Forked Vein Structure W/WO3- x with Dual Active Sites in W and Oxygen Vacancies to Enhance Methylene Self-Coupling for Efficient Conversion of Methane to Ethylene.

The directional conversion of methane to ethylene is challenging due to the dissociation of the C─H bond and the self-coupling of methyl intermediates. Herein, a novel W/WO3- x catalyst with the fork vein structure consisting of an alternating arrangement of WO3- x and W is developed. Impressively, the catalyst achieves an unprecedented C2 H4 yield of 1822.73 µmol g-1  h-1 , with a selectivity of 82.49%. The enhanced catalytic activity is ascribed to the multifunctional synergistic effect induced by oxygen vacancies and W sites in W/WO3- x . Oxygen vacancies provide abundant coordination of unsaturation sites, which promotes the adsorption and activation of CH4 , thus reducing the dissociation energy barrier of the C─H bond. The CH2 coupling barrier on the metal W surface is significantly lower compared to WO3 , so CH2 can migrate to the W site for coupling. Importantly, the W/WO3- x with high periodicity provides multiple ordered local microelectric fields, and CH2 intermediates with dipole moments undergo orientation polarization and displacement polarization driven by the electric field, thus enabling CH2 migration. This work opens a new avenue for the structural design and modulation of photocatalysts, and provides new perspectives on the migration of methylene between multiple active sites.

A novel two-dimensional Janus TiSiGeN4 monolayer with N vacancies for efficient photocatalytic nitrogen reduction.

The photocatalytic nitrogen reduction reaction (pNRR) is a clean technology that converts H2O and N2 into NH3 under environmental conditions using inexhaustible sunlight. Herein, we designed a novel two-dimensional (2D) Janus TiSiGeN4 structure and evaluated the pNRR performance of the structure with the presence of nitrogen vacancies at different positions using density functional theory (DFT) calculations. The intrinsic dipoles in the Janus TiSiGeN4 structure generate a built-in electric field, which promotes the migration of photogenerated electrons and holes towards the (001) and (00-1) surfaces, respectively, to achieve efficient charge separation. For the pNRR, the Si atoms exposed after the formation of top N vacancies can realize the efficient activation of N2 through the "acceptance-donation" mechanism, while the presence of middle N vacancies not only suppresses the hydrogen evolution reaction, a competition reaction, but also lowers the reaction barrier for the protonation of N atoms. The limiting potential of TiSiGeN4 with the coexistence of both top and middle N vacancies (TiSiGeN4-VN-mt) is as low as -0.44 V. In addition, the introduction of N vacancies generates defect levels, narrowing the band gap and improving the light response. This work provides theoretical guidance for the design of efficient pNRR photocatalysts under mild conditions.

[Relationship between serum 25-hydroxyvitamin D and handgrip strength in middle-aged and elderly people in five cities of Western China].

OBJECTIVE: To explore the association between serum 25-hydroxyvitamin D [25(OH)D] and handgrip strength in middle-aged and elderly people in 5 cities of Western China. METHODS: Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023, the relevant demographic characteristics of people were collected by questionnaire, handgrip strength was collected by physical examination, and serum 25(OH)D was detected by HPLC-MS/MS. The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regression and Chi-square test for between-group comparisons models. RESULTS: The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9% and 34.5%, respectively. The people who were older, female, and sampled in winter had lower serum 25(OH)D levels (P < 0.05). The prevalence of loss of handgrip strength among the middle-aged and elderly people was 25.3%. The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency (45. 0%) than in those with 25(OH)D insufficiency (32.6%) and 25(OH)D sufficiency (20.6%). The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency (62. 1%), followed by the 25(OH)D insufficient group (11.1%, P < 0.05). The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency (OR=2.403, 95%CI: 1.202-4.804, P=0.013). No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people. For every 5 µg/L increase in total serum 25(OH)D, the risk of handgrip strength loss reduced by 13.1% (OR=0.869, 95%CI: 0.768-0.982, P=0.025). For every 5 µg/L increase in serum 25(OH)D2, the risk of handgrip strength loss reduced by 24.1% (OR=0.759, 95%CI: 0.582-0.990, P=0.042). No significant association was found between serum 25(OH)D3 levels and the risk of handgrip strength loss. The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2% for each incremental increase in the total serum 25(OH)D levels (deficient, insufficient and sufficient) (OR=0.748, 95%CI: 0.598-0.936, P=0.011). The risk of handgrip loss was reduced by 40.0% for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants, and by 80.0% for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants. CONCLUSION: Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.

