bluuebunny/crossref_metadata_2025 huggingface dataset:
PurN Is Involved in Antibiotic Tolerance and Virulence in Staphylococcus aureus
Authors: Peng Qi , Guo Lu , Dong Yu , Bao Tingrui , Wang Huiyuan , Xu Tao , Zhang Ying , Han Jian
Published: November 2022

Staphylococcus aureus can cause chronic infections which are closely related to persister formation. Purine metabolism is involved in S. aureus persister formation, and purN, encoding phosphoribosylglycinamide formyltransferase, is an important gene in the purine metabolism process. In this study, we generated a ΔpurN mutant of the S. aureus Newman strain and assessed its roles in antibiotic tolerance and virulence. The ΔpurN in the late exponential phase had a significant defect in persistence to antibiotics. Complementation of the ΔpurN restored its tolerance to different antibiotics. PurN significantly affected virulence gene expression, hemolytic ability, and biofilm formation in S. aureus. Moreover, the LD50 (3.28 × 1010 CFU/mL) of the ΔpurN for BALB/c mice was significantly higher than that of the parental strain (2.81 × 109 CFU/mL). Transcriptome analysis revealed that 58 genes that were involved in purine metabolism, alanine, aspartate, glutamate metabolism, and 2-oxocarboxylic acid metabolism, etc., were downregulated, while 24 genes involved in ABC transporter and transferase activity were upregulated in ΔpurN vs. parental strain. Protein-protein interaction network showed that there was a close relationship between PurN and GltB, and SaeRS. The study demonstrated that PurN participates in the formation of the late exponential phase S. aureus persisters via GltB and regulates its virulence by activating the SaeRS two-component system.
Colistin Monotherapy versus Colistin plus Sitafloxacin for Therapy of Carbapenem-Resistant Acinetobacter baumannii Infections: A Preliminary Study
Authors: Sirijatuphat Rujipas , Thawornkaew Supawas , Ruangkriengsin Darat , Thamlikitkul Visanu
Published: November 2022

The in vitro study of sitafloxacin against carbapenem-resistant (CR) Acinetobacter baumannii demonstrated activity against most strains of CR A. baumannii, and the combination of colistin and sitafloxacin showed an in vitro synergistic effect against CR A. baumannii. This study aimed to compare efficacy and safety between colistin plus sitafloxacin with colistin alone for therapy for CR A. baumannii infection. This randomized controlled trial enrolled 56 patients with CR A. baumannii infection (28/group) during 2018–2021, and the treatment duration was 7–14 days. The study outcomes were 28-day mortality, clinical and microbiological responses, and adverse events. There was no significant difference in 28-day mortality between groups (32.1% combination vs. 32.1% monotherapy, p = 1.000). Favorable clinical response at the end of treatment was comparable between groups (81.5% combination vs. 77.8% monotherapy, p = 0.788). Microbiological response at the end of treatment was also comparable between groups (73.1% combination vs. 74.1% monotherapy, p = 0.934). Acute kidney injury was found in 53.8% of the combination group, and in 45.8% of the monotherapy group (p = 0.571). In conclusion, there was no significant difference in 28-day mortality between the colistin monotherapy and the colistin plus sitafloxacin groups. There was also no significant difference in adverse events between groups.
Associating Biological Activity and Predicted Structure of Antimicrobial Peptides from Amphibians and Insects
Authors: Richter Amelia , Sutherland Darcy , Ebrahimikondori Hossein , Babcock Alana , Louie Nathan , Li Chenkai , Coombe Lauren , Lin Diana , Warren René L. , Yanai Anat , Kotkoff Monica , Helbing Caren C. , Hof Fraser , Hoang Linda M. N. , Birol Inanc
Published: November 2022

Antimicrobial peptides (AMPs) are a diverse class of short, often cationic biological molecules that present promising opportunities in the development of new therapeutics to combat antimicrobial resistance. Newly developed in silico methods offer the ability to rapidly discover numerous novel AMPs with a variety of physiochemical properties. Herein, using the rAMPage AMP discovery pipeline, we bioinformatically identified 51 AMP candidates from amphibia and insect RNA-seq data and present their in-depth characterization. The studied AMPs demonstrate activity against a panel of bacterial pathogens and have undetected or low toxicity to red blood cells and human cultured cells. Amino acid sequence analysis revealed that 30 of these bioactive peptides belong to either the Brevinin-1, Brevinin-2, Nigrocin-2, or Apidaecin AMP families. Prediction of three-dimensional structures using ColabFold indicated an association between peptides predicted to adopt a helical structure and broad-spectrum antibacterial activity against the Gram-negative and Gram-positive species tested in our panel. These findings highlight the utility of associating the diverse sequences of novel AMPs with their estimated peptide structures in categorizing AMPs and predicting their antimicrobial activity.
Occurrence of Campylobacter spp. and Phenotypic Antimicrobial Resistance Profiles of Campylobacter jejuni in Slaughtered Broiler Chickens in North-Western Romania
Authors: Popa Sebastian Alexandru , Morar Adriana , Ban-Cucerzan Alexandra , Tîrziu Emil , Herman Viorel , Sallam Khalid Ibrahim , Morar Doru , Acaroz Ulaș , Imre Mirela , Florea Tijana , Mukhtar Hamid , Imre Kálmán
Published: November 2022

