bluuebunny/crossref_metadata_2025 huggingface dataset:
Unconditionally Secure Ciphers with a Short Key for a Source with Unknown Statistics
Authors: Ryabko Boris
Published: October 2023

We consider the problem of constructing an unconditionally secure cipher with a short key for the case where the probability distribution of encrypted messages is unknown. Note that unconditional security means that an adversary with no computational constraints can only obtain a negligible amount of information (“leakage”) about an encrypted message (without knowing the key). Here, we consider the case of a priori (partially) unknown message source statistics. More specifically, the message source probability distribution belongs to a given family of distributions. We propose an unconditionally secure cipher for this case. As an example, one can consider constructing a single cipher for texts written in any of the languages of the European Union. That is, the message to be encrypted could be written in any of these languages.
The Structural Convergence of New Members of the European Union: An Input-Output Perspective
Authors: Caraiani Petre
Published: October 2023

This paper aims to approach the topic of structural convergence for new member states from the perspective of input-output analysis. Using a set of input-output measures, based on the OECD RStan database, and a number of unit-root tests, both for individual time series and panel data, this paper tests whether there is convergence relative to the production structure of the German economy. Although the individual tests are somewhat mixed, the panel unit-root tests indicate the presence of convergence. The results highlight the importance of assessing structural convergence based on panel tests. They also highlight that as nominal and real convergence are gradually achieved, structural convergence should also become more prioritized.
Current Approaches to Epigenetic Therapy
Authors: Griazeva Ekaterina D. , Fedoseeva Daria M. , Radion Elizaveta I. , Ershov Pavel V. , Meshkov Ivan O. , Semyanihina Alexandra V. , Makarova Anna S. , Makarov Valentin V. , Yudin Vladimir S. , Keskinov Anton A. , Kraevoy Sergey A.
Published: October 2023

Epigenetic therapy is a promising tool for the treatment of a wide range of diseases. Several fundamental epigenetic approaches have been proposed. Firstly, the use of small molecules as epigenetic effectors, as the most developed pharmacological method, has contributed to the introduction of a number of drugs into clinical practice. Secondly, various innovative epigenetic approaches based on dCas9 and the use of small non-coding RNAs as therapeutic agents are also under extensive research. In this review, we present the current state of research in the field of epigenetic therapy, considering the prospects for its application and possible limitations.
Examining Drivers of Post-Fire Seismic Line Ecotone Regeneration in a Boreal Peatland Environment
Authors: Enayetullah Humaira , Chasmer Laura , Hopkinson Chris , Thompson Daniel , Cobbaert Danielle
Published: October 2023

Seismic lines are the dominant anthropogenic disturbance in the boreal forest of the Canadian province of Alberta, fragmenting over 1900 km2 of peatland areas and accounting for more than 80% of all anthropogenic disturbance in this region. The goal of this study is to determine whether the wildland fires that burn across seismic lines in peatlands result in the regeneration of woody vegetation within the ecotonal areas adjacent to seismic lines. We use a combination of seismic line and vegetation structural characteristics derived from multi-spectral airborne lidar across a post-fire peatland chronosequence. We found an increasing encroachment of shrubs and trees into seismic lines after many years since a fire, especially in fens, relative to unburned peatlands. Fens typically had shorter woody vegetation regeneration (average = 3.3 m ± 0.9 m, standard deviation) adjacent to seismic lines compared to bogs (average = 3.8 m ± 1.0 m, standard deviation), despite enhanced shrubification closer to seismic lines. The incoming solar radiation and seismic line age since the establishment of seismic line(s) were the factors most strongly correlated with enhanced shrubification, suggesting that the increased light and time since a disturbance are driving these vegetation changes. Shrub encroachment closer to seismic lines tends to occur within fens, indicating that these may be more sensitive to drying conditions and vegetation regeneration after several years post-fire/post-seismic line disturbance.
Comparison of Soil Microbial Community between Managed and Natural Vegetation Restoration along a Climatic Gradient in Karst Regions
Authors: Sun Zhuanzhuan , Hu Peilei , Zhang Wei , Xiao Dan , Zou Dongsheng , Ye Yingying , Wang Kelin
Published: October 2023

Managed and natural vegetation restorations are two vital measures of land restoration; however, their effects on soil microbial communities at a large scale are not clearly understood. Hence, changes in the microbial community composition after 15 years of vegetation restoration along a climatic gradient in the subtropical karst region of Southwest China were assessed based on phospholipid fatty acids (PLFAs) profiles. Managed (plantation forest) and natural (naturally recovered to shrubbery) vegetation restoration types were compared, with cropland and mature forest serving as controls. Soil microbial community abundance was significantly higher under the two vegetation restoration types than in the cropland; however, it was lower than in the mature forest. The abundance, composition, and structure of soil microbial communities did not differ significantly between plantation forest and shrubbery. Soil organic carbon or total nitrogen was the primary factor positively affecting soil microbial abundance, whereas the mean annual temperature (MAT) was recognized as the primary factor contributing to the variation in the soil microbial community structure. Moreover, temperature had opposite effects on different indicators of microbial community structure. That is, it positively and negatively affected the ratios of gram-positive to gram-negative bacterial PLFAs (GP:GN) and fungal to bacterial PLFAs (F:B), respectively. Our results show that both vegetation restoration types have the ability to improve soil productivity in karst areas. Furthermore, shifts in soil microbial community structure (GP:GN and F:B ratios) induced by warming are likely to lead to a higher proportion of labile carbon, which is sensitive to soil tillage. Hence, more attention should be paid to ecological restoration in warmer karst areas to alleviate the severe loss of soil carbon in croplands.
Assessment and Mechanism Analysis of Forest Protection against Rockfall in a Large Rock Avalanche Area
Authors: Song Kanglei , Yang Haiqing , Liang Dan , Chen Lichuan , Qu Lili , Chen Chiwei
Published: October 2023

