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Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and is associated with high rates of end-stage renal disease. Early detection and precise interventions are crucial for improving patient prognosis and quality of life. However, the current diagnosis primarily relies on renal biopsies and traditional biomarkers, which have limitations. Additionally, targeted therapeutic strategies are lacking. Exosomes, small vesicles that facilitate intercellular communication, have emerged as potential noninvasive diagnostic markers due to their stability, diverse cargo, and rapid detectability. They also hold promise as carriers for gene and drug delivery, presenting innovative opportunities in renal disease prognosis and treatment. However, research on exosomes in the context of idiopathic membranous nephropathy (IMN) remains limited, with a focus on exploring urinary exosomes as IMN markers. In this review, we summarize the current status of MN diagnosis and treatment, highlight the fundamental characteristics of exosomes, and discuss recent advancements in their application to IMN diagnosis and therapy. We provide insights into the clinical prospects of exosomes in IMN and acknowledge potential challenges. This article aims to offer forward-looking insights into the future of exosome-mediated IMN diagnosis and treatment, indicating a revolutionary transformation in this field.
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Biomarcadores , Exosomas , Glomerulonefritis Membranosa , Exosomas/metabolismo , Glomerulonefritis Membranosa/diagnóstico , Humanos , Animales , PronósticoRESUMEN
Phosphorus (P) is an essential macronutrient for plant growth and development. Rapid alkalisation factors (RALFs) play crucial roles in plant responses to nutrient stress. However, the functions of Glycine max RALFs (GmRALFs) under low P (LP) stress remain elusive. In this study, we first identified 27 GmRALFs in soybean and then revealed that, under LP conditions, GmRALF10, GmRALF11, and GmRALF22 were induced in both roots and leaves, whereas GmRALF5, GmRALF6, and GmRALF25 were upregulated in leaves. Furthermore, GmRALF22 was found to be the target gene of the transcription factor GmPHR1, which binds to the P1BS cis-element in the promoter of GmRALF22 via electrophoretic mobility shift assay and dual-luciferase experiments. Colonisation with Bacillus subtilis which delivers GmRALF22, increases the expression of the high-affinity phosphate (Pi) transporter genes GmPT2, GmPT11, GmPT13, and GmPT14, thus increasing the total amount of dry matter and soluble Pi in soybeans. RNA sequencing revealed that GmRALF22 alleviates LP stress by regulating the expression of jasmonic acid- (JA-), salicylic acid- (SA-), and immune-related genes. Finally, we verified that GmRALF22 was dependent on FERONIA (FER) to promote Arabidopsis primary root growth under LP conditions. In summary, the GmPHR1-GmRALF22 module positively regulates soybean tolerance to LP.
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Introduction: The impaired proliferative capacity of alveolar epithelial cells after injury is an important factor causing epithelial repair dysfunction, leading to the occurrence of idiopathic pulmonary fibrosis (IPF). Alveolar type 2 (AT2) cells as the stem cells of alveolar epithelium participate in the repair process after alveolar injury. Lipocalin-2 (LCN2) participates in multiple processes regulating the pathological process of alveolar epithelial cells, but the mechanisms involved are still unclear. Method: We used a BLM-treated mouse model to characterize the expression of LCN2 in lung fibrosis regions and analyzed the location of LCN2 in alveolar epithelial cells. Moreover, human pulmonary alveolar epithelial cells (HPAEpiCs) were transfected with the LCN2 overexpression plasmid vector in vitro. Recombinant human interleukin-17 (IL-17) protein (rhIL-17) at different concentrations was administered to intervene in HPAEpiCs, observing cell viability and analyzing the concentration-dependent effect of IL-17. Results: LCN2 was increased in the alveolar epithelium post-BLM injury, and highly expressed LCN2 was mainly concentrated on AT2 cells in BLM-injured lungs. Meanwhile, LCN2-overexpressing HPAEpiCs showed impaired cell viability and cell growth. HPAEpiC intervention with rhIL-17 mildly rescued the impaired cell proliferation induced by LCN2 overexpression, and the effect of IL-17 intervention was partially concentration-dependent. Conclusions: The results revealed the reversed effect of IL-17 on the impaired proliferative capacity of the alveolar epithelium induced by LCN2 overexpression. The target alveolar epithelial cells regulated by this process were AT2 cells, providing new clues for alveolar epithelium repair after injury and the treatment of lung injury diseases.
