The P2X7 receptor mediates NADPH transport across the plasma membrane.

Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a vital role in regulating redox homeostasis and reductive biosynthesis. However, if exogenous NADPH can be transported across the plasma membrane has remained elusive. In this study, we present evidence supporting that NADPH can traverse the plasma membranes of cells through a mechanism mediated by the P2X7 receptor (P2X7R). Notably, we observed an augmentation of intracellular NADPH levels in cultured microglia upon exogenous NADPH supplementation in the presence of ATP. The P2X7R-mediated transmembrane transportation of NADPH was validated with P2X7R antagonists, including OX-ATP, BBG, and A-438079, or through P2X7 knockdown, which impeded NADPH transportation into cells. Conversely, overexpression of P2X7 resulted in an enhanced capacity for NADPH transport. Furthermore, transfection of hP2X7 demonstrated the ability to complement NADPH uptake in native HEK293 cells. Our findings provide evidence for the first time that NADPH is transported across the plasma membrane via a P2X7R-mediated pathway. Additionally, we propose an innovative avenue for modulating intracellular NADPH levels. This discovery holds promise for advancing our understanding of the role of NADPH in redox homeostasis and neuroinflammation.

α-Synuclein disrupts microglial autophagy through STAT1-dependent suppression of Ulk1 transcription.

BACKGROUND: Autophagy dysfunction in glial cells is implicated in the pathogenesis of Parkinson's disease (PD). The previous study reported that α-synuclein (α-Syn) disrupted autophagy in cultured microglia. However, the mechanism of microglial autophagy dysregulation is poorly understood. METHODS: Two α-Syn-based PD models were generated via AAV-mediated α-Syn delivery into the mouse substantia nigra and striatal α-Syn preformed fibril (PFF) injection. The levels of microglial UNC-51-like kinase 1 (Ulk1) and other autophagy-related genes in vitro and in PD mice, as well as in the peripheral blood mononuclear cells of PD patients and healthy controls, were determined via quantitative PCR, western blotting and immunostaining. The regulatory effect of signal transducer and activator of transcription 1 (STAT1) on Ulk1 transcription was determined via a luciferase reporter assay and other biochemical studies and was verified through Stat1 knockdown or overexpression. The effect of α-Syn on glial STAT1 activation was assessed by immunohistochemistry and western blotting. Changes in microglial status, proinflammatory molecule expression and dopaminergic neuron loss in the nigrostriatum of PD and control mice following microglial Stat1 conditional knockout (cKO) or treatment with the ULK1 activator BL-918 were evaluated by immunostaining and western blotting. Motor behaviors were determined via open field tests, rotarod tests and balance beam crossing. RESULTS: The transcription of microglial ULK1, a kinase that controls autophagy initiation, decreased in both in vitro and in vivo PD mouse models. STAT1 plays a critical role in suppressing Ulk1 transcription. Specifically, Stat1 overexpression downregulated Ulk1 transcription, while Stat1 knockdown increased ULK1 expression, along with an increase in LC3II and a decrease in the SQSTM1/p62 protein. α-Syn PFF caused toll-like receptor 4-dependent activation of STAT1 in microglia. Ablation of Stat1 alleviated the decrease in microglial ULK1 expression and disruption of autophagy caused by α-Syn PFF. Importantly, the ULK1 activator BL-918 and microglial Stat1 cKO attenuated neuroinflammation, dopaminergic neuronal damage and motor defects in PD models. CONCLUSIONS: These findings reveal a novel mechanism by which α-Syn impairs microglial autophagy and indicate that targeting STAT1 or ULK1 may be a therapeutic strategy for PD.

Abnormal Degraded Tapetum 1 (ADT1) is required for tapetal cell death and pollen development in rice.

The timely degradation of tapetum, the innermost somatic anther cell layer in flowering plants, is critical for pollen development. Although several genes involved in tapetum development have been characterized, the molecular mechanisms underlying tapetum degeneration remain elusive. Here, we showed that mutation in Abnormal Degraded Tapetum 1 (ADT1) resulted in overaccumulation of Reactive Oxygen Species (ROS) and abnormal anther development, causing earlier tapetum Programmed Cell Death (PCD) and pollen abortion. ADT1 encodes a nuclear membrane localized protein, which is strongly expressed in the developing microspores and tapetal cells during early anther development. Moreover, ADT1 could interact with metallothionein MT2b, which was related to ROS scavenging and cell death regulation. These findings indicate that ADT1 is required for proper timing of tapetum PCD by regulating ROS homeostasis, expanding our understanding of the regulatory network of male reproductive development in rice.

