From 0D to 2D: Synthesis and bio-application of anisotropic magnetic iron oxide nanomaterials

Magnetic iron oxide nanoparticles (MIPs) have garnered significant scientific interest due to their magnetic properties and unique features, including low toxicity, colloidal stability, and surface engineering capability. Recent advances in nanoparticle synthesis have enabled the development of MIPs with precise control over their physicochemical properties, making them suitable for medical applications. Anisotropic MIPs have demonstrated shape-dependent performance in various bio-applications, leading to increased research moving from traditional zero-dimensional (0D) morphology towards one-dimensional (1D) and two-dimensional (2D) topology. While these anisotropic materials offer enhanced properties for specific applications, a critical and systematic comparison of their anisotropy effects is lacking in the literature. This review seeks to fill this current gap in the literature and provides a comprehensive summary of the last two decades of research on magnetic iron oxide materials with different shapes in biomedical applications. The paper will discuss the theoretical mechanisms of shape-dependent effects, primary synthetic approaches of 0D, 1D, and 2D MIP materials, biomedical applications, and biological behaviors. In addition, the review identifies critical challenges and open questions that need to be addressed. The proposed research directions outlined in this review have the potential to revitalize the use of “old” MIPs towards future physicochemical and biomedical applications

Bisphosphonates for osteoporosis in people with cystic fibrosis (Review)

BackgroundOsteoporosis is a bone mineralisation disorder occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post-menopausal women and people receiving long-term oral corticosteroids.ObjectivesTo assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis.Search methodsWe searched the Cystic Fibrosis and Genetic Disorders Group Trials Register of references (identified from electronic database searches and handsearches of journals and abstract books) on 13 January 2014.Additional searches of PubMed were performed on 13 January 2014.Selection criteriaRandomised controlled trials of at least six months duration studying bisphosphonates in people with cystic fibrosis.Data collection and analysisTwo authors independently selected trials and extracted data. Trial investigators were contacted to obtain missing data.Main resultsNine trials were identified and seven (with a total of 237 adult participants) were included.Data were combined (when available) from six included studies in participants without a lung transplant. Data showed that there was no significant reduction in fractures between treatment and control groups at 12 months, odds ratio 0.72 (95% confidence interval 0.13 to 3.80). No fractures were reported in studies with follow-up at 24 months. However, in patients taking bisphosphonates after six months the percentage change in bone mineral density increased at the lumbar spine, mean difference 4.61 (95% confidence interval 3.90 to 5.32) and at the hip or femur, mean difference 3.35 (95% confidence interval 1.63 to 5.07); but did not significantly change at the distal forearm, mean difference -0.49 (95% confidence interval -2.42 to 1.45). In patients taking bisphosphonates, at 12 months the percentage change in bone mineral density increased at the lumbar spine, mean difference 6.10 (95% confidence interval 5.10 to 7.10) and at the hip or femur, mean difference 4.35 (95% confidence interval 2.99 to 5.70). At 24 months, in patients treated with bisphosphonates the percentage change in bone mineral density also increased at the lumbar spine, mean difference 5.49 (95% confidence interval 4.38 to 6.60) and at the hip or femur, mean difference 6.05 (95% confidence interval 3.74 to 8.36). There was clinical heterogeneity between studies and not all studies reported all outcomes. Bone pain was the most common adverse event with intravenous agents. Flu-like symptoms were also increased in those taking bisphosphonates.In participants with a lung transplant (one study), intravenous pamidronate did not change the number of new fractures. At axial sites, bone mineral density increased with treatment compared to controls: percentage change in bone mineral density at lumbar spine, mean difference 6.20 (95% confidence interval 4.28 to 8.12); and femur mean difference 7.90 (95% confidence interval 5.78 to 10.02).Authors\u27 conclusionsOral and intravenous bisphosphonates increase bone mineral density in people with cystic fibrosis. Severe bone pain and flu-like symptoms may occur with intravenous agents. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids ameliorate or prevent these adverse events. Additional trials are also required to further assess gastrointestinal adverse effects associated with oral bisphosphonates. Trials in larger populations are needed to determine effects on fracture rate and survival

