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1.
Environ Microbiol Rep ; 16(5): e70013, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39313916

RESUMO

Wolbachia are common heritable endosymbionts that influence many aspects of ecology and evolution in various insects, yet Wolbachia-mediated intracellular metabolic responses to temperature stress have been largely overlooked. Here, we introduced the Wolbachia strain wLhui from the invasive Liriomyza huidobrensis (Blanchard) into a Drosophila Schneider 2 cell line (S2) and investigated the metabolite profile of wLhui-infected (S2_wLhui) and uninfected cell lines (S2_wu) under short-term exposure to either high (37°C), moderate (27°C), or low (7 and 17°C) temperatures. We find that Wolbachia infection, temperature stress, and their interactions significantly affect cellular metabolic profiles. Most significantly, when comparing the changes in metabolites between S2_wLhui and S2_wu, glycerophospholipids, amino acids, and fatty acids associated with metabolic pathways, microbial metabolism in diverse environments, and other pathways were significantly accumulated at either low or high temperatures. Our findings suggest Wolbachia-induced cellular physiological responses to short-term temperature stress, which may in turn affect the fitness and adaptive ability of its host as an invasive species.


Assuntos
Metaboloma , Estresse Fisiológico , Temperatura , Wolbachia , Wolbachia/metabolismo , Wolbachia/fisiologia , Wolbachia/genética , Animais , Linhagem Celular , Drosophila/microbiologia , Simbiose , Dípteros/microbiologia , Ácidos Graxos/metabolismo
2.
mSphere ; 9(8): e0038624, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39105581

RESUMO

Arthropods harbor complex microbiota that play a pivotal role in host fitness. While multiple factors, like host species and diet, shape microbiota in arthropods, their impact on community assembly in wild insects remains largely unknown. In this study, we surveyed bacterial and fungal community assembly in nine sympatric wild insect species that share a common citrus fruit diet. Source tracking analysis suggested that these insects acquire some bacteria and fungi from the citrus fruit with varying degrees. Although sharing a common diet led to microbiota convergence, the diversity, composition, and network of both bacterial and fungal communities varied significantly among surveyed insect groups. Null model analysis indicated that stochastic processes, particularly dispersal limitation and drift, are primary drivers of structuring insect bacterial and fungal communities. Importantly, the influence of each community assembly process varied strongly depending on the host species. Thus, we proposed a speculative view that the host specificity of the microbiome and mycobiome assembly is widespread in wild insects despite sharing the same regional species pool. Overall, this research solidifies the importance of host species in shaping microbiomes and mycobiomes, providing novel insights into their assembly mechanisms in wild insects. IMPORTANCE: Since the microbiome has been shown to impact insect fitness, a mechanistic understanding of community assembly has potentially significant applications but remains largely unexplored. In this paper, we investigate bacterial and fungal community assembly in nine sympatric wild insect species that share a common diet. The main findings indicate that stochastic processes drive the divergence of microbiomes and mycobiomes in nine sympatric wild insect species. These findings offer novel insights into the assembly mechanisms of microbiomes and mycobiomes in wild insects.


Assuntos
Bactérias , Dieta , Fungos , Insetos , Microbiota , Processos Estocásticos , Simpatria , Animais , Insetos/microbiologia , Fungos/classificação , Fungos/genética , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Micobioma , Citrus/microbiologia
3.
Front Microbiol ; 15: 1424568, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091307

RESUMO

Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.

4.
BMC Cancer ; 24(1): 773, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937694

RESUMO

OBJECTIVE: Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function. METHODS: In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis. RESULTS: After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma. CONCLUSIONS: Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.


