Synaptotagmin-7-mediated activation of spontaneous NMDAR currents is disrupted in bipolar disorder susceptibility variants.

Synaptotagmin-7 (Syt7) plays direct or redundant Ca2+ sensor roles in multiple forms of vesicle exocytosis in synapses. Here, we show that Syt7 is a redundant Ca2+ sensor with Syt1/Doc2 to drive spontaneous glutamate release, which functions uniquely to activate the postsynaptic GluN2B-containing NMDARs that significantly contribute to mental illness. In mouse hippocampal neurons lacking Syt1/Doc2, Syt7 inactivation largely diminishes spontaneous release. Using 2 approaches, including measuring Ca2+ dose response and substituting extracellular Ca2+ with Sr2+, we detect that Syt7 directly triggers spontaneous release via its Ca2+ binding motif to activate GluN2B-NMDARs. Furthermore, modifying the localization of Syt7 in the active zone still allows Syt7 to drive spontaneous release, but the GluN2B-NMDAR activity is abolished. Finally, Syt7 SNPs identified in bipolar disorder patients destroy the function of Syt7 in spontaneous release in patient iPSC-derived and mouse hippocampal neurons. Therefore, Syt7 could contribute to neuropsychiatric disorders through driving spontaneous glutamate release.

Effects of sludge retention time on sludge reduction by ultrasound treatment: Sludge characteristics, microbial community, and metabolism.

Both ultrasound and sludge retention time (SRT) enable the in-situ sludge reduction during wastewater treatment, but the influence of SRT on ultrasonic lysis - cryptic growth is unclear. This paper researched the influence of different SRTs on sludge lysis - cryptic growth using a sequential bio-reactor (SBR), then explained in details the changes of microorganisms in the SBR. The best SRT for sludge reduction was 30 d, and 47.29% reduction in sludge was achieved. The different SRTs changed the organic matter removal in the wastewater, and the removal rate decreased when SRT exceeded 60 d. The size of the sludge particles varied depending on the SRT, with the smallest size at SRT of 10d being 45.6 µm and the largest size at SRT of 90d being 110.0 µm. SEM showed that the sludge surface changed rough at longer SRT. FTIR and XPS showed notable effect in sludge functional group strength at SRT of 30 d. Extracellular polymeric substance (EPS) reduced the most at SRT of 30 d. The microbial communities of sludge varied with the SRT, and the unique main genus at SRT of 5, 15, 30 and 90 d were C10-SB1A, Lactococcus, Propioniciclava, Lactococcus, respectively. Furthermore, the SRT changed relative abundance of enzymes concerned with metabolism of carbon, nitrogen, and phosphorus. Similarly, SRT changed the metabolic rate, and the metabolic rate of carbon, nitrogen and phosphorus was best at SRT of 30 d.

miR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release.

microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the miR-218 knockout (KO) mouse model and the sponge/overexpression approaches, we showed that miR-218-2 but not miR-218-1 could bidirectionally regulate the contextual and spatial memory in the mice. Furthermore, miR-218-2 deficiency induced deficits in the morphology and presynaptic neurotransmitter release in the hippocampus to impair the long term potentiation. Combining the RNA sequencing analysis and luciferase reporter assay, we identified complement component 3 (C3) as a main target gene of miR-218 in the hippocampus to regulate the presynaptic functions. Finally, we showed that restoring the C3 activity in the miR-218-2 KO mice could rescue the synaptic and learning deficits. Therefore, miR-218-2 played an important role in the cognitive functions of mice through C3, which can be a mechanism for the defective cognition of miR-218 related neuronal disorders.

A comprehensive study on the co-removal of Cr (VI) and ciprofloxacin via microbial-photocatalytic coupling: Mechanistic insights and performance evaluation.

The increasing contamination of water systems by antibiotics and heavy metals has become a growing concern. The intimately coupled photocatalysis and biodegradation (ICPB) approach offers a promising strategy for the effective removal of mixed pollutants. Despite some prior research on ICPB applications, the mechanism by which ICPB eliminates mixed pollutants remains unclear. In our current study, the ICPB approach achieved approximately 1.53 times the degradation rate of ciprofloxacin (CIP) and roughly 1.82 times the reduction rate of Cr (VI) compared to photocatalysis. Remarkably, after 30 days, the ICPB achieved a 96.1% CIP removal rate, and a 97.8% reduction in Cr (VI). Our investigation utilized three-dimensional fluorescence analysis and photo-electrochemical characterization to unveil the synergistic effects of photocatalysis and biodegradation in removal of CIP and Cr (VI). Incorporation of B-Bi3O4Cl (B-BOC) photocatalyst facilitated electron-hole separation, leading to production of ·O2-, ·OH, and h+ species which interacted with CIP, while electrons reduced Cr (VI). Subsequently, the photocatalytic products were biodegraded by a protective biofilm. Furthermore, we observed that CIP, acting as an electron donor, promoted the reduction of Cr (VI). The microbial communities revealed that the number of bacteria favoring pollutant removal increased during ICPB operation, leading to a significant enhancement in performance.

