Publications by authors named "Xiang Wang"

2,493 Publications

  • Page 1 of 1

Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.

ACS Appl Mater Interfaces 2022 Aug 11. Epub 2022 Aug 11.

Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai 200032, China.

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.
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http://dx.doi.org/10.1021/acsami.2c07247DOI Listing
August 2022

Effect of Etomidate vs Propofol for Total Intravenous Anesthesia on Major Postoperative Complications in Older Patients: A Randomized Clinical Trial.

JAMA Surg 2022 Aug 10. Epub 2022 Aug 10.

Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Importance: Older patients may benefit from the hemodynamic stability of etomidate for general anesthesia. However, it remains uncertain whether the potential for adrenocortical suppression with etomidate may increase morbidity.

Objective: To test the primary hypothesis that etomidate vs propofol for anesthesia does not increase in-hospital morbidity after abdominal surgery in older patients.

Design, Setting, And Participants: This multicenter, parallel-group, noninferiority randomized clinical trial (Etomidate vs Propofol for In-hospital Complications [EPIC]) was conducted between August 15, 2017, and November 20, 2020, at 22 tertiary hospitals in China. Participants were aged 65 to 80 years and were scheduled for elective abdominal surgery. Patients and outcome assessors were blinded to group allocation. Data analysis followed a modified intention-to-treat principle.

Interventions: Patients were randomized 1:1 to receive either etomidate or propofol for general anesthesia by target-controlled infusion.

Main Outcomes And Measures: Primary outcome was a composite of major in-hospital postoperative complications (with a noninferiority margin of 3%). Secondary outcomes included intraoperative hemodynamic measurements; postoperative adrenocortical hormone levels; self-reported postoperative pain, nausea, and vomiting; and mortality at postoperative months 6 and 12.

Results: A total of 1944 participants were randomized, of whom 1917 (98.6%) completed the trial. Patients were randomized to the etomidate group (n = 967; mean [SD] age, 70.3 [4.0] years; 578 men [59.8%]) or propofol group (n = 950; mean [SD] age, 70.6 [4.2] years; 533 men [56.1%]). The primary end point occurred in 90 of 967 patients (9.3%) in the etomidate group and 83 of 950 patients (8.7%) in the propofol group, which met the noninferiority criterion (risk difference [RD], 0.6%; 95% CI, -1.6% to 2.7%; P = .66). In the etomidate group, mean (SD) cortisol levels were lower at the end of surgery (4.8 [2.7] μg/dL vs 6.1 [3.4] μg/dL; P < .001), and mean (SD) aldosterone levels were lower at the end of surgery (0.13 [0.05] ng/dL vs 0.15 [0.07] ng/dL; P = .02) and on postoperative day 1 (0.14 [0.04] ng/dL vs 0.16 [0.06] ng/dL; P = .001) compared with the propofol group. No difference in mortality was observed between the etomidate and propofol groups at postoperative month 6 (2.2% vs 3.0%; RD, -0.8%; 95% CI, -2.2% to 0.7%) and 12 (3.3% vs 3.9%; RD, -0.6%; 95% CI, -2.3% to 1.0%). More patients had pneumonia in the etomidate group than in the propofol group (2.0% vs 0.3%; RD, 1.7%; 95% CI, 0.7% to 2.8%; P = .001). Results were consistent in the per-protocol population.

Conclusions And Relevance: Results of this trial showed that, compared with propofol, etomidate anesthesia did not increase overall major in-hospital morbidity after abdominal surgery in older patients, although it induced transient adrenocortical suppression.

Trial Registration: ClinicalTrials.gov Identifier: NCT02910206.
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http://dx.doi.org/10.1001/jamasurg.2022.3338DOI Listing
August 2022

Pediatric Myopia Progression During the COVID-19 Pandemic Home Quarantine and the Risk Factors: A Systematic Review and Meta-Analysis.

Front Public Health 2022 22;10:835449. Epub 2022 Jul 22.

Department of Internal Traditional Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Background: The COVID-19 pandemic has made many countries adopt restrictive measures like home quarantine. Children were required to study at home, which made parents worried about the rapid myopic progression of their children. To compare myopia progression during the COVID-19 pandemic home quarantine with the time before it and risk factors of myopia progression, we conducted this study.

Methods: We searched PubMed, Embase, the Cochrane Library, and Web of Science to find literature from December 2019 to March 2022 related to COVID-19 pandemic home quarantine and children's myopia progression. Outcomes of myopia progression included axial length and spherical equivalent refraction. Factors of digital screen device time and outdoor activity time were analyzed.

Results: Ten studies were included in this meta-analysis. Compared to the same period before the COVID-19 pandemic, spherical equivalent refraction decreased (OR = -0.27; 95% CI = [-0.33, -0.21]; Z = 8.42; < 0.00001). However, the subgroup analysis showed that there were no significant differences in spherical equivalent refraction between the two groups in higher-grade school-aged children (grades 4 and above, 11 to 18 years old) (OR = 0.01; 95% CI = [-0.05, 0.07]; Z =0.4; = 0.69). The outcome of axial length showed no significant difference (OR = 0.06; 95% CI = [-0.31, 0.44]; Z = 0.34; = 0.74). As for risk factors, the forest plots showed that digital screen device time (OR = 4.56; 95% CI = [4.45, 4.66]; Z = 85.57; < 0.00001) and outdoor activity time (OR = -1.82; 95% CI = [-2.87, -0.76]; Z = 3.37; = 0.0008) were risk factors of myopia progression.

Conclusion: Compared with the time before the COVID-19 pandemic, myopia progression in children during COVID-19 pandemic home quarantine was accelerated, especially in younger children. Increased digital screen device and decreased outdoor activity times were risk factors. When home quarantine eases, more time on outdoor activities and less time on digital screen devices are needed for children.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/logout.php.
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http://dx.doi.org/10.3389/fpubh.2022.835449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355634PMC
August 2022

Efficacy and Safety of Curcumin and Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

Front Immunol 2022 22;13:891822. Epub 2022 Jul 22.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Background: Modern pharmacological research found that the chemical components of are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis.

