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1.
J Proteome Res ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39226440

ABSTRACT

This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

2.
Nutrients ; 16(15)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39125294

ABSTRACT

Immunodeficiency can disrupt normal physiological activity and function. In this study, donkey bone collagen peptide (DP) and its iron chelate (DPI) were evaluated their potential as immunomodulators in cyclophosphamide (Cytoxan®, CTX)-induced Balb/c mice. The femoral tissue, lymphocytes, and serum from groups of mice were subjected to hematoxylin and eosin (H&E) staining, methylthiazolyldiphenyl-tetrazolium bromide (MTT) cell proliferation assays, and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, a non-targeted metabolomics analysis based on UPLC-MS/MS and a reverse transcription polymerase chain reaction (RT-qPCR) technology were used to explore the specific metabolic pathways of DPI regulating immunocompromise. The results showed that CTX was able to significantly reduce the proliferative activity of mouse splenic lymphocytes and led to abnormal cytokine expression. After DP and DPI interventions, bone marrow tissue damage was significantly improved. In particular, DPI showed the ability to regulate the levels of immune factors more effectively than Fe2+ and DP. Furthermore, metabolomic analysis in both positive and negative ion modes showed that DPI and DP jointly regulated the levels of 20 plasma differential metabolites, while DPI and Fe2+ jointly regulated 14, and all 3 jointly regulated 10. Fe2+ and DP regulated energy metabolism and pyrimidine metabolism pathways, respectively. In contrast, DPI mainly modulated the purine salvage pathway and the JAK/STAT signaling pathway, which are the key to immune function. Therefore, DPI shows more effective immune regulation than Fe2+ and DP alone, and has good application potential in improving immunosuppression.


Subject(s)
Collagen , Cyclophosphamide , Equidae , Iron Chelating Agents , Mice, Inbred BALB C , Animals , Collagen/metabolism , Iron Chelating Agents/pharmacology , Mice , Cell Proliferation/drug effects , Peptides/pharmacology , Lymphocytes/drug effects , Lymphocytes/metabolism , Immunosuppressive Agents/pharmacology , Metabolomics , Cytokines/metabolism , Male , Bone and Bones/drug effects , Bone and Bones/metabolism , Immunosuppression Therapy
3.
Adv Sci (Weinh) ; 11(31): e2308307, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39166458

ABSTRACT

Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO-induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti-PD-L1/TGF-ß bispecific antibody in inhibiting LLC-derived subcutaneous tumor models. Thus, ALO is first identified as a novel late-stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.


Subject(s)
Autophagosomes , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lysosomes , Quinolizidines , Animals , Mice , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Autophagosomes/metabolism , Autophagosomes/drug effects , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lysosomes/metabolism , Lysosomes/drug effects , Cell Line, Tumor , Quinolizidines/pharmacology , Disease Models, Animal , Vesicular Transport Proteins/metabolism , Vesicular Transport Proteins/genetics , Disease Progression , Cell Proliferation/drug effects , Autophagy/drug effects , Apoptosis/drug effects
4.
IEEE Trans Cybern ; PP2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39159031

ABSTRACT

This study investigates the trajectory tracking problem for stochastic systems and proposes a novel adaptive gain design to enhance the transient convergence performance of the learning control scheme. Differing from the existing results that mainly focused on gain's transition from constant to decreasing ones to suppress noise influence, this study leverages the adaptive mechanisms based on noisy signals to achieve an acceleration capability by addressing diverse performance at different time instants throughout the operation interval. Specifically, an additional gain matrix is introduced into the adaptive gain design to further enhance transient convergence performance. An iterative learning control approach with such a gain design is proposed to realize high precision tracking and it is proven that the input error generated by the newly proposed learning control scheme converges almost surely to zero. The effectiveness of the proposed scheme and its improvement on the transient performance of the learning process are numerically validated.