Assuntos
Neoplasias Gástricas , Ubiquitina Tiolesterase , Ubiquitinação , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Camundongos , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Metástase Neoplásica , Perfilação da Expressão Gênica , Transição Epitelial-Mesenquimal/genética , Prognóstico , Multiômica
5.
Int J Implant Dent ; 10(1): 27, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819712

RESUMO

OBJECTIVE: To address the instability in implant surgical guides, this technique proposes an alternative anchoring mechanism in the stackable metal surgical guides utilizing cone-wedge anchors for improved stability. METHODS: Postoperative implant position superimposed onto the preoperatively planned design using Mimics Medical 21.0 and Materialise Magics 24.0 to assess 3D coronal implant deviation, 3D apical implant deviation, and implant angular deviation. RESULTS: Postoperative cone-beam computed tomography (CBCT) revealed a high level of precision in the implant placement, with an average 0.97 mm deviation at implant coronal region, 1.56 mm at implant apexes, and 2.95° angular deviation. CONCLUSION: This technique introduces a novel cone-wedge anchoring mechanism to enhance the stability of stackable metal surgical guide templates, addressing inherent instability issues. The utilization of this approach significantly improves the accuracy of implant placement procedures.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Implantação Dentária Endóssea/métodos , Implantação Dentária Endóssea/instrumentação , Cirurgia Assistida por Computador/métodos , Cirurgia Assistida por Computador/instrumentação , Metais , Imageamento Tridimensional/métodos
6.
Cells ; 13(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38607007

RESUMO

Solid tumors, with their intricate cellular architecture and genetic heterogeneity, have long posed therapeutic challenges. The advent of the CRISPR genome editing system offers a promising, precise genetic intervention. However, the journey from bench to bedside is fraught with hurdles, chief among them being the efficient delivery of CRISPR components to tumor cells. Lipid nanoparticles (LNPs) have emerged as a potential solution. This biocompatible nanomaterial can encapsulate the CRISPR/Cas9 system, ensuring targeted delivery while mitigating off-target effects. Pre-clinical investigations underscore the efficacy of LNP-mediated CRISPR delivery, with marked disruption of oncogenic pathways and subsequent tumor regression. Overall, CRISPR/Cas9 technology, when combined with LNPs, presents a groundbreaking approach to cancer therapy, offering precision, efficacy, and potential solutions to current limitations. While further research and clinical testing are required, the future of personalized cancer treatment based on CRISPR/Cas9 holds immense promise.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Sistemas CRISPR-Cas/genética , Edição de Genes , Terapia Genética , Neoplasias/genética , Neoplasias/terapia
7.
Medicine (Baltimore) ; 103(12): e37613, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517992

RESUMO

Sacubitril/Valsartan, the combination of angiotensin receptor inhibitor and neprilysin inhibitor, is now becoming the class 1 recommendation for HFrEF. Some studies have shown the positive effect of Sacubitril/Valsartan on HFrEF cancer patients, while there is devoid of evidence about the effect of this drug in aged cancer patients with HFmrEF and HFpEF. By searching the patients with a diagnosis of both cancer and Heart failure (HF) over 65, the patients who had received treatment with Sacubitril/Valsartan were selected as the candidates for Sacubitril/Valsartan group, and the patients who had received conventional HF therapy without Sacubitril/Valsartan were chosen as the control group. Data were collected for up to 9 months. We filtered 38 patients and 50 patients valid for Sacubitril/Valsartan group and control group, respectively. After initiation of heart failure management, our study found a better cardiac condition in Sacubitril/Valsartan group, having better LVEF, LVFS, NT-proBNP in 3rd, 6th, 9th month (P < .05) and better NYHA function classification after the treatment. We also observed fewer cases of deterioration on LAD (P = .029) and LVEDD (P = .023) in Sacubitril/Valsartan group. In subgroup analysis, our study showed that all 3 kinds of HF patients had better LVEF, LVFS, and NT-proBNP in Sacubitril/Valsartan group (P < .05). Our study further indicated that Sacubitril/Valsartan can improve cardiac function and benefit cardiac remolding in aged cancer patients of all 3 kinds of HF. This is the first study to provide new evidence for the use of Sacubitril/Valsartan in aged cancer patients of 3 kinds of HF.


