A quantitative study of the Golgi retention of glycosyltransferases.

How Golgi glycosyltransferases and glycosidases (hereafter glycosyltransferases) localize to the Golgi is still unclear. Here, we first investigated the post-Golgi trafficking of glycosyltransferases. We found that glycosyltransferases can escape the Golgi to the plasma membrane, where they are subsequently endocytosed to the endolysosome. Post-Golgi glycosyltransferases are probably degraded by ectodomain shedding. We discovered that most glycosyltransferases are not retrieved from post-Golgi sites, indicating that retention rather than retrieval is the primary mechanism for their Golgi localization. We therefore used the Golgi residence time to study Golgi retention of glycosyltransferases quantitatively and systematically. Quantitative analysis of chimeras of ST6GAL1 and either transferrin receptor or tumor necrosis factor α revealed the contributions of three regions of ST6GAL1, namely the N-terminal cytosolic tail, the transmembrane domain and the ectodomain, to Golgi retention. We found that each of the three regions is sufficient for Golgi retention in an additive manner. N-terminal cytosolic tail length negatively affects the Golgi retention of ST6GAL1, similar to effects observed for the transmembrane domain. Therefore, the long N-terminal cytosolic tail and transmembrane domain could act as Golgi export signals for transmembrane secretory cargos. This article has an associated First Person interview with the first author of the paper.

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

BACKGROUND: Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown. METHODS: Using single-cell RNA sequencing (scRNA-seq), immunofluorescent staining, and in vivo animal studies, we analyzed the liver tissues from untreated and GLY-treated mice. RESULTS: We generated the first scRNA-seq atlas of GLY-exposed mouse liver. GLY induced varied cell composition, shared or cell-type-specific transcriptional alterations, and dysregulated cell-cell communication and thus exerted hepatotoxicity effects. The oxidative stress and inflammatory response were commonly upregulated in several cell types. We also observed activation and upregulated phagocytosis in macrophages, as well as proliferation and extracellular matrix overproduction in hepatic stellate cells. CONCLUSIONS: Our study provides a comprehensive single-cell transcriptional picture of the toxic effect of GLY in the liver, which offers novel insights into the molecular mechanisms of the GLY-associated hepatotoxicity.

Rational Design of Tungsten Selenide @ N-Doped Carbon Nanotube for High-Stable Potassium-Ion Batteries.

Potassium-ion batteries (PIBs) are deemed as one of the most promising energy storage systems due to their high energy density and low cost. However, their commercial application is far away from satisfactory because of limited suitable electrode materials. Herein, core-shell structured WSe2 @N-doped C nanotubes are rationally designed and synthesized via selenizing WO3 @ polypyrrole for the first time. The large interlayer spacing of WSe2 can facilitate the intercalation/deintercalation of K+ . Meanwhile, the core-shell structured nanotube provides favorable interior void space to accommodate the volume expansion of WSe2 during cycling. Thus, the obtained electrode exhibits superb electrochemical performance with a high capacity of 301.7 mAh g-1 at 100 mA g-1 over 120 cycles, and 122.1 mAh g-1 can remain at 500 mA g-1 even after 1300 cycles. Ex-situ X-ray diffraction analysis reveals the K-ion storage mechanism of WSe2 @N-doped C includes intercalation and conversion reaction. Density function theory (DFT) calculation demonstrates the reasonable diffusion pathway of K+ . In addition, the obtained WSe2 @N-doped C nanotubes have been used as anode material for lithium-ion batteries, which also show good rate performance and high cycle stability. Therefore, this work offers a new methodology for the ration design of new structure electrode materials with long cycle stability.

Genetic Mapping of Behavioral Traits Using the Collaborative Cross Resource.

