Facile synthesis of MOF-808/RGO-based 3D macroscopic aerogel for enhanced photoreduction CO2.

Three-dimensional (3D) macroscopic aerogels have emerged as a critical component in the realm of photocatalysis. Maximizing the integration of materials can result in enhanced efficiency and selectivity in photocatalytic processes. In this investigation, we fabricated MOF-808/reduced graphene oxide (RGO) 3D macroscopic aerogel composite materials employing the techniques of hydrothermal synthesis and freeze-drying. The results revealed that the macroscopic aerogel material exhibited the highest performance in CO2 reduction to CO, particularly when the concentration of RGO was maintained at 5 mg mL-1. In addition, we synthesized powder materials of MR-5 composite photocatalysts and conducted a comparative analysis in terms of photocatalytic CO2 reduction performance and electron transfer efficiency. The results showthat the macroscopic aerogel material boasts a high specific surface area, an abundant internal pore structure, and increased active sites. These attributes collectively enhance light energy utilization, and electron transfer rates, thereby, improving photothermal and photoelectric conversion efficiencies. Furthermore, we conducted in-situ FT-IR measurements and found that the M/R-5 aerogel exhibited the best CO2 adsorption capacity under a CO2 flow rate of 10 mL min-1. The density functional theory results demonstrate the correlation between the formation pathway of the product and the charge transfer pathway. This study provides useful ideas for realizing photocatalytic CO2 reduction of macroscopic aerogel materials in gas-solid reaction mode.

A study on urban household water consumption behavior under drought conditions.

The increasing frequency of drought events has intensified the risk of water scarcity, posing significant challenges for urban domestic water supply. Reducing urban household water consumption is an important way to alleviate water stress during drought periods. However, due to various factors, it is difficult to determine a water-saving target that is within the residents' capacity. Here, taking Beijing, China as an example, we explored the socio-psychological factors behind urban household water use behaviors under drought conditions, and further quantified the compressible ratio of water quotas for flexible water use behaviors. Therefore, the present study was based on the theory of planned behavior (TPB) and extended TPB (ETPB) by adding drought risk perception as a variable to the theoretical framework. With the help of questionnaire method and structural equation modeling (SEM), the explanatory power of TPB and ETPB in predicting people's water saving intention and behavior was compared. Meanwhile, mathematical statistical analysis methods were employed to calculate the water quota for elastic water consumption behavior and the compressible proportion of urban residents' elastic water consumption under drought conditions. The results showed that drought risk perception has a significant positive correlation with subject norms and water reduction behavior under drought conditions. Furthermore, ETPB was more effective in analyzing water use intentions and behaviors. The predictive explanatory power of SEM for reducing water use increased from 44% to 50% after adding drought risk perception variable. In terms of quantification of elastic water use behavior, the average total water consumption in summer and winter were 71.3L/(p.d) and 52.9L/(p.d) under drought conditions, while it were 124.3 L/(p.d) and 108.9 L/(p.d) under normal conditions. And the compressible proportions of the total water quota for summer and winter elastic water use were 46.7% and 56.8%, respectively. The calculation results can provide a reference for the government to make emergency water supply decisions against drought.

Efficacy and cost-effectiveness analysis of pretreatment percutaneous endoscopic gastrostomy in unresectable locally advanced esophageal cancer patients treated with concurrent chemoradiotherapy (GASTO 1059).

BACKGROUND: We launched a single-arm phase II study to determine the efficacy and cost-effectiveness of percutaneous endoscopic gastrostomy (PEG) before concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients received pretreatment PEG and enteral nutrition during CCRT. The primary outcome was the change of weight during CCRT. The secondary outcome included nutrition status, loco-regional objective response rate (ORR), loco-regional progression-free survival (LRFS), overall survival (OS), and toxicities. A 3-state Markov model was applied for cost-effectiveness analysis. Eligible patients were matched and compared with those who had nasogastric tube feeding (NTF) or oral nutritional supplements (ONS). RESULTS: Sixty-three eligible patients received pretreatment PEG-based CCRT. The mean change of weight during CCRT was -1.4% (standard deviation, 4.4%), and after CCRT, 28.6% of patients gained weight and 98.4% had normal albumin levels. The loco-regional ORR and 1-year LRFS were 98.4% and 88.3%. The incidence of grade ≥3 esophagitis was 14.3%. After matching, another 63 patients were included in the NTF group and 63 in the ONS group. More patients gained weight after CCRT in the PEG group (p = 0.001). The PEG group showed higher loco-regional ORR (p = 0.036) and longer 1-year LRFS (p = 0.030). In cost analysis, the PEG group showed an incremental cost-effectiveness ratio of $3457.65 per quality-adjusted life-years (QALY) compared with the ONS group with a probability of cost-effectiveness of 77.7% at the $10,000 per QALY willingness-to-pay threshold. CONCLUSION: Pretreatment PEG is associated with better nutritional status and treatment outcome in ESCC patients treated with CCRT compared with ONS and NTF. Pretreatment of PEG can be cost-effective because of its significant clinical benefits.

