Small extracellular vesicles-derived from 3d cultured human nasal mucosal mesenchymal stem cells during differentiation to dopaminergic progenitors promote neural damage repair via miR-494-3p after manganese exposed mice.

Manganese (Mn) exposure is a common environmental risk factor for Parkinson's disease (PD), with pathogenic mechanisms associated with dopaminergic neuron damage and neuroinflammation. Mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) have emerged as a novel therapeutic approach for neural damage repair. The functional sEVs released from MSCs when they are induced into dopaminergic progenitors may have a better repair effect on neural injury. Therefore, we collected sEVs obtained from primary human nasal mucosal mesenchymal stem cells (hnmMSC-sEVs) or cells in the process of dopaminergic progenitor cell differentiation (da-hnmMSC-sEVs), which were cultured in a 3D dynamic system, and observed their repair effects and mechanisms of Mn-induced neural damage by intranasal administration of sEVs. In Mn-exposed mice, sEVs could reach the site of brain injury after intranasal administration, da-hnmMSC enhanced the repair effects of sEVs in neural damage and behavioral competence, as evidenced by restoration of motor dysfunction, enhanced neurogenesis, decreased microglia activation, up-regulation of anti-inflammatory factors, and down-regulation of pro-inflammatory factors. The transcriptomics of hnmMSC-sEVs and da-hnmMSC-sEVs revealed that miRNAs, especially miR-494-3p in sEVs were involved in neuroprotective and anti-inflammatory effects. Overexpression of miR-494-3p in sEVs inhibited Mn-induced inflammation and neural injury, and its repair mechanism might be related to the down-regulation of CMPK2 and NLRP3 in vitro experiments. Thus, intranasal delivery of da-hnmMSC-sEVs is an effective strategy for the treatment of neural injury repair.

Comparison of 1 Versus 2 Doses of Quadrivalent Influenza Vaccine in 3-8-Year-Old Children with Different Immunological States - Jiangsu Province, China, 2021.

What is already known about this topic?: The quadrivalent influenza vaccine (QIV) provides protection against a broader range of influenza strains by including strains of influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. What is added by this report?: This study aimed to assess the immunogenicity and safety of administering a single dose compared to two doses of QIV in children, taking into consideration their previous influenza vaccination history. What are the implications for public health practice?: This study provides evidence supporting the use of a single dose of the QIV in children aged 3-8 years who have previously received two or more doses of influenza vaccine. However, children who have not been previously vaccinated with influenza vaccine should still adhere to the recommended schedule of receiving two doses.

TRPV3 facilitates lipolysis and attenuates diet-induced obesity via activation of the NRF2/FSP1 signaling axis.

Transient receptor potential vanilloid (TRPV) ion channels play a crucial role in various cellular functions by regulating intracellular Ca2+ levels and have been extensively studied in the context of several metabolic diseases. However, the regulatory effects of TRPV3 in obesity and lipolysis are not well understood. In this study, utilizing a TRPV3 gain-of-function mouse model (TRPV3G568V/G568V), we assessed the metabolic phenotype of both TRPV3G568V/G568V mice and their control littermates, which were randomly assigned to either a 12-week high-fat diet or a control diet. We investigated the potential mechanisms underlying the role of TRPV3 in restraining obesity and promoting lipolysis both in vivo and in vitro. Our findings indicate that a high-fat diet led to significant obesity, characterized by increased epididymal and inguinal white adipose tissue weight and higher fat mass. However, the gain-of-function mutation in TRPV3 appeared to counteract these adverse effects by enhancing lipolysis in visceral fat through the upregulation of the major lipolytic enzyme, adipocyte triglyceride lipase (ATGL). In vitro experiments using carvacrol, a TRPV3 agonist, demonstrated the promotion of lipolysis and antioxidation in 3T3-L1 adipocytes after TRPV3 activation. Notably, carvacrol failed to stimulate Ca2+ influx, lipolysis, and antioxidation in 3T3-L1 adipocytes treated with BAPTA-AM, a cell-permeable calcium chelator. Our results revealed that TRPV3 activation induced the action of transcriptional factor nuclear factor erythroid 2-related factor 2 (NRF2), resulting in increased expression of ferroptosis suppressor protein 1 (FSP1) and superoxide dismutase2 (SOD2). Moreover, the inhibition of NRF2 impeded carvacrol-induced lipolysis and antioxidation in 3T3-L1 adipocytes, with downregulation of ATGL, FSP1, and SOD2. In summary, our study suggests that TRPV3 promotes visceral fat lipolysis and inhibits diet-induced obesity through the activation of the NRF2/FSP1 signaling axis. We propose that TRPV3 may be a potential therapeutic target in the treatment of obesity.

