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.

Effect of differences in O-RADS lexicon interpretation between senior and junior sonologists on O-RADS classification and diagnostic performance.

PURPOSE: To assess the consistency of Ovarian-Adnexal Reporting and Data System (O-RADS) lexicon interpretation between senior and junior sonologists and to investigate its impact on O-RADS classification and diagnostic performance. METHODS: We prospectively studied 620 patients with adnexal lesions, all of whom underwent transvaginal or transrectal ultrasound performed by a senior sonologist (R1) who selected the O-RADS lexicon description and O-RADS category for the lesion after the examination. Meanwhile, the junior sonologist (R2) analyzed the images retained by R1 and divided the lesion in the same way. Pathological findings were used as a reference standard. kappa (к) statistics were used to assess the interobserver agreement. RESULTS: Of the 620 adnexal lesions, 532 were benign and 88 were malignant. When using the O-RADS lexicon, R1 and R2 had almost perfect agreement regarding lesion category, external contour of solid lesions, presence of papillary inside cystic lesions, and fluid echogenicity (к: 0.81-1.00). Substantial agreement in solid components, acoustic shadow, vascularity and O-RADS categories (к: 0.61-0.80). Consistency in classifying classic benign lesions in the O-RADS category was only moderate (к = 0.535). No significant difference in diagnostic performance between them using O-RADS (P = 0.1211). CONCLUSION: There was good agreement between senior and junior sonologists in the interpretation of the O-RADS lexicon and in the classification of O-RADS, except for a moderate agreement in the interpretation and classification of classic benign lesions. Differences in O-RADS category delineation between sonologists had no significant effect on the diagnostic performance of O-RADS.

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.

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.

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.

Study on related factors and characteristics of multimorbidity of overweight and obesity-related diseases in children in Hunan Province / 中华预防医学杂志

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".

Effects of RNA demethylase FTO inhibitor on function ofglioblastoma stem cells / 中国药理学通报

Aim To investigate the effect of m6A demethylase FTO inhibitor(FB23-2)on human glioblastoma stem cell activity. Methods The effects of FB23-2 and Temozolomide on GSC were detected by CCK-8 assay and neurosphere formation assay. The effect of FB23-2 on self-renewal of GSC was detected by limited dilution assay in vitro. The effect of FB23-2 on the proliferation of GSC was detected by EdU method. The effect of FB23-2 on apoptosis of glioblastoma stem cells was detected by flow cytometry. Results CCK-8 assay showed that FB23-2 could effectively inhibit the cell viability of GSC with IC50 values of 7.11 μmol·L-1 and 4.63 μmol·L-1,respectively. The size and number of GSC neural sphere in FB23-2 treatment group were significantly reduced compared with control group. In vitro limited dilution experiment showed that FB23-2 effectively inhibited the self-renewal ability of GSC. EdU incorporation experiment showed that compared with the control group,the treatment group decreased to(70.59±13.74)% and(50.33±4.53)%,respectively. The apoptotic rates of the treated group were(12.16±1.90)% and(16.77±1.17)% by flow cytometry. Conclusions FTO inhibitor FB23-2 can effectively inhibit GSC growth,self-renewal and the formation of neural sphere. In addition,FB23-2 can inhibit the proliferation of GSC and induce its apoptosis.

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).

Nonadiabatic Dynamics of Polaron Hopping and Coupling with Water on Reduced TiO2.

By interplay between first-principles molecular dynamics and nonadiabatic molecular dynamics simulations based on the decoherence-induced surface-hopping approach, we investigate and quantify the mechanisms through which different electron polaron hopping regimes in the reduced anatase TiO2(101) surface influence recombination of photogenerated charge carriers, also in the presence of adsorbed water (H2O) molecules. The simulations reveal that fast hopping regimes promote ultrafast recombination of photogenerated charge-carriers. Conversely, charge recombination is delayed in the presence of slower polaron hopping and even more so if the polaron is pinned at one Ti-site, as typical following adsorption of H2O on the anatase(101) surface. These trends are related to the observed enhancement of the space and energy overlap between conduction band minimum and polaron band gap states, and the ensuing nonadiabatic couplings (NAC) strengths, during a polaronic hop. We expect these insights on the beneficial role of polaron diffusion pinning for the extended lifetime of photoexcitations in TiO2 to sustain ongoing developments of photocatalytic strategies based on this substrate.

Fetoscopy-guided bipolar cord coagulation in selective fetal reduction with complicated monochorionic diamniotic twins: a prospective cohort study.

OBJECTIVE: To assess the feasibility of fetoscopy-guided bipolar umbilical cord coagulation for selective fetal reduction in complicated monochorionic diamniotic (MCDA) twin pregnancies. METHODS: MCDA twins undergoing fetoscopy-guided bipolar cord coagulation (BCC) were enrolled prospectively between December 2015 to March 2020 in a fetal medicine center. RESULTS: Twenty-three cases undergoing fetoscopy-guided BCC were finally analyzed, including 11 cases for type 2 selective intrauterine growth restriction, 4 cases for twin-twin transfusion syndrome, and 8 cases for a severe discordant anomaly. The overall survival rate was 78.3% (18/23). CONCLUSIONS: Fetoscopy-guided BCC is effective for selective fetal reduction in complicated monochorionic twin pregnancies.

Room-temperature Pd-catalyzed methoxycarbonylation of terminal alkynes with high branched selectivity enabled by bisphosphine-picolinamide ligand.

We report the room-temperature Pd-catalyzed methoxy-carbonylation with high branched selectivity using a new class of bisphosphine-picolinamide ligands. Systematic optimization of ligand structures and reaction conditions revealed the significance of both the picolinamide and bisphosphine groups in the ligand backbone. This strategic design of ligand was leveraged to deliver various α-substituted acrylates in good to excellent yields.