Trees in forests can obstruct falling rocks and serve as a natural barrier to reduce the velocity of falling rocks. Recently, there has been growing interest in utilizing forests to safeguard against potential rockfall. Nevertheless, there is a dearth of research regarding the impact of rock size and forest structure on forest preservation against rockfall. This study takes the Jiweishan rock avalanche that occurred in China in June 2009 as an example to discuss the protection mechanism of forests against rockfall in rock avalanche disasters. Three sizes of rockfalls from the Jiweishan rock avalanche were simulated and analyzed with and without forests using Rockyfor3D software. The findings indicate that forests can mitigate the energy impact of falling rocks. Especially in the debris flow area of rock avalanches, the protective effect of trees on small-sized falling rocks is most obvious, reducing the runout distance and damage range of the debris flow. Moreover, the protective effect of forest structures on rockfall risk was explored. It was found that broad-leaved forests had the best protection against falling rocks, followed by coniferous broad-leaved mixed forests, and coniferous forests had the worst protective effect. Furthermore, increasing forest planting density and tree diameter at breast height (DBH) can result in better protection against rockfall. Thus, rational planning of forest species and planting density in areas of rockfall can effectively reduce the threat of rockfall risk. The research ideas in this study can provide a basis for evaluating the mitigation of rockfall hazards by forests and provide a reference for constructing and planning protective forests in rockfall and rock avalanche hazard areas.
An Earlier Spring Phenology Reduces Vegetation Growth Rate during the Green-Up Period in Temperate Forests
Authors: Wang Boheng , Liu Zunchi , Lu Ji , Cai Mao , Zhou Chaofan , Duan Gaohui , Yang Peng , Hu Jinfeng
Published: October 2023

Climatic warming advances the start of the growing season (SOS) and sequentially enhances the vegetation productivity of temperate forests by extending the carbon uptake period and/or increasing the growth rate. Recent research indicates that the vegetation growth rate is a main driver for the interannual changes in vegetation carbon uptake; however, the specific effects of an earlier SOS on vegetation growth rate and the underlying mechanisms are still unclear. Using 268 year-site PhenoCam observations in temperate forests, we found that an earlier SOS reduced the vegetation growth rate and mean air temperature during the green-up period (i.e., from the SOS to the peak of the growing period), but increased the accumulation of shortwave radiation during the green-up period. Interestingly, an earlier-SOS-induced reduction in the growth rate was weakened in the highly humid areas (aridity index ≥ 1) when compared with that in the humid areas (aridity index < 1), suggesting that an earlier-SOS-induced reduction in the growth rate in temperate forests may intensify with the ongoing global warming and aridity in the future. The structural equation model analyses indicated that an earlier-SOS-induced decrease in the temperature and increase in shortwave radiation drove a low vegetation growth rate. Our findings highlight that the productivity of temperate forests may be overestimated if the negative effect of an earlier SOS on the vegetation growth rate is ignored.
SRTM DEM Correction Based on PSO-DBN Model in Vegetated Mountain Areas
Authors: Sun Xinpeng , Zhou Cui , Xie Jian , Ouyang Zidu , Luo Yongfeng
Published: October 2023

The Shuttle Radar Topography Mission (SRTM) digital elevation model (DEM) is extensively utilized in various fields, such as forestry, oceanography, geology, and hydrology. However, due to limitations in radar side-view imaging, the SRTM DEM still contains gaps and anomalies, particularly in areas with an intricate topography, like forests. To enhance the accuracy of the SRTM DEM in forested regions, commonly employed approaches include regression analysis and artificial neural networks (ANN). Nevertheless, existing regression methods struggle to accurately capture the intricate nonlinear relationship between the error and influencing factors. Additionally, traditional ANN models are susceptible to overfitting, resulting in subpar accuracy. Deep Belief Network (DBN) is a highly precise algorithm in deep learning. However, the intricate combination of hyperparameters often leads to limited generalization ability and model robustness when correcting DEM. The present study proposes an error prediction model based on the DBN optimized by Particle Swarm Optimization (PSO) for SRTM DEM correction. By utilizing the PSO algorithm, we aim to identify the optimal combination of hyperparameters of DBN, including the number of neurons in the hidden layer and the learning rates. The experiment focuses on two regions in Hunan Province, China, characterized by abundant vegetation cover. The reference data utilized for comparison is ICESat/GLAS data. The experimental results demonstrate that the mean error (ME) and root mean square error (RMSE) of the SRTM DEM corrected by the proposed algorithm in these two regions are significantly reduced by 93.5%–96.0% and 21.5%–23.5%, respectively. Moreover, there is an improvement of over 26.1% in accuracy within complex terrain areas. Specifically, in broadleaf forest, the PSO-DBN method exhibits a remarkable accuracy improvement of 26.2%, while the DBN-corrected SRTM DEM shows an improvement of 15.3%. In coniferous forest, the PSO-DBN method achieves an accuracy improvement of 14.8%, whereas the DBN-corrected SRTM DEM demonstrates a gain of 5.8%. The approach provides a more effective and robust tool for correcting SRTM DEM or other similar DEMs over vegetated mountain areas.
Comprehensive Comparative Analyses of Aspidistra Chloroplast Genomes: Insights into Interspecific Plastid Diversity and Phylogeny
Authors: Huang Jie , Lu Zhaocen , Lin Chunrui , Xu Weibin , Liu Yan
Published: October 2023

