Chronic vascular pathogenesis results in the reduced serum Metrnl levels in ischemic stroke patients.

Metrnl is a secreted protein involved in neurite outgrowth, insulin sensitivity, immunoinflammatory responses, blood lipids and endothelial protection. In this study, we investigated the role of Metrnl in ischemic stroke. Fifty-eight ischemic stroke patients (28 inpatient patients within 2 weeks of onset and 30 emergency patients within 24 h of onset) and 20 healthy controls were enrolled. Serum Metrnl was measured by enzyme-linked immunosorbent assay. We showed that serum Metrnl levels were significantly reduced in both inpatient and emergency patient groups compared with the controls. Different pathological causes for ischemic stroke such as large artery atherosclerosis and small artery occlusion exhibited similar reduced serum Metrnl levels. Transient ischemic attack caused by large artery atherosclerosis without brain infarction also had lower serum Metrnl levels. Metrnl was correlated with some metabolic, inflammatory and clotting parameters. Reduced serum Metrnl was associated with the severity of intracranial arterial stenosis and the presence of ischemic stroke. In order to elucidate the mechanisms underlying the reduced serum Metrnl levels, we established animal models of ischemic stroke in normal mice, atherosclerotic apolipoprotein E-knockout mice and Metrnl-knockout mice by middle cerebral artery occlusion (MCAO) using intraluminal filament or electrocoagulation. We demonstrated that serum Metrnl levels were significantly lower in atherosclerosis mice than normal mice, whereas acute ischemic stroke injury in normal mice and atherosclerosis mice did not alter serum Metrnl levels. Metrnl knockout did not affect acute ischemic stroke injury and death. We conclude that reduced serum Metrnl levels are attributed to the chronic vascular pathogenesis before the onset of ischemic stroke. Metrnl is a potential target for prevention of ischemic stroke.

Effects of dietary yeast culture on shrimp growth, immune response, intestinal health and disease resistance against Vibrio harveyi.

The current study was conducted to evaluate the effects of different levels of yeast culture (YC) supplementation at 0% (YC 0%), 1% (YC 1%), and 2% (YC 2%) on growth, feed conversion ratio, body composition, intestinal morphology, microflora, immune response, and resistance to Vibrio harveyi infection in Litopenaeus vannamei. After 8-weeks feeding trial, the results showed significant improvement (p < .05) in the final weight, weight gain rate, specific growth rate, survival rate and low feed conversion ratio in YC groups than the control. Serum total protein, superoxide dismutase, catalase, alkaline phosphatase, acid phosphatase, lysozyme, and phenol oxidase in shrimps fed diet YC (2%) were significantly higher (p < .05), whereas significantly decreased trend in serum cholesterol, triglyceride, aspartate aminotransferase, and alanine aminotransferase (p < .05) were observed in YC (2%) diet. Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes were the core phylum bacteria found in the shrimp intestines. At the genus level, opportunistic pathogenic bacteria, Vibrio was significantly decreased (p < .05) while beneficial bacteria Pseudoalteromonas was increased in YC (2%) group. Intestinal villus height and width in shrimps fed YC diets were significantly improved than the control diet (p < .05). YC groups challenged test significantly showed (p < .05) improved shrimps immune response against V. harveyi infections with YC (2%) recording the highest percentage survival rate (70%). The present study demonstrated that supplementing YC (2%) can improve growth, intestinal microbiota, intestinal morphology, and immune response against V. harveyi infections in L. vannamei.

Influence of different oil sources on growth, disease resistance, immune response and immune-related gene expression on the hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatu), to Vibrio parahaemolyticus challenge.