Electrochemical filtration for drinking water purification: A review on membrane materials, mechanisms and roles.

Electrochemical filtration can not only enrich low concentrations of pollutants but also produce reactive oxygen species to interact with toxic pollutants with the assistance of a power supply, making it an effective strategy for drinking water purification. In addition, the application of electrochemical filtration facilitates the reduction of pretreatment procedures and the use of chemicals, which has outstanding potential for maximizing process simplicity and reducing operating costs, enabling the production of safe drinking water in smaller installations. In recent years, the research on electrochemical filtration has gradually increased, but there has been a lack of attention on its application in the removal of low concentrations of pollutants from low conductivity water. In this review, membrane substrates and electrocatalysts used to improve the performance of electrochemical membranes are briefly summarized. Meanwhile, the application prospects of emerging single-atom catalysts in electrochemical filtration are also presented. Thereafter, several electrochemical advanced oxidation processes coupled with membrane filtration are described, and the related working mechanisms and their advantages and shortcomings used in drinking water purification are illustrated. Finally, the roles of electrochemical filtration in drinking water purification are presented, and the main problems and future perspectives of electrochemical filtration in the removal of low concentration pollutants are discussed.

Extracellular Matrix-Trapped Bioinspired Lipoprotein Prolongs Tumor Retention to Potentiate Antitumor Immunity.

The immunomodulatory effects of many therapeutic agents are significantly challenged by their insufficient delivery efficiency and short retention time in tumors. Regarding the distinctively upregulated fibronectin (FN1) and tenascin C (TNC) in tumor stroma, herein a protease-activated FN1 and/or TNC binding peptide (FTF) is designed and an extracellular matrix (ECM)-trapped bioinspired lipoprotein (BL) (FTF-BL-CP) is proposed that can be preferentially captured by the TNC and/or FN1 for tumor retention, and then be responsively dissociated from the matrix to potentiate the antitumor immunity. The FTF-BL-CP treatment produces a 6.96-, 9.24-, 6.72-, 7.32-, and 6.73-fold increase of CD3+CD8+ T cells and their interferon-γ-, granzyme B-, perforin-, and Ki67-expressing subtypes versus the negative control, thereby profoundly eliciting the antitumor immunity. In orthotopic and lung metastatic breast cancer models, FTF-BL-CP produces notable therapeutic benefits of retarding tumor growth, extending survivals, and inhibiting lung metastasis. Therefore, this ECM-trapping strategy provides an encouraging possibility of prolonging tumor retention to potentiate the antitumor immunity for anticancer immunotherapy.

Single-cell transcriptomics analysis of zebrafish brain reveals adverse effects of manganese on neurogenesis.

Manganese (Mn) is considered as an important environmental risk factor for Parkinson's disease. Excessive exposure to Mn can damage various neural cells and affect the neurogenesis, resulting in neurological dysfunction. However, the specific mechanisms of Mn exposure affecting neurogenesis have not been well understood, including compositional changes and heterogeneity of various neural cells. Zebrafish have been successfully used as a neurotoxicity model due to its homology with mammals in several key regions of the brain, as well as its advantages such as small size. We performed single-cell RNA sequencing of zebrafish brains from normal and Mn-exposed groups. Our results suggested that low levels of Mn exposure activated neurogenesis in the zebrafish brain, including promoting the proliferation of neural progenitor cells and differentiation to newborn neurons and oligodendrocytes, while high levels of Mn exposure inhibited neurogenesis and neural function. Mn could affect neurogenesis through specific molecular pathways. In addition, Mn regulated intercellular communication and affected cellular communication in neural cells through specific signaling pathways. Taken together, our study elucidates the cellular composition of the zebrafish brain and adds to the understanding of the mechanisms involved in Mn-induced neurogenesis damage.

