Natural withanolides, an update.

Covering: March 2010 to December 2020. Previous review: Nat. Prod. Rep., 2011, 28, 705This review summarizes the latest progress and perspectives on the structural classification, biological activities and mechanisms, metabolism and pharmacokinetic investigations, biosynthesis, chemical synthesis and structural modifications, as well as future research directions of the promising natural withanolides. The literature from March 2010 to December 2020 is reviewed, and 287 references are cited.

Identification of HMGCR as the anticancer target of physapubenolide against melanoma cells by in silico target prediction.

Physapubenolide (PB), a withanolide-type compound extracted from the traditional herb Physalis minima L., has been demonstrated to exert remarkable cytotoxicity against cancer cells; however, its molecular mechanisms are still unclear. In this study, we demonstrated that PB inhibited cell proliferation and migration in melanoma cells by inducing cell apoptosis. The anticancer activity of PB was further verified in a melanoma xenograft model. To explore the mechanism underlying the anticancer effects of PB, we carried out an in silico target prediction study, which combined three approaches (chemical similarity searching, quantitative structure-activity relationship (QSAR), and molecular docking) to identify the targets of PB, and found that PB likely targets 3-hydroxy-methylglutaryl CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, which promotes cancer cell proliferation, migration, and metastasis. We further demonstrated that PB interacted with HMGCR, decreased its protein expression and inhibited the HMGCR/YAP pathway in melanoma cells. In addition, we found that PB could restore vemurafenib sensitivity in vemurafenib-resistant A-375 cells, which was correlated with the downregulation of HMGCR. In conclusion, we demonstrate that PB elicits anticancer action and enhances sensitivity to vemurafenib by targeting HMGCR.

Ventilation impacts on infection risk mitigation, improvement of environmental quality and energy efficiency for subway carriages.

Subway carriages are enclosed for extended periods of time, with a high density of passengers. Providing a safe, healthy, and comfortable cabin environment is a great challenge, particularly during the COVID-19 pandemic. An increase in ventilation rate can potentially reduce infection probability, which may result in worsening environmental quality (e.g., thermal comfort) and larger energy consumption. Thus, exploring the trade-off among infection risk, environmental quality (with regard to ventilation, thermal comfort, and air quality), and energy consumption is important to optimize ventilation systems for carriages. The effect of different supply air parameters (e.g., velocity and temperature) and ventilation modes of mixing ventilation (MV) & Supply air from the Floor and Return air from the Ceiling (SFRC) was studied. The questionnaires were analyzed to explore passenger dissatisfaction with the carriage environment using a MV system. Simulations were performed to predict the velocity, temperature, and CO2 concentration fields. In addition, the comprehensive benefit was evaluated by analytic hierarchy process (AHP), based on infection probability from the revisited Wells-Riley equation, Air Diffusion Performance Index (ADPI), Predicted Mean Vote (PMV), Pollutant Removal Effectiveness (PRE) and energy consumption estimated by cooling load (Lcool). Compared with MV, the optimized SFRC provided softer draft sensation and decreased CO2 concentration by 42%. The SFRC achieved better comprehensive benefits, with an infection risk reduced to 0.4%, ADPI of 80%, PMV approaching zero, PRE up to 16, and energy efficiency increased by 30%. This work contributes to the optimal design of subway carriage ventilation systems in the post-epidemic era.

Cytotoxic and Anti-Inflammatory Sesquiterpenes from the Whole Plants of Centipeda minima.

Sixteen new sesquiterpene lactones (1-16) along with 13 known analogues (17-29) were isolated from the whole plants of Centipeda minima. The structures of 1-16 were delineated by the combination of NMR spectroscopic experiments, HRESIMS, single-crystal X-ray diffraction analyses, and ECD spectra. Compounds 23-26 showed potent cytotoxicity against Hela, HCT-116, and HepG2 cells with IC50 values of 0.8-2.6, 0.4-3.3, and 1.1-2.6 µM, respectively. Compounds 8, 15, and 24 exhibited significant inhibitory activity on the production of nitric oxide in the lipopolysaccharide-activated RAW 264.7 mouse macrophage cell line, with IC50 values ranging from 0.1 to 0.2 µM.

Occupant-density-detection based energy efficient ventilation system: Prevention of infection transmission.

