Family Integrated Care Shortens the Duration of Home Oxygen Therapy in Infants With Bronchopulmonary Dysplasia.

BACKGROUND: There have been few reports on whether family integrated care (FIC) can help premature infants with moderate to severe bronchopulmonary dysplasia (BPD) to shorten the duration of home oxygen therapy (HOT). PURPOSE: To investigate the effect of FIC on the duration of HOT in premature infants with moderate to severe BPD. METHODS: The subjects were retrospectively selected from premature infants with moderate to severe BPD in our center between June 2019 and December 2021. Patients were divided into the FIC group (n = 47) and the non-FIC group (n = 34). For univariate analysis, t test, Mann-Whitney U test, Pearson χ 2 test, or Fisher exact test was performed to explore the differences between the 2 groups. For multivariate analysis, simple and multiple linear regression was conducted to explore the effect of FIC on the duration of HOT. RESULTS: (1) The duration of HOT and length of stay after grouping were significantly shorter in the FIC group than in the non-FIC group ( P < .05). (2) The results of linear regression further revealed that FIC could significantly shorten the duration of HOT (simple linear regression, FIC [A] B : -12.709, 95% confidence interval (CI): -21.665 to -3.753; multiple linear regression, FIC [B] B : -11.419, 95% CI: -18.055 to -4.783). IMPLICATIONS FOR PRACTICE AND RESEARCH: FIC improved the optimal target oxygen saturation ratio before discharge and shortened the duration of HOT in premature infants with moderate and severe BPD. FIC should be promoted in China's neonatal intensive care units, though it puts forward new requirements for nursing education and training.

6His-tatritin promotes antimicrobial defense via regulating immune ability and intestinal microbial community in grass carp (Ctenopharyngodon idella).

Antimicrobial peptides are small, cationic, and amphiphilic peptides found in most organisms, and many of these peptides have broad antimicrobial activity against Gram-negative, -positive bacteria and fungi. In the present study, a derivative of antimicrobial peptide Tatritin, 6His-Tatritin, was designed and expressed by Pichia pastoris using a constitutive vector pGAPZαA with the promoter of pGAP. The 6His-Tatritin had a broad-spectrum antibacterial activity based on the Oxford cup method and the micro broth dilution test. In addition, to explore the role of 6His-Tatritin in vivo, grass carps (Ctenopharyngodon idellus) were infected with Aeromonas hydrophila after they were fed with 6His-Tatritin as feed additives for 28 days. The results revealed that 6His-Tatritin could significantly up-regulate the expression levels of Hepcidin, Leap-2b, Nrf-2, CuZn-SOD and LZM (P < 0.05). In addition, 6His-Tatritin could significantly reduce the mortality (P < 0.05) and the intestinal injury of grass carps infected with bacteria. The 16S sequencing analysis showed that the structure of microbial community in intestine of fish was more diversified compared with control after treatment with 6His-Tatritin. In summary, the peptide of 6His-Tatritin could promote antimicrobial defense via regulating immune ability and intestinal microbial community in grass carp. This study provides an effective method and approach for the application of antimicrobial peptide Tatritin in aquaculture, and also provides insights into the function of antimicrobial peptides in immunity against pathogens in fish.

Targeted deletion of 5'HS2 enhancer of ß-globin locus control region in K562 cells.

