Search

We report an n-type Ge nanowire ferroelectric-Hf 0.5 Zr 0.5 O 2 field effect transistor (Ge NW FE-HZO FET) was experimentally demonstrated. An in-situ ALD O 3 treatment was carried out to form an atomically-thin (~0.4 nm) interfacial layer (IL) of GeO x , followed by a 2-nm FE-HZO capped with a 1-nm Al 2 O 3 layer. It is found that microwave annealing (MWA) sample shows better uniformity of FE-HZO properties compared to rapid thermal annealing (RTA). The fabricated Ge NW FE-HZO FET shows minimum subthreshold slope (SS min ) of 55 mV/decade and I ON /I OFF ratio of 8.1 × 104 with low hysteresis (30 mV) at drain voltage (V D ) of 0.1 V.

We synthesized BaTiO3–epoxy nanocomposites (particle size < 100 nm) with volume fractions up to 25 vol. %, whose high-frequency complex permittivity was characterized from 8.2 to 12.5 GHz. The maximum dielectric constant approaches 9.499 with an acceptable loss tangent of 0.113. The dielectric loss gradually saturates when the particle concentration is higher than 15 vol. %. This special feature is an important key to realizing high-k and low-loss nanocomposites. By comparing the theoretical predictions and the experimental data, four applicable effective-medium models are suggested. The retrieved dielectric constant (loss tangent) of 100-nm BaTiO3 nanopowder is in the range of 50–90 (0.1–0.15) at 8.2–12.5 GHz, exhibiting weak frequency dispersion. Two multilayer microwave devices—total reflection and antireflection coatings—are designed based on the fabricated nanocomposites. Both devices show good performance and allow broadband operation.

We synthesized BaTiO3–epoxy nanocomposites (particle size &lt, 100 nm) with volume fractions up to 25 vol. %, whose high-frequency complex permittivity was characterized from 8.2 to 12.5 GHz. The maximum dielectric constant approaches 9.499 with an acceptable loss tangent of 0.113. The dielectric loss gradually saturates when the particle concentration is higher than 15 vol. %. This special feature is an important key to realizing high-k and low-loss nanocomposites. By comparing the theoretical predictions and the experimental data, four applicable effective-medium models are suggested. The retrieved dielectric constant (loss tangent) of 100-nm BaTiO3 nanopowder is in the range of 50–90 (0.1–0.15) at 8.2–12.5 GHz, exhibiting weak frequency dispersion. Two multilayer microwave devices—total reflection and antireflection coatings—are designed based on the fabricated nanocomposites. Both devices show good performance and allow broadband operation.

Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern healthcare of the aging and diseased population. In this study, we developed a novel nano-fibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by XRD and FTIR. Cytotoxicity, cells adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells from rat. Rat forearm critical bone defect model was performed for the in vivo study. The nano-gelatin/hydroxyapatite fibers (NGF) were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of bone marrow stem cells on the nano-gelatin/hydroxyapatite fibers (NGF) could be enhanced. The osteogenic gene and protein expression were upregulated. Post implantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated nano-gelatin-hydroxyapatite fibers greatly improved healing potential on the critical sized bone defect. Although metformin-incorporated nano-gelatin/hydroxyapatite fibers had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications.

Ni-rich high-energy-density lithium ion batteries pose great risks to safety due to internal short circuits and overcharging; they also have poor performance because of cation mixing and disordering problems. For Ni-rich layered cathodes, these factors cause gas evolution, the formation of side products, and life cycle decay. In this study, a new cathode electrolyte interphase (CEI) for Ni

