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At least 1,549 records · Page 86

Post-Combat-Injury Opioid Prescription and Alcohol Use Disorder in the Military

Previous studies have identified combat exposure and combat traumatic experience as problematic drinking risk factors. Increasing evidence suggests that opioid use increases the risk of alcohol use disorder. This study investigated the association between opioid prescription use after injury and (1) alcohol use disorder and (2) severity of alcohol use disorder among deployed military servicemembers. Deidentified health records data of 9,029 deployed servicemembers from a retrospective cohort study were analyzed. Data were randomly selected from the Department of Defense Trauma Registry and included servicemembers with combat injuries during deployment in Iraq or Afghanistan (2002–2016). Pharmacy records and International Classification of Diseases, Ninth and Tenth Revision diagnosis codes were used. Three groups were identified (no opioid prescription use, nonpersistent opioid prescription use, and persistent opioid prescription use) and were compared on the basis of alcohol use disorder risk using Cox proportional hazard models. Data analyses were performed in 2021. Of the 9,029 servicemembers with combat injury, 2,262 developed alcohol use disorder (1,322 developed severe alcohol use disorder). Compared with no opioid prescription use, increased alcohol use disorder risk was associated with persistent opioid prescription use, with a hazard ratio of 1.13 (95% CI=1.02, 1.26). After covariate adjustment, increased risk remained statistically significant (hazards ratio=1.24; 95% CI=1.10, 1.39). There was no significant difference in alcohol use disorder risk between no opioid prescription use and nonpersistent opioid prescription use. The risk of severe alcohol use disorder did not vary by opioid use among servicemembers with alcohol use disorder diagnosis. Furthermore, the findings of the study suggest that the incidence of alcohol use disorder was higher among injured servicemembers with persistent opioid prescription use than among those without opioid use. If replicated in prospective studies, the findings highlight the need for clinicians to consider the current and history of alcohol use of patients in initiating treatment involving opioids.

60 APPLIED LIFE SCIENCES↗

Assessment of advanced solvent-based post-combustion CO 2 capture processes using a bi-objective optimization technique

We report the optimized performance of two advanced CO 2 capture processes is compared to that of a monoethanolamine (MEA) baseline for a gas-powered CO 2 capture retrofit of an existing coal-fired facility. The advanced temperature-swing processes utilize piperazine and mixed-salt solvents. The mixed-salt treatment involves the use of ammonia for CO 2 absorption and potassium carbonate primarily to control ammonia slip. The processes are represented in terms of energy duty requirements within a modular heat integration code developed for CO 2 capture modeling and optimization. The model includes a baseload coal plant, a gas-fired subsystem containing gas turbines and a heat recovery steam generator (HRSG), and a CO 2 capture facility. A formal bi-objective optimization procedure is applied to determine the design (e.g., detailed HRSG components and pressure levels, gas turbine capacity, CO 2 capture capacity) and time-varying operations of the facility to simultaneously maximize net present value (NPV) and minimize total capital requirement (TCR), while meeting a maximum CO 2 emission intensity constraint. For a realistic scenario constructed using historical data, optimization results indicate that both advanced processes outperform MEA in both objectives, and the mixed-salt process in turn outperforms the piperazine process. Specifically, for the scenario considered, the base case mixed-salt process achieves 16% greater NPV and 14% lower TCR than the MEA process, and 10% greater NPV and 5% lower TCR than the piperazine process. A five-case sensitivity study of the mixed-salt process indicates that it is competitive with the piperazine process and consistently outperforms the MEA process.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Impact of post-rainfall evaporation from porous roof tiles on building cooling load in subtropical China

Rainfall occurs frequently in subtropical regions of China, with the subsequent water evaporation from building roofs impacting the thermal performance and the energy consumption of buildings. In this paper, we proposed a novel simulation method using actual meteorological data to evaluate this impact. New features were developed in EnergyPlus to enable the simulation: (1) an evaporation latent heat flux source term was added to the heat balance equation of the external surface and (2) algorithms for the evaporative cooling module (ECM) were developed and implemented into EnergyPlus. The ECM experimental results showed good agreement with the simulated results. The ECM was used to assess the impact of evaporation from porous roof tiles on the cooling load of a one-floor building in subtropical China. The results show that the evaporation process decreased the maximal values of the external and internal roof surface temperatures by up to 6.4 °C and 3.2 °C, respectively, while the lower internal surface temperature decreased the room accumulated cooling load by up to 14.8% during the hot summer period. Lastly, the enhanced EnergyPlus capability can be used to evaluate the evaporative cooling performance of roofs with water-storage mediums, as well as to quantify their impact on building cooling loads.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

