Limiting Interfacial Free Water and Proton Concentration by Hydrogel Electrolytes for Stable MoO3 Anode in a Proton Battery.

Aqueous rechargeable proton batteries are attractive due to the small ionic radius, light mass, and ultrafast diffusion kinetics of proton as charge carriers. However, the commonly used acidic electrolyte is usually very corrosive to the electrode material, which seriously affects the cycle life of the battery. Here, it is proposed that decreasing water activity and limiting proton concentration can effectively prevent side reactions of the MoO3 anode such as corrosion and hydrogen precipitation by using a lean-water hydrogel electrolyte. The as-prepared polyacrylamide (PAAM)-poly2-acrylamide-2-methylpropanesulfonic acid (PAMPS)/MnSO4 (PPM) hydrogel electrolyte not only has abundant hydrophilic groups that can form hydrogen bonds with free water and inhibit solvent-electrode interaction, but also has fixed anions that can maintain a certain interaction with protons. The assembled MoO3||MnO2 full battery can stably cycle over 500 times for ≈350 h with an unprecedented capacity retention of 100% even at a low current density of 0.5 A g-1. This work gives a hint that limiting free water as well as proton concentration is important for the design of electrolytes or interfaces in aqueous proton batteries.

Unusually High-Spin Fe12C12- Metallo-Carbohedrene Clusters.

Ferromagnets constructed from nanometals of atomic precision are important for innovative advances in information storage, energy conversion, and spintronic microdevices. Considerable success has been achieved in designing molecular magnets, which, however, are challenging in preparation and may suffer from drawbacks on the incompatibility of high stability and strong ferromagnetism. Utilizing a state-of-the-art self-developed mass spectrometer and a homemade laser vaporization source, we have achieved a highly efficient preparation of pure iron clusters, and here, we report the finding of a strongly ferromagnetic metal-carbon cluster, Fe12C12-, simply by reacting the Fen- clusters with acetylene in proper conditions. The unique stability of this ferromagnetic Fe12C12- cluster is rooted in a plumb-bob structure pertaining to Jahn-Teller distortion. We classify Fe12C12- as a new member of metallo-carbohedrenes and elucidate its structural stability mechanism as well as its soft-landing deposition and magnetization measurements, providing promise for the exploration of potential applications.

Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice.

O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous post-translation modification occurring in both animals and plants. Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. We first established the metabolic glycan labelling (MGL) strategy with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. A total of 1591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within serine/threonine-enriched peptides, causing ambiguous site assignment. The identified O-GlcNAcylated proteins are involved in multiple biological processes, such as transcription, translation and plant hormone signalling. Furthermore, we discovered two O-GlcNAc transferases (OsOGTs) in rice. By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants.

Prediction of Mortality and Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury.

RATIONALE & OBJECTIVE: Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays. PREDICTORS: Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay. OUTCOMES: (1) Hospital mortality and (2) MAKE, defined as the composite of death during hospitalization or within 120 days of discharge, receipt of kidney replacement therapy in the last 48 hours of hospital stay, initiation of maintenance kidney replacement therapy within 120 days, or a ≥50% decrease in estimated glomerular filtration rate from baseline to 120 days from hospital discharge. ANALYTICAL APPROACH: Four machine-learning algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) and the SHAP (Shapley Additive Explanations) framework were used for feature selection and interpretation. Model performance was evaluated by 10-fold cross-validation and external validation. RESULTS: One developed model including 15 features outperformed the SOFA (Sequential Organ Failure Assessment) score for the prediction of hospital mortality, with areas under the curve of 0.79 (95% CI, 0.79-0.80) and 0.71 (95% CI, 0.71-0.71) in the development cohort and 0.74 (95% CI, 0.73-0.74) and 0.71 (95% CI, 0.71-0.71) in the validation cohort (P < 0.001 for both). A second developed model including 14 features outperformed KDIGO (Kidney Disease: Improving Global Outcomes) AKI severity staging for the prediction of MAKE: 0.78 (95% CI, 0.78-0.78) versus 0.66 (95% CI, 0.66-0.66) in the development cohort and 0.73 (95% CI, 0.72-0.74) versus 0.67 (95% CI, 0.67-0.67) in the validation cohort (P < 0.001 for both). LIMITATIONS: The models are applicable only to critically ill adult patients with incident AKI within the first 3 days of an ICU stay. CONCLUSIONS: The reported clinical models exhibited better performance for mortality and kidney recovery prediction than standard scoring tools commonly used in critically ill patients with AKI in the ICU. Additional validation is needed to support the utility and implementation of these models. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) occurs commonly in critically ill patients admitted to the intensive care unit (ICU) and is associated with high morbidity and mortality rates. Prediction of mortality and recovery after an episode of AKI may assist bedside decision making. In this report, we describe the development and validation of a clinical model using data from the first 3 days of an ICU stay to predict hospital mortality and major adverse kidney events occurring as long as 120 days after hospital discharge among critically ill adult patients who experienced AKI within the first 3 days of an ICU stay. The proposed clinical models exhibited good performance for outcome prediction and, if further validated, could enable risk stratification for timely interventions that promote kidney recovery.

