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1.
J Colloid Interface Sci ; 666: 201-209, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38593654

ABSTRACT

Perylene diimides (PDI) are widely used in photocatalytic oxygen evolution due to their deep valence band potentials. Here, we report the synthesis of a unique supramolecular photocatalyst (designated s-PDI-P1) by introducing hydroxyl and carboxyl groups at the imide position of PDI. This modification allows the formation of intermolecular double hydrogen bond structures between the hydroxyl groups, oxygen atoms on the perylene cores and the carboxyl groups. The resulting double hydrogen bonding structures reduce lateral slip and promote the formation of supramolecular structures with H-type π-π stacking. In addition, the intermolecular hydrogen bonding interactions between the hydroxyl groups and the oxygen atoms on the perylene cores bring the PDI molecules closer together, enhancing the conjugation of the PDI supramolecules and facilitating the formation of ultrathin nanosheet-like structures. In this study, we successfully constructed ultrathin nanosheets of the supramolecular photocatalyst s-PDI-P1 with a compact H-type π-π stacking structure, which exhibited enhanced charge transfer capability, shorter charge migration distance, and achieved a high photocatalytic oxygen evolution rate of 3.23 mmolg-1h-1. These results highlight the potential of intermolecular double hydrogen bond structures to improve the separation and migration driving force of photogenerated charges, thus providing a novel design strategy for organic photocatalysts.

2.
Phys Chem Chem Phys ; 26(15): 12199-12209, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38591717

ABSTRACT

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.

3.
Nutrients ; 16(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38613008

ABSTRACT

Sn-2 palmitate is widely used in infant formula. However, little is known about its effects on metabolism and body composition in middle-aged and elderly adults. In a double-blinded, randomized controlled trial, we enrolled Chinese adults aged 45-75 years with self-reported constipation. Individuals were randomly assigned in a 1:1 ratio to a 1,3-dioleoyl-2-palmitoyl-glycerol (OPO)-enriched oil (66% palmitic acid in the sn-2 position) or a control vegetable oil (24% palmitic acid in the sn-2 position) daily for 24 weeks. Skim milk powder was used as the carrier for both fats. Interviews and body composition were performed at baseline, week 4, week 12 and week 24. A fasting blood draw was taken except at week 4. This study was a secondary analysis and considered exploratory. A total of 111 adults (83 women and 28 men, mean age 64.2 ± 7.0 years) were enrolled, of whom 53 were assigned to the OPO group and 57 to the control group. During the intervention, blood glucose, triglyceride, the triglyceride-glucose index, total cholesterol, low-density lipoprotein cholesterol and remnant cholesterol remained stable, while high-density lipoprotein cholesterol decreased in both groups (p = 0.003). No differences in change were observed between the groups (all p > 0.05). From baseline to week 24, the level of visceral fat increased slightly (p = 0.017), while body weight, total body water, protein, soft lean mass, fat-free mass, skeletal muscle and skeletal muscle mass index (SMI) decreased in two groups (p < 0.01). At weeks 4, 12 and 24, the SMI decreased less in the OPO group than in the control group, with a trend towards significance (p = 0.090). A 24-week daily intake of sn-2-palmitate-enriched oil had no adverse impact on fasting blood glucose, lipids and body composition compared with the control vegetable oil in Chinese adults (funded by Chinese Nutrition Society National Nutrition Science Research Grant, National Key Research and Development Program of China and Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd.; ChiCTR1900026480).


Subject(s)
Blood Glucose , Palmitates , Aged , Female , Humans , Male , Middle Aged , Body Composition , China , Cholesterol, HDL , Palmitic Acid , Plant Oils , Triglycerides , East Asian People
4.
Angew Chem Int Ed Engl ; 63(21): e202401590, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38477082

ABSTRACT

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.

