Synergistic controls of water column stability and groundwater phosphate on coastal algal blooms.

Algal blooms have been identified as one major threat to coastal safety and marine ecosystem functioning, but the dominant mechanism regulating the formation of algal blooms remains controversial, ranging from physical control (via water column stability), the chemical control (via coastal nutrients) to joint control. Here we leveraged the unique data collected in the Hong Kong water over the annual cycle and past three decades, including direct observations of algal blooms and coastal nutrients and process model output of water column stability, and evaluated the differential competing hypotheses in regulating algal blooms. Our results demonstrate that the joint mechanism rather than the single mechanism effectively predicts all algal blooms. Meanwhile, we observed that the adequate nutrients (phosphate, PO43-) significantly originate from coastal groundwater. The production and fluctuation of PO43- in beach aquifers are primarily governed by groundwater temperature, leading to a sustained and sufficient supply of PO43- in a low groundwater temperature environment. Furthermore, along with submarine groundwater discharge (SGD), the ongoing release of PO43- in groundwater enters coastal waters and serves as sufficient nourishment for promoting algal blooms in coastal areas. These results highlight the importance of both physical and chemical mechanisms, as well as SGD, in regulating coastal algal blooms. These findings have practical implications for the prevention of coastal algal blooms and provide insights into mariculture, water security, and the sustainability of coastal ecosystems.

Storm accelerated subsurface Escherichia coli growth and exports to coastal waters.

Storm significantly deteriorates coastal water fecal pollution now and beyond. Questions relating to storm exerting on coastal water safety are often intertwined with both surface water and subsurface processes. Stormwater runoff is a vital metric for coastal water fecal pollution under current cognition, while the controls of subsurface system remain unclear. Here, this study leveraged two time-series field data collected in a sandy beach during storm and non-storm periods to probe subsurface Escherichia coli (E. coli) growth and exports to coastal waters under storm events. Results demonstrated that storm events can not only stimulate subsurface E. coli growth, but also accelerate subsurface E. coli exports into the receiving water. Storm-intensified rainfall injected more oxygenous rainwater in the shallow groundwater, subsequently stimulating subsurface E. coli growth. Storm-strengthened wave energy was responsible for accelerating subsurface E. coli exports through enhanced wave-induced recirculated seawater. This study proposes a new insight for the stress of storm events on microbial pollution in coastal waters. The findings are constructive to the prevention of beach ecosystem pollution and can pave the way for coastal safety management to future extreme weather.

Effective coastal Escherichia coli monitoring by unmanned aerial vehicles (UAV) thermal infrared images.

Coastal Escherichia coli (E. coli) significantly influence ocean safety and public health, thus requiring an effective E. coli pollution monitoring. However conventional detection relying on manual field sampling is time-consuming. Here, this study established an E. coli estimation model based on thermal remote sensing of unmanned aerial vehicles (UAV). This model was developed against one-year comprehensive field work in a representative sandy beach and further validated against 50 beaches in Hong Kong to evaluate its applicability. The estimated E. coli concentrations were in a reliable agreement with direct measurements. For this model, this study deployed the radon-222 (222Rn) as a bridging tracer to couple UAV thermal images and coastal E. coli concentrations. Coastal 222Rn can be reflected on the UAV thermal images, and there was a good positive correlation between the 222Rn activity and coastal E. coli concentration via one-year field data. Hence, coupling the 222Rn activity estimated from UAV thermal images and the relationship between 222Rn and E. coli, this study can readily monitor coastal E. coli by UAV. These findings highlighted that UAV technology is an effective approach to measure the E. coli concentrations and can further pave the way for an efficient coastal E. coli monitoring and public health risk warning.

Delineating E. coli occurrence and transport in the sandy beach groundwater system by radon-222.

