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Rational design of synthetically tractable HDAC6/HSP90 dual inhibitors to destroy immune-suppressive tumor microenvironment.

J Adv Res 2022 Jun 22. Epub 2022 Jun 22.

School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110031, Taiwan; TMU Research Center of Drug Discovery, Taipei Medical University, Taipei 110031, Taiwan. Electronic address:

Introduction: The tumor microenvironment is mainly flooded with immunosuppressive cells and inhibitory cytokines, resulting in the inability of effective immune cells to infiltrate and recognize tumors and even the loss of anti-cancer ability.

Objectives: We propose a novel HDAC6/HSP90 dual inhibitory strategy as well as a chemoimmunotherapeutic agent that does not only kill tumor cells but also destroys the tumor microenvironment and enhances anti-cancer immunity.

Methods: A hybrid scaffold construction approach was leveraged to furnish a series of rationally designed resorcinol-based hydroxamates as dual selective HDAC6/HSP90 inhibitors. Read More

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Reducing taperin expression restores hearing in Grxcr2 mutant mice.

Neuroscience 2022 Jun 22. Epub 2022 Jun 22.

Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States. Electronic address:

Recessive mutations in GRXCR2 cause deafness in both humans and mice. In Grxcr2 null hair cells, the sensory receptors for sound in the inner ear, stereocilia are disorganized. Reducing the expression of taperin, a protein that interacts with GRXCR2 at the base of stereocilia, corrects the morphological defects of stereocilia and restores hearing in Grxcr2 null mice. Read More

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Transfusion Guidelines in Brain Tumor Surgery: A Systematic Review and Critical Summary of Currently Available Evidence.

World Neurosurg 2022 Jun 22. Epub 2022 Jun 22.

University of Texas Southwestern Medical Center, Department of Neurological Surgery, Dallas, TX, USA.

Objective: Red blood cell (RBC) transfusion is commonly indicated in brain tumor surgery due to risk of blood loss. Current transfusion guidelines are based on evidence derived from critically ill patients and may not be optimal for brain tumor surgeries. Our study is the first to synthesize available evidence to suggest RBC transfusion thresholds in brain tumor patients undergoing surgery. Read More

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Canonical Wnt signaling works downstream of iron overload to prevent ferroptosis from damaging osteoblast differentiation.

Free Radic Biol Med 2022 Jun 22. Epub 2022 Jun 22.

Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China; Department of Orthopedics, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. Electronic address:

Excessive iron has emerged in a large population of patients suffering from degenerative or hematological diseases with a common outcome, osteoporosis. However, its underlying mechanism remains to be clarified in order to formulate effective prevention and intervention against the loss of bone-forming osteoblasts. We show herein that increased intracellular iron by ferric ammonium citrate (FAC) mimicking the so-called non-transferrin bound iron concentrations leads to ferroptosis and impaired osteoblast differentiation. Read More

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Ultrastructural tegumental changes of Trichinella spiralis adult and larval stages after in vitro exposure to Allium sativum.

Exp Parasitol 2022 Jun 22:108314. Epub 2022 Jun 22.

Clinical and Molecular Parasitology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt. Electronic address:

Albendazole (ALB) is the most used therapeutic drug for trichinellosis treatment, but it has many drawbacks. Hence, the search for alternative natural compounds is a goal for researchers. The present work aimed to test the in vitro anthelmintic effect of Tomex (Allium sativum) against adult and muscular larva of Trichinella spiralis (T. Read More

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Corneal toxicity associated with belantamab mafodotin is not restricted to the epithelium: neuropathy studied with confocal microscopy.

Am J Ophthalmol 2022 Jun 22. Epub 2022 Jun 22.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: The purpose of this study was to investigate epithelial and neuronal changes in patients with refractory/relapsed multiple myeloma (RRMM) before/during belantamab mafodotin (belamaf) treatment using confocal microscopy.

Design: Retrospective case series.