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Células Epiteliales Alveolares , Proliferación Celular , Interleucina-17 , Lipocalina 2 , Lipocalina 2/genética , Lipocalina 2/metabolismo , Interleucina-17/metabolismo , Interleucina-17/genética , Animales , Proliferación Celular/genética , Ratones , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/efectos de los fármacos , Humanos , Bleomicina/toxicidad , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
China is the biggest emitter of greenhouse gases (GHGs) in the world, and agricultural GHG emission accounts for nearly a fifth of the total emission in China. To understand the carbon absorption and emission characteristics of agricultural production systems in those arid oasis areas, a typical representative city in northwestern China, Zhangye City, was selected for study.The emission factor method was used to analyze and calculate the characteristics of changing carbon emission dynamics in the whole agricultural production system in Zhangye city region (38,592 km2) from 2010 to 2021.The results revealed that carbon emissions during agricultural planting mainly come from fertilizers, which account for the highest proportion (47.9%) of total carbon emissions in agricultural planting. Animal enteric fermentation emissions from local livestock farming are the main contributor (86%) to GHG emissions. The annual average carbon absorption intensity is 4.4 t C-eq ha-1 for crop and 2.6 t C-eq ha-1 for the agricultural production system. The ratio of total carbon emissions from agricultural production to carbon sequestration of crops is 1:1.7. We find that the total carbon sequestration slightly exceeds its total carbon emissions in the study region, with an annual average of 41% for its sustainable development index. Carbon emissions of the agricultural production system in this oasis area are mainly driven by the livestock industry, mostly CH4 emissions from cattle raising.Reducing the local carbon emissions from the livestock industry, typically the cattle raising, will play a crucial role in reducing carbon emissions from this local agricultural production system and maintaining its net positive carbon balance.
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Cadmium (Cd) exerts a toxic influence on numerous crucial growth and development processes in plants, notably affecting seed germination rate, transpiration rate, chlorophyll content, and biomass. While considerable advances in Cd uptake and detoxification of plants have been made, the mechanisms by which plants adapt to and tolerate Cd toxicity remain elusive. This review focuses on the relationship between Cd and plants and the prospects for phytoremediation of Cd pollution. We highlight the following issues: (1) the present state of Cd pollution and its associated hazards, encompassing the sources and distribution of Cd and the risks posed to human health; (2) the mechanisms underlying the uptake and transport of Cd, including the physiological processes associated with the uptake, translocation, and detoxification of Cd, as well as the pertinent gene families implicated in these processes; (3) the detrimental effects of Cd on plants and the mechanisms of detoxification, such as the activation of resistance genes, root chelation, vacuolar compartmentalization, the activation of antioxidant systems and the generation of non-enzymatic antioxidants; (4) the practical application of phytoremediation and the impact of incorporating exogenous substances on the Cd tolerance of plants.
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Biodegradación Ambiental , Cadmio , Plantas , Cadmio/toxicidad , Cadmio/metabolismo , Plantas/metabolismo , Plantas/efectos de los fármacos , Inactivación Metabólica , Transporte Biológico , HumanosRESUMEN
BACKGROUND: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events. RESULTS: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported. CONCLUSIONS: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).
