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Background This study aims to investigate the errors in structure volume and shape caused by the replication, expansion, and merging operations of the Monaco system and analyze their influence on dosimetry evaluation. Methods A retrospective collection of 30 patients undergoing radiotherapy was utilized. Cylinders with radii of 5, 10, and 30 mm were delineated in computerized tomography (CT) images from 10 patients with thoracic and abdominal issues, and the Margins function in Monaco was used to expand the margins by 0, 3, 5, and 10 mm in 2D mode. In 10 patients with vertebral metastases, the Margins function was utilized to replicate and merge targets, and the Copy Structure function was employed to replicate targets. Cross-CT replication was performed for the targets of 10 patients with nasopharyngeal carcinoma. The deviation between the processed structure volume and the ideal value was compared. The difference in the maximum dose (Dmax) before and after lens replication was evaluated in 10 patients undergoing whole-brain radiotherapy. Results Monaco's Margins function increased the volume of the processed structure during the copying procedure. The margin error was equivalent to expanding the structure by 0.3–0.4 mm, and a margin error of 0.3–0.4 mm was produced in each expansion instance. The volume deviation for a cylinder with a radius of 5 mm was 12.99%. The Merge function of Margins copied substructures and merged them. The Copy Structure function did not alter the structure during copying, but the volume was reduced by less than 1% after copying across CT. Dmax after lens replication was higher than that before replication, with a median difference of 31.3 cGy for the left lenses. Conclusion Monaco's Margins function introduces errors in organ replication, expansion, and merging, resulting in incorrect dose assessment. Physicians should be mindful of the potential effects when utilizing them.

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance ( P

Pregnant women are at increased risk of influenza-related complications. However, the rate of influenza vaccination among pregnant women in Taiwan is low. By analyzing real-world data in this study, we investigated the factors associated with influenza vaccination during pregnancy in Taiwan. This study was a cross-sectional study. We collected real-world data from 2 databases in Taiwan: the Birth Certificate Database and the National Health Insurance Research Database. The study population was pregnant between October 2014 and December 2016 in Taiwan. The multivariate logistic regression was performed to identify factors associated with influenza vaccination, including maternal sociodemographics, trimester, comorbidities, and health-care utilization. The vaccination rate of among pregnant women was 8.2%. Factors significantly associated with a high likelihood of influenza vaccination were age between 30 and 34 years (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.10-1.19), second trimester (OR: 1.80; 95% CI: 1.75-1.85), income equal to or exceeding NT$ 38 201 (OR: 1.92; 95% CI: 1.86-1.99), hypertension (OR: 1.16; 95% CI: 1.05-1.29), cardiovascular disease (OR: 1.29; 95% CI: 1.17-1.42), autoimmune disease (OR: 1.47; 95% CI: 1.38-1.58), and chronic pulmonary disease (OR: 1.24; 95% CI: 1.18-1.31). A low level of urbanization, at least 1 hospitalization in the previous year, and the presence of pregnancy complications (eg, gestational diabetes, preeclampsia, and placenta previa) were associated with a lower likelihood rate of influenza vaccination. The influenza vaccination rate among pregnant women in Taiwan was low. Age, gestational age, income level, urbanization level, hypertension, cardiovascular disease, autoimmune disease, chronic pulmonary disease, and pregnancy complications may be associated with influenza vaccination among pregnant women.

Conforming to the current replace–reduce–refine 3Rs’ guidelines in animal experiments, a series of explorative efforts have been made to set up operable biomedical imaging-guided platforms for qualitative and quantitative evaluations on pharmacological effects of tumor vascular-disrupting agents (VDAs), based on the chick embryos (CEs) with its chorioallantoic membrane (CAM), in this overview. The techniques and platforms have been hierarchically elaborated, from macroscopic to microscopic and from overall to specific aspects. A protocol of LED lamplight associated with a new deep-learning algorithm was consolidated to screen out weak CEs by using the CAM vasculature imaging. 3D magnetic resonance imaging (MRI) and laser speckle contrast imaging (LSCI) to monitor the evolution of CE and vascular changes in CAM are introduced. A LSCI–CAM platform for studying the effects of VDAs on normal and cancerous vasculature of CAM and possible molecular mechanisms has been demonstrated. Finally, practical challenges and future perspectives are highlighted. The aim of this article is to help peers in biomedical research to familiarize with the CAM platform and to optimize imaging protocols for the evaluation of vasoactive pharmaceuticals, especially anticancer vascular targeted therapy.

Objectives: Despite the development of various cancer treatment methods, chemotherapy remains the most common approach for treating cancer. The risk of tumors acquiring resistance to chemotherapy remains a significant hurdle to the successful treatment of various types of cancer. Therefore, overcoming or predicting multidrug resistance in clinical treatment is essential. The detection of circulating tumor cells (CTCs) is an important component of liquid biopsy and the diagnosis of cancer. This study aims to test the feasibility of single-cell bioanalyzer (SCB) and microfluidic chip technology in identifying patients with cancer resistant to chemotherapy and propose new methods to provide clinicians with new choices. Methods: In this study, we used rapidly isolated viable CTCs from the patient blood samples method combined with SCB technology and a novel microfluidic chip, to predict whether patients with cancer are resistant to chemotherapy. SCB and microfluidic chip were used to select single CTCs, and the accumulation of chemotherapy drug was fluorescently measured in real time on these cells in the absence and presence of permeability-glycoprotein inhibitors. Results: Initially, we successfully isolated viable CTCs from the blood samples of patients. Additionally, the present study accurately predicted the response of 4 lung cancer patients to chemotherapeutic drugs. In addition, the CTCs of 17 patients with breast cancer diagnosed at Zhuhai Hospital of Traditional Chinese and Western Medicine were assessed. The results indicated that 9 patients were sensitive to chemotherapeutic drugs, 8 patients were resistant to a certain degree, and only 1 was completely resistant to chemotherapy. Conclusion: The present study indicated that the SCB technology could be used as a prognostic assay to evaluate the CTCs response to available drugs and guide physicians to treatment options that are most likely to be effective.