The excavation of Non Ban Jak, Northeast Thailand - A report on the first three seasons

Non Ban Jak is a large, moated site located in the upper Mun Valley, Northeast Thailand. Excavations over three seasons in 2011-4 have revealed a sequence of occupation that covers the final stage of the local Iron Age. The site is enclosed by two broad moats and banks, and comprises an eastern and a western mound separated by a lower intervening area. The first season opened an 8 by 8 m square on the eastern mound, while the second and third seasons uncovered part of the low terrain rising into the western mound, encompassing an area of 25 by 10 m. The former revealed a sequence of industrial, residential and mortuary activity that involved the construction of houses, kiln firing of ceramic vessels and the interment of the dead within residences. The latter involved four phases of a late Iron Age cemetery, which again incorporated house floors and wall foundations, as well as further evidence for ceramic manufacture. The excavation sheds light on a late Iron Age town occupied at the threshold of state formation

Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1.

Obesity produces a chronic inflammatory state involving the NFκB pathway, resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1. In this study, we report that these kinases attenuate β-adrenergic signaling in white adipose tissue. Treatment of 3T3-L1 adipocytes with specific inhibitors of these kinases restored β-adrenergic signaling and lipolysis attenuated by TNFα and Poly (I:C). Conversely, overexpression of the kinases reduced induction of Ucp1, lipolysis, cAMP levels, and phosphorylation of hormone sensitive lipase in response to isoproterenol or forskolin. Noncanonical IKKs reduce catecholamine sensitivity by phosphorylating and activating the major adipocyte phosphodiesterase PDE3B. In vivo inhibition of these kinases by treatment of obese mice with the drug amlexanox reversed obesity-induced catecholamine resistance, and restored PKA signaling in response to injection of a β-3 adrenergic agonist. These studies suggest that by reducing production of cAMP in adipocytes, IKKε and TBK1 may contribute to the repression of energy expenditure during obesity. DOI: http://dx.doi.org/10.7554/eLife.01119.001

Migrants' community participation and social integration in urban areas:A scoping review

Social integration is a growing concern in global migration studies, and community participation is a way to promote migrants' social integration. This scoping review aims to determine how migrants' community participation influences their social integration in urban areas. A literature search was conducted to identify studies in English published between January 2011 and July 2021. Twenty-eight documents met the inclusion criteria. Three key elements of community participation were identified: 1) social capital, 2) the way of using public space, and 3) community participation strategies. Community participation assists migrants in dealing with inequality, marginalization, and rural-urban adaptation in developing countries. Furthermore, it exercises a mediating role in solving community problems and alleviating tensions between migrants and locals in developed countries. Community participation also helps international migrants tackle cross-cultural/ethnic challenges and compensates internal migrants for institutional segregation. Overall, community participation can fulfill migrants' instant needs, expand their social network, and facilitate psychological integration; however, it does not necessarily contribute to social integration when the participation environment is biased and lacks meaningful encounters. Finally, three research gaps are highlighted: the distinction between integration into a migrant community and broader society, the degree of participation, and a gender perspective.</p

Investigation of Cytotoxic T Lymphocyte Function during Allorejection in the Anterior Chamber of the Eye

Cytotoxic T lymphocytes (CTL) are an essential part of our immune system by killing infected and malignant cells. To fully understand this process, it is necessary to study CTL function in the physiological setting of a living organism to account for their interplay with other immune cells like CD4+ T helper cells and macrophages. The anterior chamber of the eye (ACE), originally developed for diabetes research, is ideally suited for non-invasive and longitudinal in vivo imaging. We take advantage of the ACE window to observe immune responses, particularly allorejection of islets of Langerhans cells by CTLs. We follow the onset of the rejection after vascularization on islets until the end of the rejection process for about a month by repetitive two-photon microscopy. We find that CTLs show reduced migration on allogeneic islets in vivo compared to in vitro data, indicating CTL activation. Interestingly, the temporal infiltration pattern of T cells during rejection is precisely regulated, showing enrichment of CD4+ T helper cells on the islets before arrival of CD8+ CTLs. The adaptation of the ACE to immune responses enables the examination of the mechanism and regulation of CTL-mediated killing in vivo and to further investigate the killing in gene-deficient mice that resemble severe human immune diseases

