Understanding the Neural Mechanisms of General Anesthesia from Interaction with Sleep-Wake State: A Decade of Discovery.

The development of cutting-edge techniques to study specific brain regions and neural circuits that regulate sleep-wake brain states and general anesthesia (GA), has increased our understanding of these states that exhibit similar neurophysiologic traits. This review summarizes current knowledge focusing on cell subtypes and neural circuits that control wakefulness, rapid eye movement (REM) sleep, non-REM sleep, and GA. We also review novel insights into their interactions and raise unresolved questions and challenges in this field. Comparisons of the overlapping neural substrates of sleep-wake and GA regulation will help us to understand sleep-wake transitions and how anesthetics cause reversible loss of consciousness. SIGNIFICANCE STATEMENT: General anesthesia (GA), sharing numerous neurophysiologic traits with the process of natural sleep, is administered to millions of surgical patients annually. In the past decade, studies exploring the neural mechanisms underlying sleep-wake and GA have advanced our understanding of their interactions and how anesthetics cause reversible loss of consciousness. Pharmacotherapies targeting the neural substrates associated with sleep-wake and GA regulations have significance for clinical practice in GA and sleep medicine.

Medial Septal Glutamatergic Neurons Modulate States of Consciousness during Sevoflurane Anesthesia in Mice.

BACKGROUND: Multiple neural structures involved in maintaining wakefulness have been found to promote arousal from general anesthesia. The medial septum is a critical region that modulates arousal behavior. This study hypothesized that glutamatergic neurons in the medial septum play a crucial role in regulating states of consciousness during sevoflurane general anesthesia. METHODS: Adult male mice were used in this study. The effects of sevoflurane anesthesia on neuronal activity were determined by fiber photometry. Lesions and chemogenetic manipulations were used to study the effects of the altered activity of medial septal glutamatergic neurons on anesthesia induction, emergence, and sensitivity to sevoflurane. Optogenetic stimulation was used to observe the role of acute activation of medial septal glutamatergic neurons on cortical activity and behavioral changes during sevoflurane-induced continuous steady state of general anesthesia and burst suppression state. RESULTS: The authors found that medial septal glutamatergic neuronal activity decreased during sevoflurane anesthesia induction and recovered in the early period of emergence. Chemogenetic activation of medial septal glutamatergic neurons prolonged the induction time (mean ± SD, hM3Dq-clozapine N-oxide vs. hM3Dq-saline, 297.5 ± 60.1 s vs. 229.4 ± 29.9 s, P < 0.001, n = 11) and decreased the emergence time (53.2 ± 11.8 s vs. 77.5 ± 33.5 s, P = 0.025, n = 11). Lesions or chemogenetic inhibition of these neurons produced the opposite effects. During steady state of general anesthesia and deep anesthesia-induced burst suppression state, acute optogenetic activation of medial septal glutamatergic neurons induced cortical activation and behavioral emergence. CONCLUSIONS: The study findings reveal that activation of medial septal glutamatergic neurons has arousal-promoting effects during sevoflurane anesthesia in male mice. The activation of these neurons prolongs the induction and accelerates the emergence of anesthesia.

RIPK1/RIPK3-Mediated Necroptosis is Involved in Sevoflurane-Induced Neonatal Neurotoxicity in the Rat Hippocampus.

