SP1 impacts the primordial to primary follicle transition by regulating cholesterol metabolism in granulosa cells.

The primordial to primary follicle transition (PPT) in the ovary is critical to maintain sustainable reproductive resources in female mammals. However, it is unclear how granulosa cells (GCs) of the primary follicle participate in regulating PPT. This study focused on exploring the role of transcription factor Sp1 (SP1) in regulating PPT based on the fact that SP1 is pivotal for pregranulosa cell proliferation before primordial follicle formation. The results showed that mice fertility was prolonged when Sp1 was specifically depleted from GCs (GC- Sp1 -/- ). Besides, the PPT in GC- Sp1 -/- mice was reduced, resulting in more primordial follicles being preserved. Single-cell RNA-seq also indicated that the level of cholesterol metabolism was downregulated in GC- Sp1 -/- mice. Additionally, the PPT was promoted by either overexpression of ferredoxin-1 (FDX1), one of the key genes in mediating cholesterol metabolism or supplementing cholesterol for cultured fetal ovaries. Collectively, SP1 in GCs participates in the metabolism of cholesterol partially by regulating the transcription of Fdx1 during the PPT.

The more peers are present, the more adventurous? How peer presence influences adolescent pedestrian safety.

Objective: Adolescence is a high-risk period for traffic injury. One factor that may impact adolescent safety in traffic is the presence of peers. We conducted a quasi-experimental research study to examine the impact of peer presence, peer familiarity, and peer group size on adolescent pedestrian risk-taking intentions in both sidewalk and street-crossing settings. Methods: 607 students aged 12-18 years from Nantong city, China, completed a questionnaire that presented 20 traffic scenarios. The scenarios varied based on a 3 (peer group size: no peer vs. one peer vs. multiple peers) x 2 (peer familiarity: familiar vs. unfamiliar) x 2 (traffic setting: crossing the street vs. walking on the roadside) experimental design. Adolescents' responses indicated safer vs riskier intentions in each situation. Results: Results found that: (1) Adolescents were safer when walking on the sidewalk than when crossing the street; (2) Whether crossing the street or walking on the sidewalk, adolescents' behavioral intentions were safer when there were peers present than when there were no peers present; (3) Adolescents' safety tended to be higher overall with unfamiliar peers than with familiar peers; (4) Adolescents were less safe when crossing the street with familiar peer(s) than with unfamiliar peer(s), but no differences emerged when walking on the sidewalk. Conclusions: Adolescents report safer behavior when walking with a peer or peers compared with walking alone. Familiar peers reduce adolescents' safety of behavior intentions in traffic, especially when crossing the street.

SIRT1 reduction contributes to doxorubicin-induced oxidative stress and meiotic failure in mouse oocytes.

Impaired fertility is the major side effect of chemotherapy for female cancer patients, accumulated evidence indicates this is associated with damage on oocyte quality, but the underlying mechanisms remain unclear. Previously we reported that doxorubicin (DXR) exposure, one of the most widely used chemotherapy drugs, disrupted mouse oocyte meiotic maturation in vitro. In the current study, we identified that SIRT1 expression was remarkably reduced in DXR exposure oocytes. Next, we found that increasing SIRT1 expression by resveratrol partially alleviated the effects of DXR exposure on oocyte maturation, which was counteracted by SIRT1 inhibition. Furthermore, we revealed that increasing SIRT1 expression mitigated DXR induced oocyte damage through reducing ROS levels, increasing antioxidant enzyme MnSOD expression, and preventing spindle and chromosome disorganization, lowering the incidence of aneuploidy. Importantly, by performing in vitro fertilization and embryo transfer assays, we demonstrated that increasing SIRT1 expression significantly improved the fertilization ability, developmental competence of oocytes and early embryos. In summary, our data uncover that SIRT1 reduction represents one mechanism that mediates the effects of DXR exposure on oocyte quality.

The efficacy and safety of temperature controlled dual-mode radiofrequency in women with vaginal laxity.

