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BACKGROUND: In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. METHODS: We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. RESULTS: A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm's suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. CONCLUSIONS: The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.
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Algoritmos , Nível de Saúde , Estudos Observacionais como Assunto , Humanos , Estudos Observacionais como Assunto/métodos , Estudos Observacionais como Assunto/normas , Reprodutibilidade dos Testes , Coleta de Dados/métodos , Coleta de Dados/normas , Coleta de Dados/estatística & dados numéricosRESUMO
The continuous development and application of laser technology, and the increasing energy and power of laser output have promoted the development of various types of laser optical systems. The optical components based on quartz materials are key components of high-power laser systems, and their quality directly affects the load capacity of the system. Due to the photothermal effect when the laser interacts with the quartz material and generates extremely high temperatures in a short period of time, it is impossible to experimentally solve the phenomena and physical mechanisms under extreme conditions. Therefore, it is very important to select a suitable method to investigate the thermal effect of intense laser interaction with quartz materials and explain the related physical mechanism. In this study, a three-dimensional quarter-symmetric laser heating quartz material geometry model by using nonlinear transient finite element method was established, and its transient temperature field distribution of the quartz material after being heated by a 1,064 nm continuous laser was investigated. In addition, the influence of different laser parameters (laser spot radius, heat flux and irradiation time), material parameters (material thickness, material absorption rate of laser) on the thermal effect of heating quartz material were also studied. When the laser heat flux is 20 W/cm2, the diameter of the laser spot is 10 cm, the irradiation time is 600 s and the thickness is 4 cm, the temperature after laser heating can reach 940.18°C, which is far lower than the melting point. In addition, the temperature maximum probes were set at the overall model, spot edge and rear surface respectively, and their temperature rise curves with time were obtained. It is also found that there is a significant hysteresis period for the rear surface temperature change of the quartz material compared with the overall temperature change due to heat conduction. Finally, the method proposed can also be applied to the laser heating of other non-transparent materials.
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We predict a half-quantized mirror Hall effect induced by mirror symmetry in strong topological insulator films. These films are known to host a pair of gapless Dirac cones in the first Brillouin zone associated with surface electrons. Our findings reveal that mirror symmetry assigns a unique mirror parity to each Dirac cone, resulting in a half-quantized Hall conductance of ± e 2 2 h for each cone. Despite the total electrical Hall conductance being null due to time-reversal invariance, the difference in the Hall conductance between the two cones yields a quantized Hall conductance of e 2 h for the difference in mirror currents. The effect of helical edge mirror current - a crucial feature of this quantum effect - may, in principle, be determined by means of electrical measurements. The half-quantum mirror Hall effect reveals a type of mirror-symmetry induced quantum anomaly in a time-reversal invariant lattice system, giving rise to a topological metallic state of matter with time-reversal invariance.
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Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.
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Sequenciamento de Nucleotídeos em Larga Escala , Pulmão , Musaranhos , Viroma , Animais , Musaranhos/virologia , China , Pulmão/virologia , Viroma/genética , Filogenia , Vírus de RNA/genética , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , RNA Viral/genética , Vírus da Influenza A/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Vírus da Raiva/genética , Vírus da Raiva/classificação , Vírus da Raiva/isolamento & purificação , Reservatórios de Doenças/virologiaRESUMO
Global temperatures will continue to increase in the future. The â¼640,000-km2 Loess Plateau (LP) is a typical arid and semi-arid region in China. Similar regions cover â¼41% of the Earth, and its soils are some of the most severely eroded anywhere in the world. It is very important to understand the vegetation change and its ecological threshold under climate change on the LP for the sustainable development in the Yellow River Basin. However, little is known about how vegetation on the LP will respond to climate change and what is the sustainable threshold level of vegetation cover on the LP. Here we show that the temperature on the LP has risen 0.27 °C per decade over the past 50 years, a rate that is 30% higher than the average warming rate across China. During historical times, vegetation change was regulated by environmental factors and anthropogenic activities. Vegetation coverage was about 53% on the LP from the Xia Dynasty to the Spring and Autumn and Warring States period. Over the past 70 years, however, the environment has gradually improved and the vegetation cover had increased to â¼65% by 2021. We forecast future changes of vegetation cover on the LP in 2030s, in 2050s and in 2070s using SDM (Species Distribution Model) under Low-emission scenarios, Medium-emission scenarios and High-emission scenarios. An average value of vegetation cover under the three emission scenarios will be 64.67%, 62.70% and 61.47%, respectively. According to the historical record and SDM forecasts, the threshold level of vegetation cover on the LP is estimated to be 53-65%. Currently, vegetation cover on the LP has increased to the upper limit of the threshold value (â¼65%). We conclude that the risk of ecosystem collapse on the LP will increase with further temperature increases once the vegetated area and density exceed the threshold value. It is urgent to adopt sustainable strategies such as stopping expanding vegetation area and scientifically optimizing the vegetation structure on the LP to improve the ecological sustainability of the Yellow River Basin.