Recent studies have shown that exposure to sevoflurane in developing brains causes neuronal apoptosis and cognitive dysfunction. "Necroptosis" is a novel pathway of necrosis. We introduced the caspase-specific inhibitor Z-VAD in addition to the receptor-interacting protein kinase 1 (RIPK1) inhibitor Nec-1, to ascertain the existence and importance of necroptosis. Sprague-Dawley rat pups postnatal day 7 were randomly assigned into one of five groups: control, sevoflurane + Z-VAD, sevoflurane + Nec-1, sevoflurane + Z-VAD + Nec-1 and 3% sevoflurane group. Neuronal apoptosis was evaluated by hematoxylin and eosin staining. The MTT assay was performed to evaluate cell viability. Immunofluorescence was employed to measure expression of RIPK1 and RIPK3. Western blots showing expression of RIPK1, RIPK3 and phosphorylation of mixed lineage kinase domain-like (p-MLKL) were used to explore the role of necroptosis. Binding of RIPK1/RIPK3 was detected via co-immunoprecipitation. Finally, the Morris water maze test was used to determine cognitive function. Exposure to 3% sevoflurane for 6 h induced neurotoxicity and inhibited cell viability. Neuron viability was low in the SEV, SEV + Z-VAD and SEV + Nec-1 groups. The study revealed that RIPK1 and RIPK3 protein expression increased significantly, but there was no significant differences between the SEV and SEV + Z-VAD groups. The expression of p-MLKL significantly increased in the SEV and SEV + Z-VAD groups, but not in the SEV + Nec-1 group or SEV + Z-VAD + Nec-1 group compared to the control group. Co-immunoprecipitation results showed that sevoflurane exposure enhanced binding of RIPK1/RIPK3 protein significantly. Blockade of apoptosis and necroptosis alleviated sevoflurane-induced cognitive impairment. Sevoflurane exposure elicited neurotoxicity within neonatal hippocampal neurons and tissues. Blockade of apoptosis or necroptosis alone did not attenuate sevoflurane-induced neurotoxicity (SIN). RIPK1/RIPK3-mediated necroptosis was involved in SIN in hippocampal neurons. SIN could be attenuated only by inhibiting both apoptosis and necroptosis.

Synthesis and characterization of luminescent SiO2 @Eu(phen-Si) core-shell nanospheres.

Four core-shell structured nanometre luminescent composites with different kernel sizes and different shell layer thicknesses (SiO2(500) @Eu (phen-Si)(50) , SiO2(500) @Eu (phen-Si)(15) , SiO2(250) @Eu (phen-Si)(5) and SiO2(250) @Eu (phen-Si)(10) ) were made by changing synthesis conditions. Here, initial subscript numbers in parentheses refer to the particle size of the SiO2 core, whereas the final subscript numbers in parentheses refer to shell layer thickness. In these composites, silica spheres of 500 nm or 250 nm were identified as the core. The shell layer was composited of silicon, 1,10-phenanthroline and europium perchlorate, abbreviated as Eu(phen-Si); the chemical formula of phen-Si was phen-N-(CONH (CH2 )Si(OCH2 CH3 )3 )2 . The composites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and infrared spectroscopy. The monodispersed spherical SiO2 showed characteristics of a regular microstructure and a smooth surface, as well as the advantage of dispersity, shown by SEM. The Eu(phen-Si) complex was able to self-assemble into monodispersed SiO2 spheres, as seen using TEM. Fluorescence spectra indicated that the four composites had excellent luminescence properties. Furthermore, composites composed of a SiO2 core and a 250 nm kernel size exhibited stronger fluorescence than 500 nm kernel-sized composites. Fluorescence properties were affected by shell thickness: the thicker the shell, the greater the fluorescence intensity. For the four composites, quantum yield values and fluorescence lifetime corresponded to fluorescence emission intensity data as quantum yield values and fluorescence lifetime were higher, and luminescence properties increased.

[Research progress on chemical composition and pharmacological effects of Periplocae Cortex and predictive analysis on Q-marker].

Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.

Comparison Between the Cobra Perilaryngeal Airway and Laryngeal Mask Airways Under General Anesthesia: A Systematic Review and Meta-analysis.