5.
Food Res Int ; 193: 114855, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39160046

ABSTRACT

Pepper (Capsicum spp.) is an important fruit vegetable worldwide, and it is a rich dietary source of minerals for human being. Yet, the spatio-temporal distribution of pepper fruit mineral composition and the factors influencing such variations at global scale remain unknown. A global meta-analysis of 140 publications providing 649, 562, 690, 811 datapoints was conducted to quantify and evaluate the nutritional quality, comprising potassium (K), magnesium (Mg), iron (Fe) and zinc (Zn), of pepper fruits and its influencing variables. The analysis showed that the global average of K, Mg, Fe and Zn content in pepper fruits was 20-25 g kg-1, 1-1.5 g kg-1, 80-100 mg kg-1, and 20-40 mg kg-1, respectively. There had been a downward trend in pepper fruit nutritional quality over the last decade, especially for Fe and Zn. And, the concentration of all these four nutrients were at lower levels in less developed regions, especially in Africa. Our results showed that the vegetable "green pepper" contains more K, Mg, Fe and Zn than the "hot pepper" used as spice. The concentration of K, Mg, Fe and Zn were increased with fruit yield but that of Fe and Zn were decreased with increase in single fruit weight. Nutritional quality was optimal at mean annual temperature of 10 ℃ - 20 ℃, and was adversely affected when mean annual precipitation was < 500 mm. Pepper fruits produced at pH 6.5-7.5 had higher fruit K concentration while acidic soils (pH<6.5) favored higher Fe and Zn concentrations. The higher soil organic matter (SOM) generally improved the nutritional quality of the pepper. Our results suggest that systematic selection of superior varieties and soil amelioration (adjusting pH and SOM) of the soil-crop system are needed to achieve higher nutritional quality of pepper fruit.


Subject(s)
Capsicum , Fruit , Nutritive Value , Capsicum/chemistry , Fruit/chemistry , Minerals/analysis , Spatio-Temporal Analysis , Potassium/analysis , Magnesium/analysis , Zinc/analysis , Iron/analysis
7.
Ergonomics ; : 1-13, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39150052

ABSTRACT

Few studies investigate the impact of anterior-posterior excitation frequency on the time-domain vibrational response and injury risk of the lumbar spine in seated individuals. Firstly, this study utilised a previously developed finite element model of an upright seated human body on a rigid chair without a backrest to investigate the modes that affect the anterior-posterior vibrations of the seated body. Subsequently, transient dynamic analysis was employed to calculate the lumbar spine's time-domain responses (displacement, stress, and pressure) and risk factors under anteroposterior sinusoidal excitation at varying frequencies (1-8 Hz). Modal analysis suggested the frequencies significantly affecting the lumbar spine's vibration were notably at 4.7 Hz and 5.5 Hz. The transient analysis results and risk factor assessment indicated that the lumbar responses were most pronounced at 5 Hz. In addition, risk factor assessment showed that long-term exposure to 8 Hz vibration was associated with a greater risk of lumbar injury.


Although the anterior-posterior resonance frequency of the sitting body is around 1 Hz, the anterior-posterior vibrations approaching 5 Hz and at 8 Hz inflict more significant harm upon the lumbar spine than other frequencies, thereby elevating the risk of lumbar injury and back disorders.

8.
Exp Neurol ; 380: 114910, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39098715

ABSTRACT

Structural and functional alterations in brain microvascular endothelial cells (BMECs) caused by oxygen-glucose deprivation (OGD) are involved in the pathogenesis of various brain disorders. AlkB homolog 5 (ALKBH5) is a primary m6A demethylase that regulates various cell processes, but its distinct roles in BMEC function remain to be clarified. In the present study, in mouse middle cerebral artery occlusion (MCAO) model, knockout of ALKBH5 reduced neurological deficits, infarct volumes and tissue apoptosis caused by ischemia/reperfusion injury. Evans blue leakage and decreased expression of the tight junction protein ZO-1 and Occludin were also attenuated by ALKBH5 knockout. During the exploration of the underlying mechanisms of the role of ALKBH5 in BMECs, we found that the expression of ALKBH5 was induced at both the mRNA and protein levels by hypoxia; however, its protein stability was impaired by OGD treatment. Knockdown of ALKBH5 expression increased total m6A levels and alleviated OGD-induced BMEC injury. At the same time, the selective ALKBH5 inhibitor Cpd 20m also exhibited a protective effect on cell injury. In contrast, overexpression of ALKBH5 increased the sensitivity of BMECs to OGD. Interestingly, the m6A sequencing data revealed that knockdown of ALKBH5altered the expression of many genes via m6A upregulation. The gene expression alterations were verified by real-time PCR. Taken together, our results suggest that ALKBH5, as well as its target genes, plays important roles in the regulation of brain microvascular endothelial cell function through its RNA demethylase activity.