Few studies have reported the clinical outcomes of older adult patients with acute anterior circulation large-vessel occlusion (LVO) who underwent mechanical thrombectomy (MT). Therefore, we investigated the safety, functional outcomes, and predictors of MT for anterior circulation LVO in older adults. We enrolled patients with acute anterior circulation LVO from May 2018 to October 2021 in this retrospective study. Patients were divided into older (≥80 years) and young (

Purpose: To investigate and compare 2 cone-beam computed tomography (CBCT) correction methods for CBCT-based dose calculation. Materials and Methods: Routine CBCT image sets of 12 head and neck cancer patients who received volumetric modulated arc therapy (VMAT) treatment were retrospectively analyzed. The CBCT images obtained using an on-board imager (OBI) at the first treatment fraction were firstly deformable registered and padded with the kVCT images to provide enough anatomical information about the tissues for dose calculation. Then, 2 CBCT correction methods were developed and applied to correct CBCT Hounsfield unit (HU) values. One method (HD method) is based on protocol-specific CBCT HU to physical density (HD) curve, and the other method (HM method) is based on histogram matching (HM) of HU value. The corrected CBCT images (CBCT HD and CBCT HM for HD and HM methods) were imported into the original planning system for dose calculation based on the HD curve of kVCT (the planning CT). The dose computation result was analyzed and discussed to compare these 2 CBCT-correction methods. Results: Dosimetric parameters, such as the D mean , D max and D 5% of the target volume in CBCT plan doses, were higher than those in the kVCT plan doses; however, the deviations were less than 2%. The D 2% , in parallel organs such as the parotid glands, the deviations from the CBCT HM plan dose were less than those of the CBCT HD plan dose. The differences were statistically significant ( P

Purpose: Radiotherapy is a promising treatment option for lung cancer, but patients’ responses vary. The purpose of the study was to investigate the potential of radiomics and clinical signature for predicting the radiotherapy sensitivity and overall survival of inoperable stage III and IV non-small-cell lung cancer (NSCLC) patients. Materials: This retrospective study collected 104 inoperable stage III and IV NSCLC patients at the Yunnan Cancer Hospital from October 2016 to September 2020. They were divided into radiation-sensitive and non-sensitive groups. We used analysis of variance (ANOVA) to select features and support vector machine (SVM) to build the radiomic model. Furthermore, the logistic regression method was used to screen out clinically relevant predictive factors and construct the combined model of radiomics–clinical features. Finally, survival was estimated using the Kaplan–Meier method. Results: There were 40 patients in the radiation-sensitive group and 64 in the non-sensitive group. These patients were divided into training set (73 cases) and testing set (31 cases) according to the ratio of 7:3. Nine radiomics features and one clinical feature were significantly associated with radiotherapy sensitivity. Both the radiomics model and combined model have good predictive performance (the areas under the curve (AUC) values of the testing set were 0.864 (95% confidence interval [CI]: 0.683-0.996) and 0.868 (95% CI: 0.689-1.000), respectively). Only platelet level status was associated with overall survival. Conclusion: The combined model constructed based on radiomics and clinical features can effectively identify the radiation-sensitive population and provide valuable clinical information. Patients with higher platelet levels may have a poor prognosis.

Background. Length of stay (LOS) during index solid organ transplant impacts morbidity and healthcare costs. To date, there are no studies evaluating characteristics and outcomes of simultaneous liver-kidney transplant (SLKT) index hospitalization. We examined factors associated with LOS and mortality during index SLKT admission. Methods. Adult SLKT recipients between 2002 and 2017 at 6 transplant centers across 6 UNOS regions were retrospectively enrolled in the US-Multicenter SLKT Consortium. Multivariable regression analyses assessed predictors of SLKT LOS and death during index admission. Results. Median age of cohort (N = 570) was 58 y (interquartile range: 51–64); 63% male, 75% White, 32.3% hepatitis C, 23.3% alcohol-related, 20.1% nonalcoholic steatohepatitis with median MELD-Na at SLKT 28 (23–34). Seventy-one percent were hospitalized at the time of SLKT with median LOS pretransplant of 10 d. Majority of patients were discharged alive (N = 549; 96%)‚ and 36% were discharged to subacute rehab facility. LOS for index SLKT was 19 d (Q1: 10, Q3: 34 d). Female sex (P = 0.003), Black race (P = 0.02), advanced age (P = 0.007), ICU admission at time of SLKT (P = 0.03), high MELD-Na (P = 0.003), on cyclosporine during index hospitalization (P = 0.03), pre-SLKT dialysis (P 2 wk and affected overall patient survival. Further investigation is needed to optimize healthcare resources for these patients in a financially strained healthcare landscape.

Abstract. Introduction:. When initiating urate-lowering therapy, using anti-inflammatory prophylaxis therapy for at least 3 to 6 months is strongly recommended. Previous studies have found that zhengqing fengtongning sustained-release tablets (sinomenine) can improve inflammation in the acute phase of gout; however, the efficacy of urate-lowering therapy in reducing frequency of acute flares still needs to be investigated. The aim of the present study is to explore the efficacy and safety of sinomenine for prophylaxis of acute flares when initiating urate-lowering therapy. Methods and analysis:. This randomized, placebo-controlled, double-blinded trial will include a total of 210 gout patients who meet the study criteria. The patients will be randomized (1:1) to the test group and the control group. The intervention is planned to be performed for 12 weeks with a follow-up of 12 weeks. All patients would be administered febuxostat (40 mg/d) and concomitant anti-inflammatory prophylaxis therapy. Sinomenine and colchicine placebo are administered in the sinomenine group, sinomenine placebo and colchicine are administered in the colchicine group. The primary outcome is the rate of acute gout flares in subjects within 12 weeks of the treatment period. The secondary outcomes include the times of acute gout flares and the duration of each acute flares within 12 weeks; the compliance rate in patients whose UA levels ≤6.0 mg/dL (360 μmol/L) at the weekend of 2nd, 4th, 8th, and 12th week in each group; the proportion of patients with ≥1 and ≥2 gout flares within 12 weeks; average visual analogue scale/score pain score during gout flares; and the oral dose of etoricoxib will be used to control the onset of acute flares within 12 weeks. Ethics and dissemination:. The Institutional Medical Ethics Committee have approved the trial protocol. We plan to publish the results of this study in a peer-reviewed journal. Trial registration:. ChiCTR, ChiCTR2100045114, Registered 8 April 2021 http://www.chictr.org.cn/showproj.aspx?proj=124688

