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Background: Globally, diabetes affects approximately 500 million people and is predicted to affect up to 700 million people by 2045. In Australia, the ongoing impact of colonization produces inequity in health care delivery and inequality in health care outcomes for First Nations Peoples, with diabetes rates 4 times those of non-Indigenous Australians. Evidence-based clinical practice has been shown to reduce complications of diabetes-related foot disease, including ulceration and amputation, by 50%. However, factors such as a lack of access to culturally safe care, geographical remoteness, and high costs associated with in-person care are key barriers for First Nations Peoples in accessing evidence-based care, leading to the development of innovative mobile health (mHealth) apps as a way to increase access to health services and improve knowledge and self-care management for people with diabetes., Objective: This study aims to evaluate studies investigating the use of mHealth apps for the assessment and management of diabetes-related foot health in First Nations Peoples in Australia and non-Indigenous populations globally., Methods: PubMed, Informit's Indigenous Collection database, Ovid MEDLINE, Embase, CINAHL Complete, and Scopus were searched from inception to September 8, 2022. Hand searches of gray literature and reference lists of included studies were conducted. Studies describing mHealth apps developed for the assessment and management of diabetes-related foot health were eligible. Studies must include an evaluation (qualitative or quantitative) of the mHealth app. No language, publication date, or publication status restrictions were used. Quality appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and the Health Evidence Bulletins Wales checklists for observational, cohort, and qualitative studies., Results: No studies specifically including First Nations Peoples in Australia were identified. Six studies in non-Indigenous populations with 361 participants were included. Foot care education was the main component of all mHealth apps. Of the 6 mHealth apps, 2 (33%) provided functionality for participants to enter health-related data; 1 (17%) included a messaging interface. The length of follow-up ranged from 1-6 months. Of the 6 studies, 1 (17%) reported high levels of acceptability of the mHealth app content for self-care by people with diabetes and diabetes specialists; the remaining 5 (83%) reported that participants had improved diabetes-related knowledge and self-management skills after using their mHealth app., Conclusions: The findings from this systematic review provide an overview of the features deployed in mHealth apps and indicate that this type of intervention can improve knowledge and self-care management skills in non-Indigenous people with diabetes. Future research needs to focus on mHealth apps for populations where there is inadequate or ineffective service delivery, including for First Nations Peoples and those living in geographically remote areas, as well as evaluate direct effects on diabetes-related foot disease outcomes., Trial Registration: PROSPERO CRD42022349087; https://tinyurl.com/35u6mmzd., (©Sean Sadler, James Gerrard, Angela Searle, Sean Lanting, Matthew West, Rhonda Wilson, Athula Ginige, Kerry Y Fang, Vivienne Chuter. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.10.2023.)

Background: After encountering COVID-19 patients who test positive again after discharge, our study analyzed the pathogenesis to further assess the risk and possibility of virus reactivation., Methods: A separate microarray was acquired from the Gene Expression Omnibus (GEO), and its samples were divided into two groups: a "convalescent-RTP" group consisting of convalescent and "retesting positive" (RTP) patients (group CR) and a "healthy-RTP" group consisting of healthy control and RTP patients (group HR). The enrichment analysis was performed with R software, obtaining the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the protein-protein interaction (PPI) networks of each group were established, and the hub genes were discovered using the cytoHubba plugin., Results: In this study, 6622 differentially expressed genes were identified in the group CR, among which RAB11B-AS1, DISP1, MICAL3, PSMG1, and DOCK4 were up-regulated genes, and ANAPC1, IGLV1-40, SORT1, PLPPR2, and ATP1A1-AS1 were down-regulated. 7335 genes were screened in the group HR, including the top 5 up-regulated genes ALKBH6, AMBRA1, MIR1249, TRAV18, and LRRC69, and the top 5 down-regulated genes FAM241B, AC018529.3, AL031963.3, AC006946.1, and FAM149B1. The GO and KEGG analysis of the two groups revealed a significant enrichment in immune response and apoptosis. In the PPI network constructed, group CR and group HR identified 10 genes, respectively, and TP53BP1, SNRPD1, and SNRPD2 were selected as hub genes., Conclusions: Using the messenger ribonucleic acid (mRNA) expression data from GSE166253, we found TP53BP1, SNRPD1, and SNRPD2 as hub genes in RTP patients, which is vital to the management and prognostic prediction of RTP patients., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

