Granulosa Cell-Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post-Ovulatory Follicle.

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

Ovarian overexpression of ASMT gene increases follicle numbers in transgenic sheep: Association with lipid metabolism.

Melatonin plays an important role in mammalian reproductive activities, to further understand the effects of endogenous melatonin on functions of ovary, the transgenic sheep with overexpression of melatonin synthetic enzyme gene ASMT in ovary were generated. The results showed that total melatonin content in follicular fluid of transgenic sheep was significantly greater than that in the wild type. Accordingly, the follicle numbers of transgenic sheep were also significantly greater than those in the WT. The results of follicular fluid metabolites sequencing showed that compared with WT, the differential metabolites of the transgenic sheep were significantly enriched in several signaling pathways, the largest number of metabolites was lipid metabolism pathway and the main differential metabolites were lipids and lipoid molecules. SMART-seq2 were used to analyze the oocytes and granulosa cells of transgenic sheep and WT sheep. The main differential enrichment pathway was metabolic pathway, in which lipid metabolism genes accounted for the majority. In conclusion, this is the first report to show that ovary overexpression of ASMT increased local melatonin production and follicle numbers. These results may imply that ASMT plays an important role in follicle development and formation, and melatonin intervention may be a potential method to promote this process.

Predicting the Invasiveness of Pulmonary Adenocarcinomas in Pure Ground-Glass Nodules Using the Nodule Diameter: A Systematic Review, Meta-Analysis, and Validation in an Independent Cohort.

The nodule diameter was commonly used to predict the invasiveness of pulmonary adenocarcinomas in pure ground-glass nodules (pGGNs). However, the diagnostic performance and optimal cut-off values were inconsistent. We conducted a meta-analysis to evaluate the diagnostic performance of the nodule diameter for predicting the invasiveness of pulmonary adenocarcinomas in pGGNs and validated the cut-off value of the diameter in an independent cohort. Relevant studies were searched through PubMed, MEDLINE, Embase, and the Cochrane Library, from inception until December 2022. The inclusion criteria comprised studies that evaluated the diagnostic accuracy of the nodule diameter to differentiate invasive adenocarcinomas (IAs) from non-invasive adenocarcinomas (non-IAs) in pGGNs. A bivariate mixed-effects regression model was used to obtain the diagnostic performance. Meta-regression analysis was performed to explore the heterogeneity. An independent sample of 220 pGGNs (82 IAs and 128 non-IAs) was enrolled as the validation cohort to evaluate the performance of the cut-off values. This meta-analysis finally included 16 studies and 2564 pGGNs (761 IAs and 1803 non-IAs). The pooled area under the curve, the sensitivity, and the specificity were 0.85 (95% confidence interval (CI), 0.82-0.88), 0.82 (95% CI, 0.78-0.86), and 0.73 (95% CI, 0.67-0.78). The diagnostic performance was affected by the measure of the diameter, the reconstruction matrix, and patient selection bias. Using the prespecified cut-off value of 10.4 mm for the mean diameter and 13.2 mm for the maximal diameter, the mean diameter showed higher sensitivity than the maximal diameter in the validation cohort (0.85 vs. 0.72, p < 0.01), while there was no significant difference in specificity (0.83 vs. 0.86, p = 0.13). The nodule diameter had adequate diagnostic performance in differentiating IAs from non-IAs in pGGNs and could be replicated in a validation cohort. The mean diameter with a cut-off value of 10.4 mm was recommended.

Mediating effects of depression on sleep disturbance and frailty in older adult type 2 diabetes patients in the community.