Methods: Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis.

Results: Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA.

Conclusion: Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.
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http://dx.doi.org/10.3389/fimmu.2022.891822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353077PMC
August 2022

Gonadal tumor risk in pediatric and adolescent phenotypic females with disorders of sex development and Y chromosomal constitution with different genetic etiologies.

Front Pediatr 2022 22;10:856128. Epub 2022 Jul 22.

Division of Pediatric Urology, Children's Hospital of Fudan University, Shanghai, China.

Objectives: This retrospective study sought to investigate the risk and proportion of gonadal neoplasms in phenotypic female pediatric patients with DSD and the presence of the Y chromosome and different genetic backgrounds in a single Chinese center.

Materials And Methods: From January 2012 to December 2020, pediatric and adolescent patients with DSD and the presence of the Y chromosome who had unambiguous female genitalia and underwent bilateral gonadectomy or gonadal biopsy were included in this study. Patients' demographics, karyotype, laboratory test results, gross pathology, and histology of gonadal tissue were all collected. The patients were divided into three groups based on their different genetic backgrounds, and the percentage of gonadal tumors was calculated to assess the risk of gonadal tumor and malignancy by etiology.

Results: A total of 22 patients with DSD and an unambiguous female phenotype with a Y chromosome were recruited. The mean age was 10.91 ± 4.99 years (9 months to 19 years). Gonadal neoplasia was confirmed in six (27.3%) cases by pathological examination of surgical gonadal tissue samples. Among 44 gonadal samples from these 22 patients, the following were identified: five gonadoblastomas, three dysgerminomas, and two Leydig cell tumors. The youngest patient with a tumor was a 2-year-old girl with 46,XY complete gonadal dysgenesis (46,XY CGD or Swyer syndrome) and bilateral gonadoblastoma. Patients with 46,XY complete gonadal dysgenesis (4/6; 66.7%) had the highest tumor occurrence rate. Among 10 patients with Turner syndrome with the presence of the Y chromosome, only one patient was diagnosed with a gonadal tumor. Leydig cell tumor was diagnosed in only one of six patients with 46,XY androgen synthesis/action disorders.

Conclusion: Pediatric patients with 46,XY complete gonadal dysgenesis had a significantly increased risk of developing gonadal tumors and underwent prophylactic gonadectomy as soon as the diagnosis was confirmed, whereas those with Turner syndrome with Y chromosome and 46,XY androgen synthesis/action disorders had a relatively low risk. In view of the limited number of patients, a large multicenter study with close follow-ups is needed to support these conclusions.
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http://dx.doi.org/10.3389/fped.2022.856128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353051PMC
July 2022

Central nervous system efficacy of furmonertinib (AST2818) versus gefitinib as first-line treatment for EGFR mutated non-small cell lung cancer: results from the FURLONG study.

J Thorac Oncol 2022 Aug 3. Epub 2022 Aug 3.

Shanghai Allist Pharmaceuticals, Shanghai, People's Republic of China.

Introduction: Furmonertinib (AST2818) is a pan epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with central nervous system (CNS) anti-tumor activity. We report the CNS efficacy of furmonertinib compared with gefitinib in untreated EGFR sensitizing mutation positive non-small cell lung cancer (NSCLC) from the FURLONG study.

Methods: FURLONG was a randomized, double-blind, phase 3 study conducted in 55 hospitals in People's Republic of China. Patients 1:1 randomly received furmonertinib 80mg Qd or gefitinib 250mg Qd treatment. At screening, all the patients underwent brain scan. Patients with asymptomatic steady CNS metastases at baseline constituted this pre-planned CNS subgroup analysis.

Results: A total of 358 patients were enrolled in the FURLONG study. In the 133 (37%) patients who had measurable or non-measurable CNS lesions, CNS progression-free survival (PFS) was 20.8 months (95% confidence interval [95%CI] 15.2, 25.3) in the furmonertinib group and 9.8 months (95%CI 7.2, 18.0) in the gefitinib group (hazard ratio 0.40 [95%CI 0.23, 0.71]; p=0.0011). In the 60 (17%) patients who had measurable CNS lesions, CNS objective response rate (ORR) was 91% (95%CI 72, 99) with furmonertinib and 65% (95%CI 48, 80) with gefitinib (odds ratio 6.82 [95%CI 1.23, 37.67]; p=0.0277). The least square mean difference of CNS depth of response (DepOR) between furmonertinib and gefitinib was 23% (95%CI 10, 37; p=0.0011).

Conclusions: Furmonertinib first-line treatment showed superior efficacy in CNS PFS, CNS ORR and CNS DepOR compared with gefitinib in EGFR mutated NSCLC patients with CNS metastases.
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http://dx.doi.org/10.1016/j.jtho.2022.07.1143DOI Listing
August 2022

Decreased functional coupling within default mode network in major depressive disorder with childhood trauma.

J Psychiatr Res 2022 Jul 31;154:61-70. Epub 2022 Jul 31.

Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China. Electronic address:

Objective: Childhood trauma (CT) has been supported to be a high-risk factor for major depressive disorder (MDD), but the neural mechanism linking CT and depression remains unclear. The aim of this study is to deepen our understanding of this issue by establishing the neuroimaging correlations between CT and depression.

Methods: A sample of 123 MDD patients (91 with moderate-to-severe CT and 32 with no or low CT) and 79 healthy controls (HC, 33 with moderate-to-severe CT and 46 with no or low CT) participated. All participants completed assessments of depression level, anxiety, recent perceived stress, and resting-state functional MRI scan.

Results: Participants with moderate-to-severe CT showed elevated depression level and trait anxiety, and reduced spontaneous neural activity in left inferior temporal gyrus (ITG). Abnormalities of seed-based functional connectivity (FC) of left ITG - bilateral precuneus/posterior cingulate cortex (PCC), left middle temporal gyrus (MTG), left medial orbitofrontal cortex (mOFC), and bilateral medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) were observed. CT was associated with decreased FCs in MDD, but with increased FCs in HC. The total altered FCs of left ITG - bilateral precuneus/PCC and left mOFC mediated relationship between CT and depression in MDD, and total altered FCs and trait anxiety have a significant chain mediation effect in the association between CT and depression in HC.

