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Neuron morphology gives rise to distinct axons and dendrites and plays an essential role in neuronal functionality and circuit dynamics. In rat hippocampal neurons, morphological development occurs over roughly one week in vitro. This development has been qualitatively described as occurring in 5 stages. Still, there is a need to quantify cell growth to monitor cell culture health, understand cell responses to sensory cues, and compare experimental results and computational growth model predictions. To address this need, embryonic rat hippocampal neurons were observed in vitro over six days, and their processes were quantified using both standard morphometrics (degree, number of neurites, total length, and tortuosity) and new metrics (distance between change points, relative turning angle, and the number of change points) based on the Change-Point Test to track changes in path trajectories. Of the standard morphometrics, the total length of neurites per cell and the number of endpoints were significantly different between 0.5, 1.5, and 4 days in vitro, which are typically associated with Stages 2-4. Using the Change-Point Test, the number of change points and the average distance between change points per cell were also significantly different between those key time points. This work highlights key quantitative characteristics, both among common and novel morphometrics, that can describe neuron development in vitro and provides a foundation for analyzing directional changes in neurite growth for future studies.

Summary What is this summary about? This is a summary of a publication about the FILLY study, which was published in Ophthalmology in 2020. The FILLY study looked at an investigational medicine called pegcetacoplan as a possible treatment for geographic atrophy. Geographic atrophy, also known as GA, is the late stage of an eye disease called dry age-related macular degeneration, also known as dry AMD. In people with GA, lesions form on a part of the back of the eye called the retina. GA lesions are patches of thin retina. Growth of GA lesions ultimately causes blindness, which cannot be reversed. There is currently no approved treatment for GA. Pegcetacoplan, also called APL-2, could be a possible treatment for GA. Pegcetacoplan is an investigational medicine, which means it has not yet been approved. It is currently being studied in clinical studies to see how well it works. What happened in the FILLY study? The FILLY study included participants with GA and tested how well pegcetacoplan worked compared to a sham injection (an injection that looks like the study treatment but does not have any medicine in it). The study also looked at how safe it was in adults with GA. What were the results? The main questions the researchers wanted to answer were: Did pegcetacoplan slow the growth of the study participants' GA lesions? ○ Yes. Overall, the researchers found that pegcetacoplan did slow the growth of the study participants' GA lesions. Did pegcetacoplan change the participants' vision? ○ No. Overall, the researchers found that pegcetacoplan did not change the participants' vision. What medical problems happened after the participants received pegcetacoplan? ○ The researchers kept track of any serious medical problems that happened during the study, also called serious adverse events. They also kept track of other medical problems that happened, or got worse, only at some point after the participants received the study treatment. These are called treatment emergent adverse events, also known as TEAEs. The serious adverse events and TEAEs that the participants had are described later in this summary. What do the results of the study mean? Overall, results from this study showed that participants who received pegcetacoplan had slower growth of GA lesions than participants who received the sham injection. After the participants had stopped receiving pegcetacaoplan, the effect of the treatment seemed to be reduced. Pegcetacoplan did not change how well the participants could see during their vision tests in this trial. ClinicalTrials.gov NCT number: NCT02503332

The COVID-19 pandemic and interventions addressing it raise important questions about human mobility that have geopolitical implications. This forum uses mobility and immobility during the pandemic as lenses onto the ways that routinised state power reacts to acute uncertainties, as well as how these reactions impact politics and societies. Specifically, we propose the concept of “shock mobility” as migratory routines radically reconfigured: emergency flights from epicentres, mass repatriations, lockdowns, quarantines. Patterns of shock mobility and immobility are not new categories of movement, but rather are significant alterations to the timing, duration, intensity, and relations among existing movements. Many of these alterations have been induced by governments’ reactions to the pandemic in both migrant-sending and receiving contexts, which can be especially consequential for migrants in and from the Global South. Our interventions explore these processes by highlighting experiences of Afghans and Kurds along Iran’s borders, Western Africans in Europe, Filipino workers, irregular Bangladeshis in Qatar, Central Americans travelling northwards via Mexico, and rural-urban migrants in India. In total, we argue that tracing shocks’ dynamics in a comparative manner provides an analytical means for assessing the long-term implications of the pandemic, building theories about how and why any particular post-crisis world emerges as it does, and paving the way for future empirical work.

