Relationship between dietary macronutrients intake and biological aging: a cross-sectional analysis of NHANES data.

PURPOSE: This study aimed to investigate the association between macronutrient intake and biological age. METHODS: Data were collected from 26,381 adults who participated in the United States National Health and Nutrition Examination Survey (NHANES). Two biological ages were estimated using the Klemera-Doubal method (KDM) and PhenoAge algorithms. Biological age acceleration (AA) was computed as the difference between biological age and chronological age. The associations between macronutrient intakes and AA were investigated. RESULTS: After fully adjusting for confounding factors, negative associations were observed between AA and fiber intake (KDM-AA: ß - 0.53, 95% CI - 0.62, - 0.43, P < 0.05; PhenoAge acceleration: ß - 0.30, 95% CI - 0.35, - 0.25, P < 0.05). High-quality carbohydrate intake was associated with decreased AA (KDM-AA: ß - 0.57, 95% CI - 0.67, - 0.47, P < 0.05; PhenoAge acceleration: ß - 0.32, 95% CI - 0.37, - 0.26, P < 0.05), while low-quality carbohydrate was associated with increased AA (KDM-AA: ß 0.30, 95% CI 0.21, 0.38, P < 0.05; PhenoAge acceleration: ß 0.16, 95% CI 0.11, 0.21, P < 0.05). Plant protein was associated with decreased AA (KDM-AA: ß - 0.39, 95% CI - 0.51, - 0.27, P < 0.05; PhenoAge acceleration: ß - 0.21, 95% CI - 0.26, - 0.15, P < 0.05). Long-chain SFA intake increased AA (KDM-AA: ß 0.16, 95% CI 0.08, 0.24, P < 0.05; PhenoAge acceleration: ß 0.11, 95% CI 0.07, 0.15, P < 0.05). ω-3 PUFA was associated with decreased KDM-AA (ß - 0.18, 95% CI - 0.27, - 0.08, P < 0.05) and PhenoAge acceleration (ß - 0.09, 95% CI - 0.13, - 0.04, P < 0.05). CONCLUSION: Our findings suggest that dietary fiber, high-quality carbohydrate, plant protein, and ω-3 PUFA intake may have a protective effect against AA, while low-quality carbohydrate and long-chain SFA intake may increase AA. Therefore, dietary interventions aimed at modifying macronutrient intakes may be useful in preventing or delaying age-related disease and improving overall health.

The experiences of UK-Chinese individuals during the COVID-19 pandemic: A qualitative interview study.

Infectious disease outbreaks have historically been associated with stigmatisation towards minority groups, specifically those associated with the geographical region that the disease was first identified. We aimed to investigate how the emerging COVID-19 pandemic was experienced by UK-resident individuals of Chinese ethnicity: how their perceived cultural and ethnic identity influenced their experiences, and how early insights into the pandemic in China influenced attitudes and behaviours. We undertook in-depth semi-structured interviews with individuals who self-identified as UK-Chinese. Participants were recruited from three cities in the UK. Interviews were undertaken over the telephone between 9th April 2020 and 16th July 2020. Interviews were digitally recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using inductive thematic analysis. Sixteen individuals were interviewed. Three main themes were identified: (1) Attribution of stigma, (2) Pandemic legacies, and (3) Individual versus societal responses. These reflected six sub-themes: (1) Stigmatisation through (mis)identity, (2) Markers of pandemic awareness, (3) Legacies of previous pandemics, (4) Ascription of blame, (5) Extent of freedom, and (6) Implicit faith in government. Experiences of xenophobia included accounts of physical violence. UK-Chinese individuals experienced and perceived widespread xenophobia, in the context of media representations that ascribed blame and exacerbated stigmatisation. Prior experience of respiratory epidemics, and insight into the governmental and societal response in China, contributed to the early adoption of face masks. This in turn marked UK-Chinese individuals as targets for abuse. Awareness is needed to safeguard stigmatized groups from social and economic harm in future infectious disease pandemics.

Coexistence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgA nephropathy.

