Publications by authors named "Xuemei Zhang"

713 Publications

Double Filtration Plasmapheresis (DFPP) in Severe Hypertriglyceridemia Patients - a Pilot Study.

Clin Lab 2022 Jul;68(7)

Background: Severe hypertriglyceridemia (sHTG) is an independent risk factor of atherosclerotic heart disease (ASHD) and acute pancreatitis (AP). The aim was to evaluate the efficacy and safety of DFPP in sHTG patients (TG > 1,000 mg/dL).

Methods: This was a prospective single-center study in which patients with severe symptomatic drug and diet refractory HTG were recruited. Peripheral venous access of upper extremities was used for DFPP. Blood flow rate was 100 - 120 mL/min and plasma separation rate was 800 - 1,000 mL/h. Plasma volume to treat in each case was calculated with the Kaplan formula. Anticoagulation was achieved by low molecular weight heparin. Treatment goal was triglyceride level decreased to normal (< 1.7 mmol/L). Epidemiological data, lipid, hematological parameters as well as side effects were evaluated before and after DFPP.

Results: Seven patients (6 males and 1 female) were consecutively enrolled to this trial. There was diabetes mellitus type 2 in four patients and obesity-associated nephropathy in one patient. The mean age was 42.5 years. The average TG level before plasmapheresis was 17.41 mmol/L (range 10.93 - 26.33 mmol/L). After one session, the levels of triglyceride, total cholesterol, LDL-c, HDL-c decreased significantly by 58.3%, 43.2%, 41.9%, 20.7%, respectively. The mean number of treatment sessions was 1.5 (range 1 - 3). DFPP was well-tolerated. Except for transient decrease of albumin, globulin and fibrinogen, liver and renal functions, hematological parameters did not change significantly.

Conclusions: According to our own experience, DFPP may be used safely and effectively in sHTG patients at risk of acute coronary events and AP. However, further randomized controlled trials are necessary to explore the long-term effect.
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http://dx.doi.org/10.7754/Clin.Lab.2021.211051DOI Listing
July 2022

Successive walnut plantations alter soil carbon quantity and quality by modifying microbial communities and enzyme activities.

Front Microbiol 2022 25;13:953552. Epub 2022 Jul 25.

College of Forestry, Hebei Agricultural University, Baoding, China.

Knowledge of the spatial-temporal variations of soil organic carbon (SOC) quantity and quality and its microbial regulation mechanisms is essential for long-term SOC sequestration in agroecosystems; nevertheless, this information is lacking in the process of walnut plantations. Here, we used the modified Walkley-Black method, phospholipid fatty acid analysis, and micro-plate enzyme technique to analyze the evolution of SOC stocks and quality/lability as well as microbial communities and enzyme activities at different soil depths in walnut plantations with a chronosequence of 0-, 7-, 14-, and 21-years in the Eastern Taihang Mountains, China. The results indicated that long-term walnut plantations (14-and 21-years) enhanced SOC stocks, improved SOC quality/lability (as indicated by the lability index), and promoted microbial growth and activities (i.e., hydrolase and oxidase activities) in the 0-40 cm soil layers. Besides, these above-mentioned SOC-and microbial-related indices (except for oxidase activities) decreased with increasing soil depths, while oxidase activities were higher in deeper soils (40-60 cm) than in other soils (0-40 cm). The partial least squares path model also revealed that walnut plantation ages and soil depths had positive and negative effects on microbial attributes (e.g., enzyme activities, fungal and bacterial communities), respectively. Meanwhile, the SOC stocks were closely related to the fungal community; meanwhile, the bacterial community affected SOC quality/liability by regulating enzyme activities. Comprehensively, long-term walnut plantations were conducive to increasing SOC stocks and quality through altering microbial communities and activities in the East Taihang Mountains in Hebei, China.
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http://dx.doi.org/10.3389/fmicb.2022.953552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358653PMC
July 2022

Radionuclide I-labeled albumin-indocyanine green nanoparticles for synergistic combined radio-photothermal therapy of anaplastic thyroid cancer.

Front Oncol 2022 25;12:889284. Epub 2022 Jul 25.

Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Objectives: Anaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC.

Methods: I was labeled on human serum albumin (HSA) by the standard chloramine T method. I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain I-HSA-ICG nanoparticles. Characterizations were performed . The cytotoxicity and imaging ability were investigated by cell/ experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and levels.

Results: The synthesized nanoparticles had a suitable size (25-45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/I-HSA-ICG nanoparticles could stay in tumor tissues for 4-6 days. Compared with other control groups, I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser.

Conclusions: In summary, I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.
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http://dx.doi.org/10.3389/fonc.2022.889284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358776PMC
July 2022

Effects of Different Processing Methods Based on Different Drying Conditions on the Active Ingredients of Bunge.

Molecules 2022 Jul 29;27(15). Epub 2022 Jul 29.

College of Life Science and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Compared to the traditional processing method, fresh processing can significantly enhance the preservation of biologically active ingredients and reduce processing time. This study evaluated the influences of fresh and traditional processing based on different drying conditions (sun drying, oven drying and shade drying) on the active ingredients in the roots and rhizomes of . High-performance liquid chromatography (HPLC) was utilized to determine the contents of six active ingredients in the roots and rhizomes of . The data were analyzed by fingerprint similarity evaluation, hierarchical cluster analysis (HCA) and principal component analysis (PCA). The results suggest that compared to the traditional processing method, the fresh processing method may significantly increase the preservation of biologically active ingredients. Furthermore, the findings demonstrated that among the three drying methods under fresh processing conditions, the shade-drying (21.02-26.38%) method is most beneficial for retaining the active ingredients in the roots and rhizomes of . Moreover, the fingerprint analysis identified 17 common peaks, and the similarity of fingerprints among samples processed by different methods ranged from 0.989 to 1.000. Collectively, these results suggest novel processing methods that may improve the yield of active ingredients for and may be implemented for industrial production.
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http://dx.doi.org/10.3390/molecules27154860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369592PMC
July 2022

The landscape in the gut microbiome of long-lived families reveals new insights on longevity and aging - relevant neural and immune function.

Gut Microbes 2022 Jan-Dec;14(1):2107288

Department of Gastroenterology, Key Laboratory of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Jiangsu, China.