Introduction: With the progressive aging of the population, frailty is now a significant challenge in geriatrics research. A growing amount of evidence suggests that sleep disturbance and depression have independent effects on frailty, although the underlying mechanisms are not yet clear. This study aimed to investigate the mediating role of depression in the relationship between sleep disturbance and frailty in older adult patients with type 2 diabetes (T2DM) in the community. Method: Purposive sampling was used to collect face-to-face data from 342 community-dwelling T2DM patients in Chengdu, Sichuan Province, China, between February and May 2023. The Pittsburgh Sleep Quality Index (PSQI) scale was used to evaluate sleep quality, the Simple Geriatric Depression Scale (GDS-15) was used to evaluate depressive symptoms, and the FRAIL Scale (FRAIL) was used to evaluate frailty. Linear regression equation and bootstrap self-sampling were used to verify the mediating role of depressive symptoms in sleep disturbance and frailty. Result: The study found that sleep disturbance had a direct positive effect with frailty [ß = 0.040, 95% CI: (0.013, 0.069)]. Additionally, depression had a direct positive effect on frailty [ß = 0.130, 95% CI: (0.087, 0.173)], and depression was found to partially mediate the relationship between sleep disturbance and frailty. Conclusion: Poor sleep quality and frailty are common in patients with T2DM. To reduce the frailty of older adult T2DM patients, all levels of society (government, medical institutions, and communities) must pay more attention to mental health. A variety of interventions should be considered to improve sleep quality and depression, which in turn may prevent or control frailty.

Mediating effect of self-concealment between non-suicidal self-injury and internet addiction in college students: a cross-sectional study.

BACKGROUND: Internet addiction, defined as uncontrolled behaviour resulting from the use of the Internet without the influence of addictive substances, which can seriously impair academic, occupational and social functioning. Non-suicidal self-injury, defined as self-injurious behaviour without the intent to die, and its addictive characteristics are similar to those of Internet addiction. Currently, there is a lack of research on the relationship between non-suicidal self-injury and Internet addiction. The purpose of this study was to examine the relationship between non-suicidal self-injury and internet addiction among college students and the role of self-concealment in this relationship. METHODS: In this study, data were collected online between December 2022 and January 2023 from 600 university students in Chengdu, Sichuan Province, China, using purposive sampling. The questionnaires included the Non-Suicidal Self-Injury Inventory (NSSI), the Self-Concealment Scale (SCS) and the Internet Addiction Test (IAT). RESULTS: A total of 573 valid questionnaires were recovered, with a valid recovery rate of 95.50%. CONCLUTION: The results suggest that self-concealment plays a partial mediating role between non-suicidal self-injury and internet addiction among college students. The authors emphasized the importance of internet addiction. In order to reduce the occurrence of internet addiction, schools should provide targeted interventions to promote the psychological health of college students' internet addictive behaviours.

The FSH-mTOR-CNP signaling axis initiates follicular antrum formation by regulating tight junction, ion pumps, and aquaporins.

The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intraovarian mammalian target of rapamycin-C-type natriuretic peptide pathway, activated by follicle-stimulating hormone, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mammalian target of rapamycin in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.

The solid component within part-solid nodules: 3-dimensional quantification, correlation with the malignant grade of nonmucinous pulmonary adenocarcinomas, and comparisons with 2-dimentional measures and semantic features in low-dose computed tomography.

BACKGROUND: There is no consensus on 3-dimensional (3D) quantification method for solid component within part-solid nodules (PSNs). This study aimed to find the optimal attenuation threshold for the 3D solid component proportion in low-dose computed tomography (LDCT), namely the consolidation/tumor ratio of volume (CTRV), basing on its correlation with the malignant grade of nonmucinous pulmonary adenocarcinomas (PAs) according to the 5th edition of World Health Organization classification. Then we tested the ability of CTRV to predict high-risk nonmucinous PAs in PSNs, and compare its performance with 2-dimensional (2D) measures and semantic features. METHODS: A total of 313 consecutive patients with 326 PSNs, who underwent LDCT within one month before surgery and were pathologically diagnosed with nonmucinous PAs, were retrospectively enrolled and were divided into training and testing cohorts according to scanners. The CTRV were automatically generated by setting a series of attenuation thresholds from - 400 to 50 HU with an interval of 50 HU. The Spearman's correlation was used to evaluate the correlation between the malignant grade of nonmucinous PAs and semantic, 2D, and 3D features in the training cohort. The semantic, 2D, and 3D models to predict high-risk nonmucinous PAs were constructed using multivariable logistic regression and validated in the testing cohort. The diagnostic performance of these models was evaluated by the area under curve (AUC) of receiver operating characteristic curve. RESULTS: The CTRV at attenuation threshold of -250 HU (CTRV- 250HU) showed the highest correlation coefficient among all attenuation thresholds (r = 0.655, P < 0.001), which was significantly higher than semantic, 2D, and other 3D features (all P < 0.001). The AUCs of CTRV- 250HU to predict high-risk nonmucinous PAs were 0.890 (0.843-0.927) in the training cohort and 0.832 (0.737-0.904) in the testing cohort, which outperformed 2D and semantic models (all P < 0.05). CONCLUSIONS: The optimal attenuation threshold was - 250 HU for solid component volumetry in LDCT, and the derived CTRV- 250HU might be valuable for the risk stratification and management of PSNs in lung cancer screening.

FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells.

Female subfertility is an increasing reproductive issue worldwide, which is partially related to abnormal ovarian follicular development. Granulosa cells (GCs), by providing the necessary physical support and microenvironment for follicular development, play critical roles in maintaining female fertility. We previously showed that ectopic expression of four and a half LIM domains 2 (FHL2) promoted ovarian granulosa cell tumor progression. However, its function in follicular development and fertility remains unknown. Here, we confirmed that FHL2 is highly expressed in human and mouse ovaries. FHL2 immunosignals were predominantly expressed in ovarian GCs. A Fhl2 knockout (KO) mouse model was generated to examine its roles in follicular development and fertility. Compared with wildtype, knockout of Fhl2 significantly decreased female litter size and offspring number. Furthermore, Fhl2 deficiency reduced ovarian size and impaired follicular development. RNA-sequencing analysis of GCs isolated from either KO or WT mice revealed that, Fhl2 deletion impaired multiple biological functions and signaling pathways, such as Ovarian Putative Early Atresia Granulosa Cell, ErbB, Hippo/YAP, etc. In vitro studies confirmed that FHL2 silencing suppressed GCs growth and EGF-induced GCs proliferation, while its overexpression promoted GC proliferation and decreased apoptosis. Mechanistic studies indicated that FHL2, via forming complexes with transcriptional factors AP-1 or NF-κB, regulated Egf and Egfr expression, respectively. Besides, FHL2 depletion decreased YAP1 expression, especially the active form of YAP1 (nuclear YAP1) in GCs of growing follicles. EGF, serving as an autocrine/paracrine factor, not only induced FHL2 expression and nuclear accumulation, but also stimulated YAP1 expression and activation. Collectively, our study suggests that FHL2 interacts with EGFR and Hippo/YAP signaling to regulate follicular development and maintain fertility. This study illuminates a novel mechanism for follicular development and a potential therapeutic target to address subfertility.

An ordinal radiomic model to predict the differentiation grade of invasive non-mucinous pulmonary adenocarcinoma based on low-dose computed tomography in lung cancer screening.

