to report worse current conditions, they were similar in the in-hospital, 90-day and overall mortality during the follow-up.

Sevoflurane prevents vulnerable plaque disruption in apolipoprotein E-knockout mice by increasing collagen deposition and inhibiting inflammation.

BACKGROUND: Sevoflurane may reduce the occurrence of major adverse cardiovascular events (MACCEs) in surgical patients, although the mechanisms are poorly understood. We hypothesised that sevoflurane stabilises atherosclerotic plaques by inhibiting inflammation and enhancing prolyl-4-hydroxylase α1 (P4Hα1), the rate-limiting subunit for the P4H enzyme essential for collagen synthesis. METHODS: We established a vulnerable arterial plaque model in apolipoprotein E-knockout mice (ApoE-/-) fed a high-fat diet that underwent daily restraint/noise stress, with/without a single prior exposure to sevoflurane for 6 h (1-3%; n=30 per group). In vitro, smooth muscle cells (SMCs) were incubated with tumour necrosis factor-alpha in the presence/absence of sevoflurane. Immunohistochemistry, immunoblots, and mRNA concentrations were used to quantify the effect of sevoflurane on plaque formation, expression of inflammatory cytokines, P4Hα1, and collagen subtypes in atherosclerotic plaques or isolated SMCs. RESULTS: In ApoE-/- mice, inhalation of sevoflurane 1-3% for 6 h reduced the aortic plaque size by 8-29% in a dose-dependent manner, compared with control mice that underwent restraint stress alone (P<0.05); this was associated with reduced macrophage infiltration and lower lipid concentrations in plaques. Sevoflurane reduced gene transcription and protein expression levels of pro-inflammatory cytokines (≥69-75%; P<0.05) and matrix metalloproteinases (≥39-65%; P<0.05) at both gene transcription and protein levels, compared with controls. Sevoflurane dose dependently increased Types I and III collagen deposition through enhanced protein expression of P4Hα1, both in vivo and in vitro (0.7-3.3-fold change; P<0.05). CONCLUSIONS: Sevoflurane dose dependently promotes plaque stabilisation and decreases the incidence of plaque disruption in ApoE-/- mice by increasing collagen deposition and inhibiting inflammation. These mechanisms may contribute to sevoflurane reducing MACCE.

Penehyclidine hydrochloride inhibits renal ischemia/reperfusion-induced acute lung injury by activating the Nrf2 pathway.

The nuclear factor (NF)-κB and NOD-like receptor protein 3 (NLRP3) pathways promote inflammatory signaling that injures the kidneys, whereas the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway promotes anti-inflammatory signaling that inhibits oxidative damage. Penehyclidine hydrochloride (PHC) inhibits NF-κB and activates Nrf2 signaling. We investigated whether PHC induces communication between the Nrf2 and NF-κB/NLRP3 pathways, thereby protecting against renal ischemia/reperfusion (rI/R)-induced lung inflammation. Rat alveolar macrophages (NR8383 cells) were stimulated for 24 h with PHC with or without brusatol (a Nrf2 antagonist), after which they were treated for 4 h with tert-butyl hydroperoxide (10 mM). PHC Nrf2-dependently alleviated tert-butyl hydroperoxide-induced reactive oxygen species production in alveolar macrophages. Additionally, wild-type and Nrf2-/- rats were each divided into four groups: (1) sham, (2) PHC (1 mg/kg), (3) rI/R and (4) rI/R + PHC (1 mg/kg). PHC markedly induced the Nrf2 and adenosine monophosphate-activated protein kinase pathways and suppressed rI/R-induced NF-κB and NLRP3 activation in the lungs. Nrf2 deficiency diminished the ability of PHC to ameliorate rI/R-induced histopathological alterations and reactive oxygen species release in the lungs; however, PHC inhibited NLRP3 signaling Nrf2-dependently, while it inhibited NF-κB signaling Nrf2-independently. Our findings demonstrate the beneficial effects of PHC on rI/R-induced lung inflammation.

Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BACKGROUND Cerebral ischemia-reperfusion injury is a pivotal cause of deaths due to cerebrovascular accident. Increased research efforts are needed to reveal the mechanism underlying its aggravation or alleviation. In this study, the effects of dexmedetomidine post-conditioning on the HMGB1/TLR4/NF-kappaB signaling pathway in cerebral ischemia-reperfusion rats was explored. MATERIAL AND METHODS Ninety rats were randomly divided into 5 groups - a sham group (Sham), a model group (I/R), a dexmedetomidine post-conditioning group (Dex), a recombinant high mobility group protein B1 group (rHMGB1), and a recombinant HMGB1+dexmedetomidine post-conditioning group (rHMGB1+Dex) - with 18 rats in each group. Longa grading, wet-dry weighing, TTC staining, HE staining, and immunohistochemical staining were used to assess brain damage. ELISA, RT-PCR, and Western blot analyses were performed to assess expression of IL-1ß, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and NF-kappaB. RESULTS Compared with the I/R group, the neurological function score, brain water content, infarction area, and the number of COX-2- and IBA-1-positive cells in the Dex group were significantly lower, accompanied by downregulated expression of the HMGB1/TLR4/NF-kappaB pathway, alleviated inflammation, and oxidative stress injury in brain tissue. These trends were mostly reversed in the rHMGB1 group and rHMGB1+Dex group, but not in the Dex group. Furthermore, when compared to the Dex group, there were significant increases of H2O2, MDA, NO, IL-1ß, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and p-P65 in the rHMGB1 group and rHMGB1+Dex group, in which a significant decrease of T-AOC, SOD, and p-IkappaBalpha was also detected. CONCLUSIONS Dexmedetomidine post-conditioning can alleviate cerebral ischemia-reperfusion injury in rats by inhibiting the HMGB1/TLR4/NF-kappaB signaling pathway.

Effects of sevoflurane on reproductive function of male rats and its main mechanism of action.

Objective: To study the effects of sevoflurane on reproductive function and its main mechanism of action in male rats.Materials and methods: Forty adult male Sprague-Dawley rats were divided into 4 groups and exposed to 0, 50, 300 and 1800 ppm of sevoflurane, respectively. After 15 days, the serum levels of sex hormones and inflammatory factors were detected using enzyme-linked immunosorbent assay. Left testis was taken for conventional histopathological examination and TUNEL staining. Right testis was used for sperm production and daily sperm count were evaluated daily. Johnsen score was used to categorize the spermatogenesis. The expression of related genes in the hypothalamic-pituitary-gonadal axis were analyzed by quantitative real time polymerase chain reaction (qRT-PCR).Results: Exposure to sevoflurane increased the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein 1 (MCP-1), decreased the content of serum testosterone (T), reduced the concentration of testicular sperm, the production of daily sperm and Johnsen score, and damaged vas deferens in a dose dependent manner. In addition, chronic exposure to sevoflurane down-regulated transcription of gonadotropin-releasing hormone (GnRH) and kisspeptin (Kiss)-1 as well as its receptor GPR54 in hypothalamus, attenuated GnRH receptor and LH-ß mRNA levels, but increased FSH-ß mRNA in pituitary gland, and enhanced mRNA of LH receptor and FSH receptor, but decreased INH-α and INH-ßA mRNA levels in testes.Discussion and conclusions: Sevoflurane induces disorders of spermatogenesis and causes testicular injury. The underlying mechanism may be related to the imbalance of sex hormones in the hypothalamic-pituitary-gonadal axis.

Anesthetic Agents Isoflurane and Propofol Decrease Maximal Ca2+-Activated Force and Thus Contractility in the Failing Myocardium.

In the normal heart, frequently used anesthetics such as isoflurane and propofol can reduce inotropy. However, the impact of these agents on the failing myocardium is unclear. Here, we examined whether and how isoflurane and propofol influence cardiac contractility in intact cardiac muscles from rats treated with monocrotaline to induce heart failure. We measured force and intracellular Ca2+ ([Ca2 +]i) in trabeculae from the right ventricles of the rats in the absence or presence of propofol or isoflurane. At low to moderate concentrations, both propofol and isoflurane dose-dependently depressed cardiac force generation in failing trabeculae without altering [Ca2+]i At high doses, propofol (but not isoflurane) also decreased amplitude of [Ca2+]i transients. During steady-state activation, both propofol and isoflurane impaired maximal Ca2+-activated force (Fmax) while increasing the amount of [Ca2+]i required for 50% of maximal activation (Ca50). These events occurred without apparent change in the Hill coefficient, suggesting no impairment of cooperativity. Exposing these same muscles to the anesthetics after fiber skinning resulted in a similar decrement in Fmax and rise in Ca50 but no change in the myofibrillar ATPase-Ca2+ relationship. Thus, our study demonstrates that challenging the failing myocardium with commonly used anesthetic agents such as propofol and isoflurane leads to reduced force development as a result of lowered myofilament responsiveness to Ca2+ SIGNIFICANCE STATEMENT: Commonly used anesthetics such as isoflurane and propofol can impair myocardial contractility in subjects with heart failure by lowering myofilament responsiveness to Ca2+. High doses of propofol can also reduce the overall amplitude of the intracellular Ca2+ transient. These findings may have important implications for the safety and quality of intra- and perioperative care of patients with heart failure and other cardiac disorders.