Cationic Divalent Metal Sites (M = Mn, Fe, Co) Operating as Both Nitrene-Transfer Agents and Lewis Acids toward Mediating the Synthesis of Three- and Five-Membered N-Heterocycles.

The tripodal compounds [(TMG3trphen)MII-solv](PF6)2 (M = Mn, Fe, Co; solv = MeCN, DMF) and bipodal analogues [(TMG2biphen)MII(NCMe)x](PF6)2 (x = 3 for Mn, Fe; x = 2 for Co) and [(TMG2biphen)MIICl2] have been synthesized with ligands that feature a triaryl- or diarylmethyl-amine framework and superbasic tetramethylguanidinyl residues (TMG). The dicationic M(II) sites mediate catalytic nitrene-transfer reactions between the imidoiodinane PhI═NTs (Ts = tosyl) and a panel of styrenes in MeCN to afford aziridines and low yields of imidazolines (upon MeCN insertion) with an order of productivity that favors the bipodal over the tripodal reagents and a metal preference of Fe > Co ≥ Mn. In CH2Cl2, the more acidic Fe(II) sites favor formation of 2,4-diaryl-N-tosylpyrrolidines by means of an in situ (3 + 2) cycloaddition of the initially generated 2-aryl-N-tosylaziridine with residual styrene. In the presence of ketone, 1,3-oxazolidines can be formed in practicable yields, involving a single-pot cycloaddition reaction of alkene, nitrene, and ketone (2 + 1 + 2). Mechanistic studies indicate that the most productive bipodal Fe(II) site mediates stepwise addition of nitrene to olefins to generate aziridines with good retention of stereochemistry and further enables aziridine ring opening to unmask a 1,3-zwitterion that can undergo cycloaddition with dipolarophiles (MeCN, alkene, ketone) to afford five-membered N-heterocycles.

Synaptotagmin-7 deficiency induces mania-like behavioral abnormalities through attenuating GluN2B activity.

Synaptotagmin-7 (Syt7) probably plays an important role in bipolar-like behavioral abnormalities in mice; however, the underlying mechanisms for this have remained elusive. Unlike antidepressants that cause mood overcorrection in bipolar depression, N-methyl-d-aspartate receptor (NMDAR)-targeted drugs show moderate clinical efficacy, for unexplained reasons. Here we identified Syt7 single nucleotide polymorphisms (SNPs) in patients with bipolar disorder and demonstrated that mice lacking Syt7 or expressing the SNPs showed GluN2B-NMDAR dysfunction, leading to antidepressant behavioral consequences and avoidance of overcorrection by NMDAR antagonists. In human induced pluripotent stem cell (iPSC)-derived and mouse hippocampal neurons, Syt7 and GluN2B-NMDARs were localized to the peripheral synaptic region, and Syt7 triggered multiple forms of glutamate release to efficiently activate the juxtaposed GluN2B-NMDARs. Thus, while Syt7 deficiency and SNPs induced GluN2B-NMDAR dysfunction in mice, patient iPSC-derived neurons showed Syt7 deficit-induced GluN2B-NMDAR hypoactivity that was rescued by Syt7 overexpression. Therefore, Syt7 deficits induced mania-like behaviors in mice by attenuating GluN2B activity, which enabled NMDAR antagonists to avoid mood overcorrection.

Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice.

The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By these means, we identified synaptotagmin-7 (Syt7) as a candidate risk factor for behavioral abnormalities. We then investigated Syt7 knockout (KO) mice and observed nocturnal manic-like and diurnal depressive-like behavioral fluctuations in a majority of these animals, analogous to the mood cycling symptoms of BD. We treated the Syt7 KO mice with clinical BD drugs including olanzapine and lithium, and found that the drug treatments could efficiently regulate the behavioral abnormalities of the Syt7 KO mice. To further verify whether Syt7 deficits existed in BD patients, we investigated the plasma samples of 20 BD patients and found that the Syt7 mRNA level was significantly attenuated in the patient plasma compared to the healthy controls. We therefore concluded that Syt7 is likely a key factor for the bipolar-like behavioral abnormalities.

