Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) ...derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.
The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.
Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.
Display omitted
•Recent studies on synthesis of biochar-based nano-composites are reviewed.•Biochar-based nano-composites combine the advantages of biochar with nano-materials.•Nano-particles improve ...biochar’s physicochemical properties and serve as active sites.•Multiple mechanisms are involved in contaminants removal.•Knowledge gaps in the future development should be studied.
Synthesizing biochar-based nano-composites can obtain new composites and combine the advantages of biochar with nano-materials. The resulting composites usually exhibit great improvement in functional groups, pore properties, surface active sites, catalytic degradation ability and easy to separation. These composites have excellent abilities to adsorb a range of contaminants from aqueous solutions. Particularly, catalytic material-coated biochar can exert simultaneous adsorption and catalytic degradation function for organic contaminants removal. Synthesizing biochar-based nano-composites has become an important practice for expanding the environmental applications of biochar and nanotechnology. This paper aims to review and summarize the various synthesis techniques for biochar-based nano-composites and their effects on the decontamination of wastewater. The characteristic and advantages of existing synthesis methods are summarized and discussed. Application of biochar-based nano-composites for different contaminants removal and the underlying mechanisms are reviewed. Furthermore, knowledge gaps that exist in the fabrication and application of biochar-based nano-composites are also identified.
Display omitted
•Biochars are potential sustainable precursors for activated carbon production.•Physical activation and chemical activation are applied in the production process.•Production ...parameters affect the properties of resultant activated carbon.•Multiple applications in environmental protection and energy storage are reviewed.•Future perspectives about biochar activation and applications are highlighted.
There is a growing interest of the scientific community on production of activated carbon using biochar as potential sustainable precursors pyrolyzed from biomass wastes. Physical activation and chemical activation are the main methods applied in the activation process. These methods could have significantly beneficial effects on biochar chemical/physical properties, which make it suitable for multiple applications including water pollution treatment, CO2 capture, and energy storage. The feedstock with different compositions, pyrolysis conditions and activation parameters of biochar have significant influences on the properties of resultant activated carbon. Compared with traditional activated carbon, activated biochar appears to be a new potential cost-effective and environmentally-friendly carbon materials with great application prospect in many fields. This review not only summarizes information from the current analysis of activated biochar and their multiple applications for further optimization and understanding, but also offers new directions for development of activated biochar.
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.
Main Points
P2X4R is mainly localized in the lysosomes of Schwann cells and the expression of P2X4R in Schwann cells is strikingly upregulated following nerve crush injury.
Overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery as well as accelerates nerve remyelination via BDNF release following nerve injury.
During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community ...populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions.
Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings.
The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients' treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals' mental pressures.
During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.
ARL9 is a newly identified member of the ARF family, and the clinical significance of ARL9 in colon adenocarcinoma is unknown. In this study, we aimed to explore the expression of ARL9 mRNA in colon ...adenocarcinoma, and its effect on the prognosis of patients with colon adenocarcinoma.
We investigated the differential expression of ARL9 between colon adenocarcinoma tissue and adjacent tissues through a bioinformatics analysis using The Cancer Genome Atlas (TCGA) database. The correlation between clinical characteristics and the mRNA expression level of ARL9 were analyzed. A survival analysis and a Cox regression analysis were used to determine the prognostic significance of ARL9. Finally, we conducted a gene set enrichment analysis (GSEA) to explore the ARL9 signaling pathways involved in the development of colon adenocarcinoma. The effect of the expression of ARL9 on the proliferation and migration of colon adenocarcinoma was analyzed by the CCK8 method and a cell scratch test, respectively.
The mRNA expression of ARL9 in colon adenocarcinoma tissues was higher in comparison to the level in normal adjacent tissues (P < 0.05). The mRNA expression of ARL9 was not related to sex, tumor stage, T stage, N stage, M stage, but to age. The 5-year survival rate of colon adenocarcinoma patients with high ARL9 mRNA expression levels was significantly lower than that of patients with low ARL9 mRNA expression levels (P < 0.05). Age and the high mRNA expression of ARL9 were independent risk factors for a poor prognosis in patients with colon adenocarcinoma. The GSEA suggested that ARL9 may be able to upregulate cell adhesion, extracellular matrix receptor interactions, tumor-associated pathways, and downregulate the citrate cycle and tricarboxylic acid cycle pathway, which are involved in the development of colon adenocarcinoma. After knocking down ARL9, the proliferation and migration abilities of colon adenocarcinoma cells were decreased (P < 0.01).
The mRNA expression of ARL9 is upregulated in colon adenocarcinoma, and higher mRNA expression levels are associated with a poor prognosis. Knocking down ARL9 can reduce the proliferation and migration of colon adenocarcinoma cells. ARL9 mRNA can be used as a prognostic biomarker in patients with colon adenocarcinoma.
There is a lack of effective therapeutic strategies for amyotrophic lateral sclerosis (ALS); therefore, drug repurposing might provide a rapid approach to meet the urgent need for treatment.
To ...identify therapeutic targets associated with ALS, we conducted Mendelian randomization (MR) analysis and colocalization analysis using cis-eQTL of druggable gene and ALS GWAS data collections to determine annotated druggable gene targets that exhibited significant associations with ALS. By subsequent repurposing drug discovery coupled with inclusion criteria selection, we identified several drug candidates corresponding to their druggable gene targets that have been genetically validated. The pharmacological assays were then conducted to further assess the efficacy of genetics-supported repurposed drugs for potential ALS therapy in various cellular models.
