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OBJECTIVE: This study aimed to explore the clinical detection and prognosis of coagulation function in patients with liver failure and sepsis. METHODS: The plasma fibrinogen (FIB), factor II, factor VII, factor V, factor IV, antithrombin III (ATIII), platelet (PLT), mean PLT volume (MPV), D-dimer, prothrombin activity (PTA), and fibrin degradation product (FDP) levels and thromboelastogram values were detected in patients with liver failure complicated with sepsis and compared with those in the liver failure and liver cirrhosis groups. The patients with liver failure complicated with sepsis were analyzed by univariate and multivariate logistic regression, and the regression equation was established. RESULTS: The levels of FIB, factor II, factor VII, factor V, ATIII, PLT, MPV, D-dimer, and FDP in the patients with liver failure complicated with sepsis were compared with those in the control group patients, and the differences were statistically significant (p

Objective The current study aimed to further verify the feasibility of ultrasound-guided selective pulsed radiofrequency (PRF) therapy of greater auricular nerve (GAN) in the treatment of head and neck post-herpetic neuralgia (PHN) by observing the efficacy and safety. Methods Under the guidance of high-frequency ultrasound (Frequency: 10 MHz), the GAN was identified by a radiofrequency electrode trocar with a transverse in-plane approach, which was inserted into the GAN, then the inner needle of the trocar was retracted. After adjusting the technical variables (electrode tip temperature: 42°C, output voltage: 60 V, pulse frequency: 2 Hz, pulse width: 22 ms, single duration: 240 s, two times), the radiofrequency electrode placed on the auricle and below the ear for sensory and motor tests began to work. Results The pain in the left head and neck of the patient lasted for more than 1 month, we decided to try selective PRF of GAN guided by ultrasound for the first time. Immediately after the treatment, 11-point pain intensity numerical rating scale (PI-NRS) score ranged from 5 to 1. During his hospitalization, mecobalamine and gabapentin were taken instead of opioids. Seven days after the procedure, PI-NRS score was 2, the degree of numbness the patient he felt by himself in the original lesion area relieved from 100% to 40%, the depression module of the Patient Health Questionnaire-9 (PHQ-9) score was from 7 to 5, the Generalized Anxiety Disorder-7 (GAD-7) score from 8 to 4, the range of pain areas was reduced to external auditory tract, and there were no adverse events occurring. Conclusion The ultrasound-guided selective PRF treatment of GAN was safe and effective in the improvement of PHN in the head and neck, which is worthy of clinical promotion.

Background Apios Americana Medicus (AM), a potential staple food substitution characterized as mass production, abundant nutrition and low cost, has been consumed with a long history in eastern North American. Nowadays, AM have been cultured, consumed and studied worldwide. Nevertheless, present studies focused on AM are mainly about its nutritional values, chemical compositions and biological activities, whereas these studies only remain at their infancy, and investigations concerning AM's deep processing and application are still insufficient. Besides, current studies have dedicated to learn edible AM tuber (AMT), while less studies paid attention other parts, such as flower, leaf and vine. Scope and approach In this review, we comprehensively reviewed and analyzed the current research progress of AM based on the literature published from 1924 to 2021, then systematically categorized and summarized the bioactive substances in different parts, presented and exemplified their biological activities. Furthermore, we have also thoroughly discussed the present shortage and challenges that AM faces, and predicted AM's possible orientation and perspectives in the future. Key findings and conclusions AM has abundant bioactive chemicals in different parts, and demonstrates remarkable bioactivities in antioxidant, anti-inflammation, anti-diabetes, anti-atherosclerosis, anti-hypertension, immunoregulation, anti-tumor and improvement in post-partum uterine involution. Therefore, it is suggested that AM shows potential to become future staple food candidate with diverse bioactivities, which would enlighten some innovate ideas on increasing farmers’ income, and provide potential promising strategies to solve global hunger.

PURPOSE: We aimed to evaluate the safety and effectiveness of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) guided by multiple imaging modalities for hepatocellular carcinomas (HCCs) in special (i.e., high-risk or unfavorable) locations compared with those in conventional locations. METHODS: A total of 122 HCC patients were enrolled, including 85 patients (69.7%) with HCC in conventional locations and 37 (30.3%) with HCC in special locations. The clinical data, overall survival (OS), progression-free survival (PFS), and procedure-related adverse events were analyzed. RESULTS: RFA combined with TACE was successfully performed in all patients. Three complications (2.5%) occurred, with no significant difference between the conventional (n=1, 1.2%) and special (n=2, 5.4%) locations (P = 0.218). Complete tumor necrosis rate was not significantly different between the conventional (n=73, 85.9%) and special (n=34, 91.9%) locations at one-month imaging (P = 0.353). After a follow-up of 3–48 months, the PFS was 17 months for patients with HCC in conventional locations and 14 months for patients with HCC in special locations; one-year PFS rate was 68.1% in the conventional location group, not significantly (P = 0.741) different from 59.1% in the special location group. The OS was 28 months in the conventional location group while 32 months in the special location group. The cumulative one- and two-year OS rates were 89.9% and 63.3%, respectively, in the conventional location group, not significantly different from 96.3% and 65% in the special location group (P = 0.273). Age (P = 0.043) and tumor size (P < 0.001) were significant prognostic factors for OS, and tumor size (P < 0.001) was the only significant prognostic factor for PFS. CONCLUSION: RFA guided by multiple imaging modalities combined with TACE may be safe and effective for treating HCCs in special locations.

Background: Population-based data on the risk assessment of newly diagnosed cervical cancer patients' bone metastasis (CCBM) are lacking. This study aimed to develop various predictive models to assess the risk of bone metastasis via machine learning algorithms.Materials and Methods: We retrospectively reviewed the CCBM patients from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to risk factors of the presence of bone metastasis. Clinical usefulness was assessed by Akaike information criteria (AIC) and multiple machine learning algorithms based predictive models. Concordance index (C-index) and receiver operating characteristic (ROC) curve were used to define the predictive and discriminatory capacity of predictive models.Results: A total of 16 candidate variables were included to develop predictive models for bone metastasis by machine learning. The areas under the ROC curve (AUCs) of the random forest model (RF), generalized linear model (GL), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), artificial neutral network (ANN), decision tree (DT), and naive bayesian model (NBM) ranged from 0.85 to 0.93. The RF model with 10 variables was developed as the optimal predictive model. The weight of variables indicated the top seven factors were organ-site metastasis (liver, brain, and lung), TNM stage and age.Conclusions: Multiple machine learning based predictive models were developed to identify risk of bone metastasis in cervical cancer patients. By incorporating clinical characteristics and other candidate variables showed robust risk stratification for CCBM patients, and the RF predictive model performed best among these predictive models.

