bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging role of METTL3 in inflammatory diseases: mechanisms and therapeutic applications
Authors: Song Bimei , Zeng Yue , Cao Yanqing , Zhang Jiamin , Xu Chao , Pan Yaping , Zhao Xida , Liu Jingbo
Published: August 2023

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.
Assessing the feasibility of assisted migration of corals in the Red Sea
Authors: Barreto Marcelle Muniz , Schmidt-Roach Sebastian , Zhong Huawen , Aranda Manuel
Published: August 2023

Climate change, and in particular the unprecedented rapid global warming, presents a major threat to corals, with warming rates potentially exceeding the adaptive capacities of most coral species. Assisted gene flow, the human facilitated introduction of temperature resilience alleles from warmer to threatened colder populations via the movement of individuals (assisted migration) or their gametes (selective breeding), has been suggested as a tool to transfer thermal adaptations among populations. Due to its strong latitudinal temperature gradient and extreme temperature conditions, the Red Sea constitutes an ideal location to investigate the potential of this strategy. Here, we relocated Porites lobata colonies from three reefs along the Saudi Arabian Red Sea with different mean sea surface temperature summer maxima (ranging from 30.9 °C in Duba, 32.5 °C in Thuwal, to 33.8 °C in Jazan) to a common garden experiment in the intermediate central location. Five colonies from each location were fragmented and deployed in situ in early summer of 2018 to investigate physiological differences in bleaching, survival, and growth. Results showed significantly higher bleaching in fragments from Duba, followed by 65% mortality. Even though no bleaching was observed in fragments from Jazan, mortality rates of around 20% indicated that other environmental parameters besides temperature might influence coral health and survival. These results suggest that assisted gene flow via translocation alone may be restricted in its success due to a lack of local adaptations to environmental conditions other than temperature. However, strategies like inter-populational breeding may overcome these limitations as they might allow producing offspring with both increased thermal tolerance and local adaptations.
The role of humic-type ligands in the bioavailability and stabilization of dissolved iron in the Western Tropical South Pacific Ocean
Authors: Dulaquais Gabriel , Fourrier Pierre , Guieu Cécile , Mahieu Léo , Riso Ricardo , Salaun Pascal , Tilliette Chloé , Whitby Hannah
Published: August 2023

The high N2 fixation rate observed in the Lau Basin of the western tropical South Pacific Ocean (WTSP) is fueled by iron (Fe) released from shallow hydrothermal systems. Understanding Fe bioavailability is crucial but the controls on the stability and bioavailability of hydrothermal Fe inputs are still poorly understood. Here, we provide new data on the spatial and vertical distribution of the soluble ubiquitous humic-like ligands (LFeHS) and their associated dissolved Fe (DFe) in the WTSP, including in samples near hydrothermal vents. Our data show that LFeHS are heterogenous ligands with binding sites of both strong and intermediate strengths. These ligands are primarily produced in surface waters and partially mineralized in mesopelagic waters. A substantial fraction of DFe was complexed by LFeHS (mean ~30%). The DFe complexed by LFeHS is likely bioavailable to phytoplankton and LFeHS stabilized Fe released by the mineralization of sinking biomass. However, unsaturation of LFeHS by Fe suggest that part of DFe is not available for complexation with LFeHS. Possible reasons are competition between DFe and other metals, such as dissolved copper, or the inability of LFeHS to access colloidal DFe. The study of two volcanic sites indicates that LFeHS were not produced in these hydrothermal systems. At the active site (DFe ~50 nmol L-1), LFeHS can only partially solubilize the hydrothermal DFe released in this area (1~5.5% of the total DFe). We performed controlled laboratory experiments which show that the observed low solubilization yield result from the inability of LFeHS to solubilize aged Fe oxyhydroxides (FeOx - a kinetically mediated process) and to form stable complexes with Fe(II) species. Our study provides new understanding of the role of LFeHS on the bioavailability and stabilization of hydrothermal DFe.
Risk assessment of Golani’s round herring (Etrumeus golanii) in the Greek seas (northeastern Mediterranean Sea)
Authors: Keramidas Ioannis , Tsikliras Athanassios C. , Zenetos Argyro , Karachle Paraskevi K.
Published: August 2023

