Publications by authors named "Jian Liu"

4,045 Publications

  • Page 1 of 1

Targeting MDK Abrogates IFN-γ-Elicited Metastasis inCancers of Various Origins.

Front Oncol 2022 7;12:885656. Epub 2022 Jun 7.

Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

IFN-γ is a pleiotropic cytokine with immunomodulatory and tumoricidal functions. It has been used as an anti-tumor agent in adjuvant therapies for various cancers. Paradoxically, recent advances have also demonstrated pro-tumorigenic effects of IFN-γ, especially in promoting cancer metastasis, with the mechanism remains unclear. This will undoubtedly hinder the application of IFN-γ in cancer treatment. Here, we verified that IFN-γ treatment led to activation of the epithelial-to-mesenchymal transition (EMT) programme and metastasis in cell lines of various cancers, including the kidney cancer cell line Caki-1, the lung cancer cell line A549, the cervical carcinoma cell line CaSki, the breast cancer cell line BT549 and the colon cancer cell line HCT116. We further disclosed that midkine (MDK), an emerging oncoprotein and EMT inducer, is a common responsive target of IFN-γ in these cell lines. Mechanistically, IFN-γ upregulated MDK STAT1, a principle downstream effector in the IFN-γ signalling. MDK is elevated in the majority of cancer types in the TCGA database, and its overexpression drove EMT activation and cancer metastasis in all examined cell lines. Targeting MDK using a specific MDK inhibitor (iMDK) broadly reversed IFN-γ-activated EMT, and subsequently abrogated IFN-γ-triggered metastasis. Collectively, our data uncover a MDK-dependent EMT inducing mechanism underlying IFN-γ-driven metastasis across cancers which could be attenuated by pharmacological inhibition of MDK. Based on these findings, we propose that MDK may be used as a potential therapeutic target to eliminate IFN-γ-elicited pro-metastatic adverse effect, and that combined MDK utilization may expand the application of IFN-γ in cancer and improve the clinical benefits from IFN-γ-based therapies.
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http://dx.doi.org/10.3389/fonc.2022.885656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210922PMC
June 2022

On-Chip Integrated Yb-Doped Waveguide Amplifiers on Thin Film Lithium Niobate.

Micromachines (Basel) 2022 May 30;13(6). Epub 2022 May 30.

State Key Laboratory of High Field Laser Physics and CAS Center for Excellence in Ultra-Intense Laser Science, Shanghai Institute of Optics and Fine Mechanics (SIOM), Chinese Academy of Sciences (CAS), Shanghai 201800, China.

We report the fabrication and optical characterization of Yb-doped waveguide amplifiers (YDWA) on the thin film lithium niobate fabricated by photolithography assisted chemo-mechanical etching. The fabricated Yb-doped lithium niobate waveguides demonstrates low propagation loss of 0.13 dB/cm at 1030 nm and 0.1 dB/cm at 1060 nm. The internal net gain of 5 dB at 1030 nm and 8 dB at 1060 nm are measured on a 4.0 cm long waveguide pumped by 976 nm laser diodes, indicating the gain per unit length of 1.25 dB/cm at 1030 nm and 2 dB/cm at 1060 nm, respectively. The integrated Yb-doped lithium niobate waveguide amplifiers will benefit the development of a powerful gain platform and are expected to contribute to the high-density integration of thin film lithium niobate based photonic chip.
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http://dx.doi.org/10.3390/mi13060865DOI Listing
May 2022

Global Bibliometric Developments on Solid Waste Recycling in Concrete Construction Engineering.

Materials (Basel) 2022 Jun 10;15(12). Epub 2022 Jun 10.

Library of Wuhan University of Technology, Wuhan University of Technology, Wuhan 430070, China.

The precise and visual analysis of solid waste recycling in concrete construction engineering is critical for the development of ecological civilization and for the secure supply of resources. This research makes a bibliometric analysis of the solid waste application in concrete construction engineering from 2000 to 2021 based on the Web of Science. The global bibliometric status, current research focus and future directions were used to indicate the global development of solid waste recycling in concrete construction engineering. The most reused solid wastes and most solid waste productive regions were concluded with this bibliometric analysis. China is far ahead of other countries in solid waste recycling in all aspects and heavy metal is one of the most prominent solid waste themes in China. By analyzing the most studied solid waste, fly ash appears to be the most popular and is widely used; half of the top ten-cited papers are correlated with it.
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http://dx.doi.org/10.3390/ma15124142DOI Listing
June 2022

The Effect of Pore Structure on Impact Behavior of Concrete Hollow Brick, Autoclaved Aerated Concrete and Foamed Concrete.

Materials (Basel) 2022 Jun 8;15(12). Epub 2022 Jun 8.

Department of Civil and Environmental Engineering, Harbin Institute of Technology, Shenzhen 518055, China.

Porous concrete is an energy absorption material, which has been widely used in civil engineering, traffic engineering and disaster reduction engineering. However, the effect of pore structure on the impact behavior of the porous concrete is lacked. In this study, a series of drop-weight impact tests were carried out on three typical types of porous concrete, i.e., concrete hollow brick (CHB), autoclaved aerated concrete (AAC) and foamed concrete (FC), to investigate the effect of pore structures on their impact behavior. For comparison, static load tests were also conducted as references. According to the damage to the samples, the developments of impact force, strain, contact stress-strain relationship and absorbed energy during drop-weight during the impact test were measured and analyzed. The results show that the ratio between the peak impact stress and compressive strength of CHB was 0.44, while that of AAC and FC increased to about 0.6, indicating that the small and uniform pore structure in AAC and FC had a higher resistance against impact load than the hollow cavity of CHB. In addition, the elastic recovery strain in AAC increased by about 0.2% and its strain at peak contact stress increased by about 160% for a comparison of CHB, implying that a small open pore structure could enhance ductility. Besides, the peak contact stress of FC was close to that of AAC during impact loading, while the strain at peak contact stress of FC increased by about 36% compared with AAC, revealing that the closed-pore structure could further enhance the deformation potential. Correspondingly, the energy absorption rates of CHB, AAC and FC were 85.9 kJ/s, 54.4 kJ/s and 49.7 kJ/s, respectively, where AAC decreased by about 58% compared with CHB, and FC decreased by about 10% compared with AAC.
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http://dx.doi.org/10.3390/ma15124075DOI Listing
June 2022

Effect of Transcranial Pulsed Current Stimulation on Fatigue Delay after Medium-Intensity Training.

