Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in Alzheimer's disease models.

Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in AD models.

Altruistic behaviour decreases agent's unhealthy food intake: Based on the self-determination theory model of vitality.

This study explored whether altruistic behaviour would decrease agent's unhealthy food intake, and whether vitality and state self-control would sequentially mediate this effect based on the Self-Determination Theory Model of Vitality. It included 1019 college students in total across three studies. Study 1 was a laboratory experiment. By framing a physical task as a helping behaviour or a neutral experimental task, we examined whether these framed tasks impacted participants' subsequent unhealthy food intake levels. Study 2 was an online investigation measuring the relationship between donation (vs. no donation) behaviour and participant's estimated unhealthy food intake level. Study 3 was an online experiment with a mediation test. By random assignment of conducting a donation behaviour versus a neutral task, we examined whether these behaviours affected participants' vitality, state self-control, and estimated unhealthy food intake levels. In addition, we tested a sequential mediation model with vitality and state self-control as the mediators. Both unhealthy and healthy foods were included in Study 2 and 3. Results showed that altruistic behaviour could decrease agent's unhealthy (but not healthy) food intake, and this effect was sequentially mediated by vitality and state self-control. The findings highlight that altruistic acts may buffer agents against unhealthy eating behaviour.

The combination of skeleton-engineering and periphery-engineering: a design strategy for organic doublet emitters.

The emergence and development of radical luminescent materials is a huge breakthrough toward high-performance organic light-emitting diodes (OLEDs) without spin-statistical limits. Herein, we design a series of radicals based on tris(2,4,6-trichlorophenyl)methyl (TTM) by combining skeleton-engineering and periphery-engineering strategies, and present some insights into how different chemical modifications can modulate the chemical stability and luminescence properties of radicals by quantum chemistry methods. Firstly, through the analysis of the geometric structure changes from the lowest doublet excited state (D1) to the doublet ground state (D0) states, the emission energy differences between the BN orientation isomers are explained, and it is revealed that the radical with a smaller dihedral angle difference can more effectively suppress the geometric relaxation of the excited states and bring a higher emission energy. Meanwhile, a comparison of the excited state properties in different radicals can help us to disclose the luminescence behavior, that is, the enhanced luminescent intensity of the radical is caused by the intensity borrowing between the charge transfer (CT) state and the dark locally excited (LE) state. In addition, an efficient algorithm for calculating the internal conversion rate (kIC) is introduced and implemented, and the differences in kIC values between designed radicals are explained. More specifically, the delocalization of hole and electron wave functions can reduce nonadiabatic coupling matrix elements (NACMEs), thus hindering the non-radiative decay process. Finally, the double-regulation of chemical stability and luminescence properties was realized through the synergistic effect of skeleton-engineering and periphery-engineering, and to screen the excellent doublet emitter (BN-41-MPTTM) theoretically.

Corynoxine B derivative CB6 prevents Parkinsonian toxicity in mice by inducing PIK3C3 complex-dependent autophagy.

Increasing evidence shows that autophagy impairment is involved in the pathogenesis and progression of neurodegenerative diseases including Parkinson's disease (PD). We previously identified a natural alkaloid named corynoxine B (Cory B) as a neuronal autophagy inducer. However, its brain permeability is relatively low, which hinders its potential use in treating PD. Thus we synthesized various derivatives of Cory B to find more potent autophagy inducers with improved brain bioavailability. In this study, we evaluated the autophagy-enhancing effect of CB6 derivative and its neuroprotective action against PD in vitro and in vivo. We showed that CB6 (5-40 µM) dose-dependently accelerated autophagy flux in cultured N2a neural cells through activating the PIK3C3 complex and promoting PI3P production. In MPP+-treated PC12 cells, CB6 inhibited cell apoptosis and increased cell viability by inducing autophagy. In MPTP-induced mouse model of PD, oral administration of CB6 (10, 20 mg· kg-1· d-1, for 21 days) significantly improved motor dysfunction and prevented the loss of dopaminergic neurons in the striatum and substantia nigra pars compacta. Collectively, compound CB6 is a brain-permeable autophagy enhancer via PIK3C3 complex activation, which may help the prevention or treatment of PD.

