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Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.
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Trastorno Depresivo Mayor , Humanos , Encéfalo/diagnóstico por imagen , Corteza Prefrontal , Función Ejecutiva , Lóbulo Frontal , Imagen por Resonancia Magnética , Mapeo EncefálicoRESUMEN
Eight Gram-negative, aerobic, motile with paired polar flagella and rod-shaped bacteria were isolated from six tobacco fields in Yunnan, PR China. 16S rRNA gene sequence analysis revealed that all the strains belonged to the genus Ralstonia. Among them, strain 22TCCZM03-6 had an identical 16S rRNA sequence to that of R. wenshanensis 56D2T, and the other strains were closely related to R. pickettii DSM 6297T (98.3499.86%), R. wenshanensis 56D2T (98.7099.64%), and R. insidiosa CCUG 46789T (97.3498.56%). Genome sequencing yielded sizes ranging from 5.17 to 5.72 Mb, with overall G + C contents of 63.364.1%. Pairwise genome comparisons showed that strain 22TCCZM03-6 shared average nucleotide identity (ANI) and digital DNADNA hybridization (dDDH) values above the species cut-off with R. wenshanensis 56D2T, suggesting that strain 22TCCZM03-6 is a special strain of the R. wenshanensis. Five strains, including 21MJYT02-10T, 21LDWP02-16, 22TCJT01-1, 22TCCZM01-4, and 22TCJT01-2, had ANI values >95% and dDDH values >70% when compared with each other. These five strains had ANI values of 73.3294.17% and dDDH of 22.055.20% with the type strains of the genus Ralstonia individually, supporting these five strains as a novel species in the genus Ralstonia. In addition, strains 21YRMH01-3T and 21MJYT02-11T represent two independent species. They both had ANI and dDDH values below the thresholds for species delineation when compared with the type species of the genus Ralstonia. In strains 21YRMH01-3T and 21MJYT02-10T, the main fatty acids were summed features 3, 8, and C16:0; however, strain 21MJYT02-11T contained C16:0, cyclo-C17:0, and summed features 3 as major fatty acids. The main polar lipids, including diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine, were identified from strains 21YRMH01-3T, 21MJYT02-10T, and 21MJYT02-11T. The ubiquinones Q-7 and Q-8 were also detected in these strains, with Q-8 being the predominant quinone. Based on the above data, we propose that the eight strains represent one known species and three novel species in the genus Ralstonia, for which the names Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov. are proposed. The type strains are 21YRMH01-3T (=GDMCC 1.3534T = JCM 35818T), 21MJYT02-10T (=GDMCC 1.3531T = JCM 35816T), and 21MJYT02-11T (=GDMCC 1.3532T = JCM 35817T), respectively.
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The theory of knowledge, attitude and practice (KAP) can well explain the whole process of pregnant females' practice to obtain balanced nutrition. However, the process of KAP works very differently in populations with different sociodemography. This study aims to investigate the sociodemographic determinants associated with pregnant females' nutritional KAP and find a way to locate the vulnerable pregnant females who would benefit most from intervention. A cross-sectional survey was conducted on pregnant females' KAP regarding food nutrition at the University of Chinese Academy of Science Shenzhen Hospital from December 2020 to February 2021. A total of 310 pregnant females aged 18-40 years were interviewed. And we assessed the influence of sociodemographic factors on KAP and built a model for screening the vulnerable group who would benefit most from intervention. The results showed that on nutritional knowledge and practice, only 15.2% and 47.3% were above 0.6 respectively, while 91% were above 0.75 on attitude. Age, Husband's Education Degree, Monthly Income of Family, Nutritional Knowledge and Nutritional Attitude were statistically significant predictors of the vulnerable group. There was a gap between knowledge (3.8% were good or above) and attitude (91% were good or above), attitude and practice (16.8% were good or above). Age, household registry, education level, monthly income, and nutrition knowledge were associated with nutrition practices. This study highlights that nutritional education interventions targeting certain populations may improve the conversion rate of nutrition practices, and presents a predictive model to locate the vulnerable group.
