Dot1l cooperates with Npm1 to repress endogenous retrovirus MERVL in embryonic stem cells.

Dot1l is a histone methyltransferase without a SET domain and is responsible for H3K79 methylation, which marks active transcription. In contradiction, Dot1l also participates in silencing gene expression. The target regions and mechanism of Dot1l in repressing transcription remain enigmatic. Here, we show that Dot1l represses endogenous retroviruses in embryonic stem cells (ESCs). Specifically, the absence of Dot1l led to the activation of MERVL, which is a marker of 2-cell-like cells. In addition, Dot1l deletion activated the 2-cell-like state and predisposed ESCs to differentiate into trophectoderm lineage. Transcriptome analysis revealed activation of 2-cell genes and meiotic genes by Dot1l deletion. Mechanistically, Dot1l interacted with and co-localized with Npm1 on MERVL, and depletion of Npm1 similarly augmented MERVL expression. The catalytic activity and AT-hook domain of Dot1l are important to suppress MERVL. Notably, Dot1l-Npm1 restricts MERVL by regulating protein level and deposition of histone H1. Furthermore, Dot1l is critical for Npm1 to efficiently interact with histone H1 and inhibit ubiquitination of H1 whereas Npm1 is essential for Dot1l to interact with MERVL. Altogether, we discover that Dot1l represses MERVL through chaperoning H1 by collaborating with Npm1. Importantly, our findings shed light on the non-canonical transcriptional repressive role of Dot1l in ESCs.

A high-performance computational workflow to accelerate GATK SNP detection across a 25-genome dataset.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) are the most widely used form of molecular genetic variation studies. As reference genomes and resequencing data sets expand exponentially, tools must be in place to call SNPs at a similar pace. The genome analysis toolkit (GATK) is one of the most widely used SNP calling software tools publicly available, but unfortunately, high-performance computing versions of this tool have yet to become widely available and affordable. RESULTS: Here we report an open-source high-performance computing genome variant calling workflow (HPC-GVCW) for GATK that can run on multiple computing platforms from supercomputers to desktop machines. We benchmarked HPC-GVCW on multiple crop species for performance and accuracy with comparable results with previously published reports (using GATK alone). Finally, we used HPC-GVCW in production mode to call SNPs on a "subpopulation aware" 16-genome rice reference panel with ~ 3000 resequenced rice accessions. The entire process took ~ 16 weeks and resulted in the identification of an average of 27.3 M SNPs/genome and the discovery of ~ 2.3 million novel SNPs that were not present in the flagship reference genome for rice (i.e., IRGSP RefSeq). CONCLUSIONS: This study developed an open-source pipeline (HPC-GVCW) to run GATK on HPC platforms, which significantly improved the speed at which SNPs can be called. The workflow is widely applicable as demonstrated successfully for four major crop species with genomes ranging in size from 400 Mb to 2.4 Gb. Using HPC-GVCW in production mode to call SNPs on a 25 multi-crop-reference genome data set produced over 1.1 billion SNPs that were publicly released for functional and breeding studies. For rice, many novel SNPs were identified and were found to reside within genes and open chromatin regions that are predicted to have functional consequences. Combined, our results demonstrate the usefulness of combining a high-performance SNP calling architecture solution with a subpopulation-aware reference genome panel for rapid SNP discovery and public deployment.