The complication rate and efficacy of the Cobra Perilaryngeal Airway (CobraPLA) and laryngeal mask airways (LMAs®) have been evaluated in the published literature, but the conclusions have been inconsistent. The aim of this systematic review and meta-analysis was thus to assess the performance of the CobraPLA and LMAs under general anesthesia. We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials comparing the CobraPLA with LMAs under general anesthesia. The LMAs used for comparison were the classic LMA (CLMA) and the unique LMA (ULMA). The random effect model was used if heterogeneity was observed, otherwise the fixed effect model was used. Seventeen randomized controlled trials were included; number of studies analyzed for each result are different and were up to 10. The current result suggests that no significant difference between the devices in the insertion success rate at the first attempt. The success rate of first insertion of the CobraPLA was not different from the rates for the CLMA and the ULMA (relative risk: 0.95, 95% confidence interval [CI], 0.91-1.00). CobraPLA insertion was not different from CLMA and ULMA insertion. The CobraPLA provided an oropharyngeal leak pressure higher than that provided by the CLMA (weight mean difference: 3.90, 95% CI, [1.59-6.21] cmH2O) and ULMA (weight mean difference: 6.57, 95% CI, [4.30-8.84] cmH2O). We also found a higher likelihood of blood staining in the airway with the CobraPLA than with the CLMA. In our research, the principal finding of our meta-analysis is that the success rate of first insertion of the CobraPLA was not different from the rate for each of the CLMA and the ULMA, which featured a short learning curve implying its ease of insertion. There was also no significant difference in the incidence of the best view (with a score of 4) obtained with the CobraPLA compared with the other 2 devices. The CobraPLA does seem to be superior to the CLMA and ULMA in providing a higher oropharyngeal leak pressure. The data were insufficient to establish differences in airway adverse events between the groups except for blood staining in the devices, although mucosal trauma occurred more frequently with the Cobra PLA device than with the CLMA and the ULMA.

Synthesis, characterization and luminescence of europium perchlorate with MABA-Si complex and coating structure SiO2 @Eu(MABA-Si) luminescence nanoparticles.

This article reports a novel category of coating structure SiO2 @Eu(MABA-Si) luminescence nanoparticles (NPs) consisting of a unique organic shell, composed of perchlorate europium(III) complex, and an inorganic core, composed of silica. The binary complex Eu(MABA-Si)3 ·(ClO4 )3 ·5H2 O was synthesized using HOOCC6 H4 N(CONH(CH2 )3 Si(OCH2 CH3 )3 )2 (MABA-Si) and was used as a ligand. Furthermore, the as-prepared silica NPs were successfully coated with the -Si(OCH2 CH3 )3 group of MABA-Si to form Si-O-Si chemical bonds by means of the hydrolyzation of MABA-Si. The binary complexes were characterized by elemental analysis, molar conductivity and coordination titration analysis. The results indicated that the composition of the binary complex was Eu(MABA-Si)3 ·(ClO4 )3 ·5H2 O. Coating structure SiO2 @Eu(MABA-Si) NPs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and infrared (IR) spectra. Based on the SEM and TEM measurements, the diameter of core-SiO2 particles was ~400 and 600 nm, and the thickness of the cladding layer Eu(MABA-Si) was ~20 nm. In the binary complex Eu(MABA-Si)3 ·(ClO4 )3 ·5H2 O, the fluorescence spectra illustrated that the energy of the ligand MABA-Si transferred to the energy level for the excitation state of europium(III) ion. Coating structure SiO2 @Eu(MABA-Si) NPs exhibited intense red luminescence compared with the binary complex. The fluorescence lifetime and fluorescence quantum efficiency of the binary complex and of the coating structure NPs were also calculated. The way in which the size of core-SiO2 spheres influences the luminescence was also studied. Moreover, the luminescent mechanisms of the complex were studied and explained.

Luminescence enhancement of terbium(III) perchlorate by 2,2'-dipyridyl on bis(benzylsulfinyl)methane complex and luminescence mechanism.