The aim of this study was to investigate the effects of feeding alternative dietary oils to hybrid grouper fish (♀Epinephelus fuscoguttatus × â™‚E. lanceolatu) on their growth, histological morphology of hepatocytes, disease resistance, immune response, and expression of immune-related genes. Seven experimental fish meal-based isonitrogenous and isolipidic diets were formulated containing 5% fish oil (FO; acting as controls) and various vegetable oils (VOs): corn oil (CO), sunflower oil (SO), tea oil (TO), olive oil (OO), rice oil (RO), and mixed oil (MO); comprising equal amounts of these oils). Each diet was fed to triplicate groups of 40 fish (initial mean body weight ± standard error = 15.09 ± 0.01 g) for eight weeks. The results show that 1) alternative dietary oils had no significant effects on weight gain rate, specific growth rate, protein efficiency ratio, and survival rate compared with controls (P > 0.05). The weight gain rate (WGR) and specific growth rate (SGR) of the SO group were lower than in the CO and OO groups. 2) These were no differences in morphological indexes among groups; except for the CO group, in which the condition factor and hepatosomatic index were lower than those in other groups. 3) Compared with controls, the whole-body moisture and crude protein contents in the VO groups were higher, while their crude lipid contents were lower. 4) The fatty acid contents in liver and muscle were affected by lipid type, and the contents of eicosapentaenoic acid and docosahexaenoic acid in liver and muscle in the VO groups were markedly lower than in controls. 5) Compared with control group, VO groups damaged the histological morphology of hepatocytes. 6) After a challenge with the Vibrio parahaemolyticus bacterium, there were no differences in mortality among groups. However, VO enhanced the activity of non-specific immune enzymes while down-regulating the expression of Nrf2 and inducing the expression of pro-inflammatory factors (IL1ß, TNFα, TLR22, and MyD88) in the kidney. It can be concluded that dietary VO substitution does not affect the growth of fish but damaged the histological morphology of hepatocytes and induced the expression of pro-inflammatory factors in tissues. Finally, OO and CO were recommended as the appropriate lipid replacement for FO.

Effects of different dietary carbohydrate-to-lipid ratios on growth, plasma biochemical indexes, digestive, and immune enzymes activities of sub-adult orange-spotted grouper Epinephelus coioides.

A 10-week feeding trial was conducted to investigate the effects of dietary carbohydrate-to-lipid (CHO:L) ratios on glycogen content, hematological indices, liver, and intestinal enzyme activity of sub-adult grouper Epinephelus coioides. Five iso-nitrogenous (496.0 g kg-1 protein) and iso-energetic (21.6 KJ g-1 gross energy) diets with varying CHO: L ratios of 0.65 (D1), 1.31 (D2), 2.33 (D3), 4.24 (D4), and 8.51 (D5), respectively, were fed to triplicate groups of 20 fish (average 275.1 ± 1.86 g). Results showed that the weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) of sub-adult grouper increased and then stable when dietary CHO:L ratios reach D4 (CHO:L = 4.24). The trend of feed conversion ratio (FCR) was opposite to PER. Along with the dietary CHO:L ratios, the liver and muscle glycogen level increased gradually. Plasma triglycerides (TG) and glucose (GLU) were all maximized at D5 (CHO:L = 8.51) group, cholesterol (CHOL) at D4 (CHO:L = 4.24) group. Digestive enzyme activities were significantly affected by dietary CHO:L ratios. Liver hexokinase (HK), alkaline phosphatase (AKP), and glucose-6-phosphate dehydrogenase (G6PDH) activity increased significantly as CHO:L ratios increased. Liver lysozyme (LYZ) and superoxide dismutase (SOD) activity of sub-adult grouper fed the D4 diet was significantly higher than that of the D2 (CHO:L = 1.31) diet. The trend of acid phosphatase (ACP) is opposite to AKP. The regression model analysis showed that the most suitable dietary CHO:L ratio to reach the highest SGR is 6.06.

Mysm1 epigenetically regulates the immunomodulatory function of adipose-derived stem cells in part by targeting miR-150.

