Intermittent hypoxia training enhances Aß endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer's disease.

BACKGROUND: Beta-amyloid (Aß) deposition in the brain parenchyma is a crucial initiating step in the amyloid cascade hypothesis of Alzheimer's disease (AD) pathology. Furthermore, dysfunction of plaque-associated microglia, also known as disease-associated microglia (DAM) has been reported to accelerate Aß deposition and cognitive impairment. Our previous research demonstrated that intermittent hypoxia training (IHT) improved AD pathology by upregulating autophagy in DAM, thereby enhancing oligomeric Aß (oAß) clearance. Considering that oAß internalization is the initial stage of oAß clearance, this study focused on the IHT mechanism involved in upregulating Aß uptake by DAM. METHODS: IHT was administered to 8-month-old APP/PS1 mice or 6-month-old microglial vacuolar protein sorting 35 (VPS35) knockout mice in APP/PS1 background (MG VPS35 KO: APP/PS1) for 28 days. After the IHT, the spatial learning-memory capacity of the mice was assessed. Additionally, AD pathology was determined by estimating the nerve fiber and synapse density, Aß plaque deposition, and Aß load in the brain. A model of Aß-exposed microglia was constructed and treated with IHT to explore the related mechanism. Finally, triggering receptor expressed on myeloid cells 2 (TREM2) intracellular recycling and Aß internalization were measured using a fluorescence tracing technique. RESULTS: Our results showed that IHT ameliorated cognitive function and Aß pathology. In particular, IHT enhanced Aß endocytosis by augmenting the intracellular transport function of microglial TREM2, thereby contributing to Aß clearance. Furthermore, IHT specifically upregulated VPS35 in DAM, the primary cause for the enhanced intracellular recycling of TREM2. IHT lost ameliorative effect on Aß pathology in MG VPS35 KO: APP/PS1 mice brain. Lastly, the IHT mechanism of VPS35 upregulation in DAM was mediated by the transcriptional regulation of VPS35 by transcription factor EB (TFEB). CONCLUSION: IHT enhances Aß endocytosis in DAM by upregulating VPS35-dependent TREM2 recycling, thereby facilitating oAß clearance and mitigation of Aß pathology. Moreover, the transcriptional regulation of VPS35 by TFEB demonstrates a close link between endocytosis and autophagy in microglia. Our study further elucidates the IHT mechanism in improving AD pathology and provides evidence supporting the potential application of IHT as a complementary therapy for AD.

Magnetic field-assisted adsorption of phosphate on biochar loading amorphous Zr-Ce (carbonate) oxide composite.

For metal-based phosphate adsorbents, the dispersity and utilization of surface metal active sites are crucial factors in their adsorption performance and synthesis cost. In this study, a biochar material modified with amorphous Zr-Ce (carbonate) oxides (BZCCO-13) was synthesized for the phosphate uptake, and the adsorption process was enhanced by magnetic field. The beside-magnetic field was shown to have a better influence than under-magnetic field on adsorption, with maximum adsorption capacities (123.67 mg P/g) 1.14-fold greater than that without magnetic field. The beside-magnetic field could also accelerate the adsorption rate, and the time to reach 90% maximum adsorption capacity decreased by 83%. BZCCO-13 has a wide range of application pHs from 5.0 to 10.0, with great selectivity and reusability. The results of XPS and ELNES showed that the "magnetophoresis" of Ce3+ under the magnetic field was the main reason for the enhanced adsorption performance. In addition, increased surface roughness, pore size and oxygen vacancies, enhanced mass transfer by Lorentz force under a magnetic field, all beneficially influenced the adsorption process. The mechanism of phosphate adsorption by BZCCO-13 could be attributed to electrostatic attraction and CO32-dominated ligand exchange. This study not only provided an effective strategy for designing highly effective phosphate adsorbents, but also provides a new light on the application of rare earth metal-based adsorbent in magnetic field.

Rethinking the relationships between gel like structure and sludge dewaterability based on a binary gel like structure model: Implications for the online sensing of dewaterability.

