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Global milk consumption exceeds 800 million tons a year and is still growing. Milk quality and its products are critical to human health. A teat cup makes direct contact with the cow's teats during milking and its cleanliness is very important for the quality of raw milk. In this study, the microorganism from post-milking teat cup liners were collected from six dairy farms in Shandong Province of China, the bacterial species were identified using microbial mass spectrometry, the minimum inhibitory concentrations of the isolated strains against ten antimicrobial agents were determined using the broth microdilution method, and the antimicrobial resistance genes were detected by PCR. The results indicated that the most frequently isolated bacteria in this study were Bacillus licheniformis (39/276, 14.13%), followed by Bacillus pumilus (20/276, 7.25%), Bacillus cereus (17/276, 6.16%), and Bacillus subtili (16/276, 5.80%). The isolates exhibited the highest average resistance to lincomycin (87.37%), followed by sulfadiazine (61.05%) and streptomycin (42.63%); the highest detection rate of resistance genes was Sul1 (55.43%), followed by ant(4') (51.09%), tet(M) (25.36%), blaKPC (3.62%) and qnrS (3.62%). These findings imply the necessity for enhanced measures in disinfecting cow udders and milking equipment, highlighting the persistently challenging issue of antimicrobial resistance in Shandong Province.
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SCOPE: This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an "enterotype - metabolic" model. METHODS AND RESULTS: A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7ß-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis. CONCLUSION: The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.
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Identifying depression symptoms in patients with hip fractures and studying the relationship between depression and pain intensity and pain location in hip fracture patients is of great significance for disease recovery in hip fracture patients. This cohort study analyzed 5 wave data from the China Health and Retirement Longitudinal Study in 2011, 2013, 2015, 2018, and 2020, focusing on 1222 patients with hip fractures. The study utilized the CESD-10 Depression Scale to assess depressive symptoms in hip fracture patients and conducted analyses to explore the relationship between depression symptoms, pain, and pain intensity, including binary logistic regression and examination of interaction terms between pain variables and pain intensity in key body parts. Depression symptoms are strongly associated with pain intensity in hip fracture patients, particularly in key body areas. Severe pain significantly increases the risk of depressive symptoms. Moreover, absence of pain in other key body parts is linked to depressive symptoms. Multivariate analysis reveals that higher education levels, marriage, urban residence, and self-rated good health serve as protective factors against depression, while diabetes and heart disease pose significant risks for depressive symptoms in hip fracture patients. Hip fracture pain can induce discomfort and trigger depressive symptoms, showing varied trajectories among patients. Pain intensity predicts the course of depressive symptoms, emphasizing the importance of tailored pain management strategies including medication, physical therapy, and nonpharmacological interventions. Personalized rehabilitation and mental health plans should be designed based on individual patient needs and differences.
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Depressão , Fraturas do Quadril , Dor , Humanos , Fraturas do Quadril/psicologia , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Feminino , Masculino , Idoso , Depressão/epidemiologia , Depressão/etiologia , China/epidemiologia , Dor/psicologia , Dor/etiologia , Dor/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Medição da Dor , Idoso de 80 Anos ou mais , Fatores de RiscoRESUMO
RATIONALE: Nocardia infection is commonly regarded as an opportunistic pulmonary pathogen affecting debilitated or immunocompromised individuals. Brain abscesses caused by Nocardia farcinica are rare and pose a diagnostic challenge. Traditional diagnostic techniques for identifying Nocardia species, such as blood culture, microscopy, and pathology, have shown inadequate performance. In the reported case, we applied metagenomic next-generation sequencing (mNGS) to diagnose a case of brain abscess due to N. farcinica. PATIENT CONCERNS: A 66-year-old female developed a brain abscess after sustaining a hand injury. The patient exhibited a gradual change in personality and experienced tremors in her right upper limb for a duration of 1 month. DIAGNOSES: The pathogen responsible for the multiple brain abscesses was identified in the cerebrospinal fluid as N. farcinica through mNGS. INTERVENTIONS: Antibiotic treatment included trimethoprim-sulfamethoxazole, linezolid, amikacin, meropenem, and moxifloxacin. OUTCOMES: The patient's symptoms and signs improved significantly after administration of antibiotics to which the pathogen is known to be sensitive. After 5 months of follow-up, magnetic resonance imaging of the head showed that the abscess was basically cured. The patient lived a normal life with no adverse drug reactions. LESSONS: Nocardia brain infection is characterized by an insidious onset and lacks distinctive clinical and imaging features. mNGS was advantageous for the timely identification and management of Nocardia-associated brain abscess in the present case and obviated the need for invasive brain surgery. Expeditious and precise diagnosis coupled with prompt antibiotic therapy can significantly reduce the mortality rate associated with this condition.