Streptomyces pratensis S10 Inhibits the Spread of Fusarium graminearum Invasive Hyphae and Toxisome Formation in Wheat Plants.

Fusarium head blight (FHB) of wheat, mainly caused by Fusarium graminearum, leads to severe economic losses worldwide. Effective management measures for controlling FHB are not available due to a lack of resistant cultivars. Currently, the utilization of biological control is a promising approach that can be used to help manage FHB. Previous studies have confirmed that Streptomyces pratensis S10 harbors excellent inhibitory effects on F. graminearum. However, there is no information regarding whether invasive hyphae of F. graminearum are inhibited by S10. Thus, we investigated the effects of S10 on F. graminearum strain PH-1 hypha extension, toxisome formation, and TRI5 gene expression on wheat plants via microscopic observation. The results showed that S10 effectively inhibited the spread of F. graminearum hyphae along the rachis, restricting the infection of neighboring florets via the phloem. In the presence of S10, the hyphal growth is impeded by the formation of dense cell wall thickenings in the rachis internode surrounding the F. graminearum infection site, avoiding cell plasmolysis and collapse. We further demonstrated that S10 largely prevented cell-to-cell invasion of fungal hyphae inside wheat coleoptiles using a constitutively green fluorescence protein-expressing F. graminearum strain, PH-1. Importantly, S. pratensis S10 inhibited toxisome formation and TRI5 gene expression in wheat plants during infection. Collectively, these findings indicate that S. pratensis S10 prevents the spread of F. graminearum invasive hyphae via the rachis.

Efficacy and safety of botulinum toxin A in the treatment of female pattern hair loss.

BACKGROUND: Female pattern hair loss (FPHL) is the most prevalent type of alopecia among adult women. Presently, topical minoxidil stands as the sole treatment endorsed by the FDA. Addressing cases of FPHL in individuals who develop contact dermatitis in response to minoxidil can pose a challenge for dermatologists. OBJECTIVE: To assess the efficacy and safety of subcutaneous injections of Botulinum Toxin Type A (BTA) in treating FPHL. METHODS: Enrolled outpatients with FPHL who exhibited an allergic reaction to minoxidil solution. Diagnosis of FPHL was established through clinical examination and trichoscopy. Inclusion criteria involved patients with no prior treatment within the last year and without any comorbidities. BTA, specifically 100 units, was mixed with 2 mL of 0.9% normal saline. Twenty injection target sites, spaced 2-3 cm apart, were symmetrically marked on the hairless area of the scalp. A dosage of five units was intradermally injected at each target site. Representative photographs and dermoscopic images of the scalp were captured before and after 3 months of treatment. RESULTS: A total of 10 FPHL, aged between 26 and 40 years, were included. The average age was 30.3 ± 4.64 years, and all patients had a positive family history of Androgenetic Alopecia. The average duration of the disease was 3.70 ± 1.42 years. According to patients' self-assessment, after 1 month of treatment, 10 FPHL patients reported experiencing moderate to marked improvement in symptoms related to scalp oil secretion. Three months later, dermatological assessments showed that three had mild improvement, six had no change, and one had a worsening condition. No adverse effects were observed. CONCLUSIONS: Our study suggests that the effectiveness of BTA for FPHL is limited to 3 months. However, it can be considered for tentative use after effective communication with patients. The long-term efficacy and safety of BTA in treating FPHL require further observation and study.