The SARS-CoV-2 infection rate, as well as mortality rate, is high. There is an urgent need for a high-throughput, accurate and reliable method of diagnosing COVID-19 pneumonia. We included references from databases, such as PubMed, Cochrane Library, Web of Science, and Embase, and extracted data. Then, MetaDisc and STATA were used to establish forest plots and funnel plots for meta-analysis. We collected 14 articles and performed a systematic review. The following results were obtained: sensitivity and specificity were 0.97 (0.96 to 0.98) and 0.97 (0.96 to 0.98) respectively; PLR and NLR were 24.51 (16.63-36.12) and 0.03 (0.01 to 0.10) respectively, DOR was 975.15 (430.11-2210.88), and AUC was 0.9926. When Xpress detects SARS-CoV-2 in different samples, the heterogeneity is small and the specificity and sensitivity are extremely high. We recommend the employment of Xpert Xpress analysis in rapid screening., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pinus massoniana is a typical pioneer afforestation tree species widely distributed in southern China. It is crucial to study the ecological resilience of P. massoniana to disturbances under global warming, drying, and frequent pest infestation, which can shed lights on forest mana-gements. In this study, tree-ring samples collected from old-growth P. massoniana trees in Baisong Village, Xianyou County, Fujian Province, were used to develop the first standard chronology of P. massoniana ring width (1865-2014) in this region. The results showed that the low relative humidity from July to September and the extremely high temperature from May to September were the main limiting factors for tree growth. The extremely narrow years were identified in 1869, 1889, 1986, 1991 and 1993. These extremely narrow years were exacerbated after the persistently low values of the previously two years via the superposed epoch analysis (SEA). The insect infestations were more likely to happen in dry years. Insect outbreak exerted strongest effect on tree growth in 1889. The narrow tree-rings in 1986 and 1991 were affected by both insect infestation and drought. The other extremely narrow years were mainly affected by drought. The resistance of trees to insect infestation was weaker than that to drought event. The relative resilience of trees to insect infestation was higher than that to drought event, except for 1991. The relative resilience was the highest in 1889 and the lowest in 1991 under the influence of successive extreme events. Under the enhanced drying trend since 2000, more trees had died possibly due to the combined effects of insect infestation and drought.

We sampled Pinus massoniana and Cunninghamia lanceolata in both plantation and natural forests in central and western Fujian Province, China. Using tree-ring width, tree-ring width index, and basal area increment, we reconstructed the annual growth of 109 conifer individuals from four sites for the 20-year period from 1993 to 2012. We then calculated resistance, recovery, and resilience indices of those trees in response to two consecutive extreme droughts (2003-2004 and 2011) and analyzed the differences in resistance and resilience between plantations and natural fore-sts. The results showed that there were temporal differences in moisture requirements between P. massoniana and C. lanceolata , which accounted for their inconsistent responses to drought in 2003-2004. For both species, drought induced a marked growth reduction, without any clear lag effect. The growth responses during and following the 2003-2004 drought were significantly stronger than that for the 2011 drought. Those results indicated that P. massoniana was more resilient to drought stress than C. lanceolata , and the natural forests were more sensitive than plantations, but with stronger capacity to recover. C. lanceolata plantations were more susceptible to frequent extreme drought events. To mitigate the vulnerability of plantation trees to more frequent droughts in the future, we suggested select trees from genetic provenances with strong drought resistance.

