Publications by authors named "Feng Wang"

5,711 Publications

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Nanofluorescence Probe in Detection of miR-187 and Its Correlation with Oxidative Stress Response in Cataracts.

Authors:
Feng Wang Ye Ren

Altern Ther Health Med 2022 Aug 5. Epub 2022 Aug 5.

Objective: This study aimed to explore the sensitivity of a nano-fluorescent probe in the detection of miR-187 and the correlation of miR-187 with cataract oxidative stress response.

Method: We selected 24 patients with cataracts and 24 healthy people from January 2019 to January 2021 to undergo a nano-fluorescence miR-187 test. We divided cultured human lens epithelial cells (HLECs) into 3 groups: control, overexpressed miR-187 and miR-187 silence, in order to investigate the intracellular oxidative stress response, and the activity and apoptosis of HLECs in the state of oxidative stress.

Results: The expression of miR-187 increased significantly in patients with cataracts, and the overexpression of miR-187 promoted the oxidative stress response in HLECs. In the oxidative stress environment simulated by hydrogen peroxide, the downregulation of miR-187 can significantly increase HLEC activity and reduce its apoptosis. In order to further study the role of miR-187 in cataract progression, cataract mouse models were injected with miR-187 mimic and inhibitor. The results showed that miR-187-inhibitor can inhibit the progression of cataracts.

Conclusion: The expression of miR-187 is significantly related to cataract prognosis, and down regulation of miR-187 expression has significant antioxidation capacity and can reduce HLEC apoptosis.
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August 2022

Value of Tranexamic Acid and Progressive Nursing in Accelerating Postoperative Rehabilitation After Total Knee Arthroplasty.

Altern Ther Health Med 2022 Aug 5. Epub 2022 Aug 5.

Context: Knee arthritis is the primary cause of disability in middle-aged and older adults. Total knee arthroplasty (TKA) is also a common treatment in clinics and has a remarkable effect on improving knee-joint function. However, TKA is an invasive procedure that includes a large amount of trauma. It can easily lead to an increase in perioperative blood loss coupled with a long operation time, which can increase the risk of postoperative complications, and also has a long recovery time.

Objective: The study intended to analyze the value of tranexamic acid (TXA) plus progressive nursing in accelerating the postoperative rehabilitation of patients undergoing total knee arthroplasty (TKA).

Design: The research team designed a prospective non-randomized controlled trial.

Setting: The study took place at Cangzhou Hospital of Integrated Traditional Chinese Medicine (TCM) - Western Medicine (WM) Hebei in Cangzhou, Hebei, China.

Participants: Participants were 115 patients with knee arthritis who underwent TKA at the hospital between February 2019 and October 2021.

Intervention: Of the 115 participants, 55 were assigned to the control group and received conventional nursing care, and 60 were assigned to the intervention group and after surgery received TXA plus progressive nursing.

Outcome Measures: The study measured blood loss postoperatively and identified any complications that participants experienced during treatment. At baseline and postintervention, the study also measured knee-joint range of motion (ROM), and the participants completed the Hospital for Special Surgery (HSS) knee survey, the Barthel Index for Activities of Daily Living (ADL), the Self-Rating Depression (SDS) and Self-Rating Anxiety (SAS) scales, a nursing-satisfaction survey, and the World Health Organization Quality of Life Bref (WHO-QOL-BREF) survey.

Results: Postoperatively, the blood loss in the intervention group was significantly lower than that in control group, and the knee joint ROM was significantly better in the intervention group (P < .05). In addition, the postoperative Hospital for Special Surgery (HSS) and Barthel scores in the intervention group were significantly higher, and the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores were significantly lower in the intervention group compared with control group (P < .05). Moreover, a lower incidence of complications and better quality of life were determined for the intervention group (P < .05).

Conclusions: Compared with conventional nursing, TXA plus progressive nursing can more effectively promote postoperative recovery of TKA patients; but the exact role of TXA and progressive nursing in TKA deserves further exploration.
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August 2022

Reversible phase transition for durable formamidinium-dominated perovskite photovoltaics.

Adv Mater 2022 Aug 10:e2204458. Epub 2022 Aug 10.

Beijing Key Laboratory for Theory and Technology of Advanced Battery Materials, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, School of Materials Science and Engineering, Peking University, Beijing, 100871, P. R. China.

Phase instability (especially phase transition) is one of the major obstacles to the wide application of formamidinium (FA)-dominated perovskite solar cells (PSCs). An in-depth investigation on relevant phase transition kinetics is urgently needed to explore more effective phase stabilization strategies. Herein for the first time, we monitored the reversible phase transition process of FA Cs PbI perovskite between photoactive phase (α phase) and non-photoactive phase (δ phase) under humidity, as well as the reversible healing of the degraded devices. Moreover, through in-situ atomic force microscope (AFM) characterization, the kinetic transition between α and δ phase was revealed to be the "nucleation-growth transition" process. Density functional theory (DFT) calculation was employed to analyze the thermodynamic origin of phase transition, where the driving force for α-to-δ transition was associated with configurational enthalpy, while the δ-to-α transition was dominated by the temperature-related vibrational entropy. The α phase of FA Cs PbI could be finally stabilized at elevated temperature (e.g., 60°C) under high humidity due to the increased nucleation barrier, and the resulting non-encapsulated PSCs retained over 90% of their initial efficiency after aging at 60°C and 60% relative humidity (RH) for 1000 hours. Our finding provided a deepened understanding on the phase transition process of FA Cs PbI from both thermodynamics and kinetics points of view, which also presented an effective means to stabilize the α phase of FA-dominated perovskites and devices for practical applications. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202204458DOI Listing
August 2022

The accuracy of a novel image-guided hybrid robotic system for dental implant placement: An in vitro study.