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Antibacterianos , Abscesso Encefálico , Traumatismos da Mão , Nocardiose , Nocardia , Humanos , Feminino , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Abscesso Encefálico/microbiologia , Abscesso Encefálico/etiologia , Abscesso Encefálico/diagnóstico , Nocardia/isolamento & purificação , Idoso , Antibacterianos/uso terapêutico , Traumatismos da Mão/complicações , Imageamento por Ressonância Magnética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.
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Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.
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BACKGROUND: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy, and it is mediated by long non-coding RNAs (lncRNAs). STUDY DESIGN AND METHODS: Mouse lung tissues were examined using RNA-Seq and RNA-Seq libraries 72 h after the administration of 6 Gy of X-ray irradiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and target miRNA-based mRNAs were predicted after irradiation to establish the lncRNA-miRNA-mRNA ceRNA axis. RESULTS: The analyses showed that relative to unirradiated controls, 323 mRNAs, 114 miRNAs, and 472 lncRNAs were significantly up-regulated following irradiation, whereas 1907 mRNAs, 77 miRNAs, and 1572 lncRNAs were significantly down-regulated following irradiation. Voltage-gated ion channels, trans-membrane receptor protein tyrosine kinases, and vascular endothelial growth factor have all been associated with dysregulated miRNA-mRNA relationships. KEGG pathway analysis of the dysregulated miRNA-mRNA targets revealed involvement in pathways associated with the hedgehog signaling pathway-fly, ErbB signaling, VEGF signaling, axon guidance, and focal adhesion. KEGG analysis of differentially expressed showed enrichment of mRNAs in primary immunodeficiency, the intestinal immune axis for IgA production, hematopoietic cell lineages, systemic lupus erythematosus, and Th1 and Th2 cell differentiation. Finally, the ceRNA network revealed that BNIP1 was a critical mRNA modulated by the most significant upregulation of lncRNA E230013L22Rik. CONCLUSION: In summary, the lncRNA-miRNA-mRNA ceRNA axis of RILI was constructed following irradiation in a mouse model. RNA dysregulation in the early stage of RILI may lead to severe complications at a later stage, with BNIP1 contributing to radiation-induced cellular apoptosis in RILI.
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Present study aimed to compare the effects of SSIT intervention with varying rest distributions on hormonal, physiological, and performance adaptations in soccer players. Thirty-six players were randomly divided into three SSIT groups, each performing 4 sets of 6-10 repetitions of 6-second all-out running with rest intervals at ratios of 1:3, 1:6, and 1:9. Prior to and following the 7-week training period, aerobic fitness indices and anaerobic power were evaluated using a graded exercise test with a gas collection system and a lower-body Wingate test, respectively. Also, sport-specific bio-motor abilities were determined by measuring vertical jump, 20-m sprint, and T-test change of direction speed, Yo-Yo IR1 and maximal kicking distance. Hormonal status was also monitored by evaluating testosterone and cortisol levels. Following the 7-week training period, all SSIT interventions resulted in significant enhancements (p < 0.05) in soccer-related performance, physiological parameters, and hormonal adaptations, exhibiting effect sizes that ranged from small to large. Comparative analysis indicated that the 1:9 SSIT results in greater adaptive responses (p < 0.05) in the vertical jump, peak power, testosterone, and cortisol compared to the 1:3 SSIT group. By contrast, the 1:3 SSIT group induced more adaptive responses (p < 0.05) in the mean power output, maximum oxygen consumption (VÌO2max), and Yo-Yo IR1 compared to the 1:9 SSIT group. Hence, for enhancing physical performance, especially vertical jump height, anaerobic peak power, and hormonal adaptations, the 1:9 SSIT ratio is preferable. Conversely, shorter rest intervals (specifically, the 1:3 SSIT ratio) are better suited for eliciting heightened adaptive responses in mean power output, VÌO2max, and Yo-Yo IR1 over the 7-week training period among young male soccer players.