Renoprotective activity of a new amide and a new hydroxycinnamic acid derivative from the fresh roots of Rehmannia glutinosa.

A new amide, named rehmagluamide (1), and a new hydroxycinnamic acid derivative, named nepetoidin F (2), together with six known compounds, 2'-O-methyluridine (3), puroglutamic acid (4), biliverdic acid (5), peterolactam (6), nicotinic acid (7), nicotinamide (8), were isolated from the fresh roots of Rehmannia glutinosa. All the structures of compounds were identified by the interpretation of their spectroscopic data and comparison with those reported in the literatures. The protective effects of compounds 1-7 on normal rat kidney tubule epithelioid (NRK-52e) cells injury induced by LPS were investigated. The results indicated that compounds 1, 2, and 7 exhibited protective effects against LPS-induced NRK 52e cells injury.

Design and Characterization of a Cell-Penetrating Peptide Derived from the SOX2 Transcription Factor.

SOX2 is an oncogenic transcription factor overexpressed in nearly half of the basal-like triple-negative breast cancers associated with very poor outcomes. Targeting and inhibiting SOX2 is clinically relevant as high SOX2 mRNA levels are positively correlated with decreased overall survival and progression-free survival in patients affected with breast cancer. Given its key role as a master regulator of cell proliferation, SOX2 represents an important scaffold for the engineering of dominant-negative synthetic DNA-binding domains (DBDs) that act by blocking or interfering with the oncogenic activity of the endogenous transcription factor in cancer cells. We have synthesized an interference peptide (iPep) encompassing a truncated 24 amino acid long C-terminus of SOX2 containing a potential SOX-specific nuclear localization sequence, and the determinants of the binding of SOX2 to the DNA and to its transcription factor binding partners. We found that the resulting peptide (SOX2-iPep) possessed intrinsic cell penetration and promising nuclear localization into breast cancer cells, and decreased cellular proliferation of SOX2 overexpressing cell lines. The novel SOX2-iPep was found to exhibit a random coil conformation predominantly in solution. Molecular dynamics simulations were used to characterize the interactions of both the SOX2 transcription factor and the SOX2-iPep with FGF4-enhancer DNA in the presence of the POU domain of the partner transcription factor OCT4. Predictions of the free energy of binding revealed that the iPep largely retained the binding affinity for DNA of parental SOX2. This work will enable the future engineering of novel dominant interference peptides to transport different therapeutic cargo molecules such as anti-cancer drugs into cells.

Hydrogen Migration-Triggered Diradicaloid Singlet-Fission Switch.

We present a theoretical design of the singlet-fission (SF) interconversion between two hydrogen tautomers to attract attention to electronic devices such as switches in the SF field. We develop a tuned π-electron conjugation strategy based on single-hydrogen migration to introduce diradical character and yield low-lying E(T1) levels. Specifically, these objectives could be accomplished by moving one hydrogen from a dihydrogen-substituted pyrazine-fused ring to another unsubstituted pyrazine-fused ring in tetraazatetracenes. The predicted SF efficiency would be expected to exceed 120%. To guide future SF design development, one rule of thumb regarding the S0-state and T1-state emerges from our research: In the S0-state, single-hydrogen migration is crucial for effectively localized electrons, which are the key factor in the formation of diradicals. Conversely, single-hydrogen migration induces a large area of π-electron conjugation in the T1-state, which is completely applied to the electron-hole interaction in the S0 → T1 transition, thereby providing low-lying E(T1) levels. Furthermore, a series of hydrogen tautomers of tetraazaacenes have been proposed as diradicaloid SF switches to verify the reliability of the above rule of thumb. This study will not only help researchers in the photovoltaic field to obtain the desired E(T1) in the future but also broaden the application of hydrogen migration in photovoltaic switch research and supplement the SF database.

