Does climate change increase the risk of marine toxins? Insights from changing seawater conditions.

Marine toxins produced by marine organisms threaten human health and impose a heavy public health burden on coastal countries. Lately, there has been an emergence of marine toxins in regions that were previously unaffected, and it is believed that climate change may be a significant factor. This paper systematically summarizes the impact of climate change on the risk of marine toxins in terms of changes in seawater conditions. From our findings, climate change can cause ocean warming, acidification, stratification, and sea-level rise. These climatic events can alter the surface temperature, salinity, pH, and nutrient conditions of seawater, which may promote the growth of various algae and bacteria, facilitating the production of marine toxins. On the other hand, climate change may expand the living ranges of marine organisms (such as algae, bacteria, and fish), thereby exacerbating the production and spread of marine toxins. In addition, the sources, distribution, and toxicity of ciguatoxin, tetrodotoxin, cyclic imines, and microcystin were described to improve public awareness of these emerging marine toxins. Looking ahead, developing interdisciplinary cooperation, strengthening monitoring of emerging marine toxins, and exploring more novel approaches are essential to better address the risks of marine toxins posed by climate change. Altogether, the interrelationships between climate, marine ecology, and marine toxins were analyzed in this study, providing a theoretical basis for preventing and managing future health risks from marine toxins.

The effect and mechanism of combined exposure of MC-LR and NaNO2 on liver lipid metabolism.

Microcystin-LR (MC-LR) and sodium nitrite (NaNO2) co-exist in the environment and are hepatotoxic. The liver has the function of lipid metabolism, but the impacts and mechanisms of MC-LR and NaNO2 on liver lipid metabolism are unclear. Therefore, we established a chronic exposure model of Balb/c mice and used LO2 cells for in vitro verification to investigate the effects and mechanisms of liver lipid metabolism caused by MC-LR and NaNO2. The results showed that after 6 months of exposure to MC-LR and NaNO2, the lipid droplets content was increased, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were raised in the liver (P < 0.05). Moreover, MC-LR and NaNO2 synergistically induced hepatic oxidative stress by decreasing total superoxide dismutase (T-SOD) activity and glutathione (GSH) levels and increasing malondialdehyde (MDA) content levels. In addition, the levels of Nrf2, HO-1, NQO1 and P-AMPK was decreased and Keap1 was increased in the Nrf2/HO-1 pathway. The key factors of lipid metabolism, SREBP-1c, FASN and ACC, were up-regulated in the liver. More importantly, there was a combined effect on lipid deposition of MC-LR and NaNO2 co-exposure. In vitro experiments, MC-LR and NaNO2-induced lipid deposition and changes in lipid metabolism-related changes were mitigated after activation of the Nrf2/HO-1 signaling pathway by the Nrf2 activator tertiary butylhydroquinone (TBHQ). Additionally, TBHQ alleviated the rise of reactive oxygen species (ROS) in LO2 cells induced by MC-LR and NaNO2. Overall, our findings indicated that MC-LR and NaNO2 can cause abnormal liver lipid metabolism, and the combined effects were observed after MC-LR and NaNO2 co-exposure. The Nrf2/HO-1 signal pathway may be a potential target for prevention and control of liver toxicity caused by MC-LR and NaNO2.

Exploiting the potential of a novel "in-situ latent heat recovery" in hollow-fiber vacuum membrane distillation process for simultaneously improved water production and energy efficiency.

Thermal driven membrane distillation (MD) technology is a promising method for purifying & recovering various salty (especially high salty) or contaminated wastewaters with low-grade heat sources. However, the drawbacks of "high energy consumption" and "high cooling water consumption" pose special challenges for the future development of this technology. In this article, we report an innovative strategy called "in-situ heat transfer", which is based on the jacketed structure composed of hollow fiber membranes and capillary heat exchange tubes, to simplify the migration steps of condensation latent heat in MD heat recovery process. The results indicate that the novel heat recovery strategy exhibits higher growth rates both in the flux and gained output ratio (47.4 % and 173.1 %, respectively), and further reduces the system's dependence on cooling water. In sum, under the control of the "in-situ heat transfer" mechanism, the functional coupling of "vapor condensation (exothermic)" and "feed evaporation (endothermic)" in limited-domain space is an attractive alternative solution, because it eliminates the disadvantages of the imbalance between heat supply and demand in traditional heat recovery methods. Our research may facilitate the development of MD heat recovery modules for industrial applications, which will help to further achieve the goal of energy saving and emission reduction.

