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Abstract Background FGFR genomic aberrations occur in approximately 5–10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. Methods Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. Results Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7–63.6); the median progression-free survival was 5.6 months (95% CI, 3.6–12.7) and median overall survival was 40.2 months (95% CI, 12.4–not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5–57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). Conclusions Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. Trial registration This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.

Abstract Background Peritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear. Methods We conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25. Results A total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment. Conclusions PD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality. Trial registration Registered at ClinicalTrials.gov (NCT01413074).

Exploring the impact of urbanization on carbon emissions is crucial for formulating effective emission reduction policies. Using nighttime light data and attribute data from 68 Chinese cities (2002–2021), this paper develops an urban development evaluation system with the entropy method. The Lasso method is employed to select key factors affecting carbon emissions, and hierarchical regression models are utilized to analyze these factors across different city types. The results show the following: (1) The extraction of built-up areas using integrated nighttime light data yields an overall accuracy ranging from 70.90% to 98.87%, reflecting high precision. (2) Expanding cities have predominated over the past two decades, indicating a continued upward trend in urbanization in China. (3) Urban development is influenced by internal characteristics and geographic location: contracting cities are mainly inland heavy industrial centers, while expanding cities are located in economically advanced coastal regions. Additionally, it is also impacted by the growth of surrounding cities, exemplified by the imbalance between central cities and their peripheries within metropolitan areas. (4) The expansion of built-up areas is a significant factor affecting carbon emissions across all city types. For expanding cities, managing population growth and promoting tertiary sector development are recommended, while contracting cities should focus on judicious economic planning and virescence area protection.

The low availability of phosphorus has become a common problem worldwide. Phosphorus is essential for phenotypic morphology and ginsenoside synthesis. However, the effects of Pi stress on ginseng phenotype and ginsenoside synthesis remain unclear. Phenotypic analyses and transcriptomics revealed the phenotypic construction and regulation of differential genes involved in the physiological metabolism of ginseng under low-Pi stress. Root length and stem length were found to be significantly inhibited by phosphate-deficiency stress in the half-phosphate (HP) and no-phosphate (NP) treatment groups; however, the number of fibrous roots, which are regulated by phytohormones, was found to increase. In ginseng leaves, the indexes of physiological stress, superoxide anion (221.19 nmol/g) and malonaldehyde (MDA) (0.05 μmol/min/g), reached the maximum level. Moreover, chlorophyll fluorescence images and chlorophyll content further confirmed the inhibition of ginseng photosynthesis under low-Pi stress. A total of 579 and 210 differentially expressed genes (DEGs) were shared between NP and total phosphate (TP) and HP and TP, respectively, and only 64 common DEGs were found based on the two comparisons. These DEGs were mainly related to the synthesis of phosphate transporters (PHTs), phytohormones, and ginsenosides. According to KEGG analyses, four DEGs (Pg_s 0368.2, Pg_s3418.1, Pg_s5392.5 and Pg_s3342.1) affected acetyl-CoA production by regulating glycometabolism and tricarboxylic acid cycle (TCA). In addition, related genes, including those encoding 13 PHTs, 15 phytohormones, and 20 ginsenoside synthetases, were screened in ginseng roots under Pi-deficiency stress. These results indicate that changes in the ginseng phenotype and transcriptional regulation of DEGs are involved in the Pi-deficiency stress environment of ginseng, thereby providing new information regarding the development of ginseng for low-Pi tolerance.

Understanding the key roles of nutrient elements in soil–plant systems are essential for herbal medicine production and sustainable development. However, the ecological relationships between soil quality and nutrient elements, yield, saponins, or other active compounds in American ginseng remain unclear. In this study, 20 soil indicators, 10 root nutrient indicators, 9 quality indicators, and yields were investigated. The minimum dataset was constructed by principal component analysis, key factors were screened by correlation analysis and PLS-PM analysis, and the prediction model was constructed using linear fitting and tested by a validation test. The minimum dataset, constructed based on principal component analysis, comprised five indicators: SOM, TP, AK, AMg, and ACa. Correlation analysis, PLS-PM analysis, and linear fitting showed that K and Mg were the key factors relating soil quality to the yield and quality of American ginseng and that when AMg was 0.21 g/kg and AK was 0.30 g/kg, soil organic matter was 27%, total phosphorus was 1.19 g/kg in soil, K content in roots was 15.63 g/kg, Mg content was 1.91 g/kg, and the K/Mg of 8.85 could balance American ginseng yield and quality. In predicting and validating the model, predicting the DW, total ginsenoside, Rb1, Rb2, Rc, and Rd of American ginseng using K/Mg were reliable. This study provides a scientific basis for nutrient regulation, selecting planting sites, assessing soil quality, and predicting and evaluating American ginseng quality.

GATA transcription factors are widespread in plants, exerting crucial functions in multiple processes such as flower development, photoperiod regulation, and light signal transduction. The GATA gene family has a key role in the regulation of medicinal plant adaptation to environmental stress. However, since the publication of the Ginseng (Panax ginseng C.A. Meyer) genome-wide data, there has never been an analysis of the whole GATA gene family. To understand the function of the GATA gene family more broadly, the GATA gene family members in P. ginseng were predicted using an in silico bioinformatics approach. A comprehensive and systematic analysis encompassing chromosome scaffold, expression pattern, gene structure, and phylogeny was conducted. The results showed that a total of 52 GATA gene family members were recognized in P. ginseng, distributed across 51 scaffolds. Each member encoded a diverse number of amino acid residues, extending from 138 to 1064. Moreover, the expression levels of PgGATA genes were significantly altered by nitrogen (N) and phosphorus (P) stresses. The expression levels of PgGATA6, PgGATA11, PgGATA27, PgGATA32, PgGATA37, PgGATA39, PgGATA40, and PgGATA50 exhibited significant elevation under N deficiency, whereas PgGATA15, PgGATA18, PgGATA34, PgGATA38, PgGATA41, and PgGATA44 genes showed substantial upregulation under P deficiency. In addition, PgGATA3, PgGATA4, PgGATA14, PgGATA19, and PgGATA28 were substantially upregulated under both N and P deficiency. This research establishes a theoretical foundation for the thorough examination of the functions of the PgGATA gene family and its regulation by N and P fertilization during P. ginseng cultivation.

