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Yanfang Zhou,1,* Jiemei Li,1,* Fang Lu,1 Junjie Deng,2 Jiahua Zhang,1 Peijie Fang,1 Xinsheng Peng,1 Shu-Feng Zhou3 1Guangdong Medical Universtity, Dongguan, Guangdong, People’s Republic of China; 2Department of Materials Science and Engineering, Drexel University, Philadelphia, PA, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA *These authors contributed equally to this work Abstract: Dendrimers are hyperbranched macromolecules with well-defined topological structures and multivalent functionalization sites, but they may cause cytotoxicity due to the presence of cationic charge. Recently, we have introduced alkyne-terminated poly(amidoamine) (PAMAM) dendrons of different generations (G=2,3) into chitosan to obtain dendronized chitosan derivatives [Cs-g-PAMAM (G=2,3)], which exhibited a better water solubility and enhanced plasmid DNA transfection efficiency. In this study, we attempted to examine the impact of Cs-g-PAMAM (G=2,3) at different concentrations (25 µg/mL, 50 µg/mL, and 100 µg/mL) on the morphology, surface structure, and viability of rat red blood cells (RBCs). The results showed that treatment of RBCs with Cs-g-PAMAM (G=2,3) at 50 µg/mL and 100 µg/mL induced a slightly higher hemolysis than Cs, and Cs-g-PAMAM (G=3) caused a slightly higher hemolysis than Cs-g-PAMAM (G=2), but all values were 0.05). Furthermore, Cs-g-PAMAM (G=2,3) exhibited a lower cytotoxicity in human kidney 293T cells. These results indicate that Cs-g-PAMAM (G=2,3) are hemocompatible but may disturb membrane and lipid structures at higher concentrations. Further safety and biocompatibility evaluations are warranted for Cs-g-PAMAM. Our findings prove helpful for a better understanding of the advantages of combining PAMAM dendrimers and chitosan to design and develop new, safe, and effective drug delivery vehicles. Keywords: dendronized chitosan derivative, PAMAM, RBC, hemolysis, hemocompatibility

Non-CpG methylation is associated with several cellular processes, especially neuronal development and cancer, while its effect on DNA structure remains unclear. We have determined the crystal structures of DNA duplexes containing -CGCCG- regions as CCG repeat motifs that comprise a non-CpG site with or without cytosine methylation. Crystal structure analyses have revealed that the mC:G base-pair can simultaneously form two alternative conformations arising from non-CpG methylation, including a unique water-mediated cis Watson-Crick/Hoogsteen, (w)cWH, and Watson-Crick (WC) geometries, with partial occupancies of 0.1 and 0.9, respectively. NMR studies showed that an alternative conformation of methylated mC:G base-pair at non-CpG step exhibits characteristics of cWH with a syn-guanosine conformation in solution. DNA duplexes complexed with the DNA binding drug echinomycin result in increased occupancy of the (w)cWH geometry in the methylated base-pair (from 0.1 to 0.3). Our structural results demonstrated that cytosine methylation at a non-CpG step leads to an anti→syntransition of its complementary guanosine residue toward the (w)cWH geometry as a partial population of WC, in both drug-bound and naked mC:G base pairs. This particular geometry is specific to non-CpG methylated dinucleotide sites in B-form DNA. Overall, the current study provides new insights into DNA conformation during epigenetic regulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Ideal cardiovascular health (CVH) metrics play an important role in preventing cardiovascular disease (CVD). However, there is a lack of cohort studies on CVH metrics among young Asian adults. The aims of this study were to describe early changes in CVH among young Asian adults and to investigate the association between CVH metrics and sociodemographic variables., Methods: A total of 10,000 young adults (aged 21-30 years) were recruited between 2000 and 2016. There were two CVH measurements taken from these participants over the study period. One measurement was taken at the beginning, and the other was taken five years later. Subgroup analysis of the changes in CVH metrics was divided by education level and marital status., Results: The mean age of the participants was 26.8 years. The initial prevalence of ideal CVH metrics was 52.3% and 86.8% and decreased to 43.8% and 81.2% after five years for males and females, respectively. In the subgroup analysis, males with less than a university education had a smaller ideal CVH metric decrease (6.2%) than males with more than a university education (8.9%), while females with more than a university education had a smaller ideal CVH metric decrease (5.4%) than females with less than a university education (7.3%). Married males had a smaller ideal CVH metric decrease (6.1%) than single males (9.1%), while single females had a smaller ideal CVH metric decrease (5.3%) than married females (6.2%)., Conclusions: The prevalence of ideal CVH metrics among young adults gradually decreased as age increased. Higher educational attainment and unmarried status were associated with a greater prevalence of ideal CVH metrics regardless of sex, but early CVH changes differed by sex, education level, and marital status. The prevalence of CVH changes found early among young adults can be used to monitor CVH changes quickly. Effective health promotion programs are needed to maintain CVH metrics among young adults.

