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Yan-Hua Sha,1 Song-Ling Cao,1 Lu Zhang,2 Li-Sha Lai,2 Pei-Feng Ke,1 Ke-Wei Yu,1 Xiu-Zhu Fang,2 Ren-Tang Deng,2 Ze-Min Wan,1 Xiao-Bin Wu,1 Guang Han,1 Yu-Bang Jie,2 Lan-Lan Song,2 Xian-Zhang Huang,1 Wen-Jin Fu2 1Department of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Clinical Laboratory, Houjie Hospital of Guangdong Medical University, Dongguan, Guangdong, People’s Republic of ChinaCorrespondence: Xian-Zhang Huang, Department of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China, Email huangxz020@163.com; Wen-Jin Fu, Clinical Laboratory, Houjie Hospital of Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China, Email 332689892@qq.comIntroduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated.Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs.Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) ≥ 1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD.Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.Keywords: exosome, cicrRNA, diabetic nephropathy, high glucose, microarray

Background: Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy., Objective: We aimed to explore the key genes and pathways that affect the rate progression of DN., Methods: Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6)., Results: Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway., Conclusion: Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN., (© 2024. The Author(s).)

Background: Diabetes mellitus (DM) is a prevalent chronic condition that influences spine surgery outcomes. The impact of type Ⅰ and type Ⅱ DM on adverse postoperative outcomes, mortality, prolonged length of stay (LOS), and increased in-hospital costs following cervical fusion surgery remains unclear in the past decade. This study aims to determine the specific effect of different classifications of DM on postoperative complications in patients experiencing cervical fusion surgery., Method: Data from the Nationwide Inpatient Sample database was acquired between 2010 and 2019. Patients experiencing cervical fusion were included and classified as having type I DM, type II DM, or neither. Patient demographics, hospital characteristics, operative variables, comorbidities, complications, and other postoperative outcomes were assessed. Propensity score matching analysis was used to balance baseline differences. Univariate and multivariate logistic regression were employed to determine the risk of postoperative outcomes in patients with different classifications of DM., Result: A total of 267,174 cervical spinal fusions were identified (224,255 were patients without DM, 670 patients had type I DM, and 42,249 patients had type II DM). After propensity score matching, the multivariate analysis of non-DM and type I DM patients shows significant difference in pneumonia (P=0.020). However, type Ⅱ DM served as an independent predictor of an increased risk of acute cerebrovascular disease (P=0.001), acute myocardial infarction (P=0.014), pneumonia (P=0.045), continuous trauma ventilation (P=0.016), chest pain (P<0.001), urinary tract infection (P<0.001), transfusion (P=0.005) and dysphagia (P=0.013), prolonged LOS (P<0.001) and increased costs (P=0.008)., Conclusion: Using non-DM patients as a reference, type II DM group demonstrated a higher risk of postoperative complications than type I DM group among patients receiving cervical fusion surgery. This vital distinction could enhance risk stratification and guidance for patients diagnosed with DM before cervical fusion surgery., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA)., Materials and Methods: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates. In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates., Results: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0-40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%-86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%-19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%-11.4%), 26.8% (95% CI: 2.7%-44.9%), and 51.2% (95% CI: 0%-79.1%), respectively. No significant differences were observed in the disease progression ( P = 0.829) or complete tumor disappearance ( P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355)., Conclusion: Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Background: AF is a global health concern, with systemic complications including renal dysfunction. This systematic review and meta-analysis compares the effects of rivaroxaban, a Factor Xa inhibitor, and vitamin K antagonists (VKAs) on renal outcomes in AF patients., Methods: The study protocol is registered in PROSPERO (ID: CRD42023462756). We systematically searched the PubMed, Embase and Cochrane Library databases from 1 January 2017 to 30 June 2023 for real-world studies comparing the effects of rivaroxaban and VKAs on renal outcomes in AF patients, including acute kidney injury, a .30% decrease in estimated glomerular filtration rate, doubling of serum creatinine and worsening renal function. Subgroup analyses targeted diabetes, pre-existing kidney disease, the elderly (age .65 years) and Asian populations. The risk of bias was assessed used the Robins-I tool. HRs and 95% CIs were synthesised through a random-effects model. Two sensitivity analyses were performed, using a fixed-effects model and excluding conference abstracts., Results: We identified 1,666 records. After screening, 14 studies comparing rivaroxaban and VKAs were included. Rivaroxaban exhibited superiority over VKAs in preventing: acute kidney injury (HR 0.68; 95% CI [0.61.0.77]; p<0.00001); a .30% decrease in estimated glomerular filtration rate (HR 0.71; 95% CI [0.60.0.84]; p<0.0001); doubling of serum creatinine (HR 0.50; 95% CI [0.36.0.70]; p<0.0001); and worsening renal function (HR 0.56; 95% CI [0.45.0.69]; p<0.00001). Subgroup and sensitivity analyses consistently confirmed rivaroxaban's favourable effects on renal outcomes in diabetes, pre-existing kidney disease, the elderly and Asian populations., Conclusion: Our findings support the preference of rivaroxaban over VKAs for renal outcomes in AF. The findings endorse rivaroxaban as the preferred anticoagulant to mitigate renal complications, offering clinicians valuable insights for tailored strategies., Competing Interests: Disclosure: PPD has received honoraria for scientific presentations from Bayer, Boehringer Ingelheim, Astra Zeneca, Novartis, Medtronic, Abbott, Daiichi Sankyo, Pfizer, Sanofi and Merck Serono. THHQ has received honoraria for scientific presentations from Bayer, Boehringer Ingelheim, Astra Zeneca and Menarini. HPM has received honoraria for scientific presentations from Bayer, Servier, Boehringer Ingelheim, Astra Zeneca, Boston Scientific, Medtronic, Abbott, Elixir, Biotronic and Merck Serono. SHV has received honoraria for scientific presentations from Bayer, Boehringer Ingelheim, Astra Zeneca, Menarini, Servier, Merck Serono, Dr. Reddy’s Laboratories and Gedeon Richter. HNH has received honoraria for scientific presentations from Bayer, Boehringer Ingelheim, Pfizer, Merck Serono, Novartis, Sanofi an Roche. NVQ has received honoraria for scientific presentations from Bayer, Boehringer Ingelheim and Pfizer. MTT has received honoraria for scientific presentations from Bayer, Boehringer Ingelheim, Pfizer, Merck Serono and Medtronic. SLC has received honoraria for scientific presentations from Bayer, Boehringer Ingelheim, Astra Zeneca, Novartis, Medtronic, Viatris, Daiichi Sankyo, Pfizer, Otsuka and Merck Serono. All other authors have no conflicts of interest to declare. Funding: The article processing fee was funded by Bayer Vietnam. The funder had no role in the design, execution, interpretation or writing of the study. Data availability: The data are available from the corresponding author upon reasonable request. Trial registration number: CRD42023462756, (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