Objective: To evaluate the curative effect of lauromacrogol foam sclerotherapy of uterine fibroids via transvaginal ultrasound-guided injection.Methods: Thirty premenopausal women with a total of thirty-one uterine fibroids were recruited consecutively and underwent transvaginal 3D-Power Doppler Angiography (PDA) at 0, 1, 3, and 6 months. Written informed consent was obtained from all of the patients. The changes in the fibroid 3D volume and relationships between the fibroid location and blood supply were analyzed. The relief of clinical symptoms and improvement in health-related quality of life (HRQL) were evaluated using the uterine fibroid symptom and quality-of-life (UFS-QOL) questionnaire before and after treatment for 6 months; adverse events were also assessed.Results: The mean baseline volumes ± SD were 61.2 ± 71.5 cm3 (range, 4.1 cm3 - 340.4 cm3) for the dominant fibroid. The mean values of percentage reduction in fibroid volume at 1, 3 and 6 months were 23.9% (range, 5.2% - 42.1%; 95%CI, 20.6% - 27.3%), 43.4% (range, 21.8% - 67.4%; 95%CI, 39.0% - 47.8%), and 60.0% (range, 31.8% - 83.2%; 95%CI, 55.2% - 64.9%), respectively, and the reduction was correlated with the location and blood supply. Additionally, the blood flow to the fibroids was markedly decreased. The clinical symptoms were greatly alleviated or even completely resolved, and the HRQL was notably improved (P < 0.001). Mild abdominal pain, paleness, vomiting, and cold sweat were most commonly reported adverse effects.Conclusion: Ultrasound-guided sclerotherapy of uterine fibroids with foam lauromacrogol is a simple, safe and useful method with a wide application prospect.

Background: Inflammation and nutritional status are highly associated with colorectal cancer (CRC) prognosis. This study aimed to evaluate the prognostic value of the preoperative neutrophil-BMI ratio (NBR) in patients with CRC. Methods: A retrospective analysis was performed on 2471 patients with CRC who underwent surgical resection between 2004 and 2019. Patients were divided into two groups based on the cutoff value for NBR. Cox regression and Kaplan–Meier curves were used to evaluate overall survival (OS). Results: High NBR was associated with female sex, low BMI, colon, right-sided CRC, poor differentiation, T3 to 4 stage, M1 to 2 stage, high carcinoembryonic antigen (CEA) level, III-IV stage, microsatellite instability (MSI), and no adjuvant chemotherapy (all P

Background: Household contacts of people with pulmonary tuberculosis (TB) have greater risk of developing TB. Recent guidelines conditionally recommended TB preventive treatment (TPT) for household contacts of any age living in TB high-incidence countries, expanding earlier guidance to provide TPT to household contacts under five. The all-age population of household contacts has not been estimated. Methods: Our model-based estimation included 20 countries with >80% of incident TB globally in 2019. We developed country-specific distributions of household composition by age and sex using bootstrap resampling from health surveys and census data. We incorporated age-, sex-, year-, and location-specific estimates of pulmonary TB incidence from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the population in each country sharing a household with someone with incident pulmonary TB, and quantified uncertainty using a Monte Carlo approach. Findings: We estimate that 38 million [95% uncertainty interval (UI) 33- 43 million] individuals lived in a household with someone with incident pulmonary TB in 2019 in these 20 countries. Children under five made up 12% of the population with household exposure, while adults were 65%. Zimbabwe, Mozambique, Zambia, and Pakistan had the highest proportion of the population with household exposure, while India had the highest number of contacts (11·4 million, 95% UI 9·7-13·4 million). Interpretation: Expanding TPT evaluation to household contacts of all ages in high-incidence countries could include a population more than 7-times larger than the under-5 contacts previously prioritized. This would substantially increase the impact of household contact investigation on reducing TB morbidity and mortality. Funding: JMR is supported by the National Institute of Allergy and Infectious Diseases (K01 AI138620). This research was funded in part by a 2020 developmental grant from the University of Washington / Fred Hutch Center for AIDS Research, an NIH funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. This work was funded in part by the National Science Foundation (DMS-1839116).

Background: The first confirmed case of SARS-CoV-2 in North America was identified in Washington state on January 21, 2020. We aimed to quantify the number and temporal trends of out-of-state introductions of SARS-CoV-2 into Washington. Methods: We conducted a molecular epidemiologic analysis of 11,422 publicly available whole genome SARS-CoV-2 sequences from GISAID sampled between December 2019 and September 2020. We used maximum parsimony ancestral state reconstruction methods on time-calibrated phylogenies to enumerate introductions/exports, their likely geographic source (US, non-US, and between eastern and western Washington), and estimated date of introduction. To incorporate phylogenetic uncertainty into our estimates, we conducted 5,000 replicate analyses by generating 25 random time-stratified samples of non-Washington reference sequences, 20 random polytomy resolutions, and 10 random resolutions of the reconstructed ancestral state. Findings: We estimated a minimum 287 introductions (range 244-320) into Washington and 204 exported lineages (range 188-227) of SARS-CoV-2 out of Washington. Introductions began in mid-January and peaked on March 29, 2020. Lineages with the Spike D614G variant accounted for the majority (88%) of introductions. Overall, 61% (range 55-65%) of introductions into Washington likely originated from a source elsewhere within the US, while the remaining 39% (range 35-45%) likely originated from outside of the US. Intra-state transmission accounted for 65% and 28% of introductions into eastern and western Washington, respectively. Interpretation: The SARS-CoV-2 epidemic in Washington was continually seeded by a large number of introductions. Our findings highlight the importance of genomic surveillance to monitor for emerging variants due to high levels of inter- and intra-state transmission of SARS-CoV-2. Funding Source: None.

