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1.
Exp Gerontol ; 196: 112578, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39245081

ABSTRACT

BACKGROUND: Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults. METHODS: The study was based on data collected from the 1999-2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors. RESULTS: In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80-0.94, P < 0.001) in older adults. The interaction analysis showed that the association might be affected by diabetes mellitus and smoking status. Additionally, an inflection point between the SPISE index and HF was found among older women. CONCLUSIONS: An inverse correlation was detected between the SPISE index and HF in the elderly. This could provide new insight into the prevention and management of HF in the elderly population.

2.
BMC Genomics ; 25(1): 862, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39278945

ABSTRACT

BACKGROUND: The Bucephalidae is a large family of digenean trematodes but most previous analyses of its phylogenetic position have relied on a single mitochondrial gene or morphological features. Mitochondrial genomes (mitogenomes) remain unavailable for the entire family. To address this, we sequenced the complete mitogenome of Dollfustrema vaneyi and analyzed the phylogenetic relationships with other trematodes. RESULTS: The circular genome of Dollfustrema vaneyi spanned 14,959 bp and contained 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a major non-coding region. We used concatenated amino acid and nucleotide sequences of all 36 genes for phylogenetic analyses, conducted using MrBayes, IQ-TREE and PhyloBayes. We identified pronounced topological instability across different analyses. The addition of recently sequenced two mitogenomes for the Aspidogastrea subclass along with the use of a site-heterogeneous model stabilized the topology, particularly the positions of Azygiidae and Bucephalidae. The stabilized results indicated that Azygiidae was the closest lineage to Bucephalidae in the available dataset, and together, they clustered at the base of the Plagiorchiida. CONCLUSIONS: Our study provides the first comprehensive description and annotation of the mitochondrial genome for the Bucephalidae family. The results indicate a close phylogenetic relationship between Azygiidae and Bucephalidae, and reveal their basal placement within the order Plagiorchiida. Furthermore, the inclusion of Aspidogastrea mitogenomes and the site-heterogeneous model significantly improved the topological stability. These data will provide key molecular resources for future taxonomic and phylogenetic studies of the family Bucephalidae.


Subject(s)
Genome, Mitochondrial , Phylogeny , Trematoda , Animals , Trematoda/genetics , Trematoda/classification , RNA, Transfer/genetics
3.
J Hazard Mater ; 478: 135562, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39178779

ABSTRACT

The global attention on microplastic pollution and its implications for human health has grown in recent years. Additionally, the co-existence of heavy metals may significantly alter microplastics' physicochemical characteristics, potentially amplifying their overall toxicity-a facet that remains less understood. In this study, we focused the membrane toxicity of modified polystyrene microplastics (PS-MPs) following cadmium (Cd) pretreatment. Our findings revealed that Cd-pretreated PS-MPs exacerbated their toxic effects, including diminished membrane integrity and altered phase fluidity in simulated lipid membrane giant unilamellar vesicles (GUVs), as well as heightened membrane permeability, protein damage, and lipid peroxidation in red blood cells and macrophages. Mechanistically, these augmented membrane toxicities can be partially ascribed to modifications in the surface roughness and hydrophilicity of Cd-pretreated PS-MPs, as well as to interactions between PS-MPs and lipid bilayers. Notably, hydrogen bonds emerged as a crucial mechanism underlying the enhanced interaction of PS-MPs with lipid bilayers.


Subject(s)
Cadmium , Hydrogen Bonding , Microplastics , Polystyrenes , Polystyrenes/chemistry , Polystyrenes/toxicity , Microplastics/toxicity , Microplastics/chemistry , Cadmium/toxicity , Cadmium/chemistry , Animals , Humans , Lipid Bilayers/chemistry , Macrophages/drug effects , Lipid Peroxidation/drug effects , Erythrocytes/drug effects , Unilamellar Liposomes/chemistry , Cell Membrane/drug effects , Mice
4.
Heredity (Edinb) ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095653

