bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactic Acid Bacteria in Raw-Milk Cheeses: From Starter Cultures to Probiotic Functions
Authors: Coelho Márcia C. , Malcata Francisco Xavier , Silva Célia C. G.
Published: August 2022

Traditional cheeses produced from raw milk exhibit a complex microbiota, characterized by a sequence of different microorganisms from milk coagulation and throughout maturation. Lactic acid bacteria (LAB) play an essential role in traditional cheese making, either as starter cultures that cause the rapid acidification of milk or as secondary microbiota that play an important role during cheese ripening. The enzymes produced by such dynamic LAB communities in raw milk are crucial, since they support proteolysis and lipolysis as chief drivers of flavor and texture of cheese. Recently, several LAB species have been characterized and used as probiotics that successfully promote human health. This review highlights the latest trends encompassing LAB acting in traditional raw milk cheeses (from cow, sheep, and goat milk), and their potential as probiotics and producers of bioactive compounds with health-promoting effects.
Impact of Circular Brewer’s Spent Grain Flour after In Vitro Gastrointestinal Digestion on Human Gut Microbiota
Authors: Bonifácio-Lopes Teresa , Catarino Marcelo D. , Vilas-Boas Ana A. , Ribeiro Tânia B. , Campos Débora A. , Teixeira José A. , Pintado Manuela
Published: August 2022

Brewer’s spent grain (BSG) solid residues are constituted by dietary fibre, protein, sugars, and polyphenols, which can have potential effects on human health. In this study, for the first time, the flours obtained from solid residues of solid-liquid extraction (SLE) and ohmic heating extraction (OHE) were applied throughout the gastrointestinal digestion simulation (GID), in order to evaluate their prebiotic potential and in vitro human gut microbiota fermentation. The results showed that the digestion of BSG flours obtained by the different methods lead to an increase throughout the GID of total phenolic compounds (SLE: from 2.27 to 7.20 mg gallic acid/g BSG—60% ethanol:water (v/v); OHE: 2.23 to 8.36 mg gallic acid/g BSG—80% ethanol:water (v/v)) and consequently an increase in antioxidant activity (ABTS—SLE: from 6.26 to 13.07 mg ascorbic acid/g BSG—80% ethanol:water (v/v); OHE: 4.60 to 10.60 mg ascorbic acid/g BSG—80% ethanol:water (v/v)—ORAC—SLE: 3.31 to 14.94 mg Trolox/g BSG—80% ethanol:water (v/v); OHE: from 2.13 to 17.37 mg Trolox/g BSG—60% ethanol:water (v/v)). The main phenolic compounds identified included representative molecules such as vanillic and ferulic acids, vanillin and catechin, among others being identified and quantified in all GID phases. These samples also induced the growth of probiotic bacteria and promoted the positive modulation of beneficial strains (such as Bifidobacterium spp. and Lactobacillus spp.) present in human faeces. Moreover, the fermentation by human faeces microbiota also allowed the production of short chain fatty acids (acetic, propionic, and butyric). Furthermore, previous identified polyphenols were also identified during fecal fermentation. This study demonstrates that BSG flours obtained from the solid residues of SLE and OHE extractions promoted a positive modulation of gut microbiota and related metabolism and antioxidant environment associated to the released phenolic compounds.
Factors Affecting the Leaching of Chloropropanols from Pulp Used in the Manufacture of Paper Food Packaging
Authors: Zhao Jinwei , Wang Xin , Li Jiao , Yao Shuangquan , Wang Shuangfei , Liang Chen , Qin Chengrong
Published: August 2022

Paper packaging materials are widely used in food packaging. However, it is difficult to extract trace chloropropanol from food packaging paper, so there is a lack of research on the leaching of chloropropanol from paper materials. Therefore, it is of positive significance to explore the leaching rule of chloropropanol in paper pulp for the safety of paper packaging materials, to reduce the risk of food packaging to food safety and to provide a theoretical basis for the formulation of safety standards for paper packaging materials. In order to study the content of chloropropanol in paper packaging paper more accurately, a response surface methodology was used to study the relationship between the amount of chloropropanol leaching and pulp concentration, leaching temperature and leaching time, as well as the interaction of each factor. The results showed that time, temperature and pulp concentration were the main factors affecting the leaching amount of chloropropanol from paper packaging materials. There were significant (p > 0.05) interactions between the time and pulp concentration, as well as temperature and pulp concentration. The leaching efficiency of chloropropanol was higher at a lower pulp concentration, and the leaching amount of chloropropanol was higher at a lower temperature. The temperature more significantly affected the leaching of chloropropanol in a low-concentration system than in a high-concentration system. Relevant studies have shown that the selection of solvent has an important effect on the extraction rate of target compounds. Therefore, in this experiment, different polar organic solvents (methanol, ethanol, formaldehyde solution) were added into the soaking solution to change the leaching amount of chloropropanol. The results showed that adding a certain amount of formaldehyde solution can obviously increase the leaching amount of chloropropanol in pulp.
Mellow and Thick Taste of Pu−Erh Ripe Tea Based on Chemical Properties by Sensory−Directed Flavor Analysis
Authors: Deng Sihan , Zhou Xinru , Dong Haiyu , Xu Yongquan , Gao Ying , Wang Baijuan , Liu Xiaohui
Published: August 2022

