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1.
Conserv Physiol ; 12(1): coae044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962510

RESUMO

Concerted conservation efforts have brought the giant panda (Ailuropoda melanoleuca) back from the brink of extinction, but pandas continue to face anthropogenic threats in the wild and breeding success in captivity remains low. Because stress can have detrimental impacts on reproduction, monitoring stress- and sex-steroid levels would help assess the effectiveness of conservation mitigation measures in panda populations as well as monitor the welfare and reproductive health of captive animals. In this proof-of-concept study, we used faecal sex steroid and cortisol concentrations (n = 867 samples collected from five males and five females at Beijing Zoo every 4 days over the course of 12 months) as a reference to investigate if testosterone, estradiol, progesterone and cortisol can be meaningfully measured in panda hair (n = 10) using radio-immuno-assays. Additionally, we calculated the ratio of testosterone to cortisol (T:C ratio) for each male, which can provide a biomarker of stress and physical performance. Our findings revealed distinct monthly variations in faecal sex-steroid and cortisol concentrations, reflecting reproductive seasonality and visitor-related stress among individual pandas. Notably, the oldest male had a significantly lower T:C ratio than other males. Our results confirm that the level of sex steroids and cortisol can be assayed by panda hair, and the hair cortisol concentrations correlate significantly with that in faeces with one month lag behind (r = 0.68, P = 0.03). However, the concentrations of hormones detected in saliva are lower than those in faeces by two orders of magnitude, making it difficult to ensure accuracy. By assessing the applicability of hair, faecal and salivary sampling, we can infer their utility in monitoring the reproductive status and acute and chronic stress levels of giant pandas, thereby providing a means to gauge the success of ongoing habitat restoration efforts and to discuss the feasibility of sample collection from wild populations.

2.
BMC Musculoskelet Disord ; 25(1): 521, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970016

RESUMO

BACKGROUND: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. METHODS: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. RESULTS: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). CONCLUSIONS: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.


Assuntos
Artrite Reumatoide , Densidade Óssea , Fraturas Ósseas , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Densidade Óssea/genética , Fraturas Ósseas/genética , Fraturas Ósseas/epidemiologia , Artrite Reumatoide/genética , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Doenças Reumáticas/genética , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/complicações , Fatores de Risco , Espondilite Anquilosante/genética , Espondilite Anquilosante/complicações , Espondilite Anquilosante/epidemiologia , Predisposição Genética para Doença
3.
Pest Manag Sci ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946320

RESUMO

BACKGROUND: The Red Imported Fire Ant (RIFA), scientifically known as Solenopsis invicta, is a destructive invasive species causing considerable harm to ecosystems and generating substantial economic costs globally. Traditional methods for RIFA nests detection are labor-intensive and may not be scalable to larger field areas. This study aimed to develop an innovative surveillance system that leverages artificial intelligence (AI) and robotic dogs to automate the detection and geolocation of RIFA nests, thereby improving monitoring and control strategies. RESULTS: The designed surveillance system, through integrating the CyberDog robotic platform with a YOLOX AI model, demonstrated RIFA nest detection precision rates of >90%. The YOLOX model was trained on a dataset containing 1118 images and achieved a final precision rate of 0.95, with an inference time of 20.16 ms per image, indicating real-time operational suitability. Field tests revealed that the CyberDog system identified three times more nests than trained human inspectors, with significantly lower rates of missed detections and false positives. CONCLUSION: The findings underscore the potential of AI-driven robotic systems in advancing pest management. The CyberDog/YOLOX system not only matched human inspectors in speed, but also exceeded them in accuracy and efficiency. This study's results are significant as they highlight how technology can be harnessed to address biological invasions, offering a more effective, ecologically friendly, and scalable solution for RIFA detection. The successful implementation of this system could pave the way for broader applications in environmental monitoring and pest control, ultimately contributing to the preservation of biodiversity and economic stability. © 2024 Society of Chemical Industry.

4.
Front Immunol ; 15: 1351945, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994368

RESUMO

Background: Left ventricular hypertrophy (LVH) is a common consequence of hypertension and can lead to heart failure. The immune response plays an important role in hypertensive LVH; however, there is no comprehensive method to investigate the mechanistic relationships between immune response and hypertensive LVH or to find novel therapeutic targets. This study aimed to screen hub immune-related genes involved in hypertensive LVH as well as to explore immune target-based therapeutic drugs. Materials and methods: RNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored. Results: A total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH. Conclusion: This study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions.


Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Animais , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/etiologia , Camundongos , Hipertensão/genética , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Masculino , Modelos Animais de Doenças , Redes Reguladoras de Genes , Camundongos Endogâmicos C57BL , Perfilação da Expressão Gênica
5.
Food Res Int ; 189: 114573, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876600

RESUMO

Food proteins and their peptides play a significant role in the important biological processes and physiological functions of the body. The peptides show diverse biological benefits ranging from anticancer to antihypertensive, anti-obesity, and immunomodulatory, among others. In this review, an overview of food protein digestion in the gastrointestinal tract and the mechanisms involved was presented. As some proteins remain resistant and undigested, the multifarious factors (e.g. protein type and structure, microbial composition, pH levels and redox potential, host factors, etc.) affecting their colonic fermentation, the derived peptides, and amino acids that evade intestinal digestion are thus considered. The section that follows focuses on the mechanisms of the peptides with anticancer, antihypertensive, anti-obesity, and immunomodulatory effects. As further considerations were made, it is concluded that clinical studies targeting a clear understanding of the gastrointestinal stability, bioavailability, and safety of food-based peptides are still warranted.


Assuntos
Fármacos Antiobesidade , Anti-Hipertensivos , Antineoplásicos , Proteínas Alimentares , Digestão , Peptídeos , Humanos , Anti-Hipertensivos/farmacologia , Proteínas Alimentares/metabolismo , Peptídeos/farmacologia , Antineoplásicos/farmacologia , Fármacos Antiobesidade/farmacologia , Trato Gastrointestinal/metabolismo , Animais , Fatores Imunológicos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Disponibilidade Biológica , Agentes de Imunomodulação/farmacologia
6.
Int J Obes (Lond) ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902386

RESUMO

BACKGROUND: As the second most risky environmental pollution, noise imposes threats to human health. Exposure to high-intensity noise causes hearing impairment, psychotic disorders, endocrine modifications. The relationship among low-intensity noise, obesity and lipid-regulating nuclear factor PPARα is not yet clear. METHODS: In this study, male wild-type (WT) and Pparα-null (KO) mice on a high-fat diet (HFD) were exposed to 75 dB noise for 12 weeks to explore the effect of low-intensity noise on obesity development and the role of PPARα. 3T3-L1 cells were treated with dexamethasone (DEX) and sodium oleate (OA) to verify the down-stream effect of hypothalamic-pituitary-adrenal (HPA) axis activation on the adipose tissues. RESULTS: The average body weight gain (BWG) of WT mice on HFD exposed to noise was inhibited, which was not observed in KO mice. The mass and adipocyte size of adipose tissues accounted for the above difference of BWG tendency. In WT mice on HFD, the adrenocorticotropic hormone level was increased by the noise challenge. The aggravation of fatty liver by noise exposure occurred in both mouse lines, and the transport of hepatic redundant lipid to adipose tissues were similar. The lipid metabolism in adipose tissue driven by HPA axis accorded with the BWG inhibition in vivo, validated in 3T3-L1 adipogenic stem cells. CONCLUSION: Chronic exposure to low-intensity noise aggravated fatty liver in both WT and KO mice. BWG inhibition was observed only in WT mice, which covered up the aggravation of fatty liver by noise exposure. PPARα mediates the activation of HPA axis by noise exposure in mice on HFD. Elevated adrenocorticotropic hormone (ACTH) promoted lipid metabolism in adipocytes, which contributed to the disassociation of BWG and fatty liver development in male WT mice. Summary of PPARα suppresses noise-induced body weight gain in mice on high-fat-diet. Chronic exposure to low-intensity noise exposure inhibited BWG by PPARα-dependent activation of the HPA axis.