Methods: RRMM patients underwent best corrected visual acuity (BCVA) testing and slit-lamp examination/photography, followed by corneal confocal microscopy (CCM) to evaluate the epithelium and subbasal nerve plexus (SNP) to measure corneal nerve fiber density (CNFD), -branch density (CNBD), and -fiber length (CNFL) before and during belamaf treatment. Read More

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Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction.

Am J Obstet Gynecol 2022 Jun 22. Epub 2022 Jun 22.

Institute of Developmental and Reproductive Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Department of Fetal Medicine, Queen Charlotte's and Chelsea Hospital, Imperial College NHS Trust, London, UK. Electronic address:

Background: While fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear.

Objectives: To evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome.

Study Design: Secondary analysis of the TRUFFLE 2 multicentre observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32 and 36 weeks (n=856) evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Read More

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The role of Triggering Receptor Expressed on Myeloid Cells 2 in Parkinson's disease and other neurodegenerative disorders.

Behav Brain Res 2022 Jun 22:113977. Epub 2022 Jun 22.

Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universität (FAU) Erlangen -Nürnberg, Erlangen, Germany. Electronic address:

Parkinson's disease (PD) is a progressive neurological disorder marked by cardinal clinical symptoms such as rigor, tremor, and akinesia. Albeit a loss of dopaminergic neurons from the substantia nigra pars compacta is causative for the movement impairments found in patients, molecular reasoning for this loss is still incomplete. In recent years, triggering factor expressed on myeloid cells (TREM2) gained attention in the field of neurodegeneration as it could be associated with different neurodegenerative disorders. Read More

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Matrix-bound Cyr61/CCN1 is Required to Retain the Properties of the Bone Marrow Mesenchymal Stem Cell Niche but is Depleted with Aging.

Matrix Biol 2022 Jun 22. Epub 2022 Jun 22.

Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, U.S.A; Department of Biomedical Engineering(,) University of Texas at San Antonio, San Antonio, TX 78249, U.S.A; Research Service, South Texas Veterans Health Care System, Audie Murphy VA Medical Center, San Antonio, TX, 78229(,) U.S.A. Electronic address:

Previously, we showed that extracellular matrices (ECMs), produced ex vivo by various types of stromal cells, direct bone marrow mesenchymal stem cells (BM-MSCs) in a tissue-specific manner and recapitulate physiologic changes characteristic of the aging microenvironment. In particular, BM-MSCs obtained from elderly donors and cultured on ECM produced by young BM stromal cells showed improved quantity, quality and osteogenic differentiation. In the present study, we searched for matrix components that are required for a functional BM-MSC niche, by comparing ECMs produced by BM stromal cells from "young" (≤25 y/o) versus "elderly" (≥60 y/o) donors. Read More

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Downregulation of eNOS and preserved endothelial function in endothelial-specific arginase 1-deficient mice.

Nitric Oxide 2022 Jun 22. Epub 2022 Jun 22.

Myocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Arginase 1 (Arg1) is a ubiquitous enzyme belonging to the urea cycle that catalyzes the conversion of l-arginine into l-ornithine and urea. In endothelial cells (ECs), Arg1 was proposed to limit the availability of l-arginine for the endothelial nitric oxide synthase (eNOS) and thereby reduce nitric oxide (NO) production, thus promoting endothelial dysfunction and vascular disease. The role of EC Arg1 under homeostatic conditions is in vivo less understood. Read More

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LiuweiDihuang improved cognitive functions in SAMP8 mice by inhibiting COX-2 expression and subsequent neuroinflammation.

J Ethnopharmacol 2022 Jun 22:115491. Epub 2022 Jun 22.

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China; Henan Engineering Research Center for Prevention and Treatment of Neurodegenerative Diseases, Zhengzhou, 450046, PR China. Electronic address:

Ethnopharmacological Relevance: LiuweiDihuang (LW) pills was mainly used to treatment of children's fontanelle incomplete closure, enuresis and nervous system development delays and other diseases.Following the deepening of pharmacological research, LW has a good effect on neurological diseases include senile dementia. However, the neuroprotection mechanism of LW on Alzheimer's disease (AD) through regulation of inflammation remains unclear. Read More

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Changes in soil prokaryotic communities and nitrogen cycling functions along a groundwater table drawdown gradient in desert wetlands.

