Remote Manipulation of TRPV1 Signaling by Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for Specific Cancer Therapy.

Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca2+ influx. However, controllable manipulation of TRPV1 signaling for clinical application has remained elusive due to the challenge in finding a mild and effective method of exerting external stimulus without adverse side effects in living systems. Herein, a TRPV1-targeting near-infrared (NIR) triggered nitric oxide (NO)-releasing nanoplatform (HCuS@PDA-TRPV1/BNN6) based on polydopamine (PDA) coated hollow copper sulfide nanoparticles (HCuS NPs) is developed for specific cancer therapy. Upon NIR irradiation, the NO donor BNN6 encapsulated in NIR-responsive nanovehicles can locally generate NO to activate TRPV1 channels and induce Ca2+ influx. This NIR controlled mode enables the nanoplatform to exert its therapeutic effects below the apoptotic threshold temperature (43°C), minimizing the photothermal damage to normal tissue. Integrating this special NO-mediated therapy with HCuS NPs mediated chemodynamic therapy, the designed nanoplatform exhibits a boosted anticancer activity with negligible systematic toxicity. Together, this study provides a promising strategy for site-specific cancer therapy by spatiotemporally controlled activation of surface ion channels, thus offering a solution to an unmet clinical need in cancer treatment.

Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor.

Tumor microenvironment (TME) with the particular features of severe hypoxia, insufficient endogenous H2O2, and overexpression of glutathione (GSH) markedly reduced the antitumor efficacy of monotherapy. Herein, a TME-responsive multifunctional nanoplatform (Bi2S3@Bi@PDA-HA/Art NRs) was presented for synergistic photothermal therapy (PTT), chemodynamic therapy (CDT), and photodynamic therapy (PDT) to achieve better therapeutic outcomes. The Z-scheme heterostructured bismuth sulfide@bismuth nanorods (Bi2S3@Bi NRs) guaranteed excellent photothermal performance of the nanoplatform. Moreover, its ability to produce O2 and reactive oxygen species (ROS) synchronously could relieve tumor hypoxia and improve PDT outcomes. The densely coated polydopamine/ammonium bicarbonate (PDA/ABC) and hyaluronic acid (HA) layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ "bomb-like" release of Art. The CDT treatment was achieved by activating the released Art through intracellular Fe2+ ions in an H2O2-independent manner. Furthermore, decreasing the glutathione peroxidase 4 (GPX4) levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs. Owing to the synergistic effect, this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo. Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.

Genetic changes in refractory relapsed acute myeloid leukemia with NPM1 mutation: A case report.

BACKGROUND: Acute myeloid leukemia is often associated with gene mutation or chromosome abnormality, which is an important factor affecting prognosis. The 5-year survival rate of patients with acute myeloid leukemia without hematopoietic stem cell transplantation is low. For patients who only received chemotherapy and whose first remission lasted > 5 years, there are few reports of gene spectrum changes between relapse and initial diagnosis. CASE SUMMARY: We report a 41-year-old woman who presented to our hospital with complaints of dizziness, poor appetite and wasting. She was diagnosed with acute myelomonocytic leukemia (M4b) with NPM1 mutation and only received chemotherapy. Her first remission lasted > 5 years. New genetic variants were detected upon relapse that may have been related to relapse and chemotherapy resistance. CONCLUSION: Mutations in WT1 (R394fs/A387fs)/PTPN11 T73I/ETV6 S350P and JAK2 W659R may be related to relapse and chemotherapy resistance in acute myeloid leukemia.

Electrocatalysis of Copper Sulfide Nanoparticle-Engineered Covalent Organic Frameworks for Ratiometric Electrochemical Detection of Amyloid-ß Oligomer.