Ventilation plays an important role in prevention and control of COVID-19 in enclosed indoor environment and specially in high-occupant-density indoor environments (e.g., underground space buildings, conference room, etc.). Thus, higher ventilation rates are recommended to minimize the infection transmission probability, but this may result in higher energy consumption and cost. This paper proposes a smart low-cost ventilation control strategy based on occupant-density-detection algorithm with consideration of both infection prevention and energy efficiency. The ventilation rate can be automatically adjusted between the demand-controlled mode and anti-infection mode with a self-developed low-cost hardware prototype. YOLO (You Only Look Once) algorithm was applied for occupancy detection based on video frames from surveillance cameras. Case studies show that, compared with a traditional ventilation mode (with 15% fixed fresh air ratio), the proposed ventilation control strategy can achieve 11.7% energy saving while lowering the infection probability to 2%. The developed ventilation control strategy provides a feasible and promising solution to prevent transmission of infection diseases (e.g., COVID-19) in public and private buildings, and also help to achieve a healthy yet sustainable indoor environment.

Indoor airborne disinfection with electrostatic disinfector (ESD): Numerical simulations of ESD performance and reduction of computing time.

Airborne transmissions of infectious disease (e.g. SARS-CoV-2) in indoor environments may induce serious threat to public health. Air purification devices are necessary to remove and/or inactivate airborne biological species from indoor air environment. Corona discharge in an electrostatic precipitator is capable of removing particulate matter and disinfecting biological aerosols to act as electrostatic disinfector (ESD). The ions generated by ESD can effectively inactivate bacteria/viruses. However, the available research rarely investigated disinfection effect of ESD, and it is urgent to develop quantitative ESD design methods for building mechanical ventilation applications. This study developed an integrated numerical model to simulate disinfection performance of ESD. The numerical model considers the ionized electric field, electrohydrodynamic flow, and biological disinfection. The model prediction was validated with the experimental data (E. coli): Good agreement was observed. The validated model then was used to study the influences of essential design parameters (e.g. voltage, inlet velocity) of ESD on disinfection efficiency. The effects of modeling of electrophoretic force and EHD (electrohydrodynamic) flow patterns on disinfection efficiency and computing time were also analyzed. The disinfection efficiency of well-designed ESD (with space charge density of 3.6 × 10-06 C/m3) could be as high as 100%. Compared with HEPA, ESD could save 99% of energy consumed by HEPA without sacrificing disinfection efficiency.

Six New Methyl Apiofuranosides from the Bark of Phellodendron chinense Schneid and Their Inhibitory Effects on Nitric Oxide Production.

A chemical investigation on 70% EtOH extract from the bark of Phellodendron chinense Schneid (Rutaceae) led to six new methyl apiofuranosides (1-6), and ten known compounds (7-16). All these compounds were characterized by the basic analysis of the spectroscopic data including extensive 1D-, 2D-NMR (HSQC, HMBC), and high-resolution mass spectrometry, and the absolute configurations were determined by both empirical approaches and NOESY. Inhibitory effects of compounds 1-9 and 11-16 on nitric oxide production were investigated in lipopolysaccharide (LPS)-mediated RAW 264.7 cells, as a result, most of these isolates inhibited nitric oxide (NO) release, and among them 9, 11, and 12 displayed the strongest inhibition on NO release at the concentration of 12.5 µM.

[Chemistry and biology research on bitter-taste Chinese materia medica with function of regulating glycolipid metabolism].

The bitter taste is one of the important properties among five flavors of Chinese materia medica (CMM), characterized by downbearing and discharging, drying dampness, and consolidating Yin. In common CMM, bitter-taste CMM accounts for a large proportion, indicating the importance of it. Through the efficacy of clearing away heat and dampness, reducing fire and removing toxin, bitter-taste CMM has achieved good results in treating diabetes in clinical application, proving their definite therapeutic effect on regulating glucose and lipid metabolism (main features of diabetes). At present, there are many reports about the chemical constituents and pharmacological effects of CMM on diabetes, but there are few reviews on the chemistry and biology of bitter-taste CMM. This study summarized the properties and compatibility characteristics of bitter-taste CMM for treating diabetes, and mainly analyzed the chemistry and biology basis of bitter-taste CMM with function of regulating glycolipid metabolism, laying foundation for further researches on properties theory of CMM.