HD domain of SAMHD1 influences Vpx-induced degradation at a post-interaction step

Primate SAMHD1 proteins are potent inhibitors of viruses, including retroviruses such as HIV-1, HIV-2, and SIV. Vpx, a distinctive viral protein expressed by HIV-2 and some SIVs, induces SAMHD1 degradation by forming a Vpx-DCAF1-based ubiquitin ligase complex. Either the N- or the C-terminus of SAMHD1 is critical for Vpx-induced degradation, depending on the types of SAMHD1 and Vpx proteins. However, it was not fully understood whether other regions of SAMHD1 also contribute to its depletion by Vpx. In the present study, we report that SAMHD1 from chicken (SAMHD1{sub GG}) was not degraded by SIVmac Vpx, in contrast with results for human SAMHD1 (SAMHD1{sub HS}). Results regarding to SAMHD1{sub HS} and SAMHD1{sub GG} fusion proteins supported previous findings that the C-terminus of SAMHD1{sub HS} is essential for Vpx-induced degradation. Internal domain substitution, however, revealed that the HD domain also contributes to Vpx-mediated SAMHD1 degradation. Interestingly, the HD domain influenced Vpx-mediated SAMHD1 degradation without affecting Vpx-SAMHD1 interaction. Therefore, our findings revealed that factors in addition to Vpx-SAMHD1 binding influence the efficiency of Vpx-mediated SAMHD1 degradation. - Highlights: • SAMHD1{sub GG} from chicken could not be depleted by SIVmac Vpx. • The C-terminus of human SAMHD1{sub HS} is critical for its degradation by Vpx. • The HD domain is essential for Vpx-induced degradation of SAMHD1{sub HS}. • Altering the HD domain does not affect Vpx-SAMHD1 interaction.

60 APPLIED LIFE SCIENCES↗

CACUL1/CAC1 attenuates p53 activity through PML post-translational modification

Promyelocytic leukaemia (PML) is a tumor suppressor protein covalently conjugated with SUMO family proteins, leading to the formation of PML nuclear bodies (NBs). PML-NBs provide a platform for efficient posttranslational modification of targets and protein-protein interaction, contributing to the adjustment of gene expression and chromatin integrity. Although PML SUMOylation is thought to play important roles in diverse cellular functions, the control mechanisms of adequate modification levels have remained unsolved. Here, we report that Cullin-related protein CACUL1/CAC1 (CACUL1) inhibits PML posttranslational modification. CACUL1 interacts with PML and suppresses PML SUMOylation, leading to the regulation of PML-NB size in the nucleus. We also found that Ubc9, a SUMO-conjugating enzyme, binds to CACUL1 and antagonizes the interaction between CACUL1 and PML. Furthermore, CACUL1 attenuates p53 transcriptional activity. These data suggest that CACUL1 is a novel regulator that negatively controls p53 activity through the regulation of PML SUMOylation. - Highlights: • CACUL1 suppresses PML SUMOylation. • CACUL1 regulates PML-NBs size. • CACUL1 attenuates p53 transcriptional activity.

43 PARTICLE ACCELERATORS↗

Deficiency of liver-X-receptor-α reduces glucose uptake and worsens post-myocardial infarction remodeling

