Molecular mechanism of NAD+ and NMN binding to the Nudix homology domains of DBC1.

Deleted in breast cancer 1 (DBC1) is a human nuclear protein that modulates the activities of various proteins involved in cell survival and cancer progression. Oxidized form of nicotinamide adenine dinucleotide (NAD+) is suggested to bind to the Nudix homology domains (NHDs) of DBC1, thereby regulating DBC1-Poly (ADP-ribose) polymerase 1 (PARP1) interactions, resulting in the restoration of DNA repair. Using Nuclear Magnetic Resonance (NMR) and Isothermal Titration Calorimetry (ITC), we confirmed NAD+ and its precursor nicotinamide mononucleotide (NMN) both bind the NHD domain of DBC1 (DBC1354-396). NAD+ likely interacts with DBC1354-396 through hydrogen bonding, with a binding affinity (8.99 µM) nearly twice that of NMN (17.0 µM), and the key binding sites are primarily residues E363 and D372, in the agreement with Molecular Docking experiments. Molecular Dynamics (MD) simulation further demonstrated E363 and D372's anchoring role in the binding process. Additional mutagenesis experiments of E363 and D372 confirmed their critical involvement of ligand-protein interactions. These findings lead to a better understanding of how NAD+ and NMN regulate DBC1, thereby offering insights for the development of targeted therapies and drug research focused on DBC1-associated tumors.

Different Influences of Rare Earth Eu Addition on Primary Si Refinement in Hypereutectic Al-Si Alloys with Varied Purity.

The effect of alloying the Eu element on primary Si refinement in varied purity Al-16Si alloys was studied by scanning electron microscopy (SEM), thermal analysis, micro x-ray diffraction (µ-XRD), electron probe microanalysis (EPMA), and transmission electron microscopy (TEM). The results indicate that the P impurity element in hypereutectic Al-Si alloys has a great influence on the rare earths' refinement efficiency of primary Si. Coinstantaneous primary Si refinement and eutectic Si modification by Eu was obtained in high purity (HP) Al-16Si and commercial purity (CP) Al-16Si-0.06P alloys, but the primary Si was gradually coarsened in CP Al-16Si alloys. An excellent integration of ultimate tensile strength (144.8 MPa) and elongation (9.8%) of CP hypereutectic Al-16Si-0.06P alloy was obtained by adding 0.15% Eu. The refinement of primary Si in Eu-modified HP Al-16Si alloys was related to the constitutional undercooling of Eu. There was no sufficient Eu element partition into the primary Si particles, and fewer parallel twins, rather than multiple twins, were observed within them. The refinement of primary Si in CP Al-16Si-0.06P alloys was caused by the overlay of two kinds of mechanisms including the heterogeneous nucleation mechanism of AlP and the constitutional supercooling mechanism of Eu. However, in order to refine the primary Si in CP hypereutectic Al-16Si alloys, the Eu:P weight ratio should not exceed 3.33, otherwise the refinement efficiency of primary Si will be reduced due to mutual poisoning between Eu and P. This work can be used to interpret the controversy concerning the influence of rare earths on the primary Si in hypereutectic Al-Si alloys, thereby elucidating the importance of alloy purity to primary Si refinement by rare earths.

Development of a lateral flow immunochromatographic assay for rapid detection of Mycoplasma pneumoniae-specific IgM in human serum specimens.

