Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study.

BACKGROUND: The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. METHODS: Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. RESULTS: Compared with "low IPAI" group, offspring with "high IPAI" have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted ß were - 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and - 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among "high IPAI" group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). CONCLUSIONS: Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Activity of the Caged Xanthone Morellic Acid against Vancomycin-Resistant Enterococcus Infection by Targeting the Bacterial Membrane.

Vancomycin-resistant Enterococcus (VRE) is an important nosocomial opportunistic pathogen that is associated with multidrug resistance. Here, we demonstrate that morellic acid inhibits VRE by restoring its sensitivity to vancomycin and ampicillin with low drug resistance and efficient biofilm clearance effects. Morellic acid binds to inner membrane phospholipids, such as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) of VRE, such that the fluidity and proton-motive force (PMF) interfere with the damaged inner membrane, causing intracellular reactive oxygen species (ROS) accumulation and bacterial death. Transcriptional analyses supported this effect on inner membrane-related pathways such as fatty acid biosynthesis and glycerophospholipid metabolism. Moreover, morellic acid significantly eliminated residual bacteria in the spleen, liver, kidneys, and abdominal effusion in mice. Our findings indicate the potential applications of morellic acid as an antibacterial agent or adjuvant for treating VRE infections.

Dang-Gui-Bu-Xue decoction against diabetic nephropathy via modulating the carbonyl compounds metabolic profile and AGEs/RAGE pathway.

BACKGROUND: Dang-Gui-Bu-Xue decoction (DBD) is a traditional Chinese medicine prescription clinically employed for diabetic nephropathy (DN). However, the components and pharmacological mechanisms of DBD against DN remain incompletely understood. PURPOSE: To clarify the beneficial effect of DBD on DN and to explore its nephroprotective effect's probable mechanism and the main components. METHODS: A diabetic mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injections of streptozotocin (STZ, 40 mg‧kg-1). Subsequently, the mice were maintained on a HFD and administered with DBD. The benefits of DBD against DN were comprehensively assessed by monitoring energy and water intake, blood glucose and lipids, renal functions and pathological status. The UPLC-MS/MS was measured to detect chemical constituents in DBD and absorbed components in DBD-treated plasma under physiological and pathological states. Network pharmacology was employed to forecast the probable pathways of DBD intervention in DN, with subsequent validation of these predictions through testing biochemical parameters, anti-glycation and ELISA assays, immunofluorescence, immunohistochemistry, and western blotting. Then, a chemical derivatization method paired with UPLC-MS/MS analysis was performed to detect the carbonyl compounds in renal tissue. Finally, the main components of DBD against DN were screened by anti-glycation and MTT assays. RESULTS: DBD regulated energy and water intakes, glucose and lipid metabolism disorders, renal dysfunction, glomerular filtration rate, renal interstitial glycogen accumulation and fibrosis in HFD/STZ-induced DN mice. A total of 129 distinct chemical constituents in DBD were characterized, of which 28 were detected in the DBD-treated plasma under a pathological state. The network pharmacological results suggested AGEs/RAGE and its downstream pathway may be a potential pathway for DBD intervention in DN. Further experiments confirmed that DBD reduced renal oxidative stress by modulating the AGEs/RAGE pathway. Moreover, 21 differential carbonyl compounds were detected between normal and DN mice, and DBD significantly modulated 16. Ultimately, seven components were screened out in DBD, which may be the main components of DBD regulating carbonyl compounds metabolic profile and AGEs/RAGE pathway. CONCLUSION: Our findings suggested for the first time that DBD could regulate the carbonyl compounds metabolic profile and AGEs/RAGE signaling pathway to ameliorate DN.

Titanium exposure and gestational diabetes mellitus: associations and potential mediation by perturbation of amino acids in early pregnancy.

BACKGROUND: Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. METHODS: The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. RESULTS: As parameterized in tertiles, titanium showed positive dose-response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. CONCLUSIONS: In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk.

Association between Mixed Heavy Metal Exposure and Arterial Stiffness, with Alkaline Phosphatase Identified as a Mediator.