Int J Med Robot 2022 Aug 10:e2452. Epub 2022 Aug 10.

Department of Second Dental Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: This in vitro study aims to evaluate the accuracy of dental implant placement by a novel image-guided hybrid robotic system for dental implant surgery (HRS-DIS).

Methods: The HRS-DIS with a 5 degree of freedom (DOF) serial manipulator and a 6 DOF Stewart platform was developed. To evaluate the accuracy of repeated drilling, the holes were prepared twice with a 2.2 mm drill. To evaluate the accuracy of dental implant placement, the entry, exit and angle deviations of dental implants were measured.

Results: Twenty-four holes were prepared twice, and mean (± SD) of diameters were measured as 2.2 ± 0.02 mm. A total of 160 dental implants were placed in 32 phantoms by HRS-DIS. The mean (± SD) of the entry, exit and angle deviation were 0.8 ±0.54 mm, 0.87 ± 0.54 mm and 1.0 1 ± 0.44°, respectively.

Conclusions: The results of the in vitro study preliminarily validated that the HRS-DIS could provide a high accuracy for dental implant surgery. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/rcs.2452DOI Listing
August 2022

Risk factors associated with dysphagia after anterior surgery in treatment for multilevel cervical disorder with kyphosis.

Medicine (Baltimore) 2022 Aug;101(31):e30009

Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

This is a retrospective study. Our aim was to investigate the risk factors related to dysphagia following anterior surgery treating the multilevel cervical disorder with kyphosis based on a subgroup of follow-up time. Finally, a total of 81 patients suffering from the multilevel cervical disorder with kyphosis following anterior surgery from July 2018 to June 2020 were included in our study. Patients with dysphagia were defined as the dysphagia group and without dysphagia as the no-dysphagia (NG) group based on a subgroup of follow-up time (1-week, 1-month, 3-month, 6-month, and 1-year after surgery). Clinical outcomes and radiological data were performed to compare between dysphagia group and NG. In our study, the rate of dysphagia was 67.9%, 44.4%, 34.6%, 25.9%, and 14.8% at 1-week, 1-month, 3-month, 6-month, and 1-year after surgery, respectively. Our findings showed that change of Cobb angle of C2-7 was associated with dysphagia within 3-month after surgery. Furthermore, postoperative Cobb angle of C2-7 was linked to dysphagia within 6-month after surgery. Interestingly, a history of smoking and lower preoperative SWAL-QOL score were found to be risk factors related with dysphagia at any follow-up. In the present study, many factors were found to be related to dysphagia within 3-month after surgery. Notably, a history of smoking and lower preoperative SWAL-QOL score were associated with dysphagia at any follow-up. We hope this article can provide a reference for spinal surgeons to predict which patients were susceptible to suffering from dysphagia after anterior surgery in the treatment of multilevel cervical disorder with kyphosis.
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http://dx.doi.org/10.1097/MD.0000000000030009DOI Listing
August 2022

Met1-specific motifs conserved in OTUB subfamily of green plants enable rice OTUB1 to hydrolyse Met1 ubiquitin chains.

Nat Commun 2022 Aug 9;13(1):4672. Epub 2022 Aug 9.

Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing, 100081, PR China.

Linear (Met1-linked) ubiquitination is involved inflammatory and innate immune signaling. Previous studies have characterized enzymes regulating the addition and removal of this modification in mammalian systems. However, only a few plant-derived deubiquitinases targeting Met1-linked ubiquitin chains have been reported and their mechanism of action remains elusive. Here, using a dehydroalanine-bearing Met1-diubiquitin suicide probe, we discover OTUB1 from Oryza sativa (OsOTUB1) as a Met1-linked ubiquitin chain-targeting deubiquitinase. By solving crystal structures of apo OsOTUB1 and an OsOTUB1/Met1-diubiquitin complex, we find that Met1 activity is conferred by Met1-specific motifs in the S1' pocket of OsOTUB1. Large-scale sequence alignments and hydrolysis experiments provide evidence that these motifs are a general determinant of Met1 activity in the OTUB subfamily across species. Analysis of the species distribution of OTUBs capable of hydrolysing Met1-linked ubiquitin chains shows that this activity is conserved in green plants (Viridiplantae) and does not exist in metazoans, providing insights into the evolutionary differentiation between primitive plants and animals.
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http://dx.doi.org/10.1038/s41467-022-32364-3DOI Listing
August 2022

Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy.

Pharmacol Res 2022 Aug 5;183:106392. Epub 2022 Aug 5.

Laboratory of Natural Products and Medicinal Chemistry (LNPMC), Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai 600077, India. Electronic address:

This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5 mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. It enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors.
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http://dx.doi.org/10.1016/j.phrs.2022.106392DOI Listing
August 2022

Human Umbilical Cord Wharton Jelly Cells Treatment Prevents Osteoporosis Induced by D-Galactose.

Int J Clin Pract 2022 20;2022:4593443. Epub 2022 Jul 20.

Department of Spine Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd., Shanghai 200120, China.

Methods: Sixteen male mice were randomly divided into 4 groups: control (ordinary feeding), D-gal (D-galactose) group, D-gal + MSC (human umbilical cord Wharton jelly cells), and D-gal + MSC-TNF groups. Except for the control group (fed with same amount of saline solution), other mice received gastric feeding of 250 mg/kg D-galactose every day for 8 weeks. TNF (10 ng/mL for 24 h) cocultured or noncocultured HUCWJCs (5 × 10) were suspended in 0.1 ml of sterile PBS and injected into tail veins every other week in D-gal + MSC-TNF and D-gal + MSC groups, respectively, and only 0.1 ml of sterile PBS for control and D-gal groups. The bone mass was detected by qPCR, ELISA, microcomputed tomography (CT), and hematoxylin-eosin staining. Proliferation, apoptosis, and differentiation of periosteal-derived osteoblasts (POB) were assessed. Transwell assay and scratch healing were performed to detect POB migration and invasion ability. The effect of HUCWJCs on POB signaling pathway expression was evaluated by immunoblotting.

