第758回千葉医学会例会・第9回千葉大学第三内科懇話会 25.

HCV prevalence. (TIF 566 kb

Rational design and first-principles studies of phenothiazine-based dyes for dye-sensitised solar cells

<p>We investigate a series of phenothiazine (PT)-based organic dyes by adopting different donors and different donor substitution positions as photosensitisers for application in dye-sensitised solar cells (DSSCs). First-principles calculations reveal systematic improvements of key parameters including light-harvesting efficiency, redox potential, electron injection and non-linear optical properties with donor substitutions. The non-planar structure also suppresses dye aggregation and reduces the rate of internal charge recombination. In particular, photosensitisers with combination of donor functional groups show outstanding performance on these key parameters. This study demonstrates that PT-based dyes with the studied donor groups could serve as excellent candidates of photosensitisers for future DSSC applications.</p

Phase Field Model for Morphological Transition in Nanowire Vapor–Liquid–Solid Growth

The vapor–liquid–solid (VLS) method is widely used for nanowire (NW) synthesis. However, growth of irregular NW geometries is often observed, and the mechanisms responsible are not fully understood. In this article, we present a multiphase field model for studying NW morphological transition during the VLS growth. Introducing the chemical potential and an external perturbation force by means of the method of Lagrange multipliers, the position of the catalyst droplet and the volumetric growth rate of the NW can be precisely controlled in the model. This allows us to capture the morphology of NWs growing along metastable orientations and simulate the formation of complex NW structures. Additionally, with the model’s ability to constrain the NW shape, the interface free energy change along designated droplet moving path can be evaluated, from which a free energy landscape for the catalyst droplet on top of a NW pedestal can be obtained

Table_2_Correlations between circulating methylmalonic acid levels and all-cause and cause-specific mortality among patients with diabetes.DOCX

AimsEvidence regarding serum methylmalonic acid (MMA) levels and mortality in individuals with diabetes is limited. This study aimed to evaluate the correlation between MMA and all-cause and cause-specific deaths in patients with diabetes.Materials and methodsThis is a population-based cohort study based on data from both the National Health and Nutrition Examination Survey (NHANES) and National Death Index from 1999 to 2014. We assessed the association of serum MMA concentrations with mortality using Cox proportional hazard models after adjusting for lifestyle, demographic factors, and comorbidities.ResultsAmong the 3,097 participants, 843 mortalities occurred during a median follow-up of 4.42 years. There were 242 deaths due to cardiovascular disease (CVD) and 131 cancer-associated deaths. After multivariate adjustment, elevated serum MMA levels were markedly correlated with a high risk of all-cause, CVD-, and cancer-related deaths. Each one-unit increase in the natural log-transformed MMA level correlated with increased risk of all-cause mortality (2.652 times), CVD mortality risk (3.153 times), and cancer-related mortality risk (4.514). Hazard ratios (95% confidence intervals [CIs]) after comparing participants with MMA ConclusionHigher serum MMA levels were significantly associated with higher all-cause, CVD, and cancer mortality. These findings suggest that maintaining lower MMA status may lower mortality risk in individuals with diabetes.</p

Table_1_Correlations between circulating methylmalonic acid levels and all-cause and cause-specific mortality among patients with diabetes.DOCX

AimsEvidence regarding serum methylmalonic acid (MMA) levels and mortality in individuals with diabetes is limited. This study aimed to evaluate the correlation between MMA and all-cause and cause-specific deaths in patients with diabetes.Materials and methodsThis is a population-based cohort study based on data from both the National Health and Nutrition Examination Survey (NHANES) and National Death Index from 1999 to 2014. We assessed the association of serum MMA concentrations with mortality using Cox proportional hazard models after adjusting for lifestyle, demographic factors, and comorbidities.ResultsAmong the 3,097 participants, 843 mortalities occurred during a median follow-up of 4.42 years. There were 242 deaths due to cardiovascular disease (CVD) and 131 cancer-associated deaths. After multivariate adjustment, elevated serum MMA levels were markedly correlated with a high risk of all-cause, CVD-, and cancer-related deaths. Each one-unit increase in the natural log-transformed MMA level correlated with increased risk of all-cause mortality (2.652 times), CVD mortality risk (3.153 times), and cancer-related mortality risk (4.514). Hazard ratios (95% confidence intervals [CIs]) after comparing participants with MMA ConclusionHigher serum MMA levels were significantly associated with higher all-cause, CVD, and cancer mortality. These findings suggest that maintaining lower MMA status may lower mortality risk in individuals with diabetes.</p