The transporter PHO84/NtPT1 is a target of aluminum to affect phosphorus absorption in Saccharomyces cerevisiae and Nicotiana tabacum L.

The molecular mechanism of aluminum toxicity in biological systems is not completely understood. Saccharomyces cerevisiae is one of the most used model organisms in the study of environmental metal toxicity. Using an unbiased metallomic approach in yeast, we found that aluminum treatment caused phosphorus deprivation, and the lack of phosphorus increased as the pH of the environment decreased compared to the control strain. By screening the phosphate signaling and response pathway (PHO pathway) in yeast with the synthetic lethality of a new phosphorus-restricted aluminum-sensitive gene, we observed that pho84Δ mutation conferred severe growth defect to aluminum under low-phosphorus conditions, and the addition of phosphate alleviated this sensitivity. Subsequently, the data showed that PHO84 determined the intracellular aluminum-induced phosphorus deficiency, and the expression of PHO84 was positively correlated with aluminum stress, which was mediated by phosphorus through the coordinated regulation of PHO4/PHO2. Moreover, aluminum reduced phosphorus absorption and inhibited tobacco plant growth in acidic media. In addition, the high-affinity phosphate transporter NtPT1 in tobacco exhibited similar effects to PHO84, and overexpression of NtPT1 conferred aluminum resistance in yeast cells. Taken together, positive feedback regulation of the PHO pathway centered on the high-affinity phosphate transporters is a highly conservative mechanism in response to aluminum toxicity. The results may provide a basis for aluminum-resistant microorganisms or plant engineering and acidic soil treatment.

Glutamine supplementation reverses manganese neurotoxicity by eliciting the mitochondrial unfolded protein response.

Excessive exposure to manganese (Mn) can cause neurological abnormalities, but the mechanism of Mn neurotoxicity remains unclear. Previous studies have shown that abnormal mitochondrial metabolism is a crucial mechanism underlying Mn neurotoxicity. Therefore, improving neurometabolic in neuronal mitochondria may be a potential therapy for Mn neurotoxicity. Here, single-cell sequencing revealed that Mn affected mitochondrial neurometabolic pathways and unfolded protein response in zebrafish dopaminergic neurons. Metabolomic analysis indicated that Mn inhibited the glutathione metabolic pathway in human neuroblastoma (SH-SY5Y) cells. Mechanistically, Mn exposure inhibited glutathione (GSH) and mitochondrial unfolded protein response (UPRmt). Furthermore, supplementation with glutamine (Gln) can effectively increase the concentration of GSH and triggered UPRmt which can alleviate mitochondrial dysfunction and counteract the neurotoxicity of Mn. Our findings highlight that UPRmt is involved in Mn-induced neurotoxicity and glutathione metabolic pathway affects UPRmt to reverse Mn neurotoxicity. In addition, Gln supplementation may have potential therapeutic benefits for Mn-related neurological disorders.

Accumulative Rolling Mg/PLLA Composite Membrane with Lamellar Heterostructure for Enhanced Bacteria Inhibition and Rapid Bone Regeneration.

Developing composite materials with optimized mechanics, degradation, and bioactivity for bone regeneration has long been a crucial mission. Herein, a multifunctional Mg/Poly-l-lactic acid (Mg/PLLA) composite membrane based on the "materials plain" concept through the accumulative rolling (AR) method is proposed. Results show that at a rolling ratio of 75%, the comprehensive mechanical properties of the membrane in the rolling direction are self-reinforced significantly (elongation at break ≈53.2%, tensile strength ≈104.0 MPa, Young's modulus ≈2.13 GPa). This enhancement is attributed to the directional arrangement and increased crystallization of PLLA molecular chains, as demonstrated by SAXS and DSC results. Furthermore, the AR composite membrane presents a lamellar heterostructure, which not only avoids the accumulation of Mg microparticles (MgMPs) but also regulates the degradation rate. Through the contribution of bioactive MgMPs and their photothermal effect synergistically, the membrane effectively eliminates bacterial infection and accelerates vascularized bone regeneration both in vitro and in vivo. Notably, the membrane exhibits outstanding rat skull bone regeneration performance in only 4 weeks, surpassing most literature reports. In short, this work develops a composite membrane with a "one stone, four birds" effect, opening an efficient avenue toward high-performance orthopedic materials.

