Auxiliary Carboxylate-Induced Assembly of Calix[6]arene-Polyoxotitanate Hybrid Systems with Photocatalytic Activity in the Oxidation of Sulfides.

This study used the tert-butylcalix[6]arene (TBC[6]) as the ligand and successfully synthesized six TBC[6]-stabilized titanium-oxo clusters (TOCs) by the one-step solvothermal reaction. These six compounds were [Ti4O2(TBC[6])2] (Ti4), {Ti2(TBC[6])(EtO)2(SaH2)2} (Ti2-SA, H2Sa = squaric acid), {Ti2(TBC[6])2(EtO)2(Oa)} (Ti2-OA, H2Oa = oxalic acid), [H2Ti4(TBC[6])(BA)2(EtO)10] (Ti4-BA, HBA = benzoic acid), [Ti6O2(TBC[6])(BA)4(OiPr)10] (Ti6-BA), and [Ti8(TBC[6])2(Sal)4(EtO)16] (Ti8-Sal, H2Sal = salicylic acid). These clusters contain one or two TBC[6] ligands, with the biconical or monoconical configuration, greatly increasing the variety of TOCs it could support. The introduction of auxiliary carboxylic ligands can further stimulate the growth of structures, with the cluster core gradually increased from {Ti-TBC[6]-Ti} to {Ti2-TBC[6]-Ti2}, to {Ti3-TBC[6]-Ti3}, and finally to {Ti3-TBC[6]-Ti2-TBC[6]-Ti3} with 3.1 nm length. Structural regulation may affect their solution stability, absorption spectra, and photocurrent response. The study of catalytic activities shows that these clusters can be used as recyclable heterogeneous photocatalysts for the oxidation of sulfide to sulfoxide. The catalytic efficiency of the TBC[6]-Tix system is closely related to the cluster structure, and the exposure of the Ti site on the catalyst surface can significantly enhance the catalytic activity of the clusters.

Cd-Doped Polyoxotitanium Nanoclusters with a Modifiable Organic Shell for Photoelectrochemical Water Splitting.

Incorporating heterometal and chromogenic groups into the titanium oxo cluster (TOC) nanomaterials is one of the effective strategies for the development of new high-performance photoelectrically active materials. In this Article, we report the structures and photoelectrochemical (PEC) performances of a family of TOCs, including pure [Ti12O8(OEt)16L8] ({Me-Ti12}) and six Cd-doped clusters formulated as [H4Cd2Ti10O8(OEt)16(L)8(H2O)2] ({Cd2Ti10}; L = salicylic acid and their derivatives). The six Cd-doped clusters are isostructural, containing the same {Cd2Ti10O8} core, but are protected by salicylic ligands modified with different functional groups. The compositions, structures, and solution stability of these clusters have been studied in detail by single-crystal X-ray diffraction and electrospray ionization mass spectrometry measurements. The embedding of heterometallic Cd(II) and chemical modification of organic protective shells can effectively regulate the PEC water oxidation activity of those clusters, with {F-Cd2Ti10} having the highest turnover number of 518.55 and the highest turnover frequency of 172.85 h-1. Our work highlights the potential of using TOCs that do not contain noble metals as water oxidation catalysts, and their catalytic activity can be regulated by structural modification.

MicroRNA-140 inhibits skeletal muscle glycolysis and atrophy in endotoxin-induced sepsis in mice via the WNT signaling pathway.

Sepsis is a systemic inflammatory response syndrome resulting from infection. This study aimed at exploring the role of microRNA-140 (miR-140) in septic mice. Wnt family member 11 (WNT11) was verified to be a target gene of miR-140 after bioinformatic prediction and dual luciferase reporter gene assay. Importantly, miR-140 negatively regulated WNT11. We initially induced the model of sepsis by endotoxin, and then ectopic expression and knockdown experiments were performed to explore the functional role of miR-140 in sepsis. Additionally, cross-sectional areas of muscle fiber, lactic acid production, 3-methylhistidine (3-MH) and tyrosine (Tyr) production in extensor digitorium longus (EDL) muscles, and serum levels of inflammatory factors were examined. The effect of miR-140 on the expression of WNT signaling pathway-related and apoptosis-related factors in skeletal muscle tissue was determined. The experimental results indicated that upregulated miR-140 or silenced WNT11 increased cross-sectional areas of muscle fiber while decreasing lactic acid production, skeletal muscle cell apoptosis [corresponding to downregulated B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3 and upregulated Bcl-2], and the proteolytic rate of Tyr and 3-MH. Also, overexpressed miR-140 or silenced WNT11 reduced inflammation as reflected by decreased serum levels of IL-6, IL-10, and TNF-α. Furthermore, overexpression of miR-140 was shown to suppress the activation of the WNT signaling pathway, accompanied by decreased expression of WNT11, ß-catenin, and GSK-3ß. Taken together, upregulation of miR-140 could potentially inhibit skeletal muscle lactate release, an indirect measure of glycolysis, and atrophy in septic mice through suppressing the WNT signaling pathway via inhibiting WNT11 expression.

Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes.

Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500 µM (H2O2 group), propofol at 50 µM (propofol group), and H2O2 plus propofol (H2O2 + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H2O2-induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H2O2-induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the H2O2-induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H2O2-induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.

Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro.

BACKGROUND Studies in vivo have shown that dexmedetomidine (DEX) could protect the myocardium and modulate the coronary blood flow. This study aimed to investigate the direct and concentration-dependent effects of DEX on the tone of porcine coronary artery in vitro and the underlying mechanisms. MATERIAL AND METHODS Distal branches of the porcine anterior descending coronary arteries were dissected and cut into 3-5 mm rings. The tones of coronary rings in response to cumulative DEX were measured using the PowerLab system. Coronary rings were divided into three groups: 1) endothelium-intact coronary rings without drug pretreatment (control); 2) endothelium-intact coronary rings pretreated with either yohimbine, tetraethylamine (TEA) or NG-nitro-L-arginine methyl ester (L-NAME); and 3) endothelium-denuded coronary rings pretreated with either yohimbine or TEA. RESULTS DEX induced coronary ring relaxation at lower concentrations (10^-9 to 10^-7 M) followed by constriction at higher concentrations (10^-6 to 10^-5 M). The coronary constrictive effect of higher DEX (10^-5 M) was greater in the endothelium-denuded rings than in the endothelium-intact rings. Yohimbine reduced the coronary constrictive effect of DEX at higher concentrations (10^-6 to 10^-5 M). TEA and L-NAME significantly reduced the coronary relaxing effect of DEX at lower concentrations (10^-9 to 10^-7 M) in endothelium-intact rings. TEA attenuated the coronary relaxation induced by DEX in endothelium-denuded rings. CONCLUSIONS DEX exerts bidirectional effects on porcine coronary tone. The coronary relaxing effect of DEX at lower concentrations is likely associated with endothelium integrity, NO synthesis and BKCa channel activation, while the coronary constrictive effect of DEX at higher concentrations is mediated by a2 adrenoceptors in the coronary smooth muscle cells.

Effect of intraoperative application of ketamine on postoperative depressed mood in patients undergoing elective orthopedic surgery.

PURPOSE: A depressed mood frequently occurs in perioperative patients, negatively impacting patient recovery. Recent studies suggested that ketamine has a rapid, obvious, and persistent antidepressant effect. The purpose of this study was to investigate the impact of intraoperative application of ketamine on postoperative depressive mood in patients undergoing elective orthopedic surgery. METHODS: This was a randomized, double-blind, controlled study. A total of 120 patients (ASA grade I-II) undergoing elective orthopedic surgery were divided randomly into a ketamine group (group K) and a control group (group C). In the K group, 0.5 mg/kg (0.05 ml/kg) ketamine was given at induction of anesthesia, followed by 0.25 mg/kg/h (0.025 ml/kg/h) continuous infusion for 30 min. In the C group, 0.05 ml/kg 0.9 % saline was used at induction of anesthesia, followed by 0.025 ml/kg/h continuous infusion of saline for 30 min. PHQ-9 score was recorded preoperatively (1 day before surgery) and postoperatively (on day 1 and day 5 following surgery). Blood at these time points was drawn for serum brain-derived neurotrophic factor (BDNF) level analysis. Intraoperative blood loss, surgery time, postoperative visual analog scale pain scores and perioperative complications were also recorded. RESULTS: There were no differences in age, sex, surgery time, blood loss, and preoperative PHQ-9 scores between the two groups (P > 0.05). There were no differences in PHQ-9 scores preoperatively and postoperatively for the C group (P > 0.05); however, the PHQ-9 postoperative scores were lower than the preoperative PHQ-9 scores in the K group (P < 0.01). Postoperative PHQ-9 scores of K group were lower than those of C group (P < 0.05). There were no differences in serum BDNF levels in C group pre- to postoperatively (P > 0.05). Compared with the preoperative BDNF levels of K group, postoperative BDNF levels in K group increased significantly (P < 0.01). An inverse correlation between PHQ-9 score and serum BDNF level was shown. CONCLUSION: Intraoperative application of ketamine was associated with improved scores for depressed mood and increased serum BDNF levels in patients undergoing elective orthopedic surgery.