7.
Sci Rep ; 14(1): 14212, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902448

RESUMO

Humans can easily perform various types of hugs in human contact and affection experience. With the prevalence of robots in social applications, they would be expected to possess the capability of hugs as humans do. However, it is still not an easy task for robots, considering the complex force and spatial constraints of robot hugs. In this work, we propose the HUG taxonomy, which distinguishes between different hugging patterns based on human demonstrations and prior knowledge. In this taxonomy, hugs are arranged according to (1) hugging tightness, (2) hugging style, and (3) bilateral coordination, resulting in 16 different hug types. We then further study the hug type preference of humans in different scenarios and roles. Furthermore, we propose a rule-based classification system to validate the potential of this taxonomy in human-robot hugs based on a humanoid robot with an E-skin of contact sensation. The HUG taxonomy could provide human hugging behavior information in advance, facilitating the action control of humanoid robots. We believe the results of our work can benefit future studies on human-robot hugging interactions.


Assuntos
Robótica , Humanos , Robótica/métodos
8.
Phys Rev Lett ; 132(21): 215101, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38856257

RESUMO

Polarization of drift-Alfvén waves, defined as the ratio of electrostatic to electromagnetic fluctuations, has remained unmeasurable in fusion plasmas for decades, despite its pivotal role in understanding wave dynamics and their impact on plasmas. We report the first measurements of drift-Alfvén wave polarization in a hot, magnetically confined plasma. The breakthrough is enabled by a novel methodology developed from gyrokinetic theory, utilizing fluctuations of electron temperature and density. Analysis of data from the DIII-D tokamak reveals that the waves above the geodesic acoustic mode frequency exhibit dominant electromagnetic polarization, whereas lower-frequency waves show a mix of electromagnetic and electrostatic polarization, indicating a strong coupling between shear Alfvén waves and drift-acoustic waves.

9.
J Colloid Interface Sci ; 671: 725-731, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38823113

RESUMO

Metal halide perovskites, as a new class of attractive and potential scintillators, are highly promising in X-ray imaging. However, their application is limited by the sensitivity to moisture and irradiation. To address this issue, we reported a 2D layered double perovskite material Cs4Cd1-xMnxBi2Cl12 that exhibits high stability both under ambient condition and under X-ray irradiation. Cs4Cd1-xMnxBi2Cl12 demonstrates superior scintillation performance, including excellent X-ray response linearity and a high light yield (∼34,450 photons/MeV). More importantly, the X-ray excited emission intensity maintains 92% and 94% of its original value after stored at ambient condition for over two years and after X-ray irradiation with a total dose of 11.4 Gy, respectively. By mixing with PDMS (polydimethylsiloxane), we have successfully produced a high-quality flexible film that can be bent freely while maintaining its excellent scintillation properties. The scintillating screen exhibits outstanding imaging ability with a spatial resolution of up to 16.7 line pairs per millimeter (lp/mm), also, the superiority of this scintillation screen in flexible X-ray imaging is demonstrated. These results indicate the huge potential of this high-stability double perovskite scintillator in X-ray imaging.

10.
J Int Med Res ; 52(6): 3000605241254788, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38867509

RESUMO

OBJECTIVE: Neonatal necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease. We investigated intestinal fatty acid binding protein (I-FABP), I-FABP mRNA, and interleukin-6 (IL-6) as potential diagnostic biomarkers in NEC. METHODS: Forty mice were subjected to hypoxic-ischemic intestinal injury, and then serum I-FABP protein and mRNA levels were quantified. Ileal tissue pathological scores were determined by hematoxylin and eosin staining. I-FABP expression levels and translocation in these tissues were detected using western blotting and immunofluorescence, respectively. Samples from 30 human neonates with NEC and 30 healthy neonates had serum I-FABP protein/mRNA and IL-6 levels measured. RESULTS: The mouse ileal tissue pathological score and I-FABP levels, as well as serum I-FABP and I-FABP mRNA levels, were significantly higher in the model group than in the control group. Serum I-FABP, I-FABP mRNA, and IL-6 levels were significantly higher in human neonates with NEC than in the healthy group. Logistic regression and receiver operating curve analyses revealed that I-FABP protein/mRNA and IL-6 levels could be diagnostic biomarkers for NEC. CONCLUSIONS: I-FABP protein/mRNA and IL-6 levels are useful biomarkers of intestinal ischemic injury in neonates with NEC. The combined detection of I-FABP protein/mRNA and IL-6 is recommended rather than using a single biomarker.