Withapubesides A-D: natural inducible nitric oxide synthase (iNOS) inhibitors from Physalis pubescens.

Four new steroid glycosides, withapubesides A-D (1-4), were isolated from the stems of Physalis pubescens L. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1 and 2 were deduced by single-crystal X-ray diffraction and ECD data analysis, respectively. Compound 3 has shown significant inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with an IC50 value of 12.8 µM and moderate cytostatic activity against human carcinoma cells (786-O, C4-2B, 22Rvl, A375 and A375S2) with IC50 values in the range of 3.05-9.47 µM. Molecular docking simulation demonstrated that 3 is bound in the inducible nitric oxide synthase (iNOS) active site heme pocket very well, which suggests that 3 might be a candidate for the development of iNOS inhibitors.

Physalin A induces G2/M phase cell cycle arrest in human non-small cell lung cancer cells: involvement of the p38 MAPK/ROS pathway.

Physalin A (PA) is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has long been used for the treatment of sore throat, hepatitis, and tumors in China. In the present study, we firstly investigated the effects of PA on proliferation and cell cycle distribution of the human non-small cell lung cancer (NSCLC) A549 cell line, and the potential mechanisms involved. Here, PA inhibited cell growth in dose- and time-dependent manners. Treatment of A549 cells with 28.4 µM PA for 24 h resulted in approximately 50 % cell death. PA increased the amount of intracellular ROS and the proportion of cells in G2/M. G2/M arrest was attenuated by the addition of ROS scavenger NAC. ERK and P38 were triggered by PA through phosphorylation in a time-dependent manner. The phosphorylation of ERK and P38 were not attenuated by the addition of NAC, but the use of the p38 inhibitor could reduce, at least in part, PA-induced ROS and the proportion of cells in G2/M. PA induces G2/M cell cycle arrest in A549 cells involving in the p38 MAPK/ROS pathway. This study suggests that PA might be a promising therapeutic agent against NSCLC.

Berberine directly targets AKR1B10 protein to modulate lipid and glucose metabolism disorders in NAFLD.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR) is the main active component from Coptidis rhizome, a well-known Chinese herbal medicine used for metabolic diseases, especially diabetes for thousands of years. BBR has been reported to cure various metabolic disorders, such as nonalcoholic fatty liver disease (NAFLD). However, the direct proteomic targets and underlying molecular mechanism of BBR against NAFLD remain less understood. AIM OF THE STUDY: To investigate the direct target and corresponding molecular mechanism of BBR on NAFLD is the aim of the current study. MATERIALS AND METHODS: High-fat diet (HFD)-fed mice and oleic acid (OA) stimulated HepG2 cells were utilized to verify the beneficial impacts of BBR on glycolipid metabolism profiles. The click chemistry in proteomics, DARTS, CETSA, SPR and fluorescence co-localization analysis were conducted to identify the targets of BBR for NAFLD. RNA-seq and shRNA/siRNA were used to investigate the downstream pathways of the target. RESULTS: BBR improved hepatic steatosis, ameliorated insulin resistance, and reduced TG levels in the NAFLD models. Importantly, Aldo-keto reductase 1B10 (AKR1B10) was first proved as the target of BBR for NAFLD. The gene expression of AKR1B10 increased significantly in the NAFLD patients' liver tissue. We further demonstrated that HFD and OA increased AKR1B10 expression in the C57BL/6 mice's liver and HepG2 cells, respectively, whereas BBR decreased the expression and activities of AKR1B10. Moreover, the knockdown of AKR1B10 by applying shRNA/siRNA profoundly impacted the beneficial effects on the pathogenesis of NAFLD by BBR. Meanwhile, the changes in various proteins (ACC1, CPT-1, GLUT2, etc.) are responsible for hepatic lipogenesis, fatty acid oxidation, glucose uptake, etc. by BBR were reversed by the knockdown of AKR1B10. Additionally, RNA-seq was used to identify the downstream pathway of AKR1B10 by examining the gene expression of liver tissues from HFD-fed mice. Our findings revealed that BBR markedly increased the protein levels of PPARα while downregulating the expression of PPARγ. However, various proteins of PPAR signaling pathways remained unaffected post the knockdown of AKR1B10. CONCLUSIONS: BBR alleviated NAFLD via mediating PPAR signaling pathways through targeting AKR1B10. This study proved that AKR1B10 is a novel target of BBR for NAFLD treatment and helps to find new targets for the treatment of NAFLD by using active natural compounds isolated from traditional herbal medicines as the probe.