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.

Phosphorus coordinated Rh single-atom sites on nanodiamond as highly regioselective catalyst for hydroformylation of olefins.

Single-atom Rh catalysts present superior activity relative to homogeneous catalyst in olefins hydroformylation, yet with limited success in regioselectivity control. In the present work, we develop a phosphorus coordinated Rh1 single-atom catalyst with nanodiamond as support. Benefiting from this unique structure, the catalyst exhibits excellent activity and regioselectivity in hydroformylation of arylethylenes with wide substrate generality, i.e., with high conversion (>99%) and high regioselectivity (>90%), which is comparable with the homogeneous counterparts. The coordination interaction between Rh1 and surface phosphorus species is clarified by 31P solid-state NMR and X-ray absorption spectroscopy (XAS). Rh single atoms are firmly anchored over nanodiamond through Rh-P bonds, guaranteeing good stability in the hydroformation of styrene even after six runs. Finally, by using this catalyst, two kinds of pharmaceutical molecules, Ibuprofen and Fendiline, are synthesized efficiently with high yields, demonstrating a new prospect of single-atom catalyst in pharmaceutical synthesis.

Prenatal features of 17q12 microdeletion and microduplication syndromes: A retrospective case series.

OBJECTIVE: To present the experience on prenatal features of 17q12 microdeletion and microduplication syndromes. MATERIALS AND METHODS: Prenatal chromosomal microarray analysis (CMA) were conducted between January 2015 and December 2018 at a single Chinese tertiary medical centre. Information of cases identified with 17q12 microdeletion or microduplication syndromes were retrospectively collected. Foetal ultrasonographic findings were reviewed, and other information about the gestation week at diagnosis, inheritance and pregnancy outcomes were also included. RESULTS: Ten pregnancies with 17q12 microdeletion and 4 with 17q12 microduplication were identified. The copy number variation (CNV) sizes were 1.39-1.94 Mb in the deleted cases and 1.42-1.48 Mb in the duplicated cases, respectively. All the duplicated and deleted regions included HNF1B and LHX1 genes. Most individuals with 17q12 deletion presented kidney anomalies (9/10), with renal hyperechogenicity being the most common finding (7/10). Fetuses with 17q12 duplication presented a wide phenotypic spectrum, including "double bubble" sign, structural anomalies of the heart and growth anomalies. CONCLUSIONS: Our experience further demonstrated the high correlation between 17q12 microdeletion and renal anomalies especially hyperechogenic kidneys. Structural anomalies of the heart were newly identified phenotypes of 17q12 duplication during prenatal period. Besides, growth anomalies and duodenal atresia might be associated with the duplication.

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.

Postmortem 9.4-T MRI for Fetuses With Congenital Heart Defects Diagnosed in the First Trimester.

OBJECTIVE: To evaluate the feasibility of 9. 4-T postmortem MRI (pm-MRI) for assessment of major congenital heart defects (CHD) cases terminated in the early stage of gestation. METHODS: Fetuses with CHD detected by the detailed first-trimester ultrasound scan and terminated before 18 gestational weeks were recruited between January 2018 and June 2020. All fetuses were offered 9.4-T pm-MRI examinations and those terminated over 13+6 weeks were offered conventional autopsies simultaneously. Findings of pm-MRI were compared with those of conventional autopsy and prenatal ultrasound. RESULTS: A total of 19 fetuses with major CHD were analyzed, including 6 cases of the atrioventricular septal defect, 5 cases of Tetralogy of Fallot, 3 cases of hypoplastic left heart syndrome, 1 case of tricuspid atresia, 1 case of transposition of the great arteries, 1 case of severe tricuspid regurgitation, and 2 cases of complex CHD. Pm-MRI had concordant findings in 73.7% (14/19) cases, discordant findings in 15.8% (3/19) cases, and additional findings in 10.5% (2/19) cases when compared with prenatal ultrasound. Pm-MRI findings were concordant with autopsy in all 8 CHD cases terminated over 13+6 weeks. CONCLUSION: It is feasible to exhibit the structure of fetal heart terminated in the first trimester clearly on 9.4-T pm-MRI with an optimized scanning protocol. High-field pm-MRI could provide medical imaging information of CHD for those terminated in the early stage of gestation, especially for those limited by conventional autopsy.

Research progress in synthetic biology of active compounds in Chinese medicinal plants / 中国中药杂志

Mecicinal plants boast abundant natural compounds with significant pharmacological activity, and such compounds, featuring diversified and complex structures, can be used for research and development of drugs. At present, these natural compounds are directly extracted from herbs which, however, suffer from damaged wild resources and shortage of planting resources attributing to the increasing demand. Moreover, the low content in medicinal plants and complex structures are another challenge to the research and development of drugs. Heterologous synthesis with synthetic biology methods is a solution that has attracted wide attention. Synthetic bio-logy for the production of natural active compounds in Chinese medicinal plants involves the exploration of key enzymes in compound bio-synthetic pathways from plants, analysis of enzyme functions and mechanisms, and reconstruction and optimization of biosynthetic pathways in microorganisms for efficient synthesis of compounds. This study briefed the development process of synthetic biology and the biosynthetic pathways of terpenoids, alkaloids, and flavonoids, and summarized the related strategies of synthetic biology such as the reconstruction and optimization of metabolic pathways, regulation of fermentation process, and strain improvement, and the latest applications of heterogeneous synthetic biology in the production of natural compounds from Chinese medicinals. This study is expected to serve as a reference for the efficient production of terpenoids, alkaloids, flavonoids, and other active compounds from Chinese medicinal plants with strategies of synthetic biology.

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.