[Research in evaluation and intervention of cardiovascular complications of patients with type 1 diabetes on demand].

Recently, great progress has been made in the treatment of type 1 diabetes mellitus (T1DM), however the disease still significantly shortens the life expectancy. Cardiovascular complication is the main cause of death in T1DM patients, and the morbidity is even higher than that of type 2 diabetes. The risk factors of cardiovascular complication in T1DM are different from those of type 2 diabetes. Besides hyperglycemia, dyslipidemia, hypertension, microvascular complications and unhealthy lifestyle, non-traditional risk factors also play very important roles in developing cardiovascular complication, such as hypoglycemia, blood glucose variability, insulin resistance, and autoimmune inflammation of heart. At present, there is a lack of risk assessment and prevention measures for cardiovascular complications in T1DM. It is necessary for more studies to explore whether sodium-dependent glucose transporters 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, which can improve cardiovascular and renal outcomes in type 2 diabetes mellitus, can be equally effective in T1DM.

Improving probiotic spore yield using rice straw hydrolysate.

Spore-forming Bacillus sp. has been extensively studied for their probiotic properties. In this study, an acid-treated rice straw hydrolysate was used as carbon source to produce the spores of Bacillus coagulans. The results showed that this hydrolysate significantly improved the spore yield compared with other carbon sources such as glucose. Three significant medium components including rice straw hydrolysate, MnSO4 and yeast extract were screened by Plackett-Burman design. These significant variables were further optimized by response surface methodology (RSM). The optimal values of the medium components were rice straw hydolysate of 27% (v/v), MnSO4 of 0·78 g l-1 and yeast extract of 1·2 g l-1 . The optimized medium and RSM model for spore production were validated in a 5 l bioreactor. Overall, this sporulation medium containing acid-treated rice straw hydrolysate has a potential to be used in the production of B. coagulans spores.

Pattern-recognition receptors in duck (Anas platyrhynchos): identification, expression and function analysis of toll-like receptor 3.

1. Innate immunity provides the first line of defence against pathogenic organisms through a myriad of germline encoded receptors called pattern-recognition receptors (PRRs). Toll-like receptor (TLR) 3, as an important member of PRRs, is indispensable for host defence against viral infection by recognising virus-derived RNAs. However, little is known about the structure and function of TLR3 in ducks (Anas platyrhynchos), a natural host for the avian influenza virus.2. This study cloned the full-length cDNA of duck TLR3 using reverse transcription polymerase chain reaction (RT-PCR) with rapid amplification of cDNA ends (RACE). The cDNA sequence of duck TLR3 was 4046 bp in length and encoded 895 amino acids. Multiple sequence alignment showed that duck TLR3 shared high similarity with that from other vertebrates.3. Quantitative real-time PCR (qRT-PCR) analysis suggested that TLR3 mRNA was constitutively expressed in all tissues tested, having higher levels in the kidney, liver, breast muscle, ovary and heart. After stimulation with viral- or bacterial-mimics, including LPS, poly(I:C), pam3CSK4, FLS-1, FLA-ST and R848, the TLR3 transcript was significantly upregulated. Meanwhile, overexpression of duck TLR3 significantly promoted the transcription of IFN-ß, IRF7, TRIF, Mx, STAT1 and STAT2 mRNA after stimulation with poly(I:C).4. These results suggested that TLR3 play an important role in resistance against viral and bacterial infections in ducks.

[Study on the feasibility of improving menopausal syndrome using the one-day outpatient based continuous management model].

