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Abstract: ATP-sensitive potassium (K-ATP) channels have been demonstrated to play important roles in the brain. In the present study, Kir6.2 knockout (Kir6.2−/−) mice were used to examine the contribution of Kir6.2-containing K-ATP channels to the regulation of neurotransmitter release via in vivo microdialysis studies. The results showed that the extracellular levels of monoamine and amino acid neurotransmitters in Kir6.2−/− mouse striatum were similar to those in Kir6.2+/+ mice under basal conditions. After high K+ (100mM) perfusion, the extracellular levels of DA and amino acids were increased in both genotypes. These increases, however, were significantly lower in Kir6.2−/− mice than those in Kir6.2+/+ mice. Extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC), a major metabolite of DA, were increased in Kir6.2−/− mice but decreased in Kir6.2+/+ mice in response to high K+ stimulus. The releases of 4-hydroxy-3-methoxy-phenylacetic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were attenuated to a similar extent in both mouse genotypes. Taken together, this study provides direct in vivo evidence that Kir6.2-containing K-ATP channels play regulatory roles in neurotransmitter release in the striatum. [Copyright &y& Elsevier]

Parkinson’s disease is characterized by an extensive loss of dopaminergic neurons in the substantia nigra pars compacta. The final common pathway in the demise of these cells may involve dopamine-dependent oxidative stress. Previous studies revealed a new neuronal protective role of ATP-sensitive potassium channel openers. But the exact mechanism is still unknown. In the present study, the neuroprotective effect of iptakalim, a novel ATP-sensitive potassium channel opener, was studied against rotenone-induced cytotoxicity in rat dopaminergic PC12 cells. Rotenone decreased cell viability significantly after 48 h exposure and induced dopamine release from PC12 cells concentration-dependently. Iptakalim significantly enhanced dopamine uptake and alleviated rotenone-induced PC12 cells death and reduced dopamine release induced by rotenone or GBR-12909, a classical dopamine transporter inhibitor. These results suggest that iptakalim may open mitochondrial KATP channels to modulate dopamine transporter and reduce extracellular dopamine levels, thereby it protecting PC12 cells against rotenone-induced injury. [Copyright &y& Elsevier]

SUMMARY Background and purpose: d-Serine, the endogenous co-agonist of N-methyl- d-aspartate (NM dA) receptors, has been recognized as an important gliotransmitter in the mammalian brain. d-serine has been shown to prevent psychostimulant-induced decrease in hippocampal neurogenesis. However, the mechanism whereby d-serine regulates neurogenesis has not been fully characterized. Therefore, this study was designed to investigate the impacts of d-serine on the proliferation, migration, and differentiation of primary cultured neural stem cells (NSCs). Methods and results: Immunohistochemistry analysis revealed NSCs expressed d-serine as well as serine racemase (SR). Degradation of endogenous d-serine with d-amino acid oxidase ( dAAO) significantly inhibited the proliferation and neuronal differentiation of NSCs, but failed to affect their radial migration. Reversely, addition of exogenous d-serine did not affect the proliferation and migration of NSCs, but promoted NSC differentiation into neurons. Furthermore, dAAO could suppress the amplitude of glutamate-induced Ca2+ transient, and thereby, inhibited the phosphorylation of glycogen synthase kinase3β (GSK3β), extracellular signal-regulated kinases1/2 (ERK1/2), and cAMP-responsive element-binding protein (CREB). Conclusions: Our findings demonstrate for the first time that NSCs can synthesize d-serine and, thereby, promote themselves proliferation and neuronal differentiation, which may afford a novel therapeutic strategy for the neurological disorders that require nerve cell replenishment, such as neurodegenerative diseases and stroke. [ABSTRACT FROM AUTHOR]

Abstract: The role of aquaporin-4 in water transport has been extensively investigated, while little information exists regarding its contribution to astrocytic functions such as the action to glutamatergic transmission. Since aquaporin-4 has been detected widely co-localized with glutamate transporter 1 (GLT-1) and glutamate transporters also present water transport properties, we investigated the regulative role of aquporin-4 on glutamate transporter using primary cultured astrocytes from aquaporin-4 knockout (AQP4−/−) mice. It was demonstrated that lack of aquaporin-4 down-regulated astrocytic expression of GLT-1 but not of glutamate/aspartate transporter (GLAST). The result from [3H]d,l-glutamate uptake analysis showed a lower uptake capability in AQP4−/− astrocytes. Furthermore, MTT and LDH assays indicated less cellular toxicity induced by excessive glutamate in AQP4−/− genotype. These findings provide direct evidences for the first time that aquaporin-4 plays an important role in the function of glutamate transporters. And the present study will improve our understanding of aquaporin-4-glutamanergic biology. [Copyright &y& Elsevier]

Abstract: The final common pathway in the demise of dopaminergic neurons in Parkinson’s disease may involve oxidative stress and excitotoxicity. In this study, we examined the neuroprotective effects of a novel ATP-sensitive potassium channel (KATP) opener, iptakalim (IPT), against H2O2-induced cytotoxicity in rat dopaminergic PC12 cells. Pretreatment with IPT could attenuate increased extracellular glutamate levels and inhibit calcium influxing induced by H2O2. Moreover, IPT regulated the expressions of bcl-2 and bax which were responsible for inhibiting apoptosis in PC12 cells. These protective effects of IPT were abolished by selective mitoKATP channel blocker 5-hydroxydecanoate. Therefore, IPT can protect PC12 cells against H2O2-induced oxidative injury via activating mitoKATP channel. [Copyright &y& Elsevier]

Abstract: The present study examined the effect of iptakalim (Ipt), a novel ATP-sensitive potassium (KATP) channel opener (KCO), on 1-methyl-4-phenylpyridinium ion (MPP+)-induced dopamine (DA) and glutamate efflux in extracellular fluid of rat striatum, using microdialysis technique. Rats were implanted guide cannula in the striatum and artificial cerebrospinal fluid was infused through a microdialysis probe to detect the level of DA and glutamate in the striatum. MPP+ significantly enhanced the extracellular levels of DA and its metabolites, DOPAC and HVA, as well as glutamate. Application of Ipt (1, 10, 100μM) concentration-dependently suppressed DA and its metabolites efflux induced by MPP+. Concomitantly, Ipt reduced the increase of extracellular glutamate induced by MPP+. These results suggest that Ipt can regulate DA and glutamate efflux induced by MPP+ in rat striatum. [Copyright &y& Elsevier]

Abstract: In a previous study, we demonstrated that iptakalim (Ipt) significantly ameliorated hypolocomotion and catalepsy induced by haloperidol and rotenone in rats. In order to further understand the mechanism(s), using a rat model of Parkinson''s disease (PD) established by unilateral 6-hydroxydopamine (6-OHDA) administration to the substantia nigra pars compacta (SNpc) and reverse microdialysis techniques with high performance liquid chromatography (HPLC), we investigated the effects of Ipt on extracellular levels of glutamate, dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in the striatum of conscious and freely moving rats. The results indicated that unilateral 6-OHDA-lesioned rats have a significantly higher level of extracellular glutamate and a lower level of extracellular DOPAC in the lesioned-side of the striatum, and a lower level of extracellular DA in both sides of the striatum compared to the striatum of control rats. Ipt reduced extracellular glutamate levels in both sides of striatum of the lesioned and control rats in a concentration-dependent manner. Ipt, at lower concentrations (0.01, 0.1, 1 μM), enhanced extracellular DA levels in the lesioned-side striatum of the unilateral 6-OHDA-lesioned rats, while causing no significant changes in the intact side striatum, and even a significant decline in striatum of control rats at higher concentrations of Ipt (10, 100 μM). In addition, Ipt also caused a significant decline in the extracellular DOPAC levels in the lesioned-side striatum of unilateral 6-OHDA-lesioned rats. These data suggest that the major mechanism underlying the ameliorative effects of Ipt on the behavior in 6-OHDA-lesioned rats is the alteration of levels of extracellular neurotransmitters, such as glutamate and DA in the striatum of unilateral 6-OHDA-lesioned rats. [Copyright &y& Elsevier]

Abstract: In the present study, we first investigated the effects of unilateral 6-hydroxydopamine (6-OHDA) lesioning of the substantia nigra pars compacta (SNc) on the expression of subunits of ATP-sensitive potassium channels (KATP channels) in the prefrontal cortex (PFC), striatum and hippocampus of adult rats by utilizing semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry techniques. The results show that Kir6.2 and SUR2 expression in the PFC, Kir6.1, Kir6.2 and SUR1 expression in the striatum, and Kir6.1 and Kir6.2 expression in the hippocampus of injured side increased significantly after unilateral 6-OHDA lesioning of the SNc in rats. Afterward, we studied the effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener (KCO), on parkinsonian symptoms, which were induced by acute injection of haloperidol. The results indicate that intraperitoneal injection of Ipt (0.125mg/kg, 0.25mg/kg or 0.5mg/kg) partially alleviated haloperidol-induced catalepsy and hypolocomotion. Even though the observed effects (0.5mg/kg) are better than those of l-3,4-dihydroxyphenylalanine (l-DOPA) (100mg/kg), Ipt (0.25mg/kg) failed to enhance the anti-parkinsonian actions of l-DOPA (100mg/kg). Our results suggest that KATP channels might be involved in the pathogenesis of Parkinson''s disease (PD) induced in an animal model and conceptually support the idea that KATP channels may be new therapeutic targets for PD. [Copyright &y& Elsevier]

Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV's ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection–chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV. [ABSTRACT FROM AUTHOR]

Background: α-Synuclein (α-Syn)-induced neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Dopamine D2 receptor (Drd2) has been regarded as a potential anti-inflammatory target in the therapy of neurodegenerative diseases. However, the effect of astrocytic Drd2 in α-Syn-induced neuroinflammation remains unclear.Methods: The effect of Drd2 on neuroinflammation was examined in mouse primary astrocyte in vitro and A53T transgenic mice in vivo. The inflammatory responses of astrocyte were detected using immunofluorescence, ELISA, and qRT-PCR. The details of molecular mechanism were assessed using Western blotting and protein-protein interaction assays.Results: We showed that the selective Drd2 agonist quinpirole suppressed inflammation in the midbrain of wild-type mice, but not in α-Syn-overexpressed mice. We also found that Drd2 agonists significantly alleviated LPS-induced inflammatory response in astrocytes, but failed to suppress α-Syn-induced inflammatory response. The anti-inflammation effect of Drd2 was dependent on β-arrestin2-mediated signaling, but not classical G protein pathway. α-Syn reduced the expression of β-arrestin2 in astrocytes. Increased the β-arrestin2 expression restored in the anti-inflammation of Drd2 in α-Syn-induced inflammation. Furthermore, we demonstrated that α-Syn disrupted the anti-inflammation of Drd2 via inhibiting the association of β-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and promoting TAK1-TAB1 interaction in astrocytes.Conclusions: Our study illustrates that astrocytic Drd2 inhibits neuroinflammation through a β-arrestin2-dependent mechanism and provides a new strategy for treatment of PD. Our findings also reveal that α-Syn disrupts the function of β-arrestin2 and inflammatory pathways in the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP + -induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: The Delphi consensus identified 8 symptoms and 8 consequences as the highest priorities for defining low anterior resection syndrome., Objective: To describe an exploratory scoring instrument correlating the Delphi consensus on low anterior resection syndrome with functional and quality-of-life scores following intersphincteric resection for ultralow rectal cancer., Design: This was a prospective pilot study. In accordance with the Wexner incontinence score, 5 frequency responses ranging from never (score 0) to always (score 4) were used to measure the severity of symptom- and consequence-specific variables., Settings: Colorectal surgery referral center., Patients: Among 161 eligible patients, 137 participants (85%) completed an electronic self-assessment survey regarding function and quality of life at scheduled follow-up, including 3 to 6, 12, and ≥24 months after ileostomy reversal., Main Outcome Measures: Outcome measures included patient-reported severity of the identified priorities, and their correlation with condition-specific quality of life., Results: The most frequent symptom and consequence were "emptying difficulties" and "dissatisfaction with the bowels," respectively. Aside from "emptying difficulties," the proportions of negative symptom domains increased after reversal. In particular, neither the frequency responses nor the severity scores of "emptying difficulties" differed between groups. The percentages of "always" selection for consequence domains improved at 12-month follow-up, whereas a higher rate was observed at 24 months, except for "toilet dependence" and "dissatisfaction with the bowels." We found significant improvements in the summary score of the Fecal Incontinence Quality-of-Life Scale ( p = 0.04) and our exploratory instrument ( p = 0.009) but not in functional scores measured by traditional questionnaires. Furthermore, the condition-specific quality of life strongly correlated with the Delphi consensus severity score ( rs = -0.73)., Limitations: Single-institution data and limited sample size., Conclusions: The important priorities identified by the Delphi consensus might enable a comprehensive overview and a better assessment of low anterior resection syndrome after intersphincteric resection. See Video Abstract ., Evale La Gravedad Del Sndrome De Reseccin Anterior Baja Despus De La Reseccin Interesfintrica Para El Cncer De Recto Ultrabajo Un Estudio Piloto Que Utiliza Un Instrumento Exploratorio: ANTECEDENTES:El consenso Delphi identificó ocho síntomas y ocho consecuencias como las máximas prioridades para definir el síndrome de resección anterior baja.OBJETIVO:Describir un instrumento de puntuación exploratorio que correlaciona el consenso Delphi sobre el síndrome de resección anterior baja con puntuaciones funcionales y de calidad de vida después de la resección interesfinteriana para el cáncer de recto ultrabajo.DISEÑO:Este fue un estudio piloto prospectivo. De acuerdo con la puntuación de incontinencia de Wexner, se utilizaron cinco respuestas de frecuencia que van desde nunca (puntuación 0) hasta siempre (puntuación 4) para medir la gravedad de las variables específicas de los síntomas y las consecuencias.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Entre 161 pacientes elegibles, 137 (85%) participantes completaron una encuesta electrónica de autoevaluación sobre la función y la calidad de vida en el seguimiento programado, incluidos 3 a 6, 12 y ≥ 24 meses después de la reversión de la ileostomía.MEDIDAS PRINCIPALES DE RESULTADO:Las medidas de resultado incluyeron la gravedad de estas prioridades informada por los pacientes, así como su correlación con la calidad de vida específica de la afección.RESULTADOS:El síntoma y la consecuencia más frecuentes fueron "dificultades para vaciar" e "insatisfacción con las deposiciones", respectivamente. Aparte de las "dificultades de vaciado", las proporciones de dominios de síntomas negativos aumentaron después de la reversión. En particular, tanto las respuestas de frecuencia como las puntuaciones de gravedad de las "dificultades para vaciar" no difirieron entre los grupos. Los porcentajes de "opción siempre" para los dominios de consecuencias mejoraron a los 12 meses de seguimiento, mientras que se observó una tasa más alta a los 24 meses después, excepto para "dependencia del baño" e "insatisfacción con los intestinos". Encontramos mejoras significativas en la puntuación resumida de la Escala de calidad de vida de incontinencia fecal ( p = 0,04) y nuestro instrumento exploratorio ( p = 0,009), pero no en las puntuaciones funcionales medidas con los cuestionarios tradicionales. Además, la calidad de vida específica de la condición se correlacionó fuertemente con la puntuación de gravedad del consenso Delphi (rs = -0,73).LIMITACIONES:Datos de una sola institución y tamaño de muestra limitado.CONCLUSIONES:Las importantes prioridades identificadas por el consenso Delphi podrían permitir una visión global y una mejor evaluación del síndrome de resección anterior baja después de la resección interesfintérica. (Traducción-Dr. Yesenia Rojas-Khalil )., (Copyright © The ASCRS 2024.)

Aim: Sphincter-sparing surgery can be achieved in most cases of low rectal cancer with the development of intersphincteric resection. However, abdominoperineal resection is still inevitable for patients with tumours located below the dentate line. To address this, we have developed a procedure called conformal sphincteric resection (CSR) in which the corresponding part of the subcutaneous portion of the external anal sphincter and the perianal skin on the tumour side is removed to achieve a safe distal resection margin and lateral resection margin while the dentate line and the internal anal sphincter on the tumour-free side are preserved as much as possible, to achieve sphincter preservation without compromising oncological safety and functional acceptability, and to render tumour location no longer a contraindication for sphincter-sparing surgery. This is the first study to describe the concept, indication and surgical procedure of CSR and to report its preliminary surgical, oncological and functional results., Methods: This is a retrospective, single-centre, single-arm pilot study conducted at Huashan Hospital, Fudan University. Demographic, clinicopathological, oncological and functional follow-up data were collected from 20 consecutive patients with rectal tumours located below the dentate line who underwent laparoscopic CSR by the same surgical team from June 2018 to March 2022., Results: The mean distance of the tumour's lower edge from the anal verge was 13.1 ± 6.0 mm. The mean distal resection margin was 10.6 ± 4.3 mm. All circumferential resection margins were negative. There were no instances of perioperative mortality. The complication rate was 25% but all were Clavien-Dindo Grade I. Among the 20 cases, 17 were diagnosed with adenocarcinoma, one with squamous cell carcinoma and two with adenoma featuring high-grade intraepithelial neoplasia. Pathological TNM staging revealed two, seven, five, five and one case(s) in Stages 0, I, II, III and IV, respectively. The median follow-up period was 20 months (interquartile range 22 months), with no withdrawals. The overall and disease-free survival rates were both 95%. The mean Wexner incontinence score and low anterior resection syndrome score recorded 18 months following diverting ileostomy closure were 6.3 ± 3.8 and 27.3 ± 3.6, respectively., Conclusions: This study has proposed the CSR procedure for the first time, which is a technically feasible, oncologically safe and functionally acceptable procedure for carefully selected patients with rectal tumours located below the dentate line., (© 2023 Association of Coloproctology of Great Britain and Ireland.)