Limosilactobacillus johnsoni and Limosilactobacillus mucosae and Their Extracellular Vesicles Alleviate Gut Inflammatory Injury by Mediating Macrophage Polarization in a Lipopolysaccharide-Challenged Piglet Model.

BACKGROUND: Limosilactobacillus johnsoni (L. j) and Limosilactobacillus mucosae (L. m) can alleviate the inflammatory response. OBJECTIVES: This study aimed to elucidate the underlying mechanisms by which L. j- and L. m-derived extracellular vesicles (EVs) mitigate lipopolysaccharide (LPS)-induced intestinal injury. METHODS: Piglets were assigned to 4 groups: oral phosphate-buffered saline inoculation for 2 wk prior to intraperitoneal injection of physiological saline or LPS, and oral L. j/L. m inoculation for 2 wk prior to intraperitoneal injection of LPS. The intestinal integrity, macrophage markers, cytokine levels, and microbiota were determined. The cytokine levels and macrophage phenotype were detected after L. j/L. m and their EVs were coincubated with macrophages. The levels of cytokines, tight junction proteins, and apoptosis were measured after intestinal epithelial cells were cocultured with macrophages. RESULTS: LPS challenge decreased jejunal villus length; expression levels of zonula occludens-1 (ZO-1), occludin, arginase-1 (Arg1), and interleukin (IL)-10; and number of CD163+ cells and increased the expression levels of inducible nitric oxide synthase (iNOS), IL-1ß, IL-6, and tumor necrosis factor (TNF)-α compared with that in the control. L. j and L. m pretreatment rescued the aforementioned indicators compared with LPS challenge. Pretreatment of L. j and L. m and their EVs reversed the levels of IL-1ß, IL-6, TNF-α, and IL-10 and the gene expression of iNOS and Arg1 in the LPS group in macrophages. Pretreatment with L. j and L. m-derived EVs increased ZO-1 and occludin mRNA expression and reduced IL-1ß, caspase-3, and bax gene expression in intestinal epithelial cells of the coculture system. Enzyme-treated EVs were less effective than native EVs. CONCLUSIONS: This study suggests that EVs secreted by L. j and L. m control inflammation by modulating macrophage polarization, thereby improving intestinal barrier function.

Structures and bonding properties of lithium polysulfide clusters LiSn-/0 (n = 3-5) and Li2S4-/0: size-selected anion photoelectron spectroscopy and theoretical calculations.

The structures and bonding properties of several lithium polysulfide clusters LiSn-/0 (n = 3-5) and Li2S4-/0 were investigated by size-selected anion photoelectron spectroscopy coupled with quantum chemistry calculations. The vertical detachment energies of LiS3-, LiS4-, and LiS5- were estimated to be 2.17 ± 0.08, 3.30 ± 0.08 and 3.66 ± 0.08 eV, respectively, and that of Li2S4- was estimated to be 3.21 ± 0.08 eV. It is found that LiS3- and LiS3 have planar quadrilateral structures, and LiS4- and LiS4 have distorted five-membered ring structures. LiS5- has a distorted six-membered ring structure while neutral LiS5 has a book-shaped structure. The lowest-lying structure of Li2S4- can be viewed as a S2 unit connecting to the Li-Li edge of a Li2S2 tetrahedron. The lowest-lying structure of neutral Li2S4 can be viewed as a S2 unit connecting to the S atoms of a Li2S2 quadrilateral. The natural population analysis (NPA) and electron localization function (ELF) analyses show that the excess electron of LiSn- is mainly localized over the sulfur chains, especially on the S atoms interacting with Li, thus, the most stable structures of LiSn- can be regarded as a Li+ cation interacting with a Sn2- dianion. The results may be useful for understanding the formation of lithium polysulfides in lithium sulfur batteries.