Co-occurrence of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgA nephropathy (IgAN) is extremely uncommon. To date, only a few case reports have described such patients. Here, we describe the clinical presentation, pathologic features, treatment response, and outcome data of five patients with the rare form of co-existing AAV and IgAN and compared the characteristics of these patients to AAV patients with pauci-immune glomerulonephritis (n = 10) and IgAN patients (n = 10) that were selected as controls by stratified random sampling. In addition, we summarize all the previously reported cases of AAV and IgAN. In total, including the current study, 16 AAV/IgAN overlap cases were reported. Our five patients with the coexistence of AAV and IgAN were younger than the ten AAV patients with pauci-immune glomerulonephritis (22.6 ± 8.2 years versus 48.9 ± 15.7 years, respectively, P = 0.004). Histologically, they had a significantly lower percentage of glomeruli with fibrous crescents compared with AAV patients (0.0% versus 4.0%, P = 0.038). Compared with ten IgAN patients, our five AAV/IgAN patients had higher levels of ESR (P = 0.032) and CRP (P = 0.031). After accepting treatment with a combination of steroid and immunosuppressants, all patients showed a positive response to therapy, except for one patient in our cohort and another previously reported patient. We described the clinical presentation, pathologic features, treatment response, and outcome data of five patients with overlapping AAV and IgAN. They had mild glomerular pathological lesions and a positive response to aggressive immunosuppressive therapy. They were quite similar to pauci-immune AAV patients in clinical features, except for younger age. They had a lower percentage of glomeruli with fibrous crescents compared with AAV patients. In contrast to IgAN patients, they had higher levels of ESR and CRP. The mechanism of the coexistence of IgAN and AAV needs further study.

Hepatitis C virus screening reactive among blood donors in mainland China: A systematic review and meta-analysis.

BACKGROUND: Hepatitis C virus (HCV) can be transmitted by blood transfusion. The aim of this meta-analysis is to estimate the anti-HCV reactive rate and to define the demographic characteristics of blood donors who have potential threats to blood safety in mainland China for nearly 30 years, in order to provide a safe reference for blood transfusion and corresponding guidance for policymakers to increase blood safety. MATERIALS AND METHODS: Literature reporting the anti-HCV screening reactive rate in Chinese blood donors was identified by systematic searching of four electronic databases from 1991 to 2017. The Preferred Reporting of Items for Systematic Reviews and Meta-Analyses guidelines were strictly followed, and data manipulation and statistical analysis were performed by Stata 15.0. RESULTS: Our results showed that the post-donation anti-HCV reactive rate was 0.53% (95% confidence interval [CI], 0.51%-0.55%) with a significant variation from 1.58% (95% CI, 1.13%-2.03%) before 1998 to 0.51% (95% CI, 0.48%-0.53%) after 1998 when the Blood Donation Law was implemented in China. In addition, anti-HCV screening reactive rate for family or replacement donors was significantly higher than that in individual voluntary blood donors. CONCLUSION: Our results indicated that blood centres in China should convert more eligible first-time donors into repeat donors and turn the 'real family or replacement donors' into individual voluntary blood donors to reduce the risk of transfusion-transmitted HCV. In the meantime, large surveys should be carried out among volunteer donors from high-risk populations.

The effect of discontinuation of maintenance therapy in Chinese patients with MPO-ANCA associated vasculitis who were in long-term stable remission.

There is a consensus that maintenance therapy should be used to prevent relapse of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV), but there is a debate about the optimal duration of maintenance therapy. Therefore, the purpose of this study was to determine whether discontinuation of maintenance therapy in MPO-AAV patients who were in long-term stable remission affects relapse, renal survival and patient survival. Seventy-nine patients with MPO-AAV diagnosed at Xiangya hospital from June 2010 to June 2019 who were in stable remission for at least 18 months following maintenance therapy were included. Patient records were retrospectively reviewed, and based on whether patients discontinued maintenance therapy 18 months after commencing maintenance therapy, patients were assigned into either the withdrawal group (n = 26) or maintenance group (n = 53). The endpoint was the percentage of relapse, relapse-free survival, renal survival and patient survival during follow-up. Ten relapses (38.5%) occurred in the withdrawal group (n = 26) and 8 relapses (15.1%) occurred in the maintenance group (n = 53) (p = 0.020). Compared to the withdrawal group, the maintenance group had similar relapse-free survival (log-rank test p = 0.099). But maintenance group had a better renal survival (p = 0.035), with no difference in patient survival or adverse events. This study suggests that discontinuing maintenance therapy at 18 months following induction of sustained remission leads to a significant increase in the percentage of relapse, and decreases renal survival in patients with MPO-AAV, but does not decrease relapse-free survival or patient survival.

The effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in critically ill patients with acute kidney injury: An observational study using the MIMIC database.

Background: The safety of prescribing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during acute kidney injury (AKI) remains unclear. We aimed to investigate the associations of ACEI/ARB therapy in AKI with the risk of mortality, acute kidney disease (AKD), and hyperkalemia. Methods: We conducted a retrospective monocentric study, which included patients in Massachusetts between 2008 and 2019 from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching was performed for the endpoint analysis. The association between ACEI/ARB therapy and mortality was assessed using Cox proportional hazards regression models. Logistic regression was used to assess the risk of AKD and hyperkalemia. Results: Among the 19,074 individuals with AKI admitted to the intensive care unit (ICU), 3,244 (17.0%) received ACEI/ARBs, while 15,830 (83.0%) did not. In the propensity score-matched sample of 6,358 individuals, we found a decreased risk of mortality in those who received ACEI/ARBs compared to those who did not (hazard ratio [HR] for ICU mortality: 0.34, 95% confidence interval [CI]: 0.27-0.42); HR for in-hospital mortality: 0.47, 95% CI: 0.39-0.56; HR for 30-day mortality: 0.47, 95% CI: 0.40-0.56; HR for 180-day mortality: 0.53, 95% CI: 0.45-0.62). However, the use of ACEI/ARBs was associated with a higher risk of AKD (risk ratio [RR]: 1.81; 95% CI: 1.55-2.12). There was no significant association between ACEI/ARBs and an increased risk of hyperkalemia (RR: 1.21; 95% CI: 0.96-1.51). Conclusions: ACEI/ARB treatment during an episode of AKI may decrease all-cause mortality, but increases the risk of AKD. Future randomized controlled trials are warranted to validate these findings.

Association between serum chloride levels with mortality in critically ill patients with acute kidney injury: An observational multicenter study employing the eICU database.

OBJECTIVE: The effect of the serum chloride (Cl) level on mortality in critically ill patients with acute kidney injury (AKI) remains unknown. We sought an association between mortality and serum Cl. METHODS: We identified AKI patients in the eICU Collaborative Research Database from 2014 to 2015 at 208 US hospitals. The outcomes included in-hospital and intensive care unit (ICU) mortality. Time-varying covariates Cox regression models and the Kaplan-Meier (K-M) curves were used to assess the association between serum Cl levels and mortality. Multivariable adjusted restricted cubic spline models were used to analyze the potential nonlinear relationship between mortality and serum Cl. RESULTS: In total, 4,234 AKI patients were included in the study. Compared with normochloremia (98≤chloride<108mEq/L), hypochloremia (Cl<98mEq/L) was associated with mortality (adjusted hazard ratio [HR] for in-hospital mortality 1.46, 95% confidence interval [CI] 1.20-1.80, P = 0.0003; adjusted HR for ICU mortality 1.37, 95% CI 1.05-1.80, P = 0.0187). Hyperchloremia showed no significant difference in mortality compared to normochloremia (adjusted HR for in-hospital mortality 0.89, 95% CI 0.76-1.04, P = 0.1438; adjusted HR for ICU mortality 0.87, 95% CI 0.72-1.06, P = 0.1712). Smoothing curves revealed continuous non-linear associations between serum Cl levels and mortality. The K-M curve showed that patients with hypochloremia presented with a lower survival rate. CONCLUSIONS: Lower serum Cl levels after ICU admission was associated with increased in-hospital and ICU mortality in critically ill patients with AKI. The results should be verified in well-designed prospective studies.

Interleukin-22 exacerbates angiotensin II-induced hypertensive renal injury.