Conclusion: These findings highlight the changes of default mode network (DMN) functions and trait anxiety as targets of CT. The decreased functional coupling within DMN may be involved in the mechanism of MDD following CT.
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http://dx.doi.org/10.1016/j.jpsychires.2022.07.051DOI Listing
July 2022

Liquiritin inhibits H O -induced oxidative stress injury in H9c2 cells via the AMPK/SIRT1/NF-κB signaling pathway.

J Food Biochem 2022 Aug 5:e14351. Epub 2022 Aug 5.

Department of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.

Heart failure (HF) is a serious disease with high mortality. Oxidative stress plays a vital role in its occurrence and development. Licorice is commonly used to treat HF in traditional Chinese medicine. Liquiritin, the main ingredient of licorice, has antioxidant and anti-inflammatory properties, but the mechanism against oxidative stress in cardiomyocytes has not been reported. Establishment of oxidative damage model in H9c2 cells by hydrogen peroxide (H O ). Liquiritin (5, 10, 20 μmol/L) could significantly prevent the loss of cell viability and decrease the apoptosis rate. It can reduce the levels of reactive oxygen species (ROS), malonedialdehyde (MDA), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and increase the activity of ATP, superoxidedismutase (SOD), glutathione peroxide (GSH-px), glutathione reductase (GR) and catalase (CAT) to alleviate oxidative stress and inflammation in a dose-dependent manner. Liquiritin was found to be related to AMP-Activated Protein Kinase (AMPK) pathway by molecular docking. Western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR) confirmed that liquiritin could promote AMPKα phosphorylation and sirtuin 1 (SIRT1) protein expression, and inhibit phosphorylation of nuclear factor kappa B p65 (NF-κB p65). Compound C, EX 527, and PDTC can reverse the effects of liquiritin, indicating that its antioxidant effect is achieved by regulating AMPK/SIRT1/NF-κB signaling pathway. PRACTICAL APPLICATIONS: Heart failure is one of the most common cardiovascular diseases, and its treatment remains a worldwide problem. Licorice is a food and dietary supplement that has been used widely in traditional Chinese medicine (TCM). Liquiritin is one of the main active components of licorice, which has antioxidant and anti-inflammatory pharmacological effects. This study revealed the mechanism of licorice against oxidative damage of H9c2 cardiomyocytes, and provided a scientific basis for liquiritin as an antioxidant in the treatment of heart failure.
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http://dx.doi.org/10.1111/jfbc.14351DOI Listing
August 2022

Hu'po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway.

Front Pharmacol 2022 18;13:952696. Epub 2022 Jul 18.

Department of Orthopedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Hu'po Anshen decoction (HPASD) is a traditional Chinese medicine formula comprising five herbal medicines for the treatment of concussion and fracture healing, but its pharmacological mechanism is still unclear. Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS) was used to analyze the main active components of HPASD. Rats were randomly assigned to fracture group, fracture combined with traumatic brain injury (TBI) group (FBI) and FBI combined with HPASD treatment group (FBIH). Rats in the FBIH group were given oral doses of HPASD (2.4 g/kg, 4.8 g/kg and 9.6 g/kg) for 14 or 21 consecutive days. The fracture callus formation and fracture sites were determined by radiographic analysis and micron-scale computed tomography (micro-CT) analysis. Hematoxylin and eosin (H&E) staining and a three-point bending test were applied to assess histological lesions and biomechanical properties, respectively. The levels of cytokines-/protein-related to bone formation and differentiation as well as PI3K/AKT pathway-related proteins were determined by Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or western blot assays, respectively. UPLC-Q/TOF-MS-based serum metabolomic analysis was also performed to investigate the therapeutic effects of HPASD in the treatment of FBI. UPLC/Q-TOF MS analysis showed the chemical components in HPASD, including flavonoids, amino acids, saponins, and phenylpropanoid constituents, etc. HPASD dose-dependently promoted callus formation, increased bone density, improved mechanical parameters and morphological scores, and facilitated the expressions of VEGF, PDGF, bFGF, VEGFA, CoL1A1, RUNX2, BMP2, and Aggrecan, inhibited the expression of MMP13, and activated PI3K/AKT pathway. Metabolomics analysis revealed abnormalities of malate-aspartate shuttle and glucose-alanine. HPASD accelerates fracture healing by promoting bone formation and regulating the malate-aspartate shuttle and glucose-alanine cycle, which might be associated with the activation of the PI3K/AKT pathway.
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http://dx.doi.org/10.3389/fphar.2022.952696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341486PMC
July 2022

Nanocarrier Co-formulation for Delivery of a TLR7 Agonist plus an Immunogenic Cell Death Stimulus Triggers Effective Pancreatic Cancer Chemo-immunotherapy.

ACS Nano 2022 Aug 3. Epub 2022 Aug 3.

Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, California 90095, United States.

Although toll-like receptor (TLR) agonists hold great promise as immune modulators for reprogramming the suppressive immune landscape in pancreatic ductal adenocarcinoma (PDAC), their use is limited by poor pharmacokinetics (PK) and off-target systemic inflammatory effects. To overcome these challenges as well as to attain drug synergy, we developed a lipid bilayer (LB)-coated mesoporous silica nanoparticle (silicasome) platform for co-delivery of the TLR7/8 agonist 3M-052 with the immunogenic chemotherapeutic agent irinotecan. This was accomplished by incorporating the C18 lipid tail of 3M-052 in the coated LB, also useful for irinotecan remote loading in the porous interior. Not only did the co-formulated carrier improve PK, but it strengthened the irinotecan-induced immunogenic cell death response by 3M-052-mediated dendritic cell activation at the tumor site as well as participating lymph nodes. The accompanying increase in CD8 T-cell infiltration along with a reduced number of regulatory T-cells was associated with tumor shrinkage and metastasis disappearance in subcutaneous and orthotopic KRAS-mediated pancreatic carcinoma tumor models. Moreover, this therapeutic outcome was accomplished without drug or nanocarrier toxicity. All considered, dual-delivery strategies that combine chemo-immunotherapy with co-formulated TLR agonists or other lipid-soluble immune modulators predict successful intervention in heterogeneous PDAC immune landscapes.
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http://dx.doi.org/10.1021/acsnano.2c06300DOI Listing
August 2022

Study of the microstructure of chitosan aerogel beads prepared by supercritical CO drying and the effect of long-term storage.