OBJECTIVES: To construct a radiomic model of low-dose CT (LDCT) to predict the differentiation grade of invasive non-mucinous pulmonary adenocarcinoma (IPA) and compare its diagnostic performance with quantitative-semantic model and radiologists. METHODS: A total of 682 pulmonary nodules were divided into the primary cohort (181 grade 1; 254 grade 2; 64 grade 3) and validation cohort (69 grade 1; 99 grade 2; 15 grade 3) according to scanners. The radiomic and quantitative-semantic models were built using ordinal logistic regression. The diagnostic performance of the models and radiologists was assessed by the area under the curve (AUC) of the receiver operating characteristic curve and accuracy. RESULTS: The radiomic model demonstrated excellent diagnostic performance in the validation cohort (AUC, 0.900 (95%CI: 0.847-0.939) for Grade 1 vs. Grade 2/Grade 3; AUC, 0.929 (95%CI: 0.882-0.962) for Grade 1/Grade 2 vs. Grade 3; accuracy, 0.803 (95%CI: 0.737-0.857)). No significant difference in diagnostic performance was found between the radiomic model and radiological expert (AUC, 0.840 (95%CI: 0.779-0.890) for Grade 1 vs. Grade 2/Grade 3, p = 0.130; AUC, 0.852 (95%CI: 0.793-0.900) for Grade 1/Grade 2 vs. Grade 3, p = 0.170; accuracy, 0.743 (95%CI: 0.673-0.804), p = 0.079), but the radiomic model outperformed the quantitative-semantic model and inexperienced radiologists (all p < 0.05). CONCLUSIONS: The radiomic model of LDCT can be used to predict the differentiation grade of IPA in lung cancer screening, and its diagnostic performance is comparable to that of radiological expert. KEY POINTS: • Early identifying the novel differentiation grade of invasive non-mucinous pulmonary adenocarcinoma may provide guidance for further surveillance, surgical strategy, or more adjuvant treatment. • The diagnostic performance of the radiomic model is comparable to that of a radiological expert and superior to that of the quantitative-semantic model and inexperienced radiologists. • The radiomic model of low-dose CT can be used to predict the differentiation grade of invasive non-mucinous pulmonary adenocarcinoma in lung cancer screening.

Radiomic and quantitative-semantic models of low-dose computed tomography for predicting the poorly differentiated invasive non-mucinous pulmonary adenocarcinoma.

PURPOSE: Poorly differentiated invasive non-mucinous pulmonary adenocarcinoma (IPA), based on the novel grading system, was related to poor prognosis, with a high risk of lymph node metastasis and local recurrence. This study aimed to build the radiomic and quantitative-semantic models of low-dose computed tomography (LDCT) to preoperatively predict the poorly differentiated IPA in nodules with solid component, and compare their diagnostic performance with radiologists. MATERIALS AND METHODS: A total of 396 nodules from 388 eligible patients, who underwent LDCT scan within 2 weeks before surgery and were pathologically diagnosed with IPA, were retrospectively enrolled between July 2018 and December 2021. Nodules were divided into two independent cohorts according to scanners: primary cohort (195 well/moderate differentiated and 64 poorly differentiated) and validation cohort (104 well/moderate differentiated and 33 poorly differentiated). The radiomic and quantitative-semantic models were built using multivariable logistic regression. The diagnostic performance of the models and radiologists was assessed by area under curve (AUC) of receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity. RESULTS: No significant differences of AUCs were found between the radiomic and quantitative-semantic model in primary and validation cohorts (0.921 vs. 0.923, P = 0.846 and 0.938 vs. 0.911, P = 0.161). Both the models outperformed three radiologists in the validation cohort (all P < 0.05). CONCLUSIONS: The radiomic and quantitative-semantic models of LDCT, which could identify the poorly differentiated IPA with excellent diagnostic performance, might provide guidance for therapeutic decision making, such as choosing appropriate surgical method or adjuvant chemotherapy.

[Association Between Medication Compliance and Various Risky Behaviors in Patients With Schizophrenia]. / ç²¾ç¥žåˆ†è£‚ç—‡æ‚£è€ æœè¯ä¾ä»Žæ€§ä¸Žä¸åŒç±»åž‹å±é™©è¡Œä¸ºçš„å ³è”ç ”ç©¶.