Abstract Background Cadmium (Cd) contamination in soil poses a serious safety risk for the development of medicine and food with ginseng as the raw material. Microorganisms are key players in the functioning and service of soil ecosystems, but the effects of Cd-contaminated ginseng growth on these microorganisms is still poorly understood. To study this hypothesis, we evaluated the effects of microorganisms and Cd (0, 0.25, 0.5, 1.0, 2.0, 5.0, and 10.0 mg kg-1 of Cd) exposure on the soil microbial community using Illumina HiSeq high-throughput sequencing. Results Our results indicated that Cd-contaminated soil affected the soil microbial diversity and composition, and bacterial diversity was affected more than fungal diversity in Cd-contaminated soil, especially according to Shannon indices. The abundance of the soil microbial community decreased and the composition changed according to the relative abundances at the phylum level, including those of Saccharibacteria and Gemmatimonadetes in bacteria and Mortierellomycota in fungi. The LEfSe algorithm was used to identify active biomarkers, and 45 differentially abundant bacterial taxonomic clades and 16 differentially abundant fungal taxonomic clades were identified with LDA scores higher than 4.0. Finally, a heatmap of Spearman's rank correlation coefficients and canonical discriminant analysis (CDA) indicated that some key biomarkers, Arenimonas, Xanthomonadales, Nitrosomonadaceae, Methylophilales, Caulobacterales, Aeromicrobium, Chitinophagaceae, Acidimicrobiales, Nocardioidaceae, Propionibacteriales, Frankiales, and Gemmatimonadaceae, were positively correlated with the total and available Cd (p

Calcium (Ca) is necessary for plant growth and stress resistance, which are essential for the successful cultivation of Panax quinquefolium L. (American ginseng). However, information about the physiology of Ca nutrition in this species is limited. Therefore, the objective of this study was to determine the effect of Ca on the growth and physiological performance of American ginseng. Two-year-old American ginseng plants were supplemented with the following Ca concentrations [Ca2+] in a hydroponic system: 0, 160.17, 320.34, 640.68, and 961.02 mg⋅L−1. Measurements included growth biomass accumulation, chlorophyll (Chl) content and fluorescence, photosynthetic parameters, antioxidant enzyme activity, root activity, and malondialdehyde content. Biomass, stem height, leaf area, maximum photochemical efficiency, and superoxide dismutase activity peaked at [Ca2+] of 640.68 mg⋅L−1. Actual photochemical efficiency, minimum saturating irradiance, photosynthetic rate, catalase and peroxidase activities, and root activity reached their maximum at [Ca2+] of 320.34 mg⋅L−1. Stem diameter and regulated thermal energy dissipation increased with [Ca2+]. The sum of nonregulated heat dissipation and fluorescence emission and malondialdehyde content decreased to a minimum at [Ca2+] of 320.34 mg⋅L−1. The Chl content reached a maximum at [Ca2+] of 160.17 mg⋅L−1, but the Chl a/b ratio increased with [Ca2+]; the actual photochemical efficiency and photosynthetic rate reached their maximum level at Chl a/b ratios of 2.04 and [Ca2+] of 320.34 mg⋅L−1. Therefore, the optimal [Ca2+] for American ginseng growth was 320.34 mg⋅L−1. Furthermore, an appropriate increase [Ca2+] in the growth medium may improve biomass accumulation, light energy utilization efficiency, and stress resistance in American ginseng.

Despite the high number of nerve injuries, there is a lack of an effective nerve repair strategy to restore nerve function. As crucial candidates for tissue engineering, electrospun nanofibrous scaffolds mimic native fibrous extracellular matrix and create a suitable micro-environment guiding nerve regeneration. In this review, electrospinning scaffolds fabricated using natural, synthetic, and composite materials have been summarized. Moreover, we have also summarized strategies commonly used to optimize nerve regeneration, including topologies, bioelectricity, surface functionalization with bioactive molecules, and the addition of anti-inflammatory drugs. In addition, this review has discussed the limitations of scaffolds for nerve regeneration and gives an outlook for future research.

Background Immunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge. Methods We did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. Results One hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant. Conclusions The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.

In this work, a low-temperature symmetrical solid oxide fuel cell with Ni-NCAL|SDC/NCAL|Ni-NCAL (70 SDC:30 NCAL) configuration was successfully constructed by a simple dry press method. At 500 and 550 °C, the peak power densities of the cell in ammonia were 501 and 755 mW cm−2, and in hydrogen were 670 and 895 mW cm−2, respectively. EIS data showed that the Rp values of the cell in ammonia and hydrogen at 550 °C were 0.250 and 0.246 Ω cm−2, respectively, indicating the excellent catalytic activity of the Ni-NCAL electrode toward ammonia decomposition and hydrogen oxidation. The different cell output can be ascribed to additional ammonia decomposition steps compared to hydrogen. The noticeable reaction product on the surface of the Ni foam was detrimental to ammonia decomposition. In summary, a symmetrical cell with SDC/NCAL semiconductor electrolyte and Ni-NCAL electrodes exhibited higher electrochemical performance at low temperature than the results reported to date. Therefore, higher electrochemical performance can be expected from this cell configuration with more efficient ammonia decomposition catalysts.

Abstract Cancer immunotherapy has achieved promising clinical progress over the recent years for its potential to treat metastatic tumors and inhibit their recurrences effectively. However, low patient response rates and dose‐limiting toxicity remain as major dilemmas for immunotherapy. Stimuli‐responsive nanoparticles (srNPs) combined with immunotherapy offer the possibility to amplify anti‐tumor immune responses, where the weak acidity, high concentration of glutathione, overexpressions of enzymes, and reactive oxygen species, and external stimuli in tumors act as triggers for controlled drug release. This review highlights the design of srNPs based on tumor microenvironment and/or external stimuli to combine with different anti‐tumor drugs, especially the immunoregulatory agents, which eventually realize synergistic immunotherapy of malignant primary or metastatic tumors and acquire a long‐term immune memory to prevent tumor recurrence. The authors hope that this review can provide theoretical guidance for the construction and clinical transformation of smart srNPs for controlled drug delivery in synergistic cancer immunotherapy.