Int J Environ Res Public Health 2022 Jun 8;19(12). Epub 2022 Jun 8.

College of Sports Science, Nantong University, Nantong 226019, China.

The purpose of this study was to investigate the effect of transcranial pulsed current stimulation (tPCS) on fatigue delay after medium-intensity training.

Materials And Methods: Ninety healthy college athletes were randomly divided into an experimental group ( = 45) and control group ( = 45). The experimental group received medium-intensity training for a week. After each training, the experimental group received true stimulation of tPCS (continuous 15 min 1.5 mA current intensity stimulation). The control group received sham stimulation. The physiological and biochemical indicators of participants were tested before and after the experiment, and finally 30 participants in each group were included for data analysis.

Results: In the experimental group, creatine kinase (CK), cortisol (C), time-domain heart rate variability indices root mean square of the successive differences (RMSSD), standard deviation of normal R-R intervals (SDNN), and frequency domain indicator low frequency (LF) all increased slowly after the intervention. Among these, CK, C, and SDNN values were significantly lower than those in the control group ( < 0.05). Testosterone (T), T/C, and heart rate variability frequency domain indicator high frequency (HF) in the experimental group decreased slowly after the intervention, and the HF value was significantly lower than that in the control group ( < 0.05). The changes in all of the indicators in the experimental group were smaller than those in the control group.

Conclusion: The application of tPCS after medium-intensity training enhanced the adaptability to training and had a significant effect on the maintenance of physiological state. The application of tPCS can significantly promote the recovery of autonomic nervous system function, enhance the regulation of parasympathetic nerves, and delay the occurrence of fatigue.
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http://dx.doi.org/10.3390/ijerph19127042DOI Listing
June 2022

Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice.

Antioxidants (Basel) 2022 Jun 9;11(6). Epub 2022 Jun 9.

Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China.

Hyperglycemia in diabetes mellitus impairs endothelial function and disrupts microRNA (miRNA) profiles in vasculature, increasing the risk of diabetes-associated complications, including coronary artery disease, diabetic retinopathy, and diabetic nephropathy. miR-181b was previously reported to be an anti-inflammatory mediator in vasculature against atherosclerosis. The current study aimed to investigate whether miR-181b ameliorates diabetes-associated endothelial dysfunction, and to identify potential molecular mechanisms and upstream inducer of miR-181b. We found that miR-181b level was decreased in renal arteries of diabetic patients and in advanced glycation end products (AGEs)-treated renal arteries of non-diabetic patients. Transfection of miR-181b mimics improved endothelium-dependent vasodilation in aortas of high fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice, accompanied by suppression of superoxide overproduction and vascular inflammation markers. AMPK activator-induced AMPK activation upregulated miR-181b level in human umbilical vein endothelial cells (HUVECs). Chronic exercise, potentially through increased blood flow, activated AMPK/miR-181b axis in aortas of diabetic mice. Exposure to laminar shear stress upregulated miR-181b expression in HUVECs. Overall, our findings highlight a critical role of AMPK/miR-181b axis and extend the benefits of chronic exercise in counteracting diabetes-associated endothelial dysfunction.
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http://dx.doi.org/10.3390/antiox11061137DOI Listing
June 2022

Solid-Phase Synthesis of Red Fluorescent Carbon Dots for the Dual-Mode Detection of Hexavalent Chromium and Cell Imaging.

Biosensors (Basel) 2022 Jun 20;12(6). Epub 2022 Jun 20.

Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

The excellent optical properties and biocompatibility of red fluorescence carbon dots (R-CDs) provide a new approach for the effective analysis of hexavalent chromium Cr(VI) in environmental and biological samples. However, the application of R-CDs is still limited by low yield and unfriendly synthesis route. In this study, we developed a new type of R-CDs based on a simple and green solid-phase preparation strategy. The synthesized R-CDs can emit bright red fluorescence with an emission wavelength of 625 nm and also have an obvious visible light absorption capacity. Furthermore, the absorption and fluorescence signals of the R-CDs aqueous solution are sensitive to Cr(VI), which is reflected in color change and fluorescence quenching. Based on that, a scanometric and fluorescent dual-mode analysis system for the rapid and accurate detection of Cr(VI) was established well within the limit of detection at 80 nM and 9.1 nM, respectively. The proposed methods also possess high specificity and were applied for the detection of Cr(VI) in real water samples. More importantly, the synthesized R-CDs with good biocompatibility were further successfully applied for visualizing intracellular Cr(VI) in Hela cells.
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http://dx.doi.org/10.3390/bios12060432DOI Listing
June 2022

Effective RNAi in leukemia cells is enhanced by spermine-modified pullulan combined with desloratadine.

Carbohydr Polym 2022 Sep 21;292:119646. Epub 2022 May 21.

Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China. Electronic address:

RNA interference is a very useful tool for clinical treatment as well as mechanistic studies of leukemia. However, leukemia cells are known as hard-to-transfected by non-virus carriers. The low capacity of endocytosis and lysosomal escape of synthetic carriers are two obstacles for successful RNAi in leukemia cells. In this work, we established a universal powerful strategy for mediating effective RNAi in different types of leukemia cells by sequentially using spermine-modified pullulan (PS) as siRNA carrier and desloratadine (DL) to promote the lysosomal escape. It was shown that the complex of PS and siRNA could be largely internalized by human T-cell acute lymphoblastic leukemia cells, acute myeloid leukemia cells and chronic myeloid leukemia cells in serum-containing media, and the internalized complex was able to escape from the lysosomes by the aid of DL, resulting in effective RNAi against the key genes for the different leukemia cells.
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http://dx.doi.org/10.1016/j.carbpol.2022.119646DOI Listing
September 2022

Dendrobium officinale polysaccharide promotes M1 polarization of TAMs to inhibit tumor growth by targeting TLR2.

Carbohydr Polym 2022 Sep 1;292:119683. Epub 2022 Jun 1.

