Cell dynamics in Hertwig's epithelial root sheath are regulated by ß-catenin activity during tooth root development.

ß-catenin, a key mediator of Wnt signaling, plays multiple roles in tooth development. However, the role of ß-catenin in Hertwig's epithelial root sheath (HERS) during root formation remains unclear. In this study, we generated inducible tissue-specific ß-catenin conditional knockout mice (Ctnnb1i∆shh ) to investigate how ß-catenin in HERS affects tooth root development. The inactivation of ß-catenin in HERS led to interrupted root elongation due to premature disruption of HERS. This phenotype was accompanied by reduced cell-cell adhesion and decreased expression of junctional proteins, as well as increased epithelial-to-mesenchymal transition of HERS cells upon ß-catenin depletion. Accordingly, stabilization of ß-catenin in HERS (Catnbi∆shh ) led to the formation of unfragmented HERS and resulted in the failure of HERS dissociation, with increased expression of junctional proteins. Our results suggest that fine control of ß-catenin is important for HERS to guide root formation through regulating its structural integrity.

The opposing roles of the mTOR signaling pathway in different phases of human umbilical cord blood-derived CD34+ cell erythropoiesis.

As an indispensable, even lifesaving practice, red blood cell (RBC) transfusion is challenging due to several issues, including supply shortage, immune incompatibility, and blood-borne infections since donated blood is the only source of RBCs. Although large-scale in vitro production of functional RBCs from human stem cells is a promising alternative, so far, no such system has been reported to produce clinically transfusable RBCs due to the poor understanding of mechanisms of human erythropoiesis, which is essential for the optimization of in vitro erythrocyte generation system. We previously reported that inhibition of mammalian target of rapamycin (mTOR) signaling significantly decreased the percentage of erythroid progenitor cells in the bone marrow of wild-type mice. In contrast, rapamycin treatment remarkably improved terminal maturation of erythroblasts and anemia in a mouse model of ß-thalassemia. In the present study, we investigated the effect of mTOR inhibition with rapamycin from different time points on human umbilical cord blood-derived CD34+ cell erythropoiesis in vitro and the underlying mechanisms. Our data showed that rapamycin treatment significantly suppressed erythroid colony formation in the commitment/proliferation phase of erythropoiesis through inhibition of cell-cycle progression and proliferation. In contrast, during the maturation phase of erythropoiesis, mTOR inhibition dramatically promoted enucleation and mitochondrial clearance by enhancing autophagy. Collectively, our results suggest contrasting roles for mTOR in regulating different phases of human erythropoiesis.

Laparoscopic Management of 42 Cases of Tubal Stump Pregnancy and Postoperative Reproductive Outcomes.

STUDY OBJECTIVE: Tubal stump pregnancy is a rare variant of ectopic pregnancy. The aim of this study was to evaluate laparoscopic surgery for tubal stump pregnancy and to investigate postoperative pregnancy outcomes. DESIGN: Retrospective study. SETTING: University-affiliated hospital. PATIENTS: Patients (n = 42) diagnosed with tubal stump pregnancy. INTERVENTIONS: Data were extracted from the electronic medical records system of the hospital. MEASUREMENTS AND MAIN RESULTS: Patients diagnosed with tubal stump pregnancy between June 2010 and July 2018 were included. Data included demographic characteristics, gravidity and parity, history of pelvic surgery, clinical features, and treatment. All procedures were laparoscopic. Postoperative pregnancy outcomes were identified from electronic medical records or by telephone. Patients' mean age was 30 (range, 21-39) years. Twelve of 42 tubal stump pregnancies (28.6%) had ruptured ectopic pregnancy at the time of operation. The remaining 30 cases had intact stump pregnancy during surgery. Patients were followed for a mean of 31 (range, 10-60) months. Follow-up data were available for 33 of 39 patients (3 with heterotopic tubal stump pregnancy were not included in follow-up data because all resulted in a live births and had no desire for future pregnancy). Eighteen of 28 patients (64.3%) who attempted conception had intrauterine pregnancies (IUPs) during the follow-up period; of these 18 IUPs, 14 (77.8%) resulted in live births. There was 1 case of uterine rupture in a singleton pregnancy at 20+5 weeks that resulted in fetal death. Three of 18 IUPs (16.7%) ended in the first trimester with spontaneous abortions. CONCLUSION: Laparoscopic surgery is a feasible option for tubal stump pregnancy and is associated with favorable pregnancy outcomes.

Refinement of Global Domestic Horse Biogeography Using Historic Landrace Chinese Mongolian Populations.