Human longevity has a strong familial and genetic component. Dynamic characteristics of the gut microbiome during aging associated with longevity, neural, and immune function remained unknown. Here, we aim to reveal the synergistic changes in gut microbiome associated with decline in neural and immune system with aging and further obtain insights into the establishment of microbiome homeostasis that can benefit human longevity. Based on 16S rRNA and metagenomics sequencing data for 32 longevity families including three generations, centenarians, elderly, and young groups, we found centenarians showed increased diversity of gut microbiota, severely damaged connection among bacteria, depleted in microbial-associated essential amino acid function, and increased abundance of anti-inflammatory bacteria in comparison to young and elderly groups. Some potential probiotic species, such as were enriched with aging, which might possibly support health maintenance. The level of Amyloid-β (Aβ) and brain-derived neurotrophic factor (BDNF) related to neural function showed increased and decreased with aging, respectively. The elevated level of inflammatory factors was observed in centenarians compared with young and elderly groups. The enriched in centenarians might promote longevity through up-regulating anti-inflammatory factor IL-10 expression to mediate the critical balance between health and disease. Impressively, the associated analysis for gut microbiota with the level of Aβ, BDNF, and inflammatory factors suggests could be a particularly beneficial bacteria in the improvement of impaired neural and immune function. Our results provide a rationale for targeting the gut microbiome in future clinical applications of aging-related diseases and extending life span.: : 16S ribosomal RNA; : Metagenome-assembled genomes; : Amplicon sequence variants; : Deoxyribonucleic acid; : False discovery rate: : Kyoto Encyclopedia of Genes and Genomes; : Principal coordinates analysis; : Polymerase chain reaction; : Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; : Amyloid-β (Aβ); : Brain-derived neurotrophic factor.
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http://dx.doi.org/10.1080/19490976.2022.2107288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361766PMC
August 2022

[Lysosomal enzyme analysis of mucolipidosis type II α/β and type III α/β in two Chinese pedigrees].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Aug;39(8):829-835

Department of Medical Genetics and Prenatal Diagnosis Center, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Objective: To analyze the characteristics of lysosomal enzymes in mucolipidosis (ML) type II α/β and type III α/β for the choice of enzyme evaluating indicators.

Methods: Multiple lysosomal enzymes including α-iduronidase (IDUA), α -N-acetylglucosaminidase (NAGLU), β-galactosidase-1 (GLB1), β-glucuronidase (GUSB), α-galactosidase A (GLA), glucocerebrosidase (GBA) and arylsulphatase A (ASA) in plasma and leukocyte of two Chinese pedigrees with ML type II α/β and type III α/β and healthy controls were determined. Previous publications on ML type II α/β and type III α/β during the last five years were retrieved from PubMed, CNKI and WanFang databases by using "mucolipidosis" as key word.

Results: The activities of several lysosomal enzymes were increased in the plasma of both patients: ASA, IDUA (20-fold) > GUSB (10-fold) > GLB1, GLA (5-fold) > NAGLU (2-fold), whilst there was no significant change in GBA. The activities of several lysosomal enzymes in the leukocyte of the two patients were normal. 15 lysosomal enzymes have been used in 22 previous studies, the most frequently used were hexosaminidase A and B (Hex A+B) (12 papers), α-mannosidase (α-man) (11 papers) and GUSB (10 papers). The degree of Hex A+B and α-man elevation was most obvious (24.4-fold and 24.7-fold on average respectively), followed by ASA (22.4-fold on average), GUSB is 18.8-fold on average.

Conclusion: Based on the lysosomal enzyme analysis of the two cases and literature review, ASA, GUSB, Hex A+B and α-man are recommended as the evaluating indicators for lysosomal enzyme analysis of ML type II α/β and type III α/β.
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http://dx.doi.org/10.3760/cma.j.cn511374-20210830-00706DOI Listing
August 2022

Identification of Resistance Alleles in Three Maize Populations With Teosinte Gene Introgression.

Front Plant Sci 2022 14;13:942397. Epub 2022 Jul 14.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Chengdu, China.

Fusarium ear rot (FER) is a common fungal disease in maize ( L.) caused by . Resistant germplasm resources for FER are rare in cultivated maize; however, teosintes ( ssp. and ssp. ), which are wild-type species of maize, have the potential to offer a novel source of resistance alleles to enhance pathogen resistance in modern maize. Therefore, the aim of this study was to identify favorable alleles that confer significant levels of resistance toward FER. Three populations of BCF recombinant inbred lines (RILs) were developed by crossing two different teosintes, and , with maize inbred lines B73 and Zheng58, and were screened for FER resistance. We found that and had higher resistance toward in the leaves than B73 and Zheng58. However, the resistance toward s in the leaf and ear was unrelated among RILs. FER resistance was positively correlated with grain yield in the B73 × (BD) and Zheng58 × (ZP) populations, partly because the quantitative trait loci (QTLs) of FER resistance and yield traits were located close together. Four coincident QTLs (bd5.177, bd10.140, zp4.066, and zp5.116) and two highly reliable resistance-yield synergistic QTLs (10.140 and zp4.066) were identified in the BD and ZP populations, opening up the possibility of breeding for FER resistance without reducing yield.
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http://dx.doi.org/10.3389/fpls.2022.942397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331921PMC
July 2022

Overexpression of Transcription Factor from Improves Plant Salt Tolerance.

Int J Mol Sci 2022 Jul 17;23(14). Epub 2022 Jul 17.

Department of Biology, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.

(common ice plant) is one of the facultative halophyte plants, and it serves as a model for investigating the molecular mechanisms underlying its salt stress response and tolerance. Here we cloned one of the homeobox transcription factor (TF) genes, , from the ice plant, which has 60% similarity with the Arabidopsis . Overexpression of the in Arabidopsis (OE) showed that the plants had significantly elevated relative water content (RWC), chlorophyll content, superoxide dismutase (SOD), and peroxidase (POD) activities after salt stress treatment. Our proteomic analysis identified 145 proteins to be significantly changed in abundance, and 66 were exclusively increased in the OE plants compared to the wild type (WT). After salt treatment, 979 and 959 metabolites were significantly increased and decreased, respectively, in the OE plants compared to the WT. The results demonstrate that the can improve photosynthesis, increase the leaf chlorophyll content, and affect the TCA cycle by regulating metabolites (e.g., pyruvate) and proteins (e.g., citrate synthase). Moreover, HB7 modulates the expression of stress-related proteins (e.g., superoxide dismutase, dehydroascorbate reductase, and pyrroline-5-carboxylate synthase B) to scavenge reactive oxygen species and enhance plant salt tolerance.
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http://dx.doi.org/10.3390/ijms23147879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318261PMC
July 2022

Endoscopic endonasal resection of sinonasal teratocarcinosarcoma with intracranial breakthrough: illustrative case.

