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Background: The incidence of inborn errors of metabolism (IEM) varies across countries and areas. Currently, there are no studies on IEM using newborn screening (NBS) in eastern coastal areas of China. We aimed to estimate the incidence and genetic variants of IEM and understand the spectrum of diseases caused by IEM and variants among them in this area. Methods: The NBS performed by tandem mass spectrometry (MS/MS) from 2016 to 2021 was retrospectively reviewed. Heel blood was collected from all newborns 72 h after birth. Targeted massively parallel sequencing was performed for genetic analysis. Results: Among 245,194 newborns, 95 were diagnosed with IEM, the overall incidence observed was—IEM: 1/2581; amino acid metabolism disorder: 1/4715; organic acid metabolism disorder: 1/11676; and fatty acid metabolism disorder: 1/11145. The incidence of different IEM was in the range of 1/245194 to 1/6452. Phenylketonuria (PKU, 1/7211) was the most common IEM, followed by methylmalonic acidemia (MMA, 1/27244), short‐chain acyl‐CoA dehydrogenase deficiency (SCADD, 1/30649), and citrin deficiency (CD, 1/35028). For genetic variants, the common hotspot variants found were—PAH gene for PKU: c.728G > A, c.442‐1G > A, c.611A > G, c.721C > T; PTS gene for non‐classical PKU: c.259C > T; MMACHC gene for MMA: c.658_660delAAG, c.609G > A; MMUT gene for MMA: c.1663G > A; ACADS gene for SCADD: c.1031A > G and c.1130C > T; and SLC25A13 gene for CD: c.1638_1660dup, c.852_855del. Conclusion: This study displayed the diseases and varied spectrum of IEM in eastern coastal areas of China. Implementing NBS for IEM by MS/MS combined with massively parallel sequencing can offer an improved plan for NBS to detect IEM. [ABSTRACT FROM AUTHOR]

The current study was conducted to explore the effects of dietary Clostridium butyricum (C. butyricum) and fermented calcium (Ca) butyrate produced by C. butyricum on the performance and egg quality of post‐peak laying. A total of 384 50‐week‐old hens were fed a basal diet, the basal diet with 300 mg/kg of fermented Ca butyrate or 1 × 109 CFU/kg C. butyricum for 8 weeks. Hens received a C. butyricum exhibited higher yolk properties, albumen height, and Haugh unit. A diet with fermented Ca butyrate or C. butyricum increased the egg mass and the pre‐grade yellow follicle number. RNA‐sequencing (RNA‐seq) data showed that these observations were associated with cytokine–cytokine receptor interaction and intestinal immune status. Accordingly, when compared with the basal diet group, Ca butyrate and C. butyricum addition decreased serum pro‐inflammatory cytokine levels and increased the concentration of immunoglobulin A, along with improved intestinal barrier. In addition, dietary C. butyricum inclusion induced a higher abundance of Ruminococcaceae and Lachnospiraceae at the family level. In summary, dietary fermented Ca butyrate or C. butyricum supplementation improved egg quality and ovarian function, which might be related to the enhanced intestinal barrier and immunity in post‐peak laying hens. [ABSTRACT FROM AUTHOR]

Berberine suppresses advanced glycation end products-associated diabetic retinopathy in hyperglycemic mice To determine whether the inhibitory effect of BBR on VEGF production was mediated by its inhibition of STAT3, we transfected a plasmid encoding constitutively activated STAT3 mutant (STAT3C) into BBR-treated HRECs. The cytotoxicity of BBR on HREC cells was measured by MTT assay and the inhibitory concentration (IC)20 of BBR was calculated as 25.11 M. Doses of BBR lower than the IC20 were considered non-toxic to HREC cells. The formation of advanced glycation end products (AGEs) and AGEs-related signalling pathway activation in the retina leads to the initiation of retinopathy in diabetic patients.1 In this study, we identified the natural compound berberine (BBR) as a potent AGEs inhibitor that significantly suppressed AGEs formation and its related TLR4/STAT3/VEGF signalling pathway in the retina endothelial cells, thus contributing to its therapeutic effect on diabetic retinopathy (DR). [Extracted from the article]