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Renal fibrosis is a common pathological outcome of various chronic kidney diseases, and as yet, there is no specific treatment. Dapagliflozin has shown renal protection in some clinical trials as a glucose-lowering drug, but its role and mechanism on renal fibrosis remain unclear. In this study, we used a 0.2% adenine diet-induced renal fibrosis mouse model to investigate whether dapagliflozin could protect renal function and alleviate renal fibrosis in this animal model. In vivo, we found that dapagliflozin's protective effect on renal fibrosis was associated with 1) sustaining mitochondrial integrity and respiratory chain complex expression, maintained the amount of mitochondria; 2) improving fatty acid oxidation level with increased expression of CPT1-α, PPAR-α, ACOX1, and ACOX2; 3) reducing inflammation and oxidative stress, likely via regulation of IL-1ß, IL-6, TNF-α, MCP-1, cxcl-1 expression, and glutathione (GSH) activity, superoxide dismutase (SOD) and malondialdehyde (MDA) levels; and 4) inhibiting the activation of the TGF-ß1/MAPK pathway. In HK2 cells treated with TGF-ß1, dapagliflozin reduced the expression of FN and α-SMA, improved mitochondrial respiratory chain complex expression, and inhibited activation of the TGF-ß1/MAPK pathway.
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Three Gram-stain-negative, motile, with amphilophotrichous flagella, and rod-shaped bacteria (LJ1, LJ2T and LJ3) were isolated from lower leaves with black spots on flue-cured tobacco in Yunnan, PR China. The results of phylogenetic analysis based on 16S rRNA gene sequences indicate that all the strains from tobacco were closely related to the type strains of the Pseudomonas syringae group within the P. fluorescens lineage and LJ2T has the highest sequence identities with P. cichorii DSM 50259T (99.92â%), P. capsici Pc19-1T (99.67â%) and P. ovata F51T (98.94â%) . The 16S rRNA gene sequence identities between LJ2T and other members of the genus Pseudomonas were below 98.50%. The average nucleotide identity by blast (ANIb) values between LJ2T and P. cichorii DSM 50259T, P. capsici Pc19-1T and P. ovata F51T were less than 95â%, and the in silico DNA-DNA hybridization (isDDH) values (yielded by formula 2) were less than 70â%. The major fatty acids were C16ââ:ââ1ω7c and/or C16ââ:ââ1ω6c (summed feature 3), C16ââ:ââ0 and C18ââ:ââ1ω7c and/or C18ââ:ââ1ω6c (summed feature 8). The polar lipids profile of LJ2T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified phospholipids and one unidentified glycolipid. The predominant respiratory quinone was Q-9. The DNA G+C content of LJ2T was 58.4 mol%. On the basis of these data, we concluded that LJ2T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas lijiangensis sp. nov. is proposed. The type strain of Pseudomonas lijiangensis sp. nov. is LJ2T (=CCTCC AB 2021465T=GDMCC 1.2884T=JCM 35177T).
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Fosfatidiletanolaminas , Pseudomonas , ARN Ribosómico 16S/genética , Filogenia , Composición de Base , Nicotiana , ADN Bacteriano/genética , Cardiolipinas , Técnicas de Tipificación Bacteriana , Ácidos Grasos/química , Genes Bacterianos , Análisis de Secuencia de ADN , China , Fosfolípidos , Fosfatidilcolinas , Glucolípidos , Quinonas , NucleótidosRESUMEN
BACKGROUND: Cognitive impairments are core characteristics of schizophrenia, but are largely resistant to current treatments. Several recent studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dor-solateral prefrontal cortex (DLPFC) can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients. However, results are inconsistent across studies. AIM: To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia. METHODS: Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC (n = 25) or sham stimulation (n = 22) on weekdays for four consecutive weeks. Patients performed the pattern recognition memory (PRM) task from the Cambridge Neuropsychological Test Automated Battery at baseline, at the end of rTMS treatment (week 4), and 4 wk after rTMS treatment (week 8). Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: There were no significant differences in PRM performance metrics, SANS total score, SANS subscores, PANSS total score, and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period, but PRM performance metrics (percent correct and number correct) and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group (all P < 0.05). Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment. Moreover, the improvement in visual memory was correlated with the reduction in negative symptoms at week 8. In contrast, there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8 (all P > 0.05). CONCLUSION: High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia, but these effects are delayed, potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.