Elevated arterial stiffness has been associated with exposure to heavy metals such as lead (Pb) and cadmium (Cd). However, the collective impact of multiple metals and the underlying mechanisms are not fully elucidated. The purpose of this study was to assess the combined effects of exposure to nine heavy metals on arterial stiffness and explore whether serum alkaline phosphatase (ALP) acts as a mediator in this relationship. In the retrospective analysis, data from 8,700 participants were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Arterial stiffness was measured by estimated pulse wave velocity (ePWV). The cumulative impact of exposure to multiple metals was examined using adaptive elastic-net, environmental risk score, weighted quantile sum regression, and quantile g-computation. Additionally, mediation analysis was conducted to explore the potential mediating role of serum ALP. We found that combined exposure to multiple metals was consistently associated with elevated ePWV, with Ba, Pb, and Sb exhibiting the greatest contributions. Notably, serum ALP partially mediated the associations between individual (Pb, Sb) and mixed metal exposure with ePWV, with mediation proportions at 10.76% for Pb, 18.22% for Sb, and 11.07% for mixed metal exposure. In conclusion, this study demonstrates a clear association between exposure to heavy metals, either individually or in combination, and heightened arterial stiffness. Furthermore, the findings suggest that serum ALP activity may act as a mediator in these relationships.

A Multifunctional Tactile Sensory System for Robotic Intelligent Identification and Manipulation Perception.

Humans recognize and manipulate objects relying on the multidimensional force features captured by the tactile sense of skin during the manipulation. Since the current sensors integrated in robots cannot support the robots to sense the multiple interaction states between manipulator and objects, achieving human-like perception and analytical capabilities remains a major challenge for service robots. Prompted by the tactile perception involved in robots performing complex tasks, a multimodal tactile sensory system is presented to provide in situ simultaneous sensing for robots when approaching, touching, and manipulating objects. The system comprises a capacitive sensor owning the high sensitivity of 1.11E-2 pF mm-1, a triboelectricity nanogenerator with the fast response speed of 30 ms, and a pressure sensor array capable of 3D force detection. By Combining transfer learning models, which fuses multimodal tactile information to achieve high-precision (up to 95%) recognition of the multi-featured targets such as random hardness and texture information under random sampling conditions, including random grasp force and velocity. This sensory system is expected to enhance the intelligent recognition and behavior-planning capabilities of autonomous robots when performing complex tasks in undefined surrounding environments.

Characterizing properties and environmental behaviors of organic matter in sludge using liquid chromatography organic carbon detection and organic nitrogen detection: A mini-review.

The presence of organic matter in sludge plays a significant role in sludge dewatering, anaerobic sludge digestion, resource (i.e., protein) recovery and pollutants removal (i.e., heavy metals) from sludge, as well as post-application of sludge liquid and solid digestate. This study summarized the current knowledge on using liquid chromatography organic carbon detection and organic nitrogen detection (LC-OCD-OND) for characterization and quantification of organic matter in sludge samples related with sludge treatment processes by fractionating organic matter into biopolymers, building blocks, humic substances, low molecular weight (LMW) acids, low LMW neutrals, and inorganic colloids. In addition, the fate, interaction, removal, and degradation of these fractions in different sludge treatment processes were summarized. A standardized extraction procedure for organic components in different extracellular polymeric substances (EPS) layers prior to the LC-OCD-OND analysis is highly recommended for future studies. The analysis of humic substances using the LC-OCD-OND analysis in sludge samples should be carefully conducted. In conclusion, this study not only provides a theoretical foundation and technical guidance for future experiments and practices in characterizing sludge organic matter using LC-OCD-OND, but also serves as a valuable resource for consulting engineers and other professionals involved in sludge treatment.

Exploring the impact of microfluidic chip structure on the efficacy of three-dimensional tumor microspheres cultivation.

Three-dimensional (3D) tumor microspheres can simulate the interaction and growth dynamics of tumor cells, and have been used as a new in vitro model for drug screening and tumor biology related research. The scaffold-free culture of 3D tumor microspheres on microfluidic chips has many advantages, including low cost, high throughput, convenience and flexibility. However, it is still unclear how various factors, such as chip structure, influence the culture effect of tumor microspheres. The lack of standardized evaluation and characterization of the culture effect hinders the further optimization and development of chip function. This study presents numerical simulations of multiple parts or processes of the proposed 3D culture chips with two different structural parameters based on computational fluid dynamics (CFD) methods. An evaluation system for tumor microspheres was established. The prediction of the CFD simulation was consistent with the culture results of the chips, reflecting the important role of the structural parameters of the microtrap in the formation of uniform tumor microspheres. Furthermore, the velocity of cell suspension also had a significant impact on the retention of tumor cells. Additionally, the drug screening results of tumor microspheres indicated that tumor microspheres exhibit greater drug resistance, which may be attributed to their size. These results offer valuable insights into the factors that influence the characteristics of tumor microspheres. This research provides a reference and direction for the optimal design and functional evaluation of scaffold-free 3D culture chips, and holds promise for promoting the development of novel drug research platforms.

