P(V)-Promoted Rh-Catalyzed Highly Regioselective Hydroformylation of Styrenes under Mild Conditions.

Hydroformylation of olefins is widely used in the chemical industry due to its versatility and the ability to produce valuable aldehydes with 100% atom economy. Herein, a hybrid phosphate promoter was found to efficiently promote rhodium-catalyzed hydroformylation of styrenes under remarkably mild conditions with high regioselectivities. Preliminary mechanistic studies revealed that the weak coordination between the Rhodium and the P=O double bond of this pentavalent phosphate likely induced exceptional reactivity and high ratios of branched aldehydes to linear products.

Weizhouochrones: Gorgonian-Derived Symmetric Dimers and Their Structure Elucidation Using Anisotropic NMR Combined with DP4+ Probability and CASE-3D.

Natural product dimers have intriguing structural features and often have remarkable pharmacological activities. We report here two uncommon marine gorgonian-derived symmetric dimers, weizhouochrones A (1) and B (2), with indenone-derived monomers, that were isolated from the coral Anthogorgia ochracea collected from the South China Sea. These dimers are difficult targets for structure elucidation that solely relies upon conventional NMR data such as NOEs and J-couplings. Here, to explore the application of emerging methods on the structure elucidation of challenging molecules, we explored a number of different anisotropic and computational NMR approaches. The measurements of anisotropic NMR parameters of weizhouochrone A, including residual dipolar couplings (RDCs) and residual chemical shift anisotropy (RCSA), allowed us to successfully determine the planar structure and its relative configuration. This result was corroborated by a computational NMR analysis based on DP4+ probability and computer-assisted 3D structure elucidation (CASE-3D).

Imipramine impedes glioma progression by inhibiting YAP as a Hippo pathway independent manner and synergizes with temozolomide.

Patients with malignant glioma often suffered from depression, which leads to an increased risk of detrimental outcomes. Imipramine, an FDA-approved tricyclic antidepressant, has been commonly used to relieve depressive symptoms in the clinic. Recently, imipramine has been reported to participate in the suppression of tumour progression in several human cancers, including prostate cancer, colon cancer and lymphomas. However, the effect of imipramine on malignant glioma is largely unclear. Here, we show that imipramine significantly retarded proliferation of immortalized and primary glioma cells. Mechanistically, imipramine suppressed tumour proliferation by inhibiting yes-associated protein (YAP), a recognized oncogene in glioma, independent of Hippo pathway. In addition to inhibiting YAP transcription, imipramine also promoted the subcellular translocation of YAP from nucleus into cytoplasm. Consistently, imipramine administration significantly reduced orthotopic tumour progression and prolonged survival of tumour-bearing mice. Moreover, exogenous overexpression of YAP partially restored the inhibitory effect of imipramine on glioma progression. Most importantly, compared with imipramine or temozolomide (TMZ) monotherapy, combination therapy with imipramine and TMZ exhibited enhanced inhibitory effect on glioma growth both in vitro and in vivo, suggesting the synergism of both agents. In conclusion, we found that tricyclic antidepressant imipramine impedes glioma progression by inhibiting YAP. In addition, combination therapy with imipramine and TMZ may potentially serve as promising anti-glioma regimens, thus predicting a broad prospect of clinical application.

Surgical outcomes of cesarean scar pregnancy: an 8-year experience at a single institution.

PURPOSE: To summarize the outcomes of different surgical treatment modalities for cesarean scar pregnancy (CSP) at a single institution over 8 years. METHODS: A case series of patients diagnosed with CSP who were admitted to Nanjing Drum Tower Hospital from January 2011 to December 2018 was retrospectively studied. Medical records of all the patients were carefully reviewed. Data on patient demographics, pregnancy characteristics, treatment modalities, response to therapy, and subsequent pregnancy outcomes were collected and analyzed. RESULTS: A total of 117 patients undergoing surgical treatments for CSP were included. Thirty-three patients (28.21%) underwent ultrasound-guided curettage; while, 74 (63.25%) and 10 (8.55%) patients received laparoscopy-monitored curettage and laparoscopic CSP resection, respectively. Most of the patients (21/33) who underwent ultrasound-guided surgery had type I CSP; while, 54 out of 84 patients who opted for laparoscopic surgeries had type II CSP. Eleven women underwent a uterine artery embolization procedure before the operation. There was no difference in the use of an intrauterine balloon for hemostasis among the three groups. Only 8 patients needed additional systemic methotrexate treatment. Twenty-four out of 57 women (42.11%) succeeded in conceiving again and gave birth to 21 healthy babies. Only 1 woman (1/24, 4.17%) experienced recurrence of CSP. CONCLUSIONS: These data indicated the safety and efficiency of ultrasound-guided curettage, laparoscopy-monitored curettage, and laparoscopic CSP resection for the treatment of CSP.

