Baryon Electric Charge Correlation as a Magnetometer of QCD.

The correlation between net baryon number and electric charge, χ_{11}^{BQ}, can serve as a magnetometer of QCD. This is demonstrated by lattice QCD computations using the highly improved staggered quarks with physical pion mass of M_{π}=135 MeV on N_{τ}=8 and 12 lattices. We find that χ_{11}^{BQ} along the transition line starts to increase rapidly with magnetic field strength eB≳2M_{π}^{2} and by a factor 2 at eB≃8M_{π}^{2}. Furthermore, the ratio of electric charge chemical potential to baryon chemical potential, µ_{Q}/µ_{B}, shows significant dependence on the magnetic field strength and varies from the ratio of electric charge to baryon number in the colliding nuclei in heavy ion collisions. These results can provide baselines for effective theory and model studies, and both χ_{11}^{BQ} and µ_{Q}/µ_{B} could be useful probes for the detection of magnetic fields in relativistic heavy ion collision experiments as compared with corresponding results from the hadron resonance gas model.

[Analysis of factors associated with anxiety in patients with atrial fibrillation and their caregivers].

Objective: To explore the risk factors of anxiety in patients with atrial fibrillation and their caregivers. Methods: From September 2020 to March 2021, patients with atrial fibrillation and one primary family member as caregiver of each patient from Beijing Anzhen Hospital were enrolled. Basic data of patients and their caregivers were collected, and anxiety of patients and caregivers were evaluated by Generalized Anxiety Disorder-7 scale (GAD-7). A total of 374 patients with atrial fibrillation and their caregivers were included in this study. Multivariate logistic regression analysis was used to analyze the risk factors of anxiety of patients and their caregivers. Results: The mean age of the patients was (58.3±10.6) years, and 124 (33.2%) were female. The caregivers were (53.6±11.6) years old, and 247 (66%) were female. 69 (18.4%) patients and 38 (10.2%) caregivers had mild anxiety (GAD-7:5-9 scores), 13 (3.5%) patients and 9 (2.4%) caregivers had moderate or higher anxiety (GAD-7:10-21 scores). Multivariate analysis showed that the risk factors of anxiety in patients with atrial fibrillation included EHRA score≥3 (OR=1.73,95%CI:1.03-2.89,P=0.039) and female sex (OR=1.90,95%CI:1.06-3.40,P=0.032). EHRA score of patients≥3 (OR=2.11,95%CI:1.05-4.24, P=0.036) or anxiety of patients (OR=2.76,95%CI:1.36-5.60,P=0.005) were associated with higher anxiety of caregivers. Moreover, age of≥65 years old (OR=3.97,95%CI:1.68-9.38,P=0.002), female sex (OR=3.83,95%CI:1.64-8.93,P=0.002) and number of comorbidities of caregivers≥2 (OR=2.57,95%CI:1.03-6.41,P=0.043) were also associated with anxiety of caregivers. Conclusions: Patients with severe symptoms have a higher proportion of anxiety, and their caregivers are more likely to experience anxiety. Anxiety rate is higher in caregivers of patients with anxiety.

[Antimicrobial resistance and genomic characterization of Campylobacter isolates recovered from retailed poultry meat samples in 20 provinces of China in 2020].

Objective: To understand the antimicrobial resistance and genome characteristics of Campylobacter isolates recovered from retailed poultry meat samples in 20 provinces in China in 2020. Methods: In 2020, 265 Campylobacter strains including 244 Campylobacter jejuni and 21 Campylobacter coli collected from retailed poultry meat samples in China were tested for antimicrobial resistance to 9 antimicrobial compounds by using the agar dilution method. Forty-two selected isolates were sent for whole genome sequencing and 38 high-quality genomes were analyzed for their antimicrobial resistance genes, virulence genes, sequence types and genetic diversity. Results: The resistance rates of Campylobacter isolates from poultry meats to tetracycline, nalidixic acid and ciprofloxacin were the highest (84%-100%), with 53.2% of the isolates showing multidrug resistance in this study. The resistance rates of C. coli to erythromycin, azithromycin, telithromycin, gentamicin and clindamycin were significantly higher than those of C. jejuni (P<0.05). The resistance genes conferring resistance to ß-lactams (100%, 38/38), quinolones (94.7%, 36/38), tetracycline (81.6%, 31/38) and aminoglycosides (50%, 19/38) were the most frequently detected among 38 Campylobacter genomes. C. jejuni carried more virulence genes than C. coli. In total, 19 and 17 sequence types (ST) were obtained from 20 sequenced C. jejuni and 18 C. coli isolates, respectively, including 5 novel STs. The isolates showed a high genetic diversity based on their sequence types. Conclusion: The phenomenon of antimicrobial resistance in Campylobacter from poultry meat sources in China is relatively serious, and resistance and virulence genes are widely distributed in Campylobacter. There is genetic diversity in Campylobacter.