Table_3_Correlations between circulating methylmalonic acid levels and all-cause and cause-specific mortality among patients with diabetes.DOCX

AimsEvidence regarding serum methylmalonic acid (MMA) levels and mortality in individuals with diabetes is limited. This study aimed to evaluate the correlation between MMA and all-cause and cause-specific deaths in patients with diabetes.Materials and methodsThis is a population-based cohort study based on data from both the National Health and Nutrition Examination Survey (NHANES) and National Death Index from 1999 to 2014. We assessed the association of serum MMA concentrations with mortality using Cox proportional hazard models after adjusting for lifestyle, demographic factors, and comorbidities.ResultsAmong the 3,097 participants, 843 mortalities occurred during a median follow-up of 4.42 years. There were 242 deaths due to cardiovascular disease (CVD) and 131 cancer-associated deaths. After multivariate adjustment, elevated serum MMA levels were markedly correlated with a high risk of all-cause, CVD-, and cancer-related deaths. Each one-unit increase in the natural log-transformed MMA level correlated with increased risk of all-cause mortality (2.652 times), CVD mortality risk (3.153 times), and cancer-related mortality risk (4.514). Hazard ratios (95% confidence intervals [CIs]) after comparing participants with MMA ConclusionHigher serum MMA levels were significantly associated with higher all-cause, CVD, and cancer mortality. These findings suggest that maintaining lower MMA status may lower mortality risk in individuals with diabetes.</p

Data_Sheet_1_Correlations between circulating methylmalonic acid levels and all-cause and cause-specific mortality among patients with diabetes.PDF

AimsEvidence regarding serum methylmalonic acid (MMA) levels and mortality in individuals with diabetes is limited. This study aimed to evaluate the correlation between MMA and all-cause and cause-specific deaths in patients with diabetes.Materials and methodsThis is a population-based cohort study based on data from both the National Health and Nutrition Examination Survey (NHANES) and National Death Index from 1999 to 2014. We assessed the association of serum MMA concentrations with mortality using Cox proportional hazard models after adjusting for lifestyle, demographic factors, and comorbidities.ResultsAmong the 3,097 participants, 843 mortalities occurred during a median follow-up of 4.42 years. There were 242 deaths due to cardiovascular disease (CVD) and 131 cancer-associated deaths. After multivariate adjustment, elevated serum MMA levels were markedly correlated with a high risk of all-cause, CVD-, and cancer-related deaths. Each one-unit increase in the natural log-transformed MMA level correlated with increased risk of all-cause mortality (2.652 times), CVD mortality risk (3.153 times), and cancer-related mortality risk (4.514). Hazard ratios (95% confidence intervals [CIs]) after comparing participants with MMA ConclusionHigher serum MMA levels were significantly associated with higher all-cause, CVD, and cancer mortality. These findings suggest that maintaining lower MMA status may lower mortality risk in individuals with diabetes.</p

Comprehensive characterization of the <i>in vitro</i> and <i>in vivo</i> metabolites of geniposide in rats using ultra-high-performance liquid chromatography coupled with linear ion trap–Orbitrap mass spectrometer