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Antivirales , Tratamiento Farmacológico de COVID-19 , Humanos , Masculino , Método Doble Ciego , Femenino , Persona de Mediana Edad , Antivirales/uso terapéutico , Antivirales/efectos adversos , Antivirales/administración & dosificación , Adulto , COVID-19/virología , SARS-CoV-2 , Anciano , Resultado del Tratamiento , Compuestos OrgánicosRESUMEN
Introduction: Meta-analysis was used to investigate the relationship between peripheral blood eosinophil (EOS) levels, clinical characteristics, and prognosis in chronic obstructive pulmonary disease (COPD)patients in previous literature. Aim: To analyse the correlation between peripheral blood EOS levels and clinical characteristics and prognosis of patients with COPD using meta-analysis. Material and methods: In databases such as PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wan Fang Data, literature related to the clinical characteristics or prognosis of COPD patients with high-level EOS published before July 2023 was searched for meta-analysis. Results: Through computer search and screening, 29 articles were ultimately included. The meta-analysis results showed that compared to conventional EOS levels, COPD patients with high EOS levels had a lower proportion of GOLD III-IV grade patients (OR = 00.78, 95% CI (0.68, 0.88), p < 0.001), lower CAT scores (OR = -1.01, 95% CI (-1.75, -0.28), p = 0.007), shorter hospital stay (OR = -1.33, 95% CI (-1.52, -1.14), p < 0.001), and lower mortality rate (OR = 0.53, 95% CI (0.42, 0.66), p < 0.001). The readmission rate was low (OR = 0.40, 95% CI (0.33, 0.48), p < 0.001), and there was no statistically significant difference in FEV1%pred (OR = -0.55, 95% CI (-1.33, 0.23), p = 0.17), higher FEV1/FVC values (OR = -0.45, 95% CI (-1.08, 0.18), p = 0.160), and mechanical ventilation usage rate (OR = 0.89, 95% CI (0.65, 1.21), p = 0.450) among COPD patients with different EOS levels. Conclusions: The levels of peripheral blood EOS in COPD patients are related to lung function, respiratory symptoms, etc.; Moreover, COPD patients with high-level EOS have shorter hospital stays, lower mortality and readmission rates. Therefore, ESO can be used as an auxiliary indicator for clinical symptom diagnosis of COPD patients and as an auxiliary indicator for predicting prognosis.
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Globally, there is a growing acknowledgment of Indigenous Peoples' rights to control data related to their communities. This is seen in the development of Indigenous Data Governance standards. As health data collection increases, it's crucial to apply these standards in research involving Indigenous communities. Our study, therefore, aims to systematically review research using routinely collected health data of Indigenous Peoples, understanding the Indigenous Data Governance approaches and the associated advantages and challenges. We searched electronic databases for studies from 2013 to 2022, resulting in 85 selected articles. Of these, 65 (77%) involved Indigenous Peoples in the research, and 60 (71%) were authored by Indigenous individuals or organisations. While most studies (93%) provided ethical approval details, only 18 (21%) described Indigenous guiding principles, 35 (41%) reported on data sovereignty, and 28 (33%) addressed consent. This highlights the increasing focus on Indigenous Data Governance in utilising health data. Leveraging existing data sources in line with Indigenous data governance principles is vital for better understanding Indigenous health outcomes.
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Gonadotropin-inhibitory hormone (GnIH) is a neurohormone that not only suppresses reproduction at the brain level but also regulates steroidogenesis and gametogenesis at the gonad level. However, its function in gonadal physiology has received little attention in rabbits. The main objective of this study was to evaluate the effects of GnIH on testicular development and function in prepubertal Minxinan Black rabbits (Oryctolagus cuniculus). In the present study, we investigated the serum reproductive hormone concentration, testicular parameters, morphology of seminiferous tubules, apoptosis of testicular cells, and expression of reproductive-related genes in male prepubertal Minxinan Black rabbits intraperitoneally administered with 0, 0.5, 5, or 50 µg quail GnIH-related peptides (qGnIH) for 10 days. Compared with the vehicle, administration with 5 µg of qGnIH downregulated the serum testosterone concentration and mRNA levels of spermatogenic genes (PCNA, FSHR, INHßA, HSF1, and AR) and upregulated the apoptosis rate of testicular cells; administration with 50 µg of qGnIH decreased the serum testosterone concentration and hypothalamic GnIH gene mRNA level and increased the serum LH concentration, pituitary LHß gene mRNA level, testicular weight, gonadosomatic index (GSI), and spermatogenic cell layer thickness. It is concluded that GnIH could exert dual actions on testicular development depending on the male prepubertal rabbits receiving different intraperitoneal doses.