[Effects of arsenic and its main metabolites on A549 cell apoptosis and the expression of pro-apoptotic genes Bad and Bik].

Objective: To investigate the effect of arsenic and its main metabolites on the apoptosis of human lung adenocarcinoma cell line A549 and the expression of pro-apoptotic genes Bad and Bik. Methods: In October 2020, A549 cells were recovered and cultured, and the cell viability was detected by the cell counting reagent CCK-8 to determine the concentration and time of sodium arsenite exposure to A549. The study was divided into NaAsO(2) exposure groups and metobol: le expoure groups: the metabolite comparison groups were subdivided into the control group, the monomethylarsinic acid exposure group (60 µmol/L) , and the dimethylarsinic acid exposure group (60 µmol/L) ; sodium arsenite dose groups were subdivided into 4 groups: control group (0) , 20, 40, 60 µmol/L sodium arsenite NaAsO(2). Hoechst 33342/propidium iodide double staining (Ho/PI) was used to observe cell apoptosis and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of Bad and Bik mRNA in cells after exposure. Western blotting was used to detect the protein expressions of Bad, P-Bad-S112, Bik, cleaved Bik and downstream proteins poly ADP-ribose polymerase PARP1 and cytochrome C (Cyt-C) , using spectrophotometry to detect the activity changes of caspase 3, 6, 8, 9. Results: Compared with the control group, the proportion of apoptotic cells in the 20, 40, and 60 µmol/L NaAsO(2) dose groups increased significantly (P<0.01) , and the expression levels of Bad, Bik mRNA, the protein expression levels of Bad, P-Bad-S112, Bik, cleaved Bik, PARP1, Cyt-C were increased (all P<0.05) , and the activities of Caspase 3, 6, 8, and 9 were significantly increased with significantly differences (P<0.05) . Compared with the control group, the expression level of Bad mRNA in the DMA exposure group (1.439±0.173) was increased with a significant difference (P=0.024) , but there was no significant difference in the expression level of Bik mRNA (P=0.788) . There was no significant differences in the expression levels of Bad and Bik mRNA in the poison groups (P=0.085, 0.063) . Compared with the control group, the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to MMA were 0.696±0.023, 0.707±0.014, 0.907±0.031, 1.032±0.016, and there was no significant difference between the two groups (P=0.469, 0.669, 0.859, 0.771) ; the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to DMA were 0.698±0.030, 0.705±0.022, 0.908±0.015, 1.029±0.010, and there was no difference between the two groups (P=0.479, 0.636, 0.803, 0.984) . Conclusion: Sodium arsenite induces the overexpression of Bad and Bik proteins, initiates the negative feedback regulation of phosphorylated Bad and the degradation of Bik, activates the downstream proteins PARP1, Cyt-C and Caspase pathways, and mediates the apoptosis of A549 cells.

Correlated Dirac Eigenvalues and Axial Anomaly in Chiral Symmetric QCD.

We introduce novel relations between the derivatives [∂^{n}ρ(λ,m_{l})/∂m_{l}^{n}] of the Dirac eigenvalue spectrum [ρ(λ,m_{l})] with respect to the light sea quark mass (m_{l}) and the (n+1)-point correlations among the eigenvalues (λ) of the massless Dirac operator. Using these relations we present lattice QCD results for ∂^{n}ρ(λ,m_{l})/∂m_{l}^{n} (n=1, 2, 3) for m_{l} corresponding to pion masses m_{π}=160-55 MeV and at a temperature of about 1.6 times the chiral phase transition temperature. Calculations were carried out using (2+1) flavors of highly improved staggered quarks with the physical value of strange quark mass, three lattice spacings a=0.12, 0.08, 0.06 fm, and lattices having aspect ratios 4-9. We find that ρ(λ→0,m_{l}) develops a peaked structure. This peaked structure arises due to non-Poisson correlations within the infrared part of the Dirac eigenvalue spectrum, becomes sharper as a→0, and its amplitude is proportional to m_{l}^{2}. We demonstrate that this ρ(λ→0,m_{l}) is responsible for the manifestations of axial anomaly in two-point correlation functions of light scalar and pseudoscalar mesons. After continuum and chiral extrapolations we find that axial anomaly remains manifested in two-point correlation functions of scalar and pseudoscalar mesons in the chiral limit.