Lysinibacillus cavernae sp. nov., isolated from cave soil.

A Gram-staining positive, motile, rod-shaped and subterminal endospore-forming bacterium, designated strain SYSU K30005T, was isolated from a soil sample collected from a karst cave in Libo county, Guizhou province, south-western China. Strain SYSU K30005T showed the highest 16S rRNA gene sequence similarity with Lysinibacillus fusiformis (98.6%) and Lysinibacillus sphaericus (98.2%). In phylogenetic tree, strain SYSU K30005T clade with the members of the genus Lysinibacillus. Based on the phylogenetic and 16S gene sequence result, strain SYSU K30005T was affiliated to the genus Lysinibacillus. The growth of SYSU K30005T was observed at 15-37 °C (optimum, 28 °C), pH 6.0-9.0 (optimum, pH 7.0) and in the presence of 0-4% (w/v) NaCl (optimum in 3.5% NaCl). Cell wall peptidoglycan type was A4α (Lys-Asp). The cell-wall sugars of SYSU K30005T were ribose, galactose and mannose and MK-7 was the only quinone. The fatty acids (> 5% of total fatty acids) were iso-C15:0, anteiso-C15:0, iso-C16:0 and iso-C17:0. The polar lipids profile included diphosphatidylglycerol, phosphatideylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The genomic DNA G + C content was 37.2 mol%. The average nucleotide identity values between SYSU K30005T and its closest relatives were below the cut-off level (95-96%) for species delineation. The results support the conclusion that strain SYSU K30005T represents a novel species of the genus Lysinibacillus, for which we proposed the name Lysinibacillus cavernae sp. nov. The type strain is SYSU K30005T (= KCTC 43130T = CGMCC 1.17492T).

Bacillus tepidiphilus sp. nov., isolated from tepid spring.

A novel Bacillus strain, designated SYSU G01002T, was isolated from a sediment sample collected from tepid spring in Tengchong, Yunnan province, south-west PR China. The 16S rRNA gene sequence analysis showed that the strain SYSU G01002T shared the highest sequence identity with the type strain of Bacillus alkalitolerans (97.7%). Strain SYSU G01002T grew at pH 6.0-8.0 (optimum, pH 7.0), at 28-55 °C (optimum, 45 °C) and in the presence of 0-2.5% (w/v) NaCl (optimum in the absence of NaCl). It contained meso-2,6-diaminopimelic acid as the cell-wall diamino acid and MK-7 as isoprenoid quinone. The major cellular fatty acids were iso-C15:0, iso-C17:0 and C16:0. The polar were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and unidentified phospholipid. The genomic DNA G + C content was 38.0 mol %. The digital DNA-DNA hybridization and average nucleotide identity values between SYSU G01002T and closely related members of the genus Bacillus were below the cut-off level recommended for interspecies identity. Based on the above results, strain SYSU G01002T represents a novel species of the genus Bacillus, for which the name Bacillus tepidiphilus sp. nov. is proposed. The type strain, SYSU G01002T (= KCTC 43131T = CGMCC 1.17491T).

Description of Paenibacillus antri sp. nov. and Paenibacillus mesophilus sp. nov., isolated from cave soil.

