Effect of dietary Glycyrrhiza polysaccharides on growth performance, hepatic antioxidant capacity and anti-inflammatory capacity of broiler chickens.

The primary aim of this study was to investigate the impact of varying levels of dietary Glycyrrhiza polysaccharides (GPS) on the health status of broiler chickens. A total of 288 1-day-old Arbor Acres broilers were randomly assigned to four groups with six replicates, consisting of 12 chickens in each replicate. The control group (CON) was provided with the basal diet, while the experimental groups were administered 300, 600, and 900 mg/kg of GPS in the basal diet for 42 days. The results demonstrated a significant enhancement in average daily gain (ADG) as a result of GPS supplementation (P < 0.05). The dietary GPS significantly elevated total antioxidation capability (T-AOC) and the activity of antioxidant enzymes (P < 0.05), while effectively reducing the levels of malondialdehyde (MDA) in the serum and liver (P < 0.05). Administration of GPS notably inhibited the toll-like receptor 4 (TLR4) signaling pathway (P < 0.05), decreased interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) levels (P < 0.05), and increased IL-4 and IL-10 levels (P < 0.05). Additionally, the expression of crucial regulators involved in liver lipid metabolism, including sterol regulatory element binding protein 1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were significantly reduced (P < 0.05). In contrast, the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) was significantly enhanced in the GPS-supplemented groups (P < 0.05). In conclusion, the supplementation of GPS positively influenced the growth performance, the anti-inflammatory and antioxidant capacity of the liver, as well as liver lipid metabolism in broilers.

Diagnostic performance analysis of the Integrated Care for Older People (ICOPE) screening tool for identifying decline in intrinsic capacity.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of an individual's positive attributes. The World Health Organization (WHO) recommends a two-step approach to assess IC decline among older people. The first step involves the used of the integrated care for older people (ICOPE) screening tool to identify potential issues, and the second step involves using detailed assessments for confirmation. This study aimed to assess the diagnostic performance of the ICOPE screening tool as a simple preliminary screening to identify IC decline among community-dwelling older people, which has been rarely reported in China. METHODS: This cross-sectional study included 228 community-dwelling older individuals aged ≥ 75 (mean age, 84.0 ± 4.4 years; 131 [57.5%] females) who completed the IC evaluation according to the WHO IC assessment pathway. The diagnostic performance of the ICOPE screening tool was calculated using a 2 × 2 table and a receiver operating characteristic curve. RESULTS: The proportion of possible IC decline identified by the ICOPE screening tool was 79.4%, whereas the actual IC decline assessed by the detailed assessment was 73.2%, mainly in locomotion. The ICOPE screening tool showed sensitivity and specificity of 94.6% and 62.3%, respectively, with an overall diagnostic accuracy of 86.0%. The diagnostic effectiveness of the ICOPE screening tool was 0.91 (95% confidence interval: 0.87-0.95, p = 0.020). Except for the sensory dimension, the sensitivity of the ICOPE screening tool for diagnosing impairments in each dimension of the IC was the highest in the cognition domain (100%) and the lowest in the vitality domain (51.3%), whereas the specificity was the highest in vitality (94.7%) and the lowest in cognition (55.6%). CONCLUSIONS: The ICOPE screening tool exhibits high sensitivity and can be used as an IC screening tool in community-dwelling older people. However, further improvements are needed in the vitality dimension of the ICOPE screening tool to enhance its sensitivity in identifying individuals at risk of malnutrition.

Effects of Glycyrrhiza polysaccharide on growth performance, appetite, and hypothalamic inflammation in broilers.