Amyloid-ß oligomer (AßO) is widely regarded as a reliable biomarker for the early diagnosis of Alzheimer's disease (AD). In this study, a signal on-off ratiometric electrochemical immunosensor has been developed for ultrasensitive detection of AßO. To achieve the dual-signal ratiometric strategy, ultrasmall copper sulfide nanoparticle-engineered covalent organic framework hybrid nanocomposites (CuS@COFs) were utilized as excellent electrocatalysts toward hydroquinone (HQ) oxidation to produce detectable signals. Meanwhile, electroactive thionine (Thi) and Aß antibody-modified gold nanoparticles (Thi-AuNPs-Ab bioconjugates) were designed as another electrochemical indicator. Based on these two signals, an ultrasensitive sandwich-like electrochemical immunosensor was established for AßO detection. The introduction of AßO resulted in a remarkable decline in the electrochemical signal of HQ but an increase in the signal of Thi. Under optimum conditions, the ratios between the double signals (IThi/IHQ) showed a proportional linear relationship with the AßO concentration (1 pM-1 µM) with a low detection limit of 0.4 pM (S/N = 3), and the biosensor was able to determine the content of AßO in real cerebrospinal fluid samples with satisfactory results. The ratiometric strategy proposed in our study offers a sensitive and efficient approach for early diagnosis of AD, and this work will promote the further applications of engineered COFs in electrochemical sensors.

Ion channel-targeting near-infrared photothermal switch with synergistic effect for specific cancer therapy.

Despite significant achievement in chemotherapy, the off-target actions and low pharmaceutical selectivity of the therapeutic agents still limit their clinical efficacy. Herein, a multifunctional nanoplatform which integrates chemotherapy, chemodynamic therapy (CDT) and photoactivation of TRPV1 channels has been successfully established for specific cancer therapy. Polydopamine (PDA) coated hollow prussian blue nanocages (hPBNCs) are used as the photothermal switches and drug carriers for loading chemotherapeutic drug, doxorubicin (Dox). Conjugating with the TRPV1 antibodies enables the nanoplatform to bind specifically to TRPV1 channels on the plasma membrane of the TRPV1-positive cancer cells and then activate them by local heating upon NIR irradiation, leading to the over-influx of Ca2+. Critically, the laser irradiation can be carefully controlled to not only open the TRPV1 channels but also avoid burning of tumors by hyperthermia. Moreover, the exposed hPBNCs in the acidic tumor cells can decompose endogenous H2O2 into ˙OH by Fenton reaction to realize CDT, which further aggravates cancer cell apoptosis. Together with the chemotherapy caused by Dox, our nanoplatform displays an enhanced anticancer effect both in vitro and in vivo. Our work provides a powerful means for site-specific cancer synergetic therapy with high spatial and temporal resolution.

Mitochondria-targeting multifunctional nanoplatform for cascade phototherapy and hypoxia-activated chemotherapy.

Despite considerable progress has been achieved in hypoxia-associated anti-tumor therapy, the efficacy of utilizing hypoxia-activated prodrugs alone is not satisfied owing to the inadequate hypoxia within the tumor regions. In this work, a mitochondrial targeted nanoplatform integrating photodynamic therapy, photothermal therapy and hypoxia-activated chemotherapy has been developed to synergistically treat cancer and maximize the therapeutic window. Polydopamine coated hollow copper sulfide nanoparticles were used as the photothermal nanoagents and thermosensitive drug carriers for loading the hypoxia-activated prodrug, TH302, in our study. Chlorin e6 (Ce6) and triphenyl phosphonium (TPP) were conjugated onto the surface of the nanoplatform. Under the action of TPP, the obtained nanoplatform preferentially accumulated in mitochondria to restore the drug activity and avoid drug resistance. Using 660 nm laser to excite Ce6 can generate ROS and simultaneously exacerbate the cellular hypoxia. While under the irradiation of 808 nm laser, the nanoplatform produced local heat which can increase the release of TH302 in tumor cells, ablate cancer cells as well as intensify the tumor hypoxia levels. The aggravated tumor hypoxia then significantly boosted the anti-tumor efficiency of TH302. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional hypoxia-associated chemotherapy. This work highlights the potential of using a combination of hypoxia-activated prodrugs plus phototherapy for synergistic cancer treatment.

Large Amino Acid Mimicking Selenium-Doped Carbon Quantum Dots for Multi-Target Therapy of Alzheimer's Disease.

