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Morphogen gradients are a central concept in developmental biology. Their formation often involves the secretion of morphogens from a local source, that spread by diffusion in the cell field, where molecules eventually get degraded. This implies limits to both the time and length scales over which morphogen gradients can form which are set by diffusion coefficients and degradation rates. Towards the goal of identifying plausible mechanisms capable of extending the gradient range, we here use theory to explore properties of a cell-to-cell signaling relay. Inspired by the millimeter-scalewnt-expression and signaling gradients in flatworms, we consider morphogen-mediated morphogen production in the cell field. We show that such a relay can generate stable morphogen and signaling gradients that are oriented by a local, morphogen-independent source of morphogen at a boundary. This gradient formation can be related to an effective diffusion and an effective degradation that result from morphogen production due to signaling relay. If the secretion of morphogen produced in response to the relay is polarized, it further gives rise to an effective drift. We find that signaling relay can generate long-range gradients in relevant times without relying on extreme choices of diffusion coefficients or degradation rates, thus exceeding the limits set by physiological diffusion coefficients and degradation rates. A signaling relay is hence an attractive principle to conceptualize long-range gradient formation by slowly diffusing morphogens that are relevant for patterning in adult contexts such as regeneration and tissue turn-over.We report a detailed experimental study on the structural and magnetic properties of Li3NiCuBiO6by means of various characterization techniques. It crystallizes into a monoclinic crystal structure composed of a layered magnetic honeycomb lattice along thec-axis. The existence of glassy state below 4 K is indicated by dc and ac susceptibility measurements. Magnetic contribution to the total heat capacity also peaks around the freezing temperature, and its linear temperature dependence backs our claim of a glassy state in the compound. The calculated magnetic entropy unveils that only ∼26% of the total entropy is released for the system (S=3/2), and a tremendous amount of spin entropy is still retained in the system. Further, analysis of the frequency-dependent freezing temperature with the help of power law confirms the presence of a spin glass state. Moreover, the appearance of magnetic memory and relaxation effect below freezing temperature manifest the development of the system via a large number of intermediate metastable states. All these measurements confirm the spin-glass behavior of the compound. We consider the presence of different magnetic atoms in honeycomb lattice as the main driving factor for the spin-glass ground state.Hepatocytes have important roles in liver iron homeostasis, abnormalities in which are tightly associated with liver steatosis and fibrosis. Here, we show that non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are characterized by iron-deficient hepatocytes and iron overload in hepatic stellate cells (HSCs). Iron deficiency enhances hepatocyte lipogenesis and insulin resistance through HIF2α-ATF4 signaling. Elevated secretion of iron-containing hepatocyte extracellular vesicles (EVs), which are normally cleared by Kupffer cells, accounts for hepatocyte iron deficiency and HSC iron overload in NAFLD/NASH livers. Iron accumulation results in overproduction of reactive oxygen species that promote HSC fibrogenic activation. Conversely, blocking hepatocyte EV secretion or depleting EV iron cargo restores liver iron homeostasis, concomitant with mitigation of NAFLD/NASH-associated liver steatosis and fibrosis. Taken together, these studies show that iron distribution disorders contribute to the development of liver metabolic diseases.The molecular interactions that regulate chronic inflammation underlying metabolic disease remain largely unknown. Since the CD24-Siglec interaction regulates inflammatory response to danger-associated molecular patterns (DAMPs), we have generated multiple mouse strains with single or combined mutations of Cd24 or Siglec genes to explore the role of the CD24-Siglec interaction in metaflammation and metabolic disorder. Here, we report that the CD24-Siglec-E axis, but not other Siglecs, is a key suppressor of obesity-related metabolic dysfunction. Inactivation of the CD24-Siglec-E pathway exacerbates, while CD24Fc treatment alleviates, diet-induced metabolic disorders, including obesity, dyslipidemia, insulin resistance, and nonalcoholic steatohepatitis (NASH). Mechanistically, sialylation-dependent recognition of CD24 by Siglec-E induces SHP-1 recruitment and represses metaflammation to protect against metabolic syndrome. A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease.Lactate released from skeletal muscle during high-intensity exercise gives rise to a surge in circulating lactate-derived pseudo-dipeptide metabolites including N-lactoyl-phenylalanine (Lac-Phe). In a recent Nature paper, Li et al. use genetic and pharmacological evidence to now propose Lac-Phe to be an "exercise hormone" that suppresses appetite and obesity.Disorders of carbohydrate metabolism, including hypoglycemia and lactic acidosis, are common features of malaria. In this issue of Cell Metabolism, Ramos et al. report that regulation of gluconeogenesis and glycemia by the host glucose-6-phosphatase catalytic subunit 1 (G6Pc1) is a key metabolic step that affects both Plasmodium replication and clinical outcome of disease.Obesity is linked to inflammation and downstream metabolic dysregulation. In this issue of Cell Metabolism, Hägglöf et al. show that iNKT cells enable the accumulation of T-bet+ B cells in white adipose tissue, which in turn produce chemokine and antibody mediators that exacerbate the onset and severity of metabolic disease.Astrocytes are brain cells that react to Alzheimer's disease pathology in ways that can have either beneficial or detrimental effects. In this issue of Cell Metabolism, Ju et al. outline a novel strategy for coercing astrocytes to a neuroprotective state by maintaining liver-like detoxification in the brain without producing damaging byproducts.In Atlantic salmon (Salmo salar) seasonal photoperiod is shown to regulate the onset of sexual maturation, yet which brain region(s) are involved and how light information impacts the neuroendocrine system are still not fully understood in teleosts. Detailed knowledge about the photoperiodic regulation of maturation in fish is still missing. In birds, it is shown that gonadotrophin releasing hormone (GNRH) is located in the same neurons as vertebrate ancient (VA) opsin suggesting a direct photoreceptive regulation for onset of sexual maturity. This study presents a comprehensive topographic mapping of gnrh2, gnrh3, kisspeptin 2 (kiss2) gonadotrophin inhibiting hormone (gnih) and VA opsin using in situ hybridization on mature Atlantic salmon brains. Neurons positive for gnrh3 are expressed in the olfactory bulb and ventral telencephalon while gnrh2 positive neurons are located dorsally in midbrain tegmentum. Gnih expressing cell bodies are present in the ventral thalamus and extend caudally to the hypothalamus with kiss2 expressing cells appearing in a lateral position. Aurora Kinase inhibitor VA opsin positive cells are present in the telencephalon, the rostro-dorsal ring of left habenula, the ventral thalamus and the midbrain tegmentum. The results show no similar co-location as found in birds, hypothesizing that the photoreceptive modulation of Gnrh in salmon may interact through neuronal networks. The topography analyses of the essential neuroendocrine cells related to sexual maturation in Atlantic salmon brain show that diencephalic (thalamus, hypothalamus) and midbrain (tegmentum) regions seem central for controlling sexual maturation.

