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Genome-wide Association and Meta-analysis of Age-at-Onset in Parkinson Disease: Evidence From COURAGE-PD Consortium.

Neurology 2022 May 26. Epub 2022 May 26.

Sorbonne Université (SU) Unité Mixte de Recherche (UMR) 1127, INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Background And Objectives: Considerable heterogeneity exists in the literature concerning genetic determinants of the age of onset (AAO) of Parkinson's disease (PD), which could be attributed to lack of well-powered replication cohorts. The previous largest GWAS identified nd loci on chromosome (Chr) 4 with a significant influence on AAO of PD, these have not been independently replicated. The present study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Read More

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Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging.

Neurology 2022 May 26. Epub 2022 May 26.

Cognitive Neurology Center, Lariboisiere - Fernand Widal Hospital, AP-HP, Université de Paris, Paris, France.

Objective: To elaborate a new algorithm to establish a standardized method to define cuff-offs for CSF biomarkers of Alzheimer's disease (AD) by validating the algorithm against CSF classification derived from PET imaging.

Methods: Low and high levels of CSF phosphorylated tau were first identified to establish optimal cut-offs for CSF amyloid-β peptide (Aβ) biomarkers. These Aβ cut-offs were then used to determine cut-offs for CSF tau and phosphorylated tau markers. Read More

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Pro- and anti-fibrotic effects of vascular endothelial growth factor in chronic kidney diseases.

Ren Fail 2022 Dec;44(1):881-892

Department of Nephrology, The First Hospital of Jilin University, Changchun, People's Republic of China.

Renal fibrosis is the inevitable common end-point of all progressive chronic kidney diseases. The underlying mechanisms of renal fibrosis are complex, and currently there is no effective therapy against renal fibrosis. Renal microvascular rarefaction contributes to the progression of renal fibrosis; however, an imbalance between proangiogenic and antiangiogenic factors leads to the loss of renal microvasculature. Read More

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December 2022

Determinants of High Fat Mass Index in Preschoolers Living in Brazilian Urban Areas.

J Nutr Educ Behav 2022 Jun;54(6):532-539

Faculty of Physiotherapy, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil.

Objective: Determine the social, environmental, and personal factors associated with high fat mass index in preschoolers.

Design: A quantitative, exploratory, and cross-sectional study.

Setting And Participants: Fifty-one Brazilian preschoolers from public schools living in urban areas. Read More

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Campus Food Pantry Use Is Linked to Better Health Among Public University Students.

J Nutr Educ Behav 2022 Jun;54(6):491-498

Department of Psychiatry, University of Arizona, Tucson, AZ.

Objective: To examine retrospectively whether access to a campus food pantry (CFP) is related to improvements in sleep, mental health, and physical health among college students in a public university system.

Design: Retrospective, cross-sectional study of student CFP users who completed an online survey in the summer of 2019.

Setting: Ten-campus University of California system. Read More

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Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction.

J Am Coll Cardiol 2022 May;79(21):2097-2115

State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai, China. Electronic address:

Background: Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear.

Objectives: This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI. Read More

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Mediator or moderator? The role of obesity in the association between age at menarche and blood pressure in middle-aged and elderly Chinese: a population-based cross-sectional study.

BMJ Open 2022 May 26;12(5):e051486. Epub 2022 May 26.

Department of Emergency and Critical Care Nursing, School of Nursing, Wannan Medical College, Wuhu, Anhui, China.

Objective: We investigated the moderation/mediation between the age of menarche and obesity parameters in predicting blood pressure (BP) in middle-aged and elderly Chinese.

Design: Our study is a population-based cross-sectional study.

Setting: Participants in this study came from the China Health and Retirement Longitudinal Study (CHARLS). Read More

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MicroRNA-26b regulates BMSC osteogenic differentiation of TMJ subchondral bone through β-catenin in osteoarthritis.

Bone 2022 May 23:116448. Epub 2022 May 23.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research & Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Orthodontics, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, PR China. Electronic address:

Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease of the joint. The early manifestations of TMJ-OA are abnormal remodeling of condylar subchondral bone. In bone tissue, bone marrow mesenchymal stem cells (BMSCs) and osteoblasts play important roles in the differentiation and maturation of most hematopoietic cells. Read More

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Mouse models of Alzheimer's disease for preclinical research.

Neurochem Int 2022 May 23:105361. Epub 2022 May 23.

Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. Electronic address:

Most mouse models for preclinical research into Alzheimer's disease (AD) rely on the overexpression paradigm, in which familial AD (FAD)-related genes linked to amyloid precursor protein (APP) and presenilin-1 (PSEN1) are overexpressed. Such mice have been used for over two decades as the first-generation transgenic lines for AD, with animals exhibiting AD pathologies along with additional phenotypes, leading to the serious artifacts. To overcome the intrinsic drawbacks of the overexpression paradigm, we previously developed second-generation mouse models that incorporate humanized amyloid β (Aβ) sequences and several FAD-related mutations on the mouse endogenous App gene. Read More

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Infant inflammation predicts childhood emotional and behavioral problems and partially mediates socioeconomic disadvantage.

Brain Behav Immun 2022 May 23. Epub 2022 May 23.

Murdoch Children's Research Institute, University of Melbourne, Parkville, VIC 3052, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia; Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address:

Background: Emotional and behavioral problems (EBP) are common in children. Environmental factors like socioeconomic disadvantage influence EBP pathogenesis and can trigger inflammation. However, the link between early inflammation-EBP in children is unclear. Read More

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Prospective associations of multimodal serum biomarkers with 12-week and 12-month remission in patients with depressive disorders receiving stepwise psychopharmacotherapy.

Brain Behav Immun 2022 May 23. Epub 2022 May 23.

Department of Psychological Medicine, King's College London (Institute of Psychiatry, Psychology and Neuroscience); South London and Maudsley NHS Foundation Trust, London, UK. Electronic address:

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. Read More

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Peptide location fingerprinting identifies species- and tissue-conserved structural remodelling of proteins as a consequence of ageing and disease.

Matrix Biol 2022 May 23. Epub 2022 May 23.

Divisions of Cell Matrix Biology & Regenerative Medicine and Cardiovascular Sciences, School of Biological Science, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. Electronic address:

Extracellular matrix (ECM) in the intervertebral disc (IVD), lung and artery are thought to undergo the age-dependant accumulation of damage by chronic exposure to mechanisms such as reactive oxygen species, proteases and glycation. It is unknown whether this damage accumulation is species-dependant (via differing lifespans and hence cumulative exposures) or whether it can influence the progression of age-related diseases such as atherosclerosis. Peptide location fingerprinting (PLF) is a new proteomic analysis method, capable of the non-targeted identification of structure-associated changes within proteins. Read More

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Comparison of survival rate and outcomes between conventional and navigation assisted primary total knee arthroplasty in severe varus knees: a minimum 10-year follow up.

J Arthroplasty 2022 May 23. Epub 2022 May 23.

Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address:

Background: This study aimed to compare the long-term clinical and radiographic outcomes and survival rates between navigation assisted (NAV)-total knee arthroplasty (TKA) and conventional (CON) TKA in patients with preoperative severe varus deformity.

Methods: From January 2005 to December 2011, 152 TKAs and 62 TKAs with preoperative HKA angles over 15° were enrolled in the CON-TKA and NAV-TKA group with 135.7 months follow-up, respectively. Read More

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In-vitro activity of sulbactam-durlobactam against carbapenem-resistant Acinetobacter baumannii and mechanisms of resistance.

J Glob Antimicrob Resist 2022 May 23. Epub 2022 May 23.

Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland; INSERM European Unit (IAME), University of Fribourg, Fribourg; Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg; Institute for Microbiology, University of Lausanne and University Hospital Centre, Lausanne, Switzerland.

Objectives: Multidrug-resistant Acinetobacter baumannii, particularly strains producing OXA-type carbapenemases, have rapidly emerged in health care settings as a frequent cause of serious infections with limited treatment options. This study evaluated the in-vitro activity of sulbactam (SUL) combined with durlobactam (DUR), against a collection of carbapenemase-producing A. baumannii, and investigated the mechanisms of resistance. Read More

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Bladder cancer selective chemotherapy with potent NQO1 substrate co-loaded prodrug nanoparticles.

J Control Release 2022 May 23. Epub 2022 May 23.

The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address:

Currently, clinical intravesical instillation chemotherapy has been greatly compromised by the toxicological and physiological factors. New formulations that can specifically and efficiently kill bladder cancer cells are in urgent need to overcome the low residence efficiency and dose limiting toxicity of current ones. The combination of mucoadhesive nanocarriers and cancer cell selective prodrugs can to great extent address these limitations. Read More

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L-Se-methylselenocysteine loaded mucoadhesive thermogel for effective treatment of Vulvar candidiasis.

Int J Pharm 2022 May 23:121851. Epub 2022 May 23.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Vulvar candidiasis (VVC) is a vaginitis caused by vaginal mucosa infection of Candida, which greatly impairs women's health. Although there are more and more thiazoles on the market, new classes of antifungal drugs are still missing, it is still challenging to treat azole-resistant candidal vaginitis. We found that L-Se-methylselenocysteine (L-SeMC) could effectively inhibit the growth of Candida albicans, reduce the density and length of the mycelia. Read More

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Pneumococcal urinary antigen testing for antimicrobial guidance in community-acquired pneumonia: a register-based cohort study.

