Radical-Induced Changes in Transition Metal Interfacial Magnetic Properties: A Blatter Derivative on Polycrystalline Cobalt.

In this work, we study the interface obtained by depositing a monolayer of a Blatter radical derivative on polycrystalline cobalt. By examining the occupied and unoccupied states at the interface, using soft X-ray techniques, combined with electronic structure calculations, we could simultaneously determine the electronic structure of both the molecular and ferromagnetic sides of the interface, thus obtaining a full understanding of the interfacial magnetic properties. We found that the molecule is strongly hybridized with the surface. Changes in the core level spectra reflect the modification of the molecule and the cobalt electronic structures inducing a decrease in the magnetic moment of the cobalt atoms bonded to the molecules which, in turn, lose their radical character. Our method allowed us to screen, beforehand, organic/ferromagnetic interfaces in view of their potential applications in spintronics.

Chiral π-Conjugated Double Helical Aminyl Diradical with the Triplet Ground State.

We report a neutral high-spin diradical of chiral C2-symmetric bis[5]diazahelicene with ΔEST ≈ 0.4 kcal mol-1, as determined by EPR spectroscopy/SQUID magnetometry. The diradical is the most persistent among all high-spin aminyl radicals reported to date by a factor of 20, with a half-life of up to 6 days in 2-MeTHF at room temperature. Its triplet ground state and excellent persistence may be associated with the unique spin density distribution within the dihydrophenazine moiety, which characterizes two effective 3-electron C-N bonds analogous to the N-O bond of a nitroxide radical. The enantiomerically enriched (ee ≥ 94%) (MM)- and (PP)-enantiomers of the precursors to the diradicals are obtained by either preparative chiral supercritical fluid chromatography or resolution via functionalization with the chiral auxiliary of the C2-symmetric racemic tetraamine. The barrier for the racemization of the solid tetraamine is ΔG‡ = 43 ± 0.01 kcal mol-1 in the 483-523 K range. The experimentally estimated lower limit of the barrier for the racemization of a diradical, ΔG‡ ≥ 26 kcal mol-1 in 2-MeTHF at 293 K, is comparable to the DFT-determined barrier of ΔG‡ = 31 kcal mol-1 in the gas phase at 298 K. While the enantiomerically pure tetraamine displays strong chiroptical properties, with anisotropy factor |g| = |Δε|/ε = 0.036 at 376 nm, |g| ≈ 0.005 at 548 nm of the high-spin diradical is comparable to that recently reported triplet ground-state diradical dication. Notably, the radical anion intermediate in the generation of diradical exhibits a large SOMO-HOMO inversion, SHI = 35 kcal mol-1.

From Stable Radicals to Thermally Robust High-Spin Diradicals and Triradicals.

Stable radicals and thermally robust high-spin di- and triradicals have emerged as important organic materials due to their promising applications in diverse fields. New fundamental properties, such as SOMO/HOMO inversion of orbital energies, are explored for the design of new stable radicals, including highly luminescent ones with good photostability. A relation with the singlet-triplet energy gap in the corresponding diradicals is proposed. Thermally robust high-spin di- and triradicals, with energy gaps that are comparable to or greater than a thermal energy at room temperature, are more challenging to synthesize but more rewarding. We summarize a number of high-spin di- and triradicals, based on nitronyl nitroxides that provide a relation between the experimental pairwise exchange coupling constant J/k in the high-spin species vs experimental hyperfine coupling constants in the corresponding monoradicals. This relation allows us to identify outliers, which may correspond to radicals where J/k is not measured with sufficient accuracy. Double helical high-spin diradicals, in which spin density is delocalized over the chiral π-system, have been barely explored, with the sole example of such high-spin diradical possessing alternant π-system with Kekulé resonance form. Finally, we discuss a high-spin diradical with electrical conductivity and derivatives of triangulene diradicals.

Long-Term Degradation Mechanisms in Application-Implemented Radical Thin Films.