Effects of lysed sludge reflux point on ultrasound lysis-cryptic growth in anaerobic/aerobic (A/O) wastewater treatment: Sludge reduction, microbial community, and metabolism.

Ultrasonication allows sludge reduction to be performed in situ during wastewater treatment, and the reflux point of the lysed sludge affects this performance. This study investigated the effects of reflux point (anaerobic stage, carbon/nitrogen (C/N) lowest stage, and aerobic stage) on sludge lysis-cryptic growth in an anaerobic/aerobic reactor and variations in the sludge and microbial community. The best reflux point occurred at the lowest C/N ratio stage, and a 50.96% reduction in excess sludge was achieved. The reflux of the lysed sludge to the aerobic stage reduced nitrogen and phosphorus removal. The reflux of the lysed sludge decreased the average sludge size, reaching 29.2 µm when reflux to the aerobic stage. Scanning electron microscopy showed that the sludge surface was unaffected by the reflux point. The Fourier-transform infrared spectrometry and X-ray photoelectron spectroscopy results showed that the most prominent variation in the intensity of the sludge functional groups occurred when the reflux was at the lowest C/N stage. The amount of extracellular polymeric substances decreased the most during reflux to the anaerobic stage. The sludge microbial communities varied with the reflux point, and the dominant phyla during reflux to the anaerobic, lowest C/N, and aerobic stages were Bacteroidetes, Firmicutes, and Bacteroidetes, respectively. Furthermore, the reflux point did not alter the metabolic pathway of sludge microorganisms but increased the number of enzymes in metabolic pathways.

Dual function of magnetic field in enhancing antibiotic wastewater treatment by an integrated photocatalysis and fluidized bed biofilm reactor (FBBR).

The integrated photocatalysis and fluidized bed biofilm reactor (FBBR) is an attractive wastewater treatment technique for managing wastewater containing antibiotics. However, the fast recombination of photoinduced charge and low microbial activity limit the degradation and mineralization efficiency for antibiotics. To address this, we attempt to introduce magnetic field (MF) to the integrated system with B-doped Bi3O4Cl as the photocatalysts to effectively improve removal and mineralization of ciprofloxacin (CIP). As a consequence, the degradation rate reaches 96% after 40 d in integrated system with MF. The biofilm inside the integrated system with MF carrier can mineralize the photocatalytic products, thereby increasing the total organic carbon (TOC) degradation rate by more than 32%. The electrochemical experiment indicates the Lorentz force generated by MF can accelerate charge separation, increasing the electron concentration. Simultaneously, the increased amounts of electrons lead to the generation of more ·OH and ·O2-. MF addition also results in increased biomass, increased biological respiratory activity, microbial community evolution and accelerated microbial metabolism, enabling more members to biodegrade photocatalytic intermediates. Therefore, applied MF is an efficient method to enhance CIP degradation and mineralization by the integrated system.

Long-term consumption of recycled cooking oil induces cell death and tissue damage.

Recycled cooking oil (RCO) is widely used in many small restaurants. However, the health risk posed by long-term consumption of RCO is unclear. In this study, C57 mice were treated with RCO for 34 weeks. Organ coefficients of the liver, stomach, and kidney were found to be decreased. H&E staining revealed overt lesions in the pancreas, liver, kidney, esophagus, duodenum, and ileum of RCO-treated mice. Immunohistochemistry showed significant DNA damage in the duodenum and ileum and apoptosis in the lungs of the RCO-treated mice. Immunoblotting showed elevated levels of γ-H2AX, Bcl-2/Bax, TNFα, cleaved Caspase-3 and poly ADP-ribose polymerase (PARP). Increased levels of lactate dehydrogenase (LDH) and decreased levels of succinate dehydrogenase (SDH) were also detected. These findings suggest that long-term consumption of RCO produces various toxicities in mice with important implications for humans. DNA damage followed by mitochondria-associated apoptosis, and necrosis is likely to contribute to the toxicities.

Surface-capping engineering for electrically neutral surface of perovskite films and stable solar cells.