Chiral Phase Transition Temperature in (2+1)-Flavor QCD.

We present a lattice-QCD-based determination of the chiral phase transition temperature in QCD with two degenerate, massless quarks and a physical strange quark mass using lattice QCD calculations with the highly improved staggered quarks action. We propose and calculate two novel estimators for the chiral transition temperature for several values of the light quark masses, corresponding to Goldstone pion masses in the range of 58 MeV≲m_{π}≲163 MeV. The chiral phase transition temperature is determined by extrapolating to vanishing pion mass using universal scaling analysis. Finite-volume effects are controlled by extrapolating to the thermodynamic limit using spatial lattice extents in the range of 2.8-4.5 times the inverse of the pion mass. Continuum extrapolations are carried out by using three different values of the lattice cutoff, corresponding to lattices with temporal extents N_{τ}=6, 8, and 12. After thermodynamic, continuum, and chiral extrapolations, we find the chiral phase transition temperature T_{c}^{0}=132_{-6}^{+3} MeV.

Chitosan films promote formation of olfactory neurospheres and differentiation of olfactory receptor neurons.

BACKGROUND: Olfactory dysfunction significantly impairs the life quality of patients. Therefore, a model needs to be developed for anosmia. Chitosan is a biodegradable natural polysaccharide that has been widely studied for regenerative purposes in the nervous system. However, whether chitosan promotes differentiation of olfactory receptor neurons or regulates formation of neurospheres in the olfactory system remains unexplored. METHODOLOGY: Olfactory neuroepithelial cells were isolated from embryonic wistar rats on day 17, and cultured on controls and chitosan films for 12 days. The effects of treatment were assessed using immunocytochemistry, quantitative polymerase chain reaction and western blots following culturing. The substrate of poly-L-lysine-co-laminin was adopted as a control. RESULTS: In contrast to the flat layer on controls, olfactory neuroepithelial cells form olfactory neurospheres on chitosan films with steadily increasing diameter. The olfactory neurospheres contain basal cells, as well as immature and mature olfactory receptor neurons. The expression level of olfactory marker protein is higher on chitosan films than those on controls in gene and protein levels, and the olfactory transduction elements also express a similar trend. Mature olfactory receptor neurons are found predominantly at the periphery of the olfactory neurospheres. CONCLUSIONS: Chitosan films not only facilitate formation of olfactory neurospheres, but also promote differentiation of olfactory receptor neurons. Chitosan is a potential biomaterial to establish an in vitro culture model to treat olfactory dysfunction in future.

[Impact of adherence to statins on cardiovascular adverse events in patients with coronary artery disease: a meta-analysis].

OBJECTIVE: To evaluate the impact of different adherence mode to statins on cardiovascular adverse events in patients with coronary artery disease (CAD). METHODS: Electronic searches, including PubMed, Scopus, Ovid MEDLINE, Ovid EMBASE, Ovid EBM Reviews CENTRAL, CINAHL, The Cochrane Library, Ovid PsycInfo, Wanfang data, CNKI and Science & Technology Magazine Online, were performed and all related literatures of all languages were retrieval till to March 1, 2015. The full text was obtained through manual retrieval, inter-library loan and document delivery service, or by contacting the author directly. According to inclusion and exclusion criteria, data was extracted dependently by two raters. The high adherence to statin was use defined by the ratio of statins cover time and the total time (proportion of days covered, PDC≥80%). Data were analyzed quantitatively using RevMan 5.1. Then implement subgroup analysis was made according to different statin adherence and classification of clinical outcomes. The impact of adherence to statin on cardiovascular events (all-cause mortality, non-fatal myocardial infarction, hospitalization due to unstable angina pectoris, heart insufficiency attack) in CAD patients was evaluated. RESULTS: Present analysis enrolled eight relevant retrospective and observational studies. Because there were only few literatures describing the impact of statin adherence on clinical outcomes, we also included literatures with low adherence group (4 studies in PDC<80%, 2 studies in PDC<40% and 2 studies in PDC<20%). High adherence group includes 189 556 cases; low adherence group includes 11 384 cases. Compare with low adherence group, cardiovascular events rate reduced by 32% in high adherence group (OR=0.68, 95%CI 0.58-0.80, P<0.001). Subgroup analysis with 4 literatures with PDC≥80% or<80% showed that the cardiovascular events prominently decreased in high adherence group compared to low adherence group (OR=0.63, 95%CI 0.53-0.76, P<0.001). According to 5 literatures with all-cause mortality parameter, we also found a borderline decrease in all-cause mortality in high adherence group compared to low adherence group ( OR=0.67, 95%CI 0.44-1.02, P=0.06), while non-fatal cardiovascular events were significantly reduced by 18% in high adherence group (OR=0.82, 95%CI 0.77-0.87, P<0.001). CONCLUSIONS: High adherence to statins is related to significantly lower cardiovascular events in CAD patients.

Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression.

The aim of this study was to investigate the influence of chronic dexamethasone (Dex) administration on rat diaphragm sensitivity to non-depolarizing muscle relaxants (NDMRs) and muscular nicotinic acetylcholine receptor (nAChR) expression, which may help direct future administration of NDMRs. Adult male Sprague-Dawley rats were randomized to receive a daily intraperitoneal injection of Dex (600 µg/kg body mass) or an equivalent volume of saline (N = 20 in each group) for 14 days. We evaluated isometric twitch tensions of nerve-hemidiaphragm preparations elicited by indirect supramaximal stimulation at 0.1 Hz. Real-time quantitative PCR was performed to determine the mRNA expression of two nAChR subunits (ε-subunit and γ-subunit) in the diaphragm. Dex administration markedly (P < 0.01) increased the 50% twitch depression (IC50) of the three NDMRs. The IC50 ratio, which standardized the magnitudes of the resistance, was the largest for atracurium, with the second largest for vecuronium and the smallest for rocuronium (P < 0.01). The ε- and γ-subunit mRNAs were both upregulated with an increased γ/ε ratio in rats exposed to Dex. The results indicated that chronic Dex administration induces hyposensitivity to NDMRs, the degree of which depends on the kind of neuromuscular blocker, and is associated with increased nAChR expression.

[Incidence and risk factors of metabolic syndrome in rural community population on islands in Zhejiang province].

Objective: To estimate the incidence of metabolic syndrome and explore possible risk factors for metabolic syndrome in adults of rural communities in Yuhuan county, Zhejiang province, China. Methods: During June-December, 2018, a follow-up survey was conducted in participants without metabolic syndrome at baseline survey in 2012 to obtain the information collected in questionnaire survey, anthropometric data and laboratory data. The incidence of metabolic syndrome in the participants was estimated, and Logistic regression model was used to explore the risk factors, adjusted risk ratio (aRR) and 95%CI. Results: Among 3 162 participants, 522 new metabolic syndrome cases were identified. The 6-year cumulative incidence rate of metabolic syndrome was 16.5%, and the cumulative incidence rate was higher in women (20.6%) than that in men (12.3%, P<0.001). Those incidence rates were higher in those in jobless, smoking or drinking groups. Being women (aRR=1.96, 95%CI: 1.50-2.58) and family history of hypertension (aRR=1.31, 95%CI: 1.04-1.63) were independent risk factors for metabolic syndrome. Conclusion: The follow up indicated that the incidence of metabolic syndrome was relatively high in rural adults on islands in Zhejiang, and women or those with family history of hypertension were more likely to have metabolic syndrome.

[Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome].

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.

Nano-TiO2 particles inhibit the biological behavior and mineralization of bone marrow mesenchymal stem cells transfected with CXCR4.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSC) are widely used as experimental cells with potential differentiation function. Nanomaterials are currently a research hotspot. We assessed nano-TiO2 particles' effect on the biological behavior and mineralization of CXCR4 transfected BMSCs. PATIENTS AND METHODS: After transfection of BMSC with CXCR4, cells were divided into blank group (no transfection), control group (transfection with CXCR4) and observe group (transfection with CXCR4 containing nanoparticles). Then, cell proliferation and ALP staining were measured along with analysis of Runx2 and BGP level by Western blot or RT-PCR and mineralization detection. RESULTS: With increased culture time, the observed fractionation on day 14 showed significantly reduced activity; 3 mn nano-TiO2 particles significantly inhibited cell proliferation and bone formation after CXCR4 transfection with an inhibitory effect on the osteogenic ability of CXCR4-transfected BMCS cells in a time-dependent manner. The longer the culture time, the more significantly inhibitory effect; 3 mn nano-TiO2 particles can inhibit the mineralization of BMSCs after transfection of CXCR4 to a certain extent. CONCLUSIONS: TiO2 nanoparticles have an inhibitory effect on the biological behavior and mineralization of BMSC cells transfected with CXCR4. The longer the culture time, the greater the inhibitory effect on osteogenic differentiation of BMSC cells transfected with CXCR4.

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

TGFß1I1 suppressed cell migration and invasion in colorectal cancer by inhibiting the TGF-ß pathway and EMT progress.