School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China. Electronic address:

Promoting M1 polarization of tumor-associated macrophages (TAMs) is an effective pathway for malignant tumor therapy. In this study, we aimed to demonstrate whether homogeneous Dendrobium officinale polysaccharide (DOP) could promote M1 polarization of TAMs to inhibit tumor growth, and how it promoted. Results exhibited that DOP could inhibit the tumor growth and promote the M1 polarization of TAMs in tumor-bearing mice. Macrophage depletion and replenishment experiment clearly proved that the inhibitory effect of DOP on tumor growth is dependent on promoting M1 polarization of TAMs. Moreover, we found that DOP could reach tumor microenvironment (TME) and directly bind to TAMs to promote its M1 polarization via targeting toll-like receptor 2 (TLR2) after oral administration. These results clarified that DOP could remarkably inhibit the tumor growth of tumor-bearing mice via directly targeting the TLR2 of TAMs to promote its M1 polarization.
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http://dx.doi.org/10.1016/j.carbpol.2022.119683DOI Listing
September 2022

Individualized Analysis and Treatment of Difficult Weaning From Ventilation Following Open Cardiac Surgery in Young Children With Congenital Heart Disease.

Front Cardiovasc Med 2022 1;9:768904. Epub 2022 Jun 1.

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Aims: The study explores the leading causes of postoperative extubation difficulties in pediatric patients (neonates and toddlers) with congenital heart diseases and establishes individualized treatment for different reasons.

Method: We retrospectively analyzed medical records of 4,971 pediatric patients with congenital heart defects treated in three tertiary Congenital Heart Disease Centres in China from January 2005 to December 2020, from whom we selected those with difficulty extubation but successful weaning during the postoperative period. Next, we performed an analysis of risk factors and reported the combined experience of individualized treatment for successful extubation.

Results: Seventy-five pediatric patients were identified in our database, among whom 23 had airway stenosis, 17 had diaphragmatic dysfunction, and 35 had pulmonary infection. The patients were all successfully weaned from the ventilator after an individualized treatment plan. In addition, the intubation time in the airway stenosis group was 17.7 ± 9.0, 33.6 ± 13.9 days in the diaphragmatic dysfunction group, and 11.9 ± 3.8 days in the pulmonary infection group.

Conclusion: Given the primary reasons for difficult weaning following open-heart surgery in pediatric patients with congenital heart diseases, an individualized treatment scheme can achieve the ideal therapeutic effect where patients can be weaned faster with a shorter intubation period.
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http://dx.doi.org/10.3389/fcvm.2022.768904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198256PMC
June 2022

Differences in the Impact of Heart Rate Variability on the Surgical Approach in Patients With Early Cervical Cancer: Laparoscopic versus Open Surgery.

Front Oncol 2022 3;12:804242. Epub 2022 Jun 3.

School of Medical Imaging, Bengbu Medical College, Bengbu, China.

Background: Evidence suggests that the risk of recurrence and death in patients with early cervical cancer (ECC) undergoing minimally invasive surgery is significantly higher than that in patients undergoing open surgery. However, the mechanisms underlying such a difference remain unclear. Heart rate variability (HRV) represents autonomic nerve activity, which is related to tumorgenesis and can be used as a prognostic indicator for various cancers. The main purpose of this study was to explore the difference in the effects of laparoscopic and open surgery on HRV in ECC patients.

Methods: A total of 68 ECC (FIGO IA1 with lymphovascular space invasion -IIA2) patients undergoing radical hysterectomy for the first time (84% open group vs. 16% laparoscopic group) were included. A single-lead micro-ECG recorder was used to collect 5 min electrocardiograms 1 day before the operation and 3 days after the operation, and then HRV time domain and frequency domain indices were analyzed, including mean heart rate (MeanHR), maximum heart rate (MaxHR), minimum heart rate (MinHR), the standard deviation of all normal-to-normal intervals (SDNN), the root mean square of successive interval differences (RMSSD), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), total power (TP), and the ratio of LF to HF (LF/HF).

Results: Heart rate (i.e., MeanHR, MaxHR, and MinHR) were significantly higher, and HRV (i.e., SDNN, RMSSD, LF, HF, and TP) were significantly lower after the operation than before the operation in both the laparoscopic and open groups ( < 0.05). The postoperative reduction in RMSSD and HF was significantly higher in the laparoscopic group than in the open group ( < 0.05).

Conclusions: These data suggest that radical hysterectomy can lead to increased heart rate and decreased HRV in patients with ECC, which can negatively affect cardiac autonomic regulation. Compared with open surgery, laparoscopic surgery has a greater negative impact on the HRV of ECC patients.
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http://dx.doi.org/10.3389/fonc.2022.804242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205605PMC
June 2022

MAPK/ERK-CBP-RFPL-3 Mediates Adipose-Derived Stem Cell-Induced Tumor Growth in Breast Cancer Cells by Activating Telomerase Reverse Transcriptase Expression.

Stem Cells Int 2022 7;2022:8540535. Epub 2022 Jun 7.

Department of Thyroid and Breast Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.

Adipose-derived stem cells (ASCs) improve the self-renewal and survival of fat grafts in breast reconstruction after oncology surgery. However, ASCs have also been found to enhance breast cancer growth, and its role in tumor proliferation remains largely elusive. Here, we explored a novel mechanism that mediates hTERT reactivation during ASC-induced tumor growth in breast cancer cells. In this study, we found the proliferative ability of breast cancer cells markedly increased with ASC coculture. To explore the molecular mechanism, we treated cells with anibody/inhibitor and found that the activation of MEK-ERK pathway was triggered in breast cancer cells by SCF secreted from ASCs, leading to the nuclear recruitment of CBP. As a coactivator of hTERT, CBP subsequently coordinated with RFPL-3 upregulated hTERT transcription and telomerase activity. The inhibition of CBP and RFPL-3 abrogated the activation of hTERT transcription and the promotion of proliferation in breast cancer cells with cocultured ASCs in vitro and in vivo. Collectively, our study findings indicated that CBP coordination with RFPL-3 promotes ASC-induced breast cancer cell proliferation by anchoring to the hTERT promoter and upregulating telomerase activity, which is activated by the MAPK/ERK pathway.
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http://dx.doi.org/10.1155/2022/8540535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197637PMC
June 2022

Sulforaphane alleviates high fat diet-induced insulin resistance via AMPK/Nrf2/GPx4 axis.