The digital transformation of sludge treatment processes requires online sensing of dewaterability. This topic has been attempted for many years based on macroscopic shear rheology. However, the relationship between rheological behavior and dewaterability remains noncommittal, and the reason is unclear. Herein, a binary gel-like structure model was proposed including the interactions network at the supra-flocs level and the gel-like structure at the flocs level. Multiple advanced techniques including optical tweezers were employed to precisely understand the binary gel-like structure and to classify the correlation mechanism between this gel-like structure, rheological behavior, and dewaterability. The analysis of sludge from eight wastewater treatment plants showed the binary gel-like structures at both supra-flocs and flocs levels have significant relationships with sludge dewaterability (p < 0.05). Further deconstruction of the sludge viscoelastic behavior illustrated that the gel-like structure at the supra-flocs level dominates the rheological behavior of sludge. Moreover, the direct description of the binary gel-like structure in four typical sludge treatment processes highlighted the importance of the flocs level's structure in determining the dewaterability. Overall, this study revealed that shear rheology may prefer to stress the interactions network at the supra-flocs level but mask the flocs level's structure, although the latter is important. This observation may provide a general guideline for the design of robust sensors for dewaterability.

A comprehensive assessment on sludge conditioning by pyrite acid eluent-activated peroxymonosulfate based on dewaterability, heavy metals risk and ore recovery.

Wastewater activated sludge (WAS) has poor dewaterability and contains heavy metals (HMs), limiting its land application. Therefore, in this study, a novel pyrite acid eluent-activated peroxymonosulfate (Fe2+pyrite/PMS) conditioning approach that can completely recover the residual pyrite and greatly reduce acid use was developed to improve WAS dewaterability, and the HMs chemical speciation and risks of conditioned WAS were assessed. Our results showed that under the optimized operational parameters, the capillary suction time (CST) and water content (Wc) of WAS decreased by 46.03% and 7.75%, respectively. Furthermore, during Fe2+pyrite/PMS conditioning processing, sulfate radical (SO4-) destroyed the extracellular polymeric substances (EPS) matrix, causing bound water release and the decrease of proteins/polysaccharides in outer layered EPS, even the decomposition of some protein-N in tightly bound EPS (TB-EPS) into inorganic-N. In addition, although the total concentration of HMs in the conditioned WAS matrix increased, the Ni concentration decreased in the solid fraction. Further, the risk assessment code (RAC) levels did not increase, and the eco-toxicity of Cr became weakened after Fe2+pyrite/PMS conditioning. However, after acid extraction, the pyrite residue had worsened recycle performance because the passivation layer contained S0/Sn2- on its surface, and no additional elements were detected in the pyrite residue, which had almost no effect on its further usage.

Free nitrous acid-assisted asymmetrical alternating current electrochemistry (FNA-AACE) for multi-heavy metals decontamination in waste activated sludge.

Heavy metal contamination of waste activated sludge (WAS) is a key factor limiting the land application of sludge for nutrients recovery. This study proposes a novel free nitrous acid (FNA)-assisted asymmetrical alternating current electrochemistry (FNA-AACE) process to achieve high-efficiency decontamination of multi-heavy metals (Cd, Pb, and Fe) in WAS. The optimal operating conditions, the heavy metal removal performance of FNA-AACE, and the related mechanisms for maintaining the high performance were systematically investigated. During the FNA-AACE process, FNA treatment was optimal with an exposure time of 13 h at a pH of 2.9 and an FNA concentration of 0.6 mg/g TSS. Then the sludge was washed with EDTA in a recirculating leaching system under asymmetrical alternating current electrochemistry (AACE). The 6-h working and the following electrode cleaning were defined as a working circle of AACE. After three cycles of working-cleaning periods in AACE treatment, the cumulative removal efficiency of the toxic metals Cd and Pb reached over 97% and 93%, respectively, whilst that of Fe was greater than 65%. This surpasses most previously reported efficiencies and possesses a shorter treatment duration and sustainable EDTA circulation. The mechanism analysis suggested that FNA pretreatment provoked the migration of heavy metals for leaching enhancement, as well as reduced the demand for EDTA eluent concentration and increased conductivity, which can improve the AACE efficiency. Meanwhile, the AACE process absorbed the anionic chelates of heavy metals and reduced them to zero-valent particles on the electrode, regenerating the EDTA eluent and maintaining its high extraction efficiency for heavy metals. In addition, FNA-AACE could provide different electric field operation modes, allowing it to have flexibility for the real application processes. This proposed process is expected to be coupled with anaerobic digestion in wastewater treatment plants (WWTPs) for high efficiency of heavy metal decontamination, sludge reduction, and resource/energy recovery.

