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Chronic myeloid leukemia (CML), a clonal myeloproliferative disorder of pluripotent hematopoietic stem cells, results from the Philadelphia chromosome (Ph) chromosome. The Ph is from a translocation, t(9;22)(q34q11), that creates a BCR-ABL fusion gene, which is transcribed into proteins with abnormal tyrosine kinase activity, driving the abnormal proliferation of white blood cells. Multiple myeloma (MM) is a proliferation disorder of plasma cells derived from a single clone, which may lead to uncontrolled growth, kidney injury, destructive bone lesions, hypercalcemia and anemia. It is extremely rare that MM and CML should occur in the same patient either synchronously or metachronously. To date, MM accompanied with CML has only been reported in limited studies, and the the cause behind the occurrence of both malignancies together is not understood. With the advent of novel therapies, the survival time in patients with CML and MM has improved. Therefore, the further investigation of the pathophysiology and clinical characteristics of these cases is valuable. The present study reports the case of a 79-year-old male who had been diagnosed with CML and treated with tyrosine kinase inhibitor, and then developed immunoglobulin G-κ MM after 6 years. This report should provide valid raw data for clinical research.

Understanding the responses of functional trait variation for grassland plants to grazing disturbance is highly helpful to clarify the community assembly mechanism, functional diversity maintenance, plant adaptation and their strategies. We investigated plant functional traits (plant height, root length, leaf area, root area, leaf dry matter content, shoot dry matter content, root dry matter content, specific leaf area, specific root length and root/ shoot ratio) and the responses of their variation characteristics to grazing disturbance in enclosure and grazing grasslands in Horqin Sandy Land. The results showed that the interspecific variation of functional trait was obviously higher than the intraspecific variation in degraded grassland. The relative contribution of interspecific variation to the overall trait variation ranged from 70.2% to 95.1%, while that of intraspecific variation only contributed 4.9% to 29.8%. However, that did not imply the intraspecific variation could be ignored in the community assembly. The interspecific variation in grazing grassland was lower than that in enclosed grassland, while the intraspecific variation increased but the interspecific variation decreased in grazing grassland. Grazing resulted in the decrease of leaf area and leaf dry matter content but the increase of specific root length for pastoral-resistant grasses. However, pastoral-tolerant forbs would improve their dominance in the community by decreasing specific root length and increa-sing leaf area and leaf dry matter content. The traits sensitive to grazing were leaf area, leaf dry matter content, specific root length, and specific leaf area. Leaf traits and root traits were significantly positively correlated within and with each other. Grazing would enhance the synergy of root traits while reduce the synergy of leaf traits. That meant grazing could change the trade-off strategy of functional traits in individual and population levels, and thus affect vegetation structure and function in community level.研究草地植物功能性状变异对放牧干扰的响应机制,有助于解析草地生态系统群落构建和功能多样性维持机制及植物对环境的适应及权衡策略。以科尔沁沙地退化草地为对象,研究围封和放牧草地物种多种功能性状(植株高度、根系长度、叶面积、根面积、叶片干物质含量、地上干物质含量、根系干物质含量、比叶面积、比根长和根冠比)变异特征及其对放牧干扰的响应机制。结果表明: 退化草地物种种间性状变异明显高于种内变异,种间性状变异对总体变异的贡献率占比高达70.2%～95.1%,而种内变异仅为4.9%～29.8%,但群落构建中物种的种内变异仍不可忽视。放牧草地物种种间性状变异低于围封草地,且放牧草地种内变异增加而种间变异减小。放牧导致不耐牧的优良禾本科牧草叶面积和叶片干物质含量下降而比根长增加,但耐牧的杂类草则通过增加叶面积和叶片干物质含量并降低比根长来提高在群落中的优势地位。退化草地对放牧响应较为敏感的功能性状有叶面积、叶片干物质含量、比根长和比叶面积。植物叶片性状和根系性状自身及彼此间均呈显著正相关,但放牧会增强根系性状的协同效应而减弱叶片性状的协同效应。说明放牧会驱动植物个体和种群功能性状权衡策略发生改变,进而起到调控植物群落结构和功能的作用。.