The mellow and thick taste is a unique characteristic of pu−erh ripe tea infusion, and it is closely related to the chemical composition of pu−erh ripe tea, which is less studied. This paper clarifies and compares the chemical composition of pu−erh ripe tea to that of the raw materials of sun−dried green tea, and uses membrane separation technology to separate pu−erh ripe tea into the rejection liquid and the filtration liquid. The results show that microorganisms transformed most physicochemical components, except caffeine, during the pile fermentation. It was found that total tea polyphenols, soluble proteins, total soluble sugars, theabrownin, and galloylated catechins became enriched in the rejection liquid, and the rejection liquid showed a more obvious mellow and thick characteristic. Taste interactions between crude protein, crude polysaccharide, and theabrownin were determined. They illustrated that the mellow and thick taste of pu−erh ripe tea with the addition of theabrownin increased from 4.45 to 5.13. It is of great significance to explore the chemical basis of the mellow and thick taste in pu−erh tea for guiding the pu−erh tea production process and for improving the quality of pu−erh tea.
Maximizing Recovery of Paenibacillin, a Bacterially Produced Lantibiotic, Using Continuous Foam Separation from Bioreactors
Authors: Campbell Emily P. , Kasler David R. , Yousef Ahmed E.
Published: August 2022

Industrial production of paenibacillin, and similar rare antimicrobial peptides, is hampered by low productivity of the producing microorganisms and lack of efficient methods to recover these peptides from fermentor or bioreactor end products. Preliminary data showed that paenibacillin was preferentially partitioned in foam accumulated during growth of the producer, Paenibacillus polymyxa, in aerated liquid media. This research was initiated to improve the production and recovery of paenibacillin in bioreactors by maximizing partitioning of this antimicrobial agent in the collected foam. This was completed through harvesting foam continuously during paenibacillin production, using modified bioreactor, and optimizing bioreaction conditions through response surface methodology (RSM). During initial screening, the following factors were tested using 400 mL inoculated media in 2 L bioreactors: medium (tryptic soy broth, TSB, with or without added yeast extract), airflow (0 or 0.8 L/min; LPM), stir speed (300 or 500 revolution/min; RPM), incubation temperature (30 or 36 °C), and incubation time (16 or 24 h). Results showed that airflow, time, and stir speed had significant effects (p < 0.05) on paenibacillin recovery in the collected collapsed foam (foamate). These factors were varied together to follow the path of steepest assent to maximize paenibacillin concentration. Once the local maximum was found, RSM was completed with a central composite design to fine-tune the bioreaction parameters. The optimization experiments proved that the significant parameters and their optimal conditions for paenibacillin concentration in the foam were: incubation at 30 °C for 23 h with airflow of 0.95 LPM, and agitation speed of 450 RPM. These conditions increased paenibacillin concentration, predicted by RSM, from 16 µg/mL in bioreaction without foam collection to 743 µg/mL collected in foamate. The optimized conditions also almost doubled the yield of paenibacillin measured in the foam collected from a bioreaction run (12,674 µg/400 mL bioreaction) when compared to that obtained from a run without foam collection (6400 µg/400 mL bioreaction). Results of this study could improve the feasibility of commercial production and downstream processing of paenibacillin and similar novel antimicrobial peptides. Availability of such peptides will eventually help in protecting perishable products against pathogenic and spoilage bacteria.
A New Fractional Poisson Process Governed by a Recursive Fractional Differential Equation
Authors: Zhang Zhehao
Published: August 2022

This paper proposes a new fractional Poisson process through a recursive fractional differential governing equation. Unlike the homogeneous Poison process, the Caputo derivative on the probability distribution of k jumps with respect to time is linked to all probability distribution functions of j jumps, where j is a non-negative integer less than or equal to k. The distribution functions of arrival times are derived, while the inter-arrival times are no longer independent and identically distributed. Further, this new fractional Poisson process can be interpreted as a homogeneous Poisson process whose natural time flow has been randomized, and the underlying time randomizing process has been studied. Finally, the conditional distribution of the kth order statistic from random number samples, counted by this fractional Poisson process, is also discussed.
A Model Based on Fractional Brownian Motion for Temperature Fluctuation in the Campi Flegrei Caldera
Authors: Di Crescenzo Antonio , Martinucci Barbara , Mustaro Verdiana
Published: August 2022

The aim of this research is to identify an efficient model to describe the fluctuations around the trend of the soil temperatures monitored in the volcanic caldera of the Campi Flegrei area in Naples (Italy). This study focuses on the data concerning the temperatures in the mentioned area through a seven-year period. The research is initially finalized to identify the deterministic component of the model given by the seasonal trend of the temperatures, which is obtained through an adapted regression method on the time series. Subsequently, the stochastic component from the time series is tested to represent a fractional Brownian motion (fBm). An estimation based on the periodogram of the data is used to estabilish that the data series follows an fBm motion rather than fractional Gaussian noise. An estimation of the Hurst exponent H of the process is also obtained. Finally, an inference test based on the detrended moving average of the data is adopted in order to assess the hypothesis that the time series follows a suitably estimated fBm.
The Fractal Characteristics of Soft Soil under Cyclic Loading Based on SEM
Authors: Kong Bowen , Dai Chen-Xiang , Hu Haibo , Xia Jianzhong , He Shao-Heng
Published: August 2022