Results: The malondialdehyde (MDA) in serum was higher and superoxide dismutase (SOD) was lower in the D-gal group compared to the other groups ( < 0.05). Mice in D-gal group showed significantly decreased bone mass when compared to the control group, while HUCWJCs treatment partially rescued the phenotype, as demonstrated by CT and histology ( < 0.05). Mechanically, HUCWJCs treatment partially promoted proliferation and migration and decreased apoptosis of POB induced by oxidative stress via activating the mitogen-activated protein kinase (MAPK) signaling pathway.

Conclusion: HUCWJCs can prevent the progression of osteoporosis by inhibiting oxidative stress, which may act by regulating osteoblasts fate through the MAPK signaling pathway.
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http://dx.doi.org/10.1155/2022/4593443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328953PMC
August 2022

Therapeutic Effect of Ultrasound Combined With Porous Lipid Clioquinol/PLGA Microbubbles on Ferroptosis in HL-1 Cardiac Cell Induced by Isoproterenol Attack.

Front Pharmacol 2022 22;13:918292. Epub 2022 Jul 22.

Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W/O/W) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.
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http://dx.doi.org/10.3389/fphar.2022.918292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354950PMC
July 2022

Association between leucocyte telomere length and the risk of atrial fibrillation: An updated systematic review and meta-analysis.

Ageing Res Rev 2022 Aug 3;81:101707. Epub 2022 Aug 3.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China. Electronic address:

Background And Aims: Advancing age is the most important risk factor of atrial fibrillation (AF). The shortening of telomere length is a biomarker of biologic aging. There is an increasing body of evidence that leucocyte telomere length (LTL) is associated with the risk of AF development. However, the results in these studies were controversial. The current systematic review and meta-analysis was conducted to examine the role of LTL in predicting the incidence of AF.

Methods And Results: Observational studies reporting the association between LTL and the risk of AF were retrieved through 25th June, 2022 from PubMed and Embase. A total of twelve studies including 18,293 patients were included in the present analysis. Leucocyte telomere shortening was found to be an independent predictor of AF as a continuous variable in both univariate [OR:2.14; 95%CI(1.48,3.10); P < 0.0001] and multivariate analyses [OR:1.41;95%CI(1.11,1.79); P = 0.005], as well as categorical variable in multivariate analysis [OR:1.53; 95%CI(1.04,2.27); P = 0.03]. Furthermore, leucocyte telomere shortening was significantly associated with recurrent AF [OR:4.32;95%CI(2.42,7.69); P < 0.00001] but not new-onset AF [OR:1.14; 95%CI(0.90,1.45); P = 0.29]. Leucocyte telomere shortening was also associated with an increased risk of persistent AF [OR:14.73;95%CI (3.16,68.67); P = 0.0006] and paroxysmal AF [OR:2.74;95%CI(1.45,5.18); P = 0.002]. Besides, LTL was an independent predictor for progression from paroxysmal AF to persistent AF [OR:3.2;95%CI(1.66,6.18); P = 0.0005]. Differences between males [OR:1.99; 95%CI(1.29,3.06); P = 0.002] and females [OR:0.86; 95%CI (0.29,2.56);P = 0.79] were observed.

Conclusions: Leucocyte telomere shortening predicts the risk of AF, especially recurrent AF. The predictive value is more prominent in males than in females. Shortening in LTL can predict the progression from paroxysmal to persistent AF.
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http://dx.doi.org/10.1016/j.arr.2022.101707DOI Listing
August 2022

Disseminated Talaromyces marneffei in peritoneal fluid of a patient with HIV.

Int J Lab Hematol 2022 Aug 6. Epub 2022 Aug 6.

Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.

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http://dx.doi.org/10.1111/ijlh.13946DOI Listing
August 2022

A randomized, open-label, multicenter, phase 3 study of high-dose vitamin C plus FOLFOX +/- bevacizumab versus FOLFOX +/- bevacizumab in unresectable untreated metastatic colorectal cancer.

Clin Cancer Res 2022 Aug 5. Epub 2022 Aug 5.

Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Purpose: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX +/- bevacizumab versus FOLFOX +/- bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC).

Patients And Methods: Between 2017 and 2019, histologically confirmed mCRC patients (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX +/- bevacizumab) and an experimental (high-dose vitamin C [1.5 g/kg/d, intravenously for 3 hours from D1 to D3] plus FOLFOX +/- bevacizumab) group. Randomization was based on the primary tumor location and bevacizumab prescription.

Results: The progression-free survival (PFS) of the experimental group was not superior to the control group (median PFS, 8.6 vs 8.3 months; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.70-1.05; P = 0.1). The objective response rate (ORR) and overall survival (OS) of the experimental and control group were similar (ORR, 44.3% vs 42.1%; P = 0.9; median OS, 20.7 vs 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control group, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only.

Conclusions: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in mCRC patients as first-line treatment but may be beneficial in mCRC patients harboring RAS mutation.
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http://dx.doi.org/10.1158/1078-0432.CCR-22-0655DOI Listing
August 2022

LncRNA-412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR-346.

FASEB J 2022 Sep;36(9):e22467

Hu Sheep Academy, Nanjing Agricultural University, Nanjing, China.