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BACKGROUND: The COVID-19 pandemic is associated with an increased risk of mental health problems including suicide in many subpopulations, but its influence on stable patients with major depressive disorder (MDD) has been studied fleetingly. This study examined the one-year prevalence of suicidality including suicidal ideation (SI), suicide plans (SP), and suicide attempts (SA) as well as their correlates in clinically stable MDD patients during the COVID-19 pandemic. METHODS: A cross-sectional, observational study was conducted between October 1, 2020, and October 15, 2021, in six tertiary psychiatric hospitals. Socio-demographic information, clinical data and one-year prevalence of suicidality were recorded. RESULTS: Altogether, 1718 participants who met the eligibility criteria were included. The overall one-year prevalence of suicidality during the COVID-19 pandemic was 68.04% (95% confidence intervals (CI) =65.84-70.25%), with one-year SI prevalence of 66.4% (95%CI = 64.18-68.65%), SP prevalence of 36.26% (95%CI = 33.99-38.54%), and SA prevalence of 39.35% (95%CI = 37.04-41.66%). Binary logistic regression analyses revealed male gender, married marital status, college education level and above and age were negatively associated with risk of suicidality. Urban residence, unemployed work status, experiences of cyberbullying, a history of suicide among family members or friends, and more severe fatigue, physical pain, and residual depressive symptoms were positively associated with risk of suicidality. CONCLUSIONS: Suicidality is common among clinically stable MDD patients during the COVID-19 pandemic. Regular suicide screening and preventive measures should be provided to clinically stable MDD patients during the pandemic.
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COVID-19 , Trastorno Depresivo Mayor , Suicidio , Estudios Transversales , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Humanos , Masculino , Pandemias , Prevalencia , Factores de Riesgo , Ideación SuicidaRESUMEN
PURPOSE: This study aimed to investigate the latent Epstein-Barr virus (EBV) infection status of patients with newly diagnosed Hodgkin lymphoma (HL) and to discuss the relationship between tumor cell EBV status and the prognosis of HL patients. PATIENTS AND METHODS: A total of 134 previously untreated HL patients were analyzed in the study. Epstein-Barr virus encoded RNAs (EBERs) in situ hybridization was performed to detect the EBV status of tumor cells. RESULTS: EBV positive status correlated with sex (p=0.046) and the proportion of extranodal lesions(p=0.037). There was no obvious correlation between EBV status and overall survival (OS) or failure-free survival (FFS) in all cases, but in cases over 50 years old, EBV positive group had an inferior 5-year FFS compared with EBV negative group (38.5%±13.5% vs 90.9%±8.7%, p=0.012). In FFS multivariate analysis of this age subgroup, EBV positive status was associated with significantly inferior survival (HR, 10.10; 95% CI, 1.26-81.08; p=0.030). CONCLUSION: This study demonstrates positive tumor cell EBV status is an unfavorable prognostic factor in elder HL patients.