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Adaptação Fisiológica , Desempenho Atlético , Treinamento Intervalado de Alta Intensidade , Hidrocortisona , Consumo de Oxigênio , Descanso , Corrida , Futebol , Testosterona , Humanos , Futebol/fisiologia , Hidrocortisona/sangue , Desempenho Atlético/fisiologia , Testosterona/sangue , Corrida/fisiologia , Masculino , Adolescente , Treinamento Intervalado de Alta Intensidade/métodos , Descanso/fisiologia , Consumo de Oxigênio/fisiologia , Teste de EsforçoRESUMO
Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.
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Monitoring the variations of lake water quality is essential for urban water security and sustainable eco-environment health. However, it is challenging to investigate the water quality of urban lakes at large scales due to the need for large-amount in situ data with diverse optical properties for developing the remote sensing inversion algorithms. Forel-Ule Index (FUI), a proxy of quantifying water color, whose calculation does not require in situ data of specific properties, can comprehensively reflect water quality conditions. However, the spatial and temporal distribution of water color in Chinese urban lakes is still poorly understood. To fill this research gap, this study investigated the spatial distribution of water color in 523 urban lakes (area > 0.5 km2) in China using the FUI derived from the high-quality Multi-Spectral Instrument (MSI) data onboard Sentinel-2 during the ice-free period (April-October) from 2019 to 2022. The monthly and seasonal variation patterns of water color in urban lakes were also analyzed. Our results show that green domain is the most common color of urban lakes, with about 86 % of urban lakes in China being green, and non-green lakes accounting for only 14 % of the total number of lakes. The monthly variation of FUI in urban lakes across the country and multiple geographic regions is basically the same. The monthly average FUI first increases, then decreases, and then rebounds. We also found that the seasonal variation of water color in most urban lakes in southern and northern China is opposite. This study helps to comprehensively understand the spatial and temporal variation of water color and quality of urban lakes in China, providing key basic information for the protection and governance of urban lakes.
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Mixed germ cell tumors (mGCTs) involving both the ovaries and sellar region have been rarely reported; thus, they pose significant challenges in clinical management. Our report of a case of a 26-year-old female with left ovarian mGCTs (dysgerminoma + yolk sac tumor) who presented with postoperative headaches and blurred vision contributes new information to the literature on treating mGCTs, which can lead to standardized regimens and sequencing guidelines. A physical examination revealed right temporal hemianopia, and elevated levels of alpha-fetoprotein were detected in serum and cerebrospinal fluid. Magnetic resonance imaging (MRI) of the sellar region revealed a space-occupying lesion. Pathological examination of the tumor after endoscopic transnasal resection confirmed the diagnosis of mGCTs (germinomas + yolk sac tumor). The patient received adjuvant chemotherapy and radiotherapy at reduced dosages. During follow-up, tumor markers remained within normal limits, and there was no evidence of tumor recurrence on sellar region MRI. This case highlights the rarity of the simultaneous occurrence of ovarian and sellar region mGCTs and emphasizes the importance of accurate diagnosis and multidisciplinary management.
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The ionosphere can be artificially modified by employing ground-based high-power high-frequency electromagnetic waves to irradiate the ionosphere. This modification is achieved through the nonlinear interaction between the electromagnetic waves and the ionospheric plasma, leading to changes in the physical properties and structure of the ionosphere. The degree of artificial modification of the ionosphere is closely related to the heating energy density of high-frequency pump waves. Due to the high density of neutral constituents in the lower ionosphere and the high frequency of electron-neutral collisions, the energy of heating pump waves will be absorbed and attenuated during the penetration of the low ionosphere, seriously affecting the heating effect. This paper proposes a method to reduce the absorption of ionospheric heating pump waves by releasing electron attachment chemicals into low ionosphere to form a large-scale electron density hole. A model for mitigating pump waves absorption based on SF6 release is established, and the absorption at different frequencies is quantitatively calculated. The propagation characteristics of high-frequency signals in ionospheric holes are studied using a three-dimensional ray tracing method, and the results demonstrate that the chemical release method not only reduces the absorption attenuation of heating pump waves but also forms spherical electron density holes, which exhibit a focusing effect on the heating beam and enhance the heating effect. The results are of great significance for understanding the nonlinear interaction between electromagnetic wave and ionospheric plasma and improving the ionospheric heating efficiency.
