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Attenuated strains of the intracellular pathogen Listeria monocytogenes can deliver genetically encoded payloads inside tumor cells. L. monocytogenes preferentially accumulates and propagates inside immune-suppressed tumor microenvironments. To maximize the payload impact in tumors and minimize damage to healthy tissues, it is desirable to induce payload synthesis when bacteria are eliminated from the healthy tissues but are grown to high numbers intratumorally. Here, we have engineered a tightly controlled gene expression system for intracellular L. monocytogenes inducible with a cumin derivative, cumate. Upon cumate addition, expression of a reporter gene is increased in L. monocytogenes growing in vitro by 80-fold, and in intracellular L. monocytogenes in murine tumors by 10-fold. This study demonstrates the feasibility of activating gene expression in intracellular bacteria in live animals using an edible inducer. The system is expected to enhance the efficacy and safety of the attenuated L. monocytogenes strains as antitumor payload delivery bacterial drones.

Wealth is an indicator of individual well-being. Increasing wealth is a pathway to achieving socio-economic development. Thus, it is imperative to shed light on factors that induce individual intention to increase wealth. This study investigates the effects of perception of wealth, perception of the rich, and behavioral control on personal intention to make money. A stratified sampling method was employed to obtain a sample of 991 respondents from Northern, Central, and Southern Vietnam who were invited to participate in a structured questionnaire survey in 2021. We utilized the Confirmatory Factor Analysis to validate the proposed model and tested the hypotheses using the Partial Least Squared-SEM. Empirical results highlight that individual behavioral control, explicit perception of the rich, and perception of wealth are essential determinants of individual intention to make money. Interestingly, motivation of wealth positively moderates the relationship between the perception of wealth and personal intention to make money. In addition, post-Covid-19 opportunities positively moderate two-pair relationships: perception of wealth-individual intention to make money and explicit perception of the rich-individual intention to make money. Insights from this study imply appropriate policies for the government to enhance the inspiration of people to work harder, leading to sustainable development., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Osteoporosis contributes significantly to health and economic burdens worldwide. However, the development of osteoporosis-related prediction tools has been limited for lower-middle-income countries, especially Vietnam. This study aims to develop prediction models for the Vietnamese population as well as evaluate the existing tools to forecast the risk of osteoporosis and evaluate the contribution of covariates that previous studies have determined to be risk factors for osteoporosis. The prediction models were developed to predict the risk of osteoporosis using machine learning algorithms. The performance of the included prediction models was evaluated based on two scenarios; in the first one, the original test parameters were directly modeled, and in the second the original test parameters were transformed into binary covariates. The area under the receiver operating characteristic curve, the Brier score, precision, recall and F1-score were calculated to evaluate the models' performance in both scenarios. The contribution of the covariates was estimated using the Permutation Feature Importance estimation. Four models, namely, Logistic Regression, Support Vector Machine, Random Forest and Neural Network, were developed through two scenarios. During the validation phase, these four models performed competitively against the reference models, with the areas under the curve above 0.81. Age, height and weight contributed the most to the risk of osteoporosis, while the correlation of the other covariates with the outcome was minor. Machine learning algorithms have a proven advantage in predicting the risk of osteoporosis among Vietnamese women over 50 years old. Additional research is required to more deeply evaluate the performance of the models on other high-risk populations., (© 2022. The Author(s).)

This study presents total OH reactivity, ancillary trace species, HO 2 reactivity, and complex isoprene-derived RO 2 reactivity due to ambient aerosols measured during the air quality study (AQUAS)-Kyoto campaign in September, 2020. Observations were conducted during the coronavirus disease (COVID-19) pandemic (associated with reduced anthropogenic emissions). The spatial distribution of missing OH reactivity highlights that the origin of volatile organic compounds (VOCs) may be from natural-emission areas. For the first time, the real-time loss rates of HO 2 and RO 2 onto ambient aerosols were measured continuously and alternately. Ozone production sensitivity was investigated considering unknown trace species and heterogeneous loss effects of XO 2 (≡HO 2 + RO 2 ) radicals. Missing OH reactivity enhanced the ozone production potential by a factor of 2.5 on average. Heterogeneous loss of radicals could markedly suppress ozone production under low NO/NO x conditions with slow gas-phase reactions of radicals and change the ozone regime from VOC- to NO x -sensitive conditions. This study quantifies the relationship of missing OH reactivity and aerosol uptake of radicals with ozone production in Kyoto, a low-emission suburban area. The result has implications for future NO x -reduction policies. Further studies may benefit from the combination of chemical transport models and inverse modeling over a wide spatiotemporal range.

