Identification of Fibrotic Biomarkers Associated with Macrophages in Diabetic Nephropathy.

BACKGROUND Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Renal fibrosis is an important pathological feature of kidney injury, and the therapeutic means are very limited. The functions of macrophages play important roles in renal fibrosis. There is a complicated link between altered immune metabolism and oxidative stress. Hence, we designed this study to identify the oxidative stress- and macrophage-relevant biomarkers reflecting fibrosis in DN. MATERIAL AND METHODS Differential expression analysis was performed based on the GSE96804 dataset. xCell and weighted gene co-expression network analysis were used to determine the distinctions in infiltrating immune cells between DN and control specimens. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted. A protein-protein interaction network was constructed to identify the hub genes. Hub genes were validated in an external dataset, GSE30528, and cell models. RESULTS MMP2, CASP3, and HIF-1alpha were identified as biomarkers, which were upregulated in the DN group and positively correlated with the infiltration of macrophages and M1 macrophages. In vitro, the 3 genes were highly expressed in murine MPC5 cells treated with high glucose and human THP-1 macrophages treated with advanced glycation end products. CONCLUSIONS Our results provided biomarkers for predicting the fibrotic progression of DN and confirmed that MMP2, CAPS3, and HIF-1alpha have good diagnostic value. They might be involved in the progression of DN fibrosis by regulating oxidative stress and macrophage recruitment or polarization.

Quantifying the spatiotemporal evolution characteristics of medical waste generation during the outbreak of public health emergencies.

Based on the medical waste quantity and patient data during the corona virus disease 2019 (COVID-19) outbreak in China, this study used scenario analysis to quantitatively analyze the temporal and spatial evolution of medical waste generation during the pandemics. First, the results show that the estimated medical waste per capita reached 15.4 kg/day if only patients were considered in Scenario 1, while the figures were reduced to 3.2 kg/day in Scenario 2 and 2.5 kg/day in Scenario 3 when the effects of both the patient type and the number of medical staffs were considered. The estimated results also demonstrated that the per capita medical waste related to the epidemic showed the characteristics of a U-shaped and trailing phenomenon over time. Then, the amount of medical waste related to the COVID-19 generated that generated due to COVID-19 was estimated in Hubei, Heilongjiang, Zhejiang, Henan and Hunan provinces under Scenario 2 and Scenario 3. The results indicated that the spatiotemporal evolution characteristics of five provinces show the significant differences, and the patient type has a remarkable influence on the generation of medical waste. Finally, a novel decomposition-ensemble approach was designed to make a better short-term forecasting effect for future medical waste generation in different provinces. Supplementary Information: The online version contains supplementary material available at 10.1007/s10163-022-01523-5.

Role of tumor necrosis factor-α in the mortality of hospitalized patients with severe and critical COVID-19 pneumonia.

The coronavirus disease 2019 (COVID-19) is presently the most pressing public health concern worldwide. Cytokine storm is an important factor leading to death of patients with COVID-19. This study aims to characterize serum cytokines of patients with severe or critical COVID-19. Clinical records were obtained from 149 patients who were tested at the Sino-French New City Branch of Tongji Hospital from 30 January to 30 March 2020. Data regarding the clinical features of the patients was collected and analyzed. Among the 149, 45 (30.2%) of them had severe conditions and 104 (69.8%) of that presented critical symptoms. In the meantime, 80 (53.7%) of that 149 died during hospitalization. Of all, male patients accounted for 94 (69.1%). Compared with patients in severe COVID-19, those who in critical COVID-19 had significantly higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10. Moreover, the passed-away patients had considerably higher levels of TNF-α, IL-6, IL-8, and IL-10 than those survived from it. Regression analysis revealed that serum TNF-α level was an independent risk factor for the death of patient with severe conditions. Among the proinflammatory cytokines (IL-1ß, TNF-α, IL-8, and IL-6) analyzed herein, TNF-α was seen as a risk factor for the death of patients with severe or critical COVID-19. This study suggests that anti-TNF-α treatment allows patients with severe or critical COVID-19 pneumonia to recover.

Transcription factor WRKY22 regulates canker susceptibility in sweet orange (Citrus sinensis Osbeck) by enhancing cell enlargement and CsLOB1 expression.