Background:Crohn’s disease(CD), often occurring in women of child-bearing age, can decline the fertility rate. However, whether it reduces ovarian reserve has been rarely reported. This study aimed to evaluate the ovarian reserve in women with CD from the perspective of anti-müllerian hormone(AMH), and explore the factors that can decrease ovarian reserve. Methods: A case-control retrospective study was designed. We analyzed the AMH levels in a total of 135 CD women and 878 healthy controls. Then using the technique of propensity score matching, the subjected were grouped in a ratio of 1:3, according to age, body mass index and smoking status. Finally, 121 patients were included into the CD group, and 324 into control group, with similar basic characteristics. Serum AMH levels were measured by chemiluminescence.Results: The AMH level in the CD group was significantly lower than that in the control group (2.17±2.23ug/L vs 3.95±2.01ug/L, 95%CI[1.34-2.21], P30 years (OR,2.905;95%CI[1.053-8.531], P=0.017), disease activity (OR,4.314; 95%CI[1.561-12.910], P=0.002) and thalidomide use (OR,12.628; 95%CI[4.351 -42.820], PConclusion: Ovarian reserve is lower in CD women than in healthy women. Age, CD activity and medication of thalidomide are risk factors that an aggravate the decline of ovarian reserve.

Introduction The stent revascularization for severely calcified renal artery lesions can be challenging, due to a deficiency in back-up force provided by the guide catheter. The aim of this report is to describe the use of the balloon anchoring technique to increase device maneuverability and deliverability after the failure of conventional renal artery revascularization. Technical note This technique was adopted in a patient with subtotal occlusive and severely calcified lesion in the proximal portion of the right main renal artery. Two guidewires were separately introduced into the proximal side branch (SB) and main branch (MB) of the renal artery. Anchor balloon inflated at low pressure in SB, anchoring the MB-wire and the guide catheter, thus giving us the ability to cross the tight calcified proximal cap of the MB lesion with a non-compliant balloon. After performing pre-dilatations and retrieving the anchor balloon, we implanted a balloon-expandable stent and achieved optimal final angiographic results. Conclusions The balloon anchoring technique can improve device maneuverability and deliverability during various catheterization procedures. Our report firstly demonstrates how to perform the balloon anchoring technique in renal angioplasty treatment and then explains its effectiveness in revascularization of the renal artery with challenging anatomies.

A novel nocardioform strain, CICC 11023T, was isolated from a tissue biopsy of neck lesions of a patient with primary cutaneous nocardiosis and characterized to establish its taxonomic position. The morphological, biochemical, physiological and chemotaxonomic properties of strain CICC 11023T were consistent with classification in the genus Nocardia . Whole-cell hydrolysates were rich in meso-diaminopimelic acid, galactose, arabinose and fructose. Mycolic acids were present. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and two unidentified lipids, and the predominant menaquinone was cyclo MK-8 (H4, ω-cyclo). The main fatty acids (>5 %) were C18 : 0 10-methyl (TBSA), C16 : 0, summed feature 4 (C16 : 1 trans 9/C15 : 0 iso 2OH), C15 : 0 and C17 : 0 10-methyl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the isolate is most closely related (>98 % similarity) to the type strains Nocardia ninae OFN 02.72T, Nocardia iowensis UI 122540T and Nocardia alba YIM 30243T, and phylogenetic analysis of gyrB gene sequences showed similarity (89.1–92.2 %) to Nocardia vulneris NBRC 108936T, Nocardia brasiliensis IFM 0236T and Nocardia exalbida IFM 0803T. DNA–DNA hybridization results for strain CICC 11023T compared to Nocardia type strains ranged from 20.4 to 35.4 %. The genome of strain CICC 11023T was 8.78 Mbp with a G+C content of 67.4 mol% overall. The average nucleotide identity (ANI) values between strain CICC 11023T and N. alba YIM 30243T were low (OrthoANIu=77.47 %), and the ANI values between strain CICC 11023T and N. vulneris NBRC 108936 T were low (OrthoANIu=83.75 %). Consequently, strain CICC 11023T represents a novel Nocardia species on the basis of this polyphasic study, for which the name Nocardia colli sp. nov. is proposed. The type strain is CICC 11023T (=KCTC 39837T).