Extracellular vesicle dynamics in COPD: understanding the role of miR-422a, SPP1 and IL-17 A in smoking-related pathology.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) induced by smoking poses a significant global health challenge. Recent findings highlight the crucial role of extracellular vesicles (EVs) in mediating miRNA regulatory networks across various diseases. This study utilizes the GEO database to uncover distinct expression patterns of miRNAs and mRNAs, offering a comprehensive understanding of the pathogenesis of smoking-induced COPD. This study aims to investigate the mechanisms by which extracellular vesicles (EVs) mediate the molecular network of miR-422a-SPP1 to delay the onset of COPD caused by smoking. METHODS: The smoking-related miRNA chip GSE38974-GPL7723 was obtained from the GEO database, and candidate miRs were retrieved from the Vesiclepedia database. Downstream target genes of the candidate miRs were predicted using mRNA chip GSE38974-GPL4133, TargetScan, miRWalk, and RNA22 databases. This prediction was integrated with COPD-related genes from the GeneCards database, downstream target genes predicted by online databases, and key genes identified in the core module of WGCNA analysis to obtain candidate genes. The candidate genes were subjected to KEGG functional enrichment analysis using the "clusterProfiler" package in R language, and a protein interaction network was constructed. In vitro experiments involved overexpressing miRNA or extracting extracellular vesicles from bronchial epithelial cell-derived exosomes, co-culturing them with myofibroblasts to observe changes in the expression levels of the miR-422a-SPP1-IL-17 A regulatory network, and assessing protein levels of fibroblast differentiation-related factors α-SMA and collagen I using Western blot analysis. RESULTS: The differential gene analysis of chip GSE38974-GPL7723 and the retrieval results from the Vesiclepedia database identified candidate miRs, specifically miR-422a. Subsequently, an intersection was taken among the prediction results from TargetScan, miRWalk, and RNA22 databases, the COPD-related gene retrieval results from GeneCards database, the WGCNA analysis results of chip GSE38974-GPL4133, and the differential gene analysis results. This intersection, combined with KEGG functional enrichment analysis, and protein-protein interaction analysis, led to the final screening of the target gene SPP1 and its upstream regulatory gene miR-422a. KEGG functional enrichment analysis of mRNAs correlated with SPP1 revealed the IL-17 signaling pathway involved. In vitro experiments demonstrated that miR-422a inhibition targets suppressed the expression of SPP1 in myofibroblasts, inhibiting differentiation phenotype. Bronchial epithelial cells, under cigarette smoke extract (CSE) stress, could compensate for myofibroblast differentiation phenotype by altering the content of miR-422a in their Extracellular Vesicles (EVs). CONCLUSION: The differential gene analysis of Chip GSE38974-GPL7723 and the retrieval results from the Vesiclepedia database identified candidate miRs, specifically miR-422a. Further analysis involved the intersection of predictions from TargetScan, miRWalk, and RNA22 databases, gene search on COPD-related genes from the GeneCards database, WGCNA analysis from Chip GSE38974-GPL4133, and differential gene analysis, combined with KEGG functional enrichment analysis and protein interaction analysis. Ultimately, the target gene SPP1 and its upstream regulatory gene miR-422a were selected. KEGG functional enrichment analysis on mRNAs correlated with SPP1 revealed the involvement of the IL-17 signaling pathway. In vitro experiments showed that miR-422a targeted inhibition suppressed the expression of SPP1 in myofibroblast cells, inhibiting differentiation phenotype. Furthermore, bronchial epithelial cells could compensate for myofibroblast differentiation phenotype under cigarette smoke extract (CSE) stress by altering the miR-422a content in their extracellular vesicles (EVs).

Sulfate reduction behavior in response to landfill dynamic pressure changes.

During the long-term stabilization process of landfills, the pressure field undergoes constant changes. This study constructed dynamic pressure changes scenarios of high-pressure differentials (0.6 MPa) and low-pressure differentials (0.2 MPa) in the landfill pressure field at 25 °C and 50 °C, and investigated the sulfate reduction behavior in response to landfill dynamic pressure changes. The results showed that the pressurization or depressurization of high-pressure differentials caused more significant differences in sulfate reduction behavior than that of low-pressure differentials. The lowest hydrogen sulfide (H2S) release peak concentration under pressurization was only 29.67% of that under initial pressure condition; under depressurization, the highest peak concentration of H2S was up to 21,828 mg m-3, posing a serious risk of H2S pollution. Microbial community and correlation analysis showed that pressure had a negative impact on the sulfate-reducing bacteria (SRB) community, and the SRB community adjusted its structure to adapt to pressure changes. Specific SRBs were further enriched with pressure changes. Differential H2S release behavior under pressure changes in the 25 °C pressure environments were mediated by Desulfofarcimen (ASV343) and Desulfosporosinus (ASV1336), while Candidatus Desulforudis (ASV24) and Desulfohalotomaculum (ASV94) played a key role at 50 °C. This study is helpful in the formulation of control strategies for the source of odor pollution in landfills.