Subject(s)
AlkB Homolog 5, RNA Demethylase , Endothelial Cells , Glucose , Mice, Knockout , Animals , Mice , AlkB Homolog 5, RNA Demethylase/metabolism , AlkB Homolog 5, RNA Demethylase/genetics , Endothelial Cells/metabolism , Glucose/deficiency , Brain/metabolism , Brain/pathology , Male , Microvessels/pathology , Microvessels/metabolism , Mice, Inbred C57BL , Oxygen/metabolism , Infarction, Middle Cerebral Artery/pathology , Adenosine/analogs & derivatives , Adenosine/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/pathology
9.
Crit Rev Oncol Hematol ; 202: 104470, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111457

ABSTRACT

The liver is a frequent site of metastasis in advanced gastric cancer (GC). Despite significant advancements in diagnostic and therapeutic techniques, the overall survival rate for patients afflicted with gastric cancer liver metastasis (GCLM) remains dismally low. Precision oncology has made significant progress in identifying therapeutic targets and enhancing our understanding of metastasis mechanisms through genome sequencing and molecular characterization. Therefore, it is crucial to have a comprehensive understanding of the various molecular processes involved in GCLM and the fundamental principles of systemic therapy to develop new treatment approaches. This paper aims to review recent findings on the diagnosis, potential biomarkers, and therapies targeting the multiple molecular processes of GCLM, with the goal of improving treatment strategies for patients with GCLM.


Subject(s)
Genomics , Liver Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Stomach Neoplasms/diagnosis , Liver Neoplasms/secondary , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Genomics/methods , Molecular Targeted Therapy/methods , Biomarkers, Tumor/genetics
10.
Food Chem ; 461: 140883, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39154460

ABSTRACT

This study proposed the evolution of self-assembled amphiphilic colloidal particles in Strong-Flavor (SF) Baijiu based on Ostwald ripening for the first time. The evolution process occurs in two stages: disordered amphiphilic molecules self-assemble into small colloidal particles and subsequently undergo Oswald ripening to form larger hydrophobic particles. Microscopic observations revealed the average size of oil-like spherical colloidal particles in Baijiu increased from 1.86 µm to 2.96 µm while the number of particles decreased by 39.50% during the 16-year cellaring process of SF Baijiu, consistent with the particle size trend observed via laser scattering. During fusion process, the charge-to-mass ratio of positively charged colloidal particles decreased, leading ζ-potential decreased from 23.7 mV to 4.66 mV within 16 years of storage. The electrochemical impedance spectroscopy approach tracked the unidirectional variation in the dielectric constant during evolution of SF Baijiu, reflecting the gradual expansion of colloidal particles, which aligns with the evolution trend observed in molecular dynamics simulations. By integrating direct microscopic observations of amphiphilic colloidal particles with electrochemical techniques, the evolution of Baijiu samples is capable to be evaluated in-situ, laying the foundation for intelligent Baijiu aging monitoring technology.

11.
Circulation ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39166327

ABSTRACT

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine-Optical Coherence Tomography Trial) and LoDoCo2 studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] µm versus 87.2 [95% CI, 69.9 to 104.5] µm; difference, 34.2 [95% CI, 9.7 to 58.6] µm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.

12.
Opt Lett ; 49(13): 3556-3559, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950208

ABSTRACT

Optical image encryption has long been an important concept in the fields of photonic network processing and communication. Here, we propose a convolution-like operation-based optical image encryption algorithm exploiting a silicon photonic multiplexing architecture to achieve content security. Particularly, the encryption process is completed in a 3 × 3 cross-shaped photonic micro-ring resonator (MRR) array on chip. For the first time, to the best of our knowledge, this algorithm encodes information in an integrated intensity modulation, effectively reducing the encoding difficulty. Moreover, the high reliability and scalability of optical encryption are ensured using both linear and nonlinear operations on photonic chips according to characteristics of MRRs. As the encryption and decryption experiments show, the image restoration accuracy of our optical encryption algorithm exceeds 99% under real system noise at the pixel level, indicating its noise-robust property. Meanwhile, the peak signal-to-noise ratios of the restored and encrypted images are >60 and <15 dB, respectively, revealing both the high accuracy of the restored image and the small correlation between the encrypted and original images. This work adds to the rapidly expanding field of optical image encryption on photonic chips.

13.
Adv Sci (Weinh) ; : e2400049, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952055

ABSTRACT

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

14.
Bioinspir Biomim ; 19(5)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-38986470

ABSTRACT

Tactile sensors play an important role when robots perform contact tasks, such as physical information collection, force or displacement control to avoid collision. For these manipulations, excessive contact may cause damage while poor contact cause information loss between the robotic end-effector and the objects. Inspired by skin structure and signal transmission method, this paper proposes a tactile sensing system based on the self-sensing soft pneumatic actuator (S-SPA) capable of providing tactile sensing capability for robots. Based on the adjustable height and compliance characteristics of the S-SPA, the contact process is safe and more tactile information can be collected. And to demonstrate the feasibility and advantage of this system, a robotic hand with S-SPAs could recognize different textures and stiffness of the objects by touching and pinching behaviours to collect physical information of the various objects under the positive work states of the S-SPA. The result shows the recognition accuracy of the fifteen texture plates reaches 99.4%, and the recognition accuracy of the four stiffness cuboids reaches 100%by training a KNN model. This safe and simple tactile sensing system with high recognition accuracies based on S-SPA shows great potential in robotic manipulations and is beneficial to applications in domestic and industrial fields.