Nervous necrosis virus (NNV) belongs to the Betanodavirus genus of the Nodaviridae family and is the main cause of viral nervous necrosis disease in marine fish larvae and juveniles worldwide. The NNV virion contains two positive-sense, single-stranded RNA genomes, which encode RNA-dependent RNA polymerase, coat protein, and B2 protein. Interestingly, NNV infection can shut off host translation in orange-spotted grouper (Epinephelus coioides) brain cells; however, the detailed mechanisms of this action remain unknown. In this study, we discovered that the host translation factor, polyadenylate binding protein (PABP), is a key target during NNV takeover of host translation machinery. Additionally, ectopic expression of NNV coat protein is sufficient to trigger nuclear translocalization and degradation of PABP, followed by translation shutoff. A direct interaction between NNV coat protein and PABP was demonstrated, and this binding requires the NNV coat protein N-terminal shell domain and PABP proline-rich linker region. Notably, we also showed that degradation of PABP during later stages of infection is mediated by the ubiquitin-proteasome pathway. Thus, our study reveals that the NNV coat protein hijacks host PABP, causing its relocalization to the nucleus and promoting its degradation to stimulate host translation shutoff. IMPORTANCE Globally, more than 200 species of aquacultured and wild marine fish are susceptible to NNV infection. Devastating outbreaks of this virus have been responsible for massive economic damage in the aquaculture industry, but the molecular mechanisms by which NNV affects its host remain largely unclear. In this study, we show that NNV hijacks translation in host brain cells, with the viral coat protein binding to host PABP to promote its nuclear translocalization and degradation. This previously unknown mechanism of NNV-induced host translation shutoff greatly enhances the understanding of NNV pathogenesis and provides useful insights and novel tools for development of NNV treatments, such as the use of orange-spotted grouper brain cells as an in vitro model system.

Objective: To explore the related factors influencing the length of hospital stay(LOS) of pregnant women with heart disease (PWHD) after cesarean section. Methods: A total of 306 patients with PWHD who underwent cesarean section from January 2012 to March 2019 were collected. Among them, 203 patients had not undergone heart surgery (uncorrected group) and 103 patients who had undergone heart surgery (corrected group) during the same period. Demographic, perioperative and postoperative data were recorded. Predictors associated with postoperative LOS were determined using univariate and multivariate linear regression analysis models. Results: (1) The median LOS after cesarean section in the uncorrected group was 6 days (5-8 days). The results of univariate linear regression analysis showed that 38 parameters had significant impact on LOS ( P <0.05). The results of multivariate linear regression analysis showed that 5 parameters were independent risk factors for prolonged LOS in the uncorrected group; among them, the median LOS in uncorrected group with hypertensive disorders of pregnancy was 3 days longer than that in patients with PWHD alone [7 days (5-8 days) vs 4 days (4-5 days), β =0.195, P =0.001]; the median LOS in uncorrected group with high serum creatinine was 3 days longer than normal patients [7 days (5-13 days) vs 4 days (4-5 days), β =0.145, P =0.015]; the LOS of patients who chose general anesthesia was 2 days longer than that of patients who chose spinal anesthesia [6 days (4-8 days) vs 4 days (4-5 days), β =0.154, P =0.007]; the LOS of patients with postoperative pulmonary infection was 4 days longer than that of patients without pulmonary infection [8 days (5-15 days) vs 4 days (4-5 days), β =0.269, P <0.01]; the LOS of patients who admitted to ICU after surgery was 2 days longer than that not admitted patients [6 days (5-8 days) vs 4 days (4-5 days), β =0.268, P <0.01]. (2) The median LOS after cesarean section in corrected group was 4 days (4-5 days). The results of univariate linear regression analysis showed that 8 parameters had significant impact on the LOS (all P <0.05). The results of multivariate linear regression analysis showed that 2 parameters, which were American Society of Anesthesiologists (ASA) grade ( β =0.198, P =0.028) and intraoperative blood loss ( β =0.285, P =0.003), were the independent risk factors for prolonged LOS in corrected group. Conclusion: Preoperative with hypertensive disorders of pregnancy, preoperative creatinine increase, intraoperative general anesthesia, postoperative pulmonary infection, and postoperative admission to ICU are independent predictors of prolonged LOS in uncorrected patients with PWHD; ASA classification and intraoperative bleeding are independent predictor of prolonged postoperative LOS in patients with corrected PWHD.

