Large extracellular vesicles from induced pluripotent stem cell-marrow stem cells enhance limb angiogenesis via ERK/MAPK.

Aim: This study aims to investigate the effects of large extracellular vesicles (EVs) induced by pluripotent stem cell-derived mesenchymal stem cells on lower limb ischemic disease and explore its potential mechanisms. Materials & methods: The pathology of muscles was accessed by H&E staining and immunofluorescence staining. In vitro, we conducted wound-healing assay, tube formation assay, RT qPCR, ELISA, RNA sequencing and proteomic analysis. Results: iMSCs-lEVs alleviated the injury of ischemic lower limb and promoted the recovery of lower limb function. In vitro, iMSCs-lEVs promoted the proliferation, migration, and angiogenesis of HMEC-1 cells by regulating the ERK/MAPK signing pathway. Conclusion: This study demonstrated that iMSCs-lEVs promoted endothelial cell angiogenesis via the ERK/MAPK signaling pathway, thereby improving function after lower limb ischemic injury.

[Box: see text].

Constructing cropland ecological stability assessment method based on disturbance-resistance-response processes and classifying cropland ecological types.

The cropland ecosystem stability (CES) has received increasing attention, especially in ecologically fragile areas, because of its impact on cropland quality, agricultural production and its ability to resist external disturbances. In this study, we first introduced the concepts of resilience and resistance, proposed the ecosystem disturbance-resistance-response process, and established a framework for evaluating the spatial and temporal dynamics of the CES based on RS data, and innovatively combined the RS assessment results of CES with soil field samples data to further classify cropland ecological types (CET) in a key agricultural areas of the Qinghai-Tibetan Plateau, which can effectively identify those croplands in need of priority ecological protection. Results indicate that the combined interactions of disturbance, resistance and response systems affect CES, forming a complex process with significant fluctuations and spatial variations. We also conclude that the disturbance system is positively influenced by topography and precipitation, while slope negatively affects resistance system. Hydrothermal conditions positively influence resistance system, while the response system is influenced by environmental factors at a lower intensity in six periods. It was interesting to note that soil α-biodiversity indicators are significantly and positively correlated with CES at the end of the study period. Therefore, based on the CES assessment results, we further combined the soil α-biodiversity indicators to classify the type of spatial pattern of CET and found that the eastern and northern areas have better quality, which implied an increase in the CES and a higher level of soil biodiversity, which was ideal for cropland expansion. On the contrary, we concluded that the ecosystem maintenance of the Huangshui headwaters and the northern mountainous areas needs to be strengthened in order to reverse the ecological fragility here and safeguard the cropland productive capacity.

Identification of specific markers for human pluripotent stem cell-derived small extracellular vesicles.

Pluripotent stem cell-derived small extracellular vesicles (PSC-sEVs) have demonstrated great clinical translational potential in multiple aging-related degenerative diseases. Characterizing the PSC-sEVs is crucial for their clinical applications. However, the specific marker pattern of PSC-sEVs remains unknown. Here, the sEVs derived from two typical types of PSCs including induced pluripotent stem cells (iPSC-sEVs) and embryonic stem cells (ESC-sEVs) were analysed using proteomic analysis by liquid chromatography with tandem mass spectrometry (LC-MS/MS), and surface marker phenotyping analysis by nanoparticle flow cytometry (NanoFCM). A group of pluripotency-related proteins were found to be enriched in PSC-sEVs by LC-MS/MS and then validated by Western Blot analysis. To investigate whether these proteins were specifically expressed in PSC-sEVs, sEVs derived from seven types of non-PSCs (non-PSC-sEVs) were adopted for analysis. The results showed that PODXL, OCT4, Dnmt3a, and LIN28A were specifically enriched in PSC-sEVs but not in non-PSC-sEVs. Then, commonly used surface antigens for PSC identification (SSEA4, Tra-1-60 and Tra-1-81) and PODXL were gauged at single-particle resolution by NanoFCM for surface marker identification. The results showed that the positive rates of PODXL (>50%) and SSEA4 (>70%) in PSC-sEVs were much higher than those in non-PSC-sEVs (<10%). These results were further verified with samples purified by density gradient ultracentrifugation. Taken together, this study for the first time identified a cohort of specific markers for PSC-sEVs, among which PODXL, OCT4, Dnmt3a and LIN28A can be detected with Western Blot analysis, and PODXL and SSEA4 can be detected with NanoFCM analysis. The application of these specific markers for PSC-sEVs identification may advance the clinical translation of PSCs-sEVs.