Limestone karsts are renowned for extremely high species richness and endemism. Aspidistra (Asparagaceae) is among the highly diversified genera distributed in karst areas, making it an ideal group for studying the evolutionary mechanisms of karst plants. The taxonomy and identification of Aspidistra species are mainly based on their specialized and diverse floral structures. Aspidistra plants have inconspicuous flowers, and the similarity in vegetative morphology often leads to difficulties in species discrimination. Chloroplast genomes possess variable genetic information and offer the potential for interspecies identification. However, as yet there is little information about the interspecific diversity and evolution of the plastid genomes of Aspidistra. In this study, we reported chloroplast (cp) genomes of seven Aspidistra species (A. crassifila, A. dolichanthera, A. erecta, A. longgangensis, A. minutiflora, A. nankunshanensis, and A. retusa). These seven highly-conserved plastid genomes all have a typical quartile structure and include a total of 113 unique genes, comprising 79 protein-coding genes, 4 rRNA genes and 30 tRNA genes. Additionally, we conducted a comprehensive comparative analysis of Aspidistra cp genomes. We identified eight divergent hotspot regions (trnC-GCA-petN, trnE-UUC-psbD, accD-psaI, petA-psbJ, rpl20-rps12, rpl36-rps8, ccsA-ndhD and rps15-ycf1) that serve as potential molecular markers. Our newly generated Aspidistra plastomes enrich the resources of plastid genomes of karst plants, and an investigation into the plastome diversity offers novel perspectives on the taxonomy, phylogeny and evolution of Aspidistra species.
Enhancing Genetic Gains in Grain Yield and Efficiency of Testing Sites of Early-Maturing Maize Hybrids under Contrasting Environments
Authors: Badu-Apraku Baffour , Abubakar Adamu Masari , Adu Gloria Boakyewaa , Yacoubou Abdoul-Madjidou , Adewale Samuel , Adejumobi Idris Ishola
Published: October 2023

The major challenges of maize production and productivity in Sub-Saharan Africa (SSA) include Striga hermonthica infestation, recurrent drought, and low soil nitrogen (low N). This study assessed the following: (i) accelerated genetic advancements in grain yield and other measured traits of early-maturing maize hybrids, (ii) ideal test environments for selecting early-maturing multiple-stress tolerant hybrids, and (iii) high-yielding and stable hybrids across multiple-stress and non-stress environments. Fifty-four hybrids developed during three periods of genetic enhancement (2008–2010, 2011–2013, and 2014–2016) were evaluated in Nigeria, The Republic of Benin, and Ghana under multiple stressors (Striga infestation, managed drought, and Low N) and non-stress environments from 2017 to 2019. Under multiple-stress and non-stress environments, annual genetic gains from selection in grain yield of 84.72 kg ha−1 (4.05%) and 61 kg ha−1 (1.56%), respectively, were recorded. Three mega-environments were identified across 14 stress environments. Abuja was identified as an ideal test environment for selecting superior hybrids. The hybrid TZdEI 352 × TZEI 355 developed during period 3 was the most outstanding under multiple-stress and non-stress environments. On-farm testing of this hybrid is required to verify its superior performance for commercialization in SSA. Considerable progress has been made in the genetic improvement of early-maturing maize hybrids for tolerance of multiple stressors and high yield. The identified core testing sites of this study could be used to enhance the testing and selection of promising hybrids.
Unravelling the Genetic Basis of Moisture Deficit Stress Tolerance in Wheat for Seedling Vigour-Related Traits and Root Traits Using Genome-Wide Association Study
Authors: Ramappa S , Joshi Monika A. , Krishna Hari , Dunna Vijay , Jain Neelu , Sreevathsa Rohini , Devate Narayana Bhat
Published: October 2023

A key abiotic stress that negatively affects seed germination, plant development, and crop yield is moisture deficit stress. Achieving higher vigour and uniform germination under stress conditions is essential for crop establishment and productivity and to enhance the yield. Hence, revealing wheat’s capacity to withstand moisture deficit stress during seed germination and early growth stages is fundamental in improving its overall performance. However, the genetic regulation of moisture deficit stress tolerance during the seed germination phase remains largely unexplored. In this study, a total of 193 wheat genotypes were subjected to simulated moisture deficit stress using PEG-6000 (−0.4 MPa) during the seed germination stage. The induced moisture deficit stress significantly reduced various seedling-vigour-related traits. The genetic regions linked to these traits were found using a genome-wide association study (GWAS). The analysis identified 235 MTAs with a significance −log10(p) value of >4. After applying the Bonferroni correction, the study identified 47 unique single nucleotide polymorphisms (SNPs) that are linked to candidate genes important for the trait of interest. The current study emphasises the effectiveness of genome-wide association studies (GWAS) in identifying promising candidate genes, improving wheat seedling vigour and root traits, and offering essential information for the development of wheat cultivars tolerant to moisture deficit stress.
Forcing Temperature Effects on Plant Development for Containerized Blackberry Grown Using Long-Cane Techniques
Authors: Dickson Ryan W. , Machesney Leala M. , Henderson Erika O.
Published: October 2023

