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1.
Opt Express ; 32(5): 7105-7118, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38439400

ABSTRACT

Deep-space optical communication has garnered increasing attention for its high data transfer rate, wide bandwidth, and high transmission speed. However, coronal plasma turbulence severely degrades optical signals during superior solar conjunction. In this study, we introduce the models for plasma density and generalized non-Kolmogorov turbulence power spectrum. Based on these models, we derive the variance of the phase fluctuations with the assistance of the Rytov theory in the weak turbulence regime involving various variables, such as turbulence outer scale, spectral index, relative fluctuation factor, and wavelength. Subsequently, we evaluate the bit error ratio (BER) performance of the deep-space optical communication system, considering phase fluctuations and intensity scintillations, under binary phase shift keying modulation. Numerical calculations reveal that small heliocentric distance, large relative fluctuation factor and spectral index, could induce severe phase fluctuations and high BER. Fortunately, the effects of the plasma irregularities on the BER performance can be mitigated by short optical wavelength under large outer scale.

2.
Microvasc Res ; 153: 104658, 2024 05.
Article in English | MEDLINE | ID: mdl-38266910

ABSTRACT

Endothelial permeability deterioration is involved in ventilator-induced lung injury (VILI). The integrality of vascular endothelial glycocalyx (EG) is closely associated with endothelial permeability. The hypothesis was that vascular EG shedding participates in VILI through promoting endothelial permeability. In the present study, male Sprague-Dawley (SD) rats were ventilated with high tidal volume (VT =40 ml/kg) or low tidal volume (VT =8 ml/kg) to investigate the effects of different tidal volume and ventilation durations on EG in vivo. We report disruption of EG during the period of high tidal volume ventilation characterized by increased glycocalyx structural components (such as syndecan-1, heparan sulfate, hyaluronan) in the plasma and decreased the expression of syndecan-1 in the lung tissues. Mechanistically, the disruption of EG was associated with increased proinflammatory cytokines and matrix metalloproteinase in the lung tissues. Collectively, these results demonstrate that the degradation of EG is involved in the occurrence and development of VILI in rats, and the inflammatory mechanism mediated by activation of the NF-κB signaling pathway may be partly responsible for the degradation of EG in VILI in rats. This study enhances our understanding of the pathophysiological processes underlying VILI, shedding light on potential therapeutic targets to mitigate VILI.


Subject(s)
Syndecan-1 , Ventilator-Induced Lung Injury , Rats , Male , Animals , Rats, Sprague-Dawley , Glycocalyx/metabolism , Ventilator-Induced Lung Injury/drug therapy , Ventilator-Induced Lung Injury/metabolism , Lung/metabolism
3.
PLoS Genet ; 17(12): e1009250, 2021 12.
Article in English | MEDLINE | ID: mdl-34860830

ABSTRACT

Epigenetic mechanisms are gatekeepers for the gene expression patterns that establish and maintain cellular identity in mammalian development, stem cells and adult homeostasis. Amongst many epigenetic marks, methylation of histone 3 lysine 4 (H3K4) is one of the most widely conserved and occupies a central position in gene expression. Mixed lineage leukemia 1 (MLL1/KMT2A) is the founding mammalian H3K4 methyltransferase. It was discovered as the causative mutation in early onset leukemia and subsequently found to be required for the establishment of definitive hematopoiesis and the maintenance of adult hematopoietic stem cells. Despite wide expression, the roles of MLL1 in non-hematopoietic tissues remain largely unexplored. To bypass hematopoietic lethality, we used bone marrow transplantation and conditional mutagenesis to discover that the most overt phenotype in adult Mll1-mutant mice is intestinal failure. MLL1 is expressed in intestinal stem cells (ISCs) and transit amplifying (TA) cells but not in the villus. Loss of MLL1 is accompanied by loss of ISCs and a differentiation bias towards the secretory lineage with increased numbers and enlargement of goblet cells. Expression profiling of sorted ISCs revealed that MLL1 is required to promote expression of several definitive intestinal transcription factors including Pitx1, Pitx2, Foxa1, Gata4, Zfp503 and Onecut2, as well as the H3K27me3 binder, Bahcc1. These results were recapitulated using conditional mutagenesis in intestinal organoids. The stem cell niche in the crypt includes ISCs in close association with Paneth cells. Loss of MLL1 from ISCs promoted transcriptional changes in Paneth cells involving metabolic and stress responses. Here we add ISCs to the MLL1 repertoire and observe that all known functions of MLL1 relate to the properties of somatic stem cells, thereby highlighting the suggestion that MLL1 is a master somatic stem cell regulator.