Simulation of water and nitrogen movement mechanism in cold regions during freeze-thaw period based on a distributed nonpoint source pollution model closely coupled water, heat, and nitrogen processes at the watershed scale.

The nitrogen cycle in cold regions during the freeze-thaw period is complex. Although previous studies have investigated the phenomenon of nitrogen transport and transformation, the underlying mechanisms are vague. Existing models have limitations in terms of loose coupling or weak physical mechanisms. Therefore, a new distributed nonpoint source pollution model, the water and energy transfer processes and nitrogen cycle processes model in cold regions, was developed in this study, with closely coupled water, heat, and nitrogen processes at the watershed scale. The model considered the driving effects of pressure, gravity, solute, and temperature potentials on water and nitrogen movement in soil and the transformation relationship among nitrogen forms. Physical evaluation and simulations were conducted for the Heidingzi River Watershed during two freeze-thaw periods: 2017-2018 and 2018-2019. The soil temperature absolute error was < 0.82 â„ƒ. The relative errors in stratified liquid water, soil nitrogen content, river flow rate, and river nitrogen concentration were mostly < 10%. Nitrogen transport with water had an obvious "upward agglomeration effect" during the freezing period and a "concentrated release effect" during the thawing period, which was attributed to changes in soil water potential as the freezing front moved down. Disregarding the effects of solute potential and temperature potential will result in an underestimate of the outflow of pollutants during the thawing period. The model can be applied to reveal water quality deterioration in cold regions during thawing.

Postnatal oxytocin treatment improves survival and neurodevelopmental outcomes in an animal model of neonatal abstinence syndrome.

Prenatal exposure to drugs of abuse results in neonatal abstinence syndrome (NAS). NAS causes significant morbidity and is associated with costly and lengthy hospitalization. Current pharmacotherapy is suboptimal with no FDA approved treatments. We examined the effect of postnatal oxytocin treatment on survival and neurodevelopmental outcomes in rats prenatally exposed to opioids or benzodiazepines. Sprague-Dawley rat dams were injected with escalating doses of morphine (10-50 mg/kg/day) or diazepam (2-15 mg/kg/day) throughout gestation. In an initial experiment, exposed rat pups received subcutaneous injections of 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival rates were assessed. In a second experiment, exposed rat pups received subcutaneous injections of 0.3, 1, or 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival and body weight were assessed for 30 days. In animals surviving through adolescence, neurodevelopmental outcomes and biological parameters (blood glucose, corticosterone, aldosterone) were also measured. Postnatal oxytocin treatment improved survival in animals prenatally exposed to morphine or diazepam. Preliminary evidence showed that postnatal oxytocin treatment improves long-term learning and memory processes in animals prenatally exposed to morphine or diazepam. These findings highlight the potential of oxytocin as a novel treatment for NAS resulting from prenatal exposure to opioids or benzodiazepines.

Impact of Magnesium on Oxytocin Receptor Function.

BACKGROUND AND PURPOSE: The intranasal administration of oxytocin (OT) reduces migraine headaches through activation of the oxytocin receptor (OTR). Magnesium ion (Mg2+) concentration is critical to the activation of the OTR, and a low serum Mg2+ concentration is predictive of a migraine headache. We, therefore, examined the functional impact of Mg2+ concentration on OT-OTR binding efficacy using two complimentary bioassays. EXPERIMENTAL APPROACH: Current clamp recordings of rat trigeminal ganglia (TG) neurons measured the impact of Mg2+ on an OT-induced reduction in excitability. In addition, we assessed the impact of Mg2+ on intranasal OT-induced craniofacial analgesia in rats. KEY RESULTS: While OT alone dose-dependently hyperpolarized TG neurons, decreasing their excitability, the addition of 1.75 mM Mg2+ significantly enhanced this effect. Similarly, while the intranasal application of OT produced dose-dependent craniofacial analgesia, Mg2+ significantly enhanced these effects. CONCLUSIONS AND IMPLICATIONS: OT efficacy may be limited by low ambient Mg2+ levels. The addition of Mg2+ to OT formulations may improve its efficacy in reducing headache pain as well as for other OT-dependent processes.