The complicated interactions between genetic background, environment and lifestyle factors make it difficult to study the genetic basis of complex phenotypes, such as cognition and anxiety levels, in humans. However, environmental and other factors can be tightly controlled in mouse studies. The Collaborative Cross (CC) is a mouse genetic reference population whose common genetic and phenotypic diversity is on par with that of humans. Therefore, we leveraged the power of the CC to assess 52 behavioral measures associated with locomotor activity, anxiety level, learning and memory. This is the first application of the CC in novel object recognition tests, Morris water maze tasks, and fear conditioning tests. We found substantial continuous behavioral variations across the CC strains tested, and mapped six quantitative trait loci (QTLs) which influenced these traits, defining candidate genetic variants underlying these QTLs. Overall, our findings highlight the potential of the CC population in behavioral genetic research, while the identified genomic loci and genes driving the variation of relevant behavioral traits provide a foundation for further studies.

Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking.

Most proteins in the secretory pathway are glycosylated. However, the role of glycans in membrane trafficking is still unclear. Here, we discovered that transmembrane secretory cargos, such as interleukin 2 receptor α subunit or Tac, transferrin receptor, and cluster of differentiation 8a, unexpectedly displayed substantial Golgi localization when their O-glycosylation was compromised. By quantitatively measuring their Golgi residence times, we found that the observed Golgi localization of O-glycan-deficient cargos is due to their slow Golgi export. Using a superresolution microscopy method that we previously developed, we revealed that O-glycan-deficient Tac chimeras localize at the interior of the trans-Golgi cisternae. O-Glycans were observed to be both necessary and sufficient for the efficient Golgi export of Tac chimeras. By sequentially introducing O-glycosylation sites to ST6GAL1, we demonstrated that O-glycan's effect on Golgi export is probably additive. Finally, the finding that N-glycosylated GFP substantially reduces the Golgi residence time of a Tac chimera suggests that N-glycans might have a similar effect. Therefore, both O- and N-glycans might function as a generic Golgi export signal at the trans-Golgi to promote the constitutive exocytic trafficking.

In-situ Nano-Crystallization and Solvation Modulation to Promote Highly Stable Anode Involving Alloy/De-alloy for Potassium Ion Batteries.

For advanced anode materials involving alloy/de-alloy chemistry for potassium ion batteries (PIBs), two-dimensional (2D) bismuth subcarbonate (BCO) nanosheets that possess high theoretical capacity of 631 mAh g-1 are proposed. The large lattice spacing of 0.683 nm along b axis facilitate insertion of K+ ion to boost high-capacity delivery of ca. 610 mAh g-1 , and the in situ nano-crystallization well ease volume changes of the integrated particle and shorten ion diffusion path during potassiation/depotassiation. After coupling with a concentrated KFSI-G2 electrolyte, the robust and efficient SEI built from enhanced participation of FSI- synergistically endow structural stability of the flower-like BCO, and enable a prolonged cycling performance with capacity of ca. 300 mAh g-1 at 0.2 A g-1 for 1500 cycles, achieving an ultralow decay rate of 0.007 %. Mechanistic investigations probe the electrochemistry involving alloy/de-alloy and phase transition of the electrode.

Willow-Leaf-Like ZnSe@N-Doped Carbon Nanoarchitecture as a Stable and High-Performance Anode Material for Sodium-Ion and Potassium-Ion Batteries.

ZnSe is regarded as a promising anode material for energy storage due to its high theoretical capacity and environment friendliness. Nevertheless, it is still a significant challenge to obtain superior electrode materials with stable performance owing to the serious volume change and aggregation upon cycling. Herein, a willow-leaf-like nitrogen-doped carbon-coated ZnSe (ZnSe@NC) composite synthesized through facile solvothermal and subsequent selenization process is beneficial to expose more active sites and facilitate the fast electron/ion transmission. These merits significantly enhance the electrochemical performances of ZnSe@NC for sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs). The obtained ZnSe@NC exhibits outstanding rate performance (440.3 mAh g-1 at 0.1 A g-1 and 144.4 mAh g-1 at 10 A g-1 ) and ultralong cycle stability (242.2 mAh g-1 at 8.0 A g-1 even after 3200 cycles) for SIBs. It is noted that 106.5 mAh g-1 can be retained after 550 cycles and 71.4 mAh g-1 is still remained after 1500 cycles at 200 mA g-1 when applied as anode for PIBs, indicating good cycle stability of the electrode. The possible electrochemical mechanism and the ionic diffusion kinetics of the ZnSe@NC are investigated using ex situ X-ray diffraction, high-resolution transmission electron microscopy, and a series of electrochemical analyses.

