Publications by authors named "Yuan Gao"

2,531 Publications

  • Page 1 of 1

Cytochrome P450 oxidoreductase variant A503V contributes to the increased CYP3A5 activity with tacrolimus .

Expert Opin Drug Metab Toxicol 2022 Aug 10. Epub 2022 Aug 10.

Department of Pharmacy, Medical center of Soochow University, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.

Background: Tacrolimus is a calcineurin inhibitor with a strong efficacy in prevention of graft rejection after transplantation. It is well known that cytochrome P450 3A5 (CYP3A5) has a high metabolic capacity for tacrolimus, and mutations in human cytochrome P450 oxidoreductase (POR) cause altered CYP3A5 activity. Recently, clinical studies have revealed that contributes enhanced tacrolimus clearance in CYP3A5 expressers. A503V is an amino acid sequence variant encoded by . In this study, we first evaluated the impact of A503V on CYP3A5 activity with tacrolimus as the substrate .

Research Design & Methods: Wild-type (WT) and A503V POR, with WT CYP3A5 were expressed in recombinant HepG2 cells and reconstituted proteins. Michaelis constant () and maximum velocity () of CYP3A5 with tacrolimus as substrates were determined, and catalytic efficiency is expressed as /.

Results: WT and A503V POR both down-regulated the CYP3A5 mRNA expression, and WT POR rather than A503V down-regulated the protein expression of CYP3A5 in recombinant HepG2 cells. Compared with WT POR, A503V increased metabolism of tacrolimus by CYP3A5 in both cellular and protein level.

Conclusion: A503V can affect CYP3A5-catalyzed tacrolimus metabolism , which suggests that A503V has the potential to serve as a biomarker for tacrolimus treatment in transplantation recipients.
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http://dx.doi.org/10.1080/17425255.2022.2112174DOI Listing
August 2022

Single-cell sequencing reveals clearance of blastula chromosomal mosaicism in In Vitro fertilization babies.

Genomics Proteomics Bioinformatics 2022 Aug 6. Epub 2022 Aug 6.

Department of Gynaecology and Obstetrics, The First Medical Center of PLA General Hospital, Beijing 100853, China; Reproductive Medicine and Prenatal Diagnosis Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. Electronic address:

While chromosomal mosaic embryos detected by trophectoderm (TE) biopsy offer healthy embryos available for transfer, high resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient. Here, we applied single-cell multi-omics sequencing for seven infants with blastula chromosomal mosaicism detected by TE biopsy. The chromosome ploidy was examined by single-cell genome analysis, with the cellular identity being identified by single-cell transcriptome analysis. A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed. A small number of blood cells showed copy number alterations (CNAs) on seemingly random locations at a frequency of 0%-2.5% per infant. However, none of the cells showed CNAs that were the same as those of the corresponding TE biopsies. The blastula chromosomal mosaicism may be fully self-corrected, probably through the selective loss of the aneuploid cells during development, and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies. The results provide a new reference for the evaluations of transferring chromosomal mosaic embryos in certain situations.
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http://dx.doi.org/10.1016/j.gpb.2022.07.004DOI Listing
August 2022

Comparison of the robotic bilateral axillo-breast approach and conventional open thyroidectomy in pediatric patients: a retrospective cohort study.

Thyroid 2022 Aug 9. Epub 2022 Aug 9.

the 960th Hospital of People's Liberation Army, Jinan, Shandong, China;

Background: Operations for pediatric thyroid nodules are more complicated, and usually lead to longer scars, which may impair life quality in the long term. Bilateral axillo-breast approach (BABA) robotic thyroidectomy (BABA RT) may provide a better alternative to conventional open thyroidectomy (COT) for pediatric thyroid nodules. Our study aimed to compare the surgical and oncological outcomes of BABA RT and COT in pediatric patients.

Methods: The data of 49 pediatric patients who consecutively underwent BABA RT or COT (20:29) between July 1998 and November 2021 in our center were retrospectively analyzed, including demographics, surgery extent, surgical outcomes, pathological characteristics, and oncological outcomes.

Results: All BABA RT procedures were completed successfully without conversion to open operation. The BABA RT group consisted of 5 benign and 15 malignant cases, while the COT group consisted of 19 benign and 10 malignant cases. The operation time, drain removal time, and number of lymph nodes harvested by central lymph node dissection (CND) or lateral lymph node dissection (LND) were equivalent in the BABA RT and COT groups. Notably, the postoperative hospital stay of the BABA RT group was shorter than that of the COT group [8.5 (IQR:3) vs. 11(IQR:8) days, p=0.008]. The aesthetic score of the BABA RT group was much higher than that of the COT group [9 (IQR:1) vs. 6 (IQR: 1), p<0.001]. There was no significant difference between the BABA RT and COT groups in hypoparathyroidism rate (transient, 5 vs. 4; permanent, 1 vs. 0). There was one case of chyle leakage in the COT group and no other complications in any group, such as recurrent laryngeal nerve injury. With a median follow-up of 101 (IQR:189) months, one case of local relapse and one case of pulmonary metastasis in the COT group were documented.

Conclusion: In the hands of experienced surgeons, robotic BABA thyroidectomy can be a safe and effective option for both benign and malignant thyroid nodules in children, including those with lymph node metastasis. Robotic BABA thyroidectomy can offer a better and faster postoperative course and a much better cosmetic result, which is crucial for pediatric thyroid patients.
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http://dx.doi.org/10.1089/thy.2022.0242DOI Listing
August 2022

Is no news bad news? The impact of disclosing COVID-19 tracing information on consumer dine out decisions.

Agric Econ 2022 Jun 27. Epub 2022 Jun 27.

School of Agricultural Economics and Rural Development Renmin University of China Beijing China.