This study aimed to assess the safety and effectiveness of modified endoscopic technique with a single portal from an external carpal tunnel approach for surgical operations in a suprafascial plane superficial to the transverse carpal ligament. Reversible nerve injury risk is threefold greater with a conventional endoscopic method than with open carpal tunnel release (OCTR), and this suprafascial plane endoscopic release (SPER) should circumvent the problem of hardware in the carpal tunnel encountered with the conventional endoscopic method and liable to cause iatrogenic damage to the median nerve. However, the surgical consequences of the new technique have not been studied. To fill this gap, a retrospective therapeutic study was conducted to compare negative outcomes versus open surgery. The Accordion Severity Grading System was used to grade complications from 0 to 3 according to necessity of treatment. Sequela and failure rates were also compared between the SPER and OCTR groups. Eighty-eight cases in 72 patients with idiopathic carpal tunnel syndrome (ICTS) met the inclusion criteria. SPER was performed in 28 hands in 27 patients, and OCTR in 60 hands in 49 patients. The results showed no significant difference in complication, sequela, or failure rates between groups (p > 0.05). Suprafascial plane endoscopic release, has certain advantages over the open method and was validated as a safe and effective method of treating ICTS.

To evaluate the accuracy of the lesion-to-erector spinae signal intensity ratio (SIR) on magnetic resonance imaging (MRI) for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDA).The MRI data of 21 patients with AIP and 27 patients with PDA were analysed retrospectively, and the signal intensity in pancreatic lesions and erector spinae muscles at the same level on T2-weighted imaging (T2WI), arterial phase (AP) imaging, and delayed phase (DP) imaging was measured for calculation of SIRs.The mean SIRs of the pancreatic lesions and erector spinae from T2WI, AP, and DP images of AIP patients were 0.96, 1.27, and 1.42, respectively, while those of PDA patients were 1.35, 0.80, and 0.91, respectively. The differences in the SIRs between the AIP and PDA groups were statistically significant (p0.001), with corresponding area under curve (AUC) values of 0.925, 0.906, and 0.961, respectively. The optimal cut-off values for the SIRs on T2WI, AP and DP images were 1.21, 1.01, and 1.08, respectively. SIR values 1.21 on T2WI,1.01 on AP imaging, and1.08 on DP imaging identified AIP with sensitivities of 85.7%, 90.5%, and 90.5%, respectively, and specificities of 81.5%, 74.6%, and 81.5%, respectively. The AUC values for SIRs did not differ significantly between T2WI and DP imaging or AP and DP imaging (Z = 0.778, p=0.436; Z = 1.279, p=0.201).The SIRs of pancreatic lesions and erector spinae on T2WI, AP, and DP images can be used to differentiate AIP from PDA.

Mangrove ecosystems are vulnerable to rising sea levels. When the sea level rises, the plants are exposed to increased salinity and tidal submergence. In Taiwan, the mangrove species Kandelia obovata and Rhizophora stylosa grow in different habitats and at different elevations. To understand the response of photosynthesis to salinity and submergence in mangroves adapted to different tidal elevations, gas exchange and chlorophyll fluorescence parameters were measured in K. obovata and R. stylosa under different salinity (20 and 40‰) and submergence treatments. The period of light induction of photosynthesis for the two mangrove species was >60 min. In the induction process, the increase in photosystem efficiency was faster than the increase in stomatal opening, but CO2 fixation efficiency was restricted by stomatal conductance. The constraint of stomatal opening speed is related to the conservative water-use strategy developed in response to mangrove environments. Submergence increased the photosynthetic rate of K. obovata, but not that of R. stylosa. Although R. stylosa was more salt tolerant than K. obovata, R. stylosa was not submergence tolerant in a high-salinity environment, which may be the reason for the higher intertidal elevations observed for R. stylosa in comparison with K. obovata. The photosynthetic rate and energy-dependent quenching (qE) of the two mangroves presented a negative relationship with photoinhibition, and high-salt treatment simultaneously reduced photosynthetic rate and qE. A decrease in the photosynthetic rate increased excess energy, whereas a decrease in qE decreased photoprotection; both increased photoinhibition. As the degree of photoinhibition can be easily measured in the field, it is a useful ecological monitoring index that provides a suitable reference for mangrove restoration, habitat construction and ecological monitoring.