Greek waters are the recipient of several alien species, mainly through natural dispersal following invasion and establishment of non-indigenous species (NIS) in neighboring areas, making their monitoring and mitigating their effects of paramount importance. The European Union legislation framework toward alien species invasions considers risk assessments as the top of the spear for a first assessment of NIS and their potential to become invasive or not. The Union List has already included top priority species, with very few marine species. Golani’s round herring (Etrumeus golanii) is a species of round herrings in the family Dussumieriidae, a Lessepsian migrant and belonging to a group of NIS in the Mediterranean basin that are less studied. Its distribution range is mainly limited in the southeastern Mediterranean Sea, while in the Greek seas, it has not yet been observed in the north Aegean and Ionian seas, probably due to temperature and oceanographical reasons. Its presence in the basin is recorded by commercial fisheries landings in several countries (especially purse-seiners), indicating a potentially positive effect on commercial fisheries. A risk assessment of E. golanii in Greek waters was carried out in this work, based on the Risk Assessment Scheme developed by the GB Non-Native Species Secretariat (GB Non-Native Risk Assessment—GBNNRA). An overall semi-quantitative summary of risk, in terms of likelihood of events and magnitude of impacts, was facilitated for several attributors, including confidence levels for each one. The assessment highlighted a very likely possibility of introduction in the Greek seas from neighboring countries, as well as successful establishments of populations with high confidence levels. A moderate magnitude of impact regarding its further spread was deemed, while a minor one was indicated in terms of native species pressure and a minimal one in terms of economic costs and public health. Overall, E. golanii was not characterized as an invasive alien species (IAS) and local communities could benefit from its presence (commercial fisheries); however, further studies focusing on its reproduction and spawning grounds should be implemented.
Stenotrophomonas in diversified cropping systems: friend or foe?
Authors: Kumar Abhishek , Rithesh Lellapalli , Kumar Vikash , Raghuvanshi Nikhil , Chaudhary Kautilya , Abhineet  , Pandey Abhay K.
Published: August 2023

In the current scenario, the use of synthetic fertilizers is at its peak, which is an expensive affair, possesses harmful effects to the environment, negatively affecting soil fertility and beneficial soil microfauna as well as human health. Because of this, the demand for natural, chemical-free, and organic foods is increasing day by day. Therefore, in the present circumstances use of biofertilizers for plant growth-promotion and microbe-based biopesticides against biotic stresses are alternative options to reduce the risk of both synthetic fertilizers and pesticides. The plant growth promoting rhizobacteria (PGPR) and microbial biocontrol agents are ecologically safe and effective. Owning their beneficial properties on plant systems without harming the ecosystem, they are catching the widespread interest of researchers, agriculturists, and industrialists. In this context, the genus Stenotrophomonas is an emerging potential source of both biofertilizer and biopesticide. This genus is particularly known for producing osmoprotective substances which play a key role in cellular functions, i.e., DNA replication, DNA-protein interactions, and cellular metabolism to regulate the osmotic balance, and also acts as effective stabilizers of enzymes. Moreover, few species of this genus are disease causing agents in humans that is why; it has become an emerging field of research in the present scenario. In the past, many studies were conducted on exploring the different applications of Stenotrophomonas in various fields, however, further researches are required to explore the various functions of Stenotrophomonas in plant growth promotion and management of pests and diseases under diverse growth conditions and to demonstrate its interaction with plant and soil systems. The present review discusses various plant growth and biocontrol attributes of the genus Stenotrophomonas in various food crops along with knowledge gaps. Additionally, the potential risks and challenges associated with the use of Stenotrophomonas in agriculture systems have also been discussed along with a call for further research in this area.
Exopolysaccharide is required for motility, stress tolerance, and plant colonization by the endophytic bacterium Paraburkholderia phytofirmans PsJN
Authors: Fu Benzhong , Yan Qing
Published: August 2023