<p>1. Geniposide (genipin 1-<i>O-</i>glucose), one of the major bioactive constituents isolated from Fructus Gardeniae, possesses many biological activities. In this study, an efficient strategy was developed using ultra-high-performance liquid chromatography coupled with linear ion trap–Orbitrap mass spectrometer (UPLC–LTQ–Orbitrap) to profile the <i>in vitro</i> and <i>in vivo</i> metabolic patterns of geniposide in rat liver microsomes (RLMs), plasma, urine, and various tissues. And post-acquisition data-mining methods including extracted ion chromatogram (EIC), multiple mass defect filters (MMDF), fragment ion searching (FISh), and isotope pattern filtering (IPF) were adopted to characterize the known and unknown metabolites.</p> <p>2. A total of 33 metabolites were detected and interpreted according to accurate mass measurement, diagnostic fragment ions, relevant drug biotransformation knowledge, and bibliography data. Among them, 17 metabolites were detected in the plasma, 31 metabolites were identified in the urine, six metabolites could be found in rat heart, 12 in liver, three in spleen, six in lung, 12 in kidney, six in brain, and four in RLMs.</p> <p>3. A series of corresponding reactions such as hydrolysis, hydroxylation, taurine conjugation, hydrogenation, decarboxylation, demethylation, sulfate conjugation, cysteine S-conjugation, glucosylation, and their composite reactions were all discovered.</p> <p>4. The results could provide comprehensive insights and guidance for elucidation of side effect mechanism and safety monitoring as well as for rational formulation design in drug delivery system. The newly discovered geniposide metabolites could be targets for future metabolism studies on the important chemical constituents from herbal medicines.</p

p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death

<div><p>Although our previous studies have provided evidence that oxidative stress has an essential role in total parenteral nutrition (TPN)-associated liver injury, the mechanisms involved are incompletely understood. Here, we show the existence of crosstalk between the miR-200 family of microRNAs and oxidative stress. The members of the miR-200 family are markedly enhanced in hepatic cells by hydrogen peroxide (H₂O₂) treatment. The upregulation of miR-200-3p in turn modulates the H₂O₂-mediated oxidative stress response by targeting p38α. The enhanced expression of miR-200-3p mimics p38α deficiency and promotes H₂O₂-induced cell death. Members of the miR-200 family that are known to inhibit the epithelial to mesenchymal transition (EMT) are induced by the tumor suppressor p53. Here, we show that p53 phosphorylation at Ser 33 contributes to H₂O₂-induced miR-200s transcription. In addition, we show that p38α can directly phosphorylate p53 at serine 33 upon H₂O₂ exposure. Thus, we suggest that in liver cells, the oxidative stress-induced, p38α-mediated phosphorylation of p53 at Ser33 is essential for the functional regulation of oxidative stress-induced miR-200 transcription by p53. Collectively, our data indicate that the p53-dependent expression of miR-200a-3p promotes cell death by inhibiting a p38/p53/miR-200 feedback loop.</p></div

DataSheet_1_Copper metabolism patterns and tumor microenvironment characterization in colon adenocarcinoma.docx

Copper participates in biological processes such as oxygen metabolism and iron uptake, and is a key factor in immune regulation. Based on the transcription data, mutation data and clinical data of colon adenocarcinoma (COAD) patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Profiling Interactive Analysis (GEPIA2) database, the expression and mutation of copper metabolization-related genes in COAD patients and their correlation with tumor immune microenvironment were analyzed. Copper metabolization-related genes (CMRGs) were used to construct COAD subtypes and prognostic risk models for COAD patients. Furthermore, Kaplan-Meier (K-M) curve and receiver operating characteristic (ROC) curve were used to analyze the clinical value of COAD subtypes and genotyping models in distinguishing clinical characteristics of patients, and the immune infiltration of patients with different genotypes was analyzed. Finally, the clinical tissue samples from COAD patients were used to analyze the mRNA expression of genes in risk model between tumor and normal tissues by the method of Polymerase Chain Reaction (PCR). Of the 479 CMRGs, 68 genes were differentially expressed in normal and tumor tissues of COAD patients in TCGA and GEPIA2. Two subtypes with different clinical and immunological characteristics were identified by using 482 genes related to copper metabolism. Finally, a prognostic risk model consisting of five CMRGs was constructed, which could not only predict the prognosis of patients, but also correlated with COAD subtypes. In addition, some genes (glutathione S-transferase mu 1, cyclin D1and cytochrome P450 family 2 subfamily S member 1) in risk model was show significant difference between normal and tumor tissues. The COAD subtypes identified by CMRGs can help clinically distinguish patients with different prognosis and tumor progression, and the risk score can assist in clinical evaluation of patient prognosis, serving as a valuable biomarker for COAD immunotherapy.</p