Multi-target intervention and synergistic treatment are critical for the drug development of Alzheimer's disease (AD) due to its complex and multifactional nature. Oxidative stress and amyloid ß peptides (Aß) accumulation have been recognized as therapeutic targets for AD. Herein, with ability to inhibit Aß aggregation and the broad-spectrum antioxidant properties, the large amino acid mimicking selenium-doped carbon quantum dots (SeCQDs) are presented as novel nanoagents for multi-target therapy of AD. Compared with the precursor, selenocystine, SeCQDs which maintain the intrinsic properties of both selenium and carbon quantum dots (CQDs) possess good biocompatibility and a remarkable ROS-scavenging activity. Moreover, the functionalized α-carboxyl and amino groups on edge of SeCQDs can trigger multivalent interactions with Aß, leading to the ability of SeCQDs to inhibit Aß aggregation. In vivo study demonstrated that SeCQDs can significantly ameliorate the Aß induced memory deficits, reduce Aß accumulation and inhibit neuron degeneration in AD model rats. The versatility of functionalization and potential ability to cross the blood-brain barrier (BBB) make SeCQDs as prospective nanodrugs for treating AD.

The Common Occurrence of Theileria ovis in Tibetan Sheep and the First Report of Theileria sinensis in Yaks from Southern Qinghai, China.

PURPOSE: The tick-borne protozoa piroplasms, including Theileria and Babesia, are the cause of substantial economic losses to the livestock industry. However, in southern Qinghai province, China, there are limited information on the molecular characteristics of piroplasms. This study therefore aimed at determining the prevalence and genetic diversity of piroplasms. METHODS: In order to detect piroplasms, we examined 330 yaks and 236 Tibetan sheep blood samples by nested PCR. The differences in piroplasms prevalence in relation to different risk factors was analyzed using SPSS 26. Phylogenetic analysis based on 18S rRNA sequences was inferred using MEGA 7. RESULTS: During this study, Theileria spp. were detected in 33.6% (111/330) of yaks and 94.1% (222/236) of Tibetan sheep, but no Babesia was identified. Importantly, a comparison study revealed that T. ovis infection was highly prevalent in sheep (94.1%) but infrequent in yaks (6.1%), while T. sinensis was host-specific to yaks with an infection rate of 27.6%. In addition, male animals were more likely to be infected by T. sinensis and female animals were more likely to be infected by T. ovis. And animals below 4000 m areas reported a higher infection rate with T. sinensis (26.1% vs. 2.9%, p < 0.001). Alongside these differences in prevalence, we found a significantly higher T. sinensis infection rate in separated-grazing livestock (22.2% vs. 3.7%, p < 0.001), while mixed-grazing ruminants had a higher T. ovis infection rate (50.0% vs. 39.0%, p = 0.014). Furthermore, sequence analysis revealed that the 18S rRNA sequences obtained in this study shared 86.9-100.0% identities with each other and they were clustered into T. sinensis or T. ovis. CONCLUSION: To our knowledge, this is the first report of T. sinensis in Qinghai region. In addition, high prevalence of the generally sub-clinical T. ovis in sheep indicates extensive exposure to ticks and transmission of tick-borne pathogens with a significant economic impact. This study provides insights into the distribution and genetic diversity of Theileria in China.

Vector-Borne Pathogens with Veterinary and Public Health Significance in Melophagus ovinus (Sheep Ked) from the Qinghai-Tibet Plateau.

Melophagus ovinus (sheep ked) is a hematophagous ectoparasite that mainly parasitizes sheep. In addition to causing inflammation, wool loss, and skin damage to the animal hosts, M. ovinus also serves as a vector for a variety of pathogens and is highly likely to participate in the life and transmission cycle of pathogenic organisms. Herein, we investigated the presence and molecular characterization of vector-borne pathogens in M. ovinus from Qinghai-Tibet Plateau, China. A total of 92 M. ovinus pools collected from the Qinghai province of China were screened for the presence of selected vector-borne pathogens. The overall positive rate of A. ovis, A. bovis, A. phagocytophilum, and T. ovis in M. ovinus was 39.1%, 17.4%, 9.8%, and 89.1%, respectively. All of the samples were negative for Border disease virus (BDV), other Anaplasma species, Babesia spp., Rickettsia spp., and Borrelia spp. Co-infection of different Anaplasma species and T. ovis occurred in 51.2% of all samples with T. ovis. The positive rates of A. ovis, A. bovis, and A. phagocytophilum in different regions and altitudes of the sampling sites were significantly different. Sequence and phylogenetic analysis of target genes confirmed their identity with corresponding pathogens. Our results elucidate the occurrence and molecular characterization of Anaplasma spp. and Theileria spp. in M. ovinus, which could act as potential zoonotic reservoirs. To the best of our knowledge, this is the first report of the detection of A. bovis and A. phagocytophilum DNA in M. ovinus. This study gives the first extensive molecular survey of vector-borne pathogens with veterinary and public health significance in M. ovinus from the Qinghai-Tibet Plateau, China.

