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Schematic shows the preparation of pure active water.

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-β has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-β in reducing mechanical allodynia caused by Complete Freund’s Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-β in naïve rats and the rats with CFA–induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-β in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-β antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-β is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-β at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-β produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-β injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/βR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-β is through µ-opioid receptors activation in spial cord.

Granulocyte colony-stimulating factor (G-CSF) has been reported to modulate pain function following nerve injury. However, the expression of endogenous G-CSF in the dorsal root ganglion (DRG) and the response to nerve injury remain unclear. In the present study, we demonstrated that G-CSF and G-CSFR are mainly expressed in both small- and medium-diameter DRG neurons in rats and are responsible for transmitting pain responses. G-CSF and G-CSFR were co-expressed in certain nociceptive DRG neurons. In addition, G-CSF was expressed in satellite glial cells around large-diameter DRG neurons. After sciatic nerve injury, the number of G-CSF-positive DRG neurons was increased in both the ipsilateral and contralateral lesion sites in rats. However, G-CSF expression in satellite glial cells was not affected by nerve injury. To clarify the role of G-CSF in pain, exogenous G-CSF was administered to a rat model of neuropathic pain induced by partial sciatic nerve transaction (PST). Our results indicate that treatment with G-CSF did not attenuate but exacerbated neuropathic pain. In summary, G-CSF may directly activate sensory neurons and contribute to nociceptive signaling.

The innovative plasmon-activated water (PAW) with reduced hydrogen bonds exhibits intrinsically distinct properties at room temperature, which are significantly different from the properties of untreated conventional deionized (DI) water. Examples of this are their ability to scavenge free radicals and higher vapor pressure. However, distinct properties of energetic PAW decay within the day after its creation in a metastable liquid state. In this work, we report a facile method for persisting its distinct activities by letting as-prepared PAW be quickly frozen in liquid nitrogen and letting the frozen PAW (for one month before further measurements) be quickly melted to room temperature in a warm-water bath (called treated PAW). Experimental results indicate that the activity of the higher evaporation rate of treated PAW compared to DI water can be maintained ca. 90% of magnitude, as compared to the as-prepared PAW. Also, its abilities to scavenge free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals can be maintained at ca. 70 and 80% of magnitudes, respectively. Moreover, this strategy of quickly freezing and melting treatments to PAW on persisting in distinct activity of PAW is effective in oxygen evolution reactions. This promises the stored energy and the distinct property of created liquid PAW being available in water-related fields after long-term storage.

Plasmon-activated water (PAW) with reduced hydrogen-bonded (HB) structure is created from conventional deionized (DI) water. Compared to DI water, PAW owns distinctly higher diffusion coefficient and electron transfer rate constant for electrochemical reactions. In this work, we discuss the more efficient oxygen (or hydrogen) evolution reaction (OER or HER) performed in PAW solutions, as compared to DI water solutions, in different concentrations of electrolytes at different applied potentials. Basically, the higher recorded currents based on PAW solutions are more significant when experiments are performed in lower concentrations of electrolytes and at lower applied overpotentials. Interestingly, the increased current density in percentage for OERs and HERs performed in PAW solutions compared to experiments performed in DI water solutions is less significant as the applied overpotential is increased. These interesting findings suggest that utilizing PAW with higher diffusion coefficient and electron transfer rate constant for more efficient electrochemical reactions is suitable in well diffusion- and kinetics-controlled systems. Also, in the Randles-Sevcik reaction, using the PAW solution takes more advantages in a lower concentration of K3Fe(CN)6 at a lower scan rate. This innovative concept has emerged as a promising strategy for effectively utilizing PAW in electrochemical reactions.

Melatonin is a lipophilic antioxidant generally dissolved in organic solvent before delivery. However, the presence of organics may severely depress the functional effects of melatonin. By rendering deionized water (DIW) flow through gold nano-particles under localized surface plasmon resonant illumination, we developed plasmon-activated water (PAW) which successfully increases the solubility of melatonin to 150.325%. Melatonin dissolved in PAW also exhibits stronger anti-viral and anti-oxidative activities than that dissolved in DIW in which the percentage of dengue virus infected human hepatocellular carcinoma cells is remarkably decreased (14.7% vs. 20.6%) whilst the clearance rate of hydroxyl radical is significantly enhanced (11.9% vs. 6.69%), respectively. Moreover, in vivo approaches further show that following chronic sleep deprivation, the level of oxidative stress, hepatic bioenergetics, anti-oxidative enzyme activity, and metabolic function are all significantly improved in rats received melatonin prepared in PAW than that in DIW. As the bio-activity of melatonin depends largely on its solubility, utilizing PAW as a non-organic solvent will not only enhance the anti-viral and anti-oxidative function of melatonin, but also offer great potential for clinical use of melatonin as a therapeutic strategy to depress virus infection and counteract oxidative damage in a more natural, more economic and more efficient way.

Liquid water, as the most environmentally friendly polar solvent, is popularly used in physical processes and chemical reactions. Its unique properties and activities come from the presence of intermolecular hydrogen bonds (HBs) with itself and other species. Scientists have been discussing properties other than known bulk water for a long time. However, the particular application of water being researched is limited today. Mass-produced active and stable plasmon-activated water (PAW) with a reduced HB network based on hot electron transfer (HET) from resonantly illuminated gold (Au) nanoparticles (NPs) was first created in 2014. In this work, we report its distinct intermolecular HBs with water-soluble alcohols and the solubility of hydrophobic solutes. Interestingly, the densities of PAW in methanol, ethanol, and propanol at various ratios all increased due to stronger HBs between PAW and the alcohols, particularly seen with propanol, compared to deionized water (DIW)-based systems. Moreover, these results reflect the decreased evaporation rates of PAW/alcohol solutions, especially observed for the solution with the maximum increased density, compared to DIW-based systems. Compared to DIW, the solubilities of hydrophobic antioxidants of curcumin and melatonin in PAW increased by ca. 240% and 120%, respectively. Moreover, sunflower oil was more soluble in the more-lipophilic PAW compared to conventional DIW. The distinct increased density of the alcohol/PAW solution lasted for at least 1 week. Innovative PAW has emerged as a promising green active solvent applicable for both hydrophilic and hydrophobic solutions.