ABSTRACT

Studies of forces driving interlineage variability in the evolutionary rates (both sequence and architecture) of mitochondrial genomes often produce contradictory results. Flatworms (Platyhelminthes) exhibit the fastest-evolving mitogenomic sequences among all bilaterian phyla. To test the effects of multiple factors previously associated with different aspects of mitogenomic evolution, we used mitogenomes of 223 flatworm species, phylogenetic multilevel regression models, and causal inference. Thermic host environment (endothermic vs. ectothermic) had nonsignificant impacts on both sequence evolution and mitogenomic size. Mitogenomic gene order rearrangements (GORR) were mostly positively correlated with mitogenomic size (R2 ≈ 20-30%). Longevity was not (negatively) correlated with sequence evolution in flatworms. The predominantly free-living "turbellaria" exhibited much shorter branches and faster-evolving mitogenomic architecture than parasitic Neodermata. As a result, "parasitism" had a strong explanatory power on the branch length variability (>90%), and there was a negative correlation between GORR and branch length. However, the stem branch of Neodermata comprised 63.6% of the total average branch length. This evolutionary period was also marked by a high rate of gene order rearrangements in the ancestral Neodermata. We discuss how this period of rapid evolution deep in the evolutionary history may have decoupled sequence evolution rates from longevity and GORR, and overestimated the explanatory power of "parasitism". This study shows that impacts of variables often vary across lineages, and stresses the importance accounting for the episodic nature of evolutionary patterns in studies of mitogenomic evolution.

5.
Environ Sci Technol ; 58(36): 15938-15948, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39192575

ABSTRACT

Accurately mapping ground-level ozone concentrations at high spatiotemporal resolution (daily, 1 km) is essential for evaluating human exposure and conducting public health assessments. This requires identifying and understanding a proxy that is well-correlated with ground-level ozone variation and available with spatiotemporal high-resolution data. This study introduces a high-resolution ozone modeling method utilizing the XGBoost algorithm with satellite-derived land surface temperature (LST) as the primary predictor. Focusing on China in 2019, our model achieved a cross-validation R2 of 0.91 and a root-mean-square error (RMSE) of 13.51 µg/m3. We provide detailed maps highlighting ground-level ozone concentrations in urban areas, uncovering spatial variations previously unresolved, along with time series aligning with established understandings of ozone dynamics. Our local interpretation of the machine learning model underscores the significant contribution of LST to spatiotemporal ozone variations, surpassing other meteorological, pollutant, and geographical predictors in its influence. Validation results indicate that model performance decreases as spatial resolution becomes coarser, with R2 decreasing from 0.91 for the 1 km model to 0.85 for the 25 km model. The methodology and data sets generated by this study offer new insights into ground-level ozone variability and mapping and can significantly aid in exposure assessment and epidemiological research related to this critical environmental challenge.


Subject(s)
Machine Learning , Ozone , Temperature , Ozone/analysis , Environmental Monitoring/methods , China , Air Pollutants , Humans
6.
Sci Rep ; 14(1): 15344, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38961220

ABSTRACT

Decreased myocardial capillary density has been reported as an important histopathological feature associated with various heart disorders. Quantitative assessment of cardiac capillarization typically involves double immunostaining of cardiomyocytes (CMs) and capillaries in myocardial slices. In contrast, single immunostaining of basement membrane protein is a straightforward approach to simultaneously label CMs and capillaries, presenting fewer challenges in background staining. However, subsequent image analysis always requires expertise and laborious manual work to identify and segment CMs/capillaries. Here, we developed an image analysis tool, AutoQC, for automatic identification and segmentation of CMs and capillaries in immunofluorescence images of basement membrane. Commonly used capillarization-related measurements can be derived from segmentation results. By leveraging the power of a pre-trained segmentation model (Segment Anything Model, SAM) via prompt engineering, the training of AutoQC required only a small dataset with bounding box annotations instead of pixel-wise annotations. AutoQC outperformed SAM (without prompt engineering) and YOLOv8-Seg, a state-of-the-art instance segmentation model, in both instance segmentation and capillarization assessment. Thus, AutoQC, featuring a weakly supervised algorithm, enables automatic segmentation and high-throughput, high-accuracy capillarization assessment in basement-membrane-immunostained myocardial slices. This approach reduces the training workload and eliminates the need for manual image analysis once AutoQC is trained.


Subject(s)
Basement Membrane , Image Processing, Computer-Assisted , Myocardium , Myocytes, Cardiac , Basement Membrane/metabolism , Animals , Myocytes, Cardiac/metabolism , Myocardium/metabolism , Myocardium/pathology , Image Processing, Computer-Assisted/methods , Capillaries/metabolism , Algorithms , Mice , Coronary Vessels/metabolism , Coronary Vessels/pathology
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 730-735, 2024 Jul 15.
Article in Chinese | MEDLINE | ID: mdl-39014950

ABSTRACT

OBJECTIVES: To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. METHODS: A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. RESULTS: Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). CONCLUSIONS: The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.