Two Gram-positive, rod-shaped, motile, endospore-forming strains, SYSU K30003T and SYSU K30004T, were isolated from cave soil sampled in Xingyi County, Guizhou Province, south-west PR China. The 16S rRNA gene sequence results indicated that strains SYSU K30003T and SYSU K30004T had highest sequence similarities to Paenibacillus thermoaerophilus DSM 26310T (93.2 %) and Paenibacillus haemerocallicola KCTC 33185T (97.8 %), respectively. Optimum growth for both strains occurred at pH 7.0 and 37 °C. Both strains contained meso-2,6-diaminopimelic acid in their cell-wall peptidoglycan and MK-7 was the only isoprenoid quinone detected. The polar lipid profile of strain SYSU K30004T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two aminophospholipids, an unidentified glycolipid, unidentified phospholipids and two unidentified polar lipids. The polar lipid profile of strain SYSU K30003T contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified glycolipid. The major fatty acids (>5 %) of strain SYSU K30003T were anteiso-C15:0, C16 : 0, anteiso-C17 : 0 and iso-C16 : 0, while those of strain SYSU K30004T were anteiso-C15:0, C16:0, anteiso-C17 : 0, iso-C15 : 0, iso-C16:0 and iso-C17 : 0. The genome G+C contents of strains SYSU K30003T and SYSU K30004T were 59.0 and 53.6 mol%, respectively. The average nucleotide identity values between strains SYSU K30003T and SYSU K30004T and other closely related Paenibacillus members were below the cut-off level (95-96 %) for species identification. Based on the results of phenotypic, chemotaxonomic and genome analyses, strains SYSU K30003T and SYSU K30004T represent two novel species of the genus Paenibacillus, for which the names Paenibacillus antri sp. nov. and Paenibacillus mesophilus sp. nov. are proposed. The type strains are SYSU K30003T (=KCTC 33956T=CGMCC 1.13505T) and SYSU K30004T (=KCTC 33957T=CGMCC 1.13872T).

Vulcaniibacterium gelatinicum sp. nov., a moderately thermophilic bacterium isolated from a hot spring.

The present study aimed to determine the taxonomic positions of strains designated R-5-52-3T, R-5-33-5-1-2, R-5-48-2 and R-5-51-4 isolated from hot spring water samples. Cells of these strains were Gram-stain-negative, non-motile and rod-shaped. The strains shared highest 16S rRNA gene sequence similarity with Vulcaniibacterium thermophilum KCTC 32020T (95.1%). Growth occurred at 28-55 °C, at pH 6-8 and with up to 3 % (w/v) NaCl. DNA fingerprinting, biochemical, phylogenetic and 16S rRNA gene sequence analyses suggested that R-5-52-3T, R-5-33-5-1-2, R-5-48-2 and R-5-51-4 were different strains but belonged to the same species. Hence, R-5-52-3T was chosen for further analysis and R-5-33-5-1-2, R-5-48-2 and R-5-51-4 were considered as additional strains of this species. R-5-52-3T possessed Q-8 as the only quinone and iso-C15:0, iso-C11:0, C16 : 0 and iso-C17 : 0 as major fatty acids. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified polar lipids and two unidentified phospholipids. The genomic G+C content was 71.6 mol%. Heat shock proteins (e.g. Hsp20, GroEL, DnaK and Clp ATPases) were noted in the R-5-52-3T genome, which could suggest its protection in the hot spring environment. Pan-genome analysis showed the number of singleton gene clusters among Vulcaniibacterium members varied. Average nucleotide identity (ANI) values between R-5-52-3T, Vulcaniibacterium tengchongense YIM 77520T and V. thermophilum KCTC 32020T were 80.1-85.8 %, which were below the cut-off level (95-96 %) recommended as the ANI criterion for interspecies identity. Thus, based on the above results, strain R-5-52-3T represents a novel species of the genus Vulcaniibacterium, for which the name Vulcaniibacterium gelatinicum sp. nov. is proposed. The type strain is R-5-52-3T (=KCTC 72061T=CGMCC 1.16678T).

Description of Paenibacillus tepidiphilus sp. nov., isolated from a tepid spring.

