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Abstract ZnO was grown on sapphire substrate by metal–organic chemical vapor deposition using the diethylzinc (DEZn) and oxygen (O2) as source chemicals at 500 °C. Influences of the chamber pressure and O2/DEZn ratio on the ZnO structural properties were discussed. It was found that the chamber pressure has significant effects on the morphology of ZnO and could result in various structures of ZnO including pyramid-like, worm-like, and columnar grain. When the chamber pressure was kept at 10 Torr, the lowest full width at half-maximum of ZnO (002) of 175 arc second can be obtained. On the other hand, by lowering the DEZn flow rate, the crystal quality of ZnO can be improved. Under high DEZn flow rate, the ZnO nanowall-network structures were found to grow vertically on the sapphire substrate without using any metal catalysts. It suggests that higher DEZn flow rate promotes three-dimensional growth mode resulting in increased surface roughness. Therefore, some tip on the ZnO surface could act as nucleation site. In this work, the growth process of our ZnO nanowall networks is said to follow the self-catalyzed growth mechanism under high-DEZn flow rate.

Artikkelen handler om norske menn som identifiserer seg med å leve i ufrivillig sølibat. Det er en kvalitativ studie som tar utgangspunkt i intervjuer med syv norske menn, og gir ny kunnskap om et fenomen det er forsket lite på i Norge. Overordnet undersøker artikkelen mulige sammenhenger mellom deltakernes forhandlinger om kjønn og maskuliniteter, og interessen for antifeministiske nettfora. Analysen trekker på maskulinitetsteori og begrepet hybrid maskulinitet for å undersøke distansering fra og forhandlinger med ulike maskuliniteter. Den legger vekt på at antifeministiske nettfora gjennomgående fremstår som lite interessante eller relevante for deltakerne.

Sammendrag I denne litteraturgjennomgangen om incels og nettsamfunn ønsker vi å øke kunnskapen om et fenomen som det er begrenset forskning på. Incels (akronym fra det engelske involuntary celibate) utgjør en ny distinkt nettbevegelse som definerer seg som ekstreme kvinnehatere, og som lever i ufrivillig sølibat. Gjennomgangen viser at nettfellesskapet rundt kvinnehatet har økt i omfang og blitt mer ekstremt det siste tiåret. Utover dette består incel-ideologien av flere selvmotsigende ideer om kjønn, seksualitet og maskulinitet. Det er behov for mer forskning på incels, særlig flere kvalitative og etnografiske dybdestudier med incels’ egne stemmer. Slike studier kan belyse hva fenomenet incels kan være symptom på i vår samtid, samt utforske nyansene og de ofte motstridende diskursene rundt kjønn og seksualitet i mannosfæren. Denne gjennomgangen er avgrenset til publikasjoner som er relevante for forskning på incels innenfor et feministisk medievitenskapelig perspektiv.

Artikkelen tar utgangspunkt i ei undersøking om arbeidsinnvandring til dei fire vestlandsfylka og om dette leier til behov for å utvikle eigne lokale politikkar for velferdstenester. Materialet er statistikk for regionen, dokument og nettsider, og intervju med tenesteytarar, arbeidsinnvandrarar og arbeidsgivararar i fylkeskommunane og åtte kommunar. Hovudfokus i artikkelen er kva politikk som kjem fram gjennom praksis. Funna viser at det er lagt liten vekt på arbeidsinnvandrarane sine særskilte behov, at tenestetilbodet vektlegg det som er nødvendig der og då, og at det manglar tenesteutvikling for det framtidige og langsiktige. I artikkelen blir denne lokale politikken omtala som «reaktiv pluralisme» og det vert hevda at situasjonen kunne bli betre viss arbeidsinnvandrarane blei tatt meir på alvor som medborgarar og ved at kommunane la til rette for dei som om dei skulle bli verande i lengre tid.

OBJECTIVE: The phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway is known to be activated in rheumatoid arthritis (RA) synovial tissue, which impacts cell growth, proliferation, survival, and migration. Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) functions as a negative regulator of PI 3-kinase signaling, thus blocking Akt activation. The aim of this study was to examine the effect of PTEN gene transfer in rats with collagen-induced arthritis (CIA). METHODS: Adenoviral vectors encoding human PTEN (AdPTEN) or beta-galactosidase (AdLacZ) were injected intraarticularly into rats with CIA, and their treatment responses were monitored by measures of clinical, radiographic, and histologic changes. The expression of phosphorylated Akt, total Akt, vascular endothelial growth factor (VEGF), proinflammatory cytokines, and chemokines, as well as the extent of microvessel density in the ankle joints were determined. RESULTS: AdPTEN treatment reduced Akt phosphorylation and decreased VEGF production in human RA synovial fibroblasts. Compared with AdLacZ treatment of the rats with CIA, AdPTEN treatment significantly reduced ankle circumference, articular index scores, radiography scores, and histology scores, and also decreased microvessel density and levels of VEGF and interleukin-1beta. Furthermore, PTEN gene transfer led to down-regulation of Akt activation and increased apoptosis in the ankle joints. CONCLUSION: This study is the first to demonstrate the in vivo effect of intraarticular gene delivery of PTEN on amelioration of arthritis symptoms in rats with CIA, which involved antiangiogenic, antiproliferative, and antiinflammatory effects of PTEN via inhibition of the PI 3-kinase/Akt signaling pathway. Our findings also implicate the PI 3-kinase/Akt pathway as a therapeutic target for the treatment of RA or other inflammatory diseases. [ABSTRACT FROM AUTHOR]

By looking at young Norwegians’ text messages in sexual romantic negotiations, this article examines whether text messages may provide a site for performing femininity and masculinity in ways that subvert traditional conceptions of these constructs. Although various studies on gender, sexuality and media [1] have consistently indicated gender specific usage/performances which in this article is indicated and supported by the study’s young informants’ own formulations, the discourse analysis approach employed a more complex image. Here, I focus on how the young people indicate and translate their modes and body-language into texts, paying particular attention to how signs of femininity and masculinity emerge in text message love-projects, I argue that especially for young males, text messages in love-projects offer a site where in particular young males may perform masculinity in counter-traditional ways. The article is a part of a long study of young Norwegian’s usages, self-understanding and gender performances through text message communication. [[1] Döring, Hellwig and Klimsa, 2004, Hareide 2002, Johnsen 2000, Lee and Sohn, 2004, Ling 1998, 1999, 2002, 2004, 2005, Skog 2000, 2002]

Background: The survival of critically ill patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT) is highly dependent on their nutritional status., Objectives: The prognostic nutritional index (PNI) is an indicator used to assess nutritional status and is calculated as: PNI = (serum albumin in g/dL) × 10 + (total lymphocyte count in/mm 3 ) × 0.005. In this retrospective study, we investigated the correlation between this index and clinical outcomes in critically ill patients with AKI receiving CRRT., Methods: We analyzed data from 2076 critically ill patients admitted to the intensive care unit at Changhua Christian Hospital, a tertiary hospital in central Taiwan, between January 1, 2010, and April 30, 2021. All these patients met the inclusion criteria of the study. The relationship between PNI and renal replacement therapy-free survival (RRTFS) and mortality was examined using logistic regression models, Cox proportional hazard models, and propensity score matching. High utilization rate of parenteral nutrition (PN) was observed in our study. Subgroup analysis was performed to explore the interaction effect between PNI and PN on mortality., Results: Patients with higher PNI levels exhibited a greater likelihood of achieving RRTFS, with an adjusted odds ratio of 2.43 (95% confidence interval [CI]: 1.98-2.97, p -value < 0.001). Additionally, these patients demonstrated higher survival rates, with an adjusted hazard ratio of 0.84 (95% CI: 0.72-0.98) for 28-day mortality and 0.80 (95% CI: 0.69-0.92) for 90-day mortality (all p -values < 0.05), compared to those in the low PNI group. While a high utilization rate of parenteral nutrition (PN) was observed, with 78.86% of CRRT patients receiving PN, subgroup analysis showed that high PNI had an independent protective effect on mortality outcomes in AKI patients receiving CRRT, regardless of their PN status., Conclusions: PNI can serve as an easy, simple, and efficient measure of lymphocytes and albumin levels to predict RRTFS and mortality in AKI patients with require CRRT.