The stress response of tetracycline resistance genes and bacterial communities under the existence of microplastics in typical leachate biological treatment system.

Landfill leachate is an important source of microplastics (MPs) and antibiotic-resistance genes (ARGs). Here, in the presence of polystyrene MPs (PS-MPs) and polyethylene MPs (PE-MPs), the nitrogen and phosphorus removal effect and sludge structure performance were affected in an anaerobic-anoxic-aerobic system, a typical biological leachate treatment process. The abundance of tetracycline-resistance genes (tet genes) in biofilms on the two types of MP was significantly higher than that in the leachate and sludge, and the load on PE-MPs was higher than that on PS-MPs because of the porous structure of PE-MPs. Aging of the MPs increased their surface roughness and abundance of oxygen-containing functional groups and shaped the profile of ARGs in the MP biofilms. The biofilm biomass and growth rate on the two types of MP increased with the incubation time in the first 30 days, and was affected by environmental factors. Structural equation models and co-occurrence network analysis demonstrated that the MPs indirectly affected the spectrum of ARGs by affecting biofilm formation, and, to a lesser extent, had a direct impact on the selective enrichment of ARGs. We discuss the mechanisms of the relationships between MPs and ARGs in the leachate treatment system, which will have guiding significance for future research. Our data on the colonization of microorganisms and tet genes in MPs biofilms provide new evidence concerning the accumulation and transmission of these ARGs, and are important for understanding the mechanisms of MPs in spreading pollution.

Pramipexole inhibits astrocytic NLRP3 inflammasome activation via Drd3-dependent autophagy in a mouse model of Parkinson's disease.

Inflammation is one of the pathogenic processes in Parkinson's disease (PD). Dopamine receptor agonist pramipexole (PPX) is extensively used for PD treatment in clinics. A number of studies show that PPX exerts neuroprotection on dopaminergic (DA) neurons, but the molecular mechanisms underlying the protective effects of PPX on DA neurons are not fully elucidated. In the present study, we investigated whether PPX modulated PD-related neuroinflammation and underlying mechanisms. PD model was established in mice by bilateral striatum injection of lipopolyssaccharide (LPS). The mice were administered PPX (0.5 mg·kg-1·d-1, i.p.) 3 days before LPS injection, and for 3 or 21 days after surgery, respectively, for biochemical and histological analyses. We showed that PPX administration significantly alleviated the loss of DA neurons, and suppressed the astrocyte activation and levels of proinflammatory cytokine IL-1ß in the substantia nigra of LPS-injected mice. Furthermore, PPX administration significantly decreased the expression of NLRP3 inflammasome-associated proteins, i.e., cleaved forms of caspase-1, IL-1ß, and apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) in the striatum. These results were validated in LPS+ATP-stimulated primary mouse astrocytes in vitro. Remarkably, we showed that PPX (100-400 µM) dose-dependently enhanced the autophagy activity in the astrocytes evidenced by the elevations in LC3-II and BECN1 protein expression, as well as the increase of GFP-LC3 puncta formation. The opposite effects of PPX on astrocytic NLRP3 inflammasome and autophagy were eliminated by Drd3 depletion. Moreover, we demonstrated that both pretreatment of astrocytes with autophagy inhibitor chloroquine (40 µM) in vitro and astrocyte-specific Atg5 knockdown in vivo blocked PPX-caused inhibition on NLRP3 inflammasome and protection against DA neuron damage. Altogether, this study demonstrates an anti-neuroinflammatory activity of PPX via a Drd3-dependent enhancement of autophagy activity in astrocytes, and reveals a new mechanism for the beneficial effect of PPX in PD therapy.

Streptomyces pratensis S10 Controls Fusarium Head Blight by Suppressing Different Stages of the Life Cycle and ATP Production.