Clinical-grade human embryonic stem cell-derived mesenchymal stromal cells ameliorate diabetic retinopathy in db/db mice.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) hold great promise in the treatment of diabetic retinopathy (DR), as evidenced by increasing preclinical and clinical studies. However, the absence of standardized and industrialized clinical-grade donor cells hampers the continued development and large-scale clinical application of MSCs-based therapies for DR. Previously, we have identified a unique population of MSCs generated from a clinical-grade human embryonic stem cell (hESC) line under Good Manufacturing Practice conditions that could be a potential source to address the issues. Here, we investigated the therapeutic potential of the clinical-grade hESC line-derived MSCs (hESC-MSCs) on db/db mice with DR. METHODS: hESC-MSCs were initially characterized by morphological assessment, flow cytometry analysis and trilineage differentiation assays. These cells (5 × 106 cells) were then transplanted intravenously into 12-week-old db/db mice via tail vein, with phosphate-buffered saline transplantation and untreated groups used as controls. The retinal alterations in neural functions and microvascular perfusions, and inflammatory responses in peripheral blood and retina were evaluated at 4 and 6 weeks after transplantation using electroretinography, optical coherence tomography angiography and flow cytometry, respectively. Body weight and fasting blood glucose (FBG) levels were also measured to investigate their systemic implications. RESULTS: Compared with controls, intravenous transplantation of hESC-MSCs could significantly: (i) enhance impaired retinal electroretinography functions (including amplitudes of a-, b-wave and oscillatory potentials) at 4 weeks after transplantation; (ii) alleviate microvascular dysfunctions, especially in the inner retina with significance (including reducing non-perfusion area and increasing vascular area density) at 4 weeks after transplantation; (iii) decrease FBG levels at 4 weeks after transplantation and induce weight loss up to 6 weeks after transplantation and (iv) increase both peripheral blood and retinal interleukin-10 levels at 4 weeks after transplantation and modulate peripheral blood inflammatory cytokines and chemokines levels, such as monocyte chemotactic protein-1, up to 6 weeks after transplantation. CONCLUSIONS: The findings of our study indicated that intravenous transplantation of hESC-MSCs ameliorated retinal neural and microvascular dysfunctions, regulated body weight and FBG and modulated peripheral blood and retinal inflammation responses in a mouse model of DR. These results suggest that hESC-MSCs could be a potentially effective clinical-grade cell source for the treatment of DR.

E3 ubiquitin ligase RNF187 promotes growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84.

Ubiquitination is the most common post-translational modification and is essential for various cellular regulatory processes. RNF187, which is known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 can promote the proliferation and migration of various tumor cells. However, whether it has a similar role in regulating spermatogonia is not clear. This study explored the role and molecular mechanism of RNF187 in a mouse spermatogonia cell line (GC-1). We found that RNF187 knockdown reduced the proliferation and migration of GC-1 cells and promoted their apoptosis. RNF187 overexpression significantly increased the proliferation and migration of GC-1 cells. In addition, we identified Keratin36/Keratin84 (KRT36/KRT84) as interactors with RNF187 by co-immunoprecipitation and mass spectrometry analyses. RNF187 promoted GC-1 cell growth by degrading KRT36/KRT84 via lysine 48-linked polyubiquitination. Subsequently, we found that KRT36 or KRT84 overexpression significantly attenuated proliferation and migration of RNF187-overexpressing GC-1 cells. In summary, our study explored the involvement of RNF187 in regulating the growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84. This may provide a promising new strategy for treating infertility caused by abnormal spermatogonia development.

Enantiomer Recognition Based on Chirality Transfer from Chiral Amines to Ternary Dynamic Covalent Systems.

Enantiomer recognition is usually required in organic synthesis and materials and life sciences. This paper describes an enantiomer recognition method based on ternary dynamic covalent systems constructed via the complexation of chiral amines with a chiral boronate derived from 1,4-phenylenediboric acid and an L-DOPA-modified naphthalenediimide. The ternary systems aggregate into chiral assemblies driven by π-π interactions, and the chirality is transferred from the chiral amines to assemblies with high stereospecificity. Consequently, the enantiomer composition of chiral amines and the absolute configuration of the major enantiomer can be determined according to the sign of the Cotton effect of the ternary system by using circular dichroism (CD) spectroscopy. This method offers the advantage of using the long wavelength CD signals of the boronate at around 520 nm, thereby avoiding interference with those of the carbon skeleton. This ternary system provides a novel approach to the design of enantiomer recognition systems.

Solar-Driven Multistage Device Integrating Dropwise Condensation and Guided Water Transport for Efficient Freshwater and Salt Collection.

Interfacial solar vapor generation (ISVG) is an emerging technology to alleviate the global freshwater crisis. However, high-cost, low freshwater collection rate, and salt-blockage issues significantly hinder the practical application of solar-driven desalination devices based on ISVG. Herein, with a low-cost copper plate (CP), nonwoven fabric (NWF), and insulating ethylene-vinyl acetate foam (EVA foam), a multistage device is elaborately fabricated for highly efficient simultaneous freshwater and salt collection. In the designed solar-driven device, a superhydrophobic copper plate (SH-CP) serves as the condensation layer, facilitating rapid mass and heat transfer through dropwise condensation. Moreover, the hydrophilic NWF is designed with rational hydrophobic zones and specific high-salinity solution outlets (Design-NWF) to act as the water evaporation layer and facilitate directional salt collection. As a result, the multistage evaporator with eight stages exhibits a high water collection rate of 2.25 kg m-2 h-1 under 1 sun irradiation. In addition, the desalination device based on the eight-stage evaporator obtains a water collection rate of 13.44 kg m-2 and a salt collection rate of 1.77 kg m-2 per day under natural irradiation. More importantly, it can maintain a steady production for 15 days without obvious performance decay. This bifunctional multistage device provides a feasible and efficient approach for simultaneous desalination and solute collection.