Paraburkholderia phytofirmans PsJN is an endophytic bacterium and has been shown to promote the growth and health of many different plants. Exopolysaccharide (EPS) plays important roles in plant-bacteria interaction and tolerance to environmental stresses. However, the function of EPS in PsJN and its interaction with plants remain largely unknown. In this study, a deletion mutation of bceQ gene, encoding a putative flippase for the EPS biosynthesis, was introduced in the genome of PsJN. The ΔbceQ mutant produced a significantly lower level of EPS than the wild type strain in culture media. Compared to the wild type PsJN, the ΔbceQ mutant was more sensitive to desiccation, UV damage, salt (NaCl) and iron (FeCl3) stresses, and bacteriophage infection. More importantly, the mutation of bceQ decreased the endophytic colonization of PsJN in camelina (Camelina sativa) and pea (Camelina sativa) under plant drought stress conditions. To the best of our knowledge, this is the first report that EPS production is required for the maximal colonization of an endophytic bacterium in the plant tissues under stress conditions.
Attention, attention! Posttraumatic stress disorder is associated with altered attention-related brain function
Authors: Ely Samantha L. , Zundel Clara G. , Gowatch Leah C. , Evanski Julia M. , Bhogal Amanpreet , Carpenter Carmen , Shampine MacKenna , Marusak Hilary
Published: August 2023

Posttraumatic stress disorder (PTSD) is a debilitating condition characterized by altered arousal, mood, and cognition. Studies report attentional alterations such as threat bias in individuals with PTSD, though this work has largely been conducted within emotionally-charged contexts (e.g., threatening stimuli). Emerging behavioral evidence suggests that PTSD-related attention deficits exist even in the absence of threatening cues or anxiety triggers. However, the role and functioning of attention brain circuits as they relate to PTSD remains underexplored. In this mini review, we highlight recent work using non-emotional stimuli to investigate the neurobiology of attention and disruptions to attention-related brain function among individuals with PTSD. We then discuss gaps in the current literature, including questions pertaining to the neural circuitry of attentional alterations in PTSD, as well as the contributions that trauma exposure, PTSD symptoms, comorbidities, and pre-existing vulnerabilities may have in this relationship. Finally, we suggest future directions for this emerging area of research, which may further inform knowledge surrounding the neurobiological underpinnings of PTSD and potential treatments.
The effect of intermittent versus continuous enteral feeding for critically ill patients: a meta-analysis of randomized controlled trials
Authors: Qu Jing , Xu Xiaoya , Xu Chaobo , Ding Xuzhong , Zhang Kai , Hu Leshuang
Published: August 2023

Objectives

The appropriate strategy for enteral feeding in critically ill patients still remains controversial. Therefore, we conducted this meta-analysis to compare the effect of intermittent versus continuous enteral feeding method for critically ill patients.

Methods

Electronic databases including PubMed, Embase, Scopus, and Cochrane Library were searched up to April 10th, 2023 for randomized controlled trials evaluating the effect of intermittent versus continuous enteral feeding for critically ill patients. The primary outcomes were feeding intolerances, including diarrhea, vomiting, distension, constipation, gastric retention, and aspiration pneumonia. The secondary outcomes were mortality in intensive care unit (ICU), length of stay in ICU, and achievement of nutritional goal.

Results

Thirteen studies with a total of 884 patients were analyzed in this meta-analysis. Overall, the use of intermittent enteral feeding was associated with higher incidence of diarrhea (OR 1.66, 95%CI 1.13 to 2.43, I2 = 16%) and distension (OR 2.29, 95%CI 1.16 to 4.51, I2 = 0%), lower incidence of constipation (OR 0.58, 95%CI 0.37 to 0.90, I2 = 0%), and longer length of ICU stay (MD 1.09, 95%CI 0.53 to 1.64, I2 = 0%). Moreover, no significant difference was identified for other outcome measures.

Conclusion

In critically ill patients, the implementation of intermittent enteral feeding was associated with higher incidence of diarrhea and distension, longer length of ICU stay, but lower occurrence of constipation. Nevertheless, the absence of sufficient high-quality randomized controlled clinical trials precludes any definitive conclusions regarding the optimal approach to enteral feeding in this population. There is an imperative need for more studies to further assess the efficacy of the two enteral feeding strategies.
Effects of Siraitia grosvenorii seed flour on the properties and quality of steamed bread
Authors: Zhou Wei , Guo Siyu , Zhang Sheng , Lu Zhaodi , Sun Ziyi , Ma Yulin , Shi Jinxiu , Zhang Hao
Published: August 2023