Campylobacteriosis is recognized as one of the most common food-borne zoonoses, with worldwide distribution, having undercooked poultry meat and other cross-contaminated foodstuffs as the main sources of human infections. The current study aimed to provide data on the occurrence of the thermophilic Campylobacter spp. in seven broiler chicken flocks, from three north-western Transylvanian counties of Romania, as well as to determine the antimicrobial resistance profile of the isolated C. jejuni strains. A total of 324 fresh cecal samples were collected during the slaughtering process, and screened for the presence of Campylobacter spp., using routine microbiological and molecular diagnostic tools. Overall, 85.2% (276/324; 95% CI 80.9–88.6) of the tested samples expressed positive results for Campylobacter spp., with dominant occurrence of C. coli towards C. jejuni (63.4% vs. 36.6%). From the six tested antimicrobials, the 101 isolated C. jejuni strains were resistant against ciprofloxacin (79.2%), nalidixic acid (78.2%), tetracycline (49.5%), and streptomycin (7.9%), but total susceptibility was noticed against erythromycin and gentamicin. Seven (6.9%) isolates exhibited multidrug resistance. The study results emphasize the role of broiler chicken as reservoir of Campylobacter infections for humans, as well as strengthen the necessity of the prudent using of antimicrobials in the poultry industry.
Study of SarA by DNA Affinity Capture Assay (DACA) Employing Three Promoters of Key Virulence and Resistance Genes in Methicillin-Resistant Staphylococcus aureus
Authors: Kim Byungchan , Lee Hong-Ju , Jo Sung-Hyun , Kim Min-Gyu , Lee Yeonhee , Lee Wonsik , Kim Wooseong , Joo Hwang-Soo , Kim Yun-Gon , Kim Jae-Seok , Yang Yung-Hun
Published: November 2022

Methicillin-resistant Staphylococcus aureus (MRSA), one of the most well-known human pathogens, houses many virulence factors and regulatory proteins that confer resistance to diverse antibiotics. Although they have been investigated intensively, the correlations among virulence factors, regulatory proteins and antibiotic resistance are still elusive. We aimed to identify the most significant global MRSA regulator by concurrently analyzing protein-binding and several promoters under same conditions and at the same time point. DNA affinity capture assay (DACA) was performed with the promoters of mecA, sarA, and sarR, all of which significantly impact survival of MRSA. Here, we show that SarA protein binds to all three promoters. Consistent with the previous reports, ΔsarA mutant exhibited weakened antibiotic resistance to oxacillin and reduced biofilm formation. Additionally, production and activity of many virulence factors such as phenol-soluble modulins (PSM), α-hemolysin, motility, staphyloxanthin, and other related proteins were decreased. Comparing the sequence of SarA with that of clinical strains of various lineages showed that all sequences were highly conserved, in contrast to that observed for AgrA, another major regulator of virulence and resistance in MRSA. We have demonstrated that SarA regulates antibiotic resistance and the expression of various virulence factors. Our results warrant that SarA could be a leading target for developing therapeutic agents against MRSA infections.
The Sample Error Pre-Antimicrobial Susceptibility Testing and Its Influencing Factors from the Perspective of Hospital Management: A Cross-Sectional Study
Authors: Wu Yuanyang , Wang Qianning , Zheng Feiyang , Yu Tiantian , Wang Yanting , Fan Si , Zhang Xinping
Published: November 2022

The overuse of antibiotics remains serious and has led to a dramatic increase in antimicrobial resistance, which poses a significant threat to global public health, although much action has been taken by World Health Organization and countries. As the direct evidence to guide the prescribing of antibiotics, the Antimicrobial Susceptibility Testing (AST) results were biased by sample errors, which was urgent and poorly explored in quality management. This study aimed to analyze sample errors pre-AST and its influencing factors from the perspective of hospital management, to provide evidence for promoting rational antibiotic use and antimicrobial stewardship. A cross-sectional survey of 5963 clinical nurses involved in pathogenic sample collection was conducted in 118 public hospitals in Hubei province, China. Dependent variables were sample errors attributed to resources and technology-oriented, capability-oriented, and attitude-oriented errors, which were measured by times per week. Independent variables were sample management information such as guidelines, record after collection, performance appraisal, training, and publicity activities, in which guidelines, record time, and record method were dummy variables, with 1 indicating having and 0 not. Others were continuous variables ranging from 0 to 4 times per month. Ordinary Least Square regression models were performed to analyze influencing factors on sample error times. The averages of sample errors on resource and technology-oriented, capability-oriented, and attitude-oriented were 1.48, 1.35, and 1.36 times per week, and their proportion were 25.3%, 38.9%, and 35.8%, respectively. The results showed that recording timeliness (r = −0.354, p < 0.01), record using both paper and digital methods(r = −0.060, p < 0.01), performance appraisal(r = −0.188, p < 0.01), and publicity activities (r = −0.186, p < 0.01) significantly reduced times of resource and technology-oriented errors. Performance appraisals(r = −0.171, p < 0.01) and training activities (r = −0.208, p < 0.01) had a positive impact on the reduction of capability-oriented error times. The times of attitude-oriented error decreased significantly when recording timeliness (r = −0.299, p < 0.01), implementing performance appraisal (r = −0.164, p < 0.01), and training activities (r = −0.188, p < 0.01). This study found that there was a high frequency of sample errors in quality management, especially capability-oriented and attitude-oriented errors. Sample information management, performance appraisal, training, and publicity activities were associated with the quality of samples valuable for the rational use of antibiotics.
Air Monitoring of Polychlorinated Biphenyls and Organochlorine Pesticides in Eastern Siberia: Levels, Temporal Trends, and Risk Assessment
Authors: Mamontova Elena A. , Mamontov Alexander A.
Published: November 2022