RSC Adv 2022 Jul 21;12(33):21041-21049. Epub 2022 Jul 21.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University Chongqing 400044 PR China

In order to investigate the pore properties and effect of storage time on the microstructure of CO-dried aerogels, chitosan aerogel beads were obtained from chitosan hydrogels with an initial concentration in the range of 1.5-3.0 wt% through SCCO drying and freeze-drying (as a comparison). The SCCO-dried chitosan aerogels showed a three-dimensional network structure, and had higher BET surface area (200 m g) and higher crystallinity (0.62/XRD, 0.80/ATR-FTIR) than the freeze-dried aerogels. The stability of the microstructure of the SCCO-dried chitosan aerogel beads during 10 months was studied. The BET surface area of the aerogel beads at each concentration declined by 30.5% at 2 months, 56.7% at 6 months and 67.2% at 10 months. Accelerated aging tests of the chitosan aerogel beads were carried out to study the effect of humidity on the chitosan aerogel beads. The average diameter of the chitosan aerogel decreased from 2.3 mm to 0.9 mm when stored at 65 °C with 90% relative humidity (RH). In contrast, there was no obvious change during storage at 65 °C with 20% RH. The amount of adsorbed water increased from 4% to 12% at 65 °C with 90% RH for 96 h, and the bound water content of the aerogel beads gradually increased. This study demonstrates that SCCO-dried chitosan aerogel beads could be better at maintaining their mesoporous structure, and the adsorption of water from the surrounding air had a significant effect on the microstructure and shrinkage of the chitosan aerogel beads.
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http://dx.doi.org/10.1039/d2ra01875fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301543PMC
July 2022

Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study.

Breast Cancer Res Treat 2022 Aug 2. Epub 2022 Aug 2.

Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China.

Purpose: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI).

Methods: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0-1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0-1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician.

Results: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4-104 months), patients who had PEPI 0-1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5-99.9%) for PEPI 0-1 or pCR group vs. 93.7% (95% CI 89.6-97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases.

Conclusion: PEPI 0-1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted.

Clinical Trial Registration: NCT01613560.
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http://dx.doi.org/10.1007/s10549-022-06686-1DOI Listing
August 2022

Exploring the Risk Thresholds of Soil Heavy Metals in Carbonate and Non-carbonate Rock Areas: The Case of Qianjiang District in Chongqing, China.

Bull Environ Contam Toxicol 2022 Aug 1. Epub 2022 Aug 1.

School of Earth Sciences and Resources, China University of Geosciences, 100083, Beijing, China.

To determine whether the national soil heavy metal standards (GB 15618-2018) are applicable to some carbonate and non-carbonate zones in Southwest China, rice and rhizosphere soil samples were collected in Chongqing and analyzed for heavy metal contents, pH, and other chemical parameters. In addition, regression analysis was also used to predict the risk threshold of soil heavy metals. The Cd risk screening value in GB 15618-2018 was strict for alkaline soils (pH > 7.5) as compared to those revealed in carbonate and non-carbonate areas, while the calculated pollution threshold for Cd in acidic soils (pH ≤ 5.5) in the non-carbonate area was lower than that in GB 15618-2018. Therefore, to improve the applicability of the evaluation results, a soil-crop system evaluation is recommended.
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http://dx.doi.org/10.1007/s00128-022-03580-wDOI Listing
August 2022

Second-harmonic generation in a high-index doped silica micro-ring resonator.

Opt Lett 2022 Aug;47(15):3884-3887

We report the first, to the best of our knowledge, observation of second-harmonic generation (SHG) in a high-index doped silica micro-ring resonator, due to the symmetry-breaking-induced χ at the core and cladding interface of the waveguide. The generated SH power is shown to have quadratic dependence on the in-cavity power of the fundamental pump at around 1550 nm. The pumping wavelength sweep method is adopted to fulfill the phase-matching condition for maximum conversion efficiency of SHG. This work offers a new approach to generate a visible source for the visible-light integrated optical platform from infrared-visible light conversion.
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http://dx.doi.org/10.1364/OL.463317DOI Listing
August 2022

Creating a Machine Learning Tool to Predict Acute Kidney Injury in African American Hospitalized Patients.

Pharmacy (Basel) 2022 Jun 22;10(4). Epub 2022 Jun 22.

Department of Clinical and Administrative Pharmacy Sciences, Howard University College of Pharmacy, Washington, DC 20059, USA.

Machine learning (ML) has been used to build high-performance prediction models in the past without considering race. African Americans (AA) are vulnerable to acute kidney injury (AKI) at a higher eGFR level than Caucasians. AKI increases mortality, length of hospital stays, and incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD). We aimed to establish an ML-based prediction model for the early identification of AKI in hospitalized AA patients by utilizing patient-specific factors in an ML algorithm to create a predictor tool. This is a single-center, retrospective chart review. We included participants 18 years or older and admitted to an urban academic medical center. Two hundred participants were included in the study. Our ML training set provided a result of 77% accuracy for the prediction of AKI given the attributes collected. For the test set, AKI was accurately predicted in 71% of participants. The clinical significance of this model can lead to great advancements in the care of AA patients and provide practitioners avenues to optimize their therapy of choice in AAs when given AKI risk ahead of time.
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http://dx.doi.org/10.3390/pharmacy10040068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326647PMC
June 2022

Deciphering the Mechanisms Shaping the Plastisphere Microbiota in Soil.

mSystems 2022 Jul 26:e0035222. Epub 2022 Jul 26.

Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural Universitygrid.22935.3f, Beijing, China.