OBJECTIVE: To study the effect of different maintenance doses of caffeine citrate on the success rate of ventilator weaning in very preterm infants (gestational age of ≤32 weeks) with respiratory distress syndrome (RDS). METHODS: A total of 162 preterm infants with RDS who were admitted to the hospital from January 2016 to December 2018 were enrolled in this prospective trial. These infants had a gestational age of ≤32 weeks and required invasive mechanical ventilation. They were randomly divided into a high-dose caffeine group and a low-dose caffeine group, with 81 infants in each group. Within 6 hours after birth, both groups were given caffeine at a dose of 20 mg/kg. After 24 hours, the high- and low-dose caffeine groups were given caffeine at a maintenance dose of 10 mg/kg and 5 mg/kg, respectively. The two groups were compared in terms of re-intubation rate within 48 hours after ventilator weaning, durations of ventilation and oxygen therapy, enteral feeding, weight gain, and the incidence rates of complications and adverse reactions during hospitalization. RESULTS: The high-dose caffeine group had a significantly lower re-intubation rate within 48 hours after ventilator weaning than the low-dose caffeine group (P0.05). CONCLUSIONS: A high maintenance dose of caffeine can safely and effectively reduce the incidence rate of apnea after ventilator weaning and the failure rate of ventilator weaning in RDS preterm infants with a gestational age of ≤32 weeks, and therefore, it holds promise for clinical application.

Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as prominently altered upon the middle cerebral artery occlusion in rodents. Genetically or pharmacologically inhibiting multiple points in this pathway attenuated outcomes of models of ischemia in vitro and in vivo. Therefore, the thrombin-ACSL4 axis may be a key therapeutic target to ameliorate ferroptotic neuronal injury during ischemic stroke.

This study aims to investigate the associations of hypomethylation and over expression of the TLR9 gene with systemic lupus erythematosus (SLE). Fifteen SLE patients who were diagnosed and not treated, were selected as cases, and 32 healthy subjects were enrolled as controls. DNA and total RNA of peripheral blood mononuclear cells (PBMCs) were extracted. The methylation status of the promoter region CpG motifs of the TLR9 gene was quantitatively measured using bisulfite sequencing PCR, and the mRNA expression of the TLR9 gene was determined using real-time fluorescent quantitative PCR. The methylation level of the 10 TLR9 CpG motifs of gene did not show difference between cases and controls (P>0.05). By contrast, we observed an abnormal increase of TLT9 mRNA expression in patients (P=9.379×10(-8)), which was significantly correlated with SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) (P=9.018×10(-7)). The change of TLR9 gene expression may play an important role in the pathogenesis of SLE.

This study is the first to explore the potential associations among allergic conjunctivitis (AC), air pollution, and meteorological conditions in Northeast China. Data of meteorology, ambient atmospheric pollutants, and the incidence of allergic conjunctivitis (IAC) in prefecture-level cities between the years 2014 and 2018 are analyzed. The results show an increasing trend in the AC of average growth rate per annum 7.6%, with the highest incidence in the provincial capitals. The IAC is positively correlated with atmospheric pollutants (i.e., PM2.5, PM10, CO, SO2, NO2, and O3) and meteorological factors (i.e., air temperature and wind speed), but negatively correlated with relative humidity. These results suggest that the IAC is directly proportional to pollution level and climatic conditions, and also the precedence of air pollution. We have further obtained the threshold values of atmospheric pollutants concentration and meteorological factors, a turning point above which more AC may be induced. Compared with the air quality standard advised by China and the World Health Organization (WHO), both thresholds of PM10 (70 μg m−3) and PM2.5 (45 μg m−3) are higher than current standards and pose a less environmental risk for the IAC. SO2 threshold (23 μg m−3) is comparable to the WHO standard and significantly lower than that of China’s, indicating greater environmental risks in China. Both thresholds of NO2 (27 μg m−3) and O3 (88 μg m−3) are below current standards, indicating that they are major environmental risk factors for the IAC. Our findings highlight the importance of atmospheric environmental protection and reference for health-based amendment.

p53‑reactivation and induction of massive apoptosis‑1, APR‑017 methylated (PRIMA‑1met; APR246) targets mutant p53 to restore its wild‑type structure and function. It was previously demonstrated that PRIMA‑1met effectively inhibited the growth of colorectal cancer (CRC) cells in a p53‑independent manner, and distinctly induced apoptosis by upregulating Noxa in p53‑mutant cell lines. The present study including experiments of western blotting, acridine orange staining and transmission electron microscopy revealed that PRIMA‑1met induced autophagy in CRC cells independently of p53 status. Importantly, PRIMA‑1met not only promoted autophagic vesicle (AV) formation and AV‑lysosome fusion, but also increased lysosomal degradation. Furthermore, Cell Counting Kit‑8 assay, colony formation assay and small interfering RNA transfection were performed to investigate the underling mechanisms. The study indicated that activation of the mTOR/AMPK‑ULK1‑Vps34 autophagic signaling cascade was key for PRIMA‑1met‑induced autophagy. Additionally, autophagy served a crucial role in the inhibitory effect of PRIMA‑1met in cells harboring wild‑type p53, which was closely associated with the increased expression of Noxa. Taken together, the results determined the effect of PRIMA‑1met on autophagy, and further revealed mechanistic insights into different CRC cell lines. It was concluded that PRIMA‑1met‑based therapy may be an effective strategy for CRC treatment.

