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Abstract Uterine corpus endometrial carcinoma (UCEC) is one of the most common tumours of the female reproductive system. CCAAT enhancer-binding protein alpha (CEBPA) is a member of the transcription factor family involved in regulating processes such as cell proliferation, differentiation, metabolism, and the immune response. However, the role of CEBPA in UCEC has not been clarified. Here, we performed a comprehensive analysis to explore the expression level, prognostic value, immune infiltration and biological function of CEBPA in UCEC. In this study, we found that CEBPA expression was upregulated and associated with poor prognosis in UCEC patients. KEGG and GO analyses revealed that the genes positively correlated with CEBPA were enriched primarily in immune regulation and oxidative phosphorylation. Immune infiltration analysis revealed that CEBPA is strongly correlated with immune cell infiltration in UCEC. RT-qPCR indicated that CEBPA may regulate the OXPHOS level in Ishikawa cells. CCK-8, cell cycle, Transwell and scratch wound healing assays revealed that CEBPA promoted Ishikawa cell proliferation, invasion and migration. In addition, PPI and survival analyses suggested that CEBPG may be a potential target of CEBPA in UCEC. These results demonstrated that CEBPA may be a potential therapeutic target in UCEC.

IntroductionDue to the inefficiency and high cost of the current healthcare supply chain mode, in order to adapt to the great changes in the global economy and public health, it is urgent to choose an effective mode for sustainable development of healthcare supply chain. The aim of this paper is to use artificial intelligence systems to make intelligent decisions for healthcare supply chain mode selection.MethodsFirstly, according to the economic benefits, social benefits and environmental benefits of healthcare supply chain, this paper identifies different healthcare supply chain modes in combination with artificial intelligence technology. Secondly, this paper presents the intelligent choice optimization method of healthcare supply chain mode based on deep reinforcement learning algorithm. Finally, the effect of artificial intelligence in healthcare supply chain mode selection is verified by simulation experiment.Results and DiscussionThe experimental results show that healthcare supply chain mode selected by artificial intelligence is basically consistent with the target mode, while healthcare supply chain mode selected by the basic selection method, BP neural network method and big data method is different from the target mode, which indicates that AI has more advantages in the selection of medical supply chain mode. Therefore, we recommend the application of artificial intelligence to healthcare supply chain management. This study not only makes up for the ineffective problems of existing methods, but also makes up for the gaps in the application of AI technology in the field of healthcare supply chain. The scientific value of this paper is that the proposed framework and the artificial intelligence algorithm enrich the relevant theories of healthcare supply chain research and provide methodological guidance for intelligent decision-making of healthcare supply chain. At the same time, for medical enterprises, this research provides a new practical guideline for the application of artificial intelligence in the sustainable development and modern management of healthcare supply chain.

Abstract Background Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. Methods This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. Results For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p

Background: The primary objective was to investigate how Forkhead Box A1 (FOXA1) contributes to late-onset preeclampsia (LOPE) and its impact on trophoblast invasion and migration. Methods: The prospective cohort study included 15 pregnant women with LOPE (gestational age of ≥34+0 weeks), and 18 normal pregnant women. FOXA1 expression in placental tissues was determined by immunofluorescent and immunohistochemical (IHC) staining. FOXA1 mRNA and protein expression in HTR-8/SVneo was determined by real-time quantitative polymerase chain reaction (qPCR) and western blot, respectively. Flow cytometry was utilized to analyze cell apoptosis/cycle of HTR-8/SVneo cells. Additionally, the Transwell/wound healing assays were employed to assess invasion/migration of HTR-8/SVneo cells. Student’s t-test was employed to compare measurement data of normal distribution between two groups. Results: In placental tissues of women with LOPE, FOXA1 exhibited downregulation when compared to the normal controls. No significant differences were observed in pregnancy duration, maternal age, delivery times, or 1- and 5-minute Apgar scores between the two groups. However, the LOPE group had a significantly shorter gestational week at delivery, higher systolic and diastolic blood pressure, the presence of 24-hour proteinuria, lower neonatal birth weight, and lower placental weight. FOXA1 overexpression altered the cell cycle of trophoblasts, increasing the population in the S phase and decreasing it in the G2/M phase, with no effect on the G0/G1 phase. It did not affect trophoblast apoptosis. Furthermore, FOXA1 overexpression enhanced trophoblast invasive ability and migration. However, FOXA1 overexpression did not affect the mRNA expression levels of N-cadherin, vimentin, and fibronectin in trophoblast cells. Conclusions: In summary, our findings indicate that FOXA1 was underexpressed in the placental tissues of women with LOPE. Furthermore, the overexpression of FOXA1 led to significant changes in the trophoblast cell cycle and substantially enhanced trophoblast invasion and migration capabilities.