Strain elastography as an early predictor of long-term prognosis in patients with locally advanced cervical cancers treated with concurrent chemoradiotherapy.

OBJECTIVE: To explore the value of strain elastography as an early predictor of long-term prognosis in patients with locally advanced cervical cancers treated with concurrent chemoradiotherapy (CCRT). METHODS: Strain elastography examinations were performed on 45 patients with locally advanced cervical cancers at 3 time points: prior to CCRT, and at 1 and 2 weeks after the start of CCRT. The maximum tumor diameter (Dmax), strain ratio (SR), and their percentage changes (ΔDmax and ΔSR) were calculated to predict long-term prognosis. Based on the results of physical examinations, Papanicolaou test, and pelvic magnetic resonance imaging, we classified patients into two groups: responders (complete remission) and non-responders (sustained disease, recurrence, or death). RESULTS: After a median follow-up of 30 months (range, 12-36 months), 36 of 45 (80%) patients were disease free. The Dmax as well as ΔDmax at 2 weeks during CCRT was able to predict the responder outcomes, with an area-under-the-curve (AUC) of 0.733 and 0.731, respectively. Furthermore, significant differences in SR and ΔSR at 1 and 2 weeks during therapy were shown between the responder and non-responder groups (all p < 0.05), and ΔSR at 2 weeks during CCRT presented with the highest AUC (0.91), yielding 88.9% sensitivity and 88.9% specificity with a selected cutoff value. CONCLUSIONS: Strain elastography may be useful as an early predictor of long-term outcomes after CCRT for patients with cervical cancer. KEY POINTS: • The D maxas well as ΔD maxat 2 weeks during CCRT can predict the responder outcomes. • The elastography parameters (SR and ΔSR) exhibited predictive values of favorable response after therapy initiation. • ΔSR at 2 weeks during CCRT held the best predictive value for the responder outcomes.

Synthesis and Target Identification of Benzoxepane Derivatives as Potential Anti-Neuroinflammatory Agents for Ischemic Stroke.

Benzoxepane derivatives were designed and synthesized, and one hit compound emerged as being effective in vitro with low toxicity. In vivo, this hit compound ameliorated both sickness behavior through anti-inflammation in LPS-induced neuroinflammatory mice model and cerebral ischemic injury through anti-neuroinflammation in rats subjected to transient middle cerebral artery occlusion. Target fishing for the hit compound using photoaffinity probes led to identification of PKM2 as the target protein responsible for anti-inflammatory effect of the hit compound. Furthermore, the hit exhibited an anti-neuroinflammatory effect in vitro and in vivo by inhibiting PKM2-mediated glycolysis and NLRP3 activation, indicating PKM2 as a novel target for neuroinflammation and its related brain disorders. This hit compound has a better safety profile compared to shikonin, a reported PKM2 inhibitor, identifying it as a lead compound in targeting PKM2 for the treatment of inflammation-related diseases.

Delivery of Doxorubicin from Hyaluronic Acid-Modified Glutathione-Responsive Ferrocene Micelles for Combination Cancer Therapy.

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C14) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C14 micelles. The HA-Fe-C14 micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C14/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C14/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.

Contribution of the Fetal Cardiac Axis and V-Sign Angle in First-Trimester Screening for Major Cardiac Defects.

OBJECTIVE: To estimate the potential value of fetal assessment for the cardiac axis (CAx) and V-sign angle (VSA) in the first trimester in the prediction of fetal major cardiac defects. METHODS: A cohort study was conducted from December 2015 to June 2016. Patients with singleton pregnancies and crown-rump length from 45 to 84 mm were recruited to undergo nuchal translucency sonography. The CAx on the 4-chamber view and the VSA on the 3-vessel and trachea view with Doppler mapping were measured. The estimated performance of different combinations of increased fetal nuchal translucency, CAx, and VSA in screening for major cardiac defects was examined. RESULTS: The study population of fetuses included 30 fetuses with major cardiac defects and 1538 normal fetuses. The CAx and VSA were 30° to 60° and 30° to 40°, respectively, according to the 2.5th and 97.5th percentiles in normal fetuses. When cases of isolated septal wall defects and an isolated right aortic arch were excluded, nuchal translucency above the 95th percentile, an abnormal CAx, and an abnormal VSA were observed in 63.3% (19 of 30), 63.3% (19 of 30), and 66.7% (20 of 30) of fetuses with major cardiac defects, respectively, and in 4.6% (71 of 1538), 2.0% (30 of 1538), and 5.6% (86 of 1538) of those without cardiac defects. Either an abnormal CAx or VSA was found in 93.3% (28 of 30) of the fetuses with cardiac defects and in 7.3% (113 of 1538) of those without cardiac defects. CONCLUSION: Assessment of the CAx and VSA is helpful in defining a population at risk for major cardiac defects in the first trimester.