The gradual accumulation of microplastics has aroused increasing concern for the unique niche, termed "plastisphere." As research so far has focused on their characteristics in aquatic ecosystems, our understanding of the colonization and assembly of the attached bacterial communities on microplastics in soil ecosystems remains poor. Here, we aimed to characterize the plastisphere microbiomes of two types of microplastics (polylactic acid [PLA] and polyethylene [PE]) differing in their biodegradability in two different soils. After incubation for 60 days, considerably lower alpha diversity of bacterial community was observed on the microplastic surfaces, and prominent divergences occurred in the microbial community compositions between the plastisphere and the bulk soil. The temperature, rather than polymer type, significantly induced the differences between the plastisphere communities. The rRNA gene operon () copy numbers were significantly higher in the PLA plastisphere, suggesting potential degradation. The co-occurrence network analysis showed that the PE plastisphere exhibited greater network complexity and stronger stability than those in the PLA plastisphere. The stochasticity ratio indicated the remarkable importance of stochastic process on community assembly in PE and PLA plastispheres, while the null model analysis showed the nonnegligible roles of deterministic processes in shaping the plastisphere communities. Higher contributions of homogenous selection in the PLA plastisphere were observed in comparison with the PE plastisphere, which could probably be attributed to the selective pressure induced by microplastic degradation. Our findings enhance our mechanistic understanding of the diversity patterns and assembly processes of plastisphere in soil environments and have important implications for microbial ecology and microplastic risk assessment. The increasing pervasive microplastic pollution is creating a new environmental compartment, termed plastisphere. Even though there was conclusive information characterizing the plastisphere, the underlying mechanisms shaping the bacterial communities in the plastisphere in the soil remain unclear. Therefore, we incubated two types of microplastics (PE and PLA) in two different soils and explored the differences between plastisphere and bulk soil communities. Additionally, the co-occurrence network and the assembly processes of plastisphere were subjected to further analysis. Our results highlight the importance of selective recruitment of microplastics and contribute to the understanding of the diversity patterns and assembly processes of plastisphere in soil environments.
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http://dx.doi.org/10.1128/msystems.00352-22DOI Listing
July 2022

CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma.

Mol Cancer 2022 07 25;21(1):153. Epub 2022 Jul 25.

Department of Internal Medicine, West China Hospital Cancer Center Head And Neck, Sichuan University, Chengdu, China.

Background: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear.

Methods: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells.

Results: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05).

Conclusion: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.
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http://dx.doi.org/10.1186/s12943-022-01623-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316328PMC
July 2022

A sensing platform based on zinc-porphyrin derinative in hexadecyl trimethyl ammonium bromide (CTAB) microemulsion for highly sensitive detection of theophylline.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Jul 4;281:121592. Epub 2022 Jul 4.

State Key Laboratory of Separation Membranes and Membrane Processes, School of Chemical Engineering and Technology, Tiangong University, Tianjin 300387, PR China. Electronic address:

A new porphyrin-based sensing platform in hexadecyl trimethyl ammonium bromide (CTAB) microemulsion is developed for highly sensitive detection of theophylline. In this sensing system, the zinc-porphyrin-cinnamic acid conjugate (Zn-TPPCA) works as fluorescence probe while theophylline can decrease fluorescence intensity of the probe. Further studies indicate the linear relationship between the fluorescence quenching value and the concentration of theophylline within a given range. And the introduction of CTAB microemulsion can greatly enhance sensibility and stability of this detecting system and facilitate the detection of theophylline. On the basis above, a highly sensitive sensing platform for theophylline is created with a low limit of detection (LOD) of 0.0083 μg mL under the optimal detection conditions. And further application of this method in determination of commercially available theophylline preparation shows excellent results. Subsequent studies on quenching mechanism indicate that static quenching appears between Zn-TPPCA and theophylline. Therefore, this work provides not only a highly sensitive method for determination of theophylline but also further evidence for creation of biosensors for drugs with porphyrin derivatives.
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http://dx.doi.org/10.1016/j.saa.2022.121592DOI Listing
July 2022

[Development and Evaluation of Prognostic Nomogram Model for Adult Ventricle Glioma Patients].

Sichuan Da Xue Xue Bao Yi Xue Ban 2022 Jul;53(4):588-596

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To explore the prognostic factors of adult ventricle glioma (AVG) and to construct and evaluate a survival-related prognostic nomogram model, which could provide further reference for the clinical management of AVG patients.

Methods: The patients covered in the study were selected from the Surveillance Epidemiology and End Results (SEER) database (1973-2016). They all had definite histological diagnosis of AVG. They were assigned randomly to the training cohort and the validation cohort by random number table at a 2/1 ratio. Survival analysis was performed by Kaplan-Meier analysis. Cox regression analysis was employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Then, integrating the basic characteristics of patients, the survival-related nomogram predictive model for OS and CSS in the training cohort was constructed, respectively. After that, internal cross validation and external validation of the model were carried out with the training cohort and the validation cohort in succession. The authenticity and reliability of the nomogram model were evaluated by calculating the concordance index (C-index). Calibration plots were constructed to assess the agreement between the predicted values and the observed values in the training cohort and the validation cohort.

Results: A total of 369 AVG patients, including 218 males and 151 females, were included. The median age of the patients was 53. According to the WHO classification of gliomas, 66 (17.9%) patients had grade Ⅱ gliomas, 73 (19.8%) had grade Ⅲ gliomas, and 230 (62.3%) had grade Ⅳ gliomas. Regarding the extent of resection (EOR), 59 (16.0%) had gross total resection (GTR) and 145 (39.3%) had subtotal resection (STR) or partial resection (PR). Of all the patients, 167 (45.3%) received postoperative radiotherapy and 143 (38.8%) received postoperative chemotherapy. Patients were randomized into the training cohort ( =246) and the validation cohort ( =123), and there was no significant difference ( >0.05) in the basic clinical characteristics between the training cohort and the validation cohort. In the training cohort, Cox regression analysis revealed that the independent prognostic factors for OS and CSS included age≥65, grades Ⅲ and Ⅳ according to the WHO classification of gliomas, and not receiving radiotherapy. Furthermore, 5 variables, including age, gender, WHO grades, surgery, and radiotherapy, were used to construct the nomogram model for predicting 6-month, 1-year, and 2-year OS and CSS. The results of internal cross validation in the training cohort showed that the C-indexes of OS and CSS were 0.758 and 0.765, respectively. The external validation results of the validation cohort showed that the C-indexes of OS and CSS were 0.733 and 0.719, respectively. Calibration plots for 6-month, 1-year, and 2-year OS in the training cohort showed relatively good agreement, while in the validation cohort the agreement was relatively low. The 6-month, 1-year, and 2-year CSS calibration plots had results similar to the calibration plots of OS.