We analyzed the effects of Glycyrrhiza polysaccharide (GCP) on growth performance, appetite, and hypothalamic inflammation-related indexes in broilers. One-day-old male AA broilers were randomly divided into four groups: Control, L-GCP, M-GCP, and H-GCP (0, 300, 600, and 900 mg GCP/kg feed), with six repetition cages for each treatment and 12 broilers in each repeat for a period of 42 days. From day 1 to day 21, the addition of GCP to the diet significantly improved the ADFI and the ADG of broilers, and the mRNA levels of NPY and AgRP were significantly increased while POMC and CART were decreased in the hypothalamus of broilers; GCP also significantly decreased the mRNA levels of IL-1ß, IL-6, TNF-α, TLR-4, MyD88, and NF-κB, and increased the IL-4 and IL-10 in the hypothalamus from day 1 to day 42. The concentrations of appetite-related factors and inflammatory factors in serum were changed in the same fashion. Supplementation with 600 mg/kg GCP had the optimal effect in broilers, and GCP has the potential to be used as a feed additive in the poultry production industry.

In this work, we analyzed the effects of Glycyrrhiza polysaccharide on growth performance, appetite, and hypothalamic inflammation in broilers. In the past, antibiotics were added to poultry feed to prevent disease and improve growth performance; however, the extensive use of antibiotics can negatively affect livestock and poultry, and endanger the health of consumers. Glycyrrhiza polysaccharide has many biological activities. In order to explore the possibility of Glycyrrhiza polysaccharide as a substitute for antibiotics, we evaluated the effects of Glycyrrhiza polysaccharide added to the diet of broilers for 42 days. Our research confirmed that Glycyrrhiza polysaccharide supplementation increased food intake by regulating appetite-related factors in hypothalamus and serum, and also alleviated inflammation.

Vitamin D Supplementation for the Outcomes of Patients with Gestational Diabetes Mellitus and Neonates: A Meta-Analysis and Systematic Review.

Background: Prevention and timely treatment of gestational diabetes mellitus (GDM) are important to the prognosis of pregnant women and neonates. We aimed to conduct a meta-analysis to evaluate the effects and safety of vitamin D supplementation on GDM patients and neonates, to provide insights into clinical GDM treatment. Methods: Two authors searched the Medline, PubMed, Cochrane Library, Web of Science, Embase, CNKI, and Wanfang databases for randomized controlled trials (RCTs) on the effects and safety of vitamin D supplementation in GDM patients. The quality of the included RCTs was evaluated according to Cochrane handbook. RevMan 5.3 software was used for statistical analysis. Results: A total of 20 RCTs involving 1682 GDM patients were finally included, of whom 837 received vitamin D supplementation. Vitamin D supplementation in GDM patients increased the serum 25(OH)D level (SMD = 4.07, 95% CI: (2.73, 5.41)) and HDL level (SMD = 0.41, 95% CI: (0.23, 0.58)) and reduced serum LDL (SMD = -0.49, 95% CI: (-0.68, -0.29)), TG (SMD = -0.59, 95% CI: (-1.01, -0.17)), and TC (SMD = -0.67, 95% CI: (-1.19, -0.14)) levels in GDM patients (all P < 0.05). Besides, vitamin D supplementation reduced the risk of premature birth (OR = 0.37, 95% CI: (0.22, 0.62)), hyperbilirubinemia (OR = 0.38, 95% CI: (0.25, 0.58)), and neonatal hospitalization (OR = 0.38, 95% CI: (0.25, 0.58)) of neonates (all P < 0.05). No significant publication bias in synthesized results was found (all P > 0.05). Conclusions: Vitamin D supplementation improves the blood lipid level in GDM patients and reduces adverse neonatal outcomes. The dose and duration of vitamin D supplementation for safety need to be further investigated in future high-quality studies.

Antioxidant monoammonium glycyrrhizinate alleviates damage from oxidative stress in perinatal cows.