J Infect 2022 May 23. Epub 2022 May 23.

Department of Medicine, Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.

Objectives: To evaluate the effect of pneumococcal urinary antigen test (UAT) usage on broad-spectrum antibiotic treatment in community-acquired pneumonia (CAP).

Methods: Patients admitted to 32 Swedish hospitals between 2011-2014 were retrospectively included from the Swedish National Quality Register of CAP. Using propensity score matched data, stratified by CRB-65 score, we studied the effect of performing UAT and of positive test results on treatment with broad-spectrum β-lactam monotherapy (BSBM) and antibiotics with coverage for atypical bacteria compared to narrow-spectrum β-lactam monotherapy (NSBM). Read More

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Global landscape of gut microbiome diversity and antibiotic resistomes across vertebrates.

Sci Total Environ 2022 May 23:156178. Epub 2022 May 23.

CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China. Electronic address:

Multiple factors influence gut microbiome diversity in vertebrate hosts. Most previous studies have only investigated specific factors and certain host species or taxa. However, a comprehensive assessment of the relative contributions of individual factors towards gut microbial diversity within a broader evolutionary context remains lacking. Read More

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EEG asymmetry and cognitive testing in MCI identification.

Int J Psychophysiol 2022 May 23. Epub 2022 May 23.

Institute of Gerontology, Wayne State University, USA; International Institute of Applied Gerontology, Ljubljana, Slovenia. Electronic address:

Background: Finding the baseline resting-state EEG markers for early identification of cognitive decline can contribute to the identification of individuals at risk of further change. Potential applications include identifying participants for clinical trials, early treatment, and evaluation of treatment, accessible even from a community setting.

Methods: Analyses were completed on a sample of 99 (ages 60-90) consensus-diagnosed, community-dwelling African Americans (58 cognitively typical/HC, and 41 mildly cognitively impaired/MCI), who were recruited from the Michigan Alzheimer's Disease Research Center (MADRC) and the Wayne State University Institute of Gerontology. Read More

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Structural characterization and immunomodulatory activity of a mannan from Helvella leucopus.

Int J Biol Macromol 2022 May 23. Epub 2022 May 23.

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China; Key Laboratory of Modern Biomanufacturing of Anhui Province, Hefei 230601, Anhui, China. Electronic address:

A new polysaccharide fraction HLP-1 (2.55 × 10 Da) was obtained from the fruiting bodies of Helvella leucopus. Structural characterization of HLP-1 was elucidated by infrared spectroscopy, monosaccharide composition analysis, methylation analysis, nuclear magnetic resonance spectroscopy, scanning electron microscopy and Congo red assay. Read More

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Low specific growth rate and temperature in fed-batch cultures of a beta-propeller phytase producing Pichia pastoris strain under GAP promoter trigger increased KAR2 and PSA1-1 gene expression yielding enhanced extracellular productivity.

J Biotechnol 2022 May 23. Epub 2022 May 23.

Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Biológicas, Instituto de Biotecnología, 66450 San Nicolás de los Garza, N.L. México. Electronic address:

Previously, we showed that the methylotrophic yeast Pichia pastoris (syn. Komagataella phaffii) could produce and secrete the beta-propeller phytase FTEII in an active form under the control of the AOX1 promoter and methanol as the inductor. In this work, we engineered P. Read More

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Development of β-cyclodextrin crosslinked citric acid encapsulated in polypropylene membrane protected-μ-solid-phase extraction device for enhancing the separation and preconcentration of endocrine disruptor compounds.

Chemosphere 2022 May 23:135075. Epub 2022 May 23.

Department of Fundamental and Applied Sciences, Universiti Teknologi PETRONAS, 32610, Seri Iskandar, Perak Darul Ridzuan, Malaysia.

Endocrine disruptor compounds (EDCs) such as plasticisers, surfactants, pharmaceutical products, personal care products and pesticides are frequently released into the environmental waters. Therefore, a sensitive and environmentally friendly method is entailed to quantify these compounds at their trace level concentrations. This study encapsulated the β-cyclodextrin crosslinked with citric acid in a polypropylene membrane protected-μ-solid phase extraction (BCD-CA μ-SPE) device for preconcentrating the EDCs (triclosan, triclocarban, 2-phenylphenol, 4-tert-octylphenols and bisphenol A) in real water samples before the analysis by high-performance liquid chromatography. Read More

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In vitro activity of ceftazidime-avibactam against Gram-negative strains in patients with complicated urinary tract infection and complicated intra-abdominal infection in Colombia 2014-2018.

