siRNA nanoparticle targeting Usp20 lowers lipid levels and ameliorates metabolic syndrome in mice.

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr-/- mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

Domino Effect: Gold Electrocatalyzing Lithium Reduction to Accelerate Nitrogen Fixation.

Green production of NH3 , especially the Li-mediated electrochemical N2 reduction reaction (NRR) in non-aqueous solutions, is attracting research interest. Controversies regarding the NRR mechanism greatly impede its optimization and wide applications. To understand the electrocatalytic process, we treated Au coated carbon fibrous paper (Au/CP) as the model catalyst. In situ XRD confirmed the transformation of lithium intermediates during NRR. Au greatly improved electron transfer kinetics to catalyze metallic Li formation, and accordingly highly accelerated spontaneous NRR. The Faradaic efficiency of NRR on Au/CP reached 34.0 %, and NH3 yield was as high as 50 µg h-1 cm-2 . Our research shows that the key step of Li-mediated non-aqueous NRR is electrocatalytic Li reduction and offers a novel electrocatalyst design method for Li reduction.

[Review of stimulation parameters of scalp-electroacupuncture for ischemic stroke]. / ç”µå¤´é’ˆæ²»ç–—ç¼ºè¡€æ€§è„‘å’ä¸­çš„åˆºæ¿€å‚æ•°ç ”ç©¶æ¦‚å†µ.

Scalp-electroacupuncture (scalp-EA) is an effective traditional Chinese medicine characteristic therapy for ischemic stroke and frequently employed in clinical practice, but there is still lack of normative standard of stimulation parameters. After searching the relevant articles, we summed up the stimulation parameters of scalp-EA for ischemic stroke from 5 aspects： 1) stimulating frequency (Low frequency is better when continuous waveform is used, and high frequency is better when dense-sparce waveform or discontinuous waveform employed), 2) waveform (Dense-sparce or discontinuous waves are better than continuous waves), 3) intensity (A tolerable stimulation strength may result in better outcomes), 4) needle retention time (In general, the needle retention time is 30 min, but still needing being determined), treatment course (Some studies showed that once a day EA for 3 continuous days is effective, 7 days, significantly effective, 14 days, further enhanced in the therapeutic effect), and 5) intervention time window (Generally, EA intervention within 6 h was mostly effective, shown by animal study). However, these parameters do not exist independently, and they can influence and interact with each other. It is difficult to observe the interaction among parameters only with single-dimension analysis. Hence, more and larger sample size studies, with strict inclusion and exclusion criteria, more reasonable research design (such as multiple factorial design, orthogonal experimental design, etc.) and multiple levels effect analysis are warranted.

Dyadic social interaction paradigm reveals selective role of ovarian estrogen in the caring behavior and socially transferred pain in female mice.

When a naïve observer meets with a familiar conspecific in pain, mice may have a myriad of social (sniffing, allolicking, allogrooming, huddling) and non-social (self-grooming) behaviors under dyadic social interaction (DSI) paradigm. Unlike male, female observers express more allolicking behavior toward injury site of a familiar female in pain, but with less body allogrooming. In current study, we investigated roles of natural estrus cycle phases and ovarian estrogen in these behaviors and results showed that: (1) there was no changes in above behaviors in terms of latency, time and bouts across different natural estrus cycle phases in intact female. (2) however, ovariectomy (OVX) changed estrus cycle phases, lowered circulating level of ovarian estrogen, reduced time and bouts of allolicking behavior and increased time of self-grooming without affecting other behaviors. Moreover, OVX in observers decreased social buffering effect of DSI on spontaneous pain-related behavior in demonstrator relative to naïve and sham controls. (3) treatment of OVX-female with ß-estradiol (E2) or progesterone (PROG) as replacement therapies, only E2 reversed impairment of allolicking behavior. (4) Additionally, socially transferred pain could be identified in intact female across all estrus cycle phases post-DSI, but disappeared in OVX-female, which could be reversed completely by E2 but not by PROG. (5) Finally, serum levels of estrogen, PROG, oxytocin, arginine vasopressin (AVP), prolactin, norepinephrine and 5-HT were examined by ELISA after E2, results showed only AVP level was significantly increased. These results suggest both injury site-targeted caring behavior and socially transferred pain are selectively dependent on ovarian estrogen. This article is part of the Special Issue on "Empathic Pain".

