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Low-density lipoprotein cholesterol (LDL-C) is typically estimated from total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The Friedewald, Martin-Hopkins, and National Institutes of Health equations are widely used but may estimate LDL-C inaccurately in certain patient populations, such as those with HIV. We sought to investigate the utility of machine learning for LDL-C estimation in a large cohort of women with and without HIV.We identified 7397 direct LDL-C measurements (5219 from HIV-infected individuals, 2127 from uninfected controls, and 51 from seroconvertors) from 2414 participants (age 39.4 ± 9.3 years) in the Women's Interagency HIV Study and estimated LDL-C using the Friedewald, Martin-Hopkins, and National Institutes of Health equations. We also optimized 5 machine learning methods [linear regression, random forest, gradient boosting, support vector machine (SVM), and neural network] using 80% of the data (training set). We compared the performance of each method using root mean square error, mean absolute error, and coefficient of determination (R2) in the holdout (20%) set.SVM outperformed all 3 existing equations and other machine learning methods, achieving the lowest root mean square error and mean absolute error, and the highest R2 (11.79 and 7.98 mg/dL, 0.87, respectively, compared with those obtained using the Friedewald equation: 12.45 and 9.14 mg/dL, 0.87). SVM performance remained superior in subgroups with and without HIV, with nonfasting measurements, in LDL70 mg/dL and triglycerides400 mg/dL.In this proof-of-concept study, SVM is a robust method that predicts directly measured LDL-C more accurately than clinically used methods in women with and without HIV. Further studies should explore the utility in broader populations.

Passive NOx adsorbers (PNA) adsorb NOx at low temperatures and release NOx at high temperatures, at which downstream catalytic systems, such as selective catalytic reduction catalysts, operate efficiently and can remove NOx. Pd/CeO2 is a promising catalyst for PNA applications. In this study, the promoting effect of CO on the NOx adsorption ability of Pd/CeO2 at low temperatures was investigated. The amount of NOx adsorbed significantly increased when CO was added to the feed gas. Specifically, during the first 10 min, the amount of adsorbed NOx increased more than six times in the presence of CO. A mechanism for the promoting effect of CO on low-temperature NOx adsorption was suggested by considering the decreased CO oxidation ability with increasing amount of NOx adsorbed over Pd/CeO2. The model proposes that NOx was readily adsorbed by the oxygen vacancies of CeO2 adjacent to the Pd particles, which were generated during CO oxidation, resulting in an increase in NOx adsorption. A better understanding of the CO and NO interactions would contribute to the development of ceria-based PNA materials.

Innate lymphoid cells (ILCs) play crucial roles in maintenance and defense of peripheral tissues but would undergo natural and inflammation-induced attrition over time. A potential solution to counteract the peripheral ILC attrition would be regulated mobilization of bone marrow (BM) ILC progenitors. The major multipotential ILC progenitors (ILCPs) are divided into two subsets in distinct niches of the BM. Sinusoid ILCPs emigrate from the BM to circulate the peripheral blood. In contrast, parenchyma ILCPs are more likely in cell cycling and less likely to emigrate BM. The mobilization of BM ILCPs is internally and externally controlled by the coordinated expression of the BM retention receptors (Itg-α4 and CXCR4) and the emigration receptors sphingosine-1-phosphate (S1P) receptors. The expression of the BM retention and emigration receptors is developmentally regulated in the steady state and by the inflammasome-derived IL-18. Upon infusion, sinusoid ILCPs can effectively restore peripheral ILC insufficiency and tissue integrity during inflammatory responses.

Short-chain fatty acids, such as butyrate, are major gut microbial metabolites that are beneficial for gastrointestinal health. Clostridium butyricum MIYAIRI588 (CBM588) is a bacterium that produces a robust amount of butyrate and therefore has been used as a live biotherapeutic probiotic in clinical settings. Clostridioides difficile causes life-threatening diarrhea and colitis. The gut resident microbiota plays a critical role in the prevention of C. difficile infection (CDI), as the disruption of the healthy microbiota by antibiotics greatly increases the risk for CDI. We report that CBM588 treatment in mice significantly improved clinical symptoms associated with CDI and increased the number of neutrophils and Th1 and Th17 cells in the colonic lamina propria in the early phase of CDI. The protective effect of CBM588 was abolished when neutrophils, IFN-γ, or IL-17A were depleted, suggesting that induction of the immune reactants is required to elicit the protective effect of the probiotic. The administration of tributyrin, which elevates the concentration of butyrate in the colon, also increased the number of neutrophils in the colonic lamina propria, indicating that butyrate is a potent booster of neutrophil activity during infection. However, GPR43 and GPR109a, two G protein–coupled receptors activated by butyrate, were dispensable for the protective effect of CBM588. These results indicate that CBM588 and butyrate suppress CDI, in part by boosting antimicrobial innate and cytokine-mediated immunity.