OBJECTIVE: Vaginal laxity could negatively influence women's sexual function. This study aimed to explore the efficacy and safety of temperature controlled dual-mode (monopolar and bipolar) radiofrequency (RF) in women with vaginal laxity. METHODS: A total of 102 patients with vaginal laxity were treated with temperature-controlled RF. The present study implemented Vaginal Laxity Questionnaire (VLQ), Female Sexual Function Index (FSFI) questionnaire and Sexual Satisfaction Questionnaire (SSQ) on all patients at baseline and after treatment. Pelvic Organ Prolapse Quantification System (POP-Q) system was applied to physical examination, and vaginal manometer to examine the strength of voluntary contractions of the pelvic floor muscles. RESULTS: The VLQ score was gradually increased after RF treatment at 1, 3, 6 and 12 months, accompanying by the significant improvement in total FSFI scores and the six domains (sexual desire, sexual arousal, lubrication, orgasm, satisfaction, pain). The increased sexual satisfaction based on the SSQ score was found after temperature-controlled RF. The result of POP-Q stage showed significant difference in women after treatment, with the women having Stage I of 45.10% at baseline, 36.27% at 1 month, 28.43% at 3 months, 19.61% at 6 months and 10.78% at 12 months. The mean pressure and mean duration of pelvic contractions were increased gradually at the 1-, 3-, 6- and 12- month follow-up. CONCLUSION: Temperature controlled dual-mode (monopolar and bipolar) radiofrequency may be associated with improvement of vaginal laxity, and contribute to enhancement to female sexual function and pelvic floor muscles.

Roles of individual differences and traffic environment factors on children's street-crossing behaviour in a VR environment.

OBJECTIVE: Pedestrian injuries are among the most common cause of death and serious injury to children. A range of risk factors, including individual differences and traffic environment factors, has been investigated as predictors of children's pedestrian behaviours. There is little evidence examining how risk factors might interact with each other to influence children's risk, however. The present study examined the independent and joint influences of individual differences (sex and sensation seeking) and traffic environment factors (vehicle speeds and inter-vehicle distances) on children's pedestrian safety. METHODS: A total of 300 children aged 10-13 years were recruited to complete a sensation-seeking scale, and 120 of those were selected for further evaluation based on having high or low sensation-seeking scores in each gender, with 30 children in each group. Children's pedestrian crossing behaviours were evaluated in a virtual reality traffic environment. RESULTS: Children low in sensation seeking missed more opportunities to cross and had longer start gaps to enter the roadway compared with those high in sensation seeking, and these effects were more substantial when vehicles were spread further apart but travelling slowly. Interaction effects between inter-vehicle distance and vehicle speed were also detected, with children engaging in riskier crossings when the car was moving more quickly and the vehicles were spread further than when the vehicles were moving quickly but were closer together. No sex differences or interactions emerged. CONCLUSION: Both sensation seeking and traffic environment factors impact children's behaviour in traffic, and there are interactions between traffic speeds and inter-vehicle distances that impact crossing behaviour.

Lnc-MEG3 acts as a potential biomarker for predicting increased disease risk, systemic inflammation, disease severity, and poor prognosis of sepsis via interacting with miR-21.

BACKGROUND: This study aimed to investigate the correlations of long non-coding RNA maternally expressed gene 3 (lnc-MEG3), microRNA (miR)-21, and lnc-MEG3/miR-21 axis with disease risk, inflammation, disease severity, and 28-day mortality of sepsis. METHODS: Totally, 219 sepsis patients and 219 health controls (HCs) were enrolled. Plasma samples were obtained from sepsis patients within 24 hours after admission and from HCs on enrollment to detect lnc-MEG3 and miR-21 expressions by real-time quantitative polymerase chain reaction. RESULTS: The lnc-MEG3 expression and lnc-MEG3/miR-21 axis were increased, while miR-21 expression was decreased in sepsis patients compared with HCs. Lnc-MEG3 (area under the curve (AUC): 0.887, 95% confidence interval (CI): 0.856-0.917) and lnc-MEG3/miR-21 axis (AUC: 0.934, 95% CI: 0.909-0.958) had good values for predicting elevated sepsis risk, while miR-21 (AUC: 0.801, 95% CI: 0.758-0.844) presented a good predictive value for reduced sepsis risk. Furthermore, lnc-MEG3 expression and lnc-MEG3/miR-21 axis positively correlated with, whereas miR-21 expression negatively correlated with acute pathologic and chronic health evaluation II, sequential organ failure assessment score, serum creatinine, C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-17 in sepsis patients. Additionally, lnc-MEG3 (AUC: 0.704, 95% CI: 0.626-0.783) and lnc-MEG3/miR-21 axis (AUC: 0.669, 95% CI: 0.589-0.750) exhibited acceptable values in predicting higher 28-day mortality risk, while miR-21 (AUC: 0.588, 95% CI: 0.505-0.672) presented a poor predictive value for lower 28-day mortality risk in sepsis patients. CONCLUSION: Lnc-MEG3 might serve as a potential biomarker for the development, progression, and prognosis prediction of sepsis via interacting with miR-21.