GABAergic neuronal IL-4R mediates T cell effect on memory.

Mechanisms governing how immune cells and their derived molecules impact homeostatic brain function are still poorly understood. Here, we elucidate neuronal mechanisms underlying T cell effects on synaptic function and episodic memory. Depletion of CD4 T cells led to memory deficits and impaired long-term potentiation. Severe combined immune-deficient mice exhibited amnesia, which was reversible by repopulation with T cells from wild-type but not from IL-4-knockout mice. Behaviors impacted by T cells were mediated via IL-4 receptors expressed on neurons. Exploration of snRNA-seq of neurons participating in memory processing provided insights into synaptic organization and plasticity-associated pathways regulated by immune cells. IL-4Rα knockout in inhibitory (but not in excitatory) neurons was sufficient to impair contextual fear memory, and snRNA-seq from these mice pointed to IL-4-driven regulation of synaptic function in promoting memory. These findings provide new insights into complex neuroimmune interactions at the transcriptional and functional levels in neurons under physiological conditions.

Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons.

Interleukin (IL)-17a has been highly conserved during evolution of the vertebrate immune system and widely studied in contexts of infection and autoimmunity. Studies suggest that IL-17a promotes behavioral changes in experimental models of autism and aggregation behavior in worms. Here, through a cellular and molecular characterization of meningeal γδ17 T cells, we defined the nearest central nervous system-associated source of IL-17a under homeostasis. Meningeal γδ T cells express high levels of the chemokine receptor CXCR6 and seed meninges shortly after birth. Physiological release of IL-17a by these cells was correlated with anxiety-like behavior in mice and was partially dependent on T cell receptor engagement and commensal-derived signals. IL-17a receptor was expressed in cortical glutamatergic neurons under steady state and its genetic deletion decreased anxiety-like behavior in mice. Our findings suggest that IL-17a production by meningeal γδ17 T cells represents an evolutionary bridge between this conserved anti-pathogen molecule and survival behavioral traits in vertebrates.

SYNTHESIS OF 1,3,4-OXADIAZOLES AS SELECTIVE T-TYPE CALCIUM CHANNEL INHIBITORS.

Neuropathic pain, epilepsy, insomnia, and tremor disorder may arrive from an increase of intracellular Ca2+ concentration through a dysfunction of T-type Ca2+ channels. Thus, T-type calcium channels could be a target in drug discovery for the treatments of neuropathic pain and epilepsy. From rational drug design approach, a group of 2,5-disubstituted 1,3,4-oxadiazole molecules was synthesized and their selective T-type channel inhibitions were evaluated. The synthetic strategy consists of a short sequence of three reactions: (i) condensation of thiosemicarbazide with acid chlorides; (ii) ring closing by 1,3-dibromo-5,5- dimethylhydantoin; and (iii) coupling with various acid chlorides. 5-Chloro-N-(5- phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide (11) was found to selectively inhibit T-type Ca2+ channel over Na+ and K+ channels in mouse dorsal root ganglion neurons and/or human embryonic kidney (HEK)-293 cells and to suppress seizure-induced death in mouse model. Consequently, compound 11 is a useful probe for investigation of physiologic and pathophysiologic roles of the T-channel, and provides a basis to develop a novel therapeutic to treat chronic neuropathic and inflammatory pains.

Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep.

STUDY OBJECTIVES: A major challenge in treating insomnia is to find effective medicines with fewer side effects. Activation of G-protein-gated inward rectifying K+ channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) promotes nonrapid eye movement (NREM) sleep and consolidates sleep. However, baclofen has poor brain penetration, GHB possesses abuse liability, and in rodents both drugs cause spike-wave discharges (SWDs), an absence seizure activity. We tested the hypothesis that direct GIRK activation promotes sleep without inducing SWD using ML297, a potent and selective GIRK activator. METHODS: Whole-cell patch-clamp recordings from hypocretin/orexin or hippocampal neurons in mouse brain slices were made to study neuronal excitability and synaptic activity; spontaneous activity, locomotion, contextual and tone-conditioned memory, and novel object recognition were assessed. Electroencephalogram/electromyogram (EEG/EMG) recordings were used to study GIRK modulation of sleep. RESULTS: ML297, like baclofen, caused membrane hyperpolarization, decreased input resistance, and blockade of spontaneous action potentials. Unlike baclofen, ML297 (5-10 µM) did not cause significant depression of postsynaptic excitatory and inhibitory currents (EPSCs-IPSCs), indicating preferential postsynaptic inhibition. ML297 (30 mg/kg, i.p.) inhibited wake activity and locomotion, and preferentially increased NREM sleep without altering EEG delta power, REM sleep, inducing SWDs, or impairing conditioned memory and novel object recognition. CONCLUSIONS: This study finds that direct activation of neuronal GIRK channels modulates postsynaptic membrane excitability and prolongs NREM sleep without changing sleep intensity, inducing SWDs, or impairing memory in rodents. These results suggest that direct GIRK activation with a selective compound may present an innovative approach for the treatment of chronic insomnia.