Introduction: Fine needle aspiration (FNA) biopsy is a widely accepted method for diagnosing thyroid nodules. However, the influence of maximum diameter (MD) of ACR TIRADS 5 (TR5) thyroid nodules on the FNA outcomes remains debated. This study examined the influence of MD on the FNA outcomes and investigated the optimal MD threshold for FNA in TR5 nodules., Methods: We conducted a retrospective analysis of 280 TR5 thyroid nodules from 226 patients who underwent FNA from January to June 2022 in our department. Probably malignant (PM) group was defined as Bethesda V in cytopathology with confirmed BRAF V600E mutation or Bethesda VI, the other cytopathology outcomes were defined as probably benign (PB) group. We examined factors influencing malignant cytopathology outcomes and determined the optimal MD threshold for FNA in TR5 nodules using logistic regression and restricted cubic spline (RCS) analysis., Results: Among these nodules, 58.2% (163/280) had PM outcomes. The PM group had a significantly larger MD than the PB group [6.5mm (range 5.0-8.4) vs. 5.3mm (range 4.0-7.0), p < 0.001]. In multivariate logistic regression fully adjusted for confounders, MD was significantly associated with PM outcomes [odds ratio 1.16, 95%CI 1.05-1.31; p = 0.042]. The highest quartile of MD had a greater likelihood of PM outcomes compared to the lowest quartile [odds ratio 4.71, 95% CI 1.97-11.69, p = 0.001]. The RCS analysis identified 6.2 mm as the optimal MD threshold for FNA in TR5 nodules., Conclusion: MD significantly affects the probability of malignant outcomes in FNA of TR5 thyroid nodules. A MD threshold of ≥6.2mm is suggested for FNA in these nodules., 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 © 2024 Cao, Shi, Niu, Zhao, Wei, Wu, Peng, Li and Yu.)

Total volatile basic nitrogen (TVB-N) is a vital indicator for assessing seafood freshness and edibility. Rapid on-site detection of volatile basic nitrogen (VBN) is of significant importance for food safety monitoring. In this study, highly luminescent self-assembled copper nanoclusters (Cu NCs@ p -MBA), synthesized using p -mercaptobenzoic acid ( p -MBA) as the ligand, were utilized for the sensitive detection of VBNs. Under acidic conditions, Cu NCs@ p -MBA formed compact and well-organized nanosheets through noncovalent interactions, accompanied by intense orange fluorescence emission (651 nm). The benzene carboxylic acid part of Cu NCs@ p -MBA provided the driving force for supramolecular assembly and exhibited a strong affinity for amines, particularly low-molecular-weight amines such as ammonia (NH 3 ) and trimethylamine (TMA). The quantitative determination of NH 3 and TMA showed the detection limits as low as 0.33 and 0.81 ppm, respectively. Cu NCs@ p -MBA also demonstrated good responsiveness to putrescine and histamine. Through density functional theory (DFT) calculations and molecular dynamics (MD) simulations, the precise atomic structure, assembly structure, luminescent properties, and reaction processes of Cu NCs@ p -MBA were studied, revealing the sensing mechanism of Cu NCs@ p -MBA for highly sensitive detection of VBNs. Based on the self-assembled Cu NCs@ p -MBA nanosheets, portable fluorescent labels were developed for semiquantitative, visual, and real-time monitoring of seafood freshness. Therefore, this study exemplified the high sensitivity of self-assembly induced emission (SAIE)-type Cu NCs@ p -MBA for VBNs sensing, offering an efficient solution for on-site monitoring of seafood freshness.

Background: The study aimed to investigate the diagnostic value of lupus-related pattern recognition receptors (PRRs) genes in peripheral blood mononuclear cells (PBMCs) and monocytes (MONs) for lupus nephritis (LN)., Methods: PBMCs were isolated from a cohort with 37 LN patients and 39 healthy controls (HCs), and MONs were derived from another cohort with 70 LN patients and 66 HCs. Q-PCR was used to measure the mRNA levels of CGAS, IFNB1, AIM2, IL1Β, NLRC4, NLRP3, NLRP12 and ZBP1 in the PBMCs and MONs. The Mann-Whitney U test was used to compare the data in LN patients and HCs. Eleven GEO datasets of SLE/LN were used to perform differentially expressed genes (DEGs) analysis to these PRR genes. Receiver operating characteristic (ROC) curve analysis was employed to assess the performance of individual genes or the disease prediction model established by combining multiple genes in LN diagnosis. Spearman correlation method was done to analyze the correlation between these PRRs and other clinical characteristics., Results: The mRNA levels of five genes (AIM2, NLRC4, IL1B, NLRP12 and ZBP1) in PBMCs, and seven genes (CGAS, IFNB1, AIM2, IL1B, NLRP3, NLRP12 and ZBP1) in MONs of LN patients were significantly higher than those of HCs (P < 0.05). DEGs analysis based on the GEO datasets showed that ZBP1, AIM2 and IL1B were significantly increased in several datasets. The ROC curve analysis indicated that the area under curve (AUC) of the LN prediction models derived from PBMCs or MONs were 0.82 or 0.91 respectively. In addition, the expression levels of these PRRs were correlated with other clinical features in LN patients, including Anti-Sm, ESR, serum Cr, and C3., Conclusion: Our study suggests that these lupus-related PRRs might be served as potential biomarkers of LN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Thermal ablation (TA) is a safe and effective treatment for benign thyroid nodules (BTNs). However, there has been no consensus on the optimal maximum diameter (MD) of BTNs for TA. This study aimed to identify the optimal MD of BTNs for TA based on complete disappearance rate after TA., Materials and Methods: This retrospective study included 639 BTNs treated with TA from June 2014 to January 2022. The complete disappearance rate of BTNs after TA was summarized, related influencing factors were explored, and the optimal MD of BTNs for TA was identified., Results: At the final follow-up (median: 40 months, range: 24-95 months), the overall volume reduction rate was 95.4 ± 9.0%, and 50.5% of the BTNs (323/639) completely disappeared. The MD was significantly negatively correlated with complete disappearance (odds ratio 0.89, 95% confidence interval 0.87-0.92; p  < 0.001). Calcification, comet-tail artifacts, multilocular cysts, and composition of BTNs, as well as diabetes were negatively correlated with complete disappearance. Restricted cubic spline indicated that an MD of 25.0 mm was the optimal threshold of BTNs for TA, which was confirmed by subgroup logistic regression analysis. Compared with BTNs with MD ≤ 25.0 mm, those with MD > 25.0 mm had a greater complication rate (6.5% vs. 2.4%, p  = 0.012)., Conclusions: The MD of BTNs was negatively correlated with complete disappearance after TA; an MD > 25.0 mm indicated a reduced likelihood of complete disappearance compared with an MD ≤ 25.0 mm. An MD of 25.0 mm is an appropriate threshold of BTNs for TA on the basis of complete disappearance rate.