Adipose-derived stem cells (ASCs) are highly attractive for cell-based therapies in tissue repair and regeneration because they have multilineage differentiation capacity and are immunosuppressive. However, the detailed epigenetic mechanisms of their immunoregulatory capacity are not fully defined. In this study, we found that Mysm1 was induced in ASCs treated with inflammatory cytokines. Adipose-derived stem cells with Mysm1 knockdown exhibited attenuated immunosuppressive capacity, evidenced by less inhibition of T cell proliferation, more pro-inflammatory factor secretion and less nitric oxide (NO) production in vitro. Mysm1-deficient ASCs exacerbated inflammatory bowel diseases but inhibited tumour growth in vivo. Mysm1-deficient ASCs also showed depressed miR-150 expression. When transduced with Mysm1 overexpression lentivirus, ASCs exhibited enhanced miR-150 expression. Furthermore, Mysm1-deficient cells transduced with lentivirus containing miR-150 mimics produced less pro-inflammatory factors and more NO. Our study reveals a new role of Mysm1 in regulating the immunomodulatory activities of ASCs by targeting miR-150. These novel insights into the mechanisms through which ASCs regulate immune reactions may lead to better clinical utility of these cells.

Dietary supplementation of probiotic Bacillus coagulans ATCC 7050, improves the growth performance, intestinal morphology, microflora, immune response, and disease confrontation of Pacific white shrimp, Litopenaeus vannamei.

The present study assessed the effects of probiotic bacterium Bacillus coagulans ATCC 7050 (BC) fed at different inclusion levels (0 (BO), 1 × 106 (BC1), 1 × 107 (BC2) and 1 × 108 (BC3) CFU g-1 feed) on growth, feed utilization, body composition, intestinal morphology, microflora, immune response, and resistance to Vibrio parahaemolyticus infection in Litopenaeus vannamei. After 56 days of the feeding trial, the survival rate ranged from 83.33 to 94.17% with no significant difference between dietary treatments (P > 0.05). Dietary probiotic supplementation also affected the intestinal microflora composition. At the phylum level, Proteobacteria accounted for the majority of bacteria followed by Bacteroidetes irrespective of the group. At the genus level, the abundance of opportunistic pathogenic bacteria, such as Vibrio, Tenacibaculum, and Photobacterium significantly decreased (P < 0.05) with an increasing probiotic concentration, and BC3 group experiencing the least. Additionally, increasing probiotic inclusion in diet downregulated the abundance of Muricauda, Kangiella, and Shewanella in shrimps, with the least, observed in the BC3 group. However, beneficial bacteria Pseudoalteromonas significantly increased (P < 0.05) in the intestines of shrimp fed BC3 diet (P < 0.05) compared to other groups including the control. Compared to the control, a significant increase (P < 0.05) of the probiotic treated groups in the final weight, weight gain rate (WGR), specific growth rate (SGR), condition factor (K), activity of lysozyme (LYZ), acid phosphatase (ACP), superoxide dismutase (SOD), total protein (TP), albumin (ALB) in serum, glutathione peroxidase (GSH-Px) in serum and liver, and a significant decrease (P < 0.05) in feed conversion ratio (FCR), triglyceride (TG) in serum, and Malondialdehyde (MDA) in serum and liver were achieved. Increasing probiotic treatment again improved the digestive ability, thus; a significant increase in the activities of lipase, amylase, trypsin, and an enhancement in the villus height, villus width, and muscle thickness of the intestines of the shrimps which correspondingly alleviated intestinal injury. Furthermore, the supplementation of probiotics in challenge test significantly (P < 0.05) enhanced the resistance of shrimp against V. parahaemolyticus infection recording BC3 to receive the highest relative percentage survival (RPS) value of 76%. In conclusion, higher inclusion levels of probiotic BC at 1 × 108 CFU g-1 feed (BC3) in diets can be considered to enhance the growth, intestinal morphology and microflora, immune response and resistance to Vibrio parahaemolyticus of L. vannamei.

CKIP-1 regulates the immunomodulatory function of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are self-renewing multipotent cells with immunoregulatory function, which makes them attractive candidates for regenerative medicine. However, the detailed mechanisms of their immunomodulatory capacity are not fully characterized. Here, we found that casein kinase 2 interacting protein-1 (CKIP-1) expression was induced in the murine MSC cell line C3H/10T1/2 by LPS. Knockdown of CKIP-1 did not cause significant differences on the cell cycle or immunophenotype of MSCs. However, MSCs with CKIP-1 knockdown showed enhanced immunosuppressive capacity. Real-time PCR and western blot analyses revealed that compared with the control group, MSCs with CKIP-1-knockdown exhibited higher IL-10 production and p38 MAPK phosphorylation following LPS treatment. Interestingly, the expression of CKIP-1 was decreased in MSCs following high glucose treatment. Furthermore, MSCs became more immunosuppressive after high glucose treatment, as shown by higher IL-10 production and enhanced inhibition of T cell proliferation. Collectively, our data reveal a novel role for CKIP-1 in regulating MSC-mediated immunomodulation, and indicate that MSCs become more immunosuppressive under high glucose conditions. These new insights may help in the development of future applications of MSCs.