Braz J Infect Dis 2022 May 23:102369. Epub 2022 May 23.

Universidad Antonio Nariño, Faculty of Nursing, Research Group Innovación y Cuidado, Neiva, Colombia.

Ceftazidime/avibactam (CAZ/AVI) has excellent in vitro activity against enterobacterales and Pseudomonas aeruginosa. The study aimed to analyze the in vitro antimicrobial activity of CAZ/AVI and other antibiotics against isolates of enterobacterales and P. aeruginosa from patients with complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) in Colombian hospitals between 2014 and 2018, using the Antimicrobial Testing Leadership and Surveillance (ATLAS) database. Read More

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Tenofovir disoproxil fumarate-mediated γ-globin induction is correlated with the suppression of trans-acting factors in CD34 progenitor cells: A role in the reactivation of fetal hemoglobin.

Eur J Pharmacol 2022 May 23:175036. Epub 2022 May 23.

Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. Electronic address:

Sickle-cell disease (SCD) and β-thalassemia are public health issues that affect people all over the world. Fetal hemoglobin (HbF) induction is a molecular intervention, including hydroxyurea, which has made an effort to improve current treatment. Tenofovir disoproxil fumarate (TDF) is formerly reported with improving levels of hemoglobin, mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). Read More

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The contribution of the neuroendocrine system to adaption after repeated daily ozone exposure in rats.

Toxicol Appl Pharmacol 2022 May 23:116085. Epub 2022 May 23.

Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States of America. Electronic address:

Ozone-induced lung injury/inflammation dissipates despite continued exposure for 3 or more days; however, the mechanisms of adaptation/habituation remain unclear. Since ozone effects are mediated through adrenal-derived stress hormones, which also regulate longevity of centrally-mediated stress response, we hypothesized that ozone-adaptation is linked to diminution of neuroendocrine stress-axes activation and glucocorticoid levels. Male Wistar-Kyoto-rats (12-week-old) were injected with vehicle or a therapeutically-relevant dexamethasone dose (0. Read More

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Nonalcoholic fatty liver disease and cardiovascular diseases: A Mendelian randomization study.

Metabolism 2022 May 23:155220. Epub 2022 May 23.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China. Electronic address:

Background: Evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established.

Objective: We aimed to investigate the potential causal relationship between NAFLD and CVDs, including arterial stiffness, coronary artery disease, heart failure, stroke, ischemic stroke and its subtypes using two-sample Mendelian randomization (MR). Read More

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Pigment epithelium-derived factor maintains tight junction stability after myocardial infarction in rats through inhibition of the Wnt/β-catenin signaling pathway.

Exp Cell Res 2022 May 23:113213. Epub 2022 May 23.

Thoracic Surgery Laboratory, Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China; Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China. Electronic address:

Purpose: The impairment of the coronary microcirculatory barrier caused by acute myocardial infarction (AMI) is closely related to poor prognosis. Recently, pigment epithelial-derived factor (PEDF) has been proven to be a promising cardiovascular protective drug. In this study, we demonstrated the protective role of PEDF in endothelial tight junctions (TJs) and the vascular barrier in AMI. Read More

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IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes.

Cell Rep 2022 May 16:110904. Epub 2022 May 16.

Ichor Biologics LLC, New York, NY 10027, USA; 525 Bio LLC, New York, NY 10044, USA; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Despite SARS-CoV-2 being a "novel" virus, early detection of anti-spike IgG in severe COVID-19 patients may be caused by the amplification of humoral memory responses against seasonal coronaviruses. Here, we examine this phenomenon by characterizing anti-spike IgG responses in non-hospitalized convalescent individuals across a spectrum of COVID-19 severity. We observe that disease severity positively correlates with anti-spike IgG levels, IgG cross-reactivity against other betacoronaviruses (β-CoVs), and FcγR activation. Read More

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Developing ultrasound-assisted hot-air and infrared drying technology for sweet potatoes.

Ultrason Sonochem 2022 May 20;86:106047. Epub 2022 May 20.

College of Food Science and Engineering, Henan University of Technology, Zhengzhou 450001, China.

The influence of ultrasound (US) pretreatments combined with infrared (IRD) and hot-air (HAD) drying on drying kinetics, mathematical modeling, bioactive compounds (antioxidant activities, Vitamin C, phenolics, and flavonoid contents), qualitative properties (β-carotene, total carotenoids, color indexes, textural profile), enzyme inactivation, and exergetic analysis of sweet potatoes. The US pretreatment at 40 kHz combined with IRD and HAD (70 °C) significantly lessened the drying time and water contents. Besides, it did not affect the sweet potato's bioactive components and other quality-related attributes. Read More

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