Brucellosis is a chronic infectious disease caused by brucellae or other bacteria directly invading human body. Brucellosis presents the aggregation characteristics and periodic law of infectious diseases in temporal and spatial distribution. Taking major European countries as an example, this study established the temporal and spatial distribution sequence of brucellosis, analyzed the temporal and spatial distribution characteristics of brucellosis, and quantitatively predicted its epidemic law by using different traditional or machine learning models. This paper indicates that the epidemic of brucellosis in major European countries has statistical periodic characteristics, and in the same cycle, brucellosis has the characteristics of piecewise trend. Through the comparison of the prediction results of the three models, it is found that the prediction effect of long short-term memory and convolutional long short-term memory models is better than autoregressive integrated moving average model. The first mock exam using Conv layer and data vectorizations predicted that the convolutional long short-term memory model outperformed the traditional long short-term memory model. Compared with the monthly scale, the prediction of the trend stage of brucellosis can achieve better results under the single model prediction. These findings will help understand the development trend and liquidity characteristics of brucellosis, provide corresponding scientific basis and decision support for potential risk assessment and brucellosis epidemic prevention and control, and reduce the loss of life and property.

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) was traditionally defined as an increase in serum creatinine (sCr) after cardiac surgery. Recently, serum cystatin C (sCyC) has been proposed to be a better biomarker in the prediction of AKI. The clinical utility and performance of combining sCyC and sCr in patients with AKI, particularly for the prediction of long-term outcomes, remain unknown. Methods: We measured sCyC together with sCr in 628 patients undergoing cardiac surgery. sCyC and sCr were assessed at baseline and 24 and 48 h after surgery. CSA-AKI determined by sCr (CSA-AKIsCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events (MAEs; including death of any cause and dialysis) at 3 years were assessed. Results: CSA-AKIsCr developed in 178 patients (28.3%). Three-year follow-up was available for 621 patients; MAEs occurred in 42 patients (6.8%). An increase in sCyC concentration ≥30% within 48 h after surgery was detected in 228 patients (36.3%). This was the best sCyC cutoff for CSA-AKIsCr detection (negative predictive value = 88.8%, positive predictive value = 58.3%). To evaluate the use of both sCyC and sCr as CSA-AKI diagnostic criteria, we stratified patients into 3 groups: non-CSA-AKI, CSA-AKI detected by a single marker, and CSA-AKI detected by both markers. By multivariable logistic regression analysis, the independent predictors of MAEs at 3 years were group 2 (non-CSA-AKI group as the reference, CSA-AKI detected by a single marker: odds ratio [OR] = 3.48, 95% confidence interval [CI]: 1.27–9.58, p = 0.016), group 3 (CSA-AKI detected by both markers: OR = 5.12, 95% CI: 2.01–13.09; p = 0.001), and baseline glomerular filtration rate (OR = 2.24; 95% CI: 1.27–3.95; p = 0.005). Conclusion: Combining sCyC and sCr to diagnose CSA-AKI would be beneficial for risk stratification and prognosis in patients after cardiac surgery.

Abstract Background Globally, there is increased clinical interest and uptake of hemodiafiltration (HDF) for increased removal of uremic toxins. To date, there has been no epidemiological analysis of HDF in China. We present HDF practice patterns and associated mortality risk in Shanghai. Methods This is an observational, prospectively collected, retrospective analysis of 9351 Chinese patients initiating hemodialysis in Shanghai from 2007 to 2014. The primary exposure was hemodialysis sub-modality at inception, classified into hemodiafiltration (HDF) and hemodialysis (HD), with adjustment for concommitant hemoperfusion. The primary outcome was patient mortality. We used Cox proportional hazards regression and Fine and Gray’s proportional subhazards regression, with multiple imputation of missing co-variates by the chained equation method, adjusting for demographic and clinical variables. Results Overall, patients in the cohort were younger, with a more males, and with a lower body mass index when compared to corresponding non-Asian cohorts. Mortality rate was low although it doubled over the period of observation. HDF utilization increased from 7% of patients in 2007 to 42% of patients in 2014. The majority of patients received HDF once a week. The adjusted hazard ratio of death (95% confidence intervals) for HDF versus HD was 0.85 (0.71–1.03), and corresponding sub-hazard ratio 0.86 (0.71–1.03). There was strong effect modification by age. In those aged 40–60 years, the hazard ratio (95% confidence intervals) was 0.65 (0.45–0.94), and sub-hazard ratio also 0.65 (0.45–0.95). Conclusions Our study has certain limitations resulting from the limited number of co-variates available for modelling, missing data for some co-variates, and the lack of verification of data against source documentation. Notwithstanding, there is evidence of clinical benefit from HDF in China, and potential to improve patient outcomes through the greater removal of middle and larger uremic solutes.

Abstract Background To examine serum angiopoietin-2 (Angpt-2) in relation to malnutrition, inflammation, atherosclerosis and cardiac valvular calcification, so-called MIAC syndrome and its predictive role in outcomes of peritoneal dialysis (PD) patients. Methods A prospective observational study was conducted in 324 chronic PD patients. Biochemical analysis was performed at baseline for serum angiopoietins, albumin and high sensitive C-reactive protein (hs-CRP) and echocardiography was done to detect cardiac valvular calcification. Primary study end points were fatal or nonfatal cardiovascular events and mortality. Results The median of serum Angpt-2 levels was 5.44 ng/mL (interquartile range, 3.41–7.85). Across the three tertiles of serum Angpt-2, a significant trend effect was observed for body mass index, normalized protein catabolic rate, calcium × phosphorus product, hs-CRP, brain natriuretic peptide, lower-density lipoprotein cholesterol, left ventricular ejection fraction, total weekly urea clearance and residual renal function (all p

Introduction: In China, a quarter of patients are undergoing 2-times weekly hemodialysis. Using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we tested the hypothesis that whereas survival and hospitalizations would be similar in the presence of residual kidney function (RKF), patients without RKF would fare worse on 2-times weekly hemodialysis. Methods: In our cohort derived from 15 units randomly selected from each of 3 major cities (total N = 45), we generated a propensity score for the probability of dialysis frequency assignment, estimated a survival function by propensity score quintiles, and averaged stratum-specific survival functions to generate mean survival time. We used the proportional rates model to assess hospitalizations. We stratified all analyses by RKF, as reported by patients (urine output

Abstract Background Both peritoneal small solute transport and peritoneal protein clearance are closely linked to outcomes in peritoneal dialysis (PD) patients. However, the associated factors of these two components are not fully understood so far. This study aimed to investigate the association between a panel of systemic and peritoneal inflammatory and angiogenic factors and peritoneal solute transport properties. Methods Stable PD patients in PD center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled in present study. Serum and overnight effluent markers including angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), sTie-2, VEGF, IL-6 and IL-10 were determined. Mass transfer area coefficient of creatinine (MTACcr) and peritoneal protein clearance (Prcl) were calculated. Multivariable linear regression was used to examine the association between these markers and MTACcr as well as Prcl. Results A total of 320 patients were enrolled in present study, which consisted of 166 (51.9%) males with a mean age of 56.8 ± 14.2 years and a median PD duration of 32.5 (9.0–56.3) months. Multiple regression analyses showed that BSA, history glucose exposure, dialysate IL-6 AR and dialysate Ang-1 AR were independent associated factors of MTACcr, while BSA and serum Ang-1 were independent associated factors of Prcl. Conclusions MTACcr representing peritoneal small-solute transport and Prcl representing peritoneal large molecular transport are associated with slightly different panels of inflammatory and angiogenic factors.