Implant-related infection may be catastrophic and result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Based on a transglutaminase (TGase) cross-linked/antibiotics-encapsulated gelatin-alginate hydrogel, the main aim of this study is to establish an effective antibiotic slow-release system. The second aim is to evaluate the efficacy of a hydrogel-encapsulated antibiotic-containing titanium pin in preventing implant-related infections in a rat model. The prepared gelatin/alginate/gentamicin or vancomycin hydrogel was covalently cross-linked with transglutaminase (TGase). Its drug release profile and cytotoxicity were determined and the Wistar rat animal model was performed to validate its efficacy by radiographic examination, Micro-CT (computed tomography) evaluation and histo-morphological analysis at 12 weeks after surgery. When gelatin and alginate were thoroughly mixed with TGase, both 0.5% and 1.0% TGase can effectively cross link the hydrogel, the release of antibiotic is slowed down with higher degree of TGase concentration (from 20 min to more than 120 h). In the animal study, antibiotic-impregnated hydrogel is effective in alleviating the implant-related infections. Relative to that of a positive control group, the experimental group (vancomycin treatment group) showed significant higher bone volume, more intact bony structure with only mild inflammatory cell infiltration. This newly designed hydrogel can effectively deliver antibiotics to reduce bacterial colonization and biofilm formation on the implant surface. The remaining challenges will be to confer different potent antibacterial medications with good biocompatibility and fulfill the safety, practical and economic criteria for future clinical translation.

Patients undergoing orthotopic allograft transplantation (OAT) will certainly suffer from vasculopathy. Although there are many immunosuppressive and immunomodulatory agents that are administered to patients, chronic rejection- induced vasculopathy cannot be entirely managed. Moreover, the implanted graft might become dysfunctional. In the past, we have used deionized reverse osmosis water (ROW) to stream via gold nanoparticles (AuNPs) at room temperature under powerful illumination, in order to prepare plasmon-activated water (PAW) with fewer hydrogen bonds. Compared to ROW, stable PAW can successfully remove free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals, and efficiently reduce lipopolysaccharide (LPS)-induced monocytes to release nitric oxide. Moreover, PAW can considerably induce the expression of the antioxidant gene Nrf2 in human gingival fibroblasts. Moreover, it might lower amyloid burden in mice with Alzheimer's disease. Furthermore, PAW decreased metastasis in mice grafted with Lewis lung carcinoma cells and boosted the overall survival in combination with cisplatin. Because of this possibility that PAW could prevent systemic disease, we aimed to evaluate the influence of PAW on OAT-induced vasculopathy. Here, we demonstrated that daily intake of PAW lowered the progression of vasculopathy in OAT-recipient ACI/NKyo rats by inhibiting collagen accumulation, proliferation of smooth muscle cells and fibroblasts, and T lymphocyte infiltration in the vessel wall. Moreover, the results showed reduced T and B lymphocytes, plasma cells, and macrophage activation in the spleen of the OAT-recipient ACI/NKyo rats that were administered PAW. Finally, in contrast to the control group, the OAT-recipient ACI/NKyo rats that were administered PAW exhibited higher mobilization and levels of circulating endothelial progenitor cells associated with vessel repair. Therefore, this study highlights the therapeutic roles of PAW in vasculopathy.

Animal models of haloperidol (HAL)-induced neurotoxicity and orofacial dyskinesia (OD) have long been used to study human tardive dyskinesia (TD). Similar to patients with TD, these models show strong pathophysiological characteristics such as striatal oxidative stress and neural cytoarchitecture alteration. Naringin (NAR), a bioflavonoid commonly found in citrus fruits, has potent antioxidative, anti-inflammatory, antiapoptotic, and neuroprotective properties. The present study evaluated the potential protective effects of NAR against HAL-induced OD in rats and the neuroprotective mechanisms underlying these effects. HAL treatment (1 mg/kg i.p. for 21 successive days) induced OD development, characterized by increased vacuous chewing movement (VCM) and tongue protrusion (TP), which were recorded on the 7th, 14th, and 21st day of drug treatment. NAR (30, 100, and 300 mg/kg) was administered orally 60 min before HAL injection for 21 successive days. On the 21st day, after behavioral testing, the rats were sacrificed, and the nitrosative and oxidative status, antioxidation power, neurotransmitter levels, neuroinflammation, and apoptotic markers in the striatum were measured. HAL induced OD development, with significant increases in the frequency of VCM and TP. NAR treatment (100 and 300 mg/kg) prevented HAL-induced OD significantly. Additionally, NAR treatment reduced the HAL-induced nitric oxide and lipid peroxide production, increased the antioxidation power and neurotransmitter levels in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results first demonstrate the neuroprotective effects of NAR against HAL-induced OD, suggesting that NAR may help in delaying or treating human TD in clinical settings.

