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• The non-toxigenic M. wesenbergii FACHB-908 was more sensitive to C 14 -benzalkonium chloride (BAC-14) than the two toxigenic M. aeruginosa. • Photosynthetic and metabolic responses showed higher sensitivity to BAC-14 than growth inhibition. • BAC-14 specific responses in glycerophospholipid metabolism, synchronized by dysregulation of energy metabolism and amino acid biosynthesis. • BAC-14 induced elevation of extracellular microcystin contents in the absence of growth inhibition of the two toxigenic Microcystis. Quaternary ammonium compounds (QACs) are commonly used in a variety of consumer and commercial products, typically as a component of disinfectants. During the COVID-19 pandemic, QACs became one of the primary agents utilized to inactivate the SARS-CoV-2 virus on surfaces. However, the ecotoxicological effects of QACs upon aquatic organisms have not been fully assessed. In this study, we examined the effects of a widely used QAC (benzalkonium chloride-C 14 , BAC-14) on two toxigenic Microcystis strains and one non-toxigenic freshwater Microcystis strain and carried out an analysis focused on primary, adaptive and compensatory stress responses at apical (growth and photosynthesis) and metabolic levels. This analysis revealed that the two toxic Microcystis strains were more tolerant than the non-toxic strain, with 96 hr-EC 50 values of 0.70, 0.76, and 0.38 mg/L BAC-14 for toxigenic M. aeruginosa FACHB-905, toxigenic M. aeruginosa FACHB-469, and non-toxigenic M. wesenbergii FACHB-908, respectively. The photosynthetic activities of the Microcystis , assessed via F v /F m values, were significantly suppressed under 0.4 mg/L BAC-14. Furthermore, this analysis revealed that BAC-14 altered 14, 12, and 8 metabolic pathways in M. aeruginosa FACHB-905, M. aeruginosa FACHB-469, and M. wesenbergii FACHB-908, respectively. It is noteworthy that BAC-14 enhanced the level of extracellular microcystin production in the toxigenic Microcystis strains , although cell growth was not significantly affected. Collectively, these data show that BAC-14 disrupted the physiological and metabolic status of Microcystis cells and stimulated the production and release of microcystin, which could result in damage to aquatic systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Harmful cyanobacterial blooms (CyanoHABs) impact lakes, estuaries, and freshwater reservoirs worldwide. The duration, severity, and spread of CyanoHABs have markedly increased over the past decades and will likely continue to increase. This article addresses the universal phenomena of cyanobacterial blooms occurring in many freshwater ecosystems worldwide. Based on analysis of ecophysiological traits of bloom-forming cyanobacteria and their interactions with environmental processes, we summarize and decipher the driving forces leading to the initiation, outbreak, and persistence of the blooms. Due to the coupling effects of eutrophication, rising CO2 levels and global warming, a multidisciplinary joint research approach is critical for better understanding the CyanoHAB phenomenon and its prediction, remediation, and prevention. There is an urgent need to evaluate and guide proper use of bloom control techniques at large scales, using science-based and environmentally friendly approaches. [ABSTRACT FROM AUTHOR]

Abstract Effect-based methods (EBMs) are recommended as holistic approach for diagnosis and monitoring of water quality; however, the application of EBMs is still scare in China. In the present study, water quality of the freshwater lake Taihu (China) was investigated by EBMs. Different types of water samples were collected from three bays of the lake during 2015, 2016 and 2017. A battery of seven effect-based bioassays, including both specific and non-specific toxicity assays, was used. The bioassay battery was recently suggested based on joint activities of the EU project SOLUTIONS and the NORMAN network on emerging pollutants and is also under discussion for being implemented into monitoring activities in the context of the European Water Framework Directive (WFD). Adverse effects were observed towards the primary producer, primary consumer and fish, indicating the potential ecotoxicity of water in Taihu Lake. Mutagenic and estrogenic effects were found in the Ames fluctuation assay and ERα CALUX (Chemically Activated Luciferase Gene-eXpression) assay, respectively, highlighting the potential risks on human health. Algal growth inhibition and mutagenic effects can be observed during each of the three years. Acute toxicity towards Daphnia magna and estrogen receptor agonistic effects were found in at least one of the samples collected in 2016 and 2017, but not in 2015. The endpoints for fish toxicity in the Danio rerio fish embryo test included both lethal and additionally several sublethal effects (only for samples from 2017) and were not compared between years. Algal growth inhibition, fish embryo toxicity, mutagenic effect and estrogenicity were observed in each of the three bays, while Daphnia acute toxicity was only found in Zhushan Bay. Taking together, this study provides a big picture on the water quality of Taihu Lake. The battery of effect-based tools is promising to be a routine for water quality monitoring in China. Graphical abstract Unlabelled Image Highlights • Seven effect based methods have been successfully used to diagnose and monitor water quality of Taihu Lake. • Potential ecotoxicities were observed in water samples. • Mutagenic and estrogenic effects were also found in these samples. • No androgenicity and genotoxicity was observed. [ABSTRACT FROM AUTHOR]