Pathological hypertrophy (cell enlargement) plays an important role in the development of citrus canker, but its regulators are largely unknown. Although WRKY22 is known to be involved in pathogen-triggered immunity and positively regulates resistance to bacterial pathogens in Arabidopsis, rice and pepper, the CRISPR/Cas9-mediated partial knockout of CsWRKY22 improves resistance to Xanthomonas citri subsp. citri (Xcc) in Wanjincheng orange (Citrus sinensis Osbeck). Here, we demonstrate that CsWRKY22 is a nucleus-localized transcriptional activator. CsWRKY22-overexpressing plants exhibited dwarf phenotypes that had wrinkled and thickened leaves and were more sensitive to Xcc, whereas CsWRKY22-silenced plants showed no visible phenotype changes and were more resistant to Xcc. Microscopic observations revealed that the overexpression of CsWRKY22 increased cell size in the spongy mesophyll. Transcriptome analysis showed that cell growth-related pathways, such as the auxin and brassinosteroid hormonal signaling and cell wall organization and biogenesis pathways, were significantly upregulated upon CsWRKY22 overexpression. Interestingly, CsWRKY22 activated the expression of CsLOB1, which is a key gene regulating susceptibility to citrus canker. We further confirmed that CsWRKY22 bound directly to the W-boxes just upstream of the transcription start site of CsLOB1 in vivo and in vitro. We conclude that CsWRKY22 enhances susceptibility to citrus canker by promoting host hypertrophy and CsLOB1 expression. Thus, our study provides new insights into the mechanism regulating pathological hypertrophy and the function of WRKY22 in citrus.

Overexpressing a NPR1-like gene from Citrus paradisi enhanced Huanglongbing resistance in C. sinensis.

KEY MESSAGE: Overexpression of CiNPR4 enhanced resistance of transgenic citrus plants to Huanglongbing by perceiving the salicylic acid and jasmonic acid signals and up-regulating the transcriptional activities of plant-pathogen interaction genes. Developing transgenic citrus plants with enhanced immunity is an efficient strategy to control citrus Huanglongbing (HLB). Here, a nonexpressor of pathogenesis-related gene 1 (NPR1) like gene from HLB-tolerant 'Jackson' grapefruit (Citrus paradisi Macf.), CiNPR4, was introduced into 'Wanjincheng' orange (Citrus sinensis Obseck). CiNPR4 expression was determined in transgenic citrus plants using quantitative real-time PCR analyses. The Candidatus Liberibacter asiaticus (CLas) pathogen of HLB was successfully transmitted to transgenic citrus plants by grafting infected buds. HLB symptoms developed in transgenic and wild-type (WT) plants by 9 months after inoculation. A CLas population analysis showed that 26.9% of transgenic lines exhibited significantly lower CLas titer levels compared with the CLas-infected WT plants at 21 months after inoculation. Lower starch contents and anatomical aberration levels in the phloem were observed in transgenic lines having enhanced resistance compared with CLas-infected WT plants. CiNPR4 overexpression changed the jasmonic acid, but not salicylic acid, level. Additionally, the jasmonic acid and salicylic acid levels increased after CLas infection. Transcriptome analyses revealed that the enhanced resistance of transgenic plants to HLB resulted from the up-regulated transcriptional activities of plant-pathogen interaction-related genes.

The effects of an empowerment-based self-management intervention on empowerment level, psychological distress, and quality of life in patients with poorly controlled type 2 diabetes: A randomized controlled trial.

BACKGROUND: There is considerable interest in advocating empowerment in diabetes care. Health professionals, however, often fail to realize empowerment in clinical practice, especially in patients with poorly controlled type 2 diabetes. OBJECTIVES: To evaluate the effectiveness of an empowerment-based intervention on empowerment level, psychological distress, and quality of life among patients with poorly controlled type 2 diabetes. DESIGN: An analysis of secondary outcomes of a prospective multi-center, randomized, parallel, investigator-blinded controlled trial. METHODS: A total of 242 adult patients with poorly controlled type 2 diabetes [Hemoglobin A1c (HbA1c)≥ 58 mmol/mol in the recent six months] were randomly allocated to either intervention (n = 121) or attentional control (n = 121) groups. The design of the intervention was based on the Empowerment Process Model. The intervention group received a 6-week empowerment-based transitional care program, with significant emphasis on establishing personally meaningful goals, facilitating collaborative partnership and shared decision-making, resolving life-disease conflicts via situational reflection. Participants in the attentional control group received two general health education classes and post-discharge social calls on top of routine care. Outcomes of interest include empowerment level, diabetes distress, and quality of life. Participants were invited to complete a set of questionnaires before randomization, one-week, and three-month post-intervention. Statistical analyses were performed using the generalized estimating equations based on the intention-to-treat principle. RESULTS: Comparing with the attention control group, participants in the intervention group showed significant improvements on empowerment level [(ß= 0.163; 95% confidence interval (CI): 0.011 to 0.316, p = 0.036) at one-week post-intervention and (ß= 0.176; 95% CI: 0.020 to 0.331, p = 0.027) at three-month post-intervention, respectively]. This group of patients also displayed significant reduction in terms of emotional-distress (ß= -0.424, 95% CI: -0.798 to -0.049, p = 0.027) and regimen-distress (ß= -0.397, 95% CI: -0.702 to -0.091, p = 0.011) at three-month post-intervention and physician-related distress (ß= -0.236, 95% CI: -0.466 to -0.006, p = 0.044) at one-week post-intervention. Significant improvement in quality of life (ß= 4.151, 95% CI: 1.291, 7.012, p = 0.004) at three-month post-intervention was also observed in the intervention group. CONCLUSIONS: Findings provide empirical evidence for the values of an empowerment-based intervention program for patients with poorly controlled type 2 diabetes in increasing the empowerment level and perceived quality of life and reducing diabetes distress. Long-term effects of the intervention and its underlying mechanisms need further investigation.