Summary Innate lymphoid cells (ILCs) rapidly undergo expansion in population size and functional maturation in response to cytokines that signal infection, tissue damage or changes in physiology. Optimal ILC responses are shaped, in part, by the microbiota but the mechanisms remain unclear. We report that short-chain fatty acids (SCFAs), produced by the commensal microbiota from dietary fibers, support optimal expansion of ILCs, including ILC1, ILC2 and ILC3 in the intestines through their G-protein-coupled receptors (GPCRs). While this function is primarily important for intestinal ILC populations, it can also boost ILC responses in other tissues depending on host condition. ILCs express multiple GPCRs that detect SCFAs. Interestingly, we found that the expression of SCFA receptors, such as Ffar2 and Ffar3, by ILCs is induced by SCFAs. GPCR triggering by SCFAs co-stimulates the activation of Phosphoinositide 3-kinase (PI3K), Stat3, Stat5, and mammalian target of rapamycin (mTOR), which is important for ILC proliferation. While Ffar2 signaling promotes ILC2 proliferation, SCFAs can suppress ILC2 proliferation through a non-Ffar2-mediated mechanism. In conclusion, our findings indicate that SCFAs, as the major mediator of healthy microbiota and nutritional status, function to maintain optimal numbers of ILCs in peripheral tissues during infection and inflammatory responses.

Vitamin A metabolites play important roles in T cell activation and differentiation. A conventional model of RARα function relies upon retinoic acid (RA)-liganded RARα binding to specific DNA motifs to regulate gene expression in the nucleus. However, this genomic function fails to explain many of the biological responses of the RA-RARα axis on T cells. We generated a mouse line where RARα is over-expressed in T cells to probe RARα function with unprecedented sensitivity. Using this model together with mice specifically lacking RARα in T cells, we found that RARα is required for prompt exit from metabolic quiescence in resting T cells upon T cell activation. The positive effect of RARα on metabolism is mediated through PI3K and subsequent activation of the Akt and mTOR signaling pathway. This largely non-genomic function of RARα is surprisingly ligand-independent and controls the differentiation of effector and regulatory T cell subsets.

Background This study group has previously identified IL-9–producing mucosal mast cell (MMC9) as the primary source of IL-9 to drive intestinal mastocytosis and experimental IgE-mediated food allergy. However, the molecular mechanisms that regulate the expansion of MMC9s remain unknown. Objectives This study hypothesized that IL-4 regulates MMC9 development and MMC9-dependent experimental IgE-mediated food allergy. Methods An epicutaneous sensitization model was used and bone marrow reconstitution experiments were performed to test the requirement of IL-4 receptor α (IL-4Rα) signaling on MMC9s in experimental IgE-mediated food allergy. Flow cytometric, bulk, and single-cell RNA-sequencing analyses on small intestine (SI) MMC9s were performed to illuminate MMC9 transcriptional signature and the effect of IL-4Rα signaling on MMC9 function. A bone marrow–derived MMC9 culture system was used to define IL-4–BATF signaling in MMC9 development. Results Epicutaneous sensitization– and bone marrow reconstitution–based models of IgE-mediated food allergy revealed an IL-4 signaling-dependent cell-intrinsic effect on SI MMC9 accumulation and food allergy severity. RNA-sequencing analysis of SI-MMC9s identified 410 gene transcripts reciprocally regulated by IL-4 signaling, including Il9 and Batf. In silico analyses identified a 3491-gene MMC9 transcriptional signature and identified 2 transcriptionally distinct SI MMC9 populations enriched for metabolic or inflammatory programs. Employing an in vitro MMC9-culture model system showed that generation of MMC9-like cells was induced by IL-4 and this was in part dependent on BATF. Conclusions IL-4Rα signaling directly modulates MMC9 function and exacerbation of experimental IgE-mediated food allergic reactions. IL-4Rα regulation of MMC9s is in part BATF-dependent and occurs via modulation of metabolic transcriptional programs.