Zonal demand-controlled ventilation strategy to minimize infection probability and energy consumption: A coordinated control based on occupant detection.

Due to the outbreak of COVID-19, an increased risk of airborne transmission has been experienced in buildings, particularly in confined public places. The need for ventilation as a means of infection prevention has become more pronounced given that some basic precautions (like wearing masks) are no longer mandatory. However, ventilating the space as a whole (e.g., using a unified ventilation rate) may lead to situations where there is either insufficient or excessive ventilation in localized areas, potentially resulting in localized virus accumulation or large energy consumption. It is of urgent need to investigate real-time control of ventilation systems based on local demands of the occupants to strike a balance between infection risk and energy saving. In this work, a zonal demand-controlled ventilation (ZDCV) strategy was proposed to optimize the ventilation rates in sub-zones. A camera-based occupant detection method was developed to detect occupants (with eight possible locations in sub-zones denoted as 'A' to 'H'). Linear ventilation model (LVM), dimension reduction, and artificial neural network (ANN) were integrated for rapid prediction of pollutant concentrations in sub-zones with the identified occupants and ventilation rates as inputs. Coordinated ventilation effects between sub-zones were optimized to improve infection prevention and energy savings. Results showed that rapid prediction models achieved an average prediction error of 6 ppm for CO2 concentration fields compared with the simulation under different occupant scenarios (i.e., occupant locations at ABH, ABCFH, and ABCDEFH). ZDCV largely reduced the infection risk to 2.8% while improved energy-saving efficiency by 34% compared with the system using constant ventilation rate. This work can contribute to the development of building environmental control systems in terms of pollutant removal, infection prevention, and energy sustainability.

Urban heat mitigation by green and blue infrastructure: Drivers, effectiveness, and future needs.

The combination of urbanization and global warming leads to urban overheating and compounds the frequency and intensity of extreme heat events due to climate change. Yet, the risk of urban overheating can be mitigated by urban green-blue-grey infrastructure (GBGI), such as parks, wetlands, and engineered greening, which have the potential to effectively reduce summer air temperatures. Despite many reviews, the evidence bases on quantified GBGI cooling benefits remains partial and the practical recommendations for implementation are unclear. This systematic literature review synthesizes the evidence base for heat mitigation and related co-benefits, identifies knowledge gaps, and proposes recommendations for their implementation to maximize their benefits. After screening 27,486 papers, 202 were reviewed, based on 51 GBGI types categorized under 10 main divisions. Certain GBGI (green walls, parks, street trees) have been well researched for their urban cooling capabilities. However, several other GBGI have received negligible (zoological garden, golf course, estuary) or minimal (private garden, allotment) attention. The most efficient air cooling was observed in botanical gardens (5.0 ± 3.5°C), wetlands (4.9 ± 3.2°C), green walls (4.1 ± 4.2°C), street trees (3.8 ± 3.1°C), and vegetated balconies (3.8 ± 2.7°C). Under changing climate conditions (2070-2100) with consideration of RCP8.5, there is a shift in climate subtypes, either within the same climate zone (e.g., Dfa to Dfb and Cfb to Cfa) or across other climate zones (e.g., Dfb [continental warm-summer humid] to BSk [dry, cold semi-arid] and Cwa [temperate] to Am [tropical]). These shifts may result in lower efficiency for the current GBGI in the future. Given the importance of multiple services, it is crucial to balance their functionality, cooling performance, and other related co-benefits when planning for the future GBGI. This global GBGI heat mitigation inventory can assist policymakers and urban planners in prioritizing effective interventions to reduce the risk of urban overheating, filling research gaps, and promoting community resilience.

Impact of ionizers on prevention of airborne infection in classroom.

