Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone.

BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.

Association between triglyceride-glucose index and acute kidney injury in patients with acute myocardial infarction based on medical information mart for intensive care database: A cross-sectional study.

Background: The relationship between triglyceride glucose (TyG) index and the incidence of acute kidney injury (AKI) in patients with acute myocardial infarction (AMI) is unclear. This study aims to explore the relationship between the two. Methods: Participants were enrolled from Medical Information Mart for Intensive Care IV (MIMICIV) and grouping of subjects based on the quartile interval of the TyG index. With the presence of AKI as the main outcome, a logistic regression model was constructed. The correlation of the TyG index with the results obtained was examined by using a restricted cubic spline (RCS) model.

Research progress on Sirtuins (SIRTs) family modulators.

Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions.

Molecular simulation for food protein-ligand interactions: A comprehensive review on principles, current applications, and emerging trends.

In recent years, investigations on molecular interaction mechanisms between food proteins and ligands have attracted much interest. The interaction mechanisms can supply much useful information for many fields in the food industry, including nutrient delivery, food processing, auxiliary detection, and others. Molecular simulation has offered extraordinary insights into the interaction mechanisms. It can reflect binding conformation, interaction forces, binding affinity, key residues, and other information that physicochemical experiments cannot reveal in a fast and detailed manner. The simulation results have proven to be consistent with the results of physicochemical experiments. Molecular simulation holds great potential for future applications in the field of food protein-ligand interactions. This review elaborates on the principles of molecular docking and molecular dynamics simulation. Besides, their applications in food protein-ligand interactions are summarized. Furthermore, challenges, perspectives, and trends in molecular simulation of food protein-ligand interactions are proposed. Based on the results of molecular simulation, the mechanisms of interfacial behavior, enzyme-substrate binding, and structural changes during food processing can be reflected, and strategies for hazardous substance detection and food flavor adjustment can be generated. Moreover, molecular simulation can accelerate food development and reduce animal experiments. However, there are still several challenges to applying molecular simulation to food protein-ligand interaction research. The future trends will be a combination of international cooperation and data sharing, quantum mechanics/molecular mechanics, advanced computational techniques, and machine learning, which contribute to promoting food protein-ligand interaction simulation. Overall, the use of molecular simulation to study food protein-ligand interactions has a promising prospect.

SIRT6 Reduces Rheumatoid Arthritis Injury by Inhibiting MyD88-ERK Signaling Pathway.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by destruction of synovial joints, abnormal immune responses and chronic inflammatory manifestations, which seriously affects patients' well-being. We explored this study to ascertain the effect and mechanism of silent information regulator 6 (SIRT6) on RA. METHODS: Genes of RA patients and normal volunteers were analyzed using Gene Expression Omnibus (GEO), Kyoto-Encyclopedia of Genes and Genomes (KEGG) and Disconet databases. Serum samples of RA patients and normal subjects were collected before detection of myeloid differentiation factor-88 (MyD88)-extracellular signal-regulated kinase (ERK) pathway proteins expression with Western blot. In vitro RA fibroblast-like synoviocytes (FLS) cell model (RA-FLS) was established by treating RSC-364 with recombinant rat IL-1ß (10 ng/mL) after which SIRT6 and MyD88 adenoviruses treatment was carried out. The enzyme linked immunoassay (ELISA), real time polymerase chain reaction (RT-PCR) and Western blot were respectively used to measure inflammatory factors, related messenger ribonucleic acid (mRNA) and protein expressions. Also, we constructed RA rat model with bovine type II collagen (BIIC) and complete Freund's adjuvant, before treatment with SIRT6 and MyD88 adenoviruses. RESULTS: Low expression of SIRT6 gene were detected in RA patients. Also, levels of MyD88, ERK and phosphorylated extracellular signal-regulated protein kinase (p-ERK) protein expressions in RA patients were increased, whilst that of SIRT6 protein decreased. Compared to FLS cells in Control group, inflammatory factors levels of rats in Model batch increased significantly. SIRT6 adenovirus treatment potentially and significantly inhibited inflammation including suppression of increased inflammatory factors induced by MyD88. In comparison with FLS cells in Control group, Model batch cells' MyD88, interleukin (IL)-1ß, IL-21, IL-22, IL-6, IL-17, tumor necrosis factor-alpha (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) mRNA expressions increased but SIRT6 gene treatment could reduce mRNA expression of the aforesaid factors, even after MyD88 adenovirus treatment. Besides, overpressed SIRT6 negatively regulated levels of MyD88, ERK and p-ERK proteins expressions. SIRT6 demonstrated anti-RA effect by regulating MyD88-ERK pathway and inhibiting inflammatory response in RA rats. CONCLUSIONS: SIRT6 could potentially inhibit the inflammatory response of RA via a regulatory mechanism mainly relating to MyD88-ERK signal pathway. Thus, SIRT6 and its agonists may serve as new targets for developing drugs that can potentially treat RA.