p53-reactivation and induction of massive apoptosis-1, APR-017 methylated (PRIMA-1met; APR246) targets mutant p53 to restore its wild-type structure and function. It was previously demonstrated that PRIMA-1met effectively inhibited the growth of colorectal cancer (CRC) cells in a p53-independent manner, and distinctly induced apoptosis by upregulating Noxa in p53-mutant cell lines. The present study including experiments of western blotting, acridine orange staining and transmission electron microscopy revealed that PRIMA-1met induced autophagy in CRC cells independently of p53 status. Importantly, PRIMA-1met not only promoted autophagic vesicle (AV) formation and AV-lysosome fusion, but also increased lysosomal degradation. Furthermore, Cell Counting Kit-8 assay, colony formation assay and small interfering RNA transfection were performed to investigate the underling mechanisms. The study indicated that activation of the mTOR/AMPK-ULK1-Vps34 autophagic signaling cascade was key for PRIMA-1met-induced autophagy. Additionally, autophagy served a crucial role in the inhibitory effect of PRIMA-1met in cells harboring wild-type p53, which was closely associated with the increased expression of Noxa. Taken together, the results determined the effect of PRIMA-1met on autophagy, and further revealed mechanistic insights into different CRC cell lines. It was concluded that PRIMA-1met-based therapy may be an effective strategy for CRC treatment.

Background: PRIMA-1met (APR246), a methylated form of PRIMA-1 (p53-reactivation and induction of massive apoptosis-1, APR-017), targets mutant p53 for restoring its wild-type structure and function. We previously demonstrated that PRIMA-1met was efficient in suppressing the growth of colorectal cancer (CRC) cells in a p53-independent manner, and distinctly induced apoptosis mediated by up-regulation of Noxa in p53-mutant cell lines. Here we aimed to the effect of PRIMA-1met on autophagy in different CRC cell lines, to further investigate mechanisms underlying the inhibitory effect in cells with different p53 status.Methods: 3 CRC cell lines with wild-type p53, 5 lines with mutant p53 and 1 line without p53 were obtained for this study. Using western blotting, acridine orange staining, and transmission electron microscopy detection, we assessed autophagy flux in different cells treated with PRIMA-1met, and detected expression of mTOR/AMPK-ULK1-Vps34 autophagic signaling cascade. We also evaluated cell proliferation of cells with PRIMA-1met treatment by cell counting Kit-8 proliferation assay, compared to combination of PRIAM-1met and 3-Methyladenine. Furthermore, we knocked down Noxa gene by siRNA in different CRC cells, to assess LC3 conversion after administration of PRIMA-1met. Values were expressed as mean + standard error of the mean. Comparison between groups of data was made using one-way analysis of variance.Results: In this study, we showed that PRIMA-1met induced autophagy in CRC cells independent on p53 status. PRIMA-1met not only promoted autophagic vesicles (AVs) formation and AV-lysosome fusion, but also increased lysosomal degradation. Mechanistically, activation of mTOR/AMPK-ULK1-Vps34 autophagic signaling cascade was important for PRIMA-1met-induced autophagy. Furthermore, autophagy played a crucial role in the inhibitory effect of PRIMA-1met only in cells harboring wild-type p53, which was closely related to the increased Noxa.Conclusions: Our results indicated that PRIMA-1met induced autophagy in CRC cells regardless of p53 status via activating mTOR/AMPK-ULK1-Vps34 signaling cascade. However, induced autophagy was relevant to the cytotoxicity of PRIMA-1met in cells carrying wild-type p53, along with up-regulation of Noxa. Implying that, PRIMA-1met-based therapy could be an effective strategy for CRC.Trail registration: Not applicable.