Assuntos
Aminobutiratos , Insuficiência Cardíaca , Neoplasias , Idoso , Humanos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Volume Sistólico , Tetrazóis , Valsartana/uso terapêutico
8.
Environ Geochem Health ; 46(4): 129, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483651

RESUMO

The issue of potentially toxic elements (PTEs) contamination of regional soil caused by mining activities and tailings accumulation has attracted wide attention all over the world. The East Qinling is one of the three main molybdenum mines in the world, and the concentration of PTEs such as Hg, Pb and Cu in the slag is high. Quantifying the amount of PTEs contamination in soil and identifying potential sources of contamination is vital for soil environmental management. In the present investigation, the pollution levels of 8 PTEs in the Qinling molybdenum tailings intensive area were quantitatively identified. Additionally, an integrated source-risk method was adopted for resource allocation and risk assessment based on the PMF model, the ecological risk, and the health risk assessment model. The mean concentrations of Cu, Ni, Pb, Cd, Cr, Zn, As, and Hg in the 80 topsoil samples ranged from 0.80 to 13.38 times the corresponding background values; notably high levels were observed for Pb and Hg. The source partitioning results showed that PTEs were mainly affected by four pollution sources: natural and agricultural sources, coal-burning sources, combined transport and mining industry sources, and mining and smelting sources. The health risk assessment results revealed that the risks of soil PTEs for adults are acceptable, while the risks for children exceeded the limit values. The obtained results will help policymakers to obtain the sources of PTEs of tailing ponds intensive area. Moreover, it provides priorities for the governance of subsequent pollution sources and ecological restoration.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Criança , Adulto , Humanos , Solo , Metais Pesados/toxicidade , Metais Pesados/análise , Molibdênio/análise , Chumbo/análise , Lagoas , Monitoramento Ambiental/métodos , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Mercúrio/análise , Medição de Risco , China
9.
Insect Sci ; 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369568

RESUMO

Symbiotic microorganisms are essential for the physiological processes of herbivorous pests, including the pear lace bug Stephanitis nashi, which is known for causing extensive damage to garden plants and fruit trees due to its exceptional adaptability to diverse host plants. However, the specific functional effects of the microbiome on the adaptation of S. nashi to its host plants remains unclear. Here, we identified significant microbial changes in S. nashi on 2 different host plants, crabapple and cherry blossom, characterized by the differences in fungal diversity as well as bacterial and fungal community structures, with abundant correlations between bacteria or fungi. Consistent with the microbiome changes, S. nashi that fed on cherry blossom demonstrated decreased metabolites and downregulated key metabolic pathways, such as the arginine and mitogen-activated protein kinase signaling pathway, which were crucial for host plant adaptation. Furthermore, correlation analysis unveiled numerous correlations between differential microorganisms and differential metabolites, which were influenced by the interactions between bacteria or fungi. These differential bacteria, fungi, and associated metabolites may modify the key metabolic pathways in S. nashi, aiding its adaptation to different host plants. These results provide valuable insights into the alteration in microbiome and function of S. nashi adapted to different host plants, contributing to a better understanding of pest invasion and dispersal from a microbial perspective.

10.
J Anat ; 244(6): 1054-1066, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38288680

RESUMO

The mammalian placenta's interface with the parent is a richly vascularized tissue whose development relies upon communication between many different cell types within the uterine microenvironment. The uterine blood vessels of the interface are reshaped during pregnancy into wide-bore, flaccid vessels that convey parental blood to the exchange region of the placenta. Invasive trophoblast as well as parental uterine macrophages and Natural Killer cells are involved in the stepwise remodeling of these vessels and their respective contributions to this crucial process are still being delineated. However, the earliest steps in arteriole remodeling are understudied as they are difficult to study in humans, and other species lack the deep trophoblast invasion that is so prominent a feature of placentation in humans. Here, we further characterize the rat, with deep hemochorial placentation akin to humans, as a model system in which to tease apart the earliest, relatively understudied events in spiral arteriole remodeling. We show that the rat uterine-placental interface increases in size and vascularity rapidly, before trophoblast invasion. The remodeling stages in the arterioles of the rat uterine-placental interface follow a sequence of anatomical changes similar to those in humans, and there are changes to the arterioles' muscular tunica media prior to the marked influx of immune cells. The rat is a tractable model in which to better understand the cell/cell interactions occurring in vivo in an intact tissue microenvironment over time.