The Mongolian horse is one of the oldest extant horse populations and although domesticated, most animals are free-ranging and experience minimal human intervention. As an ancient population originating in one of the key domestication centers, the Mongolian horse may play a key role in understanding the origins and recent evolutionary history of horses. Here we describe an analysis of high-density genome-wide single-nucleotide polymorphism (SNP) data in 40 globally dispersed horse populations (n = 895). In particular, we have focused on new results from Chinese Mongolian horses (n = 100) that represent 5 distinct populations. These animals were genotyped for 670K SNPs and the data were analyzed in conjunction with 35K SNP data for 35 distinct breeds. Analyses of these integrated SNP data sets demonstrated that the Chinese Mongolian populations were genetically distinct from other modern horse populations. In addition, compared to other domestic horse breeds, the Chinese Mongolian horse populations exhibited relatively high genomic diversity. These results suggest that, in genetic terms, extant Chinese Mongolian horses may be the most similar modern populations to the animals originally domesticated in this region of Asia. Chinese Mongolian horse populations may therefore retain ancestral genetic variants from the earliest domesticates. Further genomic characterization of these populations in conjunction with archaeogenetic sequence data should be prioritized for understanding recent horse evolution and the domestication process that has led to the wealth of diversity observed in modern global horse breeds.

Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/ß-catenin pathway in human ovarian cancer.

Overexpression of HOTAIR (HOX antisense intergenic RNA) is significantly correlated with tumor progression and poor prognosis in human ovarian cancer. However, the underlying mechanisms are largely unknown. In the present study, we investigated the roles of HOTAIR in the initiation and chemoresistance of ovarian cancer. As our data show, HOTAIR overexpression promoted cell cycle progression (and thus cell proliferation) by activating the wnt/ß-catenin signaling pathway. Likewise, knockdown of HOTAIR suppressed cell proliferation and arrested cell cycle at G1 phase via inhibition of wnt/ß-catenin signaling. Moreover, the results of primary culture demonstrated that elevated HOTAIR expression correlated positively with chemoresistance in ovarian cancer. In vitro and in vivo, HOTAIR induced cellular resistance to cisplatin by activating the wnt/ß-catenin pathway, which could be reversed by pre-treatment with the wnt/ß-catenin inhibitor, XAV939. In conclusion, HOTAIR promotes the initiation and chemoresistance of ovarian cancer by activating wnt/ß-catenin signaling, suggesting that HOTAIR might be a potent therapeutic target for ovarian cancer treatment.

Lexical pathway from L2 to L1 activation in intermediate proficient bilinguals: behavioral and ERP evidence.

Numerous studies have demonstrated that second language (L2) comprehension is often accompanied by activations in the first language (L1). Using both behavioral measurement and event-related potential (ERP), this study conducted two experiments to investigate whether a direct activation pathway exists from L2 lexical representation to L1 lexical representation (the lexical pathway) in intermediate proficient bilinguals. In Experiment 1, we designed a vowel letter search task on English word pairs, which enables bilinguals to prevent semantic priming in the first 300 ms processing stage after the words' onset. In Experiment 2, Mandarin-English bilinguals were recruited to complete this task on English word pairs with occasional first character repetition between the Chinese counterparts of a word pair. Results showed a significant main effect within both the P200 and N400 time windows, indicating the activation of bilinguals' L1 lexical representation during these intervals. However, the main effect of semantic relatedness was only significant in the N400 time window. These results suggest that bilinguals can activate their L1 lexical representation directly before engaging in conceptual representation. This finding supported a lexical pathway of activation from L2 lexical representation to L1 lexical representation during visual-word recognition in intermediate proficient bilinguals.

Reproductive outcome after laparoscopic ovarian cystectomy using barbed sutures versus conventional smooth sutures: A retrospective cohort study.