Human ß-thalassemia is closely associated with aberrant expression of ß-like globin genes. Human ß-like globin genes are organized in the order of 5'-ε-Gγ-Aγ-δ-ß-3' within the ß-globin locus. The expression of ß-like globin genes is regulated by 3'HS1 and five DNase I hypersensitive sites (5'HS5~5'HS1) in a locus control region. The 5'HS2 enhancer transcribes enhancer RNA and regulates the expression of ε-globin, γ-globin and ß-globin. To further study the function of 5'HS2, we detected the local 3D genomic architecture via chromatin conformation capture experiments and used CRISPR/ Cas9-based DNA fragment editing to delete 5'HS2 in human K562 leukaemia cells. In this study, we found that 5'HS2-mediated chromatin interactions were enriched in a topologically associated domain that was bordered by 3'HS1 and 5'HS5. Within this topologically associated domain, 5'HS2 is highly close to the promoter regions of HBE1, HBG2 and HBG1. Upon deletion of the 5'HS2 enhancer, 91 genes were significantly down-regulated with reduced abundance of H3K27ac at their promoter regions. These down-regulated genes are mainly associated with oxygen transport, immune response, cell adhesion, anti-oxidant and thrombosis. These data suggested that many genes associated with functions of erythrocytes were decreased at transcriptional levels upon deletion of the 5'HS2 enhancer.

Stress response and tolerance mechanisms of ammonia exposure based on transcriptomics and metabolomics in Litopenaeus vannamei.

Ammonia, one of the major limiting environment factors in aquaculture, may pose a threat to the shrimp growth, reproduction and survival. In this study, to understand molecular differences of transcriptomic and metabolomic responses and investigate the tolerance mechanisms underlying ammonia stress in Litopenaeus vannamei, ammonia-tolerant family (LV-AT) and ammonia-sensitive family (LV-AS) of these two extreme families were exposed to high-concentration (NH4Cl, 46 mg/L) ammonia for 24 h. The comparative transcriptome analysis between ammonia-treated and control (LV-C) groups revealed involvement of immune defense, cytoskeleton remodeling, antioxidative system and metabolic pathway in ammonia-stress response of L. vannamei. Likewise, metabolomics analysis showed that ammonia exposure could disturb amino acid metabolism, nucleotide metabolism and lipid metabolism, with metabolism related-genes changed according to RNA-seq analysis. The comparison of metabolite and transcript profiles between LV-AT and LV-AS indicated that LV-AT used the enhanced glycolysis and tricarboxylic acid (TCA) cycle strategies for energy supply and ammonia excretion to adapt high-concentration ammonia. Furthermore, some of genes involved in the detoxification and ammonia excretion were highly expressed in LV-AT. We speculate that the higher ability of ammonia excretion and detoxification and the accelerated energy metabolism for energy supplies might be the adaptive strategies for LV-AT relative to LV-AS after ammonia stress. Collectively, the combination of transcriptomics and metabolomics results will greatly contribute to incrementally understand the stress responses on ammonia exposure to L. vannamei and supply molecular level support for evaluating the environmental effects of ammonia on aquatic organisms. The results further constitute new sights on the potential molecular mechanisms of ammonia adaptive strategies in shrimps at the transcriptomics and metabolomics levels.

Effect of Low Temperature on Globin Expression, Respiratory Metabolic Enzyme Activities, and Gill Structure of Litopenaeus vannamei.

Low temperature frequently influences growth, development, and even survival of aquatic animals. In the present study, physiological and molecular responses to low temperature in Litopenaeus vannamei were investigated. The cDNA sequences of two oxygen-carrying proteins, cytoglobin (Cygb) and neuroglobin (Ngb), were isolated. Protein structure analysis revealed that both proteins share a globin superfamily domain. Real-time PCR analysis indicated that Cygb and Ngb mRNA levels gradually increased during decrease in temperatures from 25 to 15°C and then decreased at 10°C in muscle, brain, stomach, and heart, except for a continuing increase in gills, whereas they showed a different expression trend in the hepatopancreas. Hemocyanin concentration gradually reduced as the temperature decreased. Moreover, the activities of respiratory metabolic enzymes including lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) were measured, and it was found that LDH activity gradually increased while SDH activity decreased after low-temperature treatment. Finally, damage to gill structure at low temperature was also observed, and this intensified with further decrease in temperature. Taken together, these results show that low temperature has an adverse influence in L. vannamei, which contributes to systematic understanding of the adaptation mechanisms of shrimp at low temperature.

Clinical and genetic features of Prader-Willi syndrome in China.