A label-free fluorescent biosensor for amplified detection of T4 polynucleotide kinase activity based on rolling circle amplification and catalytic hairpin assembly.

T4 polynucleotide kinase (PNK) plays a key role in maintaining genome integrity and repairing DNA damage. In this paper, we proposed a label-free fluorescent biosensor for amplified detection of T4 PNK activity based on rolling circle amplification (RCA) and catalytic hairpin assembly (CHA). Firstly, we designed a padlock probe with a 5'-hydroxyl terminus for phosphorylation reaction, a complementary sequence of the primer for initiating RCA, and a complementary sequence of the trigger for triggering CHA. T4 PNK catalyzed the phosphorylation reaction by adding a phosphate group to the 5'-hydroxyl terminus of padlock probe, generating a phosphorylated padlock probe. Then it hybridized with the primer to generate a circular probe under the action of ligase. Subsequently, the primer initiated an RCA reaction along the circular probe to synthesize a large molecular weight product with repetitive trigger sequences. The triggers then triggered the cyclic assembly reactions between hairpin probe 1 and hairpin probe 2 to generate a large amount of complexes with free G-rich sequences. The free G-rich sequences folded into G-quadruplex structures, and the N-methylmesoporphyrin IXs were inserted into them to produce an amplified fluorescent signal. Benefiting from high amplification efficiency of RCA and CHA, this fluorescent biosensor could detect T4 PNK as low as 6.63 × 10-4 U mL-1, and was successfully applied to detect its activity in HeLa cell lysates. Moreover, this fluorescent biosensor could effectively distinguish T4 PNK from other alternatives and evaluate the inhibitory effect of inhibitor, indicating that it had great potential in drug screening and disease treatment.

Identification of Src Family Kinases as Potential Therapeutic Targets for Chemotherapy-Resistant Triple Negative Breast Cancer.

Neoadjuvant chemotherapy (NAC) remains the cornerstone of the treatment for triple negative breast cancer (TNBC), with the goal of complete eradication of disease. However, for patients with residual disease after NAC, recurrence and mortality rates are high and the identification of novel therapeutic targets is urgently needed. We quantified tyrosine phosphorylation (pTyr)-mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient-derived xenografts (PDX), to gain novel therapeutic insights. The antitumor activity of SFK inhibition was examined in vivo. Treated tumors were further subjected to phosphoproteomic and RNAseq analysis, to identify the mechanism of actions of the drug. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Treatment with dasatinib, an FDA approved SFK inhibitor, led to inhibition of tumor growth in vivo. Further analysis of post-treatment PDXs revealed multiple mechanisms of actions of the drug, confirming the multi-target inhibition of dasatinib. Analysis of pTyr in tumor specimens suggested a low prevalence of SFK-driven tumors, which may provide insight into prior clinical trial results demonstrating a lack of dasatinib antitumor activity in unselected breast cancer patients. Taken together, these results underscore the importance of pTyr characterization of tumors, in identifying new targets, as well as stratifying patients based on their activated signaling networks for therapeutic options. Our data provide a strong rationale for studying SFK inhibitors in biomarker-selected SFK-driven TNBC.

An electro-peroxone oxidation-Fe(III) coagulation sequential conditioning process for the enhanced waste activated sludge dewatering: Bound water release and organics multivariate change.