Optimal shapes of disk assembly in saturated random packings.

Particle morphology is one of the most significant factors influencing the packing structures of granular materials. With certain targeted properties or optimization criteria, inverse packing problems have drawn extensive attention in terms of their adaptability to many material design tasks. An important question hard to answer is which particle shape, especially within given shape families, forms the densest (loosest) random packing? In this paper, we address this issue for the disk assembly model in two dimensions with an infinite variety of shapes, which are simulated in the random sequential adsorption process to suppress crystallization. Via a unique shape representation method, particle shapes are transformed into genotype sequences in the continuous shape space where we utilize the genetic algorithm as an efficient shape optimizer. Specifically, we consider three representative species of disk assembly, i.e., congruent tangent disks, incongruent tangent disks, and congruent overlapping disks, and carry out shape optimization on their packing densities in the saturated random state. We numerically search optimal shapes in the three species with a variable number of constituent disks which yield the maximal and minimal packing densities. We obtain an isosceles circulo-triangle and an unclosed ring for the maximal and minimal packing density in saturated random packings, respectively. The perfect sno-cone and isosceles circulo-triangle are also specifically investigated which give remarkably high packing densities of around 0.6, much denser than those of ellipses. This study is beneficial for guiding the design of particle shapes as well as the inverse design of granular materials.

Enzymatic response and antibiotic resistance gene regulation by microbial fuel cells to resist sulfamethoxazole.

Microbial fuel cells (MFCs) are a promising and sustainable technology which can generate electricity and treat antibiotic wastewater simultaneously. However, the antibiotic resistance genes (ARGs) induced by antibiotics in MFCs increase risks to ecosystems and human health. In this study, the activities of enzymes and regulation genes related to ARGs in MFCs spiked with sulfamethoxazole (SMX) were evaluated to explore the induction mechanism of ARGs. Under lower doses of SMX (10 mg/L and 20 mg/L SMX in this study), microorganisms tend to up regulate catalase and RpoS regulon to induce sul1, sul3 and intI1. The microorganisms exposed to higher doses of SMX (30 mg/L and 40 mg/L SMX in this study) tend to up regulate superoxide dismutase and SOS response to generate sul2 and sulA. Moreover, the exposure concentrations of SMX had no significant effect on the electricity production of MFCs. This work suggested that the ARGs in MFCs might be inhibited by affecting enzymatic activities and regulatory genes according to the antibiotic concentration without affecting the electricity production.

A Novel Ionospheric Disturbance Index to Evaluate the Global Effect on BeiDou Navigation Satellite System Signal Caused by the Moderate Geomagnetic Storm on May 12, 2021.

In this paper, we propose a new method to quantitatively evaluate the quality of the carrier phase observation signals of the BeiDou Navigation Satellite System (BDS) during weak and moderate geomagnetic storms. We take a moderate geomagnetic storm that occurred on 12 May 2021 during the 25th solar cycle as an example. The results show that the newly defined PAS (Percentage of Affected Satellites) index shows significant anomaly changes during the moderate geomagnetic storm. Its variation trend has good correlations with the geomagnetic storm Kp index and Dst index. The anomaly stations are mainly distributed in the equatorial region and auroral region in the northern and southern hemispheres. The proposed PAS index has a good indication for both BDS2 and BDS3 satellites. We further validated this index by calculating the Precise Point Position (PPP) positioning error. We found that the anomaly period of PAS has strong consistency with the abnormal period of PPP positioning accuracy. This study could provide methodological support for the evaluation of the signal quality and analysis of positioning accuracy for the BeiDou satellite navigation system under different space weather conditions.

Multi-omics analysis reveals Mn exposure affects ferroptosis pathway in zebrafish brain.