Electro-scalp acupuncture regulates the expression of CYP27a1/b1, CYP24a and related inflammatory cytokines in ischemic cortex of rats with middle cerebral artery occlusion. / ç”µå¤´é’ˆè°ƒæŽ§å¤§è„‘ä¸­åŠ¨è„‰æ “å¡žå¤§é¼ ç¼ºè¡€å¤§è„‘çš®å±‚åŒºCYP27a1/b1、CYP24aåŠç›¸å ³ç‚Žæ€§ç»†èƒžå› å­è¡¨è¾¾çš„ç ”ç©¶.

OBJECTIVES: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. METHODS: Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1ß and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. RESULTS: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. CONCLUSIONS: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.

A sterol analog inhibits hedgehog pathway by blocking cholesterylation of smoothened.

The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation. Q29 suppresses Hh signaling-dependent cell proliferation and arrests Hh-dependent medulloblastoma growth. Q29 exhibits an additive inhibitory effect on medulloblastoma with vismodegib, a clinically used SMO-7TM inhibitor for treating basal cell carcinoma (BCC). Importantly, Q29 overcomes resistance caused by SMO mutants against SMO-7TM inhibitors and inhibits the activity of SMO oncogenic variants. Our work demonstrates that the SMO-CRD inhibitor can be a new way to treat Hh pathway-driven cancers.

Construction of a plasmid for expression of rat platelet-derived growth factor C and its effects on proliferation, migration and adhesion of endothelial progenitor cells.

Endothelial progenitor cells (EPCs) play a key role in restoring endothelial function and enhancing angiogenesis. Platelet-derived growth factor C (PDGF-C) is a newly discovered member of the PDGF family that binds to the PDGFR-α homodimer and the PDGFR-α/ß heterodimer. Currently, the biological effects of PDGF-C on EPCs proliferation, migration and adhesion are not well understood. In this study, the full-length coding sequence (CDS) region for the PDGF-C gene was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR). The amplified PDGF-C product was digested and inserted into the pMD 19-T simple vector and then subcloned into a pIRES2-EGFP plasmid to construct the pIRES2-EGFP-PDGF-C eukaryotic expression vector. After it was transfected to EPCs, the expression of PDGF-C protein in EPCs was verified by Western blotting analysis. Finally, we investigated the effects of PDGF-C protein overexpression on EPCs proliferation, migration and adhesion. In conclusion, we constructed a recombinant eukaryotic expression vector containing the complete CDS region of PDGF-C and expressed the full-length and functional PDGF-C protein successfully. Furthermore, PDGF-C promoted EPCs proliferation, migration and adhesion. This offers promise for the development of new therapeutic strategies for improving neovascularization and repair of blood vessel endothelium in patients with ischemic heart disease or peripheral arterial occlusive disease.

[Study on alleviating neuroinflammatory injury in ischemic stroke rats by electrical stimulation with scalp acupuncture based on IFN-γ mediated JAK/STAT1 signaling pathway].