Early Changes in Arterial Partial Pressure of Carbon Dioxide and Blood Pressure After Starting Extracorporeal Membrane Oxygenation in Children: Extracorporeal Life Support Organization Database Study of Neurologic Complications.

OBJECTIVE: Neurologic complications in pediatric patients supported by extracorporeal membrane oxygenation (ECMO) are common and lead to morbidity and mortality; however, few modifiable factors are known. DESIGN: Retrospective study of the Extracorporeal Life Support Organization registry (2010-2019). SETTING: Multicenter international database. PATIENTS: Pediatric patients receiving ECMO (2010-2019) for all indications and any mode of support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We investigated if early relative change in Pa co2 or mean arterial blood pressure (MAP) soon after starting ECMO was associated with neurologic complications. The primary outcome of neurologic complications was defined as a report of seizures, central nervous system infarction or hemorrhage, or brain death. All-cause mortality (including brain death) was used as a secondary outcome.Out of 7,270 patients, 15.6% had neurologic complications. Neurologic complications increased when the relative Pa co2 decreased by greater than 50% (18.4%) or 30-50% (16.5%) versus those who had a minimal change (13.9%, p < 0.01 and p = 0.046). When the relative MAP increased greater than 50%, the rate of neurologic complications was 16.9% versus 13.1% those with minimal change ( p = 0.007). In a multivariable model adjusting for confounders, a relative decrease in Pa co2 greater than 30% was independently associated with greater odds of neurologic complication (odds ratio [OR], 1.25; 95% CI, 1.07-1.46; p = 0.005). Within this group, with a relative decrease in Pa co2 greater than 30%, the effects of increased relative MAP increased neurologic complications (0.05% per BP Percentile; 95% CI, 0.001-0.11; p = 0.05). CONCLUSIONS: In pediatric patients, a large decrease in Pa co2 and increase in MAP following ECMO initiation are both associated with neurologic complications. Future research focusing on managing these issues carefully soon after ECMO deployment can potentially help to reduce neurologic complications.

Profiling of RNA ribose methylation in Arabidopsis thaliana.

Eukaryotic rRNAs and snRNAs are decorated with abundant 2'-O-methylated nucleotides (Nm) that are predominantly synthesized by box C/D snoRNA-guided enzymes. In the model plant Arabidopsis thaliana, C/D snoRNAs have been well categorized, but there is a lack of systematic mapping of Nm. Here, we applied RiboMeth-seq to profile Nm in cytoplasmic, chloroplast and mitochondrial rRNAs and snRNAs. We identified 111 Nm in cytoplasmic rRNAs and 19 Nm in snRNAs and assigned guide for majority of the detected sites using an updated snoRNA list. At least four sites are directed by guides with multiple specificities as shown in yeast. We found that C/D snoRNAs frequently form extra pairs with nearby sequences of methylation sites, potentially facilitating the substrate binding. Chloroplast and mitochondrial rRNAs contain five almost identical methylation sites, including two novel sites mediating ribosomal subunit joining. Deletion of FIB1 or FIB2 gene reduced the accumulation of C/D snoRNA and rRNA methylation with FIB1 playing a bigger role in methylation. Our data reveal the comprehensive 2'-O-methylation maps for Arabidopsis rRNAs and snRNAs and would facilitate study of their function and biosynthesis.

Routine Neuroimaging: Understanding Brain Injury in Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury. DESIGN: Retrospective observational single-center cohort study. SETTING: Tertiary care PICU. PATIENTS: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI. INTERVENTIONS: Extracorporeal membrane oxygenation support. MEASUREMENTS AND MAIN RESULTS: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence. CONCLUSIONS: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.

Dietary supplementation with L-arginine between days 14 and 25 of gestation enhances NO and polyamine syntheses and the expression of angiogenic proteins in porcine placentae.