Liver X receptor α (LXRα) is an endogenous protective receptor against ischemic heart diseases. However, whether LXRα regulated glucose metabolism in ischemic heart diseases has not been investigated. In this study we investigated the involvement of LXRα on glucose metabolism in cardiac remodeling after myocardial infarction (MI). MI was induced in mice by permanent ligation of the left anterior descending coronary artery (LCA). Genetic LXRα deletion significantly worsened cardiac remodeling and impaired cardiac function at 4 weeks after MI. Cardiac 18F-fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) demonstrated that the FDG standardized uptake value (SUV) was significantly lower in LXRα{sup −/−} mice as compared to WT mice. Mechanistically, GLUT1/4 and AMPK phosphorylation were significantly downregulated while CD36 expression was markedly upregulated in LXRα{sup −/−} mice. This study demonstrated that deficiency of LXRα decreased glucose uptake after MI, resulting in a metabolic shift that suppressed glucose metabolism, which was in association with adverse cardiac remodeling. - Highlights: • Deficiency of LXRα reduced glucose uptake after myocardial infarction (MI). • Loss of LXRα downregulated GLUT1/4 expressions in response to MI. • Targeting LXRα to promote glucose uptake may protect against cardiac remodeling.

60 APPLIED LIFE SCIENCES↗

Redox regulation of plant S-nitrosoglutathione reductase activity through post-translational modifications of cysteine residues

Highlights: • Plant GSNORs are inhibited by cysteine oxidative modification by H{sub 2}O{sub 2}. • GSNORs are inhibited by NO and nitroxyl though reversible cysteine modifications. • Oxidative and nitrosative inhibition of GSNOR can be reversed by reducing agents. • S-nitrosation of conserved cysteine 271 was confirmed in inhibited GSNOR enzyme. Nitric oxide (NO) is considered as a signalling molecule involved in a variety of important physiological and pathological processes in plant and animal systems. The major pathway of NO reactions in vivo represents S-nitrosation of thiols to form S-nitrosothiols. S-nitrosoglutathione reductase (GSNOR) is the key enzyme in the degradation pathway of S-nitrosoglutathione (GSNO), a low-molecular weight adduct of NO and glutathione. GSNOR indirectly regulates the level of protein S-nitrosothiol in the cells. This study was focused on the dynamic regulation of the activity of plant GSNORs through reversible S-nitrosation and/or oxidative modifications of target cysteine residues. Pre-incubation with NO/NO{sup −} donors or hydrogen peroxide resulted in a decreased reductase and dehydrogenase activity of all studied plant GSNORs. Incubation with thiol reducing agent completely reversed inhibitory effects of nitrosative modifications and partially also oxidative inhibition. In biotin-labelled samples, S-nitrosation of plant GSNORs was confirmed after immunodetection and using mass spectrometry S-nitrosation of conserved Cys271 was identified in tomato GSNOR. Negative regulation of constitutive GSNOR activity in vivo by nitrosative or oxidative modifications might present an important mechanism to control GSNO levels, a critical mediator of the downstream signalling effects of NO, as well as for formaldehyde detoxification in dehydrogenase reaction mode.

60 APPLIED LIFE SCIENCES↗

Basolateral cholesterol depletion alters Aquaporin-2 post-translational modifications and disrupts apical plasma membrane targeting

Highlights: • A role of the basolateral plasma membrane in targeting of AQP2 to the apical membrane is shown. • The levels of basolateral membrane cholesterol are involved in this mechanism. • Cholesterol depletion increases AQP2 ubiquitylation but prevents AQP2 phosphorylation. • Effects of cholesterol depletion on AQP2 are independent of changes in intracellular cAMP. • Results are important for understanding basic principles of membrane protein trafficking. Apical plasma membrane accumulation of the water channel Aquaporin-2 (AQP2) in kidney collecting duct principal cells is critical for body water homeostasis. Posttranslational modification (PTM) of AQP2 is important for regulating AQP2 trafficking. The aim of this study was to determine the role of cholesterol in regulation of AQP2 PTM and in apical plasma membrane targeting of AQP2. Cholesterol depletion from the basolateral plasma membrane of a collecting duct cell line (mpkCCD14) using methyl-beta-cyclodextrin (MBCD) increased AQP2 ubiquitylation. Forskolin, cAMP or dDAVP-mediated AQP2 phosphorylation at Ser269 (pS269-AQP2) was prevented by cholesterol depletion from the basolateral membrane. None of these effects on pS269-AQP2 were observed when cholesterol was depleted from the apical side of cells, or when MBCD was applied subsequent to dDAVP stimulation. Basolateral, but not apical, MBCD application prevented cAMP-induced apical plasma membrane accumulation of AQP2. These studies indicate that manipulation of the cholesterol content of the basolateral plasma membrane interferes with AQP2 PTM and subsequently regulated apical plasma membrane targeting of AQP2.