Blatter radical derivatives are very attractive due to their potential applications, ranging from batteries to quantum technologies. In this work, we focus on the latest insights regarding the fundamental mechanisms of radical thin film (long-term) degradation, by comparing two Blatter radical derivatives. We find that the interaction with different contaminants (such as atomic H, Ar, N, and O and molecular H2, N2, O2, H2O, and NH2) affects the chemical and magnetic properties of the thin films upon air exposure. Also, the radical-specific site, where the contaminant interaction takes place, plays a role. Atomic H and NH2 are detrimental to the magnetic properties of Blatter radicals, while the presence of molecular water influences more specifically the magnetic properties of the diradical thin films, and it is believed to be the major cause of the shorter diradical thin film lifetime in air.

Phosphodiesterase type 10A inhibitor attenuates lung fibrosis by targeting myofibroblast activation.

Pulmonary fibrosis (PF) is a fatal and irreversible respiratory disease accompanied by excessive fibroblast activation. Previous studies have suggested that cAMP signaling pathway and cGMP-PKG signaling pathway are continuously down-regulated in lung fibrosis, whereas PDE10A has a specifically expression in fibroblasts/myofibroblasts in lung fibrosis. In this study, we demonstrated that overexpression of PDE10A induces myofibroblast differentiation, and papaverine, as a PDE10A inhibitor used for vasodilation, inhibits myofibroblast differentiation in human fibroblasts, Meanwhile, papaverine alleviated bleomycin-induced pulmonary fibrosis and amiodarone-induced oxidative stress, papaverine downregulated VASP/ß-catenin pathway to reduce the myofibroblast differentiation. Our results first demonstrated that papaverine inhibits TGFß1-induced myofibroblast differentiation and lung fibrosis by VASP/ß-catenin pathway.

Salvianolic acid A improve mitochondrial respiration and cardiac function via inhibiting apoptosis pathway through CRYAB in diabetic cardiomyopathy.

Salvianolic acid A (SAA) is a traditional Chinese medicine that has a good therapeutic effect on cardiovascular disease. However, the underlying mechanisms by which SAA improves mitochondrial respiration and cardiac function in diabetic cardiomyopathy (DCM) remain unknown. This study aims to elucidate whether SAA had any cardiovascular protection on the pathophysiology of DCM and explored the potential mechanisms. Diabetes was induced in rats by 30 mg/kg of streptozotocin (STZ) treatment. After a week of stability, 5 mg/kg isoprenaline (ISO) was injected into the rats subcutaneously. 3 mg/kg SAA was orally administered for six weeks and 150 mg/kg Metformin was selected as a positive group. At the end of this period, cardiac function was assessed by ultrasound, electrocardiogram, and relevant cardiac injury biomarkers testing. Treatment with SAA improved cardiac function, glucose, and lipid levels, mitochondrial respiration, and suppressed myocardial inflammation and apoptosis. Furthermore, SAA treatment inhibits the apoptosis pathway through CRYAB in diabetic cardiomyopathy rats. As a result, this study not only provides new insights into the mechanism of SAA against DCM but also provides new therapeutic ideas for the discovery of anti-DCM compounds in the clinic.

Dan-Shen-Yin Granules Prevent Hypoxia-Induced Pulmonary Hypertension via STAT3/HIF-1α/VEGF and FAK/AKT Signaling Pathways.