Dormant containerized blackberry plants grown as long canes are forced into protected environments, such as plastic tunnels or greenhouses, to schedule harvesting for important market weeks. The time needed to produce a crop is mainly a function of temperature. In this study, the objectives were to quantify the effects of temperature on plant development rates for long-cane blackberry and develop simple models predicting the time from forcing dormant plants to first open flowers and ripe fruit as a function of average daily temperature (ADT). The crop time and ADT at the first-flower and -fruit stages were measured for the cultivars ‘Loch Ness’, ‘Osage’, ‘Ponca’, and ‘Prime-Ark® 45′ grown as long canes during a greenhouse and high-tunnel experiment, and the days to flowering and fruiting were converted to rates by calculating the reciprocal. Nonlinear models relating flowering and fruiting rates to ADT were developed for each cultivar using a combination of the experimental data and base (6 °C), optimum (25 °C), and maximum (35 °C) temperature parameters derived from a previous blackberry heat unit study. Model accuracy was evaluated by comparing the predicted to observed times to first flower and fruit per cultivar. Average daily temperature was shown to have a main influence on crop timing, as shown by a strongly positive and near 1:1 relationship between predicted and observed days to flowering/fruiting. However, there was significant variability depending on the cultivar and model accuracy within ±7 days, ranging from 50% (‘Prime-Ark® 45) to 90% (‘Loch Ness’) for the flower models and from 60% (‘Prime-Ark® 45) to 100% (‘Loch Ness’) for the fruit models. To the best of our knowledge, this study is the first to characterize the relationship between temperature and crop timing for soilless long-cane blackberry, and it provides a framework for modeling temperature effects on crop timing for these systems. The authors discuss further methods to improve model accuracy and precision for commercial use. These models can also be used for general training purposes to help educate growers on how temperature influences crop scheduling during long-cane blackberry production.
Bibliometrics and Visual Analysis of Non-Destructive Testing Technology for Fruit Quality
Authors: Ni Peng , Niu Hao , Tang Yurong , Zhang Yabo , Zhang Wenyang , Liu Yang , Lan Haipeng
Published: October 2023

This study examined the development and trends in non-destructive testing technology for fruit quality. The status of the research field and the application hotspots were investigated to provide a reference for future research in this field. Relevant studies on the non-destructive testing of fruit quality published between 1993 and 2022 were identified in the core database Web of Science. The temporal distribution, spatial distribution, literature features, research progress, and leading research hotspots were quantified and visualised using bibliometrics. The findings revealed that there continues to be active research and publications on non-destructive testing technology for fruit quality, with a good development trend. China and the USA are the major contributors to research on non-destructive testing technology for fruit quality. The major research institutions include Zhejiang University and the United States Department of Agriculture. The major papers are published in Postharvest Biology and Technology and Acta Horticulturae, among others. These studies mainly focus on agriculture, food, and gardening, among other topics. The detection indices mainly concern internal quality, such as sugar degree and soluble solids, and apparent quality, such as hardness. The detection technologies mainly include electronic nose (E-nose) technology, machine vision technology, and spectral detection technology. In the future, technological developments in artificial intelligence and deep learning will further promote the maturation and application of non-destructive testing technologies for fruit quality.
Insight into the Phylogenetic Relationships and Evolutionary History of Pepper Cultivars (Capsicum annuum L.) through Comparative Analyses of Plastomes
Authors: Yun Seona , Kim Hyeran
Published: October 2023

Pepper (Capsicum annuum L.) holds immense global importance, as it is widely cultivated for its economic value in the food industry and its health benefits. Consequently, substantial breeding progress has been made in cultivar development, whole-genome analysis, and transformation techniques aimed at enhancing agricultural traits, including fruit development and capsaicin synthesis. However, research concerning the phylogenetic relationships within C. annuum remains insufficient. In this study, we characterized the plastome sequences of seven C. annuum, including five hot pepper and two bell pepper cultivars, while also elucidating their phylogenetic relationships. Furthermore, we conducted comparative analyses to gain insight into their evolutionary history. The seven plastomes displayed typical quadripartite structures and ranged from 156,821 to 156,922 bp, displaying highly conserved sequences. In contrast to prior studies, our phylogenomic analyses revealed that C. annuum species did not form a monophyletic group. Each subclade was thought to be related to a different evolutionary history, such as hybridization, domestication from wild ancestors, and artificial selection. Therefore, we were able to discern the relationships among cultivars based on their genetic profiles of plastomes. Our findings also revealed that the Korean landraces Younggo 4, 5, 10, and 11 share the most recent common ancestor with Mexican landrace CM334.
Analysis of Antioxidant Capacity Variation among Thai Holy Basil Cultivars (Ocimum tenuiflorum L.) Using Density-Based Clustering Algorithm
Authors: Saelao Tanapon , Chutimanukul Panita , Suratanee Apichat , Plaimas Kitiporn
Published: October 2023