Ge–As–Se chalcogenide glasses were prepared and the surface damage characteristics under femtosecond laser irradiation were experimentally investigated. Femtosecond laser beams with different power intensities, focusing depths, pulse repetition rates, and pulse numbers were employed to determine the damage thresholds of the samples. The surface morphologies and feature sizes of the damage craters were studied with regard to laser energy density to evaluate the damage circumstances of the glasses. The generation of the surface damage was also recorded by using different numbers of pulses. Results showed that the damage area increased monotonically with the laser power at low energy density and tended to saturation when reaching a critical value. According to the linear circumstances of laser energy density on the damage crater area, the average damage thresholds of the Ge–As–Se glasses with different repetition rates and pulse numbers were obtained. Results showed that the damage threshold decreased with the increase in pulse repetition rate and number of pulse. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The aim was to investigate the role of μ‐opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway.What is the main finding and its importance?Our findings show that activation of μ‐opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin. The main pathology of acute respiratory distress syndrome (ARDS) is the accumulation of inflammatory cells in the lung and increased permeability of vascular endothelial cells. The μ‐opioid receptor (MOR) is a G‐protein‐coupled receptor, which stimulates angiogenesis and vascular endothelial cell proliferation. In addition, the MOR inhibits cell apoptosis via the PI3K/Akt signalling pathway. In this study, we aimed to explore the contribution of the MOR in ARDS and whether its effects are mediated via PI3K/Akt signalling. An ARDS model was established by intratracheal instillation of 5 mg kg−1 lipopolysaccharide (LPS). Lung injury was confirmed by Haematoxylin and Eosin staining, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity and vascular cell adhesion molecule 1 expression. Lung inflammation was determined by assessment of interleukin‐1β and tumour necrosis factor‐α concentrations. The protein level of p‐Akt was detected by western blot. Endomorphin‐1‐activated MORs attenuated LPS‐induced lung injury, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity, interleukin‐1β and tumour necrosis factor‐α levels and vascular cell adhesion molecule 1 expression, and elevated LPS‐induced decreased p‐Akt expression. However, the protective effect of MOR activation on lung injury was reversed by the PI3K inhibitor, wortmannin. In conclusion, MOR involvement in LPS‐induced ARDS is via the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Serine racemase (SR) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that is responsible for d-serine biosynthesis in vivo. The first X-ray crystal structure of maize SR was determined to 2.1 Å resolution and PLP binding was confirmed in solution by UV-Vis absorption spectrometry. Maize SR belongs to the type II PLP-dependent enzymes and differs from the SR of a vancomycin-resistant bacterium. The PLP is bound to each monomer by forming a Schiff base with Lys67. Structural comparison with rat and fission yeast SRs reveals a similar arrangement of active-site residues but a different orientation of the C-terminal helix. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? What are the effects of protein kinase C (PKC) and Ca2+-calmodulin-dependent protein kinase II (CaMKII) on late sodium current ( INaL), reverse Na+-Ca2+ exchange current (reverse INCX) or intracellular Ca2+ levels changed by ouabain?, What is the main finding and its importance? Ouabain, even at low concentrations (0.5-8.0 μ m), can increase INaL and reverse INCX, and these effects may contribute to the effect of the glycoside to increase Ca2+ transients and contractility. Both PKC and CaMKII activities may mediate or modulate these processes., It has been reported that the cardiac glycoside ouabain can increase the late sodium current ( INaL), as well as the diastolic intracellular calcium concentration and contractile shortening. Whether an increase of INaL participates in a pathway that can mediate the positive inotropic response to ouabain is unknown. We therefore determined the effects of ouabain on INaL, reverse Na+-Ca2+ exchange current (reverse INCX), intracellular Ca2+ ([Ca2+]i) levels and contractile shortening in rabbit isolated ventricular myocytes. Ouabain (0.1-8 μ m) markedly increased INaL and reverse INCX in a concentration-dependent manner, with significant effects at concentrations as low as 