UNLABELLED: We set out to delineate the phenotypic and genotypic characteristics of Prader-Willi syndrome (PWS), a congenital neurodevelopmental disorder caused by the lack of expression of the paternally inherited imprinted genes on chromosome 15q11-13 in 31 Chinese patients. They were genotyped to identify deletions using methylation-specific polymerase chain reaction analysis and subsequent methylation-specific multiplex ligation-dependent probe amplification analysis. Microsatellite linkage analysis was performed to distinguish maternal uniparental disomy (UPD) from imprinting defect. Clinical manifestations were recorded and compared between patients with paternal 15q11-13 deletion and UPD. Deletions in the 15q11-13 region were present in 26 (83.9 %) patients, and UPD was observed in 5 (16.1 %) patients. The mean maternal age at the time of childbirth for mUPD children (32.8 ± 5.1 years) was significantly higher than that of children with paternal 15q11-13 deletion (27.1±3.2 years, P < 0.05). All patients had neonatal hypotonia, feeding difficulties in infancy, and decreased fetal activity, but only 12.9 % of the patients showed short stature, 54.8 % presented typical facial features, and 35.5 % showed skin picking lesions. CONCLUSION: Significant heterogeneity in clinical phenotypes and genotypes in PWS were observed between Chinese and Western populations in this study. This suggests that ethnic differences may be relevant to the diagnostic criteria for PWS.

Genome-wide analysis of ATP-binding cassette (ABC) transporter in Penaeus vannamei and identification of two ABC genes involved in immune defense against Vibrio parahaemolyticus by affecting NF-κB signaling pathway.

The ATP-binding cassette (ABC) transporters have crucial roles in various biological processes such as growth, development and immune defense in eukaryotes. However, the roles of ABC transporters in the immune system of crustaceans remain elusive. In this study, 38 ABC genes were systematically identified and characterized in Penaeus vannamei. Bioinformation analysis revealed that PvABC genes were categorized into ABC A-H eight subfamilies with 17 full-transporters, 11 half transporters and 10 soluble proteins, and multiple immunity-related cis-elements were found in gene promoter regions. Expression analysis showed that most PvABC genes were widely and highly expressed in immune-related tissues and responded to the stimulation of Vibrio parahaemolyticus. To investigate whether PvABC genes mediated innate immunity, PvABCC5, PvABCF1 and PvABCB4 were selected for dsRNA interference experiment. Knockdown of PvABCF1 and PvABCC5 not PvABCB4 increased the cumulative mortality of P. vannamei and bacterial loads in hepatopancreas after infection with V. parahaemolyticus. Further analysis showed that the PvABCF1 and PvABCC5 knockdown decreased expression levels of NF-κB pathway genes and antimicrobial peptides (AMPs). Collectively, these findings indicated that PvABCF1 and PvABCC5 might restrict V. parahaemolyticus challenge by positively regulating NF-κB pathway and then promoting the expression of AMPs, which would contribute to overall understand the function of ABC genes in innate immunity of invertebrates.

Mechanism of action of icaritin on uterine corpus endometrial carcinoma based on network pharmacology and experimental evaluation.

Background: Uterine corpus endometrial carcinoma (UCEC) belongs to a group of epithelial malignant tumors. Icaritin is the main active compound of Epimedii Folium. Icaritin has been utilized to induce UCEC cells to death. Methods: We wished to identify potential targets for icaritin in the treatment of UCEC, as well as to provide a groundwork for future studies into its pharmacologic mechanism of action. Network pharmacology was employed to conduct investigations on icaritin. Target proteins were chosen from the components of icaritin for UCEC treatment. A protein-protein interaction (PPI) network was established using overlapping genes. Analyses of enrichment of function and signaling pathways were undertaken using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, to select "hub genes". Finally, experiments were carried out to ascertain the effect of icaritin on endometrial cancer (HEC-1-A) cells. Results: We demonstrated that icaritin has bioactive components and putative targets that are therapeutically important. Icaritin treatment induced sustained activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt pathway) and inhibited growth of HEC-1-A cells. Conclusion: Our data provide a rationale for preclinical and clinical evaluations of icaritin for UCEC therapy.

