Greatly isolated heterogeneous circulating tumor cells using hybrid engineered cell membrane-camouflaged magnetic nanoparticles.

BACKGROUND: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation. METHODS: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis. CONCLUSIONS: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.

Association Analysis Between Intratumoral and Peritumoral MRI Radiomics Features and Overall Survival of Neoadjuvant Therapy in Rectal Cancer.

BACKGROUND: The use of peritumoral features to determine the survival time of patients with rectal cancer (RC) is still imprecise. PURPOSE: To explore the correlation between intratumoral, peritumoral and combined features, and overall survival (OS). STUDY TYPE: Retrospective. POPULATION: One hundred sixty-six RC patients (53 women, 113 men; average age: 55 ± 12 years) who underwent radical resection after neoadjuvant therapy. FIELD STRENGTH/SEQUENCE: 3 T; T2WI sagittal, T1WI axial, T2WI axial with fat suppression, and high-resolution T2WI axial sequences, enhanced T1WI axial and sagittal sequences with fat suppression. ASSESSMENT: Radiologist A segmented 166 patients, and radiologist B randomly segmented 30 patients. Intratumoral and peritumoral features were extracted, and features with good stability (ICC ≥0.75) were retained through intra-observer analysis. Seven classifiers, including Logistic Regression (LR), Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Random Forest (RF), Extremely randomized trees (ET), eXtreme Gradient Boosting (XGBoost), and LightGBM (LGBM), were applied to select the classifier with the best performance. Next, the Rad-score of best classifier and the clinical features were selected to establish the models, thus, nomogram was built to identify the association with 1-, 3-, and 5-year OS. STATISTICAL TESTS: LASSO, regression analysis, ROC, DeLong method, Kaplan-Meier curve. P < 0.05 indicated a significant difference. RESULTS: Only Node (irregular tumor nodules in the surrounding mesentery) and ExtraMRF (lymph nodes outside the perirectal mesentery) were significantly different in 20 clinical features. Twelve intratumoral, 3 peritumoral, and 14 combined features related to OS were selected. LR, SVM, and RF classier showed the best efficacy in the intratumoral, peritumoral, and combined model, respectively. The combined model (AUC = 0.954 and 0.821) had better survival association than the intratumoral model (AUC = 0.833 and 0.813) and the peritumoral model (AUC = 0.824 and 0.687). DATA CONCLUSION: The proposed peritumoral model with radiomics features may serve as a tool to improve estimated survival time. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 4.

Identification and validation of autophagy-related genes in SSc.

Multiple organs are affected by the complex autoimmune illness known as systemic sclerosis (SSc), which has a high fatality rate. Genes linked to autophagy have been linked to the aetiology of SSc. It is yet unknown, though, whether autophagy-related genes play a role in the aetiology of SSc. After using bioinformatics techniques to examine two databases (the GSE76885 and GSE95065 datasets) and autophagy-related genes, we were able to identify 12 autophagy-related differentially expressed genes that are linked to the pathophysiology of SSc. Additional examination of the receiver operating characteristic curve revealed that SFRP4 (AUC = 0.944, P < 0.001) and CD93 (AUC = 0.904, P < 0.001) might be utilized as trustworthy biomarkers for the diagnosis of SSc. The SSc group's considerably greater CD93 and SFRP4 expression levels compared to the control group were further confirmed by qRT-PCR results. The autophagy-related genes SFRP4 and CD93 were found to be viable diagnostic indicators in this investigation. Our research sheds light on the processes by which genes linked to autophagy affect the pathophysiology of SSc.

Mechanistic study of transcription factor Sox18 during heart development.

Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/ß-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and ß-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/ß-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/ß-Catenin signaling.

Preoperative prediction of perineural invasion and lymphovascular invasion with CT radiomics in gastric cancer.