In this study, we evaluate the long-term and seasonal variations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), α-, γ-hexachlorocyclohexanes (HCH), and p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) and its metabolites through a passive air sampling method at two (urban and suburban) stations in Eastern Siberia, Russia, in 2011–2017. The median levels of HCB, ∑HCHs, ∑DDTs, ∑PCB39, and ∑PCB6 in the air were 116, 84, 55, 128, and 41 pg/m3 and 83, 21, 11, 52, and 16 pg/m3 at the urban and suburban stations, respectively. PCB and HCH levels in the air of Irkutsk decreased considerably in the 2000s, in comparison to the late 1980s and early 1990s, while an increasing trend was observed for HCB during the 2010s. The seasonality of air concentrations (with summer concentrations higher than winter concentrations) was well exhibited by PCB, HCH, and DDT, but not HCB. Significant correlations were observed between approximately all studied persistent organic pollutants and the average air temperature, quantity of precipitation, and frequency of the prevailing wind direction during the sampling period. The daily doses of PCBs, DDTs, HCHs, and HCB under human exposure by inhalation amounted to 38, 21, 27, and 35 and 17, 6, 7, and 27 pg/kg body weight per day in urban and suburban areas, respectively.
The Effect of Assimilating AMSU-A Radiance Data from Satellites and Large-Scale Flows from GFS on Improving Tropical Cyclone Track Forecast
Authors: Lai Zhijuan , Peng Shiqiu
Published: November 2022

This study aimed to investigate the effect of assimilating either AMSU-A radiance data from satellites, large-scale flows from the Global Forecast System (GFS), or both together, on improving the track forecast of tropical cyclone (TC). The scale-selective data assimilation (SSDA) approach was employed for the assimilation of large-scale GFS flows, while the conventional 3D variational data assimilation (3DVAR) method was used for that of AMSU-A radiance data. The results show that assimilating either AMSU-A radiance data or large-scale GFS flows has a significant improvement on TC track forecast, but the improvement occurs within the first 72 h and after 72 h, respectively. When assimilating both AMSU-A radiance data and large-scale GFS flows, the forecast can take advantage of both data and thus lead to the smallest 5-day mean errors of the track forecast. These results are instructive to future operational TC track forecasting.
Air Quality Assessment along China-Pakistan Economic Corridor at the Confluence of Himalaya-Karakoram-Hindukush
Authors: Ahmad Maqbool , Hussain Khadim , Nasir Jawad , Huang Zhongwei , Alam Khan , Liaquat Samreen , Wang Peng , Hussain Waqar , Mihaylova Lyudmila , Ali Ajaz , Farhan Suhaib Bin
Published: November 2022

Recently, analyses of the air quality in Pakistan have received significant interest, especially regarding the impact of air pollutant concentrations on human health. The Atlas of Baseline Environmental Profiling along the China-Pakistan Economic Corridor (CPEC) at five locations in Gilgit-Baltistan (GB) is a major landmark in this regard due to the presence of massive glaciers in the region, which are considered as water reserves for the country. Using various statistical measurements, the air quality was analyzed at the studied geographic locations. Further, air quality was evaluated based on air pollutant data acquired from ambient air monitoring laboratories. For example, 24 h concentrations of particulate matter (PM2.5) were found to range from 25.4 to 60.1 µg/m3, with peaks in the winter season at Gilgit. It was found that PM2.5 values were 1.7 and 1.3 times greater than National Environmental Quality Standards (NEQS) standards only at Gilgit and Chilas, respectively, and 1.5 to 4 times greater than the World Health Organization (WHO) standards at all locations. Similarly, PM2.5 concentrations were found to range from 31.4 to 63.9 µg/m3, peaking at Chilas in summer 2020. The observed values were 1.1 to 1.8 times and 2 to 4.2 times greater than the NEQS and WHO standards, respectively, at all locations. In addition, the average peaks of black carbon (BC) were measured at Gilgit, both in winter (16.21 µg/m3) and summer (7.83 µg/m3). These elevated levels could be attributed to the use of heavy diesel vehicles, various road activities and different meteorological conditions. Pollutants such as carbon monoxide (CO), sulfur dioxide (SO2), nitrogen oxides (NOX) and ozone (O3) were found to be within NEQS and WHO limits. Based on air quality metrics, the effect of PM2.5 on air quality was found to be moderate in Sost, Hunza and Jaglot, while it was at unhealthy levels at Gilgit and Chilas in the winter of 2019; moderate levels were observed at Sost while unhealthy levels were detected at the remaining locations in the summer of 2020. There are no specific guidelines for BC. However, it is associated with PM2.5, which was found to be a major pollutant at all locations. The concentrations of CO, SO2 and O3 were found to be at safe levels at all locations. The major fraction of air masses is received either locally or from transboundary emissions. This study demonstrates that PM2.5 and BC are the major and prevailing air pollutants within the study region, while other air pollutants were found to be within the permissible limits of the WHO and NEQS.
Nearly Sasakian Manifolds of Constant Type
Authors: Rustanov Aligadzhi
Published: November 2022

