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.

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.

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.

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 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.

Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice.

It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs' angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O2 - level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 µM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases.

In vitro Assessment of the Safety and Potential Probiotic Characteristics of Three Bacillus Strains Isolated From the Intestine of Hybrid Grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂).

Probiotics serving as an alternative to the criticized antibiotics mainly focus on improving animal's growth and health. After realizing the dangers posed by diseases that have led to lots of economic losses, aquaculture scientists have sought the usage of probiotics. However, most probiotics are ineffective in eliciting aquatic animals' preferred effects, since they are from non-fish sources. Again, there are even a few marine aquatic probiotics. Given this, a study was conducted to investigate the probiotic potential of the bacteria species isolated from the digestive tract of hybrid grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). Based on the morphological, biochemical, 16S rRNA sequencing analysis and evolutionary relationships, the isolated species were identified as Bacillus tequilensis GPSAK2 (MW548630), Bacillus velezensis GPSAK4 (MW548635), and Bacillus subtilis GPSAK9 (MW548634), which were designated as GPSAK2, GPSAK4, and GPSAK9 strains, respectively. Their probiotic potentials including their ability to tolerate high bile salt concentration, low pH, high temperatures, adhesion ability (auto-aggregation and cell-surface hydrophobicity), antimicrobial activity and biosafety test, compatibility test, hemolytic activity, and antibiotic susceptibility test were evaluated. While GPSAK2 and GPSAK9 strains were γ-hemolytic, that of GPSAK4 was α-hemolytic. All the isolates were resistant to low pH (1) and higher bile salt concentration (0.5%), showed higher viability ability after higher temperature exposure (80, 90, and 100°C), as well as higher cell-surface percentage hydrophobicity and auto-aggregation. All isolates exhibited positive compatibility with each other, signifying their ability to be used as multispecies. The three strains were susceptible to ampicillin (except GPSAK9, which was resistant), penicillin, kanamycin, ceftriaxone, chloramphenicol, erythromycin, clindamycin, furazolidone (except GPSAK2 and GPSAK9, which were moderately susceptible and resistant, respectively), polymyxin B, vancomycin (except GPSAK9, which was resistant), sulfamethoxazole (except GPSAK9, which was moderately susceptible), amikacin, minocycline, ofloxacin, norfloxacin, doxycycline, neomycin, gentamicin, tetracycline, carbenicillin, midecamycin (except GPSAK9, which was moderately susceptible), ciprofloxacin, piperacillin, and cefoperazone. All isolates demonstrated good antimicrobial activity against four pathogens, viz. Streptococcus agalactiae, Streptococcus iniae, Vibrio harveyi, and Vibrio alginolyticus. The results collectively suggest that Bacillus strains GPSAK2, GPSAK4, and GPSAK9 could serve as potential probiotic candidates that can be used to improve the growth and health status of aquatic animals, especially grouper.

Effects of reducing dietary fishmeal with yeast supplementations on Litopenaeus vannamei growth, immune response and disease resistance against Vibrio harveyi.

The aim of this experiment was to investigate the effects of reducing dietary fishmeal (FM) with yeast culture (SYC) supplementation on growth, immune response, intestinal microbiota, intestinal morphology, and disease resistance of Litopenaeus vannamei. A total of 480 shrimps with an average initial body weight of 0.35 ± 0.002 g were randomly distributed into twelve tanks. Three isonitrogenous (40.00 crude protein) and isolipidic (8.00 crude lipids) diets with yeast culture supplementing fishmeal were formulated. The groups were divided into two (2) namely control group and experimental groups. The formulations of the groups were control (0 %, without yeast culture) and the experiment groups (SYC) [(1 % of yeast culture), and (2 % of yeast culture)]. Each diet was delivered in four replicate per treatment group. The results indicate significant improvement on the growth indices (specific growth rate, weight gain rate, survival rate and lower feed conversion ratio) with yeast culture treatment group after 56 days feeding trials (P < 0.05). Total hemolymph protein, superoxide dismutase, catalase, alkaline phosphatase, acid phosphatase, lysozyme and phenoxidase were enhanced but low aspartate aminotransferase, alanine aminotransferase, and glucose were observed in shrimp fed yeast culture diets (P < 0.05). The SYC groups showed insignificant differences in hemolymph cholesterol and triglyceride. Proteobacteria, Bacteroidetes, and Actinobacteria were the dominant bacteria found in all the SYC groups. At the genus level, Vibrio was significantly decreased (P < 0.05) in 2 % yeast culture diets supplemented group whereas the beneficial bacteria Pseudoalteromonas was significantly enhanced. Moreover, intestinal villus length and width in shrimps fed yeast culture diets were improved (P < 0.05). Dietary yeast culture supplementation can improve growth, intestinal health, immune response, and resistance against Vibrio harveyi infections in L. vannamei.

Proliferation, Differentiation and Immunoregulatory Capacities of Brown and White Adipose-Derived Stem Cells from Young and Aged Mice.