Objectives: To determine whether contrast-enhanced CT radiomics features can preoperatively predict lymphovascular invasion (LVI) and perineural invasion (PNI) in gastric cancer (GC). Methods: A total of 148 patients were included in the LVI group, and 143 patients were included in the PNI group. Three predictive models were constructed, including clinical, radiomics, and combined models. A nomogram was developed with clinical risk factors to predict LVI and PNI status. The predictive performance of the three models was mainly evaluated using the mean area under the curve (AUC). The performance of three predictive models was assessed concerning calibration and clinical usefulness. Results: In the LVI group, the predictive power of the combined model (AUC=0.871, 0.822) outperformed the clinical model (AUC=0.792, 0.728) and the radiomics model (AUC=0.792, 0.728) in both the training and testing cohorts. In the PNI group, the combined model (AUC=0.834, 0.828) also had better predictive power than the clinical model (AUC=0.764, 0.632) and the radiomics model (AUC=0.764, 0.632) in both the training and testing cohorts. The combined models also showed good calibration and clinical usefulness for LVI and PNI prediction. Conclusion: CECT-based radiomics analysis might serve as a non-invasive method to predict LVI and PNI status in GC.

Dysregulated expression of GATA2 and GATA6 transcription factors in adenomyosis: implications for impaired endometrial receptivity.

OBJECTIVE: To study the effect of adenomyosis on the localized expression of the GATA binding proteins 2 and 6 (GATA2 and GATA6) zinc-finger transcription factors that are involved in proliferation of hematopoietic and endocrine cell lineages, cell differentiation, and organogenesis, potentially leading to impaired endometrial implantation. DESIGN: Laboratory based experimental study. SETTING: Academic hospital and laboratory. PATIENTS: Human endometrial stromal cells (HESCs) of reproductive age patients, 18-45 years of age, with adenomyosis were compared with patients with no pathology and leiomyomatous uteri as controls (n = 4 in each group, respectively). Additionally, midsecretory phase endometrial sections were obtained from patients with adenomyosis and control patients with leiomyoma (n = 8 in each group, respectively). INTERVENTIONS: GATA2 and GATA6 immunohistochemistry and H-SCORE were performed on the midsecretory phase endometrial sections from adenomyosis and leiomyoma control patients (n = 8 each, respectively). Control and adenomyosis patient HESC cultures were treated with placebo or 10-8 M estradiol (E2), or decidualization media (EMC) containing 10-8 M E2, 10-7 M medroxyprogesterone acetate, and 5 × 10-5 M cAMP for 6 and 10 days. Additionally, control HESC cultures (n = 4) were transfected with scrambled small interfering RNA (siRNA) (control) or GATA2-specific siRNAs for 6 days while adenomyosis HESC cultures (n = 4) were transfected with human GATA2 expression vectors to silence or induce GATA2 overexpression. MAIN OUTCOME MEASURES: Immunohistochemistry was performed to obtain GATA2 and GATA6 H-SCORES in adenomyosis vs. control patient endometrial tissue. Expression of GATA2, GATA6, insulin-like growth factor-binding protein 1 (IGFBP1), prolactin (PRL), progesterone receptor (PGR), estrogen receptor 1 (ESR1), leukemia inhibitory factor (LIF), and Interleukin receptor 11 (IL11R) messenger RNA (mRNA) levels were analyzed using by qPCR with normalization to ACTB. Silencing and overexpression experiments also had the corresponding mRNA levels of the above factors analyzed. Western blot analysis was performed on isolated proteins from transfection experiments. RESULTS: Immunohistochemistry revealed an overall fourfold lower GATA2 and fourfold higher GATA6 H-SCORE level in the endometrial stromal cells of patients with adenomyosis vs. controls. Decidual induction with EMC resulted in significantly lower GATA2, PGR, PRL and IGFBP1 mRNA levels in HESC cultures from patients with adenomyosis patient vs. controls. Leukemia inhibitory factor and IL11R mRNA levels were also significantly dysregulated in adenomyosis HESCs compared with controls. . Silencing of GATA2 expression in control HESCs induced an adenomyosis-like state with significant reductions in GATA2, increases in GATA6 and accompanying aberrations in PGR, PRL, ESR1 and LIF levels. Conversely, GATA2 overexpression via vector in adenomyosis HESCs caused partial restoration of the defective decidual response with significant increases in GATA2, PGR, PRL and LIF expression. CONCLUSION: In-vivo and in-vitro experiment results demonstrate that there is an overall inverse relationship between endometrial GATA2 and GATA6 levels in patients with adenomyosis who have diminished GATA2 levels and concurrently elevated GATA6 levels. Additionally, lower GATA2 and higher GATA6 levels, together with aberrant levels of important receptors and implantation factors, such as ESR1, PGR, IGFBP1, PRL, LIF, and IL11R mRNA in HESCs from patients with adenomyosis or GATA2-silenced control HESCs, support impaired decidualization. These effects were partially restored with GATA2 overexpression in adenomyosis HESCs, demonstrating a potential therapeutic target.