China is a hotspot for hot springs and during microbial diversity analysis of Tengchong hot spring, Yunnan province, south-west PR China, two strains designated SYSU G01001T and SY-13 were isolated. SYSU G01001T and SY-13 were Gram-stain-positive, motile and spore-forming. Colonies were white, circular, raised and punctiform. SYSU G01001T and SY-13 grew at pH 6.0-9.0 (optimum pH 8.0) and at 23-37 °C (optimum 28 °C). The 16S rRNA gene sequence similarity between SYSU G01001T and SY-13 was 99.6 % but these strains shared low sequence similarity with Paenibacillus azotifigens (97.5 %) indicating that they represented a novel species. On the basis of the results, SYSU G01001T was selected for further investigations and SY-13 was considered to represent a second strain of the species. The cell wall peptidoglycan of SYSU G01001T was meso-2,6-diaminopimelic acid and MK-7 was the only respiratory quinone. The polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), two unidentified aminolipids (AL), two unidentified amino phospholipids (APL), an unidentified phospholipid (PL) and an unidentified polar lipid (L). The G+C content of the genomic DNA was 53.9 mol%. The average nucleotide identity (ANIb and ANIm) values between SYSU G01001T and Paenibacillus azotifigens LMG 29963T were below the cut-off level (95-96 %) recommended as the average nucleotide identity (ANI) criterion for interspecies identity. On the basis of the above results strain SYSU G01001T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus tepidiphilus sp. nov. is proposed. The type strain is SYSU G01001T (=KCTC 33952T=CGMCC 1.13870T).

[DuzhongButiansu Capsules improve adenine-induced reproductive dysfunction in male rats].

OBJECTIVE: To study the effect of DuzhongButiansu Capsules (DBC) on adenine-induced reproductive dysfunction (RD) in male rats. METHODS: Eighty male SD rats were randomly divided into six groups, blank control (n = 8), solvent control (n = 8), RD model control (n = 16), Shengjing Capsules (SJC) (n = 16), low-dose DBC (n = 16) and high-dose DBC (n = 16). The RD model was made by intragastric administration of adenine at 200 mg/kg/d for 5 successive weeks in the latter four groups of animals, and in the meantime the rats in the latter three groups were treated intragastrically with SJC at 0.560 mg/kg/d and DBC at 0.242 and 0.968 mg/kg/d, respectively. At the end of the fourth week, all the rats were mated with female ones in a 1:1 ratio for 7 days. Then the male rats were killed and the right epididymides collected for detection of sperm concentration and motility, and the female ones sacrificed after fed for another 2 weeks and the numbers of pregnancies and fetal rats were recorded. The heart, liver, spleen, lung, kidney, thymus, testis, epididymis and seminal vesicle were harvested for obtainment of the visceral coefficients and semen parameters, observation of the histopathological changes in the testis, epididymis and kidneys by HE staining, measurement of the levels of serum T, E2, FSH and LH by ELISA, detection of the contents of serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) and creatinine (Scr), blood urea nitrogen (BUN), and determination of the expressions of Bax, Bcl-2, Caspase-3 and Caspase-9 proteins in the renal tissue by immunohistochemistry. RESULTS: No statistically significant difference was observed between the blank control and solvent control groups in any of the indexes obtained (P > 0.05).Compared with the blank controls, the rats in the RD model control group showed significantly decreased sperm concentration (ï¼»40.67 ± 7.37ï¼½vs ï¼»27.10 ± 2.72ï¼½ ×106/ml, P < 0.01), sperm motility (ï¼»54.75 ± 3.92ï¼½%vs ï¼»25.60 ± 4.83ï¼½%, P < 0.01) and pregnancy rate (85.7% vs 43.8%, P < 0.01). The rats in thelow- and high-dose DBCgroups exhibited remarkable increases in sperm concentration (ï¼»53.00 ± 4.55ï¼½% and ï¼»65.63 ± 12.47ï¼½% ×106/ml, P < 0.01) and sperm motility (ï¼»53.50 ± 8.83ï¼½% and ï¼»54.33 ± 7.92ï¼½ %, P < 0.01), and so did those in the high-dose DBC group in pregnancy rate (54.5%, P < 0.01).After medication, the animals showed markedly increased body weight and visceral coefficients of the testis, epididymis and seminal vesicle (P < 0.05 or P < 0.01), recovered morphology of the testis, epididymis and kidneys, reduced levels of Scr, BUN, FSH, LH and MDA in the serum (P < 0.05 or P < 0.01), increased contents of T, SOD and GSH-PX (P < 0.05 or P < 0.01), down-regulated expressions of Bax, Caspase-3 and Caspase-9 and up-regulated expression of Bcl-2 in the renal tissue (P < 0.05 or P < 0.01). CONCLUSIONS: DBC can improve adenine-induced reproductive dysfunction in male rats, which may be attributed to its effects of inhibiting the apoptosis of proteins, improving oxidative stress and elevating the levels of reproductive hormones.