Cockroaches are urban pests that are very difficult to control. Using repellents is a green, safe and effective strategy for their control. In order to find novel cockroach repellents, the repellent activity of 45 bridged-ring terpenoid derivatives synthesized from β-pinene against

This study explored the usefulness of genomic copy number variation sequencing (CNV-Seq) in the prenatal diagnosis of pregnant women.Based on prenatal diagnostic indications, CNV-Seq analysis was done in the samples from the 579 pregnant women of the 7 subgroups that included advanced maternal age (group A), high risk noninvasive prenatal test (NIPT) (group B), high risk Down's (Group C), abnormal ultrasound findings (Group D), adverse pregnancy history (Group E), chromosome abnormalities in couples (Group F), and the mixed group (Group G).A total of 57 (9.84%) cases have abnormal CNV-Seq results. Among them, 21 cases were aneuploid chromosomal number abnormalities (3.63%, 21/579), and 36 cases were CNV abnormalities (6.22%, 36/579), including 7 cases of pathogenic copy number alteration (pCNA) (1.21%, 7/579) and 29 cases variants of uncertain significance (VUS) (5.01%, 29/579). The total detection rates of abnormal CNV-Seq in Group G and Group B were 20.27% (15/74) and 15.91% (14/88), which were significantly higher than those in other groups (p0.05). Among 36 cases of abnormal CNV-Seq, 7 cases were chromosome fragment deletion or duplication, which were pathogenic CNV, and some rare chromosomal diseases were detected.Patients with a high risk of NIPT or multiple indications of prenatal diagnosis are highly suspected of chromosomal diseases. CNV-Seq is a useful tool for detecting chromosome abnormalities for prenatal diagnosis of pregnant women more accurately and provides more comprehensive information for prenatal diagnosis to reduce birth defects.

胃肠道惰性T细胞淋巴组织增殖性疾病（indolent T-cell lymphoproliferative disorder in the gastrointestinal tract，ITLPD-GIT）是一种克隆性T淋巴细胞增殖性疾病，以淋巴样细胞浸润胃肠道黏膜固有层为主要特点。迄今为止，对该病的临床病理学特征的认识较为有限。本文报道1例随访10年、单克隆淋巴样细胞浸润肠壁全层的ITLPD-GIT。患者女，58岁。持续性腹泻腹痛10年，在发病第2年行部分小肠切除，小到中等大小的淋巴样细胞局限于黏膜固有层；发病第3年及第10年分别再次行部分小肠切除，镜下见病变进展，表现为淋巴样细胞弥漫浸润肠壁全层。免疫组织化学结果显示肿瘤细胞呈CD2、CD3、CD5、CD7、CD8、T细胞胞质抗原1阳性，而CD20、CD4、CD56、颗粒酶B和EB病毒编码的RNA均阴性。Ki-67阳性指数约5%。分子检测显示T细胞受体基因呈克隆性重排。随访10年，患者长期带病生存。ITLPD-GIT是一种罕见的淋巴组织增殖性疾病，容易被漏诊或误诊；本病例进一步拓展了该病的病理形态学谱系，有助于病理医师认识及正确诊断该疾病。.

ImportanceLong-term exposure to fine particulate air pollution (PM2.5) is a known risk factor for cardiovascular events, but controversy remains as to whether the current National Ambient Air Quality Standard (12 μg/m3 for 1-year mean PM2.5) is sufficiently protective.ObjectiveTo evaluate the associations between long-term fine particulate air pollution and cardiovascular events using electronic health record and geocoded address data.Design, Setting, and ParticipantsThis retrospective cohort study included adults in the Kaiser Permanente Northern California integrated health care system during 2007 to 2016 and followed for up to 10 years. Study participants had no prior stroke or acute myocardial infarction (AMI), and lived in Northern California for at least 1 year. Analyses were conducted January 2020 to December 2022.ExposureLong-term exposure to PM2.5. Individual-level time-varying 1-year mean PM2.5 exposures for every study participant were updated monthly from baseline through the end of follow-up, accounting for address changes.Main Outcomes and MeasuresIncident AMI, ischemic heart disease (IHD) mortality, and cardiovascular disease (CVD) mortality. Cox proportional hazards models were fit with age as time scale, adjusted for sex, race and ethnicity, socioeconomic status, smoking, body mass index, baseline comorbidities, and baseline medication use. Associations below the current regulation limit were also examined.ResultsThe study cohort included 3.7 million adults (mean [SD] age: 41.1 [17.2] years; 1 992 058 [52.5%] female, 20 205 [0.5%] American Indian or Alaskan Native, 714 043 [18.8%] Asian, 287 980 [7.6%] Black, 696 796 [18.4%] Hispanic, 174 261 [4.6%] multiracial, 1 904 793 [50.2%] White). There was a 12% (95% CI, 7%-18%) increased risk of incident AMI, a 21% (95% CI, 13%-30%) increased risk of IHD mortality, and an 8% (95% CI, 3%-13%) increased risk of CVD mortality associated with a 10 μg/m3 increase in 1-year mean PM2.5. PM2.5 exposure at moderate concentrations (10.0 to 11.9 μg/m3) was associated with increased risks of incident AMI (6% [95% CI, 3%-10%]) and IHD mortality (7% [95% CI, 2%-12%]) compared with low concentrations (less than 8 μg/m3).Conclusions and RelevanceIn this study, long-term PM2.5 exposure at moderate concentrations was associated with increased risks of incident AMI, IHD mortality, and CVD mortality. This study’s findings add to the evidence that the current regulatory standard is not sufficiently protective.

Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use., Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue., Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun., Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.

An annular venturi injector (AVI) was proposed to form an intermittent flow structure in airlift pump for a good pump performance. Experiments were conducted to investigate the performance of the airlift pump with this AVI by comparing with pump performance with traditional injectors, at a series of air flow rates . It was found that airlift pump with AVI had higher flow rates of output liquid and particle, than those with the traditional injectors. This AVI promoted the gas core to collapse and formed an intermittent flow structure in rising pipe. For this intermittent structure, its slug length, firstly increased to a maximal value with increasing gas flow rate and then remained stable even under a high gas flow rate, while its slug frequency decreased with gas flow rate and then remained to a minimal value under a high gas flow rate.

Axisymmetric standing waves occur across a wide range of free surface flows. When these waves reach a critical height (steepness), wave breaking and jet formation occur. For travelling surface gravity waves, wave breaking is generally considered to limit wave height and reversible wave motion. In the ocean, the behaviour of directionally spread waves lies between the limits of purely travelling (two dimensions) and axisymmetric (three dimensions). Hence, understanding wave breaking and jet formation on axisymmetric surface gravity waves is an important step in understanding extreme and breaking waves in the ocean. We examine an example of axisymmetric wave breaking and jet formation colloquially known as the ‘spike wave’, created in the FloWave circular wave tank at the University of Edinburgh, UK. We generate this spike wave with maximum crest amplitudes of 0.15–6.0 m (0.024–0.98 when made non-dimensional by characteristic radius), with wave breaking occurring for crest amplitudes greater than 1.0 m (0.16 non-dimensionalised). Unlike two-dimensional travelling waves, wave breaking does not limit maximum crest amplitude, and our measurements approximately follow the jet height scaling proposed by Ghabache et al. (J. Fluid Mech., vol. 761, 2014, pp. 206–219) for cavity collapse. The spike wave is predominantly created by linear dispersive focusing. A trough forms, then collapses producing a jet, which is sensitive to the trough's shape. The evolution of the jets that form in our experiments is predicted well by the hyperbolic jet model proposed by Longuet–Higgins (J. Fluid Mech., vol. 127, 1983, pp. 103–121), previously applied to jets forming on bubbles.

Two-dimensional black phosphorus (BP) has unique layered structure, excellent photothermal properties, good biocompatibility and high biodegradability. In recent years, it has been found that BP has stable drug loading and light controlled sustained-release drug functions, excellent antibacterial properties and the ability to promote vascular and nerve regeneration in the medicine field, which has a broad application prospect in dentistry. This review elaborates the biological properties of two-dimensional BP and its application progress in dentistry, so as to provide new ideas for the further research and application of two-dimensional BP.二维黑磷具备独特的层状结构和出色的光学性能、良好的生物相容性和高生物降解性。近年研究显示，二维黑磷在生物医学领域具有稳定的载药和光控调节缓释药物功能、优异的抗菌活性和促血管和神经再生能力，因此在口腔医学中具有广阔的应用前景。本文就二维黑磷的生物学特性及其在口腔医学领域的研究应用进展进行综述，以期为二维黑磷的进一步研究和应用提供新思路。.

In crisis events such as wars, natural disasters and epidemics, migrant workers are among the hardest hit and most vulnerable to displacement, unemployment and the loss of income. The coronavirus p...