Synthetic biology primarily focuses on two kinds of cell chassis: living cells and nonliving systems. Living cells are autoreplicating systems that have active metabolism. Nonliving systems, including artificial cells and nanoparticles, are nonreplicating systems typically lacking active metabolism. In recent work, Cyborg bacteria that are nonreplicating-but-metabolically active have been engineered through intracellular hydrogelation. Intracellular hydrogelation is conducted by infusing gel monomers and photoactivators into cells, followed by the activation of polymerization of the gel monomers inside the cells. However, the previous work investigated only Escherichia coli cells. Extending the Cyborg-Cell method to pathogenic bacteria could enable the exploitation of their pathogenic properties in biomedical applications. Here, we focus on different strains of Pseudomonas aeruginosa , Staphylococcus aureus , and Klebsiella pneumoniae . To synthesize the Cyborg pathogens, we first reveal the impact of different hydrogel concentrations on the metabolism, replication, and intracellular gelation of Cyborg pathogens. Next, we demonstrate that the Cyborg pathogens are taken up by macrophages in a similar magnitude as wild-type pathogens through confocal microscopy and real-time PCR. Finally, we show that the macrophage that takes up the Cyborg pathogen exhibits a similar phenotypic response to the wild-type pathogen. Our work generalizes the intracellular hydrogelation approach from lab strains of E. coli to bacterial pathogens. The new Cyborg pathogens could be applied in biomedical applications ranging from drug delivery to immunotherapy.

Objective: To retrospectively evaluate clinical outcomes, including function and pain, of patients after our all arthroscopic "whole layer" rotator cuff repair technique with simultaneous biceps tenodesis procedure; factors influencing results were also evaluated. Given the frequent association of rotator cuff tear with long head of biceps lesion and the need for effective combined treatment strategies, this study aims to evaluate the efficacy of our technique and compare it with established methods. We hypothesized that our technique would significantly improve function and reduce pain in patients with rotator cuff tears and biceps pathology., Methods: This is a retrospective study that included patients older than 20 years who underwent all arthroscopic "whole layer" rotator cuff repair technique with simultaneous biceps tenodesis procedures for concomitant rotator cuff tear and long head biceps pathology, from 2016 to 2020. Patients were evaluated preoperatively and at a minimum of 2 years of follow-up using the American Shoulder and Elbow Surgeons (ASES) and visual analogue scale (VAS) scores paired t-tests were used for analysis and statistical significance was set at p < 0.05(two-tailed). The satisfaction rate and complications were also evaluated., Results: After an average follow-up of 2.3 years, 118 patients demonstrated significant improvement in both the ASES score (from 36.13 to 95.01, p < 0.001) and VAS score (from 6.81 to 0.89, p < 0.001). Ninety-four percent of the patients reported satisfaction with the surgical outcome. No complications related to Popeye deformity, biceps cramping pain, or ipsilateral shoulder reoperation were observed. Factors such as age, sex, body mass index (BMI), smoking status, alcohol consumption, hypertension, and diabetes did not influence the results. Patients showed significant improvement in both the ASES and VAS scores (p < 0.001)., Conclusion: At a mean follow-up time of 2.3 years, the all arthroscopic "whole layer" rotator cuff repair technique with simultaneous biceps tenodesis is a therapeutic and efficient procedure. The procedure revealed a satisfactory functional outcome, reduced pain, and minimal complications and reoperations., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Older patients with cardiovascular disease (CVD) are highly susceptible to adverse drug reactions due to age-related physiological changes and the presence of multiple comorbidities, polypharmacy, and potentially inappropriate medications (PIMs)., Objective: This study aimed to develop a predictive model to identify the use of PIMs in older patients with CVD., Methods: Data from 2012 to 2021 from the Changhua Christian Hospital Clinical Research Database (CCHRD) and the Kaohsiung Medical University Hospital Research Database (KMUHRD) were analyzed. Participants over the age of 65 years with CVD diagnoses were included. The CCHRD data were randomly divided into a training set (80% of the database) and an internal validation set (20% of the database), while the KMUHRD data served as an external validation set. The training set was used to construct the prediction models, and both validation sets were used to validate the proposed models., Results: A total of 48,569 patients were included. Comprehensive data analysis revealed significant associations between the use of PIMs and clinical factors such as total cholesterol, glycated hemoglobin (HbA1c), creatinine, and uric acid levels, as well as the presence of diabetes, hypertension, and cerebrovascular accidents. The predictive models demonstrated moderate power, indicating the importance of these factors in assessing the risk of PIMs., Conclusions: This study developed predictive models that improve understanding of the use of PIMs in older patients with CVD. These models may assist clinicians in making informed decisions regarding medication safety., (© 2024. The Author(s).)

Our study aims to compare the efficacy of oral antidiabetic therapy to early insulinization on glycemic control among newly diagnosed type 2 diabetes patients in real-world clinical practice. A retrospective cohort study conducted at a medical center in Taiwan analyzed 1256 eligible patients from January 2007 to December 2017. Propensity score matching resulted in well-balanced groups of 94 patients each in the oral antidiabetic drug (OAD) and early insulinization cohorts. Glycemic outcomes were assessed in both groups. Patients exclusively using OAD showed consistently lower glycated hemoglobin (HbA1c) levels at 3, 12, 24, and 36 months compared to insulin users. At later periods, 77.7% of OAD users achieved glycemic control versus 64.9% of insulin users, with a marginally significant difference. Subgroup analyses suggested a trend favoring well-controlled diabetes in the OAD group, though not statistically significant. Our study finds oral antidiabetic therapy is not inferior to early insulinization for glycemic control in newly diagnosed type 2 diabetes patients, irrespective of initial HbA1c levels. This supports oral therapy as a rational treatment option, even in cases with elevated HbA1c at diagnosis., (© 2024. The Author(s).)