Association between triglyceride-glucose index and AKI in ICU patients based on MIMICIV database: a cross-sectional study.

BACKGROUND: Methods for early prediction of the occurrence of acute kidney injury (AKI) were limited. The relationship between triglyceride glucose index (TyG) and the incidence of acute kidney injury in ICU patients is unclear. This study aims to explore the relationship between the two. METHODS: Based on their TyG index, participants from the Intensive Care Medical Information Market IV (MIMIC-IV) were divided into quartiles. A logistic regression model was constructed based on the risk of acute kidney injury as the main outcome, in order to detect a potential relationship that may exist between the TyG index and acute kidney injury in ICU patients. Finally, in order to confirm the relationship existing between the TyG index and the results, a restricted cubic spline model was used. RESULTS: In total, 54,263 patients were involved in our present study, of whom 48.2% were male. The occurrence of acute kidney injury was 25.1%. An independent relationship was observed between the TyG index and an increased risk of acute kidney injury through multivariate logistic regression analysis (OR, 1.28 [95% CI 1.22-1.35] p < 0.001). Q4 (5.344-9.911) of the TyG index quartiles was independently associated with an increase in the risk of acute kidney injury (OR, 1.43 [95% CI (1.32-1.54)] p < 0.001). Through the restricted cubic spline regression model, the risk of acute kidney injury was also demonstrated to increase linearly with an increase in the TyG index. CONCLUSION: The triglyceride glucose index is related to the risk of acute kidney injury in ICU patients. In the future, in order to further validate this finding, larger prospective studies are needed.

Sirtuin family in autoimmune diseases.

In recent years, epigenetic modifications have been widely researched. As humans age, environmental and genetic factors may drive inflammation and immune responses by influencing the epigenome, which can lead to abnormal autoimmune responses in the body. Currently, an increasing number of studies have emphasized the important role of epigenetic modification in the progression of autoimmune diseases. Sirtuins (SIRTs) are class III nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases and SIRT-mediated deacetylation is an important epigenetic alteration. The SIRT family comprises seven protein members (namely, SIRT1-7). While the catalytic core domain contains amino acid residues that have remained stable throughout the entire evolutionary process, the N- and C-terminal regions are structurally divergent and contribute to differences in subcellular localization, enzymatic activity and substrate specificity. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are predominantly found in the nucleus. SIRTs are key regulators of various physiological processes such as cellular differentiation, apoptosis, metabolism, ageing, immune response, oxidative stress, and mitochondrial function. We discuss the association between SIRTs and common autoimmune diseases to facilitate the development of more effective therapeutic strategies.

Peyer's patch-involved gut microbiota facilitates anti-HBV immunity in mice.