Fecal pollution poses a global threat to environmental safety and ecosystem, but the mechanism of microbial transport and occurrence in the beach groundwater system is still poorly explored. Here, we leveraged one-year field data of Escherichia coli (E. coli) and radon-222 (222Rn) and found that E. coli occurrence and transport in the sandy beach groundwater system can be delineated by 222Rn. The underlying mechanism behind this phenomenon is due to similar half-lives of 222Rn and E. coli in the sandy beach groundwater system. Thus, the unique relationship between 222Rn and E. coli can provide additional critical context to the microbial water quality assessments and ecosystem resilience. Also, the beach aquifer in this study is found to be a vital compartment for E. coli removal. The net E. coli removal/production capacity is identified to be highly impacted by submarine groundwater discharge. Finally, a conceptual model is constructed for a better understanding of the occurrences and characteristics of E. coli and 222Rn at multiple spatial scales. These findings are constructive to mitigate the hazardous influences of microbe on water quality, especially in recreational sandy beaches and mariculture zones.

Remote sensing of coastal algal blooms using unmanned aerial vehicles (UAVs).

The explosive growth of phytoplankton under favorable conditions in subtropical coastal waters can lead to water discolouration and massive fish kills. Traditional water quality monitoring relies on manual field sampling and laboratory analysis of chlorophyll-a (Chl-a) concentration, which is resources intensive and time consuming. The cloudy weather of Hong Kong also precludes using satellite images for algal blooms monitoring. This study for the first time demonstrates the use of an Unmanned Aerial Vehicle (UAVs) to quantitatively map surface water Chl-a distribution in coastal waters from a low altitude. An estimation model for Chl-a concentration from visible images taken by a digital camera on a UAV has been developed and validated against one-year field data. The cost-effective and robust technology is able to map the spatial and temporal variations of Chl-a concentration during an algal bloom. The proposed method offers a useful complement to traditional field monitoring for fisheries management.

Two-decade variations of fresh submarine groundwater discharge to Tolo Harbour and their ecological significance by coupled remote sensing and radon-222 model.

Although submarine groundwater discharge (SGD) comprises an insignificant proportion of the global hydrologic cycle, it contributes significantly to chemical fluxes into the coastal waters due to concentrated constituents in coastal groundwater. Large nutrient loadings derived from SGD can lead to a series of environmental and ecological problems such as algal blooms, resulting in water discoloration, severe dissolved oxygen depletion, and eventually beach closures and massive fish kills. Previous studies have demonstrated the relationship between algal blooms and SGD obtained from direct measurement with seepage meters or from geo-tracer (i.e., radon and radium) based models; these traditional methods are time-consuming, laborious and point monitoring, and can hardly achieve a high spatiotemporal resolution SGD estimation, which is vital in revealing the effects of SGD to algal blooms over a long period. Alternatively, remote sensing methods for high spatiotemporal resolution SGD localization and quantification are applicable and effective. The temperature difference or anomaly between groundwater and coastal water extracted from satellite thermal images can be used as the indicator to localize and detect SGD especially its fresh component (or fresh SGD). In this study, multi-year (2005, 2011 and 2018) radon samples in Tolo Harbour were used to train regression models between in-situ radon (Rn) activity and the temperature anomaly by Landsat satellite thermal images. The models were used to estimate two-decade variations of fresh SGD in Tolo Harbour. The synergistic analysis between the time series of fresh SGD derived from regression models and high spatiotemporal resolution ecological metrics (chlorophyll-a, algal cell counts, and E.coli) leads to the findings that the increase of the fresh SGD associated with high nutrient concentrations is witnessed 10-20 days before the observations of algal bloom events. This study makes the first attempt to demonstrate the strong relation between the SGD and algal blooms over a vicennial span, and also provides a cost effective and robust technique to estimate SGD on a bay scale.

Collagen microsphere based 3D culture system for human osteoarthritis chondrocytes (hOACs).