Spatiotemporal Distribution Characteristics of Nutrients in the Drowned Tidal Inlet under the Influence of Tides: A Case Study of Zhanjiang Bay, China.

The tidal dynamics and the characteristics of pollutant migration in the drowned-valley tidal inlet, a typical unit of coastal tidal inlets, are strongly influenced by geomorphological features. Along with the development of society and the economy, the hydrodynamic and water quality environment of the tidal inlet is also becoming more disturbed by human activities, such as reclamation of the sea and the construction of large bridges. In this study, a typical drowned-valley tidal inlet, Zhanjiang Bay (ZJB), was selected for the establishment of a model via coupling of a tidal hydrodynamic model and water quality numerical model. This model can be used to simulate the migration and diffusion of pollutants in ZJB. The spatial and temporal variation processes of water quality factors of the bay under the influence of special geomorphic units was simulated at the tidal-inlet entrance, the flood/ebb tidal delta, and the tidal basin. The results show that ZJB has strong tidal currents that are significantly affected by the terrain. Under the influence of the terrain and tidal currents, the phosphorus and nitrogen concentration at the flood-tide and ebb-tide moments showed obvious temporal and spatial differences in the ebb-tide delta, tidal-inlet entrance, flood-tide delta, and tidal basin. In this study, we analyzed the response mechanism of the water quality environment to the drowned-valley tidal inlet, and this can provide theoretical guidance and a basis for decision-making toward protecting the ecology and water security of ZJB.

Colorimetric determination of amyloid-ß peptide using MOF-derived nanozyme based on porous ZnO-Co3O4 nanocages.

A sensitive and rapid colorimetric biosensor has been developed for determination of amyloid-ß peptide (Aß) and study of amyloidogenesis based on the high peroxidase-like activity of porous bimetallic ZnO-Co3O4 nanocages (NCs). Due to the high binding ability of Aß monomer to ZnO-Co3O4 NCs, the catalytic activity of ZnO-Co3O4 NCs can be significantly suppressed by Aß monomer. This finding forms the basis for a colorimetric assay for Aß monomer detection. The detection limit for Aß monomer is 3.5 nM with a linear range of 5 to 150 nM (R2 = 0.997). The system was successfully applied to the determination of Aß monomer in rat cerebrospinal fluid. Critically, the different inhibition effects of monomeric and aggregated Aß species on the catalytic activity of ZnO-Co3O4 NCs enabled the sensor to be used for tracking the dynamic progress of Aß aggregation and screening Aß inhibitors. Compared with the commonly used thioflavin T fluorescence assay, this method provided higher sensitivity to the formation of Aß oligomer at the very early assembly stage. Our assay shows potential application in early diagnosis and therapy of Alzheimer's disease (AD).

MOF-derived porous ZnO-Co3O4 nanocages as peroxidase mimics for colorimetric detection of copper(ii) ions in serum.

Sensitive detection of copper ions (Cu2+) in biological samples is extremely important since an abnormal level of Cu2+ is linked with many diseases. Herein, we demonstrated a novel turn-on colorimetric sensor for selective detection of Cu2+ both in buffered solution and serum samples based on porous bimetallic transition metal oxide nanocages (ZnO-Co3O4 NCs) as peroxidase mimics. The ZnO-Co3O4 NCs were prepared by using ZnCo-zeolitic-imidazolate-framework (ZnCo-ZIF) as precursors via direct calcination. With the high peroxidase-like activity, the obtained ZnO-Co3O4 NCs can catalyze the oxidation of tetramethylbenzidine (TMB) in the presence of H2O2 to form a blue colored product. The inhibition effect of cysteine (Cys) on the catalytic activity of ZnO-Co3O4 NCs and its strong binding ability toward Cu2+ enabled the ZnO-Co3O4 NCs/Cys system to be utilized for sensitive detection of Cu2+, in which the catalytic activity of ZnO-Co3O4 NCs/Cys can be recovered by the introduction of Cu2+ with an obvious color change of the solution. The linear range for Cu2+ determination was 2 to 100 nM with a detection limit of 1.08 nM. More importantly, this colorimetric sensor has been successfully applied to detect Cu2+ in serum without pretreatment. Our findings are expected to expand the scope of application of nanozyme and shed light on early disease diagnosis.