Preventive Cold Acclimation Augments the Reparative Function of Endothelial Progenitor Cells in Mice.

BACKGROUND/AIMS: Chronic cold exposure may increase energy expenditure and contribute to counteracting obesity, an important risk factor for cerebrocardiovascular diseases. This study sought to evaluate whether preventive cold acclimation before ischemia onset might be a promising option for preventing cerebral ischemic injury. METHODS: After a 14-day cold acclimation period, young and aged mice were subjected to permanent cerebral ischemia, and histological analyses and behavioral tests were performed. Mouse endothelial progenitor cells (EPCs) were isolated, their function and number were determined, and the effects of EPC transplantation on cerebral ischemic injury were investigated. RESULTS: Preventive cold acclimation before ischemia onset increased EPC function, promoted ischemic brain angiogenesis, protected against cerebral ischemic injury, and improved long-term stroke outcomes in young mice. In addition, transplanted EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic injury and promote local angiogenesis compared to those from control mice, and EPCs from donor animals could integrate into the recipient ischemic murine brain. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury, which could be improved by preventive cold acclimation. Moreover, preventive cold acclimation could also enhance EPC function, promote local angiogenesis, and protect against cerebral ischemic injury in aged mice. CONCLUSIONS: Preventive cold acclimation before ischemia onset improved long-term stroke outcomes in mice at least in part via promoting the reparative function of EPC. Our findings imply that a variable indoor environment with frequent cold exposure might benefit individuals at high risk for stroke.

A preventive injection of endothelial progenitor cells prolongs lifespan in stroke-prone spontaneously hypertensive rats.

There is a pressing need for new approaches to prevent stroke. Endothelial progenitor cells (EPCs) promote vascular repair and revascularization in the ischemic brain. The present study sought to evaluate whether preventive delivery of EPCs could prevent or protect against stroke. Stroke-prone spontaneously hypertensive rats (SHR-SP) received a single injection of EPCs, and their survival time was monitored. In addition, at 28 and/or 42 days after a single injection of EPCs, SHR-SP and mice were subjected to cerebral ischemia, and cerebral ischemic injury, local angiogenesis and in vivo EPC integration were determined. Other experiments examined the effects of EPC conditioned medium, and the distribution of donor EPCs taken from GFP transgenic mice. It was found that EPC-pretreated SHR-SP showed longer lifespans than untreated controls. A single preventive injection of EPCs could produce persistent protective effects against cerebral ischemic injury (lasting at least 42 days), and promote local angiogenesis in the ischemic brain, in two types of animals (SHR-SP and normotensive mice). EPCs of donor origin could be detected in the recipient peripheral blood, and integrated into the recipient ischemic brains. Furthermore, it was suggested that mouse EPCs might exert paracrine effects on cerebral ischemic injury in addition to their direct angiogenic effects. In conclusion, a single preventive injection of EPCs prolonged the lifespan of SHR-SP, and protected against cerebral ischemic injury for at least 7 weeks. It is implied that EPC injection might be a promising candidate for a preventive role in patients at high risk for stroke.

Deubiquitinase Mysm1 regulates macrophage survival and polarization.