Assuntos
Biomarcadores , Modelos Animais de Doenças , Enterocolite Necrosante , Proteínas de Ligação a Ácido Graxo , Interleucina-6 , Camundongos Endogâmicos BALB C , RNA Mensageiro , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/sangue , Enterocolite Necrosante/patologia , Enterocolite Necrosante/genética , Enterocolite Necrosante/diagnóstico , Animais , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Interleucina-6/sangue , Interleucina-6/genética , Recém-Nascido , Humanos , Biomarcadores/sangue , Biomarcadores/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/sangue , Camundongos , Masculino , Feminino , Animais Recém-Nascidos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Íleo/metabolismo , Íleo/patologia , Estudos de Casos e Controles , Curva ROC
11.
Sci Rep ; 14(1): 12651, 2024 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825618

RESUMO

Effective disinfection methods are crucial in the cold chain transportation process of food due to the specificity of temperature and the diversity of contaminated flora. The objective of this study was to investigate the sanitizing effect of different disinfectants on various fungi at - 20 °C to achieve accurate disinfection of diverse bacterial populations. Peracetic acid, hydrogen peroxide, and potassium bisulfate were selected as low-temperature disinfectants and were combined with antifreeze. The sanitizing effect of these cryogenic disinfectants on pathogens such as Bacillus subtilis black variant spores (ATCC9372), Staphylococcus aureus (ATCC 6538), Candida albicans (ATCC 10231), Escherichia coli (8099), and poliovirus (PV-1) was sequentially verified by bactericidal and virus inactivation experiments. After a specified time of disinfection, a neutralizing agent was used to halt the sanitizing process. The study demonstrates that different disinfectants exhibit selective effects during the low-temperature disinfection process. Peracetic acid, hydrogen peroxide, and potassium monopersulfate are suitable for the low-temperature environmental disinfection of bacterial propagules, viruses, and fungal contaminants. However, for microorganisms with strong resistance to spores, a low-temperature disinfectant based on peracetic acid should be chosen for effective disinfection treatment. Our results provide a valuable reference for selecting appropriate disinfectants to sanitize various potential pathogens in the future.


Assuntos
Temperatura Baixa , Desinfetantes , Desinfecção , Peróxido de Hidrogênio , Ácido Peracético , Desinfetantes/farmacologia , Desinfecção/métodos , Peróxido de Hidrogênio/farmacologia , Ácido Peracético/farmacologia , Sulfatos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Compostos de Potássio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Poliovirus/efeitos dos fármacos
12.
In Vivo ; 38(4): 1677-1689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936893

RESUMO

BACKGROUND/AIM: Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known. MATERIALS AND METHODS: In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot. RESULTS: The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses. CONCLUSION: Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them.


Assuntos
Depressão , Modelos Animais de Doenças , Sistema Hipotálamo-Hipofisário , Hepatopatia Gordurosa não Alcoólica , Sistema Hipófise-Suprarrenal , Animais , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Camundongos , Depressão/metabolismo , Depressão/etiologia , Depressão/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Masculino , Camundongos Endogâmicos C57BL , Hormônio Liberador da Corticotropina/metabolismo , Hormônio Liberador da Corticotropina/genética , Dieta Hiperlipídica/efeitos adversos , Hormônio Adrenocorticotrópico/sangue , Fígado/metabolismo , Fígado/patologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Corticosterona/sangue
13.
Apoptosis ; 29(7-8): 1126-1144, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38824480