Objective: To investigate the status of medication adherence and various types of risky behaviors of schizophrenia patients in a certain area of western China and to explore accordingly the correlation between the two. Methods: A total of 292 667 patients with schizophrenia were enrolled in a follow-up survey between 2006 and 2018. In addition, based on the outcome-wide analysis strategy, a multivariate Cox proportional risk regression model was used to estimate and compare the impact of medication adherence on different types of risky behaviors in schizophrenia patients. Results: In this 13-year prospective cohort, 65 175 patients (31.4%) showed good medication adherence, while 142 394 patients (68.6%) showed poor medication adherence. The incidence rates of various risky behaviors during the follow-up period were as follows, minor nuisances, 12.25%, violation of the Law of the People's Republic of China on Penalties for Administration of Public Security (APS law), 3.82%, violation of criminal law, 0.94%, suicide completed, 0.28%, self-harm, 1.42%, and attempted suicide, 0.82%. Schizophrenia patients who had poor medication adherence had higher risks of committing violence against others and self-inflicted injury compared to patients with good medication adherence did, with the associated effects being minor nuisances (hazard ratio [HR]=1.31, 95% confidence interval [CI]: 1.27-1.35), violation of APS law (HR=1.47, 95% CI: 1.38-1.56), violation of criminal law (HR=1.17, 95% CI: 1.05-1.31), and self-harm (HR=1.43, 95% CI: 1.32-1.56), respectively, while the risk of suicide completed is lower in schizophrenia patients with poor medication adherence than that in patients with good medication adherence (HR=0.56, 95% CI: 0.47-0.66). There was no statistically significant association between attempted suicide and medication adherence. Conclusion: There are variations in the direction and strength of the association between medication adherence and different types of risky behaviors and further research is needed to elucidate the mechanisms of the association.

Quantitative parameters of enhanced dual-energy computed tomography for differentiating lung cancers from benign lesions in solid pulmonary nodules.

Objectives: This study aimed to investigate the ability of quantitative parameters of dual-energy computed tomography (DECT) and nodule size for differentiation between lung cancers and benign lesions in solid pulmonary nodules. Materials and Methods: A total of 151 pathologically confirmed solid pulmonary nodules including 78 lung cancers and 73 benign lesions from 147 patients were consecutively and retrospectively enrolled who underwent dual-phase contrast-enhanced DECT. The following features were analyzed: diameter, volume, Lung CT Screening Reporting and Data System (Lung-RADS) categorization, and DECT-derived quantitative parameters including effective atomic number (Zeff), iodine concentration (IC), and normalized iodine concentration (NIC) in arterial and venous phases. Multivariable logistic regression analysis was used to build a combined model. The diagnostic performance was assessed by area under curve (AUC) of receiver operating characteristic curve, sensitivity, and specificity. Results: The independent factors for differentiating lung cancers from benign solid pulmonary nodules included diameter, Lung-RADS categorization of diameter, volume, Zeff in arterial phase (Zeff_A), IC in arterial phase (IC_A), NIC in arterial phase (NIC_A), Zeff in venous phase (Zeff_V), IC in venous phase (IC_V), and NIC in venous phase (NIC_V) (all P < 0.05). The IC_V, NIC_V, and combined model consisting of diameter and NIC_V showed good diagnostic performance with AUCs of 0.891, 0.888, and 0.893, which were superior to the diameter, Lung-RADS categorization of diameter, volume, Zeff_A, and Zeff_V (all P < 0.001). The sensitivities of IC_V, NIC_V, and combined model were higher than those of IC_A and NIC_A (all P < 0.001). The combined model did not increase the AUCs compared with IC_V (P = 0.869) or NIC_V (P = 0.633). Conclusion: The DECT-derived IC_V and NIC_V may be useful in differentiating lung cancers from benign lesions in solid pulmonary nodules.

The impact of implicit theories on resilience among Chinese nurses: The chain mediating effect of grit and meaning in life.