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Rice (Oryza sativa) plants contain plastidial and cytosolic disproportionating enzymes (DPE1 and DPE2). Our previous studies showed that DPE2 acts on maltose, the major product of starch degradation in pollens, releasing one glucose to fuel pollen tube growth and fertilization, whereas DPE1 participates in endosperm starch synthesis by transferring maltooligosyl groups from amylose to amylopectin, and removing excess short maltooligosaccharides. However, little is known about their integrated function. Here, we report that the coordinated actions of DPE1 and DPE2 contribute to grain setting and filling in rice. The dpe1dpe2 mutants could not be isolated from the progeny of heterozygous parental plants but were obtained via anther culture. Unlike that reported in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum), the dpe1dpe2 rice plants grew normally but only yielded a small number of empty, unfilled seeds. In the dpe1dpe2 seeds, nutrient accumulation was substantially reduced, and dorsal vascular bundles were also severely malnourished. Zymogram analyses showed that changes in activities of the major starch-synthesizing enzymes matched well with various endosperm phenotypes of mutant seeds. Mechanistically, DPE1 deficiency allowed normal starch mobilization in leaves and pollens but affected starch synthesis in endosperm, while DPE2 deficiency blocked starch degradation, resulting in substantially decreased levels of the sugars available for pollen tube growth and grain filling. Overall, our results demonstrate the great potential of DPE1-DPE2 as an important regulatory module to realize higher crop yields and present a promising target for regulating nutrient accumulation in cereal crop endosperm.
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The characteristics of patients with endophthalmitis due to penetrating ocular trauma are still limited. The aim of the study was to fill these gaps among Chinese population. This retrospective study included patients diagnosed as penetrating ocular traumatic endophthalmitis between January 2016 to December 2018. During the past 3-year period, a total of 201 patients with antecedent penetrating eye injuries were evaluated. Of which, 42 (20.9%) patients presented a clinical course compatible with acute infectious endophthalmitis. 39 (92.86%) patients were males, and 15 (35.71%) patients had mechanical injuries from intraocular foreign body (IOFB), the rate of endophthalmitis due to IOFB was 13.43%, higher to the rate among patients without IOFB (7.46%). The duration between injury occurrence and endophthalmitis onset was 1 day in 10 (23,80%) patients; 2 to 7 days in 31 (73.80%) patients, and 7 to 14 days in 1 (2.38%) patient. After 1 year follow-up, best corrected visual acuity (BCVA) better than 20/400 was observed in 15 (35.71%) patients, counting fingers and hand move in 17 (40.48%) patients, light perception in 5 (11.9%) patients and no light perception in 5 (11.9%) patients, respectively. Patients with promising outcomes had better initial BCVA at baseline (Pâ <â .001). Endophthalmitis is a severe ocular infectious condition that may lead to irreversible vision loss. A greater attention must be paid to penetrating eye injuries within males, who had poor BCVA at baseline, particularly with obvious IOFB.