Osteoarthritis (OA) is the most common joint disease type and is accompanied by varying degrees of functional limitation. Both hyaluronic acid (HA) joint injections and pain relievers are efficient treatments for early-stage osteoarthritis. However, for the decomposition by hyaluronidase and free radicals in the knee joint, HA injection treatment has limited effect time. The cerium oxide nanoparticles (CeO2) is a long time free radical scavenger. CeO2 combined with HA expected, may extend the HA decomposition time and have a positive effect on osteoarthritis therapy. In this study, CeO2 was successfully synthesized using the hydrothermal method with a particle size of about 120 nm, which possessed excellent dispersibility in the culture medium. The in vitro OA model was established by cell treated with H2O2 for 30 min. Our study found that the inhibition of chondrocyte proliferation dose-dependently increased with H2O2 concentration but was significantly decreased by supplementation of cerium oxide nanoparticles. COL2a1 and ACAN gene expression in chondrocytes was significantly decreased after H2O2 treatment, however, the tendency was changed after cerium oxide nanoparticles treatment, which suggested that damaged chondrocytes were protected against oxidative stress. These findings suggest that cerium oxide nanoparticles are potential therapeutic applications in the early stage of OA.

The eyes require a rich oxygen and nutrient supply; hence, the high-energy demand of the visual system makes it sensitive to oxidative stress. Excessive free radicals result in mitochondrial dysfunction and lead to retinal neurodegeneration, as an early stage of retinal metabolic disorders. Retinal cells are vulnerable because of their coordinated interaction and intricate neural networks. Nutraceuticals are believed to target multiple pathways and have shown neuroprotective benefits by scavenging free radicals and promoting mitochondrial gene expression. Furthermore, encouraging results demonstrate that nutraceuticals improve the organization of retinal cells and visual functions. This review discusses the mitochondrial impairments of retinal cells and the mechanisms underlying the neuroprotective effects of nutraceuticals. However, some unsolved problems still exist between laboratory study and clinical therapy. Poor bioavailability and bioaccessibility strongly limit their development. A new delivery system and improved formulation may offer promise for health care applications.

Inflammatory pain sensation is an important symptom which protects the body against additional tissue damage and promotes healing. Discovering long-term and effective treatments for pain remains crucial in providing efficient healthcare. Electroacupuncture (EA) is a successful therapy used for pain relief. We aimed to investigate effects and mechanisms of Complete Freund&rsquo, s Adjuvant (CFA)-inducing inflammatory pain in the cerebellum, and the inhibition of this inflammatory hyperalgesia using EA at Zusanli acupoint (ST36). The results display a significant increase in mechanical and thermal sensitivities in the CFA and CFA + SHAM groups, which was significantly reduced in the CFA+EA and CFA + KO groups. This evidence was substantiated in the protein levels observed using immunoblotting, and presented with significant escalations after CFA inducing inflammatory hyperalgesia in CFA and CFA + SHAM groups. Then, they were significantly attenuated by EA in the CFA + EA group. Furthermore, the CFA + transient receptor vanilloid member 1 (TRPV1)&minus, /&minus, group indicated similar significant decreases of protein expression. Additionally, a concomitant overexpression in lobule VIa was also observed in immunofluorescence. These consequences suggest that CFA-induced inflammatory pain provokes modifications in cerebellum lobules V, VIa and VII, which can subsequently be regulated by EA treatment at the ST36 through its action on TRPV1 and related molecular pathways.

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility of patients to irinotecan and its toxicity. This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy.The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping. The primary end-point was progression-free survival (PFS), and secondary end-points were overall response rate (ORR), disease control rate (DCR), overall survival (OS), AEs and metastasectomy rate.Over a median follow-up of 26.0 months (IQR, 17.0-35.0 months), study group (n = 107) was superior to the control group (n = 106) in PFS, OS, ORR, DCR, and metastasectomy rate (all P 0.05). Furthermore, there were no significant differences in AEs ≥ grade III between the two groups, even with the 1.36-fold increase in the relative dose intensity of irinotecan in the study group. Dose escalation of irinotecan, an independent factor of ORR (P 0.001) and DCR (P = 0.006), improved PFS in mCRC patients with wild-type and mutant KRAS (P = 0.007 and P = 0.019, respectively).The current study revealed that mCRC patients, regardless of KRAS gene status, with UGT1A1 genotyping can tolerate escalated doses of irinotecan and potentially achieve a more favourable clinical outcome without significantly increased toxicities.NCT02256800.