Cyclic loading always results in great damage to the pore structure and fractal characteristics of soft soil. Scanning electron microscope (SEM) can help collect data to describe the microstructure of soft soil. This paper conducted a series of SEM tests to interpret the effect of consolidation confining pressure, circulating dynamic stress ratios and overconsolidation ratio on soil’s micro-pore structure and fractal characteristics. The results demonstrate that fractal dimension can well represent the complex characteristics of the microstructure of the soil; the larger the consolidation confining pressure, the greater the cyclic dynamic stress ratio, and the greater the overconsolidation ratio, the smaller the fractal dimension number of soil samples. Finally, an empirical fitting formula for cumulative strain considering microstructure parameters is established through data fitting.
Dynamic and Self-Healable Chitosan/Hyaluronic Acid-Based In Situ-Forming Hydrogels
Authors: Maiz-Fernández Sheila , Pérez-Álvarez Leyre , Silván Unai , Vilas-Vilela José Luis , Lanceros-Méndez Senentxu
Published: August 2022

In situ-forming, biodegradable, and self-healing hydrogels, which maintain their integrity after damage, owing to dynamic interactions, are essential biomaterials for bioapplications, such as tissue engineering and drug delivery. This work aims to develop in situ, biodegradable and self-healable hydrogels based on dynamic covalent bonds between N-succinyl chitosan (S-CHI) and oxidized aldehyde hyaluronic acid (A-HA). A robust effect of the molar ratio of both S-CHI and A-HA was observed on the swelling, mechanical stability, rheological properties and biodegradation kinetics of these hydrogels, being the stoichiometric ratio that which leads to the lowest swelling factor (×12), highest compression modulus (1.1·10−3 MPa), and slowest degradation (9 days). Besides, a rapid (3 s) self-repairing ability was demonstrated in the macro scale as well as by rheology and mechanical tests. Finally, the potential of these biomaterials was evidenced by cytotoxicity essay (>85%).
Fabrication of 3D Gelatin Hydrogel Nanocomposite Impregnated Co-Doped SnO2 Nanomaterial for the Catalytic Reduction of Environmental Pollutants
Authors: Marwani Hadi M. , Ahmad Shahid , Rahman Mohammed M.
Published: August 2022

In the catalytic reduction of various environment pollutants, cobalt-doped tin oxide, i.e., Co-SnO2 intercalated gelatin (GL) hydrogel nanocomposite was prepared via direct mixing of Co-SnO2 doped with GL. Then, it was crosslinked internally using formaldehyde within a viscous solution of gelatin polymer, which led to the formation of GL/Co-SnO2 hydrogel nanocomposite. GL/Co-SnO2 hydrogel nanocomposite was fully characterized by using field-emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), powder X-ray diffraction (XRD), and attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR). The FESEM images indicate that the Co-SnO2 composite has a spherical structure on the GL matrix while EDX elucidates the elemental composition of each atom in the crosslinked GL/Co-SnO2 hydrogel nanocomposite. The GL/Co-SnO2 nanocomposite was checked for the reduction of various pollutants, including 2-nitro-phenol (2-NP), 2,6-dinitro-phenol (2,6-DNP), 4-nitro-phenol (4-NP), Congo red (CR), and methyl orange (MO) dyes with a strong sodium borohydride (NaBH4) reducing agent. The GL/Co-SnO2 nanocomposite synergistically reduced the MO in the presence of the reducing agent with greater reduction rate of 1.036 min−1 compared to other dyes. The reduction condition was optimized by changing various parameters, such as the catalyst amount, dye concentration, and the NaBH4 amount. Moreover, the GL/Co-SnO2 nanocomposite catalyst can be easily recovered, is recyclable, and revealed minimal loss of nanomaterials.
Association between the Human Development Index and Confirmed COVID-19 Cases by Country
Authors: Heo Min-Hee , Kwon Young Dae , Cheon Jooyoung , Kim Kyoung-Beom , Noh Jin-Won
Published: August 2022

It is important to understand the ultimate control of COVID-19 in all countries around the world in relation to the characteristics of developed countries, LDCs, and the variety of transmission characteristics of COVID-19. Therefore, this study aimed to identify factors associated with confirmed cases of COVID-19 with a focus on the Human Development Index (HDI). The units of analysis used for the current study were countries, and dataset were aggregated from multiple sources. This study used COVID-19 data from Our World in Data, the Global Health Security Index, and the WORLD BANK. A total of 171 countries were included in the analysis. A multi-variable linear regression with a hierarchical framework was employed to investigate whether the HDI is associated with confirmed COVID-19 cases after controlling for the demographic and healthcare system characteristics of the study countries. For Model 2, which controlled for demographic and healthcare system characteristics, HDI (β = 0.46, p < 0.001, 95% CI = 2.64–10.87) and the number of physicians per 1000 people (β = 0.34, p < 0.01, 95% CI = 0.21–0.75) had significant associations with the total number of confirmed COVID-19 cases per million people. Countries with a high HDI level are able to conduct higher per capita testing, resulting in higher numbers of confirmed cases than in countries with lower HDI levels. This study has shown evidence that could be used by governments and international organizations to identify national characteristics and provide the international cooperation necessary to develop effective prevention and intervention methods to deal with the global pandemic.
Effect of COVID-19 Lockdowns on Eye Emergency Department, Increasing Prevalence of Uveitis and Optic Neuritis in the COVID-19 Era
Authors: Przybek-Skrzypecka Joanna , Szewczuk Alina , Kamińska Anna , Skrzypecki Janusz , Pyziak-Skupień Aleksandra , Szaflik Jacek Paweł
Published: August 2022