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Infecciones por Virus de Epstein-Barr/mortalidad , Herpesvirus Humano 4/fisiología , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/mortalidad , Latencia del Virus , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Supervivencia sin Enfermedad , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/terapia , Femenino , Enfermedad de Hodgkin/terapia , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To investigate the predictive value of methyltransferase EZH2 expression level on the clinical efficacy and long-term prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). METHODS: 161 patients with newly treated PGI-DLBCL in our hospital from August 2013 to July 2019 were selected. The expression level of EZH2 protein was detected by immunohistochemistry, and the short-term efficacy and long-term survival differences of patients with different levels of EZH2 were compared. The predictive values of EZH2 expression level on the short-term efficacy and long-term prognosis of PGI-DLBCL patients were analyzed by Log-rank test and COX risk proportional regression model. Chi-square test and Logistic regression analysis were used to analyze the influencing factors of EZH2 expression level. RESULTS: The complete response (CR) and overal response(OR) rates of those with high EZH2 expression were significantly lower than those with low EZH2 expression (P<0.001). The median OS and PFS of EZH2 high-level and low-level expression group was 37, 31 months and 49, 42 months, respectively. The cumulative OS and PFS rates of the high-level expression group were significantly lower than those of the low-level expression group, and the differences were statistically significant (P<0.05). The high expression levels of H3K27me3, EZH2, BCL-2, BCL-6, c-MYC were closely related to the shortening of OS and PFS, while the high expression level of Ki-67 was closely related to the shortening of OS (P<0.05), of which the high expression levels of H3K27me3, EZH2, BCL-2, and BCL-6 were independent risk factors for shortening of OS and PFS. The expression level of EZH2 was positively correlated with the expression level of H3K27me3, BCL-6, c-MYC and Ki-67 (r=0.741, r=0.837, r=0.809, r=0.772), and the high expression levels of H3K27me3, BCL-6 and Ki-67 were independent factors influencing the high expression of EZH2. CONCLUSION: In patients with PGI-DLBCL, the high expression of EZH2 significantly reduces the short-term CR and OR rates, which is an independent risk factor for the shortening of long-term OS and PFS rates, and it is independently related to the high expression of H3K27me3 and BCL6.
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Linfoma de Células B Grandes Difuso , Proteína Potenciadora del Homólogo Zeste 2 , Humanos , Inmunohistoquímica , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
RATIONALE: SNX10 (sorting nexin 10) has been reported to play a critical role in regulating macrophage function and lipid metabolism. OBJECTIVE: To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms. METHODS AND RESULTS: SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE-/- (apolipoprotein E) background and atherogenesis (high-cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE-/- mice. Myeloid cell-specific SNX10 deficiency (Δ knockout [KO]) attenuated atherosclerosis progression in APOE-/- mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of ΔKO mice. In vitro experiments showed that SNX10 deficiency-inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT (protein kinase B). The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB (transcription factor EB), thereby enhanced lysosomal biogenesis and LAL (lysosomal acid lipase) activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype. CONCLUSIONS: Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.
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Enfermedades de la Aorta/metabolismo , Aterosclerosis/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Reprogramación Celular/fisiología , Macrófagos/fisiología , Nexinas de Clasificación/fisiología , Animales , Apolipoproteínas E/genética , Aterosclerosis/sangre , Aterosclerosis/patología , Antígenos CD36/metabolismo , Núcleo Celular/metabolismo , Progresión de la Enfermedad , Ácidos Grasos no Esterificados/metabolismo , Células Espumosas/citología , Humanos , Lisosomas/fisiología , Macrófagos/citología , Ratones , Mitocondrias/metabolismo , Monocitos/citología , Oxidación-Reducción , Proteínas Proto-Oncogénicas c-akt/metabolismo , Nexinas de Clasificación/deficiencia , Nexinas de Clasificación/genética , Esterol Esterasa/metabolismoRESUMEN
Detecting plant-derived signal molecules using fluorescent probes is a key topic and a huge challenge for scientists. Salicylic acid (SA), a vital plant-derived defense hormone, can activate global transcriptional reprogramming to systemically express a network of prominent pathogenesis-related proteins against invasive microorganisms. This strategy is called systemic acquired resistance (SAR). Therefore, monitoring the dynamic fluctuations of SA in subcellular microenvironments can advance our understanding of different physiological and pathological functions during the SA-induced SAR mechanism, thus benefiting the discovery and development of novel immune activators that contribute to crop protection. Here, detection of signaling molecule SA in plant callus tissues was first reported and conducted by a simple non-fluorescent rhodamine-tagged architecture bearing a flexible 2-amino-N,N-dimethylacetamide pattern. This study can markedly advance and promote the usage of fluorescent SA probes for distinguishing SA in the plant kingdom.