An active learning Gaussian modeling based multi-objective evolutionary algorithm using population guided weight vector evolution strategy.

The inverse model based multi-objective evolutionary algorithm (IM-MOEA) generates offspring by establishing probabilistic models and sampling by the model, which is a new computing schema to replace crossover in MOEAs. In this paper, an active learning Gaussian modeling based multi-objective evolutionary algorithm using population guided weight vector evolution strategy (ALGM-MOEA) is proposed. To properly cope with multi-objective problems with different shapes of Pareto front (PF), a novel population guided weight vector evolution strategy is proposed to dynamically adjust search directions according to the distribution of generated PF. Moreover, in order to enhance the search efficiency and prediction accuracy, an active learning based training sample selection method is designed to build Gaussian process based inverse models, which chooses individuals with the maximum amount of information to effectively enhance the prediction accuracy of the inverse model. The experimental results demonstrate the competitiveness of the proposed ALGM-MOEA on benchmark problems with various shapes of Pareto front.

Correlation between dynamic contrast-enhanced MRI characteristics and apparent diffusion coefficient with Ki-67-positive expression in non-mass enhancement of breast cancer.

As a remarkably specific characteristic of breast cancer observed on magnetic resonance imaging (MRI), the association between the NME type breast cancer and prognosis, including Ki-67, necessitates comprehensive exploration. To investigate the correlation between dynamic contrast-enhanced MRI (DCE-MRI) characteristics and apparent diffusion coefficient (ADC) values with Ki-67-positive expression in NME type breast cancer. A total of 63 NME type breast cancer patients were retrospectively reviewed. Malignancies were confirmed by surgical pathology. All patients underwent DCE and diffusion-weighted imaging (DWI) before surgery. DCE-MRI characteristics, including tumor distribution, internal enhancement pattern, axillary adenopathy, and time-intensity curve types were observed. ADC values and lesion sizes were also measured. The correlation between these features and Ki-67 expression were assessed using Chi-square test, Fisher's exact test, and Spearman rank analysis. The receiver operating characteristic curve and area under the curve (AUC) was used to evaluate the diagnostic performance of Ki-67-positive expression. Regional distribution, TIC type, and ipsilateral axillary lymph node enlargement were correlated with Ki-67-positive expression (χ2 = 0.397, 0.357, and 0.357, respectively; P < 0.01). ADC value and lesion size were positively correlated with Ki-67-positive expression (rs = 0.295, 0.392; P < 0.05). The optimal threshold values for lesion size and ADC value to assess Ki-67 expression were determined to be 5.05 (AUC = 0.759) cm and 0.403 × 10-3 s/mm2 (AUC = 0.695), respectively. The best diagnosis performance was the ADC combined with lesion size (AUC = 0.791). The ADC value, lesion size, regional distribution, and TIC type in NME type breast cancer were correlated with Ki-67-positive expression. These features will aid diagnosis and treatment of NME type breast cancer.

Acute muscle wasting rate assessment and long-term mortality in critically ill trauma.

