bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrinogen A Alpha-Chain Amyloidosis in Two Chinese Patients
Authors: Li Zhen-Yu , Wang Shuang , Li Dan-Yang , Liu Dan , Wang Su-Xia , Yu Xiao-Juan , Liu Gang , Zhou Fu-De , Zhao Ming-Hui
Published: April 2022

Objectives

Fibrinogen A alpha-chain amyloidosis (AFib amyloidosis) is the most common form of hereditary renal amyloidosis in the United Kingdom and Europe, but has rarely been reported in Asia. In this study, we reported two AFib amyloidosis patients in China, reviewing the literature and summarizing main characteristics of AFib amyloidosis in Asia.

Methods

Two unrelated Chinese patients were diagnosed with AFib amyloidosis by clinical presentation, renal biopsy, mass spectrometry and DNA sequencing in Peking University First Hospital of China from 2014 to 2016.

Results

Both of the patients presented with proteinuria, edema and hypertension. Renal biopsies of two patients showed extensive amyloid deposits (Congo red positive) in glomeruli, and focal tubulointerstitial amyloid deposits was also found in patient 1. Besides, hepatic involvement of amyloidosis has been detected by liver biopsy in patient 1. By electron microscopy, randomly arranged fibrils in a diameter of 8–12 nm was identified in mesangial matrix and subendothelial area of glomeruli. Immunohistochemistry demonstrated amyloid deposits were strongly positive for fibrinogen Aα in glomeruli and positive for LECT2 in the interstitium of renal medulla and the liver in Patient 1. Unevenly positive staining for both fibrinogen Aα and ApoA-I were found in Patient 2. Fibrinogen Aα was the most abundant amyloidogenic protein in both patients identified by laser microdissection and mass spectrometry-based proteomic analysis. Genetic analysis revealed the fibrinogen A a-chain gene (FGA) mutation in both patients, including a new deletion mutation [c.1639delA (p.Arg547Glyfs*21; NM_000508)] in Patient 2. Genetic analysis of the LECT2 gene in patient 1 revealed a codon change from ATC to GTC at position 172 [c.172A>G (p.Ile58Val; NM_002302)], which is a common polymorphism (SNP rs31517) in all ALECT2 amyloidosis patients.

Conclusions

We reported two AFib amyloidosis patients in China, one of them coexisted with ALECT2 amyloidosis simultaneously.
Case Report: The First Reported Concurrence of Wilson Disease and Bilateral Retinitis Pigmentosa
Authors: Ye Zifan , Jia Xiuhua , Liu Xin , Zhang Qi , Wang Kaijun , Chen Min
Published: April 2022

Background

Wilson disease (WD) and retinitis pigmentosa (RP) are common genetic disorders in clinical practice, however, the concurrence of WD and RP has never been reported before. WD occurs due to mutations that cause copper metabolic abnormalities; in turn, change in copper metabolism has been suggested to be related with RP. Here, we report the first case of concurrent WD and bilateral RP, and investigate possible pathogenesis to illuminate whether the two genetic disorders are causality or coincidence.

Case Presentation

The patient was a 43-year-old Chinese female diagnosed with WD 12 years ago. She had suffered from night blindness since childhood and faced diminution of bilateral vision within 10 years, for which she was referred to our Eye Center during hospitalization for routine copper excretion treatment. The ceruloplasmin, skull magnetic resonance imaging (MRI), and abdominal ultrasound results accorded with hepatolenticular degeneration. Ocular examinations revealed corneal Kayser-Fleischer (K-F) ring, sunflower-like cataract, retinal osteocyte-like pigmentation, bilateral atrophy of outer retina, cystoid macular edema (CME), and tubular vision in both eyes. Phacoemulsification combined with intraocular lens implantation was performed in the right and left eye, but there was limited improvement in her visual acuity. Whole exome sequencing (WES) detected a deleterious homozygous mutation in the ATP7B gene related to WD, and a homozygous mutation in the CNGA1 gene very likely to cause RP.

Conclusions

We reported the first case of concurrent WD and RP. WES detected two pathogenic gene mutations, ATP7B and CNGA1. Though we cannot completely rule out a causal effect of WD-related abnormal copper metabolism with RP, we speculate that the two gene mutations lead to the coincidence of the two genetic disorders, respectively.
Crohn’s Disease Complicated by Rare Types of Intestinal Obstruction: Two Case Reports
Authors: Xia Kai , Gao Renyuan , Wu Xiaocai , Ruan Yu , Wan Jian , Wu Tianqi , Wang Fangtao , Lin Yin , Yin Lu , Chen Chunqiu
Published: April 2022

Intestinal obstruction is one of the most common complications of Crohn’s disease (CD), jeopardizing the quality of life of patients. Numerous factors may contribute to intestinal obstruction in CD. Thus far, the primary reason has been identified as intestinal fibrosis caused by repeated chronic inflammation during the active phase of CD. Herein, we report two rare complicated CD cases and provide a reference for the clinical diagnosis and treatment of similar patients. Case one involves capsule endoscope retention in the small intestine of one CD patient concurrent with intestinal obstruction. Case two is a CD patient with intestinal obstruction caused by a mesangial hernia and ileal stenosis. Individualized and minimally invasive surgical intervention ultimately resulted in the successful management of these two patients. The two cases serve as an excellent guide for diagnosing and treating CD patients who present with similar symptoms.
Black Truffles Affect Quercus aliena Physiology and Root-Associated nirK- and nirS-Type Denitrifying Bacterial Communities in the Initial Stage of Inoculation
Authors: Kang Zongjing , Li Xiaolin , Li Yan , Ye Lei , Zhang Bo , Zhang Xiaoping , Penttinen Petri , Gu Yunfu
Published: April 2022