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Células/química , Imagen Óptica/métodos , Reguladores del Crecimiento de las Plantas/análisis , Ácido Salicílico/análisis , Línea Celular , Células/inmunología , Colorantes Fluorescentes/química , Humanos , Imagen Óptica/instrumentación , Reguladores del Crecimiento de las Plantas/inmunología , Plantas/química , Plantas/inmunología , Rodaminas/química , Ácido Salicílico/inmunologíaRESUMEN
Distinguishing b- and y-ions is essential to compute amino acid sequences from either N- or C-terminus in mass spectrometry. We described herein a solvent free and real time on-plate derivatization approach that can tag N-terminus of peptides at microliter level with p-chlorobenzaldehyde or 2-hydroxy-5-methylisophthalaldehyde for matrix assisted laser desorption ionization mass spectrometry (MALDI MS). Less than 1 µL of sample solutions can be directly mixed with equal volumes of p-chlorobenzaldehyde or 2-hydroxy-5-methylisophthalaldehyde and α-cyano-4-hydroxycinnamic acid (CHCA), a matrix compound to co-crystalize with analytes for efficient absorption of laser energy and peptide ionization. When the mixture spotted on the sample plate is irradiated with the 3rd harmonic (355 nm) of Nd3+:YAG laser pulses (3 ns width), N-terminal amine groups of peptides instantly react with carbonyl groups of chlorobenzaldehyde or 2-hydroxy-5-methylisophthalaldehyde. Resultant peptides carrying with on-plate formed azomethine group (-CN-) are simultaneously protonated and isolated as precursor ions for subsequent collision-activated dissociation. The mass shift with unique Cl isotopic signature unambiguously distinguishes b ions from y ions and other ions. This method does not need extensive sample preparation and is useful for those samples with limited quantities down to sub-picomole level in sub-microliter volumes. The efficiency was demonstrated with synthetic peptides and tryptic peptides of model proteins. It was found that 2-hydroxy-5-methylisophthalaldehyde provides improved yield for peptides containing lysine residues. Unknown proteins of human saliva and bovine milk as well as phosphopeptides have been identified.
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Rayos Láser , Péptidos/química , Análisis de Secuencia de Proteína , Secuencia de Aminoácidos , Espectrometría de Masas , Estructura Molecular , Factores de TiempoRESUMEN
BACKGROUND: Previous studies presented controversies in impact of body mass index (BMI) on perioperative complications in pancreatectomy, and mainly focused on Western population. This study aimed to explore the impact of BMI on perioperative outcomes in Chinese patients undergoing pancreaticoduodenectomy. METHODS: Seven hundred and seven adult patients undergoing open pancreaticoduodenectomy between January 2005 and December 2016 at Ruijin Hospital were studied retrospectively and categorized as obese (BMI ≥25 kg/m2), overweight (BMI ≥23 kg/m2 and <25 kg/m2), or normal weight (BMI ≥18.5 kg/m2 and <23 kg/m2). Associations of these BMI groups with perioperative outcomes were evaluated. RESULTS: The overweight and obese groups experienced higher risk of clinically related postoperative pancreatic fistula (CR-POPF) (7.6% vs. 9.9% vs. 17.6%, P = 0.002) and re-operation (1.1% vs. 2.5% vs. 5.1%, P = 0.017), and longer systemic inflammation response syndrome (SIRS) duration [2 (1-9) d vs. 2 (1-7) d vs. 3 (1-10) d, P = 0.003] and postoperative hospital stay [19 (2-84) d vs. 19 (7-158) d vs. 23 (8-121) d, P = 0.023] than the normal weight group did. The multiple logistic regression models showed obese as an independent risk factor for CR-POPF (P = 0.013). The multiple linear regression analysis confirmed BMI as a predictor for prolonged postoperative hospital stay (P = 0.005). CONCLUSIONS: Higher BMI results in higher morbidity of Chinese patients undergoing open pancreaticoduodenectomy. Pancreaticoduodenectomy is still a safe surgery procedure for overweight and obese patients, with intensive perioperative management.