Cu-based catalysts have been variously used in the water gas shift reaction (WGSR) and methanol synthesis, both of which use carbon monoxide as a common reactant. According to the Bell–Evans–Polanyi principle, CO adsorption energies (Eads,CO) directly affect the activation energies for CO hydrogenation. Thus, the understanding of the relationship between Eads,CO and the chemical properties of the catalytic surface is fundamental to catalyst design. In particular, recent studies have shown that effective catalysts can be developed by controlling the exposed facets or forming alloys with other transition metal to enhance the mechanical and electronic characteristics. In bimetallic catalysts, two types of chemical effects are known to determine the adsorption energies: one is the “strain” effect caused by lattice mismatch and the other is the “ligand” effect, generated by the change in orbital electrons. We conducted calculations on Cu/M(100), (111), and (211) surfaces (M = Ni, Ir, Pd and Pt) by using spin-polarized density functional theory (DFT) calculations to find the dominant factor, as well as trends, affecting CO adsorption. Our calculations suggest the ligand effect is the dominant contribution to Eads,CO, regardless of the type of facets. We also determined that the ligand contribution is caused by the loss of electrons from the surface Cu atoms. As a result, a proportional correlation between ligand contribution and electron charge transfer was observed. On investigating the strain effect on the (111) facet, we found that the results are consistent with d-band theory, while the Eads,CO on (100) and (211) facets showed the opposite trend.

Atomically dispersed Pd in Zeolites can adsorb NO to reduce NOx emission from vehicle exhausts at low temperature. In this contribution, low temperature NO adsorption abilities of Pd/ZSM-5 and Pd/SSZ-13 are comparatively studied. Co-adsorption of NO and H2O on Pd/ZSM-5 induced PdO sintering and deactivated NO adsorption ability. On the other hand, NO adsorption ability of Pd/SSZ-13 was maintained from the 500 °C treatment under NO and H2O where PdO sintering did not occur. Therefore, Pd/SSZ-13 would be the better candidate as NO storage material to reduce NOx emission from vehicle exhaust.

IL-9, produced mainly by specialized T cells, mast cells, and group 2 innate lymphoid cells, regulates immune responses, including anti-helminth and allergic responses. Polarization of naive CD4 T cells into IL-9–producing T cells (Th9s) is induced by IL-4 and TGF-β1 or IL-1β. In this article, we report that the transcription factor growth factor–independent 1 transcriptional repressor (GFI1) plays a negative role in mouse Th9 polarization. Moreover, the expression of GFI1 is controlled by liganded RARα, allowing GFI1 to mediate the negative effect of retinoic acid on IL-9 expression. The Gfi1 gene has multiple RARα binding sites in the promoter region for recruiting nuclear coactivator steroid receptor coactivator-3 and p300 for histone epigenetic modifications in a retinoic acid–dependent manner. Retinoic acid–induced GFI1 binds the Il9 gene and suppresses its expression. Thus, GFI1 is a novel negative regulator of Il9 gene expression. The negative GFI1 pathway for IL-9 regulation provides a potential control point for Th9 activity.

The regulations on NOx emissions from diesel vehicles have been stringent in recent years. Various techniques such as lean NOx trap (LNT) and selective catalytic reduction (SCR) have been developed to lessen the NOx emissions. The urea-based SCR method, which utilizes NH3 as reducing agent to remove NOx, is widely used. Determining optimal amount of injected urea that keeps NOx at outlet below regulated NOx emission and also minimizes the amount of dosed urea is important. Model predictive control (MPC) is popularly used to determine the optimal amount of injected urea. However, applying MPC to real vehicle driving may be difficult because the on-line computation of MPC is too costly to be conducted in the engine control unit (ECU), the computation performance of which is significantly low at present. Therefore, reinforcement learning (RL) is considered as an alternative to on-line control method. In this paper, deep Q-networks (DQN), which is an off-policy RL with discrete action space and suitable to solve high dimensional problem, is applied to determine the amount of urea injection in the SCR system. The simulation of urea injection control with DQN has been conducted with respect to inlet NOx emissions of real driving data.

Glucagon-like peptide 1 receptor agonists (GLP1Ra) are commonly used in type 2 diabetes mellitus (T2DM). However, differential risk of various cancers among GLP1Ra recipients is unknown. We inquired an aggregated electronic health record database, Explorys, and compared the adjusted odds ratio (aOR) of cancers between GLP1Ra and metformin users. Findings were validated in the FDA Adverse Event Reporting System (FDA FAERS). From 1/2005 to 6/2019, we identified 619 340 and 64 230 patients in the metformin and GLP1Ra group, respectively. Within 5 years of starting antidiabetic medications, GLP1Ra was associated with significantly lower incident risk of prostate (aOR 0.81, p = .03), lung (aOR 0.81, p = .05), and colon cancer (aOR 0.85, p = .03), while the risk of thyroid cancer was significantly higher (aOR 1.65, p p = .08), lung (aOR 0.52, p p = .31), and higher risk of thyroid cancer (aOR 4.33, p GLP1Ra is associated with lower risks of prostate, lung, and colon cancer, but higher risk of thyroid cancer.