Food markets around the world have been disrupted by the COVID-19 pandemic via consumer behavior upended by fear of infection. In this article, we examine the impact of disclosing COVID-19 contact tracing information on food markets, using the restaurant industry in China as a case study. By analyzing transaction data at 87 restaurants across 10 cities, we estimate difference-in-difference (DID) models to ascertain the impact of COVID-19 infections and contact information tracing on economic activity as measured by a daily number of transactions. Empirical results show that while the overall number of new COVID-19 infections at the national level caused a dramatic drop in numbers of transactions in all restaurants, restaurants in cities that disclosed contact tracing information of COVID-19 infections experienced a 23%-35% higher number of transactions than the ones in cities that did not disclose such information during the recovery period. Ultimately, we show that in the absence of a shelter-in-place mandate, disclosing contract tracing information to mitigate consumers' uncertainties about risks of being infected can contribute to a faster recovery of food markets, in addition to reducing COVID-19 infections.
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http://dx.doi.org/10.1111/agec.12723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350169PMC
June 2022

MAPKs/AP-1, not NF-κB, is responsible for MCP-1 production in TNF-α-activated adipocytes.

Adipocyte 2022 Dec;11(1):477-486

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, Haidian, China.

Obesity is associated with the infiltration of monocytes/macrophages into adipose tissue in which MCP-1 plays a crucial role. But the regulatory mechanism of MCP-1 expression in adipocytes is not well defined. Our results demonstrated that TNF-α induced abundant MCP-1 production in adipocytes, including 3T3-L1 pre- (≈ 9 to 18-fold), mature adipocytes (≈ 4 to 6-fold), and primary adipocytes(< 2-fold), among which 3T3-L1 pre-adipocytes showed the best reactiveness. Thus, 3T3-L1 pre-adipocytes were used for the most of following experiments. At the transcriptional level, TNF-α (20 ng/mL) also promoted the mRNA expression of MCP-1. It is well recognized that the engagement of TNF-α with its receptor can trigger both NF-κB and AP-1 signalling, which was also confirmed in our study (5-fold and 2-fold). Unexpectedly and counterintuitively, multiple NF-κB inhibitors with different mechanisms failed to suppress TNF-α-induced MCP-1 production, but rather the inhibitors for any one of MAPKs (JNK, ERK and p38) could do. This study, for the first time, reveals that MAPKs/AP-1 but not NF-κB signalling is responsible for MCP-1 production in TNF-α-activated adipocytes. These findings provide important insight into the role of AP-1 signalling in adipose tissue, and may lead to the development of therapeutical repositioning strategies in metaflammation. AP-1, activator protein-1; CHX, cycloheximide; IR, insulin resistance; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; RT-qPCR, quantitative real-time PCR; T2DM, type 2 diabetes mellitus; TRE, triphorbol acetate-response element.
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http://dx.doi.org/10.1080/21623945.2022.2107786DOI Listing
December 2022

Visible Light-Induced Highly Regioselective and Stereoselective Oxysulfonylation of Alkynes for the Synthesis of ()-β-Phenoxy Vinylsulfones.

Org Lett 2022 Aug 8. Epub 2022 Aug 8.

International Joint Research Center for Molecular Science, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China.

A highly efficient visible light-induced regioselective and stereoselective oxysulfonylation of alkynes with arylsulfonate phenol esters has been developed. This photocatalyst- and metal-free method proceeds smoothly under very mild conditions and exhibits a broad substrate scope, providing ()-β-phenoxy vinylsulfones in moderate to excellent yields. Mechanistic studies indicated the involvement of an electron donor-acceptor complex-mediated radical process.
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http://dx.doi.org/10.1021/acs.orglett.2c02512DOI Listing
August 2022

Nodosin Exerts an Anti-Colorectal Cancer Effect by Inhibiting Proliferation and Triggering Complex Cell Death and .

Front Pharmacol 2022 22;13:943272. Epub 2022 Jul 22.

Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, China.

Colorectal cancer (CRC) is one of the most common digestive system cancer in the world. Its incidence and mortality are increasing annually. Presently, CRC lacks long-term effective treatment methods and drugs. Therefore, finding new treatment methods and drugs is of great significance for CRC treatment. Compounds derived from natural plants have been widely used in tumor research and treatment because of their good antitumor activity these years. This study found that nodosin, a diterpenoid extracted from the medicinal plant inhibited the growth of CRC cells SW480, HT-29 and LoVo in a dose- and time-dependent manner, with inhibitory concentrations (IC) of 7.4, 7.7, and 6.6 μM respectively. We selected highly metastatic and poorly differentiated SW480 cells for further studies. We found that nodosin could inhibit cell proliferation by inhibiting DNA synthesis and induce cell death by inducing oxidative stress, apoptosis and autophagy in cells. Through assays combined with transcriptomic analysis, it was found that nodosin could downregulate tribbles pseudokinase 3 and upregulate oxidative stress-induced growth inhibitor 1 to induce oxidative stress in cells; nodosin-induced reactive oxygen species were able to upregulate the expression of heme oxygenase 1 to induce apoptosis and the expression of cathepsin L. and light chain-3 to induce autophagy. , we found that nodosin inhibited tumor growth and induced cells to undergo apoptosis and autophagy without significant toxic effects. In conclusion, our findings suggest that nodosin exerts anti-CRC effects mainly through its ability to induce apoptosis and autophagy and . Therefore, our study contributes to the development of nodosin-based potential CRC therapeutic drugs.
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http://dx.doi.org/10.3389/fphar.2022.943272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353177PMC
July 2022

(±)-5-bromo-2-(5-fluoro-1-hydroxyamyl) Benzoate Protects Against Oxidative Stress Injury in PC12 Cells Exposed to HO Through Activation of Nrf2 Pathway.

Front Pharmacol 2022 18;13:943111. Epub 2022 Jul 18.

Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China.

