Surviving cardiac arrest after carbon monoxide poisoning treated with hyperbaric oxygen therapy.

Carbon monoxide (CO) and cyanide poisoning are frequent causes of morbidity and mortality in cases of house and industrial fires. The 14th edition of guidelines from the Undersea and Hyperbaric Medical Society does not recommend hyperbaric oxygen (HBO2) treatment in those patients who have suffered a cardiac arrest and had to receive cardiopulmonary resuscitation. In this paper, we describe the case of a 31-year-old patient who received HBO2 treatment in the setting of cardiac arrest and survived.

Adaptive laboratory evolution of Clostridium autoethanogenum to metabolize CO2 and H2 enhances growth rates in chemostat and unravels proteome and metabolome alterations.

Gas fermentation of CO2 and H2 is an attractive means to sustainably produce fuels and chemicals. Clostridium autoethanogenum is a model organism for industrial CO to ethanol and presents an opportunity for CO2-to-ethanol processes. As we have previously characterized its CO2/H2 chemostat growth, here we use adaptive laboratory evolution (ALE) with the aim of improving growth with CO2/H2. Seven ALE lineages were generated, all with improved specific growth rates. ALE conducted in the presence of 2% CO along with CO2/H2 generated Evolved lineage D, which showed the highest ethanol titres amongst all the ALE lineages during the fermentation of CO2/H2. Chemostat comparison against the parental strain shows no change in acetate or ethanol production, while Evolved D could achieve a higher maximum dilution rate. Multi-omics analyses at steady state revealed that Evolved D has widespread proteome and intracellular metabolome changes. However, the uptake and production rates and titres remain unaltered until investigating their maximum dilution rate. Yet, we provide numerous insights into CO2/H2 metabolism via these multi-omics data and link these results to mutations, suggesting novel targets for metabolic engineering in this bacterium.

Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients.

BACKGROUND: Observational studies have shown that smoking is related to the diffusing capacity of the lungs for carbon monoxide (DLCO) in individuals with idiopathic pulmonary fibrosis (IPF). Nevertheless, further investigation is needed to determine the causal effect between these two variables. Therefore, we conducted a study to investigate the causal relationship between smoking and DLCO in IPF patients using two-sample Mendelian randomization (MR) analysis. METHODS: Large-scale genome-wide association study (GWAS) datasets from individuals of European descent were analysed. These datasets included published lifetime smoking index (LSI) data for 462,690 participants and DLCO data for 975 IPF patients. The inverse-variance weighting (IVW) method was the main method used in our analysis. Sensitivity analyses were performed by MR‒Egger regression, Cochran's Q test, the leave-one-out test and the MR-PRESSO global test. RESULTS: A genetically predicted increase in LSI was associated with a decrease in DLCO in IPF patients [ORIVW = 0.54; 95% CI 0.32-0.93; P = 0.02]. CONCLUSIONS: Our study suggested that smoking is associated with a decrease in DLCO. Patients diagnosed with IPF should adopt an active and healthy lifestyle, especially by quitting smoking, which may be effective at slowing the progression of IPF.

Síndrome del pulmón encogido asociado a lupus eritematoso sistémico: estudio de 9 pacientes / Shrinking lung syndrome in systemic lupus erythematosus: A study of 9 patients

Introducción: El síndrome de pulmón encogido (SPE) es una manifestación rara del lupus eritematoso sistémico. Nuestro objetivo fue describir las características clínicas, radiológicas y funcionales de una cohorte con SPE y su evolución en el tiempo.MétodosEstudio retrospectivo entre 2009 y 2018. Se recogieron datos demográficos, clínicos, funcionales, radiológicos y de tratamiento.ResultadosDe un total de 225 pacientes, 11 presentaron SPE (prevalencia del 4,8%). Dos fueron excluidos. La edad media fue 39,33±16 años, 6 eran mujeres. Los síntomas principales fueron la disnea y el dolor pleurítico. La capacidad vital forzada media fue del 49%, la capacidad pulmonar total del 60%, la capacidad de difusión de monóxido de carbono del 66%, el factor de transferencia para el monóxido de carbono del 128%, la presión inspiratoria máxima del 66% y la presión espiratoria máxima del 82%. Todos los pacientes recibieron corticosteroides. Después de una mediana de seguimiento de 19 meses, 4 casos presentaron mejoría y 4 estabilización.ConclusionesEl SPE debe tenerse presente en todo paciente lúpico con disnea de causa no evidente. Si bien suele evolucionar con mejoría, la mayoría queda con deterioro persistente a pesar del tratamiento. (AU)