The article deals with nearly Sasakian manifolds of a constant type. It is proved that the almost Hermitian structure induced on the integral manifolds of the maximum dimension of the first fundamental distribution of the nearly Sasakian manifold is a nearly Kähler manifold. It is proved that the class of nearly Sasakian manifolds of the zero constant type coincides with the class of Sasakian manifolds. The concept of constancy of the type of an almost contact metric manifold is introduced through its Nijenhuis tensor, and the criterion of constancy of the type of an almost contact metric manifold is proved. The coincidence of both concepts of type constancy for the nearly Sasakian manifold is proved. It is proved that the almost Hermitian structure induced on the integral manifolds of the maximum dimension of the first fundamental distribution of the almost contact metric manifold of the zero constant type is the Hermitian structure.
Intravascular Ultrasonography (IVUS)—A Tool for Imaging the Eustachian Tube?
Authors: Oppel Niels , Paasche Gerrit , Bleich Andre , Lenarz Thomas , Schuon Robert
Published: November 2022

The Eustachian tube (ET) has a key role in the pathogenesis of otitis media. Until now, there has been a lack of meaningful imaging methods to investigate the ET and its surrounding tissue. The aim of the current study was to investigate the possibilities of imaging the ET using Intravascular Ultrasonography (IVUS). ETs from sheep were scanned ex vivo and in vivo with different IVUS probes. In addition to native ETs, water was also used to improve coupling. Scans were subsequently compared with histological sections and a 3D model of the ET. In addition, ETs with a stenosis induced by a hyaluronic acid depot, after stent insertion, and during lower jaw movement were examined. The IVUS catheter was inserted into the ET lumen without any problems or injuries in all cases. The surrounding structures of the ET were identified in the ultrasound image. In addition, a change in size of the ET lumen due to movement was observed, and the position of the stent and the depot of hyaluronic acid could be examined. With the use of IVUS, a non-invasive possibility to examine the ET over its course with the adjacent structures as well as after different treatments is presented.
Pomegranate Pomace Extract with Antioxidant, Anticancer, Antimicrobial, and Antiviral Activity Enhances the Quality of Strawberry-Yogurt Smoothie
Authors: Alsubhi Nouf H. , Al-Quwaie Diana A. , Alrefaei Ghadeer I. , Alharbi Mona , Binothman Najat , Aljadani Majidah , Qahl Safa H. , Jaber Fatima A. , Huwaikem Mashael , Sheikh Huda M. , Alrahimi Jehan , Abd Elhafez Ahmed N. , Saad Ahmed
Published: November 2022

Valorizing the wastes of the food industry sector as additives in foods and beverages enhances human health and preserves the environment. In this study, pomegranate pomace (PP) was obtained from the company Schweppes and exposed to the production of polyphenols and fiber-enriched fractions, which were subsequently included in a strawberry-yogurt smoothie (SYS). The PP is rich in carbohydrates and fibers and has high water-absorption capacity (WAC) and oil-absorption capacity (OAC) values. The LC/MS phenolic profile of the PP extract indicated that punicalagin (199 g/L) was the main compound, followed by granatin B (60 g/L) and pedunculagin A (52 g/L). Because of the high phenolic content of PP extract, it (p ≤ 0.05) has high antioxidant activity with SC50 of 200 µg/mL, besides scavenging 95% of DPPH radicals compared to ascorbic acid (92%); consequently, it reduced lung cancer cell lines’ viability to 86%, and increased caspase-3 activity. Additionally, it inhibited the growth of pathogenic bacteria and fungi i.e., L. monocytogenes, P. aeruginosa, K. pneumonia, A. niger, and C. glabrata, in the 45–160 µg/mL concentration range while killing the tested isolates with 80–290 µg/mL concentrations. These isolates were selected based on the microbial count of spoiled smoothie samples and were identified at the gene level by 16S rRNA gene sequence analysis. The interaction between Spike and ACE2 was inhibited by 75.6%. The PP extract at four levels (0.4, 0.8, 1.2, and 1.4 mg/mL) was added to strawberry-yogurt smoothie formulations. During 2 months storage at 4 °C, the pH values, vitamin C, and total sugars of all SYS decreased. However, the decreases were gradually mitigated in PP-SYS because of the high phenolic content in the PP extract compared to the control. The PP-SYS3 and PP-SYS4 scored higher in flavor, color, and texture than in other samples. In contrast, acidity, fat, and total soluble solids (TSS) increased at the end of the storage period. High fat and TSS content are observed in PP-SYS because of the high fiber content in PP. The PP extract (1.2 and 1.6 mg/mL) decreases the color differences and reduces harmful microbes in PP-SYS compared to the control. Using pomegranate pomace as a source of polyphenols and fiber in functional foods enhances SYS’s physiochemical and sensory qualities.
Intrinsic Disorder as a Natural Preservative: High Levels of Intrinsic Disorder in Proteins Found in the 2600-Year-Old Human Brain
Authors: Mohammed Aaron , Uversky Vladimir
Published: November 2022