Traditional Chinese medicine (TCM) plays an important role in the treatment of complex diseases, especially cardiovascular diseases. However, it is hard to identify their modes of action on account of their multiple components. The present study aims to evaluate the effects of Dan-Shen-Yin (DSY) granules on hypoxia-induced pulmonary hypertension (HPH), and then to decipher the molecular mechanisms of DSY. Systematic pharmacology was employed to identify the targets of DSY on HPH. Furthermore, core genes were identified by constructing a protein-protein interaction (PPI) network and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analysis. Related genes and pathways were verified using a hypoxia-induced mouse model and hypoxia-treated pulmonary artery cells. Based on network pharmacology, 147 potential targets of DSY on HPH were found, constructing a PPI network, and 13 hub genes were predicted. The results showed that the effect of DSY may be closely associated with AKT serine/threonine kinase 1 (AKT1), signal transducer and activator of transcription 3 (STAT3), and HIF-1 signaling pathways, as well as biological processes such as cell proliferation. Consistent with network pharmacology analysis, experiments in vivo demonstrated that DSY could prevent the development of HPH in a hypoxia-induced mouse model and alleviate pulmonary vascular remodeling. In addition, inhibition of STAT3/HIF-1α/VEGF and FAK/AKT signaling pathways might serve as mechanisms. Taken together, the network pharmacology analysis suggested that DSY exhibited therapeutic effects through multiple targets in the treatment of HPH. The inferences were initially confirmed by subsequent in vivo and in vitro studies. This study provides a novel perspective for studying the relevance of TCM and disease processes and illustrates the advantage of this approach and the multitargeted anti-HPH effect of DSY.

Puerarin-V prevents the progression of hypoxia- and monocrotaline-induced pulmonary hypertension in rodent models.

Pulmonary hypertension (PH) is a cardiopulmonary disease characterized by a progressive increase in pulmonary vascular resistance. One of the initial pathogenic factors of PH is pulmonary arterial remodeling under various stimuli. Current marketed drugs against PH mainly relieve symptoms without significant improvement in overall prognosis. Discovering and developing new therapeutic drugs that interfere with vascular remodeling is in urgent need. Puerarin is an isoflavone compound extracted from the root of Kudzu vine, which is widely used in the treatment of cardiovascular diseases. In the present study, we evaluated the efficacy of puerarin in the treatment of experimental PH. PH was induced in rats by a single injection of MCT (50 mg/kg, sc), and in mice by exposure to hypoxia (10% O2) for 14 days. After MCT injection the rats were administered puerarin (10, 30, 100 mg · kg-1 · d-1, i.g.) for 28 days, whereas hypoxia-treated mice were pre-administered puerarin (60 mg · kg-1 · d-1, i.g.) for 7 days. We showed that puerarin administration exerted significant protective effects in both experimental PH rodent models, evidenced by significantly reduced right ventricular systolic pressure (RVSP) and lung injury, improved pulmonary artery blood flow as well as pulmonary vasodilation and contraction function, inhibited inflammatory responses in lung tissues, improved resistance to apoptosis and abnormal proliferation in lung tissues, attenuated right ventricular injury and remodeling, and maintained normal function of the right ventricle. We revealed that MCT and hypoxia treatment significantly downregulated BMPR2/Smad signaling in the lung tissues and PPARγ/PI3K/Akt signaling in the lung tissues and right ventricles, which were restored by puerarin administration. In addition, we showed that a novel crystal type V (Puer-V) exerted better therapeutic effects than the crude form of puerarin (Puer). Furthermore, Puer-V was more efficient than bosentan (a positive control drug) in alleviating the abnormal structural changes and dysfunction of lung tissues and right ventricles. In conclusion, this study provides experimental evidence for developing Puer-V as a novel therapeutic drug to treat PH.

Puerarin reduces oxidative damage to vascular endothelial cells by improving mitochondrial respiratory function / 药学学报

