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1.
Cancer Sci ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39327670

RESUMEN

Although the combination of immunotherapy and radiotherapy (RT) for the treatment of malignant tumors has shown rapid development, the insight of how RT remodels the tumor microenvironment to prime antitumor immunity involves a complex interplay of cell types and signaling pathways, much of which remains to be elucidated. Four tumor samples were collected from the same abdominal wall metastasis site of the patient with gastric cancer at baseline and during fractionated RT for single-cell RNA and T-cell receptor sequencing. The Seurat analysis pipeline and immune receptor analysis were used to characterize the gastric cancer metastasis ecosystem and investigated its dynamic changes of cell proportion, cell functional profiles and cell-to-cell communication during RT. Immunohistochemical and immunofluorescent staining and bulk RNA sequencing were applied to validate the key results. We found tumor cells upregulated immune checkpoint genes in response to RT. The infiltration and clonal expansion of T lymphocytes declined within tumors undergoing irradiation. Moreover, RT led to the accumulation of proinflammatory macrophages and natural killer T cells with enhanced cytotoxic gene expression signature. In addition, subclusters of dendritic cells and endothelial cells showed decrease in the expression of antigen present features in post-RT samples. More ECM component secreted by myofibroblasts during RT. These findings indicate that RT induced the dynamics of the immune response that should be taken into consideration when designing and clinically implementing innovative multimodal cancer treatment regimens of different RT and immunotherapy approaches.

2.
Anal Methods ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263747

RESUMEN

Neuron-specific enolase (NSE), a tumor marker of small cell lung cancer (SCLC), has high application value in the early diagnosis of SCLC. In this study, a dual signal electrochemical aptasensor for NSE was constructed based on hemin/reduced graphene oxide/multi-walled carbon nanotube (H-rGO-MWCNT) nanocomposites. Hemin played a dual role, functioning not only as an in situ electrochemical probe but also exhibiting excellent peroxidase-like properties, effectively catalyzing the electroreduction of H2O2. Reduced graphene oxide and multi-walled carbon nanotubes exhibited excellent conductivity. Through their binding with hemin, the nanocomposites achieved a larger specific surface area, providing numerous active sites for capturing the NSE aptamer. In the presence of NSE, the specific adsorption between the antigen and the aptamer formed a stable antigen-aptamer structure, which inhibited the performance of hemin, resulting in the weakening of the electrochemical signals of hemin and H2O2. Leveraging these characteristics, the sensitive and cost-effective dual-signal electrochemical aptasensor has been fabricated for the detection of NSE. One signal corresponded to differential pulse voltammetry (DPV) of hemin, while the other signal was derived from chronoamperometry, capturing the catalytic reduction of H2O2. The linear ranges for NSE were 1 pg mL-1 to 1 µg mL-1 and 100 pg mL-1 to 100 ng mL-1 with the limit of detection (LOD) of 0.21 pg mL-1 and 11.22 pg mL-1 by DPV and chronoamperometry, respectively. In addition, this aptasensor exhibited good reproducibility, stability and specificity. The recovery of NSE in human blood serum samples was from 89% to 131%. It provided a promising strategy for the detection of NSE in clinical diagnostics.

3.
Foods ; 13(18)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39335843

RESUMEN

The sustainability of global agricultural produce supply chains is crucial for ensuring global food security, fostering environmental protection, and advancing socio-economic development. This study integrates bibliometric analysis, knowledge mapping, and the ABCDE framework to conduct a comprehensive qualitative and quantitative analysis of 742 relevant articles from the Web of Science core database spanning January 2009 to July 2023. Initially, bibliometric analysis and knowledge mapping reveal the annual progression of research on the sustainability of global agricultural produce supply chains, the collaborative networks among research institutions and authors, and the geographic distribution of research activities worldwide, successfully pinpointing the current research focal points. Subsequently, the ABCDE framework, constructed from the quantitative findings, helps us identify and comprehend the antecedents, barriers and challenges, impacts, and driving forces affecting the sustainability of these supply chains. The study identifies globalization and technological advancement as the primary forces shaping the sustainability of agricultural produce supply chains, despite them also posing challenges such as resource constraints and environmental pressures. Moreover, the application of innovative technologies, the optimization of organizational models, and active stakeholder engagement are key to propelling supply chains toward more sustainable development, exerting a profound impact on society, the environment, and the economy. In conclusion, this study suggests future research directions. The integrated methodology presented offers new perspectives and deep insights into the complexities of sustainable global agricultural produce supply chains, demonstrating its potential to foster knowledge innovation and practical applications, providing valuable insights for academic research and policy formulation in this domain.

