Early onset of pathological polyploidization and cellular senescence in hepatocytes lacking RAD51 creates a pro-fibrotic and pro-tumorigenic inflammatory microenvironment.

BACKGROUND AND AIMS: RAD51 recombinase (RAD51) is a highly conserved DNA repair protein and is indispensable for embryonic viability. As a result, the role of RAD51 in liver development and function is unknown. Our aim was to characterize the function of RAD51 in postnatal liver development. APPROACH AND RESULTS: RAD51 is highly expressed during liver development and during regeneration following hepatectomy and hepatic injury, and is also elevated in chronic liver diseases. We generated a hepatocyte-specific Rad51 deletion mouse model using Alb -Cre ( Rad51 -conditional knockout (CKO)) and Adeno-associated virus 8-thyroxine-binding globulin-cyclization recombination enzyme to evaluate the function of RAD51 in liver development and regeneration. The phenotype in Rad51 -CKO mice is dependent on CRE dosage, with Rad51fl/fl ; Alb -Cre +/+ manifesting a more severe phenotype than the Rad51fl/fl ; Alb -Cre +/- mice. RAD51 deletion in postnatal hepatocytes results in aborted mitosis and early onset of pathological polyploidization that is associated with oxidative stress and cellular senescence. Remarkable liver fibrosis occurs spontaneously as early as in 3-month-old Rad51fl/fl ; Alb -Cre +/+ mice. While liver regeneration is compromised in Rad51 -CKO mice, they are more tolerant of carbon tetrachloride-induced hepatic injury and resistant to diethylnitrosamine/carbon tetrachloride-induced HCC. A chronic inflammatory microenvironment created by the senescent hepatocytes appears to activate ductular reaction the transdifferentiation of cholangiocytes to hepatocytes. The newly derived RAD51 functional immature hepatocytes proliferate vigorously, acquire increased malignancy, and eventually give rise to HCC. CONCLUSIONS: Our results demonstrate a novel function of RAD51 in liver development, homeostasis, and tumorigenesis. The Rad51 -CKO mice represent a unique genetic model for premature liver senescence, fibrosis, and hepatocellular carcinogenesis.

Sex estimation using maxillary sinus volume for Chinese subjects based on cone-beam computed tomography.

BACKGROUND: Sex estimate is a key stage in forensic science for identifying individuals. Some anatomical structures may be useful for sex estimation since they retain their integrity even after highly severe events. However, few studies are focusing on the Chinese population. Some researchers used teeth for sex estimation, but comparison with maxillary sinus were lack. As a result, the objective of this research is to develop a sex estimation formula for the northwestern Chinese population by the volume of the maxillary sinus and compare with the accuracy of sex estimation based on teeth through cone-beam computed tomography (CBCT). METHODS: CBCT images from 349 samples were used to establish and verify the formula. The volume of both the left and right maxillary sinuses was measured and examined for appropriate formula coefficients. To create the formula, we randomly picked 80% of the data as the training set and 20% of the samples as the testing set. Another set of samples, including 20 males and 20 females, were used to compare the accuracy of maxillary sinuses and teeth. RESULTS: Overall, sex estimation accuracy by volume of the left maxillary sinus can reach 78.57%, while by the volume of the right maxillary sinus can reach 74.29%. The accuracy for females, which can reach 91.43% using the left maxillary sinus, was significantly higher than that for males, which was 65.71%. The result also shows that maxillary sinus volume was higher in males. The comparison with the available results using measurements of teeth for sex estimation performed by our group showed that the accuracy of sex estimation using canines volume was higher than the one using maxillary sinus volume, the accuracies based on mesiodistal diameter of canine and first molar were the same or lower than the volume of maxillary sinus. CONCLUSIONS: The study demonstrates that measurement of maxillary sinus volume based on CBCT scans was an available and alternative method for sex estimation. And we established a method to accurately assess the sex of the northwest Chinese population. The comparison with the results of teeth measurements made the conclusion more reliable.