BackgroundThe value of the electrocardiogram (ECG) for predicting long-term cardiovascular outcomes is not well defined. Machine learning methods are well suited for analysis of highly correlated data such as that from the ECG.MethodsUsing demographic, clinical, and 12-lead ECG data from the Third National Health and Nutrition Examination Survey (NHANES III), machine learning models were trained to predict 10-year cardiovascular mortality in ambulatory U.S. adults. Predictive performance of each model was assessed using area under receiver operating characteristic curve (AUROC), area under precision-recall curve (AUPRC), sensitivity, and specificity. These were compared to the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE).Results7,067 study participants (mean age: 59.2 ± 13.4 years, female: 52.5%, white: 73.9%, black: 23.3%) were included. At 10 years of follow up, 338 (4.8%) had died from cardiac causes. Compared to the PCE (AUROC: 0.668, AUPRC: 0.125, sensitivity: 0.492, specificity: 0.859), machine learning models only required demographic and ECG data to achieve comparable performance: logistic regression (AUROC: 0.754, AUPRC: 0.141, sensitivity: 0.747, specificity: 0.759), neural network (AUROC: 0.764, AUPRC: 0.149, sensitivity: 0.722, specificity: 0.787), and ensemble model (AUROC: 0.695, AUPRC: 0.166, sensitivity: 0.468, specificity: 0.912). Additional clinical data did not improve the predictive performance of machine learning models. In variable importance analysis, important ECG features clustered in inferior and lateral leads.ConclusionsMachine learning can be applied to demographic and ECG data to predict 10-year cardiovascular mortality in ambulatory adults, with potentially important implications for primary prevention.

The gut is connected to the CNS by immunological mediators, lymphocytes, neurotransmitters, microbes and microbial metabolites. A mounting body of evidence indicates that the microbiome exerts significant effects on immune cells and CNS cells. These effects frequently result in the suppression or exacerbation of inflammatory responses, the latter of which can lead to severe tissue damage, altered synapse formation and disrupted maintenance of the CNS. Herein, we review recent progress in research on the microbial regulation of CNS diseases with a focus on major gut microbial metabolites, such as short-chain fatty acids, tryptophan metabolites, and secondary bile acids. Pathological changes in the CNS are associated with dysbiosis and altered levels of microbial metabolites, which can further exacerbate various neurological disorders. The cellular and molecular mechanisms by which these gut microbial metabolites regulate inflammatory diseases in the CNS are discussed. We highlight the similarities and differences in the impact on four major CNS diseases, i.e., multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and autism spectrum disorder, to identify common cellular and molecular networks governing the regulation of cellular constituents and pathogenesis in the CNS by microbial metabolites., Neurological disorders: bugs that benefit the brain Disturbances of the microbial ecosystem in our gut create physiological disturbances that can accelerate the onset of neurological disease. The intestinal microbiome generates a diverse array of metabolites that can boost metabolic health, immune function, and other essential biological processes in the human host. Jeongho Park of Kangwon National University, Chuncheon, South Korea, and Chang Kim at the University of Michigan, Ann Arbor, USA, have reviewed research into how disruption of the healthy microbiome may contribute to Alzheimer’s, Parkinson’s, multiple sclerosis, and autism spectrum disorders. These studies indicate that such a “dysbiotic” state is generally associated with increased levels of inflammation. These disturbances are not sufficient to trigger neurological disorders on their own, but the resulting inflammatory state can act in concert with other biological risk factors to accelerate disease pathology.

While both the spleen and lymph nodes are called secondary lymphoid tissues, how lymphocytes enter these tissues are quite different from each other. This is because the architecture of the two types of organs and the mode of lymphocyte migration into these organs are quite distinct. In the spleen, T cells are passively released in the blood flow from the arterioles in the red pulp and marginal zone area. In contrast, T cells in the blood are actively captured on high endothelial venules in lymph nodes by the coordinated actions of CCR7 and several adhesion molecules. A recent finding indicates that T cells, released in the red pulp and marginal zone areas, actively find their way to the white zone by utilizing the migration track created by periarteriolar stromal cells. This finding adds one more piece to our understanding of lymphocyte migration for effective adaptive immune responses in the spleen.

Invariant NKT (iNKT) cells provide rapid innate T cell responses to glycolipid Ags from host cells and microbes. The numbers of CD1d-restricted iNKT cells are tightly controlled in mucosal tissues, but the mechanisms have been largely unclear. We found that vitamin A is a dominant factor that controls the population size of mucosal iNKT cells in mice. This negative regulation is mediated by the induction of the purinergic receptor P2X7 on iNKT cells. The expression of P2X7 is particularly high on intestinal iNKT cells, making iNKT cells highly susceptible to P2X7-mediated cell death. In vitamin A deficiency, iNKT cells fail to express P2X7 and are, therefore, resistant to P2X7-mediated cell death, leading to iNKT cell overpopulation. This phenomenon is most prominent in the intestine. We found that iNKT cells are divided into CD69+ sphingosine-1-phosphate receptor 1 (S1P1)− tissue resident and CD69− S1P1+ nonresident iNKT cells. The CD69+ S1P1− tissue-resident iNKT cells highly express P2X7 and are effectively controlled by the P2X7 pathway. The regulation of iNKT cells by vitamin A by the P2X7 pathway is important to prevent aberrant expansion of effector cytokine-producing iNKT cells. Our findings identify a novel role of vitamin A in regulating iNKT cell homeostasis in many tissues throughout the body.

