Publications by authors named "Hang Yu"

458 Publications

In situ melt pool measurements for laser powder bed fusion using multi sensing and correlation analysis.

Sci Rep 2022 Aug 12;12(1):13716. Epub 2022 Aug 12.

Grado Department of Industrial and Systems Engineering, Virginia Tech, Blacksburg, VA, 24061, USA.

Laser powder bed fusion is a promising technology for local deposition and microstructure control, but it suffers from defects such as delamination and porosity due to the lack of understanding of melt pool dynamics. To study the fundamental behavior of the melt pool, both geometric and thermal sensing with high spatial and temporal resolutions are necessary. This work applies and integrates three advanced sensing technologies: synchrotron X-ray imaging, high-speed IR camera, and high-spatial-resolution IR camera to characterize the evolution of the melt pool shape, keyhole, vapor plume, and thermal evolution in Ti-6Al-4V and 410 stainless steel spot melt cases. Aside from presenting the sensing capability, this paper develops an effective algorithm for high-speed X-ray imaging data to identify melt pool geometries accurately. Preprocessing methods are also implemented for the IR data to estimate the emissivity value and extrapolate the saturated pixels. Quantifications on boundary velocities, melt pool dimensions, thermal gradients, and cooling rates are performed, enabling future comprehensive melt pool dynamics and microstructure analysis. The study discovers a strong correlation between the thermal and X-ray data, demonstrating the feasibility of using relatively cheap IR cameras to predict features that currently can only be captured using costly synchrotron X-ray imaging. Such correlation can be used for future thermal-based melt pool control and model validation.
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http://dx.doi.org/10.1038/s41598-022-18096-wDOI Listing
August 2022

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway.

Pharm Biol 2022 Dec;60(1):1520-1532

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Context: Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases.

Objective: To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP.

Materials And Methods: Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group ( = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3β/mTOR signalling pathway.

Results: LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% ( < 0.01,  < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% ( < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13-65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway.

Discussion And Conclusion: LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.
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http://dx.doi.org/10.1080/13880209.2022.2104327DOI Listing
December 2022

Impact of Side Chain Hydrophilicity on Packing, Swelling and Ion Interactions in Oxy-bithiophene Semiconductors.

Adv Mater 2022 Aug 9:e2204258. Epub 2022 Aug 9.

Department of Physics, Imperial College, London, Exhibition Rd, South Kensington, London, SW7 2AZ, UK.

Exchanging hydrophobic alkyl-based side chains to hydrophilic glycol-based side chains is a widely adopted method for improving mixed-transport device performance, despite the impact on solid state packing and polymer-electrolyte interactions being poorly understood. Presented here is a Molecular Dynamics (MD) force field for modelling alkoxylated and glycolated polythiophenes. The force field is validated against known packing motifs for their monomer crystals. MD simulations, coupled with X-ray Diffraction (XRD), show that alkoxylated polythiophenes will pack with a 'tilted stack' and straight interdigitating side chains, whilst their glycolated counterpart will pack with a 'deflected stack' and an s-bend side chain configuration. MD simulations reveal water penetration pathways into the alkoxylated and glycolated crystals - through the π-stack and through the lamellar stack respectively. Finally, the two distinct ways tri-ethylene glycol polymers can bind to cations are revealed, showing the formation of a meta-stable single bound state, or an energetically deep double bound state, both with a strong side chain length dependance. The minimum energy pathways for the formation of the chelates are identified, showing the physical process through which cations can bind to one or two side chains of a glycolated polythiophene, with consequences for ion transport in bithiophene semiconductors. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202204258DOI Listing
August 2022

Endothelin-1 Depletion of Cartilage Oligomeric Matrix Protein Modulates Pulmonary Artery Superoxide and Iron Metabolism-associated Mitochondrial Heme Biosynthesis.

Am J Physiol Lung Cell Mol Physiol 2022 Aug 9. Epub 2022 Aug 9.

Department of Physiology, New York Medical College, Valhalla, NY, United States.

This study examines if heme biosynthesis associated iron metabolism is regulated in pulmonary arteries by endothelin-1 (ET1) potentially through modulating Cartilage Oligomeric Matrix Protein (COMP) availability. Our studies in organoid cultured endothelium-rubbed bovine pulmonary arteries (BPA) observed COMP depletion by siRNA or hypoxia increases NOX2 and superoxide, and depletes mitochondrial SOD2. ET1 also increases superoxide in a manner that potentially impairs mitochondrial heme biosynthesis. In this study, organoid culture of BPA with ET1 (10nM) increases superoxide in the mitochondrial matrix and extra mitochondrial regions associated with COMP depletion, and COMP (0.5μM) inhibited these superoxide increases. Since mitochondrial matrix superoxide could impair heme biosynthesis from protoporphyrin IX (PpIX) by decreasing Fe availability and/or ferrochelatase (FECH), we studied ET1, COMP and COMP siRNA effects on the expression of FECH, transferrin receptor-1 (TfR1, an indicator of iron availability) and soluble guanylate cyclase (sGC, a key heme-dependent protein), and on measurements of PpIX (HPLC) and heme content. ET1 decreased FECH, heme and sGC, and increased TfR1 and iron. COMP reversed these effects of ET1, and COMP decreased PpIX and increased heme in the absence of ET1. COMP siRNA increased PpIX detection and TfR1 expression, and decreased the expression of FECH and sGC. Nitric oxide (spermine NONOate) relaxation of BPA was inhibited by ET1, and this was attenuated by COMP during exposure to ET1. Thus, COMP depletion by ET1 or siRNA modulates pulmonary artery iron metabolism, which results in loss of heme biosynthesis and heme-dependent cGMP mechanisms.
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http://dx.doi.org/10.1152/ajplung.00534.2020DOI Listing
August 2022

Preparation and characterization of chitosan-based antimicrobial films containing encapsulated lemon essential oil by ionic gelation and cranberry juice.

Food Chem 2022 Jul 27;397:133781. Epub 2022 Jul 27.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, China; Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University. Electronic address:

Research about biodegradable antimicrobial films continues to receive a lot of attention due to the plastic pollution crisis and the need for environment-friendly and safe food products. In this study, we developed chitosan-based antimicrobial films using a combination of encapsulated lemon essential oil (LEO) by ionic gelation and cranberry juice and evaluated the performance of the films. Our results indicated that the incorporation of LEO microspheres and cranberry juice into the chitosan films improved the UV barrier and thermal properties as well as antioxidant activity of the films. The increase in antioxidants was consistent with the chemical components in LEO and cranberry juice as determined by GC-MS; some of which possess antioxidant properties. Furthermore, following antimicrobial activity test, considerable inhibition halo of 11 and 20 mm were observed respectively against fungi Candida albicans and Penicillium roqueforti, particularly in presence of the film containing both LEO microspheres and cranberry juice.
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http://dx.doi.org/10.1016/j.foodchem.2022.133781DOI Listing
July 2022

Hyaluronate-coated perfluoroalkyl polyamine prodrugs as bioactive siRNA delivery systems for the treatment of peritoneal cancers.