Background: Acute kidney injury (AKI) is associated with an increased incidence of poor liver graft and renal outcomes in patients who have undergone liver transplantation (LT). To date, no comprehensive study has compared patients with and without post-LT AKI and analyzed patients who recovered from AKI versus those who did not., Methods: Patients who received living LT between January 2003 and January 2019 were enrolled. We diagnosed and classified AKI patients based on AKI-KDIGO guidelines by increment of creatinine after surgery when compared with serum creatinine on the day of surgery. The recovered AKI subgroup included recipients whose estimated glomerular filtration rate (eGFR) recovered more than 90% of baseline eGFR within 90 days after surgery. The risk of chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m2) was investigated., Results: A total of 392 patients, 77.3% men and mean ± standard deviation age 54.1 ± 8.4 years, met the eligible criteria and were divided into two groups (AKI vs non-AKI) and 243 (62%) patients developed AKI within 7 days after surgery. Compared with the non-AKI group, the AKI group was associated with an adjusted hazard ratio of 1.55 (95% CI 1.12-2.14) for the risk of incident CKD. Among AKI patients, 160 (65.8%) patients recovered renal function and 83 (34.2%) patients did not. Compared with the non-AKI group, the AKI non-recovery group was associated with an adjusted hazard ratio of 2.87 (95% CI 1.95-4.21) for the risk of incident CKD, while the AKI recovery group had no significant difference in the adjusted risk of incident CKD., Conclusions: Post-LT AKI is associated with subsequent risk of CKD development. Taking into account recovery status, AKI was no longer associated with a higher risk of CKD if renal function recovered within 90 days after surgery. Identification and implementation of targeted and individualized therapies for patients at risk for AKI, particularly non-recovery AKI, is of paramount importance to reduce incident CKD during follow-up., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Monocytes were critical cells in the innate immune system. Monocyte recruitment to the lungs is a crucial process of pathophysiology in chronic obstructive pulmonary disease (COPD). Current evidence on the association between the occurrence of acute exacerbations of COPD (AECOPD) and monocytes was unclear. This study aimed to examine whether blood monocytes are associated with the occurrence of AECOPD and to determine the specific blood monocyte level to predict AECOPD. A retrospective case-control study was conducted at Changhua Christian Hospital. A total of 444 eligible patients with COPD were included between January 2017 and December 2019. Restricted cubic splines were used to analyze the nonlinear relationships between continuous white blood cell values and the occurrence of AECOPD. The association between monocytes and the occurrence of AECOPD was assessed using the logistic, lasso, and ridge regression models. Restricted cubic splines revealed nonlinear associations among the monocyte level, the continuous value of the eosinophil-to-lymphocyte ratio, and the occurrence of AECOPD. The lowest risk of occurrence of AECOPD ranged from 7.4 to 10%; < 7.4% with an absolute count < 0.62 or > 10% indicated significant risk. No significant association was noted between the eosinophil-to-lymphocyte ratio categories in the tertiles (< 0.049, 0.049 to < 0.122, and ≥ 0.122) and the risk of AECOPD. A significantly higher risk was noted in the association of the occurrence of AECOPD with the CAT score; mMRC score; wheezing cough; preexisting chronic pulmonary disease; hypertension and malignancy; use of dual- and triple, and oral long-acting bronchodilators for COPD treatment; and WBC count. We reported a nonlinear relationship between monocytes and the occurrence of AECOPD. Patients with monocyte percentage of > 10% or < 7.4% with an absolute count < 0.62 had higher risk of occurrence of AECOPD. Overall, our study demonstrated the specific value of monocytes in identifying high risks of the occurrence of AECOPD; this value is an easy-to-obtain, inexpensive biomarker in patients with AECOPD and should be further investigated in future prospective clinical studies., (© 2022. The Author(s).)

(1) Background: Little is known about the subsequent renal function change following incident infectious diseases in living-donor liver transplant (LT) recipients. (2) Methods: We studied patients who underwent living-donor LT from January 2003 to January 2019 to evaluate the association of incident hospitalization with major infections or pneumonia with adverse renal outcomes, including a sustained 40% reduction in estimated glomerular filtration rate (eGFR) and renal composite outcome (a 40% decline in eGFR, end-stage renal disease, or death.). Multivariable-adjusted time-dependent Cox models with infection as a time-varying exposure were used to estimate hazard ratio (HR) with 95% confidence interval (CI) for study outcomes. (3) Results: We identified 435 patients (mean age 54.6 ± 8.4 years and 76.3% men), of whom 102 had hospitalization with major infections during follow-up; the most common cause of infection was pneumonia (38.2%). In multiple Cox models, hospitalization with a major infection was associated with an increased risk of eGFR decline > 40% (HR, 3.32; 95% CI 2.13−5.16) and renal composite outcome (HR, 3.41; 95% CI 2.40−5.24). Likewise, pneumonia was also associated with an increased risk of eGFR decline > 40% (HR, 2.47; 95% CI 1.10−5.56) and renal composite outcome (HR, 4.37; 95% CI 2.39−8.02). (4) Conclusions: Our results illustrated the impact of a single infection episode on the future risk of adverse renal events in LT recipients. Whether preventive and prophylactic care bundles against infection and judicious modification of the immunosuppressive regimen benefit renal outcomes may deserve further study.

Background: Nutrition and inflammation have been implicated in predicting mortality in patients on peritoneal dialysis (PD). Serum albumin and globulin can be regarded for the nutritional and inflammatory status. However, there is lack of data to evaluate the synergistic effect of albumin and globulin on mortality prediction. Methods: In 554 patients initiating PD from January 2001 to July 2016, we divided them into four groups by the combination of two categories of low vs. high albumin and low vs. high globulin. The median values for albumin and globulin were chosen to classify them into low or high groups. Their associations with all-cause and cardiovascular (CV) mortality were examined in Cox regression models adjusted for confounding clinical and laboratory data. Results: Patients, 52.91 ± 15.2 years old and 47.8% men, had a median (interquartile range) value of 3.3 (2.9−3.8) g/dL for albumin and 2.8 (2.5−3.2) g/dL for globulin, respectively. Patients with low albumin and high globulin had the highest all-cause mortality and CV mortality, with adjusted hazard ratios of 3.87 (95% CI 1.83−8.20, p < 0.001) and 5.65 (95% CI 2.23−14.34, p < 0.001), respectively, compared with those with a high albumin and low globulin having the lowest mortality rate. Sensitivity analyses further confirmed this relationship. Conclusions: A patient profile of either low albumin or high globulin is linked to a higher risk for mortality, particularly for a profile of both low albumin and high globulin compared with one without either of them. Further studies are needed to explore the mechanisms underlying this phenomenon and how to improve clinical outcomes in those high-risk patients.

In this study, we established an explainable and personalized risk prediction model for in-hospital mortality after continuous renal replacement therapy (CRRT) initiation. This retrospective cohort study was conducted at Changhua Christian Hospital (CCH). A total of 2932 consecutive intensive care unit patients receiving CRRT between 1 January 2010, and 30 April 2021, were identified from the CCH Clinical Research Database and were included in this study. The recursive feature elimination method with 10-fold cross-validation was used and repeated five times to select the optimal subset of features for the development of machine learning (ML) models to predict in-hospital mortality after CRRT initiation. An explainable approach based on ML and the SHapley Additive exPlanation (SHAP) and a local explanation method were used to evaluate the risk of in-hospital mortality and help clinicians understand the results of ML models. The extreme gradient boosting and gradient boosting machine models exhibited a higher discrimination ability (area under curve [AUC] = 0.806, 95% CI = 0.770-0.843 and AUC = 0.823, 95% CI = 0.788-0.858, respectively). The SHAP model revealed that the Acute Physiology and Chronic Health Evaluation II score, albumin level, and the timing of CRRT initiation were the most crucial features, followed by age, potassium and creatinine levels, SPO2, mean arterial pressure, international normalized ratio, and vasopressor support use. ML models combined with SHAP and local interpretation can provide the visual interpretation of individual risk predictions, which can help clinicians understand the effect of critical features and make informed decisions for preventing in-hospital deaths.

Serum potassium (K+) levels between 3.5 and 5.0 mmol/L are considered safe for patients. The optimal serum K+ level for critically ill patients with acute kidney injury undergoing continuous renal replacement therapy (CRRT) remains unclear. This retrospective study investigated the association between ICU mortality and K+ levels and their variability. Patients aged >20 years with a minimum of two serum K+ levels recorded during CRRT who were admitted to the ICU in a tertiary hospital in central Taiwan between January 01, 2010, and April 30, 2021 were eligible for inclusion. Patients were categorized into different groups based on their mean K+ levels: <3.0, 3.0 to <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mmol/L; K+ variability was divided by the quartiles of the average real variation. We analyzed the association between the particular groups and in-hospital mortality by using Cox proportional hazard models. We studied 1991 CRRT patients with 9891 serum K+ values recorded within 24 h after the initiation of CRRT. A J-shaped association was observed between serum K+ levels and mortality, and the lowest mortality was observed in the patients with mean K+ levels between 3.0 and 4.0 mmol/L. The risk of in-hospital death was significantly increased in those with the highest variability (HR and 95% CI = 1.61 [1.13−2.29] for 72 h mortality; 1.39 [1.06−1.82] for 28-day mortality; 1.43 [1.11−1.83] for 90-day mortality, and 1.31 [1.03−1.65] for in-hospital mortality, respectively). Patients receiving CRRT may benefit from a lower serum K+ level and its tighter control. During CRRT, progressively increased mortality was noted in the patients with increasing K+ variability. Thus, the careful and timely correction of dyskalemia among these patients is crucial.