Siraitia grosvenorii seeds are rich in abundant active compounds beneficial to human health. To clarify the digestion characteristics of Siraitia grosvenorii seed flour (SSF) and promote the use of SSF in the processing of functional staple foods, SSF was prepared, its composition and physicochemical properties were studied, and the processing characteristics of SSF-wheat flour were systematically investigated. The results showed that the torque curve and other parameters of the dough were significantly affected by the amount of SSF added. With the increase of SSF proportion, the water absorption showed an increasing trend, while the degree of protein weakening first weakened and then enhanced. At 20% SSF, the dough was more resistant to kneading. In response to an increase in SSF, the L* value decreased significantly, and the a* and b* values increased gradually, while the specific volume decreased gradually. Additionally, the hardness, adhesiveness, and chewiness of the bread enhanced gradually, while its elasticity, cohesiveness, and resilience decreased gradually. After the addition of 30% SSF, the inner tissue of steamed bread was more delicate. With an increase in SSF proportion, the predicted glycemic index (pGI) of steamed bread weakened markedly. Overall, these results showed that SSF, as a kind of food ingredient with hypoglycemic activity, can be used in the production of new functional steamed bread products. This study provides basic research data for the development of products containing S. grosvenorii seed.
Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis
Authors: Sajjadi Elham , Venetis Konstantinos , Ivanova Mariia , Noale Marianna , Blundo Concetta , Di Loreto Eugenia , Scarfone Giovanna , Ferrero Stefano , Maggi Stefania , Veronesi Paolo , Galimberti Viviana E. , Viale Giuseppe , Peccatori Fedro A. , Fusco Nicola , Guerini-Rocco Elena
Published: August 2023

Background

Breast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME.

Methods

n = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher’s and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan–Meier method.

Results

The proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2– subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome.

Conclusion

The TME dynamics of HR+/HER2− PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage.
A proposed methodology for detecting the malignant potential of pulmonary nodules in sarcoma using computed tomographic imaging and artificial intelligence-based models
Authors: Baidya Kayal Esha , Ganguly Shuvadeep , Sasi Archana , Sharma Swetambri , DS Dheeksha , Saini Manish , Rangarajan Krithika , Kandasamy Devasenathipathy , Bakhshi Sameer , Mehndiratta Amit
Published: August 2023

The presence of lung metastases in patients with primary malignancies is an important criterion for treatment management and prognostication. Computed tomography (CT) of the chest is the preferred method to detect lung metastasis. However, CT has limited efficacy in differentiating metastatic nodules from benign nodules (e.g., granulomas due to tuberculosis) especially at early stages (<5 mm). There is also a significant subjectivity associated in making this distinction, leading to frequent CT follow-ups and additional radiation exposure along with financial and emotional burden to the patients and family. Even 18F-fluoro-deoxyglucose positron emission technology-computed tomography (18F-FDG PET-CT) is not always confirmatory for this clinical problem. While pathological biopsy is the gold standard to demonstrate malignancy, invasive sampling of small lung nodules is often not clinically feasible. Currently, there is no non-invasive imaging technique that can reliably characterize lung metastases. The lung is one of the favored sites of metastasis in sarcomas. Hence, patients with sarcomas, especially from tuberculosis prevalent developing countries, can provide an ideal platform to develop a model to differentiate lung metastases from benign nodules. To overcome the lack of optimal specificity of CT scan in detecting pulmonary metastasis, a novel artificial intelligence (AI)-based protocol is proposed utilizing a combination of radiological and clinical biomarkers to identify lung nodules and characterize it as benign or metastasis. This protocol includes a retrospective cohort of nearly 2,000–2,250 sample nodules (from at least 450 patients) for training and testing and an ambispective cohort of nearly 500 nodules (from 100 patients; 50 patients each from the retrospective and prospective cohort) for validation. Ground-truth annotation of lung nodules will be performed using an in-house-built segmentation tool. Ground-truth labeling of lung nodules (metastatic/benign) will be performed based on histopathological results or baseline and/or follow-up radiological findings along with clinical outcome of the patient. Optimal methods for data handling and statistical analysis are included to develop a robust protocol for early detection and classification of pulmonary metastasis at baseline and at follow-up and identification of associated potential clinical and radiological markers.
At-home use of parasacral transcutaneous electrical nerve stimulation for pediatric voiding dysfunction: a randomized controlled trial to assess its safety and feasibility
Authors: Malhotra Neha R. , Siegal Alexandra R. , Lange Suzanne M. , Cervantez DeeAnn , White Heidi K. , Hannon AnnMarie , Schaeffer Anthony J. , Lau Glen A.
Published: August 2023