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Trophic state index (TSI) serves as a key indicator for quantifying and understanding the lake eutrophication, which has not been fully explored for long-term water quality monitoring, especially for small and medium inland waters. Landsat satellites offer an effective complement to facilitate the temporal and spatial monitoring of multi-scale lakes. Landsat surface reflectance products were utilized to retrieve the annual average TSI for 2693 lakes over 1 km2 in China from 1984 to 2023. Our method first distinguishes lake types by pixels with a decision tree and then derives relationships between trophic state and algal biomass index. Validation with public reports and existing datasets confirmed the good consistency and reliability. The dataset provides reliable annual TSI results and credible trends for lakes under different area scales, which can serve as a reference for further research and provide convenience for lake sustainable management.
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Monitoramento Ambiental , Eutrofização , Lagos , China , Imagens de Satélites , Qualidade da Água , BiomassaRESUMO
Strain engineering has been widely used to optimize platinum-based oxygen reduction reaction (ORR) catalysts for proton exchange membrane fuel cells (PEMFCs). PtM3 (M is base metals), a well-known high-compressive-strain intermetallic alloy, shows promise as a low platinum ORR catalyst due to high intrinsic activity. However, during the alloying of Pt with a threefold amount of M, a notable phase separation between Pt and M may occur, with M particles rapidly sintering while Pt particles grow slowly, posing a challenge in achieving a well-defined PtM3 intermetallic alloy. Here, an entropy-driven Ostwald ripening reversal phenomenon is discovered that enables the synthesis of small-sized Pt(FeCoNiCu)3 intermetallic ORR catalysts. High entropy promotes the thermodynamic driving force for the alloying Pt with M, which triggers the Ostwald ripening reversal of sintered FeCoNiCu particles and facilitates the formation of uniform Pt(FeCoNiCu)3 intermetallic catalysts. The prepared Pt(FeCoNiCu)3 catalysts exhibit a high specific activity of 3.82 mA cm-2, along with a power density of ≈1.3 W cm-2 at 0.67 V and 94 °C with a cathode Pt loading of 0.1 mg cm-2 in H2-air fuel cell.
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PURPOSE: Whole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized control trials (RCTs). To fill the research gap, we conducted a meta-analysis to determine the effects of whole grains on diabetes prevention and to inform recommendations. METHODS: We searched PubMed, Clarivate Web of Science, and Cochrane Library until March 2024. We used the risk ratio (RR) of type 2 diabetes to represent the clinical outcomes for cohort studies, while the biomarkers, including fasting blood glucose and insulin, HbA1C, and HOMA-IR, were utilized to show outcomes for RCTs. Dose-response relationships between whole grain intakes and outcomes were tested with random effects meta-regression models and restricted cubic splines models. This study is registered with PROSPERO, CRD42021281639. RESULTS: Ten prospective cohort studies and 37 RCTs were included. Cohort studies suggested a 50 g/day whole grain intake reduced the risk of type 2 diabetes (RR = 0.761, 95% CI: 0.700 to 0.828, I2 = 72.39%, P < 0.001) and indicated a monotonic inverse relationship between whole grains and type 2 diabetes rate. In RCTs, whole grains significantly reduced fasting blood glucose (Mean difference (MD) = -0.103 mmol/L, 95% CI: -0.178 to -0.028; I2 = 72.99%, P < 0.01) and had modest effects on HbA1C (MD = -0.662 mmol/mol (-0.06%), 95% CI: -1.335 to 0.010; I2 = 64.55%, P = 0.05) and HOMA-IR (MD = -0.164, 95% CI: -0.342 to 0.013; I2 = 33.38%, P = 0.07). The intake of whole grains and FBG, HbA1C, and HOMA-IR were significantly dose-dependent. The restricted spline curves remained flat up to 150 g/day and decreased afterward. Subgroup analysis showed that interventions with multiple whole-grain types were more effective than those with a single type. CONCLUSION: Our study findings suggest that a daily intake of more than 150 g of whole grain ingredients is recommended as a population approach for diabetes prevention.