5.
Eur J Gastroenterol Hepatol ; 36(6): 784-792, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38526936

ABSTRACT

The aim of this study is to assess the agreement and performance of visual transient elastography (ViTE), sound touch elastography (STE), and sound touch quantification (STQ) for liver fibrosis staging using transient elastography (TE) as a standard. We finally enrolled 252 subjects with chronic liver disease (CLD) who underwent ViTE, STE, STQ, and TE examinations simultaneously in our hospital from October 2022 to July 2023. We evaluated the correlation and agreement between various technologies. And also evaluated the performances and optimal cutoffs of ViTE, STE, and STQ . The correlation coefficients of ViTE and TE, STE and TE, STQ and TE were 0.863, 0.709, and 0.727, respectively. The ICC among ViTE, STE, STQ, and TE was 0.911. The area under the receiver operating characteristics (AUROCs) of ViTE, STE, and STQ for detection of TE of ≥5 kPa, ≥10 kPa, ≥15 kPa, and ≥20 kPa were 0.867, 0.771, 0.804; 0.972, 0.935, 0.933; 0.998, 0.973, 0.968; and 1.000, 0.960, 0.954, respectively. The AUROCs of ViTE for detection of lower stages (TE≥5 kPa and ≥10 kPa) were significantly higher than STE and STQ in the overall cohort (ViTE vs. STE: Z  = 2.766, for TE ≥5 kPa; ViTE vs. STE: Z  = 2.145, ; ViTE vs. STQ: Z  = 2.587, for TE ≥10 kPa) (all P < 0.05). These methods all have coincided with performance in more advanced stages (TE ≥15 kPa and ≥20 kPa) (all P  > 0.05). These methods showed excellent correlation and agreement. ViTE performance in more advanced fibrosis differentiation is comparable to the STE and STQ while ViTE is more accurate than STE and STQ to identify patients with mild CLD stage, and can more effectively rule out compensated advanced CLD.


Subject(s)
Elasticity Imaging Techniques , Liver Cirrhosis , ROC Curve , Severity of Illness Index , Humans , Elasticity Imaging Techniques/methods , Female , Male , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Middle Aged , Adult , Reproducibility of Results , Aged , Area Under Curve , Predictive Value of Tests , Liver/diagnostic imaging , Liver/pathology
6.
Curr Med Imaging ; 20: 1-12, 2024.
Article in English | MEDLINE | ID: mdl-38389362

ABSTRACT

AIMS: There is a need to assess the severity of steatosis caused by Nonalcoholic Fatty Liver Disease (NAFLD). We explored new techniques in which Ultrasound-Guided Attenuation Parameter (UGAP), Liver Steatosis Analysis (LiSA) and Hepatorenal Index (HRI) can be applied to the grading of steatosis. MATERIALS AND METHODS: We enrolled 120 patients with or without NAFLD in this study who underwent UGAP, LiSA, HRI and controlled attenuation parameter (CAP) measurements in our hospital from September 2022 to April 2023. Spearman correlation coefficient was used to calculate the correlation between UGAP, LiSA, HRI and CAP values, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of UGAP, LiSA, and HRI for different grades of steatosis. RESULTS: The cohort was classified into four groups based on means of CAP: S0 (no steatosis): 30/120, S1 (mild): 30/120, S2 (moderate): 15/120, and S3 (severe): 45/120. The cut-off values and areas under the receiver operating characteristic curve (AUC) of UGAP, LiSA and HRI for predicting different grades of steatosis were: S≥S1:227dB/m (AUC=0.904), 241dB/m (AUC=0.873), 1.19 (AUC=0.696); S≥S2:251dB/m (AUC=0.978), 264dB/m (AUC=0.913), 1.37 (AUC=0.770); S=S3:263dB/m (AUC=0.962), 289dB/m (AUC=0.923), 1.45 (AUC=0.809). The diagnostic efficacy of UGAP and LiSA was significantly better than HRI, and there were statistically significant differences (all p<0.05). A strong correlation was found between UGAP, LiSA and CAP values (UGAP: r=0.865; LiSA: r=0.810), moderate correlation between HRI and CAP values (r=0.476). CONCLUSION: Both UGAP and LiSA have a strong correlation with CAP and are more accurate than HRI in diagnosing different grades of hepatic steatosis, which can be widely used in the diagnosis of liver steatosis.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Biopsy , Ultrasonography/methods , ROC Curve
7.
Nat Commun ; 15(1): 1235, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38336996

ABSTRACT

Hemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals in aqueous environments. Here, we show that this challenge can be addressed through reaction engineering by using immobilized peroxygenase from Agrocybe aegerita (AaeUPO) under neat reaction conditions, which allows for the selective C-H bond oxyfunctionalization of environmentally significant cyclic ethers to cyclic hemiacetals. A wide range of chiral cyclic hemiacetal products are prepared in >99% enantiomeric excess and 95170 turnover numbers of AaeUPO. Furthermore, by changing the reaction medium from pure organic solvent to alkaline aqueous conditions, cyclic hemiacetals are in situ transformed into lactones. Lactams are obtained under the applied conditions, albeit with low enzyme activity. These findings showcase the synthetic potential of AaeUPO and offer a practical enzymatic approach to produce chiral cyclic hemiacetals through C-H oxyfunctionalization under mild conditions.