Regulation of social behaviors by p-Stat3 via oxytocin and its receptor in the nucleus accumbens of male Brandt's voles (Lasiopodomys brandtii).

Social behavior plays a significant role in the formation of social structure and population regulation in both animals and humans. Oxytocin (OXT) and its receptor (OXTR) are well known for regulating social behaviors, but their upstream regulating factors are rarely investigated. We hypothesized that the phosphorylation of the signal transducer and activator of transcription 3 (p-Stat3) may regulate social and aggressive behaviors via the OXT system in the nucleus accumbens (NAc). To test this hypothesis, OXT, p-Stat3 inhibitor, OXTR antagonist, and OXT plus p-Stat3 inhibitor were infused, respectively, into the NAc in the brain of male Brandt's voles (Lasiopodomys brandtii) - a social rodent species in grassland of Inner Mongolia, China. Our data showed that blockage of p-Stat3-Tyr705 signaling pathway in the NAc not only increased aggressive behavior but also impaired social recognition of male Brandt's voles via its effects on the expression of local OXT and OXTR. These results have illustrated a novel signaling pathway of p-Stat3-Tyr705 in regulating social behaviors via the OXT system.

Total Saikosaponins of Bupleurum yinchowense reduces depressive, anxiety-like behavior and increases synaptic proteins expression in chronic corticosterine-treated mice.

BACKGROUND: Bupleurum yinchowense Shan et Y. Li is widely used to treat depressive and anxiety disorders for hundreds of years in China. Total saikosaponins (TSS) is the major ingredient of Bupleurum yinchowense. A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and subsequent mammalian target of rapamycin (mTOR) signaling is responsible for synaptic maturation and may contribution to the synaptic alteration underlying depression. The aim of the study was to investigate the antidepressant-like and anxiolytic effect of TSS in chronic corticosterone-treated mice. The effect of TSS on synaptic proteins expression and AMPA receptor-mTOR signaling pathway alteration was also evaluated. METHODS: Dose-response effect of TSS (12.5, 25, 50 mg/kg) was investigated in forced swim test (FST) in ICR male mice. In the chronic corticosterine-treated model, TSS was given intragastrically once a day for 2 weeks and continued through the behavior testing period. Behavior tests and AMPA receptor related signaling pathway were investigated. RESULTS: TSS (25 and 50 mg/kg) decreased the immobility time in the FST when compared with the control group. TSS (25 mg/kg) showed antidepressant-like and anxiolytic effects in the chronic corticosterone treatment model in mice. TSS increased hippocampal synaptic proteins (synapsin-1 and postsynaptic density protein 95) expression. Immunohistochemistry analysis showed that TSS significantly increased the synapsin-1 expression in CA3 of hippocampus. TSS also increased hippocampal phosphorylation expression of GluR1 Ser 845 (AMPA receptor subunit) and its downstream regulators extracellular signaling-regulated kinase (ERK), protein kinase B (Akt) and mTOR. CONCLUSION: TSS produces antidepressant-like and anxiolytic effects and increases synaptic proteins expression which may be mediated by induction of AMPA receptor and subsequent mTOR signaling pathway.

AnkG hemizygous mice present cognitive impairment and elevated anxiety/depressive-like traits associated with decreased expression of GABA receptors and postsynaptic density protein.