60 APPLIED LIFE SCIENCES↗

Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1

Highlights: • Nicorandil upregulates cardiomyocyte autophagy, while reduces cardiomyocytes apoptosis. • Nicorandil inhibits left ventricular remodeling and cardiac dysfunction in mice with myocardial infarction (MI). • Mst1 serves as a downstream regulator of nicorandil. Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI.

60 APPLIED LIFE SCIENCES↗

Post-ischemic administration of 5-methoxyindole-2-carboxylic acid at the onset of reperfusion affords neuroprotection against stroke injury by preserving mitochondrial function and attenuating oxidative stress

Highlights: • MICA administered at the onset of reperfusion triggers a postconditioning effect. • MICA postconditioning preserves mitochondrial function. • MICA-triggered neuroprotection involves NQO1 upregulation by the Nrf2 signaling. • Oxidative damage is attenuated by MICA postconditioning. We previously reported that 5-methoxyindole-2-carboxylic acid (MICA) could induce preconditioning effect in the ischemic brain of rat. In the present study, we addressed the question of whether MICA could also trigger a postconditioning effect in ischemic stroke. To this end, MICA (100 mg/kg body weight) was injected intraperitoneally at the onset of 24 h reperfusion following 1 h ischemia in rat brain. Results indicate that stroked animals treated with MICA showed less brain infarction volume than that of vehicle-treated animals. Further experiments revealed that brain mitochondrial complexes I and IV showed elevated enzymatic activities in MICA treated group and the elevation in complex I activity was likely contributed by seemingly enhanced expression of many complex I subunits, which was determined by mass spectral peptide sequencing. When compared with vehicle-treated rats, the preservation of complexes I and IV activities was shown to be accompanied by enhanced mitochondrial membrane potential, increased ATP production, and decreased caspase-3 activity. Additional studies also indicate the involvement of NQO1 upregulation by the Nrf2 signaling pathway in this MICA postconditioning paradigm. Consequently, attenuated oxidative stress in the MICA treated group reflected by decrease in H{sub 2}O{sub 2} production and protein carbonylation and lipid peroxidation was detected. Taken together, the present study demonstrates that MICA can also induce a postconditioning effect in the ischemic brain of rat and the underlying mechanism likely involves preservation of mitochondrial function, upregulation of cellular antioxidative capacity, and attenuation of oxidative stress.

60 APPLIED LIFE SCIENCES↗

Pre- and post-coppice production and biomass chemistry of eastern cottonwood and hybrid poplars in the southeastern US

Sustainably grown feedstocks for bioenergy and bioproducts are important tools to fight climate change, provide ecosystem services, and sequester carbon. Populus species including hybrid poplars have been utilized around the world, and in the southeastern US native eastern cottonwood (P. deltoides) is often favored due to its resistance to stem cankers. However, P. deltoides has historically been grown in single stem production and its relative performance in short rotation coppice production, prevalent in Europe, is not well documented. Therefore, this study's goals were to evaluate eastern cottonwood (D × D) and hybrid poplar (P. deltoides × P. maximowiczii (D × M) and P. deltoides × P. trichocarpa (D × T) taxa) productivity under a two-year establishment and two-year coppice cycle, analyze biomass chemistry properties, identify drivers of productivity, and select clones suited for marginal vs. optimal sites. We found that D × M and D × D grew best in both establishment and coppice rotation with production increasing after coppice. Taxa and clones exhibited few differences in select biomass chemistry properties despite differences in growth rate and stem size. Across years and sites, production was correlated with the soil's carbon to nitrogen ratio, percentage of sand, and shrink-swell potential of the soil. A D × M clone ‘9709’ tended to perform better than other tested clones on marginal sites and had the highest survival rate after four years. Overall, this research suggests that Populus species can be grown in coppice rotation in the southeastern US with the potential for hybrid poplars to be successful on certain sites in the region although longer term studies are necessary to confirm these results.

54 ENVIRONMENTAL SCIENCES↗