Objective: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms., Methods: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated., Results: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change ( p  = 0.287). From the third month, both maximum diameter and volume significantly decreased ( p  < 0.005 for all). Volume reduction rates remained stable at one and three months ( p  = 0.389 and 0.06, respectively) but increased significantly thereafter ( p  < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment ( p  > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively., Conclusions: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

Objective: To evaluate the complications associated with microwave ablation (MWA) in treating persistent/recurrent hyperparathyroidism (HPT) post-surgical or ablative treatments., Materials and Methods: From January 2015 to December 2022, 87 persistent/recurrent HPT patients (primary HPT [PHPT]: secondary HPT [SHPT] = 13:74) who underwent MWA after surgical or ablative treatment were studied. Grouping was based on ablation order (initial vs. re-MWA), prior treatment (parathyroidectomy [PTX] vs. MWA), and etiology (PHPT vs. SHPT). The study focused on documenting and comparing treatment complications and analyzing major complication risk factors., Result: Among the 87 patients, the overall complication rate was 17.6% (15/87), with major complications at 13.8% (12/87) and minor complications at 3.4% (3/87). Major complications included recurrent laryngeal nerve (RLN) palsy (12.6%) and Horner syndrome (1.1%), while minor complications were limited to hematoma (3.4%). Severe hypocalcemia noted in 21.6% of SHPT patients. No significant differences in major complication rates were observed between initial and re-MWA groups (10.7% vs. 13.8%, p  = 0.455), PTX and MWA groups (12.5% vs. 15.4%, p  = 0.770), or PHPT and SHPT groups (15.4% vs. 13.5%, p  > 0.999). Risk factors for RLN palsy included ablation of superior and large parathyroid glands (>1.7 cm). All patients recovered spontaneously except for one with permanent RLN palsy in the PTX group (2.1%)., Conclusion: Complication rates for MWA post-surgical or ablative treatments were comparable to initial MWA rates. Most complications were transient, indicating MWA as a viable and safe treatment option for persistent/recurrent HPT patients.

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet β cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic β cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-β1, TNFα, and IL-1β. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Exposure to di-(2-ethylhexyl) phthalate (DEHP) can cause neurotoxicity but the mechanism is not clear. Blood brain barrier (BBB) is one of the most important tissues to protect the brain. However, whether DEHP can disrupt the BBB or not remains unclear. The objective of this study is to investigate the potential effects of subchronic DEHP exposure on BBB integrity and discuss the role of BBB in DEHP inducible neurotoxicity with an emphasis on neuroinflammatory responses. Male adult C57BL/6J mice were orally administered with vehicle or 200 or 750 mg/kg/day DEHP for 90 days. Subchronic exposure to high-dose DEHP increased water intake but decreased body weight and brain weight. The concentrations of DEHP metabolites increased in serum from all DEHP-exposed groups while increased in brain only from the high-dose group. DEHP induced neurobehavioural alterations and damaged hippocampal neurons. DEHP increased BBB permeability by Evans blue (EB) extravasation and decreased tight junction proteins (ZO-1, occludin, and claudin-5) while presenting a neuroinflammatory feature characterized by the upregulated inflammatory mediators TNF-α and the NLRP3/caspase-1/IL-1β inflammasome pathway. Our data provide new insights into neurotoxicity caused by subchronic DEHP exposure, which is probably involved in BBB dysfunction and neuroinflammatory responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear., Methods: Cdk5 kinase activity was measured by [γ- 32 P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa., Results: P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression., Conclusion: p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

Aim: To evaluate whether platelet-to-albumin ratio (PAR) can predict diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM). Materials & methods: A total of 140 patients with T2DM and 40 healthy individuals were enrolled retrospectively. T2DM patients were divided into three groups based on the urinary albumin-to-creatinine ratio, PAR was compared and receiver operating characteristic curve was constructed to evaluate the predictive value of PAR in DN in T2DM. Results: There was a significant increase of PAR in DN among T2DM patients and PAR was positively correlated with serum creatinine, retinol-conjugated protein and β 2 -microglobulin. Moreover, PAR was a risk factor for DN in T2DM patients, which predicted DN in T2DM with high sensitivity and specificity. Conclusion: PAR can be a potential candidate to predict DN in T2DM.

Objective: To study the safety of improved hydrodissection based on the periparathyroidal fascial space during microwave ablation (MWA) for secondary hyperparathyroidism (SHPT)., Materials and Methods: Data from 337 patients (162 males and 175 females; mean age, 50.8 ± 12.8 [range, 16-84] years) who underwent MWA for SHPT were retrospectively reviewed. Among them, 177 patients underwent traditional hydrodissection (traditional group) and 160 patients underwent improved hydrodissection based on periparathyroidal fascial spaces (improved group). Safety enhancement was analyzed by comparing the complications between the two groups. The characteristics of the hydrodissected fascial spaces, complications, and the follow-up results were recorded. The baseline data, clinical parameters, laboratory indices and characteristics of SHPT lesions were analyzed to assess the risk factors associated with hoarseness., Results: Hydrodissection was successfully performed in all the enrolled patients according to the protocol. Six periparathyroid fascial spaces were hydrodissected, depending on the location of the SHPT lesions. The incidence of hoarseness due to recurrent laryngeal nerve injury, the most common complication of thermal ablation for SHPT lesions, was lower in the improved group than in the traditional group (6.9% vs. 13.0%, p  = 0.044). The median hoarseness recovery time in the improved group was shorter than that in the traditional group (2 vs. 6 months, p  < 0.001). There was no difference in technical efficiency between the two groups (improved group vs. traditional group: 75.0% vs. 70.6%; p  > 0.05)., Conclusions: Compared with traditional hydrodissection, improved hydrodissection based on periparathyroidal fascial spaces could enhance safety during MWA for SHPT.

Quinazoline and its derivatives have drawn much attention in the development of potential antitumor agents. Here, we synthesized a series of 1,2,3-triazole derivatives of quinazoline at the C6 position and evaluated for their cytotoxic activity in various human cancer cell lines. We found that compound 5a was the most cytotoxic to HCT-116 cells (IC 50 , 0.36 μM). Target profiling found that 5a directly binds to both the autophagy-associated protein SQSTM1/P62 and the E3 ligase RNF168, promoting their interaction. Consistently, 5a treatment induces a decrease in RNF168-mediated H2A ubiquitination and compromises homologous recombination-mediated DNA repair, thus increasing the sensitivity of HCT-116 to X-ray radiation. Moreover, 5a suppressed xenografted tumor growth in mice in a dose-dependent manner. Taken together, the 1,2,3-triazole derivative of quinazoline 5a may serve as a novel compound for tumor therapy based on its role in promoting a P62/RNF168 interaction.

Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD), during which hyperglycemia is composed of the major force for the deterioration to end-stage renal disease (ESRD). However, the underlying mechanism triggering the effect of hyperglycemia on DN is not very clear and the clinically available drug for hyperglycemia-induced DN is in need of urgent development. Here, we found that high glucose (HG) increased the activity of cyclin-dependent kinase 5 (CDK5) dependent on P35/25 and which upregulated the oxidative stress and apoptosis of mouse podocytes (MPC-5). TFP5, a 25-amino acid peptide inhibiting CDK5 activity, decreased the secretion of inflammation cytokines in serum and kidney, and effectively protected the kidney function in db/db mouse from hyperglycemia-induced kidney injuries. In addition, TFP5 treatment decreased HG-induced oxidative stress and cell apoptosis in MPC-5 cells and kidney tissue of db/db mouse. The principal component analysis (PCA) of RNA-seq data showed that MPC-5 cell cultured under HG, was well discriminated from that under low glucose (LG) conditions, indicating the profound influence of HG on the properties of podocytes. Furthermore, we found that HG significantly decreased the level of NGF and Sirt1, both of which correlated with CDK5 activity. Furthermore, knockdown of NGF was correlated with the decreased expression of Sirt1 while NGF overexpression leads to upregulated Sirt1 and decreased oxidative stress and apoptosis in MPC-5 cells, indicating the positive regulation between NGF and Sirt1 in podocytes. Finally, we found that K252a, an inhibitor of NGF treatment could undermine the protective role of TFP5 on hyperglycemia-induced DN in db/db mouse model. In conclusion, the CDK5-NGF/Sirt1 regulating axis may be the novel pathway to prevent DN progression and TFP5 may be a promising compound to improved hyperglycemia induced DN., 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 © 2022 Cao, Luo, Gao, Lan, Liu, Li, Bao, E., Ma, Zhang, Yang, Bao and Zheng.)