Abstract In the present study, both bioanalytical and instrumental tools were employed to examine the endocrine-disruptive potentials of water samples, cyanobloom samples, and sediment samples collected from in the northern region of Taihu Lake (China) during cyanobloom season. Results from cell-based bioassays suggested the occurrence of estrogenic, anti-estrogenic, anti-androgenic, and anti-glucocorticogenic activities, while no androgenic and glucocorticogenic activities were observed in the collected samples. Using an UPLC-MS/MS system, 29 endocrine disrupting compounds including seven estrogens, seven androgens, six progestogens, and five adrenocortical hormones and four industrial pollutants were simultaneously detected. 17, 20 and 12 chemicals were detected at least in one of the water samples, cyanobloom samples and sediment samples, respectively. Since both agonistic and antagonistic endocrine-disruptive activities were detected in the present study, commonly used receptor-based in vitro bioassays resulted in net effects, suggesting that the hormone receptor agonistic potentials might be underestimated with this practice. The EDCs detected in cyanobloom samples also highlight the necessity to consider the phytoplankton matrix for understanding the mass fluxes of endocrine disruptors in eutrophic freshwaters and to consider it in monitoring strategies. Graphical abstract Unlabelled Image Highlights • Endocrine disruptors in multiple matrices were systematically examined. • Results from bioassays suggest estrogenic but not androgenic and glucocorticogenic agonists were detected. • Antagonistic effects were widely observed in all the matrices. • Endocrine disruptors were pronouncedly detected in cyanoblooms. [ABSTRACT FROM AUTHOR]

The toxicity of cyanotoxins on plant has been reported. However, in eutrophic waters harmful cyanobacteria are associated with other environmental pollutants, such as persistent organic pollutants (POPs) and metals. Information on the phytotoxicity and bioaccumulation of coexisted cyanotoxins and these environmental pollutants is still lacking. In this study, the combined phytotoxicities of three types of cyanobacteria-associated pollutants, i.e., microcystin-LR (MC-LR), cadmium (Cd), 2, 4, 4′-Trichlorobiphenyl (PCB-28) were systematically investigated. After 7-days exposure, strong synergistic effects can be detected when Arabidopsis thaliana seeds and seedlings exposed to binary mixtures of MC-LR + PCB-28 and PCB-28 + Cd. The strongest inhibition occurred when A. thaliana exposed to their ternary mixture under both glasshouse and semi-field conditions. Moreover, bioaccumulation of MC-LR, Cd and PCB-28 was enhanced when seedlings exposed to their binary/ternary mixtures, especially when seedlings were treated with higher concentrations of toxicants (MC-LR, 1 mg L − 1 ; Cd, 10 mg L − 1 ; PCB-28, 1 μg L − 1 ). Additionally, pronounced toxic effects could be determined under 7-days after seedlings were irrigated with raw cyanobloom-containing water (collected from Lake Taihu in China)and its dilutions. Seeds production decreased significantly after the continuous irrigation with cyanoblooms-containing water. Collectively, this work will be an informative implication for risks of cyanoblooms and adequate utilization of freshwater containing cyanoblooms for crop irrigation. [ABSTRACT FROM AUTHOR]

The distribution of metals in cyanobloom-forming lakes, and potential risks of these metals during irrigation with water derived from the bloom were evaluated in this study. Seven metals were monitored throughout a cyanobacterial bloom season in Lake Taihu. Cyanobloom bio-dilution of the targeted metals could be explained by the negative relationships between total phytoplankton metal contents (Cu, Fe, Zn, Pb and Cr) and Chl a concentrations ( p < 0.05). Meanwhile, the ratios of extracellular bound to total cellular bound metals (Cu, Zn, Pb, Cr and Cd) were positively correlated with the ratios of cyanophyta to total phytoplankton ( p < 0.01), indicating the enhanced extracellular bound of these metals during cyanobloom period. Secondly, Cd, Pb and Cr were detected in several local vegetables. In comparison to reference vegetables, vegetables ( e.g. , radish, soybean, and cowpea), which were irrigated with cyanobloom broth collected from Lake Taihu, presented high health risk index (HRI) and were not safe for human consumption. Collectively, the frequent dominant colonial Microcystis blooms which performed high metal affinity might mediate the distribution of heavy metals in lake and potentially transferred these pollutants into terrestrial system. [ABSTRACT FROM AUTHOR]

Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Firstly, higher expression of KLF4 correlated with increased TAM sensitivity in breast cancer cells, and analysis of GEO datasets indicated that KLF4 expression was positively correlated with ERα and enhanced expression of KLF4 sensitized breast cancer patients to endocrine therapy. Knockdown of KLF4 in MCF-7 and BCAP37 cells led to increased TAM resistance, while ectopic KLF4 expression promoted the responsiveness to TAM in T47D and TAM-resistant MCF-7/TAM cells. Secondly, ectopic KLF4 overexpression suppressed MCF-7/TAM cell growth, invasion and migration. Moreover, KLF4 expression was down-regulated in breast cancer tumor tissues and high expression of KLF4 was associated with favorable outcomes. Mechanistically, KLF4 may enhance the responsiveness of breast cancer cells to TAM through suppressing mitogen-activated protein kinase (MAPK) signaling pathway. We found that ERK and p38 were more activated in MCF-7/TAM compared with MCF-7, and treatment with MAPK-specific inhibitors significantly suppressed cell viability. Knockdown of KLF4 activated ERK and p38 and drove MCF-7 cells to become resistant to TAM. Conversely, overexpression of KLF4 in MCF-7/TAM cells suppressed ERK and p38 signaling and resulted in increased sensitivity to TAM. Therefore, our findings suggested that KLF4 contributed to TAM sensitivity in breast cancer via phosphorylation modification of ERK and p38 signaling. Collectively, this study highlighted the significance of KLF4/MAPK signal interaction in regulating TAM resistance of breast cancer, and suggested that targeting KLF4/MAPK signaling may be a potential therapeutic strategy for breast cancer treatment, especially for the TAM-resistant patients. [ABSTRACT FROM AUTHOR]

Abstract Efficient biocoagulants/bioflocculants are desired for removal of Microcystis aeruginosa , the dominant harmful bloom-forming cyanobacterium. Herein, we reported cationic hydroxyethyl cellulose (CHEC) inactivated M. aeruginosa cells after forming coagulates and floating-flocculated them with aid of Agrobacterium mucopolysaccharides (AMP) and surfactant. CHEC exhibited cyanocidal activity at 20 mg/L, coagulating 85% of M. aeruginosa biomass within 9 h and decreasing 41% of chlorophyll a after 72 h. AMP acted as an adhesive flocculation aid that accelerated and strengthened the formation of flocs, approaching a maximum in 10 min. Flocs of M. aeruginosa were floated after foaming with cocoamidopropyl betaine (CAB), which facilitated the subsequent filter harvest. 82% of M. aeruginosa biomass was suspended on water surface after treated with the coagulation/flocculation-flotation (CFF) agents containing CHEC (25 mg/L), AMP (177 mg/L) and CAB (0.1 mg/L). All components in CFF agents at the applied concentrations did not inhibit acetylcholinesterase or Vibrio fischeri. Our findings provide new insights in developing bio-based materials for sustainable control of cyanobacterial blooms. [Display omitted] • Harmful bloom-forming M. aerugino sa was inactivated by cationic hydroxyethyl cellulose (CHEC). • Agrobacterium mucopolysaccharides (AMP) accelerated coagulation/flocculation of M. aerugino sa by CHEC. • CHEC, AMP and surfactant floating-flocculated M. aeruginosa , facilitating its harvest. [ABSTRACT FROM AUTHOR]

A novel approach that uses noninvasive ultrasound to measure the temperature distribution in solid materials is described and validated in high-temperature laboratory experiments. The approach utilizes an ultrasound propagation path with naturally occurring or purposefully introduced echogenic features that partially redirect the energy of an ultrasound excitation pulse back to the transducer, resulting in a train of echoes. Their time of flight depends on the velocity of ultrasound propagation, which changes with temperature distribution in different segments of the propagation path. We reconstruct segmental temperature distributions under different parameterizations. Several parameterizations are discussed, including piecewise constant and piecewise linear, and the parametrization that requires that the estimated temperature profile satisfies an appropriate heat conduction model. The experimental validation of the proposed approach with an alumina sample shows that even with simple parameterizations, the temperature profile is correctly captured with an accuracy that may be comparable to that of the traditional pointwise sensors. The advantages of the approach are discussed, including its suitability for real time and non-destructive temperature measurements in extreme environments and locations inaccessible to the traditional insertion sensors. [ABSTRACT FROM AUTHOR]