Biomater Adv 2022 May 17;136:212755. Epub 2022 Mar 17.

Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address:

RNA interference (RNAi) is an emerging therapeutic modality for cancer, which remains in critical need of effective delivery vectors due to the unfavorable biopharmaceutical properties of small RNAs. Polyamines are essential for functioning of mammalian cells. Dysregulated polyamine metabolism is found in many cancers and has been an attractive therapeutic target in combination therapies. Combination therapies based on drugs that affect polyamine metabolism and nucleic acids promise to enhance anticancer activity due to a cooperative effect on multiple oncogenic pathways. Here, we report bioactive polycationic prodrug (F-PaP) based on an anticancer polyamine analogue bisethylnorspermine (BENSpm) modified with perfluoroalkyl moieties. Following encapsulation of siRNA, F-PaP/siRNA nanoparticles were coated with hyaluronic acid (HA) to form ternary nanoparticles [email protected]/siRNA. The presence of perfluoroalkyl moieties and HA reduced cell membrane toxicity and improved stability of the particles with cooperatively enhanced siRNA delivery in pancreatic and colon cancer cell lines. We then tested a therapeutic hypothesis that combining BENSpm with siRNA silencing of polo-like kinase 1 (PLK1) would result in cooperative cancer cell killing. [email protected]/siPLK1 induced polyamine catabolism and cell cycle arrest, leading to enhanced apoptosis in the tested cell lines. The HA-coated nanoparticles facilitated tumor accumulation and contributed to strong tumor inhibition and favorable modulation of the immune tumor microenvironment in orthotopic pancreatic cancer model.
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http://dx.doi.org/10.1016/j.bioadv.2022.212755DOI Listing
May 2022

Elevated preoperative controlling nutritional status (CONUT) scores as a predictor of postoperative recurrence in gastrointestinal stromal tumors.

J Surg Oncol 2022 Aug 1. Epub 2022 Aug 1.

Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Background: The controlling nutritional status (CONUT) score is associated with the postoperative outcomes in various types of tumors, and its prognostic role in gastrointestinal stromal tumors (GISTs) needs to be clarified.

Methods: Patients with completely resected primary GISTs in the absence of imatinib adjuvant therapy were included. Recurrence-free survival (RFS) was estimated with the Kaplan-Meier method and compared using log-rank test. Prognostic factors were compared using Cox proportional hazards model.

Results: A total of 455 patients were included. The median follow-up time was 132.0 months (range: 7.0-253.0). Recurrence/metastasis developed in 92 (20.2%) patients. Patients were assigned to three groups: 219 (48.1%) were in normal nutrition group (CONUT = 0-1), 196 (43.1%) were in mild malnutrition group (CONUT = 2-4) and 40 (8.8%) were in moderate-severe malnutrition group (CONUT ≥ 5). Nongastric primary tumor site, large tumor size, high mitotic index, tumor rupture and high CONUT score were independent prognostic factors for shorter RFS using multivariate analysis (p < 0.05).

Conclusions: Elevated preoperative CONUT score was a predictor of recurrence for patients with resected GIST. The clinical application of the CONUT score is simple and feasible, and might contribute to the individualized treatment of GIST patients.
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http://dx.doi.org/10.1002/jso.27042DOI Listing
August 2022

A novel iridoid glycoside leonuride (ajugol) attenuates airway inflammation and remodeling through inhibiting type-2 high cytokine/chemokine activity in OVA-induced asthmatic mice.

Phytomedicine 2022 Jul 22;105:154345. Epub 2022 Jul 22.

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China; Institutes of Integrative Medicine, Fudan University, Shanghai, China. Electronic address:

Background: Asthma is a chronic airway disorder with a hallmark feature of airflow obstruction that associated with the remodeling and inflammation in the airway wall. Effective therapy for controlling both remodeling and inflammation is still urgently needed. Leonuride is the main pharmacological component identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in treatment of lung diseases. However, no pharmacological effects of leonuride in asthma were reported.

Purpose: Here we aimed to investigated whether leonuride provided a therapeutic efficacy in reversing asthma airway remodeling and inflammation and uncover the underlying mechanisms.

Study Design And Methods: Mouse models of chronic asthma were developed with ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology and asthma-related cytokines were examined. Lung tissues were analyzed using RNA sequencing to reveal the transcriptional profiling changes.

Results: After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. Leonuride suppressed airway inflammation evidenced by the significant reductions in accumulation of inflammatory cells around bronchi and vessels, leukocyte population counts and the abundance of type 2 inflammatory mediators (OVA specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On the other hand, leonuride slowed down the process of active remodeling as demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung histopathology and lower transforming growth factor (TGF)-β1 levels in serum and BALF in comparison to mice treated with OVA only. Furthermore, we uncovered transcriptional profiling alternations in lung tissue of mice after OVA exposure and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine activity stood out in leonuride target transcripts. Those upregulated (Bmp10, Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all reversely regulated by leonuride treatment.

Conclusions: Our results revealed the therapeutic efficacy of leonuride in experimental chronic asthma for the first time, and implied that its anti-inflammatory and antifibrotic properties might be mediated by regulation of type-2 high cytokine/chemokines responses.
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http://dx.doi.org/10.1016/j.phymed.2022.154345DOI Listing
July 2022

Antifeedant Mechanism of Saponin A Isolated from the Seeds of .

Molecules 2022 Jul 12;27(14). Epub 2022 Jul 12.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.

is a medicinal plant which has been used to treat various diseases in humans. However, the anti-insect activity of extracts from has not been evaluated. Here, we found that the total saponins from (TSDV) had strong antifeedant and growth inhibition activities against 4th-instar larvae of . The median antifeeding concentration (AFC) value of TSDV on larvae was 1621.81 μg/mL. TSDV affected the detoxification enzyme system of the larvae and also exerted antifeedant activity possibly through targeting the γ-aminobutyric acid (GABA) system. The AFC concentration, the carboxylesterase activity, glutathione S-transferases activity, and cytochrome P450 content increased to 258%, 205%, and 215%, respectively, and likewise the glutamate decarboxylase activity and GABA content to 195% and 230%, respectively, in larvae which fed on TSDV. However, saponin A (DVSA) showed better antifeedant activity and growth inhibition activity in larvae, compared to TSDV. DVSA also exerted their antifeedant activity possibly through targeting the GABA system and subsequently affected the detoxification enzyme system. Further, DVSA directly affected the medial sensillum and the lateral sensillum of the 4th-instar larvae. Stimulation of . with DVSA elicited clear, consistent, and robust excitatory responses in a single taste cell.
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http://dx.doi.org/10.3390/molecules27144464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323312PMC
July 2022

Phenotypic Changes of Peripheral γδ T Cell and Its Subsets in Patients With Coronary Artery Disease.