Background: The COVID-19 pandemic led to the reorganization of the health care system. A decline in health- and life-saving procedures has been reported in various medical specialties. However, data on ophthalmic emergencies during lockdowns is limited. Methods: We conducted a retrospective, observational, case-control study of 2351 patients registered at the ophthalmic emergency department of a tertiary hospital in Poland during three national COVID-19 lockdowns (March/April 2020, November 2020, and March/April 2021) and corresponding months in 2019. Results: The total number of visits declined from a mean of 720/month in the non-COVID era to 304/month during COVID-19 lockdowns (p < 0.001). Ocular trauma incidence dropped significantly from 2019 (non-COVID months) to 2020/2021 (COVID group mean 201 vs. 97 patients monthly, respectively, p = 0.03). Of note, the percentage of foreign bodies removal was significantly higher during lockdowns than corresponding time in the non-COVID era. A downward trend for vitreous detachment and macular disorders cases was observed between COVID and non-COVID time. Uveitis and optic neuritis patients were seen more often during lockdowns (p < 0.001 and p = 0.0013, respectively). In contrast, the frequency of conjunctivitis and keratitis, potentially COVID-related problems, decreased significantly in COVID-19 time (mean 138 vs. 23 per month in non-COVID vs. COVID lockdowns, respectively, p < 0.001). Conclusions: The overall number of eye emergency visits declined during COVID-19 lockdowns. Conjunctivitis and keratitis rates dropped during the lockdowns. Interestingly, the frequency of immune-mediated ocular conditions (uveitis, optic neuritis) increased significantly which might be triggered by SARS-CoV2 infection.
A Fine Line between Phytotoxicity and Blue When Producing Hydrangea macrophylla in a Nursery at a Low Substrate pH
Authors: Pietsch Grace M. , Brindley Julie C. , Owen James S. , Fulcher Amy
Published: August 2022

Hydrangea macrophylla exhibiting blue sepals (versus purple or pink) have improved marketability; however, little research has been conducted to evaluate aluminum (Al), the element responsible for bluing, on crop growth, effectiveness of bluing sepals, and characteristics of flower clusters in an outdoor nursery. This study compared substrate Al availability, crop growth, flower color, number, and size over a 56-week period in two locations. A polymer coated (90-day release) or ground aluminum sulfate [Al2(SO4)3; water soluble] was either incorporated into a non-limed pine bark substrate, applied to the surface of the substrate as a top dress, or as a routinely applied Al2(SO4)3 drench (low concn.) or applied once (high concn.). In general, application of Al increased plant foliar Al concentration, but also decreased substrate pore-water pH and increased electrical conductivity (EC) with varying effects based on the applied product’s solubility and subsequent longevity. Aluminum sulfate increased the potential of Al phytotoxicity negatively affecting root morphology and creating an undesirable rhizosphere electrochemistry due to the pH being continually acidic, <4, and the EC being temporarily increased to >1.5 mS·cm−1. These suboptimal rhizosphere conditions resulted in a lower quality or smaller plant. No plants exhibited clear, deep blue flower cluster sought by consumers. Neither the effect of pore water pH or EC could, alone or in combination, account for the lack of plant vigor or blue flower clusters when substrate and foliar Al concentrations were adequate in flowering H. macrophylla. More research is needed to investigate the effect of pore-water electrochemical properties, possible mineral nutrient co-factors that provide Al synergisms or toxicity protections, and holistic plant health on ensuring blue coloration of a vigorous H. macrophylla.
Determination of the Z-R Relationship through Spatial Analysis of X-Band Weather Radar and Rain Gauge Data
Authors: Bournas Apollon , Baltas Evangelos
Published: August 2022

In weather radar applications, the Z-R relationship is considered one of the most crucial factors for providing quality quantitative precipitation estimates. However, the relationship’s parameters vary in time and space, making the derivation of an optimal relationship for a specific weather radar system challenging. This research focused on the analysis of the spatiotemporal variability of the parameters for a newly installed X-Band weather radar in Athens, Greece, by performing correlation and optimization analyses between high temporal resolution weather radar and rain gauge datasets. The correlation analysis was performed to assess the available datasets and provide the base of quality control. Multiple Z-R relationships were then derived for the following three optimization procedures; event-based relationships, station-based relationships, and a single area-based relationship. The results highlighted the region’s spatial variability regarding the Z-R relationship and the correlation between the station location and its parameter values. Moreover, it was found that stations near the coast and the front end of precipitation systems featured parameter values typical of convective type events. Finally, a single Z-R relationship was determined under a calibration and validation scheme, Z = 321R1.53,, which was validated with good agreement.
The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer’s Disease Pathology
Authors: Pisani Flavio , Pisani Valerio , Arcangeli Francesca , Harding Alice , Singhrao Simarjit Kaur
Published: August 2022