Subject(s)
Biomimetics , Equipment Design , Robotics , Touch , Robotics/instrumentation , Touch/physiology , Biomimetics/instrumentation , Humans , Hand/physiology , Biomimetic Materials
15.
Chem Sci ; 15(26): 10135-10145, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38966363

ABSTRACT

The dual catalysis strategy is an efficient and powerful tool to fulfill the stereodivergent synthesis of stereoisomeric products from the same set of starting materials. Great attention has been given to the construction of chiral compounds with two contiguous stereocenters. However, the synthesis of two remote noncontiguous stereocenters is more challenging and is less developed, despite the high demand for synthetic tactics. We herein developed an unprecedented example of the stereodivergent preparation of synthetically useful and biologically important chiral ζ-hydroxy amino ester derivatives containing remote 1,6-noncontiguous stereocenters and a unique ß,γ-unsaturation moiety. This cascade dehydrogenation/1,6-Michael addition/hydrogenation protocol between readily-available ketoimine esters and racemic branched dienyl carbinols was rationally realized with bimetallic copper/ruthenium relay catalysis. The key features of the process were atom economy, step economy, and redox-neutrality. All four stereoisomers of chiral ζ-hydroxy amino ester derivatives were easily achieved by the orthogonal permutations of a chiral copper catalyst and chiral ruthenium catalyst. Importantly, a much more challenging stereodivergent synthesis of all eight stereoisomers of chiral peptide products containing three remote stereocenters was accomplished with excellent results through the cooperation of two chiral catalyst pairs and substrate enantiomers.

16.
ACS Nano ; 18(32): 21211-21220, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39079002

ABSTRACT

In photonics, achieving high-quality (Q) resonance is crucial for high-sensitivity devices used in applications, such as switching, sensing, and lasing. However, high-Q resonances are highly susceptible to internal losses of plasmonic devices, impeding their integration into broader systems across terahertz and visible light bands. Here, we overcome this challenge by proposing a low-Q plasmonic metasurface for ultrasensitive terahertz (THz) switching and sensing. Theoretically, we reveal an approach to constructing a low-Q resonator possessing high sensitivity to nonradiative losses. Leveraging this mechanism, we design a highly sensitive plasmonic metasurface induced by strong coupling between a quasi-bound state in the continuum and a dipole mode. By hybridizing with the germanium layer, the metadevice exhibits an ultralow pump threshold of 192 µJ/cm2 and an ultrafast switching cycle time of 7 ps. Furthermore, it also shows a high sensitivity of 224 GHz/RIU in refractive index sensing. The proposed paradigm of constructing low-Q and high-sensitivity photonic devices can be applied to biosensing, wide-band filters, and sensitive modulators.

17.
Cell Commun Signal ; 22(1): 374, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054523

ABSTRACT

BACKGROUND: High-altitude cerebral edema (HACE) is considered an end-stage acute mountain sickness (AMS) that typically occurs in people after rapid ascent to 2500 m or more. While hypoxia is a fundamental feature of the pathophysiological mechanism of HACE, emerging evidence suggests that inflammation serves as a key risk factor in the occurrence and development of this disease. However, little is known about the molecular mechanism underlying their crosstalk. METHODS: A mouse HACE model was established by combination treatment with hypobaric hypoxia exposure and lipopolysaccharides (LPS) stimulation. Lactylated-proteomic analysis of microglia was performed to reveal the global profile of protein lactylation. Molecular modeling was applied to evaluate the 3-D modeling structures. A combination of experimental approaches, including western blotting, quantitative real-time reverse transcriptionpolymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and RNA interference, were used to explore the underlying molecular mechanisms. RESULTS: We found that hypoxia exposure increased the lactate concentration and lactylation in mouse HACE model. Moreover, hypoxia aggravated the microglial neuroinflammatory response in a lactate-dependent manner. Global profiling of protein lactylation has shown that a large quantity of lysine-lactylated proteins are induced by hypoxia and preferentially occur in protein complexes, such as the NuRD complex, ribosome biogenesis complex, spliceosome complex, and DNA replication complex. The molecular modeling data indicated that lactylation could affect the 3-D theoretical structure and increase the solvent accessible surface area of HDAC1, MTA1 and Gatad2b, the core members of the NuRD complex. Further analysis by knockdown or selectively inhibition indicated that the NuRD complex is involved in hypoxia-mediated aggravation of inflammation. CONCLUSIONS: These results revealed a comprehensive profile of protein lactylation in microglia and suggested that protein lysine lactylation plays an important role in the regulation of protein function and subsequently contributes to the neuroinflammatory response under hypoxic conditions.