Hypertensive renal injury (HRI) is a main cause of end-stage renal diseases, and CD4+ T cells and the secreted inflammatory cytokines contribute to the progress of HRI. However, the exact mechanisms remain unidentified in HRI, and there is still a shortage of effective treatments. Here, we aim to explore the role of interleukin-22 (IL-22) and its underlying mechanism in HRI. Serum IL-22 level and peripheral Th22 cells frequency in patients with HRI were detected by ELISA and flow cytometry respectively. Angiotension II (Ang II) was infused subcutaneously to C57BL/6 mice for 28 days. Hypertensive mice were treated with recombinant IL-22 (rIL-22), anti-IL-22 antibody, or JAK2/STAT3 pathway blocker AG-490 respectively. Blood pressure (BP), urinary albumin/creatinine ratio (UACR), serum creatinine (Scr) and renal histopathology were measured; renal Th22 cells proportion were evaluated; inflammatory factors were evaluated by ELISA; JAK2/STAT3 pathway and fibrosis related factors expression in kidney were detected by Western blot. Serum IL-22 and Th22 cells proportion in kidney of mice were elevated after Ang II infusion. Compared to Ang II-infused mice, treatment with rIL-22 resulted in further increased UACR, Scr, renal pathological damage, inflammation and renal fibrosis, accompanied by elevated BP and JAK2/STAT3 pathway activation. Conversely, anti-IL-22 antibody reduced inflammation, renal fibrosis and BP in Ang II treated mice. AG490 could compromised the above effects of rIL-22. Taken together, recombinant IL-22 may aggravate hypertensive renal damage mediated by Ang II in mice, which may be through promoting JAK2/STAT3 pathway activation. Anti-IL-22 antibody exerts the opposite effects. These data suggest the IL-22 signaling maybe a novel therapeutic target for the treatment of hypertensive renal injury.

High levels of platelet-to-lymphocyte ratio may predict reduced risk of end stage of renal disease in Chinese patients with MPO-ANCA associated vasculitis. / 血小板/淋巴细胞比率比值升高可能预示中国MPO-ANCAç›¸å ³æ€§è¡€ç®¡ç‚Žæ‚£è€ è¿›å±•è‡³ç»ˆæœ«æœŸè‚¾ç— çš„é£Žé™©è¾ƒä½Ž.

OBJECTIVES: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality. METHODS: The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. RESULTS: A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801). CONCLUSIONS: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

Molecular and functional characterization of a conserved odorant receptor from Aedes albopictus.

BACKGROUND: The Asian tiger mosquito Aedes albopictus is a competent vector of several viral arboviruses including yellow fever, dengue fever, and chikungunya. Several vital mosquito behaviors (e.g., feeding, host-seeking, mating, and oviposition) are primarily dependent on the olfactory system for semiochemicals detection and discrimination. However, the limited number of studies hampers our understanding of the relationships between the Ae. albopictus olfactory system and the complex chemical world. METHODS: We performed RT-qPCR assay on antennae of Ae. albopictus mosquitoes of different sexes, ages and physiological states, and found odorant receptor 11 (AalbOr11) enriched in non-blood-fed female mosquitoes. Then, we examined the odorant preference with a panel of physiologically and behaviorally relevant odorants in Xenopus oocytes. RESULTS: The results indicated that AalbOr11 could be activated by ten aromatics, seven terpenes, six heterocyclics, and three alcohols. Furthermore, using post-RNA interference (RNAi) hand-in-cage assay, we found that reducing the transcript level of AalbOr11 affected the repellency activity mediated by (+)-fenchone at a lower concentration (0.01% v/v). CONCLUSIONS: Using in vitro functional characterization, we found that AalbOr11 was a broadly tuned receptor. Moreover, we found that AalbOr11 shared a conserved odorant reception profile with homologous Anopheles gambiae Or11. In addition, RNAi and bioassay suggested that AablOr11 might be one of the receptors mediating (+)-fenchone repellency activity. Our study attempted to link odor-induced behaviors to odorant reception and may lay the foundation for identifying active semiochemicals for monitoring or controlling mosquito populations.

Clinical features and outcomes of anti-neutrophil cytoplasmic autoantibody-associated vasculitis in Chinese childhood-onset patients.

Data on anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are limited in children. This study is to determine the clinical features and outcomes of childhood-onset AAV. A retrospective study was performed on patients who were diagnosed with AAV before 18 years old in Xiangya Hospital. Their medical records were analyzed by retrospective review. Sixteen patients were diagnosed with AAV before 18 years old in the past 9 years, with an average age of 13.3 ± 3.3 years and 13 of them were female. There were 15 patients with microscopic polyangiitis (MPA) and 1 with Wegener's granulomatosis. The interval between onset of disease and diagnosis of AAV was 2 (1.5-3) months. Most patients (15/16, 93.8%) had multi-organ involvement, and all patients had renal involvement with 7 (43.8%) patients requiring dialysis at presentation. Eleven patients underwent a renal biopsy, of which mixed class and sclerotic class were the most two common histological types. All patients received immunosuppressive therapy for induction therapy including intravenous administrations of methylprednisolone (MP) pulse therapy for 8 patients. 8 patients (50%) achieved remission after induction therapy. After a median follow-up of 46.3 ± 36.1 months, nine (56.3%) patients progressed to end-stage renal disease (ESRD) and 5 (31.3%) patients died. Childhood-onset AAV showed similar clinical and pathological features compared to those of adults, except that it usually occurs in girls. The most commonly involved organ was the kidney, and it had a high risk of progression to ESRD. Early diagnosis and initiation of appropriate immunomodulatory therapy would be important to improve outcomes.