To explore the mode of"one-day outpatient"based continuous management and examine its feasibility and preliminary effects for improving menopausal syndrome and mood among menopausal women.Clinical intervention study was conducted in Obstetrics and Gynecology Center of the Third Affiliated Hospital of Chongqing Medical University from May 2020 to May 2021.The continuous management mode of "one-day outpatient service" for menopause was constructed in terms of multidisciplinary resources, including offline "one-day outpatient" health education, online 7-week group continuous intervention on "healthy lifestyle" and offline half-day focus group interview. Pre-and post-scores of the modified Kupperman scale and the positive/negative emotional scale (PANAS) were measured to compare the status of menopausal syndrome and emotional experience of Seventy-eight female participants (40-60 years old), meanwhile, before and after comparison of the blood lipid and body composition indexes of participants were also performed. Paired t test or Wilcoxon signed rank test were used.Results show that the pre-and post Kupperman scores were 14.65±8.51 vs 10.26±5.83 (t=-5.59, P<0.01), and the positive emotional scores (pre- 28.53±5.85 vs post- 30.13±6.30) were improved (t=2.59, P=0.012) and negative emotional scores [pre- 20.5(10) vs post- 17.0(7)] were decreased (Z=-5.09, P<0.01). The triglyceride level of participants declined from (1.27±0.54) mmol/L to (1.09±0.38) mmol/L (t=-2.45, P<0.05). In addition, the body mass index(pre- 22.52±2.34 vs post- 22.06±2.22), percentage of body fat (pre- 31.72±6.22 vs post- 30.91±6.52)and Visceral fat area(pre- 83.96±30.26 vs post- 79.66±29.71) were all improved (t=-3.58,t=-2.57,t=-2.59, P<0.05). Therefore,the mode of"one-day outpatient"based continuous management can effectively improve menopausal syndrome and adverse mood, reduce patients' blood lipid, improve the body composition, and maybe contribute to the prevention of long-term chronic diseases.

CRISPR/Cas9-mediated knockout of the eye pigmentation gene white leads to alterations in colour of head spots in the oriental fruit fly, Bactrocera dorsalis.

The intensely studied white gene is widely used as a genetic marker in Drosophila melanogaster. Here, we cloned and characterized the white gene in an important pest of the fruit industry, Bactrocera dorsalis, to understand its functional role in pigmentation. We obtained BdWhite knockout strains, based on the wild-type strain, using the CRISPR/Cas9 genome editing system, and found that mutants lost pigmentation in the compound eye and their black head spots. We then examined differences in the expression levels of genes associated with melanin pigmentation between mutants and the wild-type strain using quantitative reverse transcription PCR. We found that transcription levels of the Bd-yellow1 were lower in the head of mutants than in the wild-type strain, and there were no significant differences in expression of the other six genes between mutants and the wild type. Since yellow is critical for melanin biosynthesis (Heinze et al., Scientific Reports. 2017;7:4582), the lower levels of expression of Bd-yellow1 in mutants led to reduced dark pigmentation in head spots. Our results provide the first evidence, to our knowledge, that white may play a functional role in cuticle pigmentation by affecting the expression of yellow.

Clinical diagnostic significance of prealbumin, cholinesterase and retinol binding protein in liver cirrhosis combined with encephalopathy.

OBJECTIVE: Hepatic encephalopathy is a common consequence of liver cirrhosis, but diagnosis can be difficult as it is based on clinical criteria alone. We hypothesised that serum prealbumin, cholinesterase and retinol binding protein (RBP) can help support the diagnosis of hepatic encephalopathy. METHODS: We enrolled 306 cirrhotic patients (110 with encephalopathy), 100 chronic hepatitis B patients and 50 healthy controls, measuring routine liver function tests (ALT, AST, GGT, ALP, and bilirubin), albumin, prothrombin time, prealbumin, cholinesterase and RBP by routine methods. Logistic regression analysis and areas under the receiver operating characteristic curves (AUCs) were used to find predictive factors for hepatic encephalopathy. RESULTS: There were differences in all laboratory indices between the three groups (all p < 0.001). In univariate analysis, albumin, prothrombin time, prealbumin, cholinesterase and RBP were significantly altered in those with encephalopathy (p < 0.01), but only prealbumin, cholinesterase and RBP levels were significant predictors in multivariate analysis, and each was linked to the severity of liver fibrosis defined by the Child-Pugh score (all p < 0.001). The AUCs (95% CI) of prealbumin, cholinesterase and RBP for diagnosing liver cirrhosis with hepatic encephalopathy were comparable at 0.85 (81-90), 0.81 (0.76-0.85) and 0.81 (0.76-0.86), respectively (all p < 0.01). CONCLUSIONS: Serum prealbumin, cholinesterase and RBP levels are of potential clinical value in diagnosis of liver cirrhosis complicated by encephalopathy.

Molecular cloning, characterisation, and expression patterns of pigeon CCAAT/enhancer binding protein-α and -ß genes.

