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1.
Nat Cell Biol ; 26(7): 1110-1123, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38997457

ABSTRACT

Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.


Subject(s)
Blood Coagulation , Blood Platelets , Mice, Inbred C57BL , Neutrophils , Neutrophils/metabolism , Animals , Humans , Blood Platelets/metabolism , Mice , Hemostasis , Cell Movement , Platelet Activation , Male , Blood Coagulation Factors/metabolism , Blood Coagulation Factors/genetics
2.
bioRxiv ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39005363

ABSTRACT

Protein science is entering a transformative phase enabled by deep mutational scans that provide an unbiased view of the residue level interactions that mediate function. However, it has yet to be extensively used to characterize the mutational and evolutionary landscapes of plant proteins. Here, we apply the method to explore sequence-function relationships within the sugar transporter AtSWEET13. DMS results describe how mutational interrogation throughout different regions of the protein affects AtSWEET13 abundance and transport function. Our results identify novel transport-enhancing mutations that are validated using the FRET sensor assays. Extending DMS results to phylogenetic analyses reveal the role of transmembrane helix 4 (TM4) which makes the SWEET family transporters distinct from prokaryotic SemiSWEETs. We show that transmembrane helix 4 is intolerant to motif swapping with other clade-specific SWEET TM4 compositions, despite accommodating single point-mutations towards aromatic and charged polar amino acids. We further show that the transfer learning approaches based on physics and ML based In silico variant prediction tools have limited utility for engineering plant proteins as they were unable to reproduce our experimental results. We conclude that DMS can produce datasets which, when combined with the right predictive computational frameworks, can direct plant engineering efforts through derivative phenotype selection and evolutionary insights.

3.
Nat Commun ; 15(1): 5981, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013884

ABSTRACT

Group 3 innate lymphoid cells (ILC3) are crucial for maintaining mucosal homeostasis and regulating inflammatory diseases, but the molecular mechanisms governing their phenotype and function are not fully understood. Here, we show that ILC3s highly express Fcer1g gene, which encodes the antibody Fc-receptor common gamma chain, FcεR1γ. Genetic perturbation of FcεR1γ leads to the absence of critical cell membrane receptors NKp46 and CD16 in ILC3s. Alanine scanning mutagenesis identifies two residues in FcεR1γ that stabilize its binding partners. FcεR1γ expression in ILC3s is essential for effective protective immunity against bacterial and fungal infections. Mechanistically, FcεR1γ influences the transcriptional state and proinflammatory cytokine production of ILC3s, relying on the CD16-FcεR1γ signaling pathway. In summary, our findings highlight the significance of FcεR1γ as an adapter protein that stabilizes cell membrane partners in ILC3s and promotes anti-infection immunity.


Subject(s)
Immunity, Innate , Lymphocytes , Mice, Inbred C57BL , Receptors, IgE , Animals , Lymphocytes/immunology , Lymphocytes/metabolism , Receptors, IgE/metabolism , Receptors, IgE/immunology , Receptors, IgE/genetics , Mice , Receptors, IgG/metabolism , Receptors, IgG/immunology , Humans , Signal Transduction , Mice, Knockout
4.
J Adv Res ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39009133

ABSTRACT

INTRODUCTION: Since the outbreak of COVID-19, microplastics (MPs) and triclosan in pharmaceuticals and personal care products (PPCPs) are markedly rising. MPs and triclosan are co-present in the environment, but their interactions and subsequent implications on the fate of triclosan in plants are not well understood. OBJECTIVE: This study aimed to investigate effects of charged polystyrene microplastics (PS-MPs) on the fate of triclosan in cabbage plants under a hydroponic system. METHODS: 14C-labeling method and liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (LC-QTOF-MS) analysis were applied to clarify the bioaccumulation, distribution, and metabolism of triclosan in hydroponics-cabbage system. The distribution of differentially charged PS-MPs in cabbage was investigated by confocal laser scanning microscopy and scanning electron microscopy. RESULTS: The results showed that MPs had a significant impact on bioaccumulation and metabolism of triclosan in hydroponics-cabbage system. PS-COO-, PS, and PS-NH3+ MPs decreased the bioaccumulation of triclosan in cabbage by 69.1 %, 81.5 %, and 87.7 %, respectively, in comparison with the non-MP treatment (control). PS-MPs also reduced the translocation of triclosan from the roots to the shoots in cabbage, with a reduction rate of 15.6 %, 28.3 %, and 65.8 % for PS-COO-, PS, and PS-NH3+, respectively. In addition, PS-NH3+ profoundly inhibited the triclosan metabolism pathways such as sulfonation, nitration, and nitrosation in the hydroponics-cabbage system. The above findings might be linked to strong adsorption between PS-NH3+ and triclosan, and PS-NH3+ may also potentially inhibit the growth of cabbage. Specially, the amount of triclosan adsorbed on PS-NH3+ was significantly greater than that on PS and PS-COO-. The cabbage biomass was reduced by 76.9 % in PS-NH3+ groups, in comparison with the control. CONCLUSION: The uptake and transformation of triclosan in hydroponics-cabbage system were significantly inhibited by charged PS-MPs, especially PS-NH3+. This provides new insights into the fate of triclosan and other PPCPs coexisted with microplastics for potential risk assessments.