The current study aims to evaluate collagen microencapsulation as an in vitro 3D culture platform for human osteoarthritic chondrocytes (hOACs), and to exemplify its feasibility in screening potential disease modifying factors. We first isolated and expanded hOACs from osteoarthritis (OA) cartilage samples harvested from multiple patients during total knee replacement (TKR) surgery. These cells were microencapsulated into collagen microspheres for subsequent 3D cultures. The change in chondrocyte phenotypes and OA phenotype was evaluated over time, using 2D monolayer culture and traditional 3D pellet culture as controls. The hOACs in the 3D collagen microsphere model resumed their in vivo phenotypes when compared to 2D monolayer. When compared with the 3D pellet model, the 3D hOAC-collagen microsphere model better recapitulated the OA phenotypes. We further demonstrated the responsiveness of the microencapsulated hOACs towards a number of external factors altering the chondrogenic phenotype, corroborating with previous studies. The hOAC encapsulated collagen microspheres better maintained the hOAC phenotype than the traditional 2D monolayer and 3D pellet cultures. The feasibility to use this hOAC-collagen microsphere in vitro model as a screening platform for disease-modifying agents has been demonstrated, contributing to future development of OA therapeutics.

Transoral vertical ramus osteotomy fixed with Kirschner pins.

Transoral vertical ramus osteotomy (VRO) has been condemned because the condyle has the potential to sag, and because it needs lengthy maxillomandibular fixation. We have therefore introduced a simple method of fixation, and examined its effectiveness and complications. After the osteotomy, the proximal and distal segments are trimmed to adapt to each other. Four Kirschner (K) pins 0.9mm in diameter are inserted percutaneously from the proximal to the distal segment while the condyle is positioned in the glenoid fossa. This is followed by a brief period of maxillomandibular fixation. We have reviewed the records of 95 patients who had unilateral or bilateral vertical ramus osteotomy fixed with K pins, after which the mean (SD) period of fixation was 19 (11) days. Fixation failed in two patients because excursion of the jaw was either too heavy or too early. The fixations were redone. All other fixations remained stable, including the 20 dual-jaw procedures in which VRO preceded maxillary osteotomy. The mean (SD) maximal mouth opening at final follow-up was 44 (7) mm, and in only one patient was it less than 30mm. Numbness of the lip or chin developed in seven patients, five of whom had other anterior mandibular procedures. Four patients had discomfort on palpation of the site of the pins, and one required removal. The new method was effective, and resulted in few complications within its limitations.

KLF10 loss in the pancreas provokes activation of SDF-1 and induces distant metastases of pancreatic ductal adenocarcinoma in the KrasG12D p53flox/flox model.

Krüppel-like transcription factor 10 (KLF10), also named as TIEG1, plays essential roles in mediating transforming growth factor beta (TGFß) signaling and has been shown to function as a tumor suppressor in multiple cancer types. However, its roles in mediating cancer progression in vivo have yet to be fully characterized. Here, we have employed two well-characterized Pdx-1CreLSL-KrasG12D and Pdx-1CreLSL-KrasG12Dp53L/L pancreatic cancer models to ablate KLF10 expression and determine the impact of KLF10 deletion on tumor development and progression. We show that loss of KLF10 cooperates with KrasG12D leading to an invasive and widely metastatic phenotype of pancreatic ductal adenocarcinoma (PDAC). Mechanistically, loss of KLF10 in PDAC is shown to increase distant metastases and cancer stemness through activation of SDF-1/CXCR4 and AP-1 pathways. Furthermore, we demonstrate that targeting the SDF-1/CXCR4 pathway in the context of KLF10 deletion substantially suppresses PDAC progression suggesting that inhibition of this pathway represents a novel therapeutic strategy for PDAC treatment.

APC haploinsufficiency coupled with p53 loss sufficiently induces mucinous cystic neoplasms and invasive pancreatic carcinoma in mice.

Adenomatous polyposis coli (APC), a tumor-suppressor gene critically involved in familial adenomatous polyposis, is integral in Wnt/ß-catenin signaling and is implicated in the development of sporadic tumors of the distal gastrointestinal tract including pancreatic cancer (PC). Here we report for the first time that functional APC is required for the growth and maintenance of pancreatic islets and maturation. Subsequently, a non-Kras mutation-induced premalignancy mouse model was developed; in this model, APC haploinsufficiency coupled with p53 deletion resulted in the development of a distinct type of pancreatic premalignant precursors, mucinous cystic neoplasms (MCNs), exhibiting pathomechanisms identical to those observed in human MCNs, including accumulation of cystic fluid secreted by neoplastic and ovarian-like stromal cells, with 100% penetrance and the presence of hepatic and gastric metastases in >30% of the mice. The major clinical implications of this study suggest targeting the Wnt signaling pathway as a novel strategy for managing MCN.