OBJECTIVE: To explore the molecular mechanism of electrical stimulation with scalp acupuncture (ESA) in alleviating neuroinflammatory injury in ischemic stroke rats based on interferon γ (IFN-γ)-mediated Janus kinase/signal transduction and transcriptional activator 1 (JAK/STAT1) signaling pathway. METHODS: Fifty-six SD rats aged 7 weeks were randomly divided into normal, model, ESA and inhibitor groups, with 14 rats in each group. The middle cerebral artery embolization rat model was established by means of thread embolization. Rats in the inhibitor group were intraperitoneally injected with the inhibitor PJ34 (5 mg/mL, 25 mg/kg) once a day for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. The percentage of cerebral infarction volume was detected by TTC staining. The positive expressions of interleukin (IL)-6 and IL-10 in cerebral cortex were detected by immunohistochemistry. The protein expression levels of IFN-γ, JAK1, JAK2 and phosphorylated (p)-STAT1 in rats cerebral cortex were detected by Western blot. RESULTS: Compared with the normal group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were increased (P<0.01), while the expression level of IL-10 was decreased (P<0.01) in the model group. Compared with the model group, the neurological deficit score and neurobehavioral score after treatment were significantly decreased (P<0.01), the percentage of cerebral infarction volume was decreased (P<0.01), the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were decreased (P<0.01), while the expression level of IL-10 was increased (P<0.01) in the ESA and inhibitor groups. ESA was superior to inhibitors in improving neurological deficit score and down-regulating p-STAT1 expression (P<0.05, P<0.01), and was inferior to inhibitor in reducing the percentage of cerebral infarction volume as well as down-regulating IFN-γ and JAK1 (P<0.01, P<0.05). CONCLUSION: Down-regulating the expression of IFN-γ and inhibiting the activity of JAK/STAT1 signaling pathway may be one of the mechanisms by which ESA alleviates neuroinflammatory injury in ischemic stroke rats.

[Effects of electro-scalp acupuncture on inflammatory response and microglial polarization in the ischemic cortex of rats with ischemic stroke].

OBJECTIVE: To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1ß, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke. METHODS: Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D3 (1,25-VitD3) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1ß, and IL-10 in the ischemic cortex. RESULTS: Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD3 group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD3 group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1ß, and IL-10 in the ischemic cortex (P<0.01, P<0.05). CONCLUSION: ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.

Impact of ligand modification on hydrogen photogeneration and light-harvesting applications using cyclometalated iridium complexes.

To explore structure-activity relationships with respect to light-harvesting behavior, a family of bis-cyclometalated iridium complexes [Ir(C^N)(2)(Hbpdc)] 2-5 (where C^N = 2-phenylbenzothiazole and its functionalized derivatives, and H(2)bpdc =2,2'-bipyridine-4,4'-dicarboxylate) was synthesized using a facile method. The photophysical and electrochemical properties of these complexes were investigated and compared to those of analogue 1 (C^N = (4-trifluoromethyl)-2-phenylbenzothiazole); they were also investigated theoretically using density functional theory. The molecular structures of complexes 2-4 were determined by X-ray crystallography, which revealed typical octahedral coordination geometry. The structural modifications involved in the complexes were accomplished through the attributes of electron-withdrawing CF(3) and electron-donating NMe(2) substituents. The UV-vis spectra of these species, except for that of 5, displayed a broad absorption in the low-energy region, which originated from metal-to-ligand charge-transfer transitions. These complexes were found to exhibit visible-light-induced hydrogen production and light-to-electricity conversion in photoelectrochemical cells. The yield of hydrogen production from water using these complexes was compared, which revealed substantial dependences on their structures, particularly on the substituent of the cyclometalated ligand. Among the systems, the highest turnover number of 1501 was achieved with complex 2, in which the electron-withdrawing CF(3) substituent was connected to a phenyl ring of the cyclometalated ligand. The carboxylate anchoring groups made the complexes highly suitable for grafting onto TiO(2) (P25) surfaces for efficient electron transfer and thus resulted in an enhancement of hydrogen evolution compared to the unattached homogeneous systems. In addition, the combined incorporation of the electron-donating NMe(2) group and the electron-withdrawing CF(3) substituent on the cyclometalated ligand caused complex 5 to not work well for hydrogen production. Their incorporation, however, enhanced the performance of 5 in the light-harvesting application in nanocrystalline TiO(2) dye-sensitized solar cells, which was attributed to the intense absorption in the visible region.

The interaction between emulsified isoflurane and lidocaine is synergism in intravenous regional anesthesia in rats.