The interplay between persistent pathogen infections with tumor microenvironment and immunotherapy in cancer.

BACKGROUND: Chronic infections by pathogenic microorganisms play a significant role in cancer development, disrupting the body's immune system and microenvironment. This interference impairs the body's ability to eliminate these microorganisms promptly, allowing them to persist by evading immune defenses. AIMS: This study aimed to explore how chronic pathogenic infections influence the immune microenvironment, impacting tumorigenesis, cancer progression, and treatment strategies. Additionally, it seeks to investigate the effects of these infections on specific immune checkpoints and identify potential targets for immunotherapy. METHODS: We conducted searches, readings, and detailed analyses of key terms in databases like PubMed and Web of Science to evaluate the impact of chronic infections by pathogenic microorganisms on the immune microenvironment. RESULTS: Our analysis demonstrates a significant association between persistent chronic infections by pathogenic microorganisms and tumorigenesis. Notable impacts on the immune microenvironment include changes in immune cell function and the regulation of immune checkpoints, offering insights into potential targets for cancer immunotherapy. DISCUSSION: This study highlights the complex relationship between chronic infections and cancer development, presenting new opportunities for cancer immunotherapy by understanding their effects on the immune microenvironment. The influence of these infections on immune checkpoints emphasizes the crucial role of the immune system in cancer treatment. CONCLUSION: Chronic infections by pathogenic microorganisms greatly affect the immune microenvironment, tumorigenesis, and cancer treatment. Unraveling the underlying mechanisms can unveil potential targets for immunotherapy, improving our comprehension of the immune response to cancer and potentially leading to more effective cancer treatments in the future.

Spatial regulation of NMN supplementation on brain lipid metabolism upon subacute and sub-chronic PM exposure in C57BL/6 mice.

BACKGROUND: Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. RESULTS: In this study, we examine the effect of ß-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. CONCLUSIONS: This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Evaluation of inhibition effect and interaction mechanism of antiviral drugs on main protease of novel coronavirus: Molecular docking and molecular dynamics studies.

The outbreak of pneumonia caused by the novel coronavirus (SARS-CoV-2) has presented a challenge to public health. The identification and development of effective antiviral drugs is essential. The main protease (3CLpro) plays an important role in the viral replication of SARS-CoV-2 and is considered to be an effective therapeutic target. In this study, according to the principle of drug repurposing, a variety of antiviral drugs commonly used were studied by molecular docking and molecular dynamics (MD) simulations to obtain potential inhibitors of main proteases. 24 antiviral drugs were docked with 5 potential action sites of 3CLpro, and the drugs with high binding strength were further simulated by MD and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations. The results showed that the drugs with high flexibility could bind to 3CLpro better than those with low flexibility. The interaction mechanism between antiviral drugs and main protease was analyzed in detail by calculating the root mean square displacement (RMSD), root mean square fluctuation (RMSF) and interaction residues properties. The results showed that the six drugs with high flexibility (Remdesivir, Simnotrelvir, Sofosbuvir, Ledipasvir, Indinavir and Raltegravir) had strong binding strength with 3CLpro, and the last four antiviral drugs can be used as potential candidates for main protease inhibitors.

Interactions between fibroblasts and monocyte-derived cells in chronic lung injuries induced by real-ambient particulate matter exposure.

Long-term exposure to fine particulate matter (PM2.5) can lead to chronic lung injury, including inflammation, idiopathic pulmonary fibrosis, and cancer. Mesenchymal cells, such as fibroblasts, myeloid-derived suppressor cells (MDSCs), and interstitial macrophages (IMs), contribute to immune regulation in lung, yet their diversity and functions upon long-term exposure to particulate matter (PM) remain inadequately characterized. In this study, we conducted a 16-week real-ambient PM exposure experiment on C57BL/6 J male mice in Shijiazhuang, China. We used single-cell RNA sequencing to analyze the cellular and molecular changes in lung tissues. Notably, we revealed a significant increase in specific fibroblast (ATX+, Col5a1+Meg3+, universal fibroblasts) and monocyte-derived cell subpopulations (monocytic-MDSCs (M-MDSCs), Lyve1loMHC-Ⅱhi IMs, Lyve1hiMHC-Ⅱlo IMs) that exhibited pro-inflammatory and pro-fibrotic functions. These cell subpopulations engaged in immunosuppressive signaling pathways and interactions with various cytokines, shaping a pulmonary microenvironment similar to those associated with cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). This altered immune environment may promote the development of pulmonary fibrosis caused by PM exposure, underscoring the intricate roles of mesenchymal cells in chronic lung injury and highlighting the cancer-causing potential of PM2.5 exposure.