Peroxygenase-Enabled Reductive Kinetic Resolution for the Enantioenrichment of Organoperoxides.

Enantiomerically pure organoperoxides serve as valuable precursors in organic transformations. Herein, we present the first examples of unspecific peroxygenase catalyzed kinetic resolution of racemic organoperoxides through asymmetric reduction. Through meticulous investigation of the reaction conditions, it is shown that the unspecific peroxygenase from Agrocybe aegerita (AaeUPO) exhibits robust catalytic activity in the kinetic resolution reactions of the model substrate with turnover numbers up to 60000 and turnover frequency of 5.6 s-1. Various aralkyl organoperoxides were successfully resolved by AaeUPO, achieving excellent enantioselectivities (e.g., up to 99 % ee for the (S)-organoperoxide products). Additionally, we screened commercial peroxygenase variants to obtain the organoperoxides with complementary chirality, with one mutant yielding the (R)-products. While unspecific peroxygenases have been extensively demonstrated as a powerful oxidative catalysts, this study highlights their usefulness in catalyzing the reduction of organoperoxides and providing versatile chiral synthons.

Development of HSP90 inhibitors-SN38 conjugates for cancer treatment.

Presently, chemotherapy remains to be one of the most important therapeutic approaches for malignant tumors. Ligands based drug conjugates are showing considerable promise as potential therapeutic agents delivery systems for cancer. Here, a series of HSP90 inhibitors-SN38 conjugates were developed through cleavable linkers for tumor-specific delivery of SN38 and reducing its side effects. In vitro assays showed that these conjugates exhibited acceptable stability in PBS and plasma, appreciable HSP90 binding affinity, and potent cytotoxic abilities. Cellular uptake behaviors also indicated that these conjugates could selectively target cancer cells in a time-dependent manner via HSP90. Among them, compound 10b with a glycine linkage exhibits appreciable in vitro and in vivo pharmacokinetic profiles, and excellent in vivo antitumor activity in Capan-1 xenograft models, demonstrating the selective targeting and accumulation of the active payload at tumor sites. Above all, these results suggest that compound 10b has the potential as a potent anticancer drug, meriting further evaluation in the future.

Dysregulation of iron homeostasis by TfR-1 renders EZH2 wild type diffuse large B-cell lymphoma resistance to EZH2 inhibition.

EZH2 has been regarded as an efficient target for diffuse large B-cell lymphoma (DLBCL), but the clinical benefits of EZH2 inhibitors (EZH2i) are limited. To date, only EPZ-6438 has been approved by FDA for the treatment of follicular lymphoma and epithelioid sarcoma. We have discovered a novel EZH1/2 inhibitor HH2853 with a better antitumor effect than EPZ-6438 in preclinical studies. In this study we explored the molecular mechanism underlying the primary resistance to EZH2 inhibitors and sought for combination therapy strategy to overcome it. By analyzing EPZ-6438 and HH2853 response profiling, we found that EZH2 inhibition increased intracellular iron through upregulation of transferrin receptor 1 (TfR-1), ultimately triggered resistance to EZH2i in DLBCL cells. We demonstrated that H3K27ac gain by EZH2i enhanced c-Myc transcription, which contributed to TfR-1 overexpression in insensitive U-2932 and WILL-2 cells. On the other hand, EZH2i impaired the occurrence of ferroptosis by upregulating the heat shock protein family A (Hsp70) member 5 (HSPA5) and stabilizing glutathione peroxidase 4 (GPX4), a ferroptosis suppressor; co-treatment with ferroptosis inducer erastin effectively overrode the resistance of DLBCL to EZH2i in vitro and in vivo. Altogether, this study reveals iron-dependent resistance evoked by EZH2i in DLBCL cells, and suggests that combination with ferroptosis inducer may be a promising therapeutic strategy.