J Neurosurg Case Lessons 2021 Oct 18;2(16):CASE21471. Epub 2021 Oct 18.

Departments of Neurosurgery.

Background: Teratocarcinosarcoma traversing the anterior skull base is rarely reported in literature. The heterogenous and invasive features of the tumor pose challenges for surgical planning. With technological advancements, the endoscopic endonasal approach (EEA) has been emerging as a workhorse of anterior skull base lesions. To date, no case has been reported of EEA totally removing teratocarcinosarcomas with intracranial extensions.

Observations: The authors provided an illustrative case of a 50-year-old otherwise healthy man who presented with left-sided epistaxis for a year. Imaging studies revealed a 31 × 60-mm communicating lesion of the anterior skull base. Gross total resection via EEA was achieved, and multilayered skull base reconstruction was performed.

Lessons: The endoscopic approach may be safe and effective for resection of extensive teratocarcinosarcoma of the anterior skull base. To minimize the risk of postoperative cerebrospinal fluid leaks, multilayered skull base reconstruction and placement of lumbar drainage are vitally important.
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http://dx.doi.org/10.3171/CASE21471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281494PMC
October 2021

Synchrotron X-ray Fluorescence Technique Identifies Contribution of Node Iron and Zinc Accumulations to the Grain of Wheat.

J Agric Food Chem 2022 Aug 19;70(30):9346-9355. Epub 2022 Jul 19.

State Key Laboratory of Crop Stress Biology for Arid Areas, Northwest A&F University, Yangling 712100, Shaanxi, China.

Increasing iron (Fe) and zinc (Zn) concentrations in crop grains with high yield is an effective measure to ensure food supply and alleviate mineral malnutrition in humans. Micronutrient concentrations in grains depend on not only their availability in soils but also their uptake in roots and translocation to shoots and grains. In this three-year field study, we investigated genotypic variation in Fe and Zn uptake and translocation within six wheat cultivars and examined in detail Fe and Zn distributions in various tissues of two cultivars with similar high yield but different grain Fe and Zn concentrations using synchrotron micro-X-ray fluorescence. Results revealed that root Fe and Zn concentrations were 11 and 44% greater in high-nutrient (HN) than in low-nutrient (LN) concentration cultivar. Although both cultivars accumulated similar amounts of Fe in shoots, HN cultivar had greater accumulation of Fe in grain and greater accumulation of Zn in both shoots and grain. Grain Zn concentration was positively correlated with shoot Zn accumulation, and grain Fe concentration was positively correlated with the ability to translocate Fe from leaves/stem to grains. In the first nodes of shoots, HN cultivar had 482% greater Fe and 36% greater Zn concentrations in the enlarged vascular bundle (EVB) than LN cultivar. In top nodes, HN cultivar had 225 and 116% greater Fe and Zn concentrations in the transit vascular bundle and 77 and 71% greater in the EVB when compared to LN cultivar. HN cultivar also had a greater ability to allocate Fe and Zn to the grain than LN cultivar. In conclusion, HN cultivar had greater capacity of Fe and Zn acquirement by roots and translocation and partitioning from shoots into grains. Screening wheat cultivars for larger Fe and Zn concentrations in shoot nodes could be a novel strategy for breeding crops with greater grain Fe and Zn concentrations.
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http://dx.doi.org/10.1021/acs.jafc.2c02561DOI Listing
August 2022

ABA-inducible DEEPER ROOTING 1 improves adaptation of maize to water deficiency.

Plant Biotechnol J 2022 Jul 7. Epub 2022 Jul 7.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Wenjing, China.

Root architecture remodelling is critical for forage moisture in water-limited soil. DEEPER ROOTING 1 (DRO1) in Oryza, Arabidopsis, and Prunus has been reported to improve drought avoidance by promoting roots to grow downward and acquire water from deeper soil. In the present study, we found that ZmDRO1 responded more strongly to abscisic acid (ABA)/drought induction in Zea mays ssp. mexicana, an ancestral species of cultivated maize, than in B73. It was proposed that this is one of the reasons why Zea mays ssp. mexicana has a more noticeable change in the downward direction angle of the root and fewer biomass penalties under water-deficient conditions. Thus, a robust, synthetic ABA/drought-inducible promoter was used to control the expression of ZmDRO1 in Arabidopsis and cultivated maize for drought-resistant breeding. Interestingly, ABA-inducible ZmDRO1 promoted a larger downward root angle and improved grain yield by more than 40% under water-limited conditions. Collectively, these results revealed that different responses to ABA/drought induction of ZmDRO1 confer different drought avoidance abilities, and we demonstrated the application of ZmDRO1 via an ABA-inducible strategy to alter the root architecture of modern maize to improve drought adaptation in the field.
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http://dx.doi.org/10.1111/pbi.13889DOI Listing
July 2022

Sandwich-Polarized Heterojunction: Efficient Charge Separation and Redox Capability Protection for Photocatalytic Overall Water Splitting.

ACS Appl Mater Interfaces 2022 Jul 7;14(28):32018-32025. Epub 2022 Jul 7.

State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China.

Photocatalytic overall water splitting is a potential strategy to address energy crisis and environmental issues. However, it remains a great challenge to design an efficient photocatalyst, which not only possesses large spatial separation of photogenerated electrons and holes (PEH) to suppress recombination, but also can preserve the redox capability to drive the reaction. Herein, we design a new type of sandwich-polarized heterojunction by inserting a polarized semiconductor into the interlayer of the conventional photocatalyst. The inserted sublayer with out-of-plane polarization can induce a large electrostatic potential difference between the top and bottom photocatalytic sublayers. Then, the band edges of the top and bottom sublayers can be shifted to form the type II band alignment. Also, the valence band maximum and conduction band minimum will be located on different photocatalytic sublayers to facilitate the spatial separation of PEH. Simultaneously, different from the conventional type II heterojunction that reduces the redox capability, the electrostatic potential difference also acts as an auxiliary booster to offset the reduced redox potential of PEH. Taking the CN/InSe/CN heterojunction as an example, the polarized InSe effectively promotes the interface transfer of PEH in 1-5 ps and extends the lifetime of PEH to ∼186 ns, which is about six times that of bilayer CN. Simultaneously, the redox power of CN is well preserved. Our work offers a promising scheme to advance the photocatalytic overall water splitting.
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http://dx.doi.org/10.1021/acsami.2c07278DOI Listing
July 2022

CD5L attenuates allergic airway inflammation by expanding CD11c alveolar macrophages and inhibiting NLRP3 inflammasome activation via HDAC2.