Subject(s)
Granulomatous Disease, Chronic , Tomography, X-Ray Computed , Humans , Granulomatous Disease, Chronic/diagnostic imaging , Infant, Newborn , Male , Female , Retrospective Studies , Thorax/diagnostic imaging
8.
Inorg Chem ; 63(31): 14665-14672, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39039656

ABSTRACT

Recently, Cr3+-activated near-infrared (NIR) phosphors have received much more attention due to their excellent photoluminescence (PL) properties. However, most of them suffer from poor thermal stability which limits further application. Herein, a novel Lu2CaGa4SnO12:Cr3+ phosphor with broadband NIR emission (λem = 750 nm) is synthesized successfully. Despite the good luminescence property, its PL intensity decreases obviously with temperature (I425 K = 79%). To improve the thermal stability, a series of Lu2+xCa1-xGa4+xSn1-xO12:Cr3+ (x = 0-1.0) solid solutions with tunable thermal quenching performance have been designed. It is found that the fluorescence intensity ratio (FIR) of 4T2 → 4A2 to 2E → 4A2 [I(4T2)/I(2E)] transitions (i.e. electron occupation) decreases monotonously with increasing [Lu3+-Ga3+] co-substitution, resulting from a strengthened crystal field strength and increased energy difference between 4T2 and 2E energy levels. Benefiting from the various thermal population and energy difference Δ', the PL thermal quenching behavior of Lu2+xCa1-xGa4+xSn1-xO12:Cr3+ can be adjusted easily, and the corresponding mechanism is explored in detail. Most notably, the emission intensity of Lu2+xCa1-xGa4+xSn1-xO12:Cr3+ at 425 K can reach up to 142% compared with that at 300 K, which may be the best for Cr3+-activated NIR phosphors. This work may provide an alternative path for the development of thermally stable broadband NIR phosphors.

9.
Int J Biol Macromol ; 272(Pt 2): 132923, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38848835

ABSTRACT

Severe bleeding from deep and irregular wounds poses a significant challenge in prehospital and surgical settings. To address this issue, we developed a novel chitosan-based hemostatic dressing with a magnetic targeting mechanism using Fe3O4, termed bovine serum albumin-modified Fe3O4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe3O4@KA/CS). This dressing enhances hemostasis by magnetically guiding the agent to the wound site. In vitro, the hemostatic efficacy of BSA/Fe3O4@KA/CS is comparable to that of commercial chitosan (Celox™) and is not diminished by the modification. In vivo, BSA/Fe3O4@KA/CS demonstrated superior hemostatic performance and reduced blood loss compared to Celox™. The hemostatic mechanism of BSA/Fe3O4@KA/CS includes the concentration of solid blood components through water absorption, adherence to blood cells, and activation of the endogenous coagulation pathway. Magnetic field targeting is crucial in directing the dressing to deep hemorrhagic sites. Additionally, safety assessments have confirmed the biocompatibility and biodegradability of BSA/Fe3O4@KA/CS. In conclusion, we introduce a novel approach to modify chitosan using magnetic guidance for effective hemostasis, positioning BSA/Fe3O4@KA/CS as a promising candidate for managing various wounds.


Subject(s)
Bandages , Chitosan , Hemostatics , Serum Albumin, Bovine , Chitosan/chemistry , Serum Albumin, Bovine/chemistry , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Porosity , Ketoglutaric Acids/chemistry , Ketoglutaric Acids/pharmacology , Cattle , Male , Hemorrhage/drug therapy , Hemorrhage/therapy , Mice
10.
ChemSusChem ; : e202400448, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38797704

ABSTRACT

The catalytic system of biological nitrogen fixation in nature primarily relies on the "FeMo cofactor" within nitrogenase enzymes. Inspired by this natural structure, we have designed a bionic inorganic counterpart, iron-doped MoSe2, for the efficient electroreduction of dinitrogen to ammonia. The introduced Fe dopant significantly enhances nitrogen fixation activity of MoSe2. Furthermore, we constructed a heterostructure catalyst, the Fe-MoSe2/Mo2C with more versatile Mo valence states. The heterostructured electrocatalyst achieves an ammonia production rate of 3.38 µg cm-2 h-1, and a Faradaic efficiency of 30.8 %, which is ~5 fold higher than that of pristine MoSe2. This study presents a novel approach for designing bionic nitrogen fixation electrocatalysts.