Conclusion: This nomogram predictive model of OS and CSS showed moderately reliable predictive performance, providing helpful reference information for clinicians to make quick and simple assessment of the survival probability of AVG patients.
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http://dx.doi.org/10.12182/20220760203DOI Listing
July 2022

Increased angiogenesis in thyroid tuberculosis identified by SPECT/CT based on RGD dimer radiotracer (99mTc-3PRGD2).

Rev Esp Med Nucl Imagen Mol (Engl Ed) 2022 26;41 Suppl 1:S31-S32. Epub 2021 May 26.

Department of Nuclear Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an, Shaanxi, China. Electronic address:

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http://dx.doi.org/10.1016/j.remnie.2021.05.010DOI Listing
July 2022

Influences of ALDH2 on Cardiomyocyte Apoptosis in Heart Failure Rats Through Regulating PINK1-Parkin Signaling Pathway-Mediated Mitophagy.

Cell Mol Biol (Noisy-le-grand) 2022 Feb 28;68(2):94-102. Epub 2022 Feb 28.

Qingpu Branch of Zhongshan Hospital, Fudan University.

The study aimed to investigate the influences of aldehyde dehydrogenase 2 (ALDH2) on cardiomyocyte apoptosis in heart failure (HF) rats through regulating the PTEN induced putative kinase 1 (PINK1)-Parkin signaling pathway-mediated mitophagy. The rat model of HF was established, and the rats were randomly divided into model group (HF model, n=20) and ALDH2 group (intervention with ALDH2, n=20), with a normal group (n=20) set. After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function index creatine kinase (CK) was measured, the status of myocardial tissue injury was determined using hematoxylin and eosin staining, and the apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The activity of ALDH2 was detected, and the expression levels of genes and proteins were measured through quantitative polymerase chain reaction (qPCR) and Western blotting assay. The model group had notably decreased fractional shortening (FS) and ejection fraction (EF) and remarkably increased left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) compared with the normal group (p<0.05). The activity of ALDH2 declined obviously in the model group. The myocardial tissue injury was severer in the model group, and the number of apoptotic cells in myocardial tissues was greater in the model group than that in other groups (p<0.05). The model group manifested higher expression levels of Caspase-3 and light chain 3 (LC3) than the ALDH2 group (p<0.05) but significantly lower expression levels of PINK1, Parkin and B-cell lymphoma-2 (Bcl-2) (p<0.05). In comparison with those in the model group, the protein expression levels of PINK1, Parkin and Bcl-2 in myocardial tissues were prominently higher in the ALDH2 group (p<0.05). ALDH2 can inhibit cardiomyocyte apoptosis in HF rats by activating the PINK1-Parkin signaling pathway-mediated mitophagy, which is conducive to the recovery of HF.
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http://dx.doi.org/10.14715/cmb/2022.68.2.14DOI Listing
February 2022

Variation of satellite-derived total suspended matter in large lakes with four types of water storage across the Tibetan Plateau, China.

Sci Total Environ 2022 Jul 19:157328. Epub 2022 Jul 19.

Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Total suspended matter (TSM), as an indicator of the concentration of fine materials in the water column including particulate nutrients, pollutants, and heavy metals, is widely used to monitor aquatic ecosystems. However, the long-term spatiotemporal variations of TSM in lakes across the Tibetan Plateau (TP) and their response to environmental factors are rarely explored. Accordingly, taking advantage of the Landsat top-of-atmosphere reflectance and in-situ data, an empirical model (R = 0.83, RMSE = 1.08 mg/L, and MAPE = 19.49 %) was developed to estimate the average autumnal TSM in large TP lakes (≥50 km) during the 1990-2020 period. For analyzing the spatiotemporal variability in TP lakes TSM, the examined lakes were classified into four types (Type A-D) based on their water storage changing in different periods. The results showed that the lakes in the southern and some northeastern parts of the TP exhibited lower TSM values than those situated in other regions. The assessment of TSM in each of these four lake types showed that more than half of them had a TSM value of <20 mg/L. Apart from Type D, the lakes with the TSM showing significantly decreasing trends were dominantly Types A-C. A relative contribution analysis involving five driving factors indicated that they contributed by >50 % to lake TSM interannual variation in 73 out of 114 watersheds, and the lakes area change demonstrated the greatest contribution (82.2 %), followed by wind speed (11.0 %). Further comparison between the entire lake and the non-expansive regions suggested that the expansive region played an indispensable role in determining the TSM value of the whole lake. This study can help to better understand the water quality condition and provide valuable information for policy-makers to maintain sustainable development in the TP region.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157328DOI Listing
July 2022

"Stripe" transcription factors provide accessibility to co-binding partners in mammalian genomes.

Mol Cell 2022 Jul 15. Epub 2022 Jul 15.

The NIH Regulome Project, National Institutes of Health, Bethesda, MD 20892, USA; Lymphocyte Nuclear Biology, NIAMS-NCI, NIH, Bethesda, MD 20892, USA. Electronic address:

Regulatory elements activate promoters by recruiting transcription factors (TFs) to specific motifs. Notably, TF-DNA interactions often depend on cooperativity with colocalized partners, suggesting an underlying cis-regulatory syntax. To explore TF cooperativity in mammals, we analyze ∼500 mouse and human primary cells by combining an atlas of TF motifs, footprints, ChIP-seq, transcriptomes, and accessibility. We uncover two TF groups that colocalize with most expressed factors, forming stripes in hierarchical clustering maps. The first group includes lineage-determining factors that occupy DNA elements broadly, consistent with their key role in tissue-specific transcription. The second one, dubbed universal stripe factors (USFs), comprises ∼30 SP, KLF, EGR, and ZBTB family members that recognize overlapping GC-rich sequences in all tissues analyzed. Knockouts and single-molecule tracking reveal that USFs impart accessibility to colocalized partners and increase their residence time. Mammalian cells have thus evolved a TF superfamily with overlapping DNA binding that facilitate chromatin accessibility.
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http://dx.doi.org/10.1016/j.molcel.2022.06.029DOI Listing
July 2022

Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation.