In this paper, we report a p-GaN/n-ZnO nanoplate/CsPbBr3 quantum dots (QDs) heterojunction light-emitting diode (LED) for dual-wavelength emission. ZnO nanoplates were prepared by vapor phase transport on the GaN thin film to form the p-GaN/n-ZnO nanoplate heterojunction. Afterwards, green CsPbBr3 QDs (band gap of 2.25 eV) were deposited on ZnO nanoplates to realize green light emission. The structure and photoluminescence of the ZnO nanoplates and CsPbBr3 QDs were characterized. The as-prepared LED device with turn-on voltage of ∼ 2.7 V displays a typical rectification behavior. The electroluminescence spectra with narrow emission peaks reveal the device presents commendable dual-wavelength electroluminescence performance at ∼ 385 nm and ∼ 512 nm and the electroluminescence intensity saturates at about 65 mA/cm2. Moreover, the detailed electroluminescence mechanism including emission originate of n-ZnO/p-GaN heterojunction was discussed based on the band diagram. Thus, our work indicates compelling potential for the practical application of perovskite LEDs.

To explore the clinical and imaging characteristics and summarize the causes of missed diagnosis of reversible posterior leukoencephalopathy syndrome (RPLS) in eclampsia. We collected the data of a total of 45 patients with RPLS who were misdiagnosed initially (27 cases were confirmed and 18 cases were suspicious) out of 804 patients with severe eclampsia who had presented themselves to the Affiliated Hospital of Xuzhou Medical University from January 2014 to December 2016. We summarized the clinical and imaging characteristics of the patients and analyzed the possible causes of the misdiagnosis. Among the 804 patients with eclampsia, 45 were misdiagnosed the first time. Their clinical manifestations included headache (20 cases), epilepsy (13 cases), blurred vision (11 cases), disturbance of consciousness (2 cases), and drowsiness (3 cases). The parietal lobe was involved in 22 cases, the occipital lobe in 15 cases, the frontal lobe in 20 cases, basal ganglia in 9 cases, and the temporal lobe in 8 cases. Low-density lesions were observed on computed tomography (CT) scans. Head magnetic resonance (MR) scans showed hypo-intense lesions on T1-weighted image (T1WI), hyper-intense lesions on the T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR), iso-intense or slightly hyper-intense lesion on diffusion-weighted imaging (DWI), and slightly hyper-intense or hypo-intense lesion on apparent diffusion coefficient (ADC). The incidence of reversible posterior leukoencephalopathy syndrome is extremely high. The clinical features include headache, mental disturbance, seizures, blurred vision, and other neurological symptoms. The lesion area is mainly limited to the parietal and occipital lobes; however, the frontal lobe, basal ganglia, temporal lobe, corpus callosum, and cerebellum can also be involved. The prognosis is good with timely and appropriate treatments.

Aging has been regarded as a treatable condition, and delaying aging could prevent some diseases. Ovarian aging, a special type of organ senescence, is the earliest-aging organ, as ovaries exhibit an accelerated rate of aging with characteristics of gradual declines in ovarian follicle quantity and quality since birth, compared to other organs. Ovarian aging is considered as the pacemaker of female body aging, which drives the aging of multiple organs of the body. Hence, anti-ovarian aging has become a research topic broadly interesting to both biomedical scientists and pharmaceutical industry. A marked progress has been made in exploration of possible anti-ovarian agents or approaches, such as calorie restriction mimetics, antioxidants, autophagy inducers etc., over the past years. This review is attempted to discuss recent advances in the area of anti-ovarian aging pharmacology and to offer new insights into our better understanding of molecular mechanisms underlying ovarian aging, which might be informative for future prevention and treatment of ovarian aging and its related diseases.

Objectives: Both coronavirus disease 2019 (COVID-19) pneumonia and influenza A (H1N1) pneumonia are highly contagious diseases. We aimed to characterize initial computed tomography (CT) and clinical features and to develop a model for differentiating COVID-19 pneumonia from H1N1 pneumonia.Methods: In total, we enrolled 291 patients with COVID-19 pneumonia from January 20 to February 13, 2020, and 97 patients with H1N1 pneumonia from May 24, 2009, to January 29, 2010 from two hospitals. Patients were randomly grouped into a primary cohort and a validation cohort using a seven-to-three ratio, and their clinicoradiologic data on admission were compared. The clinicoradiologic features were optimized by the least absolute shrinkage and selection operator (LASSO) logistic regression analysis to generate a model for differential diagnosis. Receiver operating characteristic (ROC) curves were plotted for assessing the performance of the model in the primary and validation cohorts.Results: The COVID-19 pneumonia mainly presented a peripheral distribution pattern (262/291, 90.0%); in contrast, H1N1 pneumonia most commonly presented a peribronchovascular distribution pattern (52/97, 53.6%). In LASSO logistic regression, peripheral distribution patterns, older age, low-grade fever, and slightly elevated aspartate aminotransferase (AST) were associated with COVID-19 pneumonia, whereas, a peribronchovascular distribution pattern, centrilobular nodule or tree-in-bud sign, consolidation, bronchial wall thickening or bronchiectasis, younger age, hyperpyrexia, and a higher level of AST were associated with H1N1 pneumonia. For the primary and validation cohorts, the LASSO model containing above eight clinicoradiologic features yielded an area under curve (AUC) of 0.963 and 0.943, with sensitivity of 89.7 and 86.2%, specificity of 89.7 and 89.7%, and accuracy of 89.7 and 87.1%, respectively.Conclusions: Combination of distribution pattern and category of pulmonary opacity on chest CT with clinical features facilitates the differentiation of COVID-19 pneumonia from H1N1 pneumonia.