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Bamboo leaves contain high concentrations of various biologically active compounds, such as polyphenols and volatiles, making them attractive as raw resources for antioxidant additives in the food industry. Here, we investigated the total phenolic content (TPC) and total flavonoid content (TFC) of four bamboo leaf extracts from two species (Phyllostachys edulis and Chimonocalamus delicatus) at two growth stages (first and second years). Antioxidant capacity was determined based on the radical-scavenging capacity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+). We also assessed the antifungal capacity based on mycelial growth inhibition of Colletotrichum musae (C. musae), Botrytis cinerea (B. cinereain), and Alternaria alternata (A. alternata). Pearson's correlation coefficients showed that the TPC was significantly (p < 0.01) negatively correlated with the half-maximal inhibitory concentrations against DPPH and ABTS+, whereas the TFC was positively correlated with C. musae and B. cinereain growth inhibition, which suggest that TPC and TFC might be the major contributors to the antioxidant and antifungal capacities of bamboo leaves, respectively. The volatile organic compounds (VOCs) of bamboo leaves were also analyzed using gas chromatography-ion mobility spectrometry. The VOCs included twenty-four aldehydes, eleven alcohols, four furans, seven esters, fifteen terpenes, three ketones, one pyrazine, and thirty unidentified compounds. Principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis were performed to assess the differences in the volatile profiles of the four bamboo leaf samples, from which 23 discriminatory VOCs with variable importance in the projection values > 1 were screened, and part of them were impacted by species or growth stage. These findings provide a theoretical foundation for the use of bamboo leaves.
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Pasteurella multocida serogroup F can infect a number of animals. However, the pathogenicity and genomic features of this serogroup are still largely unknown. In the present study, the pathogenicity and genomic sequences of 19 rabbit-sourced P. multocida serogroup F isolates were determined. The 19 isolates were highly pathogenic for rabbits causing severe pathologic lesions and high mortality in inoculated rabbits. Nevertheless, the pathologic lesions in rabbits caused by the 19 isolates were distinct from those caused by the previously reported high-virulent serogroup F strains J-4103 (rabbit), P-4218 (turkey), and C21724H3km7 (chicken). Moreover, the 19 isolates were avirulent to white feather broilers. The genomes of the 19 isolates were determined to understand the pathogenicity of these isolates. The finding of a number of functional genes in the 19 isolates by comparison with the low-virulent rabbit-sourced serogroup F strain s4 might contribute to the high virulence of these isolates. Notably, polymorphisms were determined in the lipopolysaccharide outer core biosynthetic genes natC and gatF among the serogroup F strains of different hosts. However, the sequences of natC and gatF from rabbit-sourced strains (except for SD11) were identical, which might be responsible for the host specific of the 19 isolates. The observations and findings in this study would be helpful for the understanding of the pathogenicity variation and host predilection of P. multocida. IMPORTANCE: The 19 rabbit-sourced Pasteurella multocida serogroup F isolates showing high virulence to rabbits were avirulent to the broilers. Notably, polymorphisms were determined in the lipopolysaccharide outer core biosynthetic genes natC and gatF among all serogroup F strains of different hosts. However, the sequences of natC and gatF from rabbit-sourced strains (except for SD11) were identical, which might be responsible for the host specific of the 19 isolates.
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Infecciones por Pasteurella , Pasteurella multocida , Animales , Conejos , Pasteurella multocida/genética , Infecciones por Pasteurella/veterinaria , Infecciones por Pasteurella/patología , Serogrupo , Pollos , Lipopolisacáridos , GenómicaRESUMEN
In arbuscular mycorrhizal (AM) symbiosis, sugars in root cortical cells could be exported as glucose or sucrose into peri-arbuscular space for use by AM fungi. However, no sugar transporter has been identified to be involved in sucrose export. An AM-inducible SWEET transporter, GmSWEET6, was functionally characterised in soybean, and its role in AM symbiosis was investigated via transgenic plants. The expression of GmSWEET6 was enhanced by inoculation with the cooperative fungal strain in both leaves and roots. Heterologous expression in a yeast mutant showed that GmSWEET6 mainly transported sucrose. Transgenic plants overexpressing GmSWEET6 increased sucrose concentration in root exudates. Overexpression or knockdown of GmSWEET6 decreased plant dry weight, P content, and sugar concentrations in non-mycorrhizal plants, which were partly recovered in mycorrhizal plants. Intriguingly, overexpression of GmSWEET6 increased root P content and decreased the percentage of degraded arbuscules, while knockdown of GmSWEET6 increased root sugar concentrations in RNAi2 plants and the percentage of degraded arbuscules in RNAi1 plants compared with wild-type plants when inoculated with AM fungi. These results in combination with subcellular localisation of GmSWEET6 to peri-arbuscular membranes strongly suggest that GmSWEET6 is required for AM symbiosis by mediating sucrose efflux towards fungi.