1. CCAAT/enhancer binding proteins (C/EBPs), as a family of transcription factors, consists of six functionally and structurally related proteins which share a conserved basic leucine zipper (bZIP) DNA-binding domain. The aim of this study was to clone the full-length coding sequences (CDS) of C/EBP-α and -ß genes, and determine the abundance of these two genes in various tissues of white king pigeon (C. livia). 2. The complete cDNA sequences of C/EBP-α and -ß genes were cloned from pigeons by using PCR combined with rapid amplification of cDNA ends (RACE). The sequences were bioinformatically analysed, and the tissue distribution determined by quantitative real-time RT-PCR (qRT-PCR). 3. The results showed that the full-length cDNA sequences of pigeon C/EBP-α and -ß genes were 2,807bp and 1,778bp, respectively. The open reading frames of C/EBP-α (978 bp) and -ß (987bp) encoded 325 amino acids and 328 amino acids, respectively. The pigeon C/EBP-α and C/EBP-ß proteins were predicted to have a conserved basic leucine zipper (bZIP) domain, which is a common structure feature of the C/EBP family. Multiple sequence alignments indicated that pigeon C/EBP-α and -ß shared more than 90% amino-acid identity with their corresponding homologues in other avian species. Phylogenetic analysis revealed that these two proteins were highly conserved across different species and evolutionary processes. QRT-PCR results indicated that the pigeon C/EBP-α and -ß mRNA transcripts were expressed in all investigated organs. The mRNA expression levels of pigeon C/EBP-α in descending order, were in spleen, heart, liver, lung, kidney and muscle. The pigeon C/EBP-ß gene had the most abundant expression in lung, followed by the kidney, with minimal expression detected in muscle. 4. This study investigated the full-length cDNA sequences, genetic characteristics and tissue distribution of pigeon C/EBP-α and -ß genes and found that they may have functions in various tissues of pigeon. This provides a foundation for further study for regulatory mechanisms of these two genes in birds.

Cloning, expression and bioinformatics analysis of a putative pigeon melanoma differentiation-associated gene 5.

1. Melanoma differentiation-associated gene 5 (MDA5) is a critical member of cytosolic pattern recognition receptors (PRRs) that recognise viral RNA and mediate type I interferon secretion in host cells. 2. The objective of the present study was to identify and characterise the structure and expression of pigeon MDA5. 3. The full-length MDA5 cDNA was cloned from pigeon spleen using RT-PCR and RACE. The distribution and expression level of pigeon MDA5 in different tissues were determined by QRT-PCR. 4. The results showed that the full-length pigeon MDA5 cDNA had 3858 nucleotides (containing a 210-bp 5'-UTR, a 3030-bp open reading frame and a 618-bp 3'-UTR) encoding a polypeptide of 1009 amino acids. The deduced amino acid sequence contained six conserved structural domains typical of RIG-I-like receptor (RLR), including two tandem arranged N-terminal caspase activation and recruitment domains (CARDs), a DEAH/DEAD box helicase domain (DExDc), a helicase superfamily c-terminal domain (HELICc), a type III restriction enzyme (ResIII) and a C-terminal regulatory domain (RD). 5. The pigeon MDA5 showed 84.8%, 87.3%, 87.9% and 87.2% amino acid sequence identities with previously described homologues from chicken, duck, goose and Muscovy ducks, respectively, and phylogenetic analysis revealed a close relationship among these MDA5. 6. Pigeon MDA5 transcript was ubiquitously expressed in all seven tissues tested in healthy pigeons and showed a high level in the thymus gland and kidney. 7. These findings lay the foundation for further research on the function and mechanism of MDA5 in innate immune responses related to vaccinations and infectious diseases in the pigeon.

Tannerella forsythia and coating color on the tongue dorsum, and fatty food liking associate with fat accumulation and insulin resistance in adult catch-up fat.

BACKGROUND/OBJECTIVES: We aimed to determine the alteration of Tannerella forsythia and coating color on the dorsal tongue, and fatty food liking in catch-up fat in adult (CUFA), as well as the probable associations between fat accumulation, insulin resistance (IR) and these changes. SUBJECTS/METHODS: T. forsythia on the tongue dorsum, fatty food liking, fat accumulation and insulin sensitivity were investigated in CUFA humans and rats, and tongue-coating color was observed in CUFA individuals. We further determined the changes of fatty food liking, fat accumulation and IR in T. forsythia-infected rodents by oral lavage. RESULTS: Increases in fat accumulation, IR, percentage of subjects with yellow tongue coating and that with T. forsythia detected were observed in CUFA individuals. Additionally, the fat ranking scores were significantly lower and the hedonic ratings of low-fat options of sampled food were lower, while the ratings of high-fat options were remarkably higher in CUFA subjects. Additionally, T. forsythia level elevated in CUFA rats, and fatty food liking, fat accumulation and IR increased in CUFA and T. forsythia-infected animals, with the increases in T. forsythia infection and fatty food liking preceding the occurrence of fat accumulation and IR. CONCLUSIONS: T. forsythia and yellow coating on the dorsal tongue and fatty food liking associate fat accumulation and IR in CUFA. Moreover, we tentatively put forward that T. forsythia, which is very important in yellow tongue-coating microbiota, and its consequent increases in fatty food liking, might be crucial in the development of fat accumulation and IR in CUFA.