Objective: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor activity of QD in Lewis lung carcinomas (LLC) in vivo and in vitro, and to elucidate the underlying mechanisms. Methods: The LLC cells were used to assess the antitumor activity of QD by Cell Counting Kit-8 assay in vitro. In vivo, mice were randomly assigned to 5 groups (n = 10/group): the model control (MC) group was intragastrically administered physiological saline (0.9% NaCl) twice daily from day 2 after tumor implantation for 2 weeks. The QD groups were intragastrically administered QD twice daily from 2 weeks before to 2 weeks after tumor implantation for 4 weeks. The mRNA levels were detected by quantitative polymerase chain reaction, the proteins expression was determined by immunohistochemistry or western blotting. Results: Compared with the model group, QD showed inhibition of proliferation of LLC cells and reductions in tumor weight and proliferating cell nuclear antigen protein expression. Furthermore, QD up-regulated p53 mRNA expression, and downregulated c-myc and Bcl-2 mRNA expression, while MMP-9, VEGF, and VEGFR protein expression was suppressed. Phosphorylated ERK1/2 levels were also reduced by QD in a dose-dependent manner. Conclusion: Our findings suggest that QD inhibited lung tumor growth and proliferation, by activation of tumor suppressor genes, inactivation of oncogenes, suppressing the potential for invasion and metastasis, and attenuating angiogenesis. The ERK/VEGF/MMPs signaling pathways may play an important role in QD-induced inhibition of malignant tumor cell proliferation.

The issue of long patient waits has attracted increasing public attention due to the negative effects of waiting on patients’ satisfaction with health care. The present study examined the associations between actual waiting time, perceived acceptability of waiting time, actual service time, perceived acceptability of service time, actual visit duration, and the level of patient satisfaction with care. We conducted a cross-sectional time study and questionnaire survey of endocrinology outpatients visiting a major teaching hospital in China. Our results show that actual waiting time was negatively associated with patient satisfaction regarding several aspects of the care they received. Also, patients who were less satisfied with the sociocultural atmosphere and the identity-oriented approach to their care tended to perceive the amounts of time they spent waiting and receiving care as less acceptable. It is not always possible to prevent dissatisfaction with waiting, or to actually reduce waiting times by increasing resources such as increased staffing. However, several improvements in care services can be considered. Our suggestions include providing clearer, more transparent information to keep patients informed about the health care services that they may receive, and the health care professionals who are responsible for those services. We also suggest that care providers are encouraged to continue to show empathy and respect for patients, that patients are provided with private areas where they can talk with health professionals and no one can overhear, and that hospital staff treat the family members or friends who accompany patients in a courteous and friendly way.

Meat qualities of free-range chicken (Xuan-Zhou) (XZ-FRC) are closely associated with slaughter age and directly influence the economic benefits of supplier and consumer's preference. Understanding of the relationship between meat qualities and ages will be of prime important to explore a better slaughter age of XZ-FRC. In this study, the quality traits of breast and thigh muscles from XZ-FRCs at 9 to 14 wk were analyzed to establish a relatively reliable method for selecting a better slaughter age. The results showed that the effects of slaughter ages on color (CIE L*, a* and b* values), shear force, centrifugal loss, and flavor of XZ-FRCs were significant (P < 0.05). There were greater differences in meat qualities, whatever breast or thigh muscles, between same or different ages. Eleven feature indexes used for colligation evaluation of slaughter age were selected by combining the quality characteristics and data analysis. The score of colligation evaluation for XZ-FRCs at 12 wk was higher than that at 9 and 14 wk, suggesting that the 12 wk was an optimal slaughter age. This work would provide a reference method that helps the producers of livestock and poultry to select a better slaughter age., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

An achiral counteranion-induced reversal of enantioselectivity in Ni(II)-catalyzed Friedel-Crafts alkylation/annulation of 2-naphthols with β,γ-unsaturated α-keto esters was achieved. Using imidazolidine pyrroloimidazolone pyridine as the ligand and Ni(acac) 2 as the Lewis acid, diverse naphthopyran derivatives were obtained in good yields (up to 94% yield) and high enantioselectivities (up to 99% ee). In the presence of Ni(OTf) 2 as the Lewis acid, a series of chiral naphthopyran derivatives were obtained in good yields and with a controlled switch in stereoselectivity. DFT calculations reveal that the achiral counteranions regulate H-bonding interactions between counteranions with the N-H of the ligand and the O-H of 2-naphthol.

Chiral sulfur pharmacophores are crucial for drug discovery in bioscience and medicinal chemistry. While the catalytic asymmetric synthesis of sulfoxides and sulfinate esters with stereogenic-at-sulfur(IV) centres is well developed, the synthesis of chiral sulfinamides remains challenging, which has primarily been attributed to the high nucleophilicity and competing reactions of amines. In this study, we have developed an efficient methodology for the catalytic asymmetric synthesis of chiral sulfinamides and sulfinate esters by the sulfinylation of diverse nucleophiles, including aromatic amines and alcohols, using our bifunctional chiral 4-arylpyridine N-oxides as catalysts. The remarkable results are a testament to the efficiency, versatility and broad applicability of the developed synthetic approach, serving as a valuable tool for the synthesis of sulfur pharmacophores. Mechanistic experiments and density functional theory calculations revealed that the initiation and stereocontrol of this reaction are induced by an acyl transfer catalyst. Our research provides an efficient approach for the construction of optically pure sulfur(IV) centres., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Despite the existence of three competing reactions for propargyloxyoxindoles, we report a chemoselectivity switch between enantioselective propargyl [2,3]-Wittig rearrangement and Conia-ene-type reactions, with suppression of the [1,2]-Wittig-type rearrangement. Using C1-symmetric imidazolidine-pyrroloimidazolone pyridine as the ligand and Ni(acac)2 as the Lewis acid, diverse 3-hydroxy 3-substituted oxindoles containing allenyl groups were obtained in up to 98% yield and 99% ee via asymmetric propargyl [2,3]-Wittig rearrangement. In the presence of AgOTf-Duanphos, chiral spiro dihydrofuran oxindoles were given in up to 98% yield and 91% ee through a Conia-ene-type reaction., (© 2024 Wiley‐VCH GmbH.)