4.
Cell Host Microbe ; 32(8): 1264-1279, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39146798

RESUMEN

Human skin is the host to various commensal microbes that constitute a substantial microbial community. The reciprocal communication between these microbial inhabitants and host cells upholds both the morphological and functional attributes of the skin layers, contributing indispensably to microenvironmental and tissue homeostasis. Thus, disruption of the skin barrier or imbalances in the microbial communities can exert profound effects on the behavior of host cells. This influence, mediated by the microbes themselves or their metabolites, manifests in diverse outcomes. In this review, we examine existing knowledge to provide insight into the nuanced behavior exhibited by the microbiota on skin cells in health and disease states. These interactions provide insight into potential cellular targets for future microbiota-based therapies to prevent and treat skin disease.


Asunto(s)
Microbiota , Piel , Simbiosis , Humanos , Piel/microbiología , Microbiota/fisiología , Enfermedades de la Piel/microbiología , Animales , Homeostasis , Interacciones Microbiota-Huesped , Bacterias/metabolismo
5.
Small ; : e2401551, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109958

RESUMEN

Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management. Herein, a novel core-shell microneedle (CSMN) patch is designed for the sequential delivery of tannic acid-magnesium (TA-Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application to infected sites, CSMN@TA-Mg/LDEV releases TA-Mg first to counteract pathogenic overload and reduce reactive oxygen species (ROS), aiding the transition to proliferative phase. Subsequently, the sustained release of LDEVs enhances the activities of keratinocytes and fibroblasts, promotes vascularization, and modulates the collagen deposition. Notably, dynamic track of microbial composition demonstrates that CSMN@TA-Mg/LDEV can both inhibit the aggressive pathogen and increase the microbial diversity at wound sites. Functional analysis further highlights the potential of CSMN@TA-Mg/LDEV in facilitating wound healing and skin barrier restoration. Moreover, it is confirmed that CSMN@TA-Mg/LDEV can accelerate wound closure and improve post-recovery skin quality in the murine infected wound. Conclusively, this innovative CSMN patch offers a rapid and high-quality alternative treatment for infected wounds and emphasizes the significance of microbial homeostasis.

6.
Sensors (Basel) ; 24(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39065987

RESUMEN

Protection suits are vital for firefighters' safety. Traditional protection suits physically protect firemen from burns, but cannot locate the position of bodily injuries caused by impact debris. Herein, we present a wearable impact debris positioning system for firefighter protection suits based on an accelerometer array. Wearable piezoelectric accelerometers are distributed regularly on the suit to detect the vibration on different body parts, which is conducive to determining the position of injured body parts. In addition, the injured parts can be displayed on a dummy body model on the upper computer with a higher localization accuracy of 4 cm. The positioning alarm system has a rapid response time of 0.11 ms, attributed to the smart signal processing method. This work provides a reliable and smart method for locating and assessing the position of bodily injuries caused by impact debris, which is significant because it enables fire commanders to rescue injured firefighters in time.