[Protective effects of N-acetyl-L-cysteine against binge drinking-induced fatty liver in mice].

Objective: To investigate the roles of N-acetyl-L-cysteine (NAC) against binge drinking-induced fatty liver in mice. Methods: SPF male C57BL/6 mice were randomly divided into 3 groups, i.e. control group, model group, and NAC/ethanol group (n=10). Mice in model and NAC/ethanol groups were exposed to 3 doses of ethanol (6 g/kg bw) to induced fatty liver, while mice in control group received equal volume and equal energy of maltodextrin solution. NAC was administered to mice at 1 h before ethanol exposure (100 mg/kg bw, i.p.). The mice were sacrificed at 6 h after the last ethanol exposure. The liver and epididymal adipose tissues were collected. Histopathological examination and biochemical assay kit were used to evaluate the fat accumulation, while Western-blot was performed to detect the protein levels of some key factors involved in fat metabolism in liver and adipose tissues. Results: Compored with control group mice, the liver index and liver weight were significantly increased compared with model group, the liver index and TG level in NAC/ethanol group mice were all significantly decreased (P<0.05). Histological examination showed NAC effectively suppressed binge drinking-induced fat accumulation in mice liver. In addition, NAC had no significant effects on the protein levels of peroxisome proliferator-activated receptor-α (PPAR-α), Acy-CoA oxidase (ACOX), sterol regulatory element binding protein 1 c (SREBP-1c) and fatty acid synthase (FAS). Furthermore, the protein levels of hormone sensitive lipase (HSL) did not significantly differ among 3 groups, whereas NAC prevented binge drinking-induced increase of HSL phosphorylation at ser563 and ser660. Conclusion: NAC could effectively attenuate binge drinking-induced fatty liver, which might be associated with the inhibition of lipid mobilization by suppressing the phosphorylation of HSL.

PCK1 expression is correlated with the plasma glucose level in the duck.

Phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1) is a key gene in gluconeogenesis and glyceroneogenesis. Although its functions have been extensively studied in mice, bats and humans, little is known in ducks. Here, PCK1 functions were studied using a duck domestication model and a 48-h fasting experiment. We found PCK1 expression significantly decreased in two breeds of domestic ducks (Jinyun Pockmark ducks and Cherry Valley ducks) as compared with wild ducks (Anas platyrhynchos). Simultaneously, plasma levels of glucose, triglycerides and free fatty acid in domestic ducks were lower than in wild ducks. When compared with fed ducks, the plasma triglyceride level was observed to be significantly decreased, while the glucose and free fatty acid levels remained constant in 48-h fasting ducks. The expression analysis of gluconeogenic genes revealed that fructose-1,6-bisphosphatase genes (FBP1 and FBP2) and the glucose-6-phosphatase gene (G6PC2) were not changed, whereas PCK1 was significantly upregulated. In addition, the reported regulators of PCK1, including forkhead box A2 (FOXA2) gene and orphan nuclear receptor NR4A family genes (NR4A1, NR4A2 and NR4A3), exhibited similar expression levels between 48-h fasting ducks and fed ducks, suggesting that PCK1 is not regulated by these genes in the duck under fasting conditions. In conclusion, PCK1 expression may affect plasma levels of glucose, triglycerides and free fatty acid during the duck domestication process. This work demonstrates for the first time in duck that PCK1 is a key gene in maintaining plasma glucose homeostasis during fasting and that the upregulated expression of PCK1 may be responsible for constant plasma free fatty acid level by the glyceroneogenesis process.

Association analysis between feed efficiency studies and expression of hypothalamic neuropeptide genes in laying ducks.