Super-enhancers (SEs) in a broad range of human cell types are large clusters of enhancers with aberrant high levels of transcription factor binding, which are central to drive expression of genes in controlling cell identity and stimulating oncogenic transcription. Cancer cells acquire super-enhancers at oncogene and cancerous phenotype relies on these abnormal transcription propelled by SEs. Furthermore, specific inhibitors targeting SEs assembly and activation have offered potential targets for treating various tumors including hematological malignancies. Here, we first review the identification, functional significance of SEs. Next, we summarize recent findings of SEs and SE-driven gene regulation in normal hematopoiesis and hematologic malignancies. The importance and various modes of SE-mediated MYC oncogene amplification are illustrated. Finally, we highlight the progress of SEs as selective therapeutic targets in basic research and clinical trials. Some open questions regarding functional significance and future directions of targeting SEs in the clinic will be discussed too. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) as postremission treatment is recommended for Philadelphia‐positive acute lymphoblastic leukemia (Ph+ ALL) in current guidelines. However, comparisons of later generation tyrosine kinase inhibitors (TKIs) plus chemotherapy with allo‐HSCT have yielded similar outcomes. This meta‐analysis was performed to evaluate allo‐HSCT in first complete remission (CR1) versus chemotherapy for adult Ph+ ALL in the TKI era. Methods: Pooled assessment of the hematologic and molecular complete response rates was performed after 3‐month TKI treatment. Hazard ratios (HRs) were determined for disease‐free survival (DFS) and overall survival (OS) benefit with allo‐HSCT. The effect of measurable residual disease status on survival benefit was also analyzed. Results: Thirty‐nine retrospective and prospective single‐arm cohort studies involving 5054 patients were included. Combined HRs indicated that in the general population, allo‐HSCT favorably influenced DFS and OS. Achieving complete molecular remission (CMR) within 3 months after starting induction was a favorable survival prognostic factor regardless of whether the patient had undergone allo‐HSCT. Among the patients with CMR, survival rates in the nontransplant subgroup were comparable with those in the transplant subgroup, with the estimated 5‐year OS of 64% versus 58% and 5‐year DFS of 58% versus 51%, respectively. The use of next‐generation TKIs results in a higher proportion of patients achieving CMR (ponatinib 82% vs. imatinib 53%), while improving survival in nontransplant patients. Conclusion: Our novel findings suggest that combination chemotherapy plus TKIs leads to a comparable survival benefit as with allo‐HSCT for MRD‐negative (CMR) patients. This study provides novel evidence for allo‐HSCT indications for Ph+ ALL in CR1 in the TKI era. In the tyrosine kinase inhibitor (TKI) era, the role and need for allogeneic hematopoietic stem cell transplantation (allo‐HSCT) have now become less certain for adult Philadelphia‐positive acute lymphoblastic leukemia in first complete remission. This meta‐analysis suggests that allo‐HSCT confers no survival advantage on measurable residual disease (MRD)–negative patients; and the use of newer generations of TKIs resulted in more patients achieving MRD‐negative status, effectively improving survival in nontransplant patients. [ABSTRACT FROM AUTHOR]

Plastic particles have been proven to be abundant in the aquatic environment, raising concerns about their potential toxic effects. In the present study, we determined the bioaccumulation potential of bisphenol A (BPA) in adult zebrafish ( Danio rerio ) in the absence and presence of nano-sized plastic particles (nanoplastics, NPPs). Results show that BPA can accumulate in the viscera, gill, head and muscle of zebrafish with 85, 43, 20, and 3 μg/g ww after 1 d exposure. NPPs were also found to accumulate in different tissues of the fish. Relative equilibrium was reached after 1 d exposure in different tissues with 39 to 636 mg/kg ww . Co-exposure of NPPs and BPA led to a 2.2 and 2.6-fold significant increment of BPA uptake in the head and viscera, if compared with BPA alone treatment after 3 d exposure. As such, we further investigated several neurotoxic biomarker alterations in the fish head. It was found that either BPA or NPPs can cause myelin basic protein (MBP)/gene up-regulation in the central nervous system (CNS); meanwhile, both contaminants exhibited significant inhibition of acetylcholinesterase (AChE) activity, which is a well-known representative biomarker for neurotoxicity. Moreover, for the co-exposure treatment, biomarkers of myeline and tubulin protein/gene expressions, dopamine content, and the mRNA expression of mesencephalic astrocyte derived neurotrophic factor (MANF) were all significantly up-regulated, suggesting that an enhanced neurotoxic effects in both CNS and dopaminergic system occurred. However, AChE activity was no more inhibited in the co-exposure treatment, which implies that solely AChE measurement may not be sufficient to identify neurotoxic effects in the cholinergic system. Overall, the present study demonstrates that the presence of NPPs can increase BPA bioavailability and cause neurotoxicity in adult zebrafish. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer/T-cell lymphoma (NKTL) is an aggressive type of non-Hodgkin lymphoma with dismal outcome. A better understanding of disease biology and key oncogenic process is necessary for the development of targeted therapy. Super-enhancers (SEs) have been shown to drive pivotal oncogenes in various malignancies. However, the landscape of SEs and SE-associated oncogenes remain elusive in NKTL. Methods: We used Nano-ChIP-seq of the active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) to profile unique SEs NKTL primary tumor samples. Integrative analysis of RNA-seq and survival data further pinned down high value, novel SE oncogenes. We utilized shRNA knockdown, CRISPR-dCas9, luciferase reporter assay, ChIP-PCR to investigate the regulation of transcription factor (TF) on SE oncogenes. Multi-color immunofluorescence (mIF) staining was performed on an independent cohort of clinical samples. Various function experiments were performed to evaluate the effects of TOX2 on the malignancy of NKTL in vitro and in vivo. Results: SE landscape was substantially different in NKTL samples in comparison with normal tonsils. Several SEs at key transcriptional factor (TF) genes, including TOX2, TBX21(T-bet), EOMES, RUNX2, and ID2, were identified. We confirmed that TOX2 was aberrantly overexpressed in NKTL relative to normal NK cells and high expression of TOX2 was associated with worse survival. Modulation of TOX2 expression by shRNA, CRISPR-dCas9 interference of SE function impacted on cell proliferation, survival and colony formation ability of NKTL cells. Mechanistically, we found that RUNX3 regulates TOX2 transcription by binding to the active elements of its SE. Silencing TOX2 also impaired tumor formation of NKTL cells in vivo. Metastasis-associated phosphatase PRL-3 has been identified and validated as a key downstream effector of TOX2-mediated oncogenesis. Conclusions: Our integrative SE profiling strategy revealed the landscape of SEs, novel targets and insights into molecular pathogenesis of NKTL. The RUNX3-TOX2-SE-TOX2-PRL-3 regulatory pathway may represent a hallmark of NKTL biology. Targeting TOX2 could be a valuable therapeutic intervene for NKTL patients and warrants further study in clinic. [ABSTRACT FROM AUTHOR]