Holy basil (Ocimum tenuiflorum L.) is a widely renowned herb for its abundance of bioactive compounds and medicinal applications. Nevertheless, there exists a dearth of knowledge regarding the variability among holy basil cultivars capable of yielding substantial bioactive compounds. This study aims to address this gap by shedding light on the diversity of antioxidant capacities within different accessions of Thai holy basil by employing a density-based clustering algorithm to categorize the holy basil cultivars that demonstrate notable antioxidant potential. The study involves the analysis of the anthocyanin, flavonoid, phenolic, and terpenoid content, as well as DPPH antioxidant activity, in 26 Thai holy basil accessions collected from diverse locations in Thailand. Among the 26 tested Thai holy basil cultivars, terpenoids were found to be the dominant class of compounds, with average values of 707 mg/gDW, while the levels of flavonoids and phenolic compounds remained below 65 mg rutin/gDW and 46 mg GAE/gDW, respectively. The DPPH assay in holy basil cultivars demonstrated that the antioxidant activity ranged between 50% and 93%. After standardizing the data, the clustering results revealed four distinct groups of cultivars: the first group, with low antioxidant levels; the second group, with high terpenoid content; the third group, with high flavonoid, DPPH antioxidant activity, and phenolic content; and the fourth group, with elevated levels of anthocyanin, DPPH antioxidant activity, and phenolic content. A strong positive correlation was observed among DPPH antioxidant activity, flavonoids, and phenolics. Specific cultivars: The Red, OC108, and OC106 holy basil cultivars in cluster 4 exhibited high anthocyanin and phenolic production. In cluster 3, the accessions OC113, OC057, OC063, and OC059 showed high DPPH antioxidant activity, flavonoids, and phenolics, while, in cluster 2, only accessions from Udon Thani, Thailand—namely OC194 and OC195—displayed high terpenoid content. Ultimately, this study significantly contributes to the inherent diversity in the antioxidant capacities among various Thai holy basil cultivars. It lays the foundation for targeted breeding strategies and informed choices regarding consumption. The comprehensive insights from this analysis hold the potential to accurately identify holy basil cultivars with promising applications in medicine, functional foods, and the nutraceutical industry.
Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder
Authors: Czarny Piotr , Ziółkowska Sylwia , Kołodziej Łukasz , Watała Cezary , Wigner-Jeziorska Paulina , Bliźniewska-Kowalska Katarzyna , Wachowska Katarzyna , Gałecka Małgorzata , Synowiec Ewelina , Gałecki Piotr , Bijak Michał , Szemraj Janusz , Śliwiński Tomasz
Published: October 2023

One of the key features of major depressive disorder (MDD, depression) is increased oxidative stress manifested by elevated levels of mtROS, a hallmark of mitochondrial dysfunction, which can arise from mitochondrial DNA (mtDNA) damage. Thus, the current study explores possibility that the single-nucleotide polymorphisms (SNPs) of genes encoding the three enzymes that are thought to be implicated in the replication, repair or degradation of mtDNA, i.e., POLG, ENDOG and EXOG, have an impact on the occurrence, onset, severity and treatment of MDD. Five SNPs were selected: EXOG c.-188T > G (rs9838614), EXOG c.*627G > A (rs1065800), POLG c.-1370T > A (rs1054875), ENDOG c.-394T > C (rs2977998) and ENDOG c.-220C > T (rs2997922), while genotyping was performed on 538 DNA samples (277 cases and 261 controls) using TaqMan probes. All SNPs of EXOG and ENDOG modulated the risk of depression, but the strongest effect was observed for rs1065800, while rs9838614 and rs2977998 indicate that they might influence the severity of symptoms, and, to a lesser extent, treatment effectiveness. Although the SNP located in POLG did not affect occurrence of the disease, the result suggests that it may influence the onset and treatment outcome. These findings further support the hypothesis that mtDNA damage and impairment in its metabolism play a crucial role not only in the development, but also in the treatment of depression.
Extensive Expression of the Virulome Related to Antibiotic Genotyping in Nosocomial Strains of Klebsiella pneumoniae
Authors: Paniagua-Contreras Gloria Luz , Bautista-Cerón Areli , Morales-Espinosa Rosario , Delgado Gabriela , Vaca-Paniagua Felipe , Díaz-Velásquez Clara Estela , de la Cruz-Montoya Aldo Hugo , García-Cortés Luis Rey , Sánchez-Yáñez María Patricia , Monroy-Pérez Eric
Published: October 2023