OBJECTIVE: To investigate the effects of barbed and conventional sutures on reproductive outcomes and ovarian reserve after laparoscopic treatment for benign non-endometrioma ovarian cysts. METHODS: This retrospective study was conducted at an affiliated women's hospital between May 2017 and December 2019. Patients with benign non-endometriotic ovarian cysts undergoing laparoscopic cystectomy were included. RESULTS: Patients received barbed sutures (221 patients) or conventional smooth sutures (203 patients) intraoperatively. The two groups had comparable baseline characteristics. The surgical duration and ovarian suturing time were significantly shorter in the barbed suture group than in the conventional smooth suture group (P < 0.001 and P = 0.002, respectively). The rate of postoperative hemoglobin decline and serum anti-Müllerian hormone decline were similar between the two groups (P > 0.05). A total of 316 (74.53%) patients experienced at least one pregnancy postoperatively: 170 (76.92%) and 146 (71.92%) patients in the barbed suture and conventional smooth suture groups, respectively (χ2 = 1.395, P = 0.238). Multivariate Poisson regression demonstrated that barbed sutures had no significant effect on the overall postoperative pregnancy rate (adjusted incidence rate ratio, 1.10; 95% confidence interval, 0.93-1.36; P = 0.382). CONCLUSION: In patients with benign non-endometriotic ovarian cysts undergoing laparoscopic ovarian cystectomy, barbed sutures had a reproductive outcome similar to that of conventional smooth sutures while providing higher surgical efficiency without adverse effects on the postoperative ovarian reserve. Barbed sutures are probably a viable option to conventional smooth sutures.

Effect of barbed suture versus conventional suture in laparo-endoscopic single-site cystectomy for ovarian mature cystic teratoma: An ambispective cohort study.

OBJECTIVE: To compare the effects of barbed suture (BS) and conventional suture (CS) on perioperative conditions and ovarian function in the excision of ovarian mature cystic teratoma (MCT) by laparo-endoscopic single-site surgery (LESS). METHODS: The present study is an ambispective cohort study conducted in an affiliated tertiary hospital between May 2019 and October 2020. Women treated by LESS cystectomy for unilateral ovarian MCT were included. BS or CS were applied in the surgery. RESULTS: BS and CS groups were matched 1:1 for age, body mass index and ovarian cyst volume (40 women per group). There were no significant differences in baseline characteristics. Mean operating time (53.89 ± 14.80 versuss 67.93 ± 19.23 min, P = 0.004) and suturing time (11.85 ± 6.68 versus 19.76 ± 12.75 min, P = 0.006) were significantly shorter in the BS group than the CS group. No significant differences were found in serum anti-Müllerian hormone (AMH) levels between groups at baseline, postoperative day 1, 3 months, and 12 months. However, serum AMH was significantly lower than baseline at postoperative day 1, 3 months, and 12 months in both groups. CONCLUSION: BS provides shorter operating and suturing time than CS, without increasing damage to ovarian function in LESS cystectomy for ovarian MCT.

Analysis of risk factors and model establishment of recurrence after endometrial polypectomy.

BACKGROUND: Currently, determining the postoperative recurrence of endometrial polyps is an unresolved issue, so we screened the risk factors to establish a nomogram for clinical practice. METHODS: From January 2012 to June 2020, 133 patients who underwent hysteroscopic endometrial polypectomy and diagnostic curettage due to suspicious endometrial polyps for the first time and were pathologically diagnosed as endometrial polyps after surgery. All patients were followed up for more than 12 months, and 9 (6.77%) cases were lost to follow-up. Logistic regression analysis of clinical factors was performed to screen independent risk factors and construct a column chart to predict the probability of adverse events. The fitting curve was used to validate the line graph. RESULTS: The ratio of patients with body mass index (BMI) <28 kg/m2 in the recurrence group was lower than in the non-recurrence group (P=0.028), as was the proportion of patients with polyp <2 cm (recurrence group vs. non-recurrence group, P=0.027) and the proportion of patients in the recurrence group treated with progesterone after surgery compared with non-recurrence group (P=0.003). However, the proportion of endometrial thickening in the recurrence group was higher than in the non-recurrence group (P=0.006). Age, BMI, polyp size, and endometrial thickening were independent risk factors for recurrence after endometrial polypectomy [odds ratio (OR) >1, P<0.05]. Progesterone therapy after surgery was an independent protective factor for recurrence after endometrial polypectomy (OR <1, P<0.05). Our nomogram was based on age, BMI, polyp size, endometrial thickening, and postoperative progesterone treatment. The maximum offset between the predicted curve and the ideal curve was 0.083, and the minimum offset between the model and the ideal model was 0.021. The height of the linear curve was close to that of the ideal curve. The U test showed P=0.898, greater than 0.05, indicating that the nomogram model passed the calibration test. The receiver operating characteristic curve was 0.886. CONCLUSIONS: Our nomogram based on age, BMI, polyp size, progesterone treatment, and endometrial thickening accurately predicted the risk of polyp recurrence after endometrial polypectomy and can be applied in clinical practice.

Bilingual Brains Learn to Use L2 Alliterations Covertly like Poets: Brain ERP Evidence.