Prostaglandin-E2 deficiency during late pregnancy and the associated increase in interleukin-1ß derived from periaortic lymph nodes lead to abortion.

Prostaglandin E2 (PGE2) is a hormone with many physiological functions. During pregnancy, it is generally believed that there is a high level of PGE2 at the final stage of pregnancy, which induces the contraction of uterine smooth muscle and promotes the occurrence of childbirth. However, we find that high PGE2 levels are present throughout late pregnancy in mice, not just during childbirth, and that PGE2 deficiency induced by indomethacin during late pregnancy causes damage to the placental labyrinth and eventually leads to abortion. Interestingly, the damage is closely related to inflammation, which involves the role of inflammatory factors produced by the periaortic lymph nodes (PLNs) near the uterus. Further, through RNA sequencing, we reveal that PLNs produce a large amount of interleukin-1ß (IL-1ß) when exposed to PGE2 deficiency, which causes damage to the placental labyrinth, probably via destroying the extracellular matrix. Finally, events leading to abortion following indomethacin administration are effectively prevented by supplementing PGE2 or by PLN removal. These results suggest that high levels of PGE2 during late pregnancy protect fetuses from inflammatory damage related to IL-1ß. This work suggests a new role of PGE2 during late pregnancy and may provide potential therapeutic strategies for pathological pregnancy.

High level of C-type natriuretic peptide induced by hyperandrogen-mediated anovulation in polycystic ovary syndrome mice.

Polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, is a complex endocrinopathy that affects the fertility of 9-18% of reproductive-aged women. However, the exact mechanism of PCOS, especially hyperandrogen-induced anovulation, is largely unknown to date. Physiologically, the natriuretic peptide type C/natriuretic peptide receptor 2 (CNP/NPR2) system is essential for sustaining oocyte meiotic arrest until the preovulatory luteinizing hormone (LH) surge. We therefore hypothesized that the CNP/NPR2 system is also involved in PCOS and contributes to arresting oocyte meiosis and ovulation. Here, based on a dehydroepiandrosterone (DHEA)-induced PCOS-like mouse model, persistent high levels of CNP/NPR2 were detected in anovulation ovaries. Meanwhile, oocytes arrested at the germinal vesicle stage correlated with persistent high levels of androgen and estrogen. We further showed that ovulation failure in these mice could be a result of elevated Nppc/Npr2 gene transcription that was directly increased by androgen (AR) and estrogen (ER) receptor signaling. Consistent with this, anovulation was alleviated by administration of either exogenous human chorionic gonadotropin (hCG) or inhibitors of AR or ER to reduce the level of CNP/NPR2. Additionally, the CNP/NPR2 expression pattern in the anovulated follicles was, to some extent, consistent with the clinical expression in PCOS patients. Therefore, our study highlights the important role an overactive CNP/NPR2 system caused by hyperandrogenism in preventing oocytes from maturation and ovulation in PCOS mice. Our findings provide insight into potential mechanisms responsible for infertility in women with PCOS.

Natriuretic peptides improve the developmental competence of in vitro cultured porcine oocytes.