Asunto(s)
Acelerometría , Bomberos , Acelerometría/instrumentación , Humanos , Ropa de Protección , Dispositivos Electrónicos Vestibles , Vibración
7.
Foods ; 13(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39063335

RESUMEN

In the new wave of globalization, China's pre-cooked meal industry has rapidly emerged as a significant player in the food supply chain domain, owing to its convenience and diverse choices. Amidst intensifying market competition, crafting a sustainable supply chain for overseas expansion has become an indispensable core element for driving corporate internationalization. This study focuses on the sustainability generation mechanism of the overseas supply chain of Chinese pre-cooked meal A-share listed companies, employing the technology-organization-environment (TOE) framework and fuzzy-set qualitative comparative analysis (fsQCA) method. Herein, an in-depth analysis of 388 data points from 17 listed companies has been conducted. The study systematically reveals the key factors affecting the sustainability of overseas supply chains and identifies three critical sustainability generation paths: the technology-driven and norm compliance model (path 1), the market sensitivity and product innovation model (path 2), and the robust operation and risk control model (path 3). The present study not only introduces a novel perspective on the application of a TOE framework within the realms of sustainable supply chain management and environmental, social, and governance (ESG) criteria but also offers clear directions for companies to enhance sustainability in their overseas expansion process. This includes strengthening technological research and development, compliance construction, market adaptability, product diversity, infrastructure construction, and risk management. Moreover, the research findings provide valuable insights for policymakers in promoting the internationalization of the pre-cooked meal industry and enhancing industry competitiveness.

8.
Front Cell Infect Microbiol ; 14: 1404431, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081866

RESUMEN

Introduction: Endogenous retroviruses (ERVs), which originated from exogenous retroviral infections of germline cells millions of years ago and were inherited by subsequent generations as per Mendelian inheritance patterns, predominantly comprise non-protein-coding sequences due to the accumulation of mutations, insertions, deletions, and truncations. Nevertheless, recent studies have revealed that ERVs play a crucial role in diverse biological processes by encoding various proteins. Methods: In this study, we successfully identified an ERV envelope (env) gene in a mink species. A phylogenetic tree of mink ERV-V env and reference sequences was constructed using Bayesian methods and maximum-likelihood inference. Results: Phylogenetic analyses indicated a significant degree of sequence conservation and positive selection within the env-surface open reading frame. Additionally, qRT-PCR revealed diverse patterns of mink ERV-V env expression in various tissues. The expression of mink ERV-V env gene in testicular tissue strongly correlated with the seasonal reproductive cycles of minks. Discussion: Our study suggests that the ERV-V env gene in mink may have been repurposed for host functions.


Asunto(s)
Retrovirus Endógenos , Visón , Filogenia , Retrovirus Endógenos/genética , Animales , Visón/virología , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Estaciones del Año , Reproducción/genética , Masculino , Testículo/virología , Teorema de Bayes
9.
Front Pharmacol ; 15: 1410998, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38828456

RESUMEN

Retinal pigment epithelial cell and neuroretinal damage in age-related macular degeneration (AMD) can lead to serious visual impairments and blindness. Studies have shown that mitophagy, a highly specialized cellular degradation system, is implicated in the pathogenesis of AMD. Mitophagy selectively eliminates impaired or non-functioning mitochondria via several pathways, such as the phosphatase and tensin homolog-induced kinase 1/Parkin, BCL2-interacting protein 3 and NIP3-like protein X, FUN14 domain-containing 1, and AMP-activated protein kinase pathways. This has a major impact on the maintenance of mitochondrial homeostasis. Therefore, the regulation of mitophagy could be a promising therapeutic strategy for AMD. Traditional Chinese medicine (TCM) uses natural products that could potentially prevent and treat various diseases, such as AMD. This review aims to summarize recent findings on mitophagy regulation pathways and the latest progress in AMD treatment targeting mitophagy, emphasizing methods involving TCM.

10.
Acta Biomater ; 184: 296-312, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38871203

RESUMEN

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus, and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo, CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. STATEMENT OF SIGNIFICANCE: Cutibacterium acnes, which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation.