Subject(s)
Brain Edema , Microglia , Microglia/metabolism , Microglia/pathology , Animals , Brain Edema/metabolism , Brain Edema/pathology , Mice , Altitude Sickness/metabolism , Altitude Sickness/pathology , Male , Mice, Inbred C57BL , Disease Models, Animal , Lipopolysaccharides/pharmacology , Altitude , Proteomics
18.
Int J Mol Sci ; 25(14)2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39063230

ABSTRACT

N6-methyladenosine (m6A) RNA modification is the most prevalent form of RNA methylation and plays a crucial role in plant development. However, our understanding of m6A modification in Masson pine (Pinus massoniana Lamb.) remains limited. In this study, a complete analysis of m6A writers, erasers, and readers in Masson pine was performed, and 22 m6A regulatory genes were identified in total, including 7 m6A writers, 7 m6A erases, and 8 readers. Phylogenetic analysis revealed that all m6A regulators involved in Masson pine could be classified into three distinct groups based on their domains and motifs. The tissue expression analysis revealed that the m6A regulatory gene may exert a significant influence on the development of reproductive organs and leaves in Masson pine. Moreover, the results from stress and hormone expression analysis indicated that the m6A regulatory gene in Masson pine might be involved in drought stress response, ABA-signaling-pathway activation, as well as resistance to Monochamus alternatus. This study provided valuable and anticipated insights into the regulatory genes of m6A modification and their potential epigenetic regulatory mechanisms in Masson pine.


Subject(s)
Adenosine , Gene Expression Regulation, Plant , Phylogeny , Pinus , Stress, Physiological , Transcriptome , Pinus/genetics , Pinus/metabolism , Stress, Physiological/genetics , Adenosine/analogs & derivatives , Adenosine/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Profiling , Epigenesis, Genetic
19.
Materials (Basel) ; 17(14)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39063690

ABSTRACT

A precise constitutive model is essential for capturing the deformation characteristics of the GH4169 superalloy in numerical simulations of thermal plastic forming processes. Hence, the aim of this study was to develop a precise modified constitutive model to describe the hot deformation behavior exhibited by the GH4169 superalloy. The isothermal cylindrical uniaxial compression tests of the GH4169 superalloy were carried out at temperatures of 950~1100 °C and strain rates of 0.01~10 s-1 using a Thermecmastor-200KN thermal-mechanical simulator. The original strain-stress curves were corrected by minimizing the effects of plastic heat and interfacial friction. Based on the true stress-strain curves, the original strain-compensated Arrhenius constitutive model was constructed using polynomial orders of 3, 5, and 10, respectively. The results showed that once the polynomial order exceeds the 5th, further increasing the order has little contribution to the accuracy of the model. To improve prediction ability, a higher precision Arrhenius constitutive model was established by extending a series of material parameters as functions that depend on temperature, strain, and strain rate, in which the error can be reduced from 4.767% to 0.901% compared with the classic strain-compensated Arrhenius constitutive model.

20.
Bioresour Technol ; 408: 131179, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39084532

ABSTRACT

An iron-retrofitted anaerobic baffled reactor (ABR) system was developed for the effective treatment of rural wastewater with reduced maintenance demand and aeration costs. Average removal efficiencies of chemical oxygen demand, total nitrogen and total phosphorus of 99.4%, 62.7% and 92.6% were achieved respectively, when the ABR system was operating at steady state. With effective bioreduction of FeIII in the anaerobic chambers, phosphorus was immobilized in the sludge as vivianite, the sole phosphorus-carrying mineral. The FeIII in the recirculated sludge induced Feammox in the ABR reactor, contributing 14.8% to total nitrogen removal. Biophase separation and enrichment of microorganisms associated with iron and nitrogen transformations were observed in the system after Fe dosing, which enhanced the removal of pollutants. The coupling of Feammox and vivianite crystallization to remove nitrogen and phosphorus in an iron-retrofitted ABR would appear to be a promising technology for rural wastewater treatment.


Subject(s)
Bioreactors , Iron , Phosphorus , Sewage , Wastewater , Water Purification , Iron/chemistry , Water Purification/methods , Anaerobiosis , Wastewater/chemistry , Biological Oxygen Demand Analysis , Nitrogen , Waste Disposal, Fluid/methods , Nutrients , Rural Population
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