Implicit theories refer to assumptions people hold about different domains, also known as mindsets. There are two implicit theories on the malleability of one's ability: entity theory and incremental theory. They constrain and regulate people's understanding and responses to an individual's behavior, leading to different social cognitive patterns and behavioral responses. Resilience is a positive adaptation in highly stressful situations that represents mechanisms for coping with and transcending difficult experiences, i.e., a person's ability to successfully adapt to change, resist the adverse effects of stressors, avoid significant dysfunction, and be chronically affected by considered a protective factor for mental health. Although previous studies showed that individuals' implicit theories are associated with resilience, this relationship has received little attention in the nursing population. It is unclear which variables may contribute to explaining the relationship between implicit theories and resilience. Therefore, the current study aims to deeply explore the relationship between implicit theories and the resilience of Chinese nurses. In addition, we also seek to demonstrate the chain mediating effects of grit and meaning in life on this relationship. We surveyed 709 Chinese nurses through online questionnaires using the self-made demographic questionnaire, the Implicit Theories Scale, the Short Grit Scale, the Meaning in Life Questionnaire, and the 10-item Connor-Davidson Resilience Scale. After controlling for demographic variables such as age, gender, educational background, marital status, professional title, and working years, the results reveal positive associations between Chinese nurses' implicit theories and their resilience, and grit and meaning in life play a partial mediating role in this relationship, respectively. Furthermore, grit and meaning in life play a chain mediating role between implicit theories and resilience. These findings contribute to understanding the psychological impact mechanism of implicit theories on nurses' resilience and provide a theoretical basis for nursing managers to formulate strategies to improve nurses' psychological resilience.

Anti-Müllerian Hormone Inhibits FSH-Induced Cumulus Oocyte Complex In Vitro Maturation and Cumulus Expansion in Mice.

Anti-Müllerian hormone (AMH) is secreted by the ovaries of female animals and exerts its biological effects through the type II receptor (AMHR2). AMH regulates follicular growth by inhibiting the recruitment of primordial follicles and reducing the sensitivity of antral follicles to FSH. Despite the considerable research on the actions of AMH in granulosa cells, the effect of AMH on the in vitro maturation of oocytes remains largely unknown. In the current study, we showed that AMH is only expressed in cumulus cells, while AMHR2 is produced in both cumulus cells and oocytes. AMH had no significant effect on COCs nuclear maturation, whereas it inhibited the stimulatory effects of FSH on COCs maturation and cumulus expansion. Moreover, AMH treatment effectively inhibited the positive effect of FSH on the mRNA expressions of Hyaluronan synthase 2 (Has2), Pentraxin 3 (Ptx3), and TNF-alpha-induced protein 6 (Tnfaip 6) genes in COCs. In addition, AMH significantly decreased the FSH-stimulated progesterone production, but did not change estradiol levels. Taken together, our results suggest that AMH may inhibit the effects of FSH-induced COCs in vitro maturation and cumulus expansion. These findings increase our knowledge of the functional role of AMH in regulating folliculogenesis.

Development and validation of qualitative and quantitative models to predict invasiveness of lung adenocarcinomas manifesting as pure ground-glass nodules based on low-dose computed tomography during lung cancer screening.

Background: Due to different management strategy and prognosis of different subtypes of lung adenocarcinomas appearing as pure ground-glass nodules (pGGNs), it is important to differentiate invasive adenocarcinoma (IA) from adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/MIA) during lung cancer screening. The aim of this study was to develop and validate the qualitative and quantitative models to predict the invasiveness of lung adenocarcinoma appearing as pGGNs based on low-dose computed tomography (LDCT) and compare their diagnostic performance with that of intraoperative frozen section (FS). Methods: A total of 223 consecutive pathologically confirmed pGGNs from March 2018 to December 2020 were divided into a primary cohort (96 IAs and 64 AIS/MIAs) and validation cohort (39 IAs and 24 AIS/MIAs) according to scans (Brilliance iCT and Somatom Definition Flash) performed at Sichuan Cancer Hospital and Institute. The following LDCT features of pGGNs were analyzed: the qualitative features included nodule location, shape, margin, nodule-lung interface, lobulation, spiculation, pleural indentation, air bronchogram, vacuole, and vessel type, and the quantitative features included the diameter, volume, and mean attenuation. Multivariate logistic regression analysis was used to build a qualitative model, quantitative model, and combined qualitative and quantitative model. The diagnostic performance was assessed according to the following factors: the area under curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity, and accuracy. Results: The AUCs of the qualitative model, quantitative model, combined qualitative and quantitative model, and the FS diagnosis were 0.854, 0.803, 0.873, and 0.870, respectively, in the primary cohort and 0.884, 0.855, 0.875, and 0.946, respectively, in the validation cohort. No significant difference of the AUCs was found among the radiological models and the FS diagnosis in the primary or validation cohort (all corrected P>0.05). Among the radiological models, the combined qualitative and quantitative model consisting of vessel type and volume showed the highest accuracy in both the primary and validation cohorts (0.831 and 0.889, respectively). Conclusions: The diagnostic performances of the qualitative and quantitative models based on LDCT to differentiate IA from AIS/MIA in pGGNs are equivalent to that of intraoperative FS diagnosis. The vessel type and volume can be preoperative and non-invasive biomarkers to assess the invasive risk of pGGNs in lung cancer screening.