This study was conducted to evaluate the antioxidant capability of dietary supplementation with monoammonium glycyrrhizinate (MAG) in perinatal cows. Glycyrrhizic acid has been shown to have strong antioxidant activity and we hypothesised that the aglycone of glycyrrhizin and MAG, could reduce damage from oxidative stress in perinatal cows by enhancing antioxidant capacity. Blood and milk samples were collected from three groups of healthy perinatal cows that were similar in body weight, parity, milk yield in the last milk cycle, etc., receiving dietary MAG supplementation ([Day 0 = parturition]: 0 g/day, [n = 13)] 3 g/day [n = 13] or 6 g/day [n = 11]) from -28 to 56 day (0 day = parturition). Compared with 0 g/day controls (CON), milk fat was significantly decreased in cows fed with MAG, and 3 g/day had the greatest effect. A diet containing 3 g/day MAG decreased the serum alanine aminotransferase (ALT) level compared with CON at -7 day post-partum. ALT was also lower at 5 day post-partum in cows fed with 3 g/day MAG compared to 6 g/day. The administration of 3 g/day and 6 g/day MAG decreased serum aspartate transaminase (AST) at 3 day post-partum. Supplementation of MAG in cows increased total antioxidant capacity (T-AOC) in serum, and cows given 3 g MAG per day had higher T-AOC than controls on post-partum 7 day. At the end of the experiment, we isolated and cultured primary hepatocytes to determine the effect of MAG on oxidative stress caused by incubation with the sodium oleate (SO). SO increased lipid synthesis, but pre-treatment with MAG prevented the fatty buildup. SO treatment increased AST and ALT levels and malondialdehyde concentration, but decreased T-AOC and superoxide dismutase (SOD). Incubation with MAG increased antioxidant capacity and inhibited oxidant damage in bovine hepatocytes. SO stimulated expression of the antioxidant genes, NAD(P)H quinone dehydrogenase 1 (NQO1) and SOD1, in the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, and catalase 1 (CAT1); this increase was accentuated by MAG pre-treatment. The results suggest that MAG can alleviate the damage caused by oxidative stress in perinatal cows by enhancing antioxidant activity.

Effects of dietary Glycyrrhiza polysaccharide on growth performance, blood parameters and immunity in weaned piglets.

The purpose of this study was to evaluate the effects of dietary Glycyrrhiza polysaccharide (GCP) on growth performance, blood parameters and immunity in weaned piglets. A total of 240 (10.33 ± 0.62 kg body weight) 35-day-old (Duroc × Landrace × White) weaned piglets were randomly assigned to four dietary treatments, with six replicate pens per treatment and 10 piglets per pen (five males and five females). The dietary treatments continued for 21 days and comprised a basal diet supplemented with 0 (control group), 500, 1000 and 2000 mg/kg GCP. The results showed that the inclusion of 1000 and 2000 mg/kg GCP increased the average daily gain and decreased the feed conversion rate compared with the control group (p < 0.05). The piglets treated with 500 and 1000 mg/kg GCP had a lower diarrhoeal incidence than the control group (p < 0.05). Moreover, supplementation with 1000 mg/kg GCP increased the counts of white blood cells, neutrophils, red blood cells, and platelets, and elevated alkaline phosphatase, total protein, globulin, glucose, triglyceride, immunoglobulin A, immunoglobulin G, and total antioxidant capacity levels (p < 0.05), and decreased malondialdehyde content compare with the control group (p < 0.05). In addition, relative to the control group, piglets fed 500 and 1000 mg/kg GCP had significantly lower expression of interleukin-6 mRNA in spleen (p < 0.05). Our results indicate that dietary supplementation with GCP can improve growth performance, blood parameters and immunity in weaned piglets. Our study suggests that adding 1000 mg/kg GCP to the diet had the most beneficial effect.

Effects of dietary Glycyrrhiza polysaccharide on growth, serum biochemistry, immunity, and egg laying in quail.