8.
Small ; : e2311041, 2024 Feb 11.
Article in English | MEDLINE | ID: mdl-38342590

ABSTRACT

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.

9.
J Colloid Interface Sci ; 660: 381-392, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38244504

ABSTRACT

Single-atom photocatalysts can modulate the utilization of photons and facilitate the migration of photogenerated carriers. However, the preparation of single-atom uniformly doped photocatalysts is still a challenging topic. Herein, we propose the preparation of Ni single-atom doped g-C3N4 photocatalysts by metal vapor exfoliation. The Ni vapor produced by calcining nickel foam at high temperature accumulates in between g-C3N4 layers and poses a certain vapor pressure to destroy the interlayer van der Waals forces of g-C3N4. Individual metal atoms are doped into the structure while exfoliating g-C3N4 into nanosheets by metal vapor. Upon optimization of Ni content, the Ni single atom doped g-C3N4 nanosheets with 2.81 wt% Ni exhibits the highest CO2 reduction performance in the absence of sacrificial agents. The generation rates of CO and CH4 are 19.85 and 1.73 µmol g-1h-1, respectively. The improved photocatalytic performance is attributed to the anchoring Ni of single atoms on g-C3N4 nanosheets, which increases both carrier separation efficiency and reaction sites. This work provides insight into the design of photocatalysts with highly dispersed single-atom.

10.
ChemSusChem ; 17(6): e202301321, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-37948039

ABSTRACT

Chiral sulfoxides are valuable building blocks in asymmetric synthesis. However, the biocatalytic synthesis of chiral sulfoxides is still challenged by low product titres. Herein, we report the use of peroxygenase as a catalyst for asymmetric sulfoxidation under non-aqueous conditions. Upon covalent immobilisation, the peroxygenase showed stability and activity under neat reaction conditions. A large variety of sulfides was converted into chiral sulfoxides in very high product concentration with moderate to satisfactory optical purity (e. g. 626 mM of (R)-methyl phenyl sulfoxide in approx. 89 % ee in 48 h). Further polishing of the ee value via cascading methionine reductase A (MsrA) gave>99 % ee of the sulfoxide. The robustness of the enzymes and high product titer is superior to the state-of-the-art methodologies. Gram-scale synthesis has been demonstrated. Overall, we demonstrated a practical and facile catalytic method to synthesize chiral sulfoxides.

11.
Eur Thyroid J ; 12(6)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37992281

ABSTRACT

Introduction: Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is relatively rare, so ultrasound doctors lack experience with the disease, which can easily lead to misdiagnosis. We describe three cases of thyroid metastasis from ccRCC detected 12, 8, and 7 years after nephrectomy. Case presentation: The first patient, a 78-year-old woman, was admitted to our institution for hoarseness and progressive dyspnea. Ultrasonography revealed bilateral thyroid nodules and abnormal cervical lymph nodes. Fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the thyroid was nondiagnostic. The other two patients, a 54-year-old man and a 65-year-old man, were admitted to our institution for a goiter pressing on the trachea. In each case, ultrasonography revealed a partially cystic nodule of the left lobe of the thyroid gland. Histological examination of three patients after thyroidectomy showed thyroid metastasis from ccRCC. Discussion/Conclusion: For patients with a history of ccRCC, long-term follow-up and routine thyroid ultrasonography should be performed. If a new thyroid nodule is found during the examination, metastases should be highly suspected. FNAB should be performed, even if benign ultrasound features seem to be in evidence. If the diagnosis of FNAB is incorrect and inconclusive, CNB should be performed.


Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Thyroid Neoplasms , Thyroid Nodule , Male , Female , Humans , Aged , Middle Aged , Carcinoma, Renal Cell/diagnostic imaging , Thyroid Neoplasms/diagnostic imaging , Thyroid Nodule/diagnostic imaging , Carcinoma/diagnosis , Ultrasonography , Kidney Neoplasms/diagnostic imaging
12.
Nanomaterials (Basel) ; 13(18)2023 Sep 09.
Article in English | MEDLINE | ID: mdl-37764554

ABSTRACT

Lithium-ion capacitors (LICs) are emerging as one of the most advanced hybrid energy storage devices, however, their development is limited by the imbalance of the dynamics and capacity between the anode and cathode electrodes. Herein, anthracite was proposed as the raw material to prepare coal-based, nitrogen-doped porous carbon materials (CNPCs), together with being employed as a cathode and anode used for dual-carbon lithium-ion capacitors (DC-LICs). The prepared CNPCs exhibited a folded carbon nanosheet structure and the pores could be well regulated by changing the additional amount of g-C3N4, showing a high conductivity, abundant heteroatoms, and a large specific surface area. As expected, the optimized CNPCs (CTK-1.0) delivered a superior lithium storage capacity, which exhibited a high specific capacity of 750 mAh g-1 and maintained an excellent capacity retention rate of 97% after 800 cycles. Furthermore, DC-LICs (CTK-1.0//CTK-1.0) were assembled using the CTK-1.0 as both cathode and anode electrodes to match well in terms of internal kinetics and capacity simultaneously, which displayed a maximum energy density of 137.6 Wh kg-1 and a protracted lifetime of 3000 cycles. This work demonstrates the great potential of coal-based carbon materials for electrochemical energy storage devices and also provides a new way for the high value-added utilization of coal materials.

13.
Support Care Cancer ; 31(10): 567, 2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37682320

ABSTRACT

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.


Subject(s)
Activities of Daily Living , Gastrointestinal Neoplasms , Humans , Quality of Life , Patient Reported Outcome Measures , Information Systems
14.
Mol Divers ; 2023 Jul 23.
Article in English | MEDLINE | ID: mdl-37481750

ABSTRACT

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.

15.
Bioorg Chem ; 137: 106582, 2023 08.
Article in English | MEDLINE | ID: mdl-37156134

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy
16.
Front Nutr ; 10: 1156404, 2023.
Article in English | MEDLINE | ID: mdl-37215204

ABSTRACT

Background: High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker that has been suggested as a predictor of cardiovascular diseases. High glycated hemoglobin (HbA1c) levels and overweight/obesity are independently associated with elevated hs-CRP; meanwhile, high HbA1c levels are frequently accompanied by overweight or obesity. However, their joint effect on elevated hs-CRP levels has not been well-established. Therefore, we evaluated whether overweight/obesity modified the association between high HbA1c levels and elevated hs-CRP. Methods: Based on cross-sectional data from the Chinese Urban Adults Diet and Health Study (CUADHS) in 2016, we included 1,630 adults aged 18-75 years (mean age 50.16 years and 33.6% male). Elevated hs-CRP was defined as serum hs-CRP ≥ 3 and <10 mg/L. The interactive effects of BMI and HbA1c levels on the risk of elevated hs-CRP levels were calculated by using multiple logistic regression models, followed by strata-specific analyses. Results: Individuals with elevated hs-CRP had a higher rate of HbA1c level than those without elevated (25.3 vs. 11.3%, P < 0.001), as well as a higher rate of overweight/obesity (67.1 vs. 43.5%, P < 0.001). Higher HbA1c levels were independently associated with an increased risk of elevated hs-CRP [adjusted odds ratio (aOR) = 2.31, 95% confidence interval (CI): 1.47, 3.65], as well as overweight/obesity with the risk of elevated hs-CRP (aOR = .31, 95% confidenc-3.73). Furthermore, overweight/obesity showed a significant synergistic effect on high HbA1c levels with a higher aOR of 5.25 (2.77, 9.95) (Pinteraction < 0.001). This synergistic effect was more prominent when stratified by age (in 18-44 years old, aOR, 95% CI = 30.90, 4.40-236.47 for interaction vs. 6.46, 1.38-30.23 for high HbA1c only) and gender (in women, aOR, 95% CI = 8.33, 3.80-18.23 for interaction vs. 2.46,1.38-4.40 for high HbA1c only). Conclusion: There are synergistic effects of high HbA1c levels and overweight/obesity on the risk of elevated hs-CRP in Chinese adults, with more significant effects in adults aged 18-44 years or females. Intervention strategies for preventing high blood glucose levels and body weight simultaneously may be important for reducing hs-CRP-related diseases. Further studies are needed to confirm this finding in other populations, and its molecular mechanisms need to be elucidated.