The interaction of serum testosterone levels and androgen receptor CAG repeat polymorphism on the risk of erectile dysfunction in aging Taiwanese men.

Testosterone has been found to play important roles in men's sexual function. However, the effects of testosterone can be modulated by androgen receptor (AR) CAG repeat polymorphism. It could also contribute to the risk of erectile dysfunction (ED). The aim of this study is to evaluate the interaction of serum testosterone levels and AR CAG repeat polymorphism on the risk of ED in aging Taiwanese men. This cross-sectional data of Taiwanese men older than 40 years were collected from a free health screening held between August 2010 and August 2011 in Kaohsiung city, Taiwan. All participants completed a health questionnaires included five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptoms Score, received a detailed physical examination and provided 20 cm3 whole blood samples for biochemical and genetic evaluation. The IIEF-5 was used to evaluate ED. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Finally, 478 men with the mean age of 55.7 ± 4.8 years were included. When TT levels were above 330 ng/dL, the effect of testosterone level on erectile function seemed to reach a plateau and a significantly negative correlation between AR CAG repeat length and the score of IIEF-5 was found (r = -0.119, p = 0.034). After adjusting for other covariates, the longer AR CAG repeat length was still an independent risk factor for ED in subjects with TT above 330 ng/dL (p = 0.006), but not in TT of 330 ng/dL or below. In conclusion, both serum testosterone levels and AR CAG repeat polymorphism can influence erectile function concomitantly. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing ED.

Microdosimetry spectra and relative biological effectiveness of 15 and 30MeV proton beams.

The relative biological effectiveness (RBE) of high-energy protons has been well investigated, but estimates of RBE for lower-energy (<40MeV) protons are scarce. In the present work, measurements were made of the lineal energy spectra using a home-made miniature tissue-equivalent proportional counter for 15 and 30MeV protons from the TR 30/15 cyclotron. Monte Carlo simulations were made for the same spectra using the FLUKA code. These spectra were coupled to several biological models to evaluate the RBE for various biological endpoints.

Dopamine D(2)/D(3) receptor binding of [(123)I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging.

INTRODUCTION: Epidepride is a compound with an affinity in picomolar range for D2/D3 receptors. The aim of this work was designed to investigate the diagnostic possibility of [(123)I]epidepride imaging platform for risperidone-treatment chronic MK-801-induced rat schizophrenia model. METHODS: Rats received repeated administration of MK-801 (dissolved in saline, i.p., 0.3 mg/kg/day) or saline for 4 weeks. After 1-week administration of MK-801, rats in MK-801+risperidone group received risperidone (0.5 mg/kg/day) intraperitoneally 15 min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [(123)I]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of specific binding in striatum and midbrain. RESULTS: Risperidone reversed chronic MK-801-induced decrease in social interaction duration. IHC and ELISA analysis showed consistent results that chronic MK-801 treatment significantly decreased striatal and midbrain D2R expression but repeated risperidone administration reversed the effect of MK-801 treatment. In addition, [(123)I]epidepride nanoSPECT/CT neuroimaging revealed that low specific [(123)I]epidepride binding ratios caused by MK-801 in striatum and midbrain were statistically alleviated after 1- and 2-week risperidone administration, respectively. CONCLUSIONS: We established a rat schizophrenia model by chronic MK-801 administration for 4 weeks. [(123)I]Epidepride nanoSPECT neuroimaging can trace the progressive alteration of D2R expression in striatum and midbrain caused by long-lasting MK-801 treatment. Besides diagnosing illness stage of disease, [(123)I]epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model.

Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease.