BACKGROUND: To investigate the predictive value of blood ammonia (BLA) quantification in the prognosis of acute liver failure (ALF). METHODS: Seventy-one patients with ALF were enrolled and BLA concentration was measured in all patients. After following up for 28 days, patients were divided into two groups: the surviving group (n = 21) and the deceased group (n = 50). An independent-samples t-test was used to compare BLA concentrations between the two groups, and receiver operating characteristic curves were used to ­evaluate the predictive value of BLA in the prognosis of ALF. A fourfold table analysis was performed with the determined BLA cutoff value. RESULTS: The average concentration of BLA in the deceased group was significantly higher compared with the surviving group (144.50 µmol/L vs. 106 µmol/L, respectively; P = .035). The cutoff BLA concentration for a good ALF prognosis was 122.5 µmol/L. The area under the curve was 0.659. Both the sensitivity and specificity were >0.6. The 95% CIs for sensitivity and specificity were 0.452-0.733 and 0.477-0.878, respectively. The fourfold table analysis revealed a positive predictive value of 83.3%, a negative predictive value of 42.9%, a misdiagnosis rate of 28.6%, and an accuracy of 63.4%. CONCLUSION: With a cutoff BLA concentration of 122.5 µmol/L, the prognosis of ALF could be predicted with high sensitivity and specificity, a positive predictive value, a low misdiagnosis rate, and good accuracy.

Lei Li,1,* Ling Chen,1,* Fang Lin,2 Jinsong Mu,2 Dan Wang,1 Wei Zhang,1 Lai Mi,1 Yuling Qin,1 Yuesu Zhou1 1Department of Emergency, Fifth Medical Center of Chinese PLA Hospital, Beijing, 100039, People’s Republic of China; 2Department of Critical Care Medicine, Fifth Medical Center of Chinese PLA Hospital, Beijing, 100039, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuesu Zhou; Yuling QinDepartment of Emergency, Fifth Medical Center of Chinese PLA Hospital, No. 100 Middle Road of West 4th Ring Road, Fengtai District, Beijing, 100039, People’s Republic of ChinaTel/Fax +86 10 66933202Email yuesu_zhou@163.com; ylqin90@163.comObjective: The present study aims to investigate the cytokines interleukin (IL)-4, IL-6, IL-10, and IL-17 in the peripheral blood of patients with acute-on-chronic liver failure combined with sepsis, patients with acute-on-chronic liver failure, and patients with liver cirrhosis; to investigate the changes in the levels of inflammatory factors in cases of coagulation dysfunction in liver failure combined with sepsis; and to discover more typical inflammatory factors for further evaluation by functional experiments.Methods: In the present study, 41 patients with acute-on-chronic liver failure and sepsis were enrolled as study subjects. These patients were compared with 20 patients with either acute-on-chronic liver failure and liver cirrhosis during the same period. The changes in IL-4, IL-6, IL-10, and IL-17 were detected in each group by enzyme-linked immunosorbent assay, and SPSS 17.0 software was adopted for data analysis.Results: There were no significant changes in the levels of IL-4 in any of the groups. However, the levels of IL-6, IL-10, and IL-17 were significantly higher in the acute-on-chronic liver failure and sepsis group than in the acute-on-chronic liver failure and the liver cirrhosis groups.Conclusion: The present study shows that when liver failure is accompanied by sepsis, the serum levels of inflammatory factors IL-6, IL-10, and IL-17 are significantly increased. This could be closely correlated with the occurrence and development of coagulation dysfunction and sepsis. These findings provide new ideas for delaying the deterioration of patients with liver failure in clinical practice.Keywords: liver failure, coagulation dysfunction, sepsis, inflammatory factor, expression

Avian influenza in human, especially the severe type, progresses rapidly and causes multiple complications, such as acute lung injury, acute respiratory distress syndrome (ARDS), pulmonary hemorrhage, pleural effusion, pancytopenia, heart failure, renal failure, multiple organ failure, sepsis, shock, and Reye syndrome. The patients often die from severe pulmonary failure. Compared with adults, children suffering from avian influenza progress more rapidly and are more vulnerable to pneumothorax and secondary infection.

Embryonic exposure to environmental chemicals may result in specific chronic diseases in adulthood. Parabens, a type of environmental endocrine disruptors widely used in pharmaceuticals and cosmetics, have been shown to cause a decline in women's reproductive function. However, whether exposure to parabens during pregnancy also negatively affect the ovarian function of the female offspring in adulthood remains unclear. This study aims to investigate the effects of prenatal propylparaben (PrP) exposure on the ovarian function of adult mice aged 46 weeks, which is equivalent to the age of 40 years in women. Pregnant ICR mice were intraperitoneally injected with human-relevant doses of PrP (i.e., 0, 7.5, 90, and 450 mg/kg/day) during the fetal sex determination period—from embryonic day E7.5 to E13.5. Our results revealed that ovarian aging was accelerated in PrP-exposed mice at 46 weeks, with altered regularity of the estrous cycle, decreased serum estrogen (E2) and progesterone (P4) levels, reduced size of the primordial follicle pool, and increased number of atretic follicles. It was found that prenatal exposure to human-relevant doses of PrP exacerbated ovarian oxidative stress, inflammation, and fibrosis, which promoted follicular atresia by activating the mitochondrial apoptosis pathway. To compensate, the depletion of primordial follicles was also accelerated by activating the PI3K/AKT/mTOR signaling pathway in PrP-exposed mice. Moreover, PrP induced hypermethylation of CpG sites in the promoter region of Cyp11a1 (a 17.16–64.28% increase) partly led to the disrupted steroidogenesis, and the altered methylation levels of imprinted genes H19 and Peg3 may also contribute to the phenotypes observed. These remarkable findings highlight the embryonic origin of ovarian aging and suggest that a reduced use of PrP during pregnancy should be advocated.