A base-assisted dearomative [2 + 1] spiroannulation of p / o -bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based S RN 1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an S N 2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

Thioglycoside bond formation via an asymmetric sulfa-Michael/aldol reaction of ( E )-β-nucleobase acrylketones and 1,4-dithiane-2,5-diol has been achieved with a cinchona alkaloid-derived bifunctional squaramide chiral catalyst. Diverse purine, benzimidazole, and imidazole substrates are well tolerated and generate 4'-thionucleoside derivatives containing three contiguous stereogenic centers with excellent results (30 examples, up to 97% yield, >20 : 1 dr and up to 99% ee). Moreover, the novel strategy provides an efficient and convenient synthetic route to construct chiral 4'-thionucleosides.

The desymmetrization of meso - vic -diols with a reversal of enantioselectivity catalyzed by chiral pyridine- N -oxides with l-proline as a single source of chirality is reported. With chiral 3-substituted ArPNO C2c and 2-substituted 4-(dimethylamino)pyridine- N -oxide C3b as catalysts, a wide range of monoesters were obtained with satisfactory results with a complete and controlled switch in stereoselectivity (up to 97:3 and 1:99 er). Chiral six-membered carbocyclic uracil nucleosides were generated with excellent enantioselectivities after derivatization. A series of control experiments and density functional theory (DFT) calculations supported that the reaction proceeded in a bifunctional activated manner, where the N -oxide groups and N-H proton of the amides were vital for catalytic reactivity and stereocontrol. The DFT calculation also supported the distance-directed switching of enantioselectivity, in which the l-prolinamide moiety moved from the C3 to C2 position on the pyridine ring, resulting in the H-bond interaction between the amide N-H and OH group of meso - vic -diol also shifted from one hydroxyl group to another.

Highly enantioselective propargyl Claisen rearrangement of O -propargyl β-ketoesters was achieved under 2.5 mol % of the chiral cobalt complex as the catalyst under mild reaction conditions. With Co(OTf) 2 as the Lewis acid and C 1 -symmetric imidazoline-pyrroloimidazolone pyridine as the ligand, diverse chiral allenyl-substituted all-carbon quaternary β-ketoesters were obtained in good yields (up to 97% yield) and high enantioselectivities (up to 98% ee).

A chiral 4-aryl-pyridine- N -oxide nucleophilic organocatalyst was used to synthesize chiral phthalidyl ester prodrugs by the acylative dynamic kinetic resolution process. By using the 3,5-dimethylphenyl-derived ArPNO catalyst, the phthalidyl esters were obtained in up to 97% yield with 97% ee at room temperature. Two phthalidyl esters of prodrugs, talosalate and talmetacin, were generated. By control experiments and density functional theory calculations, an acyl transfer mechanism was proposed.

Introduction: Acute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD., Methods: Transcriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines., Results: We identified the molecular mechanisms underlying hub genes in AIS and LUAD and found that CCNA2, CCNB1, CDKN2A , and CDK1 were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling., Discussion: Our findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qin, Yang, Chen, Huang, Xu, Qin, Liang, Lai, Huang, Xie and Chen.)

Chiral polycyclic indolines are widely present in natural products and have become the focus of extensive synthetic efforts. Here, we show the catalytic asymmetric dearomative [3 + 2] annulation of indoles with donor-acceptor aminocyclopropanes to construct tricyclic indolines. Key to the success of the reaction is the rational design of C 1 -symmetric bifunctional tridentate imidazoline-pyrroloimidazolone pyridine ligand. Under 5 mol% of Ni(OTf) 2 -ligand complex, diverse tricyclic indolines containing cyclopentamine moieties are obtained in good chemoselectivities, high diastereoselectivities, and excellent enantioselectivities. An unusual cis-configuration ligand is superior to the trans-configuration ligand and the corresponding C 2 -symmetric tridentate nitrogen ligands in the annulation reaction. Mechanistic studies by control experiments and density functional theory calculations reveal a dual activation manner, where Ni(II) complex activates the aminocyclopropane via coordination with the geminal diester, and imidazolidine NH forms a H-bond with the succinimide moiety., (© 2023. The Author(s).)

Dilated cardiomyopathy (DCM), characteristic of left ventricular or biventricular dilation with systolic dysfunction, is the most common form of cardiomyopathy, and a leading cause of heart failure and sudden cardiac death. Aggregating evidence highlights the underlying genetic basis of DCM, and mutations in over 100 genes have been causally linked to DCM. Nevertheless, due to pronounced genetic heterogeneity, the genetic defects underpinning DCM in most cases remain obscure. Hence, this study was sought to identify novel genetic determinants of DCM. In this investigation, whole-exome sequencing and bioinformatics analyses were conducted in a family suffering from DCM, and a novel heterozygous mutation in the VEZF1 gene (coding for a zinc finger-containing transcription factor critical for cardiovascular development and structural remodeling), NM&#95;007146.3: c.490A > T; p.(Lys164*), was identified. The nonsense mutation was validated by Sanger sequencing and segregated with autosome-dominant DCM in the family with complete penetrance. The mutation was neither detected in another cohort of 200 unrelated DCM patients nor observed in 400 unrelated healthy individuals nor retrieved in the Single Nucleotide Polymorphism database, the Human Gene Mutation Database and the Genome Aggregation Database. Biological analyses by utilizing a dual-luciferase reporter assay system revealed that the mutant VEZF1 protein failed to transactivate the promoters of MYH7 and ET1, two genes that have been associated with DCM. The findings indicate VEZF1 as a new gene responsible for DCM, which provides novel insight into the molecular pathogenesis of DCM, implying potential implications for personalized precisive medical management of the patients affected with DCM., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

A CuI-catalyzed C-N coupling reaction of 3-bromo-DMAP with l-prolinamides was conducted at 80 °C in 12-16 h, where the prolinamide's structure had an accelerating effect on the Ullmann-type reaction. This reaction was used to construct chiral 3-amino DMAP catalysts. Furthermore, enantioenriched DMAP analogue C8 was applied in an asymmetric Black rearrangement of 2-benzofuranylcarbonates, affording 3,3-disubstituted benzofuran-2-ones in up to 96% yield and 97% ee.