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Endoftalmite , Corpos Estranhos no Olho , Ferimentos Oculares Penetrantes , Acuidade Visual , Humanos , Endoftalmite/epidemiologia , Endoftalmite/etiologia , Masculino , Ferimentos Oculares Penetrantes/epidemiologia , Ferimentos Oculares Penetrantes/complicações , Feminino , Estudos Retrospectivos , Adulto , Corpos Estranhos no Olho/epidemiologia , Pessoa de Meia-Idade , China/epidemiologia , Adulto Jovem , AdolescenteRESUMO
Diabetes mellitus, stemming from either insulin resistance or inadequate insulin secretion, represents a complex ailment that results in prolonged hyperglycemia and severe complications. Patients endure severe ramifications such as kidney disease, vision impairment, cardiovascular disorders, and susceptibility to infections, leading to significant physical suffering and imposing substantial socio-economic burdens. This condition has evolved into an increasingly severe health crisis. There is an urgent need to develop new treatments with improved efficacy and fewer adverse effects to meet clinical demands. However, novel drug development is costly, time-consuming, and often associated with side effects and suboptimal efficacy, making it a major challenge. Artificial Intelligence (AI) and Machine Learning (ML) have revolutionized drug development across its comprehensive lifecycle, spanning drug discovery, preclinical studies, clinical trials, and post-market surveillance. These technologies have significantly accelerated the identification of promising therapeutic candidates, optimized trial designs, and enhanced post-approval safety monitoring. Recent advances in AI, including data augmentation, interpretable AI, and integration of AI with traditional experimental methods, offer promising strategies for overcoming the challenges inherent in AI-based drug discovery. Despite these advancements, there exists a notable gap in comprehensive reviews detailing AI and ML applications throughout the entirety of developing medications for diabetes mellitus. This review aims to fill this gap by evaluating the impact and potential of AI and ML technologies at various stages of diabetes mellitus drug development. It does that by synthesizing current research findings and technological advances so as to effectively control diabetes mellitus and mitigate its far-reaching social and economic impacts. The integration of AI and ML promises to revolutionize diabetes mellitus treatment strategies, offering hope for improved patient outcomes and reduced healthcare burdens worldwide.
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ABSTRACTDespite no carbapenem use in food animals, carbapenem-resistant Klebsiella pneumoniae (CRKP) perseveres within food animals, rising significant concerns regarding public health risks originating from these non-clinical reservoirs. To investigate the potential link between CRKP in food animals and its infections in humans, we conducted a cross-sectional study encompassing human clinical, meat products, and farm animals, in Qingdao city, Shandong province, China. We observed a relatively higher presence of CRKP among hospital inpatients (7.3%) compared to that in the meat products (2.7%) and farm animals (pig, 4.6%; chicken, 0.63%). Multilocus sequence typing and core-genome phylogenetic analyses confirm there is no evidence of farm animals and meat products in the clinical acquisition of K. pneumoniae isolates and carbapenem-resistant genes. However, potential transmission of K. pneumoniae of ST659 and IncX3 plasmid harbouring blaNDM-5 gene from pigs to pork and farm workers was observed. Our findings suggest a limited role of farm animals and meat products in the human clinical acquisition of K. pneumoniae, and the transmission of K. pneumoniae is more common within settings, than between them.