Objective: This study was intended to investigate the relationship between COVID-19 disease and ovarian function in reproductive-aged women.Methods: Female COVID-19 patients of reproductive age were recruited between January 28 and March 8, 2020 from Tongji Hospital in Wuhan. Their baseline and clinical characteristics, as well as menstrual conditions, were recorded. Differentials in ovarian reserve markers and sex hormones (including anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], the ratio of FSH to luteinizing hormone [LH], estradiol [E2], progesterone [P], testosterone [T], and prolactin [PRL] were compared to those of healthy women who were randomly selected and individually matched for age, region, and menstrual status. Uni- and multi-variable hierarchical linear regression analyses were performed to identify risk factors associated with ovarian function in COVID-19 women.Results: Seventy eight patients agreed to be tested for serum hormone, of whom 17 (21.79%) were diagnosed as the severe group and 39 (50%) were in the basal level group. Menstrual status (P = 0.55), menstrual volumes (P = 0.066), phase of menstrual cycle (P = 0.58), and dysmenorrhea history (P = 0.12) were similar without significant differences between non-severe and severe COVID-19 women. Significant lower serum AMH level/proportion (0.19/0.28 vs. 1.12 ng/ml, P = 0.003/0.027; AMH ≤ 1.1 ng/ml: 75/70.4 vs. 49.7%, P = 0.009/0.004), higher serum T (0.38/0.39 vs. 0.22 ng/ml, P < 0.001/0.001) and PRL (25.43/24.10 vs. 12.12 ng/ml, P < 0.001/0.001) levels were observed in basal level and the all-COVID-19 group compared with healthy age-matched control. When adjusted for age, menstrual status and parity variations in multivariate hierarchical linear regression analysis, COVID-19 disease was significantly associated with serum AMH (β = −0.191; 95% CI: −1.177–0.327; P = 0.001), T (β = 0.411; 95% CI: 11.154–22.709; P < 0.001), and PRL (β = 0.497; 95% CI: 10.787–20.266; P < 0.001), suggesting an independent risk factor for ovarian function, which accounted for 3.2% of the decline in AMH, 14.3% of the increase in T, and 20.7% of the increase in PRL.Conclusion: Ovarian injury, including declined ovarian reserve and reproductive endocrine disorder, can be observed in women with COVID-19. More attention should be paid to their ovarian function under this pandemic, especially regarding reproductive-aged women.Clinical Trial Number: ChiCTR2000030015.

Fertility and ovarian protection against chemotherapy-associated ovarian damage has formed a new field called oncofertility, which is driven by the pursuit of fertility protection as well as good life quality for numerous female cancer survivors. However, the choice of fertility and ovarian protection method is a difficult problem during chemotherapy and there is no uniform guideline at present. To alleviate ovarian toxicity caused by anticancer drugs, effective methods combined with an individualized treatment plan that integrates an optimal strategy for preserving and restoring reproductive function should be offered from well-established to experimental stages before, during, and after chemotherapy. Although embryo, oocyte, and ovarian tissue cryopreservation are the major methods that have been proven effective and feasible for fertility protection, they are also subject to many limitations. Therefore, this paper mainly discusses the future potential methods and corresponding mechanisms for fertility protection in chemotherapy-associated ovarian damage.

Background Neoadjuvant chemotherapy has been used for treatment of cervical cancer for a long time; however, the role of early non-response on prognosis is still confusing. This study was designed to assess its impact on disease-free survival (DFS). Methods Databases "PubMed", "Embase" and the "Cochrane Library" were searched out through May 2020, and both random effects model and fixed effect model were employed to calculate the main pooled results. I2 and Cochrane Q test were used to test the heterogeneity among the studies. Funnel plot with Begg's and Egger's tests was used to assess the publication bias that may exist in the study. Sensitivity analysis was performed to detect the origin of the heterogeneity. Results A total of 1,349 articles were found at first; then, after several rounds of exclusion, we identified 8 articles with 9 studies which were accordant with the standards of the inclusion. A combined analysis was performed among the 1,462 responders and 490 non-responders. For 1-year DFS, sub-analysis showed hazard ratio (HR) was 0.25 (95% CI: 0.14-0.43) using RECIST criteria; and HR was 0.52 (95% CI: 0.36- 0.75) using WHO criteria; Egger's test showed that P=0.35 for RECIST criteria and P=0.57 for WHO criteria; Begg's test showed P=0.34 for RECIST criteria and P=0.60 for WHO criteria. For 3-year DFS, HR was 0.26 (95% CI: 0.16-0.43) using RECIST criteria and was 0.47 (95% CI: 0.30-0.73) using WHO criteria. For 5-year DFS, HR was 0.26 (95% CI: 0.16-0.42) using RECIST criteria and was 0.49 (95% CI: 0.33-0.71) using WHO criteria. Conclusions Early non-response to neoadjuvant chemotherapy was significantly associated with higher recurrence of cervical cancer. Prospective randomized studies are warranted to validate this finding.

A cascaded GPS/IMU integrated positioning system based on four-wheel independent drive steering vehicle kinematics model, which solves the problem that the positioning error of usual GPS/IMU integrated positioning system will grow over time when GPS signal is interrupted, is proposed in this paper. The cascaded GPS/IMU integrated positioning system proposed in this paper consists of an attitude-velocity filter and a position filter. The attitude-velocity filter fuses the angular velocity and acceleration provided by the four-wheel independent drive steering vehicle kinematics model and provided by the IMU, then outputs the optimized angular velocity and acceleration. The attitude-velocity-position calculation unit outputs the attitude, velocity and position. The position filter fuses the position provided by the attitude-velocity-position calculation unit and provided by the GPS, and outputs the optimized position. The simulation experiments are carried out through Carsim and the custom function. The simulation results show that compared with the usual GPS/IMU integrated positioning system, the cascaded GPS/IMU integrated positioning system reduces the cumulative error and has better positioning accuracy when the GPS signal is interrupted, for example, the maximum heading angle error is reduced by 88%, the maximum velocity error is reduced by 93%, the maximum position error is reduced by 90%.

Background Recent studies have indicated that females with coronavirus disease 2019 (COVID-19) have a lower morbidity, severe case rate, and mortality and better outcome than those of male individuals. However, the reasons remained to be addressed. Methods To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at 3 branches of Tongji Hospital (N = 1902), and analyzed the correlation between menstrual status (n = 509, including 68 from Mobile Cabin Hospital), female hormones (n = 78), and cytokines related to immunity and inflammation (n = 263), and the severity/clinical outcomes in female patients, Nonmenopausal females with COVID-19 had milder severity, better outcome, and shorter hospital stays than menopausal patients. E2 might be a potential protective factor against COVID-19, partly through its regulation of cytokines, which significantly correlated with severity of infection.