BACKGROUND: Natriuretic peptides (NPs), brain and C type NPs (BNP and CNP), were involved in the maintenance of porcine oocyte meiotic arrest. The present study investigated the effects of NPs on developmental competence of immature porcine oocytes with follicles of different sizes. METHODS: Follicular fluid NP levels were examined by radioimmunoassay. The developmental competence of porcine oocytes was evaluated by cleavage and blastocyst developmental rates after in vitro fertilization (IVF) or parthenogenetic activation (PA) of cumulus oocyte complexes (COCs), which were recovered from follicle with different sizes. NP levels were examined and classified according to the cleavage potential after IVF with COCs released from these follicles. RESULTS: The BNP and CNP concentrations were increased with follicular size in follicular fluid and sustained at the set ranges of 3.0 - 6.0 mm follicles compared to 6.1 - 8.0 mm follicles. The oocytes developed from 3.0 to 6.0 mm follicles demonstrated increased embryo cleavage and blastocyst ratios after IVF, with an increased follicle size (P < 0.05). Moreover, BNP and CNP significantly promoted the blastocyst developmental rates of 3.0 - 6.0 mm follicles, but could not improve the developmental competence of oocytes from 6.1 to 8.0 mm follicles due to low NP levels. The COCs from 3.0 to 4.0 mm follicles were pre-incubated in 100 ng/ml of BNP and CNP media for 20 h before regular in vitro maturation, which demonstrated 2 to 3 folds higher developmental competencies in both PA and IVF groups compared to respective controls (P < 0.01). CONCLUSIONS: The effects of BNP and CNP supplementation in the pre-maturation culture media (PMC) on porcine developmental competence from COCs in follicles of different sizes were different and improved the developmental competence of porcine oocytes from small antral follicle in vitro.

Brain natriuretic peptide and C-type natriuretic peptide maintain porcine oocyte meiotic arrest.

Recent studies have shown that C-type natriuretic peptide (CNP) serves as a key control system during mouse oocyte maturation. We used pig models (in vitro and in vivo) to explore the role played by the natriuretic peptide family in porcine oocyte maturation. We reported the expression and location of natriuretic peptide system in different stages of porcine antral follicles. Atrial natriuretic peptide (ANP) and CNP were expressed primarily in granulosa cells, whereas brain natriuretic peptide (BNP) and natriuretic peptide receptor-B (NPRB) receptor were expressed in granulosa cells (both cumulus and mural granulosa cells) and thecal internal cells, and the natriuretic peptide receptor-A (NPRA) receptor predominantly in thecal cells. Upon in vitro culture, BNP and CNP maintained meiotic arrest of oocytes associated with cumulus cells. The expression levels of BNP, CNP, and the NPRB receptor increased upon treatment of prepubertal gilts with pregnant mare's serum gonadotropin and decreased upon subsequent human chorionic gonadotropin injection. Such dynamic changes in the expression of natriuretic peptides and their receptor paralleled the proportions of oocytes exhibiting nuclear maturation in vivo. These data indicated that BNP and CNP co-contributed to maintaining porcine meiotic arrest under physiological condition and lutenizing hormone (LH) relieved this inhibitory effect by decreasing the expression levels of BNP and CNP in vivo. Our present work, combined with previous data, improved the understanding of the oocyte meiotic arrest mechanisms and further revealed that natriuretic peptides serve as oocyte maturation inhibitor (OMI) to inhibit oocyte maturation in mammals.

[Apoptosis in Lungs and Liver after Crush Injury of Hindlimbs in Rat].

OBJECTIVE: To investigate the process of apoptosis in lungs and liver induced by crushing hindlimbs of rat, and study the mechanism of crush injury. METHODS: The rat experimental model of hindlimbs crush injury was established. The cell apoptosis in lungs and liver was detected by TUNEL assay, and the expression of Bax, Bcl-2 and caspase-3 apoptin was examined by immunohistochemistry. RESULTS: Compared with the control group, the partial muscle injury of rat's hindlimbs was more serious with more apoptosis observed in lungs and liver (P < 0.05). The expression of Bax was up-regulated and Bcl-2 was down-regulated, whereas caspase-3 expression was activated (P < 0.05). CONCLUSION: The cell apoptosis has increased significantly in lungs and liver after crush injury of hindlimbs in rat. The correlation factor released during tissue injury may mediate apoptosis process.

[Multiple risk factors models of patients with acute coronary syndromes of different genders].