Background: Intersphincteric resection is the ultimate sphincter-preserving surgical technique for ultralow rectal cancer, but quality-of-life changes after surgery remain unclear. It is also unknown which questionnaire has better associations with functional results for capturing clinical variation in quality of life., Objective: This study aimed to assess change in the quality of life and its correlation with functional outcomes among patients undergoing intersphincteric resection for ultralow rectal cancer., Design: This was a prospective, observational, single-center study., Settings: Colorectal surgery referral center., Patients: Patients with ultralow rectal cancer who underwent intersphincteric resection were included., Main Outcome Measures: The primary outcomes were quality-of-life and functional results at 3 to 6, 12, and 24 months after ileostomy closure using validated questionnaires. The secondary outcome was the relationship between quality of life and neorectal function., Results: A total of 102 patients (62.7% men) completed follow-up surveys. Wexner incontinence score and Kirwan's incontinence score significantly improved at 12 months after ileostomy reversal, but such improvement in low anterior resection syndrome score was proved until 24 months later ( p = 0.01). Condition-specific quality-of-life domains improved over time, with significant changes in lifestyle ( p = 0.02) and coping/behavior ( p = 0.01), as well as the summary score of Fecal Incontinence Quality of Life ( p = 0.02) and visual analog scale score ( p < 0.001). Among health-related quality-of-life domains, the subscale scores did not differ significantly. The functional systems scores were significantly correlated with all the domains of condition-specific quality-of-life but only a few health-related quality-of-life domains. Only weak to moderate associations with the functional outcomes were observed for both quality-of-life questionnaires., Limitations: Single-center data and limited sample size., Conclusions: Although low anterior resection syndrome persists for years after intersphincteric resection, condition-specific quality of life and functional outcomes improve over time. Compared to health-related quality-of-life questionnaires, condition-specific quality-of-life instruments might be preferable to evaluate changes in quality-of-life after surgery. See Video Abstract at http://links.lww.com/DCR/C130 ., Calidad De Vida Y Resultados Funcionales Despus De Una Reseccin Interesfintrica En Caso De Cncer Rectal Ultrabajo Estudio Prospectivo Observacional: ANTECEDENTES:La resección inter-esfintérica es la última técnica quirúrgica conservadora de esfínteres en casos de cáncer rectal ultrabajo, pero los cambios en la calidad de vida después de la cirugía siguen sin estar claros. Se desconoce también, qué tipo de cuestionario tiene mejor asociación con los resultados funcionales para así captar las variaciones clínicas en la calidad de vida.OBJETIVO:Evaluar el cambio en la calidad de vida y su correlación con los resultados funcionales durante el período postoperatorio en pacientes sometidos a resección interesfintérica por cáncer de recto ultrabajo.DISEÑO:Estudio prospectivo, observacional y de un solo centro.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Se incluyeron pacientes con cáncer de recto ultra bajo que se sometieron a resección interesfintérica con el cierre de la ileostomía.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la calidad de vida y los resultados funcionales a los 3-6, 12 y 24 meses después del cierre de la ileostomía utilizando cuestionarios validados. El resultado secundario fue la relación entre la calidad de vida y la función del néorecto.RESULTADOS:Un total de 102 pacientes (62,7% hombres) completaron las encuestas de seguimiento. La puntuación de incontinencia de Wexner y la puntuación de incontinencia de Kirwan mejoraron significativamente a los 12 meses después del cierre de la ileostomía, pero dicha mejoría en la puntuación del síndrome de resección anterior baja se demostró solo hasta 24 meses después ( p = 0,01). Las condiciones en el dominio de la calidad de vida específicos mejoraron con el tiempo, con cambios significativos en el estilo de vida ( p = 0,02) y el afrontamiento/comportamiento ( p = 0,01), así como la puntuación general de la calidad de vida y de la incontinencia fecal ( p = 0,02), puntuación de la escala analógica visual ( p < 0,001). Entre los dominios de la calidad de vida relacionada con la salud, las puntuaciones de las sub-escalas no difirieron significativamente. Las puntuaciones de los sistemas funcionales se correlacionaron significativamente con todos los dominios de la calidad de vida específica de la nueva condición, pero solo con pocos dominios de calidad de vida relacionados con la salud. Solo se observaron asociaciones débiles a moderadas con los resultados funcionales para ambos cuestionarios de calidad de vida.LIMITACIONES:Datos de un solo centro y tamaño de muestra limitado.CONCLUSIONES:Aunque el síndrome de resección anterior baja persiste durante años después de la resección interesfintérica, la calidad de vida específica de la nueva condición y los resultados funcionales mejoran con el tiempo. En comparación con los cuestionarios de calidad de vida relacionados con la salud, los instrumentos de calidad de vida específicos de la nueva condición pueden ser preferibles para evaluar los cambios en la calidad de vida después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/C130 . (Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2023.)

Malignant glioma is the most fatal, invasive brain cancer with limited treatment options. Our previous studies show that 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1), a major metabolite of indole-3-carbinol (I3C) derived from cruciferous vegetables, produces anti-tumour effect against various tumour cell lines. In this study we characterized LTr1 as a novel anti-glioma agent. Based on screening 134 natural compounds and comparing the candidates' efficacy and toxicity, LTr1 was selected as the lead compound. We showed that LTr1 potently inhibited the viability of human glioma cell lines (SHG-44, U87, and U251) with IC 50 values of 1.97, 1.84, and 2.03 μM, respectively. Furthermore, administration of LTr1 (100,300 mg· kg -1  ·d -1 , i.g. for 18 days) dose-dependently suppressed the tumour growth in a U87 xenograft nude mouse model. We demonstrated that LTr1 directly bound with TrkA to inhibit its kinase activity and the downstream PI3K/AKT pathway thus inducing significant S-phase cell cycle arrest and apoptosis in SHG-44 and U87 cells by activating the mitochondrial pathway and inducing the production of reactive oxygen species (ROS). Importantly, LTr1 could cross the blood-brain barrier to achieve the therapeutic concentration in the brain. Taken together, LTr1 is a safe and promising therapeutic agent against glioma through inhibiting TrkA/PI3K/AKT pathway., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Aims: To screen coral-derived compounds with neuroprotective activity and clarify the potential mechanism of lead compounds., Methods: The lead compounds with neuroprotective effects were screened by H 2 O 2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP + )-induced cell damage models in SH-SY5Y cells. CCK8 and LDH assays were used to detect cell viability. The anti-apoptosis of lead compounds was evaluated by flow cytometry. JC-1 and MitoSox assays were performed to examine the changes in mitochondrial membrane potential and mitochondrial ROS level. Survival of primary cortical and dopaminergic midbrain neurons was measured by MAP2 and TH immunoreactivities. The Caenorhabditis elegans (C. elegans) model was established to determine the effect of lead compounds on dopaminergic neurons and behavior changes., Results: Three compounds (No. 63, 68, and 74), derived from marine corals, could markedly alleviate the cell damage and notably reverse the loss of worm dopaminergic neurons. Further investigation indicated that compound 63 could promote the expression of Nurr1 and inhibit neuronal apoptosis signaling pathways., Conclusion: Lead compounds from marine corals exerted significant neuroprotective effects， which indicated that coral might be a new and potential resource for screening and isolating novel natural compounds with neuroprotective effects. Furthermore, this study also provided a new strategy for the clinical treatment of neurodegenerative diseases such as Parkinson's disease., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: A permanent stoma is an unintended consequence that cannot be avoided completely after intersphincteric resection for ultralow rectal cancer. Unfortunately, its incidence and risk factors have been poorly defined., Objective: The objective was to determine the cumulative incidence and risk factors of permanent stoma after intersphincteric resection for ultralow rectal cancer., Design: This study was a retrospective analysis of prospectively collected data., Settings: This study was conducted at a colorectal surgery referral center., Patients: A total of 185 consecutive patients who underwent intersphincteric resection with diverting ileostomy from 2011 to 2019 were included., Main Outcome Measures: The primary outcome was the incidence of and risk factors for the permanent stoma. The secondary outcome included differences in stoma formation between patients with partial, subtotal, and total intersphincteric resection., Results: After a median follow-up of 40 months (range, 6-107 months), 26 of 185 patients eventually required a permanent stoma, accounting for a 5-year cumulative incidence of 17.4%. The causes of permanent stoma were anastomotic morbidity (46.2%, 12/26), local recurrence (19.2%, 5/26), distant metastasis (19.2%, 5/26), fecal incontinence (3.8%, 1/26), perioperative mortality (3.8%, 1/26), patients' refusal (3.8%, 1/26), and poor general condition (3.8%, 1/26). Although the incidence of permanent stoma was significantly different between the intersphincteric resection groups (partial vs subtotal vs total: 8.3% vs 20% vs 25.8%, p = 0.02), it was not an independent predictor of stoma formation. Multivariate analysis demonstrated that anastomotic leakage (OR = 5.29; p = 0.001) and anastomotic stricture (OR = 5.13; p = 0.002) were independently predictive of permanent stoma., Limitations: This study was limited by its retrospective nature and single-center data., Conclusions: The 5-year cumulative incidence of permanent stoma was 17.4%. Anastomotic complications were identified as risk factors. Patients should be informed of the risks and benefits when contemplating the ultimate sphincter-sparing surgery. It might be preferable to decrease the probability of permanent stoma by further minimizing anastomotic complications. See Video Abstract at http://links.lww.com/DCR/B704., Incidencia Acumulada Y Factores De Riesgo De Estoma Permanente Despus De Una Reseccin Interesfntrica En Cncer Rectal Ultra Bajo: ANTECEDENTES:La necesidad de efectuar un estoma permanente es la consecuencia no intencional e inevitable por completo después de una resección interesfintérica en presencia de un cáncer rectal ultra bajo. Desafortunadamente, la incidencia y los factores de riesgo se han definido en una forma limitada.OBJETIVO:El objetivo fue determinar la incidencia acumulada y los factores de riesgo para la necesidad de efectuar un estoma permanente después de la resección intersfintérica de un cáncer rectal ultra bajo.DISEÑO:El presente estudio es un análisis retrospectivo de la información obtenida.ESCENARIO:Centro de referencia de cirugía colo-rectal.PACIENTES:Se incluyeron un total de 185 pacientes consecutivos que se sometieron a resección intersfintérica de un cáncer rectal ultra bajo con ileostomía de derivación de 2011 a 2019.MEDICION DE RESULTADOS:El resultado principal fue la identificación de la incidencia y los factores de riesgo para la presencia de un estoma permanente. En forma secundaria se describieron los resultados de las diferentes técnicas de la formación de un estoma entre los pacientes con resección interesfintérica parcial, subtotal o total.RESULTADOS:Posterior a una media de seguimiento de cuarenta meses (rango de 6 a 107), 26 de 185 pacientes requirieron en forma eventual un estoma permanente, lo que equivale a una incidencia acumulada a cinco años de 17.4 %. Las causas para dejar un estoma permanente fueron morbilidad de la anastomosis (46.2%, 12/26), recurrencia local (19.2%, 5/26), metástasis a distancia (19.2%, 5/26), incontinencia fecal (3.8%, 1/26), mortalidad perioperatoria (3.8%, 1/26), rechazo del paciente (3.8%, 1/26), y malas condiciones generales (3.8%, 1/26). Aunque la incidencia de un estoma permanente fue significativamente diferente entre los grupos de resección interesfintérica (parcial vs subtotal vs total: 8.3% vs 20% vs 25.8%, p = 0.02), no se consideró un factor predictor independiente para la formación de estoma. En el análisis multivariado se demostró que la fuga anatomótica (OR = 5.29; p = 0.001) y la estenosis anastomótica (OR = 5.13; p = 0.002) fueron factores independientes para predecir la necesidad de un estoma permanente.LIMITACIONES:La naturaleza retrospectiva del estudio y la información proveniente de un solo centro.CONCLUSIONES:La incidencia acumulada a cinco años de estoma permantente fue de 17.4%. Se consideran a las complicaciones anastomóticas como factores de riesgo. Los pacientes deberán ser informados de los riesgos y beneficios cuando se considere la posibilidad de efectuar una cirugía preservadora de esfínteres finalmente. Puede ser preferible disminuir la probabilidad de dejar un estoma permanente tratando de minimizar la posibilidad de complicaciones de la anastomosis. Consulte Video Resumen en http://links.lww.com/DCR/B704., (Copyright © The ASCRS 2021.)