This study investigated the effect of puerarin on human umbilical vein endothelial cells (HUVEC) injured with hydrogen peroxide (H2O2). HUVEC were divided into three groups: a control group, a model group (H2O2 400 μmol·L-1) and a puerarin-treated group (3, 10, 30 and 100 μmol·L-1). HUVEC were cultured with varied concentration of puerarin for 2 h and treated with H2O2 for another 24 h. Cell proliferation was detected by a CCK-8 assay. The mitochondrial membrane potential was measured by a JC-1 fluorescent probe. A transwell chamber assay was adopted to observe cell migration ability. Mitochondrial respiratory function was measured in a two-chamber titration injection respirometer (Oxygraph-2k). The expression of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) was detected by quantitative real-time PCR. The expression of pyroptosis-mediated proteins, including cleaved-cysteinyl aspartate-specific proteinase-1 (caspase-1), N-gasdermin D (N-GSDMD), NOD-like receptor protein 3 (NLRP3) and purinergic ligand-gated ion channel 7 receptor (P2X7R) was detected by Western blot. The results show that 400 μmol·L-1 H2O2 treatment for 24 h causes obvious damage to HUVEC. Compared with the model group, puerarin protected against cellular injury in a dose-dependent manner, with the greatest effect at a dose of 30 and 100 μmol·L-1. Puerarin significantly decreased the mitochondrial membrane potential and improved mitochondrial function. Puerarin inhibited cell migration induced by H2O2, suppressed the expression of IL-1β, IL-18 and TNF-α, and down-regulated the pyroptosis-mediated protein. These changes are statistically significant (P < 0.05). These findings demonstrate that puerarin has a protective effect against H2O2-induced oxidative damage of HUVEC by inhibiting the migration of HUVEC cells. The mechanism may be related to improved mitochondrial respiratory function and inhibition of pyroptosis.

Thiophene-Based Double Helices: Radical Cations with SOMO-HOMO Energy Level Inversion.

We report relatively persistent, open-shell thiophene-based double helices, radical cations 1•+ -TMS12 and 2•+ -TMS8 . Closed-shell neutral double helices, 1-TMS12 and 2-TMS8 , have nearly identical first oxidation potentials, E +/0 ≈ +1.33 V, corresponding to reversible oxidation to their radical cations. The radical cations are generated, using tungsten hexachloride in dichloromethane (DCM) as an oxidant, E +/0 ≈ +1.56 V. EPR spectra consist of a relatively sharp singlet peak with an unusually low g-value of 2.001-2.002, thus suggesting exclusive delocalization of spin density over π-conjugated system consisting of carbon atoms only. DFT computations confirm these findings, as only negligible fraction of spin density is found on sulfur and silicon atoms and the spin density is delocalized over a single tetrathiophene moiety. For radical cation, 1•+ -TMS12 , energy level of the singly occupied molecular orbital (SOMO) lies below the four highest occupied molecular orbitals (HOMOs), thus indicating the SOMO-HOMO inversion (SHI) and therefore, violating the Aufbau principle. 1•+ -TMS12 has a half-life of the order of only 5 min at room temperature. EPR peak intensity of 2•+ -TMS8 , which does not show SHI, is practically unchanged over at least 2 h.

Synthesis and Thin Films of Thermally Robust Quartet (S = 3/2) Ground State Triradical.

High-spin (S = 3/2) organic triradicals may offer enhanced properties with respect to several emerging technologies, but those synthesized to date typically exhibit small doublet quartet energy gaps and/or possess limited thermal stability and processability. We report a quartet ground state triradical 3, synthesized by a Pd(0)-catalyzed radical-radical cross-coupling reaction, which possesses two doublet-quartet energy gaps, ΔEDQ ≈ 0.2-0.3 kcal mol-1 and ΔEDQ2 ≈ 1.2-1.8 kcal mol-1. The triradical has a 70+% population of the quartet ground state at room temperature and good thermal stability with onset of decomposition at >160 °C under an inert atmosphere. Magnetic properties of 3 are characterized by SQUID magnetometry in polystyrene glass and by quantitative EPR spectroscopy. Triradical 3 is evaporated under ultrahigh vacuum to form thin films of intact triradicals on silicon substrate, as confirmed by high-resolution X-ray photoelectron spectroscopy. AFM and SEM images of the ∼1 nm thick films indicate that the triradical molecules form islands on the substrate. The films are stable under ultrahigh vacuum for at least 17 h but show onset of decomposition after 4 h at ambient conditions. The drop-cast films are less prone to degradation in air and have a longer lifetime.

Puerarin protects against myocardial ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via TLR4/Myd88/NF-κB pathway in rats / 药学学报

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

High-Spin Diradical Dication of Chiral π-Conjugated Double Helical Molecule.