Potential ecological risk assessment for trace metal(loid)s in soil surrounding coal gangue heaps based on source-oriented.

Coal is the predominant energy source in China, resulting in coal gangue. We used the absolute principal component score multiple linear regression (APCS-MLR) model and the geo-detector method (GDM) for determining the potential ecological risk, apportioning sources, and identifying driving factors for trace metal(loid)s (TMs) in soil surrounding coal gangue heaps. The average contents for the concerned TMs (Cd, Hg, As, Pb, Cr, Cu, Ni, and Zn) in the soil of interest were 0.48, 0.18, 11.0, 36.0, 129, 99.2, 68.3 and 141 mg/kg, respectively. Potential ecological risk indicated that the soil was primarily within the "Moderate risk" level, and Cd was the primary pollutant. "The number of coal gangue units" and "the distance between the sampling point and the coal gangue heap" were the key driving factors included in the geo-detector method. Combining APCS-MLR model and GDM, the source apportionment was enhanced in terms of accuracy and reliability. Natural, mining, and unrecognized sources contributed 41.1 %, 39.2 %, and 19.7 % of the TM distribution, respectively. Considering the relationship between TMs, their sources, and corresponding potential ecological risks, mining sources (mainly affected by gangue accumulation) presented a primary linkage with Cd, and its contribution to potential ecological risk was the highest, accounting for 58.2 %. Therefore, further research should focus on effectively managing and controlling the potential ecological risks originating from mining sources and Cd.

Metabolomics and gut microbiota analysis reveal the differential efficacy of areca nut and charred areca nut in treating constipation.

Background: Areca nut (AN) is a traditional Chinese herbal medicine used for centuries to treat gastrointestinal (GI) disorders. Charred AN (CAN) is a processed product of AN with similar therapeutic effects. This study aimed to investigate the therapeutic mechanisms of AN and CAN for constipation via metabolomics and gut microbiota analysis. Methods: In this study, the rats were randomly divided into 5 groups (n = 6): control, constipation model, positive drug, AN treatment, and CAN treatment groups. Constipation was induced by intragastric administration of loperamide hydrochloride, followed by 14-day treatment with mosapride, AN, or CAN. The efficacy difference between AN and CAN was assessed by evaluating the weight gain, fecal water content, GI transit rate, colonic histopathology, serum levels of GI hormones, gut microbiota, and fecal metabolites. Results: The results demonstrated that both AN and CAN could alleviate loperamide-induced constipation. Furthermore, they significantly elevated the serum levels of motilin, vasoactive intestinal peptide, substance P, and acetylcholine. 16S rRNA analysis revealed that AN regulated the relative abundance of Bacillus, UCG-005, norank_f_Muribaculaceae, Candidatus_Saccharimonas, and Ruminococcus, whereas CAN modulate the relative abundance of Lactobacillus, Bacillus, norank_f_Muribaculaceae, Ruminococcus, unclassified_f_Oscillospiraceae, and unclassified_f_Prevotellaceae. Moreover, the metabolic profile of AN- and CAN-treated rats was also different, where AN treatment involved pathways of citrate cycle (TCA) and tyrosine, alanine, aspartate, and glutamate metabolisms. Whereas CAN treatment involved pathways of steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolisms. Spearman correlation analysis indicated a close relationship between gut microbiota and fecal metabolites. Conclusion: In summary, this study revealed that AN may protect GI mucosa, enhance GI motility, and alleviate constipation symptoms by regulating the relative abundance of specific gut microbiota (Bacillus, UCG-005, norank_f_Muribaculaceae, Candidatus_Saccharimonas, Ruminococcus) as well as citrate cycle or tyrosine, alanine, aspartate, and glutamate metabolic pathways. Furthermore, CAN was observed to promote gastric emptying and intestinal propulsion, thereby alleviating constipation, by modulating the relative abundance of specific gut microbiota (Lactobacillus, Bacillus, norank_f_Muribaculaceae, Ruminococcus, unclassified_f_Oscillospiraceae, unclassified_f_Prevotellaceae) as well as steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolic pathways.