Introduction: Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. Our aim was to describe the clinical, radiological, and functional characteristics of a cohort with SLS and its evolution over time.MethodsA retrospective study was conducted between 2009 and 2018. Demographic, clinical, functional, radiological, and treatment data were collected.ResultsOut of a total of 225 patients, 11 presented with SLS (prevalence of 4.8%). Two patients were excluded. The mean age was 39.33±16 years, and 6 were female. The main symptoms were dyspnea and pleuritic pain. The mean forced vital capacity was 49%, total lung capacity was 60%, carbon monoxide diffusing capacity was 66%, carbon monoxide transference factor was 128%, maximal inspiratory pressure was 66%, and maximal expiratory pressure was 82%. All patients received corticosteroids. After a median follow-up of 19 months, 4 cases showed improvement, and 4 cases remained stable.ConclusionsSLS should be considered in every lupus patient with unexplained dyspnea. Although it often shows improvement, many cases experience persistent deterioration despite treatment. (AU)

Radiolysis of myoglobin concentrated gels by protons: specific changes in secondary structure and production of carbon monoxide.

While particle therapy has been used for decades for cancer treatment, there is still a lack of information on the molecular mechanisms of biomolecules radiolysis by accelerated ions. Here, we examine the effects of accelerated protons on highly concentrated native myoglobin, by means of Fourier transform infrared and UV-Visible spectroscopies. Upon irradiation, the secondary structure of the protein is drastically modified, from mostly alpha helices conformation to mostly beta elements at highest fluence. These changes are accompanied by significant production of carbon monoxide, which was shown to come from heme degradation under irradiation. The radiolytic yields of formation of denatured protein, carbon monoxide, and of heme degradation were determined, and found very close to each other: G+denatured Mb ≈ G+CO ≈ G-heme = 1.6 × 10-8 ± 0.1 × 10-8 mol/J = 0.16 ± 0.01 species/100 eV. The denaturation of the protein to a beta structure and the production of carbon monoxide under ion irradiation are phenomena that may play an important role in the biological effects of ionizing radiation.

Reintroducing face-to-face support alongside remote support to form a hybrid stop smoking service in England: a formative mixed methods evaluation.

BACKGROUND: During the COVID-19 pandemic, United Kingdom (UK) stop smoking services had to shift to remote delivery models due to social distancing regulations, later reintroducing face-to-face provision. The "Living Well Smokefree" service in North Yorkshire County Council adopted a hybrid model offering face-to-face, remote, or a mix of both. This evaluation aimed to assess the hybrid approach's strengths and weaknesses and explore potential improvements. METHODS: Conducted from September 2022 to February 2023, the evaluation consisted of three components. First, qualitative interviews involved 11 staff and 16 service users, analysed thematically. Second, quantitative data from the QuitManager system that monitored the numbers and proportions of individuals selecting and successfully completing a 4-week quit via each service option. Third, face-to-face service expenses data was used to estimate the value for money of additional face-to-face provision. The qualitative findings were used to give context to the quantitative data via an "expansion" approach and complementary analysis. RESULTS: Overall, a hybrid model was seen to provide convenience and flexible options for support. In the evaluation, 733 individuals accessed the service, with 91.3% selecting remote support, 6.1% face-to-face, and 2.6% mixed provision. Remote support was valued by service users and staff for promoting openness, privacy, and reducing stigma, and was noted as removing access barriers and improving service availability. However, the absence of carbon monoxide monitoring in remote support raised accountability concerns. The trade-off in "quantity vs. quality" of quits was debated, as remote support reached more users but produced fewer carbon monoxide-validated quits. Primarily offering remote support could lead to substantial workloads, as staff often extend their roles to include social/mental health support, which was sometimes emotionally challenging. Offering service users a choice of support options was considered more important than the "cost-per-quit". Improved dissemination of information to support service users in understanding their options for support was suggested. CONCLUSIONS: The hybrid approach allows smoking cessation services to evaluate which groups benefit from remote, face-to-face, or mixed options and allocate resources accordingly. Providing choice, flexible provision, non-judgmental support, and clear information about available options could improve engagement and match support to individual needs, enhancing outcomes.