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Índice de Masa Corporal , Tiempo de Internación , Obesidad/complicaciones , Fístula Pancreática/etiología , Pancreaticoduodenectomía/efectos adversos , Anciano , China , Femenino , Humanos , Peso Corporal Ideal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Síndrome de Respuesta Inflamatoria Sistémica/etiologíaRESUMEN
BACKGROUND: Primary liver cancer includes three subtypes: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and combined hepatocellular carcinoma. Patients with primary liver cancer experienced poor prognosis and high mortality, so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer. Prostate-specific membrane antigen (PSMA) expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently, but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited. AIM: To study the expression of PSMA in HCC, CCA, and liver cirrhosis. METHODS: A total of 446 formalin-fixed paraffin-embedded (FFPE) liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital. Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens (213 HCC, 203 CCA, and 30 liver cirrhosis). The tumor compartment and the associated neovascular endothelium were separately analyzed. PSMA expression was examined by two certified pathologists, and the final results were presented in a 4-point scoring system (0-3 points). Correlation between PSMA expression and clinicopathological information was also assessed. RESULTS: PSMA was expressed primarily in the neovascular endothelium associated with tumors. The positive rate of PSMA staining in HCC was significantly higher than that in CCA (86.8% vs 79.3%; P = 0.001) but was only 6.6% in liver cirrhosis (P = 0.000). HCC cases had more 3-score PSMA staining than CCA had (89/213, 41.8% vs 35/203, 17.2%; P = 0.001). PSMA expression correlated positively with the stage and grade of HCC and CCA. In both liver cancer subtypes, there were more PSMA+ cases in stages III-V diseases than in stages I and II. High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage. There was no significant association of PSMA expression with sex, age, region, α-fetoprotein, hepatitis B surface antigen, or tumor size in both tumor subtypes. CONCLUSION: Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Conductos Biliares Intrahepáticos , Humanos , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Próstata , Estudios RetrospectivosRESUMEN
INTRODUCTION: Kluyvera ascorbata infection is rare, but it has been extensively studied because of its potential to cause a wide range of infections and its ability to transfer the gene encoding for CTX-M-type extended spectrum ß-lactamases (ESBLs) to other Enterobacteriaceae. CASE PRESENTATION: The authors report a case of a 61-year-old Chinese male with a persistent postoperative infection caused by a multidrug-resistant ESBL-producing K. ascorbata. Following antimicrobial susceptibility testing, he was aggressively treated with gentamicin and levofloxacin with a favorable outcome. CONCLUSION: To our knowledge, this is the first case report of a persistent postoperative infection caused by a multidrug-resistant K. ascorbata in the oral and maxillofacial region. The authors suggest that K. ascorbata infection warrants prompt identification and aggressive antibiotic management, given that ESBL-producing K. ascorbata is resistant to penicillins and first-generation to third-generation cephalosporins.