The risk of chronic hepatitis B (CHB) infection is often affected by polyunsaturated fatty acids (PUFAs) metabolism which is strongly influenced by single nucleotide polymorphisms (SNPs) within the PUFA metabolic pathway. Given this, we designed this study to determine the relationship between specific polymorphisms within fatty acid desaturase 2 (FADS2), a key enzyme in PUFA metabolism, and CHB infection. We completed this evaluation using a case-control study comprising 230 CHB patients and 234 unrelated healthy controls in which the genetic relationships between three previously identified SNPs, isolated via mass spectrometry, and CHB infection. Our data revealed that none of these three SNPs (rs174568, rs174601, and rs2727270) were significantly associated with susceptibility to CHB infection when compared to healthy controls. However, when we stratified our cohort by sex, male subjects with the TC genotype for FADS2 exhibited a decreased risk for CHB infection (OR = 0.62, 95%CI = 0.39-0.96; OR = 0.64, 95%CI = 0.41-1.00; OR = 0.57, 95%CI = 0.36-0.90). Furthermore, age stratification revealed that both the T allele and the TC genotypes for each of the three target SNPs were less common in Chinese CHB cases in people younger than 50 years old. Correlation analysis also revealed that there was no statistically significant relationship between these three SNPs and HBV-DNA replication or hepatitis B surface antigen (HBsAg) levels. Thus, our data suggests that rs174568, rs174601, and rs2727270 may affect the CHB outcomes in various age or sex subgroups, suggesting that they may be useful predictive or diagnostic biomarkers of CHB infection in some populations., (Copyright © 2022. Published by Elsevier B.V.)

Background and Aims: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear., Approach and Results: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR., Conclusions: We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Although current computational biology software is available and has prompted the development of enzyme-substrates simulation, they are difficult to install and inconvenient to use. This makes the time-consuming and error-prone process. By far there is still a lack of a complete tool which can provide a one-stop service for the enzyme-substrates simulation process. Hence, in this study, several computational biology software was extended development and integrated as a website toolbox named Atomevo. The Atomevo is a free web server providing a user-friendly interface for enzyme-substrates simulation: (1) protein homologous modeling; (2) parallel docking module of Autodock Vina 1.2; (3) automatic modeling builder for Gromacs molecular dynamics simulation package; and (4) Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA) analysis module for receptor-ligand binding affinity analysis. We officially launched the web server and provided instructions through a case for the design and simulation of Candida antarctica lipase B (CalB) fusion protein called Maltose Binding Protein-Thioredoxin A-Candida antarctica lipase B (MBP-TrxA-CalB)., (© 2022. The Author(s).)

Objectives: To evaluate the accuracy and safety of measurements of transcutaneous carbon dioxide partial pressure (TcPCO 2 ) and transcutaneous oxygen partial pressure (TcPO 2 ) at electrode temperatures lower than the value used in clinical practice in very low birth weight infants., Methods: A total of 45 very low birth weight infants were enrolled. TcPCO 2 and TcPO 2 measurements were performed in these infants. Two transcutaneous monitors were placed simultaneously for each subject. One electrode was set and maintained at 42℃ used in clinical practice for neonates (control group), and the other was successively set at 38℃, 39℃, 40°C, and 41℃ (experimental group). The paired t -test was used to compare the measurement results between the groups. A Pearson correlation analysis was used to analyze the correlation between the measurement results of the experimental group and control group, and between the measurement results of experimental group and arterial blood gas parameters., Results: There was no significant difference in TcPCO 2 between each experimental subgroup (38-41℃) and the control group. TcPCO 2 in each experimental subgroup (38-41℃) was strongly positively correlated with TcPCO 2 in the control group ( r >0.9, P <0.05) and arterial carbon dioxide partial pressure ( r >0.8, P <0.05). There were significant differences in TcPO 2 between each experimental subgroup (38-41℃) and the control group ( P <0.05), but TcPO 2 in each experimental subgroup (38-41℃) was positively correlated with TcPO 2 in the control group ( r =0.493-0.574, P <0.05) and arterial oxygen partial pressure ( r =0.324-0.399, P <0.05). No skin injury occurred during transcutaneous measurements at all electrode temperatures., Conclusions: Lower electrode temperatures (38-41℃) can accurately measure blood carbon dioxide partial pressure in very low birth weight infants, and thus can be used to replace the electrode temperature of 42°C. Transcutaneous measurements at the lower electrode temperatures may be helpful for understanding the changing trend of blood oxygen partial pressure.

Background: The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one-carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one-carbon metabolic pathway and CHB infection., Methods: A case-control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry., Results: Three SNPs, comprising rs10717122 and rs2229717 in serine hydroxymethyltransferase1/2 (SHMT2) and rs585800 in betaine-homocysteine S-methyltransferase (BHMT), were associated with the risk of CHB. Patients with DEL allele, DEL.DEL and DEL.T genotypes of rs10717122 had a 1.40-, 2.00- and 1.83-fold increased risk for CHB, respectively. Cases inheriting TA genotype of rs585800 had a 2.19-fold risk for CHB infection. The T allele of rs2229717 was less represented in the CHB cases (odds ratio = 0.66, 95% confidence interval = 0.48-0.92). The T allele of rs2229717 was less in patients with a low hepatitis B virus-DNA level compared to the control group (odds ratio = 0.49, 95% confidence interval = 0.25-0.97) and TT genotype of rs2229717 had a significant correlation with hepatitis B surface antigen level (p = 0.0195). Further gene-gene interaction analysis showed that subjects carrying the rs10717122 DEL.DEL/DEL.T and rs585800 TT/TA genotypes had a 2.74-fold increased risk of CHB., Conclusions: The results of the present study suggest that rs10717122, rs585800 and rs2229717 and gene-gene interactions of rs10717122 and rs585800 affect the outcome of CHB infection, at the same time as indicating their usefulness as a predictive and diagnostic biomarker of CHB infection., (© 2021 John Wiley & Sons, Ltd.)