The carbon monoxide prodrug oCOm-21 increases Ca2+ sensitivity of the cardiac myofilament.

Patients undergoing cardiopulmonary bypass procedures require inotropic support to improve hemodynamic function and cardiac output. Current inotropes such as dobutamine, can promote arrhythmias, prompting a demand for improved inotropes with little effect on intracellular Ca2+ flux. Low-dose carbon monoxide (CO) induces inotropic effects in perfused hearts. Using the CO-releasing pro-drug, oCOm-21, we investigated if this inotropic effect results from an increase in myofilament Ca2+ sensitivity. Male Sprague Dawley rat left ventricular cardiomyocytes were permeabilized, and myofilament force was measured as a function of -log [Ca2+ ] (pCa) in the range of 9.0-4.5 under five conditions: vehicle, oCOm-21, the oCOm-21 control BP-21, and levosimendan, (9 cells/group). Ca2+ sensitivity was assessed by the Ca2+ concentration at which 50% of maximal force is produced (pCa50 ). oCOm-21, but not BP-21 significantly increased pCa50 compared to vehicle, respectively (pCa50 5.52 vs. 5.47 vs. 5.44; p < 0.05). No change in myofilament phosphorylation was seen after oCOm-21 treatment. Pretreatment of cardiomyocytes with the heme scavenger hemopexin, abolished the Ca2+ sensitizing effect of oCOm-21. These results support the hypothesis that oCOm-21-derived CO increases myofilament Ca2+ sensitivity through a heme-dependent mechanism but not by phosphorylation. Further analyses will confirm if this Ca2+ sensitizing effect occurs in an intact heart.

Distinguishing thrombotic thrombocytopenic purpura from primary immune thrombocytopenia accompanied by anemia using the carbon monoxide breath test.

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematological disorder. Early differentiation between TTP and primary immune thrombocytopenia (ITP) accompanied by anemia is crucial to initiate an appropriate therapeutic strategy. The objective of this study was to evaluate the predictive value of red blood cell lifespan (RBCLS), determined using the carbon monoxide breath test, in the differential diagnosis of these two diseases. METHODS: We conducted a retrospective analysis of 23 patients with TTP and 32 patients with ITP accompanied by anemia. RBCLS measurements were compared and evaluated between these two patient groups. RESULTS: TTP patients had a significantly shorter mean RBCLS (20 ± 8 days) than patients with ITP accompanied by anemia (77 ± 22 days, P < 0.001) and healthy controls (114 ± 25 days, P < 0.001). In TTP patients, RBCLS showed a significant negative correlation with reticulocyte percentage and lactic dehydrogenase levels (P < 0.001). When using a standard baseline of 75 days, RBCLS demonstrated a sensitivity of 100% and specificity of 53.1% in identifying TTP. The diagnostic accuracy could reach 93% by excluding the impact of gastrointestinal bleeding. By employing the Receiver Operator Characteristics (ROC) curve, the area under the curve for RBCLS was 0.985 (95% CI: 0-1, P < 0.01) in predicting TTP, with an optimal cut-off value of 32 days, and sensitivity and specificity of 95.7% and 96.9%, respectively. CONCLUSIONS: Our study proposes a simple and accessible method for evaluating RBCLS to differentiate between TTP and ITP accompanied by anemia.