Tetrix gibberosa (Wang Zheng) is a high-backed pygmy grasshopper species from eastern PR China. Due to its reduced hind wings and pleomorphism (length changes of hind wings and the hind pronotal process, which is generally called macropterous and brachypterous morphs), the species have been described into different species which involve several taxonomically confused genera. This study clarifies its taxonomy and distribution and provides ecological information for the species. At the same time, we comment the relationships of related genera in the subfamily Tetriginae, including Tetrix Latreille, Exothotettix Zheng Jiang, Alulatettix Liang, Aalatettix Zheng Mao, Formosatettix Tinkham, and Formosatettixoides Zheng. Additionally, we report for the first time that nematodes can parasitize pygmy grasshoppers. New synonyms are proposed: Tetrix gibberosa (Wang Zheng, 1993) = Alulatettix bulbosus Zheng Zhong, 2001, syn. nov., = Exothotettix jiangxiensis Liang Jia, 2008, syn. nov., = Tetrix glochinota Zhao, Niu Zheng, 2010, syn. nov., = Alulatettix nigromarginalis Zhang, Deng Zha, 2014, syn. nov., = Alulatettix flavotibialis Zhang, Deng Zha, 2014, syn. nov..

Complement pathway over-activation has been implicated in a variety of neurological diseases. However, the signaling pathways governing astrocytic complement activation in Parkinson's disease (PD) are poorly understood. Kir6.1, a pore-forming subunit of ATP-sensitive potassium (K-ATP) channel, is prominently expressed in astrocytes and exhibits anti-inflammatory effects. Therefore, we hypothesize that Kir6.1/K-ATP channel may regulate astrocytic complement activation in the pathogenesis of PD. In this study, astrocytic Kir6.1 knockout (KO) mice were used to examine the effect of astrocytic Kir6.1/K-ATP channel on astrocytic complement activation triggered by the lipopolysaccharide (LPS). Here, we found that astrocytic Kir6.1 KO mice showed more dopaminergic neuron loss and more astrocyte reactivity in substantia nigra compacta than controls. We also found that astrocytic Kir6.1 KO increased the expression of complement C3 in astrocytes in LPS-induced mouse model of PD. Mechanistically, astrocytic Kir6.1 KO promoted astroglial NF-κB activation to elicit extracellular release of C3, which in turn interacted with neuronal C3aR to induce neuron death. Blocking complement function by NF-κB inhibitor or C3aR antagonist rescued the aggravated neuron death induced by Kir6.1 KO. Collectively, our findings reveal that astrocytic Kir6.1/K-ATP channel prevents neurodegeneration in PD via astrocyte-neuron cross talk through NF-κB/C3/C3aR signaling and suggest that targeting astroglial Kir6.1/K-ATP channel-NF-κB-C3-neuronal C3aR signaling represents a novel therapeutic strategy for PD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Over the last decade, the roles of β-arrestins in the treatment of neuropsychological diseases have become increasingly appreciated. Fluoxetine is the first selective serotonin reuptake inhibitor developed and is approved for the clinical treatment of depression. Emerging evidence suggests that fluoxetine can directly combine with the 5-HT receptor, which is a member of the G protein-coupled receptor (GPCR) family, in addition to suppressing the serotonin transporter. In this study, we prepared a chronic mild stress (CMS)-induced depression model with β-arrestin2 -/- mice and cultured adult neural stem cells (ANSCs) to investigate the involvement of the 5-HT receptor-β-arrestin axis in the pathogenesis of depression and in the therapeutic effect of fluoxetine. We found that β-arrestin2 deletion abolished the fluoxetine-mediated improvement in depression-like behaviors and monoamine neurotransmitter levels, although β-arrestin2 knockout did not aggravate CMS-induced changes in mouse behaviors and neurotransmitters. Notably, the β-arrestin2 -/- mice had a shortened dendritic length and reduced dendritic spine density, as well as decreased neural precursor cells, compared to the WT mice under both basal and CMS conditions. We further found that β-arrestin2 knockout decreased the number of proliferating cells in the hippocampal dentate gyrus and suppressed the proliferative capability of ANSCs in vitro. Moreover, β-arrestin2 knockout aggravated the impairment of cell proliferation induced by corticosterone and further blocked the fluoxetine-mediated promotion of mouse hippocampal neurogenesis. Mechanistically, we found that the 5-HT 2B R-β-arrestin2-PI3K/Akt axis is essential to maintain the modulation of hippocampal neurogenesis in depressed mice. Our study may provide a promising target for the development of new antidepressant drugs.

The genus Phaesticus Uvarov, 1940 is revised here with updated generic characteristics and a key to the species. New synonyms and a new combination are proposed: 1) Phaesticus Uvarov, 1940 = Flatocerus Liang Zheng, 1984 syn. nov.; 2) P. mellerborgi (Stål, 1855) = P. insularis (Hancock, 1907) syn. nov., = P. carinatus Zheng, 1998 syn. nov., = P. azemii Mahmood, Idris Salmah, 2007 syn. nov., = F. brachynotus Liang, Chen Chen, 2008 syn. nov., = P. uvarovi Storozhenko Dawwrueng, 2015 syn. nov.; 3) P. moniliantennatus (Günther, 1940) = F. nankunshanensis Liang Zheng, 1984 syn. nov., = F. wuyishanensis Zheng, 1991 syn. nov., = F. guizhouensis Wang, 1992 syn. nov., = F. daqingshanensis Zheng Jiang, 1998 syn. nov., = F. dentifemura Zheng, 2003 syn. nov.; 4) P. hainanensis (Liang, 1988) comb. nov. = F. hainanensis Liang, 1988. Intraspecific variation in the lengths of the hind pronotal processes and hind wings in the family Tetrigidae are discussed in detail.