In recent years, more stringent regulatory standards (EURO 6 emission standards) with a real driving test have been adopted for diesel vehicles. To meet the new regulations, a lean NO x trap (LNT) followed by a urealess selective catalytic reduction [passive SCR (pSCR)], i.e., LNT-pSCR, has been proposed as one of the promising aftertreatment systems for light-duty vehicles. In this brief, we propose hybrid nonlinear model predictive control (NMPC) that determines the optimal timing of rich mode operation for the LNT-pSCR system. First, a 1-D fundamental dynamic model of the LNT-pSCR is derived and parameters are estimated using chassis dynamometer test data. Second, a post-injection map, which describes the characteristics of the engine raw emission flowing into the LNT-pSCR system in the period affected by the rich mode, is constructed using the data. Third, the computational burden of hybrid NMPC is reduced by considering only feasible binary input cases with a successive linearization method. The proposed algorithm that uses the successive linearized LNT model with approximated pSCR NO x conversion is solved within the sample time. The performance of NMPC is investigated using the full LNT-pSCR model as a virtual plant, and the results show that it reduces more NO x with a shorter total duration of rich modes than those of reference control.

A series of CeO2-based catalysts were investigated for soot oxidation with O2. The macroporous CeO2 catalyst (M-CeO2) showed higher soot oxidation activity than mesoporous CeO2 due to the enhanced contact between catalyst and soot caused by the large pore size of M-CeO2. Moreover, various amounts of Ag (2–20 wt.%) were introduced to M-CeO2 to increase the activity, and the Ag-incorporated macroporous CeO2 catalysts (Ag(x)_M-CeO2) were characterized. Raman spectra showed that the ratio of active oxygen species (Oxn−) were different according to amount of Ag. The ratio of highly reactive superoxide (O2−) was largest for the Ag(5)_M-CeO2 catalyst, and then it was decreased as the Ag amount increased further. In addition, XPS analysis showed that the difference in Oxn− generation could be attributed to diverse surface oxygen vacancies in the catalysts. Hence, the amount of loaded Ag affected the surface oxygen vacancies of Ag(x)_M-CeO2 and consequently the ratio of Oxn− was different according to the surface oxygen vacancies of the catalysts. Ag(5)_M-CeO2 with the appropriate surface oxygen vacancies induced the promotion of O2− generation, resulting in the best soot oxidation activity. It was concluded that the amount of Ag on CeO2 has a great influence on the catalytic soot oxidation activity, and proper surface oxygen vacancies facilitated O2− generation, whereas excessive surface oxygen vacancies hindered the formation of highly reactive Oxn−.

Microbial metabolites, produced in the intestine, have significant effects on inflammatory diseases throughout the body. Short-chain fatty acids (SCFAs) have protective effects on experimental autoimmune encephalitis (EAE) responses but the detailed roles of SCFAs and their receptors in regulating autoimmune CNS inflammation have been unclear. SCFAs metabolically regulate T cells and change the phenotype of antigen presenting cells to efficiently induce IL-10+ regulatory T cells. In line with the overall protective effect, blood levels of major SCFAs, such as acetate, propionate and butyrate, are significantly decreased in long-term active progressive multiple sclerosis (MS) patients. Importantly, SCFAs can induce CD4+ effector T cells, which are highly inflammatory when transferred into mice, suggesting that the direct effect of SCFAs on T cells can even be pro-inflammatory in the CNS. In contrast to the moderate protective effect of SCFAs, mice deficient in GPR41 or GPR43 are more resistant to EAE pathogenesis. Thus, despite the overall protective function of SCFAs, SCFAs and their receptors have the potential to regulate autoimmune CNS inflammation both positively and negatively.