Serum Sortilin Is Associated with Coronary Artery Calcification and Cardiovascular and Cerebrovascular Events in Maintenance Hemodialysis Patients.

OBJECTIVE: To analyze the role of serum sortilin in coronary artery calcification (CAC) and cardiovascular and cerebrovascular events (CCE) in maintenance hemodialysis (MHD) patients. METHODS: One hundred eleven patients with MHD ≥3 months were included in this study. The general data, clinical features, hematological data, and medication history of the patients were recorded. Eighty-five cases were examined by vascular color Doppler ultrasound, cardiac color Doppler ultrasound, lateral lumbar radiography, and coronary artery calcification score. The patients were followed up for a median time of 45 months. The primary endpoint was CCE or death from a vascular event, and the role of sortilin in this process was analyzed. RESULTS: Among 85 MHD patients, 51 cases (60.00%) had different degrees of CAC. There were significant differences in diabetes, dialysis time, serum phosphorus, calcium-phosphorus product, medical history of phosphate binders, sortilin, and carotid artery plaque between 4 different degrees of calcification groups (p < 0.05). Logistic regression analysis showed that diabetes (OR = 5.475; 95% CI: 1.794-16.71, p = 0.003), calcium-phosphorus product (OR = 2.953; 95% CI: 1.198-7.279, p = 0.019), and sortilin (OR = 1.475 per 100 pg/mL; 95% CI: 1.170-1.858, p = 0.001) were independent risk factors for CAC. During the follow-up, 28 cases of 111 patients (25.23%) suffered from CCE. There were significant differences in CCE between mild, moderate, and severe CAC groups and noncalcification groups (p < 0.05). Cox regression analysis showed that diabetes mellitus (HR 3.424; 95% CI: 1.348-8.701, p = 0.010), CAC (HR 5.210; 95% CI: 1.093-24.83, p = 0.038), and serum sortilin (HR = 8.588; 95% CI: 1.919-38.43, p = 0.005) were independent risk factors for CCE. Besides, we proposed a cutoff value of 418 pg/mL for serum sortilin level, which was able to predict the occurrence of CCE with 75.0% sensitivity and 71.9% specificity. The area under the curve was 0.778 (95% CI: 0.673-0.883). CONCLUSION: Sortilin is newly found to be independently associated with CAC and CCE in MHD patients.

Systemic immune-inflammation index predicts a reduced risk of end-stage renal disease in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis: A retrospective observational study.

Chronic inflammation has been indicated to be important in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). The systemic immune-inflammation index (SII) is a novel marker of inflammation. The present study was thus performed to explore the association between the SII at diagnosis and inflammatory response and disease activity in Chinese patients with myeloperoxidase (MPO)-AAV. Furthermore, it was evaluated whether the SII is able to predict the progression to end-stage renal disease (ESRD) and patient survival. A total of 190 patients with MPO-AAV were included in the present study. The baseline SII was positively correlated with C-reactive protein (CRP; r=0.274, P<0.0001) and the erythrocyte sedimentation rate (ESR; r=0.481, P<0.0001). However, the SII had no obvious correlation with the Birmingham vasculitis activity score. Patients with SII≥2,136.45 exhibited better cumulative renal survival rates than those with SII<2,136.45 (P=0.001). However, no significant difference in patient survival was indicated between patients with SII≥2,136.45 and those with SII<2,136.45 at diagnosis. In conclusion, the SII was positively correlated with CRP and ESR in Chinese patients with MPO-AAV. Furthermore, the SII may be an independent factor associated with a reduced risk of ESRD.

Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients.

Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease of the kidney glomerulus. It may gradually progress to end-stage renal disease (ESRD) characterized by increased proteinuria, which leads to serious consequences. Although substantial advances have been made in the understanding of the molecular bases of IMN in the last 10 years, certain questions remain largely unanswered. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from 6 patients with anti-PLA2R positive IMN and 2 healthy control subjects using single-cell RNA sequencing. We then identified distinct cell clusters through unsupervised clustering analysis of kidney specimens. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. Based on transcriptional expression patterns, we identified all previously described cell types in the kidney. The DEGs in most kidney parenchymal cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling, and MAPK signaling. Moreover, cell-cell crosstalk highlighted the extensive communication of mesangial cells, which infers great importance in IMN. IMN with massive proteinuria displayed elevated expression of genes participating in inflammatory signaling pathways that may be involved in the pathogenesis of the progression of IMN. Overall, we applied single-cell RNA sequencing to IMN to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis, and identify novel therapeutic targets of anti-PLA2R positive IMN.

Three chemosensory proteins from the sweet potato weevil, Cylas formicarius, are involved in the perception of host plant volatiles.

BACKGROUND: Chemosensory proteins (CSPs) play important roles in chemical communication, but their precise physiological functions are still unclear. Cylas formicarius is the most serious pest attacking sweet potato around the world. At present, there is no effective way to control this pest. RESULTS: Our results showed that CforCSP1, 5 and 6 genes were highly expressed in the antennae of both sexes of C. formicarius. In addition, results from a fluorescence competitive binding assay showed that the CforCSP1, 5 and 6 proteins had high binding affinities for 17 plant volatiles including eight host plant volatiles. This indicated that the three proteins may be involved in the detection of host plant volatiles. Furthermore, results from four-arm olfactometer bioassays showed that there was a significant tendency for C. formicarius to be attracted to eucalyptol, ß-carotene, benzaldehyde, vanillin and phenethyl alcohol, while it was repelled by ß-ionone. Finally, the levels of expression of the three CforCSPs in C. formicarius were successfully inhibited by RNA interference (RNAi). Behavioral experiments showed that CforCSP1, 5 and 6-deficient C. formicarius were partly anosmic to ß-cyclocitral, benzaldehyde, octyl aldehyde, and ß-ionone and exhibited a reduced ability to locate the host plant volatiles ß-carotene and vanillin. CONCLUSION: Our data suggest that CforCSP1, 5 and 6 likely are involved in the chemical communication between C. formicarius and host plant volatiles, which may play pivotal roles in oviposition and feeding site preferences. More importantly, these results could provide information for the development of monitoring and push-pull strategies for the control of C. formicarius. © 2021 Society of Chemical Industry.

A Partial Picture of the Single-Cell Transcriptomics of Human IgA Nephropathy.

The molecular mechanisms underlying renal damage of IgA nephropathy (IgAN) remain incompletely defined. Here, single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from IgAN and control subjects to define the transcriptomic landscape at single-cell resolution. We presented a comprehensive scRNA-seq analysis of human renal biopsies from IgAN. We showed for the first time that IgAN mesangial cells displayed increased expression of several novel genes including MALAT1, GADD45B, SOX4, and EDIL3, which were related to cell proliferation and matrix accumulation. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. Furthermore, we compared the results of 4 IgAN patients with the published scRNA-Seq data of healthy kidney tissues of three human donors in order to further validate the findings in our study. The results also verified that the overexpressed genes in tubule cells from IgAN patients were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. The receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. IgAN patients with overt proteinuria displayed elevated genes participating in several signaling pathways compared with microproteinuria group. It needs to be mentioned that based on number of mesangial cells and other kidney cells analyzed in this study, the results of our study are preliminary and needs to be confirmed on larger number of cells from larger number of patients and controls in future studies. Therefore, these results offer new insight into pathogenesis and identify new therapeutic targets for IgAN.

Immunoglobulin and complement-mediated glomerular diseases with an MPGN pattern of injury: Unmasking the diagnosis of lupus in a patient with hepatitis A infection.

In cases with a broad differential or atypical features, it is important to continually review the original diagnosis. Diagnosing SLE can be challenging due to its multisystem presentations; a multidisciplinary approach is beneficial.

A survey on acute kidney injury in severely and critically ill COVID-19 patients without chronic kidney disease.