Through MR analysis, we identified potential ALS druggable genes in the blood, including TBK1 OR 1.30, 95%CI (1.19, 1.42), TNFSF12 OR 1.36, 95%CI (1.19, 1.56), GPX3 OR 1.28, 95%CI (1.15, 1.43), TNFSF13 OR 0.45, 95%CI (0.32, 0.64), and CD68 OR 0.38, 95%CI (0.24, 0.58). Additionally, we identified potential ALS druggable genes in the brain, including RESP18 OR 1.11, 95%CI (1.07, 1.16), GPX3 OR 0.57, 95%CI (0.48, 0.68), GDF9 OR 0.77, 95%CI (0.67, 0.88), and PTPRN OR 0.17, 95%CI (0.08, 0.34). Among them, TBK1, TNFSF12, RESP18, and GPX3 were confirmed in further colocalization analysis. We identified five drugs with repurposing opportunities targeting TBK1, TNFSF12, and GPX3, namely fostamatinib (R788), amlexanox (AMX), BIIB-023, RG-7212, and glutathione as potential repurposing drugs. R788 and AMX were prioritized due to their genetic supports, safety profiles, and cost-effectiveness evaluation. Further pharmacological analysis revealed that R788 and AMX mitigated neuroinflammation in ALS cell models characterized by overly active cGAS/STING signaling that was induced by MSA-2 or ALS-related toxic proteins (TDP-43 and SOD1), through the inhibition of TBK1 phosphorylation.
Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation.
Failure mode and effects analysis (FMEA) is an effective risk assessment tool for detecting and reducing possible risks during a manufacturing process. However, traditional FMEA has some shortcomings ...when used in the real world. In recent years, improved FMEA approaches have been proposed to eliminate the inherent shortcomings of FMEA, but the risk ranking result obtained from those FMEA approaches may be inconsistent. Therefore, this paper integrates six FMEA approaches by using an ensemble learning technique to obtain comprehensive and reliable rankings for failure modes. Data from the assembly process of spark plugs are used to check the performance of the proposed method. Meanwhile, a comparation is designed to illustrate that the proposed FMEA method can not only obtain reliable results, but also provide meaningful management insights for practitioners.
Ceramic particle reinforced high entropy (HEA) alloy composites have attracted considerable attention due to their excellent combination of strength, ductility, and wear resistance. In this work, the ...high entropy alloy composites (Fe50Mn30Co10Cr10 matrix) with the different SiC contents (0.1, 0.5, 1, and 3 vol%) were fabricated by arc melting. The effect of SiC content on microstructure characteristics, mechanical and wear properties of Fe50Mn30Co10Cr10 composites were studied. The results showed that SiC stabilized the γ phase and refined the grain sizes. In addition, the number of ε variants were decreased with refined grain sizes. The composite with 1 vol% SiC optimized the combination of ultimate tensile strength and ductility, which is attributed to grain-boundary strengthening, twin boundary strengthening, dispersion strengthening and load-bearing strengthening. Simultaneously, the optimized composite with 1 vol% SiC displayed the best wear friction ability, in which the proper SiC content played a key role in carrying load during friction.
•Fe50Mn30Co10Cr10 with four different SiC contents (0.1, 0.5, 1, and 3 vol%) are prepared by the arc-melting.•SiC particles promote phase transformation from ε to γ, refine the grain sizes and decrease the number of ε variants.•Fe49Mn30Co10Cr10SiC1 composite optimizes the combination of ultimate tensile strength and ductility.•Fe49Mn30Co10Cr10SiC1 composite displays the best wear friction ability.
In this work, a novel adsorbent of aluminium/lanthanum loaded wheat straw biochar (Al-La-WSB), was prepared by using a facile approach and used for fluoride removal. The Al-La-WSB and its pristine ...wheat straw biochar (WSB) were characterized by scanning electronic microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray powder diffraction (XRD) methods. Batch adsorption experiments were carried out to investigate adsorbent performance, the highest removal rate was observed at pH 9, contact time of 7 h and Al-La-WSB dose of 1 g L
−1
. Lagergren pseudo-second-order kinetics and Langmuir isotherm model fitted the experimental data well. The maximum fluoride adsorption capacity of Al-La-WSB at different experiment temperature of 298, 308 and 318 K, was 51.28 mg g
-1
, 46.73 mg g
-1
and 50.25 mg g
-1
, respectively, which was better than most reported adsorbents. The Al-La-WSB performed well over a considerable wide pH range of 3-10 and carried positive charge at pH < 4.8. The presence co-existing ions of SO
4
2−
, HCO
3
−
, Cl
−
and NO
3
−
had a minor impact on fluoride adsorption besides PO
4
3−
. Regeneration experiment results showed that the Al-La-WSB had an excellent reusability. According to the adsorbent characterization and batch adsorption experiment, the adsorption of fluoride on the Al-La-WSB was primarily a chemisorption, involving electrostatic interactions and ion exchange, which nitrate ion and hydroxyl played a major role. The results suggested that the Al-La-WSB could be a great adsorbent for removing fluoride from drinking water.
PDF