Biomed Pharmacother 2022 Aug 14;152:113273. Epub 2022 Jun 14.

Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China. Electronic address:

Insulin resistance is a characteristic feature of type 2 diabetes. Sulforaphane (SFN) is a natural antioxidant extracted from the cruciferous vegetables. Recent study reported that SFN exhibits excellent anti-diabetic effects, however, the underlying mechanism is still unclear. This study aimed to investigate the therapeutic effects of SFN on a high-fat diet (HFD)-induced insulin resistance and potential mechanism. SFN was found to effectively reduce body weight, fasting blood glucose and hyperlipidemia, and improve liver function in HFD-fed mice. Furthermore, SFN effectively increased glucose uptake and improved insulin signaling in palmitic acid (PA)-induced HepG2 cells. SFN also led to increased expression of antioxidant genes downstream of Nrf2 and decreased accumulation of lipid peroxides MDA and 4-HNE, both in vivo and in vitro. Further studies revealed that SFN significantly reduced glutathione peroxidase 4 (GPx4) inactivation-mediated oxidative stress by activating the AMPK and Nrf2 signaling pathways. In PA-induced HepG2 cells and flies, the alleviation of insulin resistance by SFN was diminished by GPx4 inhibitor. Taken together, SFN ameliorated HFD-induced insulin resistance by activating the AMPK-Nrf2-GPx4 pathway, providing new insights into SFN as a therapeutic compound for the alleviation of insulin resistance.
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http://dx.doi.org/10.1016/j.biopha.2022.113273DOI Listing
August 2022

Novel Small Molecule Tyrosine Kinase 2 Pseudokinase Ligands Block Cytokine-Induced TYK2-Mediated Signaling Pathways.

Front Immunol 2022 20;13:884399. Epub 2022 May 20.

R & D Center, Shanghai Hengrui Pharmaceutical Co. Ltd., Shanghai, China.

A member of the Janus kinase (JAK) family, Tyrosine Kinase 2 (TYK2), is crucial in mediating various cytokine-signaling pathways such as interleukin-23 (IL23), interleukin-12 (IL12) and type I Interferons (IFN) which contribute to autoimmune disorders (e.g., psoriasis, lupus, and inflammatory bowel disease). Thus, TYK2 represents an attractive target to develop small-molecule therapeutics for the treatment of cytokine-driven inflammatory diseases. Selective inhibition of TYK2 over other JAK isoforms is critical to achieve a favorable therapeutic index in the development of TYK2 inhibitors. However, designing small molecule inhibitors to target the adenosine triphosphate (ATP) binding site of TYK2 kinase has been challenging due to the substantial structural homology of the JAK family catalytic domains. Here, we employed an approach to target the JAK homology 2 (JH2) pseudokinase regulatory domain of the TYK2 protein. We developed a series of small-molecule TYK2 pseudokinase ligands, which suppress the TYK2 catalytic activity through allosteric regulation. The TYK2 pseudokinase-binding small molecules in this study simultaneously achieve high affinity-binding for the TYK2 JH2 domain while also affording significantly reduced affinity for the TYK2 JAK homology 1 (JH1) kinase domain. These TYK2 JH2 selective molecules, although possessing little effect on suppressing the catalytic activity of the isolated TYK2 JH1 catalytic domain in the kinase assays, can still significantly block the TYK2-mediated receptor-stimulated pathways by binding to the TYK2 JH2 domain and allosterically regulating the TYK2 JH1 kinase. These compounds are potent towards human T-cell lines and primary immune cells as well as in human whole-blood specimens. Moreover, TYK2 JH2-binding ligands exhibit remarkable selectivity of TYK2 over JAK isoforms not only biochemically but also in a panel of receptor-stimulated JAK1/JAK2/JAK3-driven cellular functional assays. In addition, the TYK2 JH2-targeting ligands also demonstrate high selectivity in a multi-kinase screening panel. The data in the current study underscores that the TYK2 JH2 pseudokinase is a promising therapeutic target for achieving a high degree of biological selectivity. Meanwhile, targeting the JH2 domain represents an appealing strategy for the development of clinically well-tolerated TYK2 inhibitors that would have superior efficacy and a favorable safety profile compared to the existing Janus kinase inhibitors against autoimmune diseases.
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http://dx.doi.org/10.3389/fimmu.2022.884399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186491PMC
June 2022

Activation and blockade of 5-HT receptors in the dorsal hippocampus enhance working and hippocampus-dependent memories in the unilateral 6-hydroxydopamine lesioned rats.

Behav Brain Res 2022 Jun 8;431:113952. Epub 2022 Jun 8.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. Electronic address:

Cognitive dysfunction is a common symptom in Parkinson's disease (PD). Serotonin4 (5-HT) receptors are richly expressed in the dorsal hippocampus (dHIPP) and play an important role in cognitive activities. However, the mechanism underlying the role of dHIPP 5-HT receptors in PD-related cognitive dysfunction remains unclear. Here we found that unilateral 6-hydroxydopamine lesions of the medial forebrain bundle increased the protein expression of 5-HT receptors in the dHIPP, decreased hippocampal theta rhythm, and impaired working memory and hippocampus-dependent memory in the T-maze and hole-board test, respectively. Both activation and blockade of dHIPP 5-HT receptors (agonist BIMU8 and antagonist GR113808) improved working memory and hippocampus-dependent memory in the lesioned rats, but not in sham rats. Activation of dHIPP 5-HT receptors increased hippocampal theta rhythm in the lesioned rats. The neurochemical studies showed that injection of BIMU8, GR113808 or GR113808/BIMU8 in the dHIPP increased the levels of dopamine in the medial prefrontal cortex (mPFC), dHIPP and amygdala, and the level of 5-HT in the amygdala in the lesioned rats, but not in sham rats. Injection of GR113808 or GR113808/BIMU8 into the dHIPP also increased the levels of noradrenaline in the mPFC, dHIPP and amygdala only in the lesioned rats. These results suggest that activation or blockade of dHIPP 5-HT receptors may improve the cognitive impairments in parkinsonian rats, which may be due to the increase of hippocampal theta rhythm, up-regulated expressions of 5-HT receptors in the dHIPP and the changes in the levels of monoamines in the relative brain areas.
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http://dx.doi.org/10.1016/j.bbr.2022.113952DOI Listing
June 2022

Relationship between Chewing Sugar-free Gum and Dental Caries Status in China.