Correction to: The MYB transcription factor CiMYB42 regulates limonoids biosynthesis in citrus.

An amendment to this paper has been published and can be accessed via the original article.

The MYB transcription factor CiMYB42 regulates limonoids biosynthesis in citrus.

BACKGROUND: Limonoids are major bioactive compounds that are produced by the triterpenoid metabolic pathway. The detailed biochemical process of limonoid biosynthesis and the mechanism of its molecular regulation remain elusive. The identification of transcription factors that regulate limonoid biosynthetic pathways is very important for understanding the underlying regulatory mechanisms. This information could also provide tools for manipulating biosynthesis genes to modulate limonoid production. RESULTS: In this study, the CiMYB42 transcription factor was isolated to identify its role in limonoid biosynthesis. Multiple alignment analysis and phylogenetic analysis demonstrated that CiMYB42 is a typical R2R3MYB transcription factor that shares high similarity of its amino acid sequence with AtMYB42. Limonoids contents were higher in Citrus sinensis and Citrus grandis than in other species. Limonoid accumulation during leaf development also showed diverse trends in different genotypes. The expression of CiMYB42 was significantly related to the limonoid content and the expression of CiOSC in some citrus accessions. The overexpression of CiMYB42 in sweet orange resulted in significant accumulation of limonin, whereas the downregulation of CiMYB42 by RNAi resulted in a dwarf phenotype and less nomilin accumulation. Furthermore, the results of a yeast one-hybrid assay and EMSA indicated that CiMYB42 binds exclusively to the TTGTTG sequence (type II MYB core) in the promoter of CiOSC. Together, these results suggest that CiMYB42 positively regulates limonoid biosynthesis by regulating the expression of CiOSC by binding to the TTGTTG sequence (type II MYB core) of its promoter. CONCLUSIONS: CiMYB42 is an important transcription activator involved in limonoid biosynthesis that regulates the expression of CiOSC by binding to the TTGTTG sequence (type II MYB core).

The comparative study of two kinds of ß-Bi2O3/TiO2 binary composite and their removal of 17ɑ-ethynylestradiol.

In this work, we used TiO2 nanobelts and P25 particles as titanium sources to combine with ß-Bi2O3 to form ß-Bi2O3/TiO2 and ß-Bi2O3/P25 composites. The prepared samples were characterized by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), and UV-vis absorbance spectroscopy and fluorescence spectroscopy. The structure and performance of two composites were comparatively investigated, and the ß-Bi2O3 molar ratios in them were optimized and their roles in them were studied. The results showed that the TiO2 nanobelts and commercial TiO2 (P25) particles combined with ß-Bi2O3 nanosheets. The optimal molar ratios of Bi to Ti element in two kinds of composites are 1:1. The ß-Bi2O3 in P25/ß-Bi2O3 makes more contribution to the improvement of photocatalytic activity of them than that in ß-Bi2O3/TiO2 because P25 particles are distributed on ß-Bi2O3 nanosheet more uniformly. The photocatalytic activities of ß-Bi2O3/TiO2 (0.02275 min-1) and ß-Bi2O3/P25 (0.02382 min-1) are 3.72 times and 3.90 times than that of pure ß-Bi2O3 (0.0061 min-1) for EE2 removal. The enhanced photocatalytic activities of two kinds of composites are ascribed to photo-induced interfacial charge transfer on the heterojunction between ß-Bi2O3 and TiO2 or P25. From the economic view, ß-Bi2O3/P25 composites are better than ß-Bi2O3/TiO2 because TiO2 nanobelts in the ß-Bi2O3/TiO2 composite are obtained from P25 via extra hydrothermal treatment in strong alkaline environment. The free radical capture experiment indicated that the dominant reactive species are h+ and •O-2 for EE2 removal by TiO2/ß-Bi2O3 and P25/ß-Bi2O3 composites.