CRISPR Activation Screens Systematically Identify Factors that Drive Neuronal Fate and Reprogramming.

Comprehensive identification of factors that can specify neuronal fate could provide valuable insights into lineage specification and reprogramming, but systematic interrogation of transcription factors, and their interactions with each other, has proven technically challenging. We developed a CRISPR activation (CRISPRa) approach to systematically identify regulators of neuronal-fate specification. We activated expression of all endogenous transcription factors and other regulators via a pooled CRISPRa screen in embryonic stem cells, revealing genes including epigenetic regulators such as Ezh2 that can induce neuronal fate. Systematic CRISPR-based activation of factor pairs allowed us to generate a genetic interaction map for neuronal differentiation, with confirmation of top individual and combinatorial hits as bona fide inducers of neuronal fate. Several factor pairs could directly reprogram fibroblasts into neurons, which shared similar transcriptional programs with endogenous neurons. This study provides an unbiased discovery approach for systematic identification of genes that drive cell-fate acquisition.

Chronic intermittent nicotine delivery via lung alveolar region-targeted aerosol technology produces circadian pharmacokinetics in rats resembling human smokers.

Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with episodic intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. We developed an integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method. We characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet-size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. Rats were exposed to nicotine aerosol once every half hour in the dark phase of 12:12-h light-dark cycles for 10 days. We optimized the parameters of aerosol generation and exposure: plasma nicotine and cotinine concentrations reached 30-35 and 190-240 ng/ml, respectively. The nicotine levels and circadian patterns resembled the pharmacokinetic pattern of human smokers. In summary, we developed an aerosol system that can produce clinically relevant chronic intermittent nicotine exposure in unanesthetized, unrestrained rodents with route of administration and circadian blood pharmacokinetics resembling human smokers. This methodology is a novel tool for understanding the health effects of chronic intermittent nicotine exposure such as with tobacco cigarettes and electronic cigarettes for studies of behavior, pharmacology and toxicology, nicotine addiction, tobacco-related diseases, and teratogenicity, and for the discovery of therapeutics. NEW & NOTEWORTHY We developed a lung alveolar region-targeted aerosol method and a system that provides chronic intermittent nicotine exposure in freely moving rodents. The method produces in rodents clinically relevant nicotine exposure with the route and circadian pharmacokinetics resembling human smokers. This method is a novel tool for understanding the health impacts of chronic nicotine exposures such as with tobacco cigarettes and electronic cigarettes, for studying nicotine pharmacology, toxicology, addiction, and tobacco-related diseases, and for the discovery of therapeutics.

Optimization of Optomotor Response-based Visual Function Assessment in Mice.

Optomotor response/reflex (OMR) assays are emerging as a powerful and versatile tool for phenotypic study and new drug discovery for eye and brain disorders. Yet efficient OMR assessment for visual performance in mice remains a challenge. Existing OMR testing devices for mice require a lengthy procedure and may be subject to bias due to use of artificial criteria. We developed an optimized staircase protocol that utilizes mouse head pausing behavior as a novel indicator for the absence of OMR, to allow rapid and unambiguous vision assessment. It provided a highly sensitive and reliable method that can be easily implemented into automated or manual OMR systems to allow quick and unbiased assessment for visual acuity and contrast sensitivity in mice. The sensitivity and quantitative capacity of the protocol were validated using wild type mice and an inherited mouse model of retinal degeneration - mice carrying rhodopsin deficiency and exhibiting progressive loss of photoreceptors. Our OMR system with this protocol was capable of detecting progressive visual function decline that was closely correlated with the loss of photoreceptors in rhodopsin deficient mice. It provides significant advances over the existing methods in the currently available OMR devices in terms of sensitivity, accuracy and efficiency.

The Anti-Amyloid-ß and Neuroprotective Properties of a Novel Tricyclic Pyrone Molecule.