Truffles (Tuber spp.) are edible ectomycorrhizal fungi with high economic value. Bacteria in ectomycorrhizosphere soils are considered to be associated with the nutrient uptake of truffles and hosts. Whether Tuber spp. inoculation can affect the growth of Quercus aliena, the ectomycorrhizosphere soil, and the rhizosphere nirK and nirS-denitrifier communities at the ectomycorrhizae formation stage is still unclear. Therefore, we inoculated Q. aliena with the black truffles Tuber melanosporum and Tuber indicum, determined the physiological activity and morphological indices of Q. aliena seedlings, analyzed the physicochemical properties of ectomycorrhizosphere soils, and applied DNA sequencing to assess the nirK and nirS- denitrifier community structure in ectomycorrhizosphere soils. Peroxidase activity was higher in the seedlings inoculated with T. melanosporum than in the T. indicum inoculation and uninoculated control treatments. The available phosphorus contents were lower and nitrate contents were higher in those with truffle inoculation, and T. melanosporum treatment differed more from the control than the T. indicum treatment. The richness of the nirK-community was highest in the T. indicum treatment and lowest in the uninoculated treatment. The differences in nirK-community composition across treatments were not statistically significant, but the nirS communities were different. The nirS-type bacteria correlated with three environmental factors (pH, available phosphorus, and nitrate contents), whereas the nirK-type bacteria were only associated with the nitrate contents. Generally, this work revealed that inoculation with Tuber spp. would change a few nutrient contents and richness of nirK-type bacteria and had little effects on growth of Q. aliena seedlings in the initial stage of inoculation. The results of this study may provide in-depth insights into the relationships between Tuber spp. and hosts, which should be taken into account when developing truffle production methods.
Responses of Biocrust and Associated Soil Bacteria to Novel Climates Are Not Tightly Coupled
Authors: Antoninka Anita , Chuckran Peter F. , Mau Rebecca L. , Slate Mandy L. , Mishler Brent D. , Oliver Melvin J. , Coe Kirsten K. , Stark Llo R. , Fisher Kirsten M. , Bowker Matthew A.
Published: April 2022

Climate change is expanding drylands even as land use practices degrade them. Representing ∼40% of Earth’s terrestrial surface, drylands rely on biological soil crusts (biocrusts) for key ecosystem functions including soil stability, biogeochemical cycling, and water capture. Understanding how biocrusts adapt to climate change is critical to understanding how dryland ecosystems will function with altered climate. We investigated the sensitivity of biocrusts to experimentally imposed novel climates to track changes in productivity and stability under both warming and cooling scenarios. We established three common gardens along an elevational-climate gradient on the Colorado Plateau. Mature biocrusts were collected from each site and reciprocally transplanted intact. Over 20 months we monitored visible species composition and cover, chlorophyll a, and the composition of soil bacterial communities using high throughput sequencing. We hypothesized that biocrusts replanted at their home site would show local preference, and biocrusts transplanted to novel environments would maintain higher cover and stability at elevations higher than their origin, compared to at elevations lower than their origin. We expected responses of the visible biocrust cover and soil bacterial components of the biocrust community to be coupled, with later successional taxa showing higher sensitivity to novel environments. Only high elevation sourced biocrusts maintained higher biocrust cover and community stability at their site of origin. Biocrusts from all sources had higher cover and stability in the high elevation garden. Later successional taxa decreased cover in low elevation gardens, suggesting successional reversal with warming. Visible community composition was influenced by both source and transplant environment. In contrast, soil bacterial community composition was not influenced by transplant environments but retained fidelity to the source. Thus, responses of the visible and soil bacterial components of the biocrust community were not coupled. Synthesis: Our results suggest biocrust communities are sensitive to climate change, and loss of species and function can be expected, while associated soil bacteria may be buffered against rapid change.
Recent Differentiation of Aquatic Bacterial Communities in a Hydrological System in the Cuatro Ciénegas Basin, After a Natural Perturbation
Authors: García-Ulloa Manuel , Souza Valeria , Esquivel-Hernández Diego A. , Sánchez-Pérez Jazmín , Espinosa-Asuar Laura , Viladomat Mariette , Marroquín-Rodríguez Montserrat , Navarro-Miranda Marisol , Ruiz-Padilla Jair , Monroy-Guzmán Camila , Madrigal-Trejo David , Rosas-Barrera Manuel , Vázquez-Rosas-Landa Mirna , Eguiarte Luis E.
Published: April 2022

Pozas Rojas is a hydrological system comprising nine isolated shallow ponds and a deep lagoon, which were temporally merged in 2010 by increased rainfall due to a tropical cyclone. In this work, we assess which components, biotic interactions, or environment filtering effects, drive the assembly of microbial communities after a natural perturbation. Arsenic, pH, and temperature are among the most significant environmental variables between each pond, clustering the samples in two main groups, whereas microbial composition is diverse and unique to each site, with no core at the operational taxonomic unit level and only 150 core genera when studied at the genus level. Los Hundidos lagoon has the most differentiated community, which is highly similar to the epipelagic Mediterranean Sea communities. On the other hand, the shallow ponds at the Pozas Rojas system resemble more to epicontinental hydrological systems, such as some cold rivers of the world and the phreatic mantle from Iowa. Overall, despite being a sole of water body 2 years prior to the sampling, interspecific interactions, rather than environmental selection, seem to play a more important role in Pozas Rojas, bolstered by founder effects on each poza and subsequent isolation of each water body.
Molecular Mechanism of the β-Lactamase Mediated β-Lactam Antibiotic Resistance of Pseudomonas aeruginosa Isolated From a Chinese Teaching Hospital
Authors: Lin Hailong , Feng Chunlin , Zhu Tingting , Li Anqi , Liu Shuang , Zhang Lei , Li Qiaoling , Zhang Xueya , Lin Li , Lu Junwan , Lin Xi , Li Kewei , Zhang Hailin , Xu Teng , Li Changchong , Bao Qiyu
Published: April 2022