Fusarium head blight (FHB) of wheat, predominately caused by Fusarium graminearum, is an economically important plant disease worldwide. With increased fungicide resistance, controlling this filamentous fungal disease has become an enormous challenge. Biocontrol agents alone or integrated with other methods could better manage FHB. Streptomyces pratensis S10 has strong antagonistic activity against FHB as reported in our previous study. We now have investigated S10 controls of FHB in more detail by combining microscope observations, biological assays, and transcriptome profiling. S10 culture filtrates (SCF) significantly inhibited essential stages of the life cycle of F. graminearum in the laboratory and under simulated natural conditions. SCF at different concentrations inhibited conidiation of F. graminearum with an inhibition of 57.49 to 83.83% in the medium and 64.04 to 85.89% in plants. Different concentrations of SCF reduced conidia germination by 47.33 to 67.67%. Two percent (vol/vol) SCF suppressed perithecia formation of F. graminearum by 84 and 81% in the laboratory and under simulated natural conditions, respectively. The S10 also reduced the pathogenicity and penetration ability of F. graminearum by suppressing ATP production. Collectively, these findings indicate that S. pratensis S10 should be explored further for efficacy at controlling FHB.

Patters of reactive nitrogen removal at the waters in the semi-constructed wetland.

Protection and rectification patters of urban wetlands have been considered in strategies to balance services to society and negative consequences of excess reactive nitrogen (Nr) loading. However, the knowledge about strategies of semi-constructed wetlands on nitrogen (N) cycling pathways and removal Nr from the overlying water is limited. This study aimed to reveal considerable differences among rectification patterns of the typical semi-constructed wetland (Xixi wetland), comprising rational exploitation area (REA), rehabilitation and reconstruction area (RRA), and conservation area (CA) by analyzing the N distribution and N protentional pathways among them. Results pointed out that both NH4+ and NO3- concentration were prominently higher in REA, as opposed to CA and RRA. Sediments in RRA had relatively higher NH4+ content, indicating the efficiency of dissimilatory nitrate reduction (DNRA) in RRA. Moreover, there was a significant shift in the microbial community structure across different sites and sediments. Metagenomic analysis distinguished the N cycling pathways, with nitrification (M00804), denitrification (M00529), and DNRA (M00530) being the crucial pathways in the semi-constructed wetland. The relative abundance of N metabolic pathways (ko00910) varied among different types of sediments, being more abundant in shore and rhizosphere areas and less abundant in bottom sediments. Methylobacter and Nitrospira were the predominant nitrifiers in shore sediments, while Methylocystis was enriched in the bottom sediments and rhizosphere soils. Furthermore, Anaeromyxobacter, Anaerolinea, Dechloromonas, Nocardioides, and Methylocystis were identified as the primary denitrifiers with N reductase genes (nirK, nirS, or nosZ). Among these, Anaeromyxobacter, Dechloromonas, and Methylocystis were the primary contributors containing the nosZ gene in semi-constructed wetlands, driving the conversion of N2O to N2. This study provides important insights into rectification-dependent Nr removal from the overlying water in terms of N distribution and N metabolic functional microbial communities in the semi-constructed wetlands.

Sulfate reduction behavior in pressure-bearing leachate saturated zone.

Attention should be paid to the sulfate reduction behavior in a pressure-bearing leachate saturated zone. In this study, within the relative pressure range of 0-0.6 MPa, the ambient temperature with the highest sulfate reduction rate of 50°C was selected to explore the difference in sulfate reduction behavior in a pressure-bearing leachate saturated zone. The results showed that the sulfate reduction rate might further increase with an increase in pressure; however, owing to the effect of pressure increase, the generated hydrogen sulfide (H2S) could not be released on time, thereby decreasing its highest concentration by approximately 85%, and the duration extended to about two times that of the atmospheric pressure. Microbial community structure and functional gene abundance analyses showed that the community distribution of sulfate-reducing bacteria was significantly affected by pressure conditions, and there was a negative correlation between disulfide reductase B (dsrB) gene abundance and H2S release rate. Other sulfate reduction processes that do not require disulfide reductase A (dsrA) and dsrB genes may be the key pathways affecting the sulfate reduction rate in the pressure-bearing leachate saturated zone. This study improves the understanding of sulfate reduction in landfills as well as provides a theoretical basis for the operation and management of landfills.