The emergence of hyper-virulent and multidrug-resistant (MDR) strains of Klebsiella pneumoniae isolated from patients with hospital- and community-acquired infections is a serious health problem that increases mortality. The molecular analysis of virulome expression related to antimicrobial-resistant genotype and infection type in K. pneumoniae strains isolated from patients with hospital- and community-acquired infections has been poorly studied. In this study, we analyzed the overall expression of the virulence genotype associated with the antimicrobial resistance genotype and pulse field gel electrophoresis (PFGE) type (PFtype) in K. pneumoniae. We studied 25 strains of K. pneumoniae isolated from patients who developed bacteremia and pneumonia during their hospital stay and 125 strains from outpatients who acquired community-acquired infections. Susceptibility to 12 antimicrobials was determined by Kirby–Bauer. The identification of K. pneumoniae and antibiotic-resistance genes was performed using polymerase chain reaction (PCR). To promote the expression of the virulence genes of K. pneumoniae, an in vitro infection model was used in human epithelial cell lines A549 and A431. Bacterial RNA was extracted with the QIAcube robotic workstation, and reverse transcription to cDNA was performed with the Reverse Transcription QuantiTect kit (Qiagen). The determination of the expression of the virulence genes was performed by real-time PCR. In addition, 57.3% (n = 86) of the strains isolated from patients with hospital- and community-acquired infections were multidrug-resistant (MDR), mainly to beta-lactam antibiotics (CB, AM, CFX, and CF), aminoglycosides (GE), quinolones (CPF and NOF), nitrofurantoin (NF), and sulfamethoxazole/trimethoprim (SXT). The most frequently expressed genes among strains isolated from hospital- and community-acquired infections were adhesion-type, ycfm (80%), mrkD (51.3%), and fimH (30.7%); iron uptake, irp2 (84%), fyuA (68.7%), entB (64.7%), and irp1 (56.7%); and protectins, rpmA (26%), which were related to antibiotic-resistance genes, blaTEM (96%), blaSHV (64%), blaCITM (52.6%), blaCTXM-1 (44.7%), tetA (74%), sul1 (57.3%), aac(3)-IV (40.7%), and aadA1 (36%). The results showed the existence of different patterns of expression of virulome related to the genotype of resistance to antimicrobials and to the PFtypes in the strains of K. pneumoniae that cause hospital- and community-acquired infections. These findings are important and may contribute to improving medical treatment strategies against infections caused by K. pneumoniae.
Zinc Finger 521 Modulates the Nrf2-Notch Signaling Pathway in Human Ovarian Carcinoma
Authors: Scicchitano Stefania , Faniello Maria Concetta , Mesuraca Maria
Published: October 2023

The human zinc finger protein 521 (ZNF521) is a co-transcriptional factor with multiple recognized regulatory functions in a range of normal, cancer and stem cell compartments. ZNF521 regulates proliferation, progression and CSC (cancer stem cell) compartments in human ovarian cancer (hOC), which is a very aggressive and late-diagnosed female tumor. Two other important regulators of hOC are the NRF2 and NOTCH signaling pathways. In the present paper, the mRNA and protein levels of ZNF521 were correlated with those of the NRF2-NOTCH signaling components in two different hOC cell lines and in a public dataset of 381 hOC patients. The data show that high levels of ZNF521 significantly increase NRF2-NOTCH signaling expression; conversely, the silencing of ZNF521 impairs NRF2-NOTCH signaling. This experimental work shows that, in hOC, different levels of ZNF521 modulate the NRF2-NOTCH signaling pathway and also influences hOC CSC properties.
Interaction of the Gut Microbiome and Immunity in Multiple Sclerosis: Impact of Diet and Immune Therapy
Authors: Yadav Sudhir Kumar , Ito Kouichi , Dhib-Jalbut Suhayl
Published: October 2023

The bidirectional communication between the gut and central nervous system (CNS) through microbiota is known as the microbiota–gut–brain axis. The brain, through the enteric neural innervation and the vagus nerve, influences the gut physiological activities (motility, mucin, and peptide secretion), as well as the development of the mucosal immune system. Conversely, the gut can influence the CNS via intestinal microbiota, its metabolites, and gut-homing immune cells. Growing evidence suggests that gut immunity is critically involved in gut–brain communication during health and diseases, including multiple sclerosis (MS). The gut microbiota can influence the development and function of gut immunity, and conversely, the innate and adaptive mucosal immunity can influence microbiota composition. Gut and systemic immunity, along with gut microbiota, are perturbed in MS. Diet and disease-modifying therapies (DMTs) can affect the composition of the gut microbial community, leading to changes in gut and peripheral immunity, which ultimately affects MS. A high-fat diet is highly associated with gut dysbiosis-mediated inflammation and intestinal permeability, while a high-fiber diet/short-chain fatty acids (SCFAs) can promote the development of Foxp3 Tregs and improvement in intestinal barrier function, which subsequently suppress CNS autoimmunity in the animal model of MS (experimental autoimmune encephalomyelitis or EAE). This review will address the role of gut immunity and its modulation by diet and DMTs via gut microbiota during MS pathophysiology.
Is HOXA5 a Novel Prognostic Biomarker for Uterine Corpus Endometrioid Adenocarcinoma?
Authors: Song Changho , Kim Kyoung Bo , Lee Gi Su , Shin Soyoung , Kim Byoungje
Published: October 2023

Endometrial cancer (EC) is one of the most pervasive malignancies in females worldwide. HOXA5 is a member of the homeobox (HOX) family and encodes the HOXA5 protein. HOXA5 is associated with various cancers; however, its association with EC remains unclear. This study aimed to determine the association between HOXA5 gene expression and the prognosis of endometrioid adenocarcinoma, a subtype of EC (EAEC). Microarray data of HOXA5 were collected from the Gene Expression Omnibus datasets, consisting of 79 samples from GSE17025 and 20 samples from GSE29981. RNA-sequencing, clinical, and survival data on EC were obtained from The Cancer Genome Atlas cohort. Survival analysis revealed that HOXA5 overexpression was associated with poor overall survival in patients with EAEC (p = 0.044, HR = 1.832, 95% CI = 1.006–3.334). Cox regression analysis revealed that HOXA5 was an independent risk factor for poor prognosis in EAEC. The overexpression of HOXA5 was associated with a higher histological grade of EAEC, and it was also associated with TP53 mutation or the high copy number of EC. Our findings suggest the potential of HOXA5 as a novel biomarker for predicting poor survival outcomes in patients with EAEC.
Presence of Non-Diabetic Kidney Diseases in Biopsy Specimens of Diabetic Patients’ Single Center Experience
Authors: Janković Aleksandar , Dimković Nada , Todorov-Sakić Verica , Bulatović Ana , Simović Nikola , Đurić Petar , Naumović Radomir
Published: October 2023

The complications of type 2 diabetes mellitus (T2DM) are well known and one of them is diabetic chronic kidney disease (DCKD). Over time, it has become clear that patients with T2DM can have nondiabetic chronic kidney diseases (NDCKD), especially those that affect the glomeruli. Clinical indicators for identifying DCKD from NDCKD with high sensitivity and specificity have not yet been identified. Therefore, kidney biopsy remains the golden standard for DCKD diagnosis in patients with T2DM. Despite some indications for kidney biopsy, criteria for a biopsy differ between countries, regions, and doctors. The aim of the study was to analyze the biopsy findings in our T2DM population and the justification of the biopsy according to widely accepted criteria. This single center retrospective study analyzed data from 74 patients with T2DM who underwent kidney biopsy from January 2014 to January 2021. According to the biopsy data, we categorized31 patients in the DN group, patients with typical diabetic glomerulopathy, 11 patients in the mixed group, patients who had pathohistological elements for both DN and non-DN glomerulopathy, and 32 patients in the non-DN group, patients with primary glomerulopathy not linked with DM. In the non-DN and mixed groups, the most frequent glomerulopathy was mesangioproliferative glomerulonephritis, including IgA and non-IgA forms, found in 10 patients, and membranous nephropathy (MN) in 10 patients. We analyzed several parameters and only the amount of proteinuria was found to be significantly linked to biopsy findings related to DN. With the existing criteria for kidney biopsy, we managed to detect changes in the kidneys in about half of our patients with T2DM. These patients required specific treatment, different from that which we use for DCKD patients.
Integrated Transcriptome and Metabolome Analysis Reveals the Molecular Mechanism of Rust Resistance in Resistant (Youkang) and Susceptive (Tengjiao) Zanthoxylum armatum Cultivars
Authors: Han Shan , Xu Xiu , Yuan Huan , Li Shujiang , Lin Tiantian , Liu Yinggao , Li Shuying , Zhu Tianhui
Published: October 2023

Chinese pepper rust is a live parasitic fungal disease caused by Coleosporium zanthoxyli, which seriously affects the cultivation and industrial development of Z. armatum. Cultivating and planting resistant cultivars is considered the most economical and environmentally friendly strategy to control this disease. Therefore, the mining of excellent genes for rust resistance and the analysis of the mechanism of rust resistance are the key strategies to achieve the targeted breeding of rust resistance. However, there is no relevant report on pepper rust resistance at present. The aim of the present study was to further explore the resistance mechanism of pepper by screening the rust-resistant germplasm resources in the early stage. Combined with the analysis of plant pathology, transcriptomics, and metabolomics, we found that compared with susceptible cultivar TJ, resistant cultivar YK had 2752 differentially expressed genes (DEGs, 1253 up-, and 1499 downregulated) and 321 differentially accumulated metabolites (DAMs, 133 up- and 188 down-accumulated) after pathogen infection. And the genes and metabolites related to phenylpropanoid metabolism were highly enriched in resistant varieties, which indicated that phenylpropanoid metabolism might mediate the resistance of Z. armatum. This finding was further confirmed by a real-time quantitative polymerase chain reaction analysis, which revealed that the expression levels of core genes involved in phenylpropane metabolism in disease-resistant varieties were high. In addition, the difference in flavonoid and MeJA contents in the leaves between resistant and susceptible varieties further supported the conclusion that the flavonoid pathway and methyl jasmonate may be involved in the formation of Chinese pepper resistance. Our research results not only help to better understand the resistance mechanism of Z. armatum rust but also contribute to the breeding and utilization of resistant varieties.
Human Osteoblasts’ Response to Biomaterials for Subchondral Bone Regeneration in Standard and Aggressive Environments
Authors: Pagani Stefania , Salerno Manuela , Filardo Giuseppe , Locs Janis , van Osch Gerjo J.V.M. , Vecstaudza Jana , Dolcini Laura , Borsari Veronica , Fini Milena , Giavaresi Gianluca , Columbaro Marta
Published: October 2023

Osteochondral lesions, when not properly treated, may evolve into osteoarthritis (OA), especially in the elderly population, where altered joint function and quality are usual. To date, a collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HAp) scaffold (OC) has demonstrated good clinical results, although suboptimal subchondral bone regeneration still limits its efficacy. This study was aimed at evaluating the in vitro osteogenic potential of this scaffold, functionalized with two different strategies: the addition of Bone Morphogenetic Protein-2 (BMP-2) and the incorporation of strontium (Sr)-ion-enriched amorphous calcium phosphate (Sr-ACP) granules. Human osteoblasts were seeded on the functionalized scaffolds (OC+BMP-2 and OC+Sr-ACP, compared to OC) under stress conditions reproduced with the addition of H2O2 to the culture system, as well as in normal conditions, and evaluated in terms of morphology, metabolic activity, gene expression, and matrix synthesis. The OC+BMP-2 scaffold supported a better osteoblast morphology and stimulated scaffold colonization, cell activity, and extracellular matrix secretion, especially in the stressed culture environment but also in normal culture conditions, with increased expression of genes related to osteoblast differentiation. In conclusion, the incorporation of BMP-2 into the Col/Col-Mg-HAp scaffold also represents an improvement of the osteochondral scaffold in more challenging conditions, supporting further preclinical studies to optimize it for use in clinical practice.
Ethanolic Extract of Propolis Modulates Autophagy-Related microRNAs in Osteoarthritic Chondrocytes
Authors: Arias Consuelo , Salazar Luis A.
Published: October 2023

Osteoarthritis is a multifactorial joint disease characterized by degeneration, and aging stands as a significant risk factor. Autophagy, a crucial cellular homeostasis mechanism, is influenced by aging and closely linked to cartilage health. This correlation between autophagy, cell death, and OA underscores its relevance in disease progression. MicroRNAs have emerged as autophagy regulators, with miRNA-based interventions showing promise in preclinical models. Remarkably, the ethanolic extract of propolis exhibits positive effects on autophagy-related proteins and healthy cartilage markers in an in vitro osteoarthritis model. The aim of this brief report was to evaluate through in silico analysis and postulate five microRNAs that could regulate autophagy proteins (AKT1, ATG5, and LC3) and assess whether the ethanolic extract of propolis could regulate the expression of these microRNAs. Among the examined miRNAs (miR-19a, miR-125b, miR-181a, miR-185, and miR-335), the ethanolic extract of propolis induced significant changes in four of them. Specifically, miR-125b responded to EEP by counteracting IL-1β-induced effects, while miR-181a, miR-185, and miR-335 exhibited distinct patterns of expression under EEP treatment. These findings unveil a potential link between miRNAs, EEP, and autophagy modulation in OA, offering promising therapeutic insights. Nevertheless, further validation and clinical translation are warranted to substantiate these promising observations.
Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model
Authors: Hernández-Goenaga Juan , López-Abán Julio , Blanco-Gómez Adrián , Vicente Belén , Burguillo Francisco Javier , Pérez-Losada Jesús , Muro Antonio
Published: October 2023

Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions involved, a backcross strategy was employed to generate high variation in schistosomiasis susceptibility. This strategy involved crossing the resistant C57BL/6J mouse strain with the susceptible CBA/2J strain. The resulting F1 females (C57BL/6J × CBA/2J) were then backcrossed with CBA/2J males to generate the backcross (BX) cohort. The BX mice exhibited a range of phenotypes, with disease severity varying from mild to severe disease, lacking a fully resistant group. We observed four levels of infection intensity using cluster and principal component analyses and K-means based on parasitological, pathological, and immunological trait measurements. The mice were genotyped with 961 informative SNPs, leading to the identification of 19 new quantitative trait loci (QTL) associated with parasite burden, liver lesions, white blood cell populations, and antibody responses. Two QTLs located on chromosomes 15 and 18 were linked to the number of granulomas, liver lesions, and IgM levels. The corresponding syntenic human regions are located in chromosomes 8 and 18. None of the significant QTLs had been reported previously.
Metabolomic Signatures of Alzheimer’s Disease Indicate Brain Region-Specific Neurodegenerative Progression
Authors: Ambeskovic Mirela , Hopkins Giselle , Hoover Tanzi , Joseph Jeffrey T. , Montina Tony , Metz Gerlinde A. S.
Published: October 2023

Pathological mechanisms contributing to Alzheimer’s disease (AD) are still elusive. Here, we identified the metabolic signatures of AD in human post-mortem brains. Using 1H NMR spectroscopy and an untargeted metabolomics approach, we identified (1) metabolomic profiles of AD and age-matched healthy subjects in post-mortem brain tissue, and (2) region-common and region-unique metabolome alterations and biochemical pathways across eight brain regions revealed that BA9 was the most affected. Phenylalanine and phosphorylcholine were mainly downregulated, suggesting altered neurotransmitter synthesis. N-acetylaspartate and GABA were upregulated in most regions, suggesting higher inhibitory activity in neural circuits. Other region-common metabolic pathways indicated impaired mitochondrial function and energy metabolism, while region-unique pathways indicated oxidative stress and altered immune responses. Importantly, AD caused metabolic changes in brain regions with less well-documented pathological alterations that suggest degenerative progression. The findings provide a new understanding of the biochemical mechanisms of AD and guide biomarker discovery for personalized risk prediction and diagnosis.