Early diagnosis of Mycoplasma pneumoniae (MP) infection is crucial for prompt treatment and good patient outcome. However, serological tests to detect MP rapidly and conveniently are still lacking. This study aimed to use the fluorescent dye Alexa Fluor® 647 as the detection marker to develop a lateral flow immunochromatographic assay (LFIA) for detection of MP-specific IgM in serum specimen. Monoclonal mouse antibody against human IgM (µ-chain specific) and goat anti-rabbit IgG were labeled with Alexa Fluor® 647 (anti-IgM-AF647 and anti-IgG-AF647). A mixture of natural MP antigen and recombinant P1 antigen was coated as the test line (T line) and rabbit IgG was coated as the control line (C line) on a nitrocellulose (NC) membrane. The MP antigens captured IgM-anti-IgM-AF647 complex on the T line. Rabbit IgG captured anti-IgG-AF647 on the C line. The fluorescence intensity on the T line and C line was measured. Sartorius CN140 NC membrane showed higher sensitivity than CN95. The optimal reaction time for the LFIA was 10min. The area under the receiver operating characteristic curve based on 34 MP positive and 166 MP negative serum samples was 0.986 (p<0.001). The cutoff value of T/C area ratio was 0.3830. The LFIA strips did not react with serum from patients infected with non-MP pathogens including influenza viruses and bacteria causing respiratory tract infection. The intra-assay and inter-assay coefficients of variation were between 3.28% and 10.14%. The shelf life was calculated to be 2years at room temperature. The LFIA strips and the commercial EUROIMMUN kit showed consistent results on 372 serum specimens. The overall consistency rate was 96.37% with a Kappa value of 0.842 (p<0.001). The LFIA in the current study may be a sensitive and specific approach to detect early MP infection rapidly and conveniently.

Relationships of mental health problems with stress among civil servants in Guangzhou, China.

Psychosocial problems and stress-related diseases account for a high proportion of health problems. This study aimed to assess stress status and mental health, and their relationships with each other among civil servants in China. In a cross-sectional study of 600 randomly selected civil servants in 2007, we assessed mental health via the Symptom Checklist 90 (SCL-90), and stress status via a Self-Rated Stress Scale. Canonical correlation analysis was performed to assess the interrelationships among mental health symptoms and the various stressors. The participants scored higher in the total score and the seven domains of the SCL-90 (except for interpersonal sensitivity and hostility), compared with the norms documented in China. Canonical correlation analysis demonstrated positive and direct relationship in the first canonical function indicating that the nine mental health problems and various stressors were related (Canonical correlation = 0.715). Among the civil servants, mental health problems are highly associated with various stressors.

Association of somatic symptoms with depression and anxiety in clinical patients of general hospitals in Guangzhou, China.

OBJECTIVES: In high-income countries, depression and anxiety are reported to be common reasons for patients visiting nonpsychiatric services. This study aimed to assess the rate of depression and anxiety, and their associations with somatic symptoms, in patients presenting to clinics of general hospitals in Guangzhou, China. METHODS: In a hospital-based cross-sectional study of 2408 randomly selected clinical patients from 15 general hospitals, we assessed depression and anxiety via the Hospital Anxiety and Depression Scale (HADS), somatic symptoms via the Patient Health Questionnaire 15-Item Somatic Symptom Severity Scale (PHQ-15) and patients' view of the impact of somatic symptoms on their life, job and social relationships. Multiple logistic models were used to analyze the association of somatic symptoms with depression and anxiety, the underlying physical diseases and the self-rated somatic symptoms' impact on social functions. RESULTS: Of the participants, 454 (19.0%) reported moderate to high somatic symptoms (PHQ-15 score ≥ 10), 367 (15.2%) had depression (HADS-D score ≥ 7), 167 (6.9%) had anxiety (HADS-A score ≥ 10), and 125 (5.2%) had both depression and anxiety (HADS-D ≥ 7 and HADS-A ≥ 10). Patients with depression and anxiety had higher somatic symptoms and rated these symptoms as having a greater negative impact on their social functions. Relevant to other systemic diseases, only digestive system disease was associated with higher somatic symptoms and self-rated negative social impact, and great negative emotions. Stepwise multiple logistic analyses demonstrated that female sex and depression and anxiety were the main factors for the high somatic symptoms of the population. CONCLUSIONS: Among patients who visit hospital clinics in Guangzhou, China, somatic complaints are highly associated with depression and anxiety, and rarely associated with their underlying medical diseases. The findings indicate the importance of recognizing and managing depression and anxiety for these patients.