Pseudomonas aeruginosa can cause infections in the blood, lungs (pneumonia), or other parts of the body after surgery. To investigate the molecular characteristics of β-lactam antibiotic resistance of P. aeruginosa isolated from a hospital population between 2015 and 2017, in this study, the antimicrobial susceptibility and the resistance gene profile of the bacteria were determined. The Pulsed-field gel electrophoresis (PFGE) was used to characterize the clonal relatedness and sequencing and comparative genomic analysis were performed to analyze the structure of the resistance gene-related sequences. As a result, of the 260 P. aeruginosa strains analyzed, the resistance rates for 6 β-lactam antibiotics ranged from 4.6 to 9.6%. A total of 7 genotypes of 44 β-lactamase genes were identified in 23 isolates (8.9%, 23/260). Four transconjugants from different donors carrying blaCARB-3 exhibited a phenotype of reduced susceptibility to piperacillin–tazobactam, ceftazidime, and cefepime, and 2 transconjugants harboring blaIMP-45 exhibited a phenotype of reduced susceptibility to carbapenems. blaCARB positive isolates (n = 12) presented six PFGE patterns, designated groups A to F. Two bla genes (blaIMP-45 and blaOXA-1) in PA1609 related to a class 1 integron (intI1-blaIMP-45-blaOXA-1-aac(6′)-Ib7-catB3-qacE∆1-sul1) were encoded on a plasmid (pPA1609-475), while the blaCARB-3 gene of PA1616 also related to a class 1 integron was located on the chromosome. The results suggest that β-lactam antibiotic resistance and clonal dissemination exist in this hospital population. It indicates the necessity for molecular surveillance in tracking β-lactamase-producing strains and emphasizes the need for epidemiological monitoring.
Effects of Alkali Stress on the Growth and Menaquinone-7 Metabolism of Bacillus subtilis natto
Authors: Chen Xiaoqian , Shang Chao , Zhang Huimin , Sun Cuicui , Zhang Guofang , Liu Libo , Li Chun , Li Aili , Du Peng
Published: April 2022

Menaquinone-7 (MK-7) is an important vitamin K2, synthesized from the menaquinone parent ring and seven isoprene side chains. Presently, the synthesis of MK-7 stimulated by environmental stress primarily focuses on oxygen stress, while the effect of alkali stress is rarely studied. Therefore, this study researched the effects of alkali stress on the fermentation performance and gene expression of Bacillus subtilis natto. The organism’s growth characteristics, biomass, sporogenesis, MK-7 biosynthesis, and gene expression were analyzed. After a pH 8.5 stress adaptation treatment for 0.5 h and subsequent fermentation at pH 8.5, which promoted the growth of the strain and inhibited the spore formation rate. In addition, biomass was significantly increased (P < 0.05). The conversion rate of glycerol to MK-7 was 1.68 times higher than that of the control group, and the yield of MK-7 increased to 2.10 times. Transcriptomic analysis showed that the MK-7 high-yielding strain had enhanced carbon source utilization, increased glycerol and pyruvate metabolism, enhanced the Embden-Meyerhof pathway (EMP), tricarboxylic acid (TCA) circulation flux, and terpenoid biosynthesis pathway, and promoted the accumulation of acetyl-CoA, the side-chain precursor of isoprene. At the same time, the up-regulation of transketolase increased the metabolic flux of the pentose phosphate (HMP) pathway, which was conducive to the accumulation of D-erythrose 4-phosphate, the precursor of the menadione parent ring. This study’s results contribute to a better understanding of the effects of environmental stress on MK-7 fermentation by Bacillus subtilis natto and the molecular regulatory mechanism of MK-7 biosynthesis.
Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability
Authors: Wei Yili , Wang Bin , Jia Lei , Huang Weijun , Xiang Andy Peng , Fang Cong , Liang Xiaoyan , Li Weiqiang
Published: April 2022

Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially attributed to their undefined developmental origins. The lateral mesoderm is also a developmental source of MSCs that constitute appendicular skeletal elements in the developing vertebrate embryo. However, it is difficult to isolate homogeneous lateral mesoderm (LM)-derived MSCs from bone tissues or bone marrow due to the lack of understanding of their characteristics. Herein, we successfully established an efficient differentiation protocol for the derivation of MSCs with a LM origin from human pluripotent stem cells (hPSCs) under specific conditions. LM-MSCs resembled bone marrow-derived MSCs (BMSCs) with regard to cell surface markers, global gene profiles, and immunoregulatory activity and showed a homeodomain transcription factor (HOX) gene expression pattern typical of skeletal MSCs in long bones. Moreover, we demonstrated that LM-MSCs had an increased osteogenic/chondrogenic differentiation capacity and hematopoietic support potential compared to BMSCs. These homogeneous LM-MSCs may serve as a powerful tool for elucidating their precise role in bone formation and hematopoiesis and could be a potentially ideal cell source for therapeutic applications.
Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes
Authors: Karakus Emre , Schmid Andreas , Leiting Silke , Fühler Bärbel , Schäffler Andreas , Jakob Thilo , Geyer Joachim
Published: April 2022