Exploring the Influence of Halogen Coordination Effect of Stable Bimetallic MOFs on Oxygen Evolution Reaction.

The energy crisis and environmental pollution have forced scientists to explore alternative energy conversion and storage devices. The anodic reactions of these devices are all oxygen evolution reactions (OER), so the development of efficient OER electrocatalysts is of great significance. At the same time, understanding the reaction mechanism of OER is conducive to the rational design of efficient OER electrocatalysts. In general, catalytic active centers play a direct role in OER performance. In this paper, a series of stable bimetallic metal-organic frameworks (MOFs, named as Fe3 -Con -X2 , n=2, 3 and X=F, Cl, Br) with similar structure were synthesized by changing the halogen coordinated with the cobalt metal active center, aiming to investigate the influence of halogen substitution effect on OER performance. It was found that the OER activity of Fe3 -Co3 -F2 is much better than Fe3 -Co2 -Cl2 and Fe3 -Co2 -Br2 , indicating that the regulation of the electronegativity change of the coordination halogen atom can regulate the coordination electron structure of the metal active center, thereby achieving effective regulation of OER performance.

Electroacupuncture Alleviated Referral Hindpaw Hyperalgesia via Suppressing Spinal Long-Term Potentiation (LTP) in TNBS-Induced Colitis Rats.

Although referred pain or hypersensitivity has been repeatedly reported in irritable bowel syndrome (IBS) patients and experimental colitis rodents, little is known about the neural mechanisms. Spinal long-term potentiation (LTP) of nociceptive synaptic transmission plays a critical role in the development of somatic hyperalgesia in chronic pain conditions. Herein, we sought to determine whether spinal LTP contributes to the referral hyperalgesia in colitis rats and particularly whether electroacupuncture (EA) is effective to alleviate somatic hyperalgesia via suppressing spinal LTP. Rats in the colitis group (induced by colonic infusion of 2,4,6-trinitrobenzenesulfonic acid, TNBS), instead of the control and vehicle groups, displayed evident focal inflammatory destruction of the distal colon accompanied not only with the sensitized visceromotor response (VMR) to noxious colorectal distension (CRD) but also with referral hindpaw hyperalgesia indicated by reduced mechanical and thermal withdrawal latencies. EA at Zusanli (ST36) and Shangjuxu (ST37) attenuated the severity of colonic inflammation, as well as the visceral hypersensitivity and referral hindpaw hyperalgesia in colitis rats. Intriguingly, the threshold of C-fiber-evoked field potentials (CFEFP) was significantly reduced and the spinal LTP was exaggerated in the colitis group, both of which were restored by EA treatment. Taken together, visceral hypersensitivity and referral hindpaw hyperalgesia coexist in TNBS-induced colitis rats, which might be attributed to the enhanced LTP of nociceptive synaptic transmission in the spinal dorsal horn. EA at ST36 and ST37 could relieve visceral hypersensitivity and, in particular, attenuate referral hindpaw hyperalgesia by suppressing the enhanced spinal LTP.

Self-Assembly of a Phosphate-Centered Polyoxo-Titanium Cluster: Discovery of the Heteroatom Keggin Family.