In this current experiment, by applying the mixed-ligand synthesis method, two coordination polymers (CPs) containing Co(II) were created triumphantly with reaction between 1,3-bis(1-imidazoly)benzene (mbib) and Co(II) salts with the aid of diverse carboxylic ligands, and their chemical formulae are [Co 3 (opda) 3 (mbib) 4 (H 2 O) 4 ]·2H 2 O ( 1 , H 2 opda is 1,2-phenylenediacetic acid) and [Co(mpda)(mbib)]·H 2 O ( 2 , H 2 mpda is 1,3-phenylenediacetic acid). The two compounds' magnetic performances suggest that between the adjacent metal ions, there present the antiferromagnetic coupling. The evaluation of their treatment activity against chronic subdural hematoma was carried out and the relevant mechanism was studied simultaneously. Firstly, before the treatment of compound, the chronic subdural hematoma was generated. Furthermore, the enzyme-linked immunosorbent assay detection kit was implemented and in hematoma capsule, the anti-inflammatory cytokines level and pro-inflammatory cytokines level was detected. Additionally, the cytotoxicity of compounds 1 and 2 on the normal human cells was determined with Cell Counting Kit-8 assay. Above all, we proved compound 1 decreased the pro-inflammatory cytokines content and increased the anti-inflammatory cytokines content in the hematoma capsule, which is much stronger than that of compound 2 . Both compounds 1 and 2 showed no cytotoxicity on the normal human cells., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Normothermic machine perfusion (NMP) could be beneficial for organ retrieval from donors after cardiac death (DCD). Activating transcription factor 6 (ATF6) was recently shown to mitigate liver ischemia/reperfusion injury and confer protection. The aims of this study were to assess the implication of ATF6 in liver retrieval from DCD rat livers with NMP and explore the effect of pharmacologic ATF-6 activation on liver retrieval. Methods: The livers from DCD rats were exposed to 30 min of warm ischemia and 8 h cold preservation followed by 2 h NMP with or without an ATF6 activator in the perfusate. Perfusates and livers were harvested to detect ATF6 expression, liver function, and inflammation. Results: DCD livers with NMP were associated with ATF6 overexpression and activation based on IHC and WB ( P < 0.05). The ATF6 activator downregulated perfusate aminotransferases, decreased the Suzuki score, downregulated CD68 and MPO based on IHC, induced the expression of cytochrome c in mitochondria and inhibited the expression of cytochrome c in cytoplasm based on WB, reduced TNFα and IL-6 levels based on ELISA, decreased levels of MDA, GSSG and ATP, and increased SOD activity and GSH levels in the perfused livers ( P < 0.05). Conclusion: ATF6 is important for liver retrieval, and an exogenous ATF6 activator accelerates liver retrieval from DCD rats in an ex vivo NMP model., 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 © 2021 Cheng, Shi, Jin, Shi, Liu, Zhang, Cao, Yang, Guo and Zhang.)

DNA double-strand break (DSB) repair by homologous recombination (HR) is essential for ensuring genome stability. Abnormal spindle-like microcephaly-associated ( ASPM ) gene encodes a spindle protein that is commonly implicated in primary microcephaly. We found that ASPM is recruited to sites of DNA damage in a PARP2-dependent manner. ASPM interacts with BRCA1 and its E3 ligase HERC2, preventing HERC2 from accessing to BRCA1 and ensuring BRCA1 stability. Inhibition of ASPM expression promotes HERC2-mediated BRCA1 degradation, compromises HR repair efficiency and chromosome stability, and sensitizes cancer cells to ionizing radiation. Moreover, we observed a synergistic effect between ASPM and PARP inhibition in killing cancer cells. This research has uncovered a novel function for ASPM in facilitating HR-mediated repair of DSBs by ensuring BRCA1 stability. ASPM might constitute a promising target for synthetic lethality-based cancer therapy., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

An efficient technique using citric acid and glucose based natural deep eutectic solvent (G-C-NADES) was developed to obtain ultrahigh deamidated wheat gluten (UDWG) (deamidation degree (DD) > 90%). FTIR and 1 H NMR indicated intensive hydrogen bonds (HBs) in G-C-NADES supermolecules. Quantum chemical calculations and molecular dynamic simulations demonstrated that 10 wt % diluted G-C-NADES still had a myriad of HBs. Physicochemical results showed UDWG had DD up to 92.45% after G-C-NADES deamidation, that is, 22% higher than citric-acid-DWG with a weak degree of hydrolysis (1.75%). Conformational characterization demonstrated the obvious conversion from α-helix to β-sheet via FTIR, the least amount of disulfide bonds by Raman spectra, and more exposure of tryptophan residues by fluorescence measurement for UDWG. It is proven that enhanced accessible conformation of WG reached with HBs of G-C-NADESs could contribute to the improvement on nucleophilic attack of deamidation, declaring that G-C-NADES might be a potential solvent for obtaining an ultrahigh deamidation for WG to successfully guarantee the safety of wheat gluten based cereal food regarding to lowering its allergy.

Background: With the modernization of society and transportation in the last decades in China, the incidence of high-energy trauma increased sharply in China, including that of acetabular fractures., Aim: To establish different finite element models for acetabular posterior column fractures involving the quadrilateral area of the acetabulum., Methods: The three-dimensional models of the normal and fractured pelvis and the five internal fixations were established using the computed tomography data of the pelvis of a living volunteer. After the vertebral body model was inserted in the way of origin matching and all cancellous bones were copied using the duplicated cancellous bone model as the subtractive entity, the Boolean operation was performed on the pelvis model to obtain the model of the complete pelvis cortical and cancellous bones., Results: In the standing position, the maximum stress was 46.21 MPa. In the sitting position, the sacrum bore the simulated gravity load at the upper end. When comparing the five fixations, there were no significant differences in the stress mean values among groups (sitting: P = 0.9794; standing: P = 0.9741). In terms of displacement, the average displacement of the internal iliac plate group was smaller than that of the spring plate group ( P = 0.002), and no differences were observed between the other pairs of groups (all P > 0.05). In the standing position, there were no significant differences in the mean value of displacement among the groups ( P = 0.2985). It can be seen from the stress nephogram of the internal fixations in different positions that the stress of the internal fixation was mainly concentrated in the fracture segment., Conclusion: There were no significant differences among the fixations for acetabular posterior column fractures involving the quadrilateral area of the acetabulum., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA., Methods: Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications., Results: We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ2 = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ2 = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5-1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4-1740.6mL]) (χ2 = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8-83.0], Rivaroxaban: 81.0 [79.3-83.0], χ2 = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0-92.0], Rivaroxaban: 91.5 [88.3-92.8], χ2 = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ2 = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ2 = 1.13, P = 0.29)., Conclusion: In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs., Trial Registration: Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284., (Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Deep eutectic solvents (DESs) have attracted an increasing attention in the fields of biocatalysis and biopolymer processing. In this study, papain immobilized on choline chloride- lactic acid (ChCl-Lac) DES-treated chitosan exhibited excellent thermostability as compared to the free enzyme. The properties of native or DES-treated chitosan and immobilized enzyme were characterized by FT-IR, SEM, surface area and pore property analysis. Like the common enzyme immobilization, papain immobilized on DES-treated chitosan resulted in a lower catalytic efficiency and a higher thermostability than the free enzyme due to the restricted diffusion. The results also revealed that DES could control the active group content, thus achieving the appropriate microporous structure of immobilized enzyme. Meanwhile, it could also help to construct the optimal microenvironment by hydrogen-bonding interaction between enzyme, chitosan, and residual DES, which are benefit for maintaining an active conformation and subsequently a high thermostability of papain. Moreover, it was found that trace DES (10 mM) significantly promoted the activity of free papain (145%). Deactivation thermodynamics study showed that the DES could enhance the thermostability of papain especially at high temperature (half-life of 7.4 vs. 3.5 h) because of the increased Gibbs free energy of denaturation. Secondary structure analysis by circular dichroism spectroscopy (CD) agreed well with the activity and thermostability data, further confirming the formation of rigid conformation induced by a specific amount of DES. This work provides a new way of enzyme immobilization synergistically intensified by solvents and supporting materials to achieve better microporous structure and catalytic microenvironment., (Copyright © 2020 Lin, Feng, Pu, Hou and Cao.)

