Aqua­(2,2′-bipyrimidine-κ2 N,N′)(succin­ato-κ2 O 1,O 4)copper(II) dihydrate

In the crystal structure of the title compound, [Cu(C4H4O4)(C8H6N4)(H2O)]·2H2O, the CuII atom is chelated by a 2,2′-bipyrimidine (bpm) ligand and a succinate anion in the basal plane; a water mol­ecule in the apical position completes the slightly distorted square-pyramidal coordination geometry. Another carboxyl­ate O atom from an adjacent complex is located in the opposite apical direction, with a Cu⋯O distance of 2.706 (3) Å, and is not considered as a bridging atom. Extensive O—H⋯O and O—H⋯N hydrogen bonding is present in the crystal structure

Aqua­bis(2-amino-1,3-thia­zole-4-acetato-κ2 O,N 3)nickel(II)

In the crystal structure of the title compound, [Ni(C5H5N2O2S)2(H2O)], the NiII cation is located on a twofold rotation axis and chelated by two 2-amino-1,3-thia­zole-4-acetate (ata) anions in the basal coordination plane; a water mol­ecule located on the same twofold rotation axis completes the distorted square-pyramidal coordination geometry. Inter­molecular O—H⋯O and N—H⋯O hydrogen bonding, as well as π–π stacking between parallel thia­zole rings [centroid–centroid distance 3.531 (8) Å], helps to stabilize the crystal structure

Major histocompatibility complex genomic investigation of endangered Chinese alligator provides insights into the evolution of tetrapod major histocompatibility complex and survival of critically bottlenecked species

BackgroundThe major histocompatibility complex (MHC) gene family, a vital immune gene family in vertebrates, helps animals defend against pathogens. The polymorphism of MHC genes is important for a species and is considered to be caused by the numerous alleles of MHC antigen-presenting genes. However, the mechanism of this process is unclear due to the lack of data on the MHC structure. The evolutionary trajectories of the tetrapod MHC are also unclear because of insufficient studies on the reptile MHC architecture. Here, we studied the Chinese alligator (Alligator sinensis), which experienced a population bottleneck, but the population increased rapidly in the past 30 years and is proposed to have a unique MHC system to face pathogenic challenges.ResultsWe successfully constructed a 2 Mb MHC region using bacterial artificial chromosome (BAC) library and genome data of the Chinese alligator and checked the antigen-presenting genes using transcriptome data and the rapid amplification of cDNA ends (RACE) technique. The MHC architecture reported here uncovers adjacent Class I and Class II subregions and a unique CD1 subregion. This newly added information suggested that the Class I-II structure pattern was more ancient in tetrapods and helped reconstruct the evolution of the MHC region architecture. We also found multiple groups of MHC class I (MHC-I) (12 duplicated loci, belonging to three groups, two of which were novel) and MHC class II (MHC-II) (11 duplicated loci, belonging to two groups) inside the 2 Mb MHC region, and there were three more duplicated MHC-I loci outside it. These highly duplicated antigen-presenting loci had differences in expression, amino acid length of antigen-presenting exons, and splice signal of exon and intron, which together promoted the polymorphism of duplicated genes. Although the MHC antigen-presenting genes were identified as monomorphic or oligomorphic in our previous population study, the loci with high copy numbers and many differences can make up for this loss, presenting another mechanism for polymorphism in antigen presentation. These MHC-I and MHC-IIB loci with low polymorphism for each locus, but high numbers in all, may also contribute to MHC antigen-presenting binding variability in a population.ConclusionTo summarize, the fine MHC region architecture of reptiles presented in this study completes the evolutionary trajectories of the MHC structure in tetrapods, and these distinctive MHC gene groups in the Chinese alligator may have helped this species to expand rapidly in the past recent years

CXCL9 Is a Potential Biomarker of Immune Infiltration Associated With Favorable Prognosis in ER-Negative Breast Cancer

The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer

Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma is difficult to diagnose early, and most patients are already in the late stages of the disease when they are admitted to hospital. The total 5-year survival rate is less than 5%. Recent studies have showed that brucine has a good anti-tumor effect, but high toxicity, poor water solubility, short half-life, narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study evaluated the effects of brucine immuno-nanoparticles (BIN) on hepatocellular carcinoma. MATERIALS AND METHODS: Anionic polymerization, chemical modification technology, and phacoemulsification technology were used to prepare a carboxylated polyethylene glycol-polylactic acid copolymer carrier material. Chemical coupling technology was utilized to develop antihuman AFP McAb-polyethylene glycol-polylactic acid copolymer BIN. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these immune-nanoparticles were studied in vitro. The targeting, and growth, invasion, and metastasis inhibitory effects of this treatment on liver cancer SMMC-7721 cells were tested. RESULTS: BIN were of uniform size with an average particle size of 249 ± 77 nm and zeta potential of -18.7 ± 4.19 mV. The encapsulation efficiency was 76.0% ± 2.3% and the drug load was 5.6% ± 0.2%. Complete uptake and even distribution around the liver cancer cell membrane were observed. CONCLUSION: BIN had even size distribution, was stable, and had a slow-releasing effect. BIN targeted the cell membrane of the liver cancer cell SMMC-7721 and significantly inhibited the growth, adhesion, invasion, and metastasis of SMMC-7721 cells. As a novel drug carrier system, BIN are a potentially promising targeting treatment for liver cancer