Chin J Dent Res 2022 Jun;25(2):131-137

Objective: To investigate the relationship between chewing sugar-free gum (SFG) and dental caries status in China.

Methods: A total of 860 teenagers (aged 12 to 15 years) and 490 adults (aged ≥ 18 years) were recruited using a multistage stratified cluster method from economically developed areas (Beijing, Guangdong) and less economically developed areas (Hubei, Xinjiang). Each participant completed a questionnaire including oral health-related knowledge of SFG and chewing habits of SFG and agreed to undertake a clinical assessment. Potential factors associated with chewing conditions were analysed through a chi-square statistical test. A negative binominal regression analysis was performed to quantify the relationship between dental caries and consumption of SFG.

Results: The overall percentage of the survey population who consumed SFG was 43.4%, and SFG-related knowledge and awareness was only 19.4%. For decayed, missing and filled permanent teeth (DMFT), the mean value was 1.63 ± 2.41 and 2.29 ± 3.65 in the chewing group and non-chewing group, respectively. According to the negative binominal regression analysis, the caries status in the SFG chewing group was better than in the non-chewing group (adjusted prevalence rate ratio [PRR] 0.73; 95% confidence interval [CI] 0.62-0.87).

Conclusion: The chewing condition and oral health-related knowledge and awareness of SFG is low. Chewing SFG is related to a better dental caries status, so regular consumption of SFG should be recommended when promoting oral health.
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http://dx.doi.org/10.3290/j.cjdr.b3086349DOI Listing
June 2022

Nobiletin Inhibits Hypoxia-Induced Placental Damage via Modulating P53 Signaling Pathway.

Nutrients 2022 Jun 1;14(11). Epub 2022 Jun 1.

School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.

In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague-Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.
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http://dx.doi.org/10.3390/nu14112332DOI Listing
June 2022

Improving the Stability of Lithium Aluminum Germanium Phosphate with Lithium Metal by Interface Engineering.

Nanomaterials (Basel) 2022 Jun 3;12(11). Epub 2022 Jun 3.

School of Engineering, Faculty of Applied Science, University of British Columbia, 3333 University Way, Kelowna, BC V1V 1V7, Canada.

Lithium aluminum germanium phosphate (LAGP) solid electrolyte is receiving increasing attention due to its high ionic conductivity and low air sensitivity. However, the poor interface compatibility between lithium (Li) metal and LAGP remains the main challenge in developing all-solid-state lithium batteries (ASSLB) with a long cycle life. Herein, this work introduces a thin aluminum oxide (AlO) film on the surface of the LAGP pellet as a physical barrier to Li/LAGP interface by the atomic layer deposition technique. It is found that this layer induces the formation of stable solid electrolyte interphase, which significantly improves the structural and electrochemical stability of LAGP toward metallic Li. As a result, the optimized symmetrical cell exhibits a long lifetime of 360 h with an areal capacity of 0.2 mAh cm and a current density of 0.2 mA cm. This strategy provides new insights into the stabilization of the solid electrolyte/Li interface to boost the development of ASSLB.
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http://dx.doi.org/10.3390/nano12111912DOI Listing
June 2022

A novel three-dimensional quantitative assessment method for abnormal root morphology of the maxillary premolars in vivo on cone-beam computed tomography.

BMC Oral Health 2022 Jun 9;22(1):229. Epub 2022 Jun 9.

Department of Periodontology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.

Background: Previous studies have described and recorded abnormal root morphology; however, most of these studies were based on two-dimensional periapical or panoramic radiographs, and only a few studies have quantified it. We aimed to combine two-dimensional periapical radiographs and three-dimensional cone-beam computed tomography (CBCT) to conduct qualitative judgments and quantitative analyses of normal and conical roots, and explore the clinical diagnostic method of normal and conical roots based on intraoral radiographs and CBCT.

Methods: The conical root was identified visually on periapical radiographs as the clinical gold standard. All teeth were divided into the cone-rooted teeth (CRT) or normal-rooted teeth (NRT) groups. Furthermore, differences in root length (RL), root surface area (RSA), and root volume (RV) of conical and normal roots in the maxillary premolars on CBCT were compared. Receiver operator characteristic curves were generated, and the area under the curve (AUC) and cut-off values were calculated to evaluate the diagnostic value of RV, RSA, RV/RL, and RSA/RL.

Results: The RSAs of NRT and CRT were 236.88 ± 27.93 mm and 207.98 ± 27.80 mm, respectively (P = 0.000). The mean RV in the CRT group was lower than that in the NRT group, and the difference was statistically significant (253.40 ± 41.98 mm vs. 316.93 ± 49.89 mm, P = 0.000). The RSA and RV of conical roots in single root premolars were 12.29% and 19.33% less than those of normal roots, respectively. The AUC values of RSA/RL and RV/RL were 0.87 and 0.89, respectively, and the best cut-off values were 19.61 for RSA/RL (if RSA/RL was < 19.61, the teeth were considered CRT) and 24.05 for RV/RL (if RV/RL was < 24.05, the teeth were considered CRT).

Conclusions: CBCT has significant diagnostic value in the clinical evaluation of conical roots. RSA/RL and RV/RL were the best parameters with the largest AUC and high sensitivity and specificity.
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http://dx.doi.org/10.1186/s12903-022-02258-3DOI Listing
June 2022

Clinical application of cinematic rendering in maxillofacial fractures.

Int J Oral Maxillofac Surg 2022 Jun 6. Epub 2022 Jun 6.