BACKGROUND: Research has shown that acute kidney injury (AKI) has a noticeable incidence in critically ill patients with coronavirus disease 2019 (COVID-19). Patients with prior renal insufficiency are particularly susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), due to their immune dysfunction. However, most patients with COVID-19 do not have a history of kidney dysfunction, and few studies have focused on the incidence of AKI among COVID-19 patients without chronic kidney disease (CKD). In this study, we aimed to investigate the occurrence of AKI in severely and critically ill COVID-19 patients, with a particular focus on those without a CKD history. METHODS: A single-center retrospective study of 96 patients with COVID-19 in China between February 7 and March 3, 2020 was conducted. All patients were diagnosed by nucleic acid test (NAT) for SARS-CoV-2. Enrolled patients were divided into the severely or critically ill group according to the defined criteria. Patients' epidemiological, clinical, and laboratory characteristics, along with their treatment information, were collected from the medical history system. The occurrence of AKI was compared between the severe and critical patients, and between patients with or without a history of CKD. The diagnostic criteria for AKI included an increase in the serum creatinine level to ≥1.5-fold the level at baseline within 7 days according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Renal outcomes were defined as AKI or non-AKI. RESULTS: Four patients (4.2%) developed AKI, all of whom were in the critically ill group, and 3 (75%) of whom died. Out of the 90 severely and critically ill COVID-19 patients without CKD, 3 (3.3%) patients developed AKI; out of the 6 patients with CKD, 1 (16.7%) patient developed AKI. Age, disease severity, procalcitonin, C-reactive protein, and interleukin-6 were correlated with AKI onset in severely and critically ill COVID-19 patients, while lymphocyte count and estimated glomerular filtration rate at admission were inversely related to the development of AKI. CONCLUSIONS: Only 3.3% of severely and critically ill COVID-19 patients without CKD in our research cohort developed AKI. Critically ill patients may be more susceptible to AKI than severely ill patients.

Glomerular Immune Deposition in MPO-ANCA Associated Glomerulonephritis Is Associated With Poor Renal Survival.

Background: Rapidly progressive glomerulonephritis caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is typically characterized as pauci-immune glomerulonephritis. However, immune complex (IC) deposition in the glomerulus has been reported in a growing number of studies. Here, we assess the presence of glomerular immune deposits alongside renal outcome in myeloperoxidase (MPO)-ANCA associated glomerulonephritis (MPO-ANCA GN). Methods: Clinical and histopathologic characteristics of 97 patients with MPO-ANCA GN classified by renal biopsy from January 2008 to December 2019 were extracted retrospectively from electronic medical records. The extent of immune deposits in the kidney (C3, C4, C1q, IgA, IgG, IgM) at diagnosis were analyzed by immunofluorescence (IF). Patients were followed up for a median period of 15 months. The response to treatment and outcomes of renal and histological lesion changes were also assessed. Results: In our study, 41% (40/97) of patients showed positive IF (≥2+) for at least one of the six immunoglobulin or complement components tested. Patients with IC deposits showed higher levels of serum creatinine (p=0.025), lower platelet counts (p=0.009), lower serum complement C3 (sC3) (≤790 ml/L) (p=0.013) and serum IgG (p=0.018) than patients with pauci-immune (PI) deposition at diagnosis. End-stage renal disease was negatively associated with eGFR (HR 0.885, 95% CI 0.837 to 0.935, p<0.0001), platelet count (HR 0.996, 95% CI 0.992 to 1.000, p=0.046) and serum globulin (HR 0.905, 95% CI 0.854 to 0.959, p=0.001). Patients with lower sC3 levels showed a worse renal outcome than the patients with normal sC3 at diagnosis (p=0.003). Analysis of the components of the renal deposits found that patients with IgG deposits exhibited a poorer renal outcome compared to patients that were IgG negative (p=0.028). Moreover, Bowman's capsule rupture occurred less frequently in patients with IgM deposition compared with IgM negative counterparts (p=0.028). Vascular lesions and granuloma-like lesions had been seen more frequently in cases with IgA deposition than those without IgA deposition (p=0.03 and 0.015, respectively). Conclusion: In conclusion, patients with immune complex deposits in the kidney showed less platelet count, lower sC3 and sIgG levels, and higher serum creatinine levels. Patients with low sC3 at initial and with continued low sC3 during the treatment displayed a trend toward poorer kidney survival. Moreover, the IC group showed a worse renal outcome than the PI group, further enforcing the present strategy of introducing complement targeted therapies in AAV.