Background: Circadian rhythm disruption underlies the pathophysiology of psychiatric disorders, especially depression. Both pharmacological and non-pharmacological strategies affecting endogenous circadian rhythms have been developed with specificity to alter the circadian dysfunction. The current management strategy with antidepressants is far from being satisfactory in addressing this issue. In recent years, attempts at discovering new antidepressants focused on a melatonergic system which is known to be altered in depression have led to a potential option for treatment of depression. Methods: We reviewed all recently published relevant articles on melatonin and its analogues to look for their implication in the treatment of circadian rhythm disruption and depression. Results: Melatonin, a pleiotropic regulator molecule and its analogues (ramelteon, agomelatine, TIK-301, Neu- P11 and tasimelteon) have been observed to resynchronize the circadian rhythm and some were said to alleviate depressive symptoms in depressed subjects. Conclusion: This review focuses on substantial advances in the melatonin-based chronobiologic intervention and its responses in the treatment of depression.

Chronic constriction injury- (CCI-) induced neuropathic pain is the most similar model to hyperalgesia in clinical observation. Neuropathic pain is a neuronal dysfunction in the somatosensory system that may lead to spontaneous pain. In this study, electroacupuncture (EA) was applied at bilateral L4 and L6 of Hua Tuo Jia Ji points (EX-B2) for relieving neuropathic pain in rats. Eighteen Sprague-Dawley rats were randomly assigned to three groups: sham, 2-Hz EA, and 15-Hz EA groups. Following von Frey and cold plate tests, both the 2- and the 15-Hz EA groups had significantly lower mechanical and thermal hyperalgesia than the sham group. Western blot analysis results showed that γ-aminobutyric acid A (GABAA), adenosine A1 receptor (A1R), transient receptor potential cation channel subfamily V member 1 (TRPV1), TRPV4, and metabotropic glutamate receptor 3 (mGluR3) were similar in the dorsal root ganglion of all three groups. Furthermore, levels of GABAA receptors were higher in the spinal cord of rats in the 2- and 15-Hz EA groups compared with the sham control group. This was not observed for A1R, TRPV1, TRPV4, or mGluR3 receptors. In addition, all the aforementioned receptors were unchanged in the somatosensory cortex of the study rats, suggesting a central spinal effect. The study results provide evidence to support the clinical use of EA for specifically alleviating neuropathic pain.

Background The mechanisms underlying fibromyalgia (FM) pain are not understood. The US Food and Drug Administration has recommended three drugs for treating FM—namely, pregabalin, duloxetine and milnacipran; however, these medications are associated with severe side effects. Objective To create a mouse model of FM pain using dual injections of acidic saline to cause mechanical hyperalgesia and test whether ASIC3, Nav1.7 and Nav1.8 are involved in this process and whether electroacupuncture (EA) can reverse these phenomena. Methods The FM model was established by injecting acidic saline twice into 40 ICR mice. The mice were assigned to subgroups (n=8 each) treated with different EA frequencies (2, 15 and 50 Hz). ASIC3, Nav1.7 and Nav1.8 expression levels were measured by Western blotting and immunohistochemistry. Results Significant mechanical hyperalgesia was induced on day 8 in FM mice, which was reversed by 2, 15 and 50 Hz EA. ASIC3, Nav1.7 and Nav1.8 protein levels increased significantly in both the dorsal root ganglion and in the spinal cord of FM model mice. These changes were further attenuated by 2, 15 and 50 Hz EA. Conclusion Reduced nociceptive ASIC3, Nav1.7 and Nav1.8 proteins are involved in the preventive effects of EA against FM, and this series of molecules may represent targets for FM treatment.

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.