Proteomic analysis revealed the preservation of many proteins in the Heslington brain (which is at least 2600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins—“main proteins”: heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein—are engaged in the formation of non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as the main proteins and their 44 interactors, all other proteins identified in the Heslington brain, as well as the entire human proteome (20,317 manually curated proteins), and 10,611 brain proteins. These analyses revealed that all five main proteins, half of their interactors and almost one third of the Heslington brain proteins are expected to be mostly disordered. Furthermore, most of the remaining Heslington brain proteins are expected to contain sizable levels of disorder. This is contrary to the expected substantial (if not complete) elimination of the disordered proteins from the Heslington brain. Therefore, it seems that the intrinsic disorder of NFH, NFM, NFL, GFAP, and MBP, their interactors, and many other proteins might play a crucial role in preserving the Heslington brain by forming tightly folded brain protein aggregates, in which different parts are glued together via the disorder-to-order transitions.
Significant Interrelations among Serum Annexin A1, Soluble Receptor for Advanced Glycation End Products (sRAGE) and rs2070600 in Chronic Obstructive Pulmonary Disease
Authors: Kamel Amira A. , Hashem Maiada K. , AbdulKareem Ebtsam S. , Ali Amal H. , Mahmoud Ekram Abdel-Rahman , Abd-Elkader Alaa S. , Abdellatif Hebatallah , Abdelbadea Alzahra , Abdel-Rady Nessren M. , Al Anany Mona Gamal E. , Dahpy Marwa A.
Published: November 2022

Chronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity; it may be accompanied by oxidative stress and inflammation with or without underlying genetic etiology. Finding circulating biomarkers for COPD that can help early diagnosis and predict exacerbation and association with respiratory functions has been challenging. There were 40 healthy participants and 60 COPD patients in this research. The rs2070600 gene variant was examined by PCR-RFLP. Circulating sRAGE and annexin A1 levels were determined by ELISA. GSH and MDA were determined by spectrophotometry. In COPD patients, sRAGE serum levels were substantially lower, but conversely, annexin A1 levels were much greater than in controls. The rs2070600 gene polymorphism’s strong association with COPD was demonstrated by genotyping and allelic frequency distribution. The GA genotype was most distributed in COPD, and it was strongly linked to lower serum sRAGE levels. The interrelation between annexin A1, sRAGE, and COPD could be explained through effects on inflammatory mediators’ pathways. The rs2070600 gene polymorphism was found to significantly enhance the risk of COPD. Serum sRAGE and annexin A1 may be considered potential diagnostic tools for COPD. Through impacts on GSH and MDA levels that alter the release of inflammatory factors and, therefore, lung damage, it is possible to explain the relationship between annexin A1, sRAGE, and COPD.
A Review of Pseudomonas aeruginosa Metallophores: Pyoverdine, Pyochelin and Pseudopaline
Authors: Ghssein Ghassan , Ezzeddine Zeinab
Published: November 2022

P. aeruginosa is a common Gram-negative bacterium found in nature that causes severe infections in humans. As a result of its natural resistance to antibiotics and the ability of biofilm formation, the infection with this pathogen can be therapeutic challenging. During infection, P. aeruginosa produces secondary metabolites such as metallophores that play an important role in their virulence. Metallophores are metal ions chelating molecules secreted by bacteria, thus allowing them to survive in the host under metal scarce conditions. Pyoverdine, pyochelin and pseudopaline are the three metallophores secreted by P. aeruginosa. Pyoverdines are the primary siderophores that acquire iron from the surrounding medium. These molecules scavenge and transport iron to the bacterium intracellular compartment. Pyochelin is another siderophore produced by this bacterium, but in lower quantities and its affinity for iron is less than that of pyoverdine. The third metallophore, pseudopaline, is an opine narrow spectrum ion chelator that enables P. aeruginosa to uptake zinc in particular but can transport nickel and cobalt as well. This review describes all the aspects related to these three metallophore, including their main features, biosynthesis process, secretion and uptake when loaded by metals, in addition to the genetic regulation responsible for their synthesis and secretion.
Anthocyanins Profiling Analysis and RNA-Seq Revealed the Dominating Pigments and Coloring Mechanism in Cyclamen Flowers
Authors: Xia Demei , He Guoqiang , Wang Kai , Wang Taoyuan , Zhu Zhiguo , Niu Zhaoqian , Shi Gongfa , Liu Guiling
Published: November 2022

Pigments in cyclamen (Cyclamen purpurascens) endows flowers with great ornamental and medicinal values. However, little is known about the biosynthetic pathways of pigments, especially anthocyanins, in cyclamen flowers. Herein, anthocyanins profiling and RNA-Seq were used to decipher the molecular events using cyclamen genotypes of red (HXK) or white (BXK) flowers. We found that red cyclamen petals are rich in cyanidin-3-O-rutinoside, cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, malvidin-3-O-glucoside, peonidin-3-O-rutinoside, quercetin-3-O-glucoside, and ruti. In addition, our transcriptomics data revealed 3589 up-regulated genes and 2788 down-regulated genes comparing the BXK to HXK. Our rich dataset also identified eight putative key genes for anthocyanin synthesis, including four chalcone synthase (CHS, g13809_i0, g12097_i0, g18851_i0, g36714_i0), one chalcone isomerase (CHI, g26337_i0), two flavonoid 3-hydroxylase (F3′H, g14710_i0 and g15005_i0), and one anthocyanidin synthase (ANS, g18981_i0). Importantly, we found a 2.5 order of magnitude higher expression of anthocyanin 3-O-glucosyltransferase (g8206_i0), which encodes a key gene in glycosylation of anthocyanins, in HXK compared to BXK. Taken together, our multiomics approach demonstrated massive changes in gene regulatory networks and anthocyanin metabolism in controlling cyclamen flower color.
Exploring the Relationship between Biological Maturation Level, Muscle Strength, and Muscle Power in Adolescents
Authors: Yapici Hakan , Gulu Mehmet , Yagin Fatma Hilal , Eken Ozgur , Gabrys Tomasz , Knappova Vera
Published: November 2022