A novel ternary complex, Tb(2)L4 · L'·(ClO4)6 · 8H2O, has been synthesized using bis(benzylsulfinyl)methane as the first ligand L and 2,2'-dipyridyl as the second ligand L'. The ternary complex was characterized by element analysis, molar conductivity, coordination titration analysis, infrared, thermogravimetric-differential scanning calorimetric and ultraviolet spectra. The results indicated that the composition of the complex was Tb2 L4 · L'·(ClO4)6 · 8H2O (L = C(6)H(5)CH(2) SOCH(2)SOCH(2)C(6)H(5); L' = Dipy). Fourier transform infrared results revealed that the perchlorate group was bonded with the Tb(III) ion by the oxygen atom, and the coordination was bidentate. The fluorescent spectra illustrated that the complex displayed characteristic fluorescence in the solid state. After the introduction of the second ligand, 2,2-dipyridyl, the relative emission intensity and fluorescence lifetime of the ternary complex Tb(2)L(4) · L'·(ClO(4))(6) · 8H2O were enhanced compared to the binary complex TbL(2.5)(ClO4)3 · 3H2O. This indicated that the presence of both organic ligand bis(benzylsulfinyl)methane and the second ligand 2,2-dipyridyl could sensitize the fluorescence intensity of Tb(III) ion, and introduction of the 2,2-dipyridyl group resulted in an enhancement of the fluorescence of the Tb(III) ternary rare earth complex. The strongest characteristic fluorescence emission intensity of the ternary complex was 9.36 times that of the binary complex. The phosphorescence spectra and fluorescence lifetime of the complex were also measured.

Fluorescence enhancement of europium (III) perchlorate by 1,10-phenanthroline on the 1-(naphthalen-2-yl)-2-(phenylsulthio)ethanone complex and luminescence mechanism.

A novel ligand, 1-(naphthalen-2-yl)-2-(phenylsulthio)ethanone was synthesized using a new method and its two europium (Eu) (III) complexes were synthesized. The compounds were characterized by elemental analysis, coordination titration analysis, molar conductivity, infrared, thermo gravimetric analyzer-differential scanning calorimetry (TGA-DSC), (1)H NMR and UV spectra. The composition was suggested as EuL5 · (ClO4)3 · 2H2O and EuL4 · phen(ClO4)3 · 2H2O (L = C(10)H(7)COCH(2)SOC(6)H(5)). The fluorescence spectra showed that the Eu(III) displayed strong characteristic metal-centered fluorescence in the solid state. The ternary rare earth complex showed stronger fluorescence intensity than the binary rare earth complex in such material. The strongest characteristic fluorescence emission intensity of the ternary system was 1.49 times as strong as that of the binary system. The phosphorescence spectra were also discussed.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p.

BACKGROUND: Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy (DN). The regulatory relationship between long noncoding RNAs (lncRNAs) and podocyte apoptosis has recently become another research hot spot in the DN field. AIM: To investigate whether lncRNA protein-disulfide isomerase-associated 3 (Pdia3) could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism. METHODS: Using normal glucose or high glucose (HG)-cultured podocytes, the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress (ERS) were explored. LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction. Relative cell viability was detected through the cell counting kit-8 colorimetric assay. The podocyte apoptosis rate in each group was measured through flow cytometry. The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay. Finally, western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p. RESULTS: The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes. Next, lncRNA Pdia3 was involved in HG-induced podocyte apoptosis. Furthermore, the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p. LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes. CONCLUSION: Taken together, this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p, which might provide a potential therapeutic target for DN.

Comparison of the effects of dexmedetomidine, ketamine, and placebo on emergence agitation after strabismus surgery in children.

BACKGROUND: Children undergoing strabismus surgery under sevoflurane anesthesia often experience emergence agitation (EA) and postoperative vomiting (POV). This study compared the effects of intraoperative dexmedetomidine, ketamine, and placebo on postoperative EA and POV. METHODS: Eighty-four children (aged two to seven years) undergoing elective strabismus surgery under sevoflurane anesthesia were randomly assigned to one of three groups (n = 28 each). Intraoperatively, the placebo, dexmedetomidine, and ketamine groups received normal saline, dexmedetomidine 1 µg·kg(-1) iv plus a 1 µg·kg(-1)·hr(-1) infusion, and ketamine 1 mg·kg(-1) iv plus a 1 mg·kg(-1)·hr(-1) infusion, respectively. Agitation scores (Pediatric Anesthesia Emergence Delirium [PAED] scale) and POV were assessed in the postanesthetic care unit (PACU) and for 24 hr on the ward. Pain scores and times to laryngeal mask airway (LMA™) removal, resumption of mental orientation, and discharge from the PACU were also assessed. RESULTS: Seventy-eight children completed the study. Peak PAED scores for EA were lower in the dexmedetomidine (P < 0.001) and ketamine (P = 0.002) groups than in the placebo group. Incidence of POV was lower in the dexmedetomidine group (15%) than in the ketamine (44%; P = 0.02) or placebo (45.8%; P = 0.02) groups. Pain scores on the ward were lower in the dexmedetomidine (P < 0.001) and ketamine (P < 0.001) groups than in the placebo group. Time to LMA removal was similar in all groups. Time for resumption of mental orientation and time to discharge from PACU were longer in the dexmedetomidine and ketamine groups than in the placebo group. CONCLUSIONS: Dexmedetomidine and ketamine appear to prevent postoperative agitation and pain after sevoflurane anesthesia for pediatric strabismus surgery. Dexmedetomidine also prevents POV.