Identifying a key spot for electron mediator-interaction to tailor CO dehydrogenase's affinity.

Fe‒S cluster-harboring enzymes, such as carbon monoxide dehydrogenases (CODH), employ sophisticated artificial electron mediators like viologens to serve as potent biocatalysts capable of cleaning-up industrial off-gases at stunning reaction rates. Unraveling the interplay between these enzymes and their associated mediators is essential for improving the efficiency of CODHs. Here we show the electron mediator-interaction site on ChCODHs (Ch, Carboxydothermus hydrogenoformans) using a systematic approach that leverages the viologen-reactive characteristics of superficial aromatic residues. By enhancing mediator-interaction (R57G/N59L) near the D-cluster, the strategically tailored variants exhibit a ten-fold increase in ethyl viologen affinity relative to the wild-type without sacrificing the turn-over rate (kcat). Viologen-complexed structures reveal the pivotal positions of surface phenylalanine residues, serving as external conduits for the D-cluster to/from viologen. One variant (R57G/N59L/A559W) can treat a broad spectrum of waste gases (from steel-process and plastic-gasification) containing O2. Decoding mediator interactions will facilitate the development of industrially high-efficient biocatalysts encompassing gas-utilizing enzymes.

A scalar-on-quantile-function approach for estimating short-term health effects of environmental exposures.

Environmental epidemiologic studies routinely utilize aggregate health outcomes to estimate effects of short-term (eg, daily) exposures that are available at increasingly fine spatial resolutions. However, areal averages are typically used to derive population-level exposure, which cannot capture the spatial variation and individual heterogeneity in exposures that may occur within the spatial and temporal unit of interest (eg, within a day or ZIP code). We propose a general modeling approach to incorporate within-unit exposure heterogeneity in health analyses via exposure quantile functions. Furthermore, by viewing the exposure quantile function as a functional covariate, our approach provides additional flexibility in characterizing associations at different quantile levels. We apply the proposed approach to an analysis of air pollution and emergency department (ED) visits in Atlanta over 4 years. The analysis utilizes daily ZIP code-level distributions of personal exposures to 4 traffic-related ambient air pollutants simulated from the Stochastic Human Exposure and Dose Simulator. Our analyses find that effects of carbon monoxide on respiratory and cardiovascular disease ED visits are more pronounced with changes in lower quantiles of the population's exposure. Software for implement is provided in the R package nbRegQF.

Exploring Rhodospirillum rubrum response to high doses of carbon monoxide under light and dark conditions.

Environmental concerns about residues and the traditional disposal methods are driving the search for more environmentally conscious processes, such as pyrolysis and gasification. Their main final product is synthesis gas (syngas) composed of CO, CO2, H2, and methane. Syngas can be converted into various products using CO-tolerant microorganisms. Among them, Rhodospirillum rubrum is highlighted for its biotechnological potential. However, the extent to which high doses of CO affect its physiology is still opaque. For this reason, we have studied R. rubrum behavior under high levels of this gas (up to 2.5 bar), revealing a profound dependence on the presence or absence of light. In darkness, the key variable affected was the lag phase, where the highest levels of CO retarded growth to more than 20 days. Under light, R. rubrum ability to convert CO into CO2 and H2 depended on the presence of an additional carbon source, such as acetate. In those conditions where CO was completely exhausted, CO2 fixation was unblocked, leading to a diauxic growth. To enhance R. rubrum tolerance to CO in darkness, a UV-accelerated adaptive laboratory evolution (UVa-ALE) trial was conducted to isolate clones with shorter lag phases, resulting in the isolation of clones 1.4-2B and 1.7-2A. The adaptation of 1.4-2B was mainly based on mutated enzymes with a metabolic function, while 1.7-3A was mostly affected at regulatory genes, including the anti-repressor PpaA/AerR. Despite these mutations having slight effects on biomass and pigment levels, they successfully provoked a significant reduction in the lag phase (-50%). KEYPOINTS: • CO affects principally R. rubrum lag phase (darkness) and growth rate (light) • CO is converted to CO2/H2 during acetate uptake and inhibits CO2 fixation (light) • UVa-ALE clones showed a 50% reduction in the lag phase (darkness).