3D hippocampal segmentation based on spatial and frequency domain features adaptive fusion and inter⁃class boundary region enhancement / 解剖学报

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

Opsin 3 expression in human Langerhans cell histiocytosis and its mediation of ELD-1 cellular function.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a type of -histiocytic disorder characterized by aberrant function, differentiation or proliferation of mononuclear phagocyte system cells, however, the pathogenesis is not fully understood. Opsin 3 (OPN3) plays an important role in regulating cell function. OBJECTIVES: We aimed to investigate OPN3 expression in LCH and Langerhans cells and evaluate its possible regulation of cellular function in a Langerhans cell-like cell line (ELD-1). MATERIALS & METHODS: Expression of OPN3 in LCH and paired adjacent healthy skin tissue was determined using microscopic tools (immunohistochemical and immunofluorescence staining) and RNA scope. OPN3 protein and mRNA levels in primary dendritic cells and ELD-1 were measured by real-time quantitative PCR and western blotting, respectively. The effects of reduced or over-expressed OPN3 mRNA level, via a lentiviral vector, were examined on ELD-1 proliferation, migration, cell cycle and apoptosis using the Cell Counting Kit 8, EdU-594 kit, Transwell assays and Cell Cycle Analysis Kit and Annexin V-PE apoptosis kit, respectively. Lastly, the signalling pathway mediating these functions was investigated via RNA sequencing and western blotting. RESULTS: OPN3 was highly expressed in human LCH tissue compared to healthy tissue, and was expressed in primary dendritic cells and ELD-1. Knockdown of OPN3 in ELD-1 inhibited cell proliferation, the cell cycle, and cell migration, while over-expression reversed these processes. These functions correlated with induction of the MAPK (p38/JNK/ERK) signalling pathway. CONCLUSION: Our results provide insight into the role of OPN3 in LCH which may become a molecular target for the clinical treatment of LCH.

Successful surgical management of a single coronary artery with giant coronary artery aneurysm with fistula to the right ventricle.

A giant coronary artery aneurysm (GCAA) concurrent with coronary artery fistula is a rare condition, and it becomes even more unusual when combined with a single coronary artery (SCA) anomaly. Here, we report such an extremely rare case, who is a 35-year-old woman presenting with severe chest distress. A GCAA with fistula to the right ventricle was noted, occurring in a single coronary artery, diagnosed by multimodality cardiovascular imaging techniques. Both GCAA and coronary artery fistula can cause severe cardiac complications, which jeopardize life. While an SCA is mostly asymptomatic, it may also lead to sudden cardiac death as well. Therefore, surgical intervention was recommended. We chose a novel thrombus-inducing strategy to eliminate the GCAA and repair the fistula. Symptoms were relieved after the surgery, and the patient remained asymptomatic over 8 months of follow-up.

Uncovering heterogeneous cognitive trajectories in mild cognitive impairment: a data-driven approach.