Department of Radiology, Guizhou Provincial People's Hospital, Guiyang, China. Electronic address:

The purpose of this study was to evaluate the clinical application of cinematically rendered reconstructions of maxillofacial fractures. Ten surgeons and eight radiologists were shown three-dimensional images of 25 different patient cases, generated using both the volume rendering (VR) technique and the cinematic rendering (CR) technique. They were asked to mark the site of the fracture on the three-dimensional images and record the time this activity took. The effectiveness of the reconstructions to communicate with patients was assessed through the opinions of the surgeons and radiologists, as well as 25 patients. Subjective evaluations of the clinical value of the images were performed by the 18 surgeons and radiologists using a 10-item questionnaire. The percentages of correctly identified fractures of the nasal bone (P = 0.034), fracture dislocation (P < 0.001), and free bone fragments (P < 0.001) were significantly higher for CR images when compared to VR images, and identification took an average of 20.81 seconds for CR and 27.48 seconds for VR (P < 0.001). CR images were found to be more beneficial for communication with patients and scored higher for the display of fracture dislocation and free bone fragments than VR images (P < 0.05). CR images were found to have high clinical value in the visualization of maxillofacial fractures.
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http://dx.doi.org/10.1016/j.ijom.2022.05.003DOI Listing
June 2022

The quantitative relationship between coronary microcirculatory resistance and myocardial ischemia in patients with coronary artery disease.

J Biomech 2022 Jul 29;140:111166. Epub 2022 May 29.

College of Life Science and Chemistry, Faculty of Environment and Life, Beijing University of Technology, Beijing, China. Electronic address:

It was hypothesized that the microcirculatory resistance of resting state (R) might be a good predictor for ischemia. In this study, the quantitative relationship between R and myocardial ischemia in different stenosed degrees was explored and verified through retrospective analysis, and the diagnostic performance was evaluated. 136 patients were screened and divided into a training set (90 patients) and a validation set (46 patients). In the training set, R was calculated, and thresholds were determined by exploring the relationship between R and myocardial ischemia in different stenosed degrees. In the validation set, the diagnostic performance of the thresholds was verified. It was found that the 90 data mean difference (95%CI) of R between the ischemic group and the non-ischemic group was 63.03 (95 %CI: 25.72-100.34), p < 0.05. In the training set with stenosed degree 41-60%, 61-70%, 71-80%, and >81%, the average of R in the ischemic and non-ischemic groups were (80.79, 136.87), (96.41, 172.62), (128.99, 198.94) and (175.95, 310.79) mmHg/s/ml. The R thresholds were 87.18, 118.96, 142.35, and 177.39 mmHg/s/ml. In the validation set, the overall sensitivity, specificity, PPV, NPV, and accuracy were 73.3%, 77.4%, 61.1%, 85.7%, and 76.1%. In conclusion, R had a significant predictor on myocardial ischemia. As a smaller R represents greater myocardial mass perfusion, it is more likely that a stenosis will have a functional impact. Threshold analysis showed that R of different stenosed degrees was a quantitative predictor of myocardial ischemia, which could assist physicians with clinical treatment strategies.
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http://dx.doi.org/10.1016/j.jbiomech.2022.111166DOI Listing
July 2022

Network pharmacology approach and molecular docking to explore the potential mechanism of Wu-Wei-Wen-Tong Chubi capsules in rheumatoid arthritis.

Naunyn Schmiedebergs Arch Pharmacol 2022 Jun 7. Epub 2022 Jun 7.

Clinical Research Experiment Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, No. 117, Meishan Road, Shushan District, Hefei, 230031, Anhui, China.

Network pharmacology, a holistic approach based on the theory of biological network technology, integrates information from biological systems, drugs, and diseases. Here, this theory was used to predict the targets of Wu-Wei-Wen-Tong Chubi capsule (WWWT) to explore the mechanism in the treatment of rheumatoid arthritis (RA). The ingredients of each herbal medicine in WWWT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the active ingredients were screened through bioavailability (OB) ≥30% and drug-likeness (DL) ≥ 0.18. SwissTargetPrection and TCMSP were utilized to calculate and predict the targets of active ingredients. RA-related targets were obtained by searching the Genecards and OMIM databases. The common targets of RA and WWWT were used for gene ontology (GO), KEGG pathway enrichment, protein-protein interaction (PPI) analysis, and molecular docking. And then, four key genes were screened for subsequent verification experiments. In total, 90 active compounds and 330 potential targets of WWWT, 1310 targets of RA, and 135 intersection targets were found. Additionally, GO and pathway analysis identified 4610 significant GO terms and 147 significant KEGG pathways. Based on the PPI network, 11 key genes including IL-6, MMP-9, and TNF-α were screened out for molecular docking. Molecular docking showed that these key genes have good binding activities to active compounds of WWWT such as oroxylin a, kaempferol, and luteolin. Simultaneously, Western blot experimental validation demonstrated that the protein expressions of IL-6, MMP-9, TNF-α, and VEGFA significantly decreased after WWWT treatment. The mechanism of WWWT in treating RA involves multiple active compounds acting on multiple targets, and multiple pathways, which provides an important reference for further elucidation the mechanism and clinical applications of WWWT in the treatment of RA.
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http://dx.doi.org/10.1007/s00210-022-02260-0DOI Listing
June 2022

Low serum total testosterone level as a predictor of upgrading in low-risk prostate cancer patients after radical prostatectomy: A systematic review and meta-analysis.

Investig Clin Urol 2022 May 25. Epub 2022 May 25.

Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Purpose: To investigated the association between serum total testosterone and Gleason score upgrading of low-risk prostate cancer after radical prostatectomy (RP).

Materials And Methods: Medline, Web of Science, Embase, and Cochrane Library databases were searched to identify eligible studies published before October 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random or fixed effects models.

Results: Five studies comprising 1,203 low-risk prostate cancer patients were included. The results showed that low serum total testosterone (<300 ng/dL) is associated with a high rate of Gleason score upgrading after RP (OR, 2.3; 95% CI, 1.38-3.83; p<0.001; I², 92.2%). Notably, sensitivity and meta-regression analyses further strengthen the reliability of our results.

Conclusions: Our results support the idea that low serum total testosterone is associated with a high rate of Gleason score upgrading in prostate cancer patients after RP. It is beneficial for urologist to ensure close monitoring of prostate-specific antigen levels and imaging examination when choosing non-RP treatment for low-risk prostate cancer patients.
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http://dx.doi.org/10.4111/icu.20210459DOI Listing
May 2022

Age-dependent aneuploidy in mammalian oocytes instigated at the second meiotic division.