As a by-product of wastewater treatment, waste activated sludge (WAS) has complex composition, strong hydrophilic extracellular polymeric substance (EPS), which make it difficult to dewater. In this study, an electro-peroxone oxidation-Fe(III) coagulation (E-peroxone-Fe(III)) sequential conditioning approach was developed to improve WAS dewaterability. At E-peroxone oxidation stage, hydrogen peroxide was generated through 2-electron path on a carbon polytetrafluoroethylene cathode, and reacted with the sparged O3 to produce hydroxyl radicals. At the subsequent coagulation stage, Fe(III) was dosed to coagulate the small WAS fragments and release water from WAS. Along E-peroxone-Fe(III) subsequent conditioning process, the physicochemical properties of WAS, main components, functional groups and evolution of protein secondary structure, and typical amino acids in EPS, as well as the type and semi-quantitative of elements in WAS, were investigated. The results indicated that under the optimal conditions, the reductions of specific resistance to filterability (SRF) and capillary suction time (CST) for WAS equalled 78.18% and 71.06%, respectively, and its bound water content decreased from 8.87 g/g TSS to 7.67 g/g TSS. After E-peroxone oxidation, part of protein and polysaccharide migrated outside from TB-EPS to slime, the ratio of α-helix/(ß-sheet + random coil) declined, even some of organic-N disintegrated to inorganic-N. At Fe(III) coagulation stage, re-coagulation of the dispersed WAS fragments and easy extraction from inner EPS for protein and polysaccharide occurred. Furthermore, the protein secondary structure of ß-sheet increased by 13.48%, the contents of hydrophobic and hydrophilic amino acids also increased. In addition, a strong negative correlation between the hydrophobic amino acid content of Met in slime and CST or SRF (R2CST = -0.999, p < 0.05 or R2SRF = -0.948, p < 0.05) occurred, while a strong positive correlation between the hydrophilic amino acid content of Cys in TB-EPS and CST or SRF (R2CST = 0.992, p < 0.05 or R2SRF = 0.921, p < 0.05) occurred, which could be related to the WAS dewaterability.

Polarization Gradient Effect of Negative Capacitance LTFET.

In this paper, an L-shaped tunneling field effect transistor (LTFET) with ferroelectric gate oxide layer (Si: HfO2) is proposed. The electric characteristic of NC-LTFET is analyzed using Synopsys Sentaurus TCAD. Compared with the conventional LTFET, a steeper subthreshold swing (SS = 18.4 mV/dec) of NC-LTFET is obtained by the mechanism of line tunneling at low gate voltage instead of diagonal tunneling, which is caused by the non-uniform voltage across the gate oxide layer. In addition, we report the polarization gradient effect in a negative capacitance TFET for the first time. It is noted that the polarization gradient effect should not be ignored in TFET. When the polarization gradient parameter g grows larger, the dominant tunneling mechanism that affects the SS is the diagonal tunneling. The on-state current (Ion) and SS of NC-LTFET become worse.

Electrical impedance spectroscopy as a potential tool to investigate the structure and size of aggregates during water and wastewater treatment.

Microscopic structure and size are important metrics for estimating aggregates environmental behaviors during water and wastewater treatment. However, in-situ determination of these characteristics is still a challenge. Here, we drew inspiration from a block disassembly process to propose an electrical impedance spectroscopy (EIS) method and constructed a generalized framework to associate macroscale electrical properties with microscopic structure and size-related characteristics of aggregates of different hierarchies. Extracted via EIS, the proposed models were verified to be capable of describing the self-similarity of aggregates and capturing the fractal and size information. Further, the proposed models exhibited a wide range of applications, which agrees well with the data gathered from various activated sludges, other colloids, and microgels in water and wastewater treatment. Finally, the EIS method was achieved online monitoring of fractal dimension and floc size during a sludge pre-oxidation conditioning process, which was elected as an example to illustrate the potential online applications of this EIS method in real water and wastewater environment. The obtained on-line data were used to indicate the potential suitable oxidation time during sludge pre-oxidation conditioning. These observations may inspire new methods of quantifying the aggregate structure and promote intelligent and dynamic decision-making during water and wastewater treatment.