BACKGROUND: Given the complex and progressive nature of mild cognitive impairment (MCI), the ability to delineate and understand the heterogeneous cognitive trajectories is crucial for developing personalized medicine and informing trial design. The primary goals of this study were to examine whether different cognitive trajectories can be identified within subjects with MCI and, if present, to characterize each trajectory in relation to changes in all major Alzheimer's disease (AD) biomarkers over time. METHODS: Individuals with a diagnosis of MCI at the first visit and ≥ 1 follow-up cognitive assessment were selected from the Alzheimer's Disease Neuroimaging Initiative database (n = 936; age 73 ± 8; 40% female; 16 ± 3 years of education; 50% APOE4 carriers). Based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) total scores from baseline up to 5 years follow-up, a non-parametric k-means longitudinal clustering method was performed to obtain clusters of individuals with similar patterns of cognitive decline. We further conducted a series of linear mixed-effects models to study the associations of cluster membership with longitudinal changes in other cognitive measures, neurodegeneration, and in vivo AD pathologies. RESULTS: Four distinct cognitive trajectories emerged. Cluster 1 consisted of 255 individuals (27%) with a nearly non-existent rate of change in the ADAS-Cog-13 over 5 years of follow-up and a healthy-looking biomarker profile. Individuals in the cluster 2 (n = 336, 35%) and 3 (n = 240, 26%) groups showed relatively mild and moderate cognitive decline trajectories, respectively. Cluster 4, comprising about 11% of our study sample (n = 105), exhibited an aggressive cognitive decline trajectory and was characterized by a pronouncedly abnormal biomarker profile. CONCLUSIONS: Individuals with MCI show substantial heterogeneity in cognitive decline. Our findings may potentially contribute to improved trial design and patient stratification.

[Preparation and Tumor Targeting Analysis of Cell Membrane Nanovesicles Derived from Breast Cancer Cells].

Objective: To prepare cell membrane nanovesicles (NVs) derived from breast cancer cells, to explore their basic characteristics, tumor cell endocytosis, and in vivo distribution in a tumor-bearing mouse model, and to investigate their tumor targeting properties. Methods: 4T1 breast cancer cells were cultured in vitro. The cell membrane of 4T1 cells was isolated through ultracentrifugation and NVs were formulated with a liposome extruder. The size distribution of NVs was determined by way of dynamic light scattering, and the morphology properties of the NVs were examined with transmission electron microscope. The stability of NVs was analyzed by measuring the diameter changes of NVs submerged in phosphate-buffered saline (PBS). The biocompatibility of NVs was investigated by measuring the viability of dendritic cells treated with NVs at different concentrations (5, 10, 20, 50, and 100 mg·L -1) by CCK-8 assay. Fluorescence microscopy was used to analyze the cellular uptake of NVs by breast cancer cells. A mice model of breast cancer model was established with mice bearing subcutaneous xenograft of 4T1 cells. The mice were treated with Cy5.5-labeled NVs injected via the tail vein and the in vivo distribution of NVs was analyzed with an imaging system for small live animals. Results: The results showed that NVs derived from 4T1 breast cancer cells were successfully prepared. The NVs had a mean diameter of 123.2 nm and exhibited a hollow spherical structure under transmission electron microscope. No obvious change in the size of the NVs was observed after 7 days of incubation in PBS solution. CCK-8 assay results showed that the viability of dendritic cells treated with NVs at different concentrations was always higher than 90%. Fluorescence microscopic imaging showed that NVs could be efficiently internalized into breast cancer cells. in vivo biodistribution analysis revealed that breast cancer cell-derived NVs showed higher distribution in tumor tissue than the NVs prepared with normal cells did. Conclusion: We successfully prepared cell membrane NVs derived from 4T1 breast cancer cells. These NVs had efficient cellular uptake by breast cancer cells and sound tumor targeting properties.

Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathy via regulating macrophage heterogeneity.

Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance. The therapeutic effect of stem cell derived-small extracellular vesicles (sEVs) for tendinopathy has been validated in recent years. However, whether large extracellular vesicles (lEVs), another subset of extracellular vesicles, possesses the ability for the improvement of tendinopathy remains unknown. Here, we showed that lEVs secreted from iPSC-derived MSCs (iMSC-lEVs) significantly mitigated pain derived from tendinopathy in rats. Immunohistochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue. Meanwhile, in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs, and this effect was mediated by regulating p38 MAPK pathway. Moreover, liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs, including 134 new-found proteins beyond current Vesiclepedia database. By bioinformatics and Western blot analyses, we showed that DUSP2 and DUSP3, the negative regulator of p38 phosphorylation, were enriched in iMSC-lEVs and could be transported to macrophages. Further, the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients. Taken together, our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity, which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3, and might be a promising candidate for tendinopathy therapy.