Asunto(s)
Vesículas Extracelulares , Hidrogeles , Linfocitos , Microesferas , Psoriasis , Vesículas Extracelulares/metabolismo , Animales , Humanos , Psoriasis/patología , Psoriasis/inmunología , Psoriasis/terapia , Psoriasis/microbiología , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Linfocitos/inmunología , Linfocitos/metabolismo , Inmunidad Innata/efectos de los fármacos , Staphylococcus aureus , Células HaCaT
12.
Sci Total Environ ; 930: 172843, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38685421

RESUMEN

In modern industries, rare earth elements (REEs) are considered as essential metals and invaluable natural resources. Ion-adsorption deposits (IADs) are repositories of REE in the weathering crust soils, in which REEs are adsorbed on clay minerals. In the last few decades, the mining of REEs from IADs has caused substantial environmental damage owing to the overuse of leaching agents for the desorption and transport of REEs in weathering crust soils. These environmental issues have sparked extensive research interest in modeling REE transport dynamics in weathering crust soils. Nevertheless, because current models treat REE adsorption and transport independently, they do not accurately describe REE transport dynamics. Therefore, in this study, a unified workflow that synergizes adsorption and transport dynamics is proposed to predict REE transport. The adsorption of REEs on IADs was found to follow the Freundlich isotherm with the coefficient of determination exceeding 0.9826. The adsorption capacities of La3+, Sm3+, Er3+, and Y3+ reach 1.3127, 1.4423, 1.5793, and 1.1061 mg g-1 at 300 ppm, respectively. For the breakthrough curve, an advection-dispersion-adsorption-equation (ADAE) model was developed and utilized to accurately and reliably predict REE transport dynamics in soil columns. It was found the saturation time of REEs in soils is 39.22, 44.15, 50.64, and 32.17 h, respectively at 2 mL min-1 and decreased with the increase of flow velocity. The upper and lower limits of REE transport are ADAE-Freundlich and ADAE-Toth. More importantly, the model was applied to simulate REEs transport in field-scale weathering crusts over 100 years and predict REE accumulation in the highly weathered layered, which is found in natural weathering crusts. The qualitative prediction of REE transport dynamics in weathering crusts may help fundamentally lower the usage of leaching agents and mitigate concomitant the environmental impacts of mining.

13.
Nanotechnology ; 35(28)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38574484

RESUMEN

Nitrogen dioxide (NO2) is a major pollutant that poses significant risks to sustainable human life. As a result, a growing focus has been placed on the development of highly selective and sensitive gas sensors for NO2. Traditional cutting-edge non-organic NO2gas detectors often necessitate stringent production conditions and potentially harmful materials, which are not environmentally friendly, and these shortcomings have limited their widespread practical use. To overcome these challenges, we synthesized self-assembled peptide nanotubes (SPNTs) through a molecular self-assembly process. The SPNTs were then combined with SnO2in varying proportions to construct NO2gas sensors. The design of this sensor ensured efficient electron transfer and leverage the extensive surface area of the SPNTs for enhanced gas adsorption and the effective dispersion of SnO2nanoparticles. Notably, the performance of the sensor, including its sensitivity, response time, and recovery rate, along with a lower detection threshold, could be finely tuned by varying the SPNTs content. This approach illustrated the potential of bioinspired methodologies, using peptide self-assemblies, to develop integrated sensors for pollutant detection, providing a significant development in environmentally conscious sensor technology.


Asunto(s)
Nanocompuestos , Nanotubos de Péptidos , Dióxido de Nitrógeno , Compuestos de Estaño , Compuestos de Estaño/química , Dióxido de Nitrógeno/análisis , Nanotubos de Péptidos/química , Nanocompuestos/química , Temperatura
14.
Int Immunopharmacol ; 133: 112070, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38640716

RESUMEN

Skin, the largest organ of body, is a highly immunogenic tissue with a diverse collection of immune cells. Highly polymorphic human leukocyte antigen (HLA) molecules have a central role in coordinating immune responses as recognition molecules. Nevertheless, HLA gene expression patterns among diverse cell types within a specific organ, like the skin, have yet to be thoroughly investigated, with stromal cells attracting much less attention than immune cells. To illustrate HLA expression profiles across different cell types in the skin, we performed single-cell RNA sequencing (scRNA-seq) analyses on skin datasets, covering adult and fetal skin, and hair follicles as the skin appendages. We revealed the variation in HLA expression between different skin populations by examining normal adult skin datasets. Moreover, we evaluated the potential immunogenicity of multiple skin populations based on the expression of classical HLA class I genes, which were well represented in all cell types. Furthermore, we generated scRNA-seq data of developing skin from fetuses of 15 post conception weeks (PCW), 17 PCW, and 22 PCW, delineating the dynamic expression of HLA genes with cell type-dependent variation among various cell types during development. Notably, the pseudotime trajectory analysis unraveled the significant variance in HLA genes during the evolution of vascular endothelial cells. Moreover, we uncovered the immune-privileged properties of hair follicles at single-cell resolution. Our study presents a comprehensive single-cell transcriptomic landscape of HLA genes in the skin, which provides new insights into variation in HLA molecules and offers a clue for allogeneic skin transplantation.