Aging Cell 2022 Jun 3:e13649. Epub 2022 Jun 3.

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Ageing severely affects the chromosome segregation process in human oocytes resulting in aneuploidy, infertility and developmental disorders. A considerable amount of segregation errors in humans are introduced at the second meiotic division. We have here compared the chromosome segregation process in young adult and aged female mice during the second meiotic division. More than half of the oocytes in aged mice displayed chromosome segregation irregularities at anaphase II, resulting in dramatically increased level of aneuploidy in haploid gametes, from 4% in young adult mice to 30% in aged mice. We find that the post-metaphase II process that efficiently corrects aberrant kinetochore-microtubule attachments in oocytes in young adult mice is approximately 10-fold less efficient in aged mice, in particular affecting chromosomes that show small inter-centromere distances at the metaphase II stage in aged mice. Our results reveal that post-metaphase II processes have critical impact on age-dependent aneuploidy in mammalian eggs.
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http://dx.doi.org/10.1111/acel.13649DOI Listing
June 2022

Discovery of non-substrate, environmentally sensitive turn-on fluorescent probes for imaging HDAC8 in tumor cells and tissue slices.

Bioorg Med Chem 2022 May 21;68:116821. Epub 2022 May 21.

School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Histone deacetylase 8 (HDAC8) is overexpressed in multiple cancers and lack of effective chemical probes which could detect and visualize HDAC8 in tumor cells and tissues remains unsolved. In this work, three novel turn-on HDAC8 fluorescent probes 17-19 derived from solvatochromic fluorophore 4-sulfamonyl-7-aminobenzoxadiazole (SBD) conjugating with a potent HDAC8 inhibitor PCI-34051 (IC = 10 nM) as the recognition group were fabricated. The probes exhibited much stronger fluorescence when they transfer from hydrophilic environment (Φ < 8%) to hydrophobic environment (Φ > 46%). Compared with PCI-34051 (K = 9.16 × 10 M), probes 17 (K = 5.37 × 10 M), 18 (K = 3.57 × 10 M) and 19 (K = 8.89 × 10 M) possessed slightly better affinity for HDAC8. Probe 19 was selected for cell imaging and it showed significantly enhanced fluorescence only after binding into the cavity of HDAC8 in SH-SY5Y and MDA-MB-231 tumor cells. Co-localization results demonstrated that HDAC8 is expressed in cytoplasm and nucleus. Furthermore, probe 19 was successfully utilized to distinguish the expression level of HDAC8 in SH-SY5Y tumor and normal tissue slices.
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http://dx.doi.org/10.1016/j.bmc.2022.116821DOI Listing
May 2022

Intraarticularly injectable silk hydrogel microspheres with enhanced mechanical and structural stability to attenuate osteoarthritis.

Biomaterials 2022 Jul 31;286:121611. Epub 2022 May 31.

Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, United States. Electronic address:

A silk fibroin (silk) hydrogel was prepared by using diglycidyl ether (BDDE), a chemical crosslinker commonly used to generate Food and Drug Administration (FDA)-approved hyaluronic acid (HA) medical products. The silk/BDDE hydrogels exhibited high elasticity (compressive modulus of 166 ± 15.0 kPa), anti-fatigue properties, and stable structure and mechanical strength in aqueous solution. Chemical crosslinking was conducted in a high concentration (9.3 M) of lithium bromide (LiBr) solution, a salt that is commonly used to dissolve degummed silk fibers during silk solubilization. The unfolded and extended structure of silk molecules with these reaction conditions, as well as the unique ionic environment provided by LiBr facilitated a high degree of crosslinking in the hydrogel. Similar hydrogels were not obtained when the silk was dissolved in other silk fiber-dissolving reagents (e.g., Ajisawa's, formic acid (FA)/LiBr, FA/CaCl solutions), likely because partially folded silk structures and the ionic conditions with these reagents were less favorable for the crosslinking reaction. Based on these findings, silk/BDDE hydrogel spheres were prepared using an oil/water (o/w) emulsification method and biocompatibility and biodegradation were evaluated in vivo, along with other silk gel control systems (e.g., enzyme-catalyzed di-tyrosine and pulverized silk/BDDE gel particles with irregular shapes). Histological and immunohistochemical analyses demonstrated that the silk/BDDE hydrogel spheres were biocompatible and served as a bio-lubricant to treat osteoarthritis (OA). The intra-articular injection of the gel spheres reduced pain as measured with OA rats, reduced cartilage damage and resisted the digestive environment in the articular cavity for extended time frames (>4 weeks), suggesting utility for pain relief and sustained drug release for future OA treatments.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121611DOI Listing
July 2022

Structural characterization and antagonistic effect against P-selectin-mediated function of SFF-32, a fucoidan fraction from Sargassum fusiforme.

J Ethnopharmacol 2022 Sep 1;295:115408. Epub 2022 Jun 1.

Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325035, PR China. Electronic address:

Ethnopharmacological Relevance: Sargassum fusiforme (Harvey) Setchell, or Haizao, has been used in traditional Chinese medicine (TCM) since at least the eighth century a.d. S. fusiforme is an essential component of several Chinese formulas, including Haizao Yuhu Decoction, used to treat goiter, and Neixiao Lei Li Wan used to treat scrofuloderma. The pharmacological efficacy of S. fusiforme may be related to its anti-inflammatory effect.

Aim Of The Study: To determine the structural characteristics of SFF-32, a fucoidan fraction from S. fusiforme, and its antagonistic effect against P-selectin mediated function.

Materials And Methods: The primary structure of SFF-32 was determined using methylation/GC-MS and NMR analysis. Surface morphology and solution conformation of SFF-32 were determined by scanning electron microscopy (SEM), Congo red test, and circular dichroic (CD) chromatography, respectively. The inhibitory effects of SFF-32 against the binding of P-selectin to HL-60 cells were evaluated using flow cytometry, static adhesion assay, and parallel-plate flow chamber assay. Furthermore, the blocking effect of SFF-32 on the interaction between P-selectin and PSGL-1 was evaluated using an in vitro protein binding assay.