Infectious diseases (e.g., coronavirus disease 2019) dramatically impact human life, economy and social development. Exploring the low-cost and energy-saving approaches is essential in removing infectious virus particles from indoors, such as in classrooms. The application of air purification devices, such as negative ion generators (ionizers), gains popularity because of the favorable removal capacity for particles and the low operation cost. However, small and portable ionizers have potential disadvantages in the removal efficiency owing to the limited horizontal diffusion of negative ions. This study aims to investigate the layout strategy (number and location) of ionizers based on the energy-efficient natural ventilation in the classroom to improve removal efficiency (negative ions to particles) and decrease infection risk. Three infected students were considered in the classroom. The simulations of negative ion and particle concentrations were performed and validated by the experiment. Results showed that as the number of ionizers was 4 and 5, the removal performance was largely improved by combining ionizer with natural ventilation. Compared with the scenario without an ionizer, the scenario with 5 ionizers largely increased the average removal efficiency from around 20% to 85% and decreased the average infection risk by 23%. The setup with 5 ionizers placed upstream of the classroom was determined as the optimal layout strategy, particularly when the location and number of the infected students were unknown. This work can provide a guideline for applying ionizers to public buildings when natural ventilation is used. Electronic Supplementary Material ESM: the Appendix is available in the online version of this article at 10.1007/s12273-022-0959-z.

Can retro-reflective materials replace diffuse highly reflective materials for urban buildings' wall to improve outdoor thermal comfort?

In recent years, there have been numerous studies on the application of retroreflective (RR) materials to exterior building walls to relieve the urban heat island (UHI) phenomenon and save building energy consumption instead of diffuse highly reflective (DHR) materials. Experimental measurements were undertaken to investigate the impact of applying DHR and RR materials to building exterior walls on the outdoor thermal environment. DHR and RR walls were tested with three canyon aspect ratios ( H / D ) of 0.5, 1.0, and 1.5, respectively, with seven environmental indexes recorded and compared, including air temperature ( T a ), relative humidity ( R H ), sol-air temperature ( S A T ), operative temperature ( O T ), standard effective temperature ( S E T * ), change in operative temperature ( C O T ), and real-time solar reflectance ( ρ ). The results show that the RR wall is more effective in improving the outdoor thermal environment, where S A T decreased by 4.5 °C, S E T * decreased by 0.5 °C, and COT decreased by 1.2 °C, on average, while it can also improve the real-time solar reflectance ( ρ ) by 12% on average compared to the DHR wall. Moreover, it gets more effective in scenarios with a higher canyon aspect ratio.

Refined design of ventilation systems to mitigate infection risk in hospital wards: Perspective from ventilation openings setting.

To prevent respiratory infections between patients and medical workers, the transmission risk of airborne pollutants in hospital wards must be mitigated. The ventilation modes, which are regarded as an important strategy to minimize the infection risk, are challenging to be systematically designed. Studies have considered the effect of ventilation openings (inlets/outlets) or infected source locations on the airflow distribution, pollutant removal, and infection risk mitigation. However, the relationship (such as relative distance) between ventilation openings and infected sources is critical because it affects the direct exhaust of exhaled pollutants, which has not been thoroughly studied. To explore pollutant removal and infection prevention in wards, different ventilation modes (with varying ventilation openings) and infected patient locations must be jointly considered. This study investigated displacement ventilation (DV), downward ventilation (DWV), and stratum ventilation (SV) with 4, 6, and 10 scenarios of ventilation openings, respectively. The optimal ventilation mode and relative distance between outlets and infected patients were analyzed based on the simulated pollutant concentration fields and the evaluated infection risk. The pollutant removal effect and infection risk mitigation of SV in the ward were largely improved by 75% and 59% compared with DV and DWV, respectively. The average infection risk was reduced below 7% when a non-dimensional relative distance (a ratio of the actual distance to the cubic root of the ward volume) was less than 0.25 between outlets and infected patient. This study can serve as a guide for the systematic ventilation system design in hospitals during the epidemic.

Intelligent operation, maintenance, and control system for public building: Towards infection risk mitigation and energy efficiency.