Background: In the novel coronavirus pandemic, the high infection rate and high mortality have seriously affected people's health and social order. To better explore the infection mechanism and treatment, the three-dimensional structure of human bronchus has been employed in a better in-depth study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We downloaded a separate microarray from the Integrated Gene Expression System (GEO) on a human bronchial organoids sample to identify differentially expressed genes (DEGS) and analyzed it with R software. After processing with R software, Gene Ontology (GO) and Kyoto PBMCs of Genes and Genomes (KEGG) were analyzed, while a protein-protein interaction (PPI) network was constructed to show the interactions and influence relationships between these differential genes. Finally, the selected highly connected genes, which are called hub genes, were verified in CytoHubba plug-in., Results: In this study, a total of 966 differentially expressed genes, including 490 upregulated genes and 476 downregulated genes were used. Analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways related to immune response and cytokines. We construct protein-protein interaction network and identify 10 hub genes, including IL6, MMP9, IL1B, CXCL8, ICAM1, FGF2, EGF, CXCL10, CCL2, CCL5, CXCL1, and FN1. Finally, with the help of GSE150728, we verified that CXCl1, CXCL8, CXCL10, CCL5, EGF differently expressed before and after SARS-CoV-2 infection in clinical patients., Conclusions: In this study, we used mRNA expression data from GSE150819 to preliminarily confirm the feasibility of hBO as an in vitro model to further study the pathogenesis and potential treatment of COVID-19. Moreover, based on the mRNA differentiated expression of this model, we found that CXCL8, CXCL10, and EGF are hub genes in the process of SARS-COV-2 infection, and we emphasized their key roles in SARS-CoV-2 infection. And we also suggested that further study of these hub genes may be beneficial to treatment, prognostic prediction of COVID-19.

Background: Sepsis has become a global healthcare problem and continues to be one of the leading causes of death due to infection. In essence, early recognition and diagnosis of sepsis is needed to inhibit the transition into septic shock, which is correlated with higher mortality. Many studies have suggested antimicrobial de-escalation as one of the strategies to replace the empirical broad-spectrum antimicrobial treatment using a narrower antimicrobial therapy, especially among patients with sepsis. However, antimicrobial de-escalation therapeutic effects in sepsis remains unclear. We therefore performed the present study in an attempt to assess efficacy and safety of antimicrobial de-escalation therapy in patients with sepsis., Methods: We will carry out a systematic literature search to establish the potentially eligible trials from electronic databases, including EMBASE (1980 to October 16, 2020), MEDLINE via PubMed (1966 to October 16, 2020), Web of Science (1965 to October 16, 2020), Cochrane Library (CENTRAL; 2020, Issue 10), WanFang databases (last searched October 16, 2020), and China National Knowledge Infrastructure (CNKI; last searched October 16, 2020). For this study, the language restrictions are English or Chinese. Two authors independently examined quality based on the Cochrane Risk of Bias Tool V.2.0 and extracted data. Data obtained from the study will be synthesised using applicable statistical methods., Results: The results of the present study will systematically assess efficacy and safety of antimicrobial de-escalation therapy among patients with sepsis., Conclusion: The results of the present study will help to establish the efficacy and safety of antimicrobial de-escalation to treat patients with sepsis. It can also help to identify the most efficient and safe therapeutically-relevant method., Ethics and Dissemination: The present study is a meta-analysis and the pooled results are based on published evidence. Therefore, ethics approval is not necessary., Osf Registration Number: October 22, 2020.osf.io/93wym. (https://osf.io/93wym/).

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widely spread across the world. Asymptomatic or inconspicuous CT/NG infections are difficult to diagnose and treat. Traditional methods have the disadvantages of low detection rate, inaccurate results, and long detection time. However, Xpert CT/NG makes up for the aforementioned shortcomings and has research value and popularization significance., Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched, and studies were screened using Xpert CT/NG for diagnosing CT/NG. QUADAS-2 was used to evaluate the quality of the eligible studies. Then, two groups of researchers independently extracted data from these studies. Meta-analyses of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were conducted using Meta-DiSc 1.4. Finally, Deek's funnel plots were made using Stata 12.0 to evaluate publication bias., Results: 14 studies were identified, and 46 fourfold tables were extracted in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing CT were 0.94 (95% confidence interval (CI): 0.93-0.95), 0.99 (95% CI: 0.99-1.00), 97.17 (95% CI: 56.76-166.32), 0.07 (95% CI: 0.04-0.12), 1857.25 (95% CI: 943.78-3654.86), and 0.9960, respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing NG were 0.95 (95% CI: 0.93-0.96), 1.00 (95% CI: 1.00-1.00), 278.15 (95% CI: 152.41-507.63), 0.08 (95% CI: 0.06-0.12), 4290.70 (95% CI: 2161.78-8516.16), and 0.9980, respectively., Conclusions: Xpert CT/NG had high diagnostic sensitivity and specificity for CT and NG. However, more evidence is required to confirm that Xpert CT/NG might serve as the primary method for detecting CT and NG and even the gold standard for diagnosis in the future., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Tian-Ao Xie et al.)