Although long non-coding RNAs (lncRNAs) are reported to regulate follicular development and reproductive disease pathogenesis, the underlying mechanisms have not been elucidated. In this study, lncRNA expression profiling of different-sized healthy follicles from Hu sheep with different prolificacy revealed 50 613 lncRNAs. Numerous lncRNAs were differentially expressed among different comparison groups. This study characterized one novel transcript, lncRNA-412.25 (from healthy follicles with a diameter of >5 mm), which was predominantly expressed in the high prolificacy group and localized to the cytoplasm of granulosa cells (GCs). LncRNA-412.25 knockdown promoted and inhibited Hu sheep GC apoptosis and proliferation, respectively. Interestingly, lncRNA-412.25 could directly bind to miR-346, which can target the gene of leukemia inhibitory factor (LIF). Knockdown of lncRNA-412.25 promoted GC apoptosis by downregulating LIF expression, where this effect was attenuated by miR-346. Moreover, the miR-346 inhibitor mitigated the lncRNA-412.25 knockdown-induced downregulation of phosphorylated protein of signal transducer and activator of transcription 3 (STAT3), which was validated using immunofluorescence analysis. Our results demonstrated that lncRNA-412.25 regulates GC proliferation and apoptosis in Hu sheep by binding to miR-346 and then activating the LIF/STAT3 pathway. These findings provide novel insights into the mechanisms underlying prolificacy in sheep.
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http://dx.doi.org/10.1096/fj.202200632RDOI Listing
September 2022

Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study.

Br J Cancer 2022 Aug 4. Epub 2022 Aug 4.

Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Background: The aim of this study was to gain an increased understanding of the aetiology of breast cancer, by investigating possible associations between serum lipoprotein subfractions and metabolites and the long-term risk of developing the disease.

Methods: From a cohort of 65,200 participants within the Trøndelag Health Study (HUNT study), we identified all women who developed breast cancer within a 22-year follow-up period. Using nuclear magnetic resonance (NMR) spectroscopy, 28 metabolites and 89 lipoprotein subfractions were quantified from prediagnostic serum samples of future breast cancer patients and matching controls (n = 1199 case-control pairs).

Results: Among premenopausal women (554 cases) 14 lipoprotein subfractions were associated with long-term breast cancer risk. In specific, different subfractions of VLDL particles (in particular VLDL-2, VLDL-3 and VLDL-4) were inversely associated with breast cancer. In addition, inverse associations were detected for total serum triglyceride levels and HDL-4 triglycerides. No significant association was found in postmenopausal women.

Conclusions: We identified several associations between lipoprotein subfractions and long-term risk of breast cancer in premenopausal women. Inverse associations between several VLDL subfractions and breast cancer risk were found, revealing an altered metabolism in the endogenous lipid pathway many years prior to a breast cancer diagnosis.
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http://dx.doi.org/10.1038/s41416-022-01924-1DOI Listing
August 2022

Interactions between mTORC2 core subunits Rictor and mSin1 dictate selective and context-dependent phosphorylation of substrate kinases SGK1 and Akt.

J Biol Chem 2022 Aug 1:102288. Epub 2022 Aug 1.

Department of Medicine, Division of Nephrology, and Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, California, USA. Electronic address:

Mechanistic target of rapamycin complex 2 (mTORC2) is a multi-subunit kinase complex, central to multiple essential signaling pathways. Two core subunits, Rictor and mSin1, distinguish it from the related mTORC1 and support context-dependent phosphorylation of its substrates. mTORC2 structures have been determined previously, however, important questions remain, particularly regarding the structural determinants mediating substrate specificity and context-dependent activity. Here, we used cryo-EM to obtain high-resolution structures of the human mTORC2 apo-complex in the presence of substrates Akt and SGK1. Using functional assays, we then tested predictions suggested by substrate-induced structural changes in mTORC2. For the first time, we visualized in the apo-state the side chain interactions between Rictor and mTOR that sterically occlude recruitment of mTORC1 substrates and confer resistance to the mTORC1 inhibitor rapamycin. Also in the apo-state, we observed that mSin1 formed extensive contacts with Rictor via a pair of short α-helices nestled between two Rictor helical repeat clusters, as well as by an extended strand that makes multiple weak contacts with Rictor helical cluster 1. In co-complex structures, we found that SGK1, but not Akt, markedly altered the conformation of the mSin1 N-terminal extended strand, disrupting multiple weak interactions while inducing a large rotation of mSin1 residue Arg-83, which then interacts with a patch of negatively charged residues within Rictor. Finally, we demonstrate mutation of Arg-83 to Ala selectively disrupts mTORC2-dependent phosphorylation of SGK1, but not of Akt, supporting context-dependent substrate selection. These findings provide new structural and functional insights into mTORC2 specificity and context-dependent activity.
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http://dx.doi.org/10.1016/j.jbc.2022.102288DOI Listing
August 2022

Targeting the EIF2AK1 signaling pathway rescues red blood cell production in SF3B1-mutant myelodysplastic syndromes with ringed sideroblasts.

Blood Cancer Discov 2022 Aug 4. Epub 2022 Aug 4.

The University of Texas MD Anderson Cancer Center, Houston, United States.

SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and primarily affects the elderly population. Here, using single-cell technologies and functional validation studies of primary SF3B1-mutant MDS-RS samples, we show that SF3B1 mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of EIF2AK1 inhibitors to overcome transfusion dependency in patients with SF3B1-mutant MDS-RS with impaired red blood cell production.
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http://dx.doi.org/10.1158/2643-3230.BCD-21-0220DOI Listing
August 2022

A novel diagnostic model for insulinoma.

Discov Oncol 2022 Aug 2;13(1):68. Epub 2022 Aug 2.

Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

The aim is to describe a simple and feasible model for the diagnosis of insulinoma. This retrospective study enrolled 37 patients with insulinoma and 44 patients with hypoglycemia not due to insulinoma at the First Affiliated Hospital of Guangxi Medical University. General demographic and clinical characteristics; hemoglobin A1c (HbA1c), insulin and C-peptide concentrations; and the results of 2-h oral glucose tolerance tests (OGTT) were recorded, and a logistic regression model predictive of insulinoma was determined. Body mass index (BMI), HbA1c concentration, 0-h C-peptide concentration, and 0-h and 1-h plasma glucose concentrations (P < 0.05 each) were independently associated with insulinoma. A regression prediction model was established through multivariate logistics regression analysis: Logit p = 7.399+(0.310 × BMI) - (1.851 × HbA1c) - (1.467 × 0-h plasma glucose) + (1.963 × 0-h C-peptide) - (0.612 × 1-h plasma glucose). Using this index to draw a receiver operating characteristic (ROC) curve, the area under the curve (AUC) was found to be 0.957. The optimal cut-off value was - 0.17, which had a sensitivity of 89.2% and a specificity of 86.4%. Logit P ≥ - 0.17 can be used as a diagnostic marker for predicting insulinoma in patients with hypoglycemia.
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http://dx.doi.org/10.1007/s12672-022-00534-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346017PMC
August 2022

LncRNA UBE2R2-AS1, as prognostic marker, promotes cell proliferation and EMT in prostate cancer.

Histol Histopathol 2022 Aug 2:18505. Epub 2022 Aug 2.

Department of Urology, Heilongjiang Hospital, Harbin city, Heilongjiang Province, China.

Background: Long noncoding RNA ubiquitin-conjugating enzyme E2 R2 antisense RNA 1 (UBE2R2-AS1) has been recently reported to participate in the progression of tumors, including glioma and liver cancer. However, the roles of UBE2R2-AS1 in prostate cancer (PC) remained poorly understood.

Methods: The expression of UBE2R2-AS1 was determined in tumor tissues and paired adjacent tissues from PC patients using quantitative reverse transcription PCR analysis. Correlation between UBE2R2-AS1 expression and clinicopathological parameters and overall survival were investigated by Chi-square test and Kaplan-Meier method analysis. The in vitro experiments, including CCK-8 assay, colony formation, flow cytometry and transwell assay were performed to investigate the functional role of UBE2R2-AS1 knockdown or overexpression on PC cell lines (PC-3 and DU145). Related protein expression levels were measured by western blot analysis.

Results: Our data showed that UBE2R2-AS1 expression was significantly upregulated in PC tissues compared with that in adjacent tissues. The high levels of UBE2R2-AS1 were associated with high Gleason score, advanced clinical T stage, lymph node metastasis and poor prognosis. Knockdown of UBE2R2-AS1 suppressed cell proliferation, migration and invasion, induced cell cycle G0/G1 arrest and apoptosis in PC cells, along with decreased expression of PCNA, CDK4, Cyclin D1, Bcl-2, N-cadherin and Vimentin, and increased E-cadherin expression. Overexpression of UBE12R2-AS1 obtained the opposite results in PC cells.

Conclusions: Our findings suggest that UBE2R2-AS1 might be a potential diagnostic and/or therapeutic target in PC.
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http://dx.doi.org/10.14670/HH-18-505DOI Listing
August 2022

Selective oxidation of glycerol into formic acid by photogenerated holes and superoxide radicals.

ChemSusChem 2022 Aug 2. Epub 2022 Aug 2.

Dalian Institute of Chemical Physics, Group 204, Zhongshan Road 457, 116023, Dalian, CHINA.

Photocatalysis is a promising technology for conversion of the glycerol into formic acid, but photocatalytic oxidation of C-C bonds in glycerol exhibits poor selectivity towards formic acid because the photogenerated radicals (e.g., hydroxyl radicals) further oxidize formic acid to CO 2 . In this work, we revealed a synergy of photogenerated holes and superoxide radicals that achieved the selective oxidation of glycerol into formic acid over the TiO 2 catalyst. The charge separation of pristine TiO 2 was improved with the aid of oxygen, which resulted in efficient hole oxidation of the C-C bonds in glycerol to formic acid. Surface active species was controlled to prevent being converted to hydroxyl radicals on TiO 2 via controlling the oxygen and water contents , which solved the problem of formic acid peroxidation without sophisticated catalyst modifications. Mechanism studies suggested that glyceraldehyde and glycolaldehyde were the intermediates to generate formic acid. This work provides a green and efficient approach to produce formic acid as a liquid hydrogen carrier from bio-based alcohols.
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http://dx.doi.org/10.1002/cssc.202201068DOI Listing
August 2022

Wireless transmission of a 200-m PS-64QAM THz-wave signal using a likelihood-based selection radius-directed equalizer.

Opt Lett 2022 Aug;47(15):3904-3907

Based on a photonics-aided scheme, we achieve an experimental demonstration of a, to the best of our knowledge, record-breaking 200-m terahertz (THz)-wave wireless delivery at 335 GHz with the aid of a pair of high-gain polytetrafluoroethylene (PTFE) lenses. By using a 10-GBaud probabilistically shaped 64-ary quadrature amplitude modulation (PS-64QAM) signal and advanced digital signal processing (DSP) including a likelihood-based selection radius-directed equalizer (LBS-RDE), the single-carrier net bit rate of the wireless delivery reaches 44 Gbit/s. High-speed THz-wave communication with up to 200-m wireless distance is successfully realized based on a photonics-aided scheme for the first time.
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http://dx.doi.org/10.1364/OL.465696DOI Listing
August 2022

Impact of mismatch repair or microsatellite status on the prognosis and efficacy to chemotherapy in metastatic colorectal cancer patients: A bi-institutional, propensity score-matched study.