Front Immunol 2022 8;13:900334. Epub 2022 Jul 8.

National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, China.

Coronary atherosclerotic heart disease (CAD) is a chronic inflammatory cardiovascular disease with high morbidity and mortality. Growing data indicate that many immune cells are involved in the development of atherosclerosis. However, the immunological roles of γδ T cells in the initiation and progression of CAD are not fully understood. Here, we used flow cytometry to determine phenotypical changes of γδ T cells and their subpopulations in peripheral blood samples collected from 37 CAD patients. The Pearson correlation coefficient was used to analyze the relationship between the clinical parameter (serum LDL-C level) and the changes of immunophenotypes of γδ T cells. Our results demonstrated that the frequencies and absolute numbers of total γδ T cells and Vδ2 T cells were significantly decreased in CAD patients when compared to healthy individuals. However, the proportion of Vδ1 T cells was much lower in CAD patients than that of healthy individuals. Most importantly, a significant alteration of the Vδ1/Vδ2 ratio was found in CAD patients. In addition, a series of surface markers that are associated with costimulatory signals (CD28, CD40L, CD80, CD86), activation levels (CD69, CD25, HLA-DR), activating NK cell receptors (NKp30, NKp46, NKG2D) and inhibitory receptors (PD-1, CTLA-4, PD-1, Tim-3) were determined and then analyzed in the total γδ T cells, Vδ2T cells and Vδ2T cells of CAD patients and healthy individuals. The data demonstrated that immunological activities of total γδ T cells, Vδ2T cells, and Vδ2T cells of CAD patients were much lower than those in healthy individuals. Moreover, we found that there were positive correlations between the serum LDL-C levels and frequencies of CD3γδ T cells, CD69Vδ2T cells, NKG2DVδ2T cells, and NKp46Vδ2T cells. By contrast, there was an inverse correlation between the levels of serum LDL-C and the frequencies of CD69Vδ2T cells and NKp46Vδ2T cells. Accordingly, these findings could help us to better understand the roles of γδ T cells in the CAD, and shed light on the development of novel diagnostic techniques and therapeutic strategies by targeting γδ T cells for CAD patients.
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http://dx.doi.org/10.3389/fimmu.2022.900334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304556PMC
July 2022

Repair of finger pulp defects using a free second toe pulp flap anastomosed with the palmar vein.

J Orthop Surg Res 2022 Jul 16;17(1):352. Epub 2022 Jul 16.

Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, No.31 Huanghe Road, Yunhe District, Cangzhou, Hebei, China.

Purpose: To evaluate the clinical utility of surgical reconstruction of finger pulp defects using a plantar flap derived from the toes, with vascular anastomosis of the toe-finger artery and the plantar-palmar vein of the finger.

Methods: Between April 2018 and November 2020, 29 patients with finger pulp defects underwent treatment via the transplantation of pulp tissue from the second toe, with the plantar vein of the toe and the palmar vein of the finger being anastomosed during this procedure. In addition, an anastomosis of the toe and finger artery and nerve was conducted, with a flap size of 1.0 cm * 0.8 cm-2.3 cm * 4.0 cm being used for such repair. Donor tissue sites were closed without introducing deformities or other complications.

Results: In all patients in the present study, flap tissues survived and did not exhibit evidence of vascular crisis over a mean 16.8-month follow-up period (range 8-24 months). After successful skin flap grafting, they exhibited good elasticity and a soft texture. At three months post-surgery, some patients reported partial recovery of touch sensation in the transplanted tissue, while pain recovery was evident in some patients at 4-6 months post-surgery. No deformities or other complications were observed at the donor site, and the ability of patients to walk normally was not impaired.

Conclusion: The anastomosis of toe plantar flaps with the palmar vein can facilitate the repair of finger pulp injuries without the need to dissect the dorsal vein of the toe, allowing for the suturing of donor tissue sites without causing any deformities or other complications. This surgical approach can easily be conducted with satisfactory clinical outcomes.
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http://dx.doi.org/10.1186/s13018-022-03232-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287904PMC
July 2022

Hyaluronate-coated perfluoroalkyl polyamine prodrugs as bioactive siRNA delivery systems for the treatment of peritoneal cancers.

Biomater Adv 2022 May 17;136. Epub 2022 Mar 17.

Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha NE, USA.

RNA interference (RNAi) is an emerging therapeutic modality for cancer, which remains in critical need of effective delivery vectors due to the unfavorable biopharmaceutical properties of small RNAs. Polyamines are essential for functioning of mammalian cells. Dysregulated polyamine metabolism is found in many cancers and has been an attractive therapeutic target in combination therapies. Combination therapies based on drugs that affect polyamine metabolism and nucleic acids promise to enhance anticancer activity due to a cooperative effect on multiple oncogenic pathways. Here, we report bioactive polycationic prodrug (F-PaP) based on an anticancer polyamine analog bisethylnorspermine (BENSpm) modified with perfluoroalkyl moieties. Following encapsulation of siRNA, F-PaP/siRNA nanoparticles were coated with hyaluronic acid (HA) to form ternary nanoparticles [email protected]/siRNA. The presence of perfluoroalkyl moieties and HA reduced cell membrane toxicity and improved stability of the particles with cooperatively enhanced siRNA delivery in pancreatic and colon cancer cell lines. We then tested a therapeutic hypothesis that combining BENSpm with siRNA silencing of polo-like kinase 1 (PLK1) would result in cooperative cancer cell killing. [email protected]/siPLK1 induced polyamine catabolism and cell cycle arrest, leading to enhanced apoptosis in the tested cell lines. The HA-coated nanoparticles facilitated tumor accumulation and contributed to strong tumor inhibition and favorable modulation of the immune tumor microenvironment in orthotopic pancreatic cancer model. Combination anticancer therapy with polyamine prodrug-mediated delivery of siRNA. Hyaluronate coating of the siRNA nanoparticles facilitates selective accumulation in orthotopic pancreatic tumors. Perfluoroalkyl conjugation reduces toxicity and improves gene silencing effect. Nanoparticle treatment induces polyamine catabolism and cell cycle arrest leading to strong tumor inhibition and favorable modulation of immune tumor microenvironment.
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http://dx.doi.org/10.1016/j.bioadv.2022.212755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268001PMC
May 2022

Balloon Angioplasty Combined with Tirofiban as a First-Line Rescue Treatment After Failed Mechanical Thrombectomy for Middle Cerebral Artery Occlusion with Underlying Atherosclerosis.

