A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity.

Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.

[Safe zones of the maxillary posterior area for mini-implant insertion in adolescents with skeletal Class II malocclusion].

PURPOSE: The purpose of this study was to measure the interradicular spaces between the maxillary second premolar and first molar in adolescents with skeletal Class Ⅱ malocclusion, so as to obtain scientific knowledge for placing mini-implants. METHODS： Forty four cone-beam computed tomography(CBCT) images were selected, which consisted of 23 males and 21 females (average age, 14.07 years) with skeletal Class II malocclusion. CBCT was used to measure the closest interradicular distance and the shortest distance from cortical bone surface to the narrowest interradicular space apically at 1-mm intervals in 9 axial images from the cementoenamel junction(CEJ). SPSS 20.0 software package was used for statistical analysis. RESULTS: There was no significant difference in the closest interradicular distance and the shortest distance from cortical bone surface to the narrowest interradicular space between the left and right side (P>0.05), and no significant difference was found between males and females (P>0.05); The shortest distance from cortical bone surface to the narrowest interradicular space of the left apical area had positive correlation with SNA angle; The closest interradicular distance became wider toward the apical area，and the average distance of the shortest distance from cortical bone surface to the narrowest interradicular space was over 5mm in all sections. CONCLUSIONS: The distribution of interradicular spaces between the maxillary second premolar and first molar of adolescents with skeletal Class II malocclusion is learned using CBCT. These data might provide a reference for placing mini-implants.

Psychological well-being, dental esthetics, and psychosocial impacts in adolescent orthodontic patients: A prospective longitudinal study.

INTRODUCTION: We examined the role of adolescent orthodontic patients' psychological well-being attributes (self-esteem, general body image, and positive and negative affects) and the clinical indicators of dental esthetics (orthodontists' ratings on the Index of Orthodontic Treatment Need-Aesthetic Component [IOTN-AC]), and their changes from pretreatment to posttreatment as predictors of the psychosocial impact of dental esthetics. METHODS: In this prospective longitudinal study, 1090 adolescent orthodontic patients seeking treatment at the Stomatological Hospital of Chongqing Medical University in China (mean age, 14.25 years; SD, 2.03 years) were assessed before treatment, and 68.99% (n = 752) were assessed after treatment. All subjects completed a questionnaire measuring psychological well-being attributes and 3 components of the Psychosocial Impact of Dental Aesthetics (perceptive, cognitive-affective, and social-functional). Clinical indicators of dental esthetics were measured by 3 orthodontists using the IOTN-AC. RESULTS: Substantial enhancement from pretreatment to posttreatment was found in all 3 Psychosocial Impacts of Dental Aesthetics components, confirming the positive effects of orthodontic treatment on oral health-related quality of life. Psychosocial impact of dental esthetics at baseline and improvement from pretreatment to posttreatment were found to be predicted by the patients' psychological well-being attributes (self-esteem, general body image, and negative affect) and the clinical indicators (orthodontists' rating on the IOTN-AC) at baseline, as well as their pretreatment to posttreatment change. Psychological well-being attributes had comparable or greater contribution to the Psychosocial Impact of Dental Aesthetics at baseline as well as greater improvement after treatment than the clinical indicators. These biopsychological models explained 29% to 43% of the variances in psychosocial impacts of dental esthetics outcome at baseline and about 33% of the variance in pretreatment to posttreatment improvement. CONCLUSIONS: This study establishes a biopsychological model for understanding the psychosocial impact of dental esthetics and its improvement after orthodontic treatment among adolescent orthodontic patients. The findings highlight the importance of psychological parameters in orthodontic research and clinical practice.

[The relationship between centric relation-maximum intercuspation disharmony and temporomandibular dysfunction in class II patients].

OBJECTIVE: To investigate the relationship between the degree of displacement of centric relation-maximum intercuspation (CR-MI) and temporomandibular dysfunction (TMD) in Class II patients. METHODS: The questionnaire and clinical examination were administered in 107 Class II patients and students, using the Helkimo index (Di and Ai). The differences in condylar position between CR and MI in all three spatial planes were measured using the Condyle Position Indication (CPI). RESULTS: Di positively correlated with degree of CR-MI displacement in all five displacement (P < 0.05), while Ai positively correlated with degree of CR-MI displacement except horizontal displacement. Di and Ai significantly correlated with degree of CR-MI discrepancy in all five displacement (P < 0.05); With the increasing of Di and Ai rank, the degree of CR-MI displacement and CR-MI discrepancy increased. Also, symptoms of TMD were significantly correlated with the degree of CR-MI displacement and CR-MI discrepancy except horizontal displacement (P < 0.05). Severer CR-MI displacement and CR-MI discrepancy were observed in patients who had TMD symptoms. CONCLUSION: In Class II patients, degree of CR-MI displacement is an important factor of TMD, and correlated with the severity of TMD.

Purification and properties of a phytase from Candida krusei WZ-001.

A phytase from Candida krusei WZ-001 isolated from soil was purified to electrophoretic homogeneity by ion-exchange chromatography, hydrophobic interaction chromatography, and gel filtration. The phytase is composed of two different subunits with molecular masses of 116 kDa and 31 kDa on SDS-PAGE (or 120 kDa and 30 kDa on gel chromatography), with the larger subunit having a glycosylation rate of around 35%. The phytase has an optimum pH of 4.6, an optimum temperature of 40 degrees C and a pI value of 5.5. The phytase activity was stimulated by 2-mercapto-ethanol and dithiothreitol (DTT), and inhibited by Zn2+, Mg2+, iodoacetate, pI value of 5.5. The phytase activity was stimulated by 2-mercapto-ethanol ethanol and dithiothreitol (DTT), and inhibited by Zn2+, Mg2+, iodoacetate, p-chroloromercuribenzoate (pCMB) and phenylmethylsulfonyl fluoride (PMSF). The phytase displayed a broad substrate specificity and the K(m) for phytate was 0.03 mM. Phytate was sequentially hydrolyzed by the phytase. Furthermore, 1D and 2D NMR analyses and bioassay of myoinositol indicated that the end hydrolysis product of phytate was myoinositol 2-monophosphate.