Passive NOx adsorber (PNA) is one of the promising technologies for reducing NOx emissions from vehicles during cold start periods. Precious metals supported on metal oxide and zeolite have been extensively investigated as PNA materials. Hence, it is worthwhile to compare two typical PNA materials, Pd/CeO2 and Pd/SSZ-13, so as to understand the differences between them. The NOx adsorption/desorption experiments were carried out under varying NO/NO2 ratios, and the result indicated that the NOx adsorption/desorption mechanisms on Pd/CeO2 and Pd/SSZ-13 are completely different. Specifically, NO and NO2 were competitively adsorbed on Pd/SSZ-13, while the NO adsorption on Pd/CeO2 was promoted by NO2. This difference is attributed to different adsorption sites: NOx is adsorbed on the ceria surface in Pd/CeO2, whereas it is adsorbed on atomic Pd2+ sites in Pd/SSZ-13, according to DRIFTS spectra in this study. In addition, the effect of sulfur poisoning was investigated as well. Pd/SSZ-13 showed moderate sulfur tolerance, while Pd/CeO2 completely lost its PNA ability after sulfur aging.

A lean NO x trap (LNT) catalyst has been widely used for removing NO x exhaust from lean-burn engines. However, the operation range of LNT has been limited because of the poor activity of LNT catalysts at low temperatures (≤300 °C), especially in urban driving conditions. To increase NO x removal efficiency during lean-rich cycle operation, a Cu/CeO2 (CC) catalyst was added to a Pt-BaO/CeO2 (PBC) catalyst. In comparison to PBC- or CC-only catalysts, the physical mixture of PBC and CC catalysts (PBC + CC) exhibited a significant synergy for both NO x storage and reduction efficiencies. In particular, low-temperature activity below 200 °C was greatly enhanced. A Pt-BaO-Cu/CeO2 (PBCC) catalyst, which was synthesized by depositing Pt and Cu together on a ceria support, showed poorer NO x removal efficiency. The origin of the synergistic effect over PBC + CC was investigated. Under lean conditions, the CC showed much better activity for NO oxidation, allowing for faster NO x storage on PBC. Under rich conditions, H2 was generated in situ on the CC by a water-gas shift reaction then accelerated the reduction of NO x, which had been stored on PBC, with a higher selectivity to N2. This simple modification in the catalyst can provide an important clue to enhance low-temperature activity of the commercial LNT system.

Various activation conditions such as temperature, time and the concentration of H2O during hydrothermal aging (HTA) treatment were extensively investigated to identify the proper ion-exchange conditions of Pd/SSZ-13 catalyst for low temperature NO adsorption performance. In addition, we examined how the cation in SSZ-13 (i.e. NH4-, Na- or K-SSZ-13) affects the low temperature NO adsorption performance of Pd/SSZ-13 after HTA treatment. It is found that NO adsorption ability begins to increase substantially when Pd/SSZ-13 is hydrothermally aged above 650 °C. Pd/SSZ-13 demonstrated the maximum NO adsorption performance after hydrothermal aging treatment in the range of 700–750 °C, followed by the severe decline above 850 °C. Such deactivation is attributed to the agglomeration of Pd species due to the dealumination of SSZ-13, as indicated by XRD and NMR analysis. At least 15 h of HTA treatment at 750 °C is required to provide the optimum activation of Pd/SSZ-13. Water vapor is essential component to activate Pd/SSZ-13 during the hydrothermal aging treatment. Unlike NH4-SSZ-13, Na- or K-SSZ-13 cannot be activated even if the optimum hydrothermal aging condition (750 °C for 25 h with 10% H2O) is applied. EXAFS and XRD analysis provides the evidence about the sintering of Pd species of the Pd/Na- or Pd/K-SSZ-13 catalysts rather than Pd ion exchange, indicating that the pre-existing Na or K ion inhibits the ion exchange during hydrothermal aging treatment. It can be concluded that the selection of proper hydrothermal aging conditions and zeolite form is essentially required to obtain the excellent low temperature NO adsorption performance of Pd/SSZ-13 as a passive NOx adsorber.

Selective catalytic reduction of NOx by urea (urea/SCR) and Lean NOx Trap (LNT) are two leading technologies for NOx reduction under lean condition. To quickly warm up SCR catalysts, considerable efforts have been made in integrating SCR onto a diesel particulate filter, so called SDPF. With the fact that the real driving emission test has taken effect, SDPF coupled with LNT might be one of most viable solutions to meet stringent emission regulations. However, desulfation process for LNT may result in a severe deactivation of SDPF in downstream. Here, we investigated the tolerance of Cu/zeolite SCR catalysts against periodic lean/rich operation condition simulating desulfation over LNT in front of SDPF. The lean/rich aging at 620 °C has led a severe deterioration of NOx conversion over Cu/SSZ-13 hydrothermally aged 800 °C, especially in high-temperature region above 400 °C. The accelerated NH3 oxidation to NO was the primary cause for the poor NOx removal activity, originated from the alteration of Cu state. Cu ions turned out to be converted to CuOx cluster upon their exposure to rich condition, which could partly be re-dispersed as Cu2+ ion after the post-treatment at 700 °C under lean condition. Cu/SSZ-13 with low Cu content revealed better activity maintenance under the high-temperature rich condition compared to higher Cu loading counterpart. Cu/LTA recently developed showed superior tolerance against rich feed due to less reducible nature of Cu+ ion therein compared to that in Cu/SSZ-13 leading to less CuOx formation.