Residual feed intake (RFI) is now considered a more reasonable metric to evaluate animal feed efficiency. In this study, the correlation between RFI and other feed efficiency traits was investigated and gene expression within the hypothalamus was determined in low RFI (LRFI) and high RFI (HRFI) ducks. Further, several hypothalamic neuropeptide genes were measured using quantitative real-time PCR. The mean feed intake value was 160 g/day, whereas the egg mass laid (EML) and body weight were approximately 62.4 g/day and 1.46 kg respectively. Estimates for heritability of RFI, feed conversion ratio (FCR) and feed intake were 0.26, 0.18 and 0.23 respectively. RFI is phenotypically positively correlated with feed intake and FCR (P < 0.01). The expression of neuropeptide Y (NPY) and neuropeptide Y receptor Y5 (NPY5R) mRNA was higher in HRFI ducks compared with LRFI ducks (P < 0.05), whereas that of proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R) and cholecystokinin (CCK) was lower (P < 0.05). The mRNA expression of gonadotropin-releasing hormone 1 (luteinizing-releasing hormone) (GNRH1) and prolactin receptor (PRLR) was unchanged between LRFI and HRFI ducks. The results indicate that selection for LRFI could reduce feed intake without significant changes in EML, whereas selection on FCR will increase EML.

Diagnostic value of recombinant Tp0821 protein in serodiagnosis for syphilis.

UNLABELLED: Syphilis is a multistage sexually transmitted disease that remains a serious public health concern worldwide. The coexistence of Treponema pallidum with other closely related members of spirochaeta, such as Leptospira spp. and Borrelia burgdorferi, has complicated the serodiagnosis due to cross-reactive antigens. In this study, recombinant Tp0821 protein was expressed in Escherichia coli and purified by metal affinity chromatography. Then enzyme-linked immunosorbent assays (ELISAs) based on Tp0821 for the detection of specific antibodies were established. The relative positive rates of the IgM ELISA and the IgG ELISA were found to be 91·0 and 98·3%, respectively, when screening 578 syphilis specimens. The specificities were 94·3 and 100%, respectively, when cross-checking with serum samples obtained from 30 patients with Lyme disease, five patients with leptospirosis, and 52 uninfected controls. In addition, relative positive rates and specificities of Tp0821 for human sera were all 100% in Western blotting. When compared to the syphilis diagnostic tests commonly used in clinical settings, we found that the results of Tp0821-based ELISAs correlated well with the results of the treponemal tests, specifically the T. pallidum particle agglutination (TP-PA) test and the chemiluminescent immunoassay (CIA). Thus, these findings identify Tp0821 as a novel serodiagnostic candidate for syphilis. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we expressed and purified the Treponema pallidum protein Tp0821 and developed Tp0821-based enzyme-linked immunosorbent assays (ELISAs) for the detection of specific antibodies. The serodiagnostic performance of the recombinant protein was then evaluated. When compared to the results of syphilis diagnostic tests commonly used in clinical settings, we found that the reactivities of syphilitic sera with the recombinant antigen correlated well with the results of the treponemal tests, specifically the T. pallidum particle agglutination (TP-PA) test and the chemiluminescent immunoassay (CIA). Thus, the recombinant protein shows promise as a new diagnostic antigen in the ELISAs.

Systematic tracking of altered modules identifies disrupted pathways in teratozoospermia.

The objective of this study was to identify disrupted pathways in teratozoospermia by systematically tracking dysregulated modules in reweighted protein-protein interaction (PPI) networks. We inferred and reweighted the PPI networks of normal and teratozoospermia groups based on Spearman correlation coefficients. Modules in the PPI networks were explored via a clique-merging algorithm and altered modules were identified based on maximum weight bipartite matching. Furthermore, pathway-enrichment analyses of genes in altered modules were performed by Database for Annotation, Visualization, and Integrated Discovery (DAVID) to illuminate the biological pathways in teratozoospermia. A total of 20,102 genes were screened from the expression profile. We explored 2406 and 2101 modules in normal and disease PPI networks, respectively. Moreover, we obtained 875 altered modules by comparing modules in normal and teratozoospermia PPI networks. At P < 0.01, the genes involved in 2855 interactions with score changes >1 were mainly enriched in 66 pathways and the genes in altered modules were enriched in 71 pathways. The activity genes (missed and added genes in the disrupted modules) were enriched in 41 common pathways. There were 36 mutual enriched pathways under the five different conditions. Moreover, the cell cycle pathway was disrupted in the first 10 pathways of each condition. This study provides a powerful biomarker discovery platform to better understand the progression of teratozoospermia by systematically tracking dysregulated modules. This method uncovered potential diagnostic and therapeutic targets of teratozoospermia. This information might lead to improved monitoring and treatment of teratozoospermia.