Asunto(s)
Perfilación de la Expresión Génica , Antígenos HLA , Análisis de la Célula Individual , Piel , Transcriptoma , Humanos , Piel/inmunología , Piel/metabolismo , Antígenos HLA/genética , Antígenos HLA/inmunología , Folículo Piloso/inmunología , Folículo Piloso/metabolismo , Feto/inmunología , Adulto , Privilegio Inmunológico
15.
Talanta ; 274: 125965, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38552480

RESUMEN

In this paper, a few-layer WS2 nanosheets-based electrochemical biosensor was fabricated for the highly sensitive detection of breast cancer tumor marker miRNA-4484. Firstly, few-layer WS2 nanosheets were prepared by shear stripping and characterized by SEM, TEM, AFM and UV spectrophotometer. After modification of few-layer WS2 nanosheets on the electrode surface, the miRNA probe was fixed on the few-layer WS2 nanosheets by polycytosine (PolyC). Then short-chain miRNA containing PolyC was used as the blocking agent to close the excess active sites on the surface of WS2 nanosheets to complete the fabrication of the sensor biosensing interface. Finally, the current changes caused by the specific binding of miRNA-4484 to the probe were analyzed by differential pulse voltammetry (DPV). The results showed that the sensor had a good linear relationship for the detection of miRNA-4484 in the concentration range of 1 aM-100 fM, and the detection limit was as low as 1.61 aM. In addition, the electrochemical sensor had excellent selectivity, stability and reproducibility. The artificial sample tests indicated that the developed biosensors have the potential for clinical application in the future.


Asunto(s)
Biomarcadores de Tumor , Técnicas Biosensibles , Técnicas Electroquímicas , MicroARNs , Nanoestructuras , Sulfuros , Compuestos de Tungsteno , Técnicas Biosensibles/métodos , MicroARNs/análisis , Biomarcadores de Tumor/análisis , Técnicas Electroquímicas/métodos , Humanos , Sulfuros/química , Nanoestructuras/química , Compuestos de Tungsteno/química , Límite de Detección , Electrodos , Neoplasias de la Mama/diagnóstico
16.
BMC Psychol ; 12(1): 175, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532473

RESUMEN

Humble leadership has gained attention in recent years due to its potential impact on employee performance. This study explores the association between humble leadership and follower innovative behavior by investigating the moderating role of core self-evaluation (CSE) and the mediating role of leader-member exchange (LMX). The study uses data from 328 followers and their immediate leaders to test a mediated moderation model. Results show that there is a favorable association between humble leadership and LMX and followers' innovative behavior, particularly pronounced for followers who possess lower levels of CSE. The findings suggest that humble leaders should focus their development efforts on followers with low CSE to achieve complementarity congruity and improved innovation. This research enhances the existing body of knowledge by emphasizing the significance of comprehending the functions of relational procedures and the psychological resources of followers in determining the effectiveness of humble leadership. These findings have practical implications for organizations seeking to enhance their leadership effectiveness and followers' innovative behavior.