In this study, the distribution, transfer and fate of both polychlorinated biphenyls (PCBs) and cyanotoxins via phytoplankton routes were systematically investigated in two Chinese lakes. Results indicated that PCB adsorption/bioaccumulation dynamics has significantly positive correlations with the biomass of green alga and diatoms. Total lipid content of phytoplankton is the major factor that influences PCB adsorption/bioaccumulation. Cyanobacterial blooms with relatively lower lipid content could also absorb high amount of PCBs due to their high cell density in the water columns, and this process was proposed as major route for the transfer of PCBs in Chinese eutrophic freshwater. According to these findings, a novel route on fates of PCBs via phytoplankton and a green bioadsorption concept were proposed and confirmed. In the practice of mechanical collections of bloom biomass from Lake Taihu, cyanotoxin/cyanobacteria and PCBs were found to be removed simultaneously very efficiently followed this theory. [ABSTRACT FROM AUTHOR]

[Display omitted] • Modified clay (MC) is first applied for the mitigation of Aphanizomenon flos-aquae. • The settling kinetics of MC in mitigating HABs are investigated. • The mitigation of HABs using MC will be accelerated by hydraulic regulation. • Large, compact, and rapidly settling flocs are prone to form under hydraulic shear. • The kinetic mechanism of HABs removal by MC based on flow field is revealed. Modified clay is considered to be the most direct and effective method for emergency mitigation of harmful algal blooms (HABs), and it has been widely applied. However, its application on Aphanizomenon flos-aquae blooms has not been reported. Additionally, the hydraulic characteristics of modified clay in settling algal cells and the mechanism of its influence by flow fields have not been well studied, which is detrimental to the effective application of modified clay in alleviating HABs. Therefore, this study investigates the feasibility of using modified clay to alleviate Aphanizomenon flos-aquae blooms through laboratory-scale experiments and field engineering applications, and analyzes the keinetic mechanism of algal cell settling by modified clay based on flow field characteristics. The results indicate that PAC-modified clay can effectively alleviate Aphanizomenon flos-aquae blooms, achieving a removal efficiency of over 90 %. Differences in mineral composition, particle size, mineral-to-PAC ratio, and hydraulic shear significantly affect the removal performance of algal cells. The flow field characteristics of the water not only affect the removal efficiency of algal cells, but also influence the settling speed of the cells. By artificially increasing hydraulic shear and enhancing the distribution of velocity and turbulence kinetic energy in the water, the interaction between algal cell-coagulant-clay particle is promoted, resulting in the formation of larger and denser flocs, yielding faster settling performance. In the practical engineering application at Changshuiyan Reservoir, the use of boat propellers to agitate the water also verified this reinforcing effect. Aphanizomenon flos-aquae blooms were effectively alleviated, and transparency increased from the initial 0.5 m to 5.5 m. This study, for the first time, combines flow field simulation of clay particle settling to analyze the kinetic mechanism of hydraulic shear in enhancing the efficiency of modified clay in alleviating HABs from a kinetic perspective. [ABSTRACT FROM AUTHOR]

Cyanobacteria and their toxins present potential hazard to consumers of water from lakes, reservoirs and rivers, thus their removal via water treatment or at the source, is essential. Here, we report that alkyltrimethylammonium (ATMA) surfactants, such as octadecyltrimethylammonium (ODTMA) bromide, act as cyanocides that efficiently inhibit photosynthesis and growth of cyanobacteria. Green algae were found less sensitive than cyanobacteria to ATMA compounds. Fluorescence measurements and microscopic observations demonstrated that cyanobacteria cells (Aphanizomenon or Microcystis) disintegrate and lose their metabolic activity (photosynthesis) upon exposure to ATMA bromides (estimated ED 50(1hr) ranged between 1.5 and 7 μM for ODTMA-Br or hexadecyltrimethylammonium (HDTMA) bromide). Other ATMA compounds, such as tetradecyltrimethylammonium (TDTMA) or dodecyltrimethylammonium (DDTMA) bromides had similar inhibitory effect but their toxicity to cyanobacteria (measured as ED 50(1hr) for photosynthetic efficiency) decreased, as the length of the alkyl chain decreased. All ATMA compounds used in this study showed lower toxicity to green algae than to cyanobacteria. A toxicity mechanism for ATMA cations is proposed, based on real time fluorescence signals and on alteration of cell ultra-structure revealed by electron microscopy. The present study sheds light on the toxic effect of ATMA surfactants on cyanobacteria and its potential application for controlling the occurrence of cyanobacterial bloom in lakes, reservoirs or rivers to secure the safety of drinking water and to mitigate and manage bloom events. • Alkyltrimethylammonium (ATMA) surfactants inhibit photosynthesis. • Cyanobacteria show higher sensitivity to ATMA surfactants than green algae. • Toxicity of ATMA surfactants decreases with the shortening of the alkyl chain length. • Long chain ATMA surfactants can be used as effective and selective cyanocides. [ABSTRACT FROM AUTHOR]