World Neurosurg 2022 Jul 7. Epub 2022 Jul 7.

Department of Interventional Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address:

Objective: The standard rescue modality for patients with intracranial atherosclerotic stenosis after failed mechanical thrombectomy (MT) is not well established. We evaluated the safety and efficacy of balloon dilation in combination with tirofiban as the first-line salvage therapy when MT failed in these patients.

Methods: We retrospectively analyzed the records of 47 patients admitted between January 2018 and June 2021, with middle cerebral artery atherosclerotic occlusion, who underwent balloon angioplasty in combination with tirofiban as the first-line salvage therapy after the failure of MT. The recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed.

Results: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 41 (87.2%) of the 47 patients. Acute stents were deployed in another 6 patients who did not achieve successful re-perfusion after balloon angioplasty. Successful recanalization was achieved in 3 of them. One patient (2.1%, 1/47) experienced re-occlusion several days later due to the withdrawal of antiplatelet therapy for parenchymal hematoma. Seven patients (14.9%, 7/47) underwent stent angioplasty in the stable stage (range: 1-2 months) because severe residual stenosis was detected on follow-up imaging. There was only one event of periprocedural complication, namely ectopic migration of emboli. The good functional outcome rate was 55.3% (26/47), without the events of symptomatic intracranial hemorrhage and mortality.

Conclusions: Balloon angioplasty in combination with tirofiban is safe and effective for middle cerebral artery atherosclerotic occlusion after the failure of MT.
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http://dx.doi.org/10.1016/j.wneu.2022.07.001DOI Listing
July 2022

Metabolites Analysis of Anti-Myocardial Ischemia Active Components of Based on Gut Microbiota-Drug Interaction.

Int J Mol Sci 2022 Jul 5;23(13). Epub 2022 Jul 5.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, China.

has been reported to have potential therapeutic effects against myocardial ischemia. The pharmacological effects of oral natural medicines may be influenced by the participation of gut microbiota. In this study, we aimed to investigate the bidirectional regulation of gut microbiota and the main components of . We first established a quantitative method for the four main components (chlorogenic acid, syringin, acanthoside B, rutin) which were chosen by fingerprint using liquid chromatography tandem mass spectrometry (LC-MS/MS), and found that gut microbiota has a strong metabolic effect on them. Meanwhile, we identified five major rat gut microbiota metabolites (M1-M5) using liquid chromatography tandem time-of-flight mass spectrometry (LC/MS-IT-TOF). The metabolic properties of metabolites in vitro were preliminarily elucidated by LC-MS/MS for the first time. These five metabolites of may all have potential contributions to the treatment of myocardial ischemia. Furthermore, the four main components (10 μg/mL) can significantly stimulate intestinal bacteria to produce short chain fatty acids in vitro, respectively, which can further contribute to the effect in myocardial ischemia. In this study, the therapeutic effect against myocardial ischemia of was first reported to be related to the intestinal flora, which can be useful in understanding the effective substances of .
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http://dx.doi.org/10.3390/ijms23137457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267203PMC
July 2022

40 Hz Blue LED Relieves the Gamma Oscillations Changes Caused by Traumatic Brain Injury in Rat.

Front Neurol 2022 21;13:882991. Epub 2022 Jun 21.

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

Background: Photobiomodulation (PBM) using low-level light-emitting diodes (LEDs) can be rapidly applied to various neurological disorders safely and non-invasively.

Materials And Methods: Forty-eight rats were involved in this study. The traumatic brain injury (TBI) model of rat was set up by a controlled cortical impact (CCI) injury. An 8-channel cortex electrode EEG was fixed to two hemispheres, and gamma oscillations were extracted according to each electrode. A 40 hz blue LED stimulation was set at four points of the frontal and parietal regions for 60 s each, six times per day for 1 week. Modified Neurologic Severity Scores (mNSS) were used to evaluate the level of neurological function.

Results: In the right-side TBI model, the gamma oscillation decreased in electrodes Fp2, T4, C4, and O2; but significantly increased after 1 week of 40 hz Blue LED intervention. In the left-side TBI model, the gamma oscillation decreased in electrodes Fp1, T3, C3, and O1; and similarly increased after 1 week of 40 hz Blue LED intervention. Both left and right side TBI rats performed significantly better in mNSS after 40 hz Blue LED intervention.

Conclusion: TBI causes the decrease of gamma oscillations on the injured side of the brain of rats. The 40 hz Blue LED therapy could relieve the gamma oscillation changes caused by TBI and improve the prognosis of TBI.
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http://dx.doi.org/10.3389/fneur.2022.882991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253286PMC
June 2022

Berberine treats atherosclerosis via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway in gut microbiota.

Signal Transduct Target Ther 2022 07 7;7(1):207. Epub 2022 Jul 7.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.

Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR's metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P < 0.05, n = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (*P < 0.05; *P < 0.05), and 37 and 35% in plasma (***P < 0.001; *P < 0.05), after 4 months on BBR. BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins.
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http://dx.doi.org/10.1038/s41392-022-01027-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259588PMC
July 2022

Alberta Stroke Program Early CT Score and collateral status predict target mismatch in large vessel occlusion with delayed time windows.

J Neurointerv Surg 2022 Jul 5. Epub 2022 Jul 5.

Department of Interventional Radiology, Jiangsu Province People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China

Background: The Alberta Stroke Program Early CT Score (ASPECTS) and collateral score (CS) are two readily available imaging metrics for the evaluation of acute ischemic stroke (AIS) with large vessel occlusion (LVO).

Objective: To investigate the predictive value of the ASPECTS combined with CS in detecting patients with CT perfusion (CTP) target mismatch in delayed time windows.

Methods: One hundred and sixty-four patients with LVO-AIS were included. ASPECTS was assessed on non-contrast CT (NCCT). CS was evaluated on single-phase CT angiography (sCTA). Target mismatch was defined as a CTP core volume ≤70 mL, mismatch ratio ≥1.8, and absolute mismatch volume ≥15 mL. Spearman correlation analysis and receiver operating characteristic curve analyses were performed.

Results: The median NCCT ASPECTS of the 164 patients was 8 (IQR 6-9), median sCTA-CS was 2 (IQR 1-2), and median CTP core volume was 8 mL (IQR 0-29.5). There was a strong correlation between NCCT ASPECTS and CTP core volume (r=-0.756, p<0.0001) and a moderate correlation between the sCTA-CS and CTP core volume (r=-0.450, p<0.0001). Integrating NCCT ASPECTS and sCTA-CS provided a higher area under the curve (AUC) for predicting target mismatch (AUC=0.882; sensitivity, 89.1%; specificity, 77.8%; p<0.001).