BACKGROUND: Gut microbiota is crucial for immune homeostasis and is associated with the prognosis of chronic hepatitis B infection. Peyer's patches (PPs), characterized by intestinal mucosa localization, are involved in the gut microbiota-mediated immune response. However, whether and how PPs orchestrate gut microbiota-modulated anti-hepatitis B virus (HBV) response remain elusive. This study aims to elucidate the role of PPs in gut microbiota-mediated anti-HBV adaptive immunity. METHODS: We investigated the effects of gut microbiota and PPs on adaptive immune responses by transcriptomic, phenotypic, and functional analyzes from an HBV mouse model with gut commensal microbiota and PP-depleting interventions. RESULTS: Depletion of gut microbiota impaired systemic adaptive immune responses, resulting in a delayed HBV antigen clearance. Differentially expressed genes analysis of PPs revealed that pathways related to adaptive immune responses were significantly downregulated in gut microbiota-deficient mice. Notably, the depletion of PPs could abolish gut microbiota-boosted intrahepatic HBV-specific T cell response, leading to a higher serum hepatitis B surface antigen level in mice. CONCLUSION: PPs orchestrate gut microbiota-mediated intrahepatic anti-HBV cellular immunity, underlining the significance of remote manipulating the "gut microbiota-PPs" axis for achieving optimum anti-HBV response.

HBV Core-specific CD4+ T cells correlate with sustained viral control upon off-treatment in HBeAg-positive chronic hepatitis B patients.

BACKGROUND & AIMS: Treatment with nucleos(t)ide analogue (NA) efficiently suppresses viral replication in patients with chronic HBV infection, yet HBV relapses frequently upon NA withdrawal; the detailed immunomodulatory compounds for sustained viral control of HBV upon NA interruption have yet to be fully clarified. This study aimed to elucidate the role of T cells specific for distinct HBV peptides in sustained response upon discontinuation of antiviral treatment. METHODS: A total of 48 patients with HBeAg-positive chronic hepatitis B receiving NA treatment and withdrawal were included longitudinally in a retrospective and prospective cohort. Enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays were performed to detect IFN-γ producing HBV-specific T cells following stimulation with overlapping peptides covering the whole HBV genome after 10 days of in vitro expansion. RESULTS: ICS assays revealed that T cells specific for HBV Core and Polymerase induced more robust IFN-γ responses compared to Envelope and HBx. Notably, at the time of NA discontinuation, the intensity and breadth of HBV Core peptides-induced responses, predominately targeted by CD4+ T cells but not CD8+ T cells, were associated with sustained viral control upon off-treatment. Further exploration of longitudinal features in patients with sustained viral control revealed that the breadth of HBV-specific T cell responses does not increase following treatment cessation. CONCLUSION: This report emphasizes the essential role of HBV Core-specific CD4+ T cells in sustained response after therapy withdrawal, indicating it is a potential candidate for immunotherapeutic approaches in chronic HBV patients.

In vitro bioaccessibility evaluation of chlorophyll pigments in single and binary carriers.

Chlorophyll was extracted and microencapsulated using different carrier agents. Subsequently, in vitro digestion was performed, and the bioaccessibility of chlorophyll in the different encapsulation systems was carried out. The zeta potential, particle size, and PDI were significantly modified after the micellarization of digested microcapsules. I-W-Chl presented with the highest total chlorophyll recovery and micellarization rate of 54% and 43%, respectively. In the aqueous micellar fraction, the different encapsulation systems had total chlorophylls, pheophytins, and pheophorbides ranging from 13 to 49%, 42 - 77%, and 3 - 22% respectively. The bioaccessibility of total chlorophyll pigment ranging from 7% to 20% is given in the following order: I-W-Chl > WPI-Chl > Z-Chl > Ca-Chl > SCChlV > SCChlC. The result established in this study shows that the carrier agent type could inhibit or mediate the bioaccessibility of chlorophyll with the potential to be an efficient delivery system for health promoting compounds.

In vitro bioaccessibility evaluation of pheophytins in gelatin/polysaccharides carrier.