Assuntos
Placenta , Útero , Remodelação Vascular , Animais , Feminino , Gravidez , Arteríolas , Ratos , Útero/irrigação sanguínea , Placenta/irrigação sanguínea , Remodelação Vascular/fisiologia , Placentação/fisiologia , Modelos Animais , Ratos Sprague-Dawley
11.
J Biophotonics ; 17(3): e202300405, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38010214

RESUMO

A major cause of death in cancer patients is distant metastasis of tumors, in which circulating tumor cells (CTCs) are an important marker. Photoacoustic flow cytometry (PAFC) can monitor CTCs in real time, non-invasively, and label-free; we built a PAFC system and validated the feasibility of PAFC for monitoring CTCs using in vivo animal experiments. By cultivating heavily-pigmented and moderately-pigmented melanoma cells, more CTCs were detected in mice inoculated with moderately-pigmented tumor cells, resulting in more distant metastases and poorer survival status. Tumor cells with lower melanin content may produce more CTCs, increasing the risk of metastasis. CTC melanin content may be down-regulated during the metastatic which may be a potential indicator for assessing the risk of melanoma metastasis. In conclusion, PAFC can be used to assess the risk of melanoma metastasis by dynamically monitoring the number of CTCs and the CTC melanin content in future clinical diagnoses.


Assuntos
Anormalidades Craniofaciais , Melanoma , Células Neoplásicas Circulantes , Humanos , Camundongos , Animais , Melanoma/diagnóstico por imagem , Melanoma/patologia , Melaninas , Citometria de Fluxo , Células Neoplásicas Circulantes/patologia , Metástase Neoplásica
12.
J Biophotonics ; 16(9): e202300135, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37263969

RESUMO

Flow cytometry (FC) is a versatile tool with excellent capabilities to detect and measure multiple characteristics of a population of cells or particles. Notable advancements in in vivo photoacoustic FC, coherent Raman FC, microfluidic FC, and so on, have been achieved in the last two decades, which endows FC with new functions and expands its applications in basic research and clinical practice. Advanced FC broadens the tools available to researchers to conduct research involving cancer detection, microbiology (COVID-19, HIV, bacteria, etc.), and nucleic acid analysis. This review presents an overall picture of advanced flow cytometers and provides not only a clear understanding of their mechanisms but also new insights into their practical applications. We identify the latest trends in this area and aim to raise awareness of advanced techniques of FC. We hope this review expands the applications of FC and accelerates its clinical translation.


Assuntos
COVID-19 , Humanos , Citometria de Fluxo
13.
Cancers (Basel) ; 15(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36980689

RESUMO

In recent years, chemoimmunotherapy has become effective in some advanced cancers, but its effect is still limited. Transcriptional upregulation of isocitrate dehydrogenase 3α (IDH3α) can promote tumor initiation and progression. However, it is not clear whether the aberrant expression of IDH3α is related to the efficacy of chemoimmunotherapy in cancers. Here, we found that IDH3α was elevated in uterine cervical cancer (UCC) and lung adenocarcinoma (LUAD) samples by using public databases. High expression of IDH3α could promote the epithelial-mesenchymal transition (EMT), alter the intracellular redox status, promote glycolysis, and induce an acidic microenvironments in cancer cells. Furthermore, we found that inhibition of IDH3α combined with chemoimmunotherapy (cisplatin and programmed cell death ligand 1 (PD-L1) antibodies) activated the cGAS-STING pathway, promoted CD8+ T cell infiltration, and decreased tumor growth in mouse models of cervical cancer. In conclusion, our data indicate that silencing IDH3α sensitizes tumors to chemoimmunotherapy by modulating the acidic microenvironment and activating the cGAS-STING pathway.