Oxidative stress is associated with the pathogenesis of ischemic stroke (±)-5-bromo-2-(5-fluoro-1-hydroxyamyl) benzoate (BFB) is a novel compound modified by dl-3-n-butylphthalide (NBP). Here, we hypothesized that BFB may protect the PC12 cells against HO-induced oxidative stress injury through activation of the Nrf2 pathway. We measured the cell viability and levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) to determine the construction of the HO-induced models of oxidative stress in PC12 cells. Additionally, apoptotic cell death, mitochondrial membrane potential, and cellular morphology were examined to determine the effect of BFB on oxidative stress injury in HO-treated PC12 cells. The expression levels of Nrf2-related and autophagy-related genes and proteins were detected using real time quantative PCR (RT-qPCR), Western Blot, and immunofluorescence analyses. Our study showed that BFB treatment reduced the elevated levels of MDA, LDH, and ROS, and decreased cell viability and GSH in HO-treated PC12 cells. We also observed the elevated expression of Nrf2 pathway-related factors and intranuclear transitions and found that Nrf2 inhibitors (ML385) could block the protective effect of BFB. The inhibitory effect of BFB on oxidative stress may be partially regulated by Nrf2 activation, and the initiation and induction of autophagy. BFB inhibited HO-induced oxidative stress injury in PC12 cells by activating the Nrf2 pathway, initiating and inducing autophagy, suggesting that BFB may be a promising therapeutic agent in treating neurological disorders like cerebral ischemia.
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http://dx.doi.org/10.3389/fphar.2022.943111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348035PMC
July 2022

The Hypoglycemic Effect of JinQi Jiangtang Tablets Is Partially Dependent on the Palmatine-Induced Activation of the Fibroblast Growth Factor Receptor 1 Signaling Pathway.

Front Pharmacol 2022 22;13:895724. Epub 2022 Jul 22.

College of Life Sciences, Northeast Agricultural University, Harbin, China.

JinQi Jiangtang tablet (JQJTT) is a Chinese patent medicine that has been shown to be beneficial for patients with diabetes both preclinically and clinically; however, the molecular mechanism underlying the effects of JQJTT remains unclear. In this study, surface plasmon resonance fishing was employed to identify JQJTT constituent molecules that can specifically bind to fibroblast growth factor receptor 1 (FGFR1), leading to the retrieval of palmatine (PAL), a key active ingredient of JQJTT. and experiments demonstrated that PAL can significantly stimulate FGFR1 phosphorylation and upregulate glucose transporter type 1 (GLUT-1) expression, thereby facilitating glucose uptake in insulin resistance (IR) HepG2 cells as well as alleviating hyperglycemia in diabetic mice. Our results revealed that PAL functions as an FGFR1 activator and that the hypoglycemic effect of JQJTT is partially dependent on the PAL-induced activation of the FGFR1 pathway. In addition, this study contributed to the understanding the pharmacodynamic basis and mechanism of action of JQJTT and provided a novel concept for future research on PAL.
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http://dx.doi.org/10.3389/fphar.2022.895724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354937PMC
July 2022

The effects of information platform-based nursing on preventing venous thromboembolism VT in patients with hip fractures.

Chin J Traumatol 2022 Jun 17. Epub 2022 Jun 17.

Health Service Training Center of PLA General Hospital, Beijing, 100853, China. Electronic address:

Purpose: Venous thromboembolism (VTE) is a major health issue among hip fracture patients. This study aimed to develop an information platform based on a mobile application and then evaluate whether information platform-based nursing could improve patient's drug compliance and reduce the incidence of VTE in hip fracture patients.

Methods: This study retrospectively analyzed hip fracture patients who were treated with conventional prevention and intervention methods for VTE (control group) between January 2008 and November 2012, and prospectively analyzed hip fracture patients who were treated with nursing intervention based on the information platform (study group) between January 2016 and September 2017. All the patients included in the both groups were hip fracture patients who had an age of 50 years or above, treated with surgery, and hospitalized for 48 h or above. Patients were excluded if they admitted to hospital due to old fractures, had a severe bleeding after 72 h of admission, diagnosed with any type of VTE, or refused to participate in the study. The information platform was divided into medical, nursing, and patient interface. Based on the information platform, medical practitioners and nurses could perform risk assessments, monitoring management and early warnings, preventions and treatments, health educations, follow-up, and other aspects of nursing interventions for patients. This study compared essential characteristics, drug compliance, VTE occurrence, and mean length of hospitalization between the two groups. Besides, a subgroup analysis was performed in the study group according to different drug compliances. SPSS 18.0 software (IBM Corp., NY, and USA) was used for statistical analysis.

Results: Altogether 1177 patients were included in the control group, and 491 patients in the study group. Regarding baseline data, patients in the study group had more morbidities than those in the control group (p < 0.05). The difference of drug compliance between the two groups was statistically significant (p < 0.001): 761 (64.7%) of the patients in the control group and only 30 (6.1%) patients in the study group had poor drug compliance. In terms of VTE, 10.7% patients (126/1177) in the control group had VTE, and the rate in the study group was 7.1% (35/491), showing a statistically significant difference (p = 0.02). Moreover, the average length of hospitalization in the study group was also significantly lower than that in the control group (10.4 days vs. 13.7 days, p < 0.001). Subgroup analyses of the study group showed that the incidence of VTE in patients with poor, partial, and good compliances were 56.7% (17/30), 5.8% (10/171), and 2.8% (8/290), respectively, revealing a significantly huge difference (p < 0.001).

Conclusions: Poor drug compliance leads to higher VTE occurrence. The information platform-based nursing can effectively improve the compliance of hip fracture patients and thus considerably reduce the incidence of VTE. The mobile application may be an effective tool to prevent VTE in hip fracture patients.
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http://dx.doi.org/10.1016/j.cjtee.2022.06.004DOI Listing
June 2022

[Expert statement on the construction criteria of critical care department in municipal and district designated hospitals under the pandemic prevention and control].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2022 Jun;34(6):561-570

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that "dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.
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http://dx.doi.org/10.3760/cma.j.cn121430-20220530-00542DOI Listing
June 2022

Antimicrobial acylphloroglucinol meroterpenoids and acylphloroglucinols from Dryopteris crassirhizoma.

