bluuebunny/crossref_metadata_2025 huggingface dataset:
Load frequency control of new energy power system based on adaptive global sliding mode control
Authors: Liang Yang , Jiaming Qian , Xinxin Lv
Published: May 2024

Owing to the challenges of unstable generation and random load disturbance in new energy power system, this paper integrates the battery energy storage model into the traditional load frequency control (LFC) framework, and proposes a LFC scheme based on adaptive global sliding mode control to stabilize the frequency of power systems amid unpredictable load frequency deviation. First of all, the nonlinear time-varying function is added to the sliding mode surface to make the system globally robust. Then, an adaptive sliding mode control law is crafted to dynamically adjust the frequency variations caused by random load disturbance. Moreover, by utilizing the improved Lyapunov function and Bessel-Legendre inequality, the stabilization criteria of multi-area interconnected power system are built. Finally, the efficacy of the proposed method is demonstrated through single and double area LFC simulation experiments with the common system parameters.
Modeling approaches to redesign ruminant production toward sustainability—the state of the art from a literature perspective
Authors: Lobo Annelise Aila Gomes , Campana Mariana , Gameiro Augusto Hauber , Morais Jozivaldo Prudêncio Gomes de
Published: May 2024

Integrated systems allow the redesign of productive landscapes due to the insertion of different species of trees and shrubs. A diversified pasture provides the animal with a wider range and a greater amount of phytonutrients than animals fed on grains, and beyond that, tree legumes have great potential for producing biomass with excellent levels of crude protein, as well as the capacity for symbiotic nitrogen fixation. Assuming that modeling can be a relevant tool to address systemic changes, we sought to answer the following question: “how can ruminant husbandry systems be modeled to help farmers, considering the combination of pasture and crop production?” Thus, this work aims to create a modeling framework to guide the redesign of productive landscapes for ruminants in tropical conditions at the farm level. The activities to be carried out will be divided into four stages: a) bibliographical research on existing indicators and/or models for ruminant livestock farming; b) writing opinion articles (already published) and review articles (this article); c) indicating parameters for modeling the redesign of ruminant production landscapes with the use of multifunctional forage plants; and d) demonstrating the novelty by building a decision-making model for rural properties. The hypothesis of this work is that the redesign of multifunctional production landscapes can be guided by modeling obtained from experimental variables that already exist and/or are under construction, as well as from published literature.
“Exploring the synergistic relationship between Pratylenchus penetrans and Verticillium dahliae in potato cropping systems: recent developments and research gaps”
Authors: Palmisano Abigail , Parrado Luisa , Quintanilla Marisol
Published: May 2024

The plant parasitic nematode species Pratylenchus penetrans has been known to form a synergistic relationship with the fungal plant pathogen Verticillium dahliae in potato cropping systems across North America. The results of this interaction can be devastating; with plants suffering from choloris, wilting, and premature death or complete yield loss in infected fields. Many studies have been conducted in order to understand how this symbiotic connection is occurring; whether that be from competition within the soil microbial community, through the development of amendment-induced suppressive soils, or from other interactions caused by nematode activity. While the mechanisms behind the hostile interaction between V. dahliae and P. penetrans are undetermined, the purpose of this review is to compile recent developments relating to this symbiotic relationship, the effects the soil microbial community has on said relationship, as well as identify potential gaps in research.
C1q is elevated during chronic Staphylococcus epidermidis central nervous system catheter infection
Authors: Beaver Matthew , Bergdolt Lara , Dunaevsky Anna , Kielian Tammy , Skar Gwenn L.
Published: May 2024

Introduction

Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation.

Methods

We examined complement activation throughout Staphylococcus epidermidis (S. epidermidis) central nervous system (CNS) catheter infection. In addition, based on accumulating evidence that C3 plays a role in synaptic pruning in other neuroinflammatory states we determined if C3 and downstream C5 led to alterations in synaptic protein levels. Using our murine model of S. epidermidis catheter infection we quantified levels of the complement components C1q, Factor B, MASP2, C3, and C5 over the course of infection along with bacterial burdens.

Results

We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and the wealth of information regarding the emerging roles of C1q in the CNS, this suggests functions beyond pathogen elimination during S. epidermidis CNS catheter infection. To identify if C3 impacted synaptic protein levels we performed synaptosome isolation and quantified levels of VGLUT1 and PSD95 as well as pre-, post- and total synaptic puncta in cortical layer V of C3 knockout (KO) and wild type mice. We also used C5 KO and wild type mice to determine if there was any difference in pre-, post- and total synaptic puncta.

Discussion

Neither C3 nor C5 impacted synaptic protein abundance. These findings suggest that chronic elevations in C1q in the brain that persist once CNS catheter infection has resolved may be modulating disease sequalae.
TLR2/4 are novel activating receptors for SARS-CoV-2 spike protein on NK cells
Authors: Landolina Nadine , Ricci Biancamaria , Veneziani Irene , Alicata Claudia , Mariotti Francesca Romana , Pelosi Andrea , Quatrini Linda , Mortari Eva Piano , Carsetti Rita , Vacca Paola , Tumino Nicola , Azzarone Bruno , Moretta Lorenzo , Maggi Enrico
Published: May 2024

Background

In early infected or severe coronavirus disease 2019 (COVID-19) patients, circulating NK cells are consistently reduced, despite being highly activated or exhausted. The aim of this paper was to establish whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (SP) may directly trigger NK cells and through which receptor(s).