Identification of a Novel Antimicrobial Peptide From the Ancient Marine Arthropod Chinese Horseshoe Crab, Tachypleus tridentatus.

Humoral immunity is the first line of defense in the invertebrate immune system, and antimicrobial peptides play an important role in this biological process. A novel antimicrobial peptide, termed Tatritin, was identified and characterized in hemolymph of Chinese horseshoe crab, Tachypleus tridentatus, infected with Gram-negative bacteria via transcriptome analysis. Tatritin was significantly induced by bacterial infection in hemolymph and gill. The preprotein of Tatritin consists of a signal peptide (21 aa) and a mature peptide (47 aa) enriched by cysteine. The putative mature peptide was 5.6 kDa with a theoretical isoelectric point (pI) of 9.99 and showed a α-helix structure in the N-terminal and an anti-parallel ß-sheet structure in the cysteine-stabilized C-terminal region. The chemically synthesized peptide of Tatritin exhibited a broad spectrum of antimicrobial activity against Gram-negative and Gram-positive bacteria and fungi. Furthermore, Tatritin may recognize and inhibit pathogenic microorganisms by directly binding to LPS, DNA, and chitin. In addition, administration of Tatritin reduced the mortality of zebrafish after bacterial infection. Due to its broad-spectrum antimicrobial activity in vivo and in vitro and the sensitivity to drug-resistant bacterial strains, Tatritin peptide can be used as a new type of drug for infection treatment or as an immune enhancer in animals.

Risk prediction model for early postoperative death in patients with hepatocellular carcinoma: a retrospective study based on random forest algorithm and logistic regression.

BACKGROUND: At present, little is known about the risk factors of early postoperative death in patients with hepatocellular carcinoma (HCC). METHODS: We collected the data of patients who were diagnosed with primary liver cancer between 2010 and 2015 in the Surveillance, Epidemiology, and End Results database and further allocated them to the training set and validation set. Univariate and multivariate logistic regression analysis was used to determine the independent influencing factors of early postoperative death of HCC patients. Random forest and Least absolute shrinkage and selection operator regression analysis were used to screen out vital variables for the construction of the nomogram. It was evaluated by receiver operating characteristic curve, calibration curve and decision curve analysis. RESULTS: A total of 4154 patients were selected in this process, including 2647 patients with postoperative early death (outcome1) and 1507 patients with liver cancer-specific postoperative early death (outcome2). Surgery method, age category, marital status and tumor grade were the risk factors for early postoperative death. As for the liver cancer-specific early postoperative death, AJCC, surgery method, chemotherapy and tumor grade were independent prognostic factors. Early death and liver cancer-specific early death nomograms have an area under curves of 0.643 and 0.679 in the training set, respectively, and 0.617 and 0.688 in the validation set. The calibration curve and decision curve analysis shows that the nomograms have good performance. CONCLUSION: This model provides an intuitive and practical tool for future studies based on large-scale cohorts by exploring the risk factors of early death in patients with HCCs undergoing surgery.

Transcriptomic analysis of gills in nitrite-tolerant and -sensitive families of Litopenaeus vannamei.