Siderite/PMS conditioning-pressurized vertical electro-osmotic dewatering process for activated sludge volume reduction: Evolution of protein secondary structure and typical amino acid in EPS.

In this study, the siderite/PMS conditioning-pressurized vertical electro-osmotic dewatering (PEOD) process was used to reduce the volume of activated sludge (AS). The changes in water content, cell, extracellular polymeric substances (EPS) distribution, protein secondary structures and typical amino acids in EPS fractions of AS along siderite/PMS conditioning-PEOD process were investigated. Results showed that the final water content (WC) of dewatered AS was 58.02% under the RSM optimized conditioning conditions of 0.05 g/g TSS siderite dosage, 0.23 g/g TSS PMS dosage, 600 kPa mechanical pressure and 20 V voltage. At conditioning and PEOD stages, the bound water content(BWC) of AS decreased by 25.23% and 91.76%, respectively. The HO• and SO4-· generated from siderite activating PMS could lead to the disruption of cells. The ratio of Ala-to Lys (Ala/Lys) showed strong negative correlations with BWC or WC in slime (RBWC2=-0.803, p<0.01; RWC2=-0.771, p<0.01) and TB-EPS (RBWC2=-0.693, p<0.01; RWC2=-0.705, p<0.01), and could be considered as an indicator of AS dewaterability. Compared with raw AS, conditioning led to the occurrence of the denser protein structure in TB-EPS and the looser one in slime. The contact number between Ala-and water decreased in TB-EPS and increased in slime, which indicated that the migration of water adhered in TB-EPS to outer layer. At the DG, MC and EC process, while the looser protein structure in TB-EPS and the denser one in slime occurred, as well as higher contact number between Ala-and water in TB-EPS than that in slime, which indicated that more water flowed outsider of slime than TB-EPS. This implied that the variations of the compactness of protein secondary structures and the contact number between Ala-and water in EPS layers correlated with AS dewaterability.

Establishment and characterization of immortalized human breast cancer cell lines from breast cancer patient-derived xenografts (PDX).

The application of patient-derived xenografts (PDX) in drug screening and testing is a costly and time-consuming endeavor. While cell lines permit extensive mechanistic studies, many human breast cancer cell lines lack patient characteristics and clinical treatment information. Establishing cell lines that retain patient's genetic and drug response information would enable greater drug screening and mechanistic studies. Therefore, we utilized breast cancer PDX from the Mayo Breast Cancer Genome Guided Therapy Study (BEAUTY) to establish two immortalized, genomically unique breast cancer cell lines. Through extensive genetic and therapeutic testing, the cell lines were found to retain the same clinical subtype, major somatic alterations, and drug response phenotypes as their corresponding PDX and patient tumor. Our findings demonstrate PDX can be utilized to develop immortalized breast cancer cell lines and provide a valuable tool for understanding the molecular mechanism of drug resistance and exploring novel treatment strategies.

Insight to peroxone-Fe(III) joint conditioning-horizontal electro-dewatering process on water reduction in activated sludge: Performance and mechanisms.

Peroxone disintegration-Fe(III) coagulation (peroxone-Fe(III)) joint conditioning was proposed to enhance the horizontal electro-dewatering (HED) effect of activated sludge (AS). Operating parameters were optimized and the evolutions of AS physicochemical properties, water fractions distribution, organic matter, extracellular polymeric substance (EPS) key components, functional groups, and protein secondary structures during the process were identified. Under the optimized joint conditioning parameters, dewatered AS achieved a final water content of 84.88 ± 0.17% and its bound water content (BWC) was decreased by 1.88 ± 0.28 g/g dry solid. During peroxone pretreatment, the yielded HO decreased the AS floc size, disintegrated the EPS network structure and cell wall, released the bound water, and extracted proteins, polysaccharides, and humic acid-like materials. Furthermore, soluble microbial byproduct-like materials (SMBP) in the EPS layers and tyrosine in tightly bound EPS significantly increased. Protein structures were destroyed, decreasing their water affinity. Subsequent Fe(III) addition re-coagulated broken flocs fragments and EPS fractions, built water flow channels, removed tyrosine and SMBP, and reduced α-helix percentage in slime, facilitating AS dewatering. After joint conditioning, the bound water and intracellular substances were further released by HED. Therefore, the peroxone-Fe(III)-HED process exhibited an excellent performance in AS water reduction.