In addition to the endocrine and paracrine systems, peripheral tissues such as gonads, skin, and adipose tissue are involved in the intracrine mechanisms responsible for the formation of sex steroids via the transformation of dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEA/DHEAS) into potent androgenic and estrogenic hormones. Numerous studies have examined the relationship between overweight, central obesity, and plasma levels of DHEA and DHEAS. The sodium-dependent organic anion transporter Soat (Slc10a6) is a plasma membrane uptake transporter for sulfated steroids. Significantly increased expression of Slc10a6 mRNA has been previously described in organs and tissues of lipopolysaccharide (LPS)-treated mice, including white adipose tissue. These findings suggest that Soat plays a role in the supply of steroids in peripheral target tissues. The present study aimed to investigate the expression of Soat in adipocytes and its role in adipogenesis. Soat expression was analyzed in mouse white intra-abdominal (WAT), subcutaneous (SAT), and brown (BAT) adipose tissue samples and in murine 3T3-L1 adipocytes. In addition, adipose tissue mass and size of the adipocytes were analyzed in wild-type and Slc10a6−/− knockout mice. Soat expression was detected in mouse WAT, SAT, and BAT using immunofluorescence. The expression of Slc10a6 mRNA was significantly higher in 3T3-L1 adipocytes than that of preadipocytes and was significantly upregulated by exposure to lipopolysaccharide (LPS). Slc10a6 mRNA levels were also upregulated in the adipose tissue of LPS-treated mice. In Slc10a6−/− knockout mice, adipocytes increased in size in the WAT and SAT of female mice and in the BAT of male mice, suggesting adipocyte hypertrophy. The serum levels of adiponectin, resistin, and leptin were comparable in wild-type and Slc10a6−/− knockout mice. The treatment of 3T3-L1 adipocytes with DHEA significantly reduced lipid accumulation, while DHEAS did not have a significant effect. However, following LPS-induced Soat upregulation, DHEAS also significantly inhibited lipid accumulation in adipocytes. In conclusion, Soat-mediated import of DHEAS and other sulfated steroids could contribute to the complex pathways of sex steroid intracrinology in adipose tissues. Although in cell cultures the Soat-mediated uptake of DHEAS appears to reduce lipid accumulation, in Slc10a6−/− knockout mice, the Soat deletion induced adipocyte hyperplasia through hitherto unknown mechanisms.
Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
Authors: Bukowska-Olech Ewelina , Sowińska-Seidler Anna , Larysz Dawid , Gawliński Paweł , Koczyk Grzegorz , Popiel Delfina , Gurba-Bryśkiewicz Lidia , Materna-Kiryluk Anna , Adamek Zuzanna , Szczepankiewicz Aleksandra , Dominiak Paweł , Glista Filip , Matuszewska Karolina , Jamsheer Aleksander
Published: April 2022

Background: Craniosynostosis (CS) represents a highly heterogeneous genetic condition whose genetic background has not been yet revealed. The abnormality occurs either in isolated form or syndromic, as an element of hundreds of different inborn syndromes. Consequently, CS may often represent a challenging diagnostic issue.

Methods: We investigated a three-tiered approach (karyotyping, Sanger sequencing, followed by custom gene panel/chromosomal microarray analysis, and exome sequencing), coupled with prioritization of variants based on dysmorphological assessment and description in terms of human phenotype ontology. In addition, we have also performed a statistical analysis of the obtained clinical data using the nonparametric test χ2.

Results: We achieved a 43% diagnostic success rate and have demonstrated the complexity of mutations’ type harbored by the patients, which were either chromosomal aberrations, copy number variations, or point mutations. The majority of pathogenic variants were found in the well-known CS genes, however, variants found in genes associated with chromatinopathies or RASopathies are of particular interest.

Conclusion: We have critically summarized and then optimised a cost-effective diagnostic algorithm, which may be helpful in a daily diagnostic routine and future clinical research of various CS types. Moreover, we have pinpointed the possible underestimated co-occurrence of CS and intellectual disability, suggesting it may be overlooked when intellectual disability constitutes a primary clinical complaint. On the other hand, in any case of already detected syndromic CS and intellectual disability, the possible occurrence of clinical features suggestive for chromatinopathies or RASopathies should also be considered.
Novel Disease-Associated Missense Single-Nucleotide Polymorphisms Variants Predication by Algorithms Tools and Molecular Dynamics Simulation of Human TCIRG1 Gene Causing Congenital Neutropenia and Osteopetrosis
Authors: Shinwari Khyber , Rehman Hafiz Muzzammel , Liu Guojun , Bolkov Mikhail A. , Tuzankina Irina A. , Chereshnev Valery. A.
Published: April 2022

T Cell Immune Regulator 1, ATPase H + Transporting V0 Subunit A3 (TCIRG1 gene provides instructions for making one part, the a3 subunit, of a large protein complex known as a vacuolar H + -ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Single amino acid changes in highly conserved areas of the TCIRG1 protein have been linked to autosomal recessive osteopetrosis and severe congenital neutropenia. We used multiple computational approaches to classify disease-prone single nucleotide polymorphisms (SNPs) in TCIRG1. We used molecular dynamics analysis to identify the deleterious nsSNPs, build mutant protein structures, and assess the impact of mutation. Our results show that fifteen nsSNPs (rs199902030, rs200149541, rs372499913, rs267605221, rs374941368, rs375717418, rs80008675, rs149792489, rs116675104, rs121908250, rs121908251, rs121908251, rs149792489 and rs116675104) variants are likely to be highly deleterious mutations as by incorporating them into wild protein they destabilize the wild protein structure and function. They are also located in the V-ATPase I domain, which may destabilize the structure and impair TCIRG1 protein activation, as well as reduce its ATPase effectiveness. These mutants have not yet been identified in patients suffering from CN and osteopetrosis while (G405R, R444L, and D517N) reported in our study are already associated with osteopetrosis. Mutation V52L reported in our study was identified in a patient suspected for CN. Finally, these mutants can help to further understand the broad pool of illness susceptibilities associated with TCIRG1 catalytic kinase domain activation and aid in the development of an effective treatment for associated diseases.
Post-translational Modifications of the p53 Protein and the Impact in Alzheimer’s Disease: A Review of the Literature
Authors: Clark James S. , Kayed Rakez , Abate Giulia , Uberti Daniela , Kinnon Paul , Piccirella Simona
Published: April 2022