Planta Med 2022 Aug 3. Epub 2022 Aug 3.

Ten novel meroterpenoids, dryoptins/11''-epi-dryoptins A~E (1: ~10: ) with an unprecedented skeleton consisting of dimeric or trimeric acylphloroglucinols and dehydrotheonelline, two undescribed acylphloroglucinol-nerolidol meroterpenoids (11: ~12: ), and ten known acylphloroglucinol derivatives (13: ~22: ), were isolated from . The novel structures including absolute configurations were established by comprehensive spectroscopic analyses and quantum chemical electronic circular dichroism (ECD) calculations. A biosynthetic pathway of 1: ~10: was assumed. The trimeric acylphloroglucinol meroterpenoids 7: /8: showed significant antifungal activity against standard with MIC50 value of 1.61 μg/mL [fluconazole (FLC): 3.41 μg/mL], and when combined with FLC, the principal components 20: and 21: exhibited strong antifungal activities against FLC-resistant with MIC50 values of 8.39 and 7.16 μg/mL (FLC: >100 μg/mL), respectively. Moreover, compounds 2, 5/6, 18, 19, and 21 exhibited inhibitory effects against several pathogenic fungi and bacteria, with MIC values of 6.25~50 μg/mL.
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http://dx.doi.org/10.1055/a-1917-7910DOI Listing
August 2022

Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease.

Proc Jpn Acad Ser B Phys Biol Sci 2022 ;98(7):361-377

Department of Pharmacology, College of Pharmacy, Inner Mongolian Medical University.

Previous studies showed that lanthanum hydroxide (LH) has a therapeutic effect on chronic kidney disease (CKD) and vascular calcification, which suggests that it might have clinical value. However, the target and mechanism of action of LH are unclear. Metabolomics of clinical samples can be used to predict the mechanism of drug action. In this study, metabolomic profiles in patients with end-stage renal disease (ESRD) were used to screen related signaling pathways, and we verified the influence of LH on the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway by western blotting and quantitative real-time RT-qPCR in vivo and in vitro. We found that ROS and SLC16A10 genes were activated in patients with ESRD. The SLC16A10 gene is associated with six significant metabolites (L-cysteine, L-cystine, L-isoleucine, L-arginine, L-aspartic acid, and L-phenylalanine) and the PI3K-AKT signaling pathway. The results showed that LH inhibits the ESRD process and its cardiovascular complications by inhibiting the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway. Collectively, LH may be a candidate phosphorus binder for the treatment of vascular calcification in ESRD.
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http://dx.doi.org/10.2183/pjab.98.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363596PMC
August 2022

Blood uptake and urine excretion of nano- and micro-plastics after a single exposure.

Sci Total Environ 2022 Jul 26;848:157639. Epub 2022 Jul 26.

Research Center for Universal Health, School of Public Health, China Medical University, Shenyang 110122, People's Republic of China. Electronic address:

Nano- and micro-plastic (NMP) pollution has emerged as a global issue; however, uptake in the blood is controversial. Also, there is no evidence that NMPs are excreted via urine. This study was designed to clarify the time course of NMPs absorption in blood and the excretion in urine. Male mice received a single administration of fluorescent polystyrene (PS) beads (100-nm and 3-μm) via tail vein injection, gavage, or pulmonary perfusion. Blood and urine samples were measured 0.5, 1, 2, and 4 h after exposure by confocal laser scanning microscope (CLSM). Transmission electron microscopy (TEM) was performed to corroborate the findings. Fluorescence particles were detected in both blood and urine from the 100-nm and 3-μm PS-treated groups after exposure. In the 3-μm PS treated group, particles with corresponding diameters were detected after intravenous injection and pulmonary perfusion, and particles with a diameter <3 μm were detected in blood samples after gavage. The fluorescent signal in urine was particularly weak and the size was <3 μm. Significant time course changes in fluorescence intensity were demonstrated in blood and urine (P < 0.05) after intravenous injection and pulmonary perfusion in the 100-nm PS-treated group. By contrast, significant changes were detected in the urine (P < 0.05), but not the blood, after gavage. TEM confirmed the presence of particles with corresponding diameters in blood samples; however, the excretion in urine was difficult to confirm for nano-plastics (NPs) and micro-plastics (MPs) because all particles with diameters of approximately 100 nm and 3 μm had irregular shapes and no clear boundaries. Our findings revealed that both NPs and MPs enter the blood circulation through digestive and respiratory pathways. Both 100-nm and 3-μm NMPs may be excreted through urine, but further evidence is needed. The physical and chemical properties of MPs may be impacted by digestive processes in vivo.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157639DOI Listing
July 2022

A novel soluble lornoxicam-sodium chelate monohydrate with improved plasticity and tabletability.

Int J Pharm 2022 Jul 26;624:122060. Epub 2022 Jul 26.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:

Lornoxicam (LOR), a BCS II nonsteroidal anti-inflammatory drug, has been clinically utilized for moderate to severe acute pain management. However, it has poor water solubility and insufficient tabletability, leading to erratic absorption and challenge in tablet processability. This study reported a novel solid state of LOR (i.e., LOR sodium chelate monohydrate, LOR-Na·HO) with significantly improved solubility, dissolution rate and tabletability. The prepared chelate (CCDC No.: 2125157) contains LOR, Na, and HO in a molar ratio of 1:1:1, where Na ions bridged with O(5) of amide group, and N(2) of pyridine group on LOR, as well as O(4) on HO through coordination bonds. LOR-Na·HO displayed a superior dissolution rate (5 ∼ 465 folds) than commercial LOR due to its increased wettability (contact angle: 74.5° vs 85.6°) and lower solvation free energy (∼2-fold). In addition, the significant improvement in tabletability was caused by high plasticity and deformability, which was attributed to its special interlayer gliding with weak bonding interactions across layers but strong coordination bonding interactions within layers. The novel LOR-Na·HO with significantly enhanced pharmaceutical performance offers a promising strategy for further product development.
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http://dx.doi.org/10.1016/j.ijpharm.2022.122060DOI Listing
July 2022

Special issue "The advance of solid tumor research in China": Discoidin domain receptor 2 promotes colorectal cancer metastasis by regulating epithelial mesenchymal transition via activating AKT signaling.