The type of carrier agent could impact pheophytin stability and bioaccessibility. Hence, it is important to have an elaborate understanding on the extent and type of pheophytin transformation during in vitro digestion of microcapsules. Four kinds of protein/polysaccharides complex were used to fabricate pheophytin microcapsules and investigated for pigments bioaccessibility. With different carriers, pheophytin pigments showed new characteristics influencing particle size and zeta potential during in vitro digestion. Pheophytin b was widely transformed to pheophorbide b, confirming pheophorbidation of the b series in proper condition. No 151-hydroxy lactone chlorophyll or pheophytin derivatives were detected, indicating some protective effect of microencapsulation. Pheophytins loaded in gelatin-pectin complex exhibited a relatively higher recovery rate, micellarization rate, and bioaccessibility index. The result presented in this study shows that the type of carrier agent could initiate the removal of phytyl groups in pheophytins and also inhibit or mediate their bioaccessibility.

Interferon α facilitates anti-HBV cellular immune response in a B cell-dependent manner.

OBJECTIVES: Dissecting the underlying mechanism of T cells remodeling mediated by interferon α (IFN-α) is indispensable for achieving an optimum therapeutic response in chronic hepatitis B (CHB) patients. However, little is known about B cells in this process. This study aims to elucidate the roles of B cells in IFN-α-mediated anti-hepatitis B virus (HBV) cellular immunity. METHOD: The effects of B cells on IFN-α-mediated T cell response were investigated in B cell-deficient mouse model with HBV and IFN-α plasmid hydrodynamic injection. Single-cell RNA sequencing was performed to dissect the crosstalk among B cell and T cell subsets and the underlying molecule and pathway signatures on longitudinal blood samples from IFN-α-treated CHB patients. RESULTS: B cell depletion impaired the functional T cell subsets, including HBV-specific CD8+ T cells, and engendered a delayed HBV clearance. IFN-α treatment boosted the response of HBV-specific CD8+ T cells, whereas such effects disappeared in B cell-deficient mice. The underlying mechanisms were associated with IFN-α-reinforced connections of B cells toward T cells as mediated by the antigen presentation and costimulatory functions in B cells. CONCLUSION: IFN-α orchestrates protective HBV-specific cellular immunity in a B cell-dependent manner.

Dynamic Evolutionary Analysis of Land Use/Cover and Ecosystem Service Values on Hainan Island.

This study of Hainan Island, based on three periods of land use/cover data from 2008, 2013, and 2017, uses the intensity analysis model and landscape pattern index to portray the dynamic changes of land use on the island and a quantitative analysis of the spatial and temporal evolutionary characteristics of ecosystem service values (ESV) based on the equivalent factor method. At the same time, the response of ESV to landscape pattern changes is explored. The results indicate: (1) From 2008 to 2017, the cultivated land in the coastal areas around Hainan Island continued to expand, which squeezed out forest land and reduced its area. The growth of built-up areas in Haikou City and Sanya City was more dramatic. (2) A weakening trend in the intensity of land use on Hainan Island during the study period. There were significant changes in cultivated land, grassland, and bare land, with forest land, grassland, and water bodies transformed into cultivated land. Built-up areas increased mainly through the occupation of cultivated land, grassland, and water bodies. (3) The fragmentation of landscape patches and the diversity of landscapes on Hainan Island increased, with the distribution of landscape types tending to be balanced. (4) From 2008 to 2017, the overall ESV of the island showed an initial decrease before increasing; the main spatial distribution characteristic of the ESV was "high in the central and low in the surroundings". (5) The mean patch area, the Shannon diversity index, and the largest patch index showed clear positive correlations to ESV.

[Spatial Distribution, Risk, and Influencing Factors of River Water-Sediment Heavy Metals in the Lower Reaches of the Qianhe River].