Open Med (Wars) 2022 6;17(1):1183-1202. Epub 2022 Jul 6.

Department of Blood Transfusion, Shanxi Province People's Hospital, No. 29 Shuangtasi Street, Yingze District, Taiyuan, Shanxi, 030012, China.

The function of small ubiquitin-like modifier (SUMO)-related genes in hepatocellular carcinoma (HCC) remains unclear. This study aimed to analyze the expression profile and prognostic relevance of SUMO-related genes using publicly available data. A set of bioinformatics tools and experiments were integrated to explore the mechanism of the genes of interest. The least absolute shrinkage and selection operator Cox regression analysis was used to construct a prognostic model. SUMO-2 and SUMO-activating enzyme subunit 1 (SAE1) were upregulated in HCC. The enrichment analysis indicated that SUMO-2 and SAE1 might regulate the cell cycle. The downregulation of SAE1 inhibited the proliferation of HCC cells, whereas the upregulation of the gene promoted cell proliferation. IGF2BP3 contributed to the upregulation of SAE1 in an N6-methyladenosine (m6A)-dependent way. Eventually, an SAE1-related risk score (SRRS) was developed and validated in HCC. SRRS could serve as an independent prognostic factor and predict the efficiency of transarterial chemoembolization in patients with HCC.
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http://dx.doi.org/10.1515/med-2022-0510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263891PMC
July 2022

[Effect of Linggui Zhugan Decoction-containing serum on mitochondrial oxidative stress in cardiomyocytes: an exploration based on Nrf2/BNIP3 signaling pathway].

Zhongguo Zhong Yao Za Zhi 2022 Jun;47(12):3303-3311

Graduate School of Anhui University of Chinese Medicine Hefei 230031, China.

This study aimed to explore the effect of Linggui Zhugan Decoction(LGZGD)-containing serum on mitochondrial oxidative stress in cardiomyocytes based on the NF-E2-related factor2(Nrf2)/Bcl-2/adenovirus E1 B 19 kDa interacting protein(BNIP3) signaling pathway. After the preparation of LGZGD-containing serum and blank serum, H9 c2 cardiomyocytes were exposed to H_2O_2 for inducing oxidative stress in vitro. The H9 c2 cells were divided into four groups, namely normal control group, H_2O_2 model group, 20% blank serum group, and 20% LGZGD-containing serum group. After the cells were pre-treated with different types of serum for 12 h and cultured with 100 μmol·L~(-1 )H_2O_2 for 6 h, the reactive oxygen species(ROS) level in each group was detected by DCFH-DA, and the openness of mitochondrial permeability transition pore(mPTP) was measured using a calcein AM fluorescent probe. The expression levels of cytoplasmic cytochrome C(CytC), mitochondrial CytC, cytoplasmic and nuclear Nrf2, and BNIP3 were detected by Western blot. Nrf2-silenced H9 c2 cells were prepared by transfecting them with siRNA-Nrf2 for investigating the efficacy of LGZGD-containing serum in regulating ROS, mPTP, cytoplasmic and mitochondrial CytC, and BNIP3. The results showed that compared with the normal control group, H_2O_2 significantly increased the ROS content and mPTP openness(P<0.01), and the expression of Nrf2, BNIP3, and cytoplasmic CytC(P<0.01), and decreased the expression of mitochondrial CytC(P<0.01), without causing obvious change in cytoplasmic Nrf2. LGZGD-containing serum significantly lowered ROS content(P<0.01), inhibited mPTP openness(P<0.01), down-regulated the expression of cytoplasmic CytC and BNIP3(P<0.01), up-regulated mitochondrial CytC expression(P<0.01), and promoted Nrf2 nuclear translocation(P<0.05). However, after Nrf2 silencing, the reduced ROS production, diminished BNIP3 expression, and inhibited mPTP openness and CytC release induced by LGZGD-containing serum were reversed(P<0.01). These results have suggested that LGZGD-containing serum is able to alleviate the mitochondrial oxidative stress injury of cardiomyocytes by regulating the Nrf2/BNIP3 signaling pathway.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20220111.401DOI Listing
June 2022

Antimicrobial Effect of Extracellular Vesicles Derived From Human Oral Mucosal Epithelial Cells on .

Front Immunol 2022 1;13:777613. Epub 2022 Jul 1.

Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

(. ) is a commensal microorganism that colonizes the mucosal surfaces of healthy individuals. Changes in the host or environment can lead to overgrowth of . and infection of the host. Extracellular vesicles (EVs) are released by almost all cell types and play an increasingly recognized role in fighting microbial infection. The aim of the present study was to assess whether EVs derived from human oral mucosal epithelial (Leuk-1) cells can suppress the growth and invasion of . . The efficacy of Leuk-1-EVs against . was assessed by optical microscopy, laser scanning confocal microscopy, scanning electron microscopy, and transmission electron microscopy. The germ tube formation rate, the percentage of hyphae and the microcolony optical density were also used to analyze the growth of . in a coculture model with Leuk-1 cells and EVs or after inhibition of the secretion of EVs. A mouse model of oral candidiasis was established and submucosal injection of Leuk-1-EVs in the tongue was performed. Macroscopic observation, H&E staining, PAS staining, and scanning electron microscopy were used to assess antifungal effects of Leuk-1-EVs . The results showed that the growth of . was inhibited and that the morphology and ultrastructure were changed following Leuk-1-EVs treatment. The results exhibited that white lesions of the tongue, . infection, and oral mucosal inflammation of the infected mice were significantly alleviated after Leuk-1-EVs treatment. We thus reveal an antifungal capability of EVs derived from oral epithelial cells against . that is mediated by direct damage effects and potential synergy between EVs and human oral mucosal epithelial cells. This finding offers an intriguing, previously overlooked method of antifungal defense against . .
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http://dx.doi.org/10.3389/fimmu.2022.777613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283572PMC
July 2022

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV-induced skin aging by activating Nrf2 defense mechanisms.