Background: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level., Methods: We conducted a retrospective case-control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model's decisions., Results: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745-0.921] and AUC = 0.836 [95% CI 0.757-0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was <0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD., Conclusions: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model's decision-making process.

To summarize the clinical characteristics and surgical treatment experience of pregnant women with acute Stanford type A aortic dissection.We collected the clinical data of 12 cases with acute aortic dissection during pregnancy and puerperal period from June 2010 to July 2020 in Beijing Anzhen Hospital and analyzed retrospectively, and summarize the clinical characteristics, treatment and outcomes for both mother and fetus. The age of these patients was(29±5)years old, and the onset time was from 16 weeks of gestation and 1 month after delivery. All the 12 patients underwent surgical treatment. The patients in the puerperium received aortic surgery after delivery. Four of them received the aortic surgery and continued pregnancy. Five of them underwent aortic repair and cesarean section simultaneously. Surgical treatment should be actively considered in pregnancy complicated with acute Stanford type A aortic dissection. Multi-disciplinary team cooperation can effectively improve the safety of the patients and fetus.

Scrub typhus (ST), also known as tsutsugamushi disease and caused by rickettsia Orientia tsutsugamushi , is an underestimated fatal epidemic in the Asia-Pacific region, resulting in a million human infections each year. ST is easily misdiagnosed as clinical diagnosis is based on non-specific skin eschar and flu-like symptoms. Thus, the lack of accurate, convenient, and low-cost detection methods for ST poses a global health threat. To address this problem, we adopted baculovirus surface-display technology to express three variants of TSA56, the major membrane antigen of O. tsutsugamushi , as well as the passenger domain of ScaC (ScaC-PD), on insect Sf21 cell surfaces rather than biosafety level 3 bacteria in an enzyme-linked immunosorbent assay (ELISA). Recombinant TSA56 and ScaC-PD were all properly expressed and displayed on Sf21 cells. Our cell-based ELISA comprising the four antigen-displaying cell types interacted with monoclonal antibodies as well as serum samples from ST-positive field-caught rats. This cell-based ELISA presented high accuracy (96.3%), sensitivity (98.6%), and specificity (84.6%) when tested against the ST-positive rat sera. Results of a pilot study using human sera were also highly consistent with the results of immunofluorescence analyses. By adopting this approach, we circumvented complex purification and refolding processes required to generate recombinant O. tsutsugamushi antigens and reduced the need for expensive equipment and extensively trained operators. Thus, our system has the potential to become a widely used serological platform for diagnosing ST., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liao, Tsai, Lo, Lin, Lin and Chao.)

Background: This study aimed to determine the association between episodic or persistent hematuria after liver transplantation and long-term renal outcomes., Methods: Patients who underwent living donor liver transplantation between July 2005 and June 2019 were recruited and divided into two groups based on the finding of microscopic or gross hematuria after transplantation. All patients were followed up from the index date until the end date in May 2020. The risks of chronic kidney disease, death, and 30% and 50% declines in estimated glomerular filtration rate (eGFR) were compared between groups., Results: A total of 295 patients underwent urinalysis for various reasons after undergoing transplantation. Hematuria was detected in 100 patients (group A) but was not present in 195 patients (group B). Compared with group B, group A had a higher risk of renal progression, including eGFR decline >50% [aHR = 3.447 (95%CI: 2.24~5.30), p < 0.001] and worse survival. In addition, patients who took non-steroidal anti-inflammatory drugs (NSAIDs) continuously for over seven days within six months before transplant surgery had high risks of rapid renal progression, including a >30% decline in eGFR [aHR = 1.572 (95%CI: 1.12~2.21), p = 0.009)]., Conclusion: Development of hematuria after surgery in patients who underwent living donor liver transplant and were exposed to NSAIDs before surgery were associated with worse long-term renal dysfunction and survival.

Ethnopharmacological Relevance: Kucha tea plant (Camellia assamica var. kucha Chang et Wang) is regarded as a mutant variety of wild Pu'er tea plant found in few mountain areas of Yunnan, China. Its fresh young leaves and shoots are picked by the indigenous aborigines in these local areas to prepare an herbal tea for the treatment of common cold empirically., Materials and Methods: Two extra compounds of relative abundance were detected in Kucha tea in comparison with Pu'er tea, and their chemical structures were identified as chlorogenic acid and theacrine. These two compounds as well as two major compounds, strictinin and caffeine, in Kucha tea were evaluated for their cytotoxicity and inhibitory effects on human influenza virus A/Puerto Rico/8/34 by analyzing viral protein expression and progeny production., Results: No or low cytotoxicity was detected for the four Kucha compounds when their concentrations were below 100 μM. Expression of viral NS1 protein was significantly inhibited by chlorogenic acid, theacrine or strictinin, but not caffeine at a concentration of 100 μM. The relative inhibitory potency was detected as chlorogenic acid < theacrine < strictinin, and both theacrine and strictinin displayed significant inhibition at a concentration of 50 μM. According to a plaque assay, viral progeny production was significantly reduced by theacrine or strictinin, but not by chlorogenic acid or caffeine under the same concentration of 100 μM., Conclusion: It is suggested that theacrine and strictinin are two major ingredients responsible for the anti-influenza activity of Yunnan Kucha tea traditionally used for the treatment of common cold., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chibby is an antagonist of β-catenin and is considered a potential tumor suppressor protein, but the role of Chibby in hepatocellular carcinoma (HCC) has not been characterized. The expression patterns of Chibby and β-catenin in HCC specimens and paired adjacent noncancerous tissues were measured by Western blotting and immunohistochemistry. The correlations between Chibby expression and clinicopathological parameters were analyzed. Then the biological functions of Chibby were analyzed in vitro. The Chibby protein was significantly downexpressed in human primary HCC tissues compared to that in matched adjacent normal liver tissue and is a risk factor for HCC recurrence and shorter survival. Furthermore, we found that in HCC tissues the high expression of β-catenin with low expression of Chibby in the nuclei was an independent predictor for disease-free survival (DFS) ( p = 0.012) and overall survival (OS) ( p = 0.005). Subsequent genetic manipulation in vitro studies revealed that Chibby knockdown induced the expression of β-catenin and C-myc, cyclin D1 protein, which promoted cell proliferation and invasiveness. In contrast, overexpression of Chibby decreased β-catenin expression and inhibited the cell proliferation and invasiveness. Our results suggest that low expression of Chibby was associated with advanced tumor-node-metastasis (TNM) stage and poor differentiation. Furthermore, the combination of Chibby and β-catenin can predict poor prognosis in patients with HCC. Chibby inhibited HCC progression by blocking β-catenin signaling in vitro. Chibby is a biomarker and may be a potential therapeutic target for HCC.

Background: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been extensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains undetermined, especially in regard to stem cell-related pathways., Methods: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing immunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and RT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN axis on lung cancer progression was evaluated by cell migration assay and mice study., Results: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including 72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53, 51, and 57% of the patients, respectively. All of the three biomarkers were positively correlated in clinical human lung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals than those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and upregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed elevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential., Conclusions: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus, therapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer, especially when lung cancer is refractory to conventional treatment due to cancer stem cells.