Prenatal Household Air Pollution Exposure and Childhood Blood Pressure in Rural Ghana.

BACKGROUND: The association between prenatal household air pollution (HAP) exposure and childhood blood pressure (BP) is unknown. OBJECTIVE: Within the Ghana Randomized Air Pollution and Health Study (GRAPHS) we examined time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure with BP at 4 years of age and, separately, whether a stove intervention delivered prenatally and continued through the first year of life could improve BP at 4 years of age. METHODS: GRAPHS was a cluster-randomized cookstove intervention trial wherein n=1,414 pregnant women were randomized to one of two stove interventions: a) a liquefied petroleum gas (LPG) stove or improved biomass stove, or b) control (open fire cooking). Maternal HAP exposure over pregnancy and child HAP exposure over the first year of life was quantified by repeated carbon monoxide (CO) measurements; a subset of women (n=368) also performed one prenatal and one postnatal personal fine particulate matter (PM2.5) measurement. Systolic and diastolic BP (SBP and DBP) were measured in n=667 4-y-old children along with their PM2.5 exposure (n=692). We examined the effect of the intervention on resting BP z-scores. We also employed reverse distributed lag models to examine time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure and resting BP z-scores. Among those with PM2.5 measures, we examined associations between PM2.5 and resting BP z-scores. Sex-specific effects were considered. RESULTS: Intention-to-treat analyses identified that DBP z-score at 4 years of age was lower among children born in the LPG arm (LPG ß=-0.20; 95% CI: -0.36, -0.03) as compared with those in the control arm, and females were most susceptible to the intervention. Higher CO exposure in late gestation was associated with higher SBP and DBP z-score at 4 years of age, whereas higher late-first-year-of-life CO exposure was associated with higher DBP z-score. In the subset with PM2.5 measurements, higher maternal postnatal PM2.5 exposure was associated with higher SBP z-scores. DISCUSSION: These findings suggest that prenatal and first-year-of-life HAP exposure are associated with child BP and support the need for reductions in exposure to HAP, with interventions such as cleaner cooking beginning in pregnancy. https://doi.org/10.1289/EHP13225.

Hyperbaric oxygen for the treatment of carbon monoxide-induced delayed neurological sequelae: a case report and review of the literature.

Introduction: Hyperbaric oxygen treatment (HBOT) remains a recognised treatment for acute carbon monoxide (CO) poisoning, but the utility of HBOT in treating CO-induced delayed neurological sequelae (DNS) is not yet established. Case description: A 26-year old woman presented with reduced consciousness secondary to CO exposure from burning charcoal. She underwent a single session of HBOT with US Navy Treatment Table 5 within six hours of presentation, with full neurological recovery. Eight weeks later, she represented with progressive, debilitating neurological symptoms mimicking Parkinsonism. Magnetic resonance imaging of her brain demonstrated changes consistent with hypoxic ischaemic encephalopathy. The patient underwent 20 sessions of HBOT at 203 kPa (2 atmospheres absolute) for 115 minutes, and received intravenous methylprednisolone 1 g per day for three days. The patient's neurological symptoms completely resolved, and she returned to full-time professional work with no further recurrence. Discussion: Delayed neurological sequelae is a well-described complication of CO poisoning. In this case, the patient's debilitating neurocognitive symptoms resolved following HBOT. Existing literature on treatment of CO-induced DNS with HBOT consists mainly of small-scale studies and case reports, many of which similarly suggest that HBOT is effective in treating this complication. However, a large, randomised trial is required to adequately determine the effectiveness of HBOT in the treatment of CO-induced DNS, and an optimal treatment protocol.

Carbon monoxide affects early cardiac development in an avian model.