Recent genome-wide association studies (GWAS) of patient populations and genetic linkage assessments have demonstrated that the ankyrin-G (AnkG) gene is involved in neuropsychiatric disorders, including bipolar disorder, schizophrenia, and Alzheimer's disease, but it remains unclear how the genetic variants of AnkG contribute to neuropsychiatric disorders. Here, we generated AnkG hemizygous mice using the gene trapping approach. Homozygous AnkG was embryonically lethal. Western blotting and real-time polymerase chain reaction (qPCR) assessments of wild type (WT) and AnkG +/- mutant mice demonstrated a 50% reduction of ANKG levels, at the gene and protein levels, in AnkG hemizygous mice. In behavioral tests, AnkG hemizygous mice exhibited elevated anxiety- and depression-like traits, as well as cognitive impairment. Moreover, the expression levels of cognitive-related proteins (including metabotropic glutamate receptor subtype-1, brain-derived neurotrophic factor, postsynaptic density-95, GABA-B receptor, and GABA-A receptor alpha-1) were significantly decreased (P < 0.05), suggesting a possible role for AnkG in cognition. It is possible that the loss of AnkG in the brain disrupts the excitation/inhibition balance of neurotransmitters, hindering the synaptic plasticity of neurons, and consequently leading to abnormal behavioral symptoms. Therefore, AnkG possibly contributes to neuroprotection and normal brain function, and may constitute a new target for treating neuropsychiatric diseases, especially cognitive dysfunction.

Tong Luo Jiu Nao ameliorates Aß1-40-induced cognitive impairment on adaptive behavior learning by modulating ERK/CaMKII/CREB signaling in the hippocampus.

BACKGROUND: Tong Luo Jiu Nao (TLJN), a modern formula of Chinese medicine extracts on the basis of Traditional Chinese Medicine theory, has been used to treat dementia. The present study aimed to investigate its ameliorating effects on Aß1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning (RDIL) tasks, and to determine its possible mechanism of action. METHODS: Rats were pretreated with TLJN extract (0.9 and 1.8 g/kg, p.o.) for 10 daysbefore surgery, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aß1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of biochemical parameters and molecules. RESULTS: Our findings first demonstrated that TLJN can improve Aß1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus. CONCLUSION: TLJN can markedly enhance cognitions of Aß1-40 microinjection animal model in adaptive behavioral tasks. It has the potential, possibly as complementary and alternative therapy, to prevent and/or delay the deterioration of cognitive impairment in AD.

Antidepressant-like effects and mechanism of action of SYG in depression model in rats.

OBJECTIVES: The present study aimed to evaluate whether SYG, a Chinese herbal formula, could produce antidepressant-like effects in learned helplessness (LH) model and chronic mild stress (CMS) model in rats. The mechanism underlying the antidepressant-like action was investigated by exploring BDNF signaling way in the hippocampus. MATERIAL AND METHODS: SYG was administrated for 5 consecutive days (100 and 200 mg/kg/day, intragastrically) in the learned helplessness model; SYG was administered daily by gastric gavages during both the 5-week stress session and behavior tests periods in the chronic mild stress model (100 and 200 mg/kg). The serum corticosterone level was measured in the learned helplessness model. Levels of BDNF and Tyrosine-related kinase B (TrkB), were evaluated in the hippocampus of chronic mild stress model. RESULTS: A deficit in avoidance learning and higher corticosterone level were observed in learned helplessness rats. SYG significantly reduced this deficit and reversed the corticosterone alteration. CMS induced significant reduction of sucrose intake in the sucrose preference test, an increased latency to feed in the novelty-suppressed feeding test and an increased immobility time in the forced swim test as compared to the control. It was also found that BDNF and TrkB levels were decreased in CMS model. Chronic treatment of SYG significantly suppressed the behavioral changes and up-regulated the BDNF signal pathway in the hippocampus. CONCLUSION: Our results suggest that SYG alleviates depression induced by LH and CMS model. The antidepressant-like activity of SYG is likely mediated by activation the BDNF signal pathway in the hippocampus.

Degradation of NLRP3 by p62-dependent-autophagy improves cognitive function in Alzheimer's disease by maintaining the phagocytic function of microglia.