Immunology 2022 Jul 6. Epub 2022 Jul 6.

Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

Allergic asthma is an airway inflammatory disease dominated by type 2 immune responses and there is currently no curative therapy for asthma. CD5-like antigen (CD5L) has been known to be involved in a variety of inflammatory diseases. However, the role of CD5L in allergic asthma remains unclear. In the present study, mice were treated with recombinant CD5L (rCD5L) during house dust mite (HDM) and ovalbumin (OVA) challenge to determine the role of CD5L in allergic asthma, and the underlying mechanism was further explored. Compared with PBS group, serum CD5L levels of asthmatic mice were significantly decreased, and the levels of CD5L in lung tissues and bronchoalveolar lavage fluid (BALF) were significantly increased. CD5L reduced airway inflammation and Th2 immune responses in asthmatic mice. CD5L exerted its anti-inflammatory function by increasing CD11c alveolar macrophages (CD11c AMs), and the anti-inflammatory role of CD11c AMs in allergic asthma was confirmed by CD11c AMs depletion and transfer assays. In addition, CD5L increased the CD5L macrophages and inhibited NLRP3 inflammasome activation by increasing HDAC2 expression in lung tissues of asthmatic mice. Hence, our study implicates that CD5L has potential usefulness for asthma treatment.
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http://dx.doi.org/10.1111/imm.13543DOI Listing
July 2022

Metal- and base-free tandem sulfonylation/cyclization of 1,5-dienes with aryldiazonium salts the insertion of sulfur dioxide.

RSC Adv 2022 Jun 6;12(26):16745-16750. Epub 2022 Jun 6.

Department of Dermatology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, West China School of Pharmacy, Sichuan University Chengdu 610041 China

A metal- and base-free 5--trig sulfonylative cyclization between 1,5-dienes, aryldiazonium salts and SO (from SOgen) is presented. This method could successfully produce sulfonylated pyrrolin-2-ones in one pot with excellent regioselectivity and good-to-excellent yields. This strategy features mild reaction conditions and broad substrate scope. Moreover, a scale-up reaction and three synthetic applications demonstrate the practicality of this method. Lastly, control experiments indicate that the 5--trig sulfonylative cyclization may proceed in a radical pathway.
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http://dx.doi.org/10.1039/d2ra03034aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170380PMC
June 2022

Correlation between cognitive deficits and dorsolateral prefrontal cortex functional connectivity in first-episode depression.

J Affect Disord 2022 09 22;312:152-158. Epub 2022 Jun 22.

Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Introduction: Although depression is commonly accompanied by cognitive deficits, the underlying mechanism remains unclear. One possibility is that such deficits are related to abnormal brain network connections. The purpose of this study was thus to investigate changes in brain functional connectivity (FC) in depression and its relationship with cognitive deficits.

Methods: We enrolled 37 first-episode MDD patients and 53 matched healthy controls (HC). All participants completed clinical and neurocognitive assessments and underwent resting-state functional MRI. Seed-based analysis was used to define the dorsolateral prefrontal cortex (DLPFC) and FC analysis was then performed. We used bias correlation to analyze the correlation between FC and clinical and neurocognitive scores.

Results: MDD patients showed increased FC of the right DLPFC with the left inferior temporal gyrus, left cuneus, right inferior frontal gyrus, right anterior cingulate cortex, left BA39, right angular gyrus, right precuneus, left middle frontal gyrus, and right precentral gyrus. MDD patients also showed stronger FC in the left thalamus and reduced FC between the left superior occipital gyrus and left DLPFC seed region. Interestingly, increased FC was related to disease severity (with the right precentral gyrus) and social cognitive dysfunction (with the right angular gyrus) in MDD patients.

Limitations: The sample size was relatively small and it is unclear how age may influence FC changes in patients with depression.

Conclusions: These findings support changes in FC of the DLPFC in early MDD patients related to cognitive function. FC is a potential biomarker for the diagnosis of MDD.
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http://dx.doi.org/10.1016/j.jad.2022.06.024DOI Listing
September 2022

Reliability of Calculation of Dynamic Modulus for Asphalt Mixtures Using Different Master Curve Models and Shift Factor Equations.

Materials (Basel) 2022 Jun 18;15(12). Epub 2022 Jun 18.

Department of Civil and Environmental Engineering, Norwegian University of Science and Technology, Høgskoleringen 7A, 7491 Trondheim, Norway.

To develop a mechanistic-empirical pavement design system for Norwegian conditions, this paper evaluates the influence of the adoption of different models and shifting techniques on the determination of dynamic modulus master curves of asphalt mixtures. Two asphalt mixture types commonly used in Norway, namely Asphalt Concrete (AC) and Stone Mastic Asphalt (SMA) containing neat bitumen and polymer-modified bitumen, were prepared by the roller compactor, and their dynamic moduli were determined by the cyclic indirect tensile test. The dynamic modulus master curves were constructed using the standard logistic sigmoidal model, a generalized logistic sigmoidal model and the Christensen-Anderson-Marasteanu model. The shifting techniques consisted of log-linear, quadratic polynomial function, Arrhenius, William-Landel-Ferry and Kaelble methods. The absolute error, normalised square error and goodness-of-fit statistics encompassing standard error ratio and coefficient of determination were used to appraise the models and shifting methods. The results showed that the standard logistic sigmoidal model and the Williams-Landel-Ferry equation had the most suitable fits for the specimens tested. The asphalt mixtures containing neat bitumen had a better fit than the ones containing polymer-modified bitumen. The Kaelble equation and log-linear equation led to similar results. These findings provide a relevant recommendation for the mechanistic-empirical pavement design system.
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http://dx.doi.org/10.3390/ma15124325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227812PMC
June 2022

HSA-MnO-I Combined Imaging and Treatment of Anaplastic Thyroid Carcinoma.