This study was conducted to evaluate the effects of dietary supplementation with Glycyrrhiza polysaccharide (GCP) on growth performance, serum biochemistry, immunity, and egg laying in female quail. 300 1-day-old female quail were sorted into four dietary treatments with five replicate cages of 15 birds each. The basic diet in the four treatment groups was supplemented with 0, 500, 1000 and 1500 mg/kg GCP, and the experiment continued for 80 days. Results showed that dietary supplementation with GCP significantly (p < 0.05) increased average daily gain in a dose-dependent fashion, and decreased (p < 0.05) the feed-to-gain ratio and mortality. The relative weights of the thymus and bursa of Fabricius increased (p < 0.05) linearly with increasing dose of GCP from 0 to 1500 mg/kg on day 20. GCP birds showed higher serum levels of protein, glucose, immunoglobulin A and immunoglobulin M, but lower serum triglycerides (p < 0.05) on day 50. GCP increased (p < 0.05) average laying rate and average egg weight linearly from days 60 to 80, whereas feed to egg ratio was decreased (p < 0.05). Taken together, these results revealed that GCP could improve growth performance, serum biochemistry, immunity, and egg laying in female quail. Therefore, GCP may be a potential replacement for antibiotic growth promoters in poultry.

Effects of dietary Glycyrrhiza polysaccharide supplementation on growth performance, intestinal antioxidants, immunity and microbiota in weaned piglets.

The aim of this study was to evaluate the effects of dietary Glycyrrhiza polysaccharide (GCP) supplementation on growth performance, intestinal antioxidants, immunity and microbiota in weaned piglets. One hundred and twenty 28-day-old weaned piglets were randomly assigned into five groups (four replicates per group) and fed a basal diet with GCP at 0, 500, 1000, 2000 and 4000 mg/kg for four weeks, respectively. Results showed that 1000 mg/kg GCP improved piglets' ADG and ADFI and reduced FCR (p < .05). Thus, the 0 and 1000 mg/kg GCP dose were selected for subsequent experiments. We found that 1000 mg/GCP increased SOD and T-AOC and decreased MDA in the jejunal mucosa (p < .05). Dietary 1000 mg/kg GCP also resulted in high levels of sIgA, IL-10 and TGF-ß, whereas IL-2 dropped dramatically (p < .05). The relative expression levels of ZO-1, CLDN, OCLDN, TLR-4, IL-10, TGF-ß, Nrf-2, SOD1 and CAT increased in the jejunal mucosa, whereas INF-γ decreased (p < .05). 1000 mg/kg GCP treatment altered the diversity and community composition of cecal microbiota in pigs, with increasing relative abundance of Bacteroidota and Lactobacillus at phylum and genus levels (p < .05), respectively. The results suggested that dietary 1000 mg/kg GCP could improve growth performance and intestinal health of weaned piglets.

Phytoremediation Potential and Physiological Mechanisms Underlying Metallic Extraction of Suaeda glauca, Artemisia desertorum, and Atriplex canescens.

Mining activities have led to serious environmental (soil erosion, degradation of vegetation, and groundwater contamination) and human health (musculoskeletal problems, diarrheal conditions, and chronic diseases) issues at desert mining areas in northwest China. Native plant species grown naturally in desert regions show a unique tolerance to arid and semiarid conditions and are potential candidates for soil phytoremediation. Here, an ex situ experiment involving pot planting of seedlings of three native plant species (Suaeda glauca, Artemisia desertorum, and Atriplex canescens) was designed to explore their phytoremediation potential and the underlying physiological mechanism. For Zn and Cu, the three plants were all with a biological accumulation coefficient (BAC) greater than 1. For Cd, Ni, and Pb, Atriplex canescens had the highest bioaccumulation concentrations (521.52, 862.23, and 1734.59 mg/kg), with BAC values (1.06, 1.30, 1.25) greater than 1, which indicates that Atriplex canescens could be a broad-spectrum metal extraction plant. Physiological analysis (antioxidation, extracellular secretions, photosynthesis, and hydraulics) showed that the three desert plants exploited their unique strategy to protect against the stress of complex metals in soils. Moreover, the second growing period was the main heavy metal accumulation and extraction stage concomitant with highest water use efficiency (iWUE). Taken together, the three desert plants exhibited the potent heavy metal extraction ability and physiological and ecological adaptability to a harsh polluted environment in arid desert areas, providing potential resources for the bioremediation of metal-contaminated soils in an arid and semiarid desert environment.

De novo variants in FRMD5 are associated with developmental delay, intellectual disability, ataxia, and abnormalities of eye movement.