There is an urgent unmet need for new therapeutics for Alzheimer's disease (AD), the most common cause of dementia in the elderly. Therapeutic approaches targeting amyloid-ß (Aß) and its downstream toxicities have become major strategies in AD drug development. We have taken a rational design approach and synthesized a class of tricyclic pyrone (TP) compounds that show anti-Aß and other neuroprotective actions. The in vivo efficacy of a lead TP named CP2 to ameliorate AD-like pathologies has been shown in mouse models. Here we report the selection and initial characterization of a new lead TP70, which exhibited an anti-Aß therapeutic index even higher than CP2. Moreover, TP70 was able to reduce oxidative stress, inhibit acyl-coenzyme A:cholesterol acyltransferase (ACAT), and upregulate the expression of ATP-binding cassette subfamily A, member 1 (ABCA1), actions considered neuroprotective in AD. TP70 further showed excellent pharmacokinetic properties, including brain penetration and oral availability. When administered to 5xFAD mice via intraperitoneal or oral route, TP70 enhanced the overall solubility and decreased the level of cerebral Aß, including both fibrillary and soluble Aß species. Interestingly, TP70 enhanced N-methyl-D-aspartate (NMDA) receptor-mediated excitatory post-synaptic potential (EPSP) in the hippocampal CA1 area, increased the magnitude of NMDA-dependent hippocampal long-term potentiation (LTP), a cellular model of learning and memory, and prevented the Aß oligomer-impaired LTP. Significantly, a single dose of TP70 administered to aged 5xFAD mice was effective in mitigating the impaired LTP induction, recorded at 24 h after administration. Our results support a potential of TP70 in clinical development for AD in view of its synergistic neuroprotective actions, ability to positively modulate NMDA receptor-mediated hippocampal plasticity, and favorable pharmacokinetic properties in rodents.

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice.

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation and downregulated in the aged brain. In addition to revitalizing other aged tissues, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction.

Analgesic Microneedle Patch for Neuropathic Pain Therapy.

Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury.

Traumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral endpoints in patients with traumatic brain injury after early interventions. In this study, we used the SmartCage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact (CCI) injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated SmartCage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury.

Minimally Invasive Sinus Tarsi Approach With Cannulated Screw Fixation Combined With Vacuum-Assisted Closure for Treatment of Severe Open Calcaneal Fractures With Medial Wounds.

The aim of our prospective study was to investigate the clinical results and advantages of a minimally invasive sinus tarsi approach with cannulated screw fixation combined with vacuum-assisted closure for the treatment of severe open calcaneal fractures with medial wounds. A total of 31 patients (32 feet) with open calcaneal fractures who were admitted to our hospital from January 2008 to May 2013 were selected for the study and randomly divided into 2 groups: the cannulated screw group (n = 16 patients, 16 feet) and the plate group (n = 15 patients, 16 feet). The Böhler and Gissane angles were compared before and after surgery. The clinical results were evaluated using according to the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and the rate of infection. The follow-up duration for all patients ranged from 10 to 36 (mean 24) months. No statistically significant differences were found in the radiologic indicators, incidence of early postoperative complications, or American Orthopaedic Foot and Ankle Society ankle-hindfoot scores (p > .05) between the 2 groups. However, a statistically significant difference was seen in the duration of hospitalization (p < .05) between the 2 groups. A minimally invasive sinus tarsi approach with cannulated screw fixation combined with vacuum-assisted closure is an effective method for the treatment of severe open calcaneal fractures with medial wounds. It provides good reduction and requires fewer days of hospitalization.

[Simultaneous Determination of Three Components in Ficus microcarpa Leaves by HPLC].

OBJECTIVE: To develop an HPLC method for the content determination of benzoic acid, 4-hydroxyphenylacetic acid and acetosyringonecas in Ficus microcarpa Leaves. METHODS: The determination was performed on Purospher® STAR C18 (250 mm x 4.6 mm,5 µm). The mobile phase was consisted of acetonitrile-0.2% phosphoric acid aqueous solution with linear gradient elution and the flow rate of 1.0 mL/min. The column temperature was set at 35 °C and the detection wavelength was 270 nm. RESULTS: The linear range of benzoic acid, 4-hydroxyphenylacetic acid and acetosyringonecas was 0.0121-1.21 µg (r = 0.9995), 0.423-42.32 [Lg ( r = 0.9999) and 0.047-4.70 pg( r = 0. 9996) , respectively. The average recovery was 100.7, 101.2 and 96.5 respectively. CONCLUSION: This method is simple,reproducible,and can be used for determination of three components of benzoic acid, 4-hydroxyphenylacetic acid and acetosyringonecas in Ficus microcarpa Leaves.

Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with µ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. SIGNIFICANCE STATEMENT: The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These knock-in mice have NOP receptors that function both in vitro and in vivo and have provided a detailed characterization of NOP receptors in brain, spinal cord, and DRG neurons. They appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function.