Technol Cancer Res Treat 2022 Jan-Dec;21:15330338221106557

Department of Nuclear Medicine, 117865Tianjin Medical University General Hospital, Tianjin, P. R. China.

Compelling evidence suggests that nanoparticles (NPs) play a crucial role in cancer therapy. NPs templated with human serum albumin (HSA) has good retention in tumors. Manganese dioxide (MnO) has been used to enhance the effect of radiotherapy. In this study, synthesized NPs using HSA-MnO labeled I to perform both imaging and therapy for anaplastic thyroid carcinoma (ATC). HSA-MnO was synthesized via HSA using a simple biomineralization method, and then labeled with NaI by the chloramine T method. The cytotoxicity and biosafety of HSA-MnO were evaluated by the MTT test. The proliferation-inhibiting effect of HSA-MnO-I was evaluated in papillary thyroid cancer cell lines (K1, BCPAP, and KTC) and anaplastic thyroid carcinoma cell lines (Cal62, THJ16T, and ARO). For further translational application in medicine, we established a model of transplantable subcutaneously tumors in BALB\c-nu mice to assess the anti-tumor effect of HSA-MnO-I. The imaging effects of NPs were evaluated by MRI and SPECT/CT. The MTT test proved that the HSA-MnO had low toxicity. HSA-MnO-I significantly inhibited the proliferation of PTC and ATC cell lines. In addition, the results unveiled that HSA-MnO-I exhibited dual-modality MR/SPECT imaging for thyroid cancer visualization. In particular, HSA-MnO-I had an enhanced T1 signal in MR. Using SPECT/CT, we observed that HSA-MnO-I had good retention in tumor tissue, which was helpful for the diagnosis and treatment of tumor. assays indicated that the NPs led to a reduction in radioresistance in the tumor hypoxic microenvironment. The nanomaterial had a simple synthesis method, good water solubility and biosafety, and good retention in tumor tissue. Hence, it could be used for SPECT/CT and MR dual mode imaging and therapy with radioiodine of tumor cells. The experimental results provided a feasible solution for combining radiotherapy and dual-model imaging by NPs for cancer diagnosis and treatment.
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http://dx.doi.org/10.1177/15330338221106557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208040PMC
June 2022

Comparison of buckwheat genomes reveals the genetic basis of metabolomic divergence and ecotype differentiation.

New Phytol 2022 Sep 5;235(5):1927-1943. Epub 2022 Jul 5.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, National Crop Genebank Building, Zhongguancun South Street no. 12, Haidian District, Beijing, 100081, China.

Golden buckwheat (Fagopyrum dibotrys or Fagopyrum cymosum) and Tartary buckwheat (Fagopyrum tataricum) belong to the Polygonaceae and the Fagopyrum genus is rich in flavonoids. Golden buckwheat is a wild relative of Tartary buckwheat, yet golden buckwheat is a traditional Chinese herbal medicine and Tartary buckwheat is a food crop. The genetic basis of adaptive divergence between these two buckwheats is poorly understood. Here, we assembled a high-quality chromosome-level genome of golden buckwheat and found a one-to-one syntenic relationship with the chromosomes of Tartary buckwheat. Two large inversions were identified that differentiate golden buckwheat and Tartary buckwheat. Metabolomic and genetic comparisons of golden buckwheat and Tartary buckwheat indicate an amplified copy number of FdCHI, FdF3H, FdDFR, and FdLAR gene families in golden buckwheat, and a parallel increase in medicinal flavonoid content. Resequencing of 34 wild golden buckwheat accessions across the two morphologically distinct ecotypes identified candidate genes, including FdMYB44 and FdCRF4, putatively involved in flavonoid accumulation and differentiation of plant architecture, respectively. Our comparative genomic study provides abundant genomic resources of genomic divergent variation to improve buckwheat with excellent nutritional and medicinal value.
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http://dx.doi.org/10.1111/nph.18306DOI Listing
September 2022

Entacapone alleviates acute kidney injury by inhibiting ferroptosis.

FASEB J 2022 07;36(7):e22399

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.

Acute kidney injury (AKI) is a common clinical problem and an efficacious treatment is lacking. Ferroptosis, a newly discovered type of programmed cell death, has been reported to alleviate renal tubular injury in ischemia/reperfusion-induced acute kidney injury (I/R-AKI). Entacapone is a specific inhibitor of catechol-O-methyltransferase, which is used as an adjuvant drug against Parkinson's disease. We demonstrated that entacapone prevents renal I/R injury by inhibiting ferroptosis. Compared with a sham group, entacapone treatment mitigated I/R-induced pathological alterations, improved renal function, and inhibited ferroptosis. In HK-2 cells, entacapone treatment significantly reduced the lipid peroxidation and iron accumulation induced by the ferroptosis inducers erastin and RSL3, and significantly regulated expression of ferroptosis-related proteins. Entacapone upregulates p62 expression and affects the p62-KEAP1-NRF2 pathway, thereby upregulating nuclear translocation of NRF2. This action results in increased expression of the downstream SLC7A11, and significant suppression of oxidative stress and ferroptosis. Our results identify entacapone as a ferroptosis inhibitor that enhances antioxidant capacity. Entacapone may serve as a novel strategy to improve treatment of, and recovery from, I/R-AKI.
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http://dx.doi.org/10.1096/fj.202200241RRDOI Listing
July 2022

Factors associated with discontinuation of pulmonary vasodilator therapy in children with bronchopulmonary dysplasia-associated pulmonary hypertension.

J Perinatol 2022 Jun 8. Epub 2022 Jun 8.

Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Objective: To evaluate factors associated with discontinuation of pulmonary vasodilator therapy in bronchopulmonary dysplasia-related pulmonary hypertension (BPD-PH).

Study Design: Retrospective study of neonatal, echocardiographic, and cardiac catheterization data in 121 infants with BPD-PH discharged on pulmonary vasodilator therapy from 2009-2020 and followed into childhood.