• Our data confirmed not only niche differentiation but also complex. associations among three bloom-forming cyanobacteria. • Effects of environmental and biological factors were assessed on species-specific biomass. • Microcystis biomass was strongly affected by water temperature and phosphorus concentrations across the studied lakes. • The responses of Aphanizomenon and Dolichospermum to environmental conditions exhibited lake-specific patterns. Non-diazotrophic Microcystis and filamentous N 2 -fixing Aphanizomenon and Dolichospermum (formerly Anabaena) co-occur or successively dominate freshwaters globally. Previous studies indicate that dual nitrogen (N) and phosphorus (P) reduction is needed to control cyanobacterial blooms; however, N limitation may cause replacement of non-N 2 -fixing by N 2 -fixing taxa. To evaluate potentially counterproductive scenarios, the effects of temperature, nutrients, and zooplankton on the spatio-temporal variations of cyanobacteria were investigated in three large, shallow eutrophic lakes in China. The results illustrate that the community composition of cyanobacteria is primarily driven by physical factors and the zooplankton community, and their interactions. Niche differentiation between Microcystis and two N 2 -fixing taxa in Lake Taihu and Lake Chaohu was observed, whereas small temperature fluctuations in Lake Dianchi supported co-dominance. Through structural equation modelling, predictor variables were aggregated into 'composites' representing their combined effects on species-specific biomass. The model results showed that Microcystis biomass was affected by water temperature and P concentrations across the studied lakes. The biomass of two filamentous taxa, by contrast, exhibited lake-specific responses. Understanding of driving forces of the succession and competition among bloom-forming cyanobacteria will help to guide lake restoration in the context of climate warming and N:P stoichiometry imbalances. [ABSTRACT FROM AUTHOR]

Background: Despite the considerable experience gained thus far using endoscopic technologies, the role of total endoscopic thyroidectomy (ET) for papillary thyroid cancer (PTC) remains controversial. We conducted a systematic review and meta-analysis to investigate the safety and effectiveness of total ET compared with conventional open thyroidectomy (OT) in PTC.Methods: A systematic search was conducted using the PubMed, Embase and Cochrane Library electronic databases up to March 2018. The quality of included studies was evaluated using the Newcastle-Ottawa Scale. Review Manager software version 5.3 was used for the meta-analysis.Results: Twelve studies including 2,672 patients were ultimately included in the systematic review and meta-analysis. ET was associated with longer operative time (P<0.00001), drainage time (P<0.00001) and hospital stay (P=0.03), higher transient recurrent laryngeal nerve (RLN) palsy rate (P=0.004) and a greater amount of drainage fluid (P<0.0001) compared with OT. Furthermore, no significant differences were detected between ET and OT in terms of retrieved lymph nodes (P=0.17), blood loss (P=0.22), transient hypocalcemia (P=0.84), permanent hypocalcemia (P=0.58), permanent RLN palsy (P=0.14), hematoma or bleeding (P=0.15) and seroma (P=0.54). In addition, the rates of tumor recurrence were comparable (P=0.18), whereas the proportions of stimulated thyroglobulin levels <1 ng/mL measured after completion of thyroidectomy and radioactive iodine therapy were less (P=0.02) in the ET than in the OT group.Conclusion: ET is not superior to OT in terms of operation and drainage time, amount of drainage fluid, hospital stay or transient RLN palsy, but is comparable to OT in terms of retrieved lymph nodes and permanent complications. Despite the similar tumor recurrence rates between the two approaches, the level of surgical completeness in ET may not be as good as that for OT. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma in situ with microinvasion (DCISM) represents ~1% of all breast cancer cases. Risk factors for lymph node (LN) metastasis and appropriate adjuvant therapy for DCISM are still widely debated. Methods: We retrieved DCISM data from the National Cancer Institute's Surveillance, Epidemiology, and End Results registry database (1998–2013). Chi-squared tests and logistic regression models were applied to investigate the potential risks of LN metastasis. Univariate and multivariate Cox proportional hazards regressions were performed to estimate the prognostic factors of DCISM. Survival outcomes were estimated using the Kaplan–Meier method. A 1:1 propensity score matching was used to minimize potential bias. Results: Overall, 6,219 patients with DCISM met our inclusion criteria. Younger age and higher grade disease were identified as risk factors for LN metastasis. In the multivariable analysis, LN metastasis and chemotherapy were prognostic factors for worse overall survival and breast cancer-specific survival. Furthermore, propensity score matching and subgroup analysis showed that chemotherapy may not be effective for DCISM patients. Conclusion: Younger patients with high-grade disease tend to have LN involved in DCISM. Adjuvant chemotherapy might not be necessary for patients with DCISM. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxia and hypovascular tumor microenvironment. Nucleolar and spindle associated protein 1 (NUSAP1) is a microtubule-associated protein that is known to be involved in cancer biology. Our study aimed to investigate the role of NUSAP1 in glycolytic metabolism and metastasis in PDAC. Expression and prognostic value of NUSAP1 in PDAC and common gastrointestinal tumors was evaluated. The function of NUSAP1 in PDAC progression was clarified by single-cell RNA-seq and further experiments in vitro, xenograft mouse model, spontaneous PDAC mice model and human tissue microarray. The downstream genes and signaling pathways regulated by NUSAP1 were explored by RNA-Seq. And the regulation of NUSAP1 on Lactate dehydrogenase A (LDHA)-mediated glycolysis and its underlying mechanism was further clarified by CHIP-seq. NUSAP1 was an independent unfavorable predictor of PDAC prognosis that playing a critical role in metastasis of PDAC by regulating LDHA-mediated glycolysis. Mechanically, NUSAP1 could bind to c-Myc and HIF-1α that forming a transcription regulatory complex localized to LDHA promoter region and enhanced its expression. Intriguingly, lactate upregulated NUSAP1 expression by inhibiting NUSAP1 protein degradation through lysine lactylated (Kla) modification, thus forming a NUSAP1-LDHA-glycolysis-lactate feedforward loop. The NUSAP1-LDHA-glycolysis-lactate feedforward loop is one of the underlying mechanisms to explain the metastasis and glycolytic metabolic potential in PDAC, which also provides a novel insights to understand the Warburg effect in cancer. Targeting NUSAP1 would be an attractive paradigm for PDAC treatment. • NUSAP1 activates LDHA-mediated glycolysis and promotes metastasis in PDAC. • Lactate upregulates NUSAP1 protein expression feedback by lysine lactylated modification. • NUSAP1-LDHA-glycolysis-lactate loop promotes glycolytic metabolic preference in PDAC. • Targeting NUSAP1 provides an attractive paradigm for PDAC treatment. [ABSTRACT FROM AUTHOR]