OBJECTIVE: Epicardial and abdominal adipose tissues have recently been demonstrated to play inflammatory roles in coronary atherosclerosis. We sought to compare tissue adipocytokine levels of these two anatomically distinct adipose stores in patients with and without coronary artery diseases (CAD). DESIGN: Samples of abdominal and epicardial fat tissues were harvested to detect the levels of adipocytokines and proinflammatory mediators. SUBJECTS: Forty-six patients with CAD who underwent coronary artery bypass surgery and 12 non-CAD control subjects who underwent other types of open-heart surgery. MEASUREMENTS: Tissue levels of adipocytokines (adiponectin, leptin and visfatin) and proinflammatory mediators (tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)) were determined by enzyme-linked immunosorbent assay. RESULTS: Tissue levels of TNF-alpha, IL-6, leptin and visfatin were significantly higher in CAD patients relative to control subjects. In addition, significantly higher tissue levels of these four cytokines from abdominal fat depots were found compared to those from epicardial fat in CAD patients. Conversely, in comparison with control subjects, tissue levels of adiponectin were significantly reduced in CAD patients with a significantly lower tissue levels of abdominal than epicardial fat depots demonstrated. CONCLUSION: Abdominal adiposity may play more significant role than epicardial fat in the pathogenesis of coronary atherosclerosis.

Recognition and capture of breast cancer cells using an antibody-based platform in a microelectromechanical systems device.

Cancer is one of the most common diseases afflicting humans. The use of biomarkers specific for tumor cells has facilitated their identification. However, technology has not kept pace with the field of molecular biomarkers, leaving their potential unrealized. Here, we demonstrate the efficacy of recognizing and capturing cancer cells using an antibody-based, on-chip, microfluidic device. A cancer cell capture biochip consisting of microchannels of size 2.0 cm long and 500 microm wide and deep, was etched onto Polydimethylsiloxane. Epithelial membrane antigen (EMA) and Epithelial growth factor receptor (EGFR) were coated on the inner surface of the microchannels. The overall chip measured 2.0 cm x 1.5 cm x 0.5 cm. Normal and tumor breast cells in a phosphate buffered saline (PBS) suspension were flowed through the biochip channels at a rate of 15 microL/min. Breast cancer cells were preferentially captured and identified while most of normal cells passed through. The capture rates for tumor and normal cells were found to be >30% and <5%, respectively. This preliminary cancer cell capture biochip design supports our initial effort of moving a BioMEMS device, from the bench top to the clinic.

Visualization of Rab3A dissociation during exocytosis: a study by total internal reflection microscopy.

Rab3A is a small G protein in the Rab3 subfamily, and is thought to act at late stage of exocytosis. However, the detailed mechanism of its action is not completely understood. To study the role of Rab3A in exocytosis, we used a total internal reflection fluorescence microscope to examine the fluorescence changes of EGFP-Rab3A-labeled and NPY-EGFP-labeled vesicles in PC12 cells upon stimulation. The fluorescence of EGFP-Rab3A-labeled and NPY-EGFP-labeled vesicles decreased while showing different patterns. The NPY-EGFP-labeled vesicles that exocytosed showed a transient fluorescence increase before NPY-EGFP fluorescence disappearance, which represents fusion and NPY release. This transient increase was diminished in cells that co-expressed the GDP-bound Rab3A mutant. The fluorescence of EGFP-Rab3A-labeled vesicles dispersed before disappearance, which represents the dissociation of Rab3A from the vesicles. The dispersion was not found in GTP-bound Rab3A mutant-labeled vesicles. Interestingly, EGFP-Rab3A F59S, a mutant unable to bind rabphilin, dissociates slower from the vesicles than wild type Rab3A and caused a slower release of NPY-EGFP. The results provide direct evidence to support the hypothesis that GTP hydrolysis and rabphilin are involved in Rab3A dissociation from the vesicles and the occurrence of exocytosis.

Microfluidic-based diagnostics for cervical cancer cells.