Species of Cordyceps sensu lato (Hypocreales, Sordariomycetes) have always attracted much scientific attention for their abundant species diversity, important medicinal values and biological control applications. The insect superfamilies Elateroidea and Tenebrionoidea are two large groups of Coleoptera and their larvae are generally called wireworms. Most wireworms inhabit humid soil or fallen wood and are often infected with Cordyceps s.l. However, the species diversity of Cordyceps s.l. on Elateroidea and Tenebrionoidea is poorly known. In the present work, we summarise taxonomic information of 63 Cordyceps s.l. species that have been reported as pathogens of wireworms. We review their hosts and geographic distributions and provide taxonomic notes for species. Of those, 60 fungal species are accepted as natural pathogens of wireworms and three species ( Cordyceps militaris , Ophiocordyceps ferruginosa and O. variabilis ) are excluded. Two new species, O. borealis from Russia (Primorsky Krai) and O. spicatus from China (Guizhou), are described and compared with their closest allies. Polycephalomyces formosus is also described because it is reported as a pathogen of wireworms for the first time. Phylogeny was reconstructed from a combined dataset, comprising SSU, LSU and TEF1-α gene sequences. The results, presented in this study, support the establishment of the new species and confirm the identification of P. formosus ., (Ling-Sheng Zha, Vadim Yu Kryukov, Jian-Hua Ding, Rajesh Jeewon, Putarak Chomnunti.)

Aim: The aim was to evaluate the physiological variation in rectoanal inhibitory reflex (RAIR) after laparoscopic intersphincteric resection (Lap-ISR) for ultralow rectal cancer., Method: This was a retrospective study that included 56 patients who underwent Lap-ISR from a prospectively collected database. The RAIR was examined preoperatively and up to 12 months after ileostomy closure. The primary outcome included physiological variation in RAIR and its difference between partial, subtotal and total ISR. The secondary outcome was its correlation with functional outcome., Results: The reflex was present in 95% (53/56) of patients preoperatively, in 36% (20/56) before ileostomy closure, in 48% (27/56) at 3-6 months and in 61% (34/56) at 12 months after ileostomy closure. The elicited volume of RAIR was significantly increased at 12 months after ileostomy closure than at baseline (P = 0.005), but its duration and amplitude did not differ significantly. There was no significant difference in the reflex recovery between the ISR groups (partial vs. subtotal vs. total: 65% vs. 63% vs. 44%, P = 0.61). At 12 months after ileostomy closure, the RAIR-present group had favourable functional results and patient satisfaction (P < 0.05). Major faecal incontinence was found in 82% of patients in the RAIR-absent group., Conclusion: The RAIR is abolished in the majority of patients after Lap-ISR, but a time-dependent recovery could be observed in more than half of the patients. The reflex recovery is not influenced by the resection grade of the internal sphincter. However, persistent loss of the RAIR correlates with worse continence., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Cerace xanthocosma Diakonoff, 1950 belongs to the Tortricidae of Lepidoptera, distributed in China and Japan. Its mitochondrial genome is 15,344 bp in size, containing 37 genes (13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes) and a non-coding A + T-rich region. In the 37 genes, 14 genes are located on the minority-strand (N-strand) with the remaining genes on the majority-strand (J-strand). The A + T-rich region has a poly-T stretch and a motif ATAGA. Phylogenetic analysis using Bayesian Inference method shows the sister relationship between Tortricinae and Olethreutinae with the placement of C. xanthocosma as the basal lineage of Tortricinae., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Two new pygmy grasshopper species are described from PR China and are assigned to Formosatettix Tinkham, 1937, a large Asian tetrigin genus composed of species with reduced tegmina and hind wings: F. leigongshanensis Zha & Ding, sp. nov. from Guizhou and F. wulongensis Zha & Ding, sp. nov. from Chongqing. We provide descriptions of morphology and habit, supplemented with photographs. Flying organs of the genus Formosatettix are discussed and the genus is compared with other Asian genera with reduced flying organs, such as Formosatettixoides Zheng, 1994 and Alulatettix Liang, 1993 in Tetriginae, Deltonotus Hancock, 1904, Epitettix Hancock, 1907 and Pseudepitettix Zheng, 1995 in Cladonotinae, and Macromotettixoides Zheng, Wei & Jiang, 2005 and Pseudomacromotettix Zheng, Li & Lin, 2012 in Metrodorinae., (Ling-Sheng Zha, Xiao-Min Wu, Jian-Hua Ding.)

Background: Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined., Methods: Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP + )-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers., Results: We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP + -induced premature senescence, evidenced by decreased senescence-associated β-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence., Conclusions: Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.

ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to cell membrane potential, are involved in brain diseases, including Parkinson's disease (PD). Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed in astrocytes and participates in regulating its function. However, the precise role of astrocytic Kir6.1-contaning K-ATP channel (Kir6.1/K-ATP) in PD is not well characterized. In this study, astrocytic Kir6.1 knockout (KO) mice were used to examine the effect of astrocytic Kir6.1/K-ATP channel on dopaminergic (DA) neurodegeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Here, we found that astrocytic Kir6.1 KO mice showed more DA neuron loss in substantia nigra compacta (SNc), lower level of dopamine in the striatum, and more severe motor dysfunction than controls. Interestingly, this companied by increased neuroinflammation and decreased autophagy level in SNc in vivo and astrocytes in vitro. Mechanistically, astrocytic Kir6.1 KO inhibited mitophagy which resulted in an increase in the accumulation of damaged mitochondria, production of reactive oxygen species and neuroinflammation in astrocytes. Restoration of astrocytic mitophagy rescued the deleterious effects of astrocytic Kir6.1 ablation on mitochondrial dysfunction, inflammation and DA neuron death. Collectively, our findings reveal that astrocytic Kir6.1/K-ATP channel protects against DA neurodegeneration in PD via promoting mitophagy and suggest that astrocytic Kir6.1/K-ATP channel may be a promising therapeutic target for PD., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Excessive activation of the NLRP3 inflammasome is a key component contributing to the pathogenesis of various inflammatory diseases. However, the molecular mechanisms underlying its activation and regulation remain poorly defined. The objective of this study was to explore the possible function of the K + channel pore-forming subunit Kir6.1 in regulating NLRP3 inflammasome activation and insulin resistance. Here, we demonstrate that Kir6.1 depletion markedly activates the NLRP3 inflammasome, whereas enhanced Kir6.1 expression produces opposing effects both in mice in vivo and in primary cells in vitro. We also demonstrate that Kir6.1 controls insulin resistance by inhibiting NLRP3 inflammasome activation in mice. We further show that Kir6.1 physically associates with NLRP3 and thus inhibits the interactions between the NLRP3 inflammasome subunits. Our results reveal a previously unrecognized function of Kir6.1 as a negative regulator of the NLRP3 inflammasome and insulin resistance, which is mediated by virtue of its ability to inhibit NLRP3 inflammasome assembly. These data provide novel insights into the regulatory mechanism of NLRP3 inflammasome activation and suggest that Kir6.1 is a promising therapeutic target for inflammasome-mediated inflammatory diseases.

Women are believed to be more vulnerable to develop depressive symptoms during the perimenopause compared to postmenopause. The traditional bilateral ovariectomy and chronic mild stress (CMS) stimulation animal model produces a postmenopausal depressive-like state but the transition from perimenopausal period to postmenopausal period was ignored. Thus we establish a novel animal model in which the mice were stimulated by CMS for three months and removed the ovaries by two-step operation, and then evaluate whether this novel model could be much better for preclinical study used as a peri/postmenopause depressive model. The present study systemically evaluated the changes induced by two-step ovariectomy plus CMS in the mice. The depression-like behaviors, the levels of corticosterone, estrogen, pro-inflammatory factors, neurotransmitters, as well as brain-derived neurotrophic factor were determined; the changes of estrogen receptors, serotonin receptors, uterine weight and bone microarchitecture were also observed. The results show that the behaviors and biochemical indexes of mice changed gradually over time. Our study suggests that this two-step ovariectomy operation plus CMS successfully establishes a more reasonable peri/postmenopausal depression animal model which effectively simulates the clinical symptoms of peri/postmenopausal depressive women.

ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to cell membrane potential, are involved in brain diseases including stroke. Emerging evidence shows that astrocytes play important roles in the pathophysiology of cerebral ischemia. Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed in astrocytes and participates in regulating its function. However, the exact role of astrocytic Kir6.1-containg K-ATP channel (Kir6.1/K-ATP) in ischemic stroke remains unclear. Here, we found that astrocytic Kir6.1 knockout (KO) mice exhibited larger infarct areas and more severe brain edema and neurological deficits in middle cerebral artery occlusion stroke model. Both activated gliosis and neuronal loss were aggravated in astrocytic Kir6.1 KO mice. Furthermore, the protein levels of pro-apoptotic protein Bcl-2 associated X (Bax) and active caspase-3 were up-regulated and the expression of anti-apoptotic protein Bcl-2 was down-regulated in astrocytic Kir6.1 KO mice. This is accompanied by enhanced endoplasmic reticulum stress (ER stress) responses in brain tissues and in astrocytes during ischemia/reperfusion (I/R) injury. Finally, inhibition of ER stress rescued astrocyte apoptosis induced by Kir6.1 deletion during I/R injury. Collectively, our findings reveal that astrocytic Kir6.1/K-ATP channel protects brain from cerebral ischemia/reperfusion injury through inhibiting ER stress and suggest that astrocytic Kir6.1/K-ATP channel is a promising therapeutic target for ischemic stroke., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the present study, the complete mitogenome of Theretra japonica was sequenced and compared with other sequenced mitogenomes of Sphingidae species. The mitogenome of T. japonica , containing 37 genes (13 protein-coding genes, 22 tRNA genes, and two rRNA genes) and a region rich in adenine and thymine (AT-rich region), is a circular molecule with 15,399 base pairs (bp) in length. The order and orientation of the genes in the mitogenome are similar to those of other sequenced mitogenomes of Sphingidae species. All 13 protein-coding genes (PCGs) are initiated by ATN codons except for the cytochrome C oxidase subunit 1 gene ( cox1 ) which is initiated by the codon CGA as observed in other lepidopteran insects. Cytochrome C oxidase subunit 2 gene ( cox2 ) has the incomplete termination codon T and NADH dehydrogenase subunit 1 gene ( nad1 ) terminates with TAG while the remainder terminates with TAA. Additionally, the codon distributions of the 13 PCGs revealed that Ile and Leu2 are the most frequently used codon families and codons CGG, CGC, CCG, CAG, and AGG are absent. The 431 bp AT-rich region includes the motif ATAGA followed by a 23 bp poly-T stretch, short tandem repeats (STRs) of TC and TA, two copies of a 28 bp repeat 'ATTAAATTAATAAATTAA TATATTAATA' and a poly-A element. Phylogenetic analyses within Sphingidae confirmed that T. japonica belongs to the Macroglossinae and showed that the phylogenetic relationship of T. japonica is closer to Ampelophaga rubiginosa than Daphnis nerii . Phylogenetic analyses within Theretra demonstrate that T. japonica , T. jugurtha , T. suffusa , and T. capensis are clustered into one clade.

Poor early urinary outcomes after laparoscopy were reported in studies comparing laparoscopic versus open rectal cancer surgery. One possible explanation was that these studies might include a number of patients on the laparoscopic surgeons' learning curve. This study aims to evaluate whether the learning curve of laparoscopic rectal cancer surgery influences early postoperative urinary dysfunction. Between September 2009 and December 2014, 208 consecutive patients undergoing laparoscopic rectal resection for rectal cancer were enrolled in the present study. All the clinical data were obtained from a prospectively compiled database. The primary outcomes were the incidences of postoperative urinary retention (POUR) and major urinary dysfunction requiring long-term urinary catheterization. POUR and major urinary dysfunction rate were 20.2 per cent (42/208) and 4.3 per cent (9/208), respectively. The learning curve analysis for operative time using the moving average method showed stabilization at 80 cases. Surgeon experience was divided into two periods: learning curve period (1-80 cases) and experienced period (81-208 cases). Multivariate analysis showed that older age (OR = 3.250, P = 0.006) and learning curve (OR = 2.241, P = 0.024) were independent risk factors for POUR. Learning curve was not significantly associated with increased rates of major urinary dysfunction (OR = 3.378, P = 0.092). Learning curve is a significant risk factor for increased rate of POUR after laparoscopic rectal cancer surgery. Technical training may be key to shorten the learning curve and limit its impact on the postoperative urinary complications.

Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6.1/K-ATP) channel switched microglia from the detrimental M1 phenotype toward the beneficial M2 phenotype. Kir6.1 knockdown inhibited M2 polarization and simultaneously exaggerated M1 microglial inflammatory responses, while Kir6.1 overexpression promoted M2 polarization and synchronously alleviated the toxic phase of M1 microglia polarization. Furthermore, we observed that the Kir6.1 deficiency dramatically exacerbated dopaminergic neuron death companied by microglia activation in mouse model of PD. Mechanistically, Kir6.1 deficiency enhanced the activation of p38 MAPK-NF-κB pathway and increased the ratio of M1/M2 markers in the substantia nigra compacta of mouse model of PD. Suppression of p38 MAPK in vivo partially rescued the deleterious effects of Kir6.1 ablation on microglia phenotype and dopaminergic neuron death. Collectively, our findings reveal that Kir6.1/K-ATP channel modulates microglia phenotypes transition via inhibition of p38 MAPK-NF-κB signaling pathway and Kir6.1/K-ATP channel may be a promising therapeutic target for PD.

Caspase family has been recognized to be involved in dopaminergic (DA) neuronal death and to exert an unfavorable role in Parkinson's disease (PD) pathology. Our previous study has revealed that caspase-1, as an important component of NLRP3 inflammasome, induces microglia-mediated neuroinflammation in the pathogenesis of PD. However, the role of caspase-1 in DA neuronal degeneration in the onset of PD remains unclear. Here, we showed that caspase-1 knockout ameliorated DA neuronal loss and dyskinesia in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model mice. We further found that caspase-1 knockout decreased MPTP/p-induced caspase-7 cleavage, subsequently inhibited nuclear translocation of poly (ADP-ribose) polymerase 1 (PARP1), and reduced the release of apoptosis-inducing factor (AIF). Consistently, we demonstrated that caspase-1 inhibitor suppressed caspase-7/PARP1/AIF-mediated apoptosis pathway by 1-methyl-4-phenylpyridinium ion (MPP + ) stimulation in SH-SY5Y cells. Caspase-7 overexpression reduced the protective effects of caspase-1 inhibitor on SH-SY5Y cell apoptosis. Collectively, our results have revealed that caspase-1 regulates DA neuronal death in the pathogenesis of PD in mice via caspase-7/PARP1/AIF pathway. These findings will shed new insight into the potential of caspase-1 as a target for PD therapy.

α-Synuclein (α-syn) has been recognized to induce neuroinflammation and to disturb nerve repair process in Parkinson's disease. However, the potential mechanisms underlying α-syn-induced impairment of adult neurogenesis remain unclear. In the present study, A53T mutant α--synuclein transgenic (A53T tg/tg ) mice, caspase-1 knockout mice, and A53T tg/tg ;caspase-1 -/- double transgenic mice were used to prepare adult neural stem cells (ANSCs) and to investigate inflammasome-related mechanism for α-syn-impaired neurogenesis in mouse subventricular zone (SVZ). We showed that α-syn inhibited neurogenesis in the SVZ of A53T tg/tg mice and impaired proliferation and differentiation in ANSCs cultured in vitro, accompanied by reduced microRNA-7 (miR-7) expression levels. We further found that ANSC expressed NLRP3-containing inflammasome and α-syn activated both TLR4/NF-κB and NLRP3/caspase-1 signals in ANSCs. Either Nlrp3 knockdown or Caspase-1 knockout could attenuate the inhibition of proliferation in ANSCs induced by α-syn. Furthermore, we demonstrated that miR-7 post-transcriptionally controlled Nlrp3 expression besides targeting α-syn. Most notably, stereotactic injection of miR-7 mimics into lateral ventricles significantly inhibited NLRP3 inflammasome activation and improved adult neurogenesis in mouse SVZ. Our study provides a direct link between NLRP3 inflammasome activation and α-syn-impaired neurogenesis in the pathogenesis of α-synucleinopathies.

Aim: Atp13a2 (Park9) gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2), and its missense or truncation mutations leads to lysosomal dysfunction and consequently results in neuronal death in the pathogenesis of Parkinson's disease (PD). Nevertheless, the roles of ATP13A2 in the biological features of astrocytes, especially in the regulation of PD-related neuroinflammation, have not been investigated., Methods: We cultured primary neurons and astrocytes from mouse midbrain to investigate the mechanisms for astrocyte ATP13A2-regulated lysosomal function and neuroinflammation following 1-methyl-4-phenylpyridinium (MPP(+) ) treatment., Results: We found that astrocytes expressed considerable levels of ATP13A2 and deficiency of ATP13A2 in astrocyte-induced intense inflammation, which exacerbated dopaminergic neuron damage after exposure to MPP(+) . Notably, lack of ATP13A2 increased lysosomal membrane permeabilization and cathepsin B release, which in turn exacerbated activation of nod-like receptor protein 3 (NLRP3) inflammasome to produce excess IL-1β from astrocytes. Furthermore, overexpression of ATP13A2 reversed MPP(+) -induced cathepsin B release and NLRP3 inflammasome activation in astrocytes., Conclusions: Our results have revealed a novel role of ATP13A2 in modulating astrocyte-mediated neuroinflammation via NLRP3 inflammasome activation, thus bringing to light of a direct link between astrocyte lysosome and neuroinflammation in the pathological model of PD., (© 2016 John Wiley & Sons Ltd.)