BACKGROUND AND OBJECTIVES: To evaluate the relationship between acute muscle wasting rate and long-term mortality in critically ill trauma. METHODS AND STUDY DESIGN: A single-center, retrospective study was conducted in critically ill trauma. Patients with Computed Tomography scans including the L3 vertebra within 24 hours and at 1 week after trauma were recruited. Acute muscle wasting rate was defined as the mean percent variation per day of skeletal muscle index in the first week after trauma. Multivariate logistic regression analysis and receiver operating characteristic curve analysis were performed to determine whether acute muscle wasting rate could help predict hospital malnutrition and 1-year mortality. RESULTS: Skeletal muscle index was 49.3±10.7 cm2/m2 at baseline and decreased to 45.1±9.6 cm2/m2 (p<0.001) at 1 week and 39.8±10.8cm2/m2 (p<0.001) at 1 month after trauma. A sustained decrease of skeletal muscle index was observed from baseline up to 6 months (33.7±8.4cm2/m2, p<0.001) post trauma, and lasted for 1 year (37.7±5.6cm2/m2, p=0.004). Logistic regression analysis showed that acute muscle wasting rate was an independent risk factor for hospital malnutrition and 1-year mortality. Every 1% absolute increase of acute muscle wasting rate was associated with 1.82-fold higher odds of 1-year mortality in critically ill trauma. The area under curve of acute muscle wasting rate was 0.813 for hospital malnutrition prediction and 0.715 for 1-year mortality prediction. CONCLUSIONS: Acute muscle wasting rate was independently associated with higher 1-year mortality and hospital malnutrition in critically ill trauma.

Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics.

Adult hippocampal neurogenesis generates functional neurons from neural progenitor cells in the hippocampal dentate gyrus (DG) to complement and repair neurons and neural circuits, thus benefiting the treatment of depression. Increasing evidence has shown that aberrant microglial activity can disrupt the appropriate formation and development of functional properties of neurogenesis, which will play a crucial role in the occurrence and development of depression. However, the mechanisms of the crosstalk between microglia and adult hippocampal neurogenesis in depression are not yet fully understood. Therefore, in this review, we first introduce recent discoveries regarding the roles of microglia and adult hippocampal neurogenesis in the etiology of depression. Then, we systematically discuss the possible mechanisms of how microglia regulate adult hippocampal neurogenesis in depression according to recent studies, which involve toll-like receptors, microglial polarization, fractalkine-C-X3-C motif chemokine receptor 1, hypothalamic-pituitary-adrenal axis, cytokines, brain-derived neurotrophic factor, and the microbiota-gut-brain axis, etc. In addition, we summarize the promising drugs that could improve the adult hippocampal neurogenesis by regulating the microglia. These findings will help us understand the complicated pathological mechanisms of depression and shed light on the development of new treatment strategies for this disease.

Proteogenomic insights suggest druggable pathways in endometrial carcinoma.

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of ß-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

MiR-409-3p regulates the proliferation and apoptosis of THP-1 through targeting Rab10.

Acute myeloid leukemia cytogenetics and molecular subtypes are connected with microRNAs, although it is unclear how miRNAs affect AML pathogenesis. miR-409-3p expression is downregulated in bone marrows, as we have previously demonstrated in our team. Nevertheless, the tumor-suppressing activities and molecular mechanisms of miR-409-3p remain unknown. Hence, in this study, we investigate at the functional significance of miR-409-3p in the development of AML. We found that a significant decrease in miR-409-3p expression was observed in THP-1 cell. The expression of miR-409-3p was altered in THP-1 by transfecting with agomiR-409-3p and agomiR-409-3p NC. A series of experiments showed that overexpression of miR-409-3p expression significantly suppressed proliferation and increased the apoptosis of THP-1. Moreover, Rab10 was confirmed as a direct target gene of miR-409-3p and was negatively modulated by miR-409-3p. Rab10 downregulation imitated the suppressed proliferation and increased the apoptosis of THP-1. Furthermore, miR-409-3p overexpression or Rab10 knockdown obviously down-regulated the expression levels of Bcl-2, but up-regulated Bax expression. In a xenograft mouse model, miR-409-3p-overexpressed THP-1 cells resulted in much less tumor weight and size in the mice bearing the cells as compared to the mock-transfected mice. Collectively, our findings demonstrated that miR-409-3p exerted tumor suppressor gene effects in AML by directly targeting Rab10, which might provide a promising therapeutic target for AML.