Objective(s):The aim of the study was to investigate the relationship between insulin resistance (IR) and leptin (LEP) gene polymorphisms in peritoneal dialysis (PD) patients. Materials and Methods: From July 1, 2011 to August 1, 2011, patients who received chronic PD were chosen and divided into three groups (DM, high HOMR-IR, and low HOMR-IR). Two PCR products of LEP were sequenced and aligned and the distribution of polymorphisms was analyzed using χ2 analysis. In addition, serum leptin level, PD conditions, and biochemical parameters according to different genotype of G-2548A and A19G were statistically analyzed (P-value

Background/Aims: Autophagy is a dynamic catabolic process that maintains cellular homeostasis. Whether it plays a role in promoting cell survival or cell death in the process of renal ischemia/reperfusion (I/R) remains controversial, partly because renal autophagy is usually examined at a certain time point. Therefore, monitoring of the whole time course of autophagy and apoptosis may help better understand the role of autophagy in renal I/R. Methods: Autophagy and apoptosis were detected after mice were subjected to bilateral renal ischemia followed by 0-h to 7-day reperfusion, exposure of TCMK-1 cells to 24-h hypoxia, and 2 to 24-h reoxygenation. The effect of autophagy on apoptosis was assessed in the presence of autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin. Results: Earlier than apoptosis, autophagy increased from 2-h reperfusion, reached the maximum at day 2, and then began declining from day 3 when renal damage had nearly recovered to normal. Exposure to 24-h hypoxia induced autophagy markedly, but it decreased drastically after 4 and 8-h reoxygenation, which was accompanied with increased cell apoptosis. Inhibition of autophagy with 3-MA increased the apoptosis of renal tubular cells during I/R in vivo and hypoxia/reoxygenation (H/R) in vitro. In contrast, activation of autophagy by rapamycin significantly alleviated renal tissue damage and tubular cell apoptosis in the two models. Conclusion: Autophagy was induced in a time-dependent manner and occurred earlier than the onset of cell apoptosis as an early response that played a renoprotective role during renal I/R and cell H/R. Up-regulation of autophagy may prove to be a potential strategy for the treatment of acute kidney injury.

To investigate the long-term outcomes of peritoneal dialysis (PD) patients with diabetes as primary renal disease and patients with diabetes as a comorbid condition.All diabetic patients who commenced PD between January 1, 1995 and June 30, 2012 at Ren Ji Hospital, China were included. Patients were divided into diabetic nephropathy group (DN group) and non-diabetic nephropathy group (NDN group) according to their diagnosis of primary renal disease at the initiation of PD. They were followed until death, cessation of PD, transferred to other centers or to the end of study (June 30, 2013). Outcomes were analyzed by Kaplan-Meier method and Cox regression models.A total of 163 diabetic patients were enrolled in the study, including 121 (74.2%) in DN group and 42 (25.8%) in NDN group. The 1-, 2-, 3- and 5-year patient survival rates were 89%, 78%, 66% and 51% for DN group, and 85%, 63%, 53% and 25% for NDN group, respectively. Kaplan-Meier analysis showed that patients in NDN group had a worse patient survival compared with DN group (log rank 4.830, P=0.028). Patients in NDN group had a marginally shorter peritonitis-free period (log rank 3.297, P=0.069), however, there was no significant difference in technique survival (log rank 0.040, P=0.841). Multivariate Cox regression analysis showed that older age (HR 1.047, 95% CI 1.022-1.073, p

Background. IgA nephropathy (IgAN) was thought to be benign but recently found it slowly progresses and leads to ESRD eventually. The aim of this research is to investigate the value of serum IL-18 level, a sensitive biomarker for proximal tubule injury, for assessing the histopathological severity and disease progression in IgAN. Methods. Serum IL-18 levels in 76 IgAN patients and 36 healthy blood donors were measured by ELISA. We evaluated percentage of global and segmental sclerosis (GSS) and extent of tubulointerstitial damage (TID). The correlations between serum IL-18 levels with clinical, histopathological features and renal prognosis were evaluated. Results. The patients were 38.85±10.95 years old, presented with 2.61 (1.43∼4.08) g/day proteinuria. Serum IL-18 levels were significantly elevated in IgAN patients. Baseline serum IL-18 levels were significantly correlated with urinary protein excretion (r=0.494, P=0.002), Scr (r=0.61, P

Objective. We investigate whether low-protein diet would show benefits in suppressing peritoneal transport rate in peritoneal dialysis (PD) patients. Methods. This is a supplemented analysis of our previously published trial, which randomized 60 PD patients to receive low- (LP: dietary protein intake of 0.6–0.8 g/kg/d), keto-acid-supplemented low- (sLP: 0.6–0.8 g/kg/d with 0.12 g/kg/d of keto acids), or high- (HP: 1.0–1.2 g/kg/d) protein diet and lasted for one year. In this study, the variations of peritoneal transport rate were assessed. Results. While baseline D/Pcr (dialysate-to-plasma concentration ratio for creatinine at 4 hour) and D/D0glu (dialysate glucose at 4 hour to baseline dialysate glucose concentration ratio) were similar, D/Pcr in group sLP was lower, and D/D0glu was higher than those in the other two groups (P