Effect of allyl isothiocyanate on ultra-structure and the activities of four enzymes in adult Sitophilus zeamais.

Rarefaction and vacuolization of the mitochondrial matrix of AITC-treated (allyl isothiocyanate-treated) adult Sitophilus zeamais were evident according to the ultra-structural by TEM. Four important enzymes in adult S. zeamais were further studied after fumigation treatment with allyl isothiocyanate (AITC) extracted from Armoracia rusticana roots and shoots. The enzymes were glutathione S-transferase (GST), catalase (CAT), cytochrome c oxidase, and acetylcholinesterase (AChE). The results indicated that the activities of the four enzymes were strongly time and dose depended. With prolonged exposure time, treatment with 0.74µg/mL AITC inhibited the activities of cytochrome c oxidase, AChE, and CAT, but induced the activity of GST. The activities of cytochrome c oxidase, AChE, and CAT were remarkably induced at a low AITC dosage (0.25µg/mL), but were restrained with increased AITC dosage. The activity of GST was inhibited at a low AITC dosage (0.5µg/mL), but was induced at a high AITC dosage (1.5µg/mL). According to the results of TEM, toxic symptoms and enzymes activities, it suggested that mitochondrial maybe the one site of action of AITC against the adult S. zeamais and it also suggested that cytochrome c oxidase maybe one target protein of AITC against the adult S. zeamais, which need to further confirmed by protein function tested.

Design, synthesis and fungicidal activities of some novel pyrazole derivatives.

In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank) Donk, Fusarium oxysporum (S-chl) f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 µg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 27-32 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring.

Spinal interleukin-16 mediates inflammatory pain via promoting glial activation.

Proinflammatory cytokines are crucial contributors to neuroinflammation in the development of chronic pain. Here, we identified il16, which encodes interleukin-16 (IL-16), as a differentially expressed gene in spinal dorsal horn of a complete Freund's Adjuvant (CFA) inflammatory pain model in mice by RNA sequencing. We further investigated whether and how IL-16 regulates pain transmission in the spinal cord and contributes to the development of inflammatory pain hypersensitivity. RNA sequencing and bioinformatics analysis revealed elevated IL-16 transcript levels in the spinal dorsal horn after CFA injection. This increase was further confirmed by qPCR, immunofluorescence, and western blotting. Knockdown of IL-16 by intrathecal injection of IL-16 siRNA not only attenuated CFA-induced mechanical and thermal pain hypersensitivity, but also inhibited enhanced c-fos expression and glial activation in the spinal dorsal horn in male mice injected with CFA. Moreover, exogenous IL-16 induced nociceptive responses and increased c-fos expression and glial activation in spinal dorsal horn. This effect was largely impaired when CD4, the binding receptor for IL-16, was inhibited. In addition, CD4 expression was upregulated in the spinal dorsal horn after CFA injection and CD4 was present in microglia and in contact with astrocytes and activated spinal neurons. Taken together, these results suggest that enhanced IL-16-CD4 signaling triggers pain and activates microglia and astrocytes in the spinal dorsal horn, thus contributing to inflammatory pain. IL-16 may serve as a promising target for the treatment of inflammatory pain.

Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice.

Immune cells and interleukins play a crucial role in female-specific pain signaling. Interleukin 16 (IL-16) is a cytokine primarily associated with CD4+ T cell function. While previous studies have demonstrated the important role of spinal CD4+ T cells in neuropathic pain, the specific contribution of IL-16 to neuropathic pain remains unclear. In this study, by using a spinal nerve ligation (SNL)-induced neuropathic pain mice model, we found that SNL induced an increase in IL-16 mRNA levels, which persisted for a longer duration in female mice compared to male mice. Immunofluorescence analysis further confirmed enhanced IL-16- and CD4-positive signals in the spinal dorsal horn following SNL surgery in female mice. Knockdown of spinal IL-16 by siRNA or inhibition of CD4 by FGF22-IN-1, a CD4 inhibitor, attenuated established mechanical and thermal pain hypersensitivity induced by SNL. Furthermore, female mice injected with IL-16 intrathecally exhibited significant spontaneous pain, mechanical and thermal hyperalgesia, all of which could be alleviated by FGF22-IN-1 or a CD3 antibody. Additionally, IL-16 induced astrocyte activation but not microglial activation in the spinal dorsal horn of female mice. Meanwhile, astrocyte activation could be suppressed by the CD3 antibody. These results provide compelling evidence that IL-16 promotes astrocyte activation via CD4 on CD3+ T cells, which is critical for maintaining neuropathic pain in female mice.