Resemblance and clustering of mother's and father's psychopathology levels among Chinese parents of schoolchildren with psychiatric disorders.

BACKGROUND: Few studies have assessed the characteristics of spousal psychopathologies among parents of schoolchildren with and without psychological disorders (PD) in China. METHODS: Parental symptoms were measured using the General Health Questionnaire (GHQ) in 275 mothers and 278 fathers of 298 schoolchildren with PDs diagnosed in a population survey and in 825 mothers and 834 fathers of 894 schoolchildren without PDs as a 1:3 matched comparison group. Spousal GHQ scores were compared. Childhood PD type, presence of childhood comorbidities, and multiple parental and family characteristics were examined as predictors for parental GHQ scores by multiple linear regression analyses. RESULTS: The GHQ scores were significantly higher among mothers and fathers of children with any PD. Maternal GHQ scores were higher than paternal scores and significantly correlated with paternal GHQ scores in both groups. Spousal GHQ, personal PD history, and childhood PD comorbidity were significant independent predictors of both parents' GHQ scores. There were also significant associations among parental chronic disease, low family income, and paternal and maternal GHQ score, as well as among low maternal education, less common disorder (LCD) prevalence in children and maternal GHQ score. The rate of GHQ score ≥3 for both parents was significantly higher in the study group than the control group (15.1 vs.7.0%). CONCLUSIONS: Parents of children with any PD type demonstrate significantly elevated psychopathologies, and psychopathology tends to occur concomitantly and resemble that of the other spouse. Screening and treatment of parental psychiatric symptoms will benefit all family members.

ATP induced alteration in the peroxidase-like properties of hollow Prussian blue nanocubes: a platform for alkaline phosphatase detection.

Breaking the pH limitation of the enzyme-like activity of nanomaterials is of great importance for extending their applications in environmental and biomedical fields. Herein, to mimic the role of histidine residues in horseradish peroxidase (HRP), adenosine 5'-triphosphate (ATP) is reported to improve the peroxidase-like activity of hollow Prussian blue nanocubes (hPBNCs). Due to the inherited porous structures, hPBNCs can expose all the binding sites as far as possible to ATP to significantly amplify their catalytic activity and broaden their applicable pH range up to pH 12. Introduction of ATP provides the possibility of realizing efficient catalytic reactions under alkaline conditions. Upon binding with hPBNCs, ATP can enhance the stability of hPBNCs, increase the affinities of the catalysts towards substrates and improve the conductivity of hPBNCs as well as change the decomposed product from H2O2. Moreover, on the basis of the different catalytic activities of hPBNCs towards ATP, adenosine 5'-diphosphate and adenosine 5'-monophosphate, hPBNCs-ATP is utilized to construct a novel colorimetric sensor for the detection of alkaline phosphatase (ALP) activity in biological fluids, which is significantly important for the clinical diagnosis of ALP-related diseases.

Expanded mesoporous silica-encapsulated ultrasmall Pt nanoclusters as artificial enzymes for tracking hydrogen peroxide secretion from live cells.

Design of synthetic structures that possess the similar functions to natural enzymes held great promise in environmental detection and biomedical application. Herein, a new concept for the fabrication of solid-supported catalysts as peroxidase mimic have been proposed to realize high-catalytic activity and stability by utilizing expanded mesoporous silica (EMSN)-encapsulated Pt nanoclusters. Compared with PtNCs, the introduction of amino group modified EMSN would enrich H2O2 on the surface of PtNCs and increase the catalytic sites for H2O2 decomposition, which gave rise to the higher catalytic activity of EMSN-PtNCs over a broad pH range, especially in weakly acidic and neural solutions. This would facilitate their applications for real-time monitoring the secretion of H2O2 from living cancer cells stimulated by various anticancer drugs. Our findings not only pave the way to use porous matrix as the structural component for the design of the biomimetic catalysts, but also provide a simple and reliable platform to monitor H2O2 released from living cells in real time, which holds great potential for elucidating the biological roles of H2O2 and underlying molecular mechanisms of drug cytotoxicity as well as drug therapeutic effects.