Objective The aim of this study was to investigate the correlation between non-dipper circadian rhythm of blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). Methods and results All 257 patients with stage 1 to 5 CKD were enrolled in the study and classified into a CKD1-3 group and a CKD4-5 group according to renal function. The parameters and circadian rhythm of BP were measured by a GE Marquette Tonoport V Eng dynamic sphygmomanometer, and cardiac structure was examined by echocardiography. The incidence of abnormal circadian BP rhythm (non-dipper rhythm) was quite high (75.4% in all enrolled patients and 71.3% in the patients with normal BP levels) in CKD patients and increased with the deterioration of renal function. Changes of cardiac structure such as LVH in patients with non-dipper BP were more distinct than in patients with dipper BP. The development of left ventricular mass index (LVMI) correlated positively with the incidence of non-dipper BP rhythm. Multiple regression analysis showed that 24-h systolic BP (β = 0.417, P < 0.01), triglycerides (TG) (β = --0.132, P = 0.007), Hb (β = --0.394, P = 0.016) and gender (β = 0.158, P = 0.039) were independent risk factors of LVMI. Conclusions The incidence of non-dipper circadian rhythm of blood pressure was quite high in CKD patients and increased with the deterioration of renal function. Non-dipper circadian rhythm of BP is closely related with LVMI. [ABSTRACT FROM AUTHOR]

Background: Studies in recent years have shown that undercarboxylated osteocalcin (uOC) not only maintains bone mineralization, but is also involved in the regulation of atherosclerosis. However, a correlation between uOC and carotid atherosclerosis in non-dialysis patients with chronic kidney disease (CKD) has not been investigated. A total of 240 non-dialysis patients with CKD were included in the study. For these patients, the median estimated glomerular filtration rate (eGFR) was 20.05 (12.43-49.32) ml/min/1.73m². Serum uOC levels were measured using enzyme-linked immunosorbent assay (ELISA). Carotid ultrasonography was performed to assess carotid atherosclerotic plaques and intima-media thickness (IMT) in an attempt to analyze the relationship between uOC level and carotid atherosclerosis. Results: The uOC levels of non-dialysis patients with CKD were significantly lower than those of healthy controls [28.16 (21.40-45.85) ng/mL vs. 36.42 (28.05-49.28) ng/mL, P < 0.01]. The uOC levels gradually decreased as CKD progressed (P < 0.01). The uOC levels were significantly lower in patients with carotid plaques than in patients without carotid plaques [25.98 (20.14-31.35) ng/mL vs. 31.02 (25.86-36.40) ng/mL, P < 0.01]. uOC level showed significant negative correlation with IMT (r = -0.33, P < 0.01). Logistic regression analysis revealed that after adjustment for various confounding factors, decreased uOC levels were shown to indicate increased possibility of carotid atherosclerotic plaque development in non-dialysis patients with CKD (on every 1 SD decrease in the uOC level, odds ratio 1.70, 95 % confidence interval 1.24-2.98, P < 0.01). Multivariate stepwise regression analysis demonstrated that decreased uOC level (β = -0.163, P < 0.05) was an independent risk factor for increased carotid IMT in non-dialysis patients with CKD. Conclusion: Serum uOC levels in non-dialysis patients with CKD are significantly lower than those in healthy individuals, and uOC is closely associated with subclinical atherosclerosis in CKD patients. [ABSTRACT FROM AUTHOR]

Background. FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD). Methods. In the NDD study, 91 participants were randomized to low (1.1-1.75 mg/kg) or high (1.50-2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1-1.8 mg/kg), medium (1.5-2.3 mg/kg) and high (1.7-2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed. Results. In the NDD study, hemoglobin (Hb) increase 1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P < 0.0001, both). In the DD study, 59.1%, 88.9% (P = 0.008) and 100% (P = 0.0003) of the low-, medium- and high-dose subjects maintained their Hb levels after 5- and 6-weeks versus 50% of the epoetin alfa-treated subjects. Conclusions. FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program. [ABSTRACT FROM AUTHOR]

Background. Maintenance dialysis therapy is the only way to remove excess fluid in patients with anuric end-stage renal disease. The optimal ultrafiltration (UF) volume in patients on peritoneal dialysis (PD) remains controversial. [ABSTRACT FROM PUBLISHER]

Background/Aims: Acute kidney injury (AKI) is common following cardiac surgery and predicts a poor outcome. However, the early detection of AKI has proved elusive and most cases are diagnosed only following a significant rise in serum creatinine (SCr). We compared a panel of early biomarkers of AKI for the detection of AKI in patients undergoing heart surgery. This study included serum cystatin C (CyC) and urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), retinol-binding protein (RBP) and N-acetyl-β-D-glucosaminidase (NAG). Methods: We retrospectively identified 15 patients undergoing open cardiac surgery who developed AKI within 72 h postoperatively. For these, we identified 15 matched controls also having undergone surgery but without AKI. Serial serum and urine samples had prospectively been postoperatively obtained from all patients at 0, 2, 4, 6, 10, 24, 48 and 72 h after admission to the intensive care unit. AKI was defined as a >50% increase in SCr. CyC was measured by nephelometry, while NGAL, IL-18, and RBP were measured by ELISA and NAG was measured by spectrophotometry. The urinary biomarkers were normalized to urinary creatinine (UCr) concentration. Each marker was assessed at each time point for its predictive value using receiver operating characteristic curves to predict AKI. Results: Following the exclusion of 1 case due to a urinary tract infection, the final cohort consisted of 29 patients aged 62.9 ± 13.7 years with baseline SCr of 73.2 ± 11.9 μmol/l. While there were no differences in the demographics between cases and controls, the aortic clamp time was predictably higher in AKI cases than in controls (60.6 ± 13.9 vs. 43.0 ± 9.2 min, p < 0.05). Each biomarker differed significantly between cases and controls for at least one time point. The optimal area under the curve (AUC) was for CyC at 10 h (sensitivity 0.71, specificity 0.92, cutoff 1.31 mg/l), NGAL at 0 h (sensitivity 0.84, specificity 0.80, cutoff 49.15 μg/g UCr), IL-18 at 2 h (sensitivity 0.85, specificity 0.73, cutoff 285.65 ng/g UCr), RBP at 0 h (sensitivity 0.75, specificity 0.67, cutoff 2,934.65 μg/g UCr) and NAG at 4 h (sensitivity 0.86, specificity 0.67, cutoff 37.05 U/mg UCr). Using a combination of all 5 biomarkers analyzed at the optimal time point as above, we were able to obtain an AUC of 0.98 (0.93–1.02, p < 0.001) in this limited sample. Conclusion: The use of serum and urinary biomarkers for the prediction of AKI in patients undergoing cardiac surgery is highly dependent on the sampling time. Of the evaluated markers urinary NGAL had the best predictive profile. The previously unstudied marker of urinary RBP showed similar predictive power as more established markers. By combining all 5 studied biomarkers we were able to predict significantly more cases, suggesting that the use of more than one marker may be beneficial clinically. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Glucose-based peritoneal dialysis (PD) is the original PD form. However, glucose uptake from the peritoneal cavity may contribute to dysmetabolism. Methods: We retrospectively assessed metabolic syndrome (MS) and its components in 195 non-diabetic incident PD patients at baseline and after 34.3 (20.5–60.0) months of PD. MS was defined according to the Adult Treatment Panel III criteria. Results: While 22.1 of the patients met MS criteria at baseline, 69.2 (p < 0.01) exhibited MS during PD. MS burden increased significantly after PD (p < 0.01). The disorder BMI and lipids, and MS components number, correlated with peritoneal glucose exposure and PD duration (p < 0.05). In Cox analysis, age, BMI, triglyceride, C-reactive protein (CRP) and glucose exposure were all independently associated with MS development. Conclusions: PD commencement in end-stage renal disease patients was associated with an increased MS prevalence. High glucose exposure and long PD duration were associated with MS existence, along with old age, high BMI, triglyceride and CRP. [ABSTRACT FROM AUTHOR]