BACKGROUND: Activation of the NLRP3 inflammasome promotes microglia to secrete inflammatory cytokines and induce pyroptosis, leading to impaired phagocytic and clearance functions of microglia in Alzheimer's disease (AD). This study found that the autophagy-associated protein p62 interacts with NLRP3, which is the rate-limiting protein of the NLRP3 inflammasome. Thus, we aimed to prove that the degradation of NLRP3 occurs through the autophagy-lysosome pathway (ALP) and also demonstrate its effects on the function of microglia and pathological changes in AD. METHODS: The 5XFAD/NLRP3-KO mouse model was established to study the effect of NLRP3 reduction on AD. Behavioral experiments were conducted to assess the cognitive function of the mice. In addition, immunohistochemistry was used to evaluate the deposition of Aß plaques and morphological changes in microglia. BV2 cells treated with lipopolysaccharide (LPS) followed by Aß1-42 oligomers were used as in vitro AD inflammation models and transfected with lentivirus to regulate the expression of the target protein. The pro-inflammatory status and function of BV2 cells were detected by flow cytometry and immunofluorescence (IF). Co-immunoprecipitation, mass spectrometry, IF, Western blot (WB), quantitative real-time PCR, and RNA-seq analysis were used to elucidate the mechanisms of molecular regulation. RESULTS: Cognitive function was improved in the 5XFAD/NLRP3-KO mouse model by reducing the pro-inflammatory response of microglia and maintaining the phagocytic and clearance function of microglia to the deposited Aß plaque. The pro-inflammatory function and pyroptosis of microglia were regulated by NLRP3 expression. Ubiquitinated NLRP3 can be recognized by p62 and degraded by ALP, slowing down the proinflammatory function and pyroptosis of microglia. The expression of autophagy pathway-related proteins such as LC3B/A, p62 was increased in the AD model in vitro. CONCLUSIONS: P62 recognizes and binds to ubiquitin-modified NLRP3. It plays a vital role in regulating the inflammatory response by participating in ALP-associated NLRP3 protein degradation, which improves cognitive function in AD by reducing the pro-inflammatory status and pyroptosis of microglia, thus maintaining its phagocytic function.

Treatment of compressed leachate from refuse transfer stations by freeze-melt method.

A small amount of leachate with complex composition will be produced during the compressing of municipal solid waste in refuse transfer stations. In this study, the freeze-melt method, a green and efficient wastewater treatment technology, was used to treat the compressed leachate. The effects of freezing temperature, freezing duration, and ice melting method on the removal rates of contaminants were investigated. The results showed that the freeze-melt method was not selective for the removal of chemical oxygen demand (COD), total organic carbon (TOC), ammonia-nitrogen (NH3-N) and total phosphorus (TP). The removal rate of contaminants was positively correlated with freezing temperature and negatively correlated with freezing duration, and the slower the growth rate of ice, the higher the purity of ice. When the compressed leachate was frozen at -15 °C for 42 h, the removal rates of COD, TOC, NH3-N and TP were 60.00%, 58.40%, 56.89% and 55.34%, respectively. Contaminants trapped in ice were removed during the melting process, especially in the early stages of melting. The divided melting method was more beneficial than the natural melting method in removing contaminants during the initial stage of melting, which contributes to the reduction of produced water losses. This study provides a new idea for the treatment of small amounts of highly concentrated leachate generated by compression facilities distributed in various corners of the city.

Degradation mechanism of montmorillonite-enhanced antibiotic wastewater: performance, antibiotic resistance genes, microbial communities, and functional metabolism.

The effective degradation of Sulfamethoxazole (SMX) is of great importance to alleviate environmental pollution. In this study, the degradation capacity of an ordinary sequencing batch activated sludge system (SBR) and montmorillonite (MMT) system was compared for their ability to degrade different concentrations of SMX. Compared with SBR system, the MMT system exhibited higher stability and degradation capacity. The changes in the composition of tightly bound extracellular polymeric substances (TB-EPS) were likely key to the observed stability of the system. High concentrations of SMX inhibited the degradation performance of SBR. MMT-supplemented reduced the generation of antibiotic resistance genes (ARGs). Thauera is a gene that is able to degrade SMX, and its abundance in MMT system reached 7.84%. As potential hosts of ARGs, the proportions of Paenarthrobacter and Caldilineacea were significantly correlated with sulfonamide resistance genes (sul1 and sul2). Overall, MMT-supplemented system was found to be a favorable method of treating antibiotic.