Patient-Reported Outcomes Measurement Information System in patients with gastrointestinal cancer: a scoping review.

PURPOSE: The purpose of this study was to identify and evaluate the use of the Patient-Reported Outcomes Measurement Information System in patients with gastrointestinal cancer, as well as provide references for analyzing treatment outcomes, gauging prognostic risk, and assessing clinical symptoms and function in gastrointestinal cancer patients. METHODS: PubMed, Web of Science, ProQuest, Embase, and CINAHL were systematically searched using keywords and controlled vocabulary through January 2023. RESULTS: The scoping review collected 30 studies published from 2012 to 2022, including observational studies (n = 21), interventional studies (n = 4), and mixed studies (n = 5). Outcome indicators included mood, pain, fatigue, sleep, the ability to perform activities of daily living, social functioning, and other health problems. CONCLUSION: Being a self-report questionnaire, the Patient-Reported Outcomes Measurement Information System offers a full assessment of patient's symptoms and quality of life, and accurately captures their actual thoughts, feelings, and experiences. Individuals with gastrointestinal cancer made frequent use of the Patient-Reported Outcomes Measurement Information System to provide an accurate measure of their health status.

Synthesis, and biological evaluation of EGFR/HER2-NAMPT conjugates for tumor treatment.

Throughout the reported applications of EGFR inhibitors, it is usually employed with HDAC or other targets to design multi-target inhibitors for cancer treatment. In this paper, we designed a drug conjugate that targeted EGFR&HER2 and had inhibitory activity of NAMPT simultaneously. Compound 20c significantly inhibited the EGFR&HER2 and NAMPT enzyme activities, and had comparable or even higher anti-proliferative activity than lapatinib in various cancer cells with over-expressed EGFR and HER2. Importantly, 20c was expected to increase sensitivity to EGFR inhibitor-resistant cells. In Osimertinib-resistant cells (NCI-1975 cells with the L858R/T790M/C797S triple mutation and Ba/F3 cells with the Del19/T790M/C797S triple mutation), the anti-proliferative activity of compound 20c was increased by more than twofold compared with Osimertinib, so as to obtain better curative effect. This strategy is a promising method of embedding multiple pharmacophores into a single molecule, which lays a good foundation for the design and synthesis of small molecule drug conjugates with strong targeting ability and high cytotoxicity.

Joint effect of maternal pre-pregnancy body mass index and folic acid supplements on gestational diabetes mellitus risk: a prospective cohort study.

BACKGROUND: The joint effect of folic acid (FA) supplements and maternal pre-pregnancy body mass index (BMI) on gestational diabetes mellitus (GDM) has not been fully addressed. This study aimed to examine the joint effect of FA supplements and pre-pregnancy BMI on GDM. METHODS: Pregnant women at 4 to 14 weeks of gestation (n = 3186) were recruited during their first prenatal visit in Qingdao from May 1, 2019, to June 27, 2021. The main outcome was GDM at 24-28 weeks' gestation. Screening was based on 75 g 2-hour oral glucose tolerance (OGTT), a fasting glucose ≥ 5.1 mmol/L, or a 1-hour result ≥ 10.0 mmol/L, or a 2-hour result ≥ 8.5 mmol/L. The interactive effect of FA supplements and pre-pregnancy BMI on GDM was examined using logistic regression analysis and ratio of odds ratios (ROR) was used to compare subgroup differences. RESULTS: Overall, 2,095 pregnant women were included in the analysis, and GDM incidence was 17.76%. Compared with women with pre-pregnancy BMI lower than 25.0 kg/m2 and FA-Sufficient supplements ≥ 400 µg/day (FA-S) population, the adjusted odds ratios (aORs) of FA-S and FA-Deficiency supplements < 400 µg/d (FA-D) were 3.57 (95% confidence interval [CI]: 2.02-6.34) and 10.82 (95% CI: 1.69-69.45) for the obese women (BMI ≥ 30.0 kg/m2), and the aORs of FA-S and FA-D were 2.17 (95% CI: 1.60-2.95) and 3.27 (95% CI: 1.55-6.92) for overweight women (25.0 kg/m2 ≤ BMI < 30.0 kg/m2). However, the risk of GDM did not differ significantly between the FA-D and the FA-S group in pre-pregnancy obese women (ROR = 2.70, 95%CI: 0.47-2.30), or overweight women (ROR = 0.66, 95%CI: 0.30-1.49). After further stratification of FA supplementation time, F-D and FA-S in obese women showed an interaction when FA supplement intake time < 3 months. However, there was no significant difference between subgroups (ROR = 1.63, 95% CI: 0.37-7.04). CONCLUSION: Maternal pre-pregnancy BMI was associated with the incidence of GDM, the dose of FA supplementation from pre-pregnancy to early pregnancy was not found to be related to the incidence of GDM. The dosage of FA supplement was not associated with GDM irrespective of maternal pre-pregnancy BMI.