Background: Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanisms have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these 2 medications in alleviating the clinical symptoms and functional impairments observed in ADHD., Methods: Sixty-seven ADHD and 44 age-matched children with typical development were included and underwent resting-state functional magnetic resonance imaging scans at baseline. Then patients were assigned to MPH, ATX, or untreated subgroups, based on the patients' and their parents' choice, for a 12-week follow-up and underwent a second functional magnetic resonance imaging scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group., Results: Both MPH and ATX normalized the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared with ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, and the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment., Conclusions: Both MPH and ATX can normalize abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the 2 medications showed shared and unique effects on brain functions to alleviate clinical symptoms and functional impairment., (© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.)

Bifunctional chiral 4-aryl-pyridine- N -oxides (ArPNO) were reported for the acylative kinetic resolution of 3-hydroxy-3-substituted oxindoles, where the oxygen acts as the nucleophilic site. Using less sterically hindered acetic anhydride, both the recovered tertiary heterocyclic alcohols and the ester products exhibited good to excellent results with s -factors up to 167. Control experiments supported the dual activation manner, where the N -oxide group and N-H proton in ArPNO were crucial for high selectivity and enhanced catalytic reactivity. Compared with the extensively used chiral NHC, isochalcogenourea, and DMAP catalysts, we found that chiral ArPNO were also efficient organocatalysts in the kinetic resolution of tertiary alcohols.

Congenital heart disease (CHD) is the most frequent kind of birth deformity in human beings and the leading cause of neonatal mortality worldwide. Although genetic etiologies encompassing aneuploidy, copy number variations, and mutations in over 100 genes have been uncovered to be involved in the pathogenesis of CHD, the genetic components predisposing to CHD in most cases remain unclear. We recruited a family with CHD from the Chinese Han population in the present investigation. Through whole-exome sequencing analysis of selected family members, a new SOX18 variation, namely NM&#95;018419.3:c.349A>T; p.(Lys117*), was identified and confirmed to co-segregate with the CHD phenotype in the entire family by Sanger sequencing analysis. The heterozygous variant was absent from the 384 healthy volunteers enlisted as control individuals. Functional exploration via luciferase reporter analysis in cultivated HeLa cells revealed that Lys117*-mutant SOX18 lost transactivation on its target genes NR2F2 and GATA4, two genes responsible for CHD. Moreover, the genetic variation terminated the synergistic activation between SOX18 and NKX2.5, another gene accountable for CHD. The findings strongly indicate SOX18 as a novel gene contributing to CHD, which helps address challenges in the clinical genetic diagnosis and prenatal prophylaxis of CHD.

Bifunctional chiral tridentate bis(pyrroloimidazolone)pyridine (PyBPI) ligands have been designed, synthesized, and applied in an asymmetric Michael addition. With a 0.05 mol % PyBPI-Co(II) complex, β,γ-unsaturated α-keto esters reacted with 4-hydroxycoumarin to give the adducts in 93-99% yields and 90-97% ee. Experiments and DFT calculations supported the dual activation manner, in which the tridentate ligand coordinated with Co(II) to activate the keto ester, and the hydroxyl and carbonyl groups in PyBPI interacted with 4-hydroxycoumarin via two different H bonds.

Objectives: The primary objective of this study was to evaluate the effect of an innovative double-layer, single-application desensitizing/whitening technique of potassium nitrate (PN) and hydrogen peroxide (HP) diffusion at different time points., Methods and Materials: Specimens were prepared from extracted caries-free human molars (n=90). Teeth were randomly assigned into four groups: Group A (HP CTRL) treated with 25% HP for 45 minutes, group B (PN CTRL) received a single-layer treatment of 5% PN for 45 minutes, group C received the double-layer treatment of 5% PN and 25% HP for 45 minutes, and group D received a 3% PN incorporated in a 40% HP gel for 45 minutes. PN and HP concentrations were measured at 5, 15, 30, and 45 minutes using standard chemical kits. Group comparisons were made using a repeated measures analysis of variance (ANOVA) test. Pairwise tests for differences in diffusion were done, using the Tukey adjustment of p values for multiple comparisons. A significance level of 5% was used., Results: Group A showed no significant difference in HP diffusion rates between the 5- and 15-minute, 15- and 30-minute, or 30- and 45-minute time points; group D showed a similar trend; however, group C differed significantly at the 5-and 15-minute time points (p=0.0004), at the 15-and 30-minute time points (p=0.0026), and the 30- and 45-minute time points (p=0.0014). For PN diffusion, groups B and C had significantly different levels at the 15-, 30-, and 45-minute time points (p=0.0005, p=0.0002, and p<0.0001, respectively); and at the 15-, 30-, and 45-minute time points, groups D and C had significantly different PN diffusion (p=0.0327, p=0.0004, and p< 0.0001, respectively). Group C had significantly different PN diffusion at the 5- and 15-minute time points (p=0.0004), the 15- and 30-minute time points (p=0.0026), and at the 30- and 45-minute time points (p=0.0014)., Conclusion: The double-layer technique showed superior diffusion of PN into the pulp chamber and did not affect the diffusion of HP when compared to other techniques. The double-layer technique may be suggested as an alternative tooth-whitening treatment to minimize tooth sensitivity., (©Operative Dentistry, 2022.)