The purpose of this study was to investigate the relationship between adolescents’ biological maturation level and their muscle power, as well as their overall muscle strength. Overall, 691 adolescents (414 boys and 277 girls) aged 12.01–11.96 (measured for body mass, body height as well as vertical jump, muscle power, and muscle strength). There was a statistically significant difference in terms of average right and left grip strength, vertical jump, and power in the late maturation group. For the body height and vertical jump averages in male adolescents, it was observed that the body height and vertical jump averages in the late group were significantly lower than in the early and on-time maturation groups. For female adolescents’ chronological age, sitting height, body mass, BMI, left and right grip strength, and power averages were found to be significantly higher compared with the on-time group (p < 0.05). It was established that biological maturation has a substantial link with vertical jump height and power, as well as grip strength on the right and left hands.
Carbapenem-Resistant Gram-Negative Fermenting and Non-Fermenting Rods Isolated from Hospital Patients in Poland—What Are They Susceptible to?
Authors: Brauncajs Małgorzata , Bielec Filip , Macieja Anna , Pastuszak-Lewandoska Dorota
Published: November 2022

Gram-negative fermenting and non-fermenting bacteria are important etiological factors of nosocomial and community infections, especially those that produce carbapenemases. Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most frequently-detected carbapenemase-producing microorganisms. The predominant type of resistance is metallo-β-lactamase (MBL). These bacteria are predominantly isolated from bronchial alveolar lavage, urine, and blood. Carbapenemase-producing Enterobacterales (CPE) strains are always multi-drug-resistant. This significantly limits the treatment options for this type of infection, extends the time of patient hospitalization, and increases the risk of a more severe and complicated disease course. Preventing the transmission of these microorganisms should be a major public health initiative. New antibiotics and treatment regimens offer hope against these infections.
Tissue Characterization in Cardiac Amyloidosis
Authors: Musetti Veronica , Greco Francesco , Castiglione Vincenzo , Aimo Alberto , Palmieri Cataldo , Genovesi Dario , Giorgetti Assuero , Emdin Michele , Vergaro Giuseppe , McDonnell Liam A. , Pucci Angela
Published: November 2022

Cardiac amyloidosis (CA) has long been considered a rare disease, but recent advancements in diagnostic tools have led to a reconsideration of the epidemiology of CA. Amyloid light-chain (AL) and transthyretin (ATTR) amyloidoses are the most common forms of cardiac amyloidosis. Due to the distinct treatments and the different prognoses, amyloid typing is crucial. Although a non-biopsy diagnosis can be obtained in ATTR amyloidosis when certain diagnostic criteria are fulfilled, tissue characterization still represents the gold standard for the diagnosis and typing of CA, particularly in AL amyloidosis. The present review focuses on the status of tissue characterization in cardiac amyloidosis, from histochemistry to immunohistochemistry and mass spectrometry, as well as on its future directions.
NLRP3-Inflammasome Inhibition with IZD334 Does Not Reduce Cardiac Damage in a Pig Model of Myocardial Infarction
Authors: Silvis Max J. M. , Demkes Evelyne J. , Timmers Leo , Arslan Fatih , de Jager Saskia C. A. , Sluijter Joost P. G. , Mosterd Arend , de Kleijn Dominique P. V. , Bosch Lena , van Hout Gerardus P. J.
Published: November 2022

NLRP3-inflammasome-mediated signaling is thought to significantly contribute to the extent of myocardial damage after myocardial infarction (MI). The purpose of this study was to investigate the effects of the NLRP3-inflammasome inhibitor IZD334 on cardiac damage in a pig model of myocardial infarction. Prior to in vivo testing, in vitro, porcine peripheral blood mononuclear cells and whole blood were treated with increasing dosages of IZD334, a novel NLRP3-inflammasome inhibitor, and were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). After determination of the pharmacological profile in healthy pigs, thirty female Landrace pigs were subjected to 75 min of transluminal balloon occlusion of the LAD coronary artery and treated with placebo or IZD334 (1 mg/kg, 3 mg/kg, or 10 mg/kg once daily) in a blinded randomized fashion. In vitro, NLRP3-inflammasome stimulation showed the pronounced release of interleukin (IL)-1β that was attenuated by IZD334 (p < 0.001). In vivo, no differences were observed between groups in serological markers of inflammation nor myocardial IL-1β expression. After 7 days, the ejection fraction did not differ between groups, as assessed with MRI (placebo: 45.1 ± 8.7%, 1 mg/kg: 49.9 ± 6.1%, 3 mg/kg: 42.7 ± 3.8%, 10 mg/kg: 44.9 ± 6.4%, p = 0.26). Infarct size as a percentage of the area at risk was not reduced (placebo: 73.1 ± 3.0%, 1 mg/kg: 75.5 ± 7.3%, 3 mg/kg: 80.3 ± 3.9%, 10 mg/kg: 78.2 ± 8.0%, p = 0.21). In this pig MI model, we did not observe attenuation of the inflammatory response after NLRP3-inflammasome inhibition in vivo. Consecutively, no difference was observed in IS and cardiac function, while in vitro inhibition successfully reduced IL-1β release from stimulated porcine blood cells.
Investigation of Cerebral Autoregulation Using Time-Frequency Transformations
Authors: Semenyutin Vladimir , Antonov Valery , Malykhina Galina , Salnikov Vyacheslav
Published: November 2022