The comparative behavior of Pd species in ZSM-5 and SSZ-13 zeolite supports resulting from thermal treatment in the presence and absence of water was studied. Thermal treatment at 750 °C caused the atomic distribution of Pd species in ZSM-5, while clustered Pd species remained in SSZ-13. The addition of water in the feed during thermal treatment resulted in the Pd sintering in the Pd/ZSM-5 catalyst, although Pd dispersion and agglomeration were concurrently observed in the Pd/SSZ-13 catalyst, depending on the Pd loading. The prepared catalysts were vacuum-treated to induce the auto-reduction of the atomic Pd species, and to compare the mobility of the Pd species within the different zeolite frameworks. The isolated Pd species in ZSM-5 were completely reduced to form large Pd clusters after vacuum treatment, while most of the Pd species in SSZ-13 remained atomically dispersed, indicating that the Pd mobility is higher in the former than in the latter. Hence, the different behavior of Pd/ZSM-5 and Pd/SSZ-13 catalysts against the oxidative and hydrothermal treatments could be explained by the intrinsic difference in the Pd mobility within the different types of zeolite. It is likely that the smaller pore size of SSZ-13 than ZSM-5 contributed to the lesser Pd mobility in the former. The hydrothermal treatment deactivated the NO adsorption ability of the other prepared Pd/zeolite catalysts with larger pore openings (Beta and Modernite zeolites), which further supports the present proposal.

Pd/SSZ-13, which has ability to adsorb NO at low temperature, is potentially used as a passive NOx adsorber for cold start application. We investigate the changes in the physicochemical properties and low temperature NO adsorption ability of Pd/SSZ-13 resulting from the reduction treatments with H2 or CO at various temperatures. Treatment with H2 at 500 °C does not give rise to the decrease in NO adsorption ability. However, the ability begins to decrease gradually with the increasing reduction temperature from 600 to 900 °C. On the other hand, CO treatment at 500 °C induces a significant decrease in NO adsorption ability. Combined EXAFS, HAADF-STEM and H2-TPR results clearly demonstrate that CO treatment induced more severe sintering of Pd species than H2 one at the same reduction temperature. After re-oxidation at 500 °C, H2-treated sample generated Pd ion species, which are the active site for NO adsorption at low temperature, more abundantly than CO-treated one, well corresponding to the higher NO adsorption ability over the former sample. Such phenomenon is attributed to the facile sintering behavior due to the high mobility of Pd-carbonyl complex upon the treatment with CO. It can be concluded that the reduction treatments with H2 and CO have different effect on Pd sintering, which is regarded as the main deactivation mechanism of Pd/SSZ-13 passive NOx adsorber.

Early hematopoietic progenitors undergo sophisticated developmental processes to become committed progenitors for innate lymphoid cells (ILC) in hematopoietic tissues, which ultimately become mature ILC subsets in the periphery. Basic leucine zipper ATF-like transcription factor (Batf) plays important roles in lymphocyte biology. We report that Batf regulates the production of bone marrow ILC progenitors and maintenance of peripheral ILCs. Batf is most highly expressed in ILCs among all lymphocytes. Data from in vivo and in vitro ILC differentiation experiments revealed that the expression of Batf is induced in early ILC progenitors at the α-lymphoid progenitor stage in response to the cytokine IL-7. Our Chromatin immunoprecipitation and retroviral gene transfer experiments revealed that up-regulated Batf binds and activates transcription of the Nfil3 gene to promote ILC hematopoiesis. Data from bone marrow chimera and parabiosis experiments support that Batf is intrinsically necessary to maintain normal numbers of early and late ILC progenitors in the bone marrow and mature ILC1, ILC2, ILC3, and NK cells in most peripheral tissues. Batf-deficient mice have ILC3 lymphopenia and fail to control Citrobacter rodentium infection. Moreover, ILC2 responses to cytokines were defective in Batf-deficient mice. Thus, Batf is required for normal ILC responses to inflammatory cytokines and bacterial infection. These data suggest that Batf plays fairly comprehensive roles in supporting bone marrow hematopoiesis, maintenance, and effector functions of ILCs.