Accuracy comparison of tooth volume and mesiodistal diameter measurements for sex dimorphism based on cone-beam computed tomography: a study for the northern Chinese population.

Sex estimation based on teeth could help to narrow the scope for individual identification. According to the different teeth morphology among both genders, we plan to establish a sex estimation method for the northern Chinese population through mesiodistal diameter and teeth volume measurements and compare the accuracy of the two methods. In this study, measurements were taken from cone-beam computed tomography images collected from 142 males and 140 females aged 21-59 years. The mesiodistal diameter and volume of the left canines and the first molars in both upper and lower jaws were measured and analyzed for suitable coefficients. We selected 80% samples as the training set to set up the logistic regression formulas and 20% as the test set to obtain accuracy. The accuracy of sex estimation by mesiodistal diameter can reach 87.50%, and the volume is up to 78.57%. The measurement of mesiodistal diameter is less time-consuming. This work established and tested a method to estimate sex for the northern Chinese population. Results showed that sex estimation based on the mesiodistal diameter of teeth has higher accuracy than the method based on teeth volume.

An Uncertainty-Aware and Sex-Prior Guided Biological Age Estimation From Orthopantomogram Images.

Bone age, as a measure of biological age (BA), plays an important role in a variety of fields, including forensics, orthodontics, sports, and immigration. Despite its significance, accurate estimation of BA remains a challenge due to the uncertainty error between BA and chronological age (CA) caused by individual diversity and the difficult integration of multiple factors, such as sex, and identified or measured anatomical structures, into the estimation process. To address problems, we propose an uncertainty-aware and sex-prior guided biological age estimation from orthopantomogram images (OPGs), named UASP-BAE, which models uncertainty errors while setting sex dimorphism as tractive features to enhance age-related specific features, aiming to improve the accuracy of BA estimation. Furthermore, considering the global relevance of the anatomic structure, such as the mandible, teeth, maxillary sinus, etc., a cross-attention module based on CNN and self-attention is proposed to mine the local texture and global semantic features of OPGs. Moreover, we design a novel age composition loss by cross-entropy, probability bias, and regression functions, aiming at evaluating BA's uncertainty errors and results to obtain an accurate and robust model. On 10703 OPGs from 5.00 to 25.00 years of age, our model had a best MAE value of 0.8005 years and higher than the comparison popular algorithms, which also demonstrates the method's potential for improved accuracy in BA estimation.

Automatic sex estimation using deep convolutional neural network based on orthopantomogram images.

Sex estimation is very important in forensic applications as part of individual identification. Morphological sex estimation methods predominantly focus on anatomical measurements. Based on the close relationship between sex chromosome genes and facial characterization, craniofacial hard tissues morphology shows sex dimorphism. In order to establish a more labor-saving, rapid, and accurate reference for sex estimation, the study investigated a deep learning network-based artificial intelligence (AI) model using orthopantomograms (OPG) to estimate sex in northern Chinese subjects. In total, 10703 OPG images were divided into training (80%), validation (10%), and test sets (10%). At the same time, different age thresholds were selected to compare the accuracy differences between adults and minors. The accuracy of sex estimation using CNN (convolutional neural network) model was higher for adults (90.97%) compared with minors (82.64%). This work demonstrated that the proposed model trained with a large dataset could be used in automatic morphological sex-related identification with favorable performance and practical significance in forensic science for adults in northern China, while also providing a reference for minors to some extent.

A cone-beam computed tomography study of hyoid bone position and airway volume in subjects with obstructive and nonobstructive adenotonsillar hypertrophy.