We report an air-stable diradical dication of chiral D2-symmetric conjoined bis[5]diazahelicene with an unprecedented high-spin (triplet) ground state, singlet triplet energy gap, ΔEST = 0.3 kcal mol-1. The diradical dication possesses closed-shell (Kekulé) resonance forms with 16 π-electron perimeters. The diradical dication is monomeric in dibutyl phthalate (DBP) matrix at low temperatures, and it has a half-life of more than 2 weeks at ambient conditions in the presence of excess oxidant. A barrier of ∼35 kcal mol-1 has been experimentally determined for inversion of configuration in the neutral conjoined bis[5]diazahelicene, while the inversion barriers in its radical cation and diradical dication were predicted by the DFT computations to be within a few kcal mol-1 of that in the neutral species. Chiral HPLC resolution provides the chiral D2-symmetric conjoined bis[5]diazahelicene, enriched in (P,P)- or (M,M)-enantiomers. The enantiomerically enriched triplet diradical dication is configurationally stable for 48 h at room temperature, thus providing the lower limit for inversion barrier of configuration of 27 kcal mol-1. The enantiomers of conjoined bis[5]diazahelicene and its diradical dication show strong chirooptical properties that are comparable to [6]helicene or carbon-sulfur [7]helicene, as determined by the anisotropy factors, |g| = |Δε|/ε = 0.007 at 348 nm (neutral) and |g| = 0.005 at 385 nm (diradical dication). DFT computations of the radical cation suggest that SOMO and HOMO energy levels are near-degenerate.

Effectiveness of the Multidisciplinary Team Model in Treating Colorectal Cancer.

The multidisciplinary team (MDT) model involves multiple medical professionals providing integrated medical care. Colorectal cancer (CRC) has the highest prevalence of cancer in Taiwan. This study examines and evaluates the survival rates of CRC patients treated under the MDT model. In this retrospective and prospective study, 651 CRC patients were recruited. They were divided into 2 groups: the MDT group and the traditional care (TC) group. The MDT group comprised 326 patients who received care from a MDT. The TC group comprised 325 patients who received care from a TC. The outcome variables were survival rates, follow-up appointment compliance, and 14-day readmission rates. Adopting the MDT model for CRC care increased patient follow-up appointment compliance rates at the first week, first month, and third month (p = .032, p = .007, p = .001, respectively). The model also effectively reduced patients' 14-day readmission rates. The results indicated that the survival rates of the MDT care were superior to those of TC. The adoption of the MDT model to treat CRC effectively enhanced clinical treatment adherence, increased survival rates, and reduced the 14-day readmission rate.

S = 1 Tetraazacyclophane Diradical Dication with Robust Stability: A Case of Low-Temperature One-Dimensional Antiferromagnetic Chain.

One-dimensional (1D) spin-1 ( S = 1) chain of organic radicals with low local magnetic anisotropy may provide a better understanding of the low-dimensional magnetism. We report solid-state studies, including single crystal X-ray crystallography, of air-stable tetraazacyclophane diradical dication salt 12·2+·2[Al(OC(CF3)2CH3)4]- with a triplet ground state (Δ EST ≈ 0.5 kcal mol-1). The magnetic behavior for 12·2+ at low temperature is best modeled by 1D spin S = 1 Heisenberg chain with intrachain antiferromagnetic coupling of J'/ k = -5.4 K, which is associated with the interaryl C···C contacts, including π-π interactions. Zero-field splitting value, | D/ hc| ≈ 5.6 × 10-3 cm-1, for 12·2+ is rather small; thus, the 1D chains are characterized by the high degree of isotropicity | D/2 J'| ≈ 7.5 × 10-4. The diradical dication salt possesses extraordinary stability with onset of decomposition at temperature of about 180 °C (∼450 K), based on thermogravimetric analysis and EPR spectroscopy.

Effects of a Psychoeducational Intervention in Patients With Breast Cancer Undergoing Chemotherapy.