Virtual teams in a gig economy.

While the gig economy provides flexible jobs for millions of workers globally, a lack of organization identity and coworker bonds contributes to their low engagement and high attrition rates. To test the impact of virtual teams on worker productivity and retention, we conduct a field experiment with 27,790 drivers on a ride-sharing platform. We organize drivers into teams that are randomly assigned to receiving their team ranking, or individual ranking within their team, or individual performance information (control). We find that treated drivers work longer hours and generate significantly higher revenue. Furthermore, drivers in the team-ranking treatment continue to be more engaged 3 mo after the end of the experiment. A machine-learning analysis of 149 team contests in 86 cities suggests that social comparison, driver experience, and within-team similarity are the key predictors of the virtual team efficacy.

Early Emergent and Progressive Aberrant Subchondral Bone Remodeling Coupled with Aggravated Cartilage Degeneration in Developmental Dysplasia of the Hip.

OBJECTIVE: Developmental dysplasia of the hip (DDH) is the most common skeletal development in children and could result in secondary osteoarthritis. This study aims to clarify the alternations of subchondral trabecular bone remodeling and microstructural properties during the development of DDH, and the potential influence of these alternations on the overlying cartilage degeneration and DDH progression. DESIGN: Traditional straight-leg swaddling method was adopted to establish DDH model in newborn Sprague Dawley rats. Hip joint specimens from normal or DDH rats were used. Typical features of DDH in radiological examination were observed by x-ray analysis. Micro-computed tomography analysis was applied to evaluate the microstructural properties of subchondral bone at postnatal weeks 2, 4, and 6. Histological and immunohistochemical analyses were adopted to appraise subchondral bone remodeling activity and cartilage degeneration. The associations among subchondral bone, articular cartilage, and DDH severity were analyzed via multiple linear regression analysis. RESULTS: Compared with control group, the subchondral bone in DDH group displayed a gradual trend of deteriorated microstructure and worsening biomechanical properties along with aberrant bone remodeling, which might be responsible for the inhibition of stress transmission from the articular cartilage to the subchondral bone and thus leading to the cartilage degeneration and accelerated DDH progression. CONCLUSIONS: Our findings indicate that alternations of subchondral trabecular bone in a time-dependent manner could contribute to the DDH progression and the amelioration on subchondral bone might be a favorable therapeutic candidate for DDH.

The Therapeutic Effect of iMSC-Derived Small Extracellular Vesicles on Tendinopathy Related Pain Through Alleviating Inflammation: An in vivo and in vitro Study.

Background: Tendinopathy is a common cause of tendon pain. However, there is a lack of effective therapies for managing tendinopathy pain, despite the pain being the most common complaint of patients. This study aimed to evaluate the therapeutic effect of small extracellular vesicles released from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) on tendinopathy pain and explore the underlying mechanisms. Methods: Rat tendinopathy model was established and underwent the injection of iMSC-sEVs to the quadriceps tendon one week after modeling. Pain-related behaviors were measured for the following four weeks. Tendon histology was assessed four weeks after the injection. To further investigate the potential mechanism, tenocytes were stimulated with IL-1ß to mimic tendinopathy in vitro. The effect of iMSC-sEVs on tenocyte proliferation and the expression of proinflammatory cytokines were measured by CCK-8, RT-qPCR, and ELISA. RNA-seq was further performed to systematically analyze the related global changes and underlying mechanisms. Results: Local injection of iMSC-sEVs was effective in alleviating pain in the tendinopathy rats compared with the vehicle group. Tendon histology showed ameliorated tendinopathy characteristics. Upon iMSC-sEVs treatment, significantly increased tenocyte proliferation and less expression of proinflammatory cytokines were observed. Transcriptome analysis revealed that iMSC-sEVs treatment upregulated the expression of genes involved in cell proliferation and downregulated the expression of genes involved in inflammation and collagen degeneration. Conclusion: Collectively, this study demonstrated iMSC-sEVs protect tenocytes from inflammatory stimulation and promote cell proliferation as well as collagen synthesis, thereby relieving pain derived from tendinopathy. As a cell-free regenerative treatment, iMSC-sEVs might be a promising therapeutic candidate for tendinopathy.