ImportanceHow to explain the better prognosis of female coronavirus disease 2019 (COVID-19) patients than that of males?ObjectiveTo determine the correlation between menstruation status/sex hormones and prognosis of COVID-19, and to identify potential protective factors for female patients.Design, Setting, and ParticipantsA cross-sectional study of COVID-19 patients who were hospitalized at Tongji and Mobile Cabin Hospitals from Jan 28, 2020 to March 8, 2020.ExposuresConfirmed SARS-CoV-2 infection.Main Outcomes and MeasuresSex differences in severity and composite endpoints (admission to intensive care unit (ICU), use of mechanical ventilation, or death) of COVID-19 patients were compared. The correlation analysis and cox/logistic regression modeling of menstruation status/sex hormones and prognosis were conducted. Correlation between cytokines related to immunity and inflammation and disease severity or estradiol (E2) was revealed.ResultsChi square test indicated significant differences in distribution of composite endpoints (pp=0.029). E2 showed protective effect against disease severity (HR= 0.335, 95%CI = (0.105-1.070), p= 0.046). In the Mann-Whitney U test, the higher levels of IL6 and IL8 were found in severe group (p= 0.040, 0.033). The higher levels of IL2R, IL6, IL8 and IL10 were also observed in patients with composite end points (p). E2 levels were negatively correlated with IL2R, IL6, IL8 and TNFα in luteal phase (Pearson Correlation=−0.592, −0.558, −0.545, −0.623; p=0.033, 0.048, 0.054, 0.023) and with C3 in follicular phase (Pearson Correlation=-0.651; p=0.030).Conclusions and RelevanceMenopause is an independent risk factor for COVID-19. E2 and AMH are negatively correlated with COVID-19’s severity probably due to their regulation of cytokines related to immunity and inflammation.Key PointsQuestionAny differences in the outcomes between hospitalized female and male COVID-19 patients? If so, why?FindingsFemale patients display better prognosis than male patients. Non-menopausal women have shorter length of hospital stays, and AMH and E2 are negatively correlated with COVID-19’s severity. There is a negative correlation between E2 and the levels of IL6, IL8, IL2R and TNF-α, which are significantly correlated with disease severity or composite endpoint.MeaningNon-menopause and female sex hormones, especially E2 and AMH, are potential protective factors for females COVID-19 patients. E2 supplements could be potentially used for COVID-19 patients.

Pulmonary endothelial cells (ECs) are an essential component of the gas exchange machinery of the lung alveolus. Despite this, the extent and function of lung EC heterogeneity remains incompletely understood. Using single-cell analytics, we identify multiple EC populations in the mouse lung, including macrovascular endothelium (maEC), microvascular endothelium (miECs), and a new population we have termed Car4-high ECs. Car4-high ECs express a unique gene signature, and ligand-receptor analysis indicates they are primed to receive reparative signals from alveolar type I cells. After acute lung injury, they are preferentially localized in regenerating regions of the alveolus. Influenza infection reveals the emergence of a population of highly proliferative ECs that likely arise from multiple miEC populations and contribute to alveolar revascularization after injury. These studies map EC heterogeneity in the adult lung and characterize the response of novel EC subpopulations required for tissue regeneration after acute lung injury., eLife digest Animal lungs are filled with tiny air sacks called alveoli, where the gas exchanges that keep organisms alive can take place. Small blood vessels known as capillaries come in close contact with the alveoli, allowing oxygen to be extracted from the air into the blood, and carbon dioxide to be released from the blood into the air. The cells that line the inside of these capillaries (known as pulmonary endothelial cells) are important actors in these exchanges. After having been damaged, for example by viruses like influenza, the lungs need to regenerate and create new capillaries. Yet, it was still unclear how pulmonary endothelial cells participate in the healing process, and if capillaries contain several populations of endothelial cells that play different roles. To investigate this question, Niethamer et al. used an approach called single-cell analytics to examine individual endothelial cells in the alveoli of mice infected with influenza. This revealed that different subtypes of endothelial cells exist in capillaries, and that some may be able to perform slightly different jobs during lung recovery. Niethamer et al. found that all subtypes could quickly multiply after injury to create more endothelial cells and re-establish gas exchanges. However, one newly identified group (called Car4-high ECs) was particularly primed to receive orders from damaged alveoli. These cells were also often found at the sites where the alveoli were most injured. Lung injuries are a major cause of death worldwide. Understanding how pulmonary endothelial cells work when the organ is both healthy and injured should help to find ways to boost repair, and to create therapies that could target these cells.

During the study of oil and gas geochemistry, analysis of big data must be experienced, and there are some abnormal values in tremendous amount data, which will affect the analysis results of oil and gas migration. On the basis of geochemical big data of YM32 buried hill reservoirs in Tarim Basin, the mean value and standard deviation of hydrocarbon compound parameters reflecting the direction of hydrocarbon migration in the samples are analyzed, and the outliers, which less than \( {\bar{\text{X}}} \)−2D and great than \( {\bar{\text{X}}} \)+2D, are excluded. According to the content of saturated hydrocarbon and aromatics, the hydrocar bon migration factors are calculated and analyzed, and a three-step method of hydrocarbon migration tracer is formed. It is inferred that there are two oil and gas filling points of YM342-YM343 and YM50 in the YM32 buried hill reservoir, as well as four migration paths of YM342-YM343 to YM34, YM342-YM343 to YM37 to YM35, YM342-YM343 to YM33, and YM50 to YM321. The method can be used for reference in the evaluation of oil and gas reservoirs and in the search of remaining oil enrichment areas.

Background Hepatitis B virus (HBV) is considered highly prevalent in West Africa. However, major gaps in surveillance exist in Sierra Leone. Although healthcare workers (HCWs) are at high risk for HBV infection, little is known about the prevalence and knowledge of hepatitis B among HCWs in Sierra Leone. Methods A cross-sectional study of all HCWs at the No. 34 Military Hospital located in Freetown, Sierra Leone, was conducted from March 20 to April 10, 2017. Whole blood was collected and screened for HBV markers using a one-step rapid immunochromatographic test with positive samples tested for HBV DNA. Additionally, questionnaires assessing self-reported knowledge of HBV infections were administered to all participants. Data were processed and analyzed using SPSS (version 17.0) software. Results A total of 211 HCWs were included in this study with a median age of 39.0 years (range: 18–59). Of the participating HCWs, 172 (81.5%) participants were susceptible (all markers negative), 21(10.0%) were current HBV (HBsAg positive) and nine (4.3%) were considered immune because of past infection (HBsAg negative and anti-HBc positive; anti-HBs positive). Additionally, nine (4.3%) participants displayed immunity to the virus as a result of prior hepatitis B vaccination (only anti-HBs positive). Of the 21 HCWs with positive HBsAg, 13 (61.9%) had detectable HBV DNA. There was a significantly lower risk for current HBV infection among HCWs older than 39 years (OR 0.337, p = 0.046). In addition, only 14 (6.6%), 73 (34.6%) and 82 (38.9%) participants in this survey had adequate knowledge about the clinical outcome, routes of transmission, and correct preventive measures of HBV infection, respectively. Conclusions HCWs in Sierra Leone lacked adequate knowledge of the hepatitis B virus. Additionally, the low coverage rate of hepatitis B vaccination among HCWs fails to meet WHO recommendations, leaving many of the sampled HCWs susceptible to infection. This study reaffirms the need for more intensive training for HCWs in addition to strengthening vaccination programmes to protect HCWs against HBV in Sierra Leone. Electronic supplementary material The online version of this article (10.1186/s12879-018-3235-1) contains supplementary material, which is available to authorized users.