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Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Tipagem de Sequências Multilocus , Animais , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Humanos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/transmissão , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/veterinária , China/epidemiologia , Estudos Transversais , Suínos , Carbapenêmicos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Galinhas/microbiologia , Antibacterianos/farmacologia , Filogenia , Masculino , Feminino , Pessoa de Meia-Idade , Animais Domésticos/microbiologia , Testes de Sensibilidade Microbiana , Carne/microbiologia , Plasmídeos/genética , AdultoRESUMO
Volatile sulfur compounds (VSCs) significantly influence food flavor and garner considerable attention in flavor research due to their low sensory thresholds, diverse odor attributes, and high reactivity. Extensive research studies have explored VSC formation through thermal processes such as the Maillard reaction, thermal pyrolysis, oxidation, and enzymatic reactions. However, understanding of the specific reaction mechanisms and processes remains limited. This is due to the dispersed nature of existing studies, the undefined intermediates involved, and the complexity of the matrices and processing conditions. Given these limitations, the authors have shifted their focus from foods to sulfides. The structure, source, and chemical characteristics of common precursors (sulfur-containing amino acids and derivatives, thiamine, thioglucoside, and lentinic acid) and their corresponding reactive intermediates (hydrogen sulfide, thiol, alkyl sulfide, alkyl sulfenic acid, and thial) are provided, and the degradation mechanisms, reaction rules, and matrix conditions are summarized based on their chemical characteristics. Additionally, the VSC formation processes in several typical foods during processing are elucidated, adhering to these identified rules. This article provides a comprehensive overview of VSCs, from precursors and intermediates to end products, and is crucial for understanding the mechanisms behind VSC formation and managing the flavor qualities of processed foods.
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Manipulação de Alimentos , Temperatura Alta , Odorantes , Compostos de Enxofre , Compostos de Enxofre/química , Odorantes/análise , Manipulação de Alimentos/métodos , Compostos Orgânicos Voláteis/química , Paladar , Reação de Maillard , Análise de AlimentosRESUMO
BACKGROUND: The objective of this study is to evaluate the concentrations of heavy metals and radionuclides in water and fish samples collected from six designated sampling stations along the Linshui River, in close proximity to a Uranium Tailing Pond situated in China. Additionally, it seeks to estimate the bioaccumulation of heavy metals and conduct risk assessments, both carcinogenic and non-carcinogenic, for consumers. METHODS: Water and fish samples (yellowhead catfish and common carp) were systematically collected from six stations along the river from January to June 2023, adhering to ethical standards and standard protocols for assessing water quality. Samples underwent chemical preparation and analysis for heavy metals using Graphite Furnace Atomic Absorption Spectrophotometry and Cold Vapor Atomic Absorption Spectroscopy, and for radionuclides using gamma spectrometry, with all methods validated for accuracy. RESULTS: The water samples showed metal and radionuclide concentrations within acceptable limits, except for higher levels of U and Th compared to background values. Heavy metal concentrations were higher in common carp compared to yellowhead catfish, with both species exhibiting a similar trend. While non-carcinogenic health risk, as indicated by target hazard quotients, was low for consumers, the health risk data emphasized the carcinogenic threats posed by U238 and Th234. CONCLUSIONS: The study highlights the importance of implementing comprehensive river restoration measures. Additionally, the bioconcentration factor values indicate minimal accumulation of heavy metals in the muscle tissue of fish.