Food assistance is associated with improved body mass index, food security and attendance at clinic in an HIV program in central Haiti: a prospective observational cohort study

<p>Abstract</p> <p>Background</p> <p>Few data are available to guide programmatic solutions to the overlapping problems of undernutrition and HIV infection. We evaluated the impact of food assistance on patient outcomes in a comprehensive HIV program in central Haiti in a prospective observational cohort study.</p> <p>Methods</p> <p>Adults with HIV infection were eligible for monthly food rations if they had any one of: tuberculosis, body mass index (BMI) <18.5kg/m², CD4 cell count <350/mm³(in the prior 3 months) or severe socio-economic conditions. A total of 600 individuals (300 eligible and 300 ineligible for food assistance) were interviewed before rations were distributed, at 6 months and at 12 months. Data collected included demographics, BMI and food insecurity score (range 0 - 20).</p> <p>Results</p> <p>At 6- and 12-month time-points, 488 and 340 subjects were eligible for analysis. Multivariable analysis demonstrated that at 6 months, food security significantly improved in those who received food assistance versus who did not (-3.55 vs -0.16; P < 0.0001); BMI decreased significantly less in the food assistance group than in the non-food group (-0.20 vs -0.66; P = 0.020). At 12 months, food assistance was associated with improved food security (-3.49 vs -1.89, P = 0.011) and BMI (0.22 vs -0.67, P = 0.036). Food assistance was associated with improved adherence to monthly clinic visits at both 6 (P < 0.001) and 12 months (P = 0.033).</p> <p>Conclusions</p> <p>Food assistance was associated with improved food security, increased BMI, and improved adherence to clinic visits at 6 and 12 months among people living with HIV in Haiti and should be part of routine care where HIV and food insecurity overlap.</p

Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity.

Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis

The δ‐opioid receptor positive allosteric modulator BMS 986187 is a G‐protein‐biased allosteric agonist

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149355/1/bph14602.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149355/2/bph14602_am.pd

In utero ultrafine particulate matter exposure causes offspring pulmonary immunosuppression.

Early life exposure to fine particulate matter (PM) in air is associated with infant respiratory disease and childhood asthma, but limited epidemiological data exist concerning the impacts of ultrafine particles (UFPs) on the etiology of childhood respiratory disease. Specifically, the role of UFPs in amplifying Th2- and/or Th17-driven inflammation (asthma promotion) or suppressing effector T cells (increased susceptibility to respiratory infection) remains unclear. Using a mouse model of in utero UFP exposure, we determined early immunological responses to house dust mite (HDM) allergen in offspring challenged from 0 to 4 wk of age. Two mice strains were exposed throughout gestation: C57BL/6 (sensitive to oxidative stress) and BALB/C (sensitive to allergen exposure). Offspring exposed to UFPs in utero exhibited reduced inflammatory response to HDM. Compared with filtered air (FA)-exposed/HDM-challenged mice, UFP-exposed offspring had lower white blood cell counts in bronchoalveolar lavage fluid and less pronounced peribronchiolar inflammation in both strains, albeit more apparent in C57BL/6 mice. In the C57BL/6 strain, offspring exposed in utero to FA and challenged with HDM exhibited a robust response in inflammatory cytokines IL-13 and Il-17. In contrast, this response was lost in offspring exposed in utero to UFPs. Circulating IL-10 was significantly up-regulated in C57BL/6 offspring exposed to UFPs, suggesting increased regulatory T cell expression and suppressed Th2/Th17 response. Our results reveal that in utero UFP exposure at a level close to the WHO recommended PM guideline suppresses an early immune response to HDM allergen, likely predisposing neonates to respiratory infection and altering long-term pulmonary health