Alzheimer’s Disease (AD) is a complex neurodegenerative disease and remains the most common form of dementia. The pathological features include amyloid (Aβ) accumulation, neurofibrillary tangles (NFTs), neural and synaptic loss, microglial cell activation, and an increased blood–brain barrier permeability. One longstanding hypothesis suggests that a microbial etiology is key to AD initiation. Among the various periodontal microorganisms, Porphyromonas gingivalis has been considered the keystone agent to potentially correlate with AD, due to its influence on systemic inflammation. P. gingivalis together with Treponema denticola and Tannerella forsythia belong to the red complex consortium of bacteria advocated to sustain periodontitis within a local dysbiosis and a host response alteration. Since the implication of P. gingivalis in the pathogenesis of AD, evidence has emerged of T. denticola clusters in some AD brain tissue sections. This narrative review explored the potential mode of spirochetes entry into the AD brain for tracing pathology. Spirochetes are slow-growing bacteria, which can hide within ganglia for many years. It is this feature in combination with the ability of these bacteria to evade the hosts’ immune responses that may account for a long lag phase between infection and plausible AD disease symptoms. As the locus coeruleus has direct connection between the trigeminal nuclei to periodontal free nerve endings and proprioceptors with the central nervous system, it is plausible that they could initiate AD pathology from this anatomical region.
Blaze a New Trail: Plant Virus Xylem Exploitation
Authors: Sun Yong-Duo , Spellman-Kruse Arianna , Folimonova Svetlana Y.
Published: August 2022

Viruses are trailblazers in hijacking host systems for their own needs. Plant viruses have been shown to exploit alternative avenues of translocation within a host, including a challenging route through the xylem, to expand their niche and establish systemic spread, despite apparent host-imposed obstacles. Recent findings indicate that plant viruses from many families could successfully hack xylem cells in a broad range of plant hosts, including herbaceous and perennial woody plants. Similar to virus-related structures present in the phloem, virus particles and membrane-containing viral replication complexes are often observed in the xylem. Except for a few single-stranded DNA viruses in the family Geminiviridae and a negative-sense single-stranded RNA rhabdovirus, Lettuce necrotic yellows virus, the majority of the viruses that were detected in the xylem belong to the group of positive-sense RNA viruses. The diversity of the genome organization and virion morphology of those viruses indicates that xylem exploitation appears to be a widely adapted strategy for plant viruses. This review outlines the examples of the xylem-associated viruses and discusses factors that regulate virus inhabitation of the xylem as well as possible strategies of virus introduction into the xylem. In some cases, plant disease symptoms have been shown to be closely related to virus colonization of the xylem. Inhibiting viral xylem invasion could raise potential attractive approaches to manage virus diseases. Therefore, the identification of the host genes mediating virus interaction with the plant xylem tissue and understanding the underlying mechanisms call for more attention.
Regulation of Cell Signaling Pathways and Non-Coding RNAs by Baicalein in Different Cancers
Authors: Farooqi Ammad Ahmad , Kapanova Gulnara , Kalmakhanov Sundetgali , Tanbayeva Gulnur , Zhakipbekov Kairat S. , Rakhmetova Venera S. , Syzdykbayev Marat K.
Published: August 2022

Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern ‘omics’ technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/β-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.
Differential Impact of Hexuronate Regulators ExuR and UxuR on the Escherichia coli Proteome
Authors: Bessonova Tatiana A. , Fando Maria S. , Kostareva Olga S. , Tutukina Maria N. , Ozoline Olga N. , Gelfand Mikhail S. , Nikulin Alexey D. , Tishchenko Svetlana V.
Published: August 2022

ExuR and UxuR are paralogous proteins belonging to the GntR family of transcriptional regulators. Both are known to control hexuronic acid metabolism in a variety of Gammaproteobacteria but the relative impact of each of them is still unclear. Here, we apply 2D difference electrophoresis followed by mass-spectrometry to characterise the changes in the Escherichia coli proteome in response to a uxuR or exuR deletion. Our data clearly show that the effects are different: deletion of uxuR resulted in strongly enhanced expression of D-mannonate dehydratase UxuA and flagellar protein FliC, and in a reduced amount of outer membrane porin OmpF, while the absence of ExuR did not significantly alter the spectrum of detected proteins. Consequently, the physiological roles of proteins predicted as homologs seem to be far from identical. Effects of uxuR deletion were largely dependent on the cultivation conditions: during growth with glucose, UxuA and FliC were dramatically altered, while during growth with glucuronate, activation of both was not so prominent. During the growth with glucose, maximal activation was detected for FliC. This was further confirmed by expression analysis and physiological tests, thus suggesting the involvement of UxuR in the regulation of bacterial motility and biofilm formation.
Five Rice Seed-Specific NF-YC Genes Redundantly Regulate Grain Quality and Seed Germination via Interfering Gibberellin Pathway
Authors: Xu Huayu , Li Shufan , Kazeem Bello Babatunde , Ajadi Abolore Adijat , Luo Jinjin , Yin Man , Liu Xinyong , Chen Lijuan , Ying Jiezheng , Tong Xiaohong , Wang Yifeng , Niu Baixiao , Chen Chen , Zeng Xiaoshan , Zhang Jian
Published: August 2022