OBJECTIVES: To investigate hyoid bone position and airway volume in subjects with adenoid hypertrophy, tonsillar hypertrophy, and adenotonsillar hypertrophy compared to subjects with nonobstructive adenoids or tonsils and to assess the correlation between hyoid bone and airway parameters. MATERIALS AND METHODS: A total of 121 subjects were grouped based on adenoid or tonsillar hypertrophy into four groups, as follows: (1) control group (C-group), (2) adenoid hypertrophy group (AH-group), (3) adenotonsillar hypertrophy group (ATH-group), and (4) tonsillar hypertrophy group (TH-group). Hyoid bone position and airway volumes were measured. The Kruskal-Wallis test was used for intergroup comparison, followed by pairwise comparison using the Mann-Whitney U-test. Bivariate correlation was conducted using Spearman correlation coefficients. Multiple linear regression was performed to create a model for airway volume based on hyoid bone predictive variables. RESULTS: No significant difference was found between subjects with isolated adenoid or tonsillar hypertrophy compared to the C-group. However, the ATH-group exhibited a significantly decreased hyoid bone vertical distance (HV), total airway volume (TA volume), and retroglossal airway volume (RG volume) compared to the C-group. HV and age had a high potential in terms of explaining the RG volume, whereas the TA volume and retropalatal airway volume (RP volume) models were not as successful as the RG volume counterpart. CONCLUSIONS: Subjects in ATH-group were characterized by an elevated hyoid bone position and constricted TA volume and RG volume compared to those in the C-group. HV and age were predictor variables that best explained retroglossal airway volume.

Electromyographic activities of the jaw and facial muscles in subjects with different vertical skeletal patterns and breathing modes.

BACKGROUND: Mouth breathing (MB) can affect morphological changes in the craniofacial structures, electromyography is widely used for quantitative analysis of muscle function. OBJECTIVE: The aim was to evaluate the electromyographic (EMG) activities of the anterior temporalis (TA), masseter muscle (MM), orbicularis oris superior (OOS) and mentalis muscle (MT) in children with different vertical skeletal patterns and breathing modes during rest and various functional mandibular movements. METHODS: BioEMG III was used to measure the variations in EMG activities of TA, MM, OOS, and MT in 185 subjects aged 6-12 years during continuous clenching, rest, maximal intercuspation, lips closed lightly and swallowing. RESULTS: The results of logistic regression analysis showed that the model with vertical skeletal patterns as the dependent variable was ineffective (p = .106), while the model with breathing modes as the dependent variable was effective (p = .000). When considering both vertical skeletal patterns and breathing modes, the following significant differences were found. (1) In the normal-angle group, the EMG ratio in OOS with lips closed lightly of MB was significantly higher than NB (p = .005). (2) In the low-angle group, EMG ratios in TA and MM during the swallowing of MB were significantly lower than NB (p = .020, p = .040, respectively). (3) In the high-angle group, EMG ratios of MB were significantly higher in MT during continuous clenching, rest, lips closed lightly and swallowing (p = .038, p = .036, p = .005, p = .028, respectively), and OOS with lips closed lightly compared to NB (p = .005). CONCLUSION: Breathing modes and vertical skeletal patterns interacted to alter maxillofacial EMG activities, with breathing modes having a greater effect.

A non-randomized concurrent controlled trial of myofunctional treatment in the mixed dentition children with functional mouth breathing assessed by cephalometric radiographs and study models.