The authors carried out the study of the state of systemic and cerebral hemodynamics in normal conditions and in various neurosurgical pathologies using modern signal processing methods. The results characterize the condition for the mechanisms of cerebral circulation Institute of Computer Science and Control, Higher School of Cyber-Physical Systems and Control regulation, which allows for finding a solution to fundamental and specific clinical problems for the effective treatment of patients with various pathologies. The proposed method is based on the continuous wavelet transform of systemic arterial pressure and blood flow velocity signals in the middle cerebral artery recorded by non-invasive methods of photoplethysmography and transcranial doppler ultrasonography. The study of these signals in real-time in the frequency range of Mayer waves makes it possible to determine the cerebral autoregulation state in certain diseases before and after surgical interventions. The proposed method uses a cross-wavelet spectrum, which helps obtain wavelet coherence and a phase shift between the wavelet coefficients of systemic arterial pressure signals and blood flow velocity in the Mayer wave range. The obtained results enable comparing the proposed method with that based on the short-time Fourier transform. The comparison showed that the proposed method has higher sensitivity to changes in cerebral autoregulation and better localization of changes in time and frequency.
Antioxidant Intervention against Male Infertility: Time to Design Novel Strategies
Authors: Ávila Cristóbal , Vinay José Ignacio , Arese Marzia , Saso Luciano , Rodrigo Ramón
Published: November 2022

Infertility is a highly prevalent condition, affecting 9–20% of couples worldwide. Among the identifiable causes, the male factor stands out in about half of infertile couples, representing a growing problem. Accordingly, there has been a decline in both global fertility rates and sperm counts in recent years. Remarkably, nearly 80% of cases of male infertility (MI) have no clinically identifiable aetiology. Among the mechanisms likely plausible to account for idiopathic cases, oxidative stress (OS) has currently been increasingly recognized as a key factor in MI, through phenomena such as mitochondrial dysfunction, lipid peroxidation, DNA damage and fragmentation and finally, sperm apoptosis. In addition, elevated reactive oxygen species (ROS) levels in semen are associated with worse reproductive outcomes. However, despite an increasing understanding on the role of OS in the pathophysiology of MI, therapeutic interventions based on antioxidants have not yet provided a consistent benefit for MI, and there is currently no clear consensus on the optimal antioxidant constituents or regimen. Therefore, there is currently no applicable antioxidant treatment against this problem. This review presents an approach aimed at designing an antioxidant strategy based on the particular biological properties of sperm and their relationships with OS.
Development of Fluorescent Turn-On Probes for CAG-RNA Repeats
Authors: Lau Matthew Ho Yan , Wong Chun-Ho , Chan Ho Yin Edwin , Au-Yeung Ho Yu
Published: November 2022

Fluorescent sensing of nucleic acids is a highly sensitive and efficient bioanalytical method for their study in cellular processes, detection and diagnosis in related diseases. However, the design of small molecule fluorescent probes for the selective binding and detection of RNA of a specific sequence is very challenging because of their diverse, dynamic, and flexible structures. By modifying a bis(amidinium)-based small molecular binder that is known to selectively target RNA with CAG repeats using an environment-sensitive fluorophore, a turn-on fluorescent probe featuring aggregation-induced emission (AIE) is successfully developed in this proof-of-concept study. The probe (DB-TPE) exhibits a strong, 19-fold fluorescence enhancement upon binding to a short CAG RNA, and the binding and fluorescence response was found to be specific to the overall RNA secondary structure with A·A mismatches. These promising analytical performances suggest that the probe could be applied in pathological studies, disease progression monitoring, as well as diagnosis of related neurodegenerative diseases due to expanded CAG RNA repeats.
Sodium-Alginate-Functionalized Silver Nanoparticles for Colorimetric Detection of Dimethoate
Authors: Zhou Feng-Zuo , Chang Yung-Hsiang , Hu Cho-Chun , Chiu Tai-Chia
Published: November 2022

Sodium alginate (SA) was used to functionalize the surfaces of silver nanoparticles (AgNPs) to form SA-AgNPs for sensing dimethoate with a rapid and sensitive visual readout. UV–Vis spectrophotometry, Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and zeta potential measurements were used to characterize SA-AgNPs that were synthesized under the ideal conditions. SA-AgNPs were spherical with an average size of 14.6 nm. The stability of SA-AgNPs was investigated with changes in pH, salinity, and storage time. This colorimetric assay of dimethoate relied on the change in the absorption ratio (A475/A400) of SA-AgNPs, resulting in their aggregation caused by dimethoate, leading to a visual change for SA-AgNPs from yellow to pale yellow. As a result, the absorption ratio (A475/A400) of SA-AgNPs showed good linearity in the range of 0.05 to 2.0 ppm (R2 = 0.9986) with a limit of detection (LOD) of 30 ppb. Adding other pesticides did not significantly change the absorption ratio of SA-AgNPs, indicating its high selectivity as a colorimetric assay. The sensor was successfully used to detect dimethoate in actual water samples.
Paper-Based Electrochemical Biosensors for Food Safety Analysis
Authors: Kuswandi Bambang , Hidayat Mochammad Amrun , Noviana Eka
Published: November 2022