Background: Low-density lipoprotein cholesterol (LDL-C) is commonly estimated from total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) using predefined equations which assume fixed or varying relationships between these parameters and may under- or overestimate LDL-C. Machine learning (ML) algorithms allow prediction of complex non-linear relationships. We, therefore, sought to investigate the utility of ML to predict LDL-C in comparison with two widely-used methods (Friedewald and Hopkins). Methods: We identified 7397 direct LDL-C (4716 HIV, 2060 uninfected controls) measurements in the Women's Interagency HIV Study (WIHS), a prospective study of women with and without HIV undergoing serial assessments. We trained and optimized 5 ML methods (linear regression, random forest, gradient boosting machine, support vector machine, and neural networks) to predict LDL-C using TC, HDL-C, and TG in 80% of the measurements and tested model performance in a holdout test set (20% of the measurements). Results: Overall, the support vector machine model had the best performance characteristics, outperforming Friedewald’s and Hopkins methods with higher R 2 , lower root mean square error and lower mean absolute error. The support vector machine model performance remained superior in participant subgroups with and without HIV and those with non-fasting measurements. Model performance parameters for the test dataset are shown in the Figure. Conclusions: A support vector machine learning model predicts directly measured LDL-C more accurately than Friedewald and Hopkins methods, especially in non-fasting patients with HIV. Further studies are needed to provide external validation.

Background Low-density lipoprotein cholesterol (LDL-C) is estimated from total cholesterol, high-density lipoprotein cholesterol and triglycerides using predefined equations which assume fixed or varying relationships between these parameters and may underestimate or overestimate LDL-C. Data on the performance of these equations in persons with HIV are limited. We sought to investigate the utility of the 3 most widely used methods (Friedewald, Hopkins, and the recently proposed NIH equation) to predict LDL-C in persons with HIV. Methods We identified 7397 direct LDL-C (5219 HIV, 2127 uninfected controls, 51 seroconvertors) measurements in the Women's Interagency HIV Study, and used the 3 equations (Friedewald, Hopkins, and NIH) to calculate LDL-C. We compared the performance of the 3 equations using root mean square error and coefficient of determination (R2). Results Overall, the Friedewald equation had the best performance characteristics, outperforming Hopkins and NIH methods with lower root mean square error and higher R2 at lower triglyceride levels. However, this association did not hold true at higher triglyceride levels (quartiles 3 and 4), whereas the Hopkins equation had better performance characteristics in quartile 3, none of the 3 equations were optimal in quartile 4. After adjusting for fasting status and triglycerides levels, HIV+ had larger mean difference compared with directly measured LDL using all 3 methods. Conclusions All 3 methods have lower accuracy in HIV+ vs HIV- women, even after adjusting for triglyceride levels and fasting status. Further research should focus on identifying methods to estimate LDL-C in HIV.

The lean NOx aftertreatment is one of the major barriers to the widespread adoption of advanced combustion powertrains for the reduction of both greenhouse gases and toxic exhausts. Urea/SCR, selective catalytic reduction of NOx by NH3 generated through urea decomposition, is commonly regarded as the best way to reduce NOx in low temperature lean exhaust. However, the urea/SCR system has inherent drawbacks, i.e., periodic refill of the aqueous urea solution and a complicated hardware system. Here, we demonstrated a state-of-the-art catalyst that is extremely selective and efficient for reducing NOx, primarily with the most abundant reductant, CO, particularly in the presence of O2 (>5%) at low temperature. Under temperatures lower than 250 °C, IrRu/Al2O3 catalysts achieved higher NOx conversion by CO only than a commercial Cu-based urea/SCR catalyst employing NH3 as a primary reductant. Furthermore, the IrRu catalyst revealed high thermal stability and SO2 tolerance, which are very important factors for real world applications.

Short-chain fatty acids, such as butyrate, are major gut microbial metabolites that are beneficial for gastrointestinal health. Clostridium butyricum MIYAIRI588 (CBM588) is a bacterium that produces a robust amount of butyrate and therefore has been used as a live biotherapeutic probiotic in clinical settings. Clostridioides difficile causes life-threatening diarrhea and colitis. The gut resident microbiota plays a critical role in the prevention of C. difficile infection (CDI), as the disruption of the healthy microbiota by antibiotics greatly increases the risk for CDI. We report that CBM588 treatment in mice significantly improved clinical symptoms associated with CDI and increased the number of neutrophils and Th1 and Th17 cells in the colonic lamina propria in the early phase of CDI. The protective effect of CBM588 was abolished when neutrophils, IFN-γ, or IL-17A were depleted, suggesting that induction of the immune reactants is required to elicit the protective effect of the probiotic. The administration of tributyrin, which elevates the concentration of butyrate in the colon, also increased the number of neutrophils in the colonic lamina propria, indicating that butyrate is a potent booster of neutrophil activity during infection. However, GPR43 and GPR109a, two G protein–coupled receptors activated by butyrate, were dispensable for the protective effect of CBM588. These results indicate that CBM588 and butyrate suppress CDI, in part by boosting antimicrobial innate and cytokine-mediated immunity.