Improvement in early detection of orofacial clefts using the axial view of the maxilla.

OBJECTIVES: To evaluate the performance of the maxilla in the axial view in detection of orofacial clefts (OC) compared with the retronasal triangle (RNT) in the coronal view and palatine line in the sagittal view at the early stage of gestation. METHODS: A total of 2982 fetuses (including 315 twins) were enrolled for the first-trimester screening in this prospective study. The maxilla in the axial view, palatine line in the sagittal view, and RNT in the coronal view were scanned by 2-dimensional ultrasound. RESULTS: Excluded 103 cases lost to follow-up, 2879 fetuses were analyzed in our study. Obtaining rates of the satisfactory image of the maxilla in the axial view, RNT in the coronal view, and palatine line in the sagittal view were 95.2%, 93.8%, and 98.2% respectively. Abnormal axial view of the maxilla, coronal view of the RNT, and sagittal view of the palatine line were observed in 100% (8/8), 75% (6/8), and 50% (4/8) of the CLP cases respectively. CONCLUSIONS: The study demonstrates that using the axial view of maxilla in the diagnosis of OC is feasible and improved the detection of OC compared with the sagittal view of the palatine line and coronal view of the RNT in the first trimester.

Strain elastography imaging for early detection and prediction of tumor response to concurrent chemo-radiotherapy in locally advanced cervical cancer: feasibility study.

BACKGROUND: To investigate the feasibility of strain elastography imaging in early detecting and predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for locally advanced cervical cancer. METHODS: Between January 2015 and June 2016, 47 patients with locally advanced cervical cancer were enrolled in a feasibility study approved by the institutional review board. All patients underwent CCRT and received strain elastography examinations at 4 time points: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Treatment response was evaluated by MRI at the time of diagnosis and immediately after CCRT. Based on the MRI findings, the treatment outcome was characterized as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Strain ratio of the normal parametrial tissue vs. cervical tumor was calculated and compared with the clinical outcome. RESULTS: Out of the 47 patients, 36 patients who completed all 4 examinations were included in the analyses: 25 were classified as CR, 11 as PR, and 0 in the SD/PD groups. Strain ratios were significantly different among the time points in both the CR group (F = 87.004, p < 0.001) and PR group (F = 38.317, p < 0.001). Strain ratios were significantly difference between the CR and PR groups (F = 7.203 p = 0.011). Strain ratios between the CR group and PR group were significantly different at 1 week after treatment initiation (p < 0.05). Compared to the baseline, a significant decrease in the CR group was observed at week 1, week 2 and post treatment (all p < 0.001), while a significant decrease in the PR group was shown in week 2 and post treatment (both p < 0.05), but not at week 1 during CCRT (p = 0.084). CONCLUSIONS: We have conducted a prospective longitudinal study to evaluate tumor response in women receiving CCRT for cervical cancers. This study has demonstrated the potential of strain elastography imaging in monitoring and early predicting tumor response induced by CCRT.

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

[Prenatal diagnosis and follow-up of a case with Lowe syndrome caused by interstitial deletion of Xq25-26].

OBJECTIVE: To report on a sporadic case of Lowe syndrome diagnosed prenatally with ultrasound examination and genetic testing. METHODS: Detailed sonographic fetal screening was performed by an experienced sonographer at 32 weeks of gestation. Fetal cranial magnetic resonance imaging (MRI) was applied to detect potential brain abnormality. Chromosomal microarray analysis (CMA) was conducted on amniotic fluid sample from the fetus and peripheral blood sample from the mother. RESULTS: Congenital cataract and enlarged posterior fossa were detected by fetal ultrasound screening. Fetal cranial MRI found hypoplasia of the gyrus. CMA revealed that the fetus has carried a 633 kb deletion at Xq25-26.1 which encompassed the OCRL gene. The mother was a carrier of the same deletion. Clinical examination after birth confirmed that the neonate was affected with Lowe syndrome in addition with an atrial septal defect. CONCLUSION: Prenatal diagnosis of Lowe syndrome without a family history largely depends on fetal imaging. Should cataract be found by ultrasound screening, fetal MRI may be considered to rule out central nervous system anomalies. CMA assay should also be considered to facilitate the diagnosis.