Background Prognosis varies among patients within the same colon adenocarcinoma (COAD) stage, indicating the need for reliable molecular markers to enable individualized treatment. This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD. Methods Gene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database (n = 332) and The Cancer Genome Atlas database (n = 431). The relationship between gene signature and relapse-free survival was analysed in the training set (n = 93) and validated in the internal validation set (n = 94) and external validation sets (n = 145 and 431). Results Overall, 11 genes (N-myc downstream regulated gene 1 [NDRG1], fms-like tyrosine kinase 1 [FLT1], lipopolysaccharide binding protein [LBP], fatty acid binding protein 4 [FABP4], adiponectin gene [ADIPOQ], angiotensinogen gene [AGT], activin A receptor, type II-like kinase 1 [ACVRL1], CC chemokine ligand 11 [CCL11], cell division cycle 42 [CDC42], T-cell receptor alpha variable 9_2 [TRAV9_2], and proopiomelanocortin [POMC]) were identified by univariable and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Based on the risk-score model, the patients were grouped into the high-risk or low-risk groups using the median risk score as the cut-off. The area under the curve (AUC) values for 1-, 3-, and 5-year recurrence were 0.970, 0.849, and 0.859, respectively. Patients in the high-risk group had significantly poorer relapse-free survival than did those in the low-risk group. The predictive accuracy of the 11-gene signature was proven in the validation sets. Our gene signature showed better predictive performance for 1-, 3-, and 5-year recurrence than did the other four models. Conclusions The 11-gene signature showed good performance in predicting recurrence in COAD. The accuracy of the signature for prognostic classification requires further confirmation.

The association between maternal serum total bile acid (TBA) levels and small-for-gestational-age (SGA) infants is unclear. We investigated the association between various degrees of serum TBA levels and the risk of SGA infants in a Chinese population. The current study performed a cohort study among 11811 mothers with singleton pregnancy. Subjects were divided into seven categories according to maternal serum TBA levels. Interestingly, birth sizes were reduced, whereas the rate of SGA infants was increased across increasing categories of serum TBA. Compared to category 1, adjusted ORs (95%CI) for SGA infants were 0.99 (0.82–1.21) in category 2, 1.22 (0.97–1.53) in category 3, 1.99 (1.53–2.58) in category 4, 2.91 (2.16–3.93) in category 5, 4.29 (3.33–5.54) in category 6, and 9.01 (5.99–13.53) in category 7, respectively. Furthermore, adjusted ORs (95%CI) for SGA infants for each 1-SD increase in serum TBA levels were 1.36 (1.29–1.43) among all subjects, 2.40 (1.82–3.45) among subjects without cholestasis, and 1.13 (1.06–1.22) among subjects with cholestasis, respectively. These results suggest that gestational cholestasis increases the risk of SGA infants. Additionally, our results indicate strong, continuous associations of serum TBA levels below those diagnostic of cholestasis with a decreased birth sizes and an increased risk of SGA infants.

Based on the analysis of the characteristics of the students in the "One Belt and One Way" state, this paper gives a teaching reform plan for the "Computer Network" course. The specific measures of the reform include the use of multiple media for teaching and the adjustment of class time. After two years of teaching process comparison, it is found that these measures can significantly improve the learning interest and learning effect of foreign students.

Objective: To study the correlation of serum stathmin 1 (STMN1) and cathepsin D (Cath-D) levels with the invasive growth of cervical cancer. Methods: The patients with cervical cancer and those with uterine fibroids who underwent surgical resection in the Second People’s Hospital of Yichang between January 2013 and November 2017 were selected and enrolled in the malignant group and the benign group of the study respectively; the serum was collected before operation to detect the contents of STMN1 and Cath-D; the cervical cancer lesion tissues were collected from the malignant group and the normal cervical tissues were collected from the benign group to measure the expression of STMN1, Cath-D, invasion genes and invasion signal molecules. Results: STMN1 and Cath-D contents in serum as well as STMN1 and Cath-D mRNA expression in lesion tissue of malignant group were significantly higher than those of benign group, and serum STMN1 and Cath-D contents of malignant group were positively correlated with STMN1 and Cath-D mRNA expression in lesion tissue; RACK1, Twist, MMP9, mTOR, S6K1, Wnt and β-catenin mRNA expression in lesion tissue of malignant group were significantly higher than those of benign group whereas E-cadherin, GRIM19 and GSK-3β mRNA expression were significantly lower than those of benign group, and serum STMN1 and Cath-D contents of malignant group were positively correlated with RACK1, Twist, MMP9, mTOR, S6K1, Wnt and β-catenin mRNA expression in lesion tissue, and negatively correlated with E-cadherin, GRIM19 and GSK-3β mRNA expression. Conclusion: The abnormally elevated STMN1 and Cath-D in serum of patients with cervical cancer can evaluate the invasive growth of the lesion.