OBJECTIVE: To establish the multiple risk factors models for patients with acute coronary syndromes (ACS) of different genders and quantitatively assess the pathopoiesis of all factors. METHODS: A total of 2 308 consecutive ACS inpatients and a control group of 256 cases with normal coronary artery from January 2010 to December 2012 were enrolled and divided into 4 groups of female ACS (n = 970), male ACS (n = 1 338), female control (n = 136) and male control (n = 120). All demographic and clinical data were collected by the physicians and master degree candidates in the division of cardiology. RESULTS: The Logistic regression models of multiple risk factors were established for ACS by different genders. More than 45 years of age, dyslipidemia, type 2 diabetes mellitus, obesity and hypertension were all independent risk factors of ACS for different genders (P < 0.05). However, the same risk factors had different pathogenic effects on ACS between genders. The odds ratio (OR) was markedly different for females and males: per 5-year increase aged over 45 years (1.45 vs 1.13), dyslipidemia (3.45 vs 1.68), type 2 diabetes mellitus (4.06 vs 2.33), obesity (2.93 vs 1.91) and hypertension (1.78 vs 3.80) respectively (all P < 0.05). In addition, current smoking increased the risk of ACS attack in males by 5.49 (P < 0.05) while not statistically significant in females. Particularly cerebral ischemic stroke increased the risk of ACS attack by 5.49 folds in males other than females (P < 0.05). CONCLUSION: Type 2 diabetes mellitus, dyslipidemia and obesity may present higher risks of ACS attack for females than males. And smoking and hypertension are much more dangerous for males. Males with cerebral infarction are more susceptible for ACS than females.

Participation of preovulatory follicles in the activation of primordial follicles in mouse ovaries.

The mechanisms behind the selection and initial recruitment of primordial follicles (PmFs) from the non-growing PmF pool during each estrous cycle in females remain largely unknown. This study demonstrates that PmFs closest to the ovulatory follicle are preferentially activated in mouse ovaries under physiological conditions. PmFs located within 40 µm of the ovulatory follicles were more likely to be activated compared to those situated further away during the peri-ovulation period. Repeated superovulation treatments accelerated the depletion of the PmF reserve, whereas continuous suppression of ovulation delayed PmF reserve consumption. Spatial transcriptome sequencing of peri-ovulatory follicles revealed that ovulation primarily induces the degradation and remodeling of the extracellular matrix (ECM). This ECM degradation reduces mechanical stress around PmFs, thereby triggering their activation. Specifically, Cathepsin L (CTSL), a cysteine proteinase and lysosomal enzyme involved in ECM degradation, initiates the activation of PmFs adjacent to ovulatory follicles in a distance-dependent manner. These findings highlight the link between ovulation and selective PmF activation, and underscore the role of CTSL in this process under physiological conditions.

Electrophysiological correlates of processing own- and other-race faces.

Most adults have more experience in identifying faces of their own race than in identifying faces from another race, and thus may be considered as own-race face experts. This effect was investigated by recording and analyzing ERPs as well as induced gamma oscillations. The race modulation occurred post the stage of structural processing revealed by N170. Larger P2 component and induced gamma activity for own-race than other-race faces could be associated with more elaborate processing on the basis of configural computation due to more experience that we have for own-race faces.

A chloroplast membrane protein LTO1/AtVKOR involving in redox regulation and ROS homeostasis.

KEY MESSAGE: The role of LTO1/ At VKOR-DsbA in ROS homeostasis and in redox regulation of cysteine-containing proteins in chloroplast was studied in lto1 - 2 mutant, and a potential target of LTO1 was captured. A chloroplast membrane protein LTO1/AtVKOR-DsbA encoded by the gene At4g35760 was recently found to be an oxidoreductase and involved in assembly of PSII. Here, the growth of a mutant lto1-2 line of Arabidopsis was found to be severely stunted and transgenic complementation ultimately demonstrated the phenotype changes were due to this gene. A proteomic experiment identified 23 proteins presenting a differential abundance in lto1-2 compared with wild-type plants, including components in PSII and proteins scavenging active oxygen. Three scavengers of active oxygen, L-ascorbate peroxidase 1, peroxisomal catalase 2, dehydroascorbate reductase 1, are reduced in lto1-2 plants, corresponding to high levels of accumulation of reactive oxygen species (ROS). The photosynthetic activities of PSII and the quantity of core protein D1 decreased significantly in lto1-2. Further investigation showed the synthesis of D1 was not affected in mutants both at transcription and translation levels. The soluble DsbA-like domain of LTO1 was found to have reduction, oxidation and isomerization activities, and could promote the formation of disulfide bonds in a lumenal protein, FKBP13. A potential target of LTO1 was captured which was involving in chlorophyll degradation and photooxidative stress response. Experimental results imply that LTO1 plays important roles in redox regulation, ROS homeostasis and maintenance of PSII.