Etiological Study of Acute Conjunctivitis Caused by Human Adenovirus in Shanxi Province, China, between 2016 and 2019.

Human adenovirus (HAdV) is the primary cause of acute conjunctivitis. To improve our understanding of the etiology of adenoviral conjunctivitis, ocular samples were collected from 160 conjunctivitis cases in the Shanxi province of northern China between 2016 and 2019. Through preliminary identification, virus isolation, and type identification, a total of 63 HAdV isolates were obtained from the samples. Three species and seven types (HAdV-3, HAdV-4, HAdV-8, HAdV-37, HAdV-53, HAdV-64, and HAdV-85) were detected, with HAdV-64, HAdV-3, and HAdV-8 being the predominant types in 2016, 2018, and 2019, respectively. Further phylogenetic analysis indicated the relative genomic stability of seven HAdV-type strains, except for 4 HAdV-3 strains in 2018 with a novel amino acid insertion site (Pro) between P19 and S20 in the penton base gene. It is worth noting that the genomes of two Shanxi HAdV-85 strains from 2016 were almost identical to those of previously reported HAdV-85 strains that circulated in Japan in 2014 to 2018. China was the second country to sample and isolate HAdV-85, suggesting that HAdV-85 might be underreported as an ocular pathogen. Data obtained in this study provide valuable information on the prevalence of acute conjunctivitis caused by HAdV. IMPORTANCE HAdV types in cases of conjunctivitis in Shanxi province, China, in 2016 to 2019 showed evident diversity, with seven types (HAdV-3, HAdV-4, HAdV-8, HAdV-37, HAdV-53, HAdV-64, and HAdV-85) being identified, and relative genome stability of these viruses was observed. In addition, China was the second country to sample and isolate HAdV-85, which suggests that HAdV-85 might be underreported as an important pathogen associated with ocular infections. These results enhance the understanding of the etiology of adenoviral conjunctivitis and may aid in the development of prevention and control strategies for HAdV-related ocular infections in China.

Droplet Microfluidic-Based Low-Cost and High-Speed Microsphere Array Direct Writing Technology and Its Applications.

Microsphere arrays have significant applications and broad development prospects in various fields and disciplines. The simple, efficient, low-cost, automatic, and controllable preparation of microsphere arrays in multiple dimensions and morphologies is still a significant challenge. Here, a novel microsphere array direct writing technology was developed using a low-cost portable droplet microfluidic device and a high-precision XY movable platform. The proposed technology provided a powerful platform for the direct-writing preparation of microsphere arrays and was successfully applied to the precise and controllable fabrication of microsphere arrays with different sizes, shapes, structures, and arrangements. Additionally, gel microsphere arrays with metal ion patterns were fabricated using the microsphere arrays as templates and exhibited excellent performance in the visual analytical detection of heavy metal ions. Moreover, the simulated microsphere arrays offer a promising platform for rapidly generating high-viability and uniform 3D tumor spheroids. Therefore, given the superiority of this technology and the great potential of microsphere arrays, this simple high-speed microsphere array direct writing technology has a promising application in the multidisciplinary intersection of chemical, biological, and material sciences.

Retrospective investigation of the origin and epidemiology of the dengue outbreak in Yunnan, China from 2017 to 2018.

Since 2013, a dengue epidemic has broken out in Yunnan, China and neighboring countries. However, after the COVID-19 pandemic in 2019, the number of dengue cases decreased significantly. In this retrospective study, epidemiological and genetic diversity characterizations of dengue viruses (DENV) isolated in Yunnan between 2017 and 2018 were performed. The results showed that the dengue outbreak in Yunnan from 2017 to 2018 was mainly caused by DENV1 (genotype I and genotype V) and DENV2 (Asia I, Asia II, and Cosmopolitan). Furthermore, correlation analysis indicated a significant positive correlation between the number of imported and local cases (correlation coefficient = 0.936). Multiple sequence alignment and phylogenetic divergence analysis revealed that the local isolates are closely related to the isolates from Myanmar and Laos. Interestingly, recombination analysis found that the DENV1 and DENV2 isolates in this study had widespread intra-serotype recombination. Taken together, the results of the epidemiological investigation imply that the dengue outbreak in Yunnan was primarily due to imported cases. This study provides a new reference for further investigations on the prevalence and molecular epidemiology of DENV in Yunnan, China.