Mean sensitivity (MS) of tree ring is a key index representing the sensitivity of tree rings to climate. Understanding the variation of MS and its influencing factors at a large area is helpful to understand the interaction between tree growth and climate. We used 573 tree-ring width chronologies in Asia from the International Tree Ring Date Bank (ITRDB) to examine the variation of tree-ring sensitivity and potential influencing factors. The results showed that the MS of trees was high in the arid regions and cold regions. Precipitation was more important than temperature in diriving MS. Consistent with the pattern of up-down-up for precipitation, MS showed a down-up-down fluctuation with increasing altitude, indicating that precipitation affected by altitude was a key climate factor for the MS. MS had great difference due to different physiological traits among tree species. Light-adapted species, such as Juniperus przewalskii and Pinus gerardiana, had high MS due to drought tole-rance. Shade-adapted species, such as Picea and Abies, had low MS. Old trees may have high MS.

Pulmonary atresia witha ventricular septal defect and major aortopulmonary collateral arteries is an extremely rare congenital disorder characterized by a high risk of maternal mortality. We present the case of a 24-year-old primigravid woman with uncorrected pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arterieswho presented at 35+5 weeks' gestation. Based on the pathophysiology of the congenital cardiac lesion, cesarean delivery was performed under epidural anesthesia under management by a multidisciplinary team. This report highlights the anesthesia management of a rare uncorrected congenital cardiac lesion for cesarean delivery., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Non-canonical amino acids are finding increasing use in basic and applied research. Proteins that evolved naturally for biological function did so by exploiting the chemistries of the canonical amino acids; however, when proteins are repurposed for biomedical and pharmacological applications, they are often subject to conditions different from those characteristic of their original biological environments. Non-canonical amino acids can impart properties that are inaccessible within canonical protein sequence space, and can thereby lead to improved or new functionality. We describe simple methods for global replacement of canonical amino acids by their non-canonical counterparts in recombinant proteins made in high yield in bacterial expression hosts. These methods can be used to engineer both chemical and physical properties of recombinant proteins.

Adherence to medication and treatment regimen continues to rank as one of the major clinical problems worldwide. Many of the currently available strategies lack the personalised interaction needed in order to effectively connect with the patients. Our solution is to develop an interactive avatar-based reminder application to simulate a human carer to provide customised conversations with the aim of improving adherence and satisfaction. The results of our initial trial showed that information and communication provided by the avatar were useful in reminding participants to take their health supplements. This paper discusses the importance of personalised communication and information in improving adherence and satisfaction, what we have learned from our initial trial with the avatar-based reminder application, and our proposed modifications for our next trial.

Daily injections of insulin provide lifesaving benefits to millions of diabetics. But currently available prandial insulins are suboptimal: The onset of action is delayed by slow dissociation of the insulin hexamer in the subcutaneous space, and insulin forms amyloid fibrils upon storage in solution. Here we show, through the use of noncanonical amino acid mutagenesis, that replacement of the proline residue at position 28 of the insulin B-chain (ProB28) by (4S)-hydroxyproline (Hzp) yields an active form of insulin that dissociates more rapidly, and fibrillates more slowly, than the wild-type protein. Crystal structures of dimeric and hexameric insulin preparations suggest that a hydrogen bond between the hydroxyl group of Hzp and a backbone amide carbonyl positioned across the dimer interface may be responsible for the altered behavior. The effects of hydroxylation are stereospecific; replacement of ProB28 by (4R)-hydroxyproline (Hyp) causes little change in the rates of fibrillation and hexamer disassociation. These results demonstrate a new approach that fuses the concepts of medicinal chemistry and protein design, and paves the way to further engineering of insulin and other therapeutic proteins.

Non-adherence to medication and treatment regimens is considered as a major issue in the healthcare industry as it can lead to negative consequences. Various strategies have been applied to improve adherence, however many of these strategies lack the interaction and personalisation-aspect which has been shown to be crucial to the patients. This paper discusses the importance of personalised interaction in improving patients' medication adherence, and the characteristics needed in an avatar to simulate such human-human interactions.