Int J Cancer 2022 Jul 29. Epub 2022 Jul 29.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared with that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3β/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.34227DOI Listing
July 2022

TGF-β1-induced bone marrow mesenchymal stem cells (BMSCs) migration via histone demethylase KDM6B mediated inhibition of methylation marker H3K27me3.

Cell Death Discov 2022 Jul 28;8(1):339. Epub 2022 Jul 28.

Department of Orthopedic Surgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 250012, Jinan, Shandong, China.

Mesenchymal stem cells (MSCs) are widely used in clinical research and therapy. Since the number of MSCs migration is extremely crucial at the lesion site, exploring the mechanisms to enhance the migration of MSCs is necessary. Therefore, this study focused on the epigenetic mechanisms in MSCs migration. TGF-β1 stimulated bone marrow mesenchymal stem cells (BMSCs) to promote cell migration at lesion sites in vitro and in vivo. The mRNA and protein levels of several migration-related genes (N cadherin, CXCR4, FN1) were enhanced. The trimethylation marker H3K27me3 recruitment on the promoter of these genes were studied to dissect the epigenetic mechanisms. TGF-β1 elevated the levels of KDM6B leading to removal of repression marker H3K27me3 in the promoter region of N cadherins and FN1. Congruently, knockdown of demethylase KDM6B substantially affected the TGF-β1 induced BMSCs migration. This promoted the down-regulation of various migration-related genes. Collectively, epigenetic regulation played an important role in BMSCs migration, and H3K27me3 was at least partially involved in the migration of BMSCs induced by TGF-β1.
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http://dx.doi.org/10.1038/s41420-022-01132-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334584PMC
July 2022

Gelation Elimination and Crystallization Inhibition by Co-Amorphous Strategy for Amorphous Curcumin.

J Pharm Sci 2022 Jul 25. Epub 2022 Jul 25.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:

In the previous study, the development of amorphous curcumin (CUR) aimed to enhance the solubility/dissolution of CUR by disrupting its crystal lattice, but it unexpectedly showed a decreased dissolution than its crystalline counterpart on account of gel formation in its dissolution process. Whether such gelation could be eliminated by co-amorphous strategy was answered in this study. Herein, CUR by co-amorphization with chlorogenic acid (CHA) was successfully prepared using quench cooling. The formed co-amorphous material (namely CUR-CHA CM) eliminated the gelation and hence performed superior dissolution performance than crystalline/amorphous CUR. Meanwhile, it exhibited higher physical stability than amorphous CUR during dissolution as well as under long-term/accelerated conditions. To further study the such enhancement mechanism, the internal molecular interactions were investigated for CUR-CHA CM in the solid state as well as in aqueous solution. FTIR and solid-state C NMR spectra confirmed that intermolecular hydrogen bonds formed between CUR and CHA after co-amorphization. Furthermore, the nucleation of CUR was significantly inhibited by CHA in an aqueous solution, thus maintaining the supersaturated dissolution for a long time. The present study offers a feasible strategy to eliminate gelation and enhance stability of amorphous solids by co-amorphization and crystallization inhibition.
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http://dx.doi.org/10.1016/j.xphs.2022.07.014DOI Listing
July 2022

TRAF4 maintains deubiquitination of Caveolin-1 to drive glioblastoma stemness and Temozolomide resistance.

Cancer Res 2022 Jul 27. Epub 2022 Jul 27.

China Pharmaceutical University, Nanjing, China.

Glioblastoma (GBM) is the most common type of primary adult brain tumor. Glioma stem cell (GSC) residence and Temozolomide (TMZ) resistance in GBM both contribute to poor patient outcome. TRAF4 is a scaffold protein with E3 ubiquitin ligase activity that has recently been discovered to promote invasion and metastasis in several malignancies, but the effects and functions of TRAF4 in GBM remain to be determined. Here, we report that TRAF4 is preferentially overexpressed in GSCs and is required for stem-like properties as well as TMZ sensitivity in GBM cells. TRAF4 specifically interacted with the N-terminal tail of Caveolin-1 (CAV1), an important contributor to the tumorigenicity of GBM cells. TRAF4 regulated CAV1 stability by preventing ZNRF1-mediated ubiquitination and facilitating USP7-mediated deubiquitination independently of its E3 ubiquitin ligase catalytic activity. TRAF4-mediated stabilization of CAV1 activated protumorigenic AKT/ERK1/2 signaling, and disruption of this axis resulted in defects in stemness maintenance. In addition, expression of TRAF4 and CAV1 was positively correlated and predicted poor prognosis in human GBM samples. Screening of common nervous system drugs identified Risperidone interaction with TRAF4, and Risperidone treatment resulted in the dissociation of TRAF4 and CAV1. Importantly, pharmacological inhibition of TRAF4 with Risperidone potently inhibited self-renewal, abrogated tumorigenicity, and reversed TMZ resistance in GBM. Overall, TRAF4-mediated stabilization of CAV1 promotes stemness and TMZ resistance in GBM, providing a therapeutic strategy that could improve patient outcomes.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-3882DOI Listing
July 2022

Hippocampal semaphorin 3B improves depression-like behaviours in mice by upregulating synaptic plasticity and inhibiting neuronal apoptosis.

J Neurochem 2022 Jul 26. Epub 2022 Jul 26.

Hebei Key Laboratory of Neurophysiology, Shijiazhuang, China.