Our understanding of Alzheimer’s disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses. More recently, the p53 protein, well-known as a genome guardian, has gained attention for its potential role in the early evolution of AD. This is due to the central involvement of p53’s in the control of oxidative stress and potential involvement in the Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can affect brain processes, thus contributing to AD development. The following review will explore the impact of p53 PTMs on its function and consequential involvement in AD pathogenesis. The greater understanding of the role of p53 in the pathogenesis of AD could result in more targeted therapies benefiting the many patients of this debilitating disease.
AD Resemblance Atrophy Index of Brain Magnetic Resonance Imaging in Predicting the Progression of Mild Cognitive Impairment Carrying Apolipoprotein E-ε4 Allele
Authors: Mai Yingren , Cao Zhiyu , Xu Jiaxin , Yu Qun , Yang Shaoqing , Tang Jingyi , Zhao Lei , Fang Wenli , Luo Yishan , Lei Ming , Mok Vincent C. T. , Shi Lin , Liao Wang , Liu Jun ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

Background and Objective

Early identification is important for timely Alzheimer’s disease (AD) treatment. Apolipoprotein E ε4 allele (APOE-ε4) is an important genetic risk factor for sporadic AD. The AD-Resemblance Atrophy Index (RAI)—a structural magnetic resonance imaging-derived composite index—was found to predict the risk of progression from mild cognitive impairment (MCI) to AD. Therefore, we investigated whether the AD-RAI can predict cognitive decline and progression to AD in patients with MCI carrying APOE ε4.

Methods

We included 733 participants with MCI from the Alzheimer’s Disease Neuroimaging Initiative Database (ADNI). Their APOE genotypes, cognitive performance, and levels of AD-RAI were assessed at baseline and follow-up. Linear regression models were used to test the correlations between the AD-RAI and baseline cognitive measures, and linear mixed models with random intercepts and slopes were applied to investigate whether AD-RAI and APOE-ε4 can predict the level of cognitive decline. Cox proportional risk regression models were used to test the association of AD-RAI and APOE status with the progression from MCI to AD.

Results

The baseline AD-RAI was higher in the MCI converted to AD group than in the MCI stable group (P < 0.001). The AD-RAI was significantly correlated with cognition, and had a synergistic effect with APOE-ε4 to predict the rate of cognitive decline. The AD-RAI predicted the risk and timing of MCI progression to AD. Based on the MCI population carrying APOE-ε4, the median time to progression from MCI to AD was 24 months if the AD-RAI > 0.5, while the median time to progression from MCI to AD was 96 months for patients with an AD-RAI ≤ 0.5.

Conclusion

The AD-RAI can predict the risk of progression to AD in people with MCI carrying APOE ε4, is strongly correlated with cognition, and can predict cognitive decline.
Resonance as a Design Strategy for AI and Social Robots
Authors: Lomas James Derek , Lin Albert , Dikker Suzanne , Forster Deborah , Lupetti Maria Luce , Huisman Gijs , Habekost Julika , Beardow Caiseal , Pandey Pankaj , Ahmad Nashra , Miyapuram Krishna , Mullen Tim , Cooper Patrick , van der Maden Willem , Cross Emily S.
Published: April 2022

Resonance, a powerful and pervasive phenomenon, appears to play a major role in human interactions. This article investigates the relationship between the physical mechanism of resonance and the human experience of resonance, and considers possibilities for enhancing the experience of resonance within human–robot interactions. We first introduce resonance as a widespread cultural and scientific metaphor. Then, we review the nature of “sympathetic resonance” as a physical mechanism. Following this introduction, the remainder of the article is organized in two parts. In part one, we review the role of resonance (including synchronization and rhythmic entrainment) in human cognition and social interactions. Then, in part two, we review resonance-related phenomena in robotics and artificial intelligence (AI). These two reviews serve as ground for the introduction of a design strategy and combinatorial design space for shaping resonant interactions with robots and AI. We conclude by posing hypotheses and research questions for future empirical studies and discuss a range of ethical and aesthetic issues associated with resonance in human–robot interactions.
Clinical Features and Genetic Spectrum of Patients With Clinically Suspected Hereditary Progressive Spastic Paraplegia
Authors: Shi Yuzhi , Wang An , Chen Bin , Wang Xingao , Niu Songtao , Li Wei , Li Shaowu , Zhang Zaiqiang
Published: April 2022

Background and Purpose

A variety of hereditary diseases overlap with neurological phenotypes or even share genes with hereditary spastic paraplegia (HSP). The aim of this study was to determine the clinical features and genetic spectrum of patients with clinically suspected HSPs.

Methods

A total of 52 patients with clinically suspected HSPs were enrolled in this study. All the patients underwent next-generation sequencing (NGS) and triplet repeat primed PCR to screen for the dynamic mutations typical of spinocerebellar ataxia (SCA). Multiplex ligation-dependent probe amplification (MLPA) was further conducted in patients with no causative genetic mutations detected to examine for large deletions and duplications in genes of SPAST, ATL1, REEP1, PGN, and SPG11. Clinical characteristics and findings of brain MRI were analyzed in patients with definite diagnoses.