NF-YCs are important transcription factors with diverse functions in the plant kingdoms including seed development. NF-YC8, 9, 10, 11 and 12 are close homologs with similar seed-specific expression patterns. Despite the fact that some of the NF-YCs are functionally known; their biological roles have not been systematically explored yet, given the potential functional redundancy. In this study, we generated pentuple mutant pnfyc of NF-YC8-12 and revealed their functions in the regulation of grain quality and seed germination. pnfyc grains displayed significantly more chalkiness with abnormal starch granule packaging. pnfyc seed germination and post-germination growth are much slower than the wild-type NIP, largely owing to the GA-deficiency as exogenous GA was able to fully recover the germination phenotype. The RNA-seq experiment identified a total of 469 differentially expressed genes, and several GA-, ABA- and grain quality control-related genes might be transcriptionally regulated by the five NF-YCs, as revealed by qRT-PCR analysis. The results demonstrated the redundant functions of NF-YC8-12 in regulating GA pathways that underpin rice grain quality and seed germination, and shed a novel light on the functions of the seed-specific NF-YCs.
The γ-Core Motif Peptides of AMPs from Grasses Display Inhibitory Activity against Human and Plant Pathogens
Authors: Slezina Marina P. , Istomina Ekaterina A. , Kulakovskaya Ekaterina V. , Korostyleva Tatyana V. , Odintsova Tatyana I.
Published: August 2022

Antimicrobial peptides (AMPs) constitute an essential part of the plant immune system. They are regarded as alternatives to conventional antibiotics and pesticides. In this study, we have identified the γ-core motifs, which are associated with antimicrobial activity, in 18 AMPs from grasses and assayed their antimicrobial properties against nine pathogens, including yeasts affecting humans, as well as plant pathogenic bacteria and fungi. All the tested peptides displayed antimicrobial properties. We discovered a number of short AMP-derived peptides with high antimicrobial activity both against human and plant pathogens. For the first time, antimicrobial activity was revealed in the peptides designed from the 4-Cys-containing defensin-like peptides, whose role in plant immunity has remained unknown, as well as the knottin-like peptide and the C-terminal prodomain of the thionin, which points to the direct involvement of these peptides in defense mechanisms. Studies of the mode of action of the eight most active γ-core motif peptides on yeast cells using staining with propidium iodide showed that all of them induced membrane permeabilization leading to cell lysis. In addition to identification of the antimicrobial determinants in plant AMPs, this work provides short candidate peptide molecules for the development of novel drugs effective against opportunistic fungal infections and biopesticides to control plant pathogens.
Single-Circulating Tumor Cell Whole Genome Amplification to Unravel Cancer Heterogeneity and Actionable Biomarkers
Authors: Khan Tanzila , Becker Therese M. , Po Joseph W. , Chua Wei , Ma Yafeng
Published: August 2022

The field of single-cell analysis has advanced rapidly in the last decade and is providing new insights into the characterization of intercellular genetic heterogeneity and complexity, especially in human cancer. In this regard, analyzing single circulating tumor cells (CTCs) is becoming particularly attractive due to the easy access to CTCs from simple blood samples called “liquid biopsies”. Analysis of multiple single CTCs has the potential to allow the identification and characterization of cancer heterogeneity to guide best therapy and predict therapeutic response. However, single-CTC analysis is restricted by the low amounts of DNA in a single cell genome. Whole genome amplification (WGA) techniques have emerged as a key step, enabling single-cell downstream molecular analysis. Here, we provide an overview of recent advances in WGA and their applications in the genetic analysis of single CTCs, along with prospective views towards clinical applications. First, we focus on the technical challenges of isolating and recovering single CTCs and then explore different WGA methodologies and recent developments which have been utilized to amplify single cell genomes for further downstream analysis. Lastly, we list a portfolio of CTC studies which employ WGA and single-cell analysis for genetic heterogeneity and biomarker detection.
Lack of Neuroprotection with a Single Intravenous Infusion of Human Amnion Epithelial Cells after Severe Hypoxia–Ischemia in Near-Term Fetal Sheep
Authors: Davidson Joanne O. , van den Heuij Lotte G. , Dhillon Simerdeep K. , Miller Suzanne L. , Lim Rebecca , Jenkin Graham , Gunn Alistair J. , Bennet Laura
Published: August 2022

Background: Hypoxic–ischemic encephalopathy (HIE) around the time of birth results from loss of oxygen (hypoxia) and blood supply (ischemia). Exogenous infusion of multi-potential cells, including human amnion epithelial cells (hAECs), can reduce hypoxic–ischemic (HI) brain injury. However, there are few data on treatment of severe HI in large animal paradigms at term. The aim of the current study was to determine whether infusion of hAECs early after injury may reduce brain damage after ischemia in near-term fetal sheep. Methods: Chronically instrumented fetal sheep (0.85 gestation) received 30 min of global cerebral ischemia followed by intravenous infusion of hAECs from 2 h after the end of ischemia (ischemia-hAEC, n = 6) or saline (ischemia-vehicle, n = 7). Sham control animals received sham ischemia with vehicle infusion (sham control, n = 8). Results: Ischemia was associated with significant suppression of EEG power and spectral edge frequency until the end of the experiment and a secondary rise in cortical impedance from 24 to 72 h, which were not attenuated by hAEC administration. Ischemia was associated with loss of neurons in the cortex, thalamus, striatum and hippocampus, loss of white matter oligodendrocytes and increased microglial numbers in the white matter, which were not affected by hAEC infusion. Conclusions: A single intravenous administration of hAECs did not reduce electrographic or histological brain damage after 30 min of global cerebral ischemia in near-term fetal sheep.
Microvesicles and Microvesicle-Associated microRNAs Reflect Glioblastoma Regression: Microvesicle-Associated miR-625-5p Has Biomarker Potential
Authors: Simionescu Natalia , Nemecz Miruna , Petrovici Anca-Roxana , Nechifor Ioan Sebastian , Buga Razvan-Cristian , Dabija Marius Gabriel , Eva Lucian , Georgescu Adriana
Published: August 2022