Subject(s)
Adult Stem Cells/physiology , Cell Differentiation/genetics , Histone-Lysine N-Methyltransferase/genetics , Intestinal Failure/genetics , Intestinal Mucosa/pathology , Myeloid-Lymphoid Leukemia Protein/genetics , Animals , Bone Marrow Transplantation , DNA Methylation , Disease Models, Animal , Epigenesis, Genetic , Histone-Lysine N-Methyltransferase/metabolism , Humans , Intestinal Failure/pathology , Intestinal Mucosa/cytology , Jejunum/cytology , Jejunum/pathology , Mice , Mice, Transgenic , Mutagenesis , Mutation , Myeloid-Lymphoid Leukemia Protein/metabolism , Stem Cell Niche
4.
Dentomaxillofac Radiol ; 53(7): 447-458, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38960866

ABSTRACT

OBJECTIVES: In order to assist junior doctors in better diagnosing apical periodontitis (AP), an artificial intelligence AP grading system was developed based on deep learning (DL) and its reliability and accuracy were evaluated. METHODS: One hundred and twenty cone-beam computed tomography (CBCT) images were selected to construct a classification dataset with four categories, which were divided by CBCT periapical index (CBCTPAI), including normal periapical tissue, CBCTPAI 1-2, CBCTPAI 3-5, and young permanent teeth. Three classic algorithms (ResNet50/101/152) as well as one self-invented algorithm (PAINet) were compared with each other. PAINet were also compared with two recent Transformer-based models and three attention models. Their performance was evaluated by accuracy, precision, recall, balanced F score (F1-score), and the area under the macro-average receiver operating curve (AUC). Reliability was evaluated by Cohen's kappa to compare the consistency of model predicted labels with expert opinions. RESULTS: PAINet performed best among the four algorithms. The accuracy, precision, recall, F1-score, and AUC on the test set were 0.9333, 0.9415, 0.9333, 0.9336, and 0.9972, respectively. Cohen's kappa was 0.911, which represented almost perfect consistency. CONCLUSIONS: PAINet can accurately distinguish between normal periapical tissues, CBCTPAI 1-2, CBCTPAI 3-5, and young permanent teeth. Its results were highly consistent with expert opinions. It can help junior doctors diagnose and score AP, reducing the burden. It can also be promoted in areas where experts are lacking to provide professional diagnostic opinions.


Subject(s)
Algorithms , Artificial Intelligence , Cone-Beam Computed Tomography , Periapical Periodontitis , Cone-Beam Computed Tomography/methods , Humans , Periapical Periodontitis/diagnostic imaging , Reproducibility of Results , Deep Learning
5.
Development ; 147(12)2020 06 17.
Article in English | MEDLINE | ID: mdl-32439762