Papain (PA) immobilized onto magnetic nanocrystalline cellulose (PA@MNCC) was successfully fabricated and adopted as an efficient biocatalyst for the synthesis of N-(benzyloxycarbonyl)-alanyl-histidine (Z-Ala-His) dipeptide. Introducing deep eutectic solvents (DESs) as reaction media promoted the synthesis of the Z-Ala-His dipeptide. The effects of reaction conditions on the yield of papain catalytic Z-Ala-His were systematically investigated with the highest yield of 68.4%, which was higher than free papain (63.3%). Besides, this novel PA@MNCC composite can be easily recycled from the reaction system by magnetic forces. In a word, the PA@MNCC composite exhibited great potential for efficient biosynthesis of dipeptide in DESs.

This paper investigates the conformational stability of porcine pancreatic lipase (PPL) in three non-aqueous organic solvents, including dimethyl sulfoxide (DMSO), propylene glycol (PRG), and ethanol (EtOH) through molecular dynamic (MD) simulation. The root mean square deviations (RMSDs), radius of gyration (Rg), solution accessible surface area (SASA), radial distribution function (RDF), hydrogen bond (H-bond), Ramachandran plot analysis, secondary structure, and enzyme substrate affinity of the PPL in the various organic solvents were comparatively investigated. The results showed that the backbone and active pocket RMSD, and hydrophilic ASA of PPL in three solvents increase with the increase in the solvent LogP, while the Rg, hydrophobic ASA, and H-bond between the solvent and PPL decrease. Among the three organic solvents, DMSO acts as a better solvent, in which the PPL can be loose and extended, and retains its native backbone in DMSO compared to PRG and EtOH. Moreover, Ramachandran plot analysis indicated that the PPL structure quality in DMSO was higher than that in PRG and EtOH. Also, the molecular docking results showed that PPL in DMSO exhibited the highest enzyme-substrate affinity., (Copyright © 2020 Chen, Wu, Hao, Liu, He, Jiang, Xiong, Lv, Cao and Zhu.)

Aims: The purpose of study is to evaluate the effect and complication of preoperative short-term daily recombinant human erythropoietin (rhEPO) treatment for blood-saving in patients undergoing unilateral primary total knee arthroplasty (TKA)., Methods: This three-arm randomized clinical trial compared three different rhEPO-based treatment protocols for unilateral primary TKA. Group A: application of daily doses of rhEPO combined with iron supplement starting 3 days before surgery; Group B: application of daily doses of rhEPO combined with iron supplement starting the day of surgery; Group C: iron supplement alone. Perioperative hemoglobin (Hb) level gaps, total perioperative blood loss, reticulocyte levels and treatment-related complications were studied., Results: A total of 102 patients were included (35, 35 and 32 patients in Groups A, B and C, respectively). Total blood loss (TBL) in Groups A, B and C was 490.84, 806.76 and 924.21 ml, respectively. Patients in Group A had a significant lower TBL than Groups B and C (A vs. B: P = 0.010; A vs. C: P < 0.001). There was no difference as for TBL between Groups B and C (P = 0.377). Group A patients had significant smaller Hb decline than Group C on the third and fifth postoperative day (P = 0.049, P = 0.037), as well as than Group B on the fifth postoperative day (P = 0.048). There was no difference as for Hb decline between Groups B and C. No difference was shown in levels of inflammatory biomarkers or blood-saving protocol-related complications among three groups., Conclusions: Daily dose of rhEPO combined with iron supplement administered 3 days before TKA procedures could significantly decrease perioperative blood loss and improve postoperative Hb levels, without significantly elevating risks of complication, when compared with admission of rhEPO on the day of surgery and iron supplement alone. Preoperative daily rhEPO treatment could be a more effective blood-saving protocol in TKA procedures., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Pydiflumetofen is a new generation succinate dehydrogenase inhibitor currently undergoing the process of registration in China for the control of Fusarium head blight in wheat. A resistance risk assessment of Fusarium graminearum to pydiflumetofen was undertaken in this study., Results: A total of 75 pydiflumetofen-resistant mutants were generated through spontaneous selection and displayed high resistance with an average resistance factor (RF) value of 78. Four mutants were generated through UV mutagenesis and displayed very high resistance with an RF value >1000. The sequence analysis results for Sdh genes and fitness studies revealed the existence of four types of mutations. In particular, 32 spontaneous selection mutants (SP mutants) had an arginine (R) to histidine (H) transition at position 86 in FGSdhC, resulting in seriously reduced fitness. Seven SP mutants had an R to cysteine (C) transition at position 86 in FGSdhC, resulting in reduced fitness. Thirty-six SP mutants had an alanine (A) to valine (V) transition at position 83 in FGSdhC and had no fitness penalties. The efficacy of pydiflumetofen towards a mutant carrying A83V in FGSdhC in vivo was significantly decreased at 42.7%. Four UV mutants had no mutations on all Sdh genes and no fitness penalties. Cross-resistance among boscalid, fluopyram and pydiflumetofen was observed., Conclusion: Sdhc mutations were found and other target site resistance may be present in laboratory PR mutants of F. graminearum. An overall moderate risk of resistance development in F. graminearum was recommended for pydiflumetofen. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Intestinal mucosal immunity plays a vital role against Vibrio mimicus infection because it is an enteric pathogen causing serious vibriosis in fish. In the previous studies, we developed an oral double-targeted DNA vaccine of V. mimicus and demonstrated that the vaccine could elicit significantly higher intestinal mucosal immune response than did naked DNA vaccine. But, little is known underlying regulatory molecular mechanisms of the enhanced intestinal mucosal immunity. Here the transcriptome and proteome in the intestines of the grass carps immunized or not with the double-targeted DNA vaccine were investigated by using RNA-seq and iTRAQ-coupled LC-MS/MS. Compared with the control group, a total of 5339 differentially expressed genes (DEGs) and 1173 differentially expressed proteins (DEPs) were identified in the immunized fish intestines. Subsequently, the integrated analysis between transcriptome and proteome data revealed that 250 DEPs were matched with the corresponding DEGs (named associated DEPs/DEGs) at both transcriptome and proteome levels. Fifty of all the associated DEPs/DEGs were immune-related and mainly enriched in phagosome, antigen-processing and presentation, complement and coagulation cascades, NLRs and MAPK signaling pathways via Gene Ontology and KEGG pathway analyses, which suggested the coordination of the five activated pathways was essential to the enhanced intestinal mucosal immune response in the immunized fish. The protein-protein interaction analysis showed that 60 of the 63 immune-related DEPs to form an integrated network. Additionally, randomly selected DEGs and DEPs were respectively validated by quantitative real-time RT-PCR and multiple reaction monitoring (MRM) assay, indicating that the both RNA-Seq and iTRAQ results in the study were reliable. Overall, our comprehensive transcriptome and proteome data provide some key genes and their protein products for further research on the regulatory molecular mechanisms underlying the enhanced intestinal mucosal immunity., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aims: Hepatic ischemia-reperfusion (I/R) injury remains a major challenge affecting the morbidity and mortality of liver transplantation. Effective strategies to improve liver function after hepatic I/R injury are limited. Six-transmembrane epithelial antigen of the prostate 3 (Steap3), a key regulator of iron uptake, was reported to be involved in immunity and apoptotic processes in various cell types. However, the role of Steap3 in hepatic I/R-induced liver damage remains largely unclear., Approach and Results: In the present study, we found that Steap3 expression was significantly up-regulated in liver tissue from mice subjected to hepatic I/R surgery and primary hepatocytes challenged with hypoxia/reoxygenation insult. Subsequently, global Steap3 knockout (Steap3-KO) mice, hepatocyte-specific Steap3 transgenic (Steap3-HTG) mice, and their corresponding controls were subjected to partial hepatic warm I/R injury. Hepatic histology, the inflammatory response, and apoptosis were monitored to assess liver damage. The molecular mechanisms of Steap3 function were explored in vivo and in vitro. The results demonstrated that, compared with control mice, Steap3-KO mice exhibited alleviated liver damage after hepatic I/R injury, as shown by smaller necrotic areas, lower serum transaminase levels, decreased apoptosis rates, and reduced inflammatory cell infiltration, whereas Steap3-HTG mice had the opposite phenotype. Further molecular experiments showed that Steap3 deficiency could inhibit transforming growth factor-β-activated kinase 1 (TAK1) activation and downstream c-Jun N-terminal kinase (JNK) and p38 signaling during hepatic I/R injury., Conclusions: Steap3 is a mediator of hepatic I/R injury that functions by regulating inflammatory responses as well as apoptosis through TAK1-dependent activation of the JNK/p38 pathways. Targeting hepatocytes, Steap3 may be a promising approach to protect the liver against I/R injury., (© The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.)

Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC 50 value of 2.65 μM. Analyses of the phenotypic changes induced by this compound found a dose-dependent accumulation of HCT-116 cells in sub-G1 phase, indicating that compound 8d might induce apoptosis. Furthermore, we found that 8d triggered mitochondrial membrane potential depolarization, promoted reactive oxygen species formation in HCT-116 cells, and increased the percentage of early and late apoptotic cells. Finally, immunoblotting indicated that 8d increased PARP-1 and caspases 3, 7 and 9 cleavage. These data suggest that compound 8d induces apoptosis via the mitochondrial death pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chitin nanocrystal (ChiNC) was fabricated based on p-toluenesulfonic acid -choline chloride deep eutectic solvent treatment. The obtained ChiNC was about 12-44 nm in width and 206-399 nm in length. The crystalline structure and the functional groups of ChiNC were maintained during the preparation process. Moreover, porcine pancreas lipase (PPL) was successfully immobilized onto the ChiNC to form the immobilized PPL (PPL@ChiNC). The resulting PPL@ChiNC has enzyme loading and activity recovery of 35.6 mg/g and 82.5%, respectively. The thermal stability, pH and temperature adaptabilities of PPL@ChiNC was improved, comparing with free PPL. The demonstrated DES treatment process was efficient for ChiNC preparation and the as-prepared ChiNC exhibited great potentials in biocatalysis and biomedical field., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To summarize the available randomized controlled trials (RCTs) to evaluate the effect of taurine supplementation on growth in low birth weight infants (LBW)., Methods: PubMed, EmBase, and Cochrane Library electronic databases were searched for published articles through March 2017. Analysis was done to examine the effect of taurine supplementation on growth, and sensitivity analysis was performed by removing each individual study from meta-analysis., Results: Results of 9 trials totaling 216 LBW infants in the present meta-analysis were collected and analyzed. The conclusion of included studies demonstrated that taurine supplementation significantly reduced length gain (WMD:-0.18; P < 0.001), plasma glycine (WMD:-106.71; P = 0.033), alanine (WMD:-229.30; P = 0.002), leucine (WMD:-64.76; P < 0.001), tyrosine (WMD:-118.11; P < 0.001), histidine (WMD:-52.16; P < 0.001), proline (WMD: -84.29; P = 0.033), and asparagine-glutamine (WMD:-356.30; P < 0.001). However, taurine supplementation was associated with higher levels of acidic sterols (WMD:0.61; P = 0.024), total fatty acids (WMD:7.94; P = 0.050), total saturated fatty acids (WMD:9.70; P < 0.001), and unsaturated fatty acids (WMD:6.63; P < 0.001). Finally, taurine supplementation had little or no significant effect on weight gain, head circumference gain, plasma taurine, threonine, serine, citrulline, valine, methionine, isoleucine, phenylalanine, ornithine, lysine, arginine, glutamate, hydroxyproline, aspartate, dietary cholesterol, endogenous neutral sterols, cholesterol synthesis, and medium-chain triglycerides., Conclusions: The findings suggest that although there are several significant differences in plasma indeces, no significant effect on growth in LBW infants was observed with taurine supplementation.

Recently, the emergence of photoactive metal-organic frameworks (MOFs) has given great prospects for their applications as photocatalytic materials in visible-light-driven hydrogen evolution. Herein, a highly photoactive visible-light-driven material for H 2 evolution was prepared by introducing methylthio terephthalate into a MOF lattice via solvent-assisted ligand-exchange method. Accordingly, a first methylthio-functionalized porous MOF decorated with Pt co-catalyst for efficient photocatalytic H 2 evolution was achieved, which exhibited a high quantum yield (8.90 %) at 420 nm by use sacrificial triethanolamine. This hybrid material exhibited perfect H 2 production rate as high as 3814.0 μmol g -1  h -1 , which even is one order of magnitude higher than that of the state-of-the-art Pt/MOF photocatalyst derived from aminoterephthalate., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two series of thieno[2,3-d]pyrimidine derivatives bearing a dithiocarbamate side chain at the C2 position were synthesized and evaluated for cytotoxic activity in human lung cancer A549 and colon cancer HCT-116 cell lines. Compound 3n exhibited the most cytotoxic effect on A549 cells with an IC 50 value of 4.87 μM, inducing a cell cycle arrest at G2/M phase and activating the spindle assembly checkpoint (SAC). To identify the target protein(s) of 3n, we incorporated biotin with 3n through a three-carbon chain and an amide bond to synthesize probe 10. The targeted proteins were pulled down from the A549 total cell lysate by biotin-streptavidin affinity purification and analyzed by mass spectrometry. Tubulin was the only protein identified, which is related to the SAC and directly binds to probe 10 both in vivo and in vitro. Furthermore, compound 3n inhibited tubulin polymerization in vitro in a dose-dependent manner, competed with taxol in binding to tubulin, exerting cytotoxic activity toward taxol-resistant A549 cells. These results demonstrate that thieno[2,3-d]pyrimidine derivative 3n exhibits cytotoxicity in cancer cells by targeting tubulin to activate the SAC and potentially acts as a therapeutic lead compound for taxol-resistant cancers., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that glutamatergic transmission is altered in LGI1 mutant mice, and seizures can be reduced by restoring LGI1 function. Yet, the mechanism underlying ADLTE is unclear. Here, we propose that seizures in male LGI1 -/- mice are due to nonsynaptic epileptiform activity in cortical neurons. We examined the intrinsic excitability of pyramidal neurons in the temporal cortex of male LGI1 -/- mice and found that the voltage-gated K + channel Kv1.2 was significantly downregulated. We also found that cytosolic phospholipase A 2 (cPLA 2 )-cyclooxygenase 2 (Cox2) signaling was enhanced in LGI1 -/- mice. Interestingly, Cox2 inhibition effectively restored the dysregulated Kv1.2 and reduced the intrinsic excitability of pyramidal neurons. Moreover, in vivo injection of celecoxib, an FDA-approved nonsteroidal anti-inflammatory drug, rescued the defective Kv1.2 (an ∼1.9-fold increase), thereby alleviating the seizure susceptibility and extending the life of LGI1 -/- mice by 5 d. In summary, we conclude that LGI1 deficiency dysregulates cPLA 2 -Cox2 signaling to cause hyperexcitability of cortical pyramidal neurons, and celecoxib is a potential agent to manage human ADLTE. SIGNIFICANCE STATEMENT Haploinsufficiency of the leucine-rich glioma inactivated 1 (LGI1) gene is the major pathogenic basis for ADLTE, an inherited syndrome with no cure to date. Existing studies suggest that altered glutamatergic transmission in the hippocampus causes this disease, but the data are paradoxical. We demonstrate that the loss of LGI1 decreases Kv1.2 expression, enhances intrinsic excitability, and thereby causes epilepsy. Interestingly, for the first time, we show that an FDA-approved drug, celecoxib, rescues the Kv1.2 defect and alleviates seizure susceptibility in LGI1 -/- mice, as well as improving their survival. Thus, we suggest that celecoxib is a promising drug for the treatment of ADLTE patients., (Copyright © 2018 the authors 0270-6474/18/383346-12$15.00/0.)