Background Cyclophosphamide (CTX), which has been used to treat common female cancers for several years, often causes ovarian damage, early menopause and infertility. However, strategies for the effective prevention and treatment of CTX-induced ovarian damage are still lacking. Epigallocatechin gallate (EGCG) and theaflavins (TFs), key molecules derived from green tea or black tea, have been shown to exert preventive effects on many ageing-related diseases. Purpose We aimed to explore the potential preventive and protective effects of EGCG and TFs on CTX-induced ovarian damage and compare the two compounds. Study Design Six-week-old female mice were administered a low or high dose of EGCG or TFs. The low dose was equivalent to the average daily amount of tea consumed by a drinker. Methods We determined the oestrous cycle and serum hormone levels to evaluate ovarian endocrine function, and we performed mating tests for reproductivity. We also assessed the follicle count and AMH level to evaluate ovarian reserve, and we performed Masson's trichrome and Sirius red staining to evaluate ovarian fibrosis. We conducted γ-H2AX and TUNEL analyses to evaluate DNA damage, and we also measured the relevant indicators of oxidative stress and follicular activation, including NRF2, HO-1, SOD2, AKT, mTOR and RPS6. Results EGCG and TFs treatment independently improved the ovarian endocrine function and reproductivity of mice that were administered CTX. EGCG and TFs also increased the ovarian reserve of these animals. Furthermore, EGCG and TFs alleviated oxidation-induced damage to ovarian DNA in mice by activating the NRF2/HO-1 and SOD2 pathways and reducing the apoptosis of growing follicles. At the same time, EGCG and TFs reduced the overactivation of primordial follicles by inhibiting the AKT/mTOR/RPS6 pathway. Conclusion The present study showed that EGCG and TFs independently improved ovarian function in mice with CTX-induced ovarian damage, thereby providing useful information for designing a potential clinical strategy that will protect against chemotherapy-induced ovarian damage.

Based on a flexible prototype vehicle and object recognition algorithms from robotic science, the present research aims at new approaches in the development of autonomous driving vehicles. An advanced prototype vehicle, driven by four independent hub motors that provide maneuverability and driving function far beyond automotive standards, serves as the basis for investigations. Enhanced know-how from robotic disciplines comprises sensor technology, navigation algorithms and the autonomous vehicle control system. With the integrated research vehicle, several autonomous driving testing scenarios are carried out to enable comprehensive evaluation and potential assessment of different technologies and development approaches in view of future R&D activities. The study shows, that: A)4WID-4WIS (four wheel independent driving and four wheel independent steering) electric vehicle is much more flexible and efficient to achieve superior performance in aspect of dynamics and drive ability than traditional vehicles. B)Object recognition and path planning algorithms in the robotics science can be implemented in the development of autonomous driving techniques and have achieved convincing results. C)This research ensures a decoupling of the basic vehicle control from the overall robotic path planning and following system. A commonly defined interface enables the adaption of the overall control system to various vehicle types.

Objective To summarize the current understanding of neuronal intranuclear inclusion disease (NIID) and improve the understanding of the physician about this condition. Methods We searched PubMed with keywords related to NIID and selected publications which seemed appropriate. We analyzed its clinical features, pathogenesis, evaluation methods, treatment options, and research prospectives. Results NIID is a degenerative condition which can affect multiple organ systems especially central nervous system. Its clinical features greatly vary, and making the exact diagnosis is often difficult. There are several genes which have been associated with this disorder. Some specific signs on diffusion-weighted-imaging (DWI) sequence of magnetic resonance (MR) imaging are characteristics to NIID. Conclusion Intranuclear inclusions have been found in various nonneural cells of the body; therefore, the term systemic intranuclear inclusion disease is, perhaps, better suited to explain this disorder. There are several disorders which need to be ruled out before making the diagnosis, and neuroimaging and biopsy analysis should be combined to support the diagnosis.

Monogenic lung diseases that are caused by mutations in surfactant genes of the pulmonary epithelium are marked by perinatal lethal respiratory failure or chronic diffuse parenchymal lung disease with few therapeutic options. Using a CRISPR fluorescent reporter system, we demonstrate that precisely timed in utero intra-amniotic delivery of CRISPR-Cas9 gene editing reagents during fetal development results in targeted and specific gene editing in fetal lungs. Pulmonary epithelial cells are predominantly targeted in this approach, with alveolar type 1, alveolar type 2, and airway secretory cells exhibiting high and persistent gene editing. We then used this in utero technique to evaluate a therapeutic approach to reduce the severity of the lethal interstitial lung disease observed in a mouse model of the human SFTPC(I73T) mutation. Embryonic expression of SftpC(I73T) alleles is characterized by severe diffuse parenchymal lung damage and rapid demise of mutant mice at birth. After in utero CRISPR-Cas9-mediated inactivation of the mutant SftpC(I73T) gene, fetuses and postnatal mice showed improved lung morphology and increased survival. These proof-of-concept studies demonstrate that in utero gene editing is a promising approach for treatment and rescue of monogenic lung diseases that are lethal at birth.

A thin SiOyNx film was inserted below a conventional SiNx antireflection coating used in c-Si solar cells in order to improve the surface passivation and the solar cell's resistance to potential-induced degradation (PID). The effect of varying the flow ratio of the N2O and SiH4 precursors and the deposition temperature for the SiOyNx thin film upon material properties were systematically investigated. An excellent surface passivation was obtained on FZ p-type polished silicon wafers, with the best results obtained with a SiOyNx film deposited at a very low temperature of 130 °C and with an optical refractive index of 1.8. In the SiOyNx/SiNx stack structure, a SiOyNx film with ~6 nm thickness is sufficient to provide excellent surface passivation with an effective surface recombination velocity Seff