OBJECTIVES: This study aimed to examine the clinical effects of myofunctional treatment on children with functional mouth breathing by cephalometric radiographs and study models. METHODS: A total of 224 children (6-10 years old; 114 males and 110 females; SNA°: 82.24 ± 1.67°; ANB°: 2.79 ± 0.80°, 28° < SN-GoGn° < 37°) formed three groups: MB-M group (mouth breathers with myofunctional treatment,n = 75); MB-N group (mouth breathers with no treatment,n = 70); NB group (nasal breathers with no treatment, n = 79). A blind evaluation of cephalometric radiographs and study models was conducted at T1(pre-study) and T2 (post-study), respectively. RESULTS: Two hundred four children (MB-M:66, MB-N:68, NB:70) completed the present study. At T1, MB-M and MB-N groups, compared to their NB counterpart, had greater anterior lower facial height(P < 0.01) and overjet(P < 0.001) but shorter overbite and maxillary canines width (P < 0.001). At T2, the MB-N group exhibited a higher ANB angle, anterior lower facial height, and overjet, but shorter overbite and maxillary canines width (P < 0.001). From T1 to T2, the anterior lower facial height increased, overbite and the maxillary canines width further decreased in the MB-N group (P < 0.001). However, in the MB-M group, the incisors were retracted, overbite increased (P < 0.001), anterior lower facial height increased insignificantly (P > 0.05), and maxillary canines width increased slightly (P < 0.05). In the NB and MB-M groups, the mandible showed a normal tendency to grow forward, whereas, in the MB-N group, the mandible showed a tendency to grow downward (P < 0.001). CONCLUSIONS: Mouth breathers demonstrated increased anterior facial height and overjet but reduced overbite and maxillary arch width, which improved significantly following myofunctional treatment. TRIAL REGISTRATION: TCTR: TCTR20220401001 . Registered 1stApril 2022-Retrospectively registered.

Three-dimensional evaluation of pharyngeal airway and maxillary arch in mouth and nasal breathing children with skeletal Class I and II.

OBJECTIVE: This study aimed to investigate whether the subjects with mouth breathing (MB) or nasal breathing (NB) with different sagittal skeletal patterns showed different maxillary arch and pharyngeal airway characteristics. METHODS: Cone-beam computed tomography scans from 70 children aged 10 to 12 years with sagittal skeletal Classes I and II were used to measure the pharyngeal airway, maxillary width, palatal area, and height. The independent t-test and the Mann-Whitney U test were used for the intragroup analysis of pharyngeal airway and maxillary arch parameters. RESULTS: In the Skeletal Class I group, nasopharyngeal airway volume (P < 0.01), oropharyngeal airway volume (OPV), and total pharyngeal airway volume (TPV) (all P < 0.001) were significantly greater in subjects with NB than in those with MB. Furthermore, intermolar width, maxillary width at the molars, intercanine width, maxillary width at the canines, and palatal area were significantly larger in subjects with NB than in those with MB (all P < 0.001). In the Skeletal Class II group, OPV, TPV (both P < 0.05) were significantly greater in subjects with NB than in those with MB. No significant differences in pharyngeal airway parameters in the MB group between subjects with Skeletal Class I and those with Skeletal Class II. CONCLUSION: Regardless of sagittal Skeletal Class I or II, the pharyngeal airway and maxillary arch in children with MB differ from those with NB. However, the pharyngeal airway was not significantly different between Skeletal Class I and II in children with MB.

Efficiency evaluation of maxillary molar distalization using Invisalign based on palatal rugae registration.

INTRODUCTION: This study aimed to compare the predicted maxillary molar distalization with the achieved clinical outcome using the palatal rugae area for registration and superimposition of digital models. Understanding Invisalign efficiency may assist clinicians in predicting changes, thus applying specific measures to minimize the chance of midcourse correction later. METHODS: The study sample included 38 patients with a mean age of 25.4 years, eligible for Invisalign treatment and requiring distalization of maxillary molars. Two digital models were acquired using iTero intraoral scanner (Align Technology, Santa Clara, Calif) before treatment and after maxillary first and second molar distalization. The 2 digital models were superimposed using the palatal rugae area for registration. The predicted tooth movement compared to the achieved values. One hundred forty-two maxillary molars (71 first molar and 71 second molar) were measured for distal movement, and 228 maxillary anterior teeth were evaluated for anterior anchorage loss. RESULTS: The predicted distal movement of the maxillary first molar (P <0.0001) and maxillary second molar (P <0.0001) differed significantly from the actual values. There was a statistically significant correlation between the amount of distal molar movement and the amount of anchorage loss (r = 0.3900, P <0.008) for the central incisor, and (r = 0.3595, P <0.013) for the lateral incisor. CONCLUSIONS: Invisalign can be used successfully for adult patients requiring maxillary molar distalization when a mean distalization movement of 2.6 mm was prescribed. Clinicians should be aware of the countereffect if maxillary molars are planned to move distally, especially if the patient presented initially with a large overjet, so the need to prescribe overcorrection or the use of auxiliaries can be addressed earlier.