Most of chemical reactions are performed in aqueous solutions, which are conventionally prepared using laboratory-ready and environmentally friendly deionized (DI) water. Water is generally considered as a passive reactant or as a spectator solvent. In this work, we demonstrate the added reagents for reactions in aqueous solutions can be effectively reduced by utilizing plasmon-activated water (PAW) with reduced hydrogen-bonded (HB) structure instead of conventional DI water with strong HB structure. For electrochemical reactions performing the similar currents the electrolytes used in PAW-based systems are ca. 90% concentrations compared to those used in DI water-based systems. Moreover, these concentrations used in PAW in situ-based systems can be further reduced to ca. 80% of magnitudes for maintaining the similar current levels. More interestingly, the recorded current of oxygen evolution reaction (OER) on a catalytic Pt electrode in the PAW-based system (0.09 M KOH) is significantly higher than that in the DI water-based system (0.1 M KOH). That means that the efficiency of the OER performed in a low-electrolyte-concentration alkaline solution can be markedly enhanced by utilizing PAW in spite of the electrolyte concentration is reduced by 10% of magnitude compared to the DI water-based system. These interesting findings promise the PAW for the effective and green reactants and solvents.

Water scarcity is one of the most serious global challenges of our time. One of the currently resolutions to this shortage is desalination. So far, most research on desalination has focused on preparing photothermal materials which possess the property of light-to-heat conversion. However, changing the intrinsic properties of water to improve the efficiency of solar evaporation has rarely been discussed. A new concept to increase the efficiency of desalination via destroying hydrogen bonds based on gold nanoparticles-adsorbed ceramic rods (AuNPs@CRs) is proposed here for the first time. Weakening the strength of interactions within water molecules by illumination with resonant light produces easily evaporable plasmon-activated water (PAW). This proposed system exhibits high efficiencies of steam generation in different experimental environments. Meanwhile, it was 140.0% and 107.5% more efficient than untreated water in an oven and an indoor environment, respectively. The source of resonant light from sunlight on a sunny or cloudy day can also achieve this performance. In addition, the results of water pump suction and direct contact membrane distillation (DCMD) further demonstrated that the illuminated AuNPs@CR system exhibits high potential for desalination.

Otitis externa caused by fungi (otomycosis) occurs more commonly in tropical areas with high moisture than in temperate regions. Bilateral otomycosis is, however, rarely reported. In a case of bilateral otitis externa in a 56-year-old male patient in Taiwan, direct microscopic examination of the cerumen as well as isolation of strains indicated the presence of two Aspergillus species being different in each of both ears. The species were identified by DNA sequence comparisons and additional morphological confirmation of diagnostic characteristics as Aspergillus flavus and Aspergillus terreus. The rarely reported occurrence of two Aspergillus species in otitis of the same patient deserves attention in other cases of otomycosis, particularly with respect to potentially different resistances of different species against antifungals. Treatment with nystatin/neomycin was not successful, but with clotrimazole was effective.

With the great extension of the human lifespan in recent times, many aging diseases have inevitably followed. Dementia is one of the most-commom neurodegenerative aging diseases, in which inflammation-related Alzheimer’s disease (AD) is the most prevalent cause of dementia. Amyloid accumulation in the brain, which occurs before any clinical presentations, might be the first and key step in the development of AD. However, many clinical trials have attempted to remove amyloid from brains of AD patients, but none has so far been successful. Negatively charged plasmon-activated water (PAW) is created by resonantly illuminated gold (Au) nanoparticles (NPs), which reduce the hydrogen-bonded (HB) structure of water. PAW was found to possess anti-oxidative and anti-inflammatory effects. Herein, we report on an innovative strategy to retard the progression of AD by the daily consumption of PAW instead of normal deionized (DI) water. APPswe/PS1dE9 transgenic mice were treated with PAW or DI water from the age of 5 months for the next 9 months. Encouragingly, compared to DI water-treated mice, mice treated with PAW presented better memory performance on a test of novel object recognition and had a significantly lower amyloid burden according to 18F-florbetapir amyloid-PET and phosphorylated (p)-tau burden according to Western blotting and immunohistochemistry measurements. There were no obvious side effects in PAW-treated mice. Collectively, our findings support that PAW was able to reduce the amyloid and p-tau burden and improve memory in an AD mouse model. However, the protein levels of molecules involved in amyloid metabolism and oligomeric amyloid did not change. We propose that the effects of PAW of reducing the amyloid burden and improving memory function cannot be attributed to synthesis/degradation of amyloid-βprotein but probably in preventing aggregation of amyloid-β proteins or other mechanisms, including anti-inflammation. Further applications of PAW in clinical trials to prevent the progression of AD are being designed.