Fine particulate matter (PM2.5) pollution arouses public health concerns over the world. Increasing epidemiologic evidence suggests that exposure to ambient airborne PM2.5 increases the risk of female infertility. However, relatively few studies have systematically explored the harmful effect of chronic PM2.5 exposure on ovarian function and the underlying mechanisms. In this study, female C57BL/6J mice are exposed to filtered air or urban airborne PM2.5 for 4 months through a whole-body exposure system. It is found that PM2.5 exposure significantly caused the alteration of estrus cycles, reproductivity, hormone levels, and ovarian reserve. The granulosa cell apoptosis via the mitochondria dependent pathway contributes to the follicle atresia. With RNA-sequencing technique, the differentially expressed genes induced by PM2.5 exposure are mainly enriched in ovarian steroidogenesis, reactive oxygen species and oxidative phosphorylation pathways. Furthermore, it is found that increased PM2.5 profoundly exacerbated ovarian oxidative stress and inflammation in mice through the NF-κB/IL-6 signaling pathway. Notably, dietary polydatin (PD) supplement has protective effect in mice against PM2.5-induced ovarian dysfunction.These striking findings demonstrate that PM2.5 and/or air pollution is a critical factor for ovarian dysfunction through mitochondria-dependent and NF-κB/IL-6-mediated pathway, and PD may serve as a pharmaceutic candidate for air pollution-associated ovarian dysfunction.

MicroRNA-based therapies that target cardiomyocyte proliferation have great potential for the treatment of myocardial infarction (MI). In previous work, we showed that the miR-302/367 cluster regulates cardiomyocyte proliferation in the prenatal and postnatal heart. Here, we describe the development and application of an injectable hyaluronic acid (HA) hydrogel for the local and sustained delivery of miR-302 mimics to the heart. We show that the miR-302 mimics released in vitro promoted cardiomyocyte proliferation over one week, and that a single injection of the hydrogel in the mouse heart led to local and sustained cardiomyocyte proliferation for two weeks. After MI, gel/miR-302 injection caused local clonal proliferation and increased cardiomyocyte numbers in the border zone of a Confetti mouse model. Gel/miR-302 further decreased cardiac end-diastolic (39%) and end-systolic (50%) volumes, and improved ejection fraction (32%) and fractional shortening (64%) four weeks after MI and injection, compared to controls. Our findings suggest that biomaterial-based miRNA delivery systems can lead to improved outcomes in cardiac regeneration.

Rationale: Disruption of normal pulmonary development is a leading cause of morbidity and mortality in infants. Congenital lung malformations are a unique model to study the molecular pathogenesis of isolated structural birth defects, as they are often surgically resected. Objectives: To provide insight into the molecular pathogenesis of congenital lung malformations through analysis of cell-type and gene expression changes in these lesions. Methods: Clinical data, and lung tissue for DNA, RNA, and histology, were obtained from 58 infants undergoing surgical resection of a congenital lung lesion. Transcriptome-wide gene expression analysis was performed on paired affected and unaffected samples from a subset of infants (n = 14). A three-dimensional organoid culture model was used to assess isolated congenital lung malformation epithelium (n = 3). Measurements and Main Results: Congenital lung lesions express higher levels of airway epithelial related genes, and dysregulated expression of genes related to the Ras and PI3K–AKT–mTOR (phosphatidylinositol 3-kinase–AKT–mammalian target of rapamycin) signaling pathways. Immunofluorescence confirmed differentiated airway epithelial cell types throughout all major subtypes of congenital lung lesions, and three-dimensional cell culture demonstrated a cell-autonomous defect in the epithelium of these lesions. Conclusions: This study provides the first comprehensive analysis of the congenital lung malformation transcriptome and suggests that disruptions in Ras or PI3K–AKT–mTOR signaling may contribute to the pathology through an epithelial cell-autonomous defect.

In this work, a three-dimensional, serpentine channel, four-cell PEM Stack model including current collector, gas diffusion layer, catalyst layer and membrane has been developed and is used to investigate the effects of membrane dehydration on PEM Stack performance. This numerical study is conducted using finite element method and computational fluid dynamics (CFD) code. To characterize the effects of membrane dehydration, the settings of operating and boundary conditions are not uniform throughout the whole period of simulation. The simulation condition is originally preferable, indicating a normally running stack in healthy status. Further transient simulation has been conducted under four failure conditions with different reactant humidity to monitor the variation of membrane water content and PEM Stack output voltage. The relatively drier reactants carry away more production water, causing the dehydration of membrane and reducing the protonic conductivity. Under a specific demand current, the output voltage of the stack decreases with the process of membrane dehydration, curtailing the maximum power that can be derived from the stack.

To report two cases of hypereosinophilic syndrome (HES) with central nervous system involvement and explore its possible pathogenesis.We have analysed the clinical data and relevant features of two patients who presented themselves to The Affiliated Hospital of Xuzhou Medical University between 2012 and 2015. We have reviewed the relevant literature, elaborated the possible pathogenesis, and discussed the treatment options.Both patients had consistently high levels of absolute eosinophil count which led to multiple cerebral infarcts in the arterial border zone and small-vessel disease. Blood tests were taken several times during their course of disease showing elevated eosinophils. Both patients underwent head computed tomography (CT), magnetic resonance imaging, and magnetic resonance angiography, which indicated small-vessel disease and watershed infarction. Glucocorticoids, improvement cycle, and neuro-nutrition treatments resulted in a significant improvement of their clinical state.HES can involve central nervous system by causing small-vessel disease and watershed infarction, which can be its presenting features. Repeated blood tests should be done to rule out HES in central nervous system lesion.

Three different structural types of closed cooling tower (CCT) and two cooling water flow directions were considered. The experimental study were done on the cooling performance of influences of inlet air dry and wet bulb temperature, cooling water flow rate and inlet temperature, air flow rate and spray density. The experimental results show that the cooling performance of CCT with packing is obviously better than non-packing cooling tower in 7%~18.4%. And the cooling performance of CCT with packing on top and coil underneath is slightly better than CCT with coil on top and packing underneath in 4.9%. In the same conditions the cooling performance of CCT with packing under cooling water cocurrent-flow is better than that cooling water countercurrent-flow in 3.2%~9.6%. Therefore, the closed cooling tower structure with the cooling water path in bottom and out top, and with packing on top and coil underneath is recommended.

The initial ground temperature (IGT) is one of the most important parameters in designing a ground source heat pump (GSHP) system and evaluating its performance. In this paper, three initial ground temperature test methods are introduced. Except the shallow zone, the ground temperature distribution measured from direct and indirect testing method has very small difference. In direct test, the temperature sensor must be embedded when burying the tube in the borehole which is hard to operate in engineering applications. Thus the direct testing method is suggested to be applied in the scientific research. The indirect testing method could be used in engineering applications. The mean ground temperature could be calculated from temperature distribution except the shallow zone temperature. The results from three calculating methods have a quite small difference. Therefore, the arithmetic average method is suggested for scientific and engineering application to calculate the mean ground temperature. The mean ground temperature is also gotten in TRT conveniently. In the condition of velocity 0.7m/s, water was circulated in the tube system with no heat source for 30 minutes. The average water temperature could be regard as the mean ground temperature with sufficient accuracy.