Proteins containing the FERM (four-point-one, ezrin, radixin, and moesin) domain link the plasma membrane with cytoskeletal structures at specific cellular locations and have been implicated in the localization of cell-membrane-associated proteins and/or phosphoinositides. FERM domain-containing protein 5 (FRMD5) localizes at cell adherens junctions and stabilizes cell-cell contacts. To date, variants in FRMD5 have not been associated with a Mendelian disease in OMIM. Here, we describe eight probands with rare heterozygous missense variants in FRMD5 who present with developmental delay, intellectual disability, ataxia, seizures, and abnormalities of eye movement. The variants are de novo in all for whom parental testing was available (six out of eight probands), and human genetic datasets suggest that FRMD5 is intolerant to loss of function (LoF). We found that the fly ortholog of FRMD5, CG5022 (dFrmd), is expressed in the larval and adult central nervous systems where it is present in neurons but not in glia. dFrmd LoF mutant flies are viable but are extremely sensitive to heat shock, which induces severe seizures. The mutants also exhibit defective responses to light. The human FRMD5 reference (Ref) cDNA rescues the fly dFrmd LoF phenotypes. In contrast, all the FRMD5 variants tested in this study (c.340T>C, c.1051A>G, c.1053C>G, c.1054T>C, c.1045A>C, and c.1637A>G) behave as partial LoF variants. In addition, our results indicate that two variants that were tested have dominant-negative effects. In summary, the evidence supports that the observed variants in FRMD5 cause neurological symptoms in humans.

Nicotinamide reprograms adipose cellular metabolism and increases mitochondrial biogenesis to ameliorate obesity.

Obesity poses a global health challenge and is a major risk factor for diabetes mellitus, cardiovascular diseases, hypertension, stroke and certain kinds of cancers. Although the effects of nicotinamide (NAM) on liver metabolism and diseases were well documented, its effects on adipose tissue are yet to be characterized. Herein, we found that NAM supplementation significantly reduced fat mass and improved glucose tolerance in obese mice. Proteomic analysis revealed that NAM supplementation upregulates mitochondrial proteins while quantitative polymerase chain reaction showed that PPARα and PGC1α were both upregulated in adipose tissues, proposing that NAM increased mitochondrial biogenesis in adipose tissue. Indeed, NAM treatment increased proteins related to mitochondrial functions including oxidative phosphorylation, fatty acid oxidation, and TCA cycle. Furthermore, isotope-tracing assisted metabolic profiling revealed that NAM activated NAMPT and increased cellular NAD+ level by 30%. Unexpectedly, we found that NAM also increased glucose derived amino acids to enhance glutathione synthesis for maintaining cellular redox homeostasis. Taken together, our results demonstrated that NAM reprogramed cellular metabolism, enhanced adipose mitochondrial functions to ameliorate symptoms associated with obesity.

Fraction distribution and dynamic cycling of phosphorus in lacustrine sediment at Inexpressible Island, Antarctica.

Phosphorus (P) chemistry and its dynamic cycling are essential for understanding aquatic primary productivity and ecosystem structure. However, there is a lack of knowledge on P chemistry in pristine aquatic ecosystems, such as in Antarctica. Here, we applied the Standards, Measurements and Testing Program (SMT) procedure and nuclear magnetic resonance spectroscopy (NMR) to reveal P speciation in two types of lacustrine sediment cores collected from Inexpressible Island, Ross Sea, East Antarctica. The Positive Matrix Factorization Model and Generalized Additive Models were applied to quantitatively identify the P sources and estimate relative effects of various environmental factors on the speciation. Our results demonstrate that orthophosphate, mainly as Ca-P, is the major component and the ortho-monoesters are the predominant organic phosphorus (OP) form in lacustrine sediments. Ornithogenic lacustrine sediments have a higher content of P as Ca-P than sediments with little or no penguin influence. Our model further suggests that penguin guano is the most important source for Ca-P, accounting for 80%, while detrital input is the predominant source for Fe/Al-P (up to 90%). The content of ortho-monoesters, as revealed by NMR, declines with depth, reflecting mineralization process of OP in the sediments. Moreover, we observed higher relative proportions of organic P in the sediments with little guano influence and the deposition of organic P are likely facilitated by microbial mats. Overall, our data suggest that burial of P in Antarctic lakes is sensitive to different P sources and sedimentary environments. The relatively higher bioavailable phosphorus in lacustrine sediments largely controls growth of aquatic microbial mats in oligotrophic lakes and ponds in Antarctica. The sediment profile data also indicate that P burial increased during the Medieval Climate Anomaly period, and climate warming is more conducive to P burial through the expansion of penguin populations and productivity of microbial mats. Our findings represent the first systematic understanding of natural P cycling dynamics and its main controlling factors in pristine ponds with different organic sources in Antarctica.