Small extracellular vesicles from iPSC-derived mesenchymal stem cells ameliorate tendinopathy pain by inhibiting mast cell activation.

Aim: This study aimed to explore the effect of small extracellular vesicles from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) on acute pain and investigate the underlying mechanisms. Materials & methods: The pathology of tendons was accessed by hematoxylin and eosin staining, immunohistochemical and immunofluorescent staining. The pain degree was measured by pain-related behaviors. In vitro, we performed ß-hexosaminidase release assay, RT-qPCR, toluidine blue staining, ELISA and RNA sequencing. Results: iMSC-sEVs effectively alleviated acute pain in tendinopathy as well as inhibiting activated mast cell infiltration and interactions with nerve fibers in vivo. In vitro, iMSC-sEVs reduced the degranulation of mast cells and the expression of proinflammatory cytokines and genes involved in the HIF-1 signaling pathway. Conclusion: This study demonstrated that iMSC-sEVs relieved tendinopathy-related pain through inhibiting mast cell activation via the HIF-1 signaling pathway.

Lower Plasma Total Testosterone Levels Were Associated With Steeper Decline in Brain Glucose Metabolism in Non-demented Older Men.

OBJECTIVE: There is growing evidence that testosterone may be implicated in the pathogenesis of Alzheimer's disease (AD). We aimed to examine the relationship between plasma total testosterone levels and change in brain glucose metabolism over time among non-demented older people. METHODS: The association of plasma total testosterone levels with change in brain glucose metabolism among non-demented older people was investigated cross-sectionally and longitudinally. Given a significant difference in levels of plasma total testosterone between gender, we performed our analysis in a sex-stratified way. At baseline, 228 non-demented older people were included: 152 males and 76 females. RESULTS: In the cross-sectional analysis, no significant relationship between plasma total testosterone levels and brain glucose metabolism was found in males or females. In the longitudinal analysis, we found a significant association of plasma total testosterone levels with change in brain glucose metabolism over time in males, but not in females. More specifically, in males, higher levels of total testosterone in plasma at baseline were associated with slower decline in brain glucose metabolism. CONCLUSION: We found that higher levels of total testosterone in plasma at baseline were associated with slower decline in brain glucose metabolism in males without dementia, indicating that testosterone may have beneficial effects on brain function.

Mitral Valve Repair for Isolated Libman-Sacks Endocarditis in a Patient with Primary Antiphospholipid Syndrome.

Libman-Sacks endocarditis, characterized by verrucous vegetations formation, is a typical cardiac manifestation of autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Although typically mild and asymptomatic, Libman-Sacks endocarditis can lead to serious complications, including thromboembolic events, superimposed bacterial endocarditis, and severe valvular regurgitation and/or stenosis, and valve surgery may be required. Here, we report a case of mitral valve repair for a large Libman-Sacks vegetation in a 29-year-old woman with a history of APS with cerebral infarction. Transesophageal echocardiography (TEE) demonstrated an isolated large mobile vegetation on the atrial side of posterior mitral valve leaflet, with severe mitral regurgitation. Next, we organized a multidisciplinary team meeting to better evaluate the case before performing the surgery. To prevent further thromboembolic events, and due to the insufficiency of the mitral valve, the patient was accepted for mitral valve surgery, and she was discharged uneventfully 10 days after successful surgery. She was managed with long-term anticoagulation medicine after surgery and followed up for 2 years with no complications. The present case showed mitral repair is feasible and effective in young female patients of child-bearing age, and the lesion only localized mitral valve abnormalities caused by Libman-Sacks endocarditis.