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Glicemia , Diabetes Mellitus Tipo 2 , Controle Glicêmico , Ensaios Clínicos Controlados Aleatórios como Assunto , Grãos Integrais , Humanos , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/sangue , Controle Glicêmico/métodos , Glicemia/metabolismo , Estudos Prospectivos , Dieta/métodos , Dieta/estatística & dados numéricos , Hemoglobinas Glicadas/análise , Insulina/sangueRESUMO
Clostridium perfringens is ubiquitously distributed and capable of secreting toxins, posing a significant threat to animal health. Infections caused by Clostridium perfringens, such as Necrotic Enteritis (NE), result in substantial economic losses to the livestock industry annually. However, there is no effective commercial vaccine available. Hence, we set out to propose an effective approach for multi-epitope subunit vaccine construction utilizing biomolecules. We utilized immunoinformatics to design a novel multi-epitope antigen against C. perfringens (CPMEA). Furthermore, we innovated novel bacterium-like particles (BLPs) through thermal acid treatment of various Lactobacillus strains and selected BLP23017 among them. Then, we detailed the structure of CPMEA and BLPs and utilized them to prepare a multi-epitope vaccine. Here, we showed that our vaccine provided full protection against C. perfringens infection after a single dose in a mouse model. Additionally, BLP23017 notably augmented the secretion of secretory immunoglobulin A (sIgA) and enhanced antibody production. We conclude that our vaccine possess safety and high efficacy, making it an excellent candidate for preventing C. perfringens infection. Moreover, we demonstrate our approach to vaccine construction and the preparation of BLP23017 with distinct advantages may contribute to the prevention of a wider array of diseases and the novel vaccine development.
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Adjuvantes Imunológicos , Vacinas Bacterianas , Infecções por Clostridium , Clostridium perfringens , Modelos Animais de Doenças , Epitopos , Lactobacillus , Animais , Clostridium perfringens/imunologia , Camundongos , Lactobacillus/imunologia , Epitopos/imunologia , Vacinas Bacterianas/imunologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/imunologia , Biologia Computacional , Antígenos de Bactérias/imunologia , Feminino , Camundongos Endogâmicos BALB C , ImunoinformáticaRESUMO
A specialized population of mast cells residing within epithelial layers, currently known as intraepithelial mast cells (IEMCs), was originally observed over a century ago, yet their physiological functions have remained enigmatic. In this study, we unveil an unexpected and crucial role of IEMCs in driving gasdermin C-mediated type 2 immunity. During helminth infection, αEß7 integrin-positive IEMCs engaged in extensive intercellular crosstalk with neighboring intestinal epithelial cells (IECs). Through the action of IEMC-derived proteases, gasdermin C proteins intrinsic to the epithelial cells underwent cleavage, leading to the release of a critical type 2 cytokine, interleukin-33 (IL-33). Notably, mast cell deficiency abolished the gasdermin C-mediated immune cascade initiated by epithelium. These findings shed light on the functions of IEMCs, uncover a previously unrecognized phase of type 2 immunity involving mast cell-epithelial cell crosstalk, and advance our understanding of the cellular mechanisms underlying gasdermin C activation.