Nitrite stress is a major environmental factor that limits aquatic animal growth, reproduction and survival. Even so, some shrimps still can withstand somewhat high concentrations of nitrite environment. However, few studies have been conducted about the tolerance molecular mechanism of Litopenaeus vannamei in the high concentration nitrite. To identify the genes and pathways involved in the regulation of nitrite tolerance, we performed comparative transcriptomic analysis in the L. vannamei nitrite-tolerant (NT) and nitrite-sensitive (NS) families, and untreated shrimps were used as the control group. After 24 h of nitrite exposure (NaNO2, 112.5 mg/L), a total of 1521 and 868 differentially expressed genes (DEGs) were obtained from NT compared with NS and control group, respectively. Functional enrichment analysis revealed that most of these DEGs were involved in immune defense, energy metabolism processes and endoplasmic reticulum (ER) stress. During nitrite stress, energy metabolism in NT was significantly enhanced by activating the related genes expression of oxidative phosphorylation (OXPHOS) pathway and tricarboxylic acid (TCA) cycle. Meanwhile, some DEGs involved in innate immunity- related genes and pathways, and ER stress responses also were highly expressed in NT. Therefore, we speculate that accelerated energy metabolism, higher expression of immunity and ER related genes might be the important adaptive strategies for NT in relative to NS under nitrite stress. These results will provide new insights on the potential tolerant molecular mechanisms and the breeding of new varieties of nitrite tolerant L. vannamei.

Comparison of protective effects of alprostadil with Salvia miltiorrhiza against myocardial ischemia-reperfusion injury in rats.

OBJECTIVES: Our study aimed to investigate the effects of alprostadil and Salvia miltiorrhiza extract on myocardial ischemia-reperfusion injury (IRI) and related underlying molecular mechanisms. METHODS: A myocardial IRI model was established in Wistar rats via surgical ligation of the left anterior descending coronary artery followed by loosening of the occlusion. The rats were divided into four groups: saline, sham, alprostadil, and S. miltiorrhiza. Rats in the saline and sham groups were injected with normal saline by tail vein once daily for 10 consecutive days. Rats in the S. miltiorrhiza and alprostadil groups were injected with S. miltiorrhiza extract (20 µg/kg) or alprostadil. Histological differences in myocardial tissues between rats in the sham group and in the myocardial IRI model were observed by hematoxylin and eosin staining. India ink perfusion was used to quantify the number of capillary microvessels. Real-time quantitative reverse transcription polymerase chain reaction was used to determine serum expression levels of soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM), CD11b and CD18. RESULTS: The alprostadil and S. miltiorrhiza groups had significantly higher numbers of microvessels than the saline group. Serum sICAM and sVCAM expression was significantly reduced in the alprostadil and S. miltiorrhiza groups. Meanwhile, sICAM and sVCAM in the alprostadil group were markedly lower than in the S. miltiorrhiza group. Moreover, the alprostadil group had markedly lower mRNA expression of CD11b and CD18, which were clearly lower than in the S. miltiorrhiza group. CONCLUSION: Alprostadil may have cardioprotective effects for myocardial IRI, with down-regulated expression of sICAM, sVCAM, CD11b, and CD18.

1,4-Bis(5-methyl-1H-1,2,4-triazol-3-yl)benzene tetra-hydrate.

In the title compound, C(12)H(12)N(6)·4H(2)O, the two triazole rings adopt a cis configuration with a crystallographic twofold axis passing through the central benzene group. The benzene and triazole rings are almost coplanar with a dihedral angle of 5.5 (1)°. In the crystal, water mol-ecules are joined together by OW-H⋯OW hydrogen bonds to form a one-dimensional zigzag chain. These water chains are further connected to the organic mol-ecule, forming a three-dimensional network by inter-molecular OW-H⋯N and N-H⋯OW hydrogen bonds. Moreover, π-π stacking inter-actions between triazole rings [centroid-centroid distances = 3.667 (1)-3.731 (1) Å] are observed. One of the water mol-ecules shows one of the H atoms to be disordered over two positions.

[Comparative study on the infrared fingerprint of Abrus cantoniensis based on the methods of sequential analysis of dual-indexes and cluster analysis].