Introduction: The value of biomarkers at the time of nephrology consultation in predicting the prognosis of acute kidney injury (AKI) in hospitalized patients has not been well described. This study aimed to evaluate the possibility of biomarkers at the time of nephrology consultation in predicting the prognosis of AKI. Methods: We prospectively enrolled 103 hospitalized patients who developed AKI. Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL), IL-6, IL-18, N-Acetyl-β-D-Glucosaminidase (NAG), and serum Cystatin C (CysC) were measured at the time of nephrology consultation. Baseline values of serum creatinine (bScr), serum creatinine on consultation (cScr) and the peak level of serum creatinine (pScr) were recorded. All the patients were followed-up till 28 days since consultation. Serum and urinary levels of the biomarkers were compared according to the patient or kidney prognosis. Each marker was assessed for its predictive value using receiver operator characteristic (ROC) curves to predict AKI prognosis. Results: Patients were aged 54.28 ± 19.05. Male patients constituted 65% of the study group and baseline Scr was 93.54 ± 35.98 μmol/l. The mortality rate of the patients was 25.2% and kidney loss rate was 18.8% at 28 days after consultation. The level of urinary NGAL was significantly higher in death patients than that in survival patients [147.00 (31.59, 221.87) μg/ml vs. 22.43 (6.48, 89.77) μg/ml, p = 0.001], while the level of bScr, cScr, pScr, urinary IL-6 and NAG were similar in both these groups. The AUC of urinary NGAL for predicting patients' death was 0.723 (p = 0.001). Serum CysC and urinary IL-18 concentration was higher in the death patients with a marginal p value (p = 0.065 and 0.059 respectively). All the urinary markers, including NAG, NGAL, IL-6 and IL-18 were significantly higher in patients with kidney loss than in those with kidney survival, while no difference was found in Scr and serum CysC levels. The AUCs of these urinary biomarkers for predicting kidney survival were 0.663, 0.655, 0.705 and 0.663 respectively (p < 0.05). The concentrations of cScr, pScr, serum CysC, urinary IL-6 and NGAL were significantly higher in RRT patients (p < 0.05). The AUCs for predicting RRT were 0.628, 0.781, 0.768, 0.672 and 0.775 respectively. Conclusions: The level of biomarkers at the time of nephrology consultation might predict the prognosis of AKI in hospitalized patients. Further studies should be done to understand the role of the serum and urinary markers in the prognosis of AKI. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: To evaluate differences in the health-related quality of life (HRQoL) between patients with constipation receiving hemodialysis (HD) and those receiving peritoneal dialysis (PD). Methods: In this cross-sectional study, 605 dialysis patients (478 HD cases and 127 PD cases; all patients were older than 18 years) from our hospital were included. A questionnaire was used to evaluate their constipation statuses. The effect of constipation on HRQoL was assessed, using the Chinese version of the 12-item short-form (SF-12) general health survey. Karnofsky score, sociodemographic, and clinical data were also collected. We performed multiple logistic regression analysis to define independent risk factors for constipation and impaired HRQoL. Results: A total of 605 participants (326 men [53.9%] and 279 women [46.1%]) were surveyed. The incidence of constipation was 71.7% in HD patients and 14.2% in PD patients. Dialysis patients with constipation had significantly lower mean SF-12 Physical Component Summary scale and Mental Component Summary scale scores than the nonconstipation group (P < 0.05), whereas HD patients had better SF-12 Physical Component Summary and Mental Component Summary scores than PD patients (P < 0.05). When we performed multivariate logistic regression analysis, dialysis modality, diabetes, and the number of constipation-related medications were three independent risk factors associated with constipation. As for impaired HRQoL in the constipated dialysis population, dialysis modality was found to be another independent risk factor in addition to age and diabetes. Conclusion: PD patients with constipation had worse HRQoL than HD control participants. We should pay more attention to the patients with constipation receiving PD, as peritonitis caused by constipation was associated with a higher mortality. [ABSTRACT FROM AUTHOR]

Background. IgA nephropathy (IgAN) was thought to be benign but recently found it slowly progresses and leads to ESRD eventually. The aim of this research is to investigate the value of serum IL-18 level, a sensitive biomarker for proximal tubule injury, for assessing the histopathological severity and disease progression in IgAN. Methods. Serum IL-18 levels in 76 IgAN patients and 36 healthy blood donors were measured by ELISA. We evaluated percentage of global and segmental sclerosis (GSS) and extent of tubulointerstitial damage (TID). The correlations between serum IL-18 levels with clinical, histopathological features and renal prognosis were evaluated. Results. The patients were 38.85 ± 10.95 years old, presented with 2.61 (1.43∼4.08) g/day proteinuria. Serum IL-18 levels were significantly elevated in IgAN patients. Baseline serum IL-18 levels were significantly correlated with urinary protein excretion (r = 0.494, P = 0.002), Scr (r = 0.61, P < 0.001), and eGFR (r = -0.598, P < 0.001). TID scores showed a borderline significance with serum IL-18 levels (r = 0.355, P = 0.05). During follow-up, 26 patients (34.21%) had a declined renal function. Kaplan-Meier analysis found those patients with elevated IL-18 had a significant poor renal outcome (P = 0.03), and Cox analysis further confirmed that serum IL-18 levels were an independent predictor of renal prognosis (β = 1.98, P = 0.003). [ABSTRACT FROM AUTHOR]