Risk factors that affect the degree of bronchopulmonary dysplasia in very preterm infants: a 5-year retrospective study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the most common adverse consequence of premature delivery and the most common chronic lung disease in infants. BPD is associated with long-term lung diseases and neurodevelopmental disorders that can persist into the adulthood. The adverse consequences caused by severe BPD are more serious. However, there were few studies on the risk factors for severe BPD. METHODS: This is a retrospective study of preterm infants born less than 32-week gestational age (GA) and diagnosed with BPD. RESULTS: A total of 250 preterm infants with a diagnosis of BPD and GA < 32 weeks were included (137 boys [54.8%] and 113 girls [45.2%]). The birth weight ranged from 700 g to 2010 g and the mean birth weight was 1318.52 g (255.45 g). The GA ranged from 25 weeks to 31 weeks and 6 days (mean, 30 weeks). The number of cases of mild, moderate and severe BPD were 39 (15.6%), 185 (74.0%) and 26 (10.4%), respectively. There were significant differences in the rate of small for gestational age (SGA), intrauterine asphyxia, pulmonary hemorrhage, neonatal respiratory distress syndrome (NRDS), circulatory failure, pulmonary hypertension, patent ductus arteriosus (PDA), pulmonary surfactant (PS), aminophylline, caffeine, glucocorticoids, tracheal intubation, diuretics, and parenteral nutrition length among the three groups (P < 0.05). The time of parenteral nutrition (aOR = 3.343, 95%CI: 2.198 ~ 5.085) and PDA (aOR =9.441, 95%CI: 1.186 ~ 75.128) were independent risk factors for severe BPD compared with mild BPD. PDA (aOR = 5.202, 95%CI: 1.803 ~ 15.010) and aminophylline (aOR = 6.179, 95%CI: 2.200 ~ 17.353) were independent risk factors for severe BPD, while caffeine (aOR = 0.260, 95%CI: 0.092 ~ 0.736) was the protective factor for severe BPD compared with moderate BPD. The time of parenteral nutrition (aOR = 2.972, 95%CI: 1.989 ~ 4.440) and caffeine (aOR = 4.525, 95%CI: 1.042 ~ 19.649) were independent risk factors for moderate BPD compared with mild BPD. Caffeine (aOR = 3.850, 95%CI: 1.358 ~ 10.916) was the independent risk factor for moderate BPD, while PDA (aOR = 0.192, 95%CI: 0.067 ~ 0.555) and aminophylline (aOR = 0.162, 95%CI: 0.058 ~ 0.455) were protective factors for moderate BPD compared with severe BPD. The time of parenteral nutrition (aOR = 0.337, 95%CI: 0.225 ~ 0.503) and caffeine (aOR = 0.221, 95%CI: 0.051 ~ 0.960) were protective factors for mild BPD compared with moderate BPD. The time of parenteral nutrition (aOR = 0.299, 95%CI: 0.197 ~ 0.455) and PDA (aOR = 0.106, 95%CI: 0.013 ~ 0.843) were protective factors for mild BPD compared with severe BPD. CONCLUSION: The time of parenteral nutrition is the risk factor of moderate and severe BPD. PDA and aminophylline are risk factors for severe BPD. The role of caffeine in the severity of BPD is uncertain, and SGA is not related to the severity of BPD. Severe or moderate BPD can be avoided by shortening duration of parenteral nutrition, early treatment of PDA, reducing use of aminophylline and rational use of caffeine. TRIAL REGISTRATION: Retrospectively registered.