Taiwan had been considered rabies free since 1961. In 2013, Taiwan confirmed the detection of rabies virus in wild Taiwan ferret-badgers. Up to December 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. Genetic analysis indicates that TFBV is distinct from all other known rabies virus variants. To date, ferret-badger rabies is known to occur only in China and Taiwan. The temporal dynamics of rabid ferret-badgers in Taiwan suggests that the epizootic appears to have subsided to enzootic levels as of December 2014. According to the current epidemiologic data, there is only one TFBV strain in Taiwan. TFBV is still sequestered to the mountainous regions. Humans are at risk mainly through exposure to the virus from infected domestic meso-carnivores, mainly dogs and cats. Dogs and cats should be vaccinated to establish an immunological barrier to stop the spread of the disease from mountainous regions to domestic meso-carnivores., (© 2015 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.)

Poor adherence to medication can lead to negative health outcomes and increased financial burdens. We present a literature review on electronic medication reminders used for medication adherence in self care settings, to identify current and possible future trends. A structured PubMed search based on extracted MeSH terms provided a total of 45 publications which were identified as most relevant. Three main categories of electronic solutions were identified: mobile phone reminders, in-home electronic reminder devices, and portable reminder devices.

Fifteen ferret badgers (Melogale moschata subaurantiaca), collected 2010-13 and stored frozen, were submitted for rabies diagnosis by direct fluorescent antibody test and reverse transcription PCR. We detected seven positive animal samples, including some from 2010, which indicated that the ferret badger population in Taiwan had been affected by rabies prior to 2010.

Tree-ring studies in China have achieved great advances since the 1990s, particularly for the dendroclimatological studies which have made some influence around the world. However, because of the uneven development, limited attention has been currently paid on the other branches of dendrochronology. We herein briefly compared the advances of dendrochronology in China and of the world and presented suggestions on future dendrochronological studies. Large-scale tree-ring based climate reconstructions in China are highly needed by employing mathematical methods and a high quality tree-ring network of the ring-width, density, stable isotope and wood anatomy. Tree-ring based field climate reconstructions provide potentials on explorations of climate forcings during the reconstructed periods via climate diagnosis and process simulation.

The electrophoresis of a soft particle comprising a rigid core and a charged porous membrane layer in a narrow space is modeled. This simulates, for example, the capillary electrophoresis of biocolloids such as cells and microorganisms, and biosensor types of device. We show that, in addition to the boundary effect, the effects of double-layer polarization (DLP) and the electroosmotic retardation flow can be significant, yielding interesting electrophoretic behaviors. For example, if the friction coefficient of the membrane layer and/or the boundary is large, then the DLP effect can be offset by the electroosmotic retardation flow, making the particle mobility to decrease with increasing double layer thickness, which is qualitatively consistent with many experimental observations in the literature, but has not been explained clearly in previous analyses. In addition, depending upon the thickness of double layer, the friction of the membrane layer of a particle can either retard or accelerate its movement, an interesting result which has not been reported previously. This work is the first attempt to show solid evidence for the influence of a boundary on the effect of DLP and the electrophoretic behavior of soft particles. The model proposed is verified by the experimental data in the literature. The results of numerical simulation provide valuable information for the design of bio-analytical apparatus such as nanopore-based sensing applications and for the interpretation of relevant experimental data., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Recent studies have documented the association of mesenteric lymphatic route with adult respiratory distress syndrome and multiple organ failure after hemorrhagic shock. However, the mediators and mechanisms of the toxic effects of mesenteric lymph remain unclear. This study aimed to identify mediators or biomarkers in the mesenteric lymph through comparative proteomic analysis. Fourteen mature male Sprague-Dawley rats were randomly divided and subjected to trauma (laparotomy) plus hemorrhagic shock or trauma plus sham shock. Mesenteric lymph samples were collected before shock and at 3 h after resuscitation from hemorrhagic shock (or sham shock). To investigate changes in proteome profiles between preshock and 3-h postshock (or 3-h post-sham shock) mesenteric lymph samples, two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were performed. We found a more than 2-fold change in abundance of 31 protein spots in the lymph samples. Mass spectrometry analyses identified 12 distinct proteins. Four proteins were consistently upregulated in the 3-h postshock lymph samples, including serum albumin precursor, two isoforms of cytoplasmic actin, complement C3 precursor, and major urinary protein precursor. Two proteins, including haptoglobin and one unidentified protein, were consistently downregulated. The deregulation of these proteins was confirmed by Western blots. Most of these altered proteins are functionally implicated in tissue inflammation. The findings of this study provide a starting point for investigating the functions of these proteins in hemorrhagic shock-induced lung injury and hold great promise for the development of potential therapeutic interventions.