The spatial distribution of heavy metals in rivers is affected by human activities and the natural environment, posing a risk to human health related to heavy metal pollution. In order to study the characteristics, health risk levels, and influencing factors of heavy metal distribution and pollution in the lower reaches of the Qianhe River, 19 surface sediments and 20 water samples were collected, and the contents of As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn were measured by inductively coupled plasma mass spectrometry(ICP-MS). Using the DEM, air temperature, precipitation and other 11 factors as independent variables, the spatial differentiation of heavy metal pollution in sediments were explored based on geo-detector and geo-weighted regression model. The results showed that the eight heavy metal contents in the lower reaches of the Qianhe River did not exceed the "Surface Water Environmental Quality Standards" Ⅱ for water-like bodies, in which the variation coefficient of Pb element was 3.11, and the high content areas were mainly concentrated around Dongling Smelting Company and Fengxiang Railway Station. The average Rc value of adult carcinogens in water bodies was 7.72 E-06, showing a low risk level, and the children's carcinogens average Rc value was 1.17 E-04, showing a strong risk degree. The non-carcinogen risks for adults and children were both tolerable. The total high R value for children was mainly concentrated around Fengxiang Railway Station, posing a high risk. Sedimentation of heavy metals, except As and Mn, exceeded the soil background value in Shaanxi Province. The average content of Cd element was 1.12 mg·kg-1, which was 12 times the soil background value in Shaanxi Province. The pollution of Cd, Zn, and Pb was high, and distributed mainly in Changqing Village, Nanwan Village and Niujiatan Village, Gaozhuang, and Dongling Smelting Company. PLIzone of heavy metals in the sediments in the study area was 1.71, which was light pollution. DEM, temperature and precipitation were the main natural factors influencing the spatial pattern of heavy metal pollution load index(PLI) in sediments, and their nonlinear interactions were enhanced, which may play a role in the spread of heavy metals in sediments. This research can provide a scientific basis for urban planning and human health risks prevention in the Qianhe River.

Systemic inflammatory response index as an independent risk factor for ischemic stroke in patients with rheumatoid arthritis: a retrospective study based on propensity score matching.

OBJECTIVE: To investigate the relationship between systemic inflammatory response index (SIRI) and ischemic stroke (IS) in rheumatoid arthritis (RA) patients. METHODS: Fifty-two RA patients with IS, who were admitted to Wujin Hospital Affiliated with Jiangsu University between 2015 and 2019, were selected as the study group, and 236 RA patients without IS were selected as the control group. Propensity score matching (PSM) function of SPSS 26.0 was used to carry out 1:1 propensity score matching for gender, age, blood pressure, blood glucose, blood lipid, and smoking history of patients in the two groups, and the caliper value was set as 0.02 to obtain covariate balanced samples between groups. When performing blood tests, the following are determined: rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), mean platelet volume (MPV), calculated SIRI = (neutrophil × monocyte)/lymphocyte, and completed 28-joint disease activity score (DAS28-CRP). The differences in inflammatory markers between the two groups were compared, the independent risk factors were analyzed by logistic regression, and the auxiliary diagnostic value was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: A total of 48 pairs of patients were successfully matched. SIRI in the study group was higher than that in the control group (p < 0.05), and the mean platelet volume (MPV) was lower in the study group than in the control group (p < 0.05). SIRI, DAS28-CRP (r = 0.508, p < 0.01), ESR (r = 0.359, p < 0.05), and CRP (r = 0.473, p < 0.01) were positively correlated. Logistic regression analysis showed that SIRI was an independent IS risk factor in RA patients (odds ratio, 1.30; 95% confidence interval, approximately 1.008-1.678). The optimal threshold for SIRI-assisted diagnosis of patients with RA and IS was 1.62, the area under the ROC curve was 0.721 (p < 0.01), sensitivity was 54.17%, and specificity was 83.33%. CONCLUSION: SIRI was independently associated with the occurrence of ischemic stroke in patients with RA. Thus, RA patients with elevated SIRI should be closely monitored. Key points • RA patients with IS had fewer traditional risk factors such as hypertension and diabetes, while inflammatory indicators were significantly increased. • The SIRI have drawn attention in recent years as novel non-specific inflammatory markers. However, only a few studies have been conducted to investigate their value in RA. • This study completes the gaps in the research on the relationship between SIRI and the risk of IS occurrence in RA patients.