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Dysfunctional glutamate receptors (GluRs) have been implicated in neurological disorders and injuries. Hetero-tetrameric assemblies of different GluR subunits or splicing variants have distinct spatiotemporal expression patterns and pharmacological properties. Mass spectrometric imaging of GluRs-targeted small molecules is important for determining the regional preferences of these compounds. We report herein the development of a mass tag covalently bonded with glutamate or N-methyl-d-aspartate that functions as both an electron acceptor to generate mass spectrometric signals on irradiated (Bi2O3)0.07(CoO)0.03(ZnO)0.9 nanoparticles with the third harmonic (355 nm) of Nd3+:YAG laser and as the core component to target bilobed clamshell-like structures of GluRs. In this approach, different molecules produce the same tag ion. It provides a new avenue for quantitative assessment of spatial densities of different compounds, which cannot be achieved with well-established stable isotope labeling technique due to different ionization efficiency of different compounds. Various coexisting endogenous molecules are also simultaneously detected for investigation of overall physiological changes induced by these compounds. Because semiconductors do not generate background peaks, this method eliminates interferences from organic matrix materials that are used in regular MALDI (matrix assisted laser desorption ionization). The localized ionization provides high spatial resolution that can be down to sub-micrometers.
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Encéfalo/patología , Electrones , Nanopartículas , Receptores de Glutamato/metabolismo , Animales , Encéfalo/metabolismo , Marcaje Isotópico/métodos , Ratones , Nanopartículas/química , Neuroimagen/métodos , Semiconductores , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
Manipulation of biofilm formation in Shewanella is beneficial for application to industrial and environmental biotechnology. BpfA is an adhesin largely responsible for biofilm formation in many Shewanella species. However, the mechanism underlying BpfA production and the resulting biofilm remains vaguely understood. We previously described the finding that BpfA expression is enhanced by DosD, an oxygen-stimulated diguanylate cyclase, under aerobic growth. In the present work, we identify FlrA as a critical transcription regulator of the bpfA operon in Shewanella putrefaciens CN32 by transposon mutagenesis. FlrA acted as a repressor of the operon promoter by binding to two boxes overlapping the -10 and -35 sites recognized by σ70 DosD regulation of the expression of the bpfA operon was mediated by FlrA, and cyclic diguanylic acid (c-di-GMP) abolished FlrA binding to the operon promoter. We also demonstrate that FlhG, an accessory protein for flagellum synthesis, antagonized FlrA repression of the expression of the bpfA operon. Collectively, this work demonstrates that FlrA acts as a central mediator in the signaling pathway from c-di-GMP to BpfA-associated biofilm formation in S. putrefaciens CN32. IMPORTANCE: Motility and biofilm are mutually exclusive lifestyles, shifts between which are under the strict regulation of bacteria attempting to adapt to the fluctuation of diverse environmental conditions. The FlrA protein in many bacteria is known to control motility as a master regulator of flagellum synthesis. This work elucidates its effect on biofilm formation by controlling the expression of the adhesin BpfA in S. putrefaciens CN32 in response to c-di-GMP. Therefore, FlrA plays a dual role in controlling motility and biofilm formation in S. putrefaciens CN32. The cooccurrence of flrA, bpfA, and the FlrA box in the promoter region of the bpfA operon in diverse Shewanella strains suggests that bpfA is a common mechanism that controls biofilm formation in this bacterial species.
Asunto(s)
Adhesinas Bacterianas/genética , Biopelículas/crecimiento & desarrollo , Proteínas Represoras/genética , Shewanella putrefaciens/metabolismo , Transcripción Genética/genética , Adhesinas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Secuencia de Bases , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacología , Flagelos/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Regiones Promotoras Genéticas/genética , Shewanella putrefaciens/genéticaRESUMEN
The aim of this paper is to increase understanding of the relative importance of the input of geographic and local environmental factors on richness and composition of epigaeic steppe beetles (Coleoptera: Carabidae and Tenebrionidae) along a geographic (longitudinal/precipitation) gradient in the Inner Mongolia grassland. Specifically, we evaluate the associations of environmental variables representing climate and environmental heterogeneity with beetle assemblages. Beetles were sampled using pitfall traps at 25 sites scattered across the full geographic extent of the study biome in 2011-2012. We used variance partitioning techniques and multi-model selection based on the Akaike information criterion to assess the relative importance of the spatial and environmental variables on beetle assemblages. Species richness and abundance showed unimodal patterns along the geographic gradient. Together with space, climate variables associated with precipitation, water-energy balance and harshness of climate had strong explanatory power in richness pattern. Abundance pattern showed strongest association with variation in temperature and environmental heterogeneity. Climatic factors associated with temperature and precipitation variables and the interaction between climate with space were able to explain a substantial amount of variation in community structure. In addition, the turnover of species increased significantly as geographic distances increased. We confirmed that spatial and local environmental factors worked together to shape epigaeic beetle communities along the geographic gradient in the Inner Mongolia grassland. Moreover, the climate features, especially precipitation, water-energy balance and temperature, and the interaction between climate with space and environmental heterogeneity appeared to play important roles on controlling richness and abundance, and species compositions of epigaeic beetles.