Synthesis and luminescence properties of two novel lanthanide (III) complexes of acetophenonylcarboxymethyl sulphoxide.

A novel ligand containing multiple coordinating groups (sulfinyl, carboxyl and carbonyl groups), acetophenonylcarboxymethyl sulphoxide, was synthesized. Its corresponding two lanthanide (III) binary complexes were synthesized and characterized by element analysis, molar conductivity, FT-IR, TG-DTA and UV spectroscopy. Results showed that the composition of these complexes was REL3 L(-) (ClO4)2 · 3H2O (RE = Eu (III), Tb (III); L = C6 H5 COCH2 SOCH2 COOH; L(-) = C6H5 COCH2 SOCH2 COO(-)). FT-IR results indicated that acetophenonylcarboxymethyl sulphoxide was bonded with an RE (III) ion by an oxygen atom of the sulfinyl and carboxyl groups and not by an oxygen atom of the carbonyl group due to high steric hinderance. Fluorescent spectra showed that the Tb (III) complex had excellent luminescence as a result of a transfer of energy from the ligand to the excitation state energy level ((5)D4) of Tb (III). The Eu (III) complex displayed weak luminescence, attributed to low energy transfer efficiency between the triplet state energy level of its ligand and the excited state ((5)D0 ) of Eu (III). As a result, the Tb (III) complex displayed a good antenna effect for luminescence. The fluorescence decay curves of Eu (III) and Tb (III) complexes were also measured.

[Hydrothermal synthesis and luminescence properties of CePO4 : Tb flower-like clusters].

Tb(3+)-doped CePO4 flower-like clusters were hydrothermally synthesized without using any template or surfactant by varying the reactant Tb3+ cation concentration. It was observed that the flower-like clusters were composed by nanowires with a diameter of about 80-90 nm and lengths up to 1 microm. The structures, morphologies, sizes and luminescence properties of the products were studied by X-ray powder diffraction (XRD), field-emission scanning electronic microscopy (FE-SEM), and luminescence spectra. With the reactant Ce3+ /Tb3+ molar ratio of 0.850 : 0.150, the uniform flower-like clusters were actually composed of a self-assembly of the oriented nanowires through an Tb(3+)-induced in the excessive PO4(3-). It was found that the reactant Ce3+/Tb3+ molar ratio and phosphoric acid played key roles in the morphology control of the product. A possible formation mechanism for the flower-like morphology was also proposed. The luminescence properties of CePO4 : Tb flower-like cluster were performed, indicating that the strongest emission intensity was reached with 0.850 : 0.150 molar ratios of Ce3+/Tb3+.

Risk factors for difficult mask ventilation and difficult intubation among patients undergoing pharyngeal and laryngeal surgery.