The value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as complementary diagnostic tools in the diagnosis of rheumatoid arthritis: A multicenter retrospective study.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have drawn attention in recent years as novel non-specific inflammatory markers; however, only a few studies have been conducted to investigate their value in RA. OBJECTIVE: To investigate the value of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as complementary diagnostic tools in rheumatoid arthritis (RA). METHOD: This study included 1009 patients with RA, 170 patients with other rheumatic diseases, and 245 healthy individuals from four medical centers. The patients' general data, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), were retrospectively analyzed, and the NLR and PLR were calculated. Potential effective indicators were screened by logistic regression analysis, and a receiver operating characteristic (ROC) curve was plotted to evaluate their diagnostic value for RA. RESULTS: (a) The NLR and PLR were significantly higher in the RA group than in the non-RA group and the control group (P < .05). (b) Spearman's Rho showed that the NLR was positively correlated with the PLR (r = .584, P < .05), RF (r = .167, P < .01), and CRP (r = .280, P < .01) but was not significantly correlated with ESR (r = .100, P > .05). The PLR was positively correlated with RF (r = .139, P < .01), CRP (r = .297, P < .01), and ESR (r = .262, P < .05). (c) Logistic analysis showed that RF, CRP, ESR, and the NLR had diagnostic value for RA. (d) For the NLR, the area under the curve (AUC) of the ROC curve was 0.831; at the cutoff value of 2.13, the diagnostic sensitivity, specificity, accuracy, and Youden index were 76.7%, 75.9%, 76.4%, and 0.5424, respectively. CONCLUSION: The NLR was less effective than CRP and RF but was superior to ESR in the diagnosis of RA. The NLR can thus be used as a complementary diagnostic indicator in the diagnosis of RA.

The impact of mandatory policies on residents' willingness to separate household waste: A moderated mediation model.

The impact of mandatory policies on residents' willingness to separate waste and how they respond to such measures is not clearly understood. To answer this question, based on deterrence theory, theories of belief change, the theory of rational behavior, and the theory of cognitive consistency, this paper established a mechanism model for the impact of mandatory policies on residents' willingness to separate waste, and analyzed the roles of attitude, subjective norms, and new ecological paradigms. Through a questionnaire survey of 442 ordinary residents in Shanghai, hierarchical regression and bootstrapping analysis were used to verify the above model. The results showed that:(1) mandatory policies positively affected residents' attitude and subjective norms toward waste separation; (2) through the mediation of attitude and subjective norms, mandatory policies positively affected residents' willingness to separate waste; and (3) the new ecological paradigm moderated the above effects. For residents with higher ecological paradigm, the positive influence of mandatory policies on attitudes and subjective norms was stronger, and the mediation effect of attitude and subjective norms was also stronger.

Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury.

Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF-a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF-a-induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.

Rab27b is Involved in Lysosomal Exocytosis and Proteolipid Protein Trafficking in Oligodendrocytes.

Myelination by oligodendrocytes in the central nervous system requires coordinated exocytosis and endocytosis of the major myelin protein, proteolipid protein (PLP). Here, we demonstrated that a small GTPase, Rab27b, is involved in PLP trafficking in oligodendrocytes. We showed that PLP co-localized with Rab27b in late endosomes/lysosomes in oligodendrocytes. Short hairpin-mediated knockdown of Rab27b not only reduced lysosomal exocytosis but also greatly diminished the surface expression of PLP in oligodendrocytes. In addition, knockdown of Rab27b reduced the myelin-like membranes induced by co-culture of oligodendrocytes and neurons. Our data suggest that Rab27b is involved in myelin biogenesis by regulating PLP transport from late endosomes/lysosomes to the cell membrane in oligodendrocytes.

Rab27a/Slp2-a complex is involved in Schwann cell myelination.

Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion (DRG) neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/Slp2-a complex affects Schwann cell myelination in vitro.