Survey of mosquito species and mosquito-borne viruses in residential areas along the Sino-Vietnam border in Yunnan Province in China.

Mosquitoes are capable of carrying complex pathogens, and their feeding habits on the mammalian blood can easily mediate the spread of viruses. Surveillance of mosquito-based arbovirus enables the early prevention and control of mosquito-borne arboviral diseases. The climate and geography of Yunnan Province in China are ideal for mosquitoes. Yunnan shares borders with several other countries; therefore, there exists a high risk of international transmission of mosquito-mediated infectious diseases. Previous studies have focused more on the Sino-Laos and Sino-Myanmar borders. Therefore, we focused on the neighborhoods of Malipo and Funing counties in Wenshan Prefecture, Yunnan Province, China, which are located along the Sino-Vietnam border, to investigate the species of mosquitoes and mosquito-borne viruses in the residential areas of this region. This study collected 10,800 mosquitoes from 29 species of 8 genera and grouped to isolate mosquito-borne viruses. In total, 62 isolates were isolated and classified into 11 viral categories. We demonstrated a new distribution of mosquito-borne viruses among mosquitoes in border areas, including Tembusu and Getah viruses, which can cause animal outbreaks. In addition, Dak Nong and Sarawak viruses originating from Vietnam and Malaysia, respectively, were identified for the first time in China, highlighting the complexity of mosquito-borne viruses in the Sino-Vietnam border region. The awareness of the importance of viral surveillance and prevention measures in border areas should be further encouraged to prevent future outbreaks of potentially infectious diseases.

Field experiments to assess the remediation efficiency of metal-contaminated soil by flushing with ferric chloride followed by applying amendments.

The Cd, Cu, Pb, and Zn removal efficiencies achieved by flushing with FeCl3 were determined in a field experiment using soil contaminated with multiple metals. Soil was first flushed with FeCl3 and then with FeCl3 or a mixture of chelators. Flushed soil was amended with lime and organic matter to revitalize the soil, then the soil was used to grow Zea mays and Brassica juncea. The heavy metal concentrations in groundwater were determined to assess the risks of leaching caused by soil flushing. The Cd, Cu, Pb, and Zn removal efficiencies were 70%, 40%, 33%, and 17%, respectively, when FeCl3 (25 mmol (kg topsoil)-1) was applied. The second washing generally did not significantly decrease the heavy metal contents of the soil but the second FeCl3 washing did decrease the Pb content. Pb leached from topsoil was partly retained by the subsoil 20-40 cm deep. The Zea mays yields were significantly lower but the Brassica juncea yields were significantly higher after the combined soil flushing and amendment treatment than after only the amendment treatment. This indicated that soil flushing only negatively affected growth of deep-rooted Z. mays. The Cd, Cu, Pb, and Zn concentrations in Z. mays grains and the edible parts of B. juncea grown in remediated soil were below the Chinese tolerable limits for contaminants in food. Washing with FeCl3 did not increase groundwater contamination during the study. The results indicated that flushing soil with FeCl3 and subsequent amendments is a technically feasible method for remediating agricultural soil contaminated with Cd.

Effect of multiple washing operations on the removal of potentially toxic metals from an alkaline farmland soil and the strategy for agricultural reuse.