Results

The mean age of the patients studied was 36.90 ± 14.57 years. 75% (39/52) of patients manifested a phenotype of complex form of HSPs. A genetic diagnosis was made in 51.9% (27/52) of patients, of whom 40.3% (21/52) of patients had mutations in HSPs genes (SPG4/SPG6/SPG8/SPG11/SPG15/SPG78/SPG5A) and 11.5% (6/52) of patients had mutations in SCAs genes (SCA3/SCA17/SCA28). SPG4 and SPG11 were the most common cause of pure form of HSPs (5/6, 83.3%) and complex form of HSPs (5/15, 33.3%), respectively. Gait disturbance was the most common initial symptom in both the patients with HSPs (15/21) and in patients with SCAs (5/6). Dysarthria and cerebellar ataxia were detected in 28.5% (6/21) and 23.8% (5/21) of patients with HSPs, respectively, and were the most common symptoms in addition to progressive weakness and spasticity of the lower limbs. Cerebellar atrophy was seen on the brain MRI of patients with SPG5A, SCA3, and SCA28.

Conclusion

Causative genetic mutations were identified in 51.9% of patients with clinically suspected HSPs by NGS and triplet repeat primed PCR. A final diagnosis of HSPs or SCAs was made in 40.3% and 11.5% of patients, respectively. The clinical manifestations and neuroimaging findings overlapped between patients with HSPs and patients with SCAs. Dynamic mutations should be screened in patients with clinically suspected HSPs, especially in those with phenotypes of complex form of HSPs.
The Effect and Optimal Parameters of Repetitive Transcranial Magnetic Stimulation on Poststroke Dysphagia: A Meta-Analysis of Randomized Controlled Trials
Authors: Qiao Jia , Ye Qiu-ping , Wu Zhi-min , Dai Yong , Dou Zu-lin
Published: April 2022

Objective

The objectives of the study were to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for poststroke dysphagia (PSD) and explore the optimal stimulation parameters.

Method

The databases of Medline, Embase, Web of Science, and Cochrane Library were searched from the establishment to June 2021. All randomized controlled trials about rTMS treatment for PSD were enrolled. Dysphagia Grade (DG) and Penetration Aspiration Scale (PAS) were applied as the major dysphagia severity rating scales to evaluate the outcomes.

Results

A total of 12 clinical randomized controlled studies were included in our study. The summary effect size indicated that rTMS had a positive effect on PSD (SMD = −0.67, p < 0.001). The subgroup analysis for treatment duration and different stroke stages showed significant differences (treatment duration >5 days: SMD = −0.80, p < 0.001; subacute phase after stroke: SMD = −0.60, p < 0.001). Furthermore, no significant differences were observed among the other stimulation parameter subgroups (including stimulation frequency, location, and a single stimulation time) (p > 0.05).

Conclusion

rTMS is beneficial to the recovery of PSD patients, while an intervention of more than 5 days and in the subacute phase after stroke might bring new strategies and rational therapeutics to the treatment of PSD.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022299469.
Quantitative Comparison and Chemical Profile of Different Botanical Parts of Panax notoginseng From Different Regions
Authors: Gao Mengyuan , Cao Xiunan , Wei Shujie , Huang Xuhua , Ouyang Huizi , Chang Yanxu , Shi Rui , He Jun
Published: April 2022

The root of Panax notoginseng, a highly valued medicine and functional food, is the main part used for medicinal purposes. However, the stems and leaves are also used in practice. To provide a chemical basis for various uses, a quantitative comparison of 18 saponins using a non-targeted metabolomics approach was established, so as to investigate the chemical profiles of the different parts of P. notoginseng. The established strategy revealed that roots and stems, with their similar chemical characteristics, consisted mainly of protopanaxatriol-type saponins, whereas protopanaxadiol-type saponins were principally present in the leaves. Multivariate analysis further suggested that the quality of the stems and leaves of P. notoginseng was significantly affected by its geographical origin. Furthermore, 52 constituents (26 non-volatile and 26 volatile) were identified as potential markers for discriminating between different parts of the plant. Taken together, the study provides comprehensive chemical evidence for the rational application and exploitation of different parts of P. notoginseng.
Validation of a Visually Aided Dietary Assessment Tool to Estimate Dietary Intake in an Adult Swiss Population
Authors: Nève Gilles , Bur Laura , Lampert Ladina , Höchsmann Christoph , Brombach Christine , Steinemann Nina , Schmidt-Trucksäss Arno
Published: April 2022

Background

Accurately assessing dietary intake is crucial for understanding how diet affects a person’s health. In large cohorts, paper-based dietary assessment tools (DAT) such as food recalls or food frequency questionnaires have emerged as valid tools with a low burden for participants.

Objective

To validate a visually aided DAT for use in studies with Swiss adults against the gold standard of a weighed 7-day food record (7 d-FR).

Design

Fifty-one adults (n = 24 women, n = 27 males) participated in the study and were recruited within two age groups (20–40 and 50–70 y). Each participant filled out the visually aided DAT, then the 7 d-FR. The DAT was compared to the 7 d-FR for total energy intake, macronutrients, sugar, water, and portions of fruits and vegetables. Pearson correlation and Bland–Altman analyses were used for statistical analyses.