Disrupted mitochondrial homeostasis coupled with mitotic arrest generates antineoplastic oxidative stress.

Reactive oxygen species (ROS) serve as critical signals in various cellular processes. Excessive ROS cause cell death or senescence and mediates the therapeutic effect of many cancer drugs. Recent studies showed that ROS increasingly accumulate during G2/M arrest, the underlying mechanism, however, has not been fully elucidated. Here, we show that in cancer cells treated with anticancer agent TH287 or paclitaxel that causes M arrest, mitochondria accumulate robustly and produce excessive mitochondrial superoxide, which causes oxidative DNA damage and undermines cell survival and proliferation. While mitochondrial mass is greatly increased in cells arrested at M phase, the mitochondrial function is compromised, as reflected by reduced mitochondrial membrane potential, increased SUMOylation and acetylation of mitochondrial proteins, as well as an increased metabolic reliance on glycolysis. CHK1 functional disruption decelerates cell cycle, spares the M arrest and attenuates mitochondrial oxidative stress. Induction of mitophagy and blockade of mitochondrial biogenesis, measures that reduce mitochondrial accumulation, also decelerate cell cycle and abrogate M arrest-coupled mitochondrial oxidative stress. These results suggest that cell cycle progression and mitochondrial homeostasis are interdependent and coordinated, and that impairment of mitochondrial homeostasis and the associated redox signaling may mediate the antineoplastic effect of the M arrest-inducing chemotherapeutics. Our findings provide insights into the fate of cells arrested at M phase and have implications in cancer therapy.

Autophagy Contributes to the Maintenance of Genomic Integrity by Reducing Oxidative Stress.

Autophagy has been well documented to play an important role in maintaining genomic stability. However, in addition to directly engulfing and digesting the damaged organelles and chromatin fragments, autophagy can affect many cellular processes including DNA damage response, regulation of redox homeostasis, and cell division; it remains to be determined to what extent each of those processes contributes to the maintenance of genomic stability. We here examined the role of autophagy-dependent redox regulation in the maintenance of genomic stability in two cancer cell lines (HT1080 and U2OS) and mesenchymal stem cells (MSCs) using micronuclei MN, also referred to as cytoplasmic chromatin fragments, as a marker. Our results showed that the spontaneous and genotoxic stress-induced frequencies of MN in cancer cells were significantly reduced by autophagy activators rapamycin and Torin1, and the reduction in MN was accompanied by a reduction in reactive oxygen species (ROS). Increased micronucleation in senescent MSCs, in which autophagic flux is blocked, was also attenuated by rapamycin, together with a reduction in ROS. Inhibition of autophagy by chloroquine (CQ) or ATG5 depletion, on the other hand, resulted in an increased frequency of MN, though a ROS elevation in response to autophagy inhibition was only observed in MSCs. Importantly, the induction of MN by autophagy inhibition in MSCs could be abrogated by antioxidant N-acetylcysteine (NAC). In contrast to the reported impairment of CHK1 activation in Atg7-deficient mouse embryonic fibroblasts, we found that the level of phosphorylated CHK1 was increased by CQ or ATG5 depletion but decreased by rapamycin or Torin1, suggesting that the increased genomic instability by defective autophagy is not caused by insufficient activation of CHK1-homologous recombination cascade. Together, our findings suggest that redox homeostasis regulated by autophagy contributes substantially to the maintenance of genomic stability in certain contexts.