0.5 and 1 μ m. These effects of ouabain were suppressed by the INaL inhibitors TTX and ranolazine, the protein kinase C inhibitor bisindolylmaleimide and the Ca2+-calmodulin-dependent protein kinase II inhibitor KN-93. The enhancement by 0.5 μ m ouabain of ventricular myocyte contractility and intracellular Ca2+ transients was suppressed by 2.0 μ m TTX. We conclude that ouabain, even at low concentrations (0.5-8.0 μ m), can increase INaL and reverse INCX, and these effects may contribute to the effect of the glycoside to increase Ca2+ transients and contractility. Both protein kinase C and Ca2+-calmodulin-dependent protein kinase II activities may mediate or modulate these processes. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to evaluate the safety of reducing or withdrawing anti-seizure medications (ASMs) in a cohort comprising both adults and children with drug-resistant epilepsy (DRE) undergoing ketogenic diet therapy (KDT)., Methods: We conducted a comprehensive analysis of clinical profiles in adults and children with DRE who had adhered to KDT for at least 6 months. Successful withdrawal or reduction of an ASM was defined as discontinuation or dose reduction without subsequent resumption or increase and without initiation of any new ASM throughout the entire follow-up period. Changes in the ASM load were calculated specifically for adult patients., Results: The study enrolled 56 participants (34 children and 22 adults) with DRE, with 64.3% achieving successful withdrawal of at least one ASM. The probability of ASM withdrawal remained consistent for children (64.7%) versus adults (63.6%), as well as for responders (62.5%) versus non-responders (68.8%), and it was not associated with other clinical factors. Early ASM reduction (including withdrawal) after diet initiation occurred in 15 patients (26.8%), with treatment outcomes comparable to those of the remaining participants. Among the 22 adults, the mean values of ASM load reduced by 24.5%, with a similar magnitude observed for responders (24.2%) versus non-responders (25.1%). In addition, adults tend to have a slower elevation in serum ketone levels compared to children., Conclusion: This study demonstrates the safe achievability of ASM withdrawal through KDT in most patients with DRE, irrespective of age or seizure frequency reduction., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

New Findings: What is the central question of this study? What are the effects of protein kinase C (PKC) and Ca(2+) -calmodulin-dependent protein kinase II (CaMKII) on late sodium current (INaL ), reverse Na(+) -Ca(2+) exchange current (reverse INCX ) or intracellular Ca(2+) levels changed by ouabain? What is the main finding and its importance? Ouabain, even at low concentrations (0.5-8.0 μm), can increase INaL and reverse INCX , and these effects may contribute to the effect of the glycoside to increase Ca(2+) transients and contractility. Both PKC and CaMKII activities may mediate or modulate these processes. It has been reported that the cardiac glycoside ouabain can increase the late sodium current (INaL ), as well as the diastolic intracellular calcium concentration and contractile shortening. Whether an increase of INaL participates in a pathway that can mediate the positive inotropic response to ouabain is unknown. We therefore determined the effects of ouabain on INaL , reverse Na(+) -Ca(2+) exchange current (reverse INCX ), intracellular Ca(2+) ([Ca(2+) ]i ) levels and contractile shortening in rabbit isolated ventricular myocytes. Ouabain (0.1-8 μm) markedly increased INaL and reverse INCX in a concentration-dependent manner, with significant effects at concentrations as low as 0.5 and 1 μm. These effects of ouabain were suppressed by the INaL inhibitors TTX and ranolazine, the protein kinase C inhibitor bisindolylmaleimide and the Ca(2+) -calmodulin-dependent protein kinase II inhibitor KN-93. The enhancement by 0.5 μm ouabain of ventricular myocyte contractility and intracellular Ca(2+) transients was suppressed by 2.0 μm TTX. We conclude that ouabain, even at low concentrations (0.5-8.0 μm), can increase INaL and reverse INCX , and these effects may contribute to the effect of the glycoside to increase Ca(2+) transients and contractility. Both protein kinase C and Ca(2+) -calmodulin-dependent protein kinase II activities may mediate or modulate these processes., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)