5.
Zhen Ci Yan Jiu ; 49(7): 736-742, 2024 Jul 25.
Article in English, Chinese | MEDLINE | ID: mdl-39020492

ABSTRACT

OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.


Subject(s)
Corpus Striatum , Ferroptosis , Mice, Inbred C57BL , Moxibustion , Neurons , Parkinson Disease , Animals , Ferroptosis/genetics , Mice , Corpus Striatum/metabolism , Parkinson Disease/metabolism , Parkinson Disease/therapy , Parkinson Disease/genetics , Parkinson Disease/physiopathology , Male , Humans , Neurons/metabolism , Sorting Nexins/metabolism , Sorting Nexins/genetics , Down-Regulation , Motor Activity , Disease Models, Animal
6.
Phys Rev E ; 109(6-2): 065306, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39021008

ABSTRACT

In this work, the recent lattice Boltzmann (LB) model with self-tuning equation of state (EOS) [Huang et al., Phys. Rev. E 99, 023303 (2019)2470-004510.1103/PhysRevE.99.023303] is extended to three dimensions for the simulation of multiphase flows, which is based on the standard three-dimensional 27-velocity lattice and multiple-relaxation-time collision operator. To achieve the self-tuning EOS, the equilibrium moment is devised by introducing a built-in variable, and the collision matrix is improved by introducing some velocity-dependent nondiagonal elements. Meanwhile, the additional cubic terms of velocity in recovering the Newtonian viscous stress are eliminated to enhance the numerical accuracy. For modeling multiphase flows, an attractive pairwise interaction force is introduced to mimic the long-range molecular interaction, and a consistent scheme is proposed to compensate for the ɛ^{3}-order discrete lattice effect. Thermodynamic consistency in a strict sense is established for the multiphase LB model with self-tuning EOS, and the wetting condition is also treated in a thermodynamically consistent manner. As a result, the contact angle, surface tension, and interface thickness can be independently adjusted in the present theoretical framework. Numerical tests are first performed to validate the multiphase LB model with self-tuning EOS and the theoretical analyses of bulk and surface thermodynamics. The collision of equal-sized droplets is then simulated to demonstrate the applicability and effectiveness of the present LB model for multiphase flows.

7.
J Agric Food Chem ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39021280

ABSTRACT

Synthetic aromatic esters, widely employed in agriculture, food, and chemical industries, have become emerging environmental pollutants due to their strong hydrophobicity and poor bioavailability. This study attempted to address this issue by extracellularly expressing the promiscuous aminopeptidase (Aps) from Pseudomonas aeruginosa GF31 in B. subtilis, achieving an impressive enzyme activity of 13.7 U/mg. Notably, we have demonstrated, for the first time, the Aps-mediated degradation of diverse aromatic esters, including but not limited to pyrethroids, phthalates, and parabens. A biochemical characterization of Aps reveals its esterase properties and a broader spectrum of substrate profiles. The degradation rates of p-nitrobenzene esters (p-NB) with different side chain structures vary under the action of Aps, showing a preference for substrates with relatively longer alkyl side chains. The structure-dependent degradability aligns well with the binding energies between Aps and p-NB. Molecular docking and enzyme-substrate interaction elucidate that hydrogen bonding, hydrophobic interactions, and π-π stacking collectively stabilize the enzyme-substrate conformation, promoting substrate hydrolysis. These findings provide new insights into the enzymatic degradation of aromatic ester pollutants, laying a foundation for the further development and modification of promiscuous enzymes.