While the best treatment of nephrosis-inducing idiopathic membranous nephropathy (IMN) is controversial, some trials have suggested positive outcomes following treatment with oral cyclophosphamide used in combination with steroids. However, data on i.v. cyclophosphamide plus steroids in treatment of nephrotic IMN are few. The charts of every patient diagnosed with membranous nephropathy in the Renal Division of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, from January 2003 to December 2009 ( n = 189) were retrospectively analyzed. Patients with nephrotic IMN ( n = 32) were treated with monthly i.v. cyclophosphamide (500-750 mg/m) and oral prednisone for at least 6 months. Efficacy as well as safety and tolerability of this regimen were evaluated. Thirty-two patients with nephrotic IMN (56% male, age 51.5 ± 12.6 years, estimated glomerular filtration rate 73.7 ± 20.0 mL/min per 1.73 m) were included in our study. During the median follow-up duration of 30.0 (12.5-42.8) months, 40.6% of patients achieved complete remission, while 40.6% achieved partial remission. Relapse occurred in five patients in a median of 16 (11.5-26) months after cessation of immunosuppressive treatment. No patients developed renal insufficiency during the follow up, while 16 side-effects were noted in 10 patients. Complete remission rates at 3, 6 and 15 months were 0%, 12.5% and 40.6% and remission rates were 21.9%, 68.8% and 81.2%, respectively. Complement 3 deposition was significantly associated with the probability of non-remission. Monthly i.v. pulse cyclophosphamide plus oral steroids may be an alternative treatment option in Chinese patients with nephrotic IMN. This is a retrospective analysis of the efficacy of monthly i.v. pulse cyclophosphamide plus oral steroids for at least 6 months on the outcome (remission rate) of nephrotic idiopathic membranous nephropathy subjects. This regimen was effective and well tolerated. [ABSTRACT FROM AUTHOR]

Objective. To determine the prevalence of left ventricular hypertrophy (LVH) and its associated risk factors in lupus nephritis (LN) patients. Methods. 287 LN patients (age: 38.54 ± 13.31, 262 female) were recruited. Echocardiography and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Their relationship was evaluated by univariate correlation analysis and multivariate regression analysis. Results. The prevalence of LVH in this cohort was 21.25% (n = 61). Serum hs-CRP level was significantly elevated in patients with LVH compared to those without (8.03 (3.22-30.95) versus 3.93 (1.48-9.48) mg/L,P < .01), and correlated with left ventricular mass index (LVMI) (r = 0.314, P = .001).Multivariate regression analysis further confirmed that hs-CRP was an independent risk factor (β = 0.338, P = .002) for LVH in patients with LN. Conclusions. Our findings demonstrated that serum hs-CRP level is independently correlated with LVMI and suggested that measurement of hs-CRP may provide important clinical information to investigate LVH in LN patients. [ABSTRACT FROM AUTHOR]

Introduction: As economic development continues in China, it is important to evaluate recent changes in dialysis status. However, China lacks a national dialysis registry. This elevates the need to use local registry systems like the Shanghai Dialysis Registry to gain an overview of dialysis status in developed cities in China. Methods: Data were collected from the Shanghai Dialysis Registry from the beginning of 2000 to the end of 2005. All dialysis centers (n = 58) in Shanghai are included in the registry system. Results: Point prevalence of dialysis on December 31, 2005, was 5496, compared with 4842 in 2000. In 2005, 3746 patients began dialysis, yielding a treatment rate of 275.4 patients per million population. The percentage of peritoneal dialysis patients was 18% in 2005, compared with 14% in 2000. The main cause for end-stage renal disease was chronic glomerulonephritis. However, the incidence of diabetic nephropathy increased from 9.9% in 2000 to 17.2% in 2005 and counts as the second major cause of end-stage renal disease. The death rate of patients on dialysis decreased from 9.2% in 2000 to 7.5% in 2005. Cerebrovascular disease was still the leading cause of death and decreased significantly from 2.4% in 2000 to 1.5% in 2005. Dialysis adequacy, hepatitis infection control, and anemia treatment improved. Conclusions: The Shanghai dialysis population grew continuously during the period covered by this study (2000 to 2005). Clinical outcomes improved because of prompt treatment for co-morbidities. [ABSTRACT FROM AUTHOR]

Background. Upregulation of local monocyte chemoattractant protein-1 (MCP-1) production is involved in glomerular damage through macrophage recruitment and activation in diabetic nephropathy. Treatment of db/db mice with soluble receptor for advanced glycation end-products (RAGE) prevented recruitment of macrophages to the glomeruli and reduced albuminuria, suggesting that binding of ligands and RAGE may be involved in MCP-1 expression. Therefore, we investigated the role of advanced glycation end-products (AGEs) in MCP-1 production by podocytes and signalling events after RAGE activation.Methods. MCP-1 gene and protein expression were examined by using reverse transcription–polymerase chain reaction and enzyme-linked immunosorbent assay in differentiated mouse podocytes. Dichlorofluorescein-sensitive intracellular reactive oxygen species (ROS) generation was measured by confocal microscopy. RAGE, phosphorylation of mitogen-activated protein kinases, nuclear factor (NF)-κB, c-Jun and Sp1 were studied using western blotting and immunocytochemistry.Results. Both differentiated and undifferentiated podocytes expressed RAGE. MCP-1 was induced by AGEs and carboxymethyllysine (CML) in a time-dependent and dose-dependent manner in differentiated podocytes. Neutralizing antibody for RAGE suppressed AGE- and CML-induced MCP-1 production. AGEs and CML rapidly generated intracellular ROS in podocytes. Blocking of ROS by using N-acetyl-l-cysteine abolished CML and H2O2-induced MCP-1 expression. Phosphorylated extracellular signal-regulated kinase (ERK) was found in podocytes incubated with CML and was prevented by N-acetyl-l-cysteine or 7′-amino 4 [trifluoromethyl]. PD98059, an inhibitor of ERK, partially prevented CML-induced MCP-1 gene expression. NF-κB and Sp1 were translocated into the nucleus after podocytes were incubated with CML for 60 min. Parthenolide and mithramycin A, inhibitors of NF-κB and Sp1, respectively, abolished CML-induced MCP-1 gene expression in a dose-dependent manner.Conclusions. These results suggest that AGEs and CML induce MCP-1 expression in podocytes through activation of RAGE and generation of intracellular ROS. NF-κB and Sp1 regulate MCP-1 gene transcription. [ABSTRACT FROM AUTHOR]