Depression is a global health problem, and there is a pressing need for a better understanding of its pathogenesis. Semaphorin 3B (Sema 3B) is an important axon guidance molecule that is primarily expressed in neurons and contributes to synaptic plasticity. Our previous studies using a high-throughput microarray assay suggested that Sema 3B expression was tremendously decreased during the development of depression, but the specific role and mechanisms of Sema 3B in depression are still unknown. Herein, we report that levels of Sema 3B protein are decreased in the hippocampus and serum of chronic mild stress (CMS)-treated mice. Increasing the levels of Sema 3B, either by injecting AAV-Sema 3B into the hippocampus or by injecting recombinant Sema 3B protein into the lateral ventricles, alleviated CMS-induced depression-like behaviours and enhanced the resistance to acute stress by increasing dendritic spine density in hippocampal neurons. In contrast, interfering with the function of Sema 3B by injecting anti-Sema 3B antibody into the lateral ventricles decreased the resistance to acute stress. In vitro, corticosterone (CORT) treatment decreased the survival rate and protein levels of Sema 3B and synapse-associated proteins in HT22 cells. Overexpression of Sema 3B improved the decreased survival rate caused by CORT by inhibiting apoptosis and increasing levels of synaptic-associated proteins, and knockdown of Sema 3B reduces the cellular resistance to CORT and the levels of synapse-associated proteins. These findings represent the first evidence for the neuroprotective mechanism of Sema 3B against stresses, suggesting that Sema 3B could be a promising novel target for the prevention and treatment of depression.
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http://dx.doi.org/10.1111/jnc.15680DOI Listing
July 2022

Mental States: A Key Point in Scam Compliance and Warning Compliance in Real Life.

Int J Environ Res Public Health 2022 Jul 7;19(14). Epub 2022 Jul 7.

Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou 310027, China.

The internet's convenience and anonymity have facilitated different types of covert fraud, resulting in economic, mental, and social harm to victims. Understanding why people are deceived and implementing appropriate interventions is critical for fraud reduction. Based on the Bayesian brain theory, individuals' mental states may be a key point in scam compliance and warning compliance. Fraud victims with different mental states may construct various hypotheses and explanations about the fraud they are exposed to, causing different cognition and behavior patterns. Therefore, we first conducted a semi-structured in-depth interview with online fraud victims to investigate the individual and social factors that affect victims' mental states. Grounded theory analysis showed five core factors influencing scam compliance: psychological traits, empirical factors, motivation, cognitive biases, and emotional imbalance. Based on our findings of psychological processes and deception's influential factors, we then designed warnings to inform victims of fraud, particularly for those involving novel types of scams. Tested on a real-life setting, our designed warnings effectively enhanced warning compliance, allowing more fraud victims to avoid financial losses.
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http://dx.doi.org/10.3390/ijerph19148294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317489PMC
July 2022

Preparation of ZIF-8 and Its Application in Determination of Pyridoxine and Pyridoxal in Ginkgo Seeds by Ultra-Performance Liquid Chromatography.

Foods 2022 Jul 7;11(14). Epub 2022 Jul 7.

State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang 330047, China.

A new rapid and accurate method was developed for simultaneous determination of pyridoxine and pyridoxal in ginkgo seeds, using ultra-performance liquid chromatography (UPLC) equipped with a fluorescence detector. Diluted hydrochloric acid solution was used as the extracting solvent. For the pretreatment of extracts, a zeolitic imidazolate framework material (ZIF-8) was prepared and characterized. An ODS-BP column (4.6 mm × 250 mm × 5 μm) was used for separation. The conditions of sample extraction, cleaning and separation were optimized. The linear correlation coefficient (R) of the analyte was better than 0.9999, indicating good linearity. The limits of detection (LODs) of pyridoxal and pyridoxine were 0.0065 mg/kg and 0.0057 mg/kg, respectively, and limits of quantitation (LOQs) were 0.022 mg/kg and 0.019 mg/kg, respectively. The recovery of the two substances ranged from 86.2% to 110.4%, and the relative standard deviation (n = 6) was less than 7.5%. The method was applied to determine the contents of pyridoxine and pyridoxal in actual ginkgo seed samples with satisfactory results.
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http://dx.doi.org/10.3390/foods11142014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319451PMC
July 2022

The Efficacy and Safety of Deep Brain Stimulation of Combined Anterior Limb of Internal Capsule and Nucleus Accumbens (ALIC/NAcc-DBS) for Treatment-Refractory Obsessive-Compulsive Disorder: Protocol of a Multicenter, Randomized, and Double-Blinded Study.

Brain Sci 2022 Jul 16;12(7). Epub 2022 Jul 16.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Backgrounds: Deep brain stimulation (DBS) is an emerging and promising therapeutic approach for treatment-refractory obsessive-compulsive disorder (OCD). The most common DBS targets include the anterior limb of internal capsule (ALIC) and nucleus accumbens (NAcc). This protocol aims to explore the efficacy and safety of the combined ALIC- and NAcc-DBS for treatment-refractory OCD.

Methods: We will recruit 64 patients with refractory OCD from six centers, randomly allocate them to active and sham-stimulation groups through a three-month double-blind phase, then enter a three-month open-label phase. In the open-label stage, both groups experience real stimulation.

Outcome Measures: The primary outcome will be the efficacy and safety of combined ALIC- and NAcc-DBS, determined by treatment response rate between the active and sham-stimulation groups at the double-blind stage and spontaneously reported adverse events. The secondary outcomes are comparisons of change in Y-BOCS, CGI, HAMD, and HAMA scores at the third and sixth months compared to baseline between the active and sham-control groups, as well as the scores of the third month minus the sixth month between the two groups.
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http://dx.doi.org/10.3390/brainsci12070933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313119PMC
July 2022

Melatonin Receptors: A Key Mediator in Animal Reproduction.

Vet Sci 2022 Jun 22;9(7). Epub 2022 Jun 22.

College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China.