The methods of sequential analysis of dual-indexes and cluster analysis were utilized to investigate the infrared fingerprints of A. cantoniensis planted in different years and different places in Guangxi, China. The results showed that 6 samples were able to be completely separated only through 13 point smoothing, when the dual-indexes analysis was applied in the present research, and the accurate relationship between these samples could be inspected and expressed by quantitative relationships under 6-dimensional spaces; however, the effect of cluster was bad only through 13 point smoothing of raw spectra, and it was very difficult to find out the regular sequences while the cluster analysis was applied. Furthermore, the 6 samples were able to be completely separated if raw spectra were dealed with 1st derivative after 13 point smoothing, and the clustering effects were more obvious and 6 samples of A. cantoniensis were completely separated. The above two methods could be used to evaluate the quality of Chinese medicinal materials easily when the sample was not excessive quantitatively, but the method of dual-indexes analysis was more difficult than the clustering analysis if the sample size was too large, since a mass of data such as common peak ratio and variation peak ratio of the IR fingerprint spectra were processed and analyzed statistically, while this method could accurately find out the closest relationship between any samples through comparing the quantitative relationships of common peak ratio and variation peak ratio of each sample under 6-dimensional space; the precision of cluster analysis was less than dual-indexes analysis, but it was more convenient than dual-indexes analysis when large sample data were analysed. Finally the above two methods all showed that the chemical composition of the A. cantoniensis was similar in the same cultivated area, but the difference in chemical composition of A. cantoniensis in different years was distinct even they were in the same place.

Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past, present and future.

The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, are not fully understood so far. Therefore, IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine. About 20 years ago, selective granulocyte and monocyte apheresis (GMA) was invented in Japan and later approved by the Japanese health authority for IBD treatment. From then on this technique was extensively used for IBD patients in Japan and later in Europe. Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD. In 2013, GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients. However, GMA therapy has not been extensively used in China, although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile. This article reviews past history, present clinical application as well as the future prospective of GMA therapy for patients with IBD.

Immune Responses to Gram-Negative Bacteria in Hemolymph of the Chinese Horseshoe Crab, Tachypleus tridentatus.

Chinese horseshoe crab, Tachypleus tridentatus, is an ancient marine arthropod with a long evolutionary history. As a kind of living fossil species, the pathogen defenses of horseshoe crabs entirely depend on the innate immune system. Although, there are abundant immune molecules found in the horseshoe crab hemolymph, the biological mechanisms underlying their abilities of distinguishing and defending against invading microbes are still unclear. In this study, we used high-throughput sequencing at mRNA and protein levels and bioinformatics analysis methods to systematically analyze the innate immune response to Gram-negative bacteria in hemolymph of Chinese horseshoe crab. These results showed that many genes in the complement and coagulation cascades, Toll, NF-κB, C-type lectin receptor, JAK-STAT, and MAPK signaling pathways, and antimicrobial substances were activated at 12 and 24 h post-infection, suggesting that Gram-negative bacteria could activate the hemolymph coagulation cascade and antibacterial substances release via the above pathways. In addition, we conjectured that Toll and NF-κB signaling pathway were most likely to participate in the immune response to Gram-negative bacteria in hemolymph of horseshoe crab through an integral signal cascade. These findings will provide a useful reference for exploring the ancient original innate immune mechanism.

Application of positive behavior management in patients after breast cancer surgery.

BACKGROUND: As a radical treatment, breast cancer surgery has a positive psychological impact on most patients. However, some patients do not have a clear understanding of the disease, which requires a more scientific and comprehensive consideration during clinical intervention and are based on cognition. The positive behavior management model is based on this kind of background-derived new interventions, which can better serve the clinical rehabilitation process of patients. The positive behavior management model based on cognitive architecture is a new type of intervention derived from this background, which can better serve the clinical rehabilitation process of patients. AIM: To analyze the influence of a positive behavior management model based on cognitive framework on the degree of hope and self-efficacy of patients with breast cancer surgery. METHODS: Eighty-four patients with breast cancer who underwent surgical treatment in our hospital from August 2016 to December 2018 were included in the study. The patients were divided into the experimental group (n = 42) and control group (n = 42) by random number table grouping. The control group received traditional nursing intervention, while the experimental group received a positive behavior management model based on cognitive framework based on the traditional intervention of the control group. General Self-efficacy Scale, Herth Hope Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale and Cancer Patient Specific Scale were used to evaluate the two groups before and 1 wk after intervention. RESULTS: After the intervention, self-efficacy and hope level of the experimental group were significantly higher than those of the control group (P < 0.05). The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores in the experimental group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the quality of life scores between the two groups before intervention (P > 0.05). The quality of life scores in all aspects in the experimental group after intervention were significantly higher than those in the control group (P < 0.05). CONCLUSION: The positive behavior management model based on cognitive framework applied to patients with breast cancer surgery improved hope for treatment and self-efficacy, reduced negative emotion, and improved quality of life.