BACKGROUND: Compelling evidence has yet to be published regarding the positive effect of psychoeducational interventions (PEIs) on psychological distress in patients with breast cancer. The impact of PEIs on self-efficacy, resilience, and quality of life is also unclear. PURPOSE: The aim of this study was to assess the effects of a PEI on anxiety, depression, disease-specific care knowledge, self-efficacy, resilience and quality of life in patients with breast cancer during and after chemotherapy. The intervention was administered before and during five rounds of chemotherapy treatment. METHODS: A randomized controlled trial was conducted. Patients with breast cancer (N = 40) were randomly assigned to either the experimental or control group. The experimental group participated in PEI, a brief and highly structured program consisting of two parts: (a) an educational manual that addressed depression, anxiety, disease-specific care knowledge, self-efficacy, and resilience and (b) a self-assessment of learning. The control group received only traditional pamphlet education. Data were collected at four time points: before the first chemotherapy session (T1), during the third chemotherapy session (T2), during the fifth chemotherapy session (T3), and at 2 weeks after the final chemotherapy session (T4). RESULTS: Anxiety, depression, resilience, and quality of life in the experimental group showed significant differences at T4. Significant differences became apparent at T2 for knowledge and at T3 for self-efficacy. The effects of knowledge, resilience, and quality of life remained significant when group and time interactions were included in the model, showing a positive relationship between PEI and the variables of knowledge, resilience, and quality of life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Face-to-face PEI for patients with breast cancer is potentially effective in improving knowledge, resilience, and quality of life during and after chemotherapy. In the current study, PEI significantly improved disease care techniques, reduced chemotherapy-related discomfort, and improved quality of life for participants in the experimental group.

Probing Functional Changes in Exocyst Configuration with Monoclonal Antibodies.

Spatial regulation of exocytosis relies on the exocyst, a hetero-octameric protein complex that tethers vesicles to fusion sites at the plasma membrane. Nevertheless, our understanding of mechanisms regulating exocyst assembly/disassembly, localization, and function are incomplete. Here, we have exploited a panel of anti-Sec6 monoclonal antibodies (mAbs) to probe possible configurational changes accompanying transitions in exocyst function in epithelial MDCK cells. Sec6 is quantitatively associated with Sec8 in high molecular weight complexes, as shown by gel filtration and co-immunoprecipitation studies. We mapped epitopes recognized by more than 20 distinct mAbs to one of six Sec6 segments. Surprisingly, mAbs that bound epitopes in each segment labeled distinct subcellular structures. In general, antibodies to epitopes in N-terminal domains labeled Sec6 in either cytosolic or nuclear pools, whereas those that bound epitopes in C-terminal domains labeled membrane-associated Sec6. In this latter group, we identified antibodies that labeled distinct Sec6 populations at the apical junctional complex, desmosomes, endoplasmic reticulum and vimentin-type intermediate filaments. That each antibody was specific was verified by both Sec6 RNAi and competition with fusion proteins containing each domain. Comparison of non-polarized and polarized cells revealed that many Sec6 epitopes either redistribute or become concealed during epithelial polarization. Transitions in exocyst configurations may be regulated in part by the actions of Ral GTPases, because the exposure of Sec6 C-terminal domain epitopes at the plasma membrane is significantly reduced upon RalA RNAi. To determine whether spatio-temporal changes in epitope accessibility was correlated with differential stability of interactions between Sec6 and other exocyst subunits, we quantified relative amounts of each subunit that co-immunoprecipitated with Sec6 when antibodies to N-terminal or C-terminal epitopes were used. Antibodies to Sec6NT co-precipitated substantially more Sec5, -10, -15, Exo70 and -84 than did those to Sec6CT. In contrast, antibodies to Sec6CT co-precipitated more Sec3 and Sec8 than did those to Sec6NT. These results are consistent with a model in which exocyst activation during periods of rapid membrane expansion is accompanied by molecular rearrangements within the holocomplex or association with accessory proteins, which expose the Sec6 C-terminal domain when the complex is membrane-bound and conceal it when the complex is cytoplasmic.