Sub-8 nm networked cage nanofilm with tunable nanofluidic channels for adaptive sieving.

Biological cell membrane featuring smart mass-transport channels and sub-10 nm thickness was viewed as the benchmark inspiring the design of separation membranes; however, constructing highly connective and adaptive pore channels over large-area membranes less than 10 nm in thickness is still a huge challenge. Here, we report the design and fabrication of sub-8 nm networked cage nanofilms that comprise of tunable, responsive organic cage-based water channels via a free-interface-confined self-assembly and crosslinking strategy. These cage-bearing composite membranes display outstanding water permeability at the 10-5 cm2 s-1 scale, which is 1-2 orders of magnitude higher than that of traditional polymeric membranes. Furthermore, the channel microenvironments including hydrophilicity and steric hindrance can be manipulated by a simple anion exchange strategy. In particular, through ionically associating light-responsive anions to cage windows, such 'smart' membrane can even perform graded molecular sieving. The emergence of these networked cage-nanofilms provides an avenue for developing bio-inspired ultrathin membranes toward smart separation.

Advances in polychlorinated biphenyls-induced female reproductive toxicity.

Polychlorinated biphenyls (PCBs) are a class of endocrine-disrupting chemicals (EDCs) widely present in the environment. PCBs have been of concern due to their anti/estrogen-like effects, which make them more toxic to the female reproductive system. However, there is still a lack of systematic reviews on the reproductive toxicity of PCBs in females, so the adverse effects and mechanisms of PCBs on the female reproductive system were summarized in this paper. Our findings showed that PCBs are positively associated with lower pregnancy rate, hormone disruption, miscarriage and various reproductive diseases in women. In animal experiments, PCBs can damage the structure and function of the ovaries, uterus and oviducts. Also, PCBs could produce epigenetic effects and be transferred to the offspring through the maternal placenta, causing development retardation, malformation and death of embryos, and damage to organs of multiple generations. Furthermore, the mechanisms of PCBs-induced female reproductive toxicity mainly include receptor-mediated hormone disorders, oxidative stress, apoptosis, autophagy, and epigenetic modifications. Finally, we also present some directions for future research on the reproductive toxicity of PCBs. This detailed information provided a valuable reference for fully understanding the reproductive toxicity of PCBs.

The cytotoxicity of microcystin-LR: ultrastructural and functional damage of cells.

Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria, which is widely distributed in eutrophic water bodies and has multi-organ toxicity. Previous cytotoxicity studies have mostly elucidated the effects of MC-LR on intracellular-related factors, proteins, and DNA at the molecular level. However, there have been few studies on the adverse effects of MC-LR on cell ultrastructure and function. Therefore, research on the cytotoxicity of MC-LR in recent years was collected and summarized. It was found that MC-LR can induce a series of cytotoxic effects, including decreased cell viability, induced autophagy, apoptosis and necrosis, altered cell cycle, altered cell morphology, abnormal cell migration and invasion as well as leading to genetic damage. The above cytotoxic effects were related to the damage of various ultrastructure and functions such as cell membranes and mitochondria. Furthermore, MC-LR can disrupt cell ultrastructure and function by inducing oxidative stress and inhibiting protein phosphatase activity. In addition, the combined toxic effects of MC-LR and other environmental pollutants were investigated. This review explored the toxic targets of MC-LR at the subcellular level, which will provide new ideas for the prevention and treatment of multi-organ toxicity caused by MC-LR.

Treatment to surfactant containing wastewater with membrane distillation membrane with novel sandwich structure.

Surfactant containing wastewater widely exists in textile industry, which hardly to be treated by membrane technology due to its high in salinity and wetting potential. In this study, PVDF membrane was modified by constructing a PDMS-SiO2-PDMS "sandwich" structure on top of its surface via coating to achieve resistance to surfactant induced wetting. The "sandwich" layer was optimized based on the membrane performance during membrane distillation. Compared to the pristine PVDF membrane with contact angle of 92°, the water contact angle of the membrane with a "sandwich" layer of 0.44 µm increased to 153°. For the feed contained 0.5 wt% NaCl and 0.25 wt% surfactant, there was no membrane wetting occurred during the experiment period using the membrane with a "sandwich" structure, in comparison to the pristine PVDF membrane being wetted from beginning. For a challenge experiment to the developed membrane lasting for 100 h using a surfactant containing feed, there is no wetting sign observed and the stable flux is 20 kg·m-2·h-1.

Novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines as potent and selective agonists of the 5-HT2C receptor.

A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines were identified as potent and selective agonists of the 5-HT2C receptor. Optimizations performed on a previously reported series of racemic tetrahydroquinoline-based tricyclic amines, delivered an advanced drug lead, (R)-4-(3,3,3-trifluoropropyl)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,8]naphthyridine, which displayed excellent in vitro and in vivo pharmacological profiles.

Functionalized Carbon Nanotube-Mediated Transport in Membranes Containing Fixed-Site Carriers for Fast Pervaporation Desalination.

Facilitated transport membranes (FTMs) comprising fixed carrier agents hold considerable potential for obtaining selective and fast separation of mixed molecules in either gas or liquid state. However, diffusion through the membrane is inevitably affected by the resistance from the polymer matrix, where the carrier is absent. Herein, a poly(vinyl alcohol) (PVA)-based separating layer combining the merits of fixed-site transport agents and inorganic nanofillers was developed to reduce the transport resistance. Carbon nanotubes (CNTs) with different degrees of oxidation were prepared and incorporated into the sulfonic acid (-SO3H)-modified PVA matrix. The resultant composite membrane consisting of a microporous polytetrafluoroethylene substrate and a thin PVA-based separating layer (∼700 nm thick) was subject to pervaporation desalination of sodium chloride solution (35,000 ppm) at 30 °C. The effect of -SO3H as a fixed transport agent in the PVA matrix was first investigated experimentally, showing an increase of water flux by 21.8% compared with a control membrane without the transport agent. Subsequently, the CNT-incorporated FTM exhibited good stability (50 h) and improvement in water transport, which was ∼161% of the control FTM (PVA with -SO3H) without loss of selectivity. Such high and stable performance achieved in the CNT-incorporated FTM originated from the construction of low-resistance transport pathways by CNTs between -SO3H groups as well as their uniform dispersion in the polymer matrix.

Dimensional Nanofillers in Mixed Matrix Membranes for Pervaporation Separations: A Review.

Pervaporation (PV) has been an intriguing membrane technology for separating liquid mixtures since its commercialization in the 1980s. The design of highly permselective materials used in this respect has made significant improvements in separation properties, such as selectivity, permeability, and long-term stability. Mixed-matrix membranes (MMMs), featuring inorganic fillers dispersed in a polymer matrix to form an organic-inorganic hybrid, have opened up a new avenue to facilely obtain high-performance PV membranes. The combination of inorganic fillers in a polymer matrix endows high flexibility in designing the required separation properties of the membranes, in which various fillers provide specific functions correlated to the separation process. This review discusses recent advances in the use of nanofillers in PV MMMs categorized by dimensions including zero-, one-, two- and three-dimensional nanomaterials. Furthermore, the impact of the nanofillers on the polymer matrix is described to provide in-depth understanding of the structure-performance relationship. Finally, the applications of nanofillers in MMMs for PV separation are summarized.

Tetrahydroquinoline-based tricyclic amines as potent and selective agonists of the 5-HT2C receptor.

The syntheses, structure-activity relationships (SARs), and biological activities of tetrahydroquinoline-based tricyclic amines as 5-HT2C receptor agonists are reported. An early lead containing a highly unique 6,6,7-ring system was optimized for both in vitro potency and selectivity at the related 5-HT2B receptor. Orally bioactive, potent, and selective 6,6,6-tricyclic 5-HT2C agonists were identified.

Arynes double bond insertion/nucleophilic addition with vinylogous amides and carbodiimides.

Arynes are shown to insert into some C═X double bonds, leading to benzannulated four-membered rings. The strain of these rings allow for a ready, spontaneous opening to afford o-quinomethide analogues. Subsequent nucleophilic addition re-aromatizes the intermediates to achieve ortho-difunctionalization of arynes. In this report, we describe the aryne insertion into the C═C double bonds of vinylogous amides and the C═N double bonds of carbodiimides. The correlation and comparison with aryne single bond insertion chemistry will be discussed. Computational studies for the ring-opening step, as well as the nature of the o-quinomethide intermediates, will also be discussed.

Reaction of arynes with vinylogous amides: nucleophilic addition to the ortho-quinodimethide intermediate.

The reaction of arynes with vinylogous amides containing no free N-H bonds proceeds in a [2 + 2] cycloaddition fashion at ambient temperature. The electronic properties of the vinylogous amides allow for the cycloadducts undergoing a facile ring-opening process, leading to electronically biased ortho-quinodimethide intermediates. Subsequent nucleophilic addition with alcohols affords 2-substituted benzaldehydes or ketones.