Catastrophic health expenditure and health-related quality of life among older adults in Shandong, China: the moderation effect of daily care by adult children.

BACKGROUND: Catastrophic health expenditure (CHE) has a considerable impact on older people in later life, but little is known about the relationship between catastrophic health expenditure and health-related quality of life (HRQOL). The aim of this study was to examine the relationship between catastrophic health expenditure and health-related quality of life in older people, and to explore whether the daily care provided by adult children is a moderator in this relationship. METHODS: Data from the sixth National Health Services Survey in Shandong Province, China. The sample consisted of 8599 elderly people (age ≥ 60 years; 51.7% of female). Health-related quality of life was measured by the health utility value of EQ-5D-3 L. Interaction effects were analyzed using Tobit regression models and marginal effects analysis. RESULTS: The catastrophic health expenditure prevalence was 60.5% among older people in Shandong, China. catastrophic health expenditure was significantly associated with lower health-related quality of life (ß= - 0.142, P < 0.001). We found that adult children providing daily care services to their parents mitigated the effect of catastrophic health expenditure on health-related quality of life among older people (ß = 0.027, P = 0.040). CONCLUSIONS: Our findings suggested that catastrophic health expenditure was associated with health-related quality of life and the caring role of older adult children moderated this relationship. Reducing the damage caused by catastrophic health expenditure helps to improve health-related quality of life in older people. Adult children should increase intergenerational contact, provide timely financial and emotional support to reduce the negative impact of catastrophic health expenditure on health-related quality of life.

Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.

Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

BACKGROUND: Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. METHODS: This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. RESULTS: (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. CONCLUSIONS: Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

Activities of daily living limitations and the use of physical examination among older adults with informal care in China: do gender and residence make differences?

BACKGROUND: This study investigated the relationship between activities of daily living (ADL) limitations and the use of physical examination among older adults receiving informal care, and to further examine whether this relationship varies by gender and urban-rural areas. METHODS: The data in this study were obtained from the sixth Health Service of Shandong province, China. In total, 8,358 older adults aged 60 years or older who received informal care were included in the analysis. Binary logistic regression models were conducted to explore the association between ADL limitations and the use of physical examination and examine the differences between gender and urban-rural areas. RESULTS: The prevalence of limitations in ADL and physical examination utilization rate among older adults receiving informal care in Shandong Province were 14.12% and 72.31%, respectively. After adjusting for confounders, ADL limitations were negatively correlated with the utilization of physical examination services among older adults receiving informal care (OR = 0.74, 95% CI: 0.64, 0.87, P < 0.001), and there were gender and rural-urban differences. The association between ADL limitations and the use of physical examination was statistically significant in older women receiving informal care (OR = 0.65, 95% CI: 0.53, 0.80, P < 0.001). And only among urban older adults receiving informal care, those with ADL limitations had lower utilization of physical examination services than participants without ADL limitations (OR = 0.59, 95% CI: 0.47, 0.74, P < 0.001). CONCLUSIONS: Our study suggested that the relationship between ADL limitations and the use of physical examination among older adults receiving informal care differed by gender and urban-rural areas in Shandong, China. These findings implied that the government should provide more health resources and personalized physical examination service programs, especially to meet the differential needs of women and urban old adults receiving informal care, to contribute to the implementation of healthy aging strategies.

One-Step Synthesis of Polyethyleneimine-Grafted Styrene-Maleic Anhydride Copolymer Adsorbents for Effective Adsorption of Anionic Dyes.