Few studies have carried out soil washing experiments using pot experiments to simulate in situ soil washing operations, particularly for alkaline soils. This study explored the effects of multiple washing operations using pot experiments on the removal efficiencies of potentially toxic metals (PTM) from alkaline farmland soil and the reuse strategy of washed soil for safe agricultural production. The results showed that the removal efficiencies of Cd, Pb, Cu, and Zn after seven washings with a mixed chelator (EDTA, GLDA, and citric acid) were 41.1%, 47.1%, 14.7%, and 26.5%, respectively, which was close to the results of the EDTA treatment. For the alkaline soil studied, the second washing with the mixed chelators most effectively removed PTM owing to the activation of them after the first washing operation. The mixed chelator more effectively increased the proportion of stable fraction of PTM and maintained soil nutrients (e.g., nitrogen content) than EDTA, indicating little disturbance of alkaline soil quality after washing with the mixed chelator. After the amendment of the washed soil, there was no visible difference in the biomass weight of crops from the soils washed with different agents, indicating that the inhibitory effect of both washing agents on plant growth was effectively alleviated. The Cd and Pb contents in Z. mays were below the threshold of Hygienical Standard for Feeds of China (GB 13078-2017) (1 and 30 mg·kg-1). Moreover, after three cropping operations, the available concentrations of PTM in the soil washed with the mixed chelator were lower than those in the soil washed with EDTA, indicating the value and potential of agricultural reuse of alkaline farmland soil washed with the mixed chelator.

Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis.

Leptin plays a crucial role in regulating energy homoeostasis, neuroendocrine function, metabolism, and immune and inflammatory responses. The adipose tissue is a main source of leptin, but during pregnancy, leptin is also secreted primarily by the placenta. Circulating leptin levels peak during the second trimester of human pregnancy and fall after labor. Several studies indicated a strong association between elevated placental leptin levels and preeclampsia (PE) pathogenesis and elevated serum interleukin-6 (IL-6) levels in PE patients. Therefore, we hypothesized that a local increase in placental leptin production induces IL-6 production in Hofbauer cells (HBCs) to contribute to PE-associated inflammation. We first investigated HBCs-specific IL-6 and leptin receptor (LEPR) expression and compared their immunoreactivity in PE vs. gestational age-matched control placentas. Subsequently, we examined the in vitro regulation of IL-6 as well as the phosphorylation levels of intracellular signaling proteins STAT3, STAT5, NF-κB, and ERK1/2 by increasing recombinant human leptin concentrations (10 to 1000 ng/mL) in primary cultured HBCs. Lastly, HBC cultures were incubated with leptin ± specific inhibitors of STAT3 or STAT5, or p65 NF-κB or ERK1/2 MAPK signaling cascades to determine relevant cascade(s) involved in leptin-mediated IL-6 regulation. Immunohistochemistry revealed ~three- and ~five-fold increases in IL-6 and LEPR expression, respectively, in HBCs from PE placentas. In vitro analysis indicated that leptin treatment in HBCs stimulate IL-6 in a concentration-dependent manner both at the transcriptional and secretory levels (p < 0.05). Moreover, leptin-treated HBC cultures displayed significantly increased phosphorylation levels of STAT5, p65 NF-κB, and ERK1/2 MAPK and pre-incubation of HBCs with a specific ERK1/2 MAPK inhibitor blocked leptin-induced IL-6 expression. Our in situ results show that HBCs contribute to the pathogenesis of PE by elevating IL-6 expression, and in vitro results indicate that induction of IL-6 expression in HBCs is primarily leptin-mediated. While HBCs display an anti-inflammatory phenotype in normal placentas, elevated levels of leptin may transform HBCs into a pro-inflammatory phenotype by activating ERK1/2 MAPK to augment IL-6 expression.

A Resource and Task Scheduling Based Multi-Objective Optimization Model and Algorithms in Elastic Optical Networks.

The elastic optical network (EON) adopting virtual network function (VNF) is a new type of network, in which the routing, spectrum, and data center allocation are key and challenging problems, and solving these three problems simultaneously can not only improve the network efficiency for network providers, but also let users obtain better service. However, few existing works handle these three problems simultaneously. To tackle the three problems simultaneously, given a set of network function chains (i.e., a set of tasks), we set up a new multi-objective optimization model in which the total length of paths for all tasks is minimized, the totally occupied spectrums are minimized, and the loads on all data centers are most balanced, simultaneously. To solve the model, we design two new evolutionary algorithms. The experiments are conducted on 16 cases of 4 widely used types of networks, and the results indicate that the proposed model and algorithms are effective.