Joint effect of 25-hydroxyvitamin D and secondhand smoke exposure on hypertension in non-smoking women of childbearing age: NHANES 2007-2014.

BACKGROUND: Vitamin D deficiency (VDD) may increase the risk of hypertension in women of childbearing age, who may be exposed to secondhand smoke (SHS) simultaneously. Till now, few studies have investigated the joint effects of VDD and SHS on hypertension in this population. We evaluated whether exposure to SHS modified the association between VDD and hypertension. METHODS: Data from National Health and Nutrition Examination Surveys (NHANES) 2007-2014 were analyzed. Our research subjects were 2826 nonsmoking and nonpregnant women of childbearing age (20-44 years old). Hypertension was defined based either on systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 80 mmHg or on now taking prescribed medicine for hypertension. The directed acyclic graphs (DAG) and the back-door criterion were used to select a minimal sufficient adjustment set of variables (MSAs) that would identify the unconfounded effect of 25(OH)D and hypertension. The interactive effect of VDD and SHS on hypertension was evaluated by using logistic regression models, followed by strata-specific analyses. RESULTS: The prevalence of VDD in the hypertension group was significantly higher than that in the non-hypertension group (48.2% vs 41.0%, P = 0.008), as well as the exposure rate of SHS (39.1% vs 33.8%, P = 0.017). VDD was independently associated with nearly 50% increased risk of hypertension [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.01, 2.04], while no significant association was observed between SHS and hypertension. However, SHS showed a significant synergistic effect on VDD with a higher aOR of 1.79 (95% CI: 1.14, 2.80) (Pinteraction = 0.011). This synergistic effect was more obvious when stratified by BMI (in overweight women, aOR, 95% CI =4.74, 1.65-13.60 for interaction vs 2.33, 1.01-5.38 for VDD only) and race (in Non-Hispanic Black women, aOR, 95% CI =5.11, 1.58-16.54 for interaction vs 2.69, 1.10-6.62 for VDD only). CONCLUSION: There exist synergistic effects of SHS and VDD on the prevalence of hypertension in American women of childbearing age, with more significant effects in women who were overweight or Non-Hispanic Black. Further studies are warranted to verify this finding in other populations, and the molecular mechanisms underlying the joint effect of SHS and VDD need to be elucidated.

The possible role of visceral fat in early pregnancy as a predictor of gestational diabetes mellitus by regulating adipose-derived exosomes miRNA-148 family: protocol for a nested case-control study in a cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) has become alarming public health concern. It is associated with adverse pregnancy outcomes and increased risk of postpartum type 2 diabetes. Pre-pregnant body mass index (BMI), waist circumference and other anthropometric parameters have been proposed to predict GDM. However, visceral fat thickness can better reflect the distribution of body fat, and may more accurately predict the risk of GDM. Visceral fat thickness may lead to insulin resistance by regulating the adipose-derived exosomes miRNA-148 family, which affect the development of GDM. Evidence from prospective cohort studies on visceral fat thickness as a predictor of GDM and the possible mechanisms is still insufficient. METHODS: In this prospective cohort study, we will recruit 3000 women at first antenatal visit between 4 and 12 weeks of gestation. Baseline socio-demographic factors and visceral fat thickness will be assessed by questionnaire form and the ultrasonic measurement, respectively. At 20 weeks of gestation, 10 ml blood samples will be drawn and we will extract adipose-derived exosomes miRNA on the basis of nested case-control study. GDM will be screened at 24-28 weeks' gestation and the expression of miRNA-148 family between pregnant women with GDM and without GDM will be analyzed. Intermediary analysis will be used to investigate whether visceral fat thickness can predict GDM by regulating adipose-derived exosomes miRNA-148 family. DISCUSSION: We hypothesized that visceral fat thickness may predict GDM by regulating the miRNA-148 family of adipose-derived exosomes. The findings of the study will assist in further clarifying the pathophysiological mechanism of GDM, it will also provide technical support for effective screening of high-risk pregnant women with GDM.