Result: After median 4.4 years, medications were discontinued in 58%. Those in whom medications were discontinued had fewer days of invasive support, less severe BPD, lower incidence of PDA closure or cardiac catheterization, and higher incidence of fundoplication or tracheostomy decannulation (p < 0.05). On multivariable analysis, likelihood of medication discontinuation was lower with longer period of invasive respiratory support [HR 0.95 (CI:0.91-0.99), p = 0.01] and worse RV dilation on pre-discharge echocardiogram [HR 0.13 (CI:0.03-0.70), p = 0.017]. In those with tracheostomy, likelihood of medication discontinuation was higher with decannulation [HR 10.78 (CI:1.98-58.59), p < 0.001].

Conclusion: In BPD-PH, childhood discontinuation of pulmonary vasodilator therapy is associated with markers of disease severity.
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http://dx.doi.org/10.1038/s41372-022-01421-6DOI Listing
June 2022

Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate.

Nat Commun 2022 06 2;13(1):3074. Epub 2022 Jun 2.

Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA.

The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein degradation decisions. The breadth of mechanisms by which cells respond to stressors and form specific functional types of membraneless organelles, is incompletely understood. We found that Bcl2-associated athanogene 2 (BAG2) marks a distinct phase-separated membraneless organelle, triggered by several forms of stress, particularly hyper-osmotic stress. Distinct from well-known condensates such as stress granules and processing bodies, BAG2-containing granules lack RNA, lack ubiquitin and promote client degradation in a ubiquitin-independent manner via the 20S proteasome. These organelles protect the viability of cells from stress and can traffic to the client protein, in the case of Tau protein, on the microtubule. Components of these ubiquitin-independent degradation organelles include the chaperone HSP-70 and the 20S proteasome activated by members of the PA28 (PMSE) family. BAG2 condensates did not co-localize with LAMP-1 or p62/SQSTM1. When the proteasome is inhibited, BAG2 condensates and the autophagy markers traffic to an aggresome-like structure.
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http://dx.doi.org/10.1038/s41467-022-30751-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163039PMC
June 2022

Increases Drought Sensitivity by Suppressing ROS Accumulation in Arabidopsis.

Plants (Basel) 2022 May 23;11(10). Epub 2022 May 23.

Maize Research Institute, Sichuan Agricultural University, Wenjiang 611130, China.

Drought stress is known to significantly limit crop growth and productivity. Lateral organ boundary domain (LBD) transcription factors-particularly class-I members-play essential roles in plant development and biotic stress. However, little information is available on class-II genes related to abiotic stress in maize. Here, we cloned a maize class-II LBD transcription factor, and identified its function in drought stress. Transient expression, transactivation, and dimerization assays demonstrated that was localized in the nucleus, without transactivation, and could form a homodimer or heterodimer. Promoter analysis demonstrated that multiple drought-stress-related and ABA response cis-acting elements are present in the promoter region of . Overexpression of in Arabidopsis promotes plant growth under normal conditions, and suppresses drought tolerance under drought conditions. Furthermore, the overexpression of increased the water loss rate, stomatal number, and stomatal apertures. DAB and NBT staining demonstrated that the reactive oxygen species (ROS) decreased in -overexpressed Arabidopsis. A physiological index assay also revealed that SOD and POD activities in -overexpressed Arabidopsis were higher than those in wild-type Arabidopsis. These results revealed the role of in drought stress by regulating ROS levels.
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http://dx.doi.org/10.3390/plants11101382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144968PMC
May 2022

Functional analysis of PagNAC045 transcription factor that improves salt and ABA tolerance in transgenic tobacco.

BMC Plant Biol 2022 May 25;22(1):261. Epub 2022 May 25.

State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, 51 Hexing Road, Harbin, 150040, China.

Background: Salt stress causes inhibition of plant growth and development, and always leads to an increasing threat to plant agriculture. Transcription factors regulate the expression of various genes for stress response and adaptation. It's crucial to reveal the regulatory mechanisms of transcription factors in the response to salt stress.

Results: A salt-inducible NAC transcription factor gene PagNAC045 was isolated from Populus alba×P. glandulosa. The PagNAC045 had a high sequence similarity with NAC045 (Potri.007G099400.1) in P. trichocarpa, and they both contained the same conserved motifs 1 and 2, which constitute the highly conserved NAM domain at the N-terminus. Protein-protein interaction (PPI) prediction showed that PagNAC045 potentially interacts with many proteins involved in plant hormone signaling, DNA-binding and transcriptional regulation. The results of subcellular localization and transient expression in tobacco leaves confirmed the nuclear localization of PagNAC045. Yeast two-hybrid revealed that PagNAC045 protein exhibits transcriptional activation property and the activation domain located in its C-terminus. In addition, the 1063 bp promoter of PagNAC045 was able to drive GUS gene expression in the leaves and roots. In poplar leaves and roots, PagNAC045 expression increased significantly by salt and ABA treatments. Tobacco seedlings overexpressing PagNAC045 exhibited enhanced tolerance to NaCl and ABA compared to the wild-type (WT). Yeast one-hybrid assay demonstrated that a bHLH104-like transcription factor can bind to the promoter sequence of PagNAC045.

Conclusion: The PagNAC045 functions as positive regulator in plant responses to NaCl and ABA-mediated stresses.
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http://dx.doi.org/10.1186/s12870-022-03623-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131654PMC
May 2022

The clinical value of conventional ultrasound combined with contrast-enhanced ultrasound in the evaluation of BI-RADS 4 lesions detected by magnetic resonance imaging.

Br J Radiol 2022 Aug 30;95(1136):20220025. Epub 2022 May 30.

Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To determine the value of conventional ultrasound combined with contrast-enhanced ultrasound (CEUS) in Breast Imaging Reporting and Data System (BI-RADS) Category 4 lesions as detected by MRI.

Methods: A total of 176 breast lesions from 171 patients were detected by MRI and categorised as BI-RADS 4. All patients also underwent ultrasound and CEUS scans. The combination of ultrasound-BI-RADS and CEUS 5-point scoring system created the Rerated BI-RADS (referred to as CEUS-BI-RADS). The diagnostic performances of ultrasound and CEUS-BI-RADS were then compared. A test was used to compare the CEUS features of mass-like and non-mass-like enhancement types of MRI-BI-RADS 4 lesions.