Sci Total Environ 2022 Jun 22:156868. Epub 2022 Jun 22.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, College of Natural Resources and Environment, Northwest A & F University, Yangling, Shaanxi Province 712100, PR China; Research Center on Soil & Water Conservation, Institute of Soil and Water Conservation, Chinese Academy of Sciences Ministry of Water Resources, Yangling, Shaanxi Province 712100, PR China. Electronic address:

Desert wetlands are evolving into deserts by groundwater table (GWT) drawdown. However, the changes in microbial communities and functions during the GWT drawdown are unclear, which hinders the predictive power of biogeochemical processes across the desertification. Here, 16S rRNA gene sequencing, PICRUSt2 and qPCR were used to investigate soil prokaryotic diversity, composition and nitrogen cycling gene abundance at four vegetation types [flooded swamp (FS), drained swamp (DS), desert grassland (DG), and bare sandy land (BS)] along a GWT decline gradient in the Mu Us Desert, northern China. Read More

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Sleep and affective disorders in relation to Parkinson's disease risk among older women from the Women's Health Initiative.

J Affect Disord 2022 Jun 22. Epub 2022 Jun 22.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD 21225, USA.

Objectives: To evaluate sleep and affective (mood/anxiety) disorders as clinical predictors of incident Parkinson's disease (PD) among women ≥65 years of age.

Methods: We performed secondary analyses with available data from the Women's Health Initiative Clinical Trials and Observational Study linked to Medicare claims. Sleep, mood and anxiety disorders at baseline were defined using diagnostic codes. Read More

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Impact of Smoking on Visual Field Progression in a Long-term Clinical Follow-up.

Ophthalmology 2022 Jun 22. Epub 2022 Jun 22.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, United States. Electronic address:

Purpose: To investigate the effect of smoking on the rates of progressive visual field damage over time in glaucoma.

Design: Retrospective cohort study.

Participants: A total of 511 eyes of 354 patients with glaucoma followed from multicenter glaucoma registries. Read More

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The genesis and functional consequences of cortico-subthalamic beta augmentation and excessive subthalamic burst discharges after dopaminergic deprivation.

Exp Neurol 2022 Jun 22:114153. Epub 2022 Jun 22.

Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.. Electronic address:

The cardinal electrophysiological signs in Parkinson's disease (PD) include augmented beta oscillations in the motor cortex-subthalamic nucleus (MC-STN) axis and excessive burst discharges in STN. We have shown that excessive STN burst discharges have a direct causal relation with the locomotor deficits in PD. To investigate the correlation between the two cardinal signs, we characterized the courses of development of the electrophysiological abnormalities in the hemiparkinsonian rat model. Read More

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Comparative Efficacy of Silibinin and Nano-Silibinin on Lead poisoning in Male Wistar Rats.

Toxicology 2022 Jun 22:153242. Epub 2022 Jun 22.

Department of Forensic Medicine and Clinical Toxicology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Modeling of Non-Communicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; Behavioral Disorders and Substance Abuse Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Lead (Pb) is an environmental neurotoxin that can lead to toxicity. It has shown that tissues can be exposed to oxidative stress in lead poisoning. Since silymarin is a natural agent with antioxidant effects, this study aimed to investigate the antioxidant and chelation effects of silibinin and nano-silibinin on the oxidative stress status in lead-poisoned rats. Read More

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Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis.

Mol Cell 2022 Jun 18. Epub 2022 Jun 18.

Institute for Cancer Genetics, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:

Cancer mortality is primarily a consequence of its metastatic spread. Here, we report that methionine sulfoxide reductase A (MSRA), which can reduce oxidized methionine residues, acts as a suppressor of pancreatic ductal adenocarcinoma (PDA) metastasis. MSRA expression is decreased in the metastatic tumors of PDA patients, whereas MSRA loss in primary PDA cells promotes migration and invasion. Read More

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The Optimal Cesarean Skin Incision in Patients with Super Obesity.

Am J Perinatol 2022 Jun 25. Epub 2022 Jun 25.