This paper presents the fabrication, characterization, and testing of the photocatalytic potential of a non-modified titania nanotube (TNT) and Sn-modified TNT synthesized through a facile one-step hydrothermal method. Two tin compounds (SnCl2 and SnO2) and aqueous solutions (HCl and SnCl2) were utilized as precursors and acid washing solutions, respectively. Because the Sn-modified TNT was free of calcination, the resulting sample possessed a high Brunauer-Emmett-Teller surface area. In addition, the Sn-modified TNT exhibited higher electron-hole separation efficiency. The photocatalytic reaction rate for the sample with methylene blue and malachite green dye decomposition was governed on the basis of their pre-adsorption abilities. The Sn-modified TNT had more Cl species than the non-modified TNT, resulting in higher pre-adsorption abilities for the methylene blue dye. Even though the Cl species on SnO2-TNT sample surface were removed, a higher electron-hole separation efficiency and anatase-rutile mixed phase can promote the photocatalyst activity of SnO2-TNT. On the other hand, the Cl species on the surface of SnO2-TNT-HCl washing sample appeared to act as one of the adsorption sites and enhance gaseous elemental mercury removal.

Objective Parkinson's disease (PD) is a degenerative disorder of the central nervous system. PD can be classified as idiopathic, acquired or hereditary and may be caused by various factors such as oxidative stress, loss of mitochondrial function, neuronal excitotoxicity or calcium imbalance. Methods We hypothesised that electroacupuncture (EA) at KI3 would reduce neuronal excitotoxicity by regulating N-methyl-D-aspartate (NMDA) receptor function and may represent a novel therapeutic approach for PD. Results Our results showed that deficits in spatial learning (reflected by the escape latency time in the Morris water maze task) and long-term potentiation (LTP) caused by systemic 6-hydroxydopamine (6-OHDA) administration (that damages dopaminergic neurons) could be rescued by EA on day 3. In PD mice, phosphorylated NMDA receptor subunits NR1 and NR2B were elevated (134.03±10.17% and 123.46±3.47% of baseline levels, respectively) but total NR1 and NR2B was unaffected (101.37±3.87% and 102.61±4.22% of baseline, respectively). Elevated levels of pNR1 and pNR2B, and phosphorylated forms of protein kinase A, protein kinase C, α Ca2+/calmodulin-dependent protein kinase extracellular signal-regulated kinases (pERK), and cAMP response element-binding protein were also reduced following EA. Conclusions These novel findings suggest that EA can rescue learning and LTP deficits in a rodent model of PD. The results point to a possible role for EA-based approaches in the clinical treatment of learning deficits associated with PD.

Objective N-methyl-D-aspartate receptor (NMDAR) activation and downstream transduction pathways are crucial for pain signalling. Fibromyalgia (FM) is a common pain syndrome of unclear aetiology that is often drug-refractory but may benefit from treatment with electroacupuncture (EA). We examined the contributions of NMDAR signalling to FM pain and EA responses in a mouse model. Methods A model of FM was established by acid saline injection in 32 mice and subgroups (n=8 each) were treated with EA (2 Hz, 15 min daily for 4 days) or minimal acupuncture (MA). Expression of NMDAR subunits, calmodulin-dependent protein kinase II (CaMKII), cyclic AMP response element binding protein (pCREB) and their corresponding phospho-activated forms were measured by Western blotting and immunohistochemistry. Results Acid saline injection induced significant mechanical hyperalgesia (paw withdrawal threshold 2.18±0.27 g, pConclusions Reduced NMDAR−CaMKIIα−pCREB signalling is implicated in the positive effects of EA in FM. NMDAR signalling components may represent promising therapeutic targets for FM treatment.

Background: Fibromyalgia (FM) is a syndrome involving chronic pain, fatigue, sleep difficulties, morning stiffness and muscle cramping lasting longer than 3 months. The epidemiological prevalence is approximately 3–5% in women and increases with age. Antagonism of acid-sensing ion channel 3 (ASIC3) reportedly attenuates acid saline-induced FM pain in mice. Aims: Whether pre-treatment with electroacupuncture (EA) or APETx2 can attenuate mechanical hyperalgesia in this murine model remains unknown. Methods: Accordingly, we examined the analgesic effect of EA in a murine model of FM pain induced by dual injections of acid saline and investigated whether EA or APETx2 can attenuate FM pain via the ASIC3 channel. Results: EA significantly reduced mechanical hyperalgesia in this model. ASIC3 antagonism, induced by injecting APETx2, also significantly reduced mechanical hyperalgesia. The expression of ASIC3 in the dorsal root ganglia, spinal cord and thalamus was increased after FM model induction. Over-expression of these nociceptive channels was attenuated by pre-treatment with EA or an ASIC3 antagonist. Conclusion: Our data reveal that both EA and ASIC3 blockade significantly reduce FM pain in mice via the ASIC3, Nav1.7 and Nav1.8 signalling pathways. Moreover, our findings support the potential clinical use of EA for the treatment of FM pain.