Glycosylation is a protein post translational modification which plays important role in protein function, stabilization, trafficking, and turnover. Alteration of protein glycosylation is a common phenomenon during tumor progression, migration, invasion, angiogenesis, as well as metastasis. Hence, aberrant glycan structures and the induced corresponding anti-carbohydrate antibodies are potential biomarkers for cancer diagnosis. In this study, serum N-glycomes and anti-carbohydrate antibodies from normal populations and oral squamous cell carcinoma (OSCC) patients were investigated. Total serum proteins were lyophilized and subjected to chemical reduction, alkylation and trypsin digestion. The N-glycans were released, purified, permethylated, and analyzed using MALDI-TOF-Mass spectrometry. In addition, the serum anti-carbohydrate antibody profiles were also investigated by carbohydrate microarray. We found that the relative abundances of seven N-glycans were decreased or increased in serum of OSCC with diagnostic accuracy greater than 75%. The relative abundances of total tri-antennary and tetra-antennary glycans with varying degrees of fucosylation and sialylation were also increased in serum N-glycomes of OSCC. In an independent validation group of forty-eight OCCC patients, most of the high-molecular weight serum N-glycans showed significantly high sensitivity and specificity according to the identified cutoff values. Furthermore, the serum levels of two IgM antibodies were elevated accompanied with the decreased levels of nine IgG antibodies in patient serum. Taken together, these serum N-glycans and antibodies identified in this study should be considered as the candidates of potential biomarkers for OSCC diagnosis.

Purpose: To investigate the expression and localization of LIM mineralization protein 1(LMP-1) during rat pulp injury and reparation., Methods: Dental pulp injury models were established in maxillary first molars on one side of 12 Wistar rats, the isonym healthy teeth on the opposite side were used as the controls. Immunohistochemistry technique was used to observe the expression of LMP-1 at 1, 3 and 7 day after pulp injury. The results of staining were analyzed by Image-Pro Plus 6.0 and SPSS 17.0 software package., Results: LMP-1 was not detected in normal rat dental pulp. Positive staining of LMP-1 was found in odontoblasts and some dental pulp cells at 1 day after pulp injury. The expression of LMP-1 was converged at cell proliferation zone under the injury site at 3 and 7 day after injury., Conclusions: LMP-1 might play a role in the dental pulp cell proliferation and differentiation and reparative dentin formation during pulp injury and reparation.

G-quadruplex DNA ligands attract much attention because of their potential use in biology. Indeed they may interfere with G-quadrulex nucleic acid function in cells. Most of the G-quadruplex ligands so far reported (including also metal complexes) are large planar aromatic compounds that interact by π-π stacking with an external G-quartet of quadruplex. Porphyrins are well-known G-quadruplex ligands. We report herein a new porphyrin scaffold (meso-tetrakis(4-(N-methyl-pyridinium-2-yl)phenyl)porphyrin) able to strongly and selectively bind to G-quadruplex DNA. We show that even when this porphyrin is metallated with cobalt(III), i.e. it carries two water molecules as axial ligands on the cobalt ion, on each face of the porphyrin, the interaction occurs by a π-stacking-like mode with an external G-quartet of quadruplex DNA.

Paenibacillus campinasensis BL11 isolated from black liquor secretes multiple glycoside hydrolases (GHs) against all kinds of polysaccharides. GH consists of a catalytic module and non-catalytic carbohydrate-binding modules (CBMs), in which CBMs append to the catalytic module, mediating specific interactions with insoluble carbohydrates to promote the hydrolysis efficiency of the cognate enzyme. Endo-β-1,4-xylanase (XylX) is one of the GHs reveals high enzymatic activity in a wide range of pH and thermal endurance, suitable for bioconversion and bio-refinement applications. In this work, we report the resonance assignments of a family 36 CBM (characterized as CBM36) derived from XylX. Our investigations will facilitate molecular structure determination and molecular dynamics analysis of CBMs.

The RstA/RstB system is a bacterial two-component regulatory system consisting of the membrane sensor, RstB and its cognate response regulator (RR) RstA. The RstA of Klebsiella pneumoniae (kpRstA) consists of an N-terminal receiver domain (RD, residues 1-119) and a C-terminal DNA-binding domain (DBD, residues 130-236). Phosphorylation of kpRstA induces dimerization, which allows two kpRstA DBDs to bind to a tandem repeat, called the RstA box, and regulate the expression of downstream genes. Here we report the solution and crystal structures of the free kpRstA RD, DBD and DBD/RstA box DNA complex. The structure of the kpRstA DBD/RstA box complex suggests that the two protomers interact with the RstA box in an asymmetric fashion. Equilibrium binding studies further reveal that the two protomers within the kpRstA dimer bind to the RstA box in a sequential manner. Taken together, our results suggest a binding model where dimerization of the kpRstA RDs provides the platform to allow the first kpRstA DBD protomer to anchor protein-DNA interaction, whereas the second protomer plays a key role in ensuring correct recognition of the RstA box., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: To compare the operating time, root fracture and postoperative complications between split-root extraction and medial resistance removal in extraction of mandibular small-angle impacted third molars, to evaluate the advantages of split-root extraction in medially impacted tooth extraction., Methods: Forty male patients with bilaterally mandibular medial small-angle impacted third molars, having multiple roots in panoramic films, were selected. The impacted teeth on one side were extracted by using split-root method, while the similar impacted teeth on the other side were extracted by using medial resistance removal method. The operating time, root fracture, postoperative pain, facial edema, and mouth opening were recorded. SPSS11.5 software package was used and paired t test was performed to analyze the data., Results: There were significant differences in operating time and root fracture between the two methods (P<0.05). In the split-root group, the operating time was shorter and root fracture were less. After 24 hours, facial edema, limited mouth opening, and pain of the split-root group was less severe than that of the medial resistance removal group, differences were significant(P<0.05). After 72 hours, limited mouth opening of the split-root group was milder than that of the resistance removal group, the difference was significant (P<0.05). After 120 hours, there was no significant difference of any complications between the two groups., Conclusions: In extraction of mandibular medial small-angle impacted third molars with multiple roots, the operating time of split-root extraction is shorter. The root fracture possibility of split-root extraction is smaller, and postoperative complications are less common.