OBJECTIVE: Colorectal cancer (CRC) is the fourth leading cause of death worldwide and there is a need for more specific therapeutic targets and biomarkers for the disease. Transforming growth factor ß1-induced transcript 1 (TGFΒ1I1) was reported to be downregulated in CRC tissues; however, the precise roles of TGFΒ1I1 in CRC remain unclear. PATIENTS AND METHODS: The expression of TGFΒ1I1 in CRC cell lines and tissues was assessed by quantitative Polymerase Chain Reaction (qPCR). TGFΒ1I1 was overexpressed in SW620 and RKO cells. Cell viability was analyzed by a CCK-8 assay. The proportion of apoptotic cells was analyzed by flow cytometry. The EdU cell proliferation assay of SW620 and RKO cells after transfection was performed via flow cytometry. The migration potency of SW620 and RKO cells was analyzed using a cell migration assay. A wound healing assay was performed to assess the migration potency of SW620 and RKO cells. The invasion potency of SW620 and RKO cells after TGFΒ1I1 overexpression was analyzed. The protein levels of VEGF, TGF-ß, MMP9, p-Smad2/3, N-cadherin, and E-cadherin were analyzed by Western blot. RESULTS: Decreased expression of TGFΒ1I1 was found in CRC tissues and cell lines. Overexpression of TGFΒ1I1 inhibited the proliferation and induced the apoptosis of CRC cells. The overexpression of TGFΒ1I1 inhibited the migration and invasion of CRC cells. We also found that the overexpression of TGFΒ1I1 in CRC cells inhibited the TGF-ß pathway and epithelial-mesenchymal transition (EMT) progress. CONCLUSIONS: TGFΒ1I1 suppressed cell migration and invasion in CRC by inhibiting the TGF-ß pathway and EMT progress.

Facilitation of NMDAR-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3.

To evaluate the role in synaptic plasticity of ryanodine receptor type 3 (RyR3), which is normally enriched in hippocampal area CA1, we generated RyR3-deficient mice. Mutant mice exhibited facilitated CA1 long-term potentiation (LTP) induced by short tetanus (100 Hz, 100 ms) stimulation. Unlike LTP in wild-type mice, this LTP was not blocked bythe NMDA receptor antagonist D-AP5 but was partially dependent on L-type voltage-dependent Ca2+ channels (VDCCs) and metabotropic glutamate receptors (mGluRs). Long-term depression (LTD) was not induced in RyR3-deficient mice. RyR3-deficient mice also exhibited improved spatial learning on a Morris water maze task. These results suggest that in wild-type mice, in contrast to the excitatory role of Ca2+ influx, RyR3-mediated intracellular Ca2+ ([Ca2+]i) release from endoplasmic reticulum (ER) may inhibit hippocampal LTP and spatial learning.

Copper(i) complexes based on ligand systems with two different binding sites: synthesis, structures and reaction with O2.

The synthesis of the ligand systems L1 and L2 with two different N3-binding sites linked through a dibenzofuran spacer and their coordination properties towards a variety of CuI precursors are reported. The reaction of L1 with copper halides leads to the formation of a bimetallic species [(L1)(CuICl)2] (1), and metallodimers [((L1)(CuIX)2)2(µ-(Cu)(µ-X)2)] (2: X = Br, 3: X = I) in which two dicopper complexes are bridged by a (µ-(Cu)(µ-X)2)-moiety whereas L2 reacts with copper chloride to afford {[Cu(L2)Cl2]}n (8). Furthermore, starting from L1 in combination with copper(i) salts of weakly coordinating anions the dicopper complexes [(L1)(CuI(NCCH3))2](BF4)2 (4), [(L1)(CuI(NCCH3))(Cu(Y))](Y) (5: Y = OTf, 6: Y = ClO4) and [(L1)(Cu(dppe))](PF6)2 (7) were isolated, and employing L2, the complexes [(L2)(CuI(NCCH3))2](Z)2 (9: Z = PF6, 10: Z = OTf) and [(L2)(Cu(dppe))](PF6)2 (11) were obtained. Complexes 4-6 as well as 9 and 10 react rapidly with O2 to form metastable O2 adducts in acetone at -90 °C, where O2 is bound between the two copper centers within one dicopper molecule, as evidenced by UV/Vis spectroscopy, kinetic investigations, Raman spectroscopy and studies with ligands containing the isolated donor sites. The reactivity of the O2 adducts towards selected substrates was also investigated, showing their ability to act as electrophiles as well as nucleophiles.