Rice straw pretreatment mediated by choline chloride (ChCl) or lactic acid (Lac) sequences deep eutectic solvents (DESs) was investigated in this work. Hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) proved to be both important for DESs pretreatment efficiency. DESs containing lots of hydroxyl or amino groups with a high intermolecular hydrogen-bond (H-bond) strength exhibited weak biomass deconstruction abilities. The presence of strong electron-withdrawing groups in DESs was benefit for xylan removal, thus furnishing higher cellulose digestibility. The relationships between the properties of DESs, xylan removal and cellulose digestibility of pretreated biomass were established. It was found that xylan removal was negatively correlated with the pKa values of HBDs, and the enzymatic cellulose digestibility of the residues was linearly and positively related to xylan removal instead of delignification. These results provide a preliminary reference for rational design of novel DESs for biomass pretreatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: We purpose a novel factor analysis method based on kinetic cluster and α-divergence measure for extracting the blood input function and the time-activity curve of the regional tissue from dynamic myocardial positron emission computed tomography(PET) images., Methods: Dynamic PET images were decomposed into initial factors and factor images by minimizing the α-divergence between the factor model and actual image data. The kinetic clustering as a priori constraint was then incorporated into the model to solve the nonuniqueness problem, and the tissue time-activity curves and the tissue space distributions with physiological significance were generated., Results: The model was applied to the 82RbPET myocardial perfusion simulation data and compared with the traditional model-based least squares measure and the minimal spatial overlap constraint. The experimental results showed that the proposed model performed better than the traditional model in terms of both accuracy and sensitivity., Conclusion: This method can select the optimal measure by α value, and incorporate the prior information of the kinetic clustering of PET image pixels to obtain the accurate time-activity curves of the tissue, which has shown good performance in visual evaluation and quantitative evaluation.

Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins-occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To establish HPLC-MS/MS method for simultaneous determination of daphnetin, daphnoretin, and daphneticin in rat plasma after oral and intravenous administration of Daphne giraldii extract, and then use them in the calculation of pharmacokinetic parameters. Six sprague-dawley rats received intragastric administration of D. giraldii extract (daphnetin, daphnoretin and daphneticin were 88.40, 3.24 and 4.28 mg•kg⁻¹, respectively). Their drug plasma concentration was determined by LC-MS/MS with schisandrin as an internal standard to draw plasma concentration-time curve. The pharmacokinetic parameters were calculated by Kinetica 4.4. The results showed that the linear range was 5-1 000 μg•L⁻¹ for daphnetin, daphnoretin and daphneticin, and the method ological test showed conformance to the requirements.The intraday and inter-day variable coefficients (RSD) were both less than 15.0%, indicating that both of legitimate precise and accuracy were consistent with the analysis requirements of biological samples. For daphnetin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 4 h, 858.96 μg•L⁻¹, 10 566.4 μg•L⁻¹•h, 5.19 h and 9.43 h, respectively. For daphnoretin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2.92 h, 178.00 μg•L⁻¹, 905.89 μg•L⁻¹•h, 3.50 h and 6.95 h, respectively. For daphneticin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2 h, 36.67 μg•L⁻¹, 355.11 μg•L⁻¹•h, 4.95 h and 8.27 h, respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of daphnetin, daphnoretin and daphneticin., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

A novel deep eutectic solvent (DES)-DMSO cosolvent system has been, for the first time, successfully used as the reaction medium for the enzymatic acylation of dihydromyricetin (DMY) catalyzed by the immobilized lipase from Aspergillus niger (ANL). The cosolvent mixture, ChCl:Glycerol-DMSO (1:3, v/v) proved to be the optimal medium. With the newly developed cosolvent, the initial reaction rate of enzymatic acylation of DMY achieved 11.1 mM/h and the conversion of DMY was 91.6%. ANL@PD-MNPs is stable and recyclable in this cosolvent, offering 90% conversion rate after repeated use of 5 times. The lipid-solubility of DMY-16-acetate was 10 times higher than that of its raw materials DMY. The results showed that the DMY-16-acetate product exhibits good antioxidative activity. The present research illustrated that the use of DES-DMSO cosolvent may become a feasible alternative for the synthesis of DMY ester.

Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC 50 , 1.89-5.60 versus 6.52-35.13 μM). Moreover, treatment of HCT-116 cells with the complexes resulted in an obvious sub-G1 peak by cell cycle profile analysis, and an increase of cleaved PARP1 and caspases 3, 7, and 9 by immunoblotting analysis. Live cell imaging showed that nucleus shrinkage and condensation started to appear when MCF-7 cells were treated with 7a for 8 h. Fluorescent spectrophotometric analysis revealed that the complexes physically associated with calf thymus DNA. Competitive DNA binding assays uncovered that the complexes non-covalently bind to DNA. Taken together, our results indicated that the two new platinum(II) complexes 7a and 7b non-covalently bind to DNA with high affinity and exhibit cytotoxicity against cancer cells by inducing apoptosis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

A series of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at the C4-position were synthesized using piperidine and 1-bromo-3-chloropropane as starting materials via eight steps. Final compounds 8a-q and 9a-i were evaluated for their antiproliferative activity against human lung cancer A549, breast adenocarcinoma MCF-7, and colorectal cancer HCT-116 cell lines. The results showed that fourteen of twenty-six final compounds inhibited the proliferation of three cancer cell lines with IC50 values less than 10μM. When treated with a representative compound 8n, HCT-116 cells were arrested at G0/G1 phase of the cell cycle. This provided a clue to further investigation of the mechanism of action., (Copyright © 2016 Elsevier Ltd. All rights reserved.)