Department of Obstetrics and Gynecology and Reproductive Sciences, University of Maryland Medical Center, Baltimore, United States.

Objective To evaluate if supraumbilical midline vertical incision performed in patients with a hanging pannus (umbilicus at the level of the pubic bone) is a reasonable alternative to Pfannenstiel in patients with Body Mass Index (BMI) ≥ 50 kg/m2 undergoing cesarean delivery. Methods Retrospective cohort study in patients with BMI ≥50 kg/m2 undergoing cesarean delivery at a single center from 2016 to 2020. Study groups were Pfannenstiel VS supraumbilical vertical skin incision. Read More

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Leaving the Placenta In Situ in Placenta Accreta Spectrum Disorders: A Single Center Case Series.

Am J Perinatol 2022 Jun 25. Epub 2022 Jun 25.

Obstetrics & Gynecology, University of Texas Health Sciences Center at Houston, Houston, United States.

The most common treatment for placenta accreta spectrum disorders (PAS) is planned primary cesarean-hysterectomy. However, other management strategies may improve outcomes and/or allow fertility preservation. This is a series of 11 patients with PAS managed by leaving the placenta in situ at a single academic center in the U. Read More

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Tau-PET and multimodal imaging in clinically atypical multiple system atrophy masquerading as progressive supranuclear palsy.

Parkinsonism Relat Disord 2022 Jun 16;101:9-14. Epub 2022 Jun 16.

Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Introduction: Multiple system atrophy (MSA) typically presents with parkinsonism, ataxia and/or autonomic dysfunction. Occasionally, clinically atypical (ca-MSA) cases masquerade as progressive supranuclear palsy (PSP). We aimed to investigate whether different neuroimaging modalities could facilitate differentiation and whether histopathologic characteristics could explain the atypical presentation. Read More

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Combination of chitosan coating and heat shock treatments to maintain postharvest quality and alleviate cracking of Akebia trifoliate fruit during cold storage.

Food Chem 2022 May 28;394:133330. Epub 2022 May 28.

Bor Luh Food Safety Center, Department of Food Science & Technology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:

Akebia trifoliata fruit cracks easily, which shortens the shelf life and declines commercial value. This work aimed to evaluate the effects of heat shock and coating treatments on postharvest quality of A. trifoliata fruit and to elucidate the mechanism underlying retarding cracking by cell wall metabolism. Read More

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CCN-CL: A content-noise complementary network with contrastive learning for low-dose computed tomography denoising.

Comput Biol Med 2022 Jun 20;147:105759. Epub 2022 Jun 20.

School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China; Medical Imaging Department, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China. Electronic address:

In recent years, low-dose computed tomography (LDCT) has played an increasingly important role in the diagnosis CT to reduce the potential adverse effects of x-ray radiation on patients while maintaining the same diagnostic image quality. Current deep learning-based denoising methods applied to LDCT imaging only use normal dose CT (NDCT) images as positive examples to guide the denoising process. Recent studies on contrastive learning have proved that the original images as negative examples can also be helpful for network learning. Read More

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Pseudo-labeling generative adversarial networks for medical image classification.

Comput Biol Med 2022 Jun 17;147:105729. Epub 2022 Jun 17.

Department of Digital Media Technology, Hangzhou Dianzi University, Hangzhou, 310018, China. Electronic address:

Semi-supervised learning has become a popular technology in recent years. In this paper, we propose a novel semi-supervised medical image classification algorithm, called Pseudo-Labeling Generative Adversarial Networks (PLGAN), which only uses a small number of real images with few labels to generate fake images or mask images to enlarge the sample size of the labeled training set. First, we combine MixMatch to generate pseudo labels for the fake and unlabeled images to do the classification. Read More

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Geotechnical properties of fresh municipal solid wastes with different compositions under leachate exposure.

Waste Manag 2022 Jun 22;149:207-217. Epub 2022 Jun 22.

School of Engineering and Information Technology, University of New South Wales, Canberra, Northcott Drive, Campbell, ACT 2612, Australia.