Metal halide perovskite solar cells (PSCs) have developed rapidly in recent years, due to their high performance and low-cost solution-based fabrication process. These excellent properties are mainly attributed to the high defect tolerance of polycrystalline perovskite films. Meanwhile, these defects can also facilitate ion migration and carrier recombination, which cause the device performance and the long-term stability of PSCs to deteriorate heavily. Therefore, it is critical to passivate the defects, especially at the surfaces of perovskite grains where the defects are most concentrated due to the dangling bonds. Here we propose a surface-capping engineering (SCE) method to construct 'dangling-bond-free' surfaces for perovskite grains. Diamine iodide (methylenediammonium diiodide, MDAI2) was used to construct an electroneutral PbX6-MDA-PbX6(X = Cl, Br or I) layer at the perovskite surfaces. Compared to the monovalent FA+which can only coordinate one [PbX6]4-slab, the bivalent MDA2+can coordinate two [PbX6]4-slabs on both sides, thus realizing a dangling-bond-free surface. Solar cells based on SCE-perovskite films exhibited a higher power conversion efficiency (PCE) of 21.6%, compared with 19.9% of the control group; and maintained over 96% of its initial PCE after 13 h during the maximum power point tracking test under continuous AM1.5G illumination, whereas the control group only lasted 1.5 h. Constructing a dangling-bond-free capping layer on the grain boundary opens new avenues for the fabrication of ultralow-defect polycrystalline semiconductors, paving the way to further improve the PCE and lifetime of PSCs.

Cruise tourism in the context of COVID-19: Dilemmas and solutions.

COVID-19 cases on international cruise ships have attracted extensive attention from the international community as well as the world's tourism and shipping industry. This virus highlighted the plight that must be faced by cruise ships in complicated times and situations such as pandemics. The comparative method is adopted to analyze the management measures taken by the "Diamond Princess", "Costa Serena", "Westerdam" and "Grand Princess" cruises in response to the COVID-19 pandemic and then to summarize the common dilemmas faced by these cruise ships, including defects of their internal environment, unclear health-care obligations during an epidemic, weak collaboration between the parties involved and their limited performance, and widespread infodemic and unfavorable public opinion. Given these dilemmas, measures are suggested to deal with the "cruise dilemma", including establishing and defining isolation standards on boards, enhancing the capacity of international organizations, the international community's joint response to the pandemic, promoting cooperation between countries, building an effective mechanism for the broad participation of the whole society, and standardizing the release of information and reasonably guiding public social opinion.

Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder.

Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca(2+) imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.

Aqueous Solutions of Poly(ethylene oxide)-Poly(N-isopropylacrylamide): Thermosensitive Behavior and Distinct Multiple Assembly Processes.

Detailed phase transition and conformational changes taking place as a function of temperature in poly(ethylene oxide)-b-poly(N-isopropylacrylamide) (PEO-b-PNIPAM) semidiluted aqueous solutions are elucidated in the present study. By the use of elaborate vibrational spectroscopy techniques in combination with two-dimensional correlation spectroscopy (2Dcos), three transition regions including respective rich domains (<29 °C), loose aggregations (30-36 °C), and dense sphere micelles (>37 °C) are depicted. In particular, subtle variations of hydrogen bonds are detected even under the lower critical solution temperature (LCST), and the respective rich domain regime is marked with strong participation from hydrogen bonding at different concentrations and compositions. Both the formation of intermolecular hydrogen bonds and the less hydration degrees of PNIPAM segments compared with PNIPAM homopolymer at elevated temperatures verify the evolution of PNIPAM from their own domains to loose aggregations with PEO shells. Dense micelles are formed beyond the LCST of PNIPAM, while the outmost PEOs act as buffer layers and postpone the shrinkage of PNIPAM chains. Due to the existence of a buffer layer, higher phase transition temperatures compared with PNIPAM homopolymer are observed.

A versatile tripodal Cu(I) reagent for C-N bond construction via nitrene-transfer chemistry: catalytic perspectives and mechanistic insights on C-H aminations/amidinations and olefin aziridinations.