During the post-COVID-19 era, it is important but challenging to synchronously mitigate the infection risk and optimize the energy savings in public buildings. While, ineffective control of ventilation and purification systems can result in increased energy consumption and cross-contamination. This paper is to develop intelligent operation, maintenance, and control systems by coupling intelligent ventilation and air purification systems (negative ion generators). Optimal deployment of sensors is determined by Fuzzy C-mean (FCM), based on which CO2 concentration fields are rapidly predicted by combing the artificial neural network (ANN) and self-adaptive low-dimensional linear model (LLM). Negative oxygen ion and particle concentrations are simulated with different numbers of negative ion generators. Optimal ventilation rates and number of negative ion generators are decided. A visualization platform is established to display the effects of ventilation control, epidemic prevention, and pollutant removal. The rapid prediction error of LLM-based ANN for CO2 concentration was below 10% compared with the simulation. Fast decision reduced CO2 concentration below 1000 ppm, infection risk below 1.5%, and energy consumption by 27.4%. The largest removal efficiency was 81% when number of negative ion generators was 10. This work can promote intelligent operation, maintenance, and control systems considering infection prevention and energy sustainability.

Puerol and pueroside derivatives from Pueraria lobata and their anti-inflammatory activity.

Five undescribed puerols and puerosides and three known analogues were obtained from the roots of Pueraria lobata. Their structures were determined by comprehensive analysis of spectroscopic data and chemical methods. Since puerol D and puerol C were racemic compounds, resolved into their enantiomers, and their absolute configurations were determined by experimental and calculated ECD spectra. Six of the isolates were evaluated for their inhibitory activities on NO generation and the expression of inflammatory factors in the LPS-stimulated RAW 264.7 macrophage cells. The results showed that (S)-puerol C, (R)-puerol C, isokuzubutenolide A and kuzubutenolide A significantly decreased the NO production (IC50 values in the range of 16.87-39.95 µM). Meanwhile, (S)-puerol C, isokuzubutenolide A and kuzubutenolide A also reduced the mRNA expression of inflammatory factors (TNF-α, IL-1ß and IL-6).

In-kitchen aerosol exposure in twelve cities across the globe.

Poor ventilation and polluting cooking fuels in low-income homes cause high exposure, yet relevant global studies are limited. We assessed exposure to in-kitchen particulate matter (PM2.5 and PM10) employing similar instrumentation in 60 low-income homes across 12 cities: Dhaka (Bangladesh); Chennai (India); Nanjing (China); Medellín (Colombia); São Paulo (Brazil); Cairo (Egypt); Sulaymaniyah (Iraq); Addis Ababa (Ethiopia); Akure (Nigeria); Blantyre (Malawi); Dar-es-Salaam (Tanzania) and Nairobi (Kenya). Exposure profiles of kitchen occupants showed that fuel, kitchen volume, cooking type and ventilation were the most prominent factors affecting in-kitchen exposure. Different cuisines resulted in varying cooking durations and disproportional exposures. Occupants in Dhaka, Nanjing, Dar-es-Salaam and Nairobi spent > 40% of their cooking time frying (the highest particle emitting cooking activity) compared with âˆ¼ 68% of time spent boiling/stewing in Cairo, Sulaymaniyah and Akure. The highest average PM2.5 (PM10) concentrations were in Dhaka 185 ± 48 (220 ± 58) µg m-3 owing to small kitchen volume, extensive frying and prolonged cooking compared with the lowest in Medellín 10 ± 3 (14 ± 2) µg m-3. Dual ventilation (mechanical and natural) in Chennai, Cairo and Sulaymaniyah reduced average in-kitchen PM2.5 and PM10 by 2.3- and 1.8-times compared with natural ventilation (open doors) in Addis Ababa, Dar-es-Salam and Nairobi. Using charcoal during cooking (Addis Ababa, Blantyre and Nairobi) increased PM2.5 levels by 1.3- and 3.1-times compared with using natural gas (Nanjing, Medellin and Cairo) and LPG (Chennai, Sao Paulo and Sulaymaniyah), respectively. Smaller-volume kitchens (<15 m3; Dhaka and Nanjing) increased cooking exposure compared with their larger-volume counterparts (Medellin, Cairo and Sulaymaniyah). Potential exposure doses were highest for Asian, followed by African, Middle-eastern and South American homes. We recommend increased cooking exhaust extraction, cleaner fuels, awareness on improved cooking practices and minimising passive occupancy in kitchens to mitigate harmful cooking emissions.