Copy number variations in multicystic dysplastic kidney: update for prenatal diagnosis and genetic counseling.

OBJECTIVE: To assess the clinical implication of chromosomal microarray analysis (CMA) in prenatal diagnosis of MCDK. METHODS: Thirty-seven cases with MCDKs detected by prenatal ultrasound were enrolled in the study; 33 cases were isolated MCDKs and four cases were non-isolated MCDKs. CMA was performed on the Affymetrix CytoScan HD platform. The frequencies of the detected CNVs were compared with 461 cases that underwent CMA for anomalies unrelated to congenital anomalies of kidney and urinary tract (CAKUT) or 124 healthy newborns as controls. All of the annotated CNVs were validated by MLPA or qPCR. RESULTS: Pathogenic CNVs were detected in 13.5% (5/37) of MCDKs. Two 17q12 deletions, one untypical 22q11.2 deletion, and one 22q11.2 duplication were detected in four isolated MCDK cases. Duplication of 1q31.3q44 was identified in a non-isolated MCDK case. Three of the five pathogenic CNVs were inherited. We also validated eight CNVs of uncertain significance only detected in MCDKs and five CNVs with higher frequency in MCDKs. CONCLUSION: A substantial proportion of MCDKs were associated with pathogenic CNVs. Family members with the same CNV were asymptomatic or of different kind of renal malformations. It may be reasonable to perform CMA when MCDKs are identified prenatally. © 2016 John Wiley & Sons, Ltd.

Identification of copy number variations associated with congenital heart disease by chromosomal microarray analysis and next-generation sequencing.

OBJECTIVE: To determine the type and frequency of pathogenic chromosomal abnormalities in fetuses diagnosed with congenital heart disease (CHD) using chromosomal microarray analysis (CMA) and validate next-generation sequencing as an alternative diagnostic method. METHOD: Chromosomal aneuploidies and submicroscopic copy number variations (CNVs) were identified in amniocytes DNA samples from CHD fetuses using high-resolution CMA and copy number variation sequencing (CNV-Seq). RESULT: Overall, 21 of 115 CHD fetuses (18.3%) referred for CMA had a pathogenic chromosomal anomaly. In six of 73 fetuses (8.2%) with an isolated CHD, CMA identified two cases of DiGeorge syndrome, and one case each of 1q21.1 microdeletion, 16p11.2 microdeletion and Angelman/Prader Willi syndromes, and 22q11.21 microduplication syndrome. In 12 of 42 fetuses (28.6%) with CHD and additional structural abnormalities, CMA identified eight whole or partial trisomies (19.0%), five CNVs (11.9%) associated with DiGeorge, Wolf-Hirschhorn, Miller-Dieker, Cri du Chat and Blepharophimosis, Ptosis, and Epicanthus Inversus syndromes and four other rare pathogenic CNVs (9.5%). Overall, there was a 100% diagnostic concordance between CMA and CNV-Seq for detecting all 21 pathogenic chromosomal abnormalities associated with CHD. CONCLUSION: CMA and CNV-Seq are reliable and accurate prenatal techniques for identifying pathogenic fetal chromosomal abnormalities associated with cardiac defects. © 2016 John Wiley & Sons, Ltd.

[Application of chromosome microarray analysis for prenatal diagnosis of a fetus with partial duplication of 1p and uniparental disomy of chromosome 6].

OBJECTIVE: To explore the genetic cause for a fetus with structural anomaly, and to correlate the phenotype with the genotype. METHODS: Amniotic fluid was obtained following the revelation of structural anomaly by ultrasonography. Cell culture and direct DNA extraction were performed in parallel. G-banded karyotyping analysis and chromosome microarray analysis (CMA) were subsequently carried out. RESULTS: G-banded karyotyping has suggested the fetus to be a normal male. However, CMA analysis has revealed the presence of a mosaic 3.24 Mb duplication of 1p36.33p36.32 (24%) and uniparental disomy (UPD) of chromosome 6. The genetic diagnosis for the fetus was therefore 46,XY, arr 1p36.33 p36.32(849,466-4,090,472)×2-3, (6)×2 hmz. The anomaly can probably explain the ultrasound findings in the fetus. CONCLUSION: Compared with conventional cytogenetic methods, CMA has greater resolution and throughput, and can serve as a more efficient platform for the detection of chromosomal microdeletion, microduplication, loss of heterozygosity and UPD.