Results: There were 167 (167/176) breast lesions detected by ultrasound, with a detection rate of 94.89%, while all were subsequently detected by "second-look" ultrasound combined with CEUS, with a detection rate of 100%. The areas under the receiver operating characteristic curves for ultrasound and CEUS-BI-RADS were 0.810 and 0.940, respectively. The diagnostic efficiency of CEUS-BI-RADS was significantly higher than that of ultrasound alone ( = 3.264, = 0.001). For both mass-like and non-mass-like enhancement types of MRI-BI-RADS 4 lesions, CEUS-BI-RADS demonstrated satisfactory sensitivity and accuracy. Moreover, 29 (29/176) category 4 lesions were downgraded to 3 by CEUS-BI-RADS.

Conclusion: Ultrasound combined with CEUS can allow reclassification, reduce biopsy rates, and facilitate pre-surgical localisation for biopsy or surgery for MRI-BI-RADS 4 lesions.

Advances In Knowledge: For MRI-BI-RADS Category 4 lesions with a wide range of malignancies, ultrasound combined with CEUS is a promising diagnostic approach with high clinical utility.
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http://dx.doi.org/10.1259/bjr.20220025DOI Listing
August 2022

Association of chest compression pause duration prior to E-CPR cannulation with cardiac arrest survival outcomes.

Resuscitation 2022 Aug 16;177:85-92. Epub 2022 May 16.

Center for Pediatric Resuscitation, Children's Hospital of Philadelphia, Philadelphia, USA; Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, USA.

Objective: To characterize chest compression (CC) pause duration during the last 5 minutes of pediatric cardiopulmonary resuscitation (CPR) prior to extracorporeal-CPR (E-CPR) cannulation and the association with survival outcomes.

Methods: Cohort study from a resuscitation quality collaborative including pediatric E-CPR cardiac arrest events ≥ 10 min with CPR quality data. We characterized CC interruptions during the last 5 min of defibrillator-electrode recorded CPR (prior to cannulation) and assessed the association between the longest CC pause duration and survival outcomes using multivariable logistic regression.

Results: Of 49 E-CPR events, median age was 2.0 [Q1, Q3: 0.6, 6.6] years, 55% (27/49) survived to hospital discharge and 18/49 (37%) with favorable neurological outcome. Median duration of CPR was 51 [43, 69] min. During the last 5 min of recorded CPR prior to cannulation, median duration of the longest CC pause was 14.0 [6.3, 29.4] sec: 66% >10 sec, 25% >29 sec, 14% >60 sec, and longest pause 168 sec. Following planned adjustment for known confounders of age and CPR duration, each 5-sec increase in longest CC pause duration was associated with lower odds of survival to hospital discharge [adjusted OR 0.89, 95 %CI: 0.79-0.99] and lower odds of survival with favorable neurological outcome [adjusted OR 0.77, 95 %CI: 0.60-0.98].

Conclusions: Long CC pauses were common during the last 5 min of recorded CPR prior to E-CPR cannulation. Following adjustment for age and CPR duration, each 5-second incremental increase in longest CC pause duration was associated with significantly decreased rates of survival and favorable neurological outcome.
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http://dx.doi.org/10.1016/j.resuscitation.2022.05.004DOI Listing
August 2022

TLR4 regulatory region variants reduce the susceptibility of small-cell lung cancer in Chinese population.

Eur J Cancer Prev 2022 07 13;31(4):363-368. Epub 2022 May 13.

Department of Epidemiology and Health Statistics, School of Public Health.

Objectives: Toll-like receptors (TLRs) participate in the induction and regulation of immune responses and are closely related to the occurrence and development of small-cell lung cancer (SCLC). This study aimed to investigate the impact of polymorphisms in the regulatory regions of TLRs on the susceptibility of SCLC.

Methods: The case-control study included 304 SCLC patients and 304 healthy controls. TLRs gene polymorphisms were genotyped by PCR-restrictive fragment length polymorphism analysis and TaqMan assay. Unconditional logistic regression was used to estimate odds ratio (OR) and its 95% confidence interval (95% CI).

Results: Our results showed that TLR4 rs1927914 GG genotype and TLR4 rs7869402 TT genotype reduced the risk of SCLC with OR (95% CI) of 0.54 (0.32-0.90) and 0.47 (0.28-0.80), respectively. Stratified analysis suggested that TLR4 rs1927914 GG genotypes significantly reduced the risk of SCLC among male (OR = 0.35; 95% CI, 0.18-0.69; P < 0.01), the younger patients (OR = 0.49; 95% CI, 0.26-0.94; P = 0.03) and non-drinkers (OR = 0.47; 95% CI, 0.24-0.89; P = 0.02). TLR4 rs7869402 CT or TT genotype significantly reduced the susceptibility to SCLC among male patients (OR = 0.37; 95% CI, 0.19-0.71, P < 0.01), the younger patients (OR = 0.41; 95% CI, 0.22-0.79; P < 0.01), smokers (OR = 0.25; 95% CI, 0.10-0.60; P < 0.01) and drinkers (OR = 0.31; 95% CI, 0.11-0.88; P = 0.03). TLR3 rs5743303, TLR4 rs11536891, TLR5 rs1640816 and TLR7 rs3853839 had no significant correlation with the risk of SCLC.

Conclusions: These findings emphasized the important role of TLR4 in the development of SCLC.
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http://dx.doi.org/10.1097/CEJ.0000000000000737DOI Listing
July 2022

Astragaloside IV Alleviates Intestinal Barrier Dysfunction via the AKT-GSK3β-β-Catenin Pathway in Peritoneal Dialysis.

Front Pharmacol 2022 27;13:873150. Epub 2022 Apr 27.

Department of Pharmacology, School of Pharmacy and Minhang Hospital, Fudan University, Shanghai, China.