Complete chloroplast genome sequence of Mucuna prurien and its phylogenetic position.

Mucuna pruriens is traditional medicinal plant originated in South Africa. We characterize the complete plastid genome of M. pruriens, which is a circular-mapping molecule 152,119 bp in length. The genome has a large single-copy region (LSC) of 78,258 bp and a small single-copy region (SSC) of 18,735 bp, respectively. Additionally, the overall GC content of the chloroplast genome was 35.37%. The genome contains 138 genes, including 96 protein-coding, 38 tRNA, and four rRNA genes. The gene content and structure are conserved compared to other species in the genus Glycine. The chloroplast genome and existing data were used to infer its phylogenetic position. The results showed that M. pruriens clustered together with Glycine max and G. soja. These findings provide potential genetic markers that can aid in understanding the genetic diversity of M. pruriens.

Glutamine supplementation affected the gut bacterial community and fermentation leading to improved nutrient digestibility in growth-retarded yaks.

This study evaluated the effects of glutamine supplementation on nutrient digestibility, immunity, digestive enzyme activity, gut bacterial community and fermentation of growth-retarded yaks. A total of 16 growth-retarded yaks were randomly allocated to two groups: negative control (GRY) and glutamine supplementation group (GLN). Another eight growth-normal yaks were used as a positive control (GNY). Compared with GRY group, the crude protein digestibility was higher in GLN and GNY animals and the neutral detergent fiber digestibility was increased in GLN yaks. The concentrations of serum IgA, IgG, IgM and IL-10, as well as butyrate concentration and cellulase activity in the rumen and cecum were higher in GLN yaks compared to those in GRY animals. Supplementation with glutamine enhanced the chymotrypsin activity and increased the relative abundances of unclassified Peptostreptococcaceae and Romboutsia while decreased the relative abundances of unclassified Chitinophagaceae and Bacteroides in the jejunum and ileum of growth-retarded yaks. In the cecum, the relative abundance of unclassified Muribaculaceae was higher in GLN group than that in GRY group. The findings in this study suggest that the improved nutrient digestibility and immunity of growth-retarded yaks with glutamine supplementation may be through its potential impact on the lower gut host and microbial functions.

Non-invasive brain intervention techniques used in patients with disorders of consciousness.

Aim of the study: With the development of emergency medicine and intensive care technology, the number of people who survive with disorders of consciousness (DOC) has dramatically increased. The diagnosis and treatment of such patients have attracted much attention from the medical community. From the latest evidence-based guidelines, non-invasive brain intervention (NIBI) techniques may be valuable and promising in the diagnosis and conscious rehabilitation of DOC patients.Methods: This work reviews the studies on NIBI techniques for the assessment and intervention of DOC patients.Results: A large number of studies have explored the application of NIBI techniques in DOC patients. The NIBI techniques include transcranial magnetic stimulation, transcranial electric stimulation, music stimulation, near-infrared laser stimulation, focused shock wave therapy, low-intensity focused ultrasound pulsation and transcutaneous auricular vagus nerve stimulation.Conclusions: NIBI techniques present numerous advantages such as being painless, safe and inexpensive; having adjustable parameters and targets; and having broad development prospects in treating DOC patients.