WDR62 regulates mouse oocyte meiotic maturation related to p-JNK and H3K9 trimethylation.

WDR62 (WD40-repeat protein 62) participates in diverse biological process, especially mitotic spindle organization via regulating centriole biogenesis and the function of centriole-associated protein. However, the role of WDR62 exerts in spindle assembly and meiotic progression control in oocytes lacking typical centrosomes remains obscure. In a previous study, we reported that WDR62 is involved in spindle migration and asymmetric cytokinesis in mouse oocyte meiosis. In the current study, another novel function of WDR62 regulating cell cycle progression through meiotic spindle formation during oocyte meiotic maturation was found. Knockdown of WDR62 through siRNA microinjection disrupted the meiotic cell cycle and induced metaphase-I (MI) arrest coupled with severe spindle abnormality, chromosome misalignment, and aneuploid generation. Moreover, WDR62 depletion induced defective kinetochore-microtubule attachments (K-MT) and activated spindle assembly checkpoint (SAC), which could trigger the arrest of meiotic progression. Further study demonstrated that depletion of WDR62 was associated with an aberrant location of p-JNK and reduced its expression level; concomitantly, status of H3K9 trimethylation was also altered. In addition, phenotypes similar to WDR62 depletion were observed during the function-loss analysis of p-JNK using a specific inhibitor (SP600125), which signifies that WDR62 is important for spindle organization and meiotic progression, and this function might be via its regulation of p-JNK. In conclusion, this study revealed that WDR62 functions in multiple ways during oocyte meiotic maturation, which could be related to p-JNK and H3K9 trimethylation.

Psychometric Properties of the Grit-S in Chinese Nurses.

Grit, as a positive psychological trait, could affect the stability of nursing workforce and nurses' physical and mental health continuously. The Short Grit Scale (Grit-S) with fewer items than the original Grit Scale was widely used to measure individual trait-level grit. However, the psychological properties of Grit-S among Chinese nurses have not been verified. A self-designed sociodemographic questionnaire was used to investigate 709 Chinese nurses in the study, and Grit-S, Big Five Inventory-44, Brief Self-Control Scale, 10-item Connor-Davidson resilience scale, and Task Performance Scale were adopted to collect information of grit, personality, self-control, resilience, and work performance. The confirmatory factor analysis, Pearson correlation analysis, hierarchical regression analysis, and multi-group confirmatory factor analysis were conducted to verify the psychometric properties of the Grit-S. The results demonstrated that the Grit-S had sound validity and reliability among Chinese nurse samples and had good measurement invariance across nurses in general hospitals and psychiatric hospitals. The results of this study provide confidence in using the grit measurement among Chinese nurse in the future.

Improvement of image quality of laryngeal squamous cell carcinoma using noise-optimized virtual monoenergetic image and nonlinear blending image algorithms in dual-energy computed tomography.