Wastewater containing organic dyes has become one of the important challenges in water treatment due to its high salt content and resistance to natural degradation. In this work, a novelty adsorbent, PEI-SMA, was prepared by grafting polyethyleneimine (PEI) onto styrene-maleic anhydride copolymer (SMA) through an amidation reaction. The various factors, such as pH, adsorbent dosage, contact time, dye concentration, and temperature, which may affect the adsorption of PEI-SMA for Reactive Black 5 (RB5), were systematically investigated by static adsorption experiments. The adsorption process of PEI-SMA for RB5 was more consistent with the Langmuir isotherm model and the pseudo-second-order model, suggesting a single-layer chemisorption. PEI-SMA exhibits excellent adsorption performance for RB5 dye, with a maximum adsorption capacity of 1749.19 mg g-1 at pH = 2. Additionally, PEI-SMA exhibited highly efficient RB5 competitive adsorption against coexisting Cl- and SO42- ions and cationic dyes. The adsorption mechanism was explored, and it can be explained as the synergistic effect of electrostatic interaction, hydrogen bonding and π-π interaction. This study demonstrates that PEI-SMA could act as a high performance and promising candidate for the effective adsorption of anionic dyes from aqueous solutions.

Loss of SUN1 function in spermatocytes disrupts the attachment of telomeres to the nuclear envelope and contributes to non-obstructive azoospermia in humans.

One of the most severe forms of infertility in humans, caused by gametogenic failure, is non-obstructive azoospermia (NOA). Approximately, 20-30% of men with NOA may have single-gene mutations or other genetic variables that cause this disease. While a range of single-gene mutations associated with infertility has been identified in prior whole-exome sequencing (WES) studies, current insight into the precise genetic etiology of impaired human gametogenesis remains limited. In this paper, we described a proband with NOA who experienced hereditary infertility. WES analyses identified a homozygous variant in the SUN1 (Sad1 and UNC84 domain containing 1) gene [c. 663C > A: p.Tyr221X] that segregated with infertility. SUN1 encodes a LINC complex component essential for telomeric attachment and chromosomal movement. Spermatocytes with the observed mutations were incapable of repairing double-strand DNA breaks or undergoing meiosis. This loss of SUN1 functionality contributes to significant reductions in KASH5 levels within impaired chromosomal telomere attachment to the inner nuclear membrane. Overall, our results identify a potential genetic driver of NOA pathogenesis and provide fresh insight into the role of the SUN1 protein as a regulator of prophase I progression in the context of human meiosis.

Long Noncoding RNA Lx8-SINE B2 Interacts with Eno1 to Regulate Self-Renewal and Metabolism of Embryonic Stem Cells.

Long noncoding RNAs (lncRNAs) emerge as important orchestrators of biological processes in embryonic stem cells (ESCs). LncRNA Lx8-SINE B2 was recently identified as an ESC-specific lncRNA that marks pluripotency. Here, we studied the function of lncRNA Lx8-SINE B2 in ESCs. Depletion of Lx8-SINE B2 disrupted ESC proliferation, repressed the expression of pluripotency genes, activated differentiation genes, and inhibited reprogramming to induced pluripotent stem cells. The reduction of the colony formation ability of ESCs upon Lx8-SINE B2 knockdown was accompanied by the elongation of the G1 phase and the shortening of the S phase. Transcriptome analysis revealed that Lx8-SINE B2 deficiency affected multiple metabolic pathways, particularly glycolysis. Mechanistically, Lx8-SINE B2 functions as a cytoplasmic lncRNA and interacts with the glycolytic enzyme Eno1 as shown by RNA pull-down and RNA localization analysis. Lx8-SINE B2 and Eno1 interact with and regulate each other's expression, hence promoting the expression of metabolic genes and influencing glycolysis. In conclusion, we have identified lncRNA Lx8-SINE B2 as a novel regulator of ESC proliferation, cell cycle, and metabolism through working with Eno1.

Advances in flavor peptides with sodium-reducing ability: A review.

Condiments (such as sodium chloride and glutamate sodium) cause consumers to ingest too much sodium and may lead to a variety of diseases, thus decreasing their quality of life. Recently, a salt reduction strategy using flavor peptides has been established. However, the development of this strategy has not been well adopted by the food industry. There is an acute need to screen for peptides with salty and umami taste, and to understand their taste characteristic and taste mechanism. This review provides a thorough analysis of the literature on flavor peptides with sodium-reducing ability, involving their preparation, taste characteristic, taste mechanism and applications in the food industry. Flavor peptides come from a wide range of sources and can be sourced abundantly from natural foods. Flavor peptides with salty and umami tastes are mainly composed of umami amino acids. Differences in amino acid sequences, spatial structures and food matrices will cause different tastes in flavor peptides, mostly attributed to the interaction between peptides and taste receptors. In addition to being used in condiments, flavor peptides have also anti-hypertensive, anti-inflammatory and anti-oxidant abilities, offering the potential to be used as functional ingredients, thus making their future in the food industry extremely promising.