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Peixes , Metais Pesados , Rios , Urânio , Poluentes Químicos da Água , Metais Pesados/análise , Animais , China , Rios/química , Urânio/análise , Poluentes Químicos da Água/análise , Peixes/metabolismo , Radioisótopos/análise , Peixes-Gato/metabolismo , Monitoramento Ambiental/métodosRESUMO
Helicobacter pylori is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have demonstrated that H. pylori infection plays a role in regulating the function of host cells, thereby contributing to the malignant transformation of these cells. However, H. pylori infection is a chronic process, and short-term cellular experiments may not provide a comprehensive understanding of the in vivo situation, especially when considering the lower oxygen levels in the human stomach. In this study, we aimed to investigate the mechanisms underlying gastric cell dysfunction after prolonged exposure to H. pylori under hypoxic conditions. We conducted a co-culture experiment using the gastric cell line GES-1 and H. pylori for 30 generations under intermittent hypoxic conditions. By closely monitoring cell proliferation, migration, invasion, autophagy, and apoptosis, we revealed that sustained H. pylori stimulation under hypoxic conditions significantly influences the function of GES-1 cells. This stimulation induces epithelial-mesenchymal transition and contributes to the propensity for malignant transformation of gastric cells. To confirm the in vitro results, we conducted an experiment involving Mongolian gerbils infected with H. pylori for 85 weeks. All the results strongly suggest that the Nod1 receptor signaling pathway plays a crucial role in H. pylori-related apoptosis and autophagy. In summary, continuous stimulation by H. pylori affects the functioning of gastric cells through the Nod1 receptor signaling pathway, increasing the likelihood of cell carcinogenesis. The presence of hypoxic conditions further exacerbates this process.IMPORTANCEDeciphering the collaborative effects of Helicobacter pylori infection on gastric epithelial cell function is key to unraveling the development mechanisms of gastric cancer. Prior research has solely examined the outcomes of short-term H. pylori stimulation on gastric epithelial cells under aerobic conditions, neglecting the bacterium's nature as a microaerophilic organism that leads to cancer following prolonged stomach colonization. This study mimics a more genuine in vivo infection scenario by repeatedly exposing gastric epithelial cells to H. pylori under hypoxic conditions for up to 30 generations. The results show that chronic exposure to H. pylori in hypoxia substantially increases cell migration, invasion, and epithelial-mesenchymal transition, while suppressing autophagy and apoptosis. This highlights the significance of hypoxic conditions in intensifying the carcinogenic impact of H. pylori infection. By accurately replicating the in vivo gastric environment, this study enhances our comprehension of H. pylori's pathogenic mechanisms in gastric cancer.
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Transformação Celular Neoplásica , Células Epiteliais , Transição Epitelial-Mesenquimal , Mucosa Gástrica , Gerbillinae , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Helicobacter pylori/patogenicidade , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Animais , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Humanos , Células Epiteliais/microbiologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Hipóxia/microbiologia , Linhagem Celular , Proliferação de Células , Apoptose , Movimento Celular , Autofagia , Estômago/microbiologia , Estômago/patologiaRESUMO
Q-switched fiber lasers have become reliable light sources for generating high-energy pulses, which can be passively modulated by saturable absorbers with excellent nonlinear optical properties. The composite combining Ag and MXene exhibits a broadband nonlinear response and high modulation depth, making it a promising candidate for saturable absorbers in pulsed lasers. Herein, we demonstrate a Q-switched Tm:Ho co-doped fiber laser centered at 2 µm, where the Ag/MXene composite serves as a saturable absorber to generate pulses. The typical spectrum, pulse train, and radio frequency spectrum of Q-switched pulses were observed, in which the 60 dB signal-to-noise ratio was higher than that of 2 µm Q-switched fiber lasers based on other materials, demonstrating the stability of the output pulses. Additionally, the long-term stability of the laser was evaluated over 2 h, where the well-maintained central wavelength and output power also indicated the robustness of the Q-switched laser. Furthermore, the influence of the pump power on the parameters of Q-switched pulses was also investigated, which is conducive to control the output characteristics of lasers. Specifically, the pulse width of the Q-switched pulse decreased, while the repetition rate, output power, and single pulse energy all increased with the increase in pump power. These experimental results demonstrate the ability of Ag/MXene as a saturable absorber and show its potential for generating high-performance pulses in ultrafast lasers.