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Micorrizas , Simbiosis , Glycine max , Micorrizas/metabolismo , Hongos , Plantas Modificadas Genéticamente/metabolismo , Glucosa/metabolismo , Sacarosa/metabolismo , Raíces de Plantas/metabolismoAsunto(s)
Infecciones Comunitarias Adquiridas , Enfermedades Pulmonares , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Anciano , Neumonía/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Infecciones Comunitarias Adquiridas/tratamiento farmacológicoRESUMEN
Cathepsin V (CTSV) is a cysteine cathepsin protease that plays a crucial role in extracellular matrix degradation. CTSV is correlated with poor prognosis in various cancers, but the underlying mechanism remains elusive. Here, we observed that CSTV is upregulated in lung cancer and is a poor prognosis factor for lung cancer. CTSV acts as a driver in the metastasis of lung cancer both in vitro and in vivo. CTSV promotes lung cancer metastasis by downregulating adhesion molecules, including fibronectin, E-cadherin, and N-cadherin. Our data revealed that CTSV functions by mediating the fragmentation of fibronectin, E-cadherin, and N-cadherin in cleavage, remodeling the extracellular matrix (ECM). The rationally designed antibody targeting CTSV blocks its cleaving ability towards fibronectin, E-cadherin, and N-cadherin, suppressing migration and invasion. Furthermore, we found that CTSV expression is negatively correlated with immune cell infiltration and immune scores and inhibits T cell activity. Targeting CTSV with specific antibodies effectively suppressed lung cancer metastasis in a mouse model. Our study demonstrates the critical role of CTSV in the immunity and metastasis of lung cancer, suggesting that the CTSV-targeting approach is a promising strategy for lung cancer.
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Neoplasias Pulmonares , Animales , Ratones , Fibronectinas , Catepsinas/metabolismo , Moléculas de Adhesión Celular , Cadherinas/metabolismo , Movimiento Celular , Línea Celular TumoralRESUMEN
Background: Pulmonary infarction (PI) is an uncommon complication of pulmonary embolism (PE). The risk factors of PI are still relatively unclear. Methods: This was a single-center retrospective review conducted on 500 patients with PE. After applying the inclusion and exclusion criteria, 386 patients diagnosed with PE were enrolled in our study. These patients were then categorized into the PI group (n=64) and the non-PI group (n=322). A comparison was conducted between the two groups regarding the clinical characteristics. Results: The occurrence of PI secondary to PE was 16.58%. In univariate analysis, recent trauma (21.9% vs. 9.9%, P=0.007), pleuritic chest pain (46.9% vs. 17.4%, P<0.001), hemoptysis (29.7% vs. 2.5%, P<0.001), fever (26.6% vs. 8.1%, P<0.001), lower limb edema/pain (37.5% vs. 14.0%, P<0.001), white blood cell (WBC) counts (37.5% vs. 24.5%, P=0.032), C-reactive protein (CRP) (65.6% vs. 41.3%, P<0.001), and pleural effusion (45.3% vs. 18.6%, P<0.001) were associated with an increased risk of PI. Multivariate analysis demonstrated that age [odds ratio (OR) 0.975, 95% confidence interval (CI): 0.951-0.999, P=0.045], pleuritic chest pain (OR 2.878, 95% CI: 1.424-5.814, P=0.003), hemoptysis (OR 10.592, 95% CI: 3.503-32.030, P<0.001), lower limb edema/pain (OR 2.778, 95% CI: 1.342-5.749, P=0.006) and pleural effusion (OR 3.127, 95% CI: 1.531-6.388, P=0.002) were independent factors of PI due to PE. No significant difference was recorded between the two groups in treatment and mortality. Conclusions: Young patients were found to be a higher risk of PI. Pleural effusion was found to be a factor for PI. PI should be considered when pleuritic chest pain, hemoptysis, or lower limb edema/pain are present with peripheral opacity.