BACKGROUND: Dual-energy computed tomography (DECT) has been used to improve image quality of head and neck squamous cell carcinoma (SCC). This study aimed to assess image quality of laryngeal SCC using linear blending image (LBI), nonlinear blending image (NBI), and noise-optimized virtual monoenergetic image (VMI+) algorithms. METHODS: Thirty-four patients with laryngeal SCC were retrospectively enrolled between June 2019 and December 2020. DECT images were reconstructed using LBI (80 kV and M_0.6), NBI, and VMI+ (40 and 55 keV) algorithms. Contrast-to-noise ratio (CNR), tumor delineation, and overall image quality were assessed and compared. RESULTS: VMI+ (40 keV) had the highest CNR and provided better tumor delineation than VMI+ (55 keV), LBI, and NBI, while NBI provided better overall image quality than VMI+ and LBI (all corrected p < 0.05). CONCLUSIONS: VMI+ (40 keV) and NBI improve image quality of laryngeal SCC and may be preferable in DECT examination.

A Prepubertal Mice Model to Study the Growth Pattern of Early Ovarian Follicles.

Early folliculogenesis begins with the activation of the follicle and ends with the formation of the follicular antrum, which takes up most of the time of folliculogenesis. In this long process, follicles complete a series of developmental events, including but not limited to granulosa cell (GC) proliferation, theca folliculi formation, and antrum formation. However, the logical or temporal sequence of these events is not entirely clear. This study demonstrated in a mouse model that completion of early folliculogenesis required a minimum of two weeks. The oocyte reached its largest size in the Type 4-5 stage, which was therefore considered as the optimum period for studying oogenesis. Postnatal days (PD) 10-12 were regarded as the crucial stage of theca folliculi formation, as Lhcgr sharply increased during this stage. PD13-15 was the rapid growth period of early follicles, which was characterized by rapid cell proliferation, the sudden emergence of the antrum, and increased Fshr expression. The ovarian morphology remained stable during PD15-21, but antrum follicles accumulated gradually. Atresia occurred at all stages, with the lowest rate in Type 3 follicles and no differences among early Type 4-6 follicles. The earliest vaginal opening was observed at PD24, almost immediately after the first growing follicular wave. Therefore, the period of PD22-23 could be considered as a suitable period for studying puberty initiation. This study objectively revealed the pattern of early folliculogenesis and provided time windows for the study of biological events in this process.

Melatonin Alleviates the Suppressive Effect of Hypoxanthine on Oocyte Nuclear Maturation and Restores Meiosis via the Melatonin Receptor 1 (MT1)-Mediated Pathway.

It is well known that hypoxanthine (HX) inhibits nuclear maturation of oocytes by elevating the intracellular cAMP level, while melatonin (MT) is a molecule that reduces cAMP production, which may physiologically antagonize this inhibition and restore the meiosis process. We conducted in vitro and in vivo studies to examine this hypothesis. The results showed that 10-3 M MT potentiated the inhibitory effect of HX on mouse oocyte meiosis by lowering the rate of germinal vesicle breakdown (GVBD) and the first polar body (PB1). However, 10-5 M and 10-7 M MT significantly alleviated the nuclear suppression induced by HX and restored meiosis in 3- and 6-week-old mouse oocytes, respectively. We identified that the rate-limiting melatonin synthetic enzyme AANAT and melatonin membrane receptor MT1 were both expressed in oocytes and cumulus cells at the GV and MII stages. Luzindole, a non-selective melatonin membrane receptor antagonist, blocked the activity of MT on oocyte meiotic recovery (P < 0.05). This observation indicated that the activity of melatonin was mediated by the MT1 receptor. To understand the molecular mechanism further, MT1 knockout (KO) mice were constructed. In this MT1 KO animal model, the PB1 rate was significantly reduced with the excessive expression of cAPM synthases (Adcy2, Adcy6, Adcy7, and Adcy9) in the ovaries of these animals. The mRNA levels of Nppc and Npr2 were upregulated while the genes related to progesterone synthesis (Cyp11a11), cholesterol biosynthesis (Insig1), and feedback (Lhcgr, Prlr, and Atg7) were downregulated in the granulosa cells of MT1 KO mice (P < 0.05). The altered gene expression may be attributed to the suppression of oocyte maturation. In summary, melatonin protects against nuclear inhibition caused by HX and restores oocyte meiosis via MT1 by reducing the intracellular concentration of cAMP.