Nowadays, foodborne pathogens and other food contaminants are among the major contributors to human illnesses and even deaths worldwide. There is a growing need for improvements in food safety globally. However, it is a challenge to detect and identify these harmful analytes in a rapid, sensitive, portable, and user-friendly manner. Recently, researchers have paid attention to the development of paper-based electrochemical biosensors due to their features and promising potential for food safety analysis. The use of paper in electrochemical biosensors offers several advantages such as device miniaturization, low sample consumption, inexpensive mass production, capillary force-driven fluid flow, and capability to store reagents within the pores of the paper substrate. Various paper-based electrochemical biosensors have been developed to enable the detection of foodborne pathogens and other contaminants that pose health hazards to humans. In this review, we discussed several aspects of the biosensors including different device designs (e.g., 2D and 3D devices), fabrication techniques, and electrode modification approaches that are often optimized to generate measurable signals for sensitive detection of analytes. The utilization of different nanomaterials for the modification of electrode surface to improve the detection of analytes via enzyme-, antigen/antibody-, DNA-, aptamer-, and cell-based bioassays is also described. Next, we discussed the current applications of the sensors to detect food contaminants such as foodborne pathogens, pesticides, veterinary drug residues, allergens, and heavy metals. Most of the electrochemical paper analytical devices (e-PADs) reviewed are small and portable, and therefore are suitable for field applications. Lastly, e-PADs are an excellent platform for food safety analysis owing to their user-friendliness, low cost, sensitivity, and a high potential for customization to meet certain analytical needs
Intermodulation from Unisensory to Multisensory Perception: A Review
Authors: Xu Shen , Zhou Xiaolin , Chen Lihan
Published: November 2022

Previous intermodulation (IM) studies have employed two (or more) temporal modulations of a stimulus, with different local elements of the stimulus being modulated by different frequencies. Brain activities of IM obtained mainly from electroencephalograms (EEG) have been analyzed in the frequency domain. As a powerful tool, IM, which can provide a direct and objective physiological measure of neural interaction, has emerged as a promising method to decipher neural interactions in visual perception, and reveal the underlying different perceptual processing levels. In this review, we summarize the recent applications of IM in visual perception, detail the protocols and types of IM, and extend its utility and potential applications to the multisensory domain. We propose that using IM could prevail in partially revealing the potential hierarchical processing of multisensory information and contribute to a deeper understanding of the underlying brain dynamics.
Explaining L2 Lexical Learning in Multiple Scenarios: Cross-Situational Word Learning in L1 Mandarin L2 English Speakers
Authors: Escudero Paola , Smit Eline A. , Mulak Karen E.
Published: November 2022

Adults commonly struggle with perceiving and recognizing the sounds and words of a second language (L2), especially when the L2 sounds do not have a counterpart in the learner’s first language (L1). We examined how L1 Mandarin L2 English speakers learned pseudo English words within a cross-situational word learning (CSWL) task previously presented to monolingual English and bilingual Mandarin-English speakers. CSWL is ambiguous because participants are not provided with direct mappings of words and object referents. Rather, learners discern word-object correspondences through tracking multiple co-occurrences across learning trials. The monolinguals and bilinguals tested in previous studies showed lower performance for pseudo words that formed vowel minimal pairs (e.g., /dit/-/dɪt/) than pseudo word which formed consonant minimal pairs (e.g., /bɔn/-/pɔn/) or non-minimal pairs which differed in all segments (e.g., /bɔn/-/dit/). In contrast, L1 Mandarin L2 English listeners struggled to learn all word pairs. We explain this seemingly contradicting finding by considering the multiplicity of acoustic cues in the stimuli presented to all participant groups. Stimuli were produced in infant-directed-speech (IDS) in order to compare performance by children and adults and because previous research had shown that IDS enhances L1 and L2 acquisition. We propose that the suprasegmental pitch variation in the vowels typical of IDS stimuli might be perceived as lexical tone distinctions for tonal language speakers who cannot fully inhibit their L1 activation, resulting in high lexical competition and diminished learning during an ambiguous word learning task. Our results are in line with the Second Language Linguistic Perception (L2LP) model which proposes that fine-grained acoustic information from multiple sources and the ability to switch between language modes affects non-native phonetic and lexical development.
Screening for Biomarkers for Progression from Oral Leukoplakia to Oral Squamous Cell Carcinoma and Evaluation of Diagnostic Efficacy by Multiple Machine Learning Algorithms
Authors: Jing Fengyang , Zhang Jianyun , Cai Xinjia , Zhou Xuan , Bai Jiaying , Zhang Heyu , Li Tiejun
Published: November 2022

The aim of the study is to identify key genes during the progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC) and predict effective diagnoses. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to identify seven genes associated with the progression from OL to OSCC. Twelve machine learning algorithms including k-nearest neighbor (KNN), neural network (NNet), and extreme gradient boosting (XGBoost) were used to construct multi-gene models, which revealed that each model had good diagnostic efficacy. The functional mechanism or the pathways associated with these genes were evaluated using enrichment analysis, subtype clustering, and immune infiltration analysis. The enrichment analysis revealed that the genes enriched were associated with the cell cycle, cell division, and intracellular energy metabolism. The immunoassay results revealed that the genes primarily affected the infiltration of proliferating T cells and macrophage polarization. Finally, a nomogram and Kaplan–Meier survival analysis were used to predict the prognostic efficacy of key genes in OSCC patients. The results showed that genes could predict the prognosis of the patients, and patients in the high-risk group had a poor prognosis. Our study identified that the seven key genes, including DHX9, BCL2L12, RAD51, MELK, CDC6, ANLN, and KIF4A, were associated with the progression from OL to OSCC. These genes had good diagnostic efficacy and could be used as potential biomarkers for the prognosis of OSCC patients.