Role of JNK Signaling Pathway in Dexmedetomidine Post-Conditioning-Induced Reduction of the Inflammatory Response and Autophagy Effect of Focal Cerebral Ischemia Reperfusion Injury in Rats.

To investigate the effect of dexmedetomidine post-conditioning on the inflammatory response and autophagy effect of focal cerebral ischemia reperfusion injury in rats, and further to study its potential mechanisms. Water maze was conducted to evaluate spatial learning and memory ability of middle cerebral artery occlusion (MCAO) rats. TTC staining was used to observe the area of cerebral infarction. The expressions of inflammatory factors in serum were detected by ELISA. TUNEL assay, HE staining, and transmission electron microscopy were used to detect the apoptosis of neurons, neuro-cytopathic changes, and the formation of auto-phagosome in hippocampus CA1 region, respectively. The mRNA and protein expression of Beclin-1, Caspase-3, and light chain 3 (LC3) were detected by qRT-PCR and Western blot. Moreover, the activity of C-Jun N-terminal kinase (JNK) pathway was detected by Western blot. The escape latency (EL); cerebral infarction area ratio; positive apoptosis; neuron pathological changes; auto-phagosome numbers; inflammatory factor contents; mRNA and protein expressions of Beclin-1, Caspase-3 and LC3II/I; and the phosphorylation level of JNK were decreased, while the times across platform and the times stayed in the quadrant of the original platform were increased after dexmedetomidine treatment. However, the protective effect of dexmedetomidine on brain injury in MCAO rats was reversed by JNK pathway activator. Dexmedetomidine post-conditioning could improve learning and memory dysfunction caused by MCAO in rats and reduce the inflammatory response and autophagy effect. The mechanism may be related to inhibition of JNK pathway activation.

Adverse effects of post-heat treatment on the interfacial bonding strength of direct laser deposition Inconel 625/1045 composites.

Interfacial bonding strength is critical to the service life of components in the remanufacturing field. To identify the interfacial mechanical properties, a nickel-based Inconel 625 alloy powder was deposited on the AISI 1045 steel substrate by direct laser deposition. The effects of post-heat treatment on the phase transformation, composition segregation and residual stress releasing near the interface were investigated. A series of microstructural characterizations, such as SEM, FE-SEM, EDS and XRD, were used. By uniaxial tensile experiments, the interfacial bonding strength with/without post-heat treatment were compared, we found that the interfacial bonding strength of original specimen (556.8 MPa) was stronger than that of post-heat treatment (452.3 MPa). This was attributed to the fact that the thermal expansion coefficient of Inconel 625 powder (α d = 14.7) was less than that of the AISI 1045 substrate (α s = 15.6), resulting in the compressive residual stress at the edge of interface. After post-heat treatment, the release of beneficial compressive residual stress and the change of phase composition near the interface were the reasons for the decrease of interfacial bonding strength. These results indicated that post-heat treatment is not suitable for all heterogeneous bonding materials. This kind of material matching (α d < α s) is more advantageous to remanufacturing field.

Pharmacological analysis of dexmedetomidine hydrochloride in pediatric anesthesia during magnetic resonance imaging.

Dexmendetomidine hydrochloride (DEX) is a new common adrenergic receptor agonist, which not only keeps children calm but also has analgesic effect. Dexmedetomidine hydrochloride will enable children to maintain the natural non-REM sleep, which can be stimulated sedation or language arousal. The aim of this study is to observe the sedative effect and adverse drug reactions of dexmedetomidine hydrochloride injection and propofol injection in MRI examination. In this study, no children in the experimental group were required to add sedative drugs, and 2 cases in the control group were treated with sedative drugs. In experimental group, it used dexmedetomidine hydrochloride as (1.64±0.91) g/kg; in control group, dosage of narcotic drugs as (5.26±1.82) g/kg, and the total complication rate of the children in the experimental group was lower than that of the control group (P<0.05). After returning to the ward, the doses of phenobarbital sedation were dexmedetomidine group (4.28±1.53) mg/kg and propofol group (6.40±1.71) mg/kg. There was significant difference between the two groups. The total complication rate in the experimental group was lower than that in the control group (P<0.05). The quality of MRI in the test group was significantly higher than that in the control group, which showed that dexmedetomidine hydrochloride could provide a satisfactory sedative effect in the MRI examination of children. To sum up, dexmedetomidine hydrochloride is a wide range of clinical applications. It is an effective drug for the maintenance of sedation in clinical disease treatment. It is flexible in the way of administration and with less adverse reactions. It is suitable for popularization and application in clinical practice.