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The release of host mitochondrial cardiolipin is believed to be the main factor that contributes to the production of anti-cardiolipin antibodies in syphilis. However, the precise mechanism by which mitochondria release cardiolipin in this context remains elusive. This study aimed to elucidate the mechanisms underlying mitochondrial cardiolipin release in syphilis. We conducted a cardiolipin quantitative assay and immunofluorescence analysis to detect mitochondrial cardiolipin release in human microvascular endothelial cells (HMEC-1), with and without Treponema pallidum (Tp) infection. Furthermore, we explored apoptosis, a key mechanism for mitochondrial cardiolipin release. The potential mediator molecules were then analyzed through RNA-sequence and subsequently validated using in vitro knockout techniques mediated by CRISPR-Cas9 and pathway-specific inhibitors. Our findings confirm that live-Tp is capable of initiating the release of mitochondrial cardiolipin, whereas inactivated-Tp does not exhibit this capability. Additionally, apoptosis detection further supports the notion that the release of mitochondrial cardiolipin occurs independently of apoptosis. The RNA-sequencing results indicated that microtubule-associated protein2 (MAP2), an axonogenesis and dendrite development gene, was up-regulated in HMEC-1 treated with Tp, which was further confirmed in syphilitic lesions by immunofluorescence. Notably, genetic knockout of MAP2 inhibited Tp-induced mitochondrial cardiolipin release in HMEC-1. Mechanically, Tp-infection regulated MAP2 expression via the MEK-ERK-HES1 pathway, and MEK/ERK phosphorylation inhibitors effectively block Tp-induced mitochondrial cardiolipin release. This study demonstrated that the infection of live-Tp enhanced the expression of MAP2 via the MEK-ERK-HES1 pathway, thereby contributing to our understanding of the role of anti-cardiolipin antibodies in the diagnosis of syphilis.
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OBJECTIVE: To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism. METHODS: Porcine MMCs at 70 days of gestation were used as tool cells, cultured in osteogenic induction medium, identified by immunocytochemistry staining. Osteogenic potential of porcine MMCs and naringin's ability to enhance this process was tested by detecting changes in cell viability, alkaline phosphatase (ALP) activity, the expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN), and the formation of mineralized nodules, and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin. RESULTS: Immunocytochemical staining showed that the cells were Vimentin and Six2(+), E-cadherin and CK-18(-). Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability, ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin, manifested by decreased ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). CONCLUSION: Naringin, the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen (Kidney) and strengthening bone, enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.
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Zygotic genome activation (ZGA) is a pivotal event in mammalian embryogenesis, marking the transition from maternal to zygotic control of development. During the ZGA process that is characterized by the intricate cascade of gene expression, who tipped the first domino in a meticulously arranged sequence is a subject of paramount interest. Recently, Dux, Obox and Nr5a2 were identified as pioneer transcription factors that reside at the top of transcriptional hierarchy. Through co-option of retrotransposon elements as hubs for transcriptional activation, these pioneer transcription factors rewire the gene regulatory network, thus initiating ZGA. In this review, we provide a snapshot of the mechanisms underlying the functions of these pioneer transcription factors. We propose that ZGA is the starting point where the embryo's own genome begins to influence development trajectory, therefore in-depth dissecting the functions of pioneer transcription factors during ZGA will form a cornerstone of our understanding for early embryonic development, which will pave the way for advancing our grasp of mammalian developmental biology and optimizing in vitro production (IVP) techniques.
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Genoma , Fatores de Transcrição , Zigoto , Zigoto/metabolismo , Animais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Humanos , Regulação da Expressão Gênica no Desenvolvimento , Desenvolvimento Embrionário/genética , Retroelementos/genética , Ativação Transcricional/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismoRESUMO
In the field of building energy conservation, the development of biodegradable biomass aerogels with excellent mechanical performance, flame retardancy and thermal insulation properties is of particular importance. Here, a directional freeze-drying method was used for fabricating composite sodium alginate (SA) aerogels containing functionalized ammonium polyphosphate (APP) flame retardant. In particular, APP was coated with melamine (MEL) and phytic acid (PA) by a supramolecular assembly process. Through optimizing the flame retardant addition, the SA-20 AMP sample exhibited excellent flame retardant and thermal insulation properties, with the limiting oxygen index of 38.2 % and the UL-94 rating of V-0. Such aerogels with anisotropic morphology demonstrated a low thermal conductivity of 0.0288 (W/m·K) in the radial direction (perpendicular to the lamellar structure). In addition, as-obtained aerogels displayed remarkable water stability and mechanical properties, indicating significant potential for practical applications.