Epidemiological Characteristics and Their Influencing Factors Among Pulmonary Tuberculosis Patients With and Without Diabetes Mellitus: A Survey Study From Drug Resistance Surveillance in East China.

BACKGROUND: The burden of pulmonary tuberculosis (TB) and diabetes mellitus (DM) have become serious global concerns, while the comprehensive evaluations of DM status and drug resistance in TB patients are still lacking. METHODS: All details of TB cases were collected from drug resistance monitoring sentinels in Zhejiang province. Fisher's exact test or Pearson chi-square test (χ2) was used to compare the baseline characteristics among TB with different DM statuses. The logistic regression model was used to estimate the relationship between DM and different drug resistance spectra. Univariate analysis and multivariate logistic model were used to explore the possible risk factors of drug resistance in TB patients with DM and no DM. RESULTS: 936 TB cases with smear-positive in Zhejiang province were collected, in which 76 patients (8.12%) owned the co-morbidity of DM. TB-DM prevalence was higher in older, Han nationality, employed, accompanied by no health insurance and hepatitis B status. Among 860 cases of TB-no DM and 76 cases of TB-DM, drug resistance-TB accounted for 31.51% and 23.68% (P > 0.05), MR-TB accounted for 15.93% and 14.47% (P > 0.05), respectively. MDR-TB was 4.88% and 6.58% (P > 0.05). The incidence of poly-drug resistant tuberculosis (PDR-TB) in TB-no DM patients (10.70 vs. 2.63%, OR: 4.43; 95% CI, 1.07-18.36) was higher than that in the TB-DM group (P < 0.05). In univariate and multivariate analysis, none of the basic factors were statistically significant with drug resistance among TB-DM cases (all P > 0.05). Retreatment was the risk factor of drug resistance among TB-no DM cases. CONCLUSIONS: Our results showed that the drug resistance rate of the TB-DM group was not higher than that of the TB-no DM group. Patients with TB-no DM were at a higher risk for PDR-TB, but not for MDR-TB, MR-TB, and drug resistance-TB. Special attention should be paid to TB-no DM patients who have been previously treated. In the future, large-scale and well-designed prospective studies are needed to clarify the impact of DM on the drug-resistance among TB.

Sex Difference in the Association of APOE4 with Memory Decline in Mild Cognitive Impairment.

Our aim was to examine whether the influence of apolipoprotein E4 (APOE4) genotype on cognitive decline differs in male and female across the Alzheimer's disease (AD) continuum. Among individuals with normal cognition (NC; n = 415), mild cognitive impairment (MCI; n = 870), and AD (n = 334), we investigated the longitudinal associations of APOE4 genotype and sex with cognitive decline over 13 years. Our cognitive outcomes were Rey Auditory Verbal Learning Test (RAVLT) total learning score and delayed recall and Mini-Mental State Examination (MMSE) score. There were significant effects of the APOE4×sex interaction on change in verbal memory in the MCI group, but not the NC or AD group. Specifically, among individuals with MCI, female APOE4 carriers had a steeper decline in RAVLT total learning score, but not delayed recall or MMSE score compared to all other groups (APOE4 + /Male, APOE4-/Female, APOE4-/Male). In conclusion, female APOE4 carriers have faster rates of memory decline than their male counterparts among MCI individuals.

The Relationship Between Hippocampal Volumes and Delayed Recall Is Modified by APOE ε4 in Mild Cognitive Impairment.