Bifunctional nickel foam composite cathode co-modified with CoFe@NC and CNTs for electrocatalytic degradation of atrazine over wide pH range.

Bifunctional cathodes have attracted widespread interest in the heterogeneous electro-Fenton (hetero-EF) process. In this study, the bifunctional composite cathode co-modified with N-doped carbon CoFe alloy (CoFe@NC) and carbon nanotubes (CNTs), designated as CoFe@NC-CNTs/CNTs/NF, integrating hydrogen peroxide (H2O2) synthesis and catalysis, was prepared for efficient degradation of atrazine (ATZ) under the near-neutral condition (pHi = 5.9). The morphology properties, crystal structure, microstructures, and elemental composition were determined. The influences of current density, initial pH value, different anions, and water matrix on the removal of ATZ were systematically studied. In the hetero-EF process, high removal efficiencies of ATZ can be achieved over the broad pH range (3-9) under the current density of 4.5 mA cm-2. The removal efficiency of ATZ remained at 90.2 ± 0.3% after 8 cycles under the near-neutral condition (pHi = 5.9). Radical quenching tests and EPR spectra have verified that both free radical pathways such as superoxide anion (O2·-) and hydroxyl radical (·OH) and non-radical pathway such as singlet oxygen (1O2) contributed to ATZ removal. The degradation pathways and catalytic mechanism were proposed. Toxicity evaluation and Escherichia coli growth test showed that the toxicity gradually decreased during the degradation process. This work provided a new thought for developing an efficient and stable bifunctional cathode to construct an in-situ hetero-EF system for pollutants removal over the wide pH range.

CoNi alloy anchored onto N-doped porous carbon for the removal of sulfamethoxazole: Catalyst, mechanism, toxicity analysis, and application.

Developing highly efficient, stable, recyclable, and application value heterogeneous catalysts in advanced oxidation processes has essential application value in the degradation of refractory pollutants. In this paper, the CoNi alloy anchored onto N-doped porous carbon (CoNi-600@NC) catalyst was prepared using bimetallic doped metal-organic frameworks as precursors. The magnetic CoNi-600@NC can activate peroxymonosulfate (PMS) to degrade sulfamethoxazole (SMX). Therefore, SMX can be removed 100% within 25 min. CoNi-600@NC/PMS has a broad pH (3-9) application range, good applicability, and repeatability. Radical quenching, quantitative and electrochemical experiments proved that the degradation of SMX was dominated by free radical (Superoxide anions) and non-free radical pathways (surface-bound radicals). Mechanistic analysis showed that the interaction between Co-Nx/pyridine N-sites and graphitized carbon with PMS induced the formation of surface-bound active species. Moreover, CoNi nanoparticles promoted the redox cycle of metals. The synergistic catalytic mechanisms between the CoNi alloy and the abundant functional groups gave CoNi-600@NC excellent catalytic properties and applicability. Using density functional theory predicted the reaction sites of SMX and proposed four degradation pathways. The toxicity of intermediates was comprehensively evaluated. In addition, a CoNi-600@NC continuous flow reactor was constructed with a daily treatment capacity of 45 L and 100% SMX removal. This study expands the application of persulfate advanced oxidation technology by synthesizing recyclable magnetic catalysts and provides new synergistic degradation mechanisms for removing refractory organics.

Distinct neuronal excitability alterations of medial prefrontal cortex in early-life neglect model of rats.

OBJECT: Early-life neglect has irreversible emotional effects on the central nervous system. In this work, we aimed to elucidate distinct functional neural changes in medial prefrontal cortex (mPFC) of model rats. METHODS: Maternal separation with early weaning was used as a rat model of early-life neglect. The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp. RESULTS: Glutamatergic and GABAergic neurons of mPFC were distinguished by typical electrophysiological properties. The excitation of mPFC glutamatergic neurons was significantly increased in male groups, while the excitation of mPFC GABAergic neurons was significant in both female and male groups, but mainly in terms of rest membrane potential and amplitude, respectively. CONCLUSIONS: Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect, which can contribute to distinct mechanisms for emotional and cognitive manifestations.