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Alginatos , Retardadores de Chama , Géis , Alginatos/química , Géis/química , Triazinas/química , Condutividade Térmica , Ácido Fítico/química , Polifosfatos/química , Fósforo/química , Nitrogênio/químicaRESUMO
Clostridium perfringens has emerged as a growing public health concern due to its ability to cause various infections and its increasing resistance to antibiotics. To assess its current epidemiology in clinical settings, we conducted a survey involving 426 healthy individuals and 273 ICU inpatients at a provincial hospital in China. Our findings revealed a high prevalence of C. perfringens in healthy individuals (45.77%, 95% CI: 41.0%-50.6%) and ICU patients (12.82%, 95% CI: 9.1%-17.4%). The identified 220 C. perfringens isolates displayed substantial resistance to erythromycin (57.9%), clindamycin (50.7%), and tetracycline (32.0%), primarily attributed to the presence of erm(Q) (54.4%), lnu(P) (13.8%), tetB(P) (83.6%), and tetA(P) (66.7%). Notably, C. perfringens isolates from this particular hospital demonstrated a high degree of sequence type diversity and phylogenic variation, suggesting that the potential risk of infection primarily arises from the bacteria's gut colonization rather than clonal transmissions within the clinical environment. This study provides an updated analysis of the current epidemiology of C. perfringens in healthy individuals and ICU patients in China and emphasizes the need to optimize intervention strategies against its public health threat. IMPORTANCE: Clostridium perfringens is a bacterium of growing public health concern due to its ability to cause infections and its increasing resistance to antibiotics. Understanding its epidemiology in clinical settings is essential for intervention strategies. This study surveyed healthy individuals and ICU inpatients in a provincial hospital in China. It found a high prevalence of C. perfringens, indicating infection risk. The isolates also showed significant antibiotic resistance. Importantly, the study revealed diverse sequence types and phylogenetic variation, suggesting infection risk from intestinal colonization rather than clonal transmission in hospitals. This analysis emphasizes the need to optimize intervention strategies against this public health threat.
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Antibacterianos , Portador Sadio , Infecções por Clostridium , Clostridium perfringens , Unidades de Terapia Intensiva , Humanos , Clostridium perfringens/genética , Clostridium perfringens/isolamento & purificação , Clostridium perfringens/efeitos dos fármacos , Clostridium perfringens/classificação , China/epidemiologia , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/transmissão , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Antibacterianos/farmacologia , Portador Sadio/microbiologia , Portador Sadio/epidemiologia , Idoso , Prevalência , Adulto Jovem , Filogenia , Intestinos/microbiologia , Testes de Sensibilidade Microbiana , Adolescente , Farmacorresistência BacterianaRESUMO
To inhibit the deep conversion of partial oxidation products (POX-products) in C-H bonds' functionalization utilizing O2, 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin cobalt(II) and 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin copper(II) were immobilized on the surface of hybrid silica to conduct relay catalysis on the surface. Fluorocarbons with low polarity and heterogeneous catalysis were devised to decrease the convenient accessibility of polar POX-products to catalytic centers on the lower polar surface. Relay catalysis between Co and Cu was designed to utilize the oxidation intermediates alkyl hydroperoxides to transform more C-H bonds. Systematic characterizations were conducted to investigate the structure of catalytic materials and confirm their successful syntheses. Applied to C-H bond oxidation, not only deep conversion of POX-products was inhibited but also substrate conversion and POX-product selectivity were improved simultaneously. For cyclohexane oxidation, conversion was improved from 3.87% to 5.27% with selectivity from 84.8% to 92.3%, which was mainly attributed to the relay catalysis on the surface excluding products. The effects of the catalytic materials, product exclusion, relay catalysis, kinetic study, substrate scope, and reaction mechanism were also investigated. To our knowledge, a practical and novel strategy was presented to inhibit the deep conversion of POX-products and to achieve efficient and accurate oxidative functionalization of hydrocarbons. Also, a valuable protocol was provided to avoid over-reaction in other chemical transformations requiring high selectivity.