Bilinguals were documented to access their native or first language (L1) during comprehension of their second languages (L2). However, it is uncertain whether they can access L2 when reading their first language. This study used the event-related potential (ERP) technique to demonstrate the implicit and unconscious access to English words when Chinese-English bilinguals read words in Chinese, their native language. The participants were asked to judge whether the Chinese words presented in pairs were semantically related or not, meanwhile unconscious of the occasional alliteration (repetition of the first phoneme) if the Chinese words were translated into English. While the concealed prime in English translations failed to affect the reaction time, the alliteration significantly modulated N400 among advanced English learners, especially for semantically unrelated word pairs. Critically, this modulation effect was discrepant between bilinguals with high-level and normal-level English proficiency. These results indicate that L2 activation is an unconscious correlate of native-language processing depending on L2 proficiency.

Semantic and Syntactic Processing During Comprehension: ERP Evidence From Chinese QING Structure.

Previous studies used BA and BEI structures as stimuli to infer that syntax-first models seemed not applicable in Chinese. However, there were inconsistent results of both within same structures and between different structures. Since sentence structures of stimuli were non-canonical as well as lacking wide representativeness in Chinese, we examined the processing mechanism of a more representative structure in Chinese, QING (QING + NP1 + V + NP2) structure in the current study. Four conditions, including correct sentences (CORRECT), semantic-violated sentences (SEMANTIC), syntactic-violated sentences (SYNTACTIC), and combined violated sentences (COMBINED), were composed by manipulating the V between NP1 and NP2. Results with respect to three types of violation were as follows. In the initial phrase (100-300 ms), there existed an interaction between SEMANTIC consistency and the SYNTACTIC category. In the intermediate phrase (300-500 ms), the interaction continued with similar negative waves evoked by three types of violated sentences. In the final phrase (500-700 ms), both SYNTACTIC or COMBINED evoked obvious negative waves. The current research of Qing structure provided new evidence for the processing mechanism of Chinese sentence patterns. Specifically, we found that the interactive model rather than the syntax-first model may apply to the processing of this specific structure of Chinese sentences and compared the results with those reported in previous studies that examined other types of sentence structures.

Rapid implicit extraction of abstract orthographic patterns of Chinese characters during reading.

Orthographic processing is crucial in reading. For the Chinese language, sub-lexical processing has already taken place at radical level. Previous literature reported early position-specific radical representations and later position-general radical representations, implying a possible separating process of abstract position information irrespective of radicals per se from radical representations during orthographic processing. However, it remains largely unclear whether the abstract pattern of spatial arrangement of radicals can be rapidly extracted, and if so, whether this extraction takes place at the visual cortex, the very first processing center. As the visual cortex is documented to actively participate in orthographic processing, it may also play a role in the possible extraction of abstract orthographic patterns of Chinese characters. Hence, we hypothesize that abstract orthographic patterns of Chinese characters are covertly extracted at the visual cortex during reading. In this study, we investigated whether the visual cortex could rapidly extract abstract structural patterns of Chinese characters, using the event-related potential (ERP) technique. We adopted an active oddball paradigm with two types of deviant stimuli different only in one feature, structural or tonal, from standard stimuli; in each of the two sessions, subjects focused conscious attention on one feature and neglected the other. We observed that the ERPs recorded at occipital electrodes responded differentially to standard and structural deviant stimuli in both sessions, especially within the time range of the occipital P200 component. Then, we extracted three source waves arising from different levels of the visual cortex. Early response differences (from 88 to 456 ms after stimulus onset) were observed between the source waves, probably arising from left primary/secondary and bilateral associative visual cortices, in response to standard and deviant stimuli that violated abstract structural patterns, whether subjects focused their attention on the character structure or not. This suggests rapid extraction of abstract structural patterns of Chinese characters in the visual cortex, no matter the abstract structural pattern was explicit or implicit to subjects. Note that the source waves arising from right primary/secondary visual cortices in response to standard and structural deviant stimuli did not differ at all, indicating that this extraction of the abstract structural pattern of Chinese characters was left-lateralized. Besides, no difference was observed between source waves originating from any level of the visual cortex to standard and deviant stimuli that violated abstract tonal patterns, until 768 ms when a late effect related to conscious detection of targets occurred at higher levels of the visual cortex. Note that at late stages (later than 698 ms after stimulus onset), responses arising from bilateral associative visual cortices to standard and target stimuli differed for both sessions, no matter the structural or tonal feature was attended to. Our findings support the primitive intelligence of visual cortex to rapidly extract abstract orthographic patterns of Chinese characters that might be engaged in further lexical processing. Our findings also suggest that this rapid extraction can take place implicitly during reading.