Objective: To investigate whether APOE ε4 affects the association of verbal memory with neurodegeneration presented by the hippocampal volume/intracranial volume ratio (HpVR). Methods: The study sample included 371 individuals with normal cognition (NC), 725 subjects with amnestic mild cognitive impairment (aMCI), and 251 patients with mild Alzheimer's disease (AD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who underwent the rey auditory verbal learning test (RAVLT). Multiple linear regression models were conducted to assess the effect of the APOE ε4∗HpVR interaction on RAVLT in all subjects and in each diagnostic group adjusting for age, gender and educational attainment, and global cognition. Results: In all subjects, there was no significant APOE ε4 × HpVR interaction for immediate recall or delayed recall (p > 0.05). However, in aMCI subjects, there was a significant APOE ε4 × HpVR interaction for delayed recall (p = 0.008), but not immediate recall (p = 0.15). More specifically, the detrimental effect of APOE ε4 on delayed recall altered by HpVR such that this effect was most evident among subjects with small to moderate HpVR, but this disadvantage was absent or even reversed among subjects with larger HpVR. No significant interaction was observed in the NC or AD group. Conclusion: These findings highlight a potential role of APOE ε4 status in affecting the association of hippocampus size with delayed recall memory in the early stage of AD.

Primary, cardiac, fibroblastic osteosarcoma: A case report.

RATIONALE: Primary cardiac osteosarcoma is a rare tumor. To our knowledge, only 15 cases have been reported in the literature in the past 10 years. We describe a case of primary, cardiac, fibroblastic osteosarcoma in a 42-year-old woman. PATIENT CONCERNS: A 42-year-old woman with a 10-day history of chest pain. Intraoperatively, a mass was found originating from the ostium of the left inferior pulmonary vein in the left atrium, extending to the mitral orifice. Histologically, the tumor contained variable amounts of spindle cells and osseous differentiation in different areas. Primary, cardiac fibroblastic osteosarcoma had the typical appearance of interlacing hyperchromatic spindle-shaped stromal cells associated with osseous matrix. DIAGNOSES: According to the clinicopathological features, diagnosis of primary, cardiac fibroblastic osteosarcoma was made. INTERVENTIONS: Wide surgical excision of the mass was performed. OUTCOMES: Three months after the operation, transthoracic echocardiography demonstrated a 3.2 cm × 2 cm recurrent mass in the wall of the left atrium (LA). She died shortly afterwards as a result of the local disease recurrence. LESSONS: In this report, we describe a rare case of primary, cardiac fibroblastic osteosarcoma, and findings are helpful for the pathologists would like to further identify the clinicopathological features of this rare tumor.

HONH3Cl optimized CH3NH3PbI3 films for improving performance of planar heterojunction perovskite solar cells via a one-step route.

Planar heterojunction perovskite solar cells (PHJ-PSCs) constructed with one-step precursor solution spin-coating deposition (OPSSD) usually give an extremely low performance mainly due to the poor morphology and low crystallinity of the perovskite films. In this work, by incorporating a suitable HONH3Cl additive in the perovskite precursor solution, a high quality perovskite film with improved morphology and crystallinity was obtained. The UV-vis measurement of the CH3NH3I solutions without and with HONH3Cl demonstrates that the improved quality of the perovskite film can be easily attributed to a combined effect of N2, I2, H2O and CH3NH3Cl originating from the oxidation of CH3NH3I triggered by the HONH3Cl additive, which can manipulate the crystallization process of the perovskite. Accordingly, the improved performance for the HONH3Cl-induced PHJ-PSCs can also be demonstrated. At the optimized molar ratio of 1 : 1 : 0.1 for PbI2 : CH3NH3I : HONH3Cl, the PHJ-PSCs exhibit an average power conversion efficiency (PCE) of 10.61 ± 0.51%, which is much higher than that of pristine 1 : 1 : 0 based cells without additive (7.21 ± 0.61%), and the best performing HONH3Cl-induced device can yield a PCE as high as 11.12% with a Jsc of 18.42 mA cm-2, Voc of 0.95 V and FF of 0.63. Introducing suitable HONH3Cl as an additive into the perovskite precursor solution is really an effective route to enhance the performance of the PHJ-PSCs via OPSSD.