The use of biomarkers has facilitated the detection of specific tumor cells. However, the technology to apply these markers in a clinical setting has not kept pace with their increasing availability. In this project, we use an antibody-based microfluidics platform to recognize and capture cervical cancer cells. Because HPV-16 infection of cervical cells and up-regulation of alpha6-integrin cell surface receptors are correlated, we utilized alpha6-integrin as a capture antibody bound to the channel surface. Normal human glandular epithelial cells (HGEC), human cervical stromal cells (HCSC) and cervical cancer cells (HCCC) were suspended in PBS and flowed through the system. Greater than 30% of the cancer cells were captured while the capture of the normal cell types was less than 5%. The technique is sensitive and accurate. It is potentially useful in the detection of cervical cancer at all stages, as well as other of cancers with similar characteristics of cell surface antigen expression.

Mass spectra and time-resolved fluorescence spectroscopy of the reaction product of glycine with 1,2-indanedione in methanol.

The reaction products of 1,2-indanedione (a new fluorescent fingerprint reagent) with glycine in methanol, at room temperature have been studied using excitation and emission and time-resolved fluorescence spectroscopy. Gas chromatography-mass spectroscopy (GC/MS) has also been used to determine which compounds are formed. Reaction products were identified using GC/MS as 2-carboxymethyliminoindanone (MW=203 g) and 1,2-di(carboxymethylimino)indane (MW=260 g). Identified compounds show room temperature fluorescence lifetimes of tau(1)=7.69 ns and tau(2)=1.27 ns. It is not clear yet which compound is having fluorescence lifetime of 7.69 ns and which one is showing 1.27 ns.

Characteristics of pyrene phospholipid/gamma-cyclodextrin complex.

Recently, it was demonstrated that gamma-cyclodextrins (gamma-CDs) greatly accelerates transfer of hydrophobic pyrene-labeled and other fluorescent phospholipid derivatives from vesicles to cells in culture (). To understand better the characteristics of this process, we studied the interaction of gamma-CD with pyrene-labeled phosphatidylcholines (PyrPCs) using a variety of physical methods. Either one or both of the acyl chains of PC was labeled with a pyrene moiety (monoPyrPCs and diPyrPCs, respectively), and the length of the labeled chain(s) varied from 4 to 14 carbons. Fluorescent binding assays showed that the association constant decreases strongly with increasing acyl chain length. PyrPC/gamma-CD stoichiometry was 1:2 for the shorter chain species, but changed to 1:3 when the acyl chain length exceeded 8 (diPyrPCs) or 10 (monoPyrPCs) carbons. The activation energy for the formation of diPyr(10)PC/gamma-CD complex was high, i.e., +92 kJ/mol, indicating that the phospholipid molecule has to fully emerge from the bilayer before complex formation can take place. The free energy, enthalpy, and entropy of transfer of monoPyrPC from bilayer to gamma-CD complex were close to zero. The absorption, Fourier transform infrared, and fluorescence spectral measurements and lifetime analysis indicated that the pyrene moiety lies inside the CD cavity and is conformationally restricted, particularly when the labeled chain is short. The acyl chains of a PyrPC molecule seem to share a CD cavity rather than occupy different ones. The present data provide strong evidence that the ability of gamma-CD to enhance intermembrane transfer of pyrene-labeled phospholipids is based on the formation of stoichiometric complexes in the aqueous phase. This information should help in designing CD derivatives that are more efficient lipid carriers then those available at present.

The effects of cidofovir on progressive multifocal leukoencephalopathy: an MRI case study.

MRI was used to study the effects of introducing cidofovir (HPMPC, Vistide) to the antiretroviral therapy of a 33-year-old white man diagnosed as having progressive multifocal leukoencephalopathy (PML) secondary to AIDS. In response to combined cidofovir and antiretroviral therapy he showed significant clinical improvement. MRI showed a decrease in extent of existing lesions, without new ones. Blood chemistry information obtained indicated some involvement of immunologic mechanisms: the CD4:8 ratio showed improvement from an average of 0.08 before treatment to 0.13 during therapy.