8.
Child Care Health Dev ; 50(4): e13302, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38953565

ABSTRACT

BACKGROUND: In the digital age, bullying manifests in two distinct forms: traditional bullying and cyberbullying. Children's peer relationships are important predictors of bullying, and bullying in turn predicts peer relationships. However, few researchers have noted the bidirectional relationship between peer relationships and bullying. METHODS: The present study used a two-wave cross-lagged longitudinal design to fill this gap. The potential sex differences were also examined in this relationship. The sample consisted of 527 Chinese children aged 8 to 12 years (M = 9.69, SD = .96; 53.5% female). Participants completed peer nominations for peer acceptance, peer rejection and social dominance, as well as self-reports of traditional bullying and cyberbullying. RESULTS: Results showed that peer rejection at the first time point (T1) significantly and positively predicted traditional bullying perpetration, cyberbullying perpetration and cyberbullying victimization at the second time point (T2). Traditional bullying victimization at T1 significantly and negatively predicted peer acceptance and social dominance at T2. The results also revealed significant male and female differences. For instance, among boys, peer acceptance at T1 significantly and negatively predicted cyberbullying victimization at T2. In contrast, this relationship was not observed among girls. The present findings have important implications for understanding the cyclical relationship between peer relationships and bullying and providing practical guidance for improving peer relationships and reducing bullying.


Subject(s)
Bullying , Crime Victims , Interpersonal Relations , Peer Group , Humans , Male , Female , Child , Bullying/psychology , China , Crime Victims/psychology , Longitudinal Studies , Sex Factors , Cyberbullying/psychology , Social Dominance , Child Behavior/psychology , East Asian People
9.
Chemistry ; : e202401739, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954398

ABSTRACT

Metal halide materials have recently drawn increasing research interest for their excellent opto-electronic properties and structural diversity, but their resulting rigid structures render them brittle and poor formability during manufacturing. Here we demonstrate a thermoplastic luminant hybrid lead halide solid by integrating lead bromide complex into tri-n-octylphosphine oxide (TOPO) matrix. The construction of the hybrid materials can be achieved by a simple dissolution process, in which TOPO molecules act as the solvents and ligands to yield the monodispersed clusters. The combination of these functional units enables the near-room-temperature melt-processing of the materials into targeted geometry by simple molding or printing techniques, which offer possibilities for fluorescent writing inks with outstanding self-healing capacity to physical damage. The intermarriage between metal halide clusters with functional molecules expands the range of practical applications for hybrid metal halide materials.

10.
J Colloid Interface Sci ; 674: 805-812, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38955011

ABSTRACT

Lithium-sulfur (Li-S) batteries represent the most promising next-generation energy storage systems because of their high theoretical specific capacity and energy density. However, the severe shuttle effect and volume expansion of sulfur cathodes have impeded their commercial viability. Hence, accelerating the conversion of lithium polysulfides (LiPSs) is crucial for achieving efficient Li-S batteries. In this study, we employ a straightforward electrostatic self-assembly method to coat ultra-thin MXene nanosheets onto a S@MnO2 core-shell structure, resulting in a highly conductive three-dimensional network. This unique structure not only suppresses the diffusion of LiPSs but also accelerates electron and ion transfer, ensuring a rapid and efficient conversion of LiPSs. The CV curves of symmetrical cells and the Li2S deposition curves demonstrate a significant improvement in the catalytic performance of batteries with S@MnO2@MXene. The capacity of Li-S batteries achieved an impressive 842 mAh/g at the current density of 1C, with a minimal capacity decay of only 0.84 mAh/g per cycle within 500 cycles. Additionally, increasing the sulfur loading mass to 5.88 mg cm-2 resulted in an areal capacity of 6.33 mAh cm-2, demonstrating practical application potential.