Signal transducer and activator of transcription 3 (STAT3) has been shown to play a critical role in the maintenance of cancer stem cells (CSCs). Hence, the inhibition of STAT3 signaling has been suggested to be a viable therapeutic approach for cancers. Moreover, the efficacy of combinations of chemotherapeutic drugs and napabucasin, a small-molecule STAT3 inhibitor, have been assessed in various clinical trials, including those involving patients with metastatic colorectal cancer (CRC). Two recently developed small-molecule STAT3 inhibitors, SC-43 and SC-78, which can stimulate SHP-1 to inactivate STAT3, were found to have anti-tumor activity. In this study, the inhibitory effects of SC-43, SC-78, and regorafenib (a reference drug) on cell viability, STAT3 phosphorylation, and various stemness properties [e.g., sphere-forming and soft agar colony-forming abilities, CD133 + /CD44 + (stem cell-like) subpopulations, and the expression of several CSC markers] were examined for both HCT-116 and HT-29 human CRC cells. We found that SC-43 and SC-78 but not regorafenib inhibited constitutive and IL-6-induced STAT3 phosphorylation in HCT-116 and HT-29 cells, respectively. Moreover, SC-43 and SC-78 were more potent than regorafenib in suppressing the stemness properties (except stem cell-like subpopulations) of these cells. As expected, SHP-1 knockdown almost completely abolished the suppressive effects of SC-43 and SC-78 on the sphere formation in both cell lines. Furthermore, SC-43 and SC-78 showed synergistic inhibitory effects with oxaliplatin and/or irinotecan on sphere formation. Overall, our results suggest that SC-43 and SC-78 are potent STAT3 inhibitors that may potentially be used in combination therapy for CRC., Competing Interests: The authors declare that they have no conflict of interest.

Transforming growth factor-β (TGF-β) plays a central role in hepatic fibrogenesis. This study investigated the function and mechanism of bone morphogenetic protein-2 (BMP-2) in regulation of hepatic fibrogenesis. BMP-2 expression in fibrotic liver was measured in human tissue microarray and mouse models of liver fibrosis induced by bile duct ligation surgery or carbon tetrachloride administration. Adenovirus-mediated BMP-2 gene delivery was used to test the prophylactic effect on liver fibrosis. Primary hepatic stellate cells (HSC), HSC-T6 and clone-9 cell lines were used to study the interplay between BMP-2 and TGF-β1. Hepatic BMP-2 was localized in parenchymal hepatocytes and activated HSCs and significantly decreased in human and mouse fibrotic livers, showing an opposite pattern of hepatic TGF-β1 contents. BMP-2 gene delivery alleviated the elevations of serum hepatic enzymes, cholangiocyte marker CK19, HSC activation markers, and liver fibrosis in both models. Mechanistically, exogenous TGF-β1 dose dependently reduced BMP-2 expression, whereas BMP-2 significantly suppressed expression of TGF-β and its cognate type I and II receptor peptides, as well as the induced Smad3 phosphorylation levels in primary mouse HSCs. Aside from its suppressive effects on cell proliferation and migration, BMP-2 treatment prominently attenuated the TGF-β1-stimulated α-SMA and fibronectin expression, and reversed the TGF-β1-modulated epithelial-to-mesenchymal transition marker expression in mouse HSCs. The mutual regulation between BMP-2 and TGF-β1 signaling axes may constitute the anti-fibrogenic mechanism of BMP-2 in the pathogenesis of liver fibrosis. BMP-2 may potentially serve as a novel therapeutic target for treatment of liver fibrosis.

Crystal structure of the protrusion domain (P-domain) of the grouper nervous necrosis virus (GNNV) shows the presence of three-fold trimeric protrusions with two asymmetrical calcium cations along the non-crystallographic three-fold axis. The trimeric interaction natures of the interacting residues and the calcium cations with the neighboring residues within the trimeric interface have been studied by the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in the framework of the density-functional theory (DFT) approach. The results revealed that residues Leu259, Val274, Trp280, and Gln322 of subunit A, Arg261, Asp275, Ala277, and Gln322 of subunit B, Leu259, Asp260, Arg261, Ala277, Val278, and Leu324 of subunit C are the main residues involved in the trimeric interactions. Charge-dipole, dipole-dipole, and hydrogen bonding interactions make the significant contributions to these trimeric interactions. Among different interacting residues within trimeric interface, residue pair Arg261 B-Leu259C forms the strongest hydrogen bond inside the interface between subunits B and C. It was also found that calcium cations interact with residues Asp273, Val274, and Asp275 of subunits A, B, and C through charge-charge and charge transfer interactions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to profile the miRNA expression pattern in UTUC tumor tissues and identify candidate miRNAs with prognostic and/or therapeutic functions., Methods and Results: We collected 22 UTUC tissue and adjacent normal tissues samples from patients who underwent nephroureterectomy. The miRNAs signatures of three selected UTUC samples using next-generation sequencing showed that miR-30a-5p was significantly downregulated in UTUC tumors compared to adjacent normal tissues. The differentially-expressed miRNAs were specifically validated by quantitative real-time polymerase chain reaction. In addition, the miRNA expression signatures were analyzed with the transcriptome profile characterized by microarray. Further in vitro studies indicated that overexpression of miR-30a-5p significantly suppressed proliferation, migration, and epithelial-to-mesenchymal transition (EMT) in cultured BFTC-909 UTUC cells . As a potential target gene of miR-30a-5p in the tight junction pathway suggested by the pathway enrichment analysis, the reduced expression of tight junction protein claudin-5 in UTUC cells was demonstrated to be upregulated by miR-30a-5p genetic delivery., Conclusions: Taken together, our findings demonstrated that miR-30a-5p inhibits proliferation, metastasis, and EMT, and upregulates the expression of tight junction claudin-5 in UTUC cells. Thus, miR-30a-5p may provide a promising therapeutic strategy for UTUC treatment., Competing Interests: The authors declare no conflict of interest.

Background: Many cancer research studies have extensively examined the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway. There are only few reports that suggest that PTEN might affect pain; however, there is still a lack of evidence to show the role of PTEN for modulating pain. Here, we report a role for PTEN in a rodent model of neuropathic pain., Results: We found that chronic constriction injury (CCI) surgery in rats could elicit downregulation of spinal PTEN as well as upregulation of phosphorylated PTEN (phospho-PTEN) and phosphorylated mammalian target of rapamycin (phospho-mTOR). After examining such changes in endogenous PTEN in neuropathic rats, we explored the effects of modulating the spinal PTEN pathway on nociceptive behaviors. The normal rats exhibited mechanical allodynia after intrathecal (i.t.) injection of adenovirus-mediated PTEN antisense oligonucleotide (Ad-antisense PTEN). These data indicate the importance of downregulation of spinal PTEN for nociception. Moreover, upregulation of spinal PTEN by i.t. adenovirus-mediated PTEN (Ad-PTEN) significantly prevented CCI-induced development of nociceptive sensitization, thermal hyperalgesia, mechanical allodynia, cold allodynia, and weight-bearing deficits in neuropathic rats. Furthermore, upregulation of spinal PTEN by i.t. Ad-PTEN significantly attenuated CCI-induced microglia and astrocyte activation, upregulation of tumor necrosis factor-α (TNF-α) and phospho-mTOR, and downregulation of PTEN in neuropathic rats 14 days post injury., Conclusions: These findings demonstrate that PTEN plays a key, beneficial role in a rodent model of neuropathic pain.