A ninety-day toxicity and toxicokinetics of flurochloridone (FLC) were studied in male Wistar rats with oral administration at doses of 3 mg/kg and 10 mg/kg respectively, following the previous study. Apparent toxicity to reproductive system of male rats was still observed at the dose of 10 mg/kg, trace amounts of FLC were still detected 24 hours after administration, testicular weight, epididymal weight and serum testosterone were significantly reduced and sperm abnormalities in epididymis were significantly increased. No abnormalities were found in 3 mg/kg group, it indicated that no-observed-adverse-effect level (NOAEL) of FLC in male rats was 3 mg/kg/day, far below the dose of 20 mg/kg/day reported by European Food Safety Authority (EFSA). Therefore, more attention should be paid to this herbicide.

Pyramidal surface is commonly used as an antireflection structure. The weighted reflectance averaged by the AM 1.5 G spectrum is about 14%. In the photovoltaic field, lowering the surface reflectivity is an important approach to improve the conversion efficiency. Black silicon surface with low reflectivity is benefit of solar cells. But conversion efficiency of black silicon solar cell is still low due to the severe surface recombination. In this paper, shallower black silicon layer was formed on the pyramidal surface. For the sample etched 1 min, the weighted reflectance is only 13.20%, and the pyramidal one is 14.10%. The layer would not deteriorate the material. Lifetime of the substrates after high temperature phosphorous diffusion is 13.35 μs higher than the pyramidal one. The mean sheet resistance is nearly the same between the pyramidal surface and the etched pyramidal surface.

A new method based on genetic-particle swarm hybrid algorithm was presented for parameter optimization of energy management strategy for extended-range electric vehicle (E-REV). Taking a logic threshold control strategy of an E-REV as example, for the aims of minimizing fuel consumption and emissions, a constrained nonlinear programming parameter optimization model was established. Based on this model, genetic algorithm (GA) and particle swarm optimization (PSO) were improved respectively. Further, a genetic-particle swarm hybrid algorithm was put forward and applied to the multi-objective optimization of E-REV energy management strategy. Optimization results show that the hybrid optimization algorithm can avoid falling into local optimum and its search ability is much better than improved adaptive genetic algorithm (IAGA). This hybrid algorithm is also suitable for the control parameters optimization issues of other types of hybrid electric vehicles.

Currently, a conventional two‐step method has been used to generate black silicon (BS) surfaces on silicon substrates for solar cell manufacturing. However, the performances of the solar cell made with such surface generation method are poor, because of the high surface recombination caused by deep etching in the conventional surface generation method for BS. In this work, a modified wet chemical etching solution with additives was developed. A homogeneous BS layer with random porous structure was obtained from the modified solution in only one step at room temperature. The BS layer had low reflectivity and shallow etching depth. The additive in the etch solution performs the function of pH‐modulation. After 16‐min etching, the etching depth in the samples was approximately 200 nm, and the spectrum‐weighted‐reflectivity in the range from 300 nm to 1200 nm was below 5%. BS solar cells were fabricated in the production line. The decreased etching depth can improve the electrical performance of solar cells because of the decrease in surface recombination. An efficiency of 15.63% for the modified etching BS solar cells was achieved on a large area, p‐type single crystalline silicon substrate with a 624.32‐mV open circuit voltage and a 77.88% fill factor.

Light-induced plating (LIP) techniques, which are self-aligned and are used in the fabrication of well-shaped metal grids, have been widely studied and used in solar cells, particularly in laser-doped selective emitter (LDSE) ones. However, the application of LIP techniques in standard acidic-textured multi-crystalline silicon wafers with SiN x -coated surfaces can be challenging because of the presence of some unwanted metals on the SiN x surface during the plating process. This phenomenon is called over-plating, a problem in industrial LDSE multi-crystalline Si solar cell manufacturing that this paper aims to eliminate without the addition of any new process steps. The feasibility of changing the texturing process as well as the pretreatment before plating and the deposition of SiN x to reduce over-plating was investigated. The effects of over-plating on solar cell performance were also investigated to determine the mechanism of performance degradation. The cells reached a maximum efficiency of 17.2% and an average efficiency of 17.1% on large-area, commercial-grade, p-type multi-crystalline Si substrates when the over-plating problem was eliminated.

The performance and faults diagnosis research on Proton Exchange Membrane Fuel Cell (PEMFC) provide a reliable theoretical and technical support for its commercialization. Meanwhile, PEMFC research based on modeling, which uses the commercial software such as Fluent, SIMULINK etc, affords a theoretical foundation for guiding the experiments and testing the new numerical calculation methods. Hence, based on a single cell 3D (three-dimensional) PEMFC model, the paper studied the performance impacts of physical parameters, such as porosities of GDL, and physical structure, such as the thickness of GDL. Additionally, from the aspect of operating conditions, the cathode gas supply shortage fault is analyzed to study the influence on PEMFC output voltage.

Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations that cause stroke and seizures in younger individuals1. CCMs arise from endothelial cell loss of KRIT1, CCM2, or PDCD10, non-homologous proteins that form an adaptor complex2. How disruption of the CCM complex results in disease remains controversial, with numerous signaling pathways (including Rho3,4, SMAD5 and Wnt/β-catenin6) and processes such as endothelial-mesenchymal transition (EndMT)5 proposed to play causal roles. CCM2 binds MEKK37–11, and we have recently demonstrated that CCM complex regulation of MEKK3 is essential during vertebrate heart development12. Here, we investigate this mechanism in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we find that expression of the MEKK3 target genes KLF2 and KLF4, as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. In contrast, we find no evidence of EndMT or increased SMAD or Wnt signaling during early CCM formation. Endothelial-specific loss of Mekk3, Klf2, or Klf4 dramatically prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, we demonstrate that endothelial expression of KLF2 and KLF4 is elevated in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation abrogates MEKK3 interaction without affecting CCM complex formation. These studies identify gain of MEKK3 signaling and KLF2/4 function as causal mechanisms for CCM pathogenesis that may be targeted to develop new CCM therapeutics.