Adsorption and Separation of Ethyl Mercaptan from Methane by Hydroxyl Groups on the Surface of HTiNbO5-Nanosheets.

Adsorption and separation of light mercaptan (R-SH, R = C1-C4) from methane gas can effectively improve the utilization efficiency of methane and the resource conversion of organic sulfide. To further investigate the effects of composition and structural characteristics of laminates on desulfurization performance, in this paper, a two-dimensional (2D) HTiNbO5-nanosheet (HTiNbO5-NS) was constructed. In addition, the hydrogen-bonding interaction between the exposed hydroxyl active sites on the surface of HTiNbO5-NS and ethyl mercaptan (Et-SH) was constructed to realize the adsorption and separation of Et-SH from methane gas. The breakthrough adsorption capacity (Cap (BT)) of HTiNbO5-NS is 14.35 mg·g-1 in a micro fixed bed with a space velocity of 6000 h-1. The regeneration desulfurization rate (q) of the 10-cycle regeneration adsorption was ca. 96%. Furthermore, density functional theory (DFT) calculation results show that the S atoms of Et-SH and HTiNbO5-NS with the terminal hydroxyl and bridge hydroxyl have electron cloud covering to form the hydrogen-bonding interaction. In addition, the formation details of this hydrogen-bond interaction are discussed. The effects of Ti on the microstructure, hydroxyl acid, hydroxyl content, surface area, and pore volume of nanosheets were studied to explain the reasons for the differences in the properties of the two kinds of nanosheets. This work broadens the design of 2D niobium-based efficient adsorbents for R-SH based on hydrogen-bonding interaction and is helpful to enrich the application of the hydrogen-bonding interaction.

Cytological Analysis and Fine Mapping of paa1 (Post-meiosis Abnormal Anther 1) Mutant with Abnormal Tapetum and Microspore Development.

To further understand the molecular mechanism for rice male reproduction, a rice male sterile mutant paa1 was screened from the rice mutant library generated by treatment with 60Coγ-rays. Genetic analysis revealed that paa1 is controlled by a single- recessive nuclear gene, and the anthers of the paa1 mutant were smaller than those of WT plants with a white color. Histological analysis demonstrated that the anthers of the paa1 mutant began to turn abnormal at the microspore stage after meiosis, with abnormal degradation of tapetum, deformed Ubisch bodies, and defective pollen exine. TUNEL assay results also confirmed the delay of tapetum PCD in paa1. Map-based cloning was performed for the PAA1 location. As a result, PAA1 was located in a 88-kb region at the end of chromosome 10, which comprises a total of seven candidate genes, and no genes related to anther development have been reported in this region. The results indicate that PAA1 is an essential gene in regulating tapetum development and pollen/microspore formation after rice meiosis.

Vertical distribution of antibiotics and antibiotic resistance genes in a representative municipal solid waste landfill, China.

The vertical distribution of sulfonamides (SAs), tetracyclines (TCs), macrolides (MLs), and their related antibiotic resistance genes (ARGs) were comprehensively investigated and characterized in a representative municipal solid waste (MSW) landfill in China. The total concentrations of target antibiotics in the MSW landfill were SAs > TCs > MLs. The abundances of mexF (10.78 ± 0.65 log10copies/g) and sul genes (9.15 ± 0.54 log10copies/g) were relatively high, while the tet genes (7.19 ± 0.77 log10copies/g) were the lowest. Both the abundance of antibiotics and genes fluctuated with landfill depth, and the ARGs of the same antibiotics were consistent with depth change. Intl1 and sul genes (sul1, sul2) were tightly connected, and a close relationship also existed between tet genes (tetM, tetQ) and MLs resistance genes (ermB, mefA). High-throughput sequencing showed the dominant genera were Sporosarcina (38%) and Thiobacillus (17%) at sampling points A and C, while the microbial community varied with depth increase at point B were Brevundimonas (20%), Sporosarcina (20%), Pseudomonas (24%), Lysobacter (28%), and Thioalkalimicrobium (14%), respectively. Network analysis further visualized the relationship among antibiotics, genes, and microbial communities and the results indicated the non-random connection among them and the possible host of the target gene. Even at 12.0 m below the landfill surface, the pollution of antibiotics resistance was still serious, which posed difficulties for subsequent landfill remediation and pollution control.