Hypoxia-induced apoptosis and mitochondrial dysfunction in chondrocytes arising from CREB phosphorylation reduction.

Chondrocytes, which are embedded within the growth-plate or the intervertebral disc, are sensitive to environmental stresses, such as inflammation and hypoxia. However, little is known about the molecular signaling pathways underlying hypoxia-induced mitochondrial dysfunction and apoptosis in chondrocytes. We first examined the apoptosis, caspase-3 activity, and apoptosis-associated markers in human chondrocyte cell line C28/I2 under normoxia or hypoxia. We then investigated mitochondrial dysfunction and the activation of cyclic adenosine monophosphate response element-binding protein (CREB) signaling in the same human chondrocyte cell line. Our results indicated that hypoxia induced apoptosis and reduced CREB phosphorylation in chondrocytes. Upregulated mitochondrial superoxide and reactive oxygen species levels, and reduced mitochondrial membrane potential and complex IV activity were observed in hypoxia-treated C28/I2 cells. In conclusion, the present study confirmed reduced CREB phosphorylation, apoptosis induction, and mitochondrial dysfunction in the hypoxia-treated chondrocyte cells. This implies the key role played by CREB signaling in hypoxia-induced mitochondrial dysfunction and apoptosis in chondrocytes.

[Safety and prognosis of allogenetic stem cell transplantation in younger patients with multiple myeloma].

OBJECTIVE: To evaluate the safety and prognosis of allogenetic stem cells transplantation in younger patients with multiple myeloma. METHODS: We retrospectively investigated 32 young patients (median age: 45 years) diagnosed with multiple myeloma and received allogenetic stem cells transplantation in Changzheng Hospital. The non-relapse mortality, disease-related mortality, incidences of acute and chronic graft-versus-host disease (GVHD), and survivals of the patients were analyzed. RESULTS: Transplantation was successful in 31 of all the patients. Response could be evaluated in 28 patients. The complete response (CR)rate before transplantation was 25.0% (8/32), which rose to 82.1% (23/28) after transplantation.And 53.1% (17/32) of the patients developed acute GVHD, with 43.8% (14/32) developing grade Ⅰ-Ⅱ; 40.6% (13/32) of the patients developed chronic GVHD, with no extensive one. The median follow-up time was 18.1 (0.4-145.8) months.Sixteen patients died, including 10 cases of non-relapse deaths and 6 cases of disease-related deaths. The non-relapse mortality within 100 days was 9.4% (3/32). The 1-, 2-and 3-year non-relapse mortality rates were 21.9% (7/32), 28.1% (9/32) and 31.3% (10/32), respectively. The common causes of non-relapse mortality were pulmonary infection (7/10), acute GVHD (1/10), acute renal failure (1/10), and acute myocardial infarction (1/10). The disease-related mortality was 18.8% (6/32). The 1-, 2-and 3-year progression-free survival rates were 61.6%, 42.2%, and 37.5%, respectively. The median duration of progression-free survival was 20.3 months. The 1-, 2-and 3-years overall survival were 68.4%, 52.4% and 42.8%, respectively. The median duration of overall survival was 28.3 months. Patients that survived for over 2 years were all alive at the end of the follow-up. CONCLUSIONS: Allogenetic stem cell transplantation may be a promising curative therapeutic choice for young multiple myeloma patients. Transplantation-related death is the primary factor of prognosis. Pulmonary infection with infectious shock is the most common cause of non-relapse mortality. Prevention of infection after transplantation is the key to improve survivals.

IL-37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2-like Phenotype.

Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN-γ and IL-12 but positively correlated with IL-10 and TGF-ß levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN-γ and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M. tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206(+) and low CD86(+) macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF-ß and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-γ, IL-12, IL-10 and TGF-ß levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.

A parallel dual matrix method for blind signal separation.

A parallel dual matrix method that considers all cases of numerical relations between a mixing matrix and a separating matrix is proposed in this letter. Different constrained terms are used to construct cost function for every subalgorithm. These constrained terms reflect numerical relation. Therefore, a number of undesired solutions are excluded, the search region is reduced, and the convergence efficiency of the algorithm is ultimately improved. Moreover, any parallel subalgorithm is proven to converge to a desired separating matrix only if its cost function converges to zero. Computer simulations indicate that the algorithm efficiently performs blind signal separation.