Despite the proven benefits of sustainable agricultural practices (SAPs), adoption rates among farmers are still low, especially in developing countries. This paper seeks to assist policymakers devise approaches to encourage adoption by identifying the attributes of SAPs that can motivate Vietnamese coffee farmers to adopt them in production. Vietnam is the world's second largest coffee producer and the sector supports the livelihoods of over half a million people in the country. We conduct two different types of discrete choice experiments with over 300 Vietnamese coffee farmers to identify their SAP preferences. We analyse the data using cluster analysis and generalised multinomial logit models. The results are consistent across our different approaches. They show that these farmers have the strongest preferences for SAPs that can provide higher profits, lower risks (of output loss) and higher environmental benefits. These attributes received mean part-worth utilities of 0.251, 0.250 and 0.239 respectively. Attributes capturing the increase in daily operating efforts and time required to set up such practices are less important considerations. Further, the farmers are willing to pay on average between 26 and 32 million VND per hectare per year for a one level reduction in the risk of output loss and earn 15 million VND per hectare per year less in profits to achieve a one level increase in environmental benefits., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cytochromes P450 (CYPs) are a multigene superfamily of constitutively expressed and inducible enzymes responsible for the detoxification of many endogenous and exogenous compounds and for the metabolism of numerous medications. The cytochrome P450 2F2 (CYP2F2) subfamily is preferentially expressed in the respiratory tract, but its functional role in adipocytes has never been explored. We found that CYP2F2 was highly expressed during the differentiation of the C3H10T1/2 murine mesenchymal stem cells to adipocytes and here we have explored its functional role in adipocytes. The expression of thermogenic marker proteins such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), PR domain containing 16 (PRDM16), and uncoupling protein 1 (UCP1) and beige-fat specific genes were significantly increased in Cyp2f2-deficient 3T3-L1 adipocytes. Moreover, Cyp2f2 silencing led to reduced adipogenesis and lipogenesis, and enhanced lipid catabolism through the increased expression of lipolytic and fatty acid oxidative enzymes. A mechanistic study to identify molecular signals for CYP2F2-mediated negative regulation in the browning of white adipocytes revealed that CYP2F2 impairs the beta-3 adrenergic receptor (β3-AR) activation as well as its downstream regulators including protein kinase A (PKA), p38 mitogen-activated protein kinase (p38 MAPK), and activating transcription factor 2 (ATF2). This data provides evidence that CYP2F2 is a negative regulator of lipid catabolism and browning in white adipocytes, suggesting that inhibitors of CYP2F2 could be potential drugs for the treatment of obesity with a focus on enhancing energy expenditure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bone morphogenetic protein-11 (BMP11), also known as growth differentiation factor-11 (GDF11), is implicated in skeletal development and joint morphogenesis in mammals. However, its functions in adipogenesis and energy homeostasis are mostly unknown. The present study investigates crucial roles of BMP11 in cultured 3T3-L1 white and HIB1B brown adipocytes, using Bmp11 gene depletion and pharmacological inhibition of BMP11. The silencing of Bmp11 markedly decreases the expression levels of brown-fat signature proteins and beige-specific genes in white adipocytes and significantly down-regulates the expression levels of brown fat-specific genes in brown adipocytes. The deficiency of Bmp11 reduces the expressions of lipolytic protein markers in white and brown adipocytes. Moreover, BMP11 induces browning of 3T3-L1 adipocytes via coordination of multiple signalling pathways, including mTORC1-COX2 and p38MAPK-PGC-1α as non-canonical pathways, as well as Smad1/5/8 as a canonical pathway. We believe this study is the first to provide evidence of the potential roles of BMP11 for improvement of lipid catabolism in both cultured white and brown adipocytes, as well as the effect on browning of white adipocytes. Taken together, these results demonstrate the therapeutic potential for the treatment of obesity., (© 2021 John Wiley & Sons Ltd.)

Purpose: Modern science has given much attention to the treatment of obesity by activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Recent studies have identified theobromine, a derivative of cocoa, as a potent natural component actively browning white fat cells. Here, we aimed to deduce the anti-obesity effect of theobromine involving phosphodiesterase (PDE) dependent-regulatory pathway in obese animal models., Methods: For examining activity of theobromine, C57BL/6 mice were fed with high fat diet and treated with theobromine to determine the expression levels of protein markers by immunoblot analysis and gene targets by quantitative real-time PCR. Other methods used include histopathological studies, immunofluorescence and molecular docking approaches., Results: Theobromine alleviated diet-induced obesity in mice by browning of iWAT and activating BAT. Further, theobromine actively interacted with PDE4D and inhibited its activity in adipose tissues and cells potentiating energy expenditure. Moreover, the regulatory action of theobromine via inhibition of PDE4D was mediated by β3-AR signaling pathway., Conclusion: Altogether, the current results signifies critical role of theobromine in reducing obesity by regulation of lipid metabolism through inhibition of PDE4, indicating its potential as a major therapeutic medicinal compound.

The nonsteroidal anti-inflammatory drug (NSAID) ketoprofen is commonly used as a pain reliever, but its role in mediating the energy metabolism in lipids is unclear. This paper reports for the first time the critical role of ketoprofen in ameliorating white fat browning and alleviating diet-induced obesity. The effects of ketoprofen were evaluated using C57BL/6 mice fed a high fat diet and the expression levels of the target genes and proteins in the lipid metabolisms were determined by quantitative real-time PCR, immunoblot analysis, histopathology study, immunofluorescence, and molecular docking techniques. Ketoprofen induced browning in cultured 3T3-L1 white adipocytes and inguinal white adipose tissue by increasing the expression of core fat browning marker proteins as well as beige-specific genes through COX-2 activation. Ketoprofen also led to the robust activation of brown adipocytes and enhanced brown fat adipogenesis. In addition, ketoprofen elevated lipolysis, thereby increasing mitochondrial biogenesis resulting in higher fat oxidation. Furthermore, the molecular docking and mechanistic study demonstrated the recruitment of beige fat by ketoprofen via mTORC1-p38-mediated activation of the COX-2 pathway. Overall, these results indicate the unique role of ketoprofen in body weight reduction by enhancing thermogenesis, suggesting its therapeutic potential in the treatment of obesity.