Introduction

Treating pediatric voiding dysfunction involves behavioral changes that require significant time or medications that are often avoided or discontinued due to side effects. Using parasacral transcutaneous electrical nerve stimulation (PTENS) has shown to have reasonable efficacy, but the safety and feasibility of its off-label use for pediatric voiding dysfunction are not well-established. Concerns have also been raised over treatment adherence. In-home therapy might improve adherence compared with office-based therapy; however, no studies have evaluated in-home feasibility to date. This study aims to assess the safety and feasibility of off-label use of PTENS for pediatric voiding dysfunction.

Materials and methods

A single-institution prospective, randomized controlled study was conducted from March 2019 to March 2020. Participants aged 6–18 years diagnosed with voiding dysfunction, overactive bladder, or urinary incontinence were eligible for the study. Those with known neurologic disorders, implanted electrical devices, anatomic lower urinary tract abnormality, and recurrent urinary tract infections and those taking bladder medications were excluded. Children with primary monosymptomatic nocturnal enuresis were also excluded due to previous work suggesting a lack of efficacy. Participants were randomly assigned to receive 12 weeks of urotherapy alone (control) or urotherapy plus at-home PTENS treatment. Families were contacted weekly to assess for adverse events (AEs) and treatment adherence. The primary and secondary outcomes were safety, defined as the absence of AEs and treatment adherence, respectively.

Results

A total of 30 eligible participants were divided into two groups, with 15 participants in each arm. The median age was 9.4 years (interquartile range: 7.7–10.6). In total, 60% were male. Baseline demographics and urotherapy compliance were similar between the two groups. With PTENS use, two AEs were reported, including mild pruritus at the pad site and discomfort when removing pads, while no AEs were noted in the control group. In total, 60% of patients completed three 30-min sessions per week, and all participants were able to complete treatment sessions for at least 10 weeks, involving 30 min of PTENS treatment each time.

Conclusion

This randomized controlled study confirms that at-home use of PTENS is feasible with reasonable treatment adherence and minimal AEs. Future collaborative, multi-institutional studies may better determine the efficacy of this treatment modality.
Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level
Authors: Jiang Zhi , Zou Qiuping , Chen Qicheng , Zhang Junhong , Tang Hailin , Chen Jingbao , Qin You , Yang Liming , Chen Zhiqiang , Cao Lixing
Published: August 2023

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments.

Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments.

Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery.

Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.
Intercellular crosstalk mediated by tunneling nanotubes between central nervous system cells. What we need to advance
Authors: Capobianco D. L. , Simone L. , Svelto M. , Pisani F.
Published: August 2023

Long-range intercellular communication between Central Nervous System (CNS) cells is an essential process for preserving CNS homeostasis. Paracrine signaling, extracellular vesicles, neurotransmitters and synapses are well-known mechanisms involved. A new form of intercellular crosstalk mechanism based on Tunneling Nanotubes (TNTs), suggests a new way to understand how neural cells interact with each other in controlling CNS functions. TNTs are long intercellular bridges that allow the intercellular transfer of cargoes and signals from one cell to another contributing to the control of tissue functionality. CNS cells communicate with each other via TNTs, through which ions, organelles and other signals are exchanged. Unfortunately, almost all these results were obtained through 2D in-vitro models, and fundamental mechanisms underlying TNTs-formation still remain elusive. Consequently, many questions remain open, and TNTs role in CNS remains largely unknown. In this review, we briefly discuss the state of the art regarding TNTs identification and function. We highlight the gaps in the knowledge of TNTs and discuss what is needed to accelerate TNTs-research in CNS-physiology. To this end, it is necessary to: 1) Develop an ad-hoc TNTs-imaging and software-assisted processing tool to improve TNTs-identification and quantification, 2) Identify specific molecular pathways involved into TNTs-formation, 3) Use in-vitro 3D-CNS and animal models to investigate TNTs-role in a more physiological context pushing the limit of live-microscopy techniques. Although there are still many steps to be taken, we believe that the study of TNTs is a new and fascinating frontier that could significantly contribute to deciphering CNS physiology.
Genome-wide analysis of the R2R3-MYB gene family in Spatholobus suberectus and identification of its function in flavonoid biosynthesis
Authors: Qin Shuangshuang , Wei Fan , Liang Ying , Tang Danfeng , Lin Quan , Miao Jianhua , Wei Kunhua
Published: August 2023