BACKGROUND: Our previous studies have demonstrated that emulsified isoflurane (EI) produced epidural anesthesia and blockade of nerve conduction. We designed this study to observe whether EI could produce an anesthetic effect in IV regional anesthesia (IVRA) and to investigate the underlying interaction between EI and lidocaine when they were combined in IVRA. METHODS: IVRA was evaluated using tail-flick and tail-clamping tests in a rat model. In experiment 1, Sprague-Dawley rats were assigned to 4 groups (n = 10 per group), receiving 0.5 mL of 8%EI, 0.5% lidocaine, 30% Intralipid, or normal saline to observe whether EI could produce an anesthetic effect in IVRA. In experiment 2, for tail IVRA, EC(50) (median effective concentration) of EI alone and EC(50) of lidocaine alone, as well as EC(50) of lidocaine with the addition of Intralipid (0.0% EI) or with the addition of EI at different concentrations (0.4%, 0.8%, and 1.6%) were determined using an up-and-down method. Isobolographic analysis was used to evaluate the interaction between EI and lidocaine. RESULTS: For experiment 1, successful IVRA was observed in 8 of 10 rats with 8% EI, 10 of 10 rats with 0.5% lidocaine, and 0 of 10 rats with 30% Intralipid or normal saline. The anesthetic effect was not different in onset time (1.5 ± 0.9 vs 1.0 ± 0.0 minutes, P = 0.104) or recovery time (15 ± 9 vs 18 ± 12 minutes, P = 0.394) between 8% EI and 0.5% lidocaine. For experiment 2, EC(50) of EI was 4.467% ± 0.375% and EC(50) of lidocaine was 0.183% ± 0.072%; EC(50) of lidocaine was 0.173% ± 0.036% with the addition of Intralipid, and 0.064% ± 0.008%, 0.035% ± 0.005%, and 0.028% ± 0.006% with the addition of 0.4%, 0.8%, and 1.6% EI, respectively. With the addition of EI, the requirement for lidocaine was reduced in a synergistic manner. CONCLUSIONS: EI produced IVRA, and a synergistic interaction was found between EI and lidocaine for IVRA in a rat tail model.

Predictive risk scales for development of pressure ulcers in pediatric patients admitted to general ward and intensive care unit.

BACKGROUND: More than ten special scales are available to predict the risk of pressure ulcers in children. However, the performances of those scales have not yet been compared in China. AIM: To compare the Waterlow, Braden Q, and Glamorgan scales, and identify more suitable pressure ulcer evaluation scale for the pediatric intensive care unit (PICU). METHODS: Trained nurses used the Waterlow, Braden Q, and Glamorgan scales to assess pediatric patients at Sun Yat-sen Memorial Hospital (China) within 24 h of admission from May 2017 to December 2020 in two stages. Skin examination was carried out to identify pressure ulcers every 3 d for 3 wk. RESULTS: The incidence of pressure ulcers was 3/28 (10.7%) in the PICU and 5/314 (1.6%) in the general pediatric ward. For children in the general ward, the Waterlow, Braden Q, and Glamorgan scales had comparable area under the operating characteristic curve (AUC) of 0.870, 0.924, and 0.923, respectively, and optimal cut-off values of 14, 14, and 29 points. For PICU, the Waterlow, Braden Q, and Glamorgan scales had slightly lower AUC of 0.833, 0.733, and 0.800, respectively, and optimal cut-off values of 13, 16, and 27 points. Braden Q demonstrated a satisfactory specificity, and during the second stage of the study for PICU patients, the AUC of the Braden Q scale was 0.810, with an optimal cut-off value of 18.35 points. CONCLUSION: The Waterlow, Braden Q, and Glamorgan scales have comparable performance, while the Braden Q scale demonstrates a better specificity and can be successfully used by pediatric nurses to identify patients at high risk of pressure ulcers in PICU.

Intervertebral foramen injection of plerixafor attenuates neuropathic pain after chronic compression of the dorsal root ganglion: Possible involvement of the down-regulation of Nav1.8 and Nav1.9.