Integrated analysis of physiological, transcriptomic and metabolomic responses and tolerance mechanism of nitrite exposure in Litopenaeus vannamei.

Nitrite accumulation in aquatic environments is a potential risk factor that disrupts multiple physiological functions in aquatic animals. In this study, the physiology, transcriptome and metabolome of the control group (LV-C), nitrite-tolerance group (LV-NT) and nitrite-sensitive group (LV-NS) were investigated to identify the stress responses and mechanisms underlying the nitrite tolerance of Litopenaeus vannamei. After LV-NT and LV-NS were subjected to nitrite stress, the hemocyanin contents were significantly decreased, and hepatopancreas showed severe histological damage compared with LV-C. Likewise, the antioxidant enzymes were also significantly changed after nitrite exposure. The transcriptome data revealed differentially expressed genes associated with immune system, cytoskeleton remodeling and apoptosis in LV-NT and LV-NS. The combination of transcriptomic and metabolomic analysis revealed nitrite exposure disturbed metabolism processes in L. vannamei, including amino acid metabolism, nucleotide metabolism and lipid metabolism. The multiple comparative analysis implicated that higher nitrite tolerance of LV-NT than LV-NS may be attributed to enhanced hypoxia inducible factor-1α expression to regulate energy supply and gaseous exchange. Moreover, LV-NT showed higher antioxidative ability, detoxification gene expression and enhanced fatty acids contents after nitrite exposure in relative to LV-NS. Collectively, all these results will greatly provide new insights into the molecular mechanisms underlying the stress responses and tolerance of nitrite exposure in L. vannamei.

SENP2 exerts an anti­tumor effect on chronic lymphocytic leukemia cells through the inhibition of the Notch and NF­κB signaling pathways.

Chronic lymphocytic leukemia (CLL) is one of the most often diagnosed hematological malignant tumors in the Western world and a type of inert B­cell lymphoma that commonly attacks the elderly. Small ubiquitin related modifier (SUMO)­specific protease 2 (SENP2) can act as a suppressor in various types of cancer by regulating the stability of ß­catenin to affect the Notch signaling pathway; however, it has a low expression level in CLL cells. In this study, we firstly used western blot analysis and RT­qPCR to detect the protein and mRNA expression levels of SENP2 in the peripheral blood of patients with CLL and healthy volunteers. Secondly, we overexpressed or knocked down the expression of SENP2 in CLL cells and then determined the cell invasive and chemotactic ability in a Transwell assay and chemotaxis assay. We examined the sensitivity of the cells to cytarabine and dexamethasone via a CCK­8 assay and determined the cell apoptotic condition and the expression of the Notch signaling pathway using flow cytometry and western blot analysis. The results demonstrated that the patients with CLL had relatively low expression levels of SENP2. The overexpression of SENP2 in the CLL cells decreased their invasive and proliferative ability, as well as their chemotactic response and enhanced their sensitivity to cytarabine and dexamethasone, while it promoted cell apoptosis. The silencing of SENP2 in the CLL cells generally produced the opposite results. We thus hypothesized that the overexpression of SENP2 downregulated ß­catenin expression, thus inhibiting the Notch signaling pathway in CLL cells. Moreover, the nuclear factor (NF)­κB signaling pathway was also regulated by the overexpression of SENP2. On the whole, the findings of this study indicate tha SENP2 can act as a tumor suppressor in CLL cells, and may thus prove to be a novel target for CLL treatment in clinical practice.