J Cancer 2022 11;13(9):2912-2921. Epub 2022 Jul 11.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China.

Deficient mismatch repair (dMMR) or the microsatellite instability (MSI) phenotype occupied approximately 15-18% of CRC patients. Previous studies showed that dMMR/MSI status is a favorable prognostic factor for stage II/III CRC patients. For metastatic colorectal cancer (mCRC) patients, only 5% of patients have the dMMR/MSI-H phenotype. The relationship between dMMR/MSI, chemosensitivity and survival in mCRC patients of real-world is still not clear. In this study, we enrolled 77 dMMR/MSI-H mCRC patients and compared their clinicopathological characteristics with those of 510 proficient MMR (pMMR) or microsatellite stable (MSS) mCRC patients. With propensity score matching (PSM) analysis, we further compared the chemosensitivity and survival of dMMR/MSI-H mCRC patients with pMMR/MSS patients. We also analyzed the efficacy of different chemotherapy and target therapy in the dMMR/MSI-H population. In PSM cohort, the objective response rate (ORR) of mCRC patients with dMMR/MSI-H undergoing first-line palliative chemotherapy was 35.2%, which was similar with patients with pMMR/MSS (35.4%, = 1.00). The median progression-free survival (PFS) of first-line chemotherapy was significantly different (dMMR/MSI-H vs pMMR/MSS = 7.4 months vs 10.2 months; HR = 0.74; 95%CI, 0.57-0.98; = 0.03). Overall survival (OS) of patients did not significantly differ by status (dMMR/MSI-H vs pMMR/MSS = 40.0 months vs 41.3 months; HR = 1.09; 95%CI, 0.74-1.59; = 0.68). For second-line palliative chemotherapy, there was no difference in ORR ( = 0.53) or in PFS (HR = 0.88; 95%CI, 0.59-1.33; = 0.56) between dMMR/MSI-H and pMMR/MSS tumors. We also found that in the overall cohort, the ORR of patients who received oxaliplatin-based and irinotecan-based chemotherapy were 28.8% and 54.5%, respectively, which were not significantly different ( = 0.16). Our results also showed that the use of bevacizumab could lead to a significantly higher ORR in dMMR/MSI-H mCRC patients compared to chemotherapy alone (55.0% vs 22.2%; = 0.02), whereas cetuximab could not. The dMMR/MSI-H is not a prognostic factor for mCRC patients but is correlated with shorter PFS to first-line palliative chemotherapy.
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http://dx.doi.org/10.7150/jca.50285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330455PMC
July 2022

Oxysterol derivatives Oxy186 and Oxy210 inhibit WNT signaling in non-small cell lung cancer.

Cell Biosci 2022 Jul 30;12(1):119. Epub 2022 Jul 30.

Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NIH, Building 37, RM 2056B, Bethesda, MD, 20892, USA.

Background: Developmental signaling pathways such as those of Hedgehog (HH) and WNT play critical roles in cancer stem cell self-renewal, migration, and differentiation. They are often constitutively activated in many human malignancies, including non-small cell lung cancer (NSCLC). Previously, we reported that two oxysterol derivatives, Oxy186 and Oxy210, are potent inhibitors of HH/GLI signaling and NSCLC cancer cell growth. In addition, we also showed that Oxy210 is a potent inhibitor of TGF-β/SMAD signaling. In this follow-up study, we further explore the mechanism of action by which these oxysterols control NSCLC cell proliferation and tumor growth.

Results: Using a GLI-responsive luciferase reporter assay, we show here that HH ligand could not mount a signaling response in the NSCLC cell line A549, even though Oxy186 and Oxy210 still inhibited non-canonical GLI activity and suppressed the proliferation of A549 cells. Further, we uncover an unexpected activity of these two oxysterols in inhibiting the WNT/β-catenin signaling at the level of LRP5/6 membrane receptors. We also show that in a subcutaneous xenograft tumor model generated from A549 cells, Oxy186, but not Oxy210, exhibits strong inhibition of tumor growth. Subsequent RNA-seq analysis of the xenograft tumor tissue reveal that the WNT/β-catenin pathway is the target of Oxy186 in vivo.

Conclusion: The oxysterols Oxy186 and Oxy210 both possess inhibitory activity towards WNT/β-catenin signaling, and Oxy186 is also a potent inhibitor of NSCLC tumor growth.
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http://dx.doi.org/10.1186/s13578-022-00857-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338492PMC
July 2022

Construction of a I-Labeled Specific Antibody for the Noninvasive Detection of Mesothelin-Overexpressing Tumors.

Mol Pharm 2022 Jul 29. Epub 2022 Jul 29.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Mesothelin (MSLN) is a molecular biomarker of many types of solid tumors, such as mesothelioma, pancreatic cancer, and colon cancer. Owing to the significant difference in expression between cancer cells and normal cells, mesothelin has been widely used as a key target in cancer immunotherapy. In this study, we used iodine isotope (I)-labeled mesothelin antibodies to noninvasively detect MSLN expression in mice with LS174T colon cancer. The I-labeled MSLN antibody showed a high radiochemical purity (RCP, >99%) and specific activity (20.8-67.8 GBq/μmol) after purification and was stable in 5% HSA and PBS (>95% RCP at 8 days). Western blot analysis indicated that the LS174T cells showed a higher MSLN protein level than the HepG2 cells. The half maximal effective concentration (EC) values of the MSLN antibody and I-anti-MSLN were 34.77 ± 3.72 ng/mL and 32.60 ± 2.52 ng/mL ( = 0.63), respectively. The dissociation constant of I-anti-MSLN binding to MSLN protein was 16.0 nM. The radiotracer showed a significantly higher uptake in LS174T cells than in HepG2 tumor cells (1.56 ± 0.09 vs 0.81 ± 0.03, = 0.0016) 2 days postinjection. The LS174T mouse models showed extremely low organ uptake and high tumor uptake 96 h after the injection of I-anti-MSLN, and the T/M values were much higher than those of the other imaging groups (10.56 ± 1.20 for I-anti-MSLN in LS174T mice vs 3.27 ± 0.20 for I-anti-MSLN in HepG2 mice vs 3.53 ± 0.2 for I-IgG in LS174T mice). The immunochemical histology results showed that LS174T tumors were strongly positive (+++) for MSLN, while those in the HepG2 group showed slight expression (+). The dosimetry estimation study showed that the effective dose of I-anti-MSLN was 0.185 mSv/MBq, which is within the range of acceptable doses for further nuclear medicine translational research. Taken together, these results suggest that this radiotracer has the potential for detecting mesothelin-overexpressing tumors.
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http://dx.doi.org/10.1021/acs.molpharmaceut.2c00342DOI Listing
July 2022