Results

Total correlations ranged from 0.288 (sugar, p < 0.05) to 0.729 (water, p < 0.01). The older age group showed higher correlations for total energy intake, protein, fats, carbohydrates, and sugar, but not for water (p < 0.05). Correlations were moderate at r > 0.5, whereas only water and protein reached those values in the young group. Both groups overestimated total calories in kcal (+14.0%), grams of protein (+ 44.6%), fats (+36.3%), and portions of fruits and vegetables (+16.0%) but strongly underestimated sugar intake (−50.9%).

Conclusion

This DAT showed that all macronutrients and total energy intake were estimated more accurately by the older age group and therefore might be adequate to capture dietary habits in older Swiss adults.
Effect of Individual and Selected Combined Treatments With Saline Solutions and Spent Engine Oil on the Processing Attributes and Functional Quality of Tomato (Solanum lycopersicon L.) Fruit: In Memory of Professor Leila Ben Jaballah Radhouane (1958–2021)
Authors: Ilahy Riadh , Tlili Imen , Pék Zoltán , Montefusco Anna , Daood Hussein , Azam Mohamed , Siddiqui Mohammed Wasim , R'him Thouraya , Durante Miriana , Lenucci Marcello Salvatore , Helyes Lajos
Published: April 2022

The results showed that soil electrical conductivity, (EC2: 7 dS/m) increased soluble solids, lycopene content, total phenolic content, hydrophilic and lipophilic radical scavenging activities (HRSA and LRSA) by 14.2, 149, 20, 46.4, and 19.0%, respectively, compared with control. Under 0.5% spent engine oil (SEO), flavonoid content decreased by 21.7% compared with the control. HRSA and LRSA of fruits subjected to EC2/SEO1 treatment were, respectively, 45.9 and 35.5% lower than control. The a*/b* ratio was positively and significantly (P < 0.01) correlated with β-carotene (R = 0.78), lycopene (R = 0.68), total vitamin C (R = 0.71), α-tocopherol (R = 0.83), γ-tocopherol (R = 0.66), HRSA (R = 0.93), LRSA (R = 0.80), and soluble solids (R = 0.84) suggesting that it may be a promising indicator of fruit quality in areas affected by such constraints. The research revealed that combined stresses induce responses markedly different from those of individual treatments, which strain the need to focus on how the interaction between stresses may affect the functional quality of tomato fruits.
High Dietary Salt Intake Is Associated With Histone Methylation in Salt-Sensitive Individuals
Authors: Liao Yueyuan , Chu Chao , Yan Yu , Wang Dan , Ma Qiong , Gao Ke , Sun Yue , Hu Jiawen , Zheng Wenling , Mu Jianjun
Published: April 2022

Background

High salt diet is one of the important risk factors of hypertension and cardiovascular diseases. Increasingly strong evidence supports epigenetic mechanisms' significant role in hypertension. We aimed to explore associations of epigenetics with high salt diet, salt sensitivity (SS), and SS hypertension.

Methods

We conducted a dietary intervention study of chronic salt loading in 339 subjects from northern China in 2004 and divided the subjects into different salt sensitivity phenotypes. A total of 152 participants were randomly selected from the same cohort for follow-up in 2018 to explore the effect of a high-salt diet on serum monomethylation of H3K4 (H3K4me1), histone methyltransferase Set7, and lysine-specific demethylase 1 (LSD-1).

Results

Among SS individuals, the blood pressure (SBP: 140.8 vs. 132.9 mmHg; MAP: 104.2 vs. 98.7 mmHg) and prevalence of hypertension (58.8 vs. 32.8%) were significantly higher in high salt (HS) diet group than in normal salt (NS) diet group, but not in the salt-resistant (SR) individuals (P > 0.05). Serum H3K4me1 level (287.3 vs. 179.7 pg/ml, P < 0.05) significantly increased in HS group of SS individuals, but not in SR individuals. We found daily salt intake in SS individuals was positively correlated with serum H3K4me1 (r = 0.322, P = 0.005) and Set7 (r = 0.340, P = 0.005) levels after adjusting for age and gender, but not with LSD-1 (r = −0.137, P = 0.251). In addition, positive correlation between the serum H3K4me1 level and Set7 level (r = 0.326, P = 0.007) was also found in SS individuals. These correlations were not evident in SR individuals.

Conclusion

Our study indicates that high salt diet increases the serum H3K4me1 and Set7 levels in SS individuals.
Effect of a High Protein, Low Glycemic Index Dietary Intervention on Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial
Authors: Sun Ping , Huang Liping , Shuai Ping , Wan Zhengwei , Liu Yingying , Xue Jianqiang , Liu Yuping
Published: April 2022

Background:

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects people at an increasingly younger age. The primary treatment for patients with MAFLD is diet-induced weight loss; however, excessive dieting is poorly effective.

Objectives

The aim of this trial was to evaluate whether a high protein and low glycemic index (HPLG) dietary intervention would result in improvement of controlled attenuation parameter (CAP) and related metabolic markers in MAFLD.

Methods

A 12-week controlled, parallel-group, randomized intervention trial was performed. A number of 63 participants with MAFLD were enrolled and randomized between the HPLG dietary group and the balanced diet control group. Both diets had the same hypocaloric level and were prescribed ad libitum within food limit lists. The primary outcome was CAP. The main secondary outcomes were weight loss and improvement of metabolism-related indexes at week 12 after the program initiation.