A combination of morphological and photosynthetic functional traits maintains the vertical distribution of bryophytes in a subtropical cloud forest.

PREMISE: The distribution and performance of bryophyte species vary with vertical gradients, as a result of changes in environmental factors, especially light. However, the morphological and physiological drivers of bryophyte distribution along forest vertical gradients are poorly understood. METHODS: For 18 species of mosses and liverworts distributed among three vertical microhabitats (ground, tree trunk, and branch, variance in 28 morphological and photosynthetic functional traits was comparatively analyzed among the microhabitats and bryophyte life-forms in a subtropical cloud forest in Ailao Mountain, Yunnan, southwestern China. Principal component analysis (PCA) was used to summarize trait differences among bryophyte species. RESULTS: In contrast to trunk and ground dwellers, branch dwellers tended to reduce light interception (smaller leaf and cell sizes, lower chlorophyll content), protect against damage from intense irradiation (higher ratios of carotenoids to chlorophyll), raise light energy use (higher photosynthetic capacity), and cope with lower environmental moisture (pendant life-forms, thicker cell walls). The PCA showed that ecological strategies of bryophytes in response to levels of irradiation were specialized in branch dwellers, although those of ground and trunk dwellers were less distinct. CONCLUSIONS: Environmental filtering shaped the combination of functional traits and the spatial distribution of bryophytes along the vertical gradients. Bryophyte species from the upper canopy of cloud forests show narrow variation in functional traits in high-light intensity, whereas species in the lower vertical strata associated with low-light intensity used contrasting, but more diverse ecological strategies.

Effects of acid, acid-ZVI/PMS, Fe(II)/PMS and ZVI/PMS conditioning on the wastewater activated sludge (WAS) dewaterability and extracellular polymeric substances (EPS).

The effects of four conditioning approaches: Acid, Acid-zero-valent iron (ZVI)/peroxydisulfate (PMS), Fe(II)/PMS and ZVI/PMS, on wastewater activated sludge (WAS) dewatering and organics distribution in supernatant and extracellular polymeric substances (EPS) layers were investigated. The highest reduction in bound water and the most WAS destruction was achieved by Acid-ZVI/PMS, and the optimum conditions were pH 3, ZVI dosage 0.15 g/g dry solid (DS), oxone dosage 0.07 g/g DS and reaction time 10.6 min with the reductions in capillary suction time (CST) and water content (Wc) as 19.67% and 8.49%, respectively. Four conditioning approaches could result in TOC increase in EPS layers and supernatant, and protein (PN) content in tightly bound EPS (TB-EPS). After conditioning, organics in EPS layers could migrate to supernatant. Polysaccharide (PS) was easier to migrate to supernatant than PN. In addition, Acid, Acid-ZVI/PMS or Fe(II)/PMS conditioning promoted the release of some polysaccharides containing ring vibrations v PO, v C-O-C, v C-O-P functional groups from TB-EPS. ESR spectra proved that both radicals of SO4-· and ·OH contributed to dewatering and organics transformation and migration. CST value of WAS positively correlated with the ratios of PN/PS in LB-EPS and total EPS, while it negatively correlated with TOC, PN content and PS content in TB-EPS, as well as PS content in supernatant and LB-EPS. BWC negatively correlated to zeta potential and TOC value, PN content, and HA content in supernatant.

Dual Inhibition of Pyruvate Dehydrogenase Complex and Respiratory Chain Complex Induces Apoptosis by a Mitochondria-Targeted Fluorescent Organic Arsenical in†vitro and in†vivo.

Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria-targeted organic arsenical PDT-PAO-F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti-cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT-PAO-F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family-dependent apoptosis. In vivo, the acute promyelocytic leukemia was greatly alleviated in the PDT-PAO-F16 treated group in APL mice model. Our results demonstrated the organic arsenical precursor with fluorescence imaging and target-anticancer efficacy is a promising anticancer drug.

LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical.

Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling. All these changes lead to caspase family-dependent cell apoptosis in vivo and in vitro without obvious side effect. Our results provided this organic arsenical precursor as a promising anticancer candidate and suggested metabolism as a target for cancer therapies.

Variations in macro and micro physicochemical properties of activated sludge under a moderate oxidation-in situ coagulation conditioning: Relationship between molecular structure and dewaterability.

A moderate Mn(Ⅶ) oxidation-in situ Fe(Ⅲ) coagulation (Mn(Ⅶ)-Fe(Ⅱ)) conditioning strategy was proposed to improve sludge filterability and release the water bound in extracellular polymeric substances (EPS). During Mn(Ⅶ)-Fe(Ⅱ) conditioning, flocs disintegration and cell disruption, macro and micro physicochemical properties of activated sludge, especially of EPS, were investigated. Relationships between protein molecular structures in EPS fractions of three layers and sludge dewaterability were also determined. Besides, factor analysis was used to explain the variances of "functional" protein secondary structures, which may have an important effect on sludge dewaterability. Results showed that sludge filterability (CST0/CST) increased by 2.40 times and partial bound water was released at 2 min oxidation of 120 mg/g KMnO4 with subsequent FeCl2 termination at equivalent molar ratio of 1:3. During this strategy, EPS wrapping on cells surface was disintegrated, and a limited influence occurred on cells. It was also found that CST and bound water content were strongly correlated with aggregated strands, random coil and ß-turn percentages in slime (R2 >-0.82, p < 0.05). Moreover, the dewaterability also presented strong negative correlations with aggregated strands, ß-sheet and ß-turn in TB-EPS (R2 >-0.78, p < 0.05). This suggested that unfolding and despiralization of slime protein and moderate weakening rigidity of tightly bound EPS (TB-EPS) protein were beneficial for improvement of sludge dewaterability. In addition, the strong correlation between percentages of "functional" protein secondary structures and factor 1 score (R2 > 0.85, p < 0.05) demonstrated that EPS migration, rather than only EPS disintegration, may have a key impact on the formation of some protein secondary structures in slime and TB-EPS. The observed protein secondary structures, which may affect sludge dewaterability, were probably derived from inner EPS.

Comparison of two noninvasive methods for measuring the pigment content in foliose macrolichens.

Chlorophyll content in lichens is routinely used as an accurate indicator of lichen vigor, interspecific differences, and the effect of site-related environmental parameters. Traditional methods of chlorophyll extraction are destructive, time-consuming, expensive, and inoperable, especially when measuring large quantities of chlorophyll. However, non-destructive methods of measurement using portable chlorophyll meters are rarely used for lichens. Considering the characteristics of lichens such as rough blade surface and absence of chlorophyll b in cyanolichens, we compared the non-destructive methods with traditional methods and evaluated their applicability in studying lichen pigment content. Two instruments, SPAD-502 and CCM-300, were used to measure the pigment content of seven foliose lichen species. These pigment readings were compared with those determined using the dimethyl sulphoxide (DMSO) extraction method. Significant correlations were observed between SPAD/CCM values and pigments (chlorophyll and total carotenoids) extracted from chlorolichens, especially species with a smooth surface. The CCM-300 was more accurate in detecting the pigment content of foliose chlorolichens. However, both instruments showed certain limitations in the determination of pigment content in cyanolichens, especially gelatinous species. For example, CCM-300 often failed to give specific values for some cyanolichen samples, and both instruments showed low measurement accuracy for cyanolichens. Based on the high correlation observed between chlorophyll meter readings and pigments extracted from chlorolichens, equations obtained in this study enabled accurate prediction of pigment content in these lichens.