Neuropathic pain is a common chronic pain condition with major impact on quality of life. However, its physiopathologic mechanism remains unknown and pain management is still a challenge. Accumulating evidence indicated that C-X-C chemokine receptor type 4 (CXCR4) played a critical role in the process of pain. Thus, the present study aimed to investigate whether intervertebral foramen injection of CXCR4 antagonist, plerixafor, was able to relieve neuropathic pain and explore the possible underlying mechanism. Chronic compression of the dorsal root ganglion (CCD) was established as a typical model of neuropathic pain. The results indicated that CCD induced multiple pain-related behaviors and the expression of CXCR4, Nav1.8 and Nav1.9 was significantly increased in compressed dorsal root ganglion (DRG) neurons. Knocking down CXCR4 expression could significantly reduce neuropathic pain and intervertebral foramen plerixafor injection (IVFP) dramatically decreased the up-regulation of Nav1.8 and Nav1.9 and attenuated neuropathic pain. The analgesic duration of IVFP was maintained at least for 24 h which was much longer than intervertebral foramen injection of Nav1.8 blocker and local anesthetics. Therefore, our study provided evidence that IVFP could reduce the expression of Nav1.8 and Nav1.9 in DRG neurons which might contribute to, at least in part, the analgesic effect of plerixafor on CCD-induced neuropathic pain. It is concluded that IVFP was an effective and applicable treatment approach for neuropathic pain.

Reversible conduction block in isolated toad sciatic nerve by emulsified isoflurane.

BACKGROUND: Studies have shown that the local use of volatile anesthetics can produce local anesthetic effects. We designed this study to evaluate the characteristics of nerve conduction block of emulsified isoflurane (EI) and compare its nerve blockade with 1%lidocaine, by measuring compound nerve action potential (CNAP) parameters in isolated toad sciatic nerve. METHODS: One hundred isolated toad sciatic nerves were selected and randomly assigned to 10 groups of 10 each, administered 2% to 8% EI (v/v) (EI(8) group, etc.), 1% lidocaine, 30% Intralipid(R) (Huarui Pharmacy, Wuxi, Jiangsu, China), and Ringer solution (RS) for 10 minutes, respectively. All nerves were then washed and soaked with RS for 10 minutes and 30 minutes. The nerve conduction block effect was represented by CNAP parameters that were recorded by an extracellular recording technique per minute. RESULTS: The results showed that the negative amplitudes of CNAP were decreased by EI and lidocaine (P < 0.05), and the conduction velocities of CNAP were also decreased at some time points (D7-W3) (P < 0.05). After RS washing, the 2 parameters recovered gradually. The changes in the 2 parameters induced by EI had slower onset rates and faster recoveries than those produced by lidocaine (7 minutes vs 1 minute and 9 minutes vs 30 minutes). The nerve blockade induced by EI was dose dependent (P < 0.05), and the half maximal inhibition concentration of EI was 5.46%. CONCLUSIONS: EI produced completely reversible and dose-dependent nerve conduction inhibition, which had slower onset and faster recovery compared with those produced by lidocaine.

A model of intravenous regional anesthesia in rats.

BACKGROUND: We developed an IV regional anesthesia (IVRA) model using the tails of rats to allow preclinical evaluation of the safety and efficacy of drugs used in IVRA and analgesia. METHODS: Three sequential experiments were designed to determine local anesthetic and analgesic effects of drugs injected IV in the tail. The anesthesia was assessed by monitoring the response of the tail-clamp (RTC) test on the tail, whereas the analgesia was assessed by recording the latency in the tail-flick test on the tail. In the first 2 experiments, we studied the effects of different environmental temperatures (15 degrees C, 25 degrees C, and 37 degrees C) and length of tourniquet time on the tail-flick and tail-clamp tests, respectively. Based on the outcomes of these 2 experiments, the pharmacological effects of 1% lidocaine (L group) and 0.5% bupivacaine (B group) were compared with normal saline (NS group) to evaluate this model in experiment 3. RESULTS: In experiment 1, compared with its baseline, tail-flick latency increased rapidly in the 15 degrees C group (P < 0.0001), whereas there were no changes in tail-flick latency in the 25 degrees C group (P = 0.3640) and the 37 degrees C group (P = 0.0641) after the first 20 minutes of tail submersion in a water bath. RTCs in all rats were positive during the entire observation period. In experiment 2, tail-flick latency did not change compared with baseline tail-flick latency after the first 20 minutes of tourniquet application (P = 0.0902), but significantly increased at the 30-, 40-, 50-, and 60-minute intervals (P = 0.0001). RTCs in all rats were positive during the experiment. In experiment 3, local anesthesia was generated in the tail (distal to the tourniquet) in the L and B groups with a similar onset time of anesthesia (approximately 1 minute), but with a longer recovery time of anesthesia and analgesia in the B group (56.0 +/- 22.0 minutes) than the L group (31.0 +/- 19.0 minutes), whereas no anesthetic and analgesic effects were observed in the NS group. CONCLUSIONS: A reliable model for studying IVRA and analgesia has been developed in rats.