RESUMO

BACKGROUND: 5-Fluorouracil (5-FU) has been used as a standard first-line treatment for colorectal cancer (CRC) patients. Although 5-FU-based chemotherapy and immune checkpoint blockade (ICB) have achieved success in treating CRC, drug resistance and low response rates remain substantial limitations. Thus, it is necessary to construct a 5-FU resistance-related signature (5-FRSig) to predict patient prognosis and identify ideal patients for chemotherapy and immunotherapy. METHODS: Using bulk and single-cell RNA sequencing data, we established and validated a novel 5-FRSig model using stepwise regression and multiple CRC cohorts and evaluated its associations with the prognosis, clinical features, immune status, immunotherapy, neoadjuvant therapy, and drug sensitivity of CRC patients through various bioinformatics algorithms. Unsupervised consensus clustering was performed to categorize the 5-FU resistance-related molecular subtypes of CRC. The expression levels of 5-FRSig, immune checkpoints, and immunoregulators were determined using quantitative real-time polymerase chain reaction (RT‒qPCR). Potential small-molecule agents were identified via Connectivity Map (CMap) and molecular docking. RESULTS: The 5-FRSig and cluster were confirmed as independent prognostic factors in CRC, as patients in the low-risk group and Cluster 1 had a better prognosis. Notably, 5-FRSig was significantly associated with 5-FU sensitivity, chemotherapy response, immune cell infiltration, immunoreactivity phenotype, immunotherapy efficiency, and drug selection. We predicted 10 potential compounds that bind to the core targets of 5-FRSig with the highest affinity. CONCLUSION: We developed a valid 5-FRSig to predict the prognosis, chemotherapeutic response, and immune status of CRC patients, thus optimizing the therapeutic benefits of chemotherapy combined with immunotherapy, which can facilitate the development of personalized treatments and novel molecular targeted therapies for patients with CRC.


Assuntos
Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Fluoruracila , Imunoterapia , Humanos , Fluoruracila/uso terapêutico , Fluoruracila/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Prognóstico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Feminino , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/imunologia , Simulação de Acoplamento Molecular
14.
PLoS Comput Biol ; 20(6): e1012244, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38917196

RESUMO

Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.


Assuntos
Antiarrítmicos , Simulação por Computador , Modelos Cardiovasculares , Infarto do Miocárdio , Isquemia Miocárdica , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Humanos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Biologia Computacional
15.
Artigo em Inglês | MEDLINE | ID: mdl-38836736

RESUMO

Objective: This study aimed to investigate the efficacy of electroacupuncture (EA) combined with growth hormone in alleviating quadriceps atrophy and enhancing knee function following anterior cruciate ligament reconstruction. Methods: A prospective study was conducted, and a total of 90 patients exhibiting quadriceps atrophy after anterior cruciate ligament reconstruction were recruited between July 2020 and July 2022 from Shenzhen Pingle Orthopedic Hospital. They were randomly assigned to either the control group or the observation group , with 45 patients in each. The control group received routine rehabilitation training along with growth hormone treatment, while the observation group received routine rehabilitation training in addition to EA and growth hormone treatment. The study assessed the visual analogue score (VAS) for postoperative pain, knee function, and clinical outcomes in both groups. Results: The total effective rate in the observation group was significantly higher compared to the control group, with a statistically significant difference (P < .05). Initially, there were no significant differences between the two groups in peri-thigh atrophy index, VAS score, Lysholm score, knee swelling, knee stability, and range of motion (ROM) score (P > .05). However, after 3 and 6 months of treatment, significant reductions were observed in peri-thigh atrophy index, VAS score, knee swelling, and ROM score in the observation group compared to the control group (P < .05). Moreover, Lysholm score and knee stability significantly increased in the observation group (P < .05), with changes significantly higher than those in the control group (P < .05). Conclusions: EA combined with growth hormone treatment significantly reduces quadriceps atrophy and knee joint function in patients undergoing anterior cruciate ligament reconstruction. This combination therapy holds promise for enhancing rehabilitation outcomes in this patient population.

16.
Phys Rev Lett ; 132(20): 206502, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829100

RESUMO

The disorder operator is often designed to reveal the conformal field theory (CFT) information in quantum many-body systems. By using large-scale quantum Monte Carlo simulation, we study the scaling behavior of disorder operators on the boundary in the two-dimensional Heisenberg model on the square-octagon lattice with gapless topological edge state. In the Affleck-Kennedy-Lieb-Tasaki phase, the disorder operator is shown to hold the perimeter scaling with a logarithmic term associated with the Luttinger liquid parameter K. This effective Luttinger liquid parameter K reflects the low-energy physics and CFT for (1+1)D boundary. At bulk critical point, the effective K is suppressed but it keeps finite value, indicating the coupling between the gapless edge state and bulk fluctuation. The logarithmic term numerically captures this coupling picture, which reveals the (1+1)D SU(2)_{1} CFT and (2+1)D O(3) CFT at boundary criticality. Our Letter paves a new way to study the exotic boundary state and boundary criticality.