INTRODUCTION: Carbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association. METHODS: Here, we exposed chick embryos in ovo to CO at three different concentrations (3, 9, 18 ppm) plus air control (4 protocols in total) for the first 9 days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight, ventricular wall thickness, ventricular-septal thickness and atrial wall thickness. RESULTS: We found that heart weight was reduced for the low and moderate exposures compared to air, that atrial wall and ventricular wall thickness was increased for the moderate and high exposures compared to air and that ventricular septal thickness was increased for low, moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols. CONCLUSIONS: This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.

Assessment of emissions and potential occupational exposure to carbon monoxide during biowaste composting.

To date, only a few studies focused on the carbon monoxide (CO) production during waste composting; all targeted on CO inside piles. Here, the CO net emissions from compost piles and the assessment of worker's occupational risk of exposure to CO at large-scale composting plants are shown for the first time. CO net emissions were measured at two plants processing green waste, sewage sludge, or undersize fraction of municipal solid waste. Effects of the location of piles (hermetised hall vs. open yard) and turning (before vs. after) were studied. Higher CO net emission rates were observed from piles located in a closed hall. The average CO flux before turning was 23.25 and 0.60 mg‧m-2‧h-1 for hermetised and open piles, respectively, while after- 69.38 and 5.11 mg‧m-2‧h-1. The maximum CO net emissions occurred after the compost was turned (1.7x to 13.7x higher than before turning). The top sections of hermetised piles had greater CO emissions compared to sides. Additionally, 5% of measurement points of hermetised piles switched to 'CO sinks'. The 1-h concentration in hermetised composting hall can reach max. ~50 mg CO∙m-3 before turning, and >115 mg CO∙m-3 after, exceeding the WHO thresholds for a 1-h and 15-min exposures, respectively.

Azoanthracene-core structure as Cu2+-assisted CO sensing probe: Characterization, performance, and bioimaging.

Detection of endogenous CO (carbon monoxide) is an interesting topic in biology because it has been discovered as a messenger for signal transduction and therapeutic effects in vital biological activities. Fluorescence imaging has proven a powerful tool for detecting endogenous CO, which drives the development of low-cost and easy-to-use fluorescent probes. In this study, four azobenzene derivatives (A1, A2, A3, and A4) with various substituents were reported, including their geometric structures, photophysical parameters, and spectral responses to Cu2+ and CO. The relationship between substituent structure and performance was discussed along with Cu2+ quenching and CO sensing mechanisms. The optimal probe (A1), which had no substituent, efficiently quenched fluorescence in the presence of Cu2+, with its PLQY decreased from 0.33 to 0.02, PLQY = photoluminescence quantum yield. Upon CO deoxidization, A1's fluorescence could be recovered (PLQY recovered to 0.32) within 180 s. Its sensing mechanism was static by forming a non-fluorescent complex with Cu2+ (with a stoichiometric ratio of 1:1). The bioimaging performance of A1 for endogenous CO in HeLa cells was reported.

Emission performance evaluation of urban passenger car fleet through field investigation data in a megacity.

Continued improvements in living standards and the economic well-being in the megacities have led to a huge surge in vehicular density. The worst environmental outcome of the same has been persistent unsafe urban air quality, thanks to vehicular emission. Further, the existing inspection and maintenance programs, conceived to check such emission remain largely ineffective, particularly in developing countries. This is due to the absence of a thorough assessment of the vehicle's compliance with the in-use emission norms generated through reliable field investigation data. To address this gap, the present comprehensive study collected real-time tailpipe emission data from 2040 cars in Delhi, India. Exhaust emission parameters, namely, CO (carbon monoxide), HC (hydrocarbon), and SE (smoke emission), were recorded from both petrol and diesel-driven cars of private ownership, in collaboration with the emission compliance test centers. The performance of cars was assessed in terms of their compliance with the in-use BS (Bharat Stage) emission norms. The one-of-its-kind study reported the petrol cars to be highly compliant toward the BS IV norm while faring even better toward BS II for both CO and HC emissions (80-90%). The conformance to the HC norm was found to be typically better than that for CO (85-90% versus 75-80%). For the diesel-driven cars, BS III compliance levels were reported relatively better compared to BS IV (90% in the case of the former against 80% in the latter's case). Further, the study puts forward a clear indication that the in-use emission norm and maintenance status of cars have a direct and negative relationship with tailpipe emission parameters. Cars of both overseas and domestic origin have almost equal degrees of compliance with the emission norms (over 80% in any case). The study recommends the incorporation of these two critical vehicular variables, i.e., maintenance status and in-use emission standard in the emission certification policy.

