Activated immune cells undergo a metabolic switch to aerobic glycolysis akin to the Warburg effect, thereby presenting a potential therapeutic target in autoimmune disease. Dimethyl fumarate (DMF), a ...derivative of the Krebs cycle intermediate fumarate, is an immunomodulatory drug used to treat multiple sclerosis and psoriasis. Although its therapeutic mechanism remains uncertain, DMF covalently modifies cysteine residues in a process termed succination. We found that DMF succinates and inactivates the catalytic cysteine of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in mice and humans, both in vitro and in vivo. It thereby down-regulates aerobic glycolysis in activated myeloid and lymphoid cells, which mediates its anti-inflammatory effects. Our results provide mechanistic insight into immune modulation by DMF and represent a proof of concept that aerobic glycolysis is a therapeutic target in autoimmunity.
Molybdenum disulfide (MoS2) is an extremely intriguing material because of its unique electrical and optical properties. The preparation of large-area and high-quality MoS2 nanosheets is an important ...step in a wide range of applications. This study demonstrates that monolayer and few-layer MoS2 nanosheets can be obtained from electrochemical exfoliation of bulk MoS2 crystals. The lateral size of the exfoliated MoS2 nanosheets is in the 5–50 μm range, which is much larger than that of chemically or liquid-phase exfoliated MoS2 nanosheets. The MoS2 nanosheets undergo low levels of oxidation during electrochemical exfoliation. In addition, microscopic and spectroscopic characterizations indicate that the exfoliated MoS2 nanosheets are of high quality and have an intrinsic structure. A back-gate field-effect transistor was fabricated using an exfoliated monolayer MoS2 nanosheet. The on/off current ratio is over 106, and the field-effect mobility is approximately 1.2 cm2 V–1 s–1; these values are comparable to the results for micromechanically exfoliated MoS2 nanosheets. The electrochemical exfoliation method is simple and scalable, and it can be applied to exfoliate other transition metal dichalcogenides.
Liquid–fluid interfaces provide a platform both for structuring liquids into complex shapes and assembling dimensionally confined, functional nanomaterials. Historically, attention in this area has ...focused on simple emulsions and foams, in which surface‐active materials such as surfactants or colloids stabilize structures against coalescence and alter the mechanical properties of the interface. In recent decades, however, a growing body of work has begun to demonstrate the full potential of the assembly of nanomaterials at liquid–fluid interfaces to generate functionally advanced, biomimetic systems. Here, a broad overview is given, from fundamentals to applications, of the use of liquid–fluid interfaces to generate complex, all‐liquid devices with a myriad of potential applications.
Surface‐active materials at liquid–liquid interfaces can be used to generate functional, reconfigurable materials. Harnessing this capability may enable the development of new devices with applications in chemical separations and synthesis, drug delivery, and reconfigurable electronics and microfluidics. Recent progress and open questions in this field, from nanoscale to macroscopic and from fundamentals to applications, are summarized.
Indigenous populations in Canada have experienced social, economic, and political disadvantages through colonialism. The policies implemented to assimilate Aboriginal peoples have dissolved cultural ...continuity and unfavorably shaped their health outcomes. As a result, indigenous Canadians face health inequities such as chronic illness, food insecurity, and mental health crises. In 2015, the Canadian government affirmed their responsibility for indigenous inequalities following a historic report by the Truth and Reconciliation Commission of Canada. It has outlined intergenerational traumata imposed upon Aboriginals through decades of systemic discrimination in the form of the Residential School System and the Indian Act. As these policies have crossed multiple lifespans and generations, societal conceptualization of indigenous health inequities must include social determinants of health (SDOH) intersecting with the life course approach to health development to fully capture the causes of intergenerational maintenance of poor health outcomes. To provide culturally sensitive care for those who have experienced intergenerational trauma, health care providers should be aware of and understand two key SDOH inequity influencing the indigenous life course, including the residential school system and loss of socioeconomic status, over time due to colonialism.
Solid ferromagnetic materials are rigid in shape and cannot be reconfigured. Ferrofluids, although reconfigurable, are paramagnetic at room temperature and lose their magnetization when the applied ...magnetic field is removed. Here, we show a reversible paramagnetic-to-ferromagnetic transformation of ferrofluid droplets by the jamming of a monolayer of magnetic nanoparticles assembled at the water-oil interface. These ferromagnetic liquid droplets exhibit a finite coercivity and remanent magnetization. They can be easily reconfigured into different shapes while preserving the magnetic properties of solid ferromagnets with classic north-south dipole interactions. Their translational and rotational motions can be actuated remotely and precisely by an external magnetic field, inspiring studies on active matter, energy-dissipative assemblies, and programmable liquid constructs.
Policy Points The Orphan Drug Act (ODA) was the result of patient advocacy and by many measures has been strikingly successful. However, approximately 95% of the more than 7,000 known rare diseases ...still have no US Food and Drug Administration-approved treatment. The ODA's success led to sustained criticism of high drug prices, often for products that have orphan drug indications. Critics misconstrue the ODA's intent and propose reducing its incentives instead of pursuing policies focused on addressing broader prescription drug price challenges that exist in both the orphan and nonorphan drug market. Patients and their families will continue to defend the purpose and integrity of the ODA and to drive investments into rare disease research and clinical development.
Negative-pressure wound therapy (NPWT) and its variations are an established adjunctive modality for the treatment of wounds. Since its introduction, there have been an increasing number of ...publications with periods of rapid increases in the number of publications after innovations to the technology. Its application in different wound types and varying clinical scenarios has also contributed to the growing number of publications.
A comprehensive literature review (1998-2016) was performed using key words most relevant to NPWT using PubMed/Medline and OVID. Eligibility criteria included higher level evidence studies.
One thousand three hundred and forty-seven publications were identified. A total of 26 publications are included in this review: 16 comparing NPWT with standard wound dressing, 6 comparing variations of NPWT, and 4 for NPWT with instillation. The level of evidence, wound type studied, reported outcomes and impact, and key findings are tabulated and discussed.
The number of publications has grown significantly since the inception of NPWT. In part, this reflects the variations of NPWT that have developed. However, a greater number of robust, randomized, prospective studies are needed to support its wide spread use.
Gustilo-Anderson Classification Kim, Paul H.; Leopold, Seth S.
Clinical orthopaedics and related research,
11/2012, Letnik:
470, Številka:
11
Journal Article
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