Objectives We evaluated the impact of a 2014 New York City health code change requiring laboratories to indicate if a patient is pregnant or probably pregnant in the electronic laboratory report (ELR) when reporting syphilis and hepatitis B virus (HBV) cases to the New York City Department of Health and Mental Hygiene (DOHMH). Methods We calculated the number of pregnant persons with syphilis or HBV infection reported to DOHMH from January 1, 2013, through June 30, 2018. We compared the proportion in which the first report to DOHMH was an ELR with pregnancy indicated before and after the policy change. We calculated time between first ELR with pregnancy indicated and subsequent reporting by a method other than ELR and the proportion of cases in which ELR with pregnancy indicated was the only report source. Results A total of 552 new syphilis and 8414 HBV-infected cases were reported to DOHMH. From January 2013–June 2014 (pre-change) to January 2017–June 2018 (post-change), the proportion of cases in which ELR with pregnancy indicated was the first report to DOHMH increased significantly (14.7% [23/156] to 46.2% [80/173] for syphilis; 8.0% [200/2498] to 45.3% [851/1879] for HBV infection [ P < .001]). Median time between first ELR with pregnancy indicated and subsequent reporting by a method other than ELR was 9.0 days for syphilis and 51.0 days for HBV infection. ELR with pregnancy indicated was the only report for 43.1% (238/552) of syphilis cases and 23.4% (1452/6200) of HBV cases during the study period. Conclusion Including pregnancy status with ELR can increase the ability of public health departments to conduct timely interventions to prevent mother-to-child transmission.

The pulmonary epithelial glycocalyx, an anionic cell surface layer enriched in glycosaminoglycans such as heparan sulfate and chondroitin sulfate, contributes to the alveolar barrier. Direct injury to the pulmonary epithelium induces shedding of heparan sulfate into the air space; the impact of this shedding on recovery after lung injury is unknown. Using mass spectrometry, we found that heparan sulfate was shed into the air space for up to 3 wk after intratracheal bleomycin-induced lung injury and coincided with induction of matrix metalloproteinases (MMPs), including MMP2. Delayed inhibition of metalloproteinases, beginning 7 days after bleomycin using the nonspecific MMP inhibitor doxycycline, attenuated heparan sulfate shedding and improved lung function, suggesting that heparan sulfate shedding may impair lung recovery. While we also observed an increase in air space heparanase activity after bleomycin, pharmacological and transgenic inhibition of heparanase in vivo failed to attenuate heparan sulfate shedding or protect against bleomycin-induced lung injury. However, experimental augmentation of airway heparanase activity significantly worsened post-bleomycin outcomes, confirming the importance of epithelial glycocalyx integrity to lung recovery. We hypothesized that MMP-associated heparan sulfate shedding contributed to delayed lung recovery, in part, by the release of large, highly sulfated fragments that sequestered lung-reparative growth factors such as hepatocyte growth factor. In vitro, heparan sulfate bound hepatocyte growth factor and attenuated growth factor signaling, suggesting that heparan sulfate shed into the air space after injury may directly impair lung repair. Accordingly, administration of exogenous heparan sulfate to mice after bleomycin injury increased the likelihood of death due to severe lung dysfunction. Together, our findings demonstrate that alveolar epithelial heparan sulfate shedding impedes lung recovery after bleomycin.

BACKGROUND AND PURPOSE: Accurate differentiation between glioblastoma and solitary brain metastasis is of vital importance clinically. This study aimed to investigate the potential value of the inflow-based vascular-space-occupancy MR imaging technique, which has no need for an exogenous contrast agent, in differentiating glioblastoma and solitary brain metastasis and to compare it with DSC MR imaging. MATERIALS AND METHODS: Twenty patients with glioblastoma and 22 patients with solitary brain metastasis underwent inflow-based vascular-space-occupancy and DSC MR imaging with a 3T clinical scanner. Two neuroradiologists independently measured the maximum inflow-based vascular-space-occupancy–derived arteriolar CBV and DSC-derived CBV values in intratumoral regions and peritumoral T2-hyperintense regions, which were normalized to the contralateral white matter (relative arteriolar CBV and relative CBV, inflow-based vascular-space-occupancy relative arteriolar CBV, and DSC-relative CBV). The intraclass correlation coefficient, Student t test, or Mann-Whitney U test and receiver operating characteristic analysis were performed. RESULTS: All parameters of both regions had good or excellent interobserver reliability (0.74∼0.89). In peritumoral T2-hyperintese regions, DSC-relative CBV (P < .001), inflow-based vascular-space-occupancy arteriolar CBV (P = .001), and relative arteriolar CBV (P = .005) were significantly higher in glioblastoma than in solitary brain metastasis, with areas under the curve of 0.94, 0.83, and 0.72 for discrimination, respectively. In the intratumoral region, both inflow-based vascular-space-occupancy arteriolar CBV and relative arteriolar CBV were significantly higher in glioblastoma than in solitary brain metastasis (both P < .001), with areas under the curve of 0.91 and 0.90, respectively. Intratumoral DSC-relative CBV showed no significant difference (P = .616) between the 2 groups. CONCLUSIONS: Inflow-based vascular-space-occupancy has the potential to discriminate glioblastoma from solitary brain metastasis, especially in the intratumoral region.

OBJECTIVE: To explore the difference in intestinal flora composition between individuals with sub-health status and healthy subjects. METHODS: From November, 2020 to May, 2021, a total of 150 nursing staff members in Nanfang Hospital were selected for this study, including 75 participants with sub-health status (SHS group) and 75 healthy participants (control group). Fecal samples were collected from all the participants for analysis of the diversity and species composition of the intestinal flora using high-throughput sequencing for V3-V4 region of 16S rRNA gene. RESULTS: The results of α diversity analysis showed no significant difference in Chao1 index between the two groups (P=0.619), but the Shannon index was significantly higher in SHS group than in the control group (P < 0.001). The results of β diversity analysis showed significant differences in the community structure between the SHS group and the control group (R=0.227, P=0.001). At the phylum level, the intestinal flora in the two groups were composed mainly of Bacteroidota, Firmicutes and Actinobacteriata, and of Prevotella, Bacteroides, Blautia and Faecalibacterium at the genus level. Species difference analysis identified significant differences in the relative abundance between the two groups in 4 phyla, 3 classes, 3 orders, 3 families and 3 genera (P < 0.05). CONCLUSION: Compared with healthy subjects, the individuals with sub-health status have obviously unbalanced structure of the intestinal flora.

In this article the author name Ana Alastruey-Izquierdo was incorrectly written as Ana Alastruey-Izquerdo. © Mushroom Research Foundation 2022.

Background Fine particulate matter (PM2.5) exposure accelerates atherosclerosis and contains known ovotoxic chemicals. However, effects of exposure to PM2.5 on the finite ovarian follicle pool have hardly been investigated, nor have interactions between ovarian and cardiovascular effects. We hypothesized that subchronic inhalation exposure to human-relevant concentrations of PM2.5 results in destruction of ovarian follicles via apoptosis induction, as well as accelerated recruitment of primordial follicles into the growing pool. Further, we hypothesized that destruction of ovarian follicles enhances the adverse cardiovascular effects of PM2.5 in females. Results Hyperlipidemic apolipoprotein E (Apoe) null ovary-intact or ovariectomized female mice and testis-intact male mice were exposed to concentrated ambient PM2.5 or filtered air for 12 weeks, 5 days/week for 4 h/day using a versatile aerosol concentration enrichment system. Primordial, primary, and secondary ovarian follicle numbers were decreased by 45%, 40%, and 17%, respectively, in PM2.5-exposed ovary-intact mice compared to controls (P 2.5-exposed females versus controls (P 2.5 increased the percentages of primary and secondary follicles with DNA damage, assessed by γH2AX immunostaining (P 2.5 increased the percentages of apoptotic antral follicles, determined by TUNEL and activated caspase 3 immunostaining (P 2.5-exposure exacerbated the atherosclerotic effects of hyperlipidemia in females (P 2.5-compared to Air-exposed gonad-intact males and females and ovariectomized females, the changes were not consistent between exposure years and assessment methods. Conclusions These results demonstrate that subchronic PM2.5 exposure depletes the ovarian reserve by increasing recruitment of primordial follicles into the growing pool and increasing apoptosis of growing follicles. Further, PM2.5 exposure and removal of the ovaries each increase atherosclerosis progression in Apoe-/- females. Premature loss of ovarian function is associated with increased risk of osteoporosis, cardiovascular disease and Alzheimer’s disease in women. Our results thus support possible links between PM2.5 exposure and other adverse health outcomes in women.