We conducted an extensive study in Taiwan of Orientia tsutsugamushi (OT) infection in small wild mammals. Field trapping was carried out at six districts in eastern and western Taiwan as well as various offshore islands during the period 2006-2010. A total of 1061 specimens representing 11 rodent species were captured. The presence of OT infection was assessed by indirect immunofluorescence assay and polymerase chain reaction assays of 56-kDa type-specific antigen gene. The chigger infestation rate among the animals was 35% (371/1061). Among these, OT was detected in 64% (238/371) of the chiggers from the infested animals and in the spleens from 273 (34.3%) of 797 animals. Excluding animals in the Suncus murinus group, the antibody positive rate of scrub typhus was 69.1% (477 of 690 of serum samples). The prevalence of OT infection in animals from areas with a low incidence of human cases of scrub typhus was significantly lower than that in rodents obtained from regions with a high incidence of human cases of the disease (44.4%±4.0% vs. 71.2%±9.7%, p<0.001). In Taiwan, the prevalence of OT infection in wild rodents is considerably high and appears to correlate positively with the occurrence of scrub typhus in humans., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To study the effectiveness of a very brief advice (<30 s) on smoking cessation., Design: A 'proof-of-principle' single-blind, randomized controlled trial (RCT)., Setting: Medical outpatient clinics of a general hospital in Guangzhou, China., Participants: One hundred and twenty-six male current smokers randomly allocated into an intervention (n = 74) and a control group (n = 52). Intervention A health warning by physicians that half of all smokers would be killed by smoking, an advice to quit immediately and referral to a cessation clinic. The control group received none., Outcomes: Primary: seven-day quitting point prevalence at 6 months. Secondary: 7-day point prevalence at 1, 3 and 12 months, sustained abstinence at 3, 6 and 12 months, smoking reduction by half and cessation clinic attendance., Results: By intention-to-treat analysis, 7-day quitting point prevalence rates at four follow-ups were 27.0, 23.0, 21.6 and 18.9% in the intervention group, compared with 5.8, 3.8, 5.8 and 5.8% in the control group (first three P < 0.05). At 3, 6 and 12 months, sustained abstinence prevalence rates were 18.9, 17.6 and 14.9% versus 3.8, 3.8 and 3.8% (P = 0.035, 0.046, 0.074). More smokers in the intervention group had reduced smoking. Almost no participants attended the cessation clinic., Conclusion: Our findings support the need for large RCTs on minimal interventions with the 'one in two' warning.

In order to identify a novel transcript of BRPF1 (BRPF2), a clone separated from mouse cDNA library was sequenced and submitted to GenBank. The expressions of BRPF1 and BRPF2 in different mice tissues were detected using RT-PCR and Northern blotting assays. The preliminary protein functions and conservative domains were analyzed by bioinformatic methods. The results indicated that BRPF2 was a novel transcript of BRPF1. Both BRPF1 and BRPF2 transcripts could be detected in most mice tissues, including liver, embryo, epididymis, testis, ovary and muscle. However, only BRPF2 transcript could be detected in the spleen. BRPF1 mRNA encoded 1 246 aa and the predicted molecular mass was 140 kDa, while BRPF2 encoded 442 aa, partly owing to the absence of a new stop codon. The results of CDD analysis suggested that BRPF2 lost the bromodomain and the PWWP domain compared to BRPF1. Because the bromodomain and the PWWP domain are the critical structures of BRPF1 to interact with histones and recruit the other transcriptional factors, BRPF2 (without these two critical domains) may serve as a negative regulatory factor of BRPF1 and be involved in the chromosome remodeling and transcriptional regulating.

Hepatoma-derived growth factor (HDGF) stimulates the migration, invasion and metastasis in several types of cancer cells. However, the mechanism underlying HDGF-stimulated migration remains unclear. In this study, we investigated the influence of HDGF on cytoskeleton remodeling and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in non-transformed NIH/3T3 cells. Exogenous HDGF promoted the migration and the formation of dorsal ruffles and podosome rosettes. Besides, HDGF supply increased the PI3K expression and Akt phosphorylation in dose- and time-dependent manners. Application of LY294002, a PI3K inhibitor, attenuated the HDGF-induced migration, dorsal ruffles and podosome rosettes formation. Consistently, the HDGF-overexpressing NIH/3T3 transfectants exhibited significantly increased motility and elevated PI3K/Akt activities, which were repressed by LY294002 or adenovirus-mediated overexpression of endogenous PI3K antagonist, PTEN. In summary, HDGF elicits the activation of PI3K/Akt signaling cascade, thereby promoting cytoskeleton remodeling to stimulate cellular migration., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To summarize the experience in anesthetic management for correction of Ebstein's anomaly., Methods: A total of 79 patients with Ebstein's anomaly who underwent surgical repair in our hospital during the time from March 2004 to September 2010 were retrospectively summarized for their anesthetic management. Anesthesia was done for the patients undergoing correction of Ebstein's anomaly. The adults patients were premedicated with intramuscular morphine 0.2 mg/kg and diazepam 0.05 mg/kg. The children patients were premedicated with intramuscular ketamine 5 - 8 mg/kg and atropine 0.05 - 0.20 mg. General anesthesia was induced with midazolam 0.1 - 0.2 mg/kg, etomidate 0.2 - 0.3 mg/kg, sulfentanil 1.0 - 1.5 µg/kg, pipecuronium or vecuronium 0.1 - 0.2 mg/kg, and maintained with isoflurane inhalation and intermittent iv. midazolam and sulfentanil., Results: Anesthetic course was smooth. The symptom in all cases was improved significantly after operation. No patients died during perioperative period., Conclusion: The key points for the anesthetic management of Ebstein's anomaly include precise preoperative evaluation, steady hemodynamic, proper maintenance of suitable pulmonary vascular resistance and cardiac function.

Arteriovenous (AV) graft is frequently used as vascular access in hemodialysis patients. However, clotting or thrombosis of AV grafts often occurs and requires surgical removal. At present, the molecular pathogenesis underlying thrombosis of AV graft is not clear. The PTEN/Akt signaling has been implicated in the pathogenesis of vascular diseases. In this study, elevated PTEN expression and concomitant Akt inactivation was observed in endothelium of atherosclerotic brachial arteries from hemodialysis patients. To investigate whether PTEN upregulation affects endothelial function, adenovirus-mediated PTEN (Ad-PTEN) overexpression was performed in aorta rings and cultured endothelial cells. It was found that PTEN overexpression potently inhibited the microvessel sprouting in aorta rings and the angiogenic activities of endothelial cells including migration and tube formation. On the contrary, PTEN knockdown by RNA interference promoted the endothelial migration and reversed the Ad-PTEN-induced inhibition of endothelial migration. Expression analysis showed that PTEN overexpression attenuated the expression of endothelin-1 (ET-1) and endothelin B receptor (ETBR) in endothelial cells at transcriptional levels. However, exogenous ET-1 supply only partially reversed the PTEN-induced inhibition of migration and tube formation. This was delineated due to that PTEN overexpression also perturbed endothelial nitric oxide synthase (eNOS) activation and vascular endothelial growth factor (VEGF) release. In summary, PTEN upregulation induces endothelial dysfunction by attenuating the availability and signaling of multiple angiogenic pathways in endothelial cells, thereby may contribute to thrombosis of AV graft., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Orientia tsutsugamushi is the etiological agent of scrub typhus, a mite-borne, febrile illness that occurs in the Asia-Pacific region. We conducted strain characterization of O. tsutsugamushi isolates from chiggers obtained from rodents based the nucleotide sequence of the 56-kDa outer membrane protein gene. With the use of PCR, a total of 68 DNA sequences of 56-kDa antigen genes were amplified. Phylogenetic analysis revealed that there were at least six definable clusters among the 68 isolates: 37% Karp-related strains (25/68), 27% TA763 strains (18/68), 12% JG-related strains (8/68), 19% Kato-related strains (13/68), 4% divergent strains (3/68), and 1% representing a Gilliam prototype strain (1/68). Overall, the O. tsutsugamushi genotypes exhibited a high degree of diversity, similar to that seen in strains from the rest of the areas where scrub typhus is endemic. Moreover, the 56-kDa protein sequence similarity between O. tsutsugamushi isolates from mites and those from human patients (H. Y. Lu et al., Am. J. Trop. Med. Hyg. 83:658-663, 2010) were striking, thus highlighting potential risk factors for this emerging zoonotic disease.