11.
Nat Commun ; 15(1): 5521, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951553

ABSTRACT

The microgeometry of the cellular microenvironment profoundly impacts cellular behaviors, yet the link between it and the ubiquitously expressed mechanosensitive ion channel PIEZO1 remains unclear. Herein, we describe a fluorescent micropipette aspiration assay that allows for simultaneous visualization of intracellular calcium dynamics and cytoskeletal architecture in real-time, under varied micropipette geometries. By integrating elastic shell finite element analysis with fluorescent lifetime imaging microscopy and employing PIEZO1-specific transgenic red blood cells and HEK cell lines, we demonstrate a direct correlation between the microscale geometry of aspiration and PIEZO1-mediated calcium signaling. We reveal that increased micropipette tip angles and physical constrictions lead to a significant reorganization of F-actin, accumulation at the aspirated cell neck, and subsequently amplify the tension stress at the dome of the cell to induce more PIEZO1's activity. Disruption of the F-actin network or inhibition of its mobility leads to a notable decline in PIEZO1 mediated calcium influx, underscoring its critical role in cellular mechanosensing amidst geometrical constraints.


Subject(s)
Actins , Calcium , Cytoskeleton , Ion Channels , Mechanotransduction, Cellular , Humans , Ion Channels/metabolism , Actins/metabolism , HEK293 Cells , Cytoskeleton/metabolism , Calcium/metabolism , Calcium Signaling/physiology , Finite Element Analysis , Animals , Microscopy, Fluorescence/methods
12.
J Agric Food Chem ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981019

ABSTRACT

Steviol glycosides (SGs) are a natural sweetener widely used in the food and beverage industry, but the low solubility and stability of SG aqueous solutions greatly limit their application performance, especially in liquid formulations. In this work, we explore the solubility behavior of rebaudioside A (Reb A) in water, a major component of SGs, with the aim of clarifying the underlying mechanisms of the solubility and stability constraints of SGs, as well as the impact on their multifunctional properties. We demonstrate for the first time that Reb A exhibits hierarchical self-assembly in solutions, forming spherical micelles first when the concentration exceeds its critical micelle concentration (5.071 mg/mL), which then further assemble into large rod-like aggregates. The formation of such large Reb A aggregates is mainly dominated by hydrogen bonding and short-range Coulomb interaction energy, thus leading to the low solubility and precipitation of Reb A solutions. Surprisingly, aggregated Reb A structures display significantly improved organoleptic properties, revealing that self-aggregation can be developed as a simple, efficient, and green strategy for improving the taste profile of SGs. Additionally, the self-aggregation of Reb A at high concentrations impairs active encapsulation and also affects its interfacial and emulsifying properties.

13.
Pathol Res Pract ; 260: 155449, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38981345

ABSTRACT

Parathyroid carcinoma(PC) is an extremely rare malignant tumor of the parathyroid glands. The lung is the most common target organ for PC distant metastases. In this study, twelve patients diagnosed with PC with lung metastases were enrolled in the study. Hematoxylin and Eosin(H&E) stained, immunohistochemical stained and next-generation sequencing (NGS) of a 425-gene panel were performed on tumor tissue samples. At the same time, we also evaluated its histopathologic characteristics. The results indicate that the microscopic examination of metastatic lesions reveals the same structure and characteristics as PC; the tumor was composed of relatively uniform cells organized in nests and separated by thin fibrous bands and abundant blood vessels. Immunohistochemical evaluation of Ki67, CyclinD1, PTH, SYN, CgA, and CD56 was useful in diagnosing PC with lung metastases. The most frequently genetic alterations were mutations of CDC73 and copy number variation (CNV) of MCL1, with a mutation rate of 25 %. In addition, the mutations of CDC73, ATM, TP53, ALK, ERBB2, MAP3K4, TSC1, CCND1 and CNV of CDK4, MCL1, SMARCB1 overlap between metastatic lesions and primary lesions. In conclusions, PC is a rare endocrine malignant tumor that is very difficult to diagnose preoperatively and prone to clinical recurrence or distant metastasis. Genetic mutations, presentation and histological characteristic were the basis for diagnosing PC with lung metastases.