Phytother Res 2022 Aug 12;36(8):3276-3294. Epub 2022 Jul 12.

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

Oxidative stress damage can lead to premature skin aging or age-related skin disorders. Therefore, strategies to improve oxidative stress-induced aging are needed to protect the skin and to treat skin diseases. This study aimed to determine whether the flavonoid corylin derived from Psoralea corylifolia can prevent UV-induced skin aging and if so, to explore the potential molecular mechanisms. We found that corylin potently blocked UV-induced skin photoaging in mice by reducing oxidative stress and increasing the nuclear expression of nuclear factor-erythroid factor 2-related factor 2 Nrf2. We also found that corylin stimulated Nrf2 translocation into the nucleus and increased the delivery of its target antioxidant genes together with Kelch-like ECH-associated protein 1 (Keap1) to dissociate Nrf2. These findings indicate that corylin could prevent skin aging by inhibiting oxidative stress via Keap1-Nrf2 in mouse cells. Thus, Nrf2 activation might be a therapeutic target for preventing skin aging or skin diseases caused by aging. Our findings also provided evidence that warrants the further investigation of plant ingredients to facilitate the discovery of novel therapies targeting skin aging.
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http://dx.doi.org/10.1002/ptr.7501DOI Listing
August 2022

Constructing YBO (B = Ti, Sn, Zr, Ce) Compounds to Disclose the Effect of Surface Acidity-Basicity on Product Selectivity for Oxidative Coupling of Methane (OCM).

Inorg Chem 2022 Jul 12;61(29):11419-11431. Epub 2022 Jul 12.

Key Laboratory of Jiangxi Province for Environment and Energy Catalysis, School of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031, P. R. China.

To investigate the influence of surface acidity and basicity on the OCM reaction, four pure-phase YBO (B = Ti, Sn, Zr, Ce) compounds have been purposely constructed. The exquisite phase structure change results in the generation of different amounts of surface active O and O sites, which affects CH molecule activation. Furthermore, both Lewis acidic sites and basic sites are formed on the catalysts in different amounts, which are related to the lattice disorder extent and the choice of A- and B-site elements. It is elucidated with strong evidence that the surface basic sites are favorable to C product selectivity, but the surface acidic sites lead to deep oxidation of CH and the coupling products to form CO. To design and fabricate YBO catalysts with better C product selectivity for the reaction, a disordered defect fluorite structure should be engineered with A- and B- site elements having appropriate basicity.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01754DOI Listing
July 2022

Structure-Activity Relationship (SAR) of Flavones on Their Anti-Inflammatory Activity in Murine Macrophages in Culture through the NF-κB Pathway and c-Src Kinase Receptor.

J Agric Food Chem 2022 Jul 11;70(28):8788-8798. Epub 2022 Jul 11.

Department of Food Science and Technology, National University of Singapore, 2 Science Drive 2, Singapore 117542.

Flavones benefit human health through their anti-inflammatory activity; however, their structure-activity relationship is unclear. Herein, we selected 15 flavones with the same backbone but different substituents and systematically assessed their anti-inflammatory activities in RAW 264.7 regarding cellular-Src kinase (c-Src) affinity, suppression of IκBα phosphorylation, inhibition of nitric oxide (NO) and inducible nitric oxidase (iNOS) production, and downregulation of genes of proinflammatory cytokines interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). Overall, our results showed that the double bond between C2-C3 and C3'- and C4'-OH promoted anti-inflammatory activity, while C8- and C5'-OH and the methoxy group on C4' attenuated the overall anti-inflammatory and antioxidant activities. The hydroxyl groups at other positions exhibited more complicated functions. The two most effective flavones are 3',4'-dihydroxyflavone and luteolin with inhibitory concentration (IC) values for inhibiting the LPS-induced nitric oxide level are 9.61 ± 1.36 and 16.90 ± 0.74 μM, respectively. Furthermore, they suppressed the production of iNOS by approximately 90% and inhibited IL-1β and IL-6 by more than 95%. Taken together, our results established a relationship between the flavone structure and anti-inflammatory activity .
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http://dx.doi.org/10.1021/acs.jafc.2c03050DOI Listing
July 2022

Three-Dimensional Quantitative Structure and Activity Relationship of Flavones on Their Hypochlorite Scavenging Capacity.

J Agric Food Chem 2022 Jul 10;70(28):8799-8807. Epub 2022 Jul 10.

Department of Food Science and Technology, National University of Singapore, 2 Science Drive 2, Singapore 117542, Republic of Singapore.

Flavonoids, a class of polyphenolic substances widely present in the plant realm, are considered as ideal hypochlorite scavengers. However, to our knowledge, little study has focused on the structure-activity relationship between flavonoids and hypochlorite scavenging capacity. Herein, we report for the first time the three-dimensional quantitative structure and activity relationship (3D-QSAR) combined with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Four models derived from CoMFA and CoMSIA with different combinations of descriptors were built and compared; the CoMFA model, which included both steric and electrostatic fields, showed great potential ( = 0.989; = 0.818) in predictive quality according to both internal and external validation criteria. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), and orbital weighted dual descriptor (OWDD) were determined to identify the key structural moiety for scavenging capacity of flavonoids against hypochlorite. The computational results indicated that hypochlorous acid (HClO) serves as an electrophile undergoing electrophilic addition to the C6 carbon, which has the highest negative charge density, which are influenced by the functional groups on the flavones. The DFT calculated mechanism revealed the catalytic role of water of mono- and di-chlorination reactions, characterized by low activation barriers, and the involvement of neutral, instead of high-energy carbocation, intermediates.
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http://dx.doi.org/10.1021/acs.jafc.2c03860DOI Listing
July 2022
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