Pro-opiomelanocortin (POMC) is a precursor of various neuropeptides. POMC-derived neuropeptides are potent inflammation inhibitors and immunosuppressants. Evidence that osteoarthritis (OA) is an inflammatory disease is accumulating. We assessed whether intra-articular gene delivery of POMC ameliorates experimentally induced OA in a rat model. OA was induced in Wistar rats by anterior cruciate ligament-transection (ACLT) in the knee of one hind limb. Adenoviral vector encoding human POMC (AdPOMC) was injected intra-articularly into the knee joints after ACLT. The transgene expression and the inflammatory responses were evaluated using immunoblotting, immunohistochemistry and enzyme-linked immunosorbent assay. The treated joints were assessed histologically for manifestations of the disease. Human POMC was expressed in the chondrocytes and synovial membrane after the intra-articular injection. POMC gene transfer reduced nuclear factor-κB activity and the levels of interleukin-1β in HTB-94 chondrosarcoma cells and Raw 264.7 macrophages; it also reduced microvessel density in the synovium. Histological examination showed that symptoms of OA in AdPOMC-treated rats were less severe than in rats treated with either empty adenoviral vector (AdNull) or normal saline. Intra-articular injection of adenoviral vectors expressing POMC significantly suppressed the progression and severity of OA, and reduced inflammatory responses and angiogenesis. POMC gene delivery may offer novel therapeutic approach for treating OA.

This study assessed potential probiotic Lactobacillus strains isolated from the feces of breast-fed infants and from Taiwanese pickled cabbage for their possible use in probiotic fermented foods by evaluating their (i) in vitro adhesive ability, resistance to biotic stress, resistance to pathogenic bacteria, and production of β-galactosidase; (ii) milk technological properties; and (iii) in vivo adhesive ability, intestinal survival and microbial changes during and after treatment. Five Lactobacillus isolates identified as Lactobacillus reuteri F03, Lactobacillus paracasei F08, Lactobacillus rhamnosus F14, Lactobacillus plantarum C06, and Lactobacillus acidophilus C11 that showed resistance to gastric juice and bile salts were selected for further evaluation of their probiotic properties. All the strains demonstrated the ability to adhere to Caco-2 cells, particularly, strain L. plantarum C06 and L. reuteri F03 showed satisfactory abilities, which were similar to that of the reference strain L. rhamnosus GG. The strains L. paracasei F08 and L. acidophilus C11 had the highest β-galactosidase activity. Most of the strains were resistant to aminoglycosides and vancomycin but sensitive to ampicillin, erythromycin, and penicillin. All the 5 strains elicited antibacterial activity against both Gram-positive (Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus) and -negative (Escherichia coli and Salmonella enterica) pathogens. Moreover, the strains L. reuteri F03, L. paracasei F08, and L. plantarum C06 could grow rapidly in milk without nutrient supplementation and reached 10⁸ cfu/mL after 24 h of fermentation at 37 °C. The viable cell counts of the 3 strains remained above 10⁷ cfu/mL after 21 d of storage at 4 °C. In the animal feeding trial, the number of intestinal lactobacilli increased significantly after administration of milk fermented with the 3 strains, and the counts of fecal coliforms and Clostridium perfringens were markedly reduced. Lactobacillus strains could also survive in the ileal intestinal tissue of the treated rats. Technologically interesting Lactobacillus isolates may be used in the future as probiotic starter cultures for manufacturing novel fermented foods., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Single-crystalline ZnO nanorod arrays (ZNRs) were grown by metalorganic chemical vapor deposition on ZnO buffer/sapphire substrate without using any metal catalyst. The density of vertically aligned ZNRs was found to govern by the morphology and thickness of buffer layer. That is to say, the ZnO buffer layer can be used as the nucleation template to control the growth direction and density of the ZNRs. In addition, by controlling the diethyl zinc flow rate, we can manipulate the size, crystal, and optical quality of ZNRs. Finally, the possible growth mechanism of ZNRs was discussed in detail.

Uniformly distributed ZnO nanowall network structures were grown at 550 degrees C by organometallic chemical vapor deposition technique on the GaN/sapphire substrate without using any catalysts. In this research, we discussed the nanostructures and optical properties of ZnO samples grown under the same conditions but on different underlying materials (GaN/sapphire and sapphire). By adjusting the growth parameters, ZnO nanowall networks with a honeycomb-like pattern without using any metal catalysts were successfully fabricated on the GaN/sapphire and sapphire substrates. Since the lattice mismatch between ZnO and GaN is only about 1.8% while the lattice mismatch between ZnO and sapphire is about 18.4%. Lattice mismatch may not be the decisive factor in the formation process of ZnO nanowall networks. The ZnO grown on GaN epilayer had smaller full width at half maximum value than that of ZnO grown under the same growth condition on the sapphire substrate, indicating a higher crystal quality in the sample of ZnO on GaN. The room temperature PL measurement of both ZnO nanostructures grown on GaN and sapphire show strong ultraviolet peak intensity and high intensity ratio of the near band emission to the deep-level emission in a PL spectrum.

Rickettsioses are emerging infectious diseases caused by rickettsiae in association with arthropods. We report the detection of spotted fever group rickettsiae (SFGR) in Taiwan using molecular methods. Phylogenetic analyses of the 17-kd protein and citrate synthase (gltA) genes showed that SFGR TwKM01 detected in Rhipicephalus haemaphysaloides ticks was most similar to Rickettsia rhipicephali. Three TwKM01 isolates were obtained from three individual R. haemaphysaloides ticks. Small, intracellular, coccobacillary bacteria were found in infected L929 cells using immunofluorescence antibody testing and transmission electron microscopy. Two other SFGRs, TwKM02 and TwKM03, identified in Leptotrombidium chigger mites, were closely related to R. australis and R. felis URRWXCal(2), respectively. The TwKM03 strain was also detected in Ixodes granulatus ticks and widely distributed in Hualien, Kinmen, and Lienchiang counties in Taiwan. The endonucleases MaeII and HhaI selected for restriction fragment length polymorphism analysis of the gltA and 17-kd polymerase chain reaction products, respectively, were useful for genotyping Rickettsia species TwKM01, TwKM02, TwKM03, and other SFGRs. Although their infectivity and pathogenicity for vertebrates are unknown, the finding of SFGRs raises the possibility that bacteria other than Orientia tsutsugamushi, Coxiella burnetii, and R. typhi may be involved in rickettsial diseases in Taiwan.

Background and Purpose: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease associated with endothelial dysfunction and the existence of multiple species of autoantibodies. However, the association between endothelial dysfunction and renal manifestations remains unclear in Taiwanese SLE patients., Methods: Serum samples were collected from SLE patients with biopsy-proven lupus nephritis (n = 32), stable SLE patients (n = 32) and healthy controls (n = 32). The SLE Disease Activity Index (SLEDAI) of SLE patients was scored, and levels of anti-endothelial cell antibodies (AECA) and anti-endothelial activities in serum samples were measured by cell-enzyme-linked immunosorbent assay and crystal violet assay, respectively, using cultured human endothelial EA.hy926 cells., Results: Significantly higher AECA (p<0.001) and anti-endothelial activities (p<0.001) were found in sera from patients with lupus nephritis compared with that from stable SLE patients or controls. Moreover, AECA titers (p<0.001) and anti-endothelial activities (p<0.001) were strongly correlated with SLEDAI scores in these patients., Conclusion: The strong correlations of AECA and anti-endothelial activity with lupus nephritis activity support an endothelial origin for renal complications in Taiwanese SLE patients.