A Cu(I) catalyst (1), supported by a framework of strongly basic guanidinato moieties, mediates nitrene-transfer from PhI═NR sources to a wide variety of aliphatic hydrocarbons (C-H amination or amidination in the presence of nitriles) and olefins (aziridination). Product profiles are consistent with a stepwise rather than concerted C-N bond formation. Mechanistic investigations with the aid of Hammett plots, kinetic isotope effects, labeled stereochemical probes, and radical traps and clocks allow us to conclude that carboradical intermediates play a major role and are generated by hydrogen-atom abstraction from substrate C-H bonds or initial nitrene-addition to one of the olefinic carbons. Subsequent processes include solvent-caged radical recombination to afford the major amination and aziridination products but also one-electron oxidation of diffusively free carboradicals to generate amidination products due to carbocation participation. Analyses of metal- and ligand-centered events by variable temperature electrospray mass spectrometry, cyclic voltammetry, and electron paramagnetic resonance spectroscopy, coupled with computational studies, indicate that an active, but still elusive, copper-nitrene (S = 1) intermediate initially abstracts a hydrogen atom from, or adds nitrene to, C-H and C═C bonds, respectively, followed by a spin flip and radical rebound to afford intra- and intermolecular C-N containing products.

Balancing energy security and marine pollution prevention: legal challenges of utilizing nuclear power for decarbonizing maritime transportation in the Arctic region.

The Arctic region is facing growing demands for energy to support various economic activities, while also grappling with the profound impacts of climate change. Black carbon particulate matter emissions reduction is a key objective to mitigate the susceptibility of the Arctic's ecosystems to the impact of climate change. Nuclear power has been suggested as a potential source of clean energy to decarbonize maritime transport in the Arctic. However, although the operation of nuclear-powered vessels and floating nuclear power platforms in the region ensures energy security and reduces black carbon emissions, it may pose significant risks of nuclear material release and radiological accidents and raise concerns about improper radioactive waste disposal. In regulating these nuclear-powered vessels and floating nuclear power platforms in the Arctic, the existing international legal regime faced a series of challenges. This research employs a method of policy analysis to analyze these legal challenges and explores how the international community could work together to cope with the challenges that arise in the Arctic during the operation of nuclear-powered vessels and platforms for maritime decarbonization purposes.

Using Nuclear Energy for Maritime Decarbonization and Related Environmental Challenges: Existing Regulatory Shortcomings and Improvements.

In recent years, the use of nuclear energy as propulsion for merchant ships has been proposed as a means of promoting the transition toward maritime decarbonization and environmentally sustainable shipping. However, there are concerns that nuclear-powered merchant ships could pose risks to the marine environment in the event of accidents, such as collisions, machinery failure or damage, fire, or explosions. The current international regulatory framework for nuclear-powered merchant ships is insufficient to address these risks. This research aims to address this gap by conducting a policy analysis of the existing regulations and a critical examination of their effectiveness in addressing the environmental risks of nuclear-powered merchant ships. Through this analysis, the study identifies the shortcomings and insufficiencies in the current framework and explores potential solutions to improve it, with the goal of enhancing the international community's ability to mitigate the potential impacts of radioactive marine pollution from nuclear-propelled ships in an era of maritime decarbonization.

Stress and emotion in a locked campus: the moderating effects of resilience and loneliness.

The aim of this study is to investigate the dynamic relationship between Chinese students' emotions and stress during a strict lockdown period in a university setting and the context of a global pandemic. Dynamic structural equation modeling was used to investigate the moderating role of resilience and loneliness in this relationship. The participants consisted of 112 students. Based on loneliness and resilience measures and the intensive tracking of emotional stress over a 21-day period, the results of data analysis indicated that the students' overall levels of positive emotions were low and relatively independent of negative emotions. Negative emotions were significantly autoregressive and their baseline was closely related to the individual's overall feelings of stress and loneliness levels, fluctuating with feelings of stress. The results confirm the hypothesis that resilience helps to stabilize emotions. Individuals with low resilience may be more emotionally sensitive in confined environments, while receiving social support may help to alleviate low moods.

A brief review: the application of long afterglow luminescent materials in environmental remediation.

Long afterglow luminescent (LAL) materials can release their stored light after turning off the light irradiating on them. Because of this unique characteristic, the coupling of LAL materials and conventional semiconductors is an environmental-friendly method for supporting photocatalytic activity for environmental remediation. Currently, the exploration of "afterglow-catalysis" materials for the fabrication of around-the-clock photocatalytic systems is still in its infancy. Accordingly, herein, we summarize the application of LAL materials in photocatalytic environmental remediation and energy crisis alleviation to stimulate further motivation for the development of novel LAL materials. By discussing the works in the last five years on novel LAL materials, we anticipate the development of new materials, i.e., "afterglow-catalysis" composites, to realize waste-to-energy, even achieving industrialization.