14.
Sci Rep ; 14(1): 15867, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982141

ABSTRACT

The optimal configuration of a customized implant abutment is crucial for bone remodeling and is influenced by various design parameters. This study introduces an optimization process for designing two-piece zirconia dental implant abutments. The aim is to enhance bone remodeling, increase bone density in the peri-implant region, and reduce the risk of late implant failure. A 12-month bone remodeling algorithm subroutine in finite element analysis to optimize three parameters: implant placement depth, abutment taper degree, and gingival height of the titanium base abutment. The response surface analysis shows that implant placement depth and gingival height significantly impact bone density and uniformity. The taper degree has a smaller effect on bone remodeling. The optimization identified optimal values of 1.5 mm for depth, 35° for taper, and 0.5 mm for gingival height. The optimum model significantly increased cortical bone density from 1.2 to 1.937 g/cm3 in 2 months, while the original model reached 1.91 g/cm3 in 11 months. The standard deviation of density showed more uniform bone apposition, with the optimum model showing values 2 to 6 times lower than the original over 12 months. The cancellous bone showed a similar trend. In conclusion, the depth and taper have a significant effect on bone remodeling. This optimized model significantly improves bone density uniformity.


Subject(s)
Bone Remodeling , Finite Element Analysis , Humans , Dental Implant-Abutment Design/methods , Bone Density , Titanium/chemistry , Crowns , Zirconium/chemistry , Dental Abutments , Dental Implants
15.
Angew Chem Int Ed Engl ; : e202407658, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982589

ABSTRACT

Metallene is considered as an emerging family of electrocatalysts due to its atomically layered structure and unique surface stress. Here we propose a strategy to modulate the Bader charge transfer (BCT) between Pd surface and oxygenated intermediates via p-d electronic interaction by introducing single-atomp-block metal (M = In, Sn, Pb, Bi) into Pd metallene nanosheets towards efficient oxygen reduction reaction (ORR). X-ray absorption and photoelectron spectroscopy suggests that doping p-block metals could facilitate electron transfer to Pd sites and thus downshift the d-band center of Pd and weaken the adsorption energy of O intermediates. Among them, the developed Bi-Pd metallene shows extraordinarily high ORR mass activity of 11.34 A mgPd-1 and 0.86 A mgPd-1 at 0.9 V and 0.95 V in alkaline solution, respectively, representing the best Pd-based ORR electrocatalysts ever reported. In the cathode of a Zinc-air battery, Bi-Pd metallene could achieve an open-circuit voltage of 1.546 V and keep stable for 760 h at 10 mA cm-2. Theoretical calculations suggest that the BCT between Pd surface and *OO intermediates greatly affects the bond length between them (dPd-*OO) and Bi doping could appropriately reduce the amount of BCT and stretch the dPd-*OO, thus enhancing the ORR activity.

16.
Chin J Integr Med ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990479

ABSTRACT

OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.

17.
Int J Mol Sci ; 25(13)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39000319

ABSTRACT

Liver regeneration induced by partial hepatectomy (PHx) has attracted intensive research interests due to the great significance for liver resection and transplantation. The zebrafish (Danio rerio) is an excellent model to study liver regeneration. In the fish subjected to PHx (the tip of the ventral lobe was resected), the lost liver mass could be fully regenerated in seven days. However, the regulatory mechanisms underlying the liver regeneration remain largely unknown. In this study, gene expression profiles during the regeneration of PHx-treated liver were explored by RNA sequencing (RNA-seq). The genes responsive to the injury of PHx treatment were identified and classified into different clusters based on the expression profiles. Representative gene ontology (GO) enrichments for the early responsive genes included hormone activity, ribosome biogenesis and rRNA processing, etc., while the late responsive genes were enriched in biological processes such as glutathione metabolic process, antioxidant activity and cellular detoxification. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were also identified for the differentially expressed genes (DEGs) between the time-series samples and the sham controls. The proteasome was overrepresented by the up-regulated genes at all of the sampling time points. Inhibiting proteasome activity by the application of MG132 to the fish enhanced the expression of Pcna (proliferating cell nuclear antigen), an indicator of hepatocyte proliferation after PHx. Our data provide novel insights into the molecular mechanisms underlying the regeneration of PHx-treated liver.