A chemiluminescence assay for determination of lysozyme based on the use of magnetic alginate-aptamer composition and hemin@HKUST-1.

Lysozyme aptamer-functionalized magnetic alginate hydrogel was prepared for separation and enrichment of lysozyme. Luminol-labeled aptamer was used as a signal tag, and the signal tag was adsorbed on magnetic carboxylated carbon nanotubes based on the π-interaction. When lysozyme was added, the aptamer specifically binds to the lysozyme, causing the signal tag to detach from the magnetic carboxylated carbon nanotubes. When the aptamer/lysozyme complex bound to the complementary single strand of aptamer on the hemin@HKUST-1, lysozyme was released. The released lysozyme can be recombined with the signal tag adsorbed on the magnetic carboxylated carbon nanotube, allowing more signal tag to be dispersed into the solution. Determination of lysozyme was achieved by releasing the luminol-labeled aptamer to generate a chemiluminescence signal at a wavelength of 425 nm. It was proved by experiments that the synthesized hemin@HKUST-1 had a strong catalytic effect on the luminol-NaOH-H2O2 system. The chemiluminescence signal was increased nearly 100 times. The complementary pairing allowed the luminol to be immobilized on the surface of hemin@HKUST-1. The generation and consumption of short-lived reactive oxygen species were concentrated on the surface of the MOFs, which improves the chemiluminescence efficiency. The introduction of hemin@HKUST-1 and DNA solved the defects of chemiluminescence analysis. The chemiluminescence assay was able to detect lysozyme with linear range of 1.05 × 10-6 U∙mg-1 (6.00 × 10-13 mol∙L-1)-1.25 × 10-2 U∙mg-1 (7.14 × 10-9 mol∙L-1); the detection limit was 3.50 × 10-7 U∙mg-1 (2.00 × 10-13 mol∙L-1) (R2 = 0.99). The recovery of lysozyme in spiked saliva samples was 97.4-102.8%. Graphical abstract Schematic presentation of chemiluminescence assay. Lysozyme (Lys) was captured by aptamer-modified magnetic sodium alginate (M-Alg-Apt); Glycine (pH = 2) as eluent for Lys. Luminol-modified Apt (Apt-luminol) as signal tag; magnetic carbon nanotubes (MCNTs) as adsorption matrix; cDNA was complementary to Apt; hemin@HKUST-1 as catalyst.

Biomineralization-inspired nanozyme for single-wavelength laser activated photothermal-photodynamic synergistic treatment against hypoxic tumors.

Hypoxia, one of the features of most solid tumors, can severely impede the efficiency of oxygen-dependent treatments such as chemotherapy, radiotherapy and type-II photodynamic therapy. Herein, a catalase-like nanozyme RuO2@BSA (RB) was first prepared through a biomineralization strategy, and a high efficiency near-infrared photosensitizer (IR-808-Br2) was further loaded into the protein shell to generate the safe and versatile RuO2@BSA@IR-808-Br2 (RBIR) for the imaging-guided enhanced phototherapy against hypoxic tumors. RB not only acts like a catalase, but also serves as a photothermal agent that speeds up the oxygen supply under near-infrared irradiation (808 nm). The loaded NIR photosensitizer could immediately convert molecular oxygen (O2) to cytotoxic singlet oxygen (1O2) upon the same laser irradiation. Results indicated that RBIR achieved enhanced therapeutic outcomes with negligible side effects. Features such as a simple synthetic route and imaging-guided and single-wavelength-excited phototherapy make the nanozyme a promising agent for clinical applications.