The similar past pain experience evokes both observational contagious pain and consolation in stranger rat observers.

Laboratory rodents have been shown to have an ability to recognize the injury site and negative emotional state of their conspecifics in pain, resulting in empathic consoling behaviors and observational contagious pain (OCP). However, these empathic responses have been shown to be familiarity-dependent. In this report, we further explored whether the past pain experience could evoke empathic response in stranger observers. In our rodent model, two types of empathic response have been identified from naive cagemate observer (COnaive) during and after a priming dyadic social interaction (PDSI) with a cagemate demonstrator in pain (CDpain): the consolation and OCP. Consolation is represented by allolicking and allogrooming behaviors toward the CDpain, while the OCP is represented by a long-term mechanical pain hypersensitivity. The current results showed that: (1) neither the consolation nor OCP could be identified in the naive noncagemate observer (NCOnaive) during and after a PDSI with a noncagemate demonstrator in pain (NCDpain); (2) nor were the two types of empathic response seen in the NCO, who had just experienced acute pain (NCOpainexp), during and after a PDSI with a naive unfamiliar conspecific (NCDnaive). However, both the consolation and OCP were dramatically identified in the NCOpainexp during and after a PDSI with a NCD in pain (NCDpain). The current results demonstrated that the past pain experience can evoke both consolation and OCP in stranger rat observers when witnessing a conspecific in pain, implicating that the processing of empathy for pain can be modulated by past negative mood experience.

Preparation and enantioseparation characteristics of a novel chiral stationary phase based on mono (6(A)-azido-6(A)-deoxy)-per(p-chlorophenylcarbamoylated) beta-cyclodextrin.

A novel cyclodextrin (CD) derivative-mono (6(A)-azido-6(A)-deoxy)-per(p-chlorophenylcarbamoylated) beta-CD was synthesized and chemically immobilized onto the surface of amino-functionalized silica gel to afford a structurally well-defined chiral stationary phase (CSP) for high performance liquid chromatography (HPLC). The p-chlorophenyl groups introduced on the beta-CD are pi-electron deficient (i.e., pi-acidic moieties); therefore the stronger pi-pi interaction which plays an important role in chiral recognition process is expected between aromatic analytes and this type of the CSP. The enantiomeric separations of 11 piperazine derivatives as well as six racemates have been successfully achieved on this CSP in the normal and reversed phase modes.

An all-inorganic lead halide perovskite-based photocathode for stable water reduction.

Lead halide perovskites (LHPs) have been investigated for photoelectrochemical hydrogen generation from water splitting. However, the harsh requirements in preparing the environment, i.e. isolating water and oxygen, hinder the wide applications of lead halide perovskites. Herein, an all-inorganic perovskite, i.e. a CsPbBr3-based photocathode, has been prepared to generate hydrogen. It is notable that as a valuable trial for a potential large-scale production, the whole preparation process was completed in an open-air environment. The LHP photocathode achieved the highest photocurrent of about 1.2 mA cm-2 at 0 VRHE. And the photocurrent remains around 94% after continuous illumination for 1 h with the Faradaic efficiency of 90%, illustrating a good photoelectrochemical stability. The all-inorganic LHP photocathodes are facile to prepare with a relatively good performance, and can be improved via band engineering and structure optimization, of which large-scale applications can be expected.