Secondary prevention of coronary heart disease: The effect of a nursing intervention using Cox's interaction model of client health behaviour.

AIMS: Secondary prevention of coronary heart disease is of utmost importance to facilitate people to achieve health outcomes and behaviours. This study was to investigate the effect of a nursing intervention based on Cox's interaction model of client health behaviour to improve health outcomes and behaviours of secondary prevention of coronary heart disease. DESIGN: This study is a cluster randomised controlled trial. METHODS: Participants were recruited between August and November 2019 in two community settings in Hengyang city, Hunan province, China. Participants in the intervention group received a nursing intervention based on Cox's interaction model of client health behaviour and routine health education, while those in the control group received routine health education only. The outcome variables included self-management, physical activity, medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, blood pressure, body mass index (BMI), and low-density lipoprotein cholesterol (LDL-C). The influential statistical tests applied to analyse the data included χ2 tests and t tests. RESULTS: Seventy-seven participants completed this study. Compared with the control group (n = 40), the intervention group (n = 37) showed statistically significant better health outcomes and behaviours regarding self-management, physical activity (except for high energy consumption), medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, systolic blood pressure, BMI, and LDL-C. However, there was no statistically significant difference in diastolic blood pressure and high energy consumption for physical activity. CONCLUSION: A well-developed nursing intervention based on Cox's interaction model of client health behaviour could successfully improve health outcomes and behaviours of secondary prevention of coronary heart disease. Such an intervention may be incorporated into community healthcare practice by nurses to improve patient care. IMPACT: This study provides a valuable insight to facilitate further development of effective nursing interventions to improve secondary prevention of coronary heart disease in community settings.

Author Correction: AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Effect of Resourcefulness Training on Depression and Coping Styles of Patients With Coronary Heart Disease in China [RETRACTED].

BACKGROUND: Coronary heart disease (CHD) is one of the leading causes of mortality worldwide. Previous research has demonstrated that resourcefulness interventions can help individuals identify effective coping strategies to manage their conditions, reduce the incidence of depression, and improve their quality of life. However, little is known about such interventions for people with CHD in China. OBJECTIVE: This study aimed to investigate the effects of a resourcefulness training intervention on depression and coping style of patients with CHD in China. METHODS: A cluster randomized controlled trial design was used. A convenience sample of 72 patients in community settings took part in the study. Participants in the intervention group (n = 36) received an 8-week intervention based on the concept of resourcefulness, plus routine health education. Participants in the control group (n = 36) received routine health education only. Three outcomes (resourcefulness, depression, and coping styles) were measured using the Resourcefulness Scale, Center for Epidemiological Studies Depression Scale, and Medical Coping Mode Questionnaire. Data were collected at baseline and post intervention, and analyzed using frequencies, percentages, means, standard deviations, independent sample t tests, and χ tests. RESULTS: After the intervention, participants in the intervention group had significantly higher scores on resourcefulness and coping styles, and lower scores on depression than those in the control group (both Ps < .001). CONCLUSIONS: It is suggested that a well-developed resourcefulness intervention could help patients with CHD in China and beyond to be more resourceful, improve their level of depression, and choose more effective strategies to cope with stress.

Development and validation of a Chinese-language instrument measuring empowerment needs of patients after a percutaneous coronary intervention.

Patient empowerment has been shown to have some positive impacts on self-efficacy, self-esteem, and recovery. However, information about the empowerment needs of patients after a percutaneous coronary intervention is scarce. The aim of this study was to develop a Chinese-language instrument to measure empowerment needs of such patients. The initial instrument was generated based on a literature review and interviews with patients after a percutaneous coronary intervention procedure. Content validity was tested with a panel of experts using the Delphi method. In total, 226 patients were recruited for psychometric tests using the revised instrument. Expert authority coefficient was 0.92, and content validity index was 0.95. The internal consistency reliability was demonstrated by Cronbach's α coefficients (0.86 for the total score, 0.66-0.74 for the dimensions). The newly developed 19-item, five-dimension instrument has shown satisfactory validity (face/content validity and construct validity) and internal consistency reliability. The instrument could help clinical nurses who have close contact with patients after a percutaneous coronary intervention to gain a better understanding of their empowerment needs and could help develop appropriate health education to address such needs.