CREG1 Interacts with Sec8 to Promote Cardiomyogenic Differentiation and Cell-Cell Adhesion.

Understanding the regulation of cell-cell interactions during the formation of compact myocardial structures is important for achieving true cardiac regeneration through enhancing the integration of stem cell-derived cardiomyocytes into the recipient myocardium. In this study, we found that cellular repressor of E1A-stimulated genes 1 (CREG1) is highly expressed in both embryonic and adult hearts. Gain- and loss-of-function analyses demonstrated that CREG1 is required for differentiation of mouse embryonic stem (ES) cell into cardiomyocytes and the formation of cohesive myocardium-like structures in a cell-autonomous fashion. Furthermore, CREG1 directly interacts with Sec8 of the exocyst complex, which tethers vesicles to the plasma membrane. Site-directed mutagenesis and rescue of CREG1 knockout ES cells showed that CREG1 binding to Sec8 is required for cardiomyocyte differentiation and cohesion. Mechanistically, CREG1, Sec8, and N-cadherin colocalize at intercalated discs in vivo and are enriched at cell-cell junctions in cultured cardiomyocytes. CREG1 overexpression enhances the assembly of adherens and gap junctions. By contrast, its knockout inhibits the Sec8-N-cadherin interaction and induces their degradation. These results suggest that the CREG1 binding to Sec8 enhances the assembly of intercellular junctions and promotes cardiomyogenesis. Stem Cells 2016;34:2648-2660.

[Transference in the Nurse-Patient Relationship: A Case Report on a Prostate Cancer Patient].

This article explores the dilemma posed with regard to a prostate cancer patient suffering from transference syndrome. Transference is generally recognized as an unconscious and inevitable part of relationships. Both nurse and patient "transfer" their past emotional and psychological needs into present situations and react accordingly. Consequently, the emotions and behaviors of nurses influence the reactions of their patients. Nurses must better understand their contributions to the nurse-patient relationship in order to better detect patient thoughts and feelings. Furthermore, nurses must recognize the needs of their patients and maintain a neutral and uncritical attitude. We developed a case management model to provide a consultation corner for cancer patients. Additionally, in an attempt to improve the quality of life of cancer patients, the developed model encouraged medical personnel to discuss sexual, belonging, and love problems with patients and to hold attitudes of professionalism, composure, caring, and solemnity. Belonging and love are basic human needs. However, for patients with prostate cancer, this basic need cannot be satisfied. Even professionally trained medical personnel have difficulty directly addressing this problem. This paper describes the meaning of transference and the importance of this concept in the therapeutic nurse-patient relationship. Finally, developing better insights into the nurse-patient relationship will help nurses use these insights to improve the quality of patient interactions and of care.

Factors predicting survival of patients with gastric cancer.

BACKGROUND: Gastric cancer is one of the most common causes of cancer death in Taiwan. The literature has previously shown that age, tumor site, T categories, and number of metastatic nodes significantly affect prognosis. The aim of this study was to determine the long-term survival of patients with gastric cancer, as well as the effect of particular prognostic factors on survival. MATERIALS AND METHODS: This was a survival analysis study with retrospective design. We reviewed the records of 64 patients with adenocarcinoma of the stomach who had undergone gastrectomy with curative intent between 2009 and 2012 at a teaching hospital in southern Taiwan. Data extracted from patient documents included age, gender distribution, tumor location, and pathological grading. RESULTS: The median follow-up time was 4 years, and there were 31 deaths attributed to gastric cancer. Kaplan-Meier analysis revealed that retrieval of less than 15 lymph nodes from a patient was a significant predictor of survival. A significant predictor of poorer survival was higher pathological grading. CONCLUSIONS: Our results indicate that the number of lymph nodes retrieved and pathological grading could be viewed as crucial prognostic factors affecting the survival of individuals with gastric cancer.