11.
ACS Appl Mater Interfaces ; 16(19): 24580-24589, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38706440

ABSTRACT

The precise design and synthesis of active sites to improve catalyst's performance has emerged as a promising tactic for electrochemistry. However, it is challenging to combine different types of active sites and manipulate them simultaneously at atomic resolution. Here, we present a strategy to synthesize Re atom-doped Cu twin boundaries (TBs), through pulsed electrodeposition and boundary segregation. The Re-doped Cu TBs demonstrate a highly efficient nitrogen reduction reaction (NRR) performance. Re-doped Cu TBs showed a turnover frequency of ∼5889 s-1, ∼800 times higher than the pure Cu TB active centers (∼7 s-1). In addition to the "acceptance-donation" activation of N2 molecules, theoretical calculations also reveal that the Re-Re dimer on TB can boost the NRR and impede the hydrogen evolution reaction synchronously, rendering Re-doped Cu TB catalysts with high NRR activity and selectivity.

12.
J Proteomics ; 300: 105177, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38631426

ABSTRACT

Tuberculosis (TB) is a serious cause of infectious death worldwide. Recent studies have reported that about 30% of the Mtb proteome was modified post-translationally, indicating that their functions are essential for drug resistance, mycobacterial survival, and pathogenicity. Among them, lysine acetylation, reversibly regulated by acetyltransferase and deacetylase, has important roles involved in energy metabolism, cellular adaptation, and protein interactions. However, the substrate and biological functions of these two important regulatory enzymes remain unclear. Herein, we utilized the non-pathogenic M. smegmatis strain as a model and systematically investigated the dynamic proteome changes in response to the overexpressing of MsKat/MsCobB in mycobacteria. A total of 4179 proteins and 1236 acetylated sites were identified in our data. Further analysis of the dynamic changes involved in proteome and acetylome showed that MsKat/MsCobB played a regulatory role in various metabolic pathways and nucleic acid processes. After that, the quantitative mass spectrometric method was utilized and proved that the AMP-dependent synthetase, Citrate synthase, ATP-dependent specificity component of the Clp protease, and ATP-dependent DNA/RNA helicases were identified to be the substrates of MsKat. Overall, our study provided an important resource underlying the substrates and functions of the acetylation regulatory enzymes in mycobacteria. SIGNIFICANCE: In this study, we systematically analyzed the dynamic molecular changes in response to the MsKat/MsCobB overexpression in mycobacteria at proteome and lysine acetylation level by using a TMT-based quantitative proteomic approach. Pathways related with glycolysis, degradation of branched chain amino acids, phosphotransferase system were affected after disturbance of the two regulates enzymes involved in lysine acetylation. We also proved that AMP-dependent synthetase Clp protease, ATP-dependent DNA/RNA helicases and citrate synthase was the substrate of MsKat according to our proteomic data and biological validation. Together, our study underlined the substrates and functions of the acetylation regulatory enzymes in mycobacteria.


Subject(s)
Bacterial Proteins , Lysine Acetyltransferases , Mycobacterium smegmatis , Mycobacterium smegmatis/enzymology , Mycobacterium smegmatis/metabolism , Bacterial Proteins/metabolism , Lysine Acetyltransferases/metabolism , Acetylation , Proteome/metabolism , Substrate Specificity , Lysine/metabolism
13.
Stem Cell Res Ther ; 15(1): 122, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38679727

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. METHODS: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. RESULTS: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p < 0.05). MSC transplantation improved the function of 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s at 6 months of follow-up (p = 0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p = 0.002). Inflammatory cytokines (TNF-α, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p = 0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. CONCLUSION: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance, and reducing chronic inflammation, suggest that HUC-MSC therapy may be a promising potential treatment option for aging frailty. TRIAL REGISTRATION: Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Quality of Life , Umbilical Cord , Humans , Female , Male , Double-Blind Method , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/adverse effects , Aged , Mesenchymal Stem Cells/cytology , Umbilical Cord/cytology , Frailty/therapy , Middle Aged , Aging/physiology , Aged, 80 and over , Treatment Outcome
14.
Adv Mater ; 36(26): e2313955, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38547845