Conclusions: NCCT ASPECTS had a strong correlation with CTP core volumes in patients with LVO-AIS in delayed time windows. Combining NCCT ASPECTS with sCTA-CS resulted in a more accurate prediction of target mismatch. If a CTP scan is not available, NCCT ASPECTS combined with sCTA-CS may guide clinicians in making treatment decisions.
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http://dx.doi.org/10.1136/neurintsurg-2022-018960DOI Listing
July 2022

OsPP65 Negatively Regulates Osmotic and Salt Stress Responses Through Regulating Phytohormone and Raffinose Family Oligosaccharide Metabolic Pathways in Rice.

Rice (N Y) 2022 Jul 2;15(1):34. Epub 2022 Jul 2.

Guangdong Key Laboratory for Crop Germplasm Resources Preservation and Utilization, Agro-Biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China.

Although type 2C protein phosphatases (PP2Cs) have been demonstrated to play important roles in regulating plant development and various stress responses, their specific roles in rice abiotic stress tolerance are still largely unknown. In this study, the functions of OsPP65 in rice osmotic and salt stress tolerance were investigated. Here, we report that OsPP65 is responsive to multiple stresses and is remarkably induced by osmotic and salt stress treatments. OsPP65 was highly expressed in rice seedlings and leaves and localized in the nucleus and cytoplasm. OsPP65 knockout rice plants showed enhanced tolerance to osmotic and salt stresses. Significantly higher induction of genes involved in jasmonic acid (JA) and abscisic acid (ABA) biosynthesis or signaling, as well as higher contents of endogenous JA and ABA, were observed in the OsPP65 knockout plants compared with the wild-type plants after osmotic stress treatment. Further analysis indicated that JA and ABA function independently in osmotic stress tolerance conferred by loss of OsPP65. Moreover, metabolomics analysis revealed higher endogenous levels of galactose and galactinol but a lower content of raffinose in the OsPP65 knockout plants than in the wild-type plants after osmotic stress treatment. These results together suggest that OsPP65 negatively regulates osmotic and salt stress tolerance through regulation of the JA and ABA signaling pathways and modulation of the raffinose family oligosaccharide metabolism pathway in rice. OsPP65 is a promising target for improvement of rice stress tolerance using gene editing.
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http://dx.doi.org/10.1186/s12284-022-00581-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250576PMC
July 2022

Transcription factor Meis1 act as a new regulator of ischemic arrhythmias in mice.

J Adv Res 2022 07 15;39:275-289. Epub 2021 Nov 15.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China; Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University (Institute of Clinical Pharmacy, The University Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin, China. Electronic address:

Introduction: The principal voltage-gated Na channel, Na1.5 governs heart excitability and conduction. Na1.5 dysregulation is responsible for ventricular arrhythmias and subsequent sudden cardiac death (SCD) in post-infarct hearts. The transcription factor Meis1 performs a significant role in determining differentiation fate and regenerative capability of cardiomyocytes. However, the functions of Meis1 in ischemic arrhythmias following myocardial infarction (MI) are still largely undefined.

Objectives: Here we aimed to study whether Meis1 could act as a key regulator to mediate cardiac Na channel and its underlying mechanisms.

Methods: Heart-specific Meis1 overexpression was established by AAV9 virus injection in C57BL/6 mice. The QRS duration, the incidence of ventricular arrhythmias and cardiac conduction velocity were evaluated by ECG, programmed electrical stimulation and optical mapping techniques respectively. The conventional patch clamp technique was performed to explore the I characteristics of isolated mouse ventricular myocytes. In vitro, Meis1 was also overexpressed in hypoxic-treated neonatal cardiomyocytes. The analysis of immunoblotting and immunofluorescence were used to detect the changes in the expression of Na1.5 in each group.

Results: We found that forced expression of Meis1 rescued the prolongation of QRS complex, produced anti-arrhythmic activity and improved epicardial conduction velocity in infarcted mouse hearts. In terms of mechanisms, cardiac electrophysiological changes of MI mice can be ameliorated by the recovery of Meis1, which is characterized by the restoration of I current density and Na1.5 expression level of cardiomyocytes in the marginal zone of MI mouse hearts. Furthermore, in vitro studies showed that Meis1 was also able to rescue hypoxia-induced decreased expression and dysfunction of Na1.5 in ventricular myocytes. We further revealed that E3 ubiquitin ligase CDC20 led to the ubiquitination and degradation of Meis1, which blocked the transcriptional regulation of SCN5A by Meis1 and ultimately led to the electrophysiological remodeling in ischemic-hypoxic cardiomyocytes.

Conclusion: CDC20 mediates ubiquitination of Meis1 to govern the transcription of SCN5A and cardiac electrical conduction in mouse cardiomyocytes. This finding uncovers a new mechanism of Na1.5 dysregulation in infarcted heart, and provides new therapeutic strategies for malignant arrhythmias and sudden cardiac death following MI.
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http://dx.doi.org/10.1016/j.jare.2021.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263651PMC
July 2022

A sustained-release Trametinib bio-multifunction hydrogel inhibits orthodontically induced inflammatory root resorption.

RSC Adv 2022 Jun 6;12(26):16444-16453. Epub 2022 Jun 6.

Department of Orthodontics, Hospital of Stomatology, Jilin University No. 1500 Qinghua Road, ChaoYang District Changchun Jilin P. R. China +86 431 88975348 +86 431 85579371 +86 13504484365.

Orthodontic tooth movement (OTM) is a bone reconstruction process. In most cases, OTM could induce root resorption as a common side effect, called orthodontically induced inflammatory root resorption (OIIRR). OIIRR affects tooth health and interferes with the stability of orthodontic treatment. Osteoclasts, which perform bone resorption in OTM, attack cementum, causing OIIRR. Many signaling pathways are involved in the maturation and differentiation of osteoclasts, among which the ERK1/2 is one of the important pathways. In this experiment, we added Trametinib (Tra), a specific inhibitor of ERK1/2, to catechol-modified chitosan (CHI-C) and oxidized dextran (ODex) to form a CCOD-Trametinib composite hydrogel (CCOD-Tra) to prevent OIIRR. CCOD-Tra exhibited good biocompatibility, injectability, strong adhesion, good hemostatic function and sustained release of Tra. We performed local injection of CCOD-Tra into the periodontal tissues of rats. CCOD-Tra firmly adhered to the periodontal tissues and then released Tra to establish a good biological environment and maintain a drug concentration at a high level around the roots for a long time. H&E, TRAP, immunochemistry staining and micro-CT indicated that CCOD-Tra had a good effect in terms of preventing OIIRR. Cell experiments showed that CCOD-Tra reduced the expression of TRAP, MMP-9 and C-FOS in osteoclast cells through the ERK1/2 signaling pathway to inhibit the differentiation and maturation of osteoclasts. Based on the above results, we concluded that CCOD-Tra had the ability to prevent OIIRR, the high adhesion and injectability of CCOD may provide better therapeutic ideas for clinical prevention of OIIRR.
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http://dx.doi.org/10.1039/d2ra00763kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168831PMC
June 2022

Effect of Switching Antiretroviral Treatment Regimen in Patients With Drug-Resistant HIV-1 Infection: Retrospective Observational Cohort Study.