Propofol increases the Ca2+ sensitivity of BKCa in the cerebral arterial smooth muscle cells of mice.

AIM: Propofol has the side effect of hypotension especially in the elderly and patients with hypertension. Previous studies suggest propofol-caused hypotension results from activation of large conductance Ca(2+)-sensitive K channels (BKCa). In this study, the effects of propofol on the Ca(2+) sensitivity of BKCa were investigated in mice cerebral arterial smooth muscle cells. METHODS: Single smooth muscle cells were prepared from the cerebral arteries of mice. Perforated whole-cell recoding was conducted to investigate the whole-cell BKCa current and spontaneous transient outward K(+) current (STOC). Inside-out patch configuration was used to record the single channel current and to study the Ca(2+)- and voltage-dependence of BKCa. RESULTS: Propofol (56 and 112 µmol/L) increased the macroscopic BKCa and STOC currents in a concentration-dependent manner. It markedly increased the total open probability (NPo) of single BKCa channel with an EC(50) value of 76 µmol/L. Furthermore, propofol significantly decreased the equilibrium dissociation constant (K(d)) of Ca(2+) for BKCa channel. The K(d) value of Ca(2+) was 0.881 µmol/L in control, and decreased to 0.694, 0.599 and 0.177 µmol/L, respectively, in the presence of propofol 28, 56 and 112 µmol/L. An analysis of the channel kinetics revealed that propofol (112 µmol/L) significantly increased the open dwell time and decreased the closed dwell time, which stabilized BKCa channel in the open state. CONCLUSION: Propofol increases the Ca(2+) sensitivity of BKCa channels, thus lowering the Ca(2+) threshold of the channel activation in arterial smooth muscle cells, which causes greater vasodilating effects.

[Primary immunodeficiency diseases in children: clinical analysis of 35 cases].

OBJECTIVE: To summarize clinical features of primary immunodeficiency diseases (PID) in children. METHODS: The clinical data of 35 children with PID from September 2005 to December 2008 were studied retrospectively, including illness history, birth history, family history, clinical manifestations, laboratory findings, diagnosis, treatment and outcome. RESULTS: Of the 35 cases of PID, 6 cases were confirmed with combined T- and B-cell immunodeficiency, 4 cases with X-linked agammaglobulinaemia, 22 cases with selective IgG subclass deficiency, 1 case with common variable immunodeficiency and 2 cases with chronic granulomatous disease. All cases had fever and recurrent infections. Respiratory and digestive tract infections were the most common clinical manifestation. Some of the PID cases lagged behind the normal children of the same age in growth and development. Human gamma-globulin transfusion and anti-infection therapy were administered. Two patients discontinued the therapy, one was transferred to the other hospital and the other 32 patients were discharged following improvement in clinical symptoms. CONCLUSIONS: PID should be considered in children who suffer from recurrent infections and autoimmune diseases or do not respond to long-term use of antibiotics. Immunologic tests should be done as early as possible for the children.

Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways.

Dexmedetomidine (DEX), an α2 adrenoceptor agonist, has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effects of DEX on the myocardium remain unclear. The present study aimed to determine whether DEX serves an important role on cardioprotection through the endoplasmic reticulum (ER)­ and mitochondria­mediated apoptosis signaling pathways. Neonatal rat cardiomyocytes (NRCMs) were cultured and divided four groups: i) Normal culture medium with 10% fetal bovine serum (control group); ii) H2O2 at 500 µM (H2O2 group); iii) DEX at 5 µM (DEX group); and iv) H2O2 plus DEX (H2O2 + DEX group). The levels of apoptosis and oxidative stress of NRCMs were investigated by ELISA, western blotting, flow cytometry and cell immunofluorescence. DEX significantly suppressed H2O2­induced apoptosis, and increased activity of caspases 3, 8 and 9 of NRCMs. DEX inhibited mitochondria­mediated oxidative stress and apoptosis, as evidenced by decreased levels of reactive oxygen species and lactic dehydrogenase, alleviated mitochondrial membrane potential depolarization, and increased Bcl­2­associated X protein/B­cell lymphoma 2 ratio. In addition, DEX decreased the activity of caspase 12, and the expression levels of glucose­regulated protein 78 kDa and serine/threonine­protein kinase/endoribonuclease IRE1, three major signaling molecules involved in the ER stress­mediated apoptosis pathway. Preventive treatment with DEX alleviates cardiomyocyte against H2O2­induced oxidative stress injury through attenuating the mitochondria­ and ER­mediated apoptosis pathways.