Background: The prediction of difficult mask ventilation (DMV) and difficult intubation (DI) are key questions in anesthesia fields. DMV or DI related to pharyngeal and laryngeal diseases are a special kind of difficult airways. However, there is a lack of risk factors for prediction. Methods: This study retrospectively collected data from patients who were admitted to the Eye & ENT Hospital of Fudan University from May 2014 to May 2018 and underwent laryngopharyngeal surgery under general anesthesia. Results: A total of 126 patients were included. Twenty patients suffered from DMV. Preoperative laryngeal obstruction classification (OR = 7.46, 95% CI: 2.56-21.76, P < 0.001) and airway patency after sevoflurane inhalation (OR = 10.96, 95% CI: 2.70-44.43, p = 0.001) were independently associated with DMV. Seventy-six patients could be intubated at the first attempt. Preoperative laryngeal obstruction grade (OR = 0.28, 95% CI: 0.13-0.62, P = 0.002), neoplasm size (OR = 0.43, 95% CI: 0.22-0.82, P = 0.011), and airway patency after sevoflurane inhalation (OR = 0.14, 95% CI: 0.05-0.36, P < 0.001) were independently associated with first-attempt successful intubation. Conclusion: Among patients with pharyngeal and laryngeal diseases, the degree of laryngeal obstruction before the operation and the degree of airway obstruction after inhaling sevoflurane are the risk factors of DMV. The degree of laryngeal obstruction before the operation, airway obstruction after inhaling sevoflurane, and the neoplasm size are the risk factors of DI.

Medial septum glutamatergic neurons modulate nociception in chronic neuropathic pain via projections to lateral hypothalamus.

The medial septum (MS) contributes in pain processing and regulation, especially concerning persistent nociception. However, the role of MS glutamatergic neurons in pain and the underlying neural circuit mechanisms in pain remain poorly understood. In this study, chronic constrictive injury of the sciatic nerve (CCI) surgery was performed to induce thermal and mechanical hyperalgesia in mice. The chemogenetic activation of MS glutamatergic neurons decreased pain thresholds in naïve mice. In contrast, inhibition or ablation of these neurons has improved nociception thresholds in naïve mice and relieved thermal and mechanical hyperalgesia in CCI mice. Anterograde viral tracing revealed that MS glutamatergic neurons had projections to the lateral hypothalamus (LH) and supramammillary nucleus (SuM). We further demonstrated that MS glutamatergic neurons regulate pain thresholds by projecting to LH but not SuM, because the inhibition of MS-LH glutamatergic projections suppressed pain thresholds in CCI and naïve mice, yet, optogenetic activation or inhibition of MS-SuM glutamatergic projections had no effect on pain thresholds in naïve mice. In conclusion, our results reveal that MS glutamatergic neurons play a significant role in regulating pain perception and decipher that MS glutamatergic neurons modulate nociception via projections to LH.

Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain.

Dry eye disease (DED) affects nearly 55% of people worldwide; several studies have proposed that central sensitization and neuroinflammation may contribute to the developing corneal neuropathic pain of DED, while the underlying mechanisms of this contribution remain to be investigated. Excision of extra orbital lacrimal glands established the dry eye model. Corneal hypersensitivity was examined through chemical and mechanical stimulation, and open field test measured the anxiety levels. Restingstate fMRI is a method of functional magnetic resonance imaging (rs-fMRI) was performed for anatomical involvement of the brain regions. The amplitude of low-frequency fluctuation (ALFF) determined brain activity. Immunofluorescence testing and Quantitative real-time polymerase chain reaction were also performed to further validate the findings. Compared with the Sham group, ALFF signals in the supplemental somatosensory area, secondary auditory cortex, agranular insular cortex, temporal association areas, and ectorhinal cortex brain areas were increased in the dry eye group. This change of ALFF in the insular cortex was linked with the increment in corneal hypersensitivity (p < 0.01), c-Fos (p < 0.001), brain-derived neurotrophic factor (p < 0.01), TNF-α, IL-6, and IL-1ß (p < 0.05). In contrast, IL-10 levels (p < 0.05) decreased in the dry eye group. DED-induced corneal hypersensitivity and upregulation of inflammatory cytokines could be blocked by insular cortex injection of Tyrosine Kinase receptor B agonist cyclotraxin-B (p < 0.01) without affecting anxiety levels. Our study reveals that the functional activity of the brain associated with corneal neuropathic pain and neuroinflammation in the insular cortex might contribute to dry eye-related corneal neuropathic pain.