Long-term peritoneal dialysis (PD) causes intestinal dysfunction, including constipation, diarrhea, or enteric peritonitis. However, the etiology and pathogenesis of these complications are still unclear and there are no specific drugs available in the clinic. This study aims to determine whether Astragaloside IV (AS IV) has therapeutic value on PD-induced intestinal epithelial barrier dysfunction and . We established two different long-term PD treatment mice models by intraperitoneally injecting 4.25% dextrose-containing peritoneal dialysis fluid (PDF) in uremia mice and normal mice, which were served as controls. In addition, PDF was applied to T84 cells . The therapeutic effects of AS IV on PD-induced intestinal dysfunction were then examined by histopathological staining, transmission electron microscopy, western blotting, and reverse transcription polymerase chain reaction. The protein levels of protein kinase B (AKT), glycogen synthase kinase 3β (GSK-3β) and β-catenin were examined after administration of AS IV. In the present study, AS IV maintained the intestinal crypt, microvilli and desmosome structures in an orderly arrangement and improved intestinal epithelial permeability with the up-regulation of tight junction proteins . Furthermore, AS IV protected T84 cells from PD-induced damage by improving cell viability, promoting wound healing, and increasing the expression of tight junction proteins. Additionally, AS IV treatment significantly increased the levels of phosphorylation of AKT, inhibited the activity GSK-3β, and ultimately resulted in the nuclear translocation and accumulation of β-catenin. These findings provide novel insight into the AS IV-mediated protection of the intestinal epithelial barrier from damage via the AKT-GSK3β-β-catenin signal axis during peritoneal dialysis.
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http://dx.doi.org/10.3389/fphar.2022.873150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091173PMC
April 2022

Determination of 52 hidden chemical pesticides in biopesticide products by GC-MS/MS and LC-MS/MS.

J Environ Sci Health B 2022 13;57(6):504-515. Epub 2022 May 13.

Chongqing Academy of Agricultural Science, Chongqing, P.R. China.

Addition of chemical pesticides in biopesticides are expected to be common, due to effect of pest control during plant protection. These hidden chemical pesticides may cause various food safety problems if consumed. The purpose of our study was to develop a method to determine 52 hidden chemical pesticides in three formulation biopesticide products. Optimizations of different parameters, such as the instrument analysis condition for target, the extraction, and the composition of clean-up materials were carried out. The developed method used acetonitrile as an extraction solvent for all biopesticide formulations. The composition of adsorbents was based on QuEChERS, called QuSEL which was a needle filter head, containing PSA, GCB, and MgSO. Fifty-two chemical pesticides residues were then analyzed by GC-MS/MS and LC-MS/MS. The present results showed good linearity by correlation coefficients of more than 0.99 for all analyses. The LOQ ranged from 5.0 to 20.0 μg kg. Recoveries of 32 chemical pesticides ranged from 71.9% to 118.4% at the spiked level of 10, 50, and 100 μg kg, and 20 chemical pesticides ranged from 75.3% to 119.8% at the spiked level of 5, 25, and 50 μg kg. The developed method was applied for biopesticide products, and 9 samples were positive in 20 samples.
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http://dx.doi.org/10.1080/03601234.2022.2072645DOI Listing
June 2022

Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling.

Exp Mol Med 2022 May 10;54(5):601-612. Epub 2022 May 10.

Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China.

Leukemia is caused by the malignant clonal expansion of hematopoietic stem cells, and in adults, the most common type of leukemia is acute myeloid leukemia (AML). Autophagy inhibitors are often used in preclinical and clinical models in leukemia therapy. However, clinically available autophagy inhibitors and their efficacy are very limited. More effective and safer autophagy inhibitors are urgently needed for leukemia therapy. In a previous study, we showed that ΔA146Ply, a mutant of pneumolysin that lacks hemolytic activity, inhibited autophagy of triple-negative breast cancer cells by activating mannose receptor (MR) and toll-like receptor 4 (TLR4) and that tumor-bearing mice tolerated ΔA146Ply well. Whether this agent affects AML cells expressing TLR4 and MR and the related mechanisms remain to be determined. In this study, we found that ΔA146Ply inhibited autophagy and induced apoptosis in AML cells. A mechanistic study showed that ΔA146Ply inhibited autophagy by activating mammalian target of rapamycin signaling and induced apoptosis by inhibiting autophagy. ΔA146Ply also inhibited autophagy and induced apoptosis in a mouse model of AML. Furthermore, the combination of ΔA146Ply and chloroquine synergistically inhibited autophagy and induced apoptosis in vitro and in vivo. Overall, this study provides an alternative effective autophagy inhibitor that may be used for leukemia therapy.
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http://dx.doi.org/10.1038/s12276-022-00771-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166762PMC
May 2022

Novel Therapeutic Targeting of CCL3-CCR4 Axis Mediated Apoptotic Intesitnal Injury in Necrotizing Enterocolitis.

Front Immunol 2022 22;13:859398. Epub 2022 Apr 22.

Department of Clinical Laboratory, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.

Background: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal-related death, while the etiology and pathogenesis are poorly understood.

Methods: The levels of CCL3 in intestinal tissue from modeling mice and patients were measured and analyzed. HE staining, TUNEL, Annexin and FCM were used to assess pathological changes and apoptosis in intestinal tissue and epithelial cells. CCL3, CCR4, cytokines, tight junction protein ZO-1, apoptosis-related genes and ERK1/2-NF-κB signaling pathway were detected by ELISA, Q-PCR, Western blotting and immunofluorescence.

Results: CCL3 levels in the intestinal tissue significantly elevated in patients with NEC and mouse models. Blockade of CCL3 significantly alleviated NEC-related intestinal tissue damage, while administration of recombinant CCL3 aggravated intestinal injury by exacerbating intestinal epithelial cell apoptosis in NEC mice. Importantly, CCR4 blockade reversed CCL3-mediated damage to intestinal tissue and intestinal epithelial cell apoptosis both and . Further mechanistic studies showed that CCL3 regulated apoptosis-related BAX/BCL-2 expression through the activation of the ERK1/2 and NF-κB pathways, which could be reversed by anti-CCR4 treatment. Furthermore, ERK1/2 inhibition reduced CCL3-mediated phosphorylation of NF-κB in IEC-6 cells, while inhibition of NF-κB had no obvious effect on ERK1/2 phosphorylation. As expected, inhibition of NF-κB regulated BAX/BCL-2 expression and alleviated CCL3-induced epithelial cell apoptosis. These results indicate that high expression of CCL3 in NEC lesions promotes intestinal epithelial apoptosis through the CCL3-CCR4-ERK1/2-NFκB-BAX/BCL2 signalling axis, thereby exacerbating NEC-related intestinal injury.

Conclusions: Our study represents an important conceptual advance that CCL3 may be one of the key culprits of intestinal tissue damage in NEC patients, and blocking either CCL3, CCR4, or NF-κB may represent a novel effective immunotherapy for NEC.
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http://dx.doi.org/10.3389/fimmu.2022.859398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073010PMC
April 2022
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