The ectonucleotidase CD39 is pivotal in the conversion of immunostimulatory adenosine triphosphate (ATP) into immunosuppressive adenosine which potently inhibits host immune responses against cancer. This study investigated the expression level and prognostic significance of CD39 in human rectal adenocarcinoma. Our data demonstrated that CD39 staining strongly marked malignant epithelial cells where the protein and messenger RNA (mRNA) expression levels of CD39 were significantly increased compared with paracancerous controls. In addition to primary tumors, CD39 was also abundantly expressed in liver metastases and tumor-draining lymph nodes from metastatic rectal adenocarcinoma. Although patients with higher CD39 density in tumor cells were more likely to have favorable characteristics (early TNM and N stages) and overall survival, the singular parameter cannot be used as an independent factor for predicting patients' prognosis. Intriguingly, combined analysis of CD39 and CD73 expression was more efficient to foretell patient's outcome where patients with increased CD73 but decreased CD39 levels displayed a worst prognosis. Taken together, the current study revealed that malignant epithelial cells of human rectal adenocarcinoma strongly express CD39 that may play a potential role in the tumor invasion and metastasis. Although high expression of CD39 in tumor cells is correlated with favorable clinical outcome, the combination of CD39 and CD73 expression may have a better prognostic value.

Purpose: Retinal dopamine has been long implicated in the signaling pathway regulating eye growth, as evidenced by its reduced levels in myopic eyes in various species. We examined whether and how retinal dopamine levels were changed in a C57BL/6 mouse model of experimental myopia., Methods: Form-deprivation myopia (FDM) was induced in C57BL/6 mice by wearing monocular occluder for 4 weeks. Refractive errors were measured using an infrared photorefractor. Retinal dopamine/DOPAC and vitreal DOPAC levels were assessed by high-performance liquid chromatography (HPLC). Extracellular dopamine concentrations were examined by Western blot analysis of dopamine transporter (DAT) expression levels. The intactness of retinal dopaminergic system was evaluated by counting tyrosine hydroxylase (TH) immunoreactive cells, measuring the areas occupied by processes of these cells, and quantifying retinal TH expression at both protein and transcription levels., Results: Form-deprivation myopia was successfully induced in C57BL/6 mice with the refractive status of deprived eyes being significantly different from fellow eyes. Unlike most of the previous results obtained in other myopic animal models, however, no significant changes in retinal dopamine, DOPAC, DAT, and vitreal DOPAC levels were detected in deprived eyes, either in the daytime or at night. Furthermore, neither the number of dopaminergic amacrine cells, the area size occupied by the processes of these cells, nor retinal TH expression, were altered in deprived eyes., Conclusions: The retinal dopamine system remains intact in C57BL/6 mice with FDM, and retinal dopamine levels are not associated with the development of FDM in this mouse strain., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Background: ATP-sensitive potassium (K-ATP) channels couple cellular metabolism to electric activity. Although Kir6.2-composed K-ATP channel (Kir6.2/K-ATP channel) has been demonstrated to regulate inflammation, a common cause of most liver diseases, its role in liver injury remains elusive., Methods: Kir6.2 knockout mice were used to prepared LPS-induced liver injury model so as to investigate the role of Kir6.2/K-ATP channels in the injury. Histochemistry was applied to evaluate the extent of liver injury. Proinflammatory cytokines were analyzed by ELISA. Endoplasmic reticulum (ER) stress and autophagy were assessed by western blotting., Results: We showed that Kir6.2 knockout markedly promoted the infiltration of lymphocytes and neutrophils in liver and significantly elevated serum levels of alanine transaminase (ALT) in respond to LPS treatment. We further found that Kir6.2 deficiency enhanced the activation of NF-κB and NLRP3 inflammasome following LPS challenge, and thereby increased the levels of pro-inflammatory cytokines IL-1β, IL-18 and TNF-α. Treatment of wild-type mice with the K-ATP channel opener iptakalim (IPT) could protect against LPS-induced liver injury through attenuating NLRP3 inflammasome-mediated inflammatory responses. Furthermore, Kir6.2 knockout-induced activation of NLRP3 inflammasome aggravated endoplasmic reticulum (ER) stress, autophagy and subsequent hepatocyte death., Conclusion: Kir6.2 deficiency exacerbated LPS-induced liver injury by enhancing NLRP3 inflammasome-mediated inflammatory response. Thus, Kir6.2/K-ATP channel may be a potential candidate target for the treatment and prevention of liver injury.

Astrocytes play crucial roles in determining the susceptibility to oxidative stress in the brain, and uncoupling protein 2 (UCP2) has been demonstrated to regulate reactive oxygen species (ROS) production. However, it is unclear whether UCP2 is expressed in astrocytes, and whether it participates in the regulation of astrocytic functions. Here we show that UCP2 knockout exacerbated dopaminergic neuron loss in a murine model of 1,2,3,6-methyl-phenyl-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD), accompanied by overactivation of astrocytes. We further detected expression of UCP2 in primary cultures of mesencephalic astrocytes. UCP2 knockout increased intracellular ROS production and induced oxidative stress in response to l-methyl-4-phenylpyridinium (MPP(+)) treatment. Subsequently, UCP2 deficiency exacerbated endoplasmic reticulum (ER) stress, as evidenced by the upregulations of C/EBP homologous protein (CHOP), cleavage of caspase-12, and aggravated neuroinflammation via the activation of nod-like receptor protein 3 (NLRP3) inflammasomes in astrocytes. Collectively, our study indicates that UCP2 expressed in astrocytes modulates ER stress and neuroinflammation, and is crucial for the survival of dopaminergic neuron in the pathogenesis of PD. These findings gives us insights into the potential of UCP2 as a novel therapeutic avenue for PD treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To evaluate the relationship between alcohol drinking, XRCC1 codon 194 and 399 polymorphisms and risk of colorectal cancer, we conducted a case-control study with 315 colorectal cancer cases (105 colon, 210 rectal) and 439 population-based controls in Jiangsu Province of China. The XRCC1 codon 194 and 399 genotypes were identified using polymerase chain reaction and restrictrion fragment length polymorphism methods (PCR-RFLP). A structured questionnaire was used to elicit detailed information. Odds ratios (ORs) were estimated with an unconditional logistic model. In this study no significant differences were observed among the studied groups with regard to the genotype distribution of the XRCC1 codons 194 and 399 and the risk of colorectal cancer did not appear to be significantly influenced by genotype alone, whereas alcohol consumption showed a positive association (P for trend <0.01). When combined effects of XRCC1 polymorphisms and alcohol consumption were analyzed, we found that the 194Trp or 399Gln alleles further increased the colorectal cancer risk due to high alcohol intake. These findings support the conclusion that colorectal cancer susceptibility may be altered by gene-environment interactions.

Parkinson's disease (PD), one of the most common neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra. Increasing epidemiological evidence has indicated that type 2 diabetes (T2D) may be implicated in the pathogenesis of PD. However, the exact association and the underlying mechanism remain unclear. In the present study, ob/ob and db/db mice, the well accepted T2D models, were acutely treated with MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) to mimic PD-like neural injury. We found that insulin signaling impairment occurred not only in pancreas and livers, but also in the midbrain of ob/ob and db/db mice. Notably, the expressions of monomeric and oligomeric α-synuclein as well as endoplasmic reticulum stress markers (CHOP and GRP78) were significantly upregulated in both pancreas and midbrain of T2D mice, accompanied by the increased activation of NLRP3 inflammasomes to produce excess IL-1β. Furthermore, we found that acute MPTP administration aggravated the loss of dopaminergic neurons and increased the activation of glial cells in the substantia nigra of db/db mice. Collectively, these findings demonstrate that α-synuclein accumulation and neuroinflammation are aggravated in the midbrain of T2D mice and T2D mice are more susceptible to the neurotoxicity induced by MPTP. Our study indicates that metabolic inflammation exacerbates DA neuronal degeneration in the progress of PD, which will provide a novel insight into the etiology of PD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: Although extensive investigation has revealed that an astrocyte-specific protein aquaporin-4 (AQP4) participates in regulating synaptic plasticity and memory, a functional relationship between AQP4 and learning processing has not been clearly established. This study was designed to test our hypothesis that AQP4 modulates the aversive motivation in Morris water maze (MWM)., Methods and Results: Using hidden platform training, we observed that AQP4 KO mice significantly decreased their swimming velocity compared with wild-type (WT) mice. To test for a relationship between velocities and escape motivation, we removed the platform and subjected a new group of mice similar to the session of hidden platform training. We found that KO mice exhibited a gradual reduction in swimming velocity, while WT mice did not alter their velocity. In the subsequent probe trial, KO mice after no platform training significantly decreased their mean velocity compared with those KO mice after hide platform training. However, all of KO mice were not impaired in their ability to locate a visible, cued escape platform., Conclusions: Our findings, along with a previous report that AQP4 regulates memory consolidation, implicate a novel role for this glial protein in modulating the aversive motivation in spatial learning paradigm., (© 2013 John Wiley & Sons Ltd.)