Manganese (Mn) accumulates in the central nervous system and can cause neurotoxicity, but the mechanisms of Mn-induced neurotoxicity remain unclear. We performed single-cell RNA sequencing (scRNA-seq) of zebrafish brain after Mn exposure and identified 10 cell types by marker genes: cholinergic neurons, dopaminergic (DA) neurons, glutaminergic neurons, GABAergic neurons, neuronal precursors, other neurons, microglia, oligodendrocyte, radial glia, and undefined cells. Each cell type has its distinct transcriptome profile. Pseudotime analysis revealed that DA neurons had a critical role in Mn-induced neurological damage. Combined with metabolomic data, chronic Mn exposure significantly impaired amino acid and lipid metabolic processes in the brain. Furthermore, we found that Mn exposure disrupted the ferroptosis signaling pathway in the DA neurons in zebrafish. Overall, our study employed joint analysis of multi-omics and revealed ferroptosis signaling pathway is a novel potential mechanism of Mn neurotoxicity.

Associations between multiple heavy metals exposure and neural damage biomarkers in welders: A cross-sectional study.

BACKGROUND: Both occupational and environmental exposure to heavy metals are associated with various neurodegenerative diseases. However, limited evidence is available on the potential effects of exposure to metallic mixtures and neural damage. OBJECTIVES: This study aimed to evaluate the association between metal mixtures in urine and neural damage biomarkers in welders. METHODS: In this cross-sectional study, a total of 186 workers were recruited from steel mills. Twenty-three metals in urine were measured by inductively coupled plasma mass spectrometry. Serum neural damage biomarkers, including neurofilament light chain (NfL), sphingosine-1-phosphate (S1P), prolactin (PRL), and dopamine (DA) were detected using enzyme-linked immunosorbent assay kits. Multivariable linear regression, Bayesian kernel machine regression (BKMR), and Quantile g-computation (QG-C) were employed to estimate the association between metals exposure and neural damage biomarkers. RESULTS: Inverted u-shaped associations of nickel with NfL, S1P, and DA were observed in the BKMR model. A non-linear relationship was also found between Fe and PRL. Urinary cobalt was positively associated with serum PRL and had the strongest positive weights in the QG-C model. Urinary lead was associated with higher serum S1P levels. We also found the interaction among nickel, zinc, arsenic, strontium, iron, and lead with the neural damage biomarkers. CONCLUSION: This study provides new evidence of a direct association between metal mixture exposure and the serum biomarkers of neural damage. Several metals Ni, Co, Pb, Sr, As and Fe, may have adverse effects on the nervous system, while Zn may have neuroprotective effects.

Sustainable conversion of antibiotic wastewater using microbial fuel cells: Energy harvesting and resistance mechanism analysis.

In this study, tetracycline (TC) can be degraded in microbial fuel cells (MFCs) rapidly and efficiently for the synergistic effect of microbial metabolism and electrical stimulation. Different TC concentrations had different effects on the bioelectric performance of MFCs. Among them, 10 mg/L TC promoted the bioelectric properties of MFCs, the maximum power density reached 1744.4 ± 74.9 mW/cm2. In addition, we demonstrated that Geobacter and Chryseobacterium were the dominant species in the anode biofilm, while Azoarcus and Pseudomonas were the prominent species in the effluent, and the initial TC concentration affected the microbial community composition. Furthermore, the addition of TC increased the relative abundance of aadA3, sul1, adeF, cmlA, and tetC in reactors, indicating that a single antibiotic could promote the expression of self-related resistance as well as the expression of other ARGs. Moreover, the presence of TC can increase the relative content of mobile genetic elements (MGEs) and greatly increase the risk of antibiotic resistance genes (ARGs) spreading. Meanwhile, network analysis revealed that some microorganisms (such as Acidovorax caeni, Geobacter soil, and Pseudomonas thermotolerans) and MGEs may be potential hosts for multiple ARGs.

[Distribution Characteristics and the Influencing Factors of High Altitude Deterioration in People Working in Tibet]. / è¥¿è—è‡ªæ²»åŒºåœ¨èŒèŒå·¥é«˜åŽŸè¡°é€€ç—‡çš„åˆ†å¸ƒç‰¹å¾åŠå½±å“å› ç´ .