Over the past 200 years, the most famous and important heteroatom Keggin architecture in polyoxometalates has only been synthesized with Mo, W, V, or Nb. Now, the self-assembly of two phosphate (PO4 3- )-centered polyoxo-titanium clusters (PTCs) is presented, PTi16 and PTi12 , which display classic heteroatom Keggin and its trivacant structures, respectively. Because TiIV has lower oxidate state and larger ionic radius than MoVI , WVI , VV , and NbV , additional TiIV centres in these PTCs are used to stabilize the resultant heteroatom Keggin structures, as demonstrated by the cooresponding theoretical calculation results. These photoactive PTCs can be utilized as efficient photocatalysts for highly selective CO2 -to-HCOOH conversion. This new discovery indicates that the classic heteroatom Keggin family can be assembled with Ti, thus opening a research avenue for the development of PTC chemistry.

Involvement of hippocampal acetylcholinergic receptors in electroacupuncture analgesia in neuropathic pain rats.

BACKGROUND: Cumulating evidence has shown a close correlation between electroacupuncture stimulation (EAS) frequency-specific analgesic effect and central opioid peptides. However, the actions of hippocampal acetylcholinergic receptors have not been determined. This study aims to observe the effect of different frequencies of EAS on the expression of hippocampal muscarinic and nicotinic acetylcholinergic receptors (mAChRs, nAChRs) in neuropathic pain rats for revealing their relationship. METHODS: Forty male Wistar rats were randomly and equally divided into sham, CCI model, 2, 2/15 and 100 HzEA groups. The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EAS was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 30 min, once daily for 14 days except weekends. The mechanical pain thresholds (withdrawal latencies, PWLs) of bilateral hindpaws were measured. The expression levels of hippocampal M1 and M2 mAChR, and α4 and ß2 nAChR genes and proteins were detected by quantitative RT-PCR and Western blot, separately. The involvement of mAChR and nAChR in the analgesic effect of EAS was confirmed by intra-hippocampal microinjection of M1mAChR antagonist (Pirenzepine) and α4ß2 nAChR antagonist (dihydro-beta-erythroidine) respectively. RESULTS: Following EAS, the CCI-induced increase of difference values of bilateral PWLs on day 6 and 14 was significantly reduced (P < 0.05), with 2/15 Hz being greater than 100 Hz EAS on day 14 (P < 0.05). After 2 weeks' EAS, the decreased expression levels of M1 mAChR mRNA of both 2 and 2/15 Hz groups and M1 mAChR protein of the three EAS groups, α4 AChR mRNA of the 2/15 Hz group and ß2 nAChR protein of the three EAS groups were considerably increased (P < 0.05), suggesting an involvement of M1 mAChR and ß2 nAChR proteins in EAS-induced pain relief. No significant changes were found in the expression of M2 mAChR mRNA and protein, α4 nAChR protein and ß2 nAChR mRNA after CCI and EAS (P > 0.05). The analgesic effect of EAS was abolished by intra-hippocampal microinjection of M1mAChR and α4ß2 nAChR antagonists respectively. CONCLUSIONS: EAS of ST36-GB34 produces a cumulative analgesic effect in neuropathic pain rats, which is frequency-dependent and probably mediated by hippocampal M1 mAChR and ß2 nAChR proteins.

Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats.