Physical Mobility, Social Isolation and Cognitive Function: Are There Really Gender Differences?

OBJECTIVE: This study aimed to examine the mediating role of social isolation between physical mobility and cognitive function, and whether there are gender differences in the above mediating effects among Chinese older adults. METHODS: This is a prospective and cohort study. We obtained data from the 2011 (Time 1, T1), 2015 (Time 2, T2) and 2018 (Time 3, T3) waves of China Health and Retirement Longitudinal Study, including 3,395 participants aged 60 years or above. Cognition was evaluated by Telephone Interview of Cognitive Status, words recall, and figure drawing, which was widely used in previous research. We used a cross-lagged model to test the hypothesis that social isolation mediated the association between physical mobility and cognitive function among Chinese older adults. RESULTS: The total effects of T1 physical mobility limitations on T3 cognitive function (ß = -0.055, bootstrap p < 0.001) were significantly negative. Social isolation played a mediating role among both males and females (male: ß = -0.008, bootstrap p = 0.012; female: ß = -0.006, bootstrap p = 0.023), demonstrating that the mediating effect of social isolation between physical mobility and cognitive function was not gender specific. CONCLUSION: This study confirmed that social isolation mediated the association between physical mobility and cognitive function among both Chinese male and female older adults. These findings indicate that reversing social isolation can be a priority intervention target for cognitive decline prevention and promote successful ageing, particularly among older adults with impaired physical mobility.

Molecular characterization and functional analysis of galectin-1 from silver pomfret (Pampus argenteus).

Galectins, as members of lectin families, exhibit a high affinity for ß-galactosides and play diverse roles in biological processes. They function as pattern recognition receptors (PRRs) with important roles in immune defense. In this study, galectin-1, designated as SpGal-1, was identified and characterized from silver pomfret (Pampus argenteus). The SpGal-1 comprises an open reading frame (ORF) spanning 396 base pairs (bp) and encodes a deduced amino acid (aa) sequence containing a single carbohydrate recognition domain (CRD). Sublocalization analysis revealed that SpGal-1 was mainly expressed in the cytoplasm. The mRNA transcripts of SpGal-1 were ubiquitously detected in various tissues, with a higher expression level in the intestine. In addition, when exposed to Photobacterium damselae subsp. damselae (PDD) infection, both the liver and head kidney exhibited significantly increased SpGal-1 mRNA expression. The recombinant protein of SpGal-1 (named as rSpGal-1) demonstrated hemagglutination against red blood cells (RBCs) from Larimichthys crocea and P. argenteus in a Ca2+ or ß-Mercaptoethanol (ß-ME)-independent manner. Notably, rSpGal-1 could bind with various pathogen-associated molecular patterns (PAMPs) including D-galactose, D-mannose, lipopolysaccharide (LPS), and peptidoglycan (PGN), with highest affinity to PGN. Moreover, rSpGal-1 effectively interacted with an array of bacterial types encompassing Gram-positive bacteria (Staphylococcus aureus and Nocardia seriolae) and Gram-negative bacteria (PDD and Escherichia coli, among others), with the most robust binding affinity towards PDD. Collectively, these findings highlight that SpGal-1 is a crucial PRR with involvement in the host immune defense of silver pomfret.

Association between nutritional status scores and the 30-day mortality in patients with acute kidney injury: an analysis of MIMIC-III database.