Results: The main linkage types of SFF-32 were proven to →[3)-α-l-Fucp-(1→3,4)-α-l-Fucp-(1]→[4)-β-d-Manp-(1→3)-d-GlcAp-(1]→4)-β-d-Manp-(1→3)-β-d-Glcp-(1→4)-β-d-Manp-(1→2,3)-β-d-Galp-(1→4)-β-d-Manp-(1→[4)-α-l-Rhap-(1]→. The sulfated unit or terminal xylose residues were attached to the backbone through the C-3 of some fucose residues and terminal xylose residues were attached to C-3 of galactose residues. Moreover, SFF-32 disrupted P-selectin-mediated cell adhesion and rolling as well as blocked the interaction between P-selectin and its physiological ligand PSGL-1 in a dose-dependent manner.

Conclusions: Blocking the binding between P-selectin and PSGL-1 is the possible underlying mechanism by which SFF-32 inhibits P-selectin-mediated function, which demonstrated that SFF-32 may be a potential anti-inflammatory lead compound.
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http://dx.doi.org/10.1016/j.jep.2022.115408DOI Listing
September 2022

Mir-4728 is a Valuable Biomarker for Diagnostic and Prognostic Assessment of HER2-Positive Breast Cancer.

Front Mol Biosci 2022 17;9:818493. Epub 2022 May 17.

Department of Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Breast cancer remains one of the most common malignancies in female cancer patients. The rapid and accurate diagnosis of human epidermal growth factor receptor 2 (HER2) status is indispensable for breast cancer patients. The pre-miR-4728 (mir-4728) is encoded within an intron of the HER2 gene. We showed here that mir-4728 was the most significantly upregulated pre-miRNA in HER2-positive breast cancer patients (fold-change: 4.37), and it could serve as a strong diagnostic factor for the HER2 status in breast cancer patients ( < 0.0001). Moreover, mir-4728 was positively correlated with tumor recurrence and appeared to be a critical independent risk factor of tumor recurrence in patients with high tumor burden (HR: 7.558, 95% CI:1.842-31.006, = 0.005). Remarkably, HER2-positive patients with higher mir-4728 expression levels had better drug responses to targeted therapies. Furthermore, estrogen receptor (ESR), the predictive marker for endocrine therapies, was found to be the direct target of miR-4728-3p. Taken together, our results supported the potential role of mir-4728 in the diagnosis of HER2 status and the prognostic assessment of HER2-positive patients in response to targeted therapies.
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http://dx.doi.org/10.3389/fmolb.2022.818493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152170PMC
May 2022

Novel insights into probabilistic health risk and source apportionment based on bioaccessible potentially toxic elements around an abandoned e-waste dismantling site.

Sci Total Environ 2022 Sep 30;838(Pt 3):156372. Epub 2022 May 30.

College of Environmental and Resource Sciences, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Zhejiang University, Hangzhou 310058, China. Electronic address:

The study of potentially toxic element (PTE) hazards around e-waste recycling areas has attracted increasing attention but does not consider elemental bioaccessibility. Here, the respiratory and oral bioaccessibilities were incorporated into probabilistic health risk evaluation and source contribution apportionment. The results showed that soil Cd yielded the highest respiratory and oral bioaccessibility, whereas Cr in soils and vegetables attained the lowest oral bioaccessibility. When incorporating metal bioaccessibility into health risk assessment, a 48.3%-55.7% overestimation of non-cancer and cancer risks can be avoided relative to the risk assessment based on the total concentrations of PTEs. More importantly, priority control metals were misidentified without consideration of bioaccessibility. Cadmium, As, and Cr were screened as the priority metal(loid)s for targeted risk control based on the total PTEs, whereas Cd, Zn, and Cu were the priority metal(loid)s based on the bioaccessible PTEs. Furthermore, source apportionment revealed that >50% of oral bioaccessible Cd, Cu, Ni, Pb, and Zn in farmland were contributed by e-waste dismantling activities, whereas bioaccessible As and Cr mainly originated from agrochemical applications and natural sources, respectively. This study emphasizes the refinement of risk estimation and source apportionment through metal bioaccessibility adjustment, which facilitates the realistic assessment of adverse health effects in humans and the precise identification of high-risk sources.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156372DOI Listing
September 2022

Accelerating Quantum Mechanical and Molecular Mechanical (QM/MM) Molecular Dynamics Simulations with Multiple Time Step Integration and a Recalibrated Semiempirical QM/MM Hamiltonian.

J Phys Chem B 2022 Jun 2. Epub 2022 Jun 2.

Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma 73019-5251, United States.

Molecular dynamics (MD) simulations employing quantum mechanical and molecular mechanical (ai-QM/MM) potentials are considered to be the state of the art, but the high computational cost associated with the ai-QM calculations remains a theoretical challenge for their routine application. Here, we present a modified protocol of the multiple time step (MTS) method for accelerating ai-QM/MM MD simulations of condensed-phase reactions. Within a previous MTS protocol [Nam 2014, 10, 4175], reference forces are evaluated using a low-level (semiempirical QM/MM) Hamiltonian and employed at inner time steps to propagate the nuclear motions. Correction forces, which arise from the force differences between high-level (ai-QM/MM) and low-level Hamiltonians, are applied at outer time steps, where the MTS algorithm allows the time-reversible integration of the correction forces. To increase the outer step size, which is bound by the highest-frequency component in the correction forces, the semiempirical QM Hamiltonian is recalibrated in this work to minimize the magnitude of the correction forces. The remaining high-frequency modes, which are mainly bond stretches involving hydrogen atoms, are then removed from the correction forces. When combined with a Langevin or SIN(R) thermostat, the modified MTS-QM/MM scheme remains robust with an up to 8 (with Langevin) or 10 fs (with SIN(R)) outer time step (with 1 fs inner time steps) for the chorismate mutase system. This leads to an over 5-fold speedup over standard ai-QM/MM simulations, without sacrificing the accuracy in the predicted free energy profile of the reaction.
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http://dx.doi.org/10.1021/acs.jpcb.2c02262DOI Listing
June 2022
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