BACKGROUND: Electroacupuncture (EA) intervention can relieve a variety of pain; however, optimal EA protocols have not been clearly determined. In addition, although central mitogen-activated protein kinase kinase (MEK) signaling has been shown to be involved in the antinociceptive effect of acupuncture stimulation, its characteristics at different time-points of EA intervention have not been fully elucidated. Therefore, the present study investigated the relationship between the effects of different numbers of EA intervention sessions and the activation of MEK1 in the hippocampus and hypothalamus in a rat model of neuropathic pain. METHODS: After ligation of the left sciatic nerve, which induces chronic constriction injury (CCI), the acupoints Zusanli (ST36) and Yanglingquan (GB34) were applied. The thermal withdrawal latency of the hind paw was used to evaluate the effect of EA on pain thresholds. Intra-hippocampus microinjection of PD98059, a MEK inhibitor, was performed to validate the involvement of MEK in EA analgesia. The hippocampus and hypothalamus were harvested to examine the phosphorylation levels of MEK (pMEK) by western blotting. RESULTS: In CCI rats, the thermal pain threshold of the affected hind paw decreased significantly relative to the control. Following subsequent daily EA interventions, CCI-induced ipsilateral hyperalgesia was markedly improved from day 4 and the analgesic effect of EA lasted 3 days after cessation of EA. Four sessions of EA markedly suppressed CCI-induced decrease of hippocampal pMEK1 (normalized to the total MEK level). In contrast, successive sessions of EA intervention gradually down-regulated the CCI-induced up-regulation of hypothalamic pMEK1 along with the increase numbers of EA intervention. However, EA did not exert the same analgesic effect after microinjection of PD98059 into the contralateral hippocampus during the first 3 days of EA intervention. CONCLUSIONS: EA intervention can induce time-dependent cumulative analgesia in neuropathic pain rats after 4 successive sessions of daily EA intervention, which is at least in part related to the activation of hippocampal MEK1.

HSP27 Modulates Neuropathic Pain by Inhibiting P2X3 Degradation.

The role of heat shock protein 27 (HSP27), a chaperone, in neuropathic pain after nerve injury has not been systematically surveyed despite its neuroprotective and regeneration-promoting effects. In this study, we found that HSP27 expression in sensory neurons of the dorsal root ganglia (DRG) mediated nerve injury-induced neuropathic pain. Neuropathic pain behaviors were alleviated by silencing HSP27 in the DRG of a rat spinal nerve ligation (SNL) model. Local injection of an HSP27-overexpression construct into the DRG of naïve rats elicited neuropathic pain behaviors. HSP27 interacted with a purinergic receptor, P2X3, and their expression patterns corroborated the induction and reversal of neuropathic pain according to two lines of evidence: colocalization immunohistochemically and immunoprecipitation biochemically. In a cell model cotransfected with HSP27 and P2X3, the degradation rate of P2X3 was reduced in the presence of HSP27. Such an alteration was mediated by reducing P2X3 ubiquitination in SNL rats and was reversed after silencing HSP27 in the DRGs of SNL rats. In summary, the interaction of HSP27 with P2X3 provides a new mechanism of injury-induced neuropathic pain that could serve as an alternative therapeutic target.

Preparation and efficacy of antibacterial methacrylate monomer-based polymethyl methacrylate bone cement containing N-halamine compounds.

Introduction: Our objective in this study was to prepare a novel type of polymethyl methacrylate (PMMA) bone cement, analyze its material properties, and evaluate its safety and antibacterial efficacy. Methods: A halamine compound methacrylate antibacterial PMMA bone cement containing an N-Cl bond structure was formulated, and its material characterization was determined with Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The antibacterial properties of the material were studied using contact bacteriostasis and releasing-type bacteriostasis experiments. Finally, in vitro and in vivo biocompatibility experiments were performed to analyze the toxic effects of the material on mice and embryonic osteoblast precursor cells (MC3T3-E1). Results: Incorporation of the antibacterial methacrylate monomer with the N-halamine compound in the new antibacterial PMMA bone cement significantly increased its contact and releasing-type bacteriostatic performance against Staphylococcus aureus. Notably, at 20% and 25% additions of N-halamine compound, the contact and releasing-type bacteriostasis rates of bone cement samples reached 100% (p < 0.001). Furthermore, the new antibacterial bone cement containing 5%, 10%, and 15% N-halamine compounds showed good biocompatibility in vitro and in vivo. Conclusion: In this study, we found that the novel antibacterial PMMA bone cement with N-halamine compound methacrylate demonstrated good contact and releasing-type bacteriostatic properties against S. aureus. In particular, bone cement containing a 15% N-halamine monomer exhibited strong antibacterial properties and good in vitro and in vivo biocompatibility.