Longitudinal assessment of motor function following the unilateral intrastriatal 6-hydroxydopamine lesion model in mice.

Introduction: Despite the widespread use of the unilateral striatal 6-hydroxydopamine (6-OHDA) lesion model in mice in recent years, the stability of behavioral deficits in the 6-OHDA striatal mouse model over time is not yet clear, raising concerns about using this model to evaluate a compound's long-term therapeutic effects. Materials and methods: In the current study, mice were tested at regular intervals in the cylinder test and gait analysis beginning 3 days after 6-OHDA injection of 4 and 8 µg and lasting until 56 days post-lesion. Apomorphine-induced rotational test and rotarod test were also performed on Day 23 and 43 post-lesion, respectively. Immunohistochemistry for dopaminergic neurons stained by tyrosine hydroxylase (TH) was also performed. Results: Our results showed that both the 4 and 8 µg 6-OHDA lesion groups exhibited forelimb use asymmetry with a preference for the ipsilateral (injection) side on Day 3 and until Day 21 post-lesion, but did not show forelimb asymmetry on Day 28 to 56 post-lesion. The 8 µg 6-OHDA lesion group still exhibited forelimb asymmetry on Day 28 and 42 post-lesion, but not on Day 56. The gait analysis showed that the contralateral front and hind step cycles increased from Day 3 to 42 post-lesion and recovered on Day 56 post-lesion. In addition, our results displayed a dose-dependent reduction in TH+ cells and TH+ fibers, as well as dose-dependent apomorphine-induced rotations. In the rotarod test, the 8 µg 6-OHDA lesion group, but not the 4 µg group, decreased the latency to fall on the rotarod on Day 43 post-lesion. Conclusion: In summary, unilateral striatal 6-OHDA injections of 4 and 8 µg induced spontaneous motor impairment in mice, which partially recovered starting on Day 28 post-lesion. Forced motor deficits were observed in the 8 g 6-OHDA lesion group, which remained stable on Day 43 post-lesion. In addition, the rotarod test and apomorphine-induced rotational test can distinguish between lesions of different extents and are useful tools for the assessment of functional recovery in studies screening novel potential therapies.

In Situ Growth of CoS2/ZnS Nanoparticles on Graphene Sheets as an Ultralong Cycling Stability Anode for Potassium Ion Storage.

Metal sulfides are promising anodes for potassium-ion batteries (PIBs) due to their high theoretical capacity and abundant active sites; however, their intrinsic low conductivity and poor cycling stability hampered their practical applications. Given this, the rational design of hybrid structures with high stability and fast charge transfer is a critical approach. Herein, CoS2/ZnS@rGO hybrid nanocomposites were demonstrated with stable cubic phases. The synergistic effect of the obtained bimetallic sulfide nanoparticles and highly conductive 2D rGO nanosheets facilitated excellent long-term cyclability for potassium ion storage. Such hybrid nanocomposites delivered remarkable ultrastable cycling performances in PIBs of 159, 106, and 80 mA h g-1 at 1, 1.5, and 2 A g-1 after 1800, 2100, and 3000 cycles, respectively. Moreover, the full-cell configuration with a perylene tetracarboxylic dianhydride organic cathode (CoS2/ZnS@rGO∥PTCDA) exhibited a better electrochemical performance. Besides, when the CoS2/ZnS@rGO nanocomposites were applied as an anode for sodium-ion batteries, the electrode demonstrated a reversible charge capacity of 259 mA h g-1 after 600 cycles at 2 A g-1. In situ X-ray diffraction and ex situ high-resolution transmission electron microscopy characterizations further confirmed the conversion reactions of CoS2/ZnS during insertion/desertion processes. Our synthesis strategy is also a general route to other bimetallic sulfide hybrid nanocomposites. This strategy opens up a new roadmap for exploring hybrid nanocomposites with feasible phase engineering for achieving excellent electrochemical performances in energy storage applications.