Spatholobus suberectus Dunn (S. suberectus), a plant species within the Leguminosae family, has a long history of use in traditional medicines. The dried stem of S. suberectus exhibits various pharmacological activities because it contains various flavonoids. Diverse functions in plants are associated with the R2R3-MYB gene family, including the biosynthesis of flavonoids. Nonetheless, its role remains unelucidated in S. suberectus. Therefore, the newly sequenced S. suberectus genome was utilized to conduct a systematic genome-wide analysis of the R2R3-MYB gene family. The resulting data identified 181 R2R3-SsMYB genes in total, which were then categorized by phylogenetic analysis into 35 subgroups. Among the R2R3-SsMYB genes, 174 were mapped to 9 different chromosomes, and 7 genes were not located on any chromosome. Moreover, similarity in terms of exon-intron structures and motifs was exhibited by most genes in the same subgroup. The expansion of the gene family was primarily driven by segmental duplication events, as demonstrated by collinearity analysis. Notably, most of the duplicated genes underwent purifying selection, which was depicted through the Ka/Ks analysis. In this study, 22 R2R3-SsMYB genes were shown to strongly influence the level of flavonoids. The elevated expression level of these genes was depicted in the tissues with flavonoid accumulation in contrast with other tissues through qRT-PCR data. The resulting data elucidate the structural and functional elements of R2R3-SsMYB genes and present genes that could potentially be utilized for enhancing flavonoid biosynthesis in S. suberectus.
Modeling of the control logic of a UASS based on coefficient of variation spraying distribution analysis in an indoor flight simulator
Authors: Hanif Adhitya Saiful , Han Xiongzhe , Yu Seung-Hwa , Han Cheolwoo , Baek Sun Wook , Lee Chun-Gu , Lee Dae-Hyun , Kang Yeong Ho
Published: August 2023

Introduction

In the past decade, unmanned aerial spraying systems (UASS) have emerged as an effective crop treatment platform option, competing with other ground vehicle treatments. The development of this platform has provided an effective spraying system that can be used on all crop types and in all weather conditions. However, related research has not been able to develop a UASS that can be operated in windy conditions with a low drift percentage.

Methods

In this research, spraying was simulated in an indoor flight simulator by considering flight speed, altitude, wind speed, wind direction, rotor rotation, interval, spraying pattern, and nozzle type, which were used as the parameters affecting the output value of the coefficient of variation (CV) of spraying. These parameters were referenced as properties that occur in the field, and using machine learning methods, the CV value was used as a dataset to develop a model that can execute pump opening by controlling the flow rate. There are four machine learning methods used, i.e. random forest regression, gradient boosting, ada boost, and automatic relevance determination regression which are compared with simple linear regression and ridge regression as linear regression.

Results

The results revealed that the random forest regression model was the most accurate, with R2 of 0.96 and root mean square error (RMSE) of 0.04%. The developed model was used to simulate spraying with pump opening A, which connects two nozzles in front, and pump opening AB, which connects all four nozzles.

Discussion

Using the logic based on CV value and pesticide quantity, the model can execute the pump opening against the environment and UASS operation.
Nitrogen acquisition strategy and its effects on invasiveness of a subtropical invasive plant
Authors: Guan Ming , Pan Xiao-Cui , Sun Jian-Kun , Chen Ji-Xin , Kong De-Liang , Feng Yu-Long
Published: August 2023

Introduction

Preference and plasticity in nitrogen (N) form uptake are the main strategies with which plants absorb soil N. However, little effort has been made to explore effects of N form acquisition strategies, especially the plasticity, on invasiveness of exotic plants, although many studies have determined the effects of N levels (e.g. N deposition).

Methods

To address this problem, we studied the differences in N form acquisition strategies between the invasive plant Solidago canadensis and its co-occurring native plant Artemisia lavandulaefolia, effects of soil N environments, and the relationship between N form acquisition strategy of S. canadensis and its invasiveness using a 15N-labeling technique in three habitats at four field sites.