Comorbidity of chronic pain and major depression disorder (MDD) are common diseases. However, the mechanisms of electroacupuncture (EA) and the responses of N-methyl-D-aspartate receptors in the brain remain unclear. Three injections of complete Freund's adjuvant (CFA) were administered to induce chronic inflammatory pain (CIP). EA was then performed once every other day from days 14 to 28. Behavior tests of chronic pain and depression were evaluated to make sure of the successful induction of comorbidity. We used Western blotting to analyze brain tissue from the prefrontal cortex (PFC), hippocampus, and hypothalamus for levels of phosphorylated N-methyl-D-aspartate receptor subunit 1 (pNR1), NR1, pNR2B, NR2B, and calcium/calmodulin-dependent protein kinase type II alpha isoform (pCaMKIIα). The mechanical hyperalgesia, thermal hyperalgesia, and depression were observed in the CIP group. Furthermore, decreased levels of N-methyl-D-aspartate receptors (NMDARs) were also noted. Not Sham EA but EA reversed chronic pain and depression as well as the decreased levels of NMDA in the signaling pathway. The CFA injections successfully induced a significant comorbidity model. EA treated the comorbidity by upregulating the NMDA signaling pathway in the PFC, hippocampus, and hypothalamus. Our results indicated significant mechanisms of comorbidity of chronic pain and MDD and EA-analgesia that involves the regulation of the NMDAR signaling pathway. These findings may be relevant to the evaluation and treatment of comorbidity of chronic pain and MDD.

Alzheimer’s disease (AD) is the most common cause of dementia. Patients are generally to forget taking pills because of memory loss or to skip medication due to side effects; that might stop the medication and affect the results of the treatment. In this study, we combine donepezil with hydroxyapatite (HAP-DPZ) to deliver by intramuscular (IM) injection, which may prevent from patient to skip the daily medication and keep the medicine at a constant level in the blood to achieve a constant release. HAP particles synthesized by using the new oil-in-water method, the XRD pattern, and the FTIR spectrum were proved the synthesized of HAP. SEM and DLS showed the particle size of synthesized HAP-DPZ was in the range of 0.9–3 μm, which all in the optimal range for cellular uptake. In the drug release profile, DPZ could be released from HAP-DPZ by endosome/lysosome complex to achieve control releasing. In vitro study, there was no cytotoxicity found in HAP-DPZ. In the animal study, only one injection of HAP-DPZ administration, rats revealed well-focused searching strategies with the longest swimming time and most finding times in the quadrant where the platform was initially after three weeks.

The development of a novel alloplastic graft with both osteoinductive and osteoconductive properties is still necessary. In this study, we tried to synthesize a biomimetic hydroxyapatite microspheres (gelatin/nano-hydroxyapatite microsphere embedded with stromal cell-derived factor-1: GHM-S) from nanocrystalline hydroxyapatites and to investigate their therapeutic potential and effects on bone regeneration. In this study, hydroxyapatite was synthesized by co-precipitation of calcium hydroxide and orthophosphoric acid to gelatin solution. The microbial transglutaminase was used as the agent to crosslink the microspheres. The morphology, characterization, and thermal gravimetric analysis of microspheres were performed. SDF-1 release profile and in vitro biocompatibility and relative osteogenic gene expression were analyzed, followed by in vivo micro-computed tomography study and histological analysis. The synthesized hydroxyapatite was found to be similar to hydroxyapatite of natural bone tissue. The stromal cell-derived factor-1 was embedded into gelatin/hydroxyapatite microsphere to form the biomimetic hydroxyapatite microsphere. The stromal cell-derived factor-1 protein could be released in a controlled manner from the biomimetic hydroxyapatite microsphere and form a concentration gradient in the culture environment to attract the migration of stem cells. Gene expression and protein expression indicated that stem cells could differentiate or develop into pre-osteoblasts. The effect of bone formation by the biomimetic hydroxyapatite microsphere was assessed by an in vivo rats&rsquo, alveolar bone defects model and confirmed by micro-CT imaging and histological examination. Our findings demonstrated that the biomimetic hydroxyapatite microsphere can enhance the alveolar bone regeneration. This design has potential be applied to other bone defects.