Melatonin, a hormone produced by the mammalian pineal gland, influences various physiological activities, many of which are related to animal reproduction, including neuroendocrine function, rhythm regulation, seasonal behavior, gonadogenesis, gamete development and maturation, sexual maturation, and thermoregulation. Melatonin exerts beneficial actions mainly via binding with G-protein-coupled receptors (GPCR), termed MT1 and MT2. Melatonin receptors are crucial for mediating animal reproduction. This paper reviews the characteristics of melatonin receptors including MT1 and MT2, as well as their roles in mediating signal transduction and biological effects, with a focus on their function in animal reproduction. In addition, we briefly summarize the developments in pharmacological research regarding melatonin receptors as drug targets. It is expected that this review will provide a reference for further exploration and unveiling of melatonin receptor function in reproductive regulation.
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http://dx.doi.org/10.3390/vetsci9070309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320721PMC
June 2022

Impact of the COVID-19 Pandemic on Air Quality in Metropolitan New Jersey.

Water Air Soil Pollut 2022 20;233(8):289. Epub 2022 Jul 20.

Department of Earth and Environmental Sciences, Rutgers University, Newark, NJ 07102 USA.

Improved air quality has been the silver lining of the pandemic since early 2020. The air quality in northern New Jersey (NJ) was continuously measured during the COVID-19 pandemic and through the three stages of recovery, i.e., the Stay-at-home stage, Reopening stage 1, and Reopening stage 2. A significant change in air quality was observed during the Stay-at-home stage (March 16 to May 16, 2020) as most people stayed home and industrial activity decreased 60%. Compared to 2019, carbon dioxide (CO) decreased 17%, carbon monoxide (CO) decreased 7%, and nitrogen oxides (NO) decreased 51% during the Stay-at-home stage in 2020. However, the ground-level ozone (O) increased in 2020 because of the reduced NO emission and the possibly increased levels of volatile organic compounds (VOCs) due to warmer weather. With the step-by-step reopening process, the difference in local CO levels between 2019 and 2020 was reduced, and the NO concentration returned to its 2019 level. The CO concentrations were positively correlated with CO, and the NO concentrations were negatively correlated with O. Under the COVID-19 pandemic in 2020, NJ consumed 14% less natural gas and 21% less gasoline; therefore, the CO, CO, and NO emissions and concentration levels were reduced besides the effects of meteorology parameters on air quality in metropolitan New Jersey. Our findings support that replacing fossil fuels with electric or renewable energy in the transportation systems and industry could be beneficial for the concentration reduction of certain greenhouse gases.

Supplementary Information: The online version contains supplementary material available at 10.1007/s11270-022-05764-w.
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http://dx.doi.org/10.1007/s11270-022-05764-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296220PMC
July 2022

Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19.

Int J Biol Sci 2022 11;18(12):4690-4703. Epub 2022 Jul 11.

Faculty of Health Sciences, University of Macau, Macau, China.

There is increasing amount of evidence indicating the close interplays between the replication cycle of SARS-CoV-2 and the autophagy-lysosome pathway in the host cells. While autophagy machinery is known to either assist or inhibit the viral replication process, the reciprocal effects of the SARS-CoV-2 on the autophagy-lysosome pathway have also been increasingly appreciated. More importantly, despite the disappointing results from the clinical trials of chloroquine and hydroxychloroquine in treatment of COVID-19, there is still ongoing effort in discovering new therapeutics targeting the autophagy-lysosome pathway. In this review, we provide an update-to-date summary of the interplays between the autophagy-lysosome pathway in the host cells and the pathogen SARS-CoV-2 at the molecular level, to highlight the prognostic value of autophagy markers in COVID-19 patients and to discuss the potential of developing novel therapeutic strategies for COVID-19 by targeting the autophagy-lysosome pathway. Thus, understanding the nature of such interactions between SARS-CoV-2 and the autophagy-lysosome pathway in the host cells is expected to provide novel strategies in battling against this global pandemic.
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http://dx.doi.org/10.7150/ijbs.72544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305279PMC
July 2022

Selenium Deficiency Leads to Inflammation, Autophagy, Endoplasmic Reticulum Stress, Apoptosis and Contraction Abnormalities Affecting Intestinal Flora in Intestinal Smooth Muscle of Mice.

Front Immunol 2022 6;13:947655. Epub 2022 Jul 6.

College of Veterinary Medicine, Jilin University, Changchun, China.

Selenium (Se) is a micronutrient that plays a predominant role in various physiological processes in humans and animals. Long-term lack of Se will lead to many metabolic diseases. Studies have found that chronic Se deficiency can cause chronic diarrhea. The gut flora is closely related to the health of the body. Changes in environmental factors can cause changes in the intestinal flora. Our study found that Se deficiency can disrupt intestinal flora. Through 16s high-throughput sequencing analysis of small intestinal contents of mice, we found that compared with CSe group, the abundance of Lactobacillus, Bifidobacterium, and Ileibacterium in the low selenium group was significantly increased, while Romboutsia abundance was significantly decreased. Histological analysis showed that compared with CSe group, the small intestine tissues of the LSe group had obvious pathological changes. We examined mRNA expression levels in the small intestine associated with inflammation, autophagy, endoplasmic reticulum stress, apoptosis, tight junctions, and smooth muscle contraction. The mRNA levels of , , , , , , , , , , , , , , , , , , , , , , , , , , , and in the LSe group were significantly increased. The mRNA levels of , and were significantly decreased in the LSe group compared with the CSe group. These results suggest that changes in the abundance of Lactobacillus, bifidobacterium, ileum, and Romboutsia may be associated with cellular inflammation, autophagy, endoplasmic reticulum stress, apoptosis, tight junction, and abnormal smooth muscle contraction. Intestinal flora may play an important role in chronic diarrhea caused by selenium deficiency.
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http://dx.doi.org/10.3389/fimmu.2022.947655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299101PMC
July 2022

Spatial-topographic nestedness of interoceptive regions within the networks of decision making and emotion regulation: Combining ALE meta-analysis and MACM analysis.

Neuroimage 2022 Jul 22;260:119500. Epub 2022 Jul 22.