ABSTRACT

Leukemia is a widespread hematological malignancy characterized by an elevated white blood cell count in both the blood and the bone marrow. Despite notable advancements in leukemia intervention in the clinic, a large proportion of patients, especially acute leukemia patients, fail to achieve long-term remission or complete remission following treatment. Therefore, leukemia therapy necessitates optimization to meet the treatment requirements. In recent years, a multitude of materials have undergone rigorous study to serve as delivery vectors or direct intervention agents to bolster the effectiveness of leukemia therapy. These materials include liposomes, protein-based materials, polymeric materials, cell-derived materials, and inorganic materials. They possess unique characteristics and are applied in a broad array of therapeutic modalities, including chemotherapy, gene therapy, immunotherapy, radiotherapy, hematopoietic stem cell transplantation, and other evolving treatments. Here, an overview of these materials is presented, describing their physicochemical properties, their role in leukemia treatment, and the challenges they face in the context of clinical translation. This review inspires researchers to further develop various materials that can be used to augment the efficacy of multiple therapeutic modalities for novel applications in leukemia treatment.


Subject(s)
Leukemia , Humans , Leukemia/therapy , Animals , Liposomes/chemistry , Polymers/chemistry , Biocompatible Materials/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry
15.
Polymers (Basel) ; 16(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38543468

ABSTRACT

A traumatic hemorrhage is fatal due to the great loss of blood in a short period of time; however, there are a few biomaterials that can stop the bleeding quickly due to the limited water absorption speed. Here, a highly absorbent polymer (HPA), polyacrylate, was prepared as it has the best structure-effectiveness relationship. Within a very short period of time (2 min), HPA continually absorbed water until it swelled up to its 600 times its weight; more importantly, the porous structure comprised the swollen dressing. This instantaneous swelling immediately led to rapid hemostasis in irregular wounds. We optimized the HPA preparation process to obtain a rapidly water-absorbent polymer (i.e., HPA-5). HPA-5 showed favorable adhesion and biocompatibility in vitro. A rat femoral arteriovenous complete shear model and a tail arteriovenous injury model were established. HPA exhibited excellent hemostatic capability with little blood loss and short hemostatic time compared with CeloxTM in both of the models. The hemostatic mechanisms of HPA consist of fast clotting by aggregating blood cells, activating platelets, and accelerating the coagulation pathway via water absorption and electrostatic interaction. HPA is a promising highly water-absorbent hemostatic dressing for rapid and extensive blood clotting after vessel injury.

16.
ACS Omega ; 9(9): 10276-10285, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38463329

ABSTRACT

l-threonine as an important precursor substance of l-isoleucine and improving its accumulation in Escherichia coli became an important idea to construct a chassis strain with high l-isoleucine production. Meanwhile, the effect of l-threonine metabolic pathway disruption in E. coli for the improved production of l-isoleucine remains unrevealed. In the present study, a mutant strain of E. coli was engineered by inactivating specific metabolic pathways (e.g., Δtdh, ΔltaE, and ΔyiaY) that were associated with l-threonine metabolism but unrelated to l-isoleucine synthesis. This was done with the aim to reduce the breakdown of l-threonine and, thereby, increase the production of l-isoleucine. The results obtained demonstrated a 72.3% increment in l-isoleucine production from 4.34 to 7.48 g·L-1 in the mutant strain compared with the original strain, with an unexpected 10.3% increment in bacterial growth as measured at OD600. Transcriptome analysis was also conducted on both the mutant strain NXU102 and the original strain NXU101 in the present study to gain a comprehensive understanding of their physiological attributes. The findings revealed a notable disparity in 1294 genes between the two strains, with 658 genes exhibiting up-regulation and 636 genes displaying down-regulation. The activity of tricarboxylic acid (TCA) cycle-related genes was found to decrease, but oxidative phosphorylation-related genes were highly up-regulated, which explained the increased activity of the mutant strain. For instance, l-lysine catabolism-related genes were found to be up-regulated, which reconfigured the carbon flow into the TCA cycle. The augmentation of acetic acid degradation pathway-related genes assisted in the reduction in acetic acid accumulation that could retard cell growth. Notably, substantial up-regulation of the majority of genes within the aspartate pathway could potentially account for the increased production of l-isoleucine in the present study. In this paper, a chassis strain with an l-isoleucine yield of 7.48 g·L-1 was successfully constructed by cutting off the threonine metabolic pathway. Meanwhile, transcriptomic analysis revealed that the cutting off of the threonine metabolic pathway induced perturbation of genes related to the pathways associated with the synthesis of l-isoleucine, such as the tricarboxylic acid cycle, glycolysis, and aspartic acid pathway.