Abstract Background Epithelial ovarian cancer (EOC) is the leading cause of deaths among patients with gynecologic malignancies. In recent years, cancer stem cells (CSCs) have attracted great attention, which have been regarded as new biomarkers and targets in cancer diagnoses as well as therapies. However, therapeutic failure caused by chemotherapy resistance in late-stage EOC occurs frequently. The 5-year survival rate of patients with EOC remains at about 30%. Methods In this study, the expression of acylglycerol kinase (AGK) was analyzed among patients with EOC. The effect of AGK on EOC cell proliferation and tumorigenicity was studied using Western blotting, flow cytometry, EdU assay and in vivo xenotransplantation assays. Furthermore, AGK induced CSC-like properties and was resistant to cisplatin chemotherapy in the EOC cells, which were investigated through sphere formation assays and the in vivo model of chemoresistance. Finally, the relationship between AGK and RPL39 (Ribosomal protein L39) in mitochondria as well as their effect on the mitochondrial function was analyzed through methods including transmission electron microscopy, microarray, biotin identification and immunoprecipitation. Results AGK showed a markedly upregulated expression in EOC, which was significantly associated with the poor survival of patients with EOC, the expression of AGK-promoted EOC cell proliferation and tumorigenicity. AGK also induced CSC-like properties in the EOC cells and was resistant to cisplatin chemotherapy. Furthermore, the results indicated that AGK not only maintained mitochondrial cristae morphogenesis, but also increased the production of reactive oxygen species and Δψm of EOC cells in a kinase-independent manner. Finally, our results revealed that AGK played its biological function by directly interacting with RPL39. Conclusions We demonstrated that AGK was a novel CSC biomarker for EOC, which the stemness of EOC was promoted and chemotherapy resistance was developed through physical as well as functional interaction with RPL39.

Abstract Background Thalassemia is a genetic blood disorder characterized by decreased hemoglobin production. Severe anemia can damage organs and severe threat to life safety. Allogeneic transplantation of bone marrow-derived hematopoietic stem cell (HSCs) at present represents a promising therapeutic approach for thalassemia. However, immune rejection and lack of HLA-matched donors limited its clinical application. In recent years, human-induced pluripotent stem cells (hiPSCs) technology offers prospects for autologous cell-based therapy since it could avoid the immunological problems mentioned above. Methods In the present study, we established a new hiPSCs line derived from amniotic cells of a fetus with a homozygous β41-42 (TCTT) deletion mutation in the HBB gene and a heterozygous Westmead mutation (C > G) in the HBA2 gene. We designed a CRISPR-Cas9 to target these casual mutations and corrected them. Gene-corrected off-target analysis was performed by whole-exome capture sequencing. The corrected hiPSCs were analyzed by teratoma formation and erythroblasts differentiation assays. Results These mutations were corrected with linearized donor DNA through CRISPR/Cas9-mediated homology-directed repair. Corrections of hiPSCs were validated by sequences. The corrected hiPSCs retain normal pluripotency. Moreover, they could be differentiated into hematopoietic progenitors, which proves that they maintain the multilineage differentiation potential. Conclusions We designed sgRNAs and demonstrated that these sgRNAs facilitating the CRISPR-Cas9 genomic editing system could be applied to correct concurrent α- and β-thalassemia in patient-derived hiPSCs. In the future, these corrected hiPSCs can be applied for autologous transplantation in patients with concurrent α- and β-thalassemia.

Clay minerals have a specific adsorption capability for anions, which increases the amount of net negative charge on the surface, leading to the increased adsorption of rare-earth ions in clay minerals and some change from exchangeable to non-exchangeable. Further, anions show a shielding effect on rare-earth ions. The shielding capacity of anions in the leaching agents for rare-earth ions was measured in this study. The relationship between the solid-phase concentration of rare-earth ions shielded and the anion concentration was consistent with the Langmuir model. Based on the Kerr model describing the exchange of rare-earth ions by ammonium ions, an ion-exchange model considering the shielding influence of anions was proposed. The accuracy of the proposed model was higher than that of the Kerr model. When the leaching agent was ammonium sulfate, the calculation accuracy of XW and AY samples was increased by 1.15% and 5.75%, respectively. The improvement in accuracy positively correlated with the proportion of iron oxides, aluminium oxides, and Kaolin. The established ion-exchange model can provide accurate source and sink terms for the numerical simulation of the leaching process of ion-adsorption-type rare-earth ores.

Ion-adsorption-type rare-earth ores (IATREOs) that have experienced granite weathering have good permeability, and their leaching process involves the solute transport problem, which is dominated by convection. Because of the oscillation and dispersion errors of existing numerical methods for solving the convective-dominated solute transport equation, the results have low precision in the twin leaching process. In this paper, the convection–dispersion equation is decoupled into the dispersion equation, the convection equation, and the source-sink equation; the Crank–Nicolson and implicit difference methods are used to solve the dispersion equation and the source-sink equation, respectively. The solution of the convection equation is achieved on the basis of its physical interpretation. Therefore, a decoupling method for the convective-dominated solute transport equation is established. In comparison to the two examples with analytical solutions, the calculation errors of the method established in this paper are less than 2.00%, and it can solve the oscillation and dispersion problems. The rationality of the method is further demonstrated through the column leaching experiment of IATREOs. In comparison to the test results, the coefficients of determination of the breakthrough curves of rare-earth ions and ammonium ions calculated by the proposed method are all greater than 0.850, and the peak concentration error of rare-earth ions is less than 7.00%. This indicates that the proposed method can simulate the leaching process well. Furthermore, by combining the multiple/half method and the dichotomy method, an optimization method for determining the leaching agent amount was established to analyze the relationship between the leaching agent and the ratio of dispersion to pillar length. The results can provide a solution that can be used to mine IATREOs from experience to theory.

During the last glacial, Dansgaard–Oeschger (DO) events are mostly characterized by moderate and shorter fluctuations. Here, we present the three-year-resolution stalagmite isotopic record from Shouyuangong Cave (SYG), southern China, revealing a detailed history of Asian summer monsoon (ASM) and local environmental changes during the middle and late period of DO 14. During this period, the SYG1 δ18O is characterized by the persistence of centennial-scale oscillations. These centennial δ18O enrichment excursions are clearly mirrored in the δ13C signal. This correlation suggests that changes in soil CO2 production at this site are closely correlated with centennial-scale ASM variability. Furthermore, power spectrum analysis shows that δ18O and δ13C display the common periodicities consistent with solar activity cycles, implicating a control of solar activity on the ASM and soil humidity. Particularly, weak solar activity generally corresponds to weak ASM and a decline in soil CO2 production. One possible link between them is that external forcing controls the ASM intensity via the thermal contrast between the ocean and land. Subsequently, the balance of soil moisture co-varies with the hydrological responses. Finally, the soil CO2 production is further amplified by ecological effect.

Thalassemia is a group of single-gene recessive inherited hemoglobin disorders caused by a mutation or deletion of one or more globin genes, which results in abnormal globin chain synthesis and hemoglobin formation. In this study, human iPSC lines HNMUi002-A, HNMUi003-A, HNMUi004-A, HNMUi005-A, HNMUi006-A, HNMUi007-A, HNMUi008-A, HNMUi009-A, HNMUi010-A were generated from the amniotic fluid cells or urine-derived cells isolated from 9 patients with thalassemia. The iPSC lines exhibited the normal karyotype, expressed pluripotency markers, and carried α- or β- globin gene mutations. These pluripotent stem cell lines will serve as useful tools for studying pathophysiological mechanism of thalassemia.

Patau syndrome is a rare congenital malformation syndrome due to the presence of an extra chromosome 13. In this paper, we report the generation of an induced pluripotent stem cell line from the fibroblasts isolated from chorionic villi of an early spontaneously aborted foetus with Patau syndrome. The Patau syndrome villus induced pluripotent stem cell line retains the original trisomy 13 karyotype, expresses pluripotency markers and induces teratoma formation in NOD-SCID mice. This pluripotent stem cell model of Patau syndrome should serve as a tool to study this congenital malformation syndrome.

Objective: To compare effect of immunoprevention or immunotherapy based on denderitic cells (DCs), or supernatants on pancreatic carcinoma and hepatocelluar carcinoma in vitro and in vivo. Methods: DCs and monouclear cells (immunoeffecetor cells) were stimulated with hGM-CSF, hIL-4, hTNF-α, PC3 TA or BEL7402 TA and hIL-2, then DCs and immunoeffector cells were cocultured, and supernatants were harvested. In vitro, the immunoeffector cells were divided into A0 group (without DCs stimulated), A1 group (DCs stimulated, cultured with cytokines cocktail), A2 group (DCs stimulated, cultured with cytokines cocktail and tumor antigen, DCs vaccine). Cytoxicity assay was performed with lactate dehydogenase method. In vivo, the nude mice were allocated in 3 groups: prevention group, receiving immunoeffector cells activated by DCs vaccine 2 days before inoculation with PC3 or BEL7402; treatment group, receiving immunoeffector cells activated by DCs vaccine after development of implanted tumor in all nude mice; control group, receiving equivalents amount of RPMI1640 cultured liquid. On the 45th day, all the nude mice were sacrificed and the tumor was weighed. Results: The maximal inhibition rate of the A0, A1 and A2 were 3.5%, 68.1%, 81.0% in the BEL7402; 4.5%, 33.0%, 62.4% in the PC3. The differences in tumor weight among three groups were significant, but the differemce were not significant between the PC3 and BEL7402. Conclusions: DCs vaccine or supernatants may play an important role in treating and preventing against malignant tumor.

Two single track multi-layer walls with linear energy inputs (LEIs) of 219 and 590 J/mm were deposited by cold metal transfer-based wire arc additive manufacturing system. Combined with the X-ray diffraction technique, scanning electron microscope and uniaxial tensile tests, the influences of LEI and cooling rate (CR) on the microstructure evolution, mechanical properties and fracture mechanisms of the studied steel are analyzed. It is observed that the microstructures of the studied steel are mainly composed of δ-ferrite and austenite dendrites. σ phase is formed on the δferrite–austenite interface under low CR. Meanwhile, the primary dendrites’ spacing decreases with the decrease in LEI or the increase in CR, and the maximal primary dendrites’ spacing is 32 μm. The values of elongation to fracture roughly decline with the decrease in LEI or the increase in CR, but the variations of ultimate tensile strength and yield stress show an opposite trend. In addition, the mesoscopic damages in the studied steel under low LEI are mainly caused by the coalescence of pores. While under high LEI, the cracks are induced by the dislocations piling up around δ-ferrite.

In this paper, we establish new oscillation criteria for second order neutral dynamic equations with distributed delay by employing the generalized Riccati transformation. The obtained theorems essentially improve the oscillation results in the literature. And two examples are provided to illustrate to the versatility of our main results.

Temperature strongly influences lettuce (Lactuca sativa L.) seed germination. Different lettuce genotypes respond differently to higher temperatures or thermal stress. In this study, we evaluated the germination performance of 304 lettuce accessions incubated at three temperature settings, 21 °C, 28 °C and 35 °C, respectively, for 40 h. At 21 °C, seeds of all 304 accessions germinated with very well an average germination percentage of 87.72%; at 28 °C, the average germination percentage dropped to 42.84% and at 35 °C, the germination decreased to 1.01%. Then, we investigated changes in metabolic profiles of lettuce seed response to thermal stress using an untargeted metabolomics approach. Results suggested that seeds of thermal-sensitive and thermal-tolerant cultivars employed different metabolic strategies in response to thermal stress during germination. Thermal-sensitive buds accumulated more significant amounts of organic acids, amino acids, sugars, sterols, phenolic compounds and terpenoids compared to thermal-tolerant buds at 21 °C. Thermal-tolerant lettuce cultivar accumulated higher concentrations of amino acids, organic acids, sugars, sesquiterpene lactones, sterols, and fatty acids derivatives during the germination at 35 °C compared to germinated at 21 °C. This investigation paves the way to link the metabolomics to other external and internal factors affecting lettuce seed germination under thermal stress.

Non-Camellia tea is a part of the colorful Chinese tea culture, and is also widely used as beverage and medicine in folk for disease prevention and treatment. In this study, 37 samples were collected, including 33 kinds of non-Camellia teas and 4 kinds of teas (Camellia). Traditional functions of non-Camellia teas were investigated. Furthermore, non-Camellia teas of original plants were characterized and identified by molecular methods. Four candidate regions (rbcL, matK, ITS2, psbA-trnH) were amplified by polymerase chain reaction. In addition, DNA barcodes were used for the first time to discriminate the commercial non-Camellia tea and their adulterants, and to evaluate their safety. This study showed that BLASTN and the relevant phylogenetic tree are efficient tools for identification of the commercial non-Camellia tea and their adulterants. However, some sequences from original plants have not been found and there is a limitation of sequence number of original plants in GenBank. Submitting more original plant sequences to the GenBank will be helpful for evaluating the safety of non-Camellia teas.

Upland and lowland rice (Oryza sativa L.) represent two of the most important rice ecotypes adapted to ago-ecosystems with contrasting soil-water conditions. Upland rice, domesticated in the water-limited environment, contains valuable drought-resistant characters that can be used in water-saving breeding. Knowledge about the divergence between upland and lowland rice will provide valuable cues for the evolution of drought-resistance in rice. Genetic differentiation between upland and lowland rice was explored by 47 Simple Sequence Repeats (SSRs) located in drought responding expressed sequence tags (ESTs) among 377 rice landraces. The morphological traits of drought-resistance were evaluated in the field experiments. Different outlier loci were detected in the japonica and indica subspecies, respectively. Considerable genetic differentiation between upland and lowland rice on these outlier loci was estimated in japonica (Fst = 0.258) and indica (Fst = 0.127). Furthermore, populations of the upland and lowland ecotypes were clustered separately on these outlier loci. A significant correlation between genetic distance matrices and the dissimilarity matrices of drought-resistant traits was determined, indicating a certain relationship between the upland-lowland rice differentiation and the drought-resistance. Divergent selections occur between upland and lowland rice on the drought-resistance as the Qsts of some drought-resistant traits are significantly higher than the neutral Fst. In addition, the upland- and lowland-preferable alleles responded differently among ecotypes or allelic types under osmotic stress. This shows the evolutionary signature of drought resistance at the gene expression level. The findings of this study can strengthen our understanding of the evolution of drought-resistance in rice with significant implications in the improvement of rice drought-resistance.

Background: Osteosarcoma (OS), a bone tumor with high ability of invasion and metastasis, has seriously affected the health of children and adolescents. Many studies have suggested a connection between OS and the epithelialmesenchymal transition (EMT). We aimed to integrate EMT-Related genes (EMT-RGs) to predict the prognosis, immune infiltration, and therapeutic response of patients with OS. Methods: We used consensus clustering to identify potential EMT-Related OS molecular subtypes. Somatic mutation, tumor immune microenvironment, and functional enrichment analyses were performed for each subtype. We next constructed an EMT-Related risk signature and evaluated it by Kaplan-Meier (K-M) analysis survival and receiver operating characteristic (ROC) curves. Moreover, we constructed a nomogram tomore accurately predict OS patients' clinical outcomes. Response effects of immunotherapy in OS patients was analyzed by Tumor Immune Dysfunction and Exclusion (TIDE) analysis, while sensitivity for chemotherapeutic agents was analyzed using oncoPredict. Finally, the expression patterns of hub genes were investigated by single-cell RNA sequencing (scRNA-seq) data analysis. Results: A total of 53 EMT-RDGs related to prognosis were identified, separating OS samples into two separate subgroups. The EMT-high subgroup showed favourable overall survival and more active immune response. Significant correlations were found between EMT-Related DEGs and functions as well as pathways linked to the development of OS. Additionally, a risk signature was established and OS patients were divided into two categories based on the risk scores. The signature presented a good predictive performance and could be recognized as an independent predictive factor for OS. Furthermore, patients with higher risk scores exhibited better sensitivity for five drugs, while no significant difference existed in immunotherapy response between the two risk subgroups. scRNAseq data analysis displayed different expression patterns of the hub genes. Conclusion: We developed a novel EMT-Related risk signature that can be considered as an independent predictor for OS, which may help improve clinical outcome prediction and guide personalized treatments for patients with OS. [ABSTRACT FROM AUTHOR]

Purpose: Human gut microbiota has been shown to be significantly associated with various inflammatory diseases. Therefore, this study aimed to develop an excellent auxiliary tool for the diagnosis of juvenile idiopathic arthritis (JIA) based on fecal microbial biomarkers. Method: The fecal metagenomic sequencing data associated with JIA were extracted from NCBI, and the sequencing data were transformed into the relative abundance of microorganisms by professional data cleaning (KneadData, Trimmomatic and Bowtie2) and comparison software (Kraken2 and Bracken). After that, the fecal microbes with high abundance were extracted for subsequent analysis. The extracted fecal microbes were further screened by least absolute shrinkage and selection operator (LASSO) regression, and the selected fecal microbe biomarkers were used for model training. In this study, we constructed six different machine learning (ML) models, and then selected the best model for constructing a JIA diagnostic tool by comparing the performance of the models based on a combined consideration of area under receiver operating characteristic curve (AUC), accuracy, specificity, F1 score, calibration curves and clinical decision curves. In addition, to further explain the model, Permutation Importance analysis and Shapley Additive Explanations (SHAP) were performed to understand the contribution of each biomarker in the prediction process. Result: A total of 231 individuals were included in this study, including 203 JIA patients and Non-JIA individuals. In the analysis of diversity at the genus level, the alpha diversity represented by Shannon value was not significantly different between the two groups, while the belt diversity was slightly different. After selection by LASSO regression, 10 fecal microbe biomarkers were selected for model training. By comparing six different models, the XGB model showed the best performance, which average AUC, accuracy and F1 score were 0.976, 0.914 and 0.952, respectively, thus being used to construct the final JIA diagnosis model. Conclusion: A JIA diagnosis model based on XGB algorithm was constructed with excellent performance, which may assist physicians in early detection of JIA patients and improve the prognosis of JIA patients. [ABSTRACT FROM AUTHOR]