Genome editing of human induced pluripotent stem cells (iPSCs) is instrumental for functional genomics, disease modeling, and regenerative medicine. However, low editing efficiency has hampered the applications of CRISPR–Cas9 technology in creating knockin (KI) or knockout (KO) iPSC lines, which is largely due to massive cell death after electroporation with editing plasmids. Here, we report that the transient delivery of BCL-XL increases iPSC survival by ∼10-fold after plasmid transfection, leading to a 20- to 100-fold increase in homology-directed repair (HDR) KI efficiency and a 5-fold increase in non-homologous end joining (NHEJ) KO efficiency. Treatment with a BCL inhibitor ABT-263 further improves HDR efficiency by 70% and KO efficiency by 40%. The increased genome editing efficiency is attributed to higher expressions of Cas9 and sgRNA in surviving cells after electroporation. HDR or NHEJ efficiency reaches 95% with dual editing followed by selection of cells with HDR insertion of a selective gene. Moreover, KO efficiency of 100% can be achieved in a bulk population of cells with biallelic HDR KO followed by double selection, abrogating the necessity for single cell cloning. Taken together, these simple yet highly efficient editing strategies provide useful tools for applications ranging from manipulating human iPSC genomes to creating gene-modified animal models.

Summary We have developed an improved episomal vector system for efficient generation of integration-free induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells. More recently, we reported that the use of an optimized CRISPR-Cas9 system together with a double-cut donor increases homology-directed repair-mediated precise gene knockin efficiency by 5- to 10-fold. Here, we report the integration of blood cell reprogramming and genome editing in a single step. We found that expression of Cas9 and KLF4 using a single vector significantly increases genome editing efficiency, and addition of SV40LT further enhances knockin efficiency. After these optimizations, genome editing efficiency of up to 40% in the bulk iPSC population can be achieved without any selection. Most of the edited cells show characteristics of iPSCs and genome integrity. Our improved approach, which integrates reprogramming and genome editing, should expedite both basic research and clinical applications of precision and regenerative medicine., Graphical Abstract, Highlights • Co-expressing Cas9 and KLF4 increases editing efficiency in reprogrammed iPSCs • Inclusion of SV40LT further increases knockin efficiency • Most of the gene edited cells show characteristics of iPSCs and genome integrity, In this article, Dr. Zhang and colleagues describe an episomal vector system for one-step generation and genome editing (knockin) of integration-free iPSCs from peripheral blood mononuclear cells (PB MNCs). Up to 40% knockin editing efficiencies in bulk iPSCs can be achieved by co-expression of Cas9 and KLF4 in a single vector and with addition of SV40LT.

Objective: To analyze spontaneous abortion rate and its associated risk factors in patients with polycystic ovary syndrome (PCOS) after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Methods: This was a retrospective cohort study on 2,231 PCOS patients undergoing IVF/ICSI treatment. For comparison, we enrolled another 2,231 patients with tubular factors in control group. Spontaneous abortion rate and chromosomal abnormality rate were compared between the two groups. Furthermore, clinical data were compared between the patients with spontaneous abortion and those with ongoing pregnancy using univariate and multivariate analysis for risk factors of spontaneous abortion in PCOS patients. Results: Patients in the PCOS group had significantly higher spontaneous abortion rate (24.15%) than that in the control group (12.75%, P < 0.001). Chromosomal abnormality rate was significantly lower in the PCOS group (36.05%, 31/86) than in the control group (55.56%, 50/90, P = 0.009). In the PCOS group, patients with spontaneous abortion had significantly elder age, higher body mass index (BMI), and homeostasis model assessment for insulin resistance (HOMA-IR) than those with ongoing pregnancy. The logistic regression analysis confirmed that the age, BMI, and HOMA-IR were the risk factors of spontaneous abortion in the PCOS patients. There were no significant differences between groups in the type of cycles, the quality of embryos transferred, the number of embryos transferred, fasting blood glucose, fasting insulin, and so on. Conclusions: Compared with non-PCOS patients, PCOS patients had higher spontaneous abortion rate, but the chromosomal abnormality was not a major factor for the high spontaneous abortion rate in the PCOS patients. Age, BMI, and HOMA-IR were risk factors for spontaneous abortion after IVF/ICSI-ET in PCOS patients.