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Interleucina-33 , Mastócitos , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros , Animais , Camundongos , Comunicação Celular/imunologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Interleucina-33/metabolismo , Interleucina-33/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/imunologia , Proteínas Citotóxicas Formadoras de Poros/metabolismoRESUMO
Identification of promising seed cells plays a pivotal role in achieving tissue regeneration. This study demonstrated that LepR-expressing cells (LepR+ cells) are required for maintaining periodontal homeostasis at the adult stage. We further investigated how LepR+ cells behave in periodontal healing using a ligature-induced periodontitis (PD) and a self-healing murine model with LepRCre/+; R26RtdTomato/+ mice. Lineage tracing experiments revealed that the largely suppressed osteogenic ability of LepR+ cells results from periodontal inflammation. Periodontal defects were partially recovered when the ligature was removed, in which the osteogenic differentiation of LepR+ cell lineage was promoted and contributed to the newly formed alveolar bone. A cell ablation model established with LepRCre/+; R26RtdTomato/+; R26RDTA/+ mice further proved that LepR+ cells are an important cell source of newly formed alveolar bone. Expressions of ß-catenin and LEF1 in LepR+ cells were upregulated when the inflammatory stimuli were removed, which are consistent with the functional changes observed during periodontal healing. Furthermore, the conditional upregulation of WNT signaling or the application of sclerostin neutralized antibody promoted the osteogenic function of LepR+ cells. In contrast, the specific knockdown of ß-catenin in LepR+ human periodontal ligament cells with small interfering RNA caused arrested osteogenic function. Our findings identified the LepR+ cell lineage as a critical cell population for endogenous periodontal healing post PD, which is regulated by the WNT signaling pathway, making it a promising seed cell population in periodontal tissue regeneration.
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Osteogênese , Periodontite , Adulto , Camundongos , Humanos , Animais , beta Catenina/metabolismo , Ligamento Periodontal/metabolismo , Inflamação , Via de Sinalização Wnt/fisiologia , Diferenciação Celular , Células CultivadasRESUMO
The lake eutrophication is highly variable in both time and location, and greatly restricts the sustainable development of water resources. The lack of national eutrophication evaluation for multi-scale lakes limits the pertinent governance and sustainable management of water quality. In this study, a remote sensing approach was developed to capture 40-year dynamics of trophic state index (TSI) for nationwide lakes in China. 32% of lakes (N = 1925) in China were eutrophic and 26% were oligotrophic, and a longitudinal pattern was discovered, with the 40-year average TSI of 62.26 in the eastern plain compared to 23.72 in the Tibetan Plateau. A decreasing trend was further observed in the past four decades with a correlation of -0.16, which was mainly discovered in the Tibetan Plateau lakes (r > -0.90, p < 0.01). The contribution of climate change and human activities was quantified and varied between lake zones, with anthropogenic factors playing a dominant role in the east plain lakes (88%, N = 473) and large lakes are subject to a more complex driving mechanism (≥ 3 driving factors). The study expands the spatiotemporal scale for eutrophication monitoring and provides an important base for strengthening lake management and ecological services.
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Background: Thyroid hormone receptor-associated protein 3 (THRAP3) is of great significance in DNA damage response, pre-mRNA processing, and nuclear export. However, the biological activities of THRAP3 in pan-cancer remain unexplored. We aimed to conduct a comprehensive analysis of THRAP3 and validate its expression levels in lung cancer. Methods: A pan-cancer analysis was conducted to study the correlation of THRAP3 expression with clinical outcome and the tumor microenvironment based on the available bioinformatics databases. The protein levels of THRAP3 were explored in lung cancer by immunohistochemistry (IHC) analysis. Single-cell sequencing (ScRNA-seq) analysis was employed to investigate the proportions of each cell type in lung adenocarcinoma (LUAD) and adjacent normal tissues, along with the expression levels of THRAP3 within each cell type. Results: THRAP3 is upregulated in multiple cancer types but exhibits low expression in lung squamous cell carcinoma (LUSC). immunohistochemistry results showed that THRAP3 is a lowly expression in LUAD and LUSC. THRAP3 elevation had a poor prognosis in kidney renal clear cell carcinoma and a prolonged survival time in kidney chromophobe, brain lower-grade glioma and skin cutaneous melanoma, as indicated by the KM curve. Single-cell analysis confirmed that the proportions of T/B cells, macrophages, and fibroblasts were significantly elevated in LUAD tissues, and THRAP3 is specifically overexpressed in mast cells. Conclusion: Our findings uncover that THRAP3 is a promising prognostic biomarker and immunotherapeutic target in multiple cancers, but in LUAD and LUSC, it may be a protective gene.