Methods

SP-stimulated human NK cells have been evaluated for the expression of activation markers, cytokine release, and cytotoxic activity, as well as for gene expression profiles and NF-kB phosphorylation, and they have been silenced with specific small interfering RNAs.

Results

SPs from the Wuhan strain and other variants of concern (VOCs) directly bind and stimulate purified NK cells by increasing activation marker expression, cytokine release, and cytolytic activity, prevalently in the CD56brightNK cell subset. VOC-SPs differ in their ability to activate NK cells, G614, and Delta-Plus strains providing the strongest activity in the majority of donors. While VOC-SPs do not trigger ACE2, which is not expressed on NK cells, or other activating receptors, they directly and variably bind to both Toll-like receptor 2 (TLR2) and TLR4. Moreover, SP-driven NK cell functions are inhibited upon masking such receptors or silencing the relative genes. Lastly, VOC-SPs upregulate CD56dimNK cell functions in COVID-19 recovered, but not in non-infected, individuals.

Conclusions

TLR2 and TLR4 are novel activating receptors for SP in NK cells, suggesting a new role of these cells in orchestrating the pathophysiology of SARS-CoV-2 infection. The pathogenic relevance of this finding is highlighted by the fact that free SP providing NK cell activation is frequently detected in a SARS-CoV-2 inflamed environment and in plasma of infected and long-COVID‐19 subjects.
An optimized method for IgE-mediated degranulation of human lung mast cells
Authors: Gong Yitao , Johnsson Anna-Karin , Säfholm Jesper , Al-Ameri Mamdoh , Sachs Erik , Vali Kasra , Nilsson Gunnar , Rönnberg Elin
Published: May 2024

Background

Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma. Human mast cells are heterogeneous, and mast cells from different anatomical sites have been shown to respond differently to certain stimuli and drugs. The origin of the mast cells is therefore of importance when setting up a model system, and human lung mast cells are highly relevant cells to study in the context of asthma. We therefore set out to optimize a protocol of IgE-mediated activation of human lung mast cells.

Methods

Human lung mast cells were extracted from lung tissue obtained from patients undergoing pulmonary resection by enzyme digestion and mechanical disruption followed by CD117 magnetic-activated cell sorting (MACS) enrichment. Different culturing media and conditions for the IgE-mediated degranulation were tested to obtain an optimized method.

Results

IgE crosslinking of human lung mast cells cultured in serum-free media gave a stronger response compared to cells cultured with 10% serum. The addition of stem cell factor (SCF) did not enhance the degranulation. However, when the cells were put in fresh serum-free media 30 minutes prior to the addition of anti-IgE antibodies, the cells responded more vigorously. Maximum degranulation was reached 10 minutes after the addition of anti-IgE. Both CD63 and CD164 were identified as stable markers for the detection of degranulated mast cells over time, while the staining with anti-CD107a and avidin started to decline 10 minutes after activation. The levels of CD203c and CD13 did not change in activated cells and therefore cannot be used as degranulation markers of human lung mast cells.

Conclusions

For an optimal degranulation response, human lung mast cells should be cultured and activated in serum-free media. With this method, a very strong and consistent degranulation response with a low donor-to-donor variation is obtained. Therefore, this model is useful for further investigations of IgE-mediated mast cell activation and exploring drugs that target human lung mast cells, for instance, in the context of asthma.
Anemoside B4 attenuates abdominal aortic aneurysm by limiting smooth muscle cell transdifferentiation and its mediated inflammation
Authors: Chu Shuhan , Shan Dan , He Luling , Yang Shilin , Feng Yulin , Zhang Yifeng , Yu Jun
Published: May 2024

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by local abnormal dilation of the aorta accompanied by vascular smooth muscle cell (VSMC) dysfunction and chronic inflammation. VSMC dedifferentiation, transdifferentiation, and increased expression of matrix metalloproteinases (MMPs) are essential causes of AAA formation. Previous studies from us and others have shown that Anemoside B4 (AB4), a saponin from Pulsatilla chinensis, has anti-inflammatory, anti-tumor, and regulatory effects on VSMC dedifferentiation. The current study aimed to investigate whether AB4 inhibits AAA development and its underlying mechanisms. By using an Ang II induced AAA model in vivo and cholesterol loading mediated VSMC to macrophage transdifferentiation model in vitro, our study demonstrated that AB4 could attenuate AAA pathogenesis, prevent VSMC dedifferentiation and transdifferentiation to macrophage-like cells, decrease vascular inflammation, and suppress MMP expression and activity. Furthermore, KLF4 overexpression attenuated the effects of AB4 on VSMC to macrophage-like cell transition and VSMC inflammation in vitro. In conclusion, AB4 protects against AAA formation in mice by inhibiting KLF4 mediated VSMC transdifferentiation and inflammation. Our study provides the first proof of concept of using AB4 for AAA management.
A high-precision interpretable framework for marine dissolved oxygen concentration inversion
Authors: Li Xin , Liu Zhenyi , Yang Zongchi , Meng Fan , Song Tao
Published: May 2024

Variations in Marine Dissolved Oxygen Concentrations (MDOC) play a critical role in the study of marine ecosystems and global climate evolution. Although artificial intelligence methods, represented by deep learning, can enhance the precision of MDOC inversion, the uninterpretability of the operational mechanism involved in the “black-box” often make the process difficult to interpret. To address this issue, this paper proposes a high-precision interpretable framework (CDRP) for intelligent MDOC inversion, including Causal Discovery, Drift Detection, RuleFit Model, and Post Hoc Analysis. The entire process of the proposed framework is fully interpretable: (i) The causal relationships between various elements are further clarified. (ii) During the phase of concept drift analysis, the potential factors contributing to changes in marine data are extracted. (iii) The operational rules of RuleFit ensure computational transparency. (iv) Post hoc analysis provides a quantitative interpretation from both global and local perspectives. Furthermore, we have derived quantitative conclusions about the impacts of various marine elements, and our analysis maintains consistency with conclusions in marine literature on MDOC. Meanwhile, CDRP also ensures the precision of MDOC inversion: (i) PCMCI causal discovery eliminates the interference of weakly associated elements. (ii) Concept drift detection takes more representative key frames. (iii) RuleFit achieves higher precision than other models. Experiments demonstrate that CDRP has reached the optimal level in single point buoy data inversion task. Overall, CDRP can enhance the interpretability of the intelligent MDOC inversion process while ensuring high precision.
Formulation and structural insight of biocompatible microemulsion for enhanced release profile of anticancer methotrexate
Authors: Siddique Muhammad Yasir , Zafar Sehrish , Rizwan Linta , Saleem Muhammad Atif , Haider Sajjad , Azeem Waqar , Alam Kamran , Iqbal Yasir , Sumrra Sajjad Hussain , Nazar Muhammad Faizan
Published: May 2024

Microemulsions (μEs) are particularly suitable systems for the efficient delivery of anticancer drugs due to their thermodynamic stability, structural flexibility, and patient-friendly chemotherapies. Moreover, μE formulations can efficiently encapsulate the anticancer drugs and deliver them to the desired location. Herein, three new Tween-60-based µE formulations were developed to enhance the dissolution profile of anticancer methotrexate (MTX). For this, μE formulations using an appropriate ratio of castor oil (∼9%), water (∼11%), and Tween-60 (∼40%) were used, while ethanol, 2-propanol, and 1-butanol were selected as co-surfactants for each formulation, respectively. Preliminarily, the phase compatibility of the μE ingredients, the average μE region, and the structural transformation in the microstructure of μE were delineated by mapping the pseudoternary phase diagram, as well as electrical conductivity, viscosity, and optical microscopic measurements. The size distribution profile of the as-formulated μEs analyzed by dynamic light scattering (DLS) revealed the fine monomodal assembly of MTX-μE nanodroplets (∼65 nm), which remained stable over a half year of storage. FTIR analysis showed good compatibility of MTX with μE ingredients with no apparent chemical interaction, while fluorescence measurements endorsed the acquisition of MTX in nonpolar microenvironments. Furthermore, an enhanced dissolution rate (>98% ± 1.5%, p ≤ 0.001) and superior bioavailability of the lyophilized non-aggregated methotrexate nanoparticles (MTX-NPs) were achieved, making them a suitable formulation for oral administration.
International regulatory and publicly-funded initiatives to advance drug repurposing
Authors: Spin Eva Louise , Mantel-Teeuwisse Aukje K. , Pasmooij Anna Maria Gerdina
Published: May 2024

Introduction

Although drug repurposing holds great potential in addressing unmet needs, successful practical implementation is challenging and has been less widespread than anticipated. Regulators may play a critical role in addressing this, and recent years have seen the conception of regulator-initiated and publicly-funded repurposing initiatives, with significant regulator involvement.

Methods

International regulators and public funders (n = 8) were interviewed to obtain insight in how repurposing can be advanced from a regulatory perspective. Transcripts were thematically analyzed.

Results

Most initiatives employed a broad concept of repurposing. While patient access was the main focus, label extension remained the gold standard. Commonly perceived barriers were a lack of regulatory expertise, limited downstream drug development, insufficient financial incentives, inadequate awareness of challenges, and poor collaboration. Ways for regulators to facilitate repurposing include early and accessible involvement fostering education, collaboration, and awareness. Increased stakeholder engagement, including internationally, was recommended. Legislative changes may enable the current repurposing ecosystem to evolve.

Discussion

Regulators may play a central role in advancing repurposing by reconsidering their responsibilities within the current regulatory framework, both in mitigating repurposing pitfalls and actively encouraging repurposing initiatives by industry and non-traditional drug developers.
Most accurate mutations in SARS-CoV-2 genomes identified in Uzbek patients show novel amino acid changes
Authors: Ayubov Mirzakamol S. , Mirzakhmedov Mukhammadjon K. , Yusupov Abdurakhmon N. , Asrorov Akmal M. , Nosirov Bakhtiyor V. , Usmanov Dilshod E. , Shermatov Shukhrat E. , Ubaydullaeva Khurshida A. , Abdukarimov Abdusattor , Buriev Zabardast T. , Abdurakhmonov Ibrokhim Y.
Published: May 2024

Purpose

The rapid changes in the coronavirus genomes created new strains after the first variation was found in Wuhan in 2019. SARS-CoV-2 genotypes should periodically undergo whole genome sequencing to control it because it has been extremely helpful in combating the virus. Many diagnoses, treatments, and vaccinations have been developed against it based on genome sequencing. With its practical implications, this study aimed to determine changes in the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic by genome sequencing, thereby providing crucial insights for developing effective control strategies that can be directly applied in the field.

Design

We meticulously generated 17 high-quality whole-genome sequence data from 48 SARS-CoV-2 genotypes of COVID-19 patients who tested positive by PCR in Tashkent, Uzbekistan. Our rigorous approach, which includes stringent quality control measures and multiple rounds of verification, ensures the accuracy and reliability of our findings.

Methods

Our study employed a unique combination of genome sequencing and bioinformatics web tools to analyze amino acid (AA) changes in the virus genomes. This approach allowed us to understand the genetic changes in the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic.

Results

Our study revealed significant nucleotide polymorphisms, including non-synonymous (missense) and synonymous mutations in the coding regions of the sequenced sample genomes. These findings, categorized by phylogenetic analysis into the G clade (or GK sub-clade), contribute to our understanding of the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic. A total of 134 mutations were identified, consisting of 65 shared and 69 unique mutations. These nucleotide changes, including one frameshift mutation, one conservative and disruptive insertion-deletion, four upstream region mutations, four downstream region mutations, 39 synonymous mutations, and 84 missense mutations, are crucial in the ongoing battle against the virus.

Conclusion

The comprehensive whole-genome sequencing data presented in this study aids in tracing the origins and sources of circulating SARS-CoV-2 variants and analyzing emerging variations within Uzbekistan and globally. The genome sequencing of SARS-CoV-2 from samples collected in Uzbekistan in late 2021, during the peak of the pandemic’s second wave nationwide, is detailed here. Following acquiring these sequences, research efforts have focused on developing DNA and plant-based edible vaccines utilizing prevalent SARS-CoV-2 strains in Uzbekistan, which are currently undergoing clinical trials.
The effect of environmental calcium on gene expression, biofilm formation and virulence of Vibrio parahaemolyticus
Authors: Li Xue , Chang Jingyang , Zhang Miaomiao , Zhou Yining , Zhang Tingting , Zhang Yiquan , Lu Renfei
Published: May 2024

Calcium (Ca2+) can regulate the swarming motility and virulence of Vibrio parahaemolyticus BB22. However, the effects of Ca2+ on the physiology of V. parahaemolyticus RIMD2210633, whose genomic composition is quite different with that of BB22, have not been investigated. In this study, the results of phenotypic assays showed that the biofilm formation, c-di-GMP production, swimming motility, zebrafish survival rate, cytoxicity against HeLa cells, and adherence activity to HeLa cells of V. parahaemolyticus RIMD2210633 were significantly enhanced by Ca2+. However, Ca2+ had no effect on the growth, swarming motility, capsular polysaccharide (CPS) phase variation and hemolytic activity. The RNA sequencing (RNA-seq) assay disclosed 459 significantly differentially expressed genes (DEGs) in response to Ca2+, including biofilm formation-associated genes and those encode virulence factors and putative regulators. DEGs involved in polar flagellum and T3SS1 were upregulated, whereas majority of those involved in regulatory functions and c-di-GMP metabolism were downregulated. The work helps us understand how Ca2+ affects the behavior and gene expression of V. parahaemolyticus RIMD2210633.
Gut microbiota and functional dyspepsia: a two-sample Mendelian randomization study
Authors: Xv Yichuan , Chen Jiaxu , Lin Jiang
Published: May 2024

Background

Numerous studies have established that alterations in the gut microbiota (GM) constitute an embedded mechanism in functional dyspepsia (FD). However, the specific GM taxa implicated in the pathological process of FD have remained unclear.

Methods

A two-sample Mendelian randomization analysis was initially conducted to examine the causal relationships between GM and FD, utilizing GWAS data from the MiBioGen Consortium (18,340 cases) and FinnGenn (8,875 cases vs. 320,387 controls). The MR study primarily employed the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to test for heterogeneity and pleiotropy. Single-nucleotide polymorphisms of causal GM taxa were mapped to genes, which were subsequently assessed for causal relationships with FD employing the same methodology.

Results

IVW results revealed that the genus Clostridium innocuum group (OR: 1.12, 95% CI: 1.02–1.24, P = 0.020) and genus Ruminiclostridium 9 were positively associated with FD risk (OR: 1.27, 95% CI: 1.03–1.57, P = 0.028), while the genus Lachnospiraceae FCS020 group tended to exert a negative effect on FD risk (OR = 0.84, 95% CI: 0.73–0.98, P = 0.023). Among GM-related genes, a notable association was observed between RSRC1 and increased FD risk (OR = 1.13, 95% CI: 1.07–1.20, P < 0.001). In sensitivity analyses, no significant pleiotropy or heterogeneity of the results was found.

Conclusions

This study furnished evidence for distinct effects of specific GM taxa on FD risk and hinted at a potential biological mechanism, thereby offering theoretical underpinning for future microbiotherapy of FD.
Combining postgraduate research training, public engagement, and primary school science education—a Superbugs Master (MSc) class
Authors: Tyrrell Jonathan Mark , Ayanikkad Haritha Udayan , Nalleppillil-Gopakumar Vasudev , Oyebode Rachel , Nnamdi Blessing Chiamaka , Hatch Sarah , Eberl Matthias
Published: May 2024

Since 2018, the ‘Superbugs’ initiative at Cardiff University (United Kingdom) has been delivering projects that take a research-driven approach to public engagement, involving rigorous evaluation of the methodologies of delivery and the mechanics of communication. The overall aim of Superbugs is to raise awareness and improve public knowledge of microbiology, infection and antimicrobial resistance (AMR). In the present project, four postgraduate students were recruited to undertake research projects as part of their Master of Science (MSc) studies. After a period of literature appraisals, the students chose to focus on the topic of personal and food hygiene and were tasked with collecting information on effective strategies for educating young children. Taking advantage of a focus group of primary school teachers, the students then designed evidence-informed educational activities and the evaluation strategies by which the impact of these would be assessed. A pilot delivery of these activities was carried out in a community setting at a local public library, before final delivery as part of a school outreach workshop. The MSc students produced three new elements of educational material; a story book, a treasure hunt and an interactive card game, primarily built around the concepts of challenge and gamification. Feedback collected from primary school pupils aged 6–7 years old and teachers indicated that the activities developed were successful in both being engaging to young people and resulting in an improved knowledge on the chosen topics. Taken together, we present evidence that postgraduate research training, underpinned by active and service learning, represents a valid and effective way of delivering impactful public engagement. In turn, the experience holds benefit for the students not only in terms of their academic study and core scientific skills, but also their wider appreciation and confidence in being effective engagers and science communicators.
Tools and methodology to in silico phage discovery in freshwater environments
Authors: Dantas Carlos Willian Dias , Martins David Tavares , Nogueira Wylerson Guimarães , Alegria Oscar Victor Cardenas , Ramos Rommel Thiago Jucá
Published: May 2024

Freshwater availability is essential, and its maintenance has become an enormous challenge. Due to population growth and climate changes, freshwater sources are becoming scarce, imposing the need for strategies for its reuse. Currently, the constant discharge of waste into water bodies from human activities leads to the dissemination of pathogenic bacteria, negatively impacting water quality from the source to the infrastructure required for treatment, such as the accumulation of biofilms. Current water treatment methods cannot keep pace with bacterial evolution, which increasingly exhibits a profile of multidrug resistance to antibiotics. Furthermore, using more powerful disinfectants may affect the balance of aquatic ecosystems. Therefore, there is a need to explore sustainable ways to control the spreading of pathogenic bacteria. Bacteriophages can infect bacteria and archaea, hijacking their host machinery to favor their replication. They are widely abundant globally and provide a biological alternative to bacterial treatment with antibiotics. In contrast to common disinfectants and antibiotics, bacteriophages are highly specific, minimizing adverse effects on aquatic microbial communities and offering a lower cost–benefit ratio in production compared to antibiotics. However, due to the difficulty involving cultivating and identifying environmental bacteriophages, alternative approaches using NGS metagenomics in combination with some bioinformatic tools can help identify new bacteriophages that can be useful as an alternative treatment against resistant bacteria. In this review, we discuss advances in exploring the virome of freshwater, as well as current applications of bacteriophages in freshwater treatment, along with current challenges and future perspectives.
Catabolite control protein C contributes to virulence and hydrogen peroxide-induced oxidative stress responses in Listeria monocytogenes
Authors: Ogunleye Seto C. , Islam Shamima , Chowdhury Q. M. Monzur Kader , Ozdemir Ozan , Lawrence Mark L. , Abdelhamed Hossam
Published: May 2024

Listeria monocytogenes causes listeriosis, an infectious and potentially fatal disease of animals and humans. A diverse network of transcriptional regulators, including LysR-type catabolite control protein C (CcpC), is critical for the survival of L. monocytogenes and its ability to transition into the host environment. In this study, we explored the physiological and genetic consequences of deleting ccpC and the effects of such deletion on the ability of L. monocytogenes to cause disease. We found that ccpC deletion did not impact hemolytic activity, whereas it resulted in significant reductions in phospholipase activities. Western blotting revealed that the ΔccpC strain produced significantly reduced levels of the cholesterol-dependent cytolysin LLO relative to the wildtype F2365 strain. However, the ΔccpC mutant displayed no significant intracellular growth defect in macrophages. Furthermore, ΔccpC strain exhibited reduction in plaque numbers in fibroblasts compared to F2365, but plaque size was not significantly affected by ccpC deletion. In a murine model system, the ΔccpC strain exhibited a significantly reduced bacterial burden in the liver and spleen compared to the wildtype F2365 strain. Interestingly, the deletion of this gene also enhanced the survival of L. monocytogenes under conditions of H2O2-induced oxidative stress. Transcriptomic analyses performed under H2O2-induced oxidative stress conditions revealed that DNA repair, cellular responses to DNA damage and stress, metalloregulatory proteins, and genes involved in the biosynthesis of peptidoglycan and teichoic acids were significantly induced in the ccpC deletion strain relative to F2365. In contrast, genes encoding internalin, 1-phosphatidylinositol phosphodiesterase, and genes associated with sugar-specific phosphotransferase system components, porphyrin, branched-chain amino acids, and pentose phosphate pathway were significantly downregulated in the ccpC deletion strain relative to F2365. This finding highlights CcpC as a key factor that regulates L. monocytogenes physiology and responses to oxidative stress by controlling the expression of important metabolic pathways.
Mechanism on the promotion of host growth and enhancement of salt tolerance by Bacillaceae isolated from the rhizosphere of Reaumuria soongorica
Authors: Bao Xinguang , Chong Peifang , He Cai , Wang Xueying , Zhang Feng
Published: May 2024

Salt stress is a major abiotic stress that affects the growth of Reaumuria soongorica and many psammophytes in the desert areas of Northwest China. However, various Plant Growth-Promoting Rhizobacteria (PGPR) have been known to play an important role in promoting plant growth and alleviating the damaging effects of salt stress. In this study, three PGPR strains belonging to Bacillaceae were isolated from the rhizosphere of Reaumuria soongorica by morphological and molecular identification. All isolated strains exhibited capabilities of producing IAA, solubilizing phosphate, and fixing nitrogen, and were able to tolerate high levels of NaCl stress, up to 8–12%. The results of the pot-based experiment showed that salt (400 mM NaCl) stress inhibited Reaumuria soongorica seedlings’ growth performance as well as biomass production, but after inoculation with strains P2, S37, and S40, the plant’s height significantly increased by 26.87, 17.59, and 13.36%, respectively (p < 0.05), and both aboveground and root fresh weight significantly increased by more than 2 times compared to NaCl treatment. Additionally, inoculation with P2, S37, and S40 strains increased the content of photosynthetic pigments, proline, and soluble protein in Reaumuria soongorica seedlings under NaCl stress, while reducing the content of malondialdehyde and soluble sugars. Metabolomic analysis showed that strain S40 induces Reaumuria soongorica seedling leaves metabolome reprogramming to regulate cell metabolism, including plant hormone signal transduction and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. Under NaCl stress, inoculation with strain S40 upregulated differential metabolites in plant hormone signal transduction pathways including plant hormones such as auxins (IAA), cytokinins, and jasmonic acid. The results indicate that inoculation with Bacillaceae can promote the growth of Reaumuria soongorica seedlings under NaCl stress and enhance salt tolerance by increasing the content of photosynthetic pigments, accumulating osmoregulatory substances, regulating plant hormone levels This study contributes to the enrichment of PGPR strains capable of promoting the growth of desert plants and has significant implications for the psammophytes growth and development in desert regions, as well as the effective utilization and transformation of saline-alkali lands.
Cloning and sequencing analysis of whole Spiroplasma genome in yeast
Authors: Mizutani Masaki , Omori Sawako , Yamane Noriko , Suzuki Yo , Glass John I. , Chuang Ray-Yuan , Fukatsu Takema , Kakizawa Shigeyuki
Published: May 2024

Cloning and transfer of long-stranded DNA in the size of a bacterial whole genome has become possible by recent advancements in synthetic biology. For the whole genome cloning and whole genome transplantation, bacteria with small genomes have been mainly used, such as mycoplasmas and related species. The key benefits of whole genome cloning include the effective maintenance and preservation of an organism's complete genome within a yeast host, the capability to modify these genome sequences through yeast-based genetic engineering systems, and the subsequent use of these cloned genomes for further experiments. This approach provides a versatile platform for in-depth genomic studies and applications in synthetic biology. Here, we cloned an entire genome of an insect-associated bacterium, Spiroplasma chrysopicola, in yeast. The 1.12 Mbp whole genome was successfully cloned in yeast, and sequences of several clones were confirmed by Illumina sequencing. The cloning efficiency was high, and the clones contained only a few mutations, averaging 1.2 nucleotides per clone with a mutation rate of 4 × 10−6. The cloned genomes could be distributed and used for further research. This study serves as an initial step in the synthetic biology approach to Spiroplasma.
Dissecting and tracing the gut microbiota of infants with botulism: a cross sectional and longitudinal study
Authors: Wang Dai , Li Kexin , Wang Lijuan , Teng Zhongqiu , Luo Xia , Sun Hui , Huang Ying , Hu Songnian , Xu Xuefang , He Zilong
Published: May 2024

Background

Infant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum. However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum. Our goal was to reveal the differences in the intestinal microbiota of botulism-infected and healthy infants as well as the dynamic changes over time through multi-omics analysis.

Methods

We performed 16S rRNA sequencing of 20 infants’ stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants’ intestinal microbiota as well as function over time series.

Results

We found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0C. botulinum isolates from the patients were typed into ST31 and ST32.

Conclusion

Differences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants.
Dysregulation of protein succinylation and disease development
Authors: Hou Xiaoli , Zhu Lijuan , Xu Haiying , Shi Jie , Ji Shaoping
Published: May 2024

As a novel post-translational modification of proteins, succinylation is widely present in both prokaryotes and eukaryotes. By regulating protein translocation and activity, particularly involved in regulation of gene expression, succinylation actively participates in diverse biological processes such as cell proliferation, differentiation and metabolism. Dysregulation of succinylation is closely related to many diseases. Consequently, it has increasingly attracted attention from basic and clinical researchers. For a thorough understanding of succinylation dysregulation and its implications for disease development, such as inflammation, tumors, cardiovascular and neurological diseases, this paper provides a comprehensive review of the research progress on abnormal succinylation. This understanding of association of dysregulation of succinylation with pathological processes will provide valuable directions for disease prevention/treatment strategies as well as drug development.
Bioinformatics gene analysis for potential biomarkers and therapeutic targets of Parkinson’s disease based on neutrophil extracellular traps
Authors: Wang Qiang , Gu Youquan , Chen Jun , Liu Xiaoyan , Xie Chen , Wang Xueping
Published: May 2024

Introduction

Neutrophil extracellular traps (NETs) provide key innate immune mechanisms, and studies have shown innate immunity and adaptive immunity are directly linked to Parkinson’s disease (PD) pathology. However, limited research has been conducted on NETs in the context of PD.

Methods

A differential analysis was implemented to acquire differentially expressed genes (DEGs) between PD and control as well as between high- and low-score groups determined by a gene set variation analysis (GSVA). Then, the genes within the critical module, obtained through a weighted gene co-expression network analysis (WGCNA), were intersected with the DEGs to identify the overlapping genes. Then, five kinds of algorithms in the protein–protein interaction (PPI) were performed to identify potential biomarkers. Subsequently, a nomogram for forecasting PD probability was created. An enrichment analysis and an immune infiltration analysis were performed on the identified biomarkers. qRT-PCR was performed to validate the expression trends of three biomarkers.

Results

We revealed 798 DEGs between PD and control groups as well as 168 DEGs between high- and low-score groups obtained by differential analyses. The pink module containing 926 genes was identified as the critical module. According to the intersection of these gene sets, a total of 43 overlapping genes were screened out. Furthermore, GPR78, CADM3, and CACNA1E were confirmed as biomarkers. Moreover, we found that biomarkers mainly participated in pathways, such as the ‘hydrogen peroxide catabolic process’, and ‘cell cycle’; five kinds of differential immune cells between PD and control groups were identified. Finally, the qRT-PCR analysis demonstrated the up-regulation of GPR78, CADM3, and CACNA1E in the PD group.

Discussion

Our study authenticated GPR78, CADM3, and CACNA1E as the biomarkers associated with PD. These findings provide an original reference for the diagnosis and treatment of PD.
Case report: Compound heterozygous variants detected by next-generation sequencing in a Tunisian child with ataxia-telangiectasia
Authors: Ammous-Boukhris Nihel , Abdelmaksoud-Dammak Rania , Ben Ayed-Guerfali Dorra , Guidara Souhir , Jallouli Olfa , Kamoun Hassen , Charfi Triki Chahnez , Mokdad-Gargouri Raja
Published: May 2024

Ataxia-telangiectasia (A-T) is an autosomal recessive primary immunodeficiency disorder (PID) caused by biallelic mutations occurring in the serine/threonine protein kinase (ATM) gene. The major role of nuclear ATM is the coordination of cell signaling pathways in response to DNA double-strand breaks, oxidative stress, and cell cycle checkpoints. Defects in ATM functions lead to A-T syndrome with phenotypic heterogeneity. Our study reports the case of a Tunisian girl with A-T syndrome carrying a compound heterozygous mutation c.[3894dupT]; p.(Ala1299Cysfs3;rs587781823), with a splice acceptor variant: c.[5763-2A>C;rs876659489] in the ATM gene that was identified by next-generation sequencing (NGS). Further genetic analysis of the family showed that the mother carried the c.[5763-2A>C] splice acceptor variant, while the father harbored the c.[3894dupT] variant in the heterozygous state. Molecular analysis provides the opportunity for accurate diagnosis and timely management in A-T patients with chronic progressive disease, especially infections and the risk of malignancies. This study characterizes for the first time the identification of compound heterozygous ATM pathogenic variants by NGS in a Tunisian A-T patient. Our study outlines the importance of molecular genetic testing for A-T patients, which is required for earlier detection and reducing the burden of disease in the future, using the patients’ families.
Vascular architecture characters and risk factors analysis of unstable moyamoya disease
Authors: Zhao Liming , Wu Ruiyu , Xue Bingqian , Gao Tao , Liu Yang , Sun Yuxue , Guo Gaochao , Li Tianxiao , Li Chaoyue
Published: May 2024

Background

In some MMD patients, the digital subtraction angiography (DSA) examination found, occlusion in the ipsilateral internal carotid artery or middle cerebral artery, accompanied by the formation of numerous moyamoya vessels. Conversely, the contralateral internal carotid artery or middle cerebral artery shows signs of stenosis without the presence of moyamoya vessels. Notably, cerebral perfusion studies reveal a similar or even more severe reduction in perfusion on the occluded side compared to the stenotic side. Importantly, clinical symptoms in these patients are typically attributed to ischemia caused by the stenotic side. This condition is referred to as unstable moyamoya disease (uMMD).

Objective

This clinical research focuses on evaluating risk factors related to MMD and developing strategies to minimize postoperative complications. The study aims to analyze vascular characteristics and identify potential risk factors in patients with uMMD.

Methods

The authors reviewed consecutive cases with complete clinical and radiological documentation of patients who underwent surgery between January 2018 and June 2023. Univariate analysis and multivariate logistic regression analysis were employed to understand the risk factors and prognosis of postoperative complications in uMMD.

Results

Postoperative complications were retrospectively analyzed in 1481 patients (aged 14 to 65). Among them, 1,429 patients were assigned to the conventional treatment group, while 52 were in the unstable moyamoya disease group. The uMMD treatment group showed a significantly higher incidence of early postoperative complications such as RIND, cerebral infarction, and cerebral hemorrhage (p < 0.05). Univariate and multivariate logistic regression analyses were conducted on the postoperative complications of 52 uMMD patients. Initial symptoms of stenosis ≤50% (univariate: p = 0.008, multivariate: p = 0.015; OR [95% CI] =23.149 [1.853–289.217]) and choosing occluded side surgery (univariate: p = 0.043, multivariate: p = 0.018; OR [95% CI] =0.059 [0.006–0.617]) were identified as significant risk factors for postoperative neurological complications.

Conclusion

Compared to the conventional treatment group, uMMD has higher complication rates, with vascular stenosis degree and surgical side selection identified as significant risk factors. A comprehensive understanding of preoperative clinical symptoms and vascular characteristics in moyamoya disease patients, coupled with the formulation of rational surgical plans, contributes positively to decreasing postoperative mortality and disability rates in uMMD.
Clinical value of auditory nerve enhancement in idiopathic sudden sensorineural hearing loss: a retrospective study
Authors: Sun Xiao , Chen Lei , Hu Na , Xiong Wenping , Wang Yingjun , Lu Kunpeng , Duan Fujia , Wang Haibo , Wang Mingming
Published: May 2024

Background

The pathogenesis of idiopathic sudden sensorineural hearing loss remains unclear, and no substantial breakthroughs have been achieved in its treatment. Therefore, we conducted this study with the aim to investigate the clinical features and prognostic factors of patients with idiopathic sudden sensorineural hearing loss and auditory nerve enhancement by using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) of the inner ear.

Methods

We retrospectively analyzed the clinical data of adult patients, who experienced sudden unilateral deafness and were admitted to the Department of Otolaryngology, Shandong Provincial ENT Hospital, between December 2020 and July 2021. Patients were divided into an auditory nerve enhancement group and a normal inner ear group, according to 3D-FLAIR MRI findings. Differences in sex, age, side, disease course, underlying diseases, dizziness/vertigo, vestibular function, degree of deafness, hearing classification, and treatment efficacy were analyzed.

Results

Of the 112 cases of sudden idiopathic deafness, 16.07% exhibited enhancement of the auditory nerve on inner-ear 3D-FLAIR MRI. Statistically significant differences in the degree and type of hearing loss were detected between the two groups (p < 0.05). The rates of abnormal results in the caloric, vestibular-evoked myogenic potential, and video head impulse tests were higher in the auditory nerve enhancement group. The cure rate (11.1%) in patients with auditory nerve enhancement was lower than that in patients with normal inner ear MRI findings (28.7%); however, the difference was not statistically significant.

Conclusion

Findings from 3D-FLAIR MRI scans of the inner ear indicated that patients with sudden deafness and auditory nerve enhancement experienced severe hearing loss, aggravated vestibular function injury, and a significantly decreased cure rate. Prompt treatment, ideally within 2 weeks of disease onset, can facilitate hearing recovery.