14.
Front Cardiovasc Med ; 10: 1052699, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36755798

RESUMO

Background: The incidence of immune checkpoint inhibitors (ICI)-related adverse cardiovascular events (ACEs) may be underestimated, and there are few reports on the incidence and risk factors of ICI-induced left ventricular dysfunction (LVD). Objectives: This study aimed to investigate the incidence of ACEs caused by ICI, in particular to analyze the incidence and risk factors of LV systolic and diastolic dysfunction. Materials and methods: A prospective clinical study was performed on patients who received ICI in our hospital from November 2020 to October 2021. They received regular cardiovascular examinations, including echocardiography, ECG, cTnT, and NT-proBNP, etc. The incidence of various ACEs was counted, and the risk factors of LVD were analyzed. Results: A total of 106 cancer patients treated with ICI were recruited. During the follow-up, 41 patients (38.68%) developed various ECG abnormalities, 39 patients (36.79%) developed LVDD, 9 patients (8.49%) developed CTRCD, and 2 patients (1.89%) developed new pericardial effusion. The patients with elevated cTnT, CK-MB, and NT-proBNP were 10 (9.43%), 8 (7.55%), and 8 (7.5%), respectively. Thirteen of the 52 patients with LVD had hypertension, while 4 of the 54 patients without LVD had hypertension (OR = 4.17, 95% CI: 1.26-13.78; P = 0.019). The baseline LVEF and LVFS of patients with LVD were 61.54 ± 4.15% and 33.78 ± 2.73%, while those of the control group were 64.16 ± 3.68% and 34.95 ± 2.84, respectively (P = 0.003 and P = 0.048). Compared with patients without LVD, patients with LVD had lower e' (6.99 ± 1.33 cm/s vs. 7.64 ± 1.39 cm/s, P = 0.029) and higher E to e' ratio (11.89 ± 3.15 cm/s vs. 10.43 ± 2.52, P = 0.024). Multiple regression analysis showed that a history of hypertension (HR = 26.52, 95% CI: 2.479-283.667, P = 0.007) and lower baseline e' (HR = 0.04, 95% CI: 0.003-0.709, P = 0.028) were risk factors for developing LVD. Conclusion: Patients treated with ICI may develop multiple ACEs, including acute myocarditis, pericarditis, ECG abnormalities, and elevated cardiac biomarkers. ICI may lead to a high incidence of LVD, and echocardiography is helpful for early detection of LVD. Patients with hypertension or poor LV systolic or diastolic function at baseline were predictors of LVD after ICI treatment.

15.
Microbiol Spectr ; 11(1): e0365922, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36645314

RESUMO

The efficient storage of materials before bioethanol production could be key to improving pretreatment protocol and facilitating biodegradation, in turn improving the cost-effectiveness of biomass utilization. Biological inoculants were investigated for their effects on ensiling performance, biodegradability of silage materials, and final bioethanol yield from sweet sorghum. Two cellulolytic microbial consortia (CF and PY) were used to inoculate silages of sweet sorghum, with and without combined lactic acid bacteria (Xa), for up to 60 days of ensiling. We found that the consortia notably decreased pH and ammonia nitrogen content while increasing lactic acid/acetic acid ratios. The microbes also functioned in synergy with Xa, significantly reducing lignocellulose content and improving biomass preservation. First-order exponential decay models captured the kinetics of nonstructural carbohydrates and suggested high water-soluble carbohydrate (grams per kilogram dry matter [DM]) preservation potential in PY-Xa (33.48), followed by CF-Xa (30.51). Combined addition efficiently improved enzymatic hydrolysis and enhanced bioethanol yield, and sweet sorghum treated with PY-Xa had the highest ethanol yield (28.42 g L-1). Thus, combined bioaugmentation of synergistic microbes provides an effective method of improving biomass preservation and bioethanol production from sweet sorghum silages. IMPORTANCE Ensiling is an effective storage approach to ensure stable year-round supply for downstream biofuel production; it offers combined facilities of storage and pretreatment. There are challenges in ensiling sweet sorghum due to its coarse structure and high fiber content. This study provides a meaningful evaluation of the effects of adding microbial consortia, with and without lactic acid bacteria, on changes in key properties of sweet sorghum. This study highlighted the bioaugmented ensiling using cellulolytic synergistic microbes to outline a cost-effective strategy to store and pretreat sweet sorghum for bioethanol production.