JMIR Public Health Surveill 2022 Jun 24;8(6):e33429. Epub 2022 Jun 24.

West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Background: Evidence on the efficacy of antiretroviral therapy (ART) regimen switches on the mortality of patients with HIV drug resistance (HIVDR) is limited.

Objective: We aim to provide policy guidance for ART regimen selection and evaluate the effectiveness of ART regime switches for people living with HIV and HIV-1 drug resistance.

Methods: This retrospective observational cohort study included 179 people living with HIV and HIV-1 drug resistance from 2011 to 2020. The time that participants switched treatment regimens either to protease inhibitor (PI)-based ART regimens (PIs) or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens (NNRTIs) was taken as an observation starting point and followed up every 12 months. The parametric g-formula was used to estimate the 5-year risk of mortality under the situations of (1) natural course, (2) immediate switch to NNRTIs, (3) immediate switch to PIs, and (4) if CD4(+) T cells<200 switched to PIs.

Results: The follow-up time of the 179 patients ranged from 30 to 119 months. The median follow-up time was 90 months. During a follow-up of 15,606 person-months, 27 individuals died in the cohort. The estimated 5-year risk of mortality under natural course, immediate switch to NNRTIs, immediate switch to PIs, and if CD4(+), and switch to PIs if T cells<200 were 11.62% (95% CI 7.82-17.11), 31.88% (95% CI 20.79-44.94), 2.87% (95% CI 0.32-7.07), and 5.30% (95% CI 2.07-10.21), respectively. The risk ratios (RRs) of immediate switch to NNRTIs, immediate switch to PIs, and switch to PIs if CD4(+) T cells<200, compared with natural course mortality rate, were 2.74 (95% CI 2.01-3.47), 0.25 (95% CI: 0.04-0.54), and 0.46 (95% CI 0.22-0.71), respectively. The risk differences were 20.26% (95% CI 10.96-28.61), -8.76% (95% CI -13.34 to -5.09) and -6.32% (95% CI -9.75 to -3.11), respectively.

Conclusions: Our study found that a PI-based ART regimen was beneficial for reducing mortality in people living with HIV and HIV-1 drug resistance. More effort should be given to find HIV-1 drug resistance earlier to ensure a timely adjustment to PI-based ART, thereby maximizing the benefit of early switch treatment for people living with HIV and HIV-1 drug resistance.
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http://dx.doi.org/10.2196/33429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270715PMC
June 2022

Quality assurance based on deep learning for pelvic OARs delineation in radiotherapy.

Curr Med Imaging 2022 Jun 21. Epub 2022 Jun 21.

Department of Radiation Oncology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR. China.

Background: Correct delineation of organs at risk (OARs) is an important step for radiotherapy and it is also a time-consuming process that depends on many factors.

Objective: An automatic quality assurance (QA) method based on deep learning (DL) was proposed to improve efficiency for detecting contouring errors of OARs.

Materials And Methods: A total of 180 planning CT scan sets at the pelvic site and the corresponding OARs contours from clinics were enrolled in this study. Among them, 140 cases were randomly chosen as the training datasets, 20 cases were used as the validation datasets, and the remaining 20 cases were used as the test datasets. DL-based models were trained through data curation for data cleaning based on the Dice similarity coefficient and the 95th percentile Hausdorff distance between the original contours and the predicted contours. All contouring errors could be classified into two types:minor modification required and major modification required. The pass criteria were established using Bias-Corrected and Accelerated bootstrap on 20 manually reviewed validation datasets. The performance of the QA method was evaluated with the metrics of sensitivity, specificity, the area under the receiving operator characteristic curve (AUC) and detection rate sensitivity on the 20 test datasets.

Results: For all OARs, segmentation results after data curation were superior to those without. The sensitivity of the QA method was greater than 0.890 and the specificity was higher than 0.975. The AUCs were 0.948, 0.966, 0.965 and 0.932 for the bladder, right femoral head, left femoral head and rectum, respectively. Almost all major errors could be detected by the automatic QA method, and the lowest detection rate sensitivity of minor errors was 0.863 for the rectum.

Conclusions: QA of OARs is an important step for the correct implementation of radiotherapy. The DL-based QA method proposed in this study showed a high potential to automatically detect contouring errors with high precision. The method can be integrated into the existing radiotherapy procedures to improve the efficiency of delineating the OARs.
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http://dx.doi.org/10.2174/1573405618666220621121225DOI Listing
June 2022

Metabolomic changes upon conjugated linoleic acid supplementation and predictions of body composition responsiveness.

J Clin Endocrinol Metab 2022 Jun 15. Epub 2022 Jun 15.

School of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.

Context: Conjugated linoleic acid (CLA) may optimize body composition, yet mechanisms underlining its benefits were not clear in human.

Objective: To reveal the CLA-induced changes in plasma metabolome associated with body composition improvement and the predictive performance of baseline metabolome on intervention responsiveness.

Methods: Plasma metabolome from overnight fasted samples at pre- and post-intervention of 65 participants in a 12-week randomized, placebo-controlled trial (3.2 g/day CLA vs. 3.2 g/day sunflower oil) were analyzed using untargeted LC-MS metabolomics. Mixed linear model and machine learning were applied to assess differential metabolites between treatments, and to identify optimal panel (based on baseline conventional variables vs. metabolites) predicting responders of CLA-derived body composition improvement (increased muscle variables or decreased adiposity variables) based on dual-energy X-ray absorptiometry.

Results: Compared to placebo, CLA altered 57 metabolites (P < 0.10) enriched in lipids/lipid-like molecules including glycerophospholipids (n=7), fatty acyls (n=6), sphingolipids (n=3). CLA-upregulated cholic acid (or downregulated aminopyrrolnitrin) was inversely correlated with changes in muscle and adiposity variables. Inter-individual variability in response to CLA-derived body composition change. The areas under the receiver operator characteristics curves of optimal metabolite panels were higher than that of optimal conventional panels in predicting favorable responders of waist circumference (0.93 [0.82-1.00] vs 0.64 [0.43-0.85]), visceral adiposity index (0.95 [0.88-1.00] vs 0.58 [0.35-0.80]), appendicular fat mass (0.97 [0.92-1.00] vs 0.73 [0.55-0.91]) upon CLA supplementation (all FDR P<0.05).