A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure

Elevated circulating GPHB5 levels in women with insulin resistance and polycystic ovary syndrome: A cross-sectional study and multiple intervention studies

ObjectiveGPHB5 has been found to be associated with glucose and lipid metabolism in animal studies. However, the association of GPHB5 with IR and metabolic disorders remains unknown, and there is a lack of research in humans. Our aim in this study was to investigate the relationship between circulating GPHB5 and metabolic disorders in humans.MethodsBioinformatics analysis was performed to understand the relationship between GPHB5 and metabolic disorders. GPHB5 mRNA expression in mice and rats was determined using RT-qPCR. Circulating GPHB5 concentrations were measured with an ELISA kit. EHC and OGTT were performed in humans.ResultsBioinformatics analysis shows that GPHB5 is associated with metabolic disorders and PCOS. GPHB5 mRNA expression levels in the metabolic-related tissues of HFD-fed mice, db/db and ob/ob mice, and PCOS rats were significantly higher than those of WT mice or rats. In human studies, we find that circulating GPHB5 levels were significantly higher in women with IR and PCOS. GPHB5 levels were positively correlated with age, BMI, WHR, BP, FBG, 2 h-BG, FIns, 2 h-Ins, TC, LDL-C, HbA1c, and FFA, but negatively correlated with adiponectin. Furthermore, GPHB5 was positively correlated with DHEAS and FAI, while negatively correlated with SHBG, FSH, SHBG and FSH. The increased GPHB5 concentration was related to IR and PCOS. After the treatment of metformin, GLP-1RA (Lira), and TZDs, circulating GPHB5 levels were decreased.ConclusionsOur results reveal that circulating GPHB5 could be a biomarker and potential therapeutic target for IR and PCOS in women

Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case–Control Study

AbstractBackgroundBoth type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3β (GSK-3β) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients.MethodsThe cognitive ability was evaluated using Minimum Mental State Examination (MMSE) and Clinical Dementia Rating (CDR), and the mild cognitive impairment (MCI) was diagnosed by Petersen's criteria. GSK-3β activity in platelet, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting, the amplification refractory mutation system (ARMS) PCR and the Connecticut Chemosensory Clinical Research Center (CCCRC) test, respectively. The odds ratio (OR) and 95% confidence intervals (95% CI) of the biomarkers for MCI diagnosis were calculated by logistic regression. The diagnostic capability of the biomarkers was evaluated by receiver operating characteristics (ROC) analyses.FindingsWe recruited 694 T2DM patients from Jan. 2012 to May. 2015 in 5 hospitals (Wuhan), and 646 of them met the inclusion criteria and were included in this study. 345 patients in 2 hospitals were assigned to the training set, and 301 patients in another 3 hospitals assigned to the validation set. Patients in each set were randomly divided into two groups: T2DM without MCI (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). There were no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ε2, ApoE ε3, tGSK3β and pS9GSK3β between the two groups. Compared with the T2DM-nMCI group, T2DM-MCI group showed lower MMSE score with older age, ApoE ε4 allele, higher olfactory score and higher rGSK-3β (ratio of total GSK-3β to Ser9-phosphorylated GSK-3β) in the training set and the validation set. The OR values of age, ApoE ε4 gene, olfactory score and rGSK-3β were 1.09, 2.09, 1.51, 10.08 in the training set, and 1.06, 2.67, 1.47, 7.19 in the validation set, respectively. The diagnostic accuracy of age, ApoE ε4 gene, olfactory score and rGSK-3β were 0.76, 0.72, 0.66, 0.79 in the training set, and 0.70, 0.68, 0.73, 0.79 in the validation set, respectively. These four combined biomarkers had the area under the curve (AUC) of 82% and 86%, diagnostic accuracy of 83% and 81% in the training set and the validation set, respectively.InterpretationAging, activation of peripheral circulating GSK-3β, expression of ApoE ε4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy

ATOMS : ALMA Three-millimeter Observations of Massive Star-forming regions - I. Survey description and a first look at G9.62+0.19

The ATOMS, standing for ALMA Three-millimeter Observations of Massive Star-forming regions, survey has observed 146 active star-forming regions with ALMA band 3, aiming to systematically investigate the spatial distribution of various dense gas tracers in a large sample of Galactic massive clumps, to study the roles of stellar feedback in star formation, and to characterize filamentary structures inside massive clumps. In this work, the observations, data analysis, and example science of the ATOMS survey are presented, using a case study for the G9.62+0.19 complex. Toward this source, some transitions, commonly assumed to trace dense gas, including CS J = 2-1, HCO+ J = 1-0, and HCN J = 1-0, are found to show extended gas emission in low-density regions within the clump; less than 25 per cent of their emission is from dense cores. SO, CH3OH, (HCN)-C-13, and HC3N show similar morphologies in their spatial distributions and reveal well the dense cores. Widespread narrow SiO emission is present (over similar to 1 pc), which may be caused by slow shocks from large-scale colliding flows or HII regions. Stellar feedback from an expanding HII region has greatly reshaped the natal clump, significantly changed the spatial distribution of gas, and may also account for the sequential high-mass star formation in the G9.62+0.19 complex. The ATOMS survey data can be jointly analysed with other survey data, e.g. MALT90, Orion B, EMPIRE, ALMA IMF, and ALMAGAL, to deepen our understandings of 'dense gas' star formation scaling relations and massive protocluster formation.Peer reviewe