Overexpressing GH3.1 and GH3.1L reduces susceptibility to Xanthomonas citri subsp. citri by repressing auxin signaling in citrus (Citrus sinensis Osbeck).

The auxin early response gene Gretchen Hagen3 (GH3) plays dual roles in plant development and responses to biotic or abiotic stress. It functions in regulating hormone homeostasis through the conjugation of free auxin to amino acids. In citrus, GH3.1 and GH3.1L play important roles in responding to Xanthomonas citri subsp. citri (Xcc). Here, in Wanjingcheng orange (Citrus sinensis Osbeck), the overexpression of CsGH3.1 and CsGH3.1L caused increased branching and drooping dwarfism, as well as smaller, thinner and upward curling leaves compared with wild-type. Hormone determinations showed that overexpressing CsGH3.1 and CsGH3.1L decreased the free auxin contents and accelerated the Xcc-induced decline of free auxin levels in transgenic plants. A resistance analysis showed that transgenic plants had reduced susceptibility to citrus canker, and a transcriptomic analysis revealed that hormone signal transduction-related pathways were significantly affected by the overexpression of CsGH3.1 and CsGH3.1L. A MapMan analysis further showed that overexpressing either of these two genes significantly downregulated the expression levels of the annotated auxin/indole-3-acetic acid family genes and significantly upregulated biotic stress-related functions and pathways. Salicylic acid, jasmonic acid, abscisic acid, ethylene and zeatin levels in transgenic plants displayed obvious changes compared with wild-type. In particular, the salicylic acid and ethylene levels involved in plant resistance responses markedly increased in transgenic plants. Thus, the overexpression of CsGH3.1 and CsGH3.1L reduces plant susceptibility to citrus canker by repressing auxin signaling and enhancing defense responses. Our study demonstrates auxin homeostasis' potential in engineering disease resistance in citrus.

Effectiveness of a patient-centred, empowerment-based intervention programme among patients with poorly controlled type 2 diabetes: A randomised controlled trial.

BACKGROUND: Despite extensive efforts and advances in evidence-based diabetes management, poor glycaemic control still remains a challenge in many countries. There is a paucity of research addressing the needs of patients with poorly controlled type 2 diabetes, or exploring the effectiveness of empowerment-based interventions in this vulnerable population. OBJECTIVES: To evaluate the effectiveness of a patient-centred, empowerment-based programme on glycaemic control and self-management behaviours among patients with poorly controlled type 2 diabetes. DESIGN: A prospective multi-centre, single-blind, randomised controlled trial. SETTINGS AND PARTICIPANTS: Adult patients with poorly controlled type 2 diabetes [Haemoglobin A1c (HbA1c) ≥7.5% in the recent six months] were recruited from two tertiary hospitals in Xi'an city, China. METHODS: A total of 242 eligible patients were recruited and randomly assigned to the intervention or attentional control groups after baseline measurement. Participants in the intervention group received a 6-week patient-centred, empowerment-based self-management programme, which is theoretically grounded on the principles of the Empowerment Process Model-setting personally meaningful goals, taking action towards goals and reflecting on the impact of action plans. Those in the attentional control group received health education classes and post-discharge follow-up. Outcome measures included glycaemic control (measured by HbA1c) and self-management behaviours. Data were collected at baseline, and at 8th and 20th week after enrolment. Intervention effect were analysed using the generalised estimating equation model on the basis of the intention-to-treat principle. RESULTS: Compared with the attention control group, the intervention group showed a non-significant HbA1c reduction of 0. 476% (Cohen's d effect size=0.31, p=0.162). The intervention group exhibited significant improvements in general diet management at the 8th-week (ß=0.740; p=0.013), specific diet management at 8th-week (ß=0.646; p=0.022) and 20th-week (ß=0.517; p=0.043), and blood glucose self-monitoring at both the 8th- (ß=0.793; p=0.009) and 20th-week (ß=0.739; p=0.017) follow-ups. No intervention-related adverse events were observed. CONCLUSIONS: Findings indicate that the patient-centred, empowerment-based self-management intervention program did not induce a significant HbA1c reduction. Whereas this intervention yields improvements in diet management and blood glucose self-monitoring among patients with poorly controlled type 2 diabetes.