Impact of baseline characteristics on glycemic effects of add-on saxagliptin or acarbose to metformin therapy: Subgroup analysis of the SMART study in Chinese patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: This secondary analysis of the 24-week SMART study examined the efficacy of add-on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus, based on baseline characteristics. MATERIALS AND METHODS: Randomized patients (n = 481) were classified into subgroups based on their baseline age (<65, ≥65 years), body mass index (BMI; <24, 24-<28, ≥28 kg/m2 ), glycated hemoglobin (HbA1c; <8%, 8-<9%, 9-<10%, ≥10%) and renal function (creatinine clearance 50-<80, ≥80 mL/min). Treatment effects on primary outcome (HbA1c) and key secondary outcomes of fasting plasma glucose (FPG), 2-h postprandial glucose and homeostatic model assessment of ß-cell function were assessed across patient subgroups. RESULTS: For saxagliptin, reductions in HbA1c from baseline to week 24 were consistent across different subgroups regardless of baseline age, body mass index, HbA1c and renal function (range -0.66 to -1.16%). Saxagliptin was associated with consistent reductions in FPG (-0.60 to -1.33 mmol/L) and 2-h postprandial glucose (-0.48 to -1.95 mmol/L) across the majority of subgroups studied. The efficacy of acarbose on FPG attenuated progressively with increasing baseline HbA1c (+0.86 to -1.43 mmol/L); an increase from baseline FPG was observed in patients with HbA1c >9%. The effect of acarbose on postprandial glucose was also variable (+0.23 to -3.38 mmol/L). CONCLUSIONS: As add-on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, body mass index and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%).

A "signal-on" chemiluminescence biosensor for thrombin detection based on DNA functionalized magnetic sodium alginate hydrogel and metalloporphyrinic metal-organic framework nanosheets.

A "signal-on" chemiluminescence biosensor was established for detecting thrombin. The thrombin aptamer1-functionalized magnetic sodium alginate (Malg-Apt1) hydrogel was synthesized by physical interaction between sodium alginate and Ca2+, and it was used in the biosensor for separating and enriching thrombin. Ethylenediamine tetraacetic acid (EDTA) was used to chelate with Ca2+ to dissolve the hydrogel and release thrombin. A metalloporphyrinic metal-organic framework nanosheet, named as Cu-TCPP(Co) MOFs, was prepared as signal amplification strategy. Cu-TCPP(Co) MOFs/Au-ssDNA (ssDNA: single-strand DNA) was synthesized for controllable further amplification of chemiluminescent signal. The thrombin aptamer2-functionalized magnetic carbon nanotubes (MCNTs-Apt2) were used as a matrix, and Cu-TCPP(Co) MOFs/Au-ssDNA was adsorbed on the MCNTs by the complementary pairing of the partial bases between ssDNA and Apt2. Compared with ssDNA, Apt2 has a stronger interaction with thrombin. Therefore, thrombin can trigger the release of Cu-TCPP(Co) MOFs/Au-ssDNA to achieve signal amplification. Under the optimal conditions, the biosensor could detect thrombin as low as 2.178 × 10-13 mol/L with the range from 8.934 × 10-13 to 5.956 × 10-10 mol/L and exhibited excellent selectively. Moreover, the "signal-on" chemiluminescence biosensor showed potential application for the detection of thrombin in body fluids.

Cardioprotective effects of galectin-3 inhibition against ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (IR) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a ß-galactoside-binding lectin, acts as a biomarker in heart disease. However, it remains unclear whether manipulating galectin-3 affects the susceptibility of the heart to IR injury. In this study, RNA sequencing (RNA-seq) analysis identified that Lgals3 (galecin-3) plays an indispensable role in IR-induced cardiac damage. Immunostaining and immunoblot assays confirmed that the expression of galectin-3 was markedly increased in myocardial IR injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental IR injury was significantly attenuated by galectin-3 inhibitors including pectin (1%, i.p.) from citrus and binding peptide G3-C12 (5.0 mg/kg, i.p.). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed IR-mediated cardiomyocyte apoptosis. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) levels were well-preserved and IR-induced changes of mitochondrial cyto c, cytosol cyto c, caspase-9, caspase-3, Bcl-2 and Bax in the galectin-3 inhibitor-treated groups were observed. Our findings indicate that the pathological upregulation of galectin-3 contributes to IR-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential.