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5′-Adenylated oligonucleotides (AppOligos) are widely used for single-stranded DNA/RNA ligation in next-generation sequencing (NGS) applications such as microRNA (miRNA) profiling. The ligation between an AppOligo adapter and target molecules (such as miRNA) no longer requires ATP, thereby minimizing potential self-ligations and simplifying library preparation procedures. AppOligos can be produced by chemical synthesis or enzymatic modification. However, adenylation via chemical synthesis is inefficient and expensive, while enzymatic modification requires pre-phosphorylated substrate and additional purification. Here we cloned and characterized the Pfu RNA ligase encoded by the PF0353 gene in the hyperthermophilic archaea Pyrococcus furiosus. We further engineered fusion enzymes containing both Pfu RNA ligase and T4 polynucleotide kinase. One fusion enzyme, 8H-AP, was thermostable and can directly catalyze 5′-OH-terminated DNA substrates to adenylated products. The newly discovered Pfu RNA ligase and the engineered fusion enzyme may be useful tools for applications using AppOligos.

The visible physical dysfunction and invisible psychological effects after stroke prevent young patients from returning to their pre-stroke roles and social activities.To comprehensively analyze the psychological experience and social reintegration needs of young stroke patients, which may be beneficial for improving quality of life and social reintegration after stroke.We conducted a comprehensive literature search of 10 databases. The screening and quality assessment of the included articles were performed by the Qualitative Assessment and Review Instrument (QARI). Meta-aggregation was conducted to synthesize the findings of the included studies. We summarized the certainty of confidence using the Confidence in Evidence from Reviews of Qualitative Research (CERQual) approach.A total of 5506 studies were screened, of which 12 were included. Data synthesis suggested two new themes: (a) the self-growth process from denial of stroke to accepting stroke (high CERQual confidence), and (b) desire to regain pre-stroke normality, but having difficulty in the social reintegration process (high CERQual confidence).Stroke, as a traumatic event, disrupts the life structure of young patients, and their needs of reintegration are not adequately considered. Interventions based on the principle of individuation should focus on this issue to restore continuity in life after stroke.

Junctional adhesion molecule-C (JAM-C) is an important regulator of many physiological processes, ranging from maintenance of tight junction integrity of epithelia to regulation of cell migration, homing and proliferation. Preeclampsia (PE) is a trophoblast-related syndrome with abnormal placentation and insufficient trophoblast invasion. However, the role of JAM-C in normal pregnancy and PE pathogenesis is unknown.The expression and location of JAM-C in placentas were determined by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. The expression of differentiation and invasion markers were detected by qRT-PCR or western blot. The effects of JAM-C on migration and invasion of trophoblasts were examined using wound-healing and invasion assays. Additionally, a mouse model was established by injection of JAM-C-positive adenovirus to explore the effects of JAM-C in vivo.In normal pregnancy, JAM-C was preferentially expressed on cytotrophoblast (CTB) progenitors and progressively decreased when acquiring invasion properties with gestation advance. However, in PE patients, the expression of JAM-C was upregulated in extravillous trophoblasts (EVTs) and syncytiotrophoblasts (SynTs) of placentas. It was also demonstrated that JAM-C suppressed the differentiation of CTBs into EVTs in vitro. Consistently, JAM-C inhibited the migration and invasion capacities of EVTs through GSK3β/β-catenin signaling pathway. Importantly, Ad-JAMC-infected mouse model mimicked the phenotype of human PE.JAM-C plays an important role in normal placentation and upregulated JAM-C in placentas contributes to PE development.

Background: Preeclampsia is a complicated syndrome with marked heterogeneity. The biomarker-based classification for this syndrome is more constructive to the targeted prevention and treatment of preeclampsia. It has been reported that preeclamptic patients had elevated microRNA-155 (miR-155) in placentas or circulation. Here, we investigated the characteristics of patients with high placental miR-155 (pl-miR-155). Methods: Based on the 95th percentile (P95) of pl-miR-155 in controls, preeclamptic patients were divided into high miR-155 group (≥P95) and normal miR-155 group ( Results: About one-third of preeclamptic patients had high pl-miR-155 expression, which was positively correlated with circulating miR-155 levels. These patients could be clustered as 1 group, according to clinical manifestation, placental pathology, or transcriptomes by t-distributed stochastic neighbor embedding and hierarchical clustering analysis. Further, the pregnant mice with placental restricted miR-155 overexpression could simulate the changes of clinical signs, pathology, and transcriptome of placentas in patients with high pl-miR-155. AntagomiR-155 treatment relieved the preeclampsia-like phenotype and improved the placental vascular development in mice. Conclusions: There is at least 1 type of preeclampsia with upregulated miR-155 presenting more severe clinical manifestations. MiR-155 may be a potential therapeutic target in patients with high pl-miR-155.

Preeclampsia (PE) is a pregnancy-related syndrome characterized by new-onset hypertension and proteinuria after gestational 20 weeks. Oxidative stress, resulting from the imbalance between the production of oxidants and antioxidants in placentas, is recognized as a key pathology of PE. To date, the molecules that regulate antioxidants production remain unclear. CD151, a member of tetraspanins, is an important regulator of many physiological functions. However, the function of CD151 in oxidative stress and its association with pregnancy-related complications are currently unknown. In the present study, we have demonstrated that CD151 was a key regulator of antioxidants in placentas. Compared with the placentas of the controls, the placentas of PE patients exhibited decreased CD151 expression accompanying with decreased antioxidant gene expression (HO-1, NQO-1, GCLC and SOD-1). In vitro, overexpression of CD151 in trophoblast cells could enhance HO-1, NQO-1, GCLC and SOD-1 expression but downregulation of CD151 decreased those antioxidant genes expression, which indicates CD151 is the upstream of antioxidants. Importantly, the phenotype of PE (hypertension and proteinuria) was mimicked in the downregulating CD151 induced mouse model. Moreover, the beneficial effect of CD151 in trophoblast cells was hindered when ERK and Nrf2 signaling were blocked. Overall, our results revealed CD151 might be a new target for PE treatment.

Sepsis is a highly life-threatening disease. Long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) participates in the processes of inflammation and organ injury in several diseases, whereas its role in sepsis patients is still unclear. The aim was to explore the clinical value of lncRNA UCA1 in sepsis patients.One hundred seventy-four sepsis patients and 100 age and gender-matched controls were enrolled. LncRNA UCA1 in peripheral blood mononuclear cell samples was examined, and the level of inflammatory cytokines in serum samples was assessed.LncRNA UCA1 was highly expressed in sepsis patients compared with controls. LncRNA UCA1 was positively correlated with tumor necrosis factor-α, interleukin (IL)-6, IL-17, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in sepsis patients, while it was not correlated with these inflammatory cytokines in controls. lncRNA UCA1 upregulation was related to raised APACHE II score and SOFA score in sepsis patients. Moreover, lncRNA UCA1 was increased in sepsis deaths compared with sepsis survivors and was independently correlated with increased 28-day sepsis mortality risk. Further receiver operating characteristic curves presented that lncRNA UCA1 had a good value to predict 28-motality risk, while its combination with other independent factors (including age, history of chronic kidney disease, G+ bacterial infection, Fungus infection, C-reactive protein, and APACHE II score) exerted a great predictive value for 28-day mortality risk.LncRNA UCA1 is upregulated and correlates with multiple pro-inflammatory cytokines, terrible disease severity, and poor prognosis in sepsis patients.

Declining forests usually face uncertain regeneration dynamics and recovery trajectories, which are challenging to forest management. In this study, we investigated the decline pattern of Castanopsis fargesii and examined the effects on conspecific seedling regeneration. We found that 61.45% of adult individuals were in decline and the smaller DBH size classes of trees (10–40 cm) had a greater probability of decline. Most of the intermediate decline (94.52%) and nondecline individuals (95.23%) did not worsen, and the crowns of 21.91% of the intermediate decline trees were recovered during 2013–2018. Adult tree decline had a negative effect on seed production (mean mature seed density of nondecline, intermediate decline, and high decline individuals was 167.3, 63.3, and 2.1 seeds/m2, respectively), but no effect on key seed traits. The seed survival rate of declining trees was greater than that of nondeclining trees at both the seed production and seed dispersal stages. The seed to seedling transition rates in canopy gaps, decline habitats, and nondecline habitats were 7.94%, 9.47%, and 109.24%, respectively. The survival rate and height growth of newly germinated seedlings were positively correlated with the light condition, which was notably accelerated in the canopy gaps. Taken together, these results indicate that the reduction in seed production of some adult trees had a weakly negative effect on new seedling recruitment, while the improved environmental condition after the decline significantly enhanced the survival and growth of both advanced and new germinated seedlings. Looking at the overall life history, the short‐term defoliation and mortality of some C. fargesii adult trees can be regarded as a natural forest disturbance that favors conspecific seedling regeneration. High‐intensity management measures would be unnecessary in cases of an emerging intermediate decline in this forest.

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21–5 p to inhibit miR-21–5 p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC–EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC–EMT and administration of miR-21–5 p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21–5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.

8-oxoguanine (8-oxoG) is one of the most prevalent genotoxic lesions, and it is generated in DNA attacked by reactive oxygen species (ROS). Adenine misincorporated opposite to 8-oxoG during replication is excised by MutY homolog (MUTYH), an important protein of the base excision repair (BER) system. Mutyh plays an important role in the maintenance of genomic integrity, but the functional consequences of Mutyh deficiency are not fully understood. In the current study, we investigated the histological and functional changes of five tissues (hippocampus, heart, liver, kidney and lung) and their molecular basis in Mutyh-/- and wild-type mice exposed to D-galactose (D-gal). Our data indicated that Mutyh deficiency hindered the weight gain of experimental mice and induced substantial alterations of 8-oxoG content and superoxide dismutase (SOD) activity, but no significant histological and functional impairment appeared in the investigated tissues of Mutyh- deficient mice without D-gal exposure. Under low-dose D-gal exposure, Mutyh deficiency altered expression of genes involved in mitochondrial unfolded protein response (UPRmt) in the heart, liver and lung, and caused an enhanced expression of mitochondrial dynamics proteins (MDPs) in hippocampus and liver. The stress responses could maintain mitochondrial proteostasis and function. However, such responses were not noted when experiencing excessive damage burden induced by high-dose D-gal exposure, in which Mutyh deficiency increased accumulation of 8-oxoG and aggravated mitonuclear protein imbalance, as well as histological lesions in heart, liver and kidney. A higher sensitivity to ROS-induced cardiotoxicity with high-dose D-gal exposure was noticed in Mutyh-/- mice. However, no differences in learning and memory impairments were observed between Mutyh-/- and wild-type mice with high-dose D-gal exposure. In conclusion, our data demonstrated that Mutyh deficiency has different impacts on various tissues based on the degree of oxidative stress.

BackgroundOwing to the low prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in lupus nephritis (LN), there is no study about the differences between proteinase 3 (PR3)-ANCA positivity and myeloperoxidase (MPO)-ANCA positivity in LN until now.MethodsHere we perform a retrospective study to determine whether there are differences in clinic-pathological characteristics and renal outcomes between PR3-ANCA-positive LN patients and MPO-ANCA-positive LN patients.ResultsA total of 26 (27.4%) PR3-ANCA-positive LN patients and 69 (72.6%) MPO-ANCA-positive LN patients ( p ConclusionMPO-ANCA-positive LN patients had more severely impaired baseline renal function and less active lupus serology. More severely chronic pathological changes, including interstitial fibrosis and tubular atrophy on renal specimens, occurred in MPO-ANCA-positive LN patients. We found that MPO-ANCA-positive LN patients had worse renal outcomes.

In continuation of our program to discover new potential antifungal agents, thirty-two neuchromenin analogues were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi, and structure−activity relationships (SAR) were derived. Compounds 6b-c, and 6l showed obvious inhibition activity on each of the fungi at 50 μg/mL. For the corresponding fungi, 7 of the compounds showed average inhibition rates of >80% at 50 μg/mL; especially, compounds 6b, 6d-e, and 6i-l displayed more potent antifungal activity against A. solani than that of thiabendazole (a positive control). Moreover, compound 6c also exhibited good activity against C. lunata with EC50 values of 12.7 μg/mL, and the value was much superior to that of thiabendazole (EC50 = 59.7 μg/mL). SAR analysis showed that the presence of conjugated structure, bearing a C=C bond conjugated to the C=O group, obviously decreased the activity; the type and position of the substituted R5 significantly influenced the activity. Furthermore, the significantly bioactive compounds 6b-e, 6g, 6i and 6l showed very low toxicities against HL-7702, BEL-7402 and HCT-8 cells. Resistance development assay indicated that compounds 6b-e and 6l failed to induce the two tested strains of fungi to develop resistance. SEM analysis initially revealed that compound 6d may exert its antifungal effect by damaging fungal cell wall.

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/ΔNp63α pathway.

In this study, flower molybdenum disulfide (MoS2) was surface-modified with polyethyleneimine(PEI) to prepare PEI/MoS2 composite adsorbents for Cr(VI) enrichment in aqueous solution. The physicochemical properties of PEI/MoS2 were characterized by SEM, TEM, XRD, FTIR, BET and XPS methods. The influences of PEI loading, solution pH, contact time, adsorption temperature, and initial Cr(VI) ion concentration on the adsorption performance of PEI/MoS2 for Cr(VI) were investigated. Under the optimal conditions, and the initial Cr(VI) ion concentration is 50 mg L− 1, the adsorption capacity of PEI/MoS2 is 120.7 mg g− 1. The adsorption rate is fast, equilibrium time is 6 h. Competitive adsorption studies of the Cr(VI), Co(II), Zn(II) and Cd(II) quaternion system were also investigated, the results indicated that selectively adsorbed amount of Cr(VI) on PEI/MoS2 is significantly higher than that of Co(II), Zn(II) and Cd(II) ions. The adsorption process was spontaneous and conformed to Freundlich isotherm and pseudo-second kinetic model. The consecutive adsorption-desorption experiments indicated that the PEI/MoS2 has excellent reusability.

Background: Junctional adhesion molecule-C (JAM-C) is an important regulator of many physiological processes, ranging from the maintenance of tight junction integrity of epithelia to regulation of cell migration, homing and proliferation. Preeclampsia (PE) is a trophoblast-related syndrome with abnormal implantation and insufficient trophoblast invasion of spiral arteries. What’s the role of JAM-C in trophoblasts differentiation and migration in normal pregnancy and PE pathogenesis? Methods: The expression and location of JAM-C in the placental tissues were determined by qRT-PCR, western blot and immunohistochemistry. RNA-sequencing was used to characterize the role of JAM-C in primary CTBs. The effects of JAM-C on migration and invasion of trophoblasts were determined using wound-healing and Matrigel invasion assays. The expression of differentiated and invasion markers were detected by qRT-PCR or western blot. Additionally, twenty pregnant mice were included. Fetal resorption rate, systolic blood pressure (SBP) and urinary protein level were measured and smooth muscle cell (SMC) coverage were analyzed by immunostaining. Findings: In normal pregnancy, JAM-C was preferentially expressed on cytotrophoblast (CTB) progenitors and progressively decreased when acquiring invasion properties with gestational advance. As RNA-seq analysis demonstrated that JAM-C inhibited the differentiation, migration and invasion of trophoblasts. However, in PE patients, the expression of JAM-C is up-regulated in extravillous trophoblasts (EVTs) and syncytiotrophoblasts (SynTs) of placentas. Over-expression of JAM-C in human trophoblast stem cells (hTSCs) negatively regulated the differentiation potentiality. In HTR-8/SV neo cells, JAM-C inhibits migration and invasion through GSK3β/β-catenin signaling pathway . Importantly, the mouse model induced by JAM-C mimics the human PE phenomenon and impaired spiral arteries remodeling. Interpretation: JAM-C plays an important role in normal placentation and that its abnormal increase in placentas contributes to PE development. Funding Statement: This study was funded by grants from National Key R&D Program of China (2018YFC1004404), Jiangsu Provincial Key Medical Center (YXZXB2016004), National Natural Science Foundation of China (82071666, 81701474, 81701475, 81801470), and Jiangsu Biobank of Clinical Resources (BM2015004). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: This study was reviewed and approved by the Ethics Committee (2018-034-01) of Affiliated Drum Tower Hospital, Nanjing University Medical School. Written informed consent was obtained from all participants before surgery.

Polysaccharide is one of the necessary macromolecules in life activities, and it is also a very promising natural product for tumor prevention and treatment. In this study, two homogeneous polysaccharides (APS-4I and APS-4II) were isolated from Angelica sinensis (Oliv.) Diels. APS-4I was a linear glucan with molecular weight of 16.1 kDa, which was composed of 88.4% α-1,6-Glcp, 4.1% α-1,2-Glcp, 3.9% α-1,3-Glcp, and 2.8% α-T-Glcp. APS-4II was a novel polysaccharide with molecular weight of 11.1 kDa, which consisted of 55.4% α-1,6-Glcp, 10.4% α-1,3,5-Araf, 8.7% α-T-Araf, 9.2% α-1,5-Araf, 4.0% α-1,3-Araf, 3.6% α-1,4-Galp, and 9.1% β-1,3-Galp. NMR results demonstrated that APS-4II has a backbone composed of →6)-α-Glcp-(1 → 6)-α-Glcp-(1 → 5)-α-Araf-. (1 → 5)-α-Araf-(1 → 3,5)-α-Araf-(1 → 3)-β-Galp-(1 → 3)-β-Galp-(1 → 4)-α-Galp-(1 → 3)-α-Araf-(1 → 3,5)-α-Araf-(1→. Both APS-4I and APS-4II inhibited the tumor growth of B16-bearing mice, and the suppressive effect of APS-4II reached 64.7 ± 7.3%. Meanwhile, there were higher lymphocyte numbers and the levels of IL-2, IFN-γ, and TNF-α in peripheral blood of APS-4II-treated mice than those in APS-4I-treated mice. Furthermore, APS-4II showed a higher inhibitory effect on the proliferation of B16 cells and stronger promoting effects on the proliferation of splenocytes, the phagocytosis of peritoneal macrophages, and the cytotoxicity of NK cells. These results demonstrated that APS-4II could be a promising therapeutic agent for melanoma.

Background The present study aimed to explore the correlation of long non‐coding RNA highly up‐regulating in liver cancer (lncRNA HULC) with disease risk, inflammatory cytokines, biochemical indexes, disease severity, infective features, and 28‐day mortality of sepsis. Methods Totally 174 sepsis patients and 100 controls were enrolled. Peripheral blood samples were collected from sepsis patients after diagnosis and from controls at enrollment, respectively, and further for separation of peripheral blood mononuclear cell (PBMC) and serum samples. PBMC samples were for lncRNA HULC detection, and serum samples were for inflammatory cytokine detection. Results LncRNA HULC expression was increased in sepsis patients compared with controls. Moreover, lncRNA HULC was positively associated with TNF‐α, IL‐6, IL‐17, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, serum creatinine, white blood cell, and C‐reactive protein in sepsis patients, but not in controls. Furthermore, in sepsis patients, lncRNA HULC expression was positively correlated with acute physiology and chronic health evaluation II score and sequential organ failure assessment score, but not correlated with primary infection sites or primary infection organisms; meanwhile, lncRNA HULC expression was increased in deaths compared with survivors; subsequent receiver operating characteristic curve indicated that lncRNA HULC presented good value in predicting increased 28‐day mortality (AUC: 0.785, 95% CI: 0.713–0.857), and its independent predictive value for mortality was also verified by multivariate analysis. Conclusion LncRNA HULC is correlated with higher disease risk, severity, and inflammation and serves as an independent factor for predicting increased mortality, suggesting its potential in promoting accuracy of prognostic prediction for sepsis management., Totally 174 sepsis patients and 100 controls were enrolled and their peripheral blood samples were collected and separated for lncRNA HULC and inflammatory cytokine detection. Results indicated that lncRNA HULC expression was increased in sepsis patients compared with controls; LncRNA HULC was positively associated with higher inflammation level in sepsis patients, but not in controls; In sepsis patients, lncRNA HULC expression was positively correlated with increased disease severity, and serves as an independent factor for predicting increased mortality.

The optimisation design of air-cored axial flux permanent magnet (PM) generator is a complex non-linear problem with constraints, multi-objective, multivariable and multi-peak value. The different variables will affect the same optimisation goal. In this paper, a multi-objective optimisation design of air-cored axial flux PM generator based on Taguchi-response surface method (RSM) is proposed. The main characteristics of generator efficiency, power quality, induction electromotive force and other main characteristics are taken as optimisation objectives. The parameter ranges that influence the optimisation objectives of the motor are selected as optimisation variables. First, the orthogonal matrix is established according to the number of selected parameters and the level factor of each parameter and the finite element method is used to solve the experimental matrix. Then, the mean and variance of the simulation results are analysed. The optimisation mathematical model was established between the target and the impact factor by using RSM for the conflicting factors, which can determine the optimal variable parameters. The effectiveness of the optimisation method is verified by finite element analysis and prototype experiments. The results show that the performance of optimised core less flux PM generator has been greatly improved.

Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.

Introduction We evaluated the current status of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detection in invasive breast carcinoma (IBC) in various laboratories across China. Materials and Methods The Breast Pathology Study Group of the Chinese Society of Pathologists collected HR and HER2 data from 12,467 IBC cases from 19 representative clinical centers in China. The data from every center were compared with the pooled data from the other centers. Results The assessment of HR status showed that the overall positive estrogen receptor (ER) and progesterone receptor (PR) rates were 71.7% and 63.7% (range, 60.9%-87.9% and 43.9%-84.8%), respectively. The ER results in 3 centers and the PR results in 6 centers were outside the 99.5% confidence interval and were considered to be outliers (P Conclusions As the largest study of HR and HER2 status in Chinese patients with IBC, the data from the present study have indicated that the overall rates of HR and HER2 were comparable to those reported in previous studies. However, the rates varied among the laboratories. Individual centers had not met the target values, and they need to improve the detection.

Intrauterine adhesion (IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2 (bFGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of bFGF 100 µg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients (2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved. Histological study showed blood vessel density increased obviously. Three patients (3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the bFGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.

To investigate the expressions of multidrug resistance-associated protein 1 (MRP1) gene, serum transforming growth factor beta-1 (TGF-β1) and interleukin-8 (IL-8) in patients with breast cancer during chemotherapy, and to analyze their correlations in chemotherapy.346 breast cancer patients admitted to the Department of Surgery (Breast) of Nanjing Drum Tower Hospital from March 2015 to December 2017 were included as study subjects. All selected patients received chemotherapy in our hospital. Quantitative reverse transcription- polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were adopted to detect the expression levels of MRP1 mRNA, as well as MRP1, TGF-β1 and IL-8 proteins in patients before chemotherapy and at 1, 2, 4 and 8 weeks after chemotherapy. Correlations of MRP1 protein/mRNA with clinical features of patients were analyzed, and Pearson's correlation analysis was performed to examine correlations of MRP1 protein/mRNA with TGF-β1 and IL-8 proteins.The expressions of MRP1 mRNA as well as MRP1, TGF-β1 and IL-8 proteins were increased with the prolongation of chemotherapy time, and there were statistically significant differences between the two time points (psemi;0.05). No correlations of MRP1 with the clinical patient features with breast cancer were found. Pearson's correlation analysis showed that the expression level of MRP1 was positively correlated with the expression levels of TGF-β1 (r=0.732, p=0.012) and IL-8 (r=0.709, p=0.018), and the expression level of TGF-β1 was positively related to that of IL-8 (r=0.714, p=0.015).With the prolongation of chemotherapy time in breast cancer patients, the expression level of MRP1 also increased which may affect the therapeutic effect of chemotherapy in breast cancer patients and lead to drug resistance. TGF-β1 and IL-8 may be closely associated with the mechanism of drug resistance in MRP1-guided breast cancer chemotherapy.

Aldolase A (ALDOA) facilitated aerobic glycolysis in cancer cells is a potential target in the treatment of hepatocellular carcinoma (HCC). However, only few effective inhibitors of ALDOA have been reported until now. In this research, we found a polysaccharide called HDPS-4II from Holotrichia diomphalia Bates, which can specifically bind to ALDOA with a dissociation constant of 2.86 μM. HDPS-4II with a molecular weight of 19 kDa was a linear triple-helix glucan composed of ɑ-d-1,4-Glcp and ɑ-d-1,6-Glcp in a ratio of 1.0:10.0. HDPS-4II significantly inhibited aldolase enzyme activity, glycolysis, and further inhibited the expression of phosphorylated AMPKα in HCC cells. Through analyzing ALDOA-overexpressing and -knockdown cells, it was confirmed that ALDOA mediated the viability and glycolysis inhibition of HDPS-4II. Moreover, HDPS-4II administration markedly inhibited tumor growth in mice xenografted with HCCs. These findings suggest that HDPS-4II, as an ALDOA antagonist, is a promising remedy in the treatment and prevention of HCC.

Chromosomal fusions are common in normal and cancer cells and can produce aberrant gene products that promote transformation. The mechanisms driving these fusions are poorly understood, but recurrent fusions are widespread. This suggests an underlying mechanism, and some authors have proposed a possible role for RNA in this process. The unicellular eukaryote Oxytricha trifallax displays an exorbitant capacity for natural genome editing, when it rewrites its germline genome to form a somatic epigenome. This developmental process provides a powerful model system to directly test the influence of small noncoding RNAs on chromosome fusion events during somatic differentiation. Here we show that small RNAs are capable of inducing chromosome fusions in 4 distinct cases (out of 4 tested), including one fusion of 3 chromosomes. We further show that these RNA-mediated chromosome fusions are heritable over multiple sexual generations and that transmission of the acquired fusion is associated with endogenous production of novel piRNA molecules that target the fused junction. We also demonstrate the capacity of a long noncoding RNA (lncRNA) to induce chromosome fusion of 2 distal germline loci. These results underscore the ability of short-lived, aberrant RNAs to act as drivers of chromosome fusion events that can be stably transmitted to future generations.

Background Cytomegalovirus (CMV) is a significant cause of fetal abnormalities in developed world. Whether this could be applied in developing world remains unknown. Objectives To investigate CMV infection in severe fetal malformations in China. Study design During 2007–2014, 436 fetuses (237 males) with severe malformations and terminated pregnancy at median gestational age of 26+1 weeks were enrolled. CMV DNA was detected in fetal kidneys and other tissues by real-time PCR, and CMV IgG and IgM were measured by ELISA. Results CMV DNA was positive in kidneys and other tissues of seven (1.60%) fetuses. Hematoxylin-eosin staining showed intranuclear and intracytoplasmic inclusion bodies in kidneys of three fetuses, which was also positive for CMV antigens in immunohistochemistry. CMV DNA was found in 5 (6.1%) of 82 fetuses with central nervous system anomalies, 1 (11.1%) of 9 fetuses with abdominal anomalies, 1 (0.59%) of 168 fetuses with multiple congenital malformations, and none of fetuses with other anomalies (177). Of 293 pregnant women with plasma available, 279 (95.2%) were CMV IgG positive only and 6 (2.1%) were CMV IgG and IgM positive. Of 5 mothers with infected fetuses 1 (20%) was CMV IgG and IgM positive, while 5 (1.7%) of 288 mothers with uninfected fetuses were positive respectively (P = 0.099). Conclusions Congenital CMV infection in fetuses with severe congenital malformations is rare, indicating no close association between CMV infection and severe fetal malformations in China. Maternal screening for CMV may have minimal value in identifying fetal malformations in developing world.

Table S1. Biological safety and biological activity analysis of the clinical-grade cells$ recognized by the National Institutes for Food and Drug Control (NIFDC). $: This table is translated from NIFDC report numbers, SH20140138 for UC-MSC. (DOCX 21Â kb)

Supplementary material. (DOCX 17Â kb)

Table S2. Serum levels of C-reactive protein, leukocyte count and neutrophil percentage at 1Â day after surgery in each patient. (DOCX 14Â kb)

Background Intrauterine adhesions (IUA) are the most common cause of uterine infertility and are caused by endometrium fibrotic regeneration following severe damage to the endometrium. Although current stem cell treatment options using different types of autologous stem cells have exhibited some beneficial outcomes in IUA patients, the reported drawbacks include variable therapeutic efficacies, invasiveness and treatment unavailability. Therefore, the development of new therapeutic stem cell treatments is critical to improving clinical outcomes. Methods Twenty-six patients who suffered from infertility caused by recurrent IUA were enrolled in this prospective, non-controlled, phase I clinical trial with a 30-month follow-up. During the procedure, 1 × 107 umbilical cord-derived mesenchymal stromal cells (UC-MSCs), loaded onto a collagen scaffold, were transplanted into the uterine cavity following an adhesion separation procedure. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and the biological molecules related to endometrial proliferation and differentiation were assessed both before and 3 months after cell therapy. Results No treatment-related serious adverse events were found. Three months after the operation, the average maximum endometrial thickness in patients increased, and the intrauterine adhesion score decreased compared to those before the treatment. A histological study showed the upregulation of ERα (estrogen receptor α), vimentin, Ki67 and vWF (von Willebrand factor) expression levels and the downregulation of ΔNP63 expression level, which indicates an improvement in endometrial proliferation, differentiation and neovascularization following treatment. DNA short tandem repeat (STR) analysis showed that the regenerated endometrium contained patient DNA only. By the end of the 30-month follow-up period, ten of the 26 patients had become pregnant, and eight of them had delivered live babies with no obvious birth defects and without placental complications, one patient in the third trimester of pregnancy, and one had a spontaneous abortion at 7 weeks. Conclusions Transplanting clinical-grade UC-MSCs loaded onto a degradable collagen scaffold into the uterine cavity of patients with recurrent IUA following adhesiolysis surgery is a safety and effective therapeutic method. Trial registration Clinicaltrials.gov. NCT02313415, Registered December 6, 2014. Electronic supplementary material The online version of this article (10.1186/s13287-018-0904-3) contains supplementary material, which is available to authorized users.

The COP (Coefficient of Performance) of the ground-source heat pump (GSHP) system decreased gradually year after year mainly caused by imbalance of thermal energy inputting, especially in heating-dominated climate zones. An experimental system of solar seasonal storage coupling with ground-source heat pump was designed and implemented. This system was installed in a group of new buildings of the new campus in Tianjin, China, which is located in cold climate zone and heat demand is dominated. To make evaluation to this system, a mathematical method was developed to calculate the COP of GSHP system and the coupled system. In this thermal storage experiment process, a system with 1500 m2 solar thermal collectors and 580 sets of 120 m deep ground thermal exchangers was involved in this research. Results show that the soil temperature has not descended but increased by 0.21 °C, and the COP of system and heat pump unit increased 3.4% and 2.4% respectively compared to the operation data without solar seasonal storage process during last year. Although the effectiveness of solar seasonal storage coupled is not conspicuous as expected during the testing period, it indicates that the tendency of COP declination is prevented, and further illustrating that improving the COP of the system is a long-term work, the application of solar seasonal storage coupled with GSHP system should be encouraged for long-term operation.

Aims: This study aimed to compare the clinicopathological features, incidence, and prognosis between type II ovarian carcinoma (OC) and fallopian tube carcinoma (FTC) in Chinese women and to analyze the origin of high-grade serous carcinoma (HGSC). Methods: Three hundreds and seventy-four OC cases and 45 FTC cases were retrospectively studied with histomorphology, tissue microarray, and immunohistochemistry. Results: Our data showed that the characteristics of OC and FTC in Chinese women were younger at diagnosis with worse prognosis. There was no significant difference between type II OC and FTC in the clinicopathological information and survival. Serous tubal intraepithelial carcinoma (STIC) were found in 41.7% (43/103) of ovarian high-grade serous carcinoma (HGSC) and 52.4% (22/42) cases of tubal HGSC, and 26 patients were found with only fallopian tube (FT) mucosal invasive carcinoma. Seventy-eight of 87 cases of ovarian HGSC with tubal lesions (STIC and/or FT mucosal invasive carcinoma) was in advanced stage. There was no significant difference between newly assigned FTC (ovarian HGSC with tubal lesions and FTC) and type II OC without tubal lesions in many clinicopathological parameters, expression of immunohistochemical indicators and survival, but type I OC was quite much different from the former two. Conclusions: Our data suggested that OC of type II and FTC might be originated from the same organ, and strongly supported the dualistic model of epithelial ovarian cancer. Moreover, this study provided a further clinical basis for the prophylactic salpingectomy to reduce the risk of OC.

Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.