Aim: To assess midterm results of stapled transanal rectal resection (STARR) for obstructed defecation syndrome (ODS) and predictive factors for outcome., Methods: From May 2007 to May 2009, 75 female patients underwent STARR and were included in the present study. Preoperative and postoperative workup consisted of standardized interview and physical examination including proctoscopy, colonoscopy, anorectal manometry, and defecography. Clinical and functional results were assessed by standardized questionnaires for the assessment of constipation constipation scoring system (CSS), Longo's ODS score, and symptom severity score (SSS), incontinence Wexner incontinence score (WS), quality of life Patient Assessment of Constipation-Quality of Life Questionnaire (PAC-QOL), and patient satisfaction visual analog scale (VAS). Data were collected prospectively at baseline, 12 and 30 mo., Results: The median follow-up was 30 mo (range, 30-46 mo). Late postoperative complications occurred in 11 (14.7%) patients. Three of these patients required procedure-related reintervention (one diverticulectomy and two excision of staple granuloma). Although the recurrence rate was 10.7%, constipation scores (CSS, ODS score and SSS) significantly improved after STARR (P < 0.0001). Significant reduction in ODS symptoms was matched by an improvement in the PAC-QOL and VAS (P < 0.0001), and the satisfaction index was excellent in 25 (33.3%) patients, good in 23 (30.7%), fairly good in 14 (18.7%), and poor in 13 (17.3%). Nevertheless, the WS increased after STARR (P = 0.0169). Incontinence was present or deteriorated in 8 (10.7%) patients; 6 (8%) of whom were new onsets. Univariate analysis revealed that the occurrence of fecal incontinence (preoperative, postoperative or new-onset incontinence; P = 0.028, 0.000, and 0.007, respectively) was associated with the success of the operation., Conclusion: STARR is an acceptable procedure for the surgical correction of ODS. However, its impact on symptomatic recurrence and postoperative incontinence may be problematic.

Traditional pesticide residue detection methods are usually complicated, time-consuming, and destructive. Rapid, nondestructive, online real-time is the development direction of the pesticide testing. In the present paper, we use surface enhanced Raman spectroscopy (SERS) technique to detect the organophosphorus pesticide residue of phorate and fenthion on apple to investigate a fast, nondestructive detection method for the pesticide of phorate and tiguron on apples. The results show that the characteristic frequencies of the two organophosphorus pesticides are easier to identify using surface-enhanced Raman spectroscopy. We select Raman signal at 728 cm(-1) for phorate and that at 1 512 cm(-1) for fenthion as target peak for quantitative analysis, and use an internal standard to establish phorate and fenthion linear regression model. This method can be used as a quantitative analysis reference of phorate and fenthion.

Background and Purpose: ATP-sensitive potassium (K-ATP) channels couple energy metabolism with electric activity, which play important roles in brain diseases including stroke. However, the impacts of Kir6.1-containing K-ATP channels that mainly expressed on glia in stroke remain unclear., Methods and Results: In this study, we found that expression of Kir6.1 was significantly decreased in the ischemic brain area of C57BL/6J mice after 1-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. Then, we subjected Kir6.1 heterozygote knockout (Kir6.1(+/-) ) mice to cerebral ischemia/reperfusion (I/R) injury and found that Kir6.1(+/-) mice exhibited exacerbated neurological disorder and enlarged infarct size, companied by glial over-activation and blood-brain barrier (BBB) damages. Furthermore, we showed that Kir6.1 knockdown aggravated endoplasmic reticulum (ER) stress and thereby increased the levels of proinflammatory factors tumor necrosis factor-α and interleukin-1β (TNF-α and IL-1β) in mouse brain., Conclusions: Our findings reveal that Kir6.1 knockdown exacerbates cerebral I/R-induced brain damages via increasing ER stress and inflammatory response, indicating that Kir6.1-containing K-ATP channels may be a potential therapeutic target for stroke., (© 2013 John Wiley & Sons Ltd.)

Objective: To investigate the perioperative and postoperative long-term complications of procedure for prolapse and hemorrhoids(PPH) for the treatment of circular internal hemorrhoids and circular mixed hemorrhoids., Methods: A retrospective study was performed in 2152 patients with circular internal hemorrhoids and circular mixed hemorrhoids eligible for PPH from January 2002 to December 2011. The perioperative and postoperative long-term complications were recorded and assessed., Results: The median length of follow-up was 73 months. Perioperative complications and adverse events were reported including acute urinary retention(n=360, 16.7%) which was managed by temporary cathether indwelling, anastomotic bleeding(n=45, 2.1%) managed by surgical or endoscopic procedures, chronic anoperineal sustained pain(n=30, 1.4%) managed by local treatment or stapler removal, and thrombosed external hemorrhoid(n=28, 1.2%) managed by conservative treatment or resection. Long-term postoperative complications were reported including mild fecal incontinence(n=112, 6.3%), postoperative recurrence(n=82, 4.6%), anal distention and defecatory urgency(n=50, 2.8%), anastomotic stenosis(n=4, 0.2%). Postoperative recurrence developed in 82 patients(4.6%), 28 of whom were managed by repeat PPH and 54 by conservative treatment., Conclusion: PPH appears to be a safe technique for patients with circular internal hemorrhoids and circular mixed hemorrhoids.

We cloned the complete coding sequences of porcine Gpr3, Gpr6, and Gpr12 genes. Further, on the basis of their high levels of sequence similarity, these genes are identified as a subfamily of G protein-coupled receptors. These putative protein sequences also showed high sequence identity with other mammalian orthologs, including several highly conserved motifs. A wide expression of the Gpr3 gene in pigs was observed through tissue distribution analysis by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR, specially in the brain, pituitary, fat, liver and oocyte, where its strong expression was observed. The Gpr3 gene was found to be located on chromosome 6 and a single exon coded for the entire open-reading frame. Expression of porcine Gpr3 in HEK293 cells resulted in constitutive activation of adenylate cyclase (AC) similar in amplitude to that produced by fully stimulated G(s)-coupled receptors. Moreover, sphingosine 1-phosphate (S1P) could increase AC activation via the constitutively active Gpr3 receptor. When a Gpr3-green fluorescent protein (GFP) construct was expressed in HEK293 cells, GFP-labeled Gpr3 protein was shown to be localized in the plasmalemma and subcellular membranes. After S1P treatment, agonist-mediated internalization could be visualized by confocal microscopy. In short, our findings suggest the porcine Gpr3, Gpr6, and Gpr12 genes as a subfamily of G protein-coupled receptors, and porcine Gpr3 was a constitutively active G protein-coupled receptor. Constitutive activation of AC and agonist-mediated internalization of Gpr3 receptor could be modulated by the S1P, suggesting that S1P might act as an activator for porcine Gpr3 receptor.

Aims: The present study was to understand whether early adult depressive females implicated their offspring., Methods: Seven-week-old female mice were subject to chronic mild stress (CMS) to establish the animal model of depression. The behavioral performance of their offspring were tested via neonatal reflexes tests, hole-board test, and morris water maze test in different ages. Astrocyte number, hippocampal volume, and neurogenesis were analyzed via immunohistochemical blotting. Glucocorticoid receptor (GR) expression and serum cortisol levels were measured by western blotting and ELISA., Results: Female depressive mice had normal fertility, but their offspring had lowered neonatal survival rate and body weight from neonatal period to early adulthood. The offspring of female depressive mice exhibited the impairments of neonatal reflex attainment and memory, but had higher emotionality as adults. Furthermore, the astrocyte number, hippocampal volume, and neurogenesis were reduced in the offspring. However, the expressions of GR were increased in the hippocampus of offspring., Conclusion: This study reveals that female early adult depressive mice have normal reproductive ability, but make long-term detrimental impacts on the behavioral performance and brain development of their offspring., (© 2012 Blackwell Publishing Ltd.)

Surface enhanced Raman spectroscopy (SERS) has shown the advantage of detecting low concentration biofluids presently. Saliva SERS of 21 lung cancer patients and 22 normal people were measured and differentiated in the present paper. Intensities of most peaks of lung cancer patients are weaker than that of normal people, while some stronger but with a small change rate. Those peaks were assigned to proteins and nucleic acids which indicate a corresponding decrease of those substances in saliva. Principal component analysis (PCA) and linear discriminant analysis (LDA) were used to deduce and discriminate the two groups of data, resulting in accuracy, sensitivity, and specificity being 84%, 94%, and 81%, respectively.