Assuntos
Lactobacillales , Sorghum , Sorghum/química , Sorghum/microbiologia , Silagem/análise , Silagem/microbiologia , Fermentação , Biomassa , Consórcios Microbianos
16.
Br J Clin Pharmacol ; 89(7): 2076-2087, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35502121

RESUMO

AIMS: The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. METHODS: A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. RESULTS: After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% [95% CI: 71.1, 71.6] vs. 73.3% [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4% [95% CI: 3.3, 3.5] vs. 3.2% [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0% [95% CI: 20.8, 21.3] vs. 19.5% [95% CI: 19.2, 19.8]). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4-inhibitor therapy after experiencing an ADE. CONCLUSION: We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Citocromo P-450 CYP3A , Estudos de Coortes , Estudos Retrospectivos
17.
Cells ; 11(17)2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36078096

RESUMO

BACKGROUND: Limited therapeutic options are available for advanced LUAD without driver gene mutations. Anti-CDK therapy has shown effectiveness in several kind of cancers, however, the mechanisms still need to be elucidated. MATERIALS AND METHODS: The lncRNA associated with CDK1 and the immunomodulatory factors that regulate CDK1 were found by bioinformatics analysis and experimental verification. The prognostic model and immune resistance mechanism of lung adenocarcinoma were revealed by single cell analysis, immune infiltration analysis, and signal pathway analysis. RESULTS: LINC00261 was found to be an important CDK1-related lncRNA with a better prognosis in LUAD. In addition, high CDK1 expression indicates a poor immunotherapy response, which may be associated with overexpression of CXCL8. CXCL8 decreased in patients who were immunotherapy-responsive but increased in patients who were immunotherapy-resistant. Signaling pathway analysis suggested that increased CXCL8 and decreased LINC00261 may participate in hypoxia-induced tumor angiogenesis and cause a poor prognosis for the patients. CXCL8 and CDK1 may change G2-M transformation and EMT and promote tumor proliferation. CONCLUSION: This study explained that LINC00261, CDK1, and CXCL8 may have a mutual regulation relationship, which affects the occurrence of LUAD and the efficacy of immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Interleucina-8 , RNA Longo não Codificante , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/terapia , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Humanos , Imunoterapia , Interleucina-8/genética , Interleucina-8/metabolismo , Pulmão/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais
18.
NPJ Biofilms Microbiomes ; 8(1): 31, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477734

RESUMO

Deterministic and stochastic forces both drive microbiota assembly in animals, yet their relative contribution remains elusive, especially in wild aquatic-insect-associated fungal communities. Here, we applied amplicon sequencing to survey the assembly mechanisms of the fungal community in 155 wild stonefly individuals involving 44 species of 20 genera within eight families collected from multiple locations in China. Analysis showed that fungal diversity and network complexity differed significantly among the eight stonefly families, and that the fungal communities in stoneflies exhibited a significant distance-decay pattern across large spatial scales. Both a structural equation model and variance partitioning analysis revealed that environmental factors (e.g., geographical, climatic) outweigh host attributes in shaping the fungal community of stoneflies. Using neutral and null model analyses, we also find that deterministic processes play a larger role than stochasticity in driving the fungal community assembly. However, the relative contribution of ecological processes including dispersal, drift, and selection, varied strongly with host taxonomy. Furthermore, environmental conditions also significantly affect the strength of these ecological processes. Overall, our findings illustrate that variations in host attributes and environment factors may moderate the relative influence of deterministic and stochastic processes to fungal community composition in wild stoneflies, which provides new insights into mechanisms of microbial community assembly in aquatic arthropods.