Mind, Brain Imaging and Neuroethics Research Unit, Institute of Mental Health, Royal Ottawa Mental Health Centre and University of Ottawa, Ottawa, Ontario K1Z 7K4, Canada; Mental Health Center, Zhejiang University School of Medicine, Hangzhou 310013, Zhejiang Province, China; Centre for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou 310013, Zhejiang Province, China.

Prominent theories propose that interoception modulates our behavioral and emotional responses involving decision-making and emotion regulation. Are the regions implicated in interoception also spatially related to and possibly nested within the networks of decision making and emotion regulation? Addressing this question, we performed three meta-analyses of functional magnetic resonance imaging studies to identify the regions that are commonly activated by the three domains using activation likelihood estimation (ALE). Additionally, we assessed the coactivation pattern of identified common regions using meta-analytic connectivity modeling (MACM). The results showed major overlaps of interoception with both decision making and emotion regulation in specifically the right dorsal anterior insula. The pairwise contrast analyses confirmed this finding and revealed conjunction-based activities in decision making and emotion regulation in the dorsal anterior cingulate cortex (dACC). MACM based on the identified insula revealed a widespread convergent coactivation pattern with the left anterior insula, dACC, and bilateral thalamus which, together, constitute the salience network. Among these co-activated regions, bilateral insula and the dACC were shared among all three domains. These results suggest that the regions mediating interoception including intero-exteroceptive integration and salience attribution are contained and thus spatially nested within the more extensive networks recruited during decision making and emotion regulation.
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http://dx.doi.org/10.1016/j.neuroimage.2022.119500DOI Listing
July 2022

Gelation switch of polyamorphic indomethacin depending on the thermal procedure.

Eur J Pharm Biopharm 2022 Aug 21;177:249-259. Epub 2022 Jul 21.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:

Amorphous indomethacin (IMC) prepared under different thermal procedures via melt quenching method showed significantly different dissolution behaviors. This study aims to investigate the influence of thermal procedures on the formation of IMC polyamorphism and to explore the mechanism for their different dissolution behaviors. Amorphous IMC samples were prepared by melting crystalline IMC under a series of temperatures (160-195 °C), respectively, followed by quenching in liquid nitrogen. Samples obtained under 170 °C exhibited bi-halo shapes at ∼15° and ∼26° (2θ), while the ones above 175 °C showed a single halo at ∼21° (2θ), suggesting amorphous IMC prepared under different thermal procedures probably have different local molecular arrangements. In comparison to crystalline IMC, amorphous IMC obtained under 170 °C showed significantly higher dissolution profiles with good dispersibility in aqueous medium, however, all amorphous IMC samples prepared above 175 °C demonstrated much lower dissolution with significant gelation, which seemed like a gelation switch existed for polyamorphic IMC when the preparation temperature was between 170 and 175 °C. Based on physicochemical characterizations, amorphous IMC prepared under 170 °C had higher surface free energy, more surficial hydrophilic groups and better wettability than the ones made above 175 °C. Molecular dynamics simulations revealed that the amorphous samples prepared below 170 °C had similar binding energy values in the range of 310.045-325.479 kcal/mol, while those prepared above 175 °C were significantly lower within 212.193-235.073 kcal/mol. Such binding energy difference might be responsible for their different local molecular arrangements after different thermal procedures. The current study deeply reminds us that the thermal procedure of preparation methods may significantly affect the physicochemical properties of amorphous materials, which should be paid special attention to the polymorphic selection during pharmaceutical development.
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http://dx.doi.org/10.1016/j.ejpb.2022.07.008DOI Listing
August 2022

Shaping outcome of ProTaper NEXT for root canal preparation in mandibular incisors: a micro-CT study.

BMC Oral Health 2022 07 22;22(1):302. Epub 2022 Jul 22.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, 14#, 3Rd Section of RenMin South Road, Chengdu, 610041, People's Republic of China.

Background: Relatively high incidence of single canals with oval or round shape were observed in human mandibular incisors. In order to investigate the influence of the root canal morphology on root canal preparation, the shaping outcome of ProTaper NEXT in oval and round canals of mandibular incisors were evaluated by using micro-computed tomography (micro-CT) analysis.

Methods: This experiment was approved by the School Medical Ethics Committee. The sample size calculation was conducted using G*Power software. Intact mandibular incisors with a single canal were selected. Oval canals (2 < aspect ratio (AR) ≤ 4) and round canals (AR ≤ 2) were pair-matched according to canal length, and assigned to two experimental groups (13 per group). ProTaper NEXT was used for root canal preparation for both groups. Untouched canal wall (UCW), root canal morphological parameters and three-dimensional (3D) dentin thickness were evaluated in the entire root canal and each canal third after micro-CT scanning.

Statistical Analysis: Data were collected and analyzed with Mann-Whitney test and Friedman test using SPSS statistics software 25 (P < 0.05). Additionally, correlations of UCW area with canal morphological parameters were also investigated.

Results: After root canal preparation, no significant difference was observed in all analyzed parameters in the apical third between oval and round canal groups (P > 0.05). In the coronal two thirds of the canal, the post-operative structure model index (SMI), form factor and roundness were significantly increased, while the AR was significantly decreased in both groups (P < 0.05). In addition, in the coronal two thirds, significantly more UCW and higher UCWΔ% was observed in oval canal group (P < 0.05). Furthermore, UCW correlated very strongly to canal major diameter (0.924) and initial volume (0.938), and strongly to canal form factor (- 0.724), minor diameter (0.799) and canal area (0.882). Proximal dentin wall was associated with significantly thinner pre-operative dentin thickness and higher amount of dentin removal after root canal preparation in both oval and round canal groups.

Conclusions: (1) Both types of canals were more conical after root canal preparation, but oval root canals tend to leave more UCW area than round canals in the coronal two thirds of mandibular incisors, which contributes to the challenge for endodontic infection control. (2) Root canal preparation usually results in excessive dentin removal in the proximal dentin wall comparing with buccal and lingual walls in both types of canals of mandibular incisors.
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http://dx.doi.org/10.1186/s12903-022-02335-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308234PMC
July 2022
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