The human telomerase reverse transcriptase (hTERT) promoter can selectively drive transgene expression in many telomerase-positive human cancer cells. Here we evaluated combination therapy of adenoviral vector Ad-hTERT-CD encoding E. coli cytosine deaminase (CD) driven by the hTERT promoter and low-dose etoposide (0.1 microg/mL) for treating bladder cancer. Ad-hTERT-CD conferred sensitivity to 5-fluorocytosine (5-FC) in bladder cancer cells, which could be enhanced by etoposide treatment, but not in normal cells. Such effect was correlated with up-regulation of hypoxia-inducible factor (HIF)-1alpha expression. By contrast, etoposide activated p53 and down-regulated hTERT promoter activity in normal cells. Etoposide also increased adenoviral infection via enhancement of coxsackie-adenovirus receptor expression on bladder cancer and normal cells. Combination index analysis revealed that combined therapy of Ad-hTERT-CD (10(9) plaque-forming units)/5-FC (200 mg/kg) with etoposide (2 mg/kg) synergistically suppressed tumor growth and prolonged survival in mice bearing syngeneic MBT-2 bladder tumors. This combination therapy regimen induced complete tumor regression and generated antitumor immunity in 75% of tumor-bearing mice. Furthermore, increased infiltrating CD4(+) and CD8(+) T cells and necrosis within tumors were found in mice receiving combination therapy of Ad-hTERT-CD and etoposide compared with those treated with either treatment alone. Thus, the potential high therapeutic index of the combination therapy may be an appealing therapeutic intervention for bladder cancer. Furthermore, because a majority of human tumors exhibit high telomerase activity, adenovirus-mediated CD gene therapy driven by the hTERT promoter in combination with low-dose etoposide may be applicable to a broad spectrum of cancers.

Pro-opiomelanocortin (POMC) is the precursor of several neuropeptides, such as corticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and the endogenous opioid, beta-endorphin (EP). ACTH-dependent Cushing's syndrome is characterized by ACTH overproduction and is associated with an increased risk of cardiovascular disease. Endothelial dysfunction has been recognized as an early marker of cardiovascular disease. However, the mechanism underlying endothelial dysfunction by ACTH overexpression in Cushing's patients remains elusive. Endothelial cells, the primary cells producing endothelin (ET)-1, are both the source and target of POMC-derived peptides. In the present study, we generated adenovirus vectors (Ad) encoding POMC (Ad-POMC) and green fluorescent protein (GFP; Ad-GFP) to investigate whether POMC gene transfer altered the ET-1 homeostasis and angiogenic functions in human EA.hy926 endothelial cells. Via adenovirus gene delivery, the POMC-transduced EA.hy926 cells released significantly elevated ACTH and beta-EP levels (P < 0.001). In addition, POMC gene delivery significantly decreased the ET-1 release (P < 0.001) without affecting the ET-1 messenger RNA (mRNA) level. Despite no effect on the secretion of matrix metalloproteinases (MMPs) and cell proliferation, POMC gene delivery significantly inhibited the migration (P < 0.01) and tube-forming capability (P < 0.01) of endothelial cells. Moreover, the POMC-induced inhibition of tube formation could be partially reversed by adding exogenous ET-1 (P < 0.05). In summary, the attenuated ET-1 release and angiogenic processes by POMC overexpression may contribute to endothelial dysfunction, thereby providing a link between Cushing's syndrome and cardiovascular diseases.

The purpose of this study was to evaluate the efficacy of gene delivery of angiogenesis inhibitor, vasostatin (VS), in suppressing experimental model of choroidal neovascularization (CNV). A mammalian expression vector carrying VS, pCMV3-VS, was constructed and evaluated for its ability to produce VS in transfected cells using western blot analysis and a cell viability assay. CNV was induced in Brown Norway rats by fundus argon laser photocoagulation and evaluated by fundus fluorescein angiography (FAG). Ten days post-laser treatment, gene delivery was achieved by intramuscular (IM) injection of poly-(N-vinyl pyrrolidone) (PVP) polymer conjugated with pCMV3-VS (PVP-VS) or a control vector (PVP-vector). Systemic VS expression was analysed by western blot analysis and enzyme linked immunosorbent assay (ELISA), and the extent of CNV was monitored by FAG analysis at different time intervals post-PVP treatment. Transfection of pCMV3-VS into muscle cells resulted in increased production and release of exogenous VS, which specifically inhibited the proliferation of endothelial cells. Besides, IM injection of PVP-VS, but not PVP-vector, led to elevated VS level in plasma for 30 days. After laser photocoagulation, rats injected with PVP-VS exhibited significantly lower incidence of CNV comparing with animals of control groups (P < 0.01) for at least 42 days. Moreover, rats treated with PVP-VS also showed a significant reduction in the CNV lesions compared with control groups (P < 0.001) for at least 42 days. Above all, no overt adverse effects were observed in rats received PVP-VS. These results demonstrate the potential of IM VS gene delivery for CNV treatment.

Liver is the primary source for collagen XVIII, the precursor of angiogenesis inhibitor, endostatin. However, the role of endostatin/collagen XVIII expression during liver carcinogenesis remains elusive. Therefore, we studied its expression in five hepatoma cell lines and 105 hepatocellular carcinoma specimens. The poorly differentiated hepatoma cell lines exhibited increased endostatin/collagen XVIII levels compared with the well-differentiated ones. In hepatoma tissues, endostatin/collagen XVIII expression was detected in various types of liver cells and was significantly stronger in adjacent nontumor tissues than that in tumors (P<0.001). Endostatin/collagen XVIII expression in nontumor tissues correlated with tumor stages (P=0.014) and expression of vascular endothelial growth factor (P=0.007), but not the stages of hepatic fibrosis (P>0.05). Kaplan-Meier analysis showed that patients with higher endostatin/collagen XVIII expression had significantly shorter overall survival (P=0.011) and disease-free survival (P=0.0034). Moreover, endostatin/collagen XVIII level was an independent prognostic factor for tumor recurrence (P=0.034) by multivariate analysis. In conclusion, increased endostatin/collagen XVIII expression correlated with hepatoma progression and predicted poor prognosis for patients with hepatocellular carcinoma.

Purpose: This study was designed to investigate the effects of the locally supplied endogenous angiogenesis inhibitor vasostatin (VS) on corneal angiogenesis., Methods: Recombinant VS was expressed and purified. The effects of VS on the proliferation of endothelial cells were investigated using the methyl thiazolyl tetrazolium (MTT) assay in the absence or presence of angiogenic factors such as basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). Corneal neovascularization was induced by implantation of hydron pellets containing bFGF in rat corneal micropockets. The potency of VS to inhibit corneal angiogenesis was investigated by incorporation of VS with bFGF in hydron pellets or topical application of VS containing eye drops to rat eyes implanted with bFGF pellets. The extent of corneal neovascularization was evaluated by microscopic and histological analyses., Results: VS potently inhibited the growth of endothelial cells in the absence or presence of angiogenic factors such as bFGF or VEGF. In the rat corneal micropocket assay, concurrent incorporation of VS abolished the bFGF induced neovascularization. When formulated in a methylcellulose eye drop, VS remained intact and functional in a 4 degrees C solution for more than 7 days. Topical application of VS eye drops potently inhibited bFGF induced neovascularization in rat corneas., Conclusions: The present study effectively demonstrated the potential feasibility of local application of VS for treatment of corneal angiogenesis.