Objective: To evaluate the effect of baricitinib on inhibiting radiographic progression of structural joint damage over 5 years in patients with active rheumatoid arthritis (RA)., Methods: Patients completed 1 of 3 phase III baricitinib trials (ClinicalTrials.gov: NCT01711359, NCT01710358, or NCT01721057) and entered the long-term extension RA-BEYOND (NCT01885078), in which patients received once-daily 4 mg or 2 mg baricitinib. Across these trials, patients initially receiving methotrexate (MTX) or adalimumab (ADA) switched to baricitinib 4 mg at Week 52. Patients initially receiving placebo (PBO) switched to baricitinib 4 mg at Week 24. Radiographs were scored at baseline and Years 2, 3, 4, and 5. Change from baseline in van der Heijde modified total Sharp score (ΔmTSS) was computed., Results: Overall, 2125 of 2573 (82.6%) randomized patients entered RA-BEYOND; 1837 of 2125 (86.4%) entered this analysis. From Years 3 to 5, higher proportions of disease-modifying antirheumatic drug (DMARD)-naïve patients on initial baricitinib (monotherapy or with MTX) had no progression vs initial MTX (ΔmTSS ≤ 0 at Year 5: 59.6% baricitinib 4 mg; 66.2% baricitinib 4 mg + MTX; 40.7% MTX). Higher proportions of patients with inadequate response (IR) to MTX on initial baricitinib or ADA vs PBO had no progression (ΔmTSS ≤ 0 at Year 5: 54.8% baricitinib 4 mg; 55.0% ADA; 50.3% PBO). Higher proportions of patients with conventional synthetic DMARD-IR on initial baricitinib 4 mg had less progression vs initial PBO or baricitinib 2 mg (ΔmTSS ≤ 0 at Year 5: 66.7% baricitinib 4 mg; 58.2% baricitinib 2 mg; 60.0% PBO)., Conclusion: Oral baricitinib maintained lower levels of radiographic progression than initial conventional synthetic DMARD or PBO through 5 years in patients with active RA., (© 2022 by the Journal of Rheumatology.)

Objective: To identify the risk factors of hypertrophic scarring (HS) after thyroidectomy and construct a risk prediction model., Methods: From November 2018 to March 2019, the clinical data of patients undergoing thyroidectomy were collected for retrospective analysis. According to the occurrence of HS, the patients were divided into an HS group and a non-HS group. Univariate analysis and binary logistic regression analysis were conducted to explore the independent risk factors for HS. Receiver operating characteristic analysis was also carried out., Results: In this sample, 121 of 385 patients developed HS, an incidence of 31.4%. Univariate analysis showed significant differences in sex, age, postoperative infection, history of abnormal wound healing, history of pathologic scar, family history of pathologic scar, and scar prevention measures between the two groups (P < .05). Binary logistic regression analysis indicated that age 45 years or younger (odds ratio [OR], 1.815), history of abnormal wound healing (OR, 4.247), history of pathologic scarring (OR, 9.840), family history of pathologic scarring (OR, 5.708), and absence of preventive scar measures (OR, 5.566) were independent factors for HS after thyroidectomy. The area under the receiver operating characteristic curve was 0.837. When the optimal diagnostic cutoff value was 0.206, the sensitivity was 0.661, and the specificity was 0.932., Conclusions: The development of HS after thyroidectomy is related to many factors, and the proposed risk prediction model based on the combined risk factors shows a good predictive value for postoperative HS. When researchers consider the prevention and treatment of scarring in patients at risk, the incidence of HS in different populations can provide theoretical support for clinical decision-making., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The first ring-opening of D-A oxiranes with N-heteroaromatics in a chemoselective C-C bond cleavage manner was achieved. In the presence of 5 mol% of Y(OTf)3 as the catalyst, diverse N-heteroaromatics, including benzotriazoles, purines, substituted benzimidazole, imidazole and pyrazole, reacted well with various D-A oxiranes, providing acyclic nucleoside analogues containing a N-glycosidic bond in up to 97% yield and up to >95 : 5 regioselectivity. Through simple transformation, the Ganciclovir analogue could also be obtained.

Objectives: The aim of this study was to investigate the association between survival of anti-MDA5 autoantibody-positive/negative patients with myositis-associated interstitial lung disease (MA-ILD) and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), C-reactive protein-albumin ratio (CAR), and erythrocyte sedimentation rate-albumin ratio (EAR). Method: The study included 104 patients diagnosed with MA-ILD between January 2017 and February 2019 at the First Affiliated Hospital, University of Science and Technology of China. The clinical and laboratory results were compared between survivors and non-survivors in anti-MDA5 autoantibody-positive and anti-MDA5 autoantibody-negative patients. Cox proportional hazard models were used for univariable and multivariate analyses to determine survival-related factors. A logistic regression model was used to establish a joint diagnosis, and the feasibility of the combined diagnosis to evaluate the prognosis of MA-ILD was explored. Results: Among 47 anti-MDA5-positive patients with MA-ILD, EAR was an independent predictor of survival. When separated into high and low subgroups, high MLR (> 0.604) and EAR (> 1.458) were predictive of survival (p < 0.05). High MLR, high EAR, and age combined with lactate dehydrogenase were the highest (0.886) in predicting the prognosis of MA-ILD, and were higher than the area under the curve diagnosed separately. In 57 anti-MDA5-negative patients with MA-ILD, NLR and high EAR (> 0.872) were independent predictors of survival (p < 0.05). Conclusion: MLR and EAR are associated with prognosis in anti-MDA5-positive patients. NLR and EAR are associated with prognosis in anti-MDA5-negative patients. Using NLR, MLR, and EAR, inflammatory conditions of MA-ILD can be predicted and possible outcomes estimated.