The aim of this study was to compare posterior subtenon triamcinolone (PSTA) application and intravitreal dexamethasone phosphate (DEX) implant in the treatment of diabetic macular edema (DME) in vitrectomized eyes.

This retrospective study included 64 (48.12%) patients who received PSTA and 69 (51.88%) patients who received DEX implants in DME treatment after vitrectomy. Best corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were analyzed before injection; at 1, 3, and 6 months after injection. The postinjection values were statistically compared with the preinjection value.

All postinjection CMT values in both groups were lower than the preinjection value (p < 0.05 for all). There were statistically significant increases in all postinjection BCVAs of the DEX group and postinjection 1-month BCVA of the PSTA group (p < 0.05 for all). However, there was no significant difference in BCVA values of the PSTA group at 3 and 6 months after injection (p > 0.05 for both). There was no statistically significant difference in all postinjection IOP values of the PSTA group (p > 0.05 for all). However, significant increases in IOP were observed in the DEX group at 1 and 3 months after injection (p < 0.05 and p = 0.02, respectively). The number of additional injections between the 3rd and 6th months after the initial injection was statistically higher in the PSTA group (p = 0.006).

Both intravitreal DEX and PSTA administration are effective in the treatment of DME after vitrectomy. However, visual improvement persisted longer, and the need for additional injections was less in patients who received DEX.

Both intravitreal DEX and PSTA administration are effective in the treatment of DME after vitrectomy. However, visual improvement persisted longer, and the need for additional injections was less in patients who received DEX.

The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke.

A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset.

A total of 6,t first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control.

The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control.