Mobile phone use while cycling among e-bikers in China: Reasoned or social reactive?

INTRODUCTION: China has the largest number of e-bikers in the world, and e-bike crashes cause thousands of fatalities and tens of thousands of serious injuries annually. Mobile phone use while e-biking is a violation of Chinese law and associated with increased crash risk. The current study investigated mobile phone use behavior while cycling among Chinese e-bikers and the psychological factors surrounding why individuals might choose to engage in this risk-taking behavior. METHOD: In particular, this study investigates whether the decision to use a mobile phone while cycling is explained through reasoned decision making or is a social reactive decision, or both, as defined by the prototype willingness model (PWM). Questionnaire data were collected from 784 Chinese adults with e-bike experience. RESULTS: Results showed that 40.2 % of the participants reported mobile phone use while cycling e-bikes in the past month. Both behavioral intention and behavioral willingness were predictors of mobile phone while using e-bikes, and they were approximately equal in their magnitude of predictive power (ßBI = 0.25; ßBW = 0.26). E-bikers' attitudes, perceived behavioral control, and perception of prototype similarity and favorability were strong predictors of intention, willingness, and self-reported behavior to use mobile phones while e-biking. CONCLUSIONS: Both social reactive decision-making and reasoned decision-making contribute to decisions to use a mobile phone while riding an e-bike. PRACTICAL APPLICATIONS: Results have implications for guiding development of interventions to prevent and reduce mobile phone use when e-bike cycling.

Molecular imaging-guided extracellular vesicle-based drug delivery for precise cancer management: Current status and future perspectives.

Extracellular vesicles (EVs), the mediators of intercellular communication, have attracted the attention of researchers for the important roles they play in cancer treatment. Compared with other inorganic nano-materials, EVs possess the advantages of higher biocompatibility, better physiochemical stability, easier surface modification, and excellent biosafety. They can be used as an advanced drug delivery system with an improved therapeutic index for various therapeutic agents. Engineered EV-based imaging and therapeutic agents (engineered EVs) have emerged as useful tools in targeted cancer diagnosis and therapy. Non-invasive tracing of engineered EVs contributes to a better evaluation of their functions in cancer progression, in vivo dynamic biodistribution, therapeutic response, and drug-loading efficiency. Recent advances in real-time molecular imaging (MI), and innovative EV labeling strategies have led to the development of novel tools that can evaluate the pharmacokinetics of engineered EVs in cancer management, which may accelerate further clinical translation of novel EV-based drug delivery platforms. Herein, we review the latest advances in EVs, their characteristics, and current examples of EV-based targeted drug delivery for cancer. Then, we discuss the prominent applications of MI for tracing both natural and engineered EVs. Finally, we discuss the current challenges and considerations of EVs in targeted cancer treatment and the limitations of different MI modalities. In the coming decades, EV-based therapeutic applications for cancer with improved drug loading and targeting abilities will be developed, and better anti-cancer effects of drug delivery nanoplatform will be achieved.

Peroxy radical chemistry during ozone photochemical pollution season at a suburban site in the boundary of Jiangsu-Anhui-Shandong-Henan region, China.