• The toxicity pathways of paraquat to Microcystis aeruginosa were elucidated. • Enhanced energy metabolisms and antioxidative systems were induced by paraquat. • Exposed to high level paraquat led to growth inhibition regardless of cell metabolism acclimation. • A proposed adverse outcome pathway of paraquat was established in M. aeruginosa. Chemical pollutants, such as herbicides, released into the aquatic environment adversely affect the phytoplankton community structure. While majority of herbicides are specifically designed to target photosynthetic processes, they also can be toxic to phytoplankton; however, despite the photosynthetic toxicity, some herbicides can target multiple physiological processes. Therefore, a full picture of toxicity pathway of herbicide to phytoplankton is necessary. In the present study, the cyanobacterium Microcystis aeruginosa was exposed to two levels (17 μg L−1 (EC 10) and 65 μg L−1 (EC 50)) of paraquat for 72 h. The physiological and metabolic responses were analyzed to elucidate the toxicity pathway and establish the adverse outcome pathway of paraquat to M. aeruginosa. The results revealed that enhanced glycolysis (upregulation of pyruvic acid level) and tricarboxylic acid cycle (upregulation of the levels of malic acid, isocitric acid and citric acid) exposed to EC 10 level of paraquat, which probably acted as a temporary strategy to maintain a healthy energy status in M. aeruginosa cells. Meanwhile, the expressions of glutathione and benzoic acid were enhanced to scavenge the excessive reactive oxygen species (ROS). Additionally, the accumulation of pigments (chlorophyll a and carotenoid) might play a supplementary role in the acclimation to EC 10 level paraquat treatment. In cells exposed to paraquat by EC 50 level, the levels of SOD, CAT, glutathione and benzoic acid increased significantly; however, the ROS exceeded the tolerance level of antioxidant system in M. aeruginosa. The adverse effects were revealed by inhibition of chlorophyll a fluorescence, the decreases in several carbohydrates (e.g., glucose 1-phosphate, fructose and galactose) and total protein content. Consequently, paraquat-induced oxidative stress caused the growth inhibition of M. aeruginosa. These findings provide new insights into the mode of action of paraquat in M. aeruginosa. [Display omitted] [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. CCA has become a global health problem with rising incidence and mortality that threatens the health of human beings. The immune microenvironment of CCA is characterized by abundant cancer-associated fibroblast and suppressive immune components. The increasing body of knowledge and recent developments in transcriptomic studies have given insight into the immune landscape of CCA, paving the way for better application of immunotherapy. Immunotherapy mainly applies in a limited subset of CCA with deficient mismatch and high microsatellite instability. With limited response rates and treatment efficacy, researchers are looking into novel strategies on combination strategies and alternatives, such as immune vaccines and adoptive cell therapy. Biomarker identification is also critical for patient selection. We present an up-to-date summary of the current research on immunotherapy for CCA patients, covering pre-clinical and clinical exploration beyond immune checkpoint inhibitors, immune vaccines, and adoptive cell therapy. In addition, we review the promising biomarkers for CCA immunotherapy and discuss recent development. [ABSTRACT FROM AUTHOR]