Yaswanth Kuthati,1 Venkata Naga Goutham Davuluri,2 Chih-Ping Yang,3 Hsiao-Cheng Chang,1 Chih-Peng Chang,2 Chih Shung Wong1,41Department of Anesthesiology, Cathy General Hospital, Taipei, Taiwan; 2Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Anesthesiology, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; 4Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, TaiwanBackground: In recent years, several melatonin (MLT) receptor agonists have been approved by FDA for the treatment of sleep disorders and depression. Very few studies have shed light on their efficacy against neuropathic pain (NP). IIK-7 is an MT-2 agonist known to promote sleep. Whether IIK-7 suppresses NP has not been reported, and the signaling profile is unknown.Objective: To investigate the effect of melatonin type 2 receptor agonist IIK-7 on partial sciatic nerve transection-induced NP in rats and elucidate the underlying molecular mechanisms.Methods: NP was induced by the PSNT in the left leg of adult male Wistar rats. On post-transection day 7, rats were implanted with intrathecal (i.t) catheter connected to an infusion pump and divided in to four groups: sham-operated/vehicle, PSNT/vehicle, PSNT/0.5 μg/hr IIK-7 and PSNT/0.5 μg IIK-7/1 μg 4-p/hr. To test the MT-2 dependence on IIK-7 activity, the animals were implanted with a single i.t catheter and injected MT-2 antagonist 4-Phenyl-2-propionamidotetralin (4-p) 20 mins prior to IIK-7 injection on day 7 after PSNT. The antinociceptive response was measured using a mechanical paw withdrawal threshold. Activation of microglial cells and the expression of NP-associated proteins in the spinal cord dorsal horn was assessed by immunofluorescence assay (IFA) and Western blotting (WB). Reactive oxygen species (ROS) scavenging ability of IIK-7 was evaluated by using bone marrow-derived macrophages (BMDM).Results: Treatment with the MT-2 agonist IIK-7 significantly alleviated PSNT-induced mechanical allodynia and glial activation along with the inhibition of P44/42 MAPK, HMGB-1, STAT3, iNOS and casp-3 proteins.Conclusion: IIK-7 attenuates NP through the suppression of glial activation and suppression of proteins involved in inflammation and apoptosis. MT-2 receptor agonists may establish a promising and unique therapeutic approach for the treatment of NP.Keywords: neuropathic pain, MT-2 receptor, IIK-7, allodynia

Due to increasing global warming resulting from the greenhouse effect, subsequent environmental impacts and corresponding ecological influences are unavoidable. These problems are becoming more serious with time. Due to rising temperatures, the survival crisis of polar bears is a very often reported issue, because polar bears are encountering shortened seasons for catching prey on their sea-ice habitat. In this work, we report an innovative and facile strategy to save polar bears via prolonging the existence of ice layers based on plasmon-activated water (PAW). PAW with a reduced hydrogen-bonded network can be created by letting bulk deionized (DI) water flow through supported gold nanoparticles (AuNPs) under resonant illumination. Experimental results indicated that the freezing time of PAW was faster than that of DI water. In contrast, the melting time of frozen PAW was slower than that of the frozen DI water. Because the PAW with reduced hydrogen bonds (HBs) is in a high-energy state, it can more easily transform into a stronger HB structure in a low-energy state during cooling when freezing. This is accompanied by the release of more available energy, resulting in more-perfect tetrahedral symmetrical ice. Similar results were observed for solutions with 3 wt% NaCl, which is similar to the salinity of sea water. Moreover, the heat required to melt frozen PAW was ca. 7.6% higher than that of frozen DI water. These interesting phenomena suggest that prolonging the existence of solid ice can be achieved in a PAW-based system. Moreover, a system of AuNP-coated filter paper in DI water or in a DI water solution (3 wt% NaCl) under resonant illumination could work to prolong the presence of solid ice, compared to a system of AuNP-free filter paper. This innovative concept has emerged as a practical strategy to save polar bears and for other related applications.

Liquid water is the most commonly used environmental-friendly solvent and reactant in chemical reactions and physical processes. Conventionally, it is considered as a passive reactant. In this work, we investigate the potential of plasmon-activated water (PAW) with intrinsically reduced hydrogen-bonded structures compared to normal deionized (DI) water to serve as an active green energy resource. The efficiency of the electrochemical oxidation of water performed on a platinum electrode to form hydrogen peroxide is significantly enhanced in PAW compared to that in DI water. In addition, the limiting current density of the oxygen reduction reaction on a platinum/carbon-coated disk electrode is also enhanced when using PAW (in 0.9 wt % NaCl or in 0.1 M KOH). Moreover, the cell capacitance with semitransparent platinum-coated fluorine-doped SnO2 electrodes is significantly increased from ca. 2 × 10–9 to 6.1 × 10–7 F when decreasing the applied frequency from 10 to 0.1 Hz in a cell containing PAW instead of DI water (without the supporting electrolyte). More interestingly, compared to that in DI water, the efficiencies of the hydrogen evolution reaction in an acid solution (0.05 M H2SO4) and the oxygen evolution reaction in an alkaline solution (0.1 M KOH) performed with PAW in situ increase by about 20% with nanoscale-granulated gold electrodes under resonant illumination. These increases are more significant in neutral solutions for hydrogen evolution reactions and oxygen evolution reactions.

Chronic kidney disease (CKD) is inflammation-related. Patients with chronic renal failure who undergo hemodialysis (HD) have some acute adverse effects caused by dialysis-induced oxidative stress, protein adsorption, platelet adhesion, and activation of coagulation and inflammation. Here, resonantly illuminated gold nanoparticles-modified artificial kidney (AuNPs@AK) for achieving high efficiency accompanying therapeutic strategy for CKD during HD is proposed. The efficiency in removing uremic toxins increased obviously, especially in the presence of protein (closer to the real blood). The excited AuNPs@AK expressed negatively charged surface reduced some acute adverse effects caused by dialysis-induced protein adsorption, platelet adhesion, and activation of coagulation, thus avoiding thrombosis during HD. Unlike to traditional HD which provides only one function of removing uremic toxins, the solution collected from the outlet of the sample channel of excited AuNPs@AK showed an efficient free radical scavenger that could decrease dialysis-induced oxidative stress. In the CKD mouse model, this antioxidative solution from excited AuNPs@AK further decreased fibronectin expression and attenuated renal fibrosis, suggesting a reduced inflammatory response. These successful in vitro and in vivo approaches suggest that resonantly illuminated AuNPs@AK in HD take multiadvantages in shortening treatment time and reducing risk of adverse effects, which promise trailblazing therapeutic strategies for CKD.

A novel strategy for an environmentally friendly etching process is proposed based on the vapor from hot electron-activated (HEA) water, in which, HEA water with a weakly hydrogen-bonded structure is neutral. Compared to the vapor from deionized (DI) water, the vapor from HEA water exhibits a facile etching process to a glass sheet after exposing it to vapor at room temperature. The etched glass sheet demonstrates a granular surface morphology with a hydrophobic structure. In addition, the resulting nanostructured glass shows a uniform signal intensity of surface-enhanced Raman scattering (SERS) of rhodamine 6G (R6G). This is favorable for developing reliable sensors. The adhesion of deposited metals on the etched glass is also enhanced. Furthermore, the distortion and reformation of the deposited gold nanoparticles (AuNPs) by vapor from HEA water were observed. It suggests that this vapor has higher energy than conventional DI water does. This innovative concept has emerged as a promising strategy for environmentally friendly nanostructured etching.

Opioids are commonly prescribed for clinical pain management, however, dose-escalation, tolerance, dependence, and addiction limit their usability for long-term chronic pain. The associated poor sleep pattern alters the circadian neurobiology, and further compromises the pain management. Here, we aim to determine the correlation between constant light exposure and morphine tolerance and explore the potential of melatonin as an adjuvant of morphine for neuropathic pain treatment. Methods: Wistar rats were preconditioned under constant light (LL) or a regular light/dark (LD) cycle before neuropathic pain induction by chronic constriction injury. An intrathecal (i.t.) osmotic pump was used for continued drug delivery to induce morphine tolerance. Pain assessments, including the plantar test, static weight-bearing symmetry, and tail-flick latency, were used to determine the impact of the light disruption or exogenous melatonin on the morphine tolerance progression. Results: constant light exposure significantly aggravates morphine tolerance in neuropathic rats. Continued infusion of low-dose melatonin (3 &mu, g/h) attenuated morphine tolerance in both neuropathic and na&iuml, ve rats. This protective effect was independent of melatonin receptors, as shown by the neutral effect of melatonin receptors inhibitors. The transcriptional profiling demonstrated a significant enhancement of proinflammatory and pain-related receptor genes in morphine-tolerant rats. In contrast, this transcriptional pattern was abolished by melatonin coinfusion along with the upregulation of the Kcnip3 gene. Moreover, melatonin increased the antioxidative enzymes SOD2, HO-1, and GPx1 in the spinal cord of morphine-tolerant rats. Conclusion: Dysregulated circadian light exposure significantly compromises the efficacy of morphine&rsquo, s antinociceptive effect, while the cotreatment with melatonin attenuates morphine tolerance/hyperalgesia development. Our results suggest the potential of melatonin as an adjuvant of morphine in clinical pain management, particularly in patients who need long-term opioid treatment.

In electrochemical preparations of surface-enhanced Raman scattering (SERS)-active substrates, reactions are generally performed in aqueous solutions using deionized water (DIW) with 0.1 N electrolytes. The prepared SERS-active substrates are then thoroughly rinsed with DIW and dried for subsequent SERS measurements. In this work, we present comprehensive advantages of utilizing innovative plasmon-activated water (PAW) with reduced hydrogen bonds, compared to conventional DIW, on the subsequent signal intensities and reproducibility of SERS performances. Electrochemically roughened gold (Au) and silver (Ag) substrates were additionally immersed in PAW for 15 min to remove impurities, and the relative standard deviations (RSDs) of the SERS signals of model probe molecules of rhodamine 6G (R6G) were lower compared to those of substrates soaked in DIW. Moreover, for the SERS-active substrates prepared with Au/Ag nanocomposites using galvanic replacement reactions (GRRs), the RSD of the SERS signal of R6G was lower for the roughened Ag substrate immersed in the PAW solution containing positively charged Au ions, compared to that which was immersed in a DIW solution. Also, the corresponding SERS signals were higher for Au/Ag nanocomposites based on PAW systems. Similarly, SERS-active filter paper with Au/Ag nanocomposites prepared in a PAW solution, compared to a DIW solution, also demonstrated a better SERS effect. This strategy based on optimally prepared SERS-active Au substrates is also practically applicable for sensing imidacloprid and acetamiprid, commonly used pesticide that are generally detected in farm crops. These interesting findings indicate that SERS-active substrates prepared using PAW are sufficiently sensitive and reliable to develop SERS sensors.

It is recognized that the properties of liquid water can be markedly different from those of bulk one when it is in contact with hydrophobic surfaces or is confined in nano-environments. Because our knowledge regarding water structure on the molecular level of dynamic equilibrium within a picosecond time scale is far from completeness all of water’s conventionally known properties are based on inert “bulk liquid water” with a tetrahedral hydrogen-bonded structure. Actually, the strength of water’s hydrogen bonds (HBs) decides its properties and activities. In this review, an innovative idea on preparation of metastable plasmon-activated water (PAW) with intrinsically reduced HBs, by letting deionized (DI) water flow through gold-supported nanoparticles (AuNPs) under resonant illumination at room temperature, is reported. Compared to DI water, the created stable PAW can scavenge free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals and effectively reduce NO release from lipopolysaccharide-induced inflammatory cells. Moreover, PAW can dramatically induce a major antioxidative Nrf2 gene in human gingival fibroblasts. This further confirms its cellular antioxidative and anti-inflammatory properties. In addition, innovatively therapeutic strategy of daily drinking PAW on inflammatory-related diseases based on animal disease models is demonstrated, examples being chronic kidney disease (CKD), chronic sleep deprivation (CSD), and lung cancer.

Many human diseases are inflammation-related, such as cancer and those associated with aging. Previous studies demonstrated that plasmon-induced activated (PIA) water with electron-doping character, created from hot electron transfer via decay of excited Au nanoparticles (NPs) under resonant illumination, owns reduced hydrogen-bonded networks and physchemically antioxidative properties. In this study, it is demonstrated PIA water dramatically induced a major antioxidative Nrf2 gene in human gingival fibroblasts which further confirms its cellular antioxidative and anti-inflammatory properties. Furthermore, mice implanted with mouse Lewis lung carcinoma (LLC-1) cells drinking PIA water alone or together with cisplatin treatment showed improved survival time compared to mice which consumed only deionized (DI) water. With the combination of PIA water and cisplatin administration, the survival time of LLC-1-implanted mice markedly increased to 8.01 ± 0.77 days compared to 6.38 ± 0.61 days of mice given cisplatin and normal drinking DI water. This survival time of 8.01 ± 0.77 days compared to 4.62 ± 0.71 days of mice just given normal drinking water is statistically significant (p = 0.009). Also, the gross observations and eosin staining results suggested that LLC-1-implanted mice drinking PIA water tended to exhibit less metastasis than mice given only DI water.

The role of the hepato-protective agent plasmon-activated water (PAW) as an innovative anti-oxidant during chronic sleep deprivation (SD) is realized in this study. PAW possesses reduced hydrogen-bonded structure, higher chemical potential and significant anti-oxidative properties. In vitro tests using rat liver cell line (Clone-9) have demonstrated that PAW is non-cytotoxic and does not change the cellular migration capacity. The in vivo experiment on SD rats suffering from intense oxidative damage to the liver, an extremely common phenomenon in the present-time with deleterious effects on metabolic function, is performed by feeding PAW to replace deionized (DI) water. Experimental results indicate that PAW markedly reduces oxidative stress with enhanced bioenergetics in hepatocytes. PAW also effectively restores hepatocytic trans-membrane ion homeostasis, preserves membranous structures, and successfully improves liver function and metabolic activity. In addition, the hepato-protective effects of PAW are evidently demonstrated by the reduced values of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) and the recovery of total protein and albumin levels. With clear evidences of PAW for protecting liver from SD-induced injury, delivering PAW as a powerful hepato-protective agent should be worthy of trailblazing new clinical trials in a healthier, more natural, and more convenient way.

Interesting properties of water with distinguishable hydrogen-bonding structure on interfacial phase or in confined environment have drawn wide attentions. However, these unique properties of water are only found within the interfacial phase and confined environment, thus, their applications are limited. In addition, quantitative evaluation on these unique properties associating with the enhancement of water's physical and chemical activities represents a notable challenge. Here we report a practicable production of free-standing liquid water at room temperature with weak hydrogen-bonded structure naming Au nanoparticles (NPs)-treated (AuNT) water via treating by plasmon-induced hot electron transfer occurred on resonantly illuminated gold NPs (AuNPs). Compared to well-known untreated bulk water (deionized water), the prepared AuNT water exhibits many distinct activities in generally physical and chemical reactions, such as high solubilities to NaCl and O2. Also, reducing interaction energy within water molecules provides lower overpotential and higher efficiency in electrolytic hydrogen production. In addition, these enhanced catalytic activities of AuNT water are tunable by mixing with deionized water. Also, most of these tunable activities are linearly proportional to its degree of nonhydrogen-bonded structure (DNHBS), which is derived from the O-H stretching in deconvoluted Raman spectrum.

The properties of confined liquid water, or liquid water in contact with hydrophobic surfaces, are significantly different from those of bulk liquid water. However, all of water's commonly described properties are related to inert "bulk liquid water" which comprises a tetrahedral hydrogen-bonded network. In this work, we report an innovative and facile method for preparing small water clusters (SWCs) with reduced affinity hydrogen bonds by letting bulk water flow through supported Au nanoparticles (NPs) under resonant illumination to give NP-treated (AuNT) water at constant temperature. Utilizing localized surface plasmon resonance on illuminated Au NPs, the strong hydrogen bonds of bulk water can be disordered when water is located at the illuminated Au/water interface. The prepared SWCs are free of Au NPs. The energy efficiency for creating SWCs is ∼17%. The resulting stable AuNT water exhibits distinct properties at room temperature, which are significantly different from the properties of untreated bulk water, examples being their ability to scavenge free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals and to effectively reduce NO release from lipopolysaccharide-induced inflammatory cells.

Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. We designed this investigation to examine whether ultra-low dose naloxone administered alone or in combination with morphine could alter the concentration of the excitatory amino acids (EAAs) glutamate and aspartate, as well as the expression of tumor necrosis factor-α (TNF-α) and its receptors (TNFR1 and TNFR2) in the spinal cord dorsal horn of rats with partial sciatic nerve transection (PST).Male Wistar rats underwent intrathecal catheter implantation for drug delivery and were divided in 7 groups: sham-operated + saline (sham), PST + saline (S), PST + 15 ng naloxone (n), PST + 15 µg naloxone (N), PST + 10 µg morphine (M), PST + 15 ng naloxone + 10 µg morphine (Mn), PST + 15 µg naloxone + 10 µg morphine (MN). Thermal withdrawal latency and mechanical withdrawal threshold, TNF-α and TNFR expression in the spinal cord and dorsal root ganglia, and EAAs glutamate and aspartate concentration in cerebrospinal fluid dialysates were measured.Ten days after PST, rats developed hyperalgesia (P0.0001) and allodynia (P0.0001), and increased TNF-α (P0.0001) and TNFR1 expression (P = 0.0009) were measured in the ipsilateral spinal cord dorsal horn. The antihyperalgesic and antiallodynic effects of morphine (10 μg) were abolished by high-dose naloxone (15 μg; P = 0.0031) but enhanced by ultra-low dose naloxone (15 ng; P = 0.0015), and this was associated with a reduction of TNF-α (P0.0001) and TNFR1 (P = 0.0009) expression in the spinal cord dorsal horn and EAAs concentration (glutamate: P = 0.0001; aspartate: P = 0.004) in cerebrospinal fluid dialysate. Analysis of variance (ANOVA) or Student t test with Bonferroni correction were used for statistical analysis.Ultra-low dose naloxone enhances the antihyperalgesia and antiallodynia effects of morphine in PST rats, possibly by reducing TNF-α and TNFR1 expression, and EAAs concentrations in the spinal dorsal horn. Ultra-low dose naloxone may be a useful adjuvant for increasing the analgesic effect of morphine in neuropathic pain conditions.

Theoretical calculations indicate that the properties of confined liquid water, or liquid water at surfaces, are dramatically different from those of liquid bulk water. Here we present an experimentally innovative strategy on comprehensively efficient oxygen evolution reaction (OER) utilizing plasmon-induced activated water, creating from hot electron decay at resonantly illuminated Au nanoparticles (NPs). Compared to conventional deionized (DI) water, the created water owns intrinsically reduced hydrogen-bonded structure and a higher chemical potential. The created water takes an advantage in OER because the corresponding activation energy can be effectively reduced by itself. Compared to DI water-based solutions, the OER efficiencies at Pt electrodes increased by 69.3%, 21.1% and 14.5% in created water-based acidic, neutral and alkaline electrolyte solutions, respectively. The created water was also effective for OERs in photoelectrochemically catalytic and in inert systems. In addition, the efficiency of OER increased by 47.5% in created water-based alkaline electrolyte solution prepared in situ on a roughened Au electrode. These results suggest that the created water has emerged as an innovative activator in comprehensively effective OERs.

Water is a ubiquitous solvent in biological, physical and chemical processes. Unique properties of water result from water’s tetrahedral hydrogen-bonded (HB) network (THBN). The original THBN is destroyed when water is confined in a nanosized environment or localized at interfaces, resulting in corresponding changes in HB-dependent properties. In this work, we present an innovative idea to validate the reserve energy of high-energy water and applications of high-energy water to promote water’s fundamental activities of solubility, ionic conductivity and extraction at room temperature. High-energy water with reduced HBs was created by utilizing hot electrons with energies from the decay of surface plasmon excited at gold (Au) nanoparticles (NPs). Compared to conventional deionized (DI) water, solubilities of alkali metal-chloride salts in high-energy water were significantly increased, especially for salts that release heat when dissolved. The ionic conductivity of NaCl in high-energy water was also markedly higher, especially when the electrolyte’s concentration was extremely low. In addition, antioxidative components, such as polyphenols and 2,3,5,4’-tetrahydroxystilbene-2-O-beta-d-glucoside (THSG) from teas and Polygonum multiflorum (PM), could more effectively be extracted using high-energy water. These results demonstrate that high-energy water has emerged as a promising innovative solvent for promoting water’s fundamental activities via effective energy transfer.

Splitting water for hydrogen production using light, or electrical energy, is the most developed ‘green technique’. For increasing efficiency in hydrogen production, currently, the most exciting and thriving strategies are focused on efficient and inexpensive catalysts. Here, we report an innovative idea for efficient hydrogen evolution reaction (HER) utilizing plasmon-activated liquid water with reduced hydrogen-bonded structure by hot electron transfer. This strategy is effective for all HERs in acidic, basic and neutral systems, photocatalytic system with a g-C3N4 (graphite carbon nitride) electrode, as well as in an inert system with an ITO (indium tin oxide) electrode. Compared to deionized water, the efficiency of HER increases by 48% based on activated water ex situ on a Pt electrode. Increase in energy efficiency from activated water is 18% at a specific current yield of −20 mA in situ on a nanoscale-granulated Au electrode. Moreover, the onset potential of −0.023 V vs RHE was very close to the thermodynamic potential of the HER (0 V). The measured current density at the corresponding overpotential for HER in an acidic system was higher than any data previously reported in the literature. This approach establishes a new vista in clean green energy production.

Objective: Analyzing changes in regional cerebral blood flow (rCBF) with SPECT in complex regional pain syndrome type 1 (CRPS 1), formerly known as reflex sympathetic dystrophy, is an optimal method for evaluating effective pain relief. We attempted to investigate the correlation of changes in rCBF with pain relief during treatments of sympathetic blockade and multimodal epidural pain control. Case Report: We describe a patient with severe CRPS 1 in whom conventional treatment failed to relieve the pain. Combined repeated lumbar sympathetic blocks and long-term epidural morphine, bupivacaine, and ketamine administration provided satisfactory pain relief and functional activity recovery. Six normal control subjects having one Tc-99m HMPAO scan each and the patient with CRPS having 3 Tc-99m HMPAO scans (once before treatment and twice at 4 months and 6 months after treatment, respectively). The patient with CRPS showed lower rCBF than normal controls in the left thalamus and higher rCBF than normal controls in the right parietal lobe and left frontal lobe. After subsequent treatment, the subtraction images showed increased rCBF in the left thalamus and decreased rCBF in the right parietal and left frontal lobes. Conclusions: Tc-99m HMPAO SPECT showed a relationship of rCBF in the thalamus, parietal lobe, and frontal lobe with pain relief. rCBF alterations may provide an indicator for the quality of pain management for neuropathic pains. Subtraction analysis between pre- and posttreatment, by using statistical parametric mapping (version 2), can be used as an objective indicator for the effectiveness of therapy.

Colonic surgery is associated with severe postoperative pain and postoperative ileus, which contribute to delayed hospital discharge. In previous studies, we demonstrated that IM dextromethorphan (DM) provided preemptive analgesia and improved postoperative pain. The benefit of thoracic epidural anesthesia (TEA) and postoperative epidural analgesia on postoperative pain was well demonstrated. The goal of this study was to investigate the effect of preincisional IM DM combined with intraoperative TEA and postoperative patient-controlled epidural analgesia (PCEA) on pain and bowel function after colonic surgery. Patients were randomized into 3 equal groups to receive: 1) chlorpheniramine maleate (CPM) 20 mg and general anesthesia (CPM-GA); 2) CPM 20 mg and GA combined with TEA (CPM-TEA); or 3) DM 40 mg (containing 20 mg of CPM) and GA combined with TEA (DM-TEA). The CPM, DM, and TEA with lidocaine were administered after GA induction via an IM injection and 30 min before the skin incision. All patients received postoperative PCEA for pain control. Analgesic effects were evaluated for 72 h after surgery using visual analog scale pain scores at rest and moving, time to first PCEA request for pain relief, total PCEA consumption, and the time to first passage of flatus. Statistically significant improvement of postoperative pain and bowel function was observed in the following order: DM-TEA > CPM-TEA > CPM-GA. Compared with the CPM-TEA group, the DM-TEA group averaged 1.6 points lower on first-hour pain scores, 40 min longer to first PCEA request, 15.8 mL less PCEA drug over 72 h, and 14.7 h earlier bowel function (all P < 0.01). We conclude that the combination of preincisional DM (40 mg IM), intraoperative TEA, and postoperative PCEA enhances analgesia and facilitates recovery of bowel function, suggesting possible synergistic interaction with local anesthetics and opioids.

The applicability of the physical stability of protein solution monitored by isothermal titration calorimetry (ITC) was evaluated. The second virial coefficient, b2, derived from the dilution enthalpies of protein solution measured by ITC under various experimental conditions was studied. The protein applied in this work is human recombinant interferon-alpha2a (hrIFN-alpha2a), which is a commercial drug applied for the treatment of virus-infected diseases. The results obtained were used to predict the possibility of hrIFN-alpha2a aggregation, and the prediction can be further confirmed by size-exclusion chromatography (SEC). Various factors affecting the stability of protein solution were investigated, for example, temperature, salts, surfactants, and mechanical stress. Specifically, the results show that the dilution enthalpy of hrIFN-alpha2a increased with increasing temperature and NaCl concentration, while b2 decreased, indicating that the attraction between hrIFN-alpha2a molecules was enhanced under these conditions. On studying the effect of mechanical stress, the data obtained reveals that the introduction of centrifugal or vortex force strengthened the attractive forces between hrIFN-alpha2a molecules. These implications were supported by SEC data, demonstrating that the amount of aggregated hrIFN-alpha2a was increased. As a consequence, the methodologies presented in this investigation offer a possibility of monitoring the physical stability of protein solution at various stages of recovery, purification as well as the development of appropriate drug storage formulations.

Measurements of mean velocities, turbulence intensities, and Reynolds stresses are presented for spatially periodic flows in a duct of width-to-height ratio 2 with a detached solid-rib array. The Reynolds number based on the duct hydraulic diameter and cross-sectional bulk mean velocity (Ub), the pitch to rib-height ratio, and the rib-height to duct-height ratio were 2 × 104, 10, and 0.133, respectively. The rib-detached-distance to rib-height ratio was varied from 0 to 3.25 (duct axis) to study its effect on wake length and asymmetry, convective velocity and turbulent kinetic energy immediately behind the rib, maximum turbulent shear stress, and turbulence anisotropy. The results showed that the dominant fluid dynamic factors responsible for the reported peak values of local Nusselt number around the detached rib could be identified. Moreover, the turbulence structure parameter distribution and anisotropy were analyzed to examine the basic assumptions embedded in the turbulence models. Furthermore, the secondary-flow mean velocities were found to be one to two order of magnitude smaller than Ub.

Dural puncture or a rent in the dura with prolonged cerebrospinal fluid leakage may cause noninfectious arachnoiditis and may be associated with urinary and fecal incontinence. Visceral dysfunction is common for patients with noninfectious arachnoiditis of the lumbosacral nerve roots after dural puncture. We report a case of postdural puncture headache associated with abdominal pain and diarrhea. An epidural blood patch was performed, and all symptoms resolved after 5 days. After exclusion of organic and psychological disorders, this treatment might be considered for patients who are experiencing abdominal pain and diarrhea after dural puncture.

Uremic toxins are mainly represented by blood urine nitrogen (BUN) and creatinine (Crea) whose removal is critically important in hemodialysis (HD) for kidney disease. Patients undergoing HD have a complex illness, resulting from: inadequate removal of organic waste, dialysis-induced oxidative stress and membrane-induced inflammation. Here we report innovative breakthroughs for efficient and safe HD by using a plasmon-induced dialysate comprising Au nanoparticles (NPs)-treated (AuNT) water that is distinguishable from conventional deionized (DI) water. The diffusion coefficient of K3Fe(CN)6 in saline solution can be significantly increased from 2.76, to 4.62 × 10(-6) cm s(-1), by using AuNT water prepared under illumination by green light-emitting diodes (LED). In vitro HD experiments suggest that the treatment times for the removals of 70% BUN and Crea are reduced by 47 and 59%, respectively, using AuNT water instead of DI water in dialysate, while additionally suppressing NO release from lipopolysaccharide (LPS)-induced inflammatory cells.

IMPLICATIONS Small-dose IV vasopressin infusion may be beneficial in acute brain injury patients with unstable hemodynamics who are refractory to fluid resuscitation and catecholamine vasopressors.

The asymmetric syntheses of 1-deoxycastanospermine (6) and 1-deoxy-8a-epi-castanospermine (7) have been completed. A key step in these syntheses was the stereoselective addition of 2-furyllithium to the 4-O-tert-butyldiphenylsilyl-protected threose derivative 13 to give the C(7)-C(8) syn-adduct 14 as the major product. The diastereoselectivity of this reaction is particularly noteworthy since the related addition of 2-furyllithium to the corresponding 4-O-benzyl-protected aldehyde 8 proceeded in the opposite stereochemical sense to give primarily the C(7)-C(8) anti-adduct 10. Oxidation of the furan ring in 14 followed by refunctionalization led to the azido ketone 20, followed by reductive amination gave 6 or 7

Repeated lumbar sympathetic blockade (LSB) with local anesthetics is generally used in complex regional pain syndrome (CRPS) of the lower extremities if the initial block has been successful. However, the symptoms of CRPS may inevitably recur in spite of repeated LSB. Clonidine, an alpha2-adrenoceptor agonist, has both anesthetic and analgesic sparing effects, and when added to local anesthetics may enhance peripheral and central neural block due to its local or central analgesic effects. It is reasonable that clonidine has been used in chronic pain conditions such as neuropathic and sympathetically maintained pain. Here we report two cases of CRPS type 1 who got excellent analgesia and alleviation of clinical symptoms after receiving an LSB with lidocaine and clonidine.

In this study we examined the onset times of sensory and motor block during epidural ropivacaine anesthesia with and without the addition of fentanyl to the epidural solution. Forty-five young male patients undergoing knee arthroscopic surgery were randomly allocated into 3 groups of 15 patients each: epidural fentanyl (EF; epidural administration of 15 mL of 1% ropivacaine plus 100 mug fentanyl followed by IV injection of 2 mL of normal saline); IV fentanyl (IF; epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline followed by IV injection of 100 mug fentanyl); and control (C; epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline followed by IV injection of 2 mL of normal saline). The sensory and motor blocks were assessed by pinprick and modified Bromage scale, respectively. The hemodynamic changes, postepidural shivering, and side effects of epidural fentanyl were also recorded. There was no difference in the distribution of age, weight, and height among the 3 groups. The onset time of sensory block to the T10 dermatome was significantly more rapid in the EF group (13.0 +/- 3.0 min) than in the IF group (16.2 +/- 3.5 min, P < 0.05) or C group (17.7 +/- 3.6 min, P < 0.05). The onset times of motor block up to Bromage scale 1 and 2 were significantly more rapid in the EF group (11.9 +/- 4.6 and 24.4 +/- 5.9 min) than in the IF group (16.9 +/- 4.7 and 30.8 +/- 5.6 min, P < 0.05) or C group (18.3 +/- 4.9 and 32.7 +/- 5.7 min, P < 0.05). There was no difference in the incidence of shivering among the three groups. Pruritus was observed in three patients of the EF group and one patient of the IF group. No nausea, vomiting, respiratory depression, urinary retention, or hypotension was observed in any patient. We conclude that epidural administration of the mixture of 100 mug fentanyl and 1% ropivacaine solution accelerated the onset of sensory and motor blocks during epidural ropivacaine anesthesia without significant fentanyl-related side effects.

Bradycardia is commonly seen in high spinal anesthesia, however, evolution of cardiac arrest from sudden onset of severe bradycardia is infrequent. Prompt recognization and resuscitative measures are of paramount importance because they may insure a complete recovery without sequela as an aftermath. We report herein a case of severe sinus bradycardia induced by clipping of the appendix during appendectomy under spinal anesthesia with the sensory block up to T5 dermatome. Prompt intravenous atropine failed to regain normal sinus rhythm, and cardiac arrest ensued. Cardiac massage, manual ventilation with oxygen and low-dose epinephrine successfully resuscitated the patient. The possible mechanisms and management of this complication are also discussed.

The typical postdural puncture headache manifests as postural frontal, frontotemporal, or occipital headache, which is worsened by ambulation, and improved by decubitus. Accompanying symptoms are nausea, vomiting, and neck stiffness. Various rare presentations after dural puncture, such as upper back pain, arm pain, thoracic pain, bowel and bladder dysfunction have been sparsely reported. We report two cases who sustained arm and upper back pain after spinal anesthesia, and epidural blood patch gave them a complete relief of the symptoms.