BACKGROUND AND OBJECTIVES: Adipose tissue is a source of mesenchymal stem cells, which have the potential to differentiate into various types of cells. Adipose-derived stem cells (ADSCs) are now recognized as an accessible, abundant, and reliable stem cells suitable for tissue engineering and regenerative medicine applications. However, few literatures gave a comprehensive report on the capacities of ADSCs harvested from different sites. Especially, the capacities of ADSCs from aged mice remained unclear. In this study, we investigated several main capacities of brown adipose derived stem cells (B-ADSCs) and white adipose derived stem cells (W-ADSCs) from both young and aged mice. METHODS AND RESULTS: When isolated from young mice, B-ADSCs showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs. Carboxy fluorescein diacetate succinimidyl ester (CFSE) labeling test suggested no significant difference in immunosuppression capacity between B-ADSCs and W-ADSCs. Similarly, no difference between these two were found in several immune related molecules, such as programmed death-ligand 1 (PD-L1), intercellular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), interleukin 10 (IL10), and suppressor of cytokine signaling 1 (socs1). When isolated from aged mice, B-ADSCs also showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs; however, it demonstrated an attenuated immunosuppression capacity compared to W-ADSCs. CONCLUSIONS: In summary, our data showed that ADSCs' characteristics were tissue source dependent and changed with age. It provided evidence for choosing the right tissue-specific ADSCs for clinical application and fundamental research.

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.

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.

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.

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.

Real microgravity condition promoted regeneration capacity of induced pluripotent stem cells during the TZ-1 space mission.

Induced pluripotent stem cells (iPSCs) are reprogrammed somatic cells that gained self-renewal and differentiation capacity similar to embryonic stem cells. Taking the precious opportunity of the TianZhou-1 spacecraft mission, we studied the effect of space microgravity (µg) on the self-renewal capacity of iPSCs. Murine iPSCs carrying pluripotency reporter Oct4-GFP were used. The Oct4-EGFP-iPSCs clones were loaded into the bioreactor and exposed to µg in outer space for 14 days. The control experiment was performed in identical device but on the ground in earth gravity (1 g). iPSCs clones were compact and highly expressed Oct4 before launch. In µg condition, cells in iPSC clones spread out more rapidly than those in ground 1 g condition during the first 3 days after launch. However, in 1 g condition, as the cell density increases, the Oct4-GFP signal dropped significantly during the following 3 days. Interestingly, in µg condition, iPSCs originated from the spread-out clones during the first 3 days appeared to cluster together and reform colonies that activated strong Oct4 expression. On the other hand, iPSC clones in 1 g condition were not able to recover Oct4 expression after overgrown. Our study for the first time performed real-time imaging on the proliferation process of iPSCs in space and found that in µg condition, cell behaviour appeared to be more dynamic than on the ground.

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.

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.

Pterostilbene inhibits reactive oxygen species production and apoptosis in primary spinal cord neurons by activating autophagy via the mechanistic target of rapamycin signaling pathway.

Autophagy is an important self-adaptive mechanism that is involved in inhibiting reactive oxygen species (ROS) in spinal cord neurons. Pterostilbene, a natural plant extract, has been demonstrated to possess antioxidant effects; however, it has not yet been investigated whether pterostilbene could activate autophagy and protect spinal cord neurons from oxidative stress. In the present study, primary spinal cord neurons of Sprague Dawley rats were cultured. Cell counting kit­8 analysis was used to detect cytotoxicity of pterostilbene. Cells were treated with various doses of pterostilbene for 24 and 48 h, respectively, and H2O2 was used to induce ROS production. Western blot analysis was performed to assess the protein expression of microtubule­associated protein 1 light chain 3 (LC3)­II, Beclin­1, p62, p­p70S6K and p­mechanistic target of rapamycin (mTOR). Furthermore, the green fluorescent protein (GFP)­LC3 assay was used to detect the level of autophagy level and activation mechanism. 2',7'­Dichlorofluorescin diacetate and MitoSOX Red staining were used to detect ROS production, and Terminal deoxynucleotidyl­transferase­mediated dUTP nick end labelling assay was used to analyze apoptosis percentage. ATG5 small interfering (si)RNA transfection was used to analyze the involvement of autophagy. A dose­dependent increase in the expression of LC3­II and Beclin­1, as well as the p62 decline, were observed in the pterostilbene­treated neurons; however, p­p70S6K and p­mTOR expression was inhibited by pterostilbene. Pterostilbene increased the expression of LC3­II in H2O2­treated cells, and GFP­LC3 analysis demonstrated an increased number of autophagosomes. Furthermore, pterostilbene significantly inhibited the ROS production and apoptosis induced by H2O2; however, ATG5 siRNA transfection significantly reversed the protection of pterostilbene. These results indicate that pterostilbene may inhibit the ROS production and apoptosis in spinal cord neurons by activating autophagy via the mTOR signaling pathway.

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.