Introduction: Hyperuricemia in the general population remains controversial, in terms of it being considered a risk factor for chronic kidney disease (CKD). Within this context, we evaluated the effects of hyperuricemia on renal function in older Taiwanese adults., Methods: From January 2002 to December 2006, we conducted a community-based medical screening program involving 31,331 subjects older than 40 years. According to the National Kidney Foundation guidelines, stage 3 to 5 patients with CKD were included for analysis. Age, body mass index, systolic blood pressure, fasting plasma glucose, triglyceride, cholesterol and proteinuria were considered potential confounders., Results: Participants with hyperuricemia tended to have higher systolic blood pressure, sugar levels, body mass index, and cholesterol and triglyceride levels but lower estimated glomerular filtration rate (eGFR) levels; eGFR negatively correlated with serum uric acid level. By using multiple logistic regression models before and after adjusting for any confounding factors, we noted that participants with hyperuricemia had a 4.036-fold (odds ratios = 4.036) and 3.649-fold (odds ratios = 3.649) increased risk for CKD, respectively, compared with the control group. We used multiple linear regression analysis to examine the association of serum uric acid level and eGFR at different stages of CKD; significance was found only in participants with stage 3 CKD and not in participants with stages 4 or 5., Conclusions: Hyperuricemia is an independent risk factor for CKD in middle-aged and elderly Taiwanese adults. Thus, an effective screening program that identifies people with hyperuricemia is warranted.

Background: The prevalence and incidence of chronic kidney disease (CKD) are relatively high in Taiwanese patients than in patients of other countries, particularly in the older age groups. Dyslipidemia in patients with CKD has been recognized as a risk factor for disease progression but the role of triglycerides (TGs) remains controversial. With this regard, we evaluated the effects of hypertriglyceridemia on renal function in Taiwanese adults (aged >or=40 years)., Methods: From January 2002 to December 2006, we conducted a community-based medical screening program in Chiayi County with 18,422 subjects (aged >or=40 years). The CKD was defined as an estimated glomerular filtration rate of <60 mL min 1.73 m. Age, body mass index, systolic blood pressure, fasting plasma glucose, and serum total cholesterol were considered as potential confounders., Result: The CKD was prevalent in 24.2% of the middle-aged and elderly population. By using multiple logistic regression models, we determined that old age and elevated levels of body mass index, systolic blood pressure, fasting plasma glucose, and cholesterol were associated with CKD. The adjusted odds ratios of CKD in participants with serum TG >==200 mg/dL was 1.901 (95% confidence interval: 1.07-3.36; P < 0.05) and in participants with serum TG > 500 mg/dL it increased to 2.205 (1.33-3.64, P < 0.05)., Conclusion: Hypertriglyceridemia is an independent risk factor for CKD in Taiwanese adults. Thus, an effective screening program that identifies people with hypertriglyceridemia is warranted.

The aim of the present study was to investigate the role of p38 MAPK in the renal tubular epithelial-mesenchymal transition (TEMT) induced by high glucose. In in vivo study, the rats were randomly divided into control (C), diabetes mellitus (DM) and insulin-treated DM groups. Immunohistochemical staining and Western blot were employed to determine the expression of p38 MAPK and p-p38 MAPK protein in renal cortex of rats. In in vitro study, primary renal tubular epithelial cells (PTECs) were cultured with normal glucose (5.5 mmol/L), high glucose (20 mmol/L D-glucose), high osmolality (20 mmol/L D-mannitol) and SB202190 (a p38 MAPK inhibitor) plus high glucose respectively for 72 h. The expressions of p38 MAPK, p-p38 MAPK, Snail1, transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA) and E-cadherin protein and mRNA were detected by immunocytochemical staining, Western blot and RT-PCR. The p38 MAPK and p-p38 MAPK were specifically upregulated by high glucose in both in vivo and in vitro studies. The p38 MAPK activation was abolished by insulin controlling hyperglycemia to normal level in DM rats and inhibited dramatically by SB202190 in high glucose-cultured PTECs. The protein and mRNA of alpha-SMA were markedly increased in PTECs cultured with high glucose and were 12-fold and 8-fold respectively over that in the normal glucose, which were significantly suppressed by SB202190. SB202190 down-regulated the high glucose-induced Snail1 protein expression in PETCs, and restored partly the depression of E-cadherin protein and mRNA. These results suggest that p38 MAPK mediates high glucose-induced TEMT via transcription factor Snail1.