Syntheses and fluorescence properties of two novel lanthanide (III) perchlorate complexes with bis(benzylsulfinyl)methane.

A novel ligand with double sulfinyl groups, bis(benzylsulfinyl)methane, was synthesized by a new method and its two lanthanide (III) complexes were synthesized and characterized by element analysis, molar conductivity, coordination titration analysis, IR, TG-DSC, (1)HNMR and UV spectra. The results indicated that the composition of these complexes was REL(2.5)(ClO(4))(3)·3H(2)O (RE = Tb (III), Dy (III), L = C(6)H(5)CH(2)SOCH(2)SOCH(2)C(6)H(5)). The FT-IR results revealed that the perchlorate group was bonded with the lanthanide ion by the oxygen atoms, and the coordination was bidentate. The fluorescent spectra illustrated that both the Tb (III) and Dy (III) complexes displayed characteristic fluorescence in solid state, especially for the Tb (III) complex, the peak of (5)D(4) → (7)F(5) of the Tb (III) ion in 544 nm was stronger than that of others. It indicated that the Tb (III) complex could emit purer green fluorescence. By analysis fluorescence and phosphorescence spectra, it was found that the ligand had the advantage to absorb energy and transfer it to the Tb (III) and Dy (III) ions. The phosphorescence spectra and fluorescence lifetimes of the complexes were also measured.

Absolute structures of monoterpenoids with a δ-lactone-containing skeleton from Ligularia hodgsonii.

Bioactivity-directed fractionation of a methanol extract of Ligularia hodgsonii afforded two new monoterpenoids, liguhodgcins A (1) and B (2), with an unusual δ-lactone-containing skeleton. Moreover, liguhodgcin A (1) contained a chlorine atom. The structures and absolute configurations of the two compounds were elucidated using NMR spectroscopy, X-ray crystallography, ECD data, and computational approaches. A probable biosynthesis pathway to 1 and 2 was also proposed and discussed. The cytotoxicity of compounds 1 and 2 was evaluated against the human leukemia (HL-60), human hepatoma (SMMC-7721), and human cervical carcinoma (HeLa) cell lines.

Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease and lupus nephritis (LN) represents a major clinical manifestation. Studies have shown that elevated inducible co-stimulator (ICOS) in SLE. The purpose of the study was to investigate the expression of ICOS on T cells in patients with LN. Flow cytometry (FCM) was used to analyze the expression of ICOS on peripheral blood T lymphocytes in LN patients, SLE patients without nephritis, and healthy controls. The expression of ICOS on CD4 + CD45RO + and CD8 + CD4RO + T cells was significantly increased in SLE patients when compared with healthy controls (P < 0.001). In addition, ICOS expression in patients with nephritis was higher than those without nephritis (P < 0.01). Taken together, our results suggest that ICOS co-stimulatory pathway is important in the pathogenesis of LN; blockade of the pathway might represent a novel therapeutic strategy for the treatment of LN.

Fluorescence enhancement of rare earth Tb(III) by Tm(III) in benzyl benzoylmethyl sulphoxide complexes.

A series of rare earth complexes [(Tb(x) Tm(y))L5 (ClO4)2](ClO4)·3H(2) O (x:y = 1.000:0.000, 0.999:0.001, 0.995:0.005, 0.990:0.010, 0.950:0.050, 0.900:0.100, 0.800:0.200, 0.700:0.300; L = C(6) H5 CH2 SOCH2 COC6 H5) (Tb(III) luminescence ion; Tm(III) doped inert ion) were synthesized and characterized by elemental analysis, infrared spectra (IR) and (1) H-NMR. The photophysical properties of these complexes were studied in detail using ultraviolet absorption spectra, fluorescent spectra and lifetimes. The fluorescence spectra of complexes indicated that the fluorescence emission intensity was significantly enhanced by Tm(III). The complexes showed the best luminescence properties when the mole ratio Tb(III):Tm(III) was 0.990:0.010. The fluorescence intensity could be increased to 390%. Additionally, phosphorescence spectra and the luminescence mechanisms are discussed.