Nobiletin reduces LPL-mediated lipid accumulation and pro-inflammatory cytokine secretion through upregulation of miR-590 expression.

Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inflammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis.

Synthesis and biological evaluation of paclitaxel and vorinostat co-prodrugs for overcoming drug resistance in cancer therapy in vitro.

Paclitaxel (PTX) is the first-line treatment drug for breast cancer. However, drug resistance after a course of treatment and low selectivity restricted its clinical utility sometimes. In this study, we successfully bound PTX and vorinostat (SAHA) to form co-prodrugs based on the synergistic anticancer effects. The PTX-SAHA co-prodrugs were conjugated by glycine (1a) and succinic acid (1b) respectively and the former has shown better activity in cytotoxicity, cell cycle arrest and western-blot experiments. Therefore, 1a was further prepared to nanomicelles with mPEG2000-PLA1750 as the carrier by using thin film method. PTX-SAHA co-prodrug nanomicelles were spherical with a particle size of 20-100 nm. In vitro drug release test showed 1a nanomicelles had sustained release effect, which could reduce the resistance of PTX. In vitro cytotoxicity was evaluated by SRB assay in HCT-116 cells, MCF-7 cells and drug-resistant MCF-7/ADR cells. The results showed 1a nanomicelles had comparable or even better cytotoxicity than PTX especially in the MCF-7/ADR cells. All the results suggested that PTX-SAHA co-prodrug nanomicelles were promising treatment for PTX resistance cancer.

AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition.

Deregulated Polycomb repressive complex 2 (PRC2) is intimately involved in tumorigenesis and progression, making it an invaluable target for epigenetic cancer therapy. Disrupting the EZH2-EED interaction, which is required for PRC2 enzymatic activity, is a promising strategy for cancer treatment. However, this kind of inhibitors are still limited. The in-cell protein-protein interaction screening was conducted for approximately 1300 compounds by NanoBRET technology. Co-immunoprecipitation (Co-IP), protein thermal shift assay (PTSA), and cellular thermal shift assay (CETSA) were performed to investigate the regulation of PRC2 by AZD9291. The anti-tumor effects of AZD9291 on breast cancer (BC) cells and diffuse large B-cell lymphoma (DLBCL) cells were detected. MicroRNA array assay, luciferase reporter assay, and qRT-PCR were conducted to identify the interaction and regulation among AZD9291, EZH2, and miR-34a. We discovered that, AZD9291, a potent and selective EGFR inhibitor, disrupted the interaction of EZH2-EED, leading to impairment of PRC2 activity and downregulation of EZH2 protein. In addition, AZD9291 declined EZH2 mRNA expression via upregulating the expression of a tumor suppressor, miR-34a. Our results suggest that AZD9291 can serve as a lead compound for further development of antagonist of PRC2 protein-protein interactions and EZH2 mRNA may be a direct target of miR-34a through non-canonical base pairing.

Quantitative structure-retention relationships of the chromatographic retentions of phthalic acid ester contaminants in foods.

The harmful health effects caused by phthalic acid esters have been supported from the increasing scientific evidence, developing the efficient methodologies to monitor the levels of phthalic acid esters in various foods become especially important from the aspects of human exposure assessment and their migration mechanistic understanding. In this study, quantitative structure-retention relationship studies on both the gas and liquid chromatographic retention times of 23 phthalic acid esters were performed by genetic function approximation, and the optimal quantitative structure-retention relationship models (r2  > 0.980, r2 CV  > 0.960, and r2 pred  > 0.865) passed the statistical tests of cross-validation, randomization, external prediction, Roy' rm 2 metrics, Golbraikh-Tropsha' criteria and applicability domain. The established predictive models elucidate the structural requirements for the retention of phthalic acid esters over different chromatographic columns, which were finally used to predict the retention times of 11 new phthalic acid esters. Hopefully, this work could provide useful guidelines for better understanding and accurate prediction of the retention behavior of undetermined phthalic acid esters when lacking standard samples or under poor experimental conditions, and make the simultaneous identification and quantification of numerous phthalic acid esters possible.