Background Intrahepatic cholestasis of pregnancy (ICP) is common in pregnant women and is diagnosed by detecting serum total bile acid (TBA) levels. We aimed to investigate the association between serum total bile acid (TBA) levels during late pregnancy and the incidence of small-for-gestational-age (SGA) infants in a Chinese population.Methods The present study was a retrospective cohort study that included 11811 eligible mother-and-singleton-offspring pairs. The correlations between TBA levels and birth sizes, including birth weight, birth length, head circumference and chest circumference, were explored. The relative risk (RR) with 95%CI for SGA infants were estimated among subjects with ICP by multiple logistic regression analysis.Results Serum TBA levels were inversely linked with birth sizes. According to TBA levels, 11120 pregnant women were controls, 563 mild ICP, and 128 severe ICP. Birth sizes in ICP groups were lower than control group, and were the lowest in severe ICP group. Further analysis showed that 24.51% neonates were SGA infants among subjects with mild ICP (adjusted RR: 3.44; 95%CI: 2.72, 4.34) and 39.06% among subjects with severe ICP (adjusted RR: 6.54; 95%CI: 4.27, 10.02), higher than 7.39% among controls. For adjusted models, linear regression analysis showed that each 1μmol/L increase in TBA levels was associated with 11.1g (95%CI: -12.7, -9.5) decrease in birth weight, 0.045cm (95%CI: -0.053, -0.036) decrease in birth length, 0.034cm (95%CI: -0.040, -0.028) decrease in head circumference, and 0.041cm (95%CI: -0.047, -0.034) decrease in chest circumference, respectively.Conclusion Elevated TBA levels during late pregnancy are associated with an increased risk of SGA infants.

Purpose. Peroxisome proliferator-activated receptor-γ(PPAR-γ) is a nuclear hormone receptor with a key role in lipid metabolism. Previous studies have identified various roles of PPAR-γin cell cycle progression, cellular proliferation, and tumor progression. However, no report has described a role for PPAR-γin human nasopharyngeal carcinoma (NPC). Notably, some studies have reported a relationship between PPAR-γand E2F transcription factor 2 (E2F2), which has been identified as a regulator of cell cycle, apoptosis, and the DNA damage response. Notably, E2F2 has also been reported to correlate with a poor prognosis in patients with various malignancies.Methods. We used immunohistochemical (IHC) and western blot methods to evaluate PPAR-γand E2F2 expression and function in nonkeratinizing NPC and nasopharyngitis (NPG) tissue samples, as well as western blotting and CCK8 analyses in the NPC cell lines, CNE1 and CNE2.Results. We observed lower levels of PPAR-γexpression in nonkeratinizing NPC tissues compared with NPG tissues and determined an association between a low level of PPAR-γexpression with a more advanced tumor stage. Furthermore, strong E2F2 expression was detected in nonkeratinizing NPC tissues. We further demonstrated that rosiglitazone, a PPAR-γagonist, reduced E2F2 expression and proliferation in NPC cell lines.Conclusions. Our study results revealed a novel role for the PPAR-γ–E2F2 pathway in controlling NPC cell proliferation and metastasis.

We propose a scheme for asymmetric bidirectional controlled teleportation by using a six-qubit cluster state as quantum channel. In our scheme, Alice can transmit an arbitrary two-qubit entangled state to Bob and at the same time Bob can teleport an arbitrary single-qubit state to Alice under the control of the supervisor Charlie.

Two previously undescribed seco-type C19-diterpenoid alkaloids, stylosines A and B (1–2), which possess an unprecedented opened D ring by the C(15)–C(16) broken bond forming a five-membered C(15)−O–C(14) lactone ring, together with 14 known diterpenoid alkaloids were isolated from the roots of Aconitum stylosum (Ranunculaceae). Compound 1 is the first reported C19-diterpenoid alkaloid with an α-orientation at H-13. Their structures were determined by extensive spectroscopic analyses, NMR calculations and DP4+ analysis. A plausible biosynthetic pathway of the undescribed compounds was proposed. Compounds 1 and 2 showed significant inhibitory activity against the production of inflammatory cytokines (interleukin 1β, cyclooxygenase-2, and tumor necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Compounds 1 and 2 exhibited antibacterial activity against Staphylococcus aureus with MIC values of 2.00 and 32.00 μg/mL, respectively.