Self-terminated oligomer additives synthesized from bismaleimide and barbituric acid derivatives improve the safety and performance of lithium-ion batteries (LIBs). This study investigates the interface interaction of these additives and the cathode material. Two additives were synthesized by Michael addition (additive A) and aza-Michael addition (additive B). The electrochemical performances of bare and modified LiNi0.6Mn0.2Co0.2O2 (NMC622) materials are studied. The cycling stability and rate capability of NMC622 considerably improve on surface modification with additive B. According to the differential scanning calorimetry results, the exothermic heat of fully deliathiated NMC622 is dramatically decreased through surface modification with both additives. The electrode surface kinetics and interface interaction phenomena of the additives are determined through surface plasma resonance measurements in operando gas chromatography-mass spectroscopy (GCMS) and in situ soft X-ray absorption spectroscopy (XAS). The binding rate constant of additive B onto NMC622 particles is 1.2-2.3 × 104 M-1 s-1 in the temperature range of 299-311 K, which is ascribed to the strong binding affinity toward the electrode surface. This affinity enhances Li+ diffusion, which allows the electrode modified by additive B to provide high electrochemical performance with superior thermal stability. In operando GCMS reveals that gas evolution due to the electrolyte degradation at the NMC622 surface contributes to safety hazards in the bare NMC622 material. In situ soft XAS indicates the occurrence of structural transformation in the bare NMC622 material after it is fully charged and at elevated temperatures. The NMC622 material is stabilized by incorporating additives. The unique performance of additive B can be attributed to its linear structure that allows superior electrode surface adhesion compared with that of additive A. Therefore, this study presents an optimized working principle of self-terminated oligomers, which can be developed and applied to improve the safety and performance of LIBs.

Background: Inflammatory pain occurs when local tissue injury activates macrophages and neutrophils, hence increasing pro-inflammatory cytokine and chemokine levels. Toll-like receptor 2 (TLR2) antagonism reportedly suppresses neuropathic and inflammatory pain. Aims: In the present study, we investigated the effect of electroacupuncture (EA) on TLR2 and related signalling molecules in a complete Freund’s adjuvant (CFA)-induced mouse model of inflammatory pain to determine whether EA can attenuate inflammatory pain via the TLR2 signalling pathway. Methods: EA significantly reduced mechanical and thermal hyperalgesia in the animal model. A similar effect was produced by TLR2 antagonism induced by CU-CPT22 injection. Results: TLR2 expression in the dorsal root ganglia, spinal cord and thalamus increased following induction of inflammation. Expression levels of downstream molecules such as pPI3K, pAkt and pmTOR also increased, as did those of MAPK subfamily members such as pERK, pp38 and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were also involved. Conclusion: Increased expression of the above molecules was attenuated by both EA and TLR2 antagonism. Our results show that EA attenuates inflammatory pain via TLR2 signalling.

Conspecific male animals fight for resources such as food and mating opportunities but typically stop fighting after assessing their relative fighting abilities to avoid serious injuries. Physiologically, how the fighting behavior is controlled remains unknown. Using the fighting fish Betta splendens, we studied behavioral and neurotranscriptomic changes during the fight between the two opponents. At the behavioral level, surface-breathing and biting/striking occurred only during intervals between mouth-lockings. Eventually, the behaviors of the two opponents became synchronized, with each pair showing a unique behavioral pattern. At the physiological level, we examined the expression patterns of 23,306 brain transcripts using RNA-sequencing data from brains of fighting pairs after a 20-min (D20) and a 60-min (D60) fight. The two opponents in each D60 fighting pairs showed a strong gene expression correlation, whereas those D20 fighting pair showed a weak correlation. Moreover, each fighting pair in the D60 group showed pair-specific gene expression patterns in the grade of membership analysis (GoM) and were grouped as a pair in the heatmap clustering. The observed pair-specific individualization in neurotranscriptomic synchronization (PINS) suggested that this synchronization provides physiological bases for the behavioral synchronization. An analysis using the synchronized genes in fighting pairs of the D60 found genes enriched for ion transport, synaptic function, and learning and memory. PINS could be a general phenomenon and may provide a new cornerstone to investigate coordinating and sustaining social interactions between two interacting partners of higher animals.