[Identification of Panax notoginseng base on solid three-dimensional fluorescence fingerprint spectra technology].

OBJECTIVE: To establish the solid three-dimensional fluorescence fingerprint spectra for the main root and branch root of Panax notoginseng. METHODS: With the Xuesaitong power as a control, the solid three-dimensional fluorescence technique was employed to establish the fingerprint spectra. RESULTS: The fluorescence peaks of Xuesaitong power were at 230 nm/330 nm,280 nm/660 nm,300 nm/340 nm, 370 nm/590 nm, 440 nm/550 nm, and 490 nm/610 nm. Among of them, the 300 nm/340 nm peak was the strongest. The fluorescence peaks of Panax notoginseng main root power were at 230 nm/340 nm,290 nm/340 nm,370 nm/480 nm,and 430 nm/540 nm. Among of them, the peak at 290 nm/340 nm was the strongest. The branch root of Panax notoginseng was at 280 nm/450 nm,290 nm/350 nm and 350 nm/440 nm,and the peak at 350 nm/440 nm was the strongest. All of them had the peak at 290-300 nm/340-350 nm, this peak was the strongest in Xuesaitong and Panax notoginseng main root power, but 350 nm/440 nm was the strongest in the branch root of Panax notoginseng. Only the peak at 230 nm/330-340 nm was not detected in the branch root of Panax notoginseng. CONCLUSION: The solid three-dimensional fluorescence fingerprints spectra are established. Using peaks at 290-300 nm/340-350 nm and 230 nm/330-340 nm as characteristics of the fluorescence peak can efficiently identify main root and branch root of Panax notoginseng.

Hydrogen-free palladium-catalyzed intramolecular anti-Markovnikov hydroaminocarbonylation of 2-(1-methylvinyl)anilines.

The palladium-catalyzed intramolecular hydroaminocarbonylation of 2-(1-methylvinyl)aniline derivatives has been achieved using dppp (1,3-bis(diphenylphosphino)propane) as a ligand under hydrogen-free conditions. The reaction involves the generation of an active palladium hydride species with a catalytic amount of TsOH. This amide bond formation reaction was applied to the synthesis of various 4-substituted 3,4-dihydroquinolone derivatives with both high yield and regioselectivity.

Chiral spirosiladiphosphines: ligand development and applications in Rh-catalyzed asymmetric hydrosilylation/cyclization of 1,6-enynes with enhanced reactivity.

Spirodiphosphines have been successfully applied in various asymmetric catalytic transformations. However, controlling the coordinating conformations by the direct displacement of the spiro atom remains elusive. Herein, we report the application of Si-centered spirodiphosphine (Si-SDP) ligands in the enantioselective hydrosilylation/cyclization of 1,6-enynes. The Si-SDPs showed superior reactivity to existing C2-symmetric diphosphines, allowing the generation of a range of chiral pyrrolidines with high yields and enantioselectivity (up to 96% yield and 92% ee) at room temperature with low catalyst loading. The mechanistic observations were consistent with the modified Chalk-Harrod mechanism, and the high reactivity of Si-SDPs was further leveraged for the room-temperature Rh-catalyzed hydrosilylation of alkynes.

Immune cells and RBCs derived from human induced pluripotent stem cells: method, progress, prospective challenges.

Blood has an important role in the healthcare system, particularly in blood transfusions and immunotherapy. However, the occurrence of outbreaks of infectious diseases worldwide and seasonal fluctuations, blood shortages are becoming a major challenge. Moreover, the narrow specificity of immune cells hinders the widespread application of immune cell therapy. To address this issue, researchers are actively developing strategies for differentiating induced pluripotent stem cells (iPSCs) into blood cells in vitro. The establishment of iPSCs from terminally differentiated cells such as fibroblasts and blood cells is a straightforward process. However, there is need for further refinement of the protocols for differentiating iPSCs into immune cells and red blood cells to ensure their clinical applicability. This review aims to provide a comprehensive overview of the strategies and challenges facing the generation of iPSC-derived immune cells and red blood cells.