Ion-modulated radical doping of spiro-OMeTAD for more efficient and stable perovskite solar cells.

Science 2022 07 28;377(6605):495-501. Epub 2022 Jul 28.

Department of Physics, Chemistry and Biology (IFM), Linköping University, 58183 Linköping, Sweden.

Record power conversion efficiencies (PCEs) of perovskite solar cells (PSCs) have been obtained with the organic hole transporter 2,2',7,7'-tetrakis(,-di--methoxyphenyl-amine)9,9'-spirobifluorene (spiro-OMeTAD). Conventional doping of spiro-OMeTAD with hygroscopic lithium salts and volatile 4--butylpyridine is a time-consuming process and also leads to poor device stability. We developed a new doping strategy for spiro-OMeTAD that avoids post-oxidation by using stable organic radicals as the dopant and ionic salts as the doping modulator (referred to as ion-modulated radical doping). We achieved PCEs of >25% and much-improved device stability under harsh conditions. The radicals provide hole polarons that instantly increase the conductivity and work function (WF), and ionic salts further modulate the WF by affecting the energetics of the hole polarons. This organic semiconductor doping strategy, which decouples conductivity and WF tunability, could inspire further optimization in other optoelectronic devices.
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http://dx.doi.org/10.1126/science.abo2757DOI Listing
July 2022

How can net petroleum importers achieve risk aversion in a globalized world: a multi-regional input-output perspective.

Environ Sci Pollut Res Int 2022 Jul 28. Epub 2022 Jul 28.

School of Economic and Management, China University of Petroleum (East China), Qingdao, 266580, Shandong Province, China.

Net embodied petroleum importers face greater petroleum security risks in international trade due to their high foreign dependence. Therefore, paying better attention to the national flows and drivers of embodied petroleum consumption can effectively serve net embodied petroleum importers to avoid petroleum security risks and formulate environmental protection policy. This study utilized the multi-regional input-output model to determine the top five embodied petroleum net importers (i.e., the USA, Japan, Germany, the UK, and France) under the economic globalization, and traced the flows of embodied petroleum consumption through international trade. Combined with the logarithmic mean Divisia index method, this study also deeply investigated the drivers of changes embodied petroleum in net imports. The results show that from the perspective of international trade, the USA was not only the largest importer but also the largest exporter of embodied petroleum. Among the trade flows of embodied petroleum, the largest trade flow was from China to the USA, which indicated that China was the world factory and the USA was the consumer power. The embodied petroleum trade markets of Germany, the UK, and France was mainly distributed in Europe & Eurasia resulted from European economic integration. The largest contributor to the decrease of embodied petroleum imports in the top 4 net importers was the petroleum intensity effect. Meanwhile, the import dependence effect was the largest contributor to the increase of France's embodied petroleum net imports. In order to further avoid the risk of petroleum security, it is an effective path worth exploring to construct the diversified petroleum product import strategy and improve energy efficiency.
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http://dx.doi.org/10.1007/s11356-022-22017-9DOI Listing
July 2022

Distribution, Assessment, and Source of Heavy Metals in Sediments of the Qinjiang River, China.

Int J Environ Res Public Health 2022 Jul 26;19(15). Epub 2022 Jul 26.

Guangxi Key Laboratory of Green Chemical Materials and Safety Technology, Beibu Gulf University, Qinzhou 515000, China.

Heavy metals are toxic, persistent, and non-degradable. After sedimentation and adsorption, they accumulate in water sediments. The aim of this study was to assess the extent of heavy metal pollution of Qinjiang River sediments and its effects on the ecological environment and apportioning sources. The mean total concentrations of Mn, Zn, Cr, Cu, and Pb are 3.14, 2.33, 1.39, 5.79, and 1.33 times higher than the background values, respectively. Co, Ni, and Cd concentrations are lower than the background values. Fe, Co, Ni, Cd, Cr, Cu, and Pb are all primarily in the residual state, while Mn and Zn are primarily in the acid-soluble and oxidizable states, respectively. Igeo, RI, SQGs, and RAC together indicate that the pollution status and ecological risk of heavy metals in Qinjiang River sediments are generally moderate; among them, Fe, Co, Ni, Cd, Cr, and Pb are not harmful to the ecological environment of the Qinjiang River. Cu is not readily released because of its higher residual composition, suggesting that Cu is less harmful to the ecological environment. Mn and Zn, as the primary pollution factors of the Qinjiang River, are harmful to the ecological environment. This heavy metal pollution in surface sediments of the Qinjiang River primarily comes from manganese and zinc ore mining. Manganese carbonate and its weathered secondary manganese oxide are frequently associated with a significant amount of residual copper and Cd, as a higher pH is suitable for the deposition and enrichment of these heavy metals. Lead-zinc ore and its weathering products form organic compounds with residual Fe, Co, Cr, and Ni, and their content is related to salinity. The risk assessment results of heavy metals in sediments provide an important theoretical basis for the prevention and control of heavy metal pollution in Qinjiang River.
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http://dx.doi.org/10.3390/ijerph19159140DOI Listing
July 2022

Spatially-directed magnetic molecularly imprinted polymers with good anti-interference for simultaneous enrichment and detection of dual disease-related bio-indicators.