Asunto(s)
Escarabajos , Pradera , Análisis Espacial , Distribución Animal , Animales , Biodiversidad , China , ClimaRESUMEN
Transforming growth factor-ß (TGF-ß)/Smad signaling has been implicated in connective tissue growth factor (CTGF) expression in vascular smooth muscle cells (VSMC). Reactive oxygen species (ROS) are involved in activation of TGF-ß/Smad signaling. However, detailed mechanisms underlying the process remain unclear. In present study, we demonstrated TGF-ß1 strongly induced CTGF expression, Smad3 activation, NADPH oxidase 4 (Nox4) expression and increased ROS production in primary rat VSMC in vitro. NADPH oxidases inhibitor diphenylene iodonium (DPI) eliminated TGF-ß1-induced CTGF expression and ROS generation. In addition, small-interfering RNA (siRNA) silencing of Smad3 or Nox4 significantly suppressed TGF-ß1-mediated CTGF expression in VSMC. Furthermore, Nox4 silencing or inhibition eliminated TGF-ß1-induced Smad3 activation and interaction between Nox4 and Smad3. In vivo studies further identified a positive correlation of Nox4 levels with Smad3 activation and CTGF expression in atherosclerotic arteries of patients and animal models. These data established that a novel mechanistic link of Nox4-dependent activation of Smad3 to increased TGF-ß1-induced CTGF in the process of vascular remodeling, which suggested a new potential pathway for therapeutic interventions.
Asunto(s)
Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Músculo Liso Vascular/metabolismo , NADPH Oxidasa 4/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Factor de Crecimiento del Tejido Conjuntivo/genética , Regulación de la Expresión Génica , Humanos , Ratones , NADPH Oxidasa 4/genética , Compuestos Onio/farmacología , ARN Interferente Pequeño/genética , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genética , Proteína smad3/genética , Factor de Crecimiento Transformador beta1/genética , Remodelación Vascular/genéticaRESUMEN
This paper studies the taxonomy of the genus Osorius Guérin-Méneville, 1829 (Coleoptera: Staphylinidae, Osoriinae) and reports 10 new species and three new records from China: Osorius depressicapitatus sp. nov. (Yunnan and Xizang), O. guizhouensis sp. nov. (Guizhou), O. huangi sp. nov. (Hunan), O. limatidepressus sp. nov. (Sichuan), O. micromidas sp. nov. (Yunnan), O. minutoserratus sp. nov. (Yunnan), O. rectomarginatus sp. nov. (Yunnan, Guangxi, Hainan, Fujian, Guangdong and Xizang), O. striolatus sp. nov. (Hunan and Guangdong), O. trichinosis sp. nov. (Guizhou and Zhejiang), O. tuberocapitatus sp. nov. (Hubei), O. aspericeps Fauvel, 1905, new record of China (Yunnan, Sichuan, Xizang and Zhejiang), O. frontalis Fauvel, 1905, new record of China (Sichuan), and O. punctulatus Motschulsky, 1857, new record of China (Yunnan and Fujian). The number of the Chinese Osorius species is thus increased to 21 in total. The paper provides line drawings for 21 species and redescriptions for the species recorded for the first time in China. A key to Chinese species is also included.