17.
Acta Pharmacol Sin ; 44(10): 2113-2124, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37225847

ABSTRACT

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.


Subject(s)
Enhancer of Zeste Homolog 2 Protein , Lymphoma, Large B-Cell, Diffuse , Humans , Benzamides/pharmacology , Benzamides/therapeutic use , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Enhancer of Zeste Homolog 2 Protein/drug effects , Enzyme Inhibitors/pharmacology , Homeostasis , Lymphoma, Large B-Cell, Diffuse/metabolism , Receptors, Transferrin/metabolism , Iron/metabolism
18.
BMC Pregnancy Childbirth ; 23(1): 202, 2023 Mar 23.
Article in English | MEDLINE | ID: mdl-36959594

ABSTRACT

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.


Subject(s)
Diabetes, Gestational , Pregnancy , Female , Humans , Diabetes, Gestational/epidemiology , Diabetes, Gestational/diagnosis , Overweight/epidemiology , Folic Acid , Body Mass Index , Prospective Studies , Obesity/complications , Obesity/epidemiology , Dietary Supplements , Risk Factors
19.
Biotechnol Genet Eng Rev ; : 1-15, 2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36703541

ABSTRACT

The long non-coding RNA LINC02489 has been shown to be significantly downregulated in advanced ovarian cancer (OC). However, the function of LINC02489 remains unknown. This study aims to explain the role and mechanism of LINC02489 in OC. The expression of LINC02489 was examined by qRT-PCR in primary OC tissues. Additionally, MTT, wound healing, transwell, and flow cytometry assays were used to analyze the function of LINC02489. The mechanism of LINC02489 in OC was investigated by high-throughput RNA-sequencing, qRT-PCR, western blot, and N6-methyladenosine (m6A) meRIP. A total of 1101 and 827 genes are significantly down-regulated and up-regulated in metastatic and chemoresistant OC tissues. The expression of LINC02489 is decreased in metastatic and chemoresistant OC tissues compared with the primary OC tissues (p < 0.05). Overexpression of LINC02489 inhibits proliferation, invasion, and migration of drug-resistant OC cells. In the LINC02489 overexpressed chemoresistant SKOV3 cells, the m6A modified LINC02489 is significantly up-regulated. Furthermore, the expression of PKNOX2 is increased during overexpression of LINC02489, while the expression of PTEN and mTOR plummets. This study demonstrates that LINC02489 can inhibit the invasion and migration of chemoresistant OC cells by increasing its m6A modification and up-regulating PKNOX2 expression. In addition, LINC02489 regulates the invasion ability of OC cells through the PTEN/mTOR signaling pathway, thereby regulating the sensitivity of SKOV3 cells to paclitaxel. This result provides a potential therapeutic target for chemoresistant OC.

20.
Environ Sci Pollut Res Int ; 30(11): 29844-29858, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36418827

ABSTRACT

Heavy metal ion (HMI) in wastewater is a kind of resource that is wrongly placed. Recovery of heavy metal from lead-acid wastewater desires efficient and reusable functional materials. In this paper, graphene oxide-like with diazanyl groups (GOLA) was synthesized by a nucleophilic substitution reaction of graphene oxide-like with hydroxyl groups (GOLH) with diazane. GOLA exhibited good stability and recyclability in wastewater. The maximal adsorption capacity (qmax) values of GOLA for Pb(II), Cd(II), Cu(II), Ni(II), and Cr(III) ions were 505.80, 401.99, 83.48, 82.29, and 147.77 mg/g, respectively. The equilibrium time of GOLA adsorbing HMIs was 20 min. GOLA was employed to recover lead ions from lead-acid wastewater to give Pb(OH)2 and reusable water. Therefore, this paper provides a useful method of recycling lead from lead-acid wastewater.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Wastewater , Lead , Water Pollutants, Chemical/analysis , Metals, Heavy/analysis , Water , Adsorption , Kinetics , Hydrogen-Ion Concentration
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