ABSTRACT

Methylation of histone 3 lysine 4 (H3K4) is a major epigenetic system associated with gene expression. In mammals there are six H3K4 methyltransferases related to yeast Set1 and fly Trithorax, including two orthologs of fly Trithorax-related: MLL3 and MLL4. Exome sequencing has documented high frequencies of MLL3 and MLL4 mutations in many types of human cancer. Despite this emerging importance, the requirements of these paralogs in mammalian development have only been incompletely reported. Here, we examined the null phenotypes to establish that MLL3 is first required for lung maturation, whereas MLL4 is first required for migration of the anterior visceral endoderm that initiates gastrulation in the mouse. This collective cell migration is preceded by a columnar-to-squamous transition in visceral endoderm cells that depends on MLL4. Furthermore, Mll4 mutants display incompletely penetrant, sex-distorted, embryonic haploinsufficiency and adult heterozygous mutants show aspects of Kabuki syndrome, indicating that MLL4 action, unlike MLL3, is dosage dependent. The highly specific and discordant functions of these paralogs in mouse development argues against their action as general enhancer factors.


Subject(s)
Histone-Lysine N-Methyltransferase/metabolism , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Abnormalities, Multiple/veterinary , Alleles , Animals , Embryo, Mammalian/metabolism , Embryonic Development , Face/abnormalities , Face/pathology , Female , Genotype , Hematologic Diseases/genetics , Hematologic Diseases/pathology , Hematologic Diseases/veterinary , Histone-Lysine N-Methyltransferase/chemistry , Histone-Lysine N-Methyltransferase/genetics , Lung/growth & development , Lung/metabolism , Male , Mice , Mice, Knockout , Mutagenesis , Pregnancy , Respiratory Insufficiency/etiology , Time Factors , Vestibular Diseases/genetics , Vestibular Diseases/pathology , Vestibular Diseases/veterinary
6.
Appl Opt ; 62(10): D97-D103, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37132774

ABSTRACT

To quantify the architecture and select the ideal ideotype, it is vital to accurately measure the dimension of each part of the mantis shrimp. Point clouds have become increasingly popular in recent years as an efficient solution. However, the current manual measurement is labor intensive and costly and has high uncertainty. Automatic organ point cloud segmentation is a prerequisite and core step for phenotypic measurements of mantis shrimps. Nevertheless, little work focuses on mantis shrimp point cloud segmentation. To fill this gap, this paper develops a framework for automated organ segmentation of mantis shrimps from multiview stereo (MVS) point clouds. First, a Transformer-based MVS architecture is applied to generate dense point clouds from a set of calibrated phone images and estimated camera parameters. Next, an improved point cloud segmentation (named ShrimpSeg) that exploits both local and global features based on contextual information is proposed for organ segmentation of mantis shrimps. According to the evaluation results, the per-class intersection over union of organ-level segmentation is 82.4%. Comprehensive experiments demonstrate the effectiveness of ShrimpSeg, outperforming other commonly used segmentation methods. This work may be helpful for improving shrimp phenotyping and intelligent aquaculture at the level of production-ready.


Subject(s)
Aquaculture , Electric Power Supplies
7.
World J Surg Oncol ; 21(1): 297, 2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37723513

ABSTRACT

BACKGROUND: An understanding of the impact of goal-directed fluid therapy (GDFT) on the outcomes of patients undergoing one-lung ventilation (OLV) for thoracic surgery remains incomplete and controversial. This meta-analysis aimed to assess the effect of GDFT compared to other fluid therapy strategies on the incidence of postoperative complications in patients with OLV. METHODS: The Embase, Cochrane Library, Web of Science, and MEDLINE via PubMed databases were searched from their inception to November 30, 2022. Forest plots were constructed to present the results of the meta-analysis. The quality of the included studies was evaluated using the Cochrane Collaboration tool and Risk Of Bias In Non-Randomized Study of Interventions (ROBINS-I). The primary outcome was the incidence of postoperative complications. Secondary outcomes were the length of hospital stay, PaO2/FiO2 ratio, total fluid infusion, inflammatory factors (TNF-α, IL-6), and postoperative bowel function recovery time. RESULTS: A total of 1318 patients from 11 studies were included in this review. The GDFT group had a lower incidence of postoperative complications [odds ratio (OR), 0.47; 95% confidence interval (95% CI), 0.29-0.75; P = 0.002; I 2, 67%], postoperative pulmonary complications (OR 0.48, 95% CI 0.27-0.83; P = 0.009), and postoperative anastomotic leakage (OR 0.51, 95% CI 0.27-0.97; P = 0.04). The GDFT strategy reduces total fluid infusion. CONCLUSIONS: GDFT is associated with lower postoperative complications and better survival outcomes after thoracic surgery for OLV.