BACKGROUND: Studies have proven that the risk of acute kidney injury (AKI) increased in patients with malnutrition. Prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) were general tools to predict the risk of mortality, but the prognostic value of them for in-hospital mortality among patients with AKI have not been validated yet. Herein, this study aims to explore the association between PNI and GNRI and 30-day mortality in patients with AKI. METHODS: Demographic and clinical data of 863 adult patients with AKI were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database in 2001-2012 in this retrospective cohort study. Univariate and multivariate Cox proportional regression analyses were used to explore the association between PNI and GNRI and 30-day mortality. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of age, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology (SAPS-II) score were also performed. RESULTS: Totally, 222 (26.71%) patients died within 30 days. After adjusting for covariates, PNI ≥ 28.5 [HR = 0.71, 95%CI: (0.51-0.98)] and GNRI ≥ 83.25 [HR = 0.63, 95%CI: (0.47-0.86)] were both associated with low risk of 30-day mortality. These relationships were also found in patients who aged ≥ 65 years old. Differently, high PNI level was associated with low risk of 30-day mortality among patients with SOFA score < 6 or SAPS-II score < 43, while high GNRI was associated with low risk of 30-day mortality among those who with SOFA score ≥ 6 or SAPS-II score ≥ 43 (all P < 0.05). CONCLUSION: PNI and GNRI may be potential predictors of 30-day mortality in patients with AKI. Whether the PNI is more recommended for patients with mild AKI, while GNRI for those with severe AKI is needed further exploration.

Association between white blood cell count to hemoglobin ratio and risk of in-hospital mortality in patients with lung cancer.

BACKGROUND: The objective of this study was to investigate the association between white blood cell count to hemoglobin ratio (WHR) and risk of in-hospital mortality in patients with lung cancer. METHODS: In this retrospective cohort study, the medical records of patients with lung cancer were retrieved from the electronic ICU (eICU) Collaborative Research Database between 2014 and 2015. The primary outcome was in-hospital mortality. The secondary outcome was the length of stay in intensive care unit (ICU). The cut-off value for the WHR was calculated by the X-tile software. The Cox model was applied to assess the association between WHR and in-hospital mortality among patients with lung cancer and the linear regression model was used to investigate the association between WHR and length of ICU stay. Subgroup analyses of age (< 65 years or > = 65 years), Acute Physiology and Chronic Health Evaluation (APACHE) score (< 59 or > = 59), gender, ventilation (yes or no), and vasopressor (yes or no) in patients with lung cancer were conducted. RESULTS: Of the 768 included patients with lung cancer, 153 patients (19.92%) died in the hospital. The median total follow-up time was 6.88 (4.17, 11.23) days. The optimal cut-off value for WHR was 1.4. ICU lung cancer patients with WHR > = 1.4 had a significantly higher risk of in-hospital mortality [Hazard ratio: (HR): 1.65, 95% confidence interval (CI): 1.15 to 2.38, P = 0.007) and length of stay in ICU (HR: 0.63, 0.01, 95% CI: 1.24 to 0.045, P = 0.045). According to the subgroup analysis, WHR was found to be associated with in-hospital mortality in patients with higher APACHE score (HR: 1.60, 95% CI: 1.06 to 2.41, P = 0.024), in male patients (HR: 1.87, 95% CI: 1.15 to 3.04, P = 0.012), and in patients with the treatment of ventilation (HR: 2.33, 95% CI: 1.49 to 3.64, P < 0.001). CONCLUSION: This study suggests the association between WHR and risk of in-hospital mortality in patients with lung cancer and length of stay, which indicates the importance of attention to WHR for patients with lung cancer.

The intellectual base and global trends in contrast-induced acute kidney injury: a bibliometric analysis.

Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired kidney injury. A comprehensive analysis of the current state of research in the field of CI-AKI will help to reveal trends and hot topics in the field. To date, there are no published bibliometric analyses related to CI-AKI studies. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights. The literature was collected from the Web of Science Core Collection. The data were analyzed visually using CiteSpace and VOSviewer software. We collected a total of 4775 papers, with the United States and Guangdong Acad Med Sci as the major publishing powers in terms of country/region and institution. J AM COLL CARDIOL was the journal with the most published and cocited articles. Cluster analysis showed that clinical trials are the current research hotspot. The areas of risk assessment, prevention strategies, risk factors, and vascular lesions have been popular in recent years. Research on the mechanism of injury in CI-AKI will be the focus of future research, which will be crucial to reduce the clinical incidence of CI-AKI. In summary, this study provides a comprehensive analysis of the development process in the field of CI-AKI and discusses future research directions based on the analysis of objective data from many studies on CI-AKI.

[Genetic analysis of a child with atypical Hemolytic uremic syndrome and nephrotic-range proteinuria].

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria. METHODS: A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents. RESULTS: The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria. CONCLUSION: For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.