17.
Article in English | MEDLINE | ID: mdl-38335071

ABSTRACT

Plant stomatal phenotype traits play an important role in improving crop water use efficiency, stress resistance and yield. However, at present, the acquisition of phenotype traits mainly relies on manual measurement, which is time-consuming and laborious. In order to obtain high-throughput stomatal phenotype traits, we proposed a real-time recognition network SLPA-Net for stomata localization and phenotypic analysis. After locating and identifying stomatal density data, ellipse fitting is used to automatically obtain phenotype data such as apertures. Aiming at the problems of small stomata and high similarity to background, we introduced ECANet to improve the accuracy of stoma and aperture location. In order to effectively alleviate the unbalance problem in bounding box regression, we replaced the Loss function with a more effective Focal EIoU Loss. The experimental results show that SLPA-Net has excellent performance in the migration generalization and robustness of stomata and apertures detection and identification, as well as the correlation between stomata phenotype data obtained and artificial data.


Subject(s)
Phenotype , Plant Stomata , Plant Stomata/physiology , Plant Stomata/genetics , Computational Biology/methods , Image Processing, Computer-Assisted/methods , Algorithms , Neural Networks, Computer
18.
Thromb Haemost ; 124(7): 599-612, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38242171

ABSTRACT

Sepsis represents a syndromic response to infection and frequently acts as a common pathway leading to fatality in the context of various infectious diseases globally. The pathology of severe sepsis is marked by an excess of inflammation and activated coagulation. A substantial contributor to mortality in sepsis patients is widespread microvascular thrombosis-induced organ dysfunction. Multiple lines of evidence support the notion that sepsis induces endothelial damage, leading to the release of glycosaminoglycans, potentially causing microvascular dysfunction. This review aims to initially elucidate the relationship among endothelial damage, excessive inflammation, and thrombosis in sepsis. Following this, we present a summary of the involvement of glycosaminoglycans in coagulation, elucidating interactions among glycosaminoglycans, platelets, and inflammatory cells. In this section, we also introduce a reasoned generalization of potential signal pathways wherein glycosaminoglycans play a role in clotting. Finally, we discuss current methods for detecting microvascular conditions in sepsis patients from the perspective of glycosaminoglycans. In conclusion, it is imperative to pay closer attention to the role of glycosaminoglycans in the mechanism of microvascular thrombosis in sepsis. Dynamically assessing glycosaminoglycan levels in patients may aid in predicting microvascular conditions, enabling the monitoring of disease progression, adjustment of clinical treatment schemes, and mitigation of both acute and long-term adverse outcomes associated with sepsis.


Subject(s)
Blood Coagulation , Glycosaminoglycans , Sepsis , Humans , Sepsis/blood , Sepsis/complications , Glycosaminoglycans/blood , Animals , Blood Platelets/metabolism , Microvessels , Signal Transduction , Inflammation/blood , Microcirculation , Thrombosis/blood
19.
Carbohydr Polym ; 329: 121758, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38286539

ABSTRACT

In this study, a novel and accurate quantitative analysis method for the direct determination of chitosan (CS) in aqueous solutions using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is presented. By detecting the mass spectrum response intensity of a series of CS characteristic ion pairs, the sample concentration (abscissa) was linearly fitted with the total ion current (TIC) response intensity of its characteristic ion pairs (ordinate). A reliable standard curve was derived for quantifying CS in the range of 125-4000 ng/mL. Under the detection conditions, this CS quantification method yielded acceptable specificity (no interference peak), linearity (with correlation coefficient (r2) values >0.999), precision (acceptable limit RSDr < 3 %, RSDR < 6 %), accuracy (RE within the acceptable limits of ±5 %), and stability (acceptable limit RE within ±5 %, RSDr < 3 %). Moreover, the applicability of measurement was verified when a series of substrates did not interact with CS in the solution. Results have verified the applicability of this method for determining CS content in different composites. This study provides a method for determining CS content with significant practical value and economic benefit.


Subject(s)
Chitosan , Tandem Mass Spectrometry , Chromatography, Liquid , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods
20.
Int J Mol Sci ; 25(2)2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38255822

ABSTRACT

Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein-protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1ß and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.


Subject(s)
Animal Experimentation , Sepsis , Animals , Humans , Mice , Biomarkers , Cell Adhesion , Computational Biology , Disease Models, Animal , Sepsis/genetics
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