Subject(s)
Hepatectomy , Liver Regeneration , Signal Transduction , Transcriptome , Zebrafish , Animals , Zebrafish/genetics , Liver Regeneration/genetics , Liver/metabolism , Gene Expression Profiling , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Gene Ontology
18.
Sensors (Basel) ; 24(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39000817

ABSTRACT

Parallax processing and structure preservation have long been important and challenging tasks in image stitching. In this paper, an image stitching method based on sliding camera to eliminate perspective deformation and asymmetric optical flow to solve parallax is proposed. By maintaining the viewpoint of two input images in the mosaic non-overlapping area and creating a virtual camera by interpolation in the overlapping area, the viewpoint is gradually transformed from one to another so as to complete the smooth transition of the two image viewpoints and reduce perspective deformation. Two coarsely aligned warped images are generated with the help of a global projection plane. After that, the optical flow propagation and gradient descent method are used to quickly calculate the bidirectional asymmetric optical flow between the two warped images, and the optical-flow-based method is used to further align the two warped images to reduce parallax. In the image blending, the softmax function and registration error are used to adjust the width of the blending area, further eliminating ghosting and reducing parallax. Finally, by comparing our method with APAP, AANAP, SPHP, SPW, TFT, and REW, it has been proven that our method can not only effectively solve perspective deformation, but also gives more natural transitions between images. At the same time, our method can robustly reduce local misalignment in various scenarios, with higher structural similarity index. A scoring method combining subjective and objective evaluations of perspective deformation, local alignment and runtime is defined and used to rate all methods, where our method ranks first.

19.
bioRxiv ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38979333

ABSTRACT

Dedicated water channels are involved in the facilitated diffusion of water molecules across the cell membrane in plants. Transporter proteins are also known to transport water molecules along with substrates, however the molecular mechanism of water permeation is not well understood in plant transporters. Here, we show plant sugar transporters from the SWEET (Sugar Will Eventually be Exported Transporter) family act as water-conducting carrier proteins via a variety of passive and active mechanisms that allow diffusion of water molecules from one side of the membrane to the other. This study provides a molecular perspective on how plant membrane transporters act as water carrier proteins, a topic that has not been extensively explored in literature. Water permeation in membrane transporters could occur via four distinct mechanisms which form our hypothesis for water transport in SWEETs. These hypothesis are tested using molecular dynamics simulations of the outward-facing, occluded, and inward-facing state of AtSWEET1 to identify the water permeation pathways and the flux associated with them. The hydrophobic gates at the center of the transport tunnel act as a barrier that restricts water permeation. We have performed in silico single and double mutations of the hydrophobic gate residues to examine the changes in the water conductivity. Surprisingly, the double mutant allows the water permeation to the intracellular half of the membrane and forms a continuous water channel. These computational results are validated by experimentally examining the transport of hydrogen peroxide molecules by the AtSWEET family of transporters. We have also shown that the transport of hydrogen peroxide follows the similar mechanism as water transport in AtSWEET1. Finally, we conclude that similar water-conduction states are also present in other SWEET transporters due to the high sequence and structure conservation exhibited by this transporter family.

20.
bioRxiv ; 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38979323

ABSTRACT

The pericellular matrix (PCM) is the immediate microniche surrounding resident cells in various tissue types, regulating matrix turnover, cell-matrix cross-talk and disease initiation. This study elucidated the structure-mechanical properties and mechanobiological functions of the PCM in fibrocartilage, a family of connective tissues that sustain complex tensile and compressive loads in vivo. Studying the murine meniscus as the model tissue, we showed that fibrocartilage PCM contains thinner, random collagen fibrillar networks that entrap proteoglycans, a structure distinct from the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM). In comparison to the ECM, the PCM has a lower modulus and greater isotropy, but similar relative viscoelastic properties. In Col5a1 +/- menisci, the reduction of collagen V, a minor collagen localized in the PCM, resulted in aberrant fibril thickening with increased heterogeneity. Consequently, the PCM exhibited a reduced modulus, loss of isotropy and faster viscoelastic relaxation. This disrupted PCM contributes to perturbed mechanotransduction of resident meniscal cells, as illustrated by reduced intracellular calcium signaling, as well as upregulated biosynthesis of lysyl oxidase and tenascin C. When cultured in vitro, Col5a1 +/- meniscal cells synthesized a weakened nascent PCM, which had inferior properties towards protecting resident cells against applied tensile stretch. These findings underscore the PCM as a distinctive microstructure that governs fibrocartilage mechanobiology, and highlight the pivotal role of collagen V in PCM function. Targeting the PCM or its molecular constituents holds promise for enhancing not only meniscus regeneration and osteoarthritis intervention, but also addressing diseases across various fibrocartilaginous tissues.

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