18.
J Environ Manage ; 361: 121258, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38815428

RESUMO

The rising accumulation of poly(ethylene terephthalate) (PET) waste presents an urgent ecological challenge, necessitating an efficient and economical treatment technology. Here, we developed chemical-biological module clusters that perform chemical pretreatment, enzymatic degradation, and microbial assimilation for the large-scale treatment of PET waste. This module cluster included (i) a chemical pretreatment that involves incorporating polycaprolactone (PCL) at a weight ratio of 2% (PET:PCL = 98:2) into PET via mechanical blending, which effectively reduces the crystallinity and enhances degradation; (ii) enzymatic degradation using Thermobifida fusca cutinase variant (4Mz), that achieves complete degradation of pretreated PET at 300 g/L PET, with an enzymatic loading of 1 mg protein per gram of PET; and (iii) microbial assimilation, where Rhodococcus jostii RHA1 metabolizes the degradation products, assimilating each monomer at a rate above 90%. A comparative life cycle assessment demonstrated that the carbon emissions from our module clusters (0.25 kg CO2-eq/kg PET) are lower than those from other established approaches. This study pioneers a closed-loop system that seamlessly incorporates pretreatment, degradation, and assimilation processes, thus mitigating the environmental impacts of PET waste and propelling the development of a circular PET economy.


Assuntos
Biodegradação Ambiental , Poliésteres , Polietilenotereftalatos , Polietilenotereftalatos/química , Polietilenotereftalatos/metabolismo , Poliésteres/metabolismo , Poliésteres/química , Hidrolases de Éster Carboxílico
19.
Am J Infect Control ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740285

RESUMO

BACKGROUND: In December 2022, the epidemic prevention and control policy was upgraded, and China entered a different stage of epidemic control. This study aims to identify implications for better infection control and health care supply during the epidemic. METHODS: A longitudinal quantitative and qualitative study was performed based on 2 comprehensive questionnaire surveys among 497 hospital infection prevention and control practitioners (HIPCPs) before and during the epidemic peak in Tianjin, China. RESULTS: The workload (8.2 hours vs 10.14 hours, P = 0) and self-reported mental health problems (23.5% vs 61.8%, P < .05) among the HIPCPs increased significantly in the peak period. Ward reconstruction and resource coordination were the most needed jobs in hospital infection control, and rapidly increased medical waste during the epidemic needs to be considered in advance. Community support for health care personnel and their families, maintaining full PPE to reduce simultaneous infection of medical staff, and clinical training of infectious diseases for medical staff, especially doctors, in advance are the most important things we learned. CONCLUSION: Although it has been 4 years since the first outbreak of coronavirus disease 2019, more improvements should be made to prepare for the next epidemic of potential diseases.

20.
Ultrasonics ; 141: 107344, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772060

RESUMO

Ultrasonic microneedle patches, a class of ultrasound-driven transdermal drug delivery systems, are promising in addressing bacterial biofilms. This device has been proven to be more effective in treating Staphylococcus aureus biofilms than drug in free solution. However, there exists a notable gap in understanding how various excitation conditions and material parameters affect drug delivery efficiency. This study aims to fill this void by conducting an comprehensive multi-physics numerical analysis of ultrasonic microneedle patches, with the ultimate goal of enhancing drug delivery. First, we investigate the impact of various ultrasound frequencies on drug penetration depths. The findings reveal that local resonance can accelerate drug release within a shorter time window (first 1.5 h), whereas non-resonant frequencies enable more profound and prolonged diffusion. This information is crucial for medical professionals in selecting the most effective frequency for optimal drug administration. Furthermore, our investigation extends to the effects of applied voltage on temperature distribution, a critical aspect for ensuring medical safety during the application of these patches. Additionally, we examine how particles of different sizes respond to acoustic pressure and streaming fields, providing valuable insights for tailoring drug delivery strategies to specific therapeutic needs. Overall, our findings offer comprehensive guidelines for the effective use of ultrasonic microneedle patches, potentially shifting the paradigm in patient care and enhancing the overall quality of life.


Assuntos
Biofilmes , Sistemas de Liberação de Medicamentos , Agulhas , Staphylococcus aureus , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Staphylococcus aureus/fisiologia , Ondas Ultrassônicas , Antibacterianos/administração & dosagem , Administração Cutânea
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