From N-benzoylpyridinium imides to pyrazolo[1,5-a]pyridines: a mechanistic discussion on a stoichiometric Cu protocol.

A Cu-mediated preparation of 2-substitiuted pyrazolo[1,5-a]pyridines from N-benzoylpyridinium imides and terminal alkynes is described using stoichiometric Cu(OAc)2 as both the mediator and the oxidant. Extensive DFT calculations suggest a Cu(III) intermediate via disproportionation of Cu(II).

Effect of Preparation Methods on Crystallization Behavior and Tensile Strength of Poly(vinylidene fluoride) Membranes.

Poly(vinylidene fluoride) (PVDF) membranes were prepared by non solvent induced phase separation (NIPS), melt spinning and the solution-cast method. The effect of preparation methods with different membrane formation mechanisms on crystallization behavior and tensile strength of PVDF membranes was investigated. Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) and X-ray diffraction (XRD) were employed to examine the crystal form of the surface layers and the overall membranes, respectively. Spherulite morphologies and thermal behavior of the membranes were studied by polarized light optical microscopy (PLO) and differential scanning calorimetry (DSC) separately. It was found that the crystallization behavior of PVDF membranes was closely related to the preparation methods. For membranes prepared by the NIPS method, the skin layers had a mixture of α and ß phases, the overall membranes were predominantly α phase, and the total crystallinity was 60.0% with no spherulite. For melt spinning membranes, the surface layers also showed a mixture of α and ß phases, the overall membranes were predominantly α phase. The total crystallinity was 48.7% with perfect spherulites. Whereas the crystallization behavior of solution-cast membranes was related to the evaporation temperature and the additive, when the evaporation temperature was 140 °C with a soluble additive in the dope solution, obvious spherulites appeared. The crystalline morphology of PVDF exerted a great influence on the tensile strength of the membranes, which was much higher with perfect spherulites.

Aryne cycloaddition with 3-oxidopyridinium species.

The [3 + 2] cycloaddition of arynes with 3-oxidopyridinium species is examined using the Kobayashi benzyne precursor. The reaction affords a bicyclo[3.2.1] skeleton under mild conditions. A [7 + 2] cycloaddition mode with a subsequent pyridine ring-opening event has also been observed.

Synthesis of substituted 1H-indazoles from arynes and hydrazones.

The 1H-indazole skeleton can be constructed by a [3 + 2] annulation approach from arynes and hydrazones. Under different reaction conditions, both N-tosylhydrazones and N-aryl/alkylhydrazones can be used to afford a variety of indazoles. The former reaction affords 3-substituted indazoles either via in situ generated diazo compounds or through an annulation/elimination process. The latter reaction leads to 1,3-disubstituted indazoles likely through an annulation/oxidation process. The reactions operate under mild conditions and can accommodate aryl, vinyl, and less satisfactorily, alkyl groups.

Aryne [3 + 2] cycloaddition with N-sulfonylpyridinium imides and in situ generated N-sulfonylisoquinolinium imides: a potential route to pyrido[1,2-b]indazoles and indazolo[3,2-a]isoquinolines.

The aryne [3 + 2] cycloaddition process with pyridinium imides breaks the aromaticity of the pyridine ring. By equipping the imide nitrogen with a sulfonyl group, the intermediate readily eliminates a sulfinate anion to restore the aromaticity, leading to the formation of pyrido[1,2-b]indazoles. The scope and limitation of this reaction are discussed. As an extension of this chemistry, N-tosylisoquinolinium imides, generated in situ from N'-(2-alkynylbenzylidene)-tosylhydrazides via an AgOTf-catalyzed 6-endo-dig electrophilic cyclization, readily undergo aryne [3 + 2] cycloaddition to afford indazolo[3,2-a]-isoquinolines in the same pot, offering a highly efficient route to these potential anticancer agents.

Synthesis of 2H-indazoles by the [3 + 2] dipolar cycloaddition of sydnones with arynes.

A rapid and efficient synthesis of 2H-indazoles has been developed using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd-catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles.

Synthesis of pyrido[1,2-b]indazoles via aryne [3 + 2] cycloaddition with N-tosylpyridinium imides.

The [3 + 2] cycloaddition of arynes with N-tosylpyridinium imides, followed by an elimination of Ts(-), affords pyrido[1,2-b]indazoles under mild reaction conditions in good yields.