MACF1 alleviates aging-related osteoporosis via HES1.

Ageing-related osteoporosis is becoming an emerging threat to human health along with the ageing of human population. The decreased rate of osteogenic differentiation and bone formation is the major cause of ageing-related osteoporosis. Microtubule actin cross-linking factor 1 (MACF1) is an important cytoskeletal factor that promotes osteogenic differentiation and bone formation. However, the relationship between MACF1 expression and ageing-related osteoporosis remains unclear. This study has investigated the expression pattern of MACF1 in bone tissues of ageing-related osteoporosis patients and ageing mice. The study has further elucidated the mechanism of MACF1 promoting bone formation by inhibiting HES1 expression and activity. Moreover, the therapeutic effect of MACF1 on ageing-related osteoporosis and post-menopausal osteoporosis was evaluated through in situ injection of the MACF1 overexpression plasmid. The study supplemented the molecular mechanisms between ageing and bone formation, and provided novel targets and potential therapeutic strategy for ageing-related osteoporosis.

Antagonistic action of Streptomyces pratensis S10 on Fusarium graminearum and its complete genome sequence.

Wheat scab, mainly caused by Fusarium graminearum, can decrease wheat yield and grain quality. Chemical pesticides are currently the main control method but have an inevitable negative consequence on the environment and in food safety. This research studies a promising substitute, Streptomyces pratensis S10, which was isolated from tomato leaf mould and shows a significant inhibition effect on F. graminearum based on antagonism assays. The biocontrol mechanism is studied by enhanced green fluorescent protein labelling, quantitative real-time PCR, the Doskochilova 8 solvents system test and complete genome sequencing. Strain S10 can colonize in the wheat root, control wheat scab and decrease deoxynivalenol (DON) content. The control effects in vitro, planta and the plot experiments were 92.86%, 68.67% and 40.87% to 86.62%, respectively. S10 decreased DON content by inhibiting the mycelium growth and DON synthesis gene expression. The active substances of the S10 secondary metabolites had a high-temperature resistance and 29 putative biosynthetic gene clusters in its genome. The S10 control mechanism is multivariate, which shows potential in controlling wheat scab.

BMAL1 regulation of microglia-mediated neuroinflammation in MPTP-induced Parkinson's disease mouse model.

Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.

Rapid nanowelding of silver nanowires by focused-light-scanning for high-performance flexible transparent electrodes.

Silver nanowires (AgNWs) have been considered as one of the most promising flexible transparent electrodes (FTEs) material for next-generation optoelectronic devices. However, the large contact resistance between AgNWs could deteriorate the conductivity of FTEs. In the present work, high-performance AgNWs FTEs were obtained by means of focused-light-scanning (FLS), which could lead to the large-area, rapid and high-quality welding between AgNWs within a short time, forming the reliable and stable AgNWs network. The results of the optoelectronic tests show that after FLS, the sheet resistance of the AgNWs FTEs sharply decreased from 5113 Ω/sq to 7.7 Ω/sq, with maintaining a high transmittance (∼94%). Finally, a high-performance flexible transparent heater was fabricated by using FLS, showing reach a relatively high temperature in a short response time and rapid response at low input voltage. The findings offer an effective pathway to greatly improve the conductivity of AgNWs FTEs.

Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone.

Piezo channels are mechanosensitive ion channels located in the cell membrane and function as key cellular mechanotransducers for converting mechanical stimuli into electrochemical signals. Emerged as key molecular detectors of mechanical forces, Piezo channels' functions in bone have attracted more and more attention. Here, we summarize the current knowledge of Piezo channels and review the research advances of Piezo channels' function in bone by highlighting Piezo1's role in bone cells, including osteocyte, bone marrow mesenchymal stem cell (BM-MSC), osteoblast, osteoclast, and chondrocyte. Moreover, the role of Piezo channels in bone diseases is summarized.