Effects of the turbocharged Miller cycle strategy on the performance improvement and emission characteristics of diesel engines.

The turbocharged Miller cycle strategy is studied to improve the power density of diesel engines and reduce emissions. A thermodynamic model and a 1D simulation model of turbocharged diesel engine are established. Results show that the introduction of the Miller cycle reduces the thermal efficiency under naturally aspirated conditions because of the low effective compression ratio, whereas it increases the thermal efficiency under a turbocharged condition owing to the energy recovered by the turbocharger. Under restricted combustion pressure and fixed intake mass, the thermal efficiency first increases and then decreases with increasing Miller cycle ratio, and the peaks occur at approximately 30%-50%. The gain of isochoric combustion ratio overlaps the loss of effective compression ratio due to the Miller cycle on the lower side, whereas it reverses on the higher side. With maximum and equal intake mass, the maximum power initially increases and subsequently decreases with increasing Miller cycle ratio, reaching a peak at 40%. Under a fixed isochoric combustion ratio, the thermal efficiency first increases and then decreases with increasing intake mass, and the optimum intake mass corresponding to the highest thermal efficiency decreases with increasing Miller cycle ratio. The lower the restricted combustion pressure is, the higher the gain in power and thermal efficiency by the Miller cycle strategy. Based on the calculation of the 1D model validated using a practical engine, the power can be increased from 41.6 kW/L to 100 kW/L while the brake thermal efficiency can be increased from 34.98% into 38.55% by increasing the Miller cycle ratio from 19% to 30% and the combustion pressure from 17.7 MPa to 35 MPa. With the application of the supercharged Miller cycle, when the Miller cycle ratio is 30% and the power intensity is increased from 60 kW/L to 100 kW/L, NOx decreases by 32.4%, CO decreases by 28%, showing a tendency to decrease and then stabilize, and HC increases by 5.3%. When the power is 80 kW/L and the Miller cycle ratio is increased from 10% to 30%, NOx decreases by 8.6%, CO decreases by 2%, and HC increases by 0.04%.

Carbon monoxide-releasing nanomotors based on endogenous biochemical reactions for tumor therapy.

The lack of selective release ability in the tumor microenvironment and the limited efficacy of monotherapy are important factors that limit the current use of carbon monoxide (CO) donors for tumor therapy. Herein, inspired by endogenous biochemical reactions in vivo, one kind of CO-releasing nanomotor was designed for the multimodal synergistic treatment of tumor. Specifically, glucose oxidase (GOx) and 5-aminolevulinic acid (5-ALA) were co-modified onto metal-organic framework material (MIL-101) to obtain MIL-GOx-ALA nanomotors (M-G-A NMs), which exhibit excellent biocompatibility and degradation ability in tumor microenvironment. Subsequently, the released 5-ALA generates CO in the tumor microenvironment through an endogenous reaction and further acts on mitochondria to release large amounts of reactive oxygen species (ROS), which directly kill tumor cells. Furthermore, the produced ROS and the degradation products of M-G-A NMs can also provide the reaction substrate for the Fenton reaction, thereby enhancing chemodynamic therapy (CDT) and inducing apoptosis of tumor cells. Both in vitro and in vivo experimental data confirm the successful occurrence of the above process, and the combination of CO gas therapy/enhanced CDT can effectively inhibit tumor growth. This CDT-enhancing agent designed based on endogenous biochemical reactions has good prospects for tumor treatment application.