Amplification and sequencing of 16S amplicons are widely used for profiling the structure of oral microbiota. However, it remains not clear whether and to what degree DNA extraction and targeted 16S rRNA hypervariable regions influence the analysis. Based on a mock community consisting of five oral bacterial species in equal abundance, we compared the 16S amplicon sequencing results on the Illumina MiSeq platform from six frequently employed DNA extraction procedures and three pairs of widely used 16S rRNA hypervariable primers targeting different 16S rRNA regions. Technical reproducibility of selected 16S regions was also assessed. DNA extraction method exerted considerable influence on the observed bacterial diversity while hypervariable regions had a relatively minor effect. Protocols with beads added to the enzyme-mediated DNA extraction reaction produced more accurate bacterial community structure than those without either beads or enzymes. Hypervariable regions targeting V3-V4 and V4-V5 seemed to produce more reproducible results than V1-V3. Neither sequencing batch nor change of operator affected the reproducibility of bacterial diversity profiles. Therefore, DNA extraction strategy and 16S rDNA hypervariable regions both influenced the results of oral microbiota biodiversity profiling, thus should be carefully considered in study design and data interpretation.

As a novel biomarker, there is inconsistent evidence regarding the association between anti-Müllerian hormone (AMH) and live birth rate in freezing-all embryo transfer cycles. We aim to assess the prognostic effect of baseline AMH on clinical outcomes, especially live birth rate in freezing-all embryo transfer cycles. A total of 828 non-polycystic ovary patients that underwent their first frozen-thawed embryo transfers in our center between January 2010 and January 2015 were recruited in this retrospective analysis. Patients were stratified into three groups based on their baseline AMH concentration: low AMH group (1.4 ng/mL), middle AMH group (1.4-5.8 ng/mL) and high AMH group (5.8 ng/mL). The results showed that low AMH level was associated with adverse clinical outcomes. The differences in implantation rate (21.9% vs. 43.2% vs. 58.8%, P0.001), clinical pregnancy rate (32.0% vs. 55.2% vs. 65.7%, P0.001), live birth delivery rate (21.8% vs. 43.6% vs. 52.7%, P0.001) and miscarriage rate (31.8% vs. 17.5% vs. 15.4%, P=0.014) among the three groups were statistically significant. After adjusting confounders (i.e. age, baseline FSH level, AFC, endometrium thickness, endometrium preparation protocols, number of embryos transferred, etiologies of infertility), differences in live birth rate, clinical pregnancy rate and implantation rate between groups remained significant. The further age subgroup analysis demonstrated that low AMH concentration was significantly associated with poor outcomes both in young and advanced patients. The area under the curve for serum AMH, age, AFC and FSH were 0.635, 0.634, 0.615 and 0.543 respectively, for predicting live birth. In conclusion, baseline AMH was an independent prognostic factor of live birth rate of freezing-all embryo transfers, but its predictive value on live birth rate was of limited clinical value.

A novel and rapid low-density solvent-based dispersive liquid–liquid microextraction technique combined with magnetic solid-phase extraction (MSPE) was developed for preconcentration and separation of synthetic phenolic antioxidants (SPAs) in vegetable oils prior to high-performance liquid chromatography. 1-Heptanol was used as extractant and decanoic acid@Fe3O4 nanoparticles (DA@Fe3O4 NPs) as carrier to retrieve and separate the 1-heptanol. In that manner, the upper extractant containing the SPAs is the target of the MSPE step rather than the SPAs directly. Thanks to the interaction between carboxyl group present on the surface of the magnetic nanoparticles and the alcohol functional group of the extractant, the DA@Fe3O4 NPs facilitates the recollection of the 1-heptanol after extraction. The main parameters affecting the extraction recoveries of four SPAs were investigated, and the proposed method provided a good linearity in the range of 50–2000 ng mL−1, low limits of detection (1.2–5.8 ng mL−1), and good repeatability of the extractions (relative standard deviations ≤6.7%, n = 5), and recoveries were ranged from 90.2% to 99.5%.