Correlative Effects of Carbon Support Structures and Surface Properties on ORR Catalytic Activities of Loaded Catalysts.

As a complex three-phase heterogeneous catalyst, the oxygen reduction reaction (ORR) catalyst activity is determined by the interfacial and surface structures and chemical state of the catalyst support. As a typical biomass carbon-based support, rice husk-based porous carbon (RHPC) has natural unique hierarchical porous structures, which easily regulate the microstructure and surface properties. This study explored the correlative effects of RHPC structure and surface properties on ORR catalytic activity through the typical modification methods, namely, alkali etching, high temperature, oxidation, and ball milling. The various factors for the joint effects are defined as the specific surface area, oxygen-containing functional groups, graphite edge defects, resistivity, and contact angle. The analysis of such joint influences is difficult to quantitatively evaluate due to the large number of experimental factors and small sample sizes. Partial least-squares (PLS) can better deal with such problems. Therefore, a PLS regression model was established to evaluate the relative weight of each factor on the catalytic activity for the RHPC-based support catalysts. The results reveal that the regression coefficients of four factors yield similar magnitude for the effect of the half-wave potential (E1/2). However, graphite edge defects had a more significant impact on the limiting diffusion current density (J) and electron transfer number (n). Furthermore, an optimal support named BM-RHPC-3 was prepared with more defects and oxygen-containing functional groups, which prepared Fe-NS/BM-RHPC-3 presenting the best ORR catalytic activity (E1/2 = 0.880 V, J of 5.15 mA cm-2), superior to Pt/C (E1/2 = 0.844 V, J of 4.99 mA cm-2). The statistical regression model is validated with a relative error of less than 5% between predicted and true values for analyzing RHPC-based ORR catalysts' catalytic performance. It shows the feasibility of experiment-informed learning for data-driven material discovery and design.

Spin-dependent Seebeck effect in zigzag-edge antimonene nanoribbons.

In spin caloritronics, the spin-dependent Seebeck effect provides a method for significantly reducing Joule heating and achieving ultra-high integration density. Here, we investigate the electronic transport and spin thermoelectric properties of zigzag-edge antimonene nanoribbons (ZANRs) with different widths using first-principles calculations. The results show that the ZANRs exhibit an excellent spin-dependent Seebeck effect. By modulating the ribbon width, thermal spin devices could generate large spin-dependent currents with small charge currents, making them ideal for spintronic applications with low power consumption and high efficiency. Interestingly, the spin current of ZANRs goes up oscillatingly as the ribbon width decreases, which is beneficial for device miniaturization. Our findings may offer insights into the development of spin caloritronic devices.

Exosomes derived from hypoxic alveolar epithelial cells promote the phenotypic transformation of pulmonary artery smooth muscle cells via the Rap1 pathway.

Background: Hypoxic pulmonary hypertension (HPH) is one of the important pathophysiological changes in chronic pulmonary heart disease. Hypoxia promotes the phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs). Extracellular exosomes regulate vascular smooth muscle cell (VSMC) phenotypic switch. Aim: Given the importance of exosomes and alveolar epithelial cells (AECs) in HPH, the present study aimed to address the issue of whether AEC-derived exosomes promote HPH by triggering PASMC phenotypic switch. Methods: Cell Counting Kit-8 (CCK-8), TRITC-phalloidin staining, and Western blotting were used to examine the effects of AEC-derived exosomes on cell proliferation, intracellular actin backbone distribution, and expression of phenotypic marker proteins in PASMCs. Transcriptomics sequencing was used to analyze differentially expressed genes (DEGs) between groups. Results: Hypoxia-induced exosomes (H-exos) could promote the proliferation of PASMCs, cause the reduction of cellular actin microfilaments, promote the expression of synthetic marker proteins (ELN and OPN), reduce the expression of contractile phenotypic marker proteins (SM22-α and α-SMA), and induce the phenotypic transformation of PASMCs. Transcriptomics sequencing analysis showed that the Rap1 signaling pathway was involved in the phenotypic transformation of PASMCs induced by H-exos. Conclusion: The present study identified that hypoxia-induced AEC-derived exosomes promote the phenotypic transformation of PASMCs and its mechanism is related to the Rap1 signaling pathway.

Co-catalysis strategy for low-oxidant-consumption Fenton-like chemistry: From theoretical understandings to practical applications and future guiding strategies.