Background/Purpose Spinal cord injury (SCI) is a devastating medical condition for which no effective pharmacological interventions exist. l -Theanine (LT), a major amino acid component of green tea, exhibits potent antioxidative and anti-inflammatory activities and protects against various neural injuries. Here, we evaluated the potential therapeutic effects of LT on the recovery of behavioral motor functions after SCI in rats and the underlying neuroprotective mechanisms. Methods SCI was induced by applying vascular clips to the dura through a four-level T5–T8 laminectomy, and saline or LT (10/30 mg/kg) was intrathecally administered at 1-, 6-, and 24-h post-SCI. At 72-h post-SCI, half of the rats from each group for each parameter were sacrificed, and their spinal cord was excised for measurement of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase, catalase, tumor necrosis factor-α, interleukin-1β/-6, myeloperoxidase, and caspase-3. The remaining rats from each group were subjected to Bresnahan locomotor-rating scale (BBB), inclined-plane, toe-spread, and hindfoot bar-grab tests at 1-, 4-, 7-, 10-, and 14-days post-SCI. Results LT treatment reduced NO and MDA levels, increased antioxidative strength, and markedly suppressed the levels of neuroinflammatory and apoptotic markers in the spinal cord after SCI. Moreover, LT treatment drastically promoted the recovery of behavioral motor functions post-SCI. Conclusion Our findings revealed that LT can enhance the recovery of behavioral motor functions after SCI in rats, which related to the suppression of post-traumatic oxidative response, neural inflammation, and apoptosis. This evidence indicates that LT holds considerable potential for use in the clinical treatment/prevention of SCI-induced motor dysfunction.

Recent years have seen a rapidly rising number of oxygenated water brands that claim to impart health benefits and increase athletic performance by improving oxygen availability in the body. Drinks with higher dissolved oxygen concentrations have in recent times gained popularity as potential ergogenic aids, despite the lack of evidence regarding their efficacy. The aim of this study was to characterize oxygenated water and assess the improvement in uric acid metabolism while identifying performance enhancements in animals administered oxygenated water. Oxygenated water was characterized by hydrogen and oxygen nuclear magnetic resonance (NMR) spectroscopy. Hyperuricemia in rats was induced by treatment with oxonic acid potassium salt, and the animals were given oxygenated drinking water before, during, or after oxonic acid treatment. Serum uric acid was measured to confirm the effects on uric acid metabolism. Following oxygenation, the full width at half maximum (FWHM) was reduced to 11.56 Hz and 64.16 Hz in the hydrogen and oxygen NMR spectra, respectively. Oxygenated water molecule clusters were reduced in size due to the reduction in FWHM. Oxygen concentration did not vary significantly with increased temperature. However, standing time played a critical role in the amount of oxygen dissolved in the water. The rat studies indicated that oxygenated water reduced serum uric acid levels and their rate of increase and enhanced uric acid metabolism. A significant improvement in uric acid metabolism and rate of increase in serum uric acid concentration was observed in hyperuricemic rats administered oxygenated water compared to that in rats administered regular water. High oxygen concentrations enhanced the rate of oxygen absorption, leading to increased glycolysis and mitochondrial protein synthesis. Therefore, oxygenated water is a potential adjuvant therapy or health food for treatment of hyperuricemia.

The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit

This study reports the ferroelectric (FE) layer of Hf0.5Zr0.5O2 (HZO) film on a Ge gate-all-around field-effect-transistor (GAAFET) with inversion mode (IM) and junctionless (JL) mode, and is the first that discuss the association of the JL field-effect transistor conduction mechanism in the subthreshold region with the transient negative capacitance (TNC) effect of the FE layer are discussed. The IM Ge FE-GAAFET exhibited a minimum subthreshold slope (SSmin) of 55 mV dec−1 and a high ION/IOFF ratio of >106. The sub-60 mV dec−1 SS result demonstrates surface potential amplification, which is attributed to the TNC effect. Furthermore, the Ge JL FE-GAAFETs exhibited an SSmin of 58 mV dec−1, a high ION/IOFF ratio (>105), and reverse drain-induced barrier lowering when compared with baseline HfO2 devices. These IM and JL Ge FE-GAAFETs are highly suitable for low-power integrated circuit applications.