The apolipoprotein E (APOE) ɛ4 allele is the best-known genetic risk factor for developing sporadic Alzheimer's disease (AD). According to neuroimaging studies, the APOE ɛ4 allele is associated with localized altered brain function. However, in long-range circuitry, APOE ɛ4 allele-related alterations in functional communication between hemispheres have rarely been directly investigated. We examined the alteration of resting-state functional connectivity (RSFC) between inter-hemispheric homotopic regions in cognitively intact, elderly APOE ɛ4 carriers. The voxel-mirrored homotopic connectivity method was used to assess the inter-hemispheric RSFC. The current study included 13 cognitively intact, elderly APOE ɛ4 carriers (with at least one copy of APOE ɛ4 allele) and 22 well-matched ɛ3 homozygotes. Comparisons between the two groups were conducted, and subsequently, the correlation between the differential inter-hemispheric RSFC and cognitive ability was analyzed. Compared with ɛ3 homozygotes, APOE ɛ4 carriers showed decreased inter-hemispheric RSFC in the bilateral medial temporal lobe (MTL) and orbital frontal cortex (OFC). Moreover, in APOE ɛ4 carriers, the inter-hemispheric RSFC of the MTL correlated with the Wechsler Memory Scale-Logical Memory (WMS-LM) (immediate and delayed performance, r = 0.64, p <  0.05; r = 0.65, p <  0.05, respectively), and the inter-hemispheric RSFC of the OFC correlated with the WMS-LM delayed performance (r = 0.71, p <  0.05). In our study, the presence of the APOE ɛ4 allele was linked with decreased inter-hemispheric RSFC, which was attributed to memory performance in carriers. [ABSTRACT FROM AUTHOR]

Exosomes are stable nanovesicles secreted by cells into the circulation. Their reported sizes differ substantially, which likely reflects the difference in the isolation techniques used, the cells that secreted them, and the methods used in their characterization. We analyzed the influence of the last factor on the measured sizes and shapes of hydrated and desiccated exosomes isolated from the serum of a pancreatic cancer patient and a healthy control. We found that hydrated exosomes are close-to-spherical nanoparticles with a hydrodynamic radius that is substantially larger than the geometric size. For desiccated exosomes, we found that the desiccated shape and sizing are influenced by the manner in which drying occurred. Isotropic desiccation in aerosol preserves the near-spherical shape of the exosomes, whereas drying on a surface likely distorts their shapes and influences the sizing results obtained by techniques that require surface fixation prior to analysis. [ABSTRACT FROM AUTHOR]

Background: Tamoxifen resistance remains a clinical challenge for hormone receptor-positive breast cancer. Recently, dysregulations in autophagy have been suggested as a potential mechanism for tamoxifen resistance. Although the long noncoding RNA H19 is involved in various stages of tumorigenesis, its role in tamoxifen resistance remains unknown. Here, we assessed the role of H19 in the development of tamoxifen-resistant breast cancer. Methods: Quantitative real-time PCR analyzed expression of H19 in tamoxifen-resistant breast cancer tissues. Knockdown of H19 was used to assess the sensitivity to tamoxifen in vitro and in vivo. Both knockdown and overexpression of H19 were used to analyze the status of autophagy. Real-time quantitative methylation-specific polymerase chain reaction, chromatin immunoprecipitation, immunofluorescence, and Western blot were used to explore the tamoxifen resistance mechanism of H19. Results: In this study, we observed that the expression of H19 was substantially upregulated in tamoxifen-resistant breast cancer cell line and tumor tissues, and knockdown of H19 enhanced the sensitivity to tamoxifen both in vitro and in vivo. Furthermore, knockdown of H19 significantly inhibited autophagy in MCF7 tamoxifen-resistant (MCF7/TAMR) cells. Conversely, overexpression of H19 promoted autophagy. Interestingly, overexpression of H19 in MCF7 tamoxifen-sensitive cells could recapitulate tamoxifen resistance. Moreover, an increase in methylation in the promoter region of Beclin1 was observed in MCF7/TAMR-shH19 cells. In the double knockdown groups, both shH19+shSAHH and shH19+shDNMT3B rescued the Beclin1 promoter region methylation levels and reactivated autophagy functions. A chromatin immunoprecipitation assay further validated that DNMT3B binds to the Beclin1 promoter region and the knockdown of H19 increases this binding. Conclusions: Our findings demonstrate that H19 induces autophagy activation via the H19/SAHH/DNMT3B axis, which could contribute to tamoxifen resistance in breast cancer. [ABSTRACT FROM AUTHOR]