Results

A total of 59 participants completed the intervention and were included in the final analysis. The mean age was 39.3 ± 8.9 years and 66.1% were men. In this trial, protein and carbohydrate intakes were significantly higher and lower, respectively, in the HPLG group compared to controls (p < 0.001). At week 12, CAP was significantly reduced in both groups (p < 0.001). However, a significantly greater reduction in liver fat was observed in the HPLG group compared to the control group (p = 0.011), with mean relative reductions of 30.90 dB/m (95% CI, 21.53 to 40.26, p < 0.001) and 15.43 dB/m (95% CI, 7.57 to 23.30, p < 0.001), respectively. From baseline to week 12, a significantly greater loss in bodyweight was recorded in participants in the HPLG group (6.52 kg; 95% CI, 5.50 to 7.54, p < 0.001) compared to control subjects (2.00 kg; 95% CI, 0.89 to 3.11, p = 0.001). Moreover, body fat percentage in the HPLG group was significantly reduced compared with the control group (p = 0.002). Within-group improvements in visceral fat, blood pressure, cardiovascular risk factors, and blood glucose-related indicators were detected in patients with MAFLD assigned to the HPLG diet (p < 0.05), but not in those prescribed the control diet (p > 0.05).

Conclusion

Under our experimental conditions, and compared to the traditional balanced diet, an HPLG diet led to a significant CAP remission, bodyweight or fat reduction, and improvement of metabolic markers in patients with MAFLD.

Clinical Trial Registration

ClinicalTrials.gov, identifier: NCT03972631.
Excess DHA Induces Liver Injury via Lipid Peroxidation and Gut Microbiota-Derived Lipopolysaccharide in Zebrafish
Authors: Ding Qianwen , Hao Qiang , Zhang Qingshuang , Yang Yalin , Olsen Rolf Erik , Ringø Einar , Ran Chao , Zhang Zhen , Zhou Zhigang
Published: April 2022

Being highly unsaturated, n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) are prone to lipid peroxidation. In this study, zebrafish were fed with low-fat diet (LFD), high-fat diet (HFD), or 2% DHA-supplemented HFD (HFDHA2.0). To study the possible negative effects of the high level of dietary DHA, growth rates, blood chemistry, liver histology, hepatic oxidative stress, apoptosis, and inflammatory processes were assessed. The cell studies were used to quantify the effects of DHA and antioxidant on cellular lipid peroxidation and viability. The possible interaction between gut microbiota and zebrafish host was evaluated in vitro. HFDHA2.0 had no effect on hepatic lipid level but induced liver injury, oxidative stress, and hepatocellular apoptosis, including intrinsic and death receptor-induced apoptosis. Besides, the inclusion of 2% DHA in HFD increased the abundance of Proteobacteria in gut microbiota and serum endotoxin level. In the zebrafish liver cell model, DHA activated intrinsic apoptosis while the antioxidant 4-hydroxy-Tempo (tempo) inhibited the pro-apoptotic negative effects of DHA. The apoptosis induced by lipopolysaccharide (LPS) was unaffected by the addition of tempo. In conclusion, the excess DHA supplementation generates hepatocellular apoptosis-related injury to the liver. The processes might propagate along at least two routes, involving lipid peroxidation and gut microbiota-generated LPS.
Biotechnological Processes Simulating the Natural Fermentation Process of Bee Bread and Therapeutic Properties—An Overview
Authors: Barta Daniel Gabriel , Cornea-Cipcigan Mihaiela , Margaoan Rodica , Vodnar Dan Cristian
Published: April 2022

Recent signs of progress in functional foods and nutraceuticals highlighted the favorable impact of bioactive molecules on human health and longevity. As an outcome of the fermentation process, an increasing interest is developed in bee products. Bee bread (BB) is a different product intended for humans and bees, resulting from bee pollen's lactic fermentation in the honeycombs, abundant in polyphenols, nutrients (vitamins and proteins), fatty acids, and minerals. BB conservation is correlated to bacteria metabolites, mainly created by Pseudomonas spp., Lactobacillus spp., and Saccharomyces spp., which give lactic acid bacteria the ability to outperform other microbial groups. Because of enzymatic transformations, the fermentation process increases the content of new compounds. After the fermentation process is finalized, the meaningful content of lactic acid and several metabolites prevent the damage caused by various pathogens that could influence the quality of BB. Over the last few years, there has been an increase in bee pollen fermentation processes to unconventional dietary and functional supplements. The use of the chosen starters improves the bioavailability and digestibility of bioactive substances naturally found in bee pollen. As a consequence of enzymatic changes, the fermentation process enhances BB components and preserves them against loss of characteristics. In this aspect, the present review describes the current biotechnological advancements in the development of BB rich in beneficial components derived from bee pollen fermentation and its use as a food supplement and probiotic product with increased shelf life and multiple health benefits.
Evolution of Physicochemical Properties, Phenolic Acid Accumulation, and Dough-Making Quality of Whole Wheat Flour During Germination Under UV-B Radiation
Authors: Tian Chao , Wang Yue , Yang Tianbao , Sun Qingjie , Ma Meng , Li Man
Published: April 2022

The effects of ultraviolet-B (UV-B) radiation on the physiological properties, phenolic acid accumulation, and dough-making quality of wheat during germination were investigated. UV-B radiation inhibited the wheat sprout length and reduced the dry matter loss. As phenolic acids were principally present in the kernels' bran, UV-B radiation could promote their accumulation in the interior of germinated wheat (GW). The total phenolic compounds, ascorbic acid, and antioxidant activity were also enhanced significantly during germination with UV-B. UV-B improved the development time, stability time, rheological properties, and viscosity of GW, and inhibited the α-amylase activity, the destruction of the amorphous region of starch particles, and the proteins degradation process during germination, and thus the deterioration of dough-making quality caused by germination was inhibited. Therefore, UV-B radiation could be a potential approach to enhance the nutritional and dough-making quality of germinated whole wheat flour.