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OBJECTIVE: The aim of this study is to investigate the clinical characteristics of acute asthma exacerbations (AEs) with community-acquired pneumonia (CAP) in adults and establish a CAP prediction model for hospitalized patients with AEs. METHODS: We retrospectively collected clinical data from 308 patients admitted to Beijing Luhe Hospital, Capital Medical University, for AEs from December 2017 to August 2021. The patients were divided into CAP and non-CAP groups based on whether they had CAP. We used the Lasso regression technique and multivariate logistic regression analysis to select optimal predictors. We then developed a predictive nomogram based on the optimal predictors. The bootstrap method was used for internal validation. We used the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) to assess the nomogram's discrimination, accuracy, and clinical practicability. RESULTS: The prevalence of CAP was 21% (65/308) among 308 patients hospitalized for AEs. Independent predictors of CAP in patients hospitalized with an AE (P < 0.05) were C-reactive protein > 10 mg/L, fibrinogen > 4 g/L, leukocytes > 10 × 109 /L, fever, use of systemic corticosteroids before admission, and early-onset asthma. The AUC of the nomogram was 0.813 (95% CI: 0.753-0.872). The concordance index of internal validation was 0.794. The calibration curve was satisfactorily consistent with the diagonal line. The DCA indicated that the nomogram provided a higher clinical net benefit when the threshold probability of patients was 3% to 89%. CONCLUSIONS: The nomogram performed well in predicting the risk of CAP in hospitalized patients with AEs, thereby providing rapid guidance for clinical decision-making.
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Asma , Infecciones Comunitarias Adquiridas , Neumonía , Humanos , Adulto , Nomogramas , Estudios Retrospectivos , Asma/diagnóstico , Asma/epidemiología , Proteína C-Reactiva , Infecciones Comunitarias Adquiridas/epidemiología , Neumonía/epidemiologíaRESUMEN
Cadmium (Cd) has long been recognized as toxic pollutant to crops worldwide. The biosynthesis of glutathione-dependent phytochelatin (PC) plays crucial roles in the detoxification of Cd in plants. However, its regulatory mechanism remains elusive. Here, we revealed that Arabidopsis transcription factor WRKY45 confers Cd tolerance via promoting the expression of PC synthesis-related genes PCS1 and PCS2, respectively. Firstly, we found that Cd stress induces the transcript levels of WRKY45 and its protein abundance. Accordingly, in contrast to wild type Col-0, the increased sensitivity to Cd is observed in wrky45 mutant, while overexpressing WRKY45 plants are more tolerant to Cd. Secondly, quantitative real-time PCR revealed that the expression of AtPCS1 and AtPCS2 is stimulated in overexpressing WRKY45 plants, but decreased in wrky45 mutant. Thirdly, WRKY45 promotes the expression of PCS1 and PCS2, electrophoresis mobility shift assay analysis uncovered that WRKY45 directly binds to the W-box cis-element of PCS2 promoter. Lastly, the overexpression of WRKY45 in Col-0 leads to more accumulation of PCs in Arabidopsis, and the overexpression of PCS1 or PCS2 in wrky45 mutant plants rescues the phenotypes induced by Cd stress. In conclusion, our results show that AtWRKY45 positively regulates Cd tolerance in Arabidopsis via activating PCS1 and PCS2 expression.