Macrophages play pivotal roles in innate and adaptive immune response, tissue homeostasis and cancer development. Their development and heterogeneity are tightly controlled by epigenetic program and transcription factors. Deubiquitinase Mysm1 plays crucial roles in regulating stem cell maintenance and immune cell development. Here we show that Mysm1 expression is up regulated during bone marrow macrophage development. Mysm1 deficient cells exhibit accelerating proliferation with more cells going to S phase and higher cyclin D1, cyclin D2 and c-Myc expression. However, compared to WT counterparts, more cell death is also detected in Mysm1 deficient cells no matter M-CSF deprived or not. In LPS-condition medium, Mysm1-/- macrophages show more pro-inflammatory factors IL-1ß, TNFα and iNOS production. In addition, much higher expression of surface marker CD86 is detected in Mysm1-/- macrophages. In vivo tumor model data demonstrate that in contrast to WT macrophages promoting tumor growth, Mysm1-/- macrophages inhibit tumor growth, showing the properties of M1 macrophages. Collectively, these data indicate that Mysm1 is essential for macrophage survival and plays an important role in macrophage polarization and might be a target for cell therapy.

Prolonged Fasting Improves Endothelial Progenitor Cell-Mediated Ischemic Angiogenesis in Mice.

BACKGROUND/AIMS: Prolonged fasting (PF) was shown to be of great potency to promote optimal health and reduce the risk of many chronic diseases. This study sought to determine the effect of PF on the endothelial progenitor cell (EPC)-mediated angiogenesis in the ischemic brain and cerebral ischemic injury in mice. METHODS: Mice were subjected to PF or periodic PF after cerebral ischemia, and histological analysis and behavioral tests were performed. Mouse EPCs were isolated and examined, and the effects of EPC transplantation on cerebral ischemic injury were investigated in mice. RESULTS: It was found that PF significantly increased the EPC functions and angiogenesis in the ischemic brain, and attenuated the cerebral ischemic injury in mice that was previously subjected to cerebral ischemia. Periodic PF might reduce cortical atrophy and improve long-term neurobehavioral outcomes after cerebral ischemia in mice. The eNOS and MnSOD expression and intracellular NO level were increased, and TSP-2 expression and intracellular O2- level were reduced in EPCs from PF-treated mice compared to control. In addition, transplanted EPCs might home into ischemic brain, and the EPCs from PF-treated mice had a stronger ability to promote angiogenesis in ischemic brain and reduce cerebral ischemic injury compared to the EPCs from control mice. The EPC-conditioned media from PF-treated mice exerted a stronger effect on cerebral ischemic injury reduction compared to that from control mice. CONCLUSION: Prolonged fasting promoted EPC-mediated ischemic angiogenesis and improved long-term stroke outcomes in mice. It is implied that prolonged fasting might potentially be an option to treat ischemic vascular diseases.

Molecular cloning, characterization and expression analysis of Wnt4, Wnt5, Wnt6, Wnt7, Wnt10 and Wnt16 from Litopenaeus vannamei.

The Wnt (Wg-type MMTV integration site) signaling represents as the negative regulator of virus-induced innate immune responses. Wnt genes act as ligands to activate the Wnt signaling. To know more about the information of Wnt genes in invertebrates, Litopenaeus vannamei Wnt genes (LvWnts) were identified and characterized. In this study, Six Wnt genes (LvWnt4, LvWnt5, LvWnt6, LvWnt7, LvWnt10 and LvWnt16) were obtained in L. vannamei. The complete cDNAs open reading frames (ORF) of LvWnt4, LvWnt5, LvWnt6, LvWnt7, LvWnt10 and LvWnt16 were 1077 bp, 1107 bp, 1350 bp, 1047 bp, 1509 bp and 1158 bp (GenBank accession no. KU169896, KU169897, KU169898, KU169899, KU169900 and KU169901), encoding 358, 368, 449, 348, 502 and 385 amino acid (aa) residues respectively. All the six members of LvWnts contain a Wnt1 domain, which is considered as an important feature of Wnt gene family. ClustalW analysis with amino acid sequences revealed that the proportion of identity with other species was more than 48% for all the LvWnts except LvWnt10 (36-41%). The phylogenetic relationship analysis illustrated that different subtype of Wnts formed their own separate branches and were placed in branch of invertebrates respectively with strong bootstrap support. The constitutive expressions of LvWnts were confirmed by RT-PCR in all the examined five developmental stages and eleven tissues of L. vannamei with different express patterns. LvWnt4, LvWnt5 and LvWnt10 were expressed highest in nerve while LvWnt6, LvWnt7 and LvWnt16 were expressed highest in intestine, stomach and gill, respectively. In addition, all the LvWnts were regulated by white spot syndrome virus (WSSV) challenges at different levels in hepatopancreas, gill and hemocytes, suggesting that Wnt genes may play a role in the defense against pathogenic virus infection in innate immune of L. vannamei.

Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma.

Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. Methods uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively. The distribution of uPAR in MM cells was examined using immunofluorescence staining. The pathological changes in different stages of MM patients were studied by HE staining. Results uPAR level in bone marrow fluid of MM patients (1.52±0.32 µg/ml) was found to be higher than that in the control group (0.98±0.15 µg/ml). Interestingly, uPAR protein (0.686±0.075 vs. 0.372±0.043, P<0.05) and mRNA (2.51±0.46 vs. 4.46±1.15, P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage. The expression of uPAR in MM bone marrow was confirmed by immunofluorescence staining. Moreover, HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma. Conclusion Our study reveals that uPAR expression is positively correlated with the development and progress of MM.

Dietary intake of sugar substitutes aggravates cerebral ischemic injury and impairs endothelial progenitor cells in mice.

BACKGROUND AND PURPOSE: In our current food supply, sugar substitutes are widely used in beverages and other food products. However, there is limited information about the link between dietary consumption of sugar substitutes and stroke to date. This study sought to determine the effect of various sugar substitutes on the cerebral ischemic injury and endothelial progenitor cells, which have been implicated to play an important role in vascular repair and revascularization in ischemic brain tissues, in mice. METHODS: After treatment with sucrose and various sugar substitutes (the doses are in the range of corresponding acceptable daily intake levels) and vehicle for 6 weeks, mice were subjected to permanent left middle cerebral artery occlusion, and the infarct volumes, angiogenesis, and neurobehavioral outcomes were determined. In addition, the number and function of endothelial progenitor cells were also examined. RESULTS: After long-term treatment with fructose, erythritol (sugar alcohols), acesulfame K (artificial sweeteners), or rebaudioside A (rare sugars), the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) was significantly aggravated, angiogenesis in ischemic brain was reduced, and endothelial progenitor cell function was impaired in mice compared with control. However, the similar impairments were not found in sucrose (with the same dose as fructose's)-treated mice. CONCLUSIONS: Long-term consumption of sugar substitutes aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of endothelial progenitor cells and the reduction of angiogenesis in ischemic brain. This result implies that dietary intake of sugar substitutes warrants further attention in daily life.

Molecular characterization and functional analysis of Cactin gene from Litopenaeus vannamei.

Cactin (Cactus interactor) is a conserved protein which was initially discovered as a novel interactor of Drosophila IkB protein Cactus. Cactin was always characterized as a negative regulator of many different developmental processes, but only found to play an immune role in humans. To better know the immune function of Cactin gene, Litopenaeus vannamei Cactin (LvCactin) was identified and characterized in this study. The full-length cDNA of LvCactin is 3, 150 bp long, with an open reading frame (ORF) encoding a Cactin_mid domain in the N-terminus 356­547 residues and a CactinC_cactus domain in the C-terminal 731­855 residues. The LvCactin protein was located in the cytoplasm and LvCactin mRNA was constitutively expressed in healthy L. vannamei, with the highest expression level in the eyestalk. LvCactin could be regulated in hemocytes after lipopolysaccharide (LPS), poly I:C, CpG-ODN2006, Vibrio parahaemolyticus, Staphylococcus aureus, and white spot syndrome virus (WSSV) challenges. Dual-luciferase reporter assays in Drosophila Schneider 2 cells revealed that LvCactin inhibited the promoters of Drosophila and shrimp antimicrobial peptide (AMP) genes. Knockdown of LvCactin by RNA interference (RNAi) increased the expression of shrimp AMP genes PEN4, crustin and ALF2 but not Lyz2. However, the mortality rates of LvCactin-knockdown shrimp in response to V. parahaemolyticus or WSSV infections were not significantly different from those of the control group. Taken together, all the results suggested that LvCactin may play a role in innate immune in L. vannamei.