Subject(s)
One-Lung Ventilation , Thoracic Surgery , Humans , One-Lung Ventilation/adverse effects , Goals , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Fluid Therapy/adverse effects
8.
Opt Express ; 30(9): 15327-15343, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35473255

ABSTRACT

The influence of oceanic turbulence and pointing error impairments on the underwater wireless optical communication (UWOC) systems is considered in this study. We propose a generalized fading model, which comprises the path loss due to the absorption and scattering, the oceanic turbulence (modeled by Málaga distribution), and the pointing error impairments resulting from ocean movements. Thereafter, closed-form expressions of the average symbol error probability (SEP) and average channel capacity are proposed for optical waves propagate in oceanic turbulence with the M-ary pulse position modulation (PPM) and under the constraints of the limited average-power and peak-power. The Monte Carlo simulations are conducted to validate the analytical results and demonstrate that the fading parameters, including the mean-squared temperature, the salinity-temperature contribution factor, jitters, and water conditions, significantly affect the system performance. Moreover, the thermal noise and quantum noise in ocean environment have more serious impact than the background noise. Finally, we prove that the UWOC systems with the pure peak-power constraint performs better than that limited by average-power and peak-power.

9.
Opt Express ; 30(21): 38804-38820, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-36258437

ABSTRACT

The influence of the ocean depth and anisotropic tilt angle on vertical underwater wireless optical communication (UWOC) systems is considered in this study. We propose a power spectrum model of oceanic turbulence with an anisotropic tilt angle for the first time. Thereafter, the expression of the scintillation index is derived for a spherical wave propagating over anisotropic oceanic turbulence in the vertical link. In addition, considering the temperature and salinity, relevant data of the Atlantic and Pacific oceans at different depths are selected to study further the effect of ocean depth on the scintillation index. The results indicate that the scintillation index strongly depends on the ocean depth and anisotropic tilt angle. Moreover, the scintillation index is also related to other parameters, such as temperature and salinity, kinematic viscosity, the anisotropic factor, optical wavelength, and propagation distance. The presented results can be beneficial in designing optical wireless communication systems in the ocean environment.

10.
Entropy (Basel) ; 23(6)2021 Jun 04.
Article in English | MEDLINE | ID: mdl-34199779

ABSTRACT

Cyber-physical systems (CPS) have been widely employed as wireless control networks. There is a special type of CPS which is developed from the wireless networked control systems (WNCS). They usually include two communication links: Uplink transmission and downlink transmission. Those two links form a closed-loop. When such CPS are deployed for time-sensitive applications such as remote control, the uplink and downlink propagation delay are non-negligible. However, existing studies on CPS/WNCS usually ignore the propagation delay of the uplink and downlink channels. In order to achieve the best balance between uplink and downlink transmissions under such circumstances, we propose a heuristic framework to obtain the optimal scheduling strategy that can minimize the long-term average control cost. We model the optimization problem as a Markov decision process (MDP), and then give the sufficient conditions for the existence of the optimal scheduling strategy. We propose the semi-predictive framework to eliminate the impact of the coupling characteristic between the uplink and downlink data packets. Then we obtain the lookup table-based optimal offline strategy and the neural network-based suboptimal online strategy. Numerical simulation shows that the scheduling strategies obtained by this framework can bring significant performance improvements over the existing strategies.

11.
Development ; 144(14): 2606-2617, 2017 07 15.
Article in English | MEDLINE | ID: mdl-28619824

ABSTRACT

Germ cell development involves major reprogramming of the epigenome to prime the zygote for totipotency. Histone 3 lysine 4 (H3K4) methylations are universal epigenetic marks mediated in mammals by six H3K4 methyltransferases related to fly Trithorax, including two yeast Set1 orthologs: Setd1a and Setd1b. Whereas Setd1a plays no role in oogenesis, we report that Setd1b deficiency causes female sterility in mice. Oocyte-specific Gdf9-iCre conditional knockout (Setd1bGdf9 cKO) ovaries develop through all stages; however, follicular loss accumulated with age and unfertilized metaphase II (MII) oocytes exhibited irregularities of the zona pellucida and meiotic spindle. Most Setd1bGdf9 cKO zygotes remained in the pronuclear stage and displayed polyspermy in the perivitelline space. Expression profiling of Setd1bGdf9 cKO MII oocytes revealed (1) that Setd1b promotes the expression of the major oocyte transcription factors including Obox1, 2, 5, 7, Meis2 and Sall4; and (2) twice as many mRNAs were upregulated than downregulated, suggesting that Setd1b also promotes the expression of negative regulators of oocyte development with multiple Zfp-KRAB factors implicated. Together, these findings indicate that Setd1b serves as maternal effect gene through regulation of the oocyte gene expression program.


Subject(s)
Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Oogenesis/genetics , Oogenesis/physiology , Animals , Blastocyst/cytology , Blastocyst/metabolism , Epigenesis, Genetic , Female , Gene Expression Profiling , Gene Expression Regulation, Developmental , Growth Differentiation Factor 9/deficiency , Growth Differentiation Factor 9/genetics , Growth Differentiation Factor 9/metabolism , Histone-Lysine N-Methyltransferase/deficiency , Male , Maternal Inheritance , Mice , Mice, Knockout , Mice, Transgenic , Oocytes/cytology , Oocytes/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Single-Cell Analysis , Transcription Factors/genetics , Transcription Factors/metabolism , Zona Pellucida/metabolism , Zona Pellucida/pathology , Zygote/cytology , Zygote/metabolism
12.
J Opt Soc Am A Opt Image Sci Vis ; 37(10): 1622-1629, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-33104609

ABSTRACT

The influence of anisotropic weak-to-strong oceanic turbulence on the performance of underwater optical communication (UWOC) systems is investigated in this paper. The Málaga distribution fading model is used to model the statistical distribution of a spherical wave propagating through anisotropic oceanic turbulence, which is a versatile model of weak-to-strong turbulence. First, the scintillation index for a spherical wave propagating in oceanic turbulence is formulated, and closed-form expressions for the outage probability and average channel capacity of the UWOC systems are then proposed in terms of Meijer's G function. The simulation results demonstrate that both the outage probability and the average channel capacity strongly depend on the parameters of oceanic turbulence, such as the ratio of temperature to the contribution of salinity to the refractive index spectrum, the rate of dissipation of kinetic energy per unit mass of fluid, and the rate of dissipation of mean-squared temperature; they are also related to system parameters such as wavelength and aperture diameter. Numerical results are provided to verify the accuracy of our proposed expressions for outage probability and average channel capacity, and perfect agreement is observed.

13.
Entropy (Basel) ; 21(6)2019 Jun 08.
Article in English | MEDLINE | ID: mdl-33267290

ABSTRACT

Due to the high splitting-gain of dense small cells, Ultra-Dense Network (UDN) is regarded as a promising networking technology to achieve high data rate and low latency in 5G mobile communications. In UDNs, each User Equipment (UE) may receive signals from multiple Base Stations (BSs), which impose severe interference in the networks and in turn motivates the possibility of using Coordinated Multi-Point (CoMP) transmissions to further enhance network capacity. In CoMP-based Ultra-Dense Networks, a great challenge is to tradeoff between the gain of network throughput and the worsening backhaul latency. Caching popular files on BSs has been identified as a promising method to reduce the backhaul traffic load. In this paper, we investigated content placement strategies and user association algorithms for the proactive caching ultra dense networks. The problem has been formulated to maximize network throughput of cell edge UEs under the consideration of backhaul load, which is a constrained non-convex combinatorial optimization problem. To decrease the complexity, the problem is decomposed into two suboptimal problems. We first solved the content placement algorithm based on the cross-entropy (CE) method to minimize the backhaul load of the network. Then, a user association algorithm based on the CE method was employed to pursue larger network throughput of cell edge UEs. Simulation were conducted to validate the performance of the proposed cross-entropy based schemes in terms of network throughput and backhaul load. The simulation results show that the proposed cross-entropy based content placement scheme significantly outperform the conventional random and Most Popular Content placement schemes, with with 50% and 20% backhaul load decrease respectively. Furthermore, the proposed cross-entropy based user association scheme can achieve 30% and 23% throughput gain, compared with the conventional N-best, No-CoMP, and Threshold based user association schemes.

14.
Tissue Eng Part C Methods ; 30(6): 255-267, 2024.
Article in English | MEDLINE | ID: mdl-38756098

ABSTRACT

Human amniotic epithelial cells (hAECs) are novel and promising therapeutic agents for patients suffering from degenerative diseases. Studies have demonstrated that the therapeutic effects of hAECs mainly depend on their paracrine components. Currently, appropriate pretreatment is a widely confirmed strategy for enhancing the repair potential of stem cells; however, the effect of proinflammatory factor pretreatment on hAECs and their secretome is still unclear. In this study, we used the well-characterized proinflammatory factors tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) to stimulate hAECs and analyzed the effect of TNF-α and IFN-γ on hAECs, including gene expression profile, paracrine proteins, and microRNAs (miRNAs) in exosomes. Results showed that TNF-α and IFN-γ pretreatment improved the viability of hAECs but inhibited the proliferation of hAECs. TNF-α and IFN-γ pretreatment altered the gene expression profile of hAECs, and upregulated differentially expressed genes were predominantly enriched in biological adhesion, antioxidant activity, and response to IFN-beta. In addition, TNF-α and IFN-γ pretreatment enhanced the paracrine secretion of cytokines by hAECs. The upregulated differentially expressed proteins were mainly enriched in tissue remodeling proteins and cytokine-cytokine receptor. Notably, the expression of miRNAs in exosomes from hAECs was also changed by TNF-α and IFN-γ pretreatment. The target genes of upregulated exosomal miRNAs substantially contributed to the response to stimulus, metabolic pathways, and PI3K-Akt signaling pathway. Our findings improve our understanding of the biological characteristics of hAECs after proinflammatory factor pretreatment and provide novel insights to strengthen and optimize the therapeutic potential of hAECs and their secretome in regenerative medicine.


Subject(s)
Amnion , Epithelial Cells , Humans , Amnion/cytology , Amnion/metabolism , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Secretome , Exosomes/metabolism , Interferon-gamma/pharmacology , Interferon-gamma/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Cell Proliferation/drug effects , MicroRNAs/metabolism , MicroRNAs/genetics , Cell Survival/drug effects , Female , Cytokines/metabolism , Cells, Cultured , Inflammation Mediators/metabolism
15.
Elife ; 122024 Mar 06.
Article in English | MEDLINE | ID: mdl-38446538

ABSTRACT

The scarcity of hematopoietic stem cells (HSCs) restricts their use in both clinical settings and experimental research. Here, we examined a recently developed method for expanding rigorously purified murine HSCs ex vivo. After 3 weeks of culture, only 0.1% of cells exhibited the input HSC phenotype, but these accounted for almost all functional long-term HSC activity. Input HSCs displayed varying potential for ex vivo self-renewal, with alternative outcomes revealed by single-cell multimodal RNA and ATAC sequencing profiling. While most HSC progeny offered only transient in vivo reconstitution, these cells efficiently rescued mice from lethal myeloablation. The amplification of functional HSC activity allowed for long-term multilineage engraftment in unconditioned hosts that associated with a return of HSCs to quiescence. Thereby, our findings identify several key considerations for ex vivo HSC expansion, with major implications also for assessment of normal HSC activity.


Subject(s)
Hematopoietic Stem Cells , RNA , Animals , Mice , Cell Division , Phenotype
16.
Acta Pharm Sin B ; 14(9): 3901-3915, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39309495

ABSTRACT

The intestinal mucus barrier is an important line of defense against gut pathogens. Damage to this barrier brings bacteria into close contact with the epithelium, leading to intestinal inflammation. Therefore, its restoration is a promising strategy for alleviating intestinal inflammation. This study showed that Abelmoschus manihot polysaccharide (AMP) fortifies the intestinal mucus barrier by increasing mucus production, which plays a crucial role in the AMP-mediated amelioration of colitis. IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10. Moreover, bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila. These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota. This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

17.
Adv Sci (Weinh) ; : e2402393, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39229959

ABSTRACT

Sleep deprivation (SD) is observed to adversely affect the reproductive health of women. However, its precise physiological mechanisms remain largely elusive. In this study, using a mouse model of SD, it is demonstrated that SD induces the depletion of ovarian primordial follicles, a phenomenon not attributed to immune-mediated attacks or sympathetic nervous system activation. Rather, the excessive secretion of stress hormones, namely norepinephrine (NE) and epinephrine (E), by overactive adrenal glands, has emerged as a key mediator. The communication pathway mediated by the KIT ligand (KITL)-KIT between granulosa cells and oocytes plays a pivotal role in primordial follicle activation. SD heightened the levels of NE/E that stimulates the activation of the KITL-KIT/PI3K and mTOR signaling cascade in an ß2 adrenergic receptor (ADRB2)-dependent manner, thereby promoting primordial follicle activation and consequent primordial follicle loss in vivo. In vitro experiments further corroborate these observations, revealing that ADRB2 upregulates KITL expression in granulosa cells via the activation of the downstream cAMP/PKA pathway. Together, these results reveal the significant involvement of ADRB2 signaling in the depletion of ovarian primordial follicles under sleep-deprived conditions. Additionally, ADRB2 antagonists are proposed for the treatment or prevention of excessive activation of primordial follicles induced by SD.

18.
Appl Biochem Biotechnol ; 196(2): 878-895, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37256487

ABSTRACT

Six compounds were isolated and purified from the crude acetone extract of Aspergillus niger xj. Characterization of all compounds was done by NMR and MS. On the basis of chemical and spectral analysis structure, six compounds were elucidated as metazachlor (1), nonacosane (2), palmitic acid (3), 5,5'-oxybis(5-methylene-2-furaldehyde) (4), dimethyl 5-nitroisophthalate (5) and cholesta-3,5-dien-7-one (6), respectively, and compounds 1, 4, 5 and 6 were isolated for the first time from A. niger. To evaluate the antibacterial activity of compounds 1-6 against three plant pathogenic bacteria (Agrobacterium tumefaciens T-37, Erwinia carotovora EC-1 and Ralstonia solanacearum RS-2), and the minimum inhibitory concentrations (MICs) were determined by broth microdilution method in 96-well microtiter plates. Results of the evaluation of the antibacterial activity showed that T-37 strain was more susceptible to metazachlor with the lowest MIC of 31.25 µg/mL. The antibacterial activity of metazachlor has rarely been reported, thus the antibacterial mechanism of metazachlor against T-37 strain were investigated. The permeability of cell membrane demonstrated that cells membranes were broken by metazachlor, which caused leakage of ions in cells. SDS-PAGE of T-37 proteins indicated that metazachlor could damage bacterial cells through the destruction of cellular proteins. Scanning electron microscopy results showed obvious morphological and ultrastructural changes in the T-37 cells, further confirming the cell membrane damages caused by metazachlor. Overall, our findings demonstrated that the ability of metazachlor to suppress the growth of T-37 pathogenic bacteria makes it potential biocontrol agents.


Subject(s)
Anti-Bacterial Agents , Aspergillus niger , Aspergillus , Aspergillus niger/metabolism , Fermentation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Acetamides , Bacteria/metabolism , Microbial Sensitivity Tests , Plant Extracts
19.
J Agric Food Chem ; 72(35): 19274-19285, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39185617

ABSTRACT

Using antifungal agrochemicals as the most economical solution might reduce plant diseases caused by pathogenic fungi, which have a significant negative impact on the quality and yield of food worldwide. In this work, 33 compounds (G) containing 1,2,3-triazole and malononitrile structures were synthesized. When the compounds were tested in vitro against six fungal species, they exhibited significant fungicidal activity toward Botrytis cinerea and Rhizoctonia solani. Compounds G17 and G30 displayed promising in vivo efficacy, with an EC50 of 0.19 and 0.27 mg/L respectively against R. solani. Fungal ergosterol production was suppressed by compounds G17 and G30, according to a preliminary analysis of their mechanism of action on R. solani using transcriptomics and scanning electron microscopy. It has been shown through experimentation that compounds G17 and G30 prevent R. solani from synthesizing ergosterol. Ultimately, it was anticipated that compounds G17 and G30 would be discovered to be low-toxic.


Subject(s)
Botrytis , Fungicides, Industrial , Nitriles , Rhizoctonia , Triazoles , Triazoles/chemistry , Triazoles/pharmacology , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Fungicides, Industrial/chemical synthesis , Rhizoctonia/drug effects , Nitriles/chemistry , Nitriles/pharmacology , Botrytis/drug effects , Drug Design , Structure-Activity Relationship , Plant Diseases/microbiology , Molecular Structure
20.
Leukemia ; 38(5): 1115-1130, 2024 May.
Article in English | MEDLINE | ID: mdl-38555405

ABSTRACT

Infant and adult MLL1/KMT2A-rearranged (MLLr) leukemia represents a disease with a dismal prognosis. Here, we present a functional and proteomic characterization of in utero-initiated and adult-onset MLLr leukemia. We reveal that fetal MLL::ENL-expressing lymphomyeloid multipotent progenitors (LMPPs) are intrinsically programmed towards a lymphoid fate but give rise to myeloid leukemia in vivo, highlighting a complex interplay of intra- and extracellular factors in determining disease subtype. We characterize early proteomic events of MLL::ENL-mediated transformation in fetal and adult blood progenitors and reveal that whereas adult pre-leukemic cells are mainly characterized by retained myeloid features and downregulation of ribosomal and metabolic proteins, expression of MLL::ENL in fetal LMPPs leads to enrichment of translation-associated and histone deacetylases signaling proteins, and decreased expression of inflammation and myeloid differentiation proteins. Integrating the proteome of pre-leukemic cells with their secretome and the proteomic composition of the extracellular environment of normal progenitors highlights differential regulation of Igf2 bioavailability, as well as of VLA-4 dimer and its ligandome, upon initiation of fetal- and adult-origin leukemia, with implications for human MLLr leukemia cells' ability to communicate with their environment through granule proteins. Our study has uncovered opportunities for targeting ontogeny-specific proteomic vulnerabilities in in utero-initiated and adult-onset MLLr leukemia.


Subject(s)
Myeloid-Lymphoid Leukemia Protein , Myeloid-Lymphoid Leukemia Protein/genetics , Myeloid-Lymphoid Leukemia Protein/metabolism , Humans , Mice , Animals , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Gene Rearrangement , Proteomics/methods , Fetus/metabolism , Adult , Female , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Leukemia/genetics , Leukemia/pathology , Leukemia/metabolism
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