Objective: To perform an evaluation of the risk to healthcare personnel of exposure to cisplatin during a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure in an operating room environment., Methods: Breathing zone air samples were taken from the operating room (OR) before, during and after the procedure of HIPEC filter membrane adsorption and the liquid impact method was applied to collect air samples. The samples of surface wipe from the floor of the OR were taken after the procedure. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of cisplatin in all the samples., Results: Thirty-six air samples and three surface wipes were collected from three different locations of healthcare personnel breathing zones. All the breathing zone air samples were negative for cisplatin; however, cisplatin contamination was detected on three surface wipes from the floor, but in a lowconcentration(≤ 2.25 ng)., Conclusion: The results suggest that the risk of inhalation of cisplatin was extremely low for the healthcare personnel during the procedure of HIPEC, but the contamination of the OR floor should be taken into consideration., Competing Interests: Conflicts of interest All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In the present work, 103 novel acyclic nucleosides were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo . The structure-activity relationship (SAR) studies revealed that most target compounds inhibited the growth of colon cancer cells in vitro , of which 3-(6-chloro-9 H -purin-9-yl)dodecan-1-ol ( 9b ) exhibited the most potent effect against the HCT-116 and SW480 cells with IC 50 values of 0.89 and 1.15 μM, respectively. Furthermore, all of the ( R )-configured acyclic nucleoside derivatives displayed more potent anticancer activity compared to their ( S )-counterparts. Mechanistic studies revealed that compound 9b triggered apoptosis in the cancer cell lines via depolarization of the mitochondrial membrane and effectively inhibited colony formation. Importantly, compound 9b inhibited the growth of the SW480 xenograft in a mouse model with low systemic toxicity. These results indicated that acyclic nucleoside compounds are viable as potent and effective anticancer agents, and compound 9b may serve as a promising lead compound that merits further attention in future anticancer drug discovery.

A generally useful Ni(II)/trisoxazoline-catalyzed asymmetric sulfa-Michael/Aldol cascade reaction is introduced to access chiral 3-amine-tetrahydrothiophene derivatives containing a quaternary stereocenter (32 examples, up to 93% yield, > 20:1 dr and 92% ee). Moreover, the novel strategy offers an efficient and convenient approach to construct chiral thionucleoside analogues.

A novel concept that conversion of chiral 2-substituted DMAP into its DMAP- N -oxide could significantly enhance the catalytic activity and still be used as an acyl transfer catalyst is presented. A new type of chiral 2-substituted DMAP- N -oxides, derived from l-prolinamides, has been rationally designed, facilely synthesized, and applied in the dynamic kinetic resolution of azlactones. Using simple MeOH as the nucleophile, various l-amino acid derivatives were produced in high yields (up to 98% yield) and enantioselectivities (up to 96% ee). Furthermore, α-deuterium labeled l-phenylalanine derivative was also obtained. Experiments and DFT calculations revealed that in 2-substituted DMAP- N -oxide, the oxygen atom acted as the nucleophilic site and the N-H bond functioned as the H-bond donor. High enantioselectivity of the reaction was governed by steric factors, and the addition of benzoic acid reduced the activation energy by participating in the construction of a H-bond bridge. The theoretical chemical study indicated that only when attack directions of the chiral catalyst were fully considered could the correct calculation results be obtained. This work paves the way for the utilization of the C2 position of the pyridine ring and the development of chiral 2-substituted DMAP- N -oxides as efficient acyl transfer catalysts.

Purpose : Glucocorticoids are the only therapeutics that can delay the progression of Duchenne musculardystrophy (DMD), the most prevalent type of inherited neuromuscular disorder in males. However, beyond theiranti-inflammatory effects, glucocorticoids have other underlying mechanisms that remain unclear. Moreover, muscleand circulating levels of insulin growth factor-1 (IGF-1) often decrease in response to glucocorticoids. Therefore, wehypothesized that glucocorticoids, either alone or in combination with IGF-1, can improve myogenic differentiation. Materials and methods : Established C2C12 myoblasts were employed as an in vitro model of myogenic differentiation,and myogenic differentiation markers, as assessed by Western blot (myogenin, MyoD, and MyHC protein expression),cellular morphology analysis (fusion index) and RT-PCR (MCK mRNA expression), were measured. Results : Myogenic differentiation markers were increased by glucocorticoid treatment. Furthermore, this effect was furtherenhanced by IGF-1, and these results suggest that glucocorticoids, either alone or together with IGF-1, can promotemyogenic differentiation. Akt and GSK-3β play important roles in myogenic differentiation. Interestingly, the levels ofboth phosphorylated Ser473-Akt and phosphorylated Ser9-GSK-3β were increased by glucocorticoid and IGF-1 cotreatment.Pharmacological manipulation with LY294002 and LiCl was employed to inhibit Akt and GSK-3β, respectively.We found that cellular differentiability was inhibited by LY294002 and enhanced by LiCl, indicating that theAkt/GSK-3β signaling pathway is activated by glucocorticoid and IGF-1 treatment to promote myogenic differentiation. Conclusions : Glucocorticoids together with IGF-1 promote myogenic differentiation through the Akt/GSK-3βpathway. Thus, these results further our knowledge of myogenic differentiation and may offer a potential alternativestrategy for DMD treatment based on glucocorticoid and IGF-1.

A highly enantioselective cyclopropanation to synthesize pyrimidine-substituted diester D-A cyclopropanes is reported. Various N1-vinylpyrimidines react well with phenyliodonium ylides, delivering chiral cyclopropanes in up to 97% yield with up to 99% ee. Through simple [3+2] annulation with benzaldehyde or ethyl glyoxylate, different chiral pyrimidine nucleoside analogues with a sugar ring could be obtained.

Objective: To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored., Methods: We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group., Results: The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05)., Conclusion: The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.

A straight synthetic approach to fused polycyclic tropane scaffold formation through an asymmetric dearomatization cycloaddition process of 2-nitrobenzofurans with cyclic azomethine ylides was successfully developed. In the presence of a chiral copper complex, derived from Cu(OAc) 2 and a diphosphine ligand, a series of fused polycyclic tropane derivatives were obtained in high yields (75-91%) with excellent enantioselectivities (90-98%). The utility of this method was showcased by the facile transformation of product.

A highly efficient Pd-catalyzed asymmetric formal [3+2] cycloaddition using α-N-heterocyclic acrylates to react with vinyl epoxides has been achieved for the first time to access chiral functionalized tetrahydrofuran skeletons (34 examples, up to 93% yield, >20 : 1 dr and 99% ee). Meanwhile, using a palladium/(S,S)-tBu-FOXAP catalyst or a palladium/(R)-Segphos catalyst, purine or pyrimidine isonucleoside analogs are constructed in high yields and stereoselectivity, respectively. The commercial availability of the catalysts, broad substrate scope and easy transformation of the products make this methodology an attractive method in asymmetric synthesis.