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Arabidopsis , Cadmio , Factores de Transcripción , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Cadmio/toxicidad , Productos Agrícolas , Regulación de la Expresión Génica , Factores de Transcripción/metabolismo , TungstenoRESUMEN
Background: Tendinopathy is a growing global concern affecting many people, like athletes, workers, and the elderly. Despite its commonality among the sporting population, there is no practical clinical guideline for patellar tendinopathy (PT). Furthermore, there is conflicting evidence between clinical guidelines on shockwave therapy's application and clinical utility for Achilles tendinopathy (AT) and plantar fasciitis (PF). Thus, our aim of this study is to evaluate the evidence for shockwave therapy; to provide a Grading of Recommendation, Assessment, Development and Evaluation (GRADE) level of the evidence and effectiveness of shockwave therapy for patellar tendinopathy, Achilles tendinopathy, and Plantar fasciitis. Method: Medical Literature Analysis and Retrieval System Online (Medline), Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro) and China National Knowledge Infrastructure database (CNKI) were searched to find relevant studies published before December 14th, 2022. Results: Our study showed that for PT in the short term, extracorporeal shockwave therapy (ESWT) or ESWT + eccentric exercise (EE) has a negligible effect on pain and function compared to a placebo or placebo + EE. On the contrary, ESWT significantly affects pain compared to conservative treatment (CT). For AT, ESWT has a small inconclusive effect on pain and function in the short term compared to EE. On the other hand, a placebo outperformed ESWT in improving function for AT but not pain outcomes. PF showed that ESWT significantly affects short- and long-term pain and function. When ESWT was compared to other interventions such as low laser therapy (LLLT), corticosteroid injection (CSI), or CT, there was a small inconclusive effect on pain and function in the short term. Conclusion: There is low-moderate evidence that ESWT has a negligible effect on pain and function for PT and AT. However, high-quality evidence suggests ESWT has a large effect on pain and function for PF. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396835, identifier CRD42023396835.
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Tendón Calcáneo , Tratamiento con Ondas de Choque Extracorpóreas , Fascitis Plantar , Ondas de Choque de Alta Energía , Enfermedades Musculoesqueléticas , Tendinopatía , Anciano , Humanos , Fascitis Plantar/terapia , Ondas de Choque de Alta Energía/uso terapéutico , Tendinopatía/terapiaRESUMEN
5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 µM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg-1·d-1, intraperitoneal injection) effectively suppressed the growth of both types of tumors. These results demonstrate that USP14 and UCHL5 play an important role in the development of CRC and resistance to 5-FU. Targeting USP14 and UCHL5 with b-AP15 may represent a promising therapeutic strategy for the treatment of CRC.
Asunto(s)
Neoplasias Colorrectales , Complejo de la Endopetidasa Proteasomal , Animales , Ratones , Humanos , Complejo de la Endopetidasa Proteasomal/metabolismo , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Ratones Desnudos , Apoptosis , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos , Ubiquitina TiolesterasaRESUMEN
In recent years, the discharge of major pollutants in China's wastewater has been decreasing but remains at a high level. Controlling the discharge of pollutants in sewage is of great importance for protecting water quality and maintaining ecological balance. Based on data collected from 31 provinces in China from 2011 to 2020 (except 2018), this study analyzes the spatiotemporal variation emissions of the wastewater pollutants: chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN), and total phosphorus (TP). The entropy method was used to evaluate the effectiveness of water pollution control in different provinces. Our results revealed that the total emission per gross domestic product (GDP) for COD, NH3-N, TN and TP in China decreased by 50.7%, 81.9%, 65.4% and 70.8%, respectively. In terms of regional annual emission differences, the Northwest region was the lowest compared with other regions, accounting for 4.87%-6.59% of the national pollutant emissions, and the Central China region was the highest, accounting for 22.4%-26.05% of the national pollutant emissions. The average value of pollutant emissions per unit of GDP decreased year-to-year overall, but Guangxi and Tibet showed a trend of first decreasing and then increasing. The correlation results indicated a significant correlation (0.977) between TN and TP emissions in wastewater in China during 2011-2020. Through clustering and Multidimensional Scaling model (MDS) analysis, Beijing and Shanghai have been performing well in controlling water pollution discharge, while the provinces of Tibet and Guangxi must still increase their efforts in water pollution control. Furthermore, these results demonstrate the experience and achievements of the Chinese government in the treatment of wastewater pollution and provide a useful reference for treatment of wastewater pollution in the world.