Exploring the impact of urbanization on carbon emissions is crucial for formulating effective emission reduction policies. Using nighttime light data and attribute data from 68 Chinese cities (2002–2021), this paper develops an urban development evaluation system with the entropy method. The Lasso method is employed to select key factors affecting carbon emissions, and hierarchical regression models are utilized to analyze these factors across different city types. The results show the following: (1) The extraction of built-up areas using integrated nighttime light data yields an overall accuracy ranging from 70.90% to 98.87%, reflecting high precision. (2) Expanding cities have predominated over the past two decades, indicating a continued upward trend in urbanization in China. (3) Urban development is influenced by internal characteristics and geographic location: contracting cities are mainly inland heavy industrial centers, while expanding cities are located in economically advanced coastal regions. Additionally, it is also impacted by the growth of surrounding cities, exemplified by the imbalance between central cities and their peripheries within metropolitan areas. (4) The expansion of built-up areas is a significant factor affecting carbon emissions across all city types. For expanding cities, managing population growth and promoting tertiary sector development are recommended, while contracting cities should focus on judicious economic planning and virescence area protection. [ABSTRACT FROM AUTHOR]

The low availability of phosphorus has become a common problem worldwide. Phosphorus is essential for phenotypic morphology and ginsenoside synthesis. However, the effects of Pi stress on ginseng phenotype and ginsenoside synthesis remain unclear. Phenotypic analyses and transcriptomics revealed the phenotypic construction and regulation of differential genes involved in the physiological metabolism of ginseng under low-Pi stress. Root length and stem length were found to be significantly inhibited by phosphate-deficiency stress in the half-phosphate (HP) and no-phosphate (NP) treatment groups; however, the number of fibrous roots, which are regulated by phytohormones, was found to increase. In ginseng leaves, the indexes of physiological stress, superoxide anion (221.19 nmol/g) and malonaldehyde (MDA) (0.05 μmol/min/g), reached the maximum level. Moreover, chlorophyll fluorescence images and chlorophyll content further confirmed the inhibition of ginseng photosynthesis under low-Pi stress. A total of 579 and 210 differentially expressed genes (DEGs) were shared between NP and total phosphate (TP) and HP and TP, respectively, and only 64 common DEGs were found based on the two comparisons. These DEGs were mainly related to the synthesis of phosphate transporters (PHTs), phytohormones, and ginsenosides. According to KEGG analyses, four DEGs (Pg_s 0368.2, Pg_s3418.1, Pg_s5392.5 and Pg_s3342.1) affected acetyl-CoA production by regulating glycometabolism and tricarboxylic acid cycle (TCA). In addition, related genes, including those encoding 13 PHTs, 15 phytohormones, and 20 ginsenoside synthetases, were screened in ginseng roots under Pi-deficiency stress. These results indicate that changes in the ginseng phenotype and transcriptional regulation of DEGs are involved in the Pi-deficiency stress environment of ginseng, thereby providing new information regarding the development of ginseng for low-Pi tolerance. [ABSTRACT FROM AUTHOR]

Understanding the key roles of nutrient elements in soil–plant systems are essential for herbal medicine production and sustainable development. However, the ecological relationships between soil quality and nutrient elements, yield, saponins, or other active compounds in American ginseng remain unclear. In this study, 20 soil indicators, 10 root nutrient indicators, 9 quality indicators, and yields were investigated. The minimum dataset was constructed by principal component analysis, key factors were screened by correlation analysis and PLS-PM analysis, and the prediction model was constructed using linear fitting and tested by a validation test. The minimum dataset, constructed based on principal component analysis, comprised five indicators: SOM, TP, AK, AMg, and ACa. Correlation analysis, PLS-PM analysis, and linear fitting showed that K and Mg were the key factors relating soil quality to the yield and quality of American ginseng and that when AMg was 0.21 g/kg and AK was 0.30 g/kg, soil organic matter was 27%, total phosphorus was 1.19 g/kg in soil, K content in roots was 15.63 g/kg, Mg content was 1.91 g/kg, and the K/Mg of 8.85 could balance American ginseng yield and quality. In predicting and validating the model, predicting the DW, total ginsenoside, Rb1, Rb2, Rc, and Rd of American ginseng using K/Mg were reliable. This study provides a scientific basis for nutrient regulation, selecting planting sites, assessing soil quality, and predicting and evaluating American ginseng quality. [ABSTRACT FROM AUTHOR]

GATA transcription factors are widespread in plants, exerting crucial functions in multiple processes such as flower development, photoperiod regulation, and light signal transduction. The GATA gene family has a key role in the regulation of medicinal plant adaptation to environmental stress. However, since the publication of the Ginseng (Panax ginseng C.A. Meyer) genome-wide data, there has never been an analysis of the whole GATA gene family. To understand the function of the GATA gene family more broadly, the GATA gene family members in P. ginseng were predicted using an in silico bioinformatics approach. A comprehensive and systematic analysis encompassing chromosome scaffold, expression pattern, gene structure, and phylogeny was conducted. The results showed that a total of 52 GATA gene family members were recognized in P. ginseng, distributed across 51 scaffolds. Each member encoded a diverse number of amino acid residues, extending from 138 to 1064. Moreover, the expression levels of PgGATA genes were significantly altered by nitrogen (N) and phosphorus (P) stresses. The expression levels of PgGATA6, PgGATA11, PgGATA27, PgGATA32, PgGATA37, PgGATA39, PgGATA40, and PgGATA50 exhibited significant elevation under N deficiency, whereas PgGATA15, PgGATA18, PgGATA34, PgGATA38, PgGATA41, and PgGATA44 genes showed substantial upregulation under P deficiency. In addition, PgGATA3, PgGATA4, PgGATA14, PgGATA19, and PgGATA28 were substantially upregulated under both N and P deficiency. This research establishes a theoretical foundation for the thorough examination of the functions of the PgGATA gene family and its regulation by N and P fertilization during P. ginseng cultivation. [ABSTRACT FROM AUTHOR]