Recently, great effects have been made for the co-catalysis strategy to solve the bottlenecks of Fenton system. A series of co-catalysis strategies using various inorganic metal co-catalysts and organic co-catalysts have been developed in various oxidant (i.e., hydrogen peroxide (H2O2) and persulfate) systems with significantly promotion of catalytic performances and lower oxidant consumption (only 5-10 % of conventional Fenton/Fenton-like systems). However, the developments of these co-catalysis strategies from theoretical understandings to practical applications and future guiding strategies were overlooked, which was an essential problem that must be considered for the future scale-up applications of co-catalysis systems. In this paper, these co-catalysis strategies with low-oxidant-consumption characteristics have been reviewed by the comparison of their co-catalysis mechanisms, as well as their advantages and disadvantages. We also discussed the recent developments of amplifying devices based on the co-catalysis systems. The scale-up performances of co-catalysis strategies based on these amplifying devices have also been assessed. In addition, future guiding strategies for the development of co-catalysis strategy with low-oxidant-consumption characteristics have also been first time outlined by the combination of the technical-economic analysis (TEA), life cycle assessment (LCA) and machine learning (ML). Finally, the paper systematically discusses the development opportunities, technical bottlenecks and future development directions of co-catalysis strategies with the prospect of large-scale applications. Basically, this work provides a systematic review on co-catalysis strategy with low-oxidant-consumption characteristic from theoretical understandings to practical applications and future guiding strategies.

DDIT3 switches osteogenic potential of BMP9 to lipogenic by attenuating Wnt/ß-catenin signaling via up-regulating DKK1 in mesenchymal stem cells.

Bone morphogenetic protein 9 (BMP9) functions as a potent inducer of osteogenic differentiation in mesenchymal stem cells (MSCs), holding promise for bone tissue engineering. However, BMP9 also concurrently triggers lipogenic differentiation in MSCs, potentially compromising its osteogenic potential. In this study, we explored the role of DNA damage inducible transcript 3 (DDIT3) in regulating the balance between BMP9-induced osteogenic and lipogenic differentiation in MSCs. Utilizing techniques such as PCR, Western blot, histochemical staining, and in vivo experiments, we analyzed the osteogenic and lipogenic markers induced by BMP9 and delved into the underlying molecular mechanism. We found a significant upregulation of DDIT3 in C3H10T1/2 cells treated with BMP9. This upregulation led to a reduction in BMP9-induced osteogenic markers but an enhancement in lipogenic markers. Conversely, knocking down DDIT3 produced the opposite effects. Furthermore, BMP9-induced bone formation was decreased in the presence of DDIT3, but adipocyte formation was increased. Further investigations demonstrated that BMP9 increased the phosphorylation level of GSK-3ß and promoted nuclear translocation of ß-catenin, both of which were suppressed by DDIT3. Moreover, DDIT3 decreased the total ß-catenin protein level while BMP9 increased the DKK1 protein level, which was further enhanced by DDIT3. Notably, knocking down DKK1 partially reversed the effect of DDIT3 on reducing BMP9-induced osteogenic markers and increasing lipogenic markers. Our findings indicated that DDIT3 enhances lipogenic differentiation by diminishing BMP9's osteogenic potential, possibly through inhibiting Wnt/ß-catenin signaling via DKK1 upregulation in MSCs.

Multitrait Genetic Analysis Identifies Novel Pleiotropic Loci for Depression and Schizophrenia in East Asians.

BACKGROUND AND HYPOTHESIS: While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited. STUDY DESIGN: To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We utilized the most comprehensive dataset available for East Asians and quantified the genetic overlap between depression, SCZ, and their related traits via a multitrait genome-wide association study. Global and local genetic correlations were estimated by LDSC and ρ-HESS. Pleiotropic loci were identified by the multitrait analysis of GWAS (MTAG). STUDY RESULTS: Besides the significant correlation between depression and SCZ, our analysis revealed genetic correlations between depression and obesity-related traits, such as weight, BMI, T2D, and HDL. In SCZ, significant correlations were detected with HDL, heart diseases and use of various medications. Conventional meta-analysis of depression and SCZ identified a novel locus at 1q25.2 in East Asians. Further multitrait analysis of depression, SCZ and related traits identified ten novel pleiotropic loci for depression, and four for SCZ. CONCLUSIONS: Our findings demonstrate shared genetic underpinnings between depression and SCZ in East Asians, as well as their associated traits, providing novel candidate genes for the identification and prioritization of therapeutic targets specific to this population.