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Carotenoids are widely researched due to their correlation with the mitigation of severe illnesses such as cancer, cardiovascular disease, and macular degeneration, which points out the critical significance of natural pigments. Carotenoid production from microorganisms has many advantages compared to plants or algae because of its rapid growth rate, cost-effectiveness, and independence from geographical factors. The genus Rhodosporidium, specifically the species Rhodosporidium toruloides, is renowned for generating carotenoid-rich biomass in biotechnology. However, the quantity and composition of carotenoid products obtained highly depend on the specific medium and culture conditions. In this research, carotenoid extraction by combining DMSO and acetone can result in high efficiency. Furthermore, the fermentation medium for R. toruloides was successfully optimized with affordable ingredients, including glucose, NaCl, H2O2, KH2PO4, MgSO4.7H2O, NH4Cl2, Na2HPO4, and yeast extract. The reassessment of the optimal model revealed strong compatibility between the predictive and experimental models regarding dry biomass and carotenoid content. The low residual glucose amount ultimately revealed adequate glucose consumption as a substrate for growth and carotenoid production.

Abstract Modern communication and navigation systems are increasingly relying on atomic clocks. As timing precision requirements increase, demands for lower SWaP (size, weight, and power) clocks rise. However, it has been challenging to break through the general trade-off trend between the clock stability performance and SWaP. Here we demonstrate micro mercury trapped ion clock (M2TIC) prototypes integrated with novel micro-fabricated technologies to simultaneously achieve high performance and low SWaP. The M2TIC prototypes could reach the $$10^{-14}$$ 10 - 14 -stability level in 1 day with a SWaP of 1.1 L, 1.2 kg, and under 6 W of power. This stability level is comparable to the widely used rack-mount Microchip 5071A cesium frequency standard. These standalone prototypes survived regular commercial shipping across the North American continent to a government laboratory, where their performance was independently tested. The M2TIC sets a new reference point for SWaP and performance and opens opportunities for high-performance clocks in terrestrial and space applications.

Hybrid systems coupling electron spins and optomechanical responses are of potential use in quantum information systems and sensing technology. Here, the authors demonstrate optical levitation of nanodiamonds and the control of their nitrogen vacancy spins in vacuum.

Feynman’s ratchet is a microscopic machine in contact with two heat reservoirs, at temperatures T _A and T _B , that was proposed by Richard Feynman to illustrate the second law of thermodynamics. In equilibrium ( T _A = T _B ), thermal fluctuations prevent the ratchet from generating directed motion. When the ratchet is maintained away from equilibrium by a temperature difference ( ${T}_{A}\ne {T}_{B}$ ), it can operate as a heat engine, rectifying thermal fluctuations to perform work. While it has attracted much interest, the operation of Feynman’s ratchet as a heat engine has not been realized experimentally, due to technical challenges. In this work, we realize Feynman’s ratchet with a colloidal particle in a one-dimensional optical trap in contact with two heat reservoirs: one is the surrounding water, while the effect of the other reservoir is generated by a novel feedback mechanism, using the Metropolis algorithm to impose detailed balance. We verify that the system does not produce work when T _A = T _B , and that it becomes a microscopic heat engine when ${T}_{A}\ne {T}_{B}$ . We analyze work, heat and entropy production as functions of the temperature difference and external load. Our experimental realization of Feynman’s ratchet and the Metropolis algorithm can also be used to study the thermodynamics of feedback control and information processing, the working mechanism of molecular motors, and controllable particle transportation.

Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer biology and therapeutics.

ABL gene translocations create constitutively active tyrosine kinases that are causative in chronic myeloid leukemia, acute lymphocytic leukemia and other hematopoietic malignancies. Consistent retention of ABL SH3/SH2 autoinhibitory domains, however, suggests that these leukemogenic tyrosine kinase fusion proteins remain subject to regulation. We resolve this paradox, demonstrating that BCR-ABL1 kinase activity is regulated by RIN1, an ABL SH3/SH2 binding protein. BCR-ABL1 activity was increased by RIN1 overexpression and decreased by RIN1 silencing. Moreover, Rin1(-/-) bone marrow cells were not transformed by BCR-ABL1, ETV6-ABL1 or BCR-ABL1(T315I), a patient-derived drug-resistant mutant, as judged by growth factor independence. Rescue by ectopic RIN1 verified a cell autonomous mechanism of collaboration with BCR-ABL1 during transformation. Sensitivity to the ABL kinase inhibitor imatinib was increased by RIN1 silencing, consistent with RIN1 stabilization of an activated BCR-ABL1 conformation having reduced drug affinity. The dependence on activation by RIN1 to unleash full catalytic and cell transformation potential reveals a previously unknown vulnerability that could be exploited for treatment of leukemic cases driven by ABL translocations. The findings suggest that RIN1 targeting could be efficacious for imatinib-resistant disease and might complement ABL kinase inhibitors in first-line therapy.

Carotenoids are widely researched due to their correlation with the mitigation of severe illnesses such as cancer, cardiovascular disease, and macular degeneration, which points out the critical significance of natural pigments. Carotenoid production from microorganisms has many advantages compared to plants or algae because of its rapid growth rate, cost-effectiveness, and independence from geographical factors. The genus Rhodosporidium, specifically the species Rhodosporidium toruloides, is renowned for generating carotenoid-rich biomass in biotechnology. However, the quantity and composition of carotenoid products obtained highly depend on the specific medium and culture conditions. In this research, carotenoid extraction by combining DMSO and acetone can result in high efficiency. Furthermore, the fermentation medium for R. toruloides was successfully optimized with affordable ingredients, including glucose, NaCl, H2O2, KH2PO4, MgSO4.7H2O, NH4Cl2, Na2HPO4, and yeast extract. The reassessment of the optimal model revealed strong compatibility between the predictive and experimental models regarding dry biomass and carotenoid content. The low residual glucose amount ultimately revealed adequate glucose consumption as a substrate for growth and carotenoid production. [ABSTRACT FROM AUTHOR]

Global demand for sustainable agri-food products creates opportunities for smallholder farmers. But on-farm verification of sustainable practices is costly, making third-party certification inaccessible to many poor farmers. Digital technologies for tracing agri-food products from farm to fork could help: novel traceability systems, based on blockchain technology, can make data about on-farm practices transparently available to downstream stakeholders, enabling them to verify sustainability claims without external audits. There is limited understanding, however, of how such digital tracing systems fit local needs and capacities in smallholder contexts. Through a grounded theory approach, we explore the potential of digital traceability for sustainability monitoring in a case study in the Ucayali region of Peru. Based on interviews with local cocoa sector stakeholders, we identify two major challenges: first, setting up digital traceability systems requires investments that do not seem justified by corresponding increases in income. And second, relying on farmer-supplied data creates the risk of inaccurate information due to insufficient capacity as well as incentives for providing distorted data. Our findings suggest that strong cooperation along the supply chain is needed to ensure adequate return on farmer-side costs and investments. Focusing on sustainability metrics at the community level, in addition to the farm level, may be promising, as these metrics can be reliably collected by external stakeholders and add value beyond existing third-party certification standards. Our case study provides recommendations for local policy makers and supply chain stakeholders to develop inclusive digital sustainability tracing systems with smallholder farmers.