Validating Rat Model of Empathy for Pain: Effects of Pain Expressions in Social Partners.

Pain can be socially transferred between familiar rats due to empathic responses. To validate rat model of empathy for pain, effects of pain expressions in a cagemate demonstrator (CD) in pain on empathic pain responses in a naïve cagemate observer (CO) after 30 min priming dyadic social interactions (PDSI) were evaluated. The CD rats were prepared with four pain models: bee venom (BV), formalin, complete Freund's adjuvant (CFA), and spared nerve injury (SNI). Both BV and formalin tests are characterized by displayable and eye-identifiable spontaneous pain-related behaviors (SPRB) immediately after treatment, while CFA and SNI models are characterized by delayed occurrence of evoked pain hypersensitivity but with less eye-identifiable SPRB. After 30 min PDSI with a CD immediately after BV and formalin, respectively, the empathic mechanical pain hypersensitivity (EMPH) could be identified at both hind paws in CO rats. The BV-or formalin-induced EMPH in CO rats lasted for 4-5 h until full recovery. However, EMPH failed to develop in CO after socially interacting with a CD immediately after CFA, or 2 h after BV when SPRB completely disappeared. The CO's EMPH was partially relieved when socially interacting with an analgecized CD whose SPRB had been significantly suppressed. Moreover, repeated exposures to a CD in pain could enhance EMPH in CO. Finally, social transfer of pain hypersensitivity was also identified in CO who was being co-housed in pairs with a conspecific treated with CFA or SNI. The results suggest that development of EMPH in CO rats would be determined not only by extent of familiarity but also by visually identifiable pain expressions in the social partners during short period of PDSI. However, the visually unidentifiable pain can also be transferred to naïve cagemate when being co-housed in pairs with a distressed conspecific. In summary, the vicariously social contagion of pain between familiar rats is dependent upon not only expressions of pain in social partners but also the time that dyads spent in social communications. The rat model of empathy for pain is a highly stable, reproducible and valid model for studying the neural mechanisms of empathy in lower animals.

SDF1-CXCR4 Signaling Contributes to the Transition from Acute to Chronic Pain State.

Emerging evidence has demonstrated the involvement of stromal cell-derived factor 1 (SDF1, also known as CXCL12)-CXCR4 signaling in a variety of pain state. However, the underlying mechanisms of SDF1-CXCR4 signaling leading to the maintenance of chronic pain states are poorly understood. In the present study, we sought to explore the role of SDF1-CXCR4 signaling in the forming of neuroplasticity by applying a model of the transition from acute to chronic pain state, named as hyperalgesic priming. Utilizing intraplantar bee venom (BV) injection, we successfully established hyperalgesic priming state and found that peripheral treating with AMD3100, a CXCR4 antagonist, or knocking down CXCR4 by intraganglionar CXCR4 small interfering RNA (siRNA) injection could prevent BV-induced primary mechanical hyperalgesia and hyperalgesic priming. Moreover, we showed that single intraplantar active SDF1 protein injection is sufficient to induce acute mechanical hyperalgesia and hyperalgesic priming through CXC4. Intraplantar coinjection of ERK inhibitor, U0126, and PI3K inhibitor, LY294002, as well as two protein translation inhibitors, temsirolimus and cordycepin, prevented the development of SDF1-induced acute mechanical hyperalgesia and hyperalgesic priming. Finally, on the models of complete Freund's adjuvant (CFA)-induced chronic inflammatory pain and spared nerve injury (SNI)-induced chronic neuropathic pain, we observed that knock-down of CXCR4 could both prevent the development and reverse the maintenance of chronic pain state. In conclusion, our present data suggested that through regulating ERK and PI3K-AKT pathways-mediated protein translation SDF1-CXCR4 signaling mediates the transition from acute pain to chronic pain state and finally contributes to the development and maintenance of chronic pain.