Hollow Prussian Blue nanocubes as peroxidase mimetic and enzyme carriers for colorimetric determination of ethanol.

The peroxidase-like activity of hollow Prussian Blue nanocubes (hPBNCs) is used, in combination with the enzyme alcohol oxidase (AOx), in a colorimetric ethanol assay. Different from other nanozymes, the large cavity structure of the hPBNCs provides a larger surface and more binding sites for AOx to be bound on their surface or in the pores. This extremely enhances the sensitivity of the assay system. In the presence of ethanol, AOx is capable of catalyzing the oxidation of alcohols to aldehydes, accompanied by the generation of hydrogen peroxide (H2O2). The hPBNCs act as peroxidase mimics and then can catalyze the oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) by H2O2, resulting in a color change of the solution from colorless to blue with a strong absorption at 652 nm. The lower detection limit for ethanol is 1.41 µg∙mL-1. Due to the high catalytic activity of hPBNCs in weakly acidic and neutral solutions, the system was successfully applied to the determination of ethanol in mice blood. This is critically important for studying the alcohol consumption and monitoring the ethanol toxicokinetics. Graphical abstract Schematic representation of hollow Prussian Blue nanocubes (hPBNCs) used as both a peroxidase mimetic and as a carrier for alcohol oxidase. Utilizing hPBNCs along with the ethanol conversion enzyme, a sensitive colorimetric assay for ethanol was developed and applied to blood samples with satisfactory results.

Dual isotopic evidence for nitrate sources and active biological transformation in the Northern South China Sea in summer.

Nitrate (NO3-) concentrations and their dual isotopic compositions (δ15N-NO3- and δ18O-NO3-) were measured to constrain N sources and their cyclic processes in summer using samples from the water column of the northern South China Sea (NSCS). Our data revealed that higher NO3- concentrations and δ15N-NO3- values were observed in the upper waters of the coastal areas near the Pearl River Estuary (PRE). The Bayesian stable isotope mixing model was used to calculated the proportion of nitrate sources, the results indicated that the nitrate in the upper waters of the coastal areas near PRE were mainly influenced by manure and sewage (63%), atmospheric deposition (19%), soil organic nitrogen (12%) and reduced N fertilizer (6%). For the upper waters of the outer areas, low NO3- concentrations and δ15N-NO3- values, but high δ18O-NO3- values, reflected that NO3- was mainly influenced by Kuroshio water intrusion (60%), atmospheric deposition (32%) and nitrogen fixation/nitrification (8%). Complex processes were found in bottom waters. Nitrification and phytoplankton assimilation may be responsible for the higher nitrate concentrations and δ15N-NO3- values. Our study, therefore, utilizes the nitrate dual isotope to help illustrate the spatial variations in nitrate sources and complex nitrogen cycles in the NSCS.

Selective antibiotic resistance genes in multiphase samples during biofilm growth in a simulated drinking water distribution system: Occurrence, correlation and low-pressure ultraviolet removal.