Results

Total biomass, root biomass, and the uptakes of soil dissolved inorganic N (DIN) per quadrat were higher for the invasive relative to the native species in all three habitats. The invader always preferred dominant soil N forms: NH4+ in habitats with NH4+ as the dominant DIN and NO3- in habitats with NO3- as the dominant DIN, while A. lavandulaefolia consistently preferred NO3- in all habitats. Plasticity in N form uptake was higher in the invasive relative to the native species, especially in the farmland. Plant N form acquisition strategy was influenced by both DIN levels and the proportions of different N forms (NO3-/NH4+) as judged by their negative effects on the proportional contributions of NH4+ to plant N (fNH4+) and the preference for NH4+ (βNH4+). In addition, total biomass was positively associated with fNH4+ or βNH4+ for S. canadensis, while negatively for A. lavandulaefolia. Interestingly, the species may prefer to absorb NH4+ when soil DIN and/or NO3-/NH4+ ratio were low, and root to shoot ratio may be affected by plant nutrient status per se, rather than by soil nutrient availability.

Discussion

Our results indicate that the superior N form acquisition strategy of the invader contributes to its higher N uptake, and therefore to its invasiveness in different habitats, improving our understanding of invasiveness of exotic plants in diverse habitats in terms of utilization of different N forms.
Understanding the search for more autonomy in Greater Manchester: an alternative perspective on the politics of devolution in England
Authors: Harding Alan , Peake-Jones Sian
Published: August 2023

Critical social scientific accounts of the confused and inconsistent process of “devolution” in England in recent years have rightly emphasized the place that Greater Manchester and, most recently, the Greater Manchester Combined Authority, has occupied at the forefront of UK metropolitan institutional reform. They typically give little credit, however, to the long-running, independent processes of mobilization and institution-building that have resulted in Greater Manchester achieving this vanguard position. This article challenges the idea that contemporary metropolitan governance in Greater Manchester can be seen merely as a pawn in the hands of a regressive, centralist state or else as an undemocratic vehicle designed to enable a city elite to dominate its metropolitan neighbors. In taking a longer historical perspective than is common to critical accounts, the article demonstrates that metropolitanization in England has not followed a coherent centralizing script and neither has the current Combined Authority been constrained, or chosen, to adopt the narrow economic development logic its critics allege. The latter is exemplified by an empirical examination of the work done in Greater Manchester on the theme of work and health. The article concludes with an assessment of how a fragile and very English form of devolution might develop in the difficult context in which the UK now finds itself, arguing that social scientific analysis can perform much better in identifying ways in which further enhancements of sub-national autonomy can support the realization of progressive social and environmental goals.
Case report: Urbanized non-human primates as sentinels for human zoonotic diseases: a case of acute fatal toxoplasmosis in a free-ranging marmoset in coinfection with yellow fever virus
Authors: Sousa Davi E. R. , Wilson Tais M. , Macêdo Isabel L. , Romano Alessandro P. M. , Ramos Daniel G. , Passos Pedro H. O. , Costa Gabriela R. T. , Fonseca Vagner S. , Mares-Guia Maria Angélica M. M. , Giovanetti Marta , Alcantara Luiz Carlos Junior , de Filippis Ana Maria B. , Paludo Giane R. , Melo Cristiano B. , Castro Márcio B.
Published: August 2023

Free-ranging non-human primates (NHP) can live in anthropized areas or urban environments in close contact with human populations. This condition can enable the emergence and transmission of high-impact zoonotic pathogens. For the first time, we detected a coinfection of the yellow fever (YF) virus with Toxoplasma gondii in a free-ranging NHP in a highly urbanized area of a metropolis in Brazil. Specifically, we observed this coinfection in a black-tufted marmoset found dead and taken for a necropsy by the local health surveillance service. After conducting an epidemiological investigation, characterizing the pathological features, and performing molecular assays, we confirmed that the marmoset developed an acute fatal infection caused by T. gondii in coinfection with a new YF virus South American-1 sub-lineage. As a result, we have raised concerns about the public health implications of these findings and discussed the importance of diagnosis and surveillance of zoonotic agents in urbanized NHPs. As competent hosts of zoonotic diseases such as YF and environmental sentinels for toxoplasmosis, NHPs play a crucial role in the One Health framework to predict and prevent the emergence of dangerous human pathogens.
Gold complex compounds that inhibit drug-resistant Staphylococcus aureus by targeting thioredoxin reductase
Authors: Tharmalingam