This paper investigates the geotechnical properties of a type of synthetic municipal solid waste (MSW). The tests were conducted on five groups of synthetic MSW compositions, based on the field characterization of fresh MSW samples collected from Mugga Lane landfill site, ACT, Australia. Compaction, hydraulic conductivity, compression, drained and undrained shear properties of the MSWs with water and leachate addition to the field moisture content were studied. Read More

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Impact of slurry removal frequency on CH emission and subsequent biogas production; a one-year case study.

Waste Manag 2022 Jun 22;149:199-206. Epub 2022 Jun 22.

Department of Biological and Chemical Engineering, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark.

Anaerobic digestion of animal slurry to produce biogas is the dominated treatment approach and a storage period is normally applied prior to digestion. Pre-storage, however, contributes to CH emissions and results in loss of biogas potential. Manure management was found to be an efficient approach to reduce not only the on-site CH emission but may also have extended influence on CH emission/losses for storage and subsequent biogas process, while the connection remains unclear. Read More

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Targeting miR-30d reverses pathological cardiac hypertrophy.

EBioMedicine 2022 Jun 22;81:104108. Epub 2022 Jun 22.

Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai 200444, China. Electronic address:

Background: Pathological cardiac hypertrophy occurs in response to numerous stimuli and precedes heart failure (HF). Therapies that ameliorate pathological cardiac hypertrophy are highly needed.

Methods: The expression level of miR-30d was analyzed in hypertrophy models and serum of patients with chronic heart failure by qRT-PCR. Read More

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Artemisia Leaf Extract protects against neuron toxicity by TRPML1 activation and promoting autophagy/mitophagy clearance in both in vitro and in vivo models of MPP+/MPTP-induced Parkinson's disease.

Phytomedicine 2022 Jun 15;104:154250. Epub 2022 Jun 15.

Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan. Electronic address:

Background: Parkinson's disease (PD) is a neurodegenerative disorder involving the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Cellular clearance mechanisms, including the autophagy-lysosome pathway, are commonly affected in the pathogenesis of PD. The lysosomal Ca channel mucolipin TRP channel 1 (TRPML1) is one of the most important proteins involved in the regulation of autophagy. Read More

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Astragaloside Ⅳ alleviates ulcerative colitis by regulating the balance of Th17/Treg cells.

Phytomedicine 2022 Jun 19;104:154287. Epub 2022 Jun 19.

Formula-Pattern Research Center, Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang, Jiangxi 330004, China. Electronic address:

Background: Restoring immune homeostasis by targeting the Th17/Treg response is a potentially valuable therapeutic strategy for ulcerative colitis (UC). Astragaloside IV (AS-Ⅳ) is a phytochemical naturally occurring in Astragalus membranaceus that has good anti-inflammatory, anti-oxidant and anti-stress properties. However, the effects of AS-IV on the homeostasis of Th17/Treg cells in colitis mice remains unknown. Read More

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Cadmium-induced splenic lymphocytes anoikis is not mitigated by activating Nrf2-mediated antioxidative defense response.

J Inorg Biochem 2022 Jun 2;234:111882. Epub 2022 Jun 2.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Cadmium (Cd) is a widely used heavy metal which is reported to exert extensive harm to the environment and human health. Owing to Cd being an element it is continuously enriched in the environment. The mechanism of splenic toxicity by Cd, however, is not yet clear. Read More

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Aging relieves the promotion effects of polyamide microplastics on parental transfer and developmental toxicity of TDCIPP to zebrafish offspring.

J Hazard Mater 2022 Jun 18;437:129409. Epub 2022 Jun 18.

School of Environment, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang 453007, China. Electronic address:

Understanding the role of microplastics (MPs) in the biological fate and toxicity of organic pollutants in food webs is vital for its risk assessment. However, contradictory results and the neglect of MP aging as a factor have led to a research gap, which needs to be filled. Our study discovered that polyamide (PA, a ubiquitous MP in water) MPs clearly facilitated bioaccumulation of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in the F0 zebrafish gonads and parental transfer of TDCIPP to the F1 offspring. Read More

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