Broadband Emission Induced by Band-Edge Carrier Reconfiguration in 2D Hybrid Lead Halide Perovskites.

Broadband emission in hybrid lead halide perovskites (LHPs) has gained significant attention due to its potential applications in optoelectronic devices. The origin of this broadband emission is primarily attributed to the interactions between electrons and phonons. Most investigations have focused on the impact of structural characteristics of LHPs on broadband emission, while neglecting the role of electronic mobility. In this work, the study investigates the electronic origins of broadband emission in a family of 2D LHPs. Through spectroscopic experiments and density functional theory calculations, the study unveils that the electronic states of the organic ligands with conjugate effect in LHPs can extend to the band edges. These band-edge carriers are no longer localized only within the inorganic layers, leading to electronic coupling with molecular states in the barrier and giving rise to additional interactions with phonon modes, thereby resulting in broadband emission. The high-pressure photoluminescence measurements and theoretical calculations reveal that hydrostatic pressure can induce the reconfiguration of band-edge states of charge carriers, leading to different types of band alignment and achieving macroscopic control of carrier dynamics. The findings can provide valuable guidance for targeted synthesis of LHPs with broadband emission and corresponding design of state-of-the-art optoelectronic devices.

Drug release and solubility properties of two zeolitic metal-organic frameworks influenced by their hydrophobicity/hydrophilicity.

Metal-organic frameworks (MOFs) have shown significant potential for drug delivery applications. However, there remains a scarcity of comprehensive research addressing the influence of surface properties of MOFs on drug release kinetics and drug solubility. This study focuses on examining the influence of MOFs hydrophilicity and hydrophobicity on the controlled release and solubility of drugs. To achieve this, we prepared drug-loaded nanoparticles through in situ synthesis and created a drug-MOF co-amorphous system using the ball milling technique. Under neutral conditions, the hydrophilic MOF-based drug delivery system demonstrated a comparatively slower drug release profile than its hydrophobic counterpart. This observation suggests that the hydrophilic system holds promise in mitigating drug side effects by enabling improved control over drug release. The implementation of hydrophobic MOFs in co-amorphous systems yields a more pronounced effect on enhancing solubility compared to hydrophilic MOFs. This study offers valuable insights for achieving optimal drug release kinetics and solubility by delicately manipulating surface properties of MOFs.

Effects of low molecular weight heparin combined with hyperbaric oxygen on neurologic function and coagulation factors in patients with intracranial venous thrombosis.

OBJECTIVE: To investigate the effects of low molecular weight heparin (LMWH) combined with hyperbaric oxygen (HBO) on the neurologic function and coagulation factors of patients with intracranial venous thrombosis (ICVT). METHODS: The clinical data of 80 patients with ICVT admitted to the No. 2 Hospital of Baoding from February 2020 to January 2021 were retrospectively analyzed. Patients were assigned to a control group (n=32) and a research group (n=48) according to different treatment methods. The neurological function score, and the levels of D-dimer (D-D), fibrinogen (FIB), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were compared between the two groups. The two groups were also compared regarding the curative effect, toxic and side effects, as well as quality of life (QoL). RESULTS: After treatment, the National Institutes of Health Stroke Scale (NIHSS) score was significantly lower in the research group compared to the control group. At 1, 2 and 3 weeks after treatment, the levels of D-D and FIB, as well as inflammatory factors TNF-α and CRP were lower in the research group compared to the control group. The overall response rate was significantly higher in the research group compared to the control group, while there was no significant difference in the total incidence of toxic and adverse effects between the two groups. After treatment, the QoL of patients assessed by the Generic Quality of Life Inventory-74 (GQOLI-74) from the domains of physical, social, and psychological function as well as material life status was significantly better in the research group. CONCLUSIONS: LMWH combined with HBO can effectively improve the clinical efficacy and neurologic function of patients with ICVT and reduce the levels of coagulation factors and inflammatory factors.

Ultra-Performance Liquid Chromatography-Mass Spectrometry-Based Untargeted Metabolomics Reveals the Key Potential Biomarkers for Castor Meal-Induced Enteritis in Juvenile Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂).