Objective: To comprehensively investigate and analyze the distribution characteristics of high altitude deterioration (HADT) among people working in 7 cities of Tibet Autonomous Region, to examine the relevant influencing factors, and to provide baseline survey data for further research on HADT. Methods: A self-designed questionnaire was used to conduct a self-administered survey among employees in seven prefectures or cities (Lhasa City, Qamdo City, Shigatse City, Nyingchi City, Shannan City, Naqu City, and Ngari Prefecture) in Tibet. The respondents were selected through random cluster sampling. The survey covered 21 symptoms involving 4 systems of the human body, including the respiratory, nervous, circulatory, and digestive systems. The distributive characteristics of HADT (as manifested by maladaptation to high altitude) were described and Spearman's correlation was used to examine the influencing factors of maladaptation to high altitude. Results: A total of 3 901 respondents were included in the sample analyzed in the study, including 2 107 (54%) native Tibetans and 1 794 (46%) immigrant Han people. There were 1 994 males (51%) and 1 907 females (49%). Their age ranged from 20 to 57 years, averaging (34.45±8.11) years. The subjects lived at a high altitude for a duration of 0.5 to 54 years, averaging (19.51±13.84) years. The overall rates of maladaptation for the 21 symptoms among native Tibetans and immigrant Han people were 60.10% (26 578/44 247) and 73.20% (27 565/37 674), respectively. The maladaptation rates of the native Tibetan population for the respiratory, nervous, circulatory, and digestive systems of the human body were all lower than those of the immigrant Han population (P<0.001). There were no significant differences in the maladaptation rates of employees from different regions of Tibet (66.21% for Ngari Prefecture, 65.02% for Qamdo City, 66.67% for Lhasa City, 62.29% for Shigatse City, 65.03% for Shannan City, 64.42% for Nyingchi City, and 61.65% for Naqu City). The type of high-altitude residents (i.e., being native Tibetan or immigrant Han) was the main influencing factor for high-altitude maladaptation of the respiratory, nervous, circulatory, and digestive systems (P<0.001). According to the findings of the correlation analysis, age, type of high-altitude residents, and the duration of residence at a high altitude were associated with high-altitude maladaptation of the respiratory system, while type of high-altitude residents was the only factor associated with maladaptation of the nervous system, circulatory system, and digestive systems. Age and duration of living at at high altitude had significant effect on self-perceived dyspnea, a type of maladaptation of the respiratory system (P<0.001). Duration of high-altitude residence had significant effect on cyanotic lips or redness in the cheeks, a type of maladaptation of the circulatory system, and self-perceived loss of appetite, a type of maladaptation of the digestive system (P<0.05). Conclusion: More attention should be given to the HADT among employees of public institutions and enterprises who are living in Tibet Autonomous Region and immigrant Han people, in particular, should pay special attention to the protection of their respiratory, nervous, circulatory, and digestive systems.

Transcriptome Evidence Reveals Mitochondrial Unfolded Protein Response Participate in SH-SY5Y Cells Exposed to Manganese.

BACKGROUND: Overexposure to manganese (Mn) can lead to neurodegenerative damage, resulting in manganism with similar syndromes to Parkinson's disease (PD). However, little is known about changes in transcriptomics induced by the toxicological level of Mn. In this study, we conducted RNA-seq to explore the candidate genes and signaling pathways included by Mn in human SH-SY5Y neuroblastoma cells. METHODS: The differentially expressed genes (DEGs) between the Mn-treated group and the control group were screened, and weighted gene co-expression network analysis (WGCNA) was employed to identify hub genes. Then, pathway enrichment analyses for those candidate genes were performed in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We further validated the concentration- and time-response effects of Mn exposure (0-500 µM, 3-12 h) on mitochondrial unfolded protein response (UPRMT) by real-time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results showed 179 up-regulated differentially expressed genes (DEGs) and 681 down-regulated DEGs after Mn exposure. Based on the intersection of DEGs genes and hub genes, 73 DEGs were related to neurotoxicity. The comprehensive pathway analysis showed Mn had widespread effects on the mitogen-activated protein kinase (MAPK) signaling pathway, unfolded protein response, longevity regulating pathway, inflammatory bowel disease, and mitophagy signaling pathway. After Mn exposure, the expressions of activating transcription factor 3 (ATF3) and C-C motif chemokine ligand 2 (CCL2) increased, while the expressions of C/EBP homologous protein (CHOP), caseinolytic protease P (CLPP), and Lon protease 1 (LONP1) decreased in a concentration- and time-dependent manner. CONCLUSIONS: Overall, our study suggests that UPRMT is a new sight in understanding the mechanism of Mn-induced neurotoxicity.