Nanoscale 2022 Aug 11;14(31):11343-11352. Epub 2022 Aug 11.

School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.

As the changes of biomarkers directly reflect the occurrence of degenerative diseases, accurate detection of biomarkers is of great significance for disease diagnosis and control. However, single index detection has high uncertainties to accurately reflect the pathological characteristics because of the complexity of the human internal environment and the extremely trace concentration of indicators. To this end, a method for simultaneous detection of dual-biomarkers based on anti-interference magnetic molecularly imprinted polymers (D-mag-MIPs) is thereby proposed, and successfully applied in human urine analysis for the detection of Parkinson's disease bio-indicators 4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA). In this work, carboxyl functionalized ferric oxide served as a magnetic core, laying a solid foundation for batch detection. Hyperbranched polyethylenimine, whose abundant amino groups can provide multiple interaction forces to templates with high affinity, is employed as a functional monomer. Relative to single-template MIPs, D-mag-MIPs achieve the detection of dual bio-indicators in a one-time test, reducing the false positive result probability and enhancing the detection accuracy. The proposed methodology has been evaluated to exhibit good anti-interference, satisfactory precision, low detection limits, wide linear ranges and fast batch detection for DA and DOPAC. This work thus offers an alternative and efficient pathway for convenient batch detection of dual bio-indicators from biofluids at once.
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http://dx.doi.org/10.1039/d2nr03356aDOI Listing
August 2022

Recent Advances in CXCL12/CXCR4 Antagonists and Nano-Based Drug Delivery Systems for Cancer Therapy.

Pharmaceutics 2022 Jul 25;14(8). Epub 2022 Jul 25.

School of Pharmacy, Weifang Medical University, Weifang 261053, China.

Chemokines can induce chemotactic cell migration by interacting with G protein-coupled receptors to play a significant regulatory role in the development of cancer. CXC chemokine-12 (CXCL12) can specifically bind to CXC chemokine receptor 4 (CXCR4) and is closely associated with the progression of cancer via multiple signaling pathways. Over recent years, many CXCR4 antagonists have been tested in clinical trials; however, Plerixafor (AMD3100) is the only drug that has been approved for marketing thus far. In this review, we first summarize the mechanisms that mediate the physiological effects of the CXCL12/CXCR4 axis. Then, we describe the use of CXCL12/CXCR4 antagonists. Finally, we discuss the use of nano-based drug delivery systems that exert action on the CXCL12/CXCR4 biological axis.
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http://dx.doi.org/10.3390/pharmaceutics14081541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332179PMC
July 2022

Rapid Detection of Antimicrobial Resistance in Mycoplasma genitalium by High-Resolution Melting Analysis with Unlabeled Probes.

Microbiol Spectr 2022 Jul 26:e0101422. Epub 2022 Jul 26.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

With looming resistance to fluoroquinolones in Mycoplasma genitalium, public health control strategies require effective antimicrobial resistance (AMR) diagnostic methods for clinical and phenotypic AMR surveillance. We developed a novel AMR detection method, MG-AsyHRM, based on the combination of asymmetric high-resolution melting (HRM) technology and unlabeled probes, which simultaneously performs M. genitalium identification and genotypes eight mutations in the gene that are responsible for most cases of fluoroquinolone resistance. These enhancements expand the traditional HRM from the conventional detection of single-position mutations to a method capable of detecting short fragments with closely located AMR positions with a high diversity of mutations. Based on the results of clinical sample testing, this method produces an accordance of 98.7% with the Sanger sequencing method. Furthermore, the specificity for detecting S83I, S83N, S83R, and D87Y variants, the most frequently detected mutations in fluoroquinolone resistance, was 100%. This method maintained a stable and accurate performance for genomic copies at rates of ≥20 copies per reaction, demonstrating high sensitivity. Additionally, no specific cross-reactions were observed when testing eight common sexually transmitted infection (STI)-related agents. Notably, this work highlights the significant potential of our method in the field of AMR testing, with the results suggesting that our method can be applied in a range of scenarios and to additional pathogens. In summary, our method enables high throughput, provides excellent specificity and sensitivity, and is cost-effective, suggesting that this method can be used to rapidly monitor the molecular AMR status and complement current AMR surveillance. Mycoplasma genitalium was recently added to the antimicrobial-resistant (AMR) threats "watch list" of the U.S. Centers for Disease Control and Prevention because this pathogen has become extremely difficult to treat as a result of increased resistance. M. genitalium is also difficult to culture, and therefore, molecule detection is the only method available for AMR testing. In this work, we developed a novel AMR detection method, MG-AsyHRM, based on the combination of asymmetrical HRM technology and unlabeled probes, and it simultaneously performs M. genitalium identification and genotypes eight mutations in the gene that are responsible for most cases of fluoroquinolone resistance. The MG-AsyHRM method is a high-throughput, low-cost, simple, and culture-free procedure that can enhance public health and management of M. genitalium infections and AMR control, providing a strong complement to phenotypic AMR surveillance to address the spread of fluoroquinolone resistance.
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http://dx.doi.org/10.1128/spectrum.01014-22DOI 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
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