Ambient peroxy radical (RO2⁎ = HO2 + RO2) concentrations were measured at a suburban site in a major prefecture-level city (Huaibei) in the boundary of Jiangsu-Anhui-Shandong-Henan region, which is the connecting belt of air pollution in the Beijing-Tianjin-Hebei region and the Yangtze River Delta. Measurements were carried out during the period of September to October 2021 to elucidate the formation mechanism of O3 pollution. The observed maximum concentration of peroxy radicals was 73.8 pptv. A zero-dimensional box model (Framework for 0-Dimensional Atmospheric Modeling, F0AM) based on Master Chemical Mechanism (MCM3.3.1) was used to predict radical concentrations for comparison with observations. The model reproduced the daily variation of peroxy radicals well, but discrepancies still appear in the morning hours. As in previous field campaigns, systematic discrepancies between modelled and measured RO2⁎ concentrations are observed in the morning for NO mixing ratios higher than 1 ppbv. Between 6:00 and 9:00 am, the model significantly underpredicts RO2⁎ by a mean factor of 7.2. This underprediction can be explained by a missing RO2⁎ source of 1.2 ppbv h-1 which originated from the photochemical conversion of an alkene-like chemical species. From the model results it shows that the main sources of ROx (= OH + HO2 + RO2) are the photolysis of oxygenated volatile organic compounds (OVOCs, 33 %), O3 and HONO (25 %), and HCHO (24 %). And the major sinks of ROx transitioned from a predominant reaction of radicals with NOx in the morning to a predominant peroxy self- and cross-reaction in the late afternoon. The introduction of an alkene-like species increased RO2 radical concentration and resulted in 14 % increase in net daily integrated ozone production, indicating the possible significance of the mechanism of alkene-like species oxidation to peroxy radicals. This study provides important information for subsequent ozone pollution control policies in Jiangsu-Anhui-Shandong-Henan region.

Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis.

Ovarian granulosa cell tumors (GCTs) originate from granulosa cells (GCs) and represent the most common sex cord-stromal tumor in humans. However, the developmental regulations and molecular mechanisms underlying their etiology are largely unknown. In the current study, we combined a multi-fluorescent reporter mouse model with a conditional knockout mouse model, in which the tumor suppressor genes Pten and p27 were deleted in GCs, to perform cell lineage tracing of mutant GCs. We found that only 30% of ovaries with substantial mutant GCs developed into GCTs that derived from a single mutant GC. In-depth molecular analysis of the process of tumorigenesis demonstrated that up-regulation of immune evasion genes Cd24a and Cd47 led, in part, to the transition of mutant GCs to GCTs. Therefore, treatment with the Cd47 inhibitor RRX-001 was tested and found to efficiently suppress the growth of GCTs in vivo. Together, our study has revealed an immune evasion mechanism via CD24/CD47 upregulation to GCT formation, shedding light on the future potential clinical therapies for GCTs.

Long-Term Axial Length Shortening in Myopic Orthokeratology: Incident Probability, Time Course, and Influencing Factors.

Purpose: Long-term axial length (AL) shortening in myopia is uncommon but noteworthy. Current understanding on the condition is limited due to difficulties in case collection. The study reported percentage, probability, and time course of long-term AL shortening in myopic orthokeratology based on a large database. Methods: This study reviewed 142,091 medical records from 29,825 subjects in a single-hospital orthokeratology database that were collected over 10 years. Long-term AL shortening was defined as a change in AL of -0.1 mm or less at any follow-up beyond 1 year. Incident probability was calculated based on multivariate logistic regression. Time course was estimated using mixed-effect regression model. Results: A total of 10,093 subjects (mean initial age, 11.70 ± 2.52 years; 58.8% female) with 80,778 visits were included. The number of subjects experienced long-term AL shortening was 1,662 (16.47%; 95% confidence interval, 15.75%-17.21%). Initial age showed significant impact on the incident occurrence (OR, 1.37; 95% confidence interval, 1.34-1.40; P < 0.001). The estimated probability of AL shortening was approximately 2% for subjects with initial age of 6 years and 50% for those aged 18. Among the 1662 AL shortening cases, the median magnitude of the maximum AL reduction was 0.19 mm. The shortening process mostly occurred within the initial 2 years. Subject characteristics had limited associations with the shortening rate. Conclusions: Long-term AL shortening is possible in subjects receiving myopic orthokeratology. Although age notably affect the incident probability, the time course seems to not vary significantly.