The intensification of aquaculture to help kerb global food security issues has led to the quest for more economical new protein-rich ingredients for the feed-based aquaculture since fishmeal (FM, the ingredient with the finest protein and lipid profile) is losing its acceptability due to high cost and demand. Although very high in protein, castor meal (CM), a by-product after oil-extraction, is disposed-off due to the high presence of toxins. Concurrently, the agro-industrial wastes' consistent production and disposal are of utmost concern; however, having better nutritional profiles of these wastes can lead to their adoption. This study was conducted to identify potential biomarkers of CM-induced enteritis in juvenile hybrid-grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂) using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) alongside their growth and distal intestinal (DI) health evaluation. A total of 360 fish (initial weight = 9.13 ± 0.01g) were randomly assigned into three groups, namely, fish-meal (FM) (control), 4% CM (CM4), and 20% CM (CM20). After the 56-days feeding-trial, the DI tissues of FM, CM4, and CM20 groups were collected for metabolomics analysis. Principal components analysis and partial least-squares discriminant-analysis (PLS-DA, used to differentiate the CM20 and CM4, from the FM group with satisfactory explanation and predictive ability) were used to analyze the UPLC-MS data. The results revealed a significant improvement in the growth, DI immune responses and digestive enzyme activities, and DI histological examinations in the CM4 group than the others. Nonetheless, CM20 replacement caused DI physiological damage and enteritis in grouper as shown by AB-PAS staining and scanning electron microscopy examinations, respectively. The most influential metabolites in DI contents identified as the potential biomarkers in the positive and negative modes using the metabolomics UPLC-MS profiles were 28 which included five organoheterocyclic compounds, seven lipids, and lipid-like molecules, seven organic oxygen compounds, two benzenoids, five organic acids and derivatives, one phenylpropanoids and polyketides, and one from nucleosides, nucleotides, and analogues superclass. The present study identified a broad array of DI tissue metabolites that differed between FM and CM diets, which provides a valuable reference for further managing fish intestinal health issues. A replacement level of 4% is recommended based on the growth and immunity of fish.

Effects of dietary chitosan and Bacillus subtilis on the growth performance, non-specific immunity and disease resistance of cobia, Rachycentron canadum.

The present study was performed to investigate the effects of various levels of dietary Bacillus subtilis and chitosan on the growth performance, non-specific immunity and protection against Vibrio harveyi infection in cobia, Rachycentron canadum. Fish were fed with the control diet and six different experimental diets containing three graded levels of B. subtilis at 2 × 10(10) CFU g(-1) (0.0, 1.0, 2.0 g kg(-1) diet) for each of two levels of chitosan (3.0 and 6.0 g kg(-1) diet). The results of 8 weeks feeding trial showed that the survival rate ranged from 81.3% to 84.0% with no significant difference (P > 0.05). The SGR (%) in the fish fed with dietary treatments was significantly higher than that of the control fish except diet 6 group with 2.0 g kg(-1)B. subtilis and 3.0 g kg(-1) chitosan. The serum lysozyme activities were significantly higher in 6.0 g kg(-1) chitosan groups and no significant differences were observed among B. subtilis levels. The serum ACP activities were significantly higher in 3.0 g kg(-1) chitosan groups at 0.0 and 1.0 g kg(-1)B. subtilis levels; at low chitosan level, the cobia fed diets with 1.0 g kg(-1)B. subtilis had significantly higher serum ACP activity, but at high chitosan level, the cobia fed diets with 2.0 g kg(-1)B. subtilis had significantly higher serum ACP activity. The phagocytosis and respiratory burst activity in the fish fed with dietary treatments was significantly higher than that of the control fish except diet 3 group with 6.0 g kg(-1) chitosan. Moreover, fish fed the diet containing 2.0 g kg(-1)B. subtilis and 6.0 g kg(-1) chitosan had significantly higher post-challenge survival on the 7th day following V. harveyi infection and post-challenge survival showed clearly the synergistic effect of chitosan and B. subtilis. Based on these results, the combination of 1.0 g kg(-1)B. subtilis and 6.0 g kg(-1) chitosan is optimal for the growth, innate immunity and disease resistance of cobia with an 8-week oral administration.