Dietary supplementation with 0.4 or 0.8% L-arginine (Arg) to gilts between days 14 and 25 of gestation enhances embryonic survival and vascular development in placentae; however, the underlying mechanisms are largely unknown. This study tested the hypothesis that Arg supplementation stimulated placental expression of mRNAs and proteins that enhance angiogenesis, including endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), placental growth factor (PGF), GTP cyclohydrolase-I (GTP-CH1), ornithine decarboxylase (ODC1), and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2). Beginning on the day of breeding, gilts were fed daily 2 kg of a corn-soybean meal-based diet supplemented with 0.0 (control), 0.4, or 0.8% Arg. On day 25 of gestation, gilts were hysterectomized to obtain uteri and conceptuses for histochemical and biochemical analyses. eNOS and VEGFR1 proteins were localized to endothelial cells of maternal uterine blood vessels and to the uterine luminal epithelium, respectively. Compared with the control, dietary supplementation with 0.4 or 0.8% Arg increased (P < 0.05) the amounts of nitrite plus nitrate (NOx; oxidation products of NO) and polyamines in allantoic and amniotic fluids, concentrations of NOx, tetrahydrobiopterin (BH4, an essential cofactor for all NOS isoforms) and polyamines in placentae, as well as placental protein abundances of GTP-CH1 (the key enzyme for BH4 production) and ODC1 (the key enzyme for polyamine synthesis). Placental  mRNA levels for GTP-CH1, eNOS, PGF, VEGF, and VEGFR2 increased in response to both 0.4% and 0.8% Arg supplementation. Collectively, these results indicate that dietary Arg supplementation to gilts between days 14 and 25 of pregnancy promotes placental angiogenesis by increasing the expression of mRNAs and proteins for angiogenic factors as well as NO and polyamine syntheses.

Serum IL-17 levels are higher in critically ill patients with AKI and associated with worse outcomes.

BACKGROUND: Interleukin-17 (IL-17) antagonism in rats reduces the severity and progression of AKI. IL-17-producing circulating T helper-17 (TH17) cells is increased in critically ill patients with AKI indicating that this pathway is also activated in humans. We aim to compare serum IL-17A levels in critically ill patients with versus without AKI and to examine their relationship with mortality and major adverse kidney events (MAKE). METHODS: Multicenter, prospective study of ICU patients with AKI stage 2 or 3 and without AKI. Samples were collected at 24-48 h after AKI diagnosis or ICU admission (in those without AKI) [timepoint 1, T1] and 5-7 days later [timepoint 2, T2]. MAKE was defined as the composite of death, dependence on kidney replacement therapy or a reduction in eGFR of ≥ 30% from baseline up to 90 days following hospital discharge. RESULTS: A total of 299 patients were evaluated. Patients in the highest IL-17A tertile (versus lower tertiles) at T1 had higher acuity of illness and comorbidity scores. Patients with AKI had higher levels of IL-17A than those without AKI: T1 1918.6 fg/ml (692.0-5860.9) versus 623.1 fg/ml (331.7-1503.4), p < 0.001; T2 2167.7 fg/ml (839.9-4618.9) versus 1193.5 fg/ml (523.8-2198.7), p = 0.006. Every onefold higher serum IL-17A at T1 was independently associated with increased risk of hospital mortality (aOR 1.35, 95% CI: 1.06-1.73) and MAKE (aOR 1.26, 95% CI: 1.02-1.55). The highest tertile of IL-17A (vs. the lowest tertile) was also independently associated with higher risk of MAKE (aOR 3.03, 95% CI: 1.34-6.87). There was no effect modification of these associations by AKI status. IL-17A levels remained significantly elevated at T2 in patients that died or developed MAKE. CONCLUSIONS: Serum IL-17A levels measured by the time of AKI diagnosis or ICU admission were differentially elevated in critically ill patients with AKI when compared to those without AKI and were independently associated with hospital mortality and MAKE.

Gallic acid mitigates LPS-induced inflammatory response via suppressing NF-κB signalling pathway in IPEC-J2 cells.

Gallic acid is a phenolic compound that exhibits antibacterial, antioxidative and anti-inflammatory functions. In a previous study, we found that dietary supplementation with gallic acid decreased incidence of diarrhoea and protected intestinal integrity in weaning piglets. However, the underlying mechanism remains unclear. Here, a pig intestinal epithelial cell line (IPEC-J2) was used as an in vitro model to explore the antioxidant and anti-inflammatory capacity of gallic acid. IPEC-J2 cells were stimulated with hydrogen peroxide (H2 O2 ) and lipopolysaccharide (LPS) to establish oxidative and inflammatory models, respectively. Results showed that H2 O2 significantly decreased catalase (CAT) secretion and CAT mRNA abundance in the cells (p < 0.05), while pretreatment with gallic acid did not prevent the decrease in CAT expression induced by H2 O2 . However, gallic acid pretreatment mitigated the increased expression of the tumour necrosis factor-α and interleukin-8 genes caused by LPS in IPEC-J2 cells (p < 0.05). In addition, pretreatment with gallic acid significantly suppressed phosphorylation of NF-κB and IκBα in LPS-stimulated IPEC-J2 cells. Moreover, LPS stimulation decreased the protein abundance of zona occludens 1 (ZO-1) and occludin, while pretreatment with gallic acid preserved expression level of tight junction proteins ZO-1 and occludin in LPS-stimulated IPEC-J2 cells (p < 0.05). In conclusion, gallic acid may mitigate LPS-induced inflammatory responses by inhibiting the NF-κB signalling pathway, exerting positive effects on the barrier function of IPEC-J2 cells.

Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease.

Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.

An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F.

Variation in female reproductive traits, such as fertility, fecundity, and fecundability, are heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits have been challenging. Here, we explore the functional significance and evolutionary history of a G/A polymorphism at SNP rs2523393, which is an eQTL for HLA-F and is significantly associated with fecundability (the probability of being pregnant within a single menstrual cycle). We replicated the association between the rs2523393 genotype and HLA-F expression by using GTEx data and demonstrate that HLA-F is upregulated in the endometrium during the window of implantation and by progesterone in decidual stromal cells. Next, we show that the rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. Remarkably, we found that the A allele is derived in the human lineage and that the G/A polymorphism arose before the divergence of modern and archaic humans and segregates at intermediate to high frequencies across human populations. Remarkably, the derived A allele is has also been identified in a GWAS as a risk allele for multiple sclerosis. These data suggest that the polymorphism is maintained by antagonistic pleiotropy and a reproduction-health tradeoff in human evolution.

Outcomes of Pediatric Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVE: The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation. DATA SOURCES: A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020. STUDY SELECTION: A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included. DATA EXTRACTION: Study characteristics and outcome estimates were extracted from each article. DATA SYNTHESIS: Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients' articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43-48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27-33%; p < 0.01). CONCLUSIONS: The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy.

Dynamic transcriptome, accessible genome, and PGR cistrome profiles in the human myometrium.

The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were examined by RNAseq, ATACseq, and PGR ChIPseq assays to profile transcriptome, assessible genome, and PGR occupancy. NP and TP specimens exhibit 2890 differentially expressed genes, reflecting an increase of metabolic, inflammatory, and PDGF signaling, among others, in adaptation to pregnancy. At the epigenome level, patterns of accessible genome change between NP and TP myometrium, leading to the altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors, and MEF2A transcription factors. PGR genome occupancy exhibits a significant difference between the two stages of the myometrium, concomitant with distinct transcriptomic profiles including genes such as ENO1, LHDA, and PLCL1 in the glycolytic and calcium signaling pathways. Over-representation of SRF, MYOD, and STAT binding motifs in PGR occupying sites further suggests interactions between PGR and major muscle regulators for myometrial gene expression. In conclusion, changes in accessible genome and PGR occupancy are part of the myometrial remodeling process and may serve as mechanisms to formulate the state-specific transcriptome profiles.

Dietary L-arginine supplementation during days 14-25 of gestation enhances aquaporin expression in the placentae and endometria of gestating gilts.

This study tested the hypothesis that dietary L-arginine (Arg) supplementation to pregnant gilts enhanced the expression of water channel proteins [aquaporins (AQPs)] in their placentae and endometria. Gilts were fed twice daily 1 kg of a corn and soybean meal-based diet supplemented with 0.0%, 0.4%, or 0.8% Arg between Days 14 and 25 of gestation. On Days 25 and 60 of gestation, gilts were hysterectomized to obtain placentae and endometria. On Day 25 of gestation, supplementation with 0.4% Arg increased (P < 0.05) the abundance of placental AQP9 protein, whereas supplementation with 0.8% Arg increased (P < 0.05) placental AQP1 and AQP9 proteins, compared with controls. On Day 60 of gestation, supplementation with 0.4% Arg increased (P < 0.05) endometrial AQP1 protein, whereas supplementation with 0.8% Arg increased (P < 0.05) endometrial AQP5 and AQP9 proteins. Supplementation with 0.8% Arg increased the endometrial expression of AQP1, AQP5, and AQP9 proteins located in the luminal epithelium and glandular epithelium of endometria, and placental transport of 3H2O. Collectively, these results indicate that dietary Arg supplementation stimulates the expression of selective AQPs in porcine placenta and endometria, thereby enhancing water transport from mother to fetus and expanding the chorioallantoic membranes during the period of placentation.

The risk of depression among racially diverse people living with HIV: the impact of HIV viral suppression.

Understanding the correlates of depression in HIV patients can help identify groups whose members are at increased risk for depression. We conducted a cross-sectional retrospective study among racially diverse, indigent patients living with HIV (PLWH) who were obtaining care in an urban safety-net hospital system and had completed a Patient Health Questionnaire-9 (PHQ-9) in 2014 or 2015. We collected demographics, HIV risk factors, HIV viral loads, CD4 counts, missed visits, and emergency department (ED) visits. Data from the Substance Abuse and Mental Illness Symptoms Screener (SAMISS) were abstracted. Missing data on substance use and CD4 cell counts were imputed to examine the odds of depression (PHQ-9 ≥ 10) by multivariable analysis for a complete case and sensitivity analysis. Stratified analysis by HIV viral suppression (VS) was used to determine the odds of depression among subgroups. Of the 5126 HIV patients (70.8% male,56.3% Black, 44.6% MSM, 6.0% IDU), 1271 (24.8%) experienced depression (PHQ ≥ 10). In a multivariable logistic model female gender, White race, injection drug use (IDU) or men who have sex with men (MSM) as an HIV risk factor, making ≥1 ED visit, having missed any HIV visit, having AIDS, and having a positive drug screen by SAMISS increased the odds for depression. Those who had achieved HIV VS or received efavirenz had lower odds of depression. Even among those with AIDS, those failing to achieve VS were at increased odds for depression, whereas those achieving VS were not. Moderate to severe depression is prevalent among PLWH. Among those with AIDS, HIV VS modifies the odds of depression.

Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study.

BACKGROUND: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. METHODS: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. RESULTS: Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. CONCLUSIONS: In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.

A fixed multi-site interaction charge model for an accurate prediction of the QM/MM interactions.

A fixed multi-site interaction charge (FMIC) model was proposed for the accurate prediction of intermolecular electrostatic interactions based on the quantum mechanical linear response of a molecule to an external electric field. In such a model, some additional off-center interaction sites were added for capturing multipole interactions for a given molecule. By multivariate least-square fitting analysis of the calculated QM/MM interactions of a given molecule with the electrostatic environment and the electrostatic potentials of the environment at the pre-defined distributed interaction sites, the FMIC of the molecule was obtained. The model system of CO in myoglobin (Mb) was utilized to demonstrate the derivation of the FMIC. The accuracy of FMIC in predicting the electrostatic interactions between CO and the Mb environment was investigated using 10 000 different Mb-CO configurations generated from the 400 ps QM/MM MD simulation. In comparison to the QM/MM calculations at the B3LYP/aug-cc-pVTZ/ff99SB level, the mean unsigned error (MUE) of the results based on the FMIC model was merely 0.10 kcal mol-1, and the root mean square error (RMSE) was only 0.13 kcal mol-1, which are significantly lower than the results predicted by the ESP charge model (MUE = 1.45 kcal mol-1, and RMSE = 1.7 kcal mol-1, respectively). The transferability of FMIC was tested by applying the obtained FMIC in the wild type Mb-CO system to the mutants of V68F and H64L Mb-CO systems. The MUEs of the obtained results for 10 000 different configurations are both smaller than 0.2 kcal mol-1 for the V68F and H64L Mb-CO systems in comparison to the B3LYP/aug-cc-pVTZ/ff99SB calculations, and the RMSEs are also lower than 0.2 kcal mol-1 for both mutants. The applications of FMIC were extended to model the electrostatic interactions between a hydrogen fluoride molecule and 492 waters in a truncated octahedron box; our study showed that the FMIC could give satisfactory results with a MUE of 0.12 kcal mol-1 and a RMSE of 0.16 kcal mol-1 in comparison to the B3LYP/aug-cc-pVDZ/TIP3P calculations for 10 000 different configurations generated using the 10 ns classical MD simulation. Therefore, the FMIC method provides an accurate and efficient tool for predicting intermolecular electrostatic interactions, which can be utilized in the future development of molecular force fields.