The present study was aimed to explore the expressions of transforming growth factor-β1 (TGF-β1) and Snail1 in renal tissues of diabetic rats, and their role in tubular epithelial-mesenchymal transition (TEMT). Induced diabetic rats were randomly divided into 2-, 4-, 8-, 12-, 16-, 20-, 24-week and 16wA, 20wA, 24wA groups. The rats in 16wA, 20wA and 24wA groups were treated with insulin to control blood glucose to the normal level from the 13th week. The age-matched rats were set as controls. Blood glucose, 24-hour urine protein, serum creatinine (Scr), kidney index of rats were measured. PAS staining was used to observe the renal pathological changes. Immunohistochemical staining and (or) Western blot were employed to determine the expressions of TGF-β1, Snail1, E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin (FN) proteins. The expressions of Snail1 and E-cadherin mRNAs in renal cortex were examined by RT-PCR. Blood glucose, 24-hour urine protein, Scr and kidney index increased remarkably in diabetic rats as compared with those in the control groups (P<0.05, P<0.01) and insulin-treated rats (P<0.01). TGF-β1 and Snail1 protein expressions could not be detected by immunohistochemical staining in the normal renal tissues, however, the strongly positive staining was observed in diabetic rat renal tubules. A time-dependent loss of TGF-β1 and Snail1 expressions was detected in the kidney of insulin-treated rats. In diabetic rats tubular α-SMA positive staining was seen at the 16th week. E-cadherin expression was lost in diabetic rats. The expressions of TGF-β1, Snail1 proteins and Snail1 mRNA were significantly up-regulated in diabetic rats, while down-regulated in insulin-treated rats (P<0.01). The expressions of E-cadherin protein and mRNA in the cortex were contrary to the expressions of TGF-β1 and Snail1. Therefore, TGF-β1 and Snail1 are possibly involved in the pathogenesis of TEMT in diabetic nephropathy rats.

Objective: To study the effect of lipid-regulating function for extracts and their prescriptions from Semen Cassiae and Crataegus pinnatifida Bge. var. major N. E. Br. on serum lipid of hyperlipidema mice., Methods: 1 week after being administered with extract of Semen Cassiae, extract of Crataegus pinatifida Bge. var. major N. E. Br. and different proportion mixture of them (180 mg/ kg), mice were treated with ip 75% fresh yelkfluid. The contents of TC, TG, HDL-C, LDL-C, apo AI and apo B were observed after 24 h., Results: The levels of TC, TG, LDL-C and apoB in therapeutic group were lower than those in hyperlipidemic model group (P < 0.05, P < 0.01), especially in different proportion mixture groups., Conclusion: Lipid-regulating active part of Semen Cassiae and Crataegus pinatifida Bge. var. major N. E. Br. might inhibit hyperlipidemic formation, and mixture groups were more effective than those of its single extract.

Various methods have been explored to enhance antibody-based cancer therapy. The use of multivalent antibodies or fragments against tumor antigens has generated a great deal of interest, as various cellular signals, including induction of apoptosis, inhibition of cell growth/survival, or internalization of the surface molecules, can be triggered or enhanced on extensive cross-linking of the target/antibody complex by the multivalent form of the antibody. The goal of the studies reported here was to develop multivalent antibody constructs via grafting of antibody molecules onto liposome membranes to enhance antibody activity. Using trastuzumab and rituximab as examples, up to a 25-fold increase in the antibody potency in cell viability assay was observed when the antibodies were presented in the multivalent liposome formulation. Key cell survival signaling molecules, such as phosphorylated Akt and phosphorylated p65 nuclear factor-kappaB, were down-regulated on treatment with multivalent liposomal trastuzumab and liposomal rituximab, respectively. Potent in vivo antitumor activity was shown for liposomal trastuzumab. The data presented here showed the potential of liposome technology to enhance the therapeutic effect of antibodies via a mechanism that modulates cell survival through clustering of the target/antibody complex.