Assuntos
Microbiota , Micobioma , Animais , China , Humanos , Insetos , Processos Estocásticos
19.
J Healthc Eng ; 2022: 5732357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35368947

RESUMO

Acute abdomen is a clinical emergency disease with acute abdominal pain as the main prominent feature. Through severe disease changes in intra-abdominal, extrapelvic, and retroperitoneal tissues and organs, symptoms and clinical signs led by abdominal pain are formed. This article mainly explores the role of CT imaging diagnosis in common acute abdominal diseases in general surgery. In this paper, the use of computer-aided CT scan imaging technology in pulmonary nodules was firstly investigated, and the image segmentation algorithms based on CT images were given, including the spatial domain fuzzy C-mean clustering separation algorithm and the spatial domain fuzzy clustering level set semiautomatic separation algorithm, then the treatment of acute abdomen under the concept of ERAS was explored, and the treatment of ERAS under CT images of the acute abdomen was analyzed and studied. The empirical research results show that the ERAS's concept is guided by the undergoing national nutritional support with the traditional perioperative management. Compared to 12.9% of complications in traditional CPM groups, the recall rate of complications after ERAS group was only 6.01%, the improvement was obvious and the results were statistically significant (P < 0.05). Postoperative hospitalization time was also 4.62 days from 7.93 days, thus controlling the clinical risks of perioperative periods, providing a benefit to patient life.


Assuntos
Algoritmos , Tomografia Computadorizada por Raios X , Análise por Conglomerados , Humanos , Tomografia Computadorizada por Raios X/métodos
20.
Microbiol Spectr ; 10(2): e0026622, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35343791

RESUMO

The microbiota of invasive animal species may be pivotal to their adaptation and spread, yet the processes driving the assembly and potential sources of host-microbiota remain poorly understood. Here, we characterized microbiota of four Liriomyza leaf miner fly species totaling 310 individuals across 43 geographical populations in China and assessed whether the microbiota of the wild leaf miner was acquired from the soil microbiota or the host plant microbiota, using high-throughput 16S rRNA sequencing. Bacterial communities differed significantly among four leaf miner species but did not mirror host phylogeny. Microbiota diversity in the native L. chinensis was significantly higher than in three invasive leaf miners (i.e., L. trifolii, L. huidobrensis, and L. sativae), yet the microbial community of the invasive species exhibited a more connected and complex network structure. Structural equation models revealed that host species identity was more important than environmental factors (e.g., geography, climate, or plants) in shaping microbiota composition. Using neutral and null model analyses, we found that deterministic processes like variable selection played a primary role in driving microbial community assembly, with some influence by stochastic processes like drift. The relative degree of these processes governing microbiota was likely correlated with host species but independent of either geographical or climatic factors. Finally, source tracking analysis showed that leaf miners might acquire microbes from their host plant rather than the soil. Our results provide a robust assessment of the ecological processes governing bacterial community assembly and potential sources of microbes in invasive leaf miners. IMPORTANCE The invasion of foreign species, including leaf miners, is a major threat to world biota. Host-associated microbiota may facilitate host adaption and expansion in a variety of ways. Thus, understanding the processes that drive leaf miner microbiota assembly is imperative for better management of invasive species. However, how microbial communities assemble during the leaf miner invasions and how predictable the processes remain unexplored. This work quantitatively deciphers the relative importance of deterministic process and stochastic process in governing the assembly of four leaf miner microbiotas and identifies potential sources of leaf miner-colonizing microbes from the soil-plant-leaf miner continuum. Our study provides new insights into the mechanisms underlying the drive of leaf miner microbiota assembly.


Assuntos
Bactérias , Microbiota , Animais , Bactérias/genética , Microbiota/genética , RNA Ribossômico 16S/genética , Solo , Microbiologia do Solo
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