A Reciprocal Interaction between ß-Catenin and Osterix in Cementogenesis.

Although accumulating evidence indicates that both ß-catenin and osterix (Osx) are essential for bone and tooth development, few studies have investigated the interaction of these two key proteins in the context of cementogenesis. In this study, we used transgenic mice with constitutively active ß-catenin and inactive Osx in the dental mesenchyme to address this question. We found that cementoblasts with constitutively active ß-catenin require Osx to produce excessive cellular cementum, and that ablation of Osx prevents this abnormal accumulation. Importantly, cementoblasts transduced with retrovirus expressing constitutively active ß-catenin exhibited upregulation of Osx expression through direct binding to the promoter region of Osx. Osx regulates Lef1 expression and consequently could regulate T-cell factor/lymphoid enhancer factor (Tcf/Lef) binding activity in Wnt/ß-catenin signaling. However, the loss of Tcf/Lef binding activity by Osx ablation was not rescued by transduction of retrovirus expressing constitutively active ß-catenin or ectopic Lef1 overexpression. These results suggest that the Tcf/Lef binding activity of Wnt/ß-catenin signaling is Osx-dependent during cementogenesis. Moreover, Osx differentially regulates the expression of various Tcf family members, suggesting that Osx regulates cementogenesis by utilizing various Tcf/Lef-dependent mechanisms. This is the first report to show that downstream Osx signaling through Tcf/Lefs is critical for cementogenesis.

Nfic regulates tooth root patterning and growth.

Molecular interactions between epithelium and mesenchyme are important for root formation. Nuclear factor I-C (Nfic) has been identified as a key regulator of root formation. However, the mechanisms of root formation and their interactions between Hertwig's epithelial root sheath (HERS) and mesenchyme remain unclear. In this study, we investigated the role of Nfic in root patterning and growth during molar root development. The molars of Nfic knockout mice exhibited an enlarged pulp chamber and apical displacement of the pulpal floor, characteristic features of taurodontism, due to delayed furcation formation. In developing molar roots of mutant mice at P14, BrdU positive cells decreased in the apical mesenchyme of the elongation region whereas those cells increased in the dental papilla of the furcation region. Whereas cytokeratin 14 and laminin were localized in HERS cells of mutant molars, Smoothened (Smo) and Gli1 were downregulated in preodontoblasts. In contrast, cytokeratin 14 and Smo were localized in the cells of the furcation region of mutant molars. These results indicate that Nfic regulates cell proliferation in the dental mesenchyme and affects the fate of HERS cells in a site-specific manner. From the results, it is suggested that Nfic is required for root patterning and growth during root morphogenesis.

[Effect of processing time on the surface properties of titanium micro-arc oxidation film].

OBJECTIVE: To explore the effect of changes of processing time on the surface properties of titanium coating formed by micro-arc oxidation (MAO). METHODS: Forty-four disc-shaped pure titanium specimens with 10 mm diameter and 1 mm thickness were equally divided into 4 groups and processed by MAO technique in electrolytes containing 0.2 mol/L calcium acetate (CA) and 0.02 mol/L ß-glycerol phosphate disodium salt pentahydrate (ß-GP). The processing time were set at 1 min, 5 min, 10 min and 15 min respectively. The topograph of the MAO film surface and the film-substrate interface was observed by a scanning electron microscopy (SEM), and the composition was analyzed by an energy dispersive spectroscope (EDS) incorporated in the SEM. The phase and the microstructure of the film were analyzed by X-ray diffraction (XRD). The roughness of the film was measured using a roughness tester. The surface static contact angle was detected by a contact angle measurement instrument and the surface energy was calculated accordingly. RESULTS: With the increase of processing time from 1 min to 15 min, the pore size increased from (1.30 ± 0.07) µm to (1.55 ± 0.09) µm, and film thickness increased from (10.2 ± 1.1) µm to (20.9 ± 2.9) µm. The content of the Ca in the film increased accordingly, and Ca/P increased from 1.99 to 2.45, and the surface energy increased from 24.62 mJ/m(2) to 39.49 mJ/m(2). Meanwhile, the XRD pattern indicated that rutile increased but anatase and titanium decreased gradually. At the time of 15 min, part of the MAO film peeled off. CONCLUSIONS: Processing time has impact on the thickness, surface topography, crystal component and surface energy of titanium MAO coating. MAO film treated for 5 - 10 min demonstrated favorable surface properties.