Asunto(s)
Autoevaluación Diagnóstica , Liderazgo , Humanos
17.
JCI Insight ; 9(5)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300707

RESUMEN

Geleophysic dysplasia-1 (GD1) is an autosomal recessive disorder caused by ADAMTS-like 2 (ADAMTSL2) variants. It is characterized by distinctive facial features, limited joint mobility, short stature, brachydactyly, and life-threatening cardiorespiratory complications. The clinical spectrum spans from perinatal lethality to milder adult phenotypes. We developed and characterized cellular and mouse models, to replicate the genetic profile of a patient who is compound heterozygous for 2 ADAMTSL2 variants, namely p.R61H and p.A165T. The impairment of ADAMTSL2 secretion was observed in both variants, but p.A165T exhibited a more severe impact. Mice carrying different allelic combinations revealed a spectrum of phenotypic severity, from lethality in knockout homozygotes to mild growth impairment observed in adult p.R61H homozygotes. Homozygous and hemizygous p.A165T mice survived but displayed severe respiratory and cardiac dysfunction. The respiratory dysfunction mainly affected the expiration phase, and some of these animals had microscopic post-obstructive pneumonia. Echocardiograms and MRI studies revealed a significant systolic dysfunction, accompanied by a reduction of the aortic root size. Histology verified the presence of hypertrophic cardiomyopathy with myocyte hypertrophy, chondroid metaplasia, and mild interstitial fibrosis. This study revealed a substantial correlation between the degree of impaired ADAMTSL2 secretion and the severity of the observed phenotype in GD1.


Asunto(s)
Proteínas ADAMTS , Enfermedades del Desarrollo Óseo , Deformidades Congénitas de las Extremidades , Adulto , Humanos , Animales , Ratones , Proteínas ADAMTS/genética , Enfermedades del Desarrollo Óseo/genética , Mutación , Fenotipo
18.
New Phytol ; 242(1): 262-277, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38332248

RESUMEN

Plants are simultaneously attacked by different pests that rely on sugars uptake from plants. An understanding of the role of plant sugar allocation in these multipartite interactions is limited. Here, we characterized the expression patterns of sucrose transporter genes and evaluated the impact of targeted transporter gene mutants and brown planthopper (BPH) phloem-feeding and oviposition on root sugar allocation and BPH-reduced rice susceptibility to Meloidogyne graminicola. We found that the sugar transporter genes OsSUT1 and OsSUT2 are induced at BPH oviposition sites. OsSUT2 mutants showed a higher resistance to gravid BPH than to nymph BPH, and this was correlated with callose deposition, as reflected in a different effect on M. graminicola infection. BPH phloem-feeding caused inhibition of callose deposition that was counteracted by BPH oviposition. Meanwhile, this pivotal role of sugar allocation in BPH-reduced rice susceptibility to M. graminicola was validated on rice cultivar RHT harbouring BPH resistance genes Bph3 and Bph17. In conclusion, we demonstrated that rice susceptibility to M. graminicola is regulated by BPH phloem-feeding and oviposition on rice through differences in plant sugar allocation.


Asunto(s)
Hemípteros , Oryza , Tylenchoidea , Animales , Femenino , Hemípteros/fisiología , Azúcares/metabolismo , Oryza/metabolismo
19.
Account Res ; : 1-21, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38164053

RESUMEN

Despite the increasing prominence of research collaboration, a growing number of studies have confirmed that increasing team size can have limited performance benefits. However, the mechanism of this phenomenon has yet to be established. This study, therefore, quantified responsibility diffusion based on author contribution information and explored its mediating role in the relationship between collaboration size and citation impact (citation count in a four-year window). The results show the following: (1) An inverted U-shaped relationship exists between team size and citation count. (2) Responsibility diffusion plays a partial mediating role between team size and citation count. (3) As team size increases, the degree of responsibility diffusion increases. Lastly, (4) responsibility diffusion has an inverted U-shaped curvilinear relationship with citation count (e.g., a moderate degree of responsibility diffusion has the highest impact). These findings offer a new understanding of the mechanism by which collaboration size influences research performance. This study also has practical implications for solving research collaboration dilemmas based on a group-cognition perspective.

20.
Acta Pharmacol Sin ; 45(4): 815-830, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38066346

RESUMEN

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.


Asunto(s)
Diabetes Mellitus Experimental , Luteolina , Cicatrización de Heridas , Animales , Humanos , Ratas , Autofagia/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Luteolina/farmacología , Luteolina/uso terapéutico , Calidad de Vida , Sirtuina 1/genética , Sirtuina 1/metabolismo , Cicatrización de Heridas/efectos de los fármacos
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