Conclusions: Post-intervention metabolite alterations were identified, involving in lipid/energy metabolism, associated with body composition changes. Baseline metabolite profiling enhanced the prediction accuracy on responsiveness of CLA-induced body composition benefits.
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http://dx.doi.org/10.1210/clinem/dgac367DOI Listing
June 2022

Effect of Nrf2 on Phenotype Changes of Macrophages in the Anterior Vaginal Wall of Women With Pelvic Organ Prolapse.

Female Pelvic Med Reconstr Surg 2022 May 31. Epub 2022 May 31.

From the Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Zhengzhou University.

Objective: The aim of this study was to observe the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) on the phenotype changes of macrophages in the anterior vaginal wall of patients with pelvic organ prolapse (POP).

Methods: The tissues of the anterior vaginal wall of the control group (n = 30) and POP groups (n = 60) were collected during operation. The expressions of Nrf2, iNOS (representative factor of M1 macrophages), and CD206 (representative factor of M2 macrophages) were determined by immunohistochemical staining and Western blot. Morphological changes and collagen distribution of the anterior vaginal wall were observed by hematoxylin-eosin staining and Masson trichrome staining.

Results: Compared with the control group, the expression levels of Nrf2 and CD206 protein in the anterior vaginal wall tissues of the POP groups were significantly decreased (P < 0.05), and were negatively proportional to the degree of prolapse (P < 0.05). The expression of iNOS was significantly increased and was directly proportional to the degree of prolapse (P < 0.05). Hematoxylin-eosin staining and Masson trichrome staining showed that the collagen fibers are more sparsely arranged and disordered in the POP group than the control.

Conclusions: In patients with POP, the expression of antioxidant factor Nrf2 is reduced in the vaginal anterior wall tissues and the antioxidant capacity is weakened, leading to the blocked polarization of macrophages and the accumulation of a large number of M1 macrophages in the tissue, affecting the occurrence and development of POP.
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http://dx.doi.org/10.1097/SPV.0000000000001212DOI Listing
May 2022

A Reduced F-Dependent Nitrite Reductase in an Anaerobic Methanotrophic Archaeon.

J Bacteriol 2022 07 13;204(7):e0007822. Epub 2022 Jun 13.

Department of Biochemistry, Virginia Techgrid.438526.e, Blacksburg, Virginia, USA.

Anaerobic methanotrophic archaea (ANME), which oxidize methane in marine sediments through syntrophic associations with sulfate-reducing bacteria, carry homologs of coenzyme F-dependent sulfite reductase (Fsr) of Methanocaldococcus jannaschii, a hyperthermophilic methanogen from deep-sea hydrothermal vents. Fsr (Fsr) and ANME-Fsr belong to two phylogenetically distinct groups, FsrI and FsrII, respectively. FsrI reduces sulfite to sulfide with reduced F (FH), protecting methyl coenzyme M reductase (Mcr), an essential enzyme for methanogens, from sulfite inhibition. However, the function of FsrIIs in ANME, which also rely on Mcr and live in sulfidic environments, is unknown. We have determined the catalytic properties of FsrII from a member of ANME-2c. Since ANME remain to be isolated, we expressed ANME2c-FsrII in a closely related methanogen, Methanosarcina acetivorans. Purified recombinant FsrII contained siroheme, indicating that the methanogen, which lacks a native sulfite reductase, produced this coenzyme. Unexpectedly, FsrII could not reduce sulfite or thiosulfate with FH. Instead, it acted as an FH-dependent nitrite reductase (FNiR) with physiologically relevant values (nitrite, 5 μM; FH 14 μM). From kinetic, thermodynamic, and structural analyses, we hypothesize that in FNiR, FH-derived electrons are delivered at the oxyanion reduction site at a redox potential that is suitable for reducing nitrite (E' [standard potential], +440 mV) but not sulfite (E', -116 mV). These findings and the known nitrite sensitivity of Mcr suggest that FNiR may protect nondenitrifying ANME from nitrite toxicity. Remarkably, by reorganizing the reductant processing system, Fsr transforms two analogous oxyanions in two distinct archaeal lineages with different physiologies and ecologies. Coenzyme F-dependent sulfite reductase (Fsr) protects methanogenic archaea inhabiting deep-sea hydrothermal vents from the inactivation of methyl coenzyme M reductase (Mcr), one of their essential energy production enzymes. Anaerobic methanotrophic archaea (ANME) that oxidize methane and rely on Mcr, carry Fsr homologs that form a distinct clade. We show that a member of this clade from ANME-2c functions as F-dependent nitrite reductase (FNiR) and lacks Fsr activity. This specialization arose from a distinct feature of the reductant processing system and not the substrate recognition element. We hypothesize FNiR may protect ANME Mcr from inactivation by nitrite. This is an example of functional specialization within a protein family that is induced by changes in electron transfer modules to fit an ecological need.
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http://dx.doi.org/10.1128/jb.00078-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295563PMC
July 2022

A Study on the Mechanism of the Sedative-hypnotic Effect of Cinnamomum camphora chvar. Borneol Essential Oil Based on Network Pharmacology.

J Oleo Sci 2022 Jul 10;71(7):1063-1073. Epub 2022 Jun 10.

State Key Laboratory of Food Science and Technology, Jiangnan University.

In this paper, we investigated the sedative-hypnotic effect of Cinnamomum camphora chvar. Borneol essential oil (BEO, 16.4% borneol), a by-product of steam distillation of Cinnamomum camphora chvar. Borneol, from which natural crystalline borneol (NCB, 98.4% borneol) is obtained. Using locomotor activity tests and pentobarbital sodium-induced sleep test, it was found that BEO significantly reduced locomotor activity (p < 0.05), shortened sleep latency (p < 0.0001), prolonged sleep duration (p < 0.05), and had a sedative-hypnotic effect. We constructed the "components-targets-signaling pathways" and "proteinprotein interaction" (PPI) network of BEO using network pharmacology. The results show that the 24 active components of BEO acted on 17 targets, mainly through response to alkaloid and catecholamine transport, and neuroactive ligand-receptor interaction. The PPI network identified 12 key proteins, mainly dopamine receptor (DR)D2, opioid receptor mu 1 (OPRM1), and opioid receptor kappa 1 (OPRK1), and we further analyzed the active components and targets of BEO through molecular docking. The results showed that the active components and targets obtained by network pharmacology analyses had good binding activity, which reflected their multi-component, multi-target, multi-pathway action characteristics. This paper provides a theoretical basis for further study of the mechanism of action of BEO in the treatment of insomnia.
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http://dx.doi.org/10.5650/jos.ess21278DOI Listing
July 2022

Small EPIDERMAL PATTERNING FACTOR-LIKE2 peptides regulate awn development in rice.

Plant Physiol 2022 Jun 11. Epub 2022 Jun 11.

Guangdong Provincial Key Laboratory of Plant Molecular Breeding, College of Agriculture, South China Agricultural University, Guangzhou, 510642, China.

The EPIDERMAL PATTERNING FACTOR (EPF) and EPF-LIKE (EPFL) family of small secreted peptides act to regulate many aspects of plant growth and development; however, their functions are not widely characterized in rice (Oryza sativa). Here, we used CRISPR/Cas9 technology to individually knock out each of 11 EPF/EPFL genes in the rice cultivar Kasalath. Loss of function of most OsEPF/EPFL genes generated no obvious phenotype alteration, whilst disruption of OsEPFL2 in Kasalath caused a short or no awn phenotype and reduced grain size. OsEPFL2 is strongly expressed in the young panicle, consistent with a role in regulating awn and grain development. Haplotype analysis indicated that OsEPFL2 can be classified into six major haplotypes. Nucleotide diversity and genetic differentiation analyses suggested that OsEPFL2 was positively selected during the domestication of rice. Our work to systematically investigate the function of EPF/EPFL peptides demonstrates that different members of the same gene family have been independently selected for their ability to regulate a similar biological function and provides perspective on rice domestication.
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http://dx.doi.org/10.1093/plphys/kiac278DOI Listing
June 2022

Development of UPLC-MS/MS method for determining hainanmycin in foods of animal origin.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2022 Aug 9;39(8):1401-1411. Epub 2022 Jun 9.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

Hainanmycin is a polyether antibiotic. Toxicological studies have shown the adverse effects of hainanmycin on animals and humans. At present, no study is available on the detection of hainanmycin in edible tissues of animals. Hence, a fast and accurate detection method for hainanmycin is essential. This study aimed to develop a new analytical method based on ultra-high-performance liquid chromatography-tandem mass spectrometry to detect hainanmycin in 10 matrices, including milk, eggs, fat, kidney, muscles and livers of chicken, beef and sheep. The limit of detection and the limit of quantitation of the 10 matrices were 0.1-0.4 μg/kg and 0.25-1 μg/kg, respectively, and were far below the maximum residue limits of other polyether anticoccidial drugs (1-150 μg/kg). The recoveries of hainanmycin ranged from 79% to 105%, and the relative standard deviation ranged from 2.8% to 12.0%. The research results prove that the proposed method is operational and simple in detecting hainanmycin, and has high precision and accuracy in a variety of matrices.
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http://dx.doi.org/10.1080/19440049.2022.2083693DOI Listing
August 2022

Adsorption behavior of Cr(VI) by biomass-based adsorbent functionalized with deep eutectic solvents (DESs).

BMC Chem 2022 Jun 2;16(1):41. Epub 2022 Jun 2.

Department of Chemistry & Life Science, Hubei University of Education, Wuhan, 430205, China.

This study was aimed to evaluate the performance of DESs functionalized peanut shell (PSD) as biosorbent for removing Cr(VI) from water. The effects of pretreatment, initial concentration, adsorption temperature, kinetics, adsorption isotherm, and thermodynamics were investigated. Scanning electron microscopy (SEM) and Point of Zero charge (pHpzc) techniques were used for characterization of the adsorbents. The results showed that the rigid structure of peanut shell was broken down after DESs modification and the point of zero charge was 6.02 for peanut shell and 6.84 for PSD, which exhibited a slightly acid character. Based on the comparisons of linear and nonlinear analysis of four kinetic models and four isotherms, the pseudo-second-order kinetic model was found to be suitable for describing the adsorption process. The presence of a boundary effect was observed within the range of research, indicating that internal diffusion was not the only rate-controlling step. The equilibrium data were well represented by the Langmuir model rather than the Freundlich, Temkin, and Dubinin-Radushkevich models. The maximum capacity derived was 5.36 mg g. Changes in Gibb's free energy, enthalpy, and entropy revealed that Cr(VI) adsorption onto modified peanut-shell powders was a spontaneous and endothermic process. However, the highest desorption efficiency was only 8.77% by using NaOH as a desorbing agent.
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http://dx.doi.org/10.1186/s13065-022-00834-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161602PMC
June 2022

The respiratory cytotoxicity of typical organophosphorus flame retardants on five different respiratory tract cells: Which are the most sensitive one?

Environ Pollut 2022 Aug 30;307:119564. Epub 2022 May 30.

Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China; Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Key Laboratory of City Cluster Environmental Safety and Green Development (Department of Education, China), School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address:

Triphenyl phosphate (TPHP) is a frequently used flame retardant and indoor semi-volatile pollutant exposing humans with endocrinal disrupting effects. However, its respiratory tract toxicity remains unclear. Herein, we mainly focused on exploring the cytotoxicity of TPHP to the cells from five different parts of the human respiratory tract (from top to bottom): human nasal epithelial (HNEpC) cells, human bronchial epithelial (16HBE) cells, normal nasopharyngeal epithelial (NP69) cells, human lung epithelial cells (Beas-2B) cells, and human lung fibrocells (HFL1 cells) cells. The cell viability, micronucleus induction, endoplasmic reticulum stress gene, intracellular Ca concentration, mitochondrial membrane potential (MMP) were investigated in short-term as well as extended exposure of TPHP. HFL1 and HNEpC cells were found to be irreversible damage, while other three type cells achieved homeostasis through self-rescue. Moreover, expression of downstream genes of Nrf2 signaling pathway were upregulated for 1.3-7.0 times and glutathione detoxification enzyme activity changed for 2-10 (U/mg protein) in HNEpC cells. Furthermore, the vascular endothelial growth factor (VEGF), a disease-related factor, increased 1.0-3.5-fold in HNEpC cells. RNA-sequencing results suggested that protein linkage recombination, molecular function regulation and metabolic processes signal pathway were all affected by TPHP exposure in HNEpC. This is a first report to compare respiratory cytotoxicity in whole human respiratory tract under OPFR exposure and found HNEpC cells were the most sensitive target of TPHP. Molecular biological mechanisms uncovered that TPHP exposure in HNEpC can induce the activation of MAPK signal pathway and demonstrate potential respiratory growth differentiation and stress disorder in human nasal cells upon TPHP exposure.
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http://dx.doi.org/10.1016/j.envpol.2022.119564DOI Listing
August 2022
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