The aim of this study was to gain comprehensive insights into the characteristics of antibiotic resistance genes (ARGs) in multiphase samples from drinking water distribution pipelines using a simulated biofilm reactor. During 120 d of continuous operation, common parameters and six ARGs (ermA, ermB, aphA2, ampC, sulII, and tetO) in samples of three phases (water, particle, and biofilm) from the reactor were investigated, which demonstrated secondary contamination by ARGs. Abundances of the six ARGs in the reactor effluent increased gradually, and in the 120 d effluent, the relative abundances of aphA2 and sulII were the highest, at 9.9 × 10-4 and 1.3 × 10-3, respectively, with a 1.5-fold and 2.8-fold increase, compared with those in the influent. The relative abundances of the six ARGs in the biofilm phase increased significantly (P < 0.05) at 120 d, which was caused by robust bacteria in biofilm that was newly exposed following the detachment of a large piece of aging biofilm. In the particle phase, four of the ARGs did not change significantly during the 120 d period. The six ARGs in the samples of three phases showed a negative correlation with residual chlorine in the pipe water, which demonstrated that low abundance of ARGs in the samples of three phases was related to the improvement of residual chlorine. The proportion of cultivable bacteria illustrated that the robust and active bacteria were negatively correlated with the six ARGs in the biofilm. Total organic carbon (TOC) in the pipeline showed a positive correlation with the proportion of cultivable bacteria in both the water and biofilm phases, which indicated that a TOC reduction in the pipeline contributed to low abundance of ARGs. With low-pressure ultraviolet (LP-UV) irradiation of 20 mJ/cm2, ARGs in the samples of three phases were efficiently controlled, which showed that LP-UV can be used for ARG removal in terminal water for supplemental bactericidal treatment of pipeline effluent.

Hierarchical level features based trainable segmentation for electron microscopy images.

BACKGROUND: The neuronal electron microscopy images segmentation is the basic and key step to efficiently build the 3D brain structure and connectivity for a better understanding of central neural system. However, due to the visual complex appearance of neuronal structures, it is challenging to automatically segment membranes from the EM images. METHODS: In this paper, we present a fast, efficient segmentation method for neuronal EM images that utilizes hierarchical level features based on supervised learning. Hierarchical level features are designed by combining pixel and superpixel information to describe the EM image. For pixels in a superpixel have similar characteristics, only part of them is automatically selected and used to reduce information redundancy. To each selected pixel, 34 dimensional features are extracted by traditional way. Each superpixel itself is viewed as a unit to extract 35 dimensional features with statistical method. Also, 3 dimensional context level features among multi superpixels are extracted. Above three kinds of features are combined as a feature vector, namely, hierarchical level features to use for segmentation. Random forest is used as classifier and is trained with hierarchical level features to perform segmentation. RESULTS: In small sample condition and with low-dimensional features, the effectiveness of our method is verified on the data set of ISBI2012 EM Segmentation Challenge, and its rand error, warping error and pixel error attain to 0.106308715, 0.001200104 and 0.079132453, respectively. CONCLUSIONS: Comparing to pixel level or superpixel level features, hierarchical level features have better discrimination ability and the proposed method is promising for membrane segmentation.

Sleeping site selection of Francois's langur (Trachypithecus francoisi) in two habitats in Mayanghe National Nature Reserve, Guizhou, China.

Sleeping site selection is an important aspect of the behavioral biology of primates. Comparison of different habitats for the same species in this context enhances understanding of their adaptation to altered environments. We collected data on sleep-related behaviors for 6 groups of Francois's langur (Trachypithecus francoisi) in two habitats, in Mayanghe National Nature Reserve, Guizhou, China. Regardless of habitat, all sleeping sites were located in areas of steep terrain of ≥60°. In undisturbed habitat, sleeping sites were located only in evergreen broadleaf forest with rock caves and crevices surrounded mainly by a vegetation layer of shrub + rock. In disturbed habitat, sleeping sites were also located in mixed evergreen and deciduous broadleaf forest and in grassland, including rock caves, crevices, and pits, surrounded mainly by arbor + shrub and shrub + rock. Wild food availability was higher in undisturbed habitat than disturbed habitat, but food abundance around sleeping sites was lower. Water sources included river and seasonal gully or pond. There was strong positive correlation between use of sleeping sites away from the river valley and occurrence of seasonal water sources. The number of sleeping sites varied across groups, numbering 6, 7, and 10 for three specific groups. Few sleeping sites were used all year round. Six consecutive nights was the longest recorded run. Francois's langurs' sleeping habits differed between two habitats. In undisturbed habitat, minimizing predation risk appeared to predominate, expressed by choosing steep terrain, open visual field, and inconspicuous presleeping behavior. In disturbed habitat, along with predation avoidance, food resources may strongly influence sleeping site selection, as demonstrated by the richer food abundance and greater foraging activity around the site. Finally, water resources may influence choice of sites distant from the river; such sites were used less frequently during water shortages.