Glioblastoma (GB) is the most aggressive and recurrent form of brain cancer in adults. We hypothesized that the identification of biomarkers such as certain microRNAs (miRNAs) and the circulating microvesicles (MVs) that transport them could be key to establishing GB progression, recurrence and therapeutic response. For this purpose, circulating MVs were isolated from the plasma of GB patients (before and after surgery) and of healthy subjects and characterized by flow cytometry. OpenArray profiling and the individual quantification of selected miRNAs in plasma and MVs was performed, followed by target genes’ prediction and in silico survival analysis. It was found that MVs’ parameters (number, EGFRvIII and EpCAM) decreased after the surgical resection of GB tumors, but the inter-patient variability was high. The expression of miR-106b-5p, miR-486-3p, miR-766-3p and miR-30d-5p in GB patients’ MVs was restored to control-like levels after surgery: miR-106b-5p, miR-486-3p and miR-766-3p were upregulated, while miR-30d-5p levels were downregulated after surgical resection. MiR-625-5p was only identified in MVs isolated from GB patients before surgery and was not detected in plasma. Target prediction and pathway analysis showed that the selected miRNAs regulate genes involved in cancer pathways, including glioma. In conclusion, miR-625-5p shows potential as a biomarker for GB regression or recurrence, but further in-depth studies are needed.
Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach
Authors: Rossi Michael T. , Langston Jordan C. , Singh Narender , Merali Carmen , Yang Qingliang , Merali Salim , Prabhakarpandian Balabhaskar , Kilpatrick Laurie E. , Kiani Mohammad F.
Published: August 2022

A key aspect of cytokine-induced changes as observed in sepsis is the dysregulated activation of endothelial cells (ECs), initiating a cascade of inflammatory signaling leading to leukocyte adhesion/migration and organ damage. The therapeutic targeting of ECs has been hampered by concerns regarding organ-specific EC heterogeneity and their response to inflammation. Using in vitro and in silico analysis, we present a comprehensive analysis of the proteomic changes in mouse lung, liver and kidney ECs following exposure to a clinically relevant cocktail of proinflammatory cytokines. Mouse lung, liver and kidney ECs were incubated with TNF-α/IL-1β/IFN-γ for 4 or 24 h to model the cytokine-induced changes. Quantitative label-free global proteomics and bioinformatic analysis performed on the ECs provide a molecular framework for the EC response to inflammatory stimuli over time and organ-specific differences. Gene Ontology and PANTHER analysis suggest why some organs are more susceptible to inflammation early on, and show that, as inflammation progresses, some protein expression patterns become more uniform while additional organ-specific proteins are expressed. These findings provide an in-depth understanding of the molecular changes involved in the EC response to inflammation and can support the development of drugs targeting ECs within different organs. Data are available via ProteomeXchange (identifier PXD031804).
Long-Chain Acyl-CoA Synthetases Promote Poplar Resistance to Abiotic Stress by Regulating Long-Chain Fatty Acid Biosynthesis
Authors: Wei Hui , Movahedi Ali , Zhang Yanyan , Aghaei-Dargiri Soheila , Liu Guoyuan , Zhu Sheng , Yu Chunmei , Chen Yanhong , Zhong Fei , Zhang Jian
Published: August 2022

Long-chain acyl-CoA synthetases (LACSs) catalyze fatty acids (FAs) to form fatty acyl-CoA thioesters, which play essential roles in FA and lipid metabolisms and cuticle wax biosynthesis. Although LACSs from Arabidopsis have been intensively studied, the characterization and function of LACSs from poplar are unexplored. Here, 10 poplar PtLACS genes were identified from the poplar genome and distributed to eight chromosomes. A phylogenetic tree indicated that PtLACSs are sorted into six clades. Collinearity analysis and duplication events demonstrated that PtLACSs expand through segmental replication events and experience purifying selective pressure during the evolutionary process. Expression patterns revealed that PtLACSs have divergent expression changes in response to abiotic stress. Interaction proteins and GO analysis could enhance the understanding of putative interactions among protein and gene regulatory networks related to FA and lipid metabolisms. Cluster networks and long-chain FA (LCFA) and very long-chain FA (VLCFA) content analysis revealed the possible regulatory mechanism in response to drought and salt stresses in poplar. The present study provides valuable information for the functional identification of PtLACSs in response to abiotic stress metabolism in poplar.
Epigenomic Features and Potential Functions of K+ and Na+ Favorable DNA G-Quadruplexes in Rice
Authors: Feng Yilong , Luo Zhenyu , Huang Ranran , Yang Xueming , Cheng Xuejiao , Zhang Wenli
Published: August 2022

DNA G-quadruplexes (G4s) are non-canonical four-stranded DNA structures involved in various biological processes in eukaryotes. Molecularly crowded solutions and monovalent cations have been reported to stabilize in vitro and in vivo G4 formation. However, how K+ and Na+ affect G4 formation genome-wide is still unclear in plants. Here, we conducted BG4-DNA-IP-seq, DNA immunoprecipitation with anti-BG4 antibody coupled with sequencing, under K+ and Na+ + PEG conditions in vitro. We found that K+-specific IP-G4s had a longer peak size, more GC and PQS content, and distinct AT and GC skews compared to Na+-specific IP-G4s. Moreover, K+- and Na+-specific IP-G4s exhibited differential subgenomic enrichment and distinct putative functional motifs for the binding of certain trans-factors. More importantly, we found that K+-specific IP-G4s were more associated with active marks, such as active histone marks, and low DNA methylation levels, as compared to Na+-specific IP-G4s; thus, K+-specific IP-G4s in combination with active chromatin features facilitate the expression of overlapping genes. In addition, K+- and Na+-specific IP-G4 overlapping genes exhibited differential GO (gene ontology) terms, suggesting they may have distinct biological relevance in rice. Thus, our study, for the first time, explores the effects of K+ and Na+ on global G4 formation in vitro, thereby providing valuable resources for functional G4 studies in rice. It will provide certain G4 loci for the biotechnological engineering of rice in the future.
Linkage Mapping Reveals QTL for Flowering Time-Related Traits under Multiple Abiotic Stress Conditions in Maize
Authors: Leng Pengfei , Khan Siffat Ullah , Zhang Dengfeng , Zhou Guyi , Zhang Xuhuan , Zheng Yanxiao , Wang Tianyu , Zhao Jun
Published: August 2022

Variation in flowering plays a major role in maize photoperiod adaptation during long-term domestication. It is of high value to investigate the genetic basis of maize flowering under a wide range of environmental conditions in order to overcome photoperiod sensitivity or enhance stress tolerance. A recombinant inbred line (RIL) population derived from a cross between Huangzaosi and Mo17, composed of 121 lines and genotyped by 8329 specifically developed markers, was field evaluated in two consecutive years under two planting densities (67,500 and 120,000 plants ha−1) and two water treatments (normal irrigation and drought stress at the flowering stage). The days to silking (DTS), days to anthesis (DTA), and anthesis to silking interval (ASI) were all evaluated. Within the RIL population, DTS and DTA expanded as planting density and water deficit increased. For DTA, DTS, ASI, and ASI-delay, a total of 22, 17, 21, and 11 QTLs were identified, respectively. More than two significant QTLs were identified in each of the nine chromosomal intervals. Under diverse conditions and locations, six QTLs (quantitative trait locus) for DTS and DTA were discovered in Chr. 8: 118.13–125.31 Mb. Three chromosome regions, Chr. 3: 196.14–199.89 Mb, Chr. 8: 169.02–172.46 Mb, and Chr. 9: 128.12–137.26 Mb, all had QTLs for ASI-delay under normal and stress conditions, suggesting their possible roles in stress tolerance enhancement. These QTL hotspots will promote early-maturing or multiple abiotic stress-tolerant maize breeding, as well as shed light on the development of maize varieties with a broad range of adaptations.
Editorial for Special Issue “Advances in the Pathogenesis and Treatment of Immune-Mediated Inflammatory Diseases”
Authors: van Hamburg Jan Piet , Tas Sander W.
Published: August 2022

This Special Issue focuses on the rapidly evolving field of immune-mediated inflammatory diseases (IMIDs) and the achievements that were made over the last 10 years [...]
Synthesis of Tin-Doped Three-Dimensional Flower-like Bismuth Tungstate with Enhanced Photocatalytic Activity
Authors: Zhu Xiaodong , Qin Fengqiu , Zhang Xiuping , Zhong Yuanyuan , Wang Juan , Jiao Yu , Luo Yuhao , Feng Wei
Published: August 2022

Photocatalytic degradation of harmful organic matter is a feasible and environmentally friendly method. Bi2WO6 has become a hotspot of photocatalysts because of its unique layered structure and visible light response. In the present study, Sn doping was adopted to modified Bi2WO6 by hydrothermal method. The Sn-doped Bi2WO6 photocatalysts were characterized by XRD, SEM, TEM, BET, XPS, PL, and DRS, respectively. The results show that Sn-doped Bi2WO6 shows three-dimensional (3D) flower-like morphology, which is composed of two-dimensional (2D) nanosheets. Sn4+ ions enter into the Bi2WO6 lattice, producing a degree of Bi2WO6 lattice distortion, which is in favor of reducing the recombination of photogenerated electrons and holes. Moreover, the specific surface area of Bi2WO6 is significantly increased after doping, which is beneficial to providing more active sites. The photocatalytic results show that 2%Sn-Bi2WO6 exhibits the highest photocatalytic activity. After 60 min of irradiation, the photocatalytic degradation degree of methylene blue (MB) increases from 80.6% for pure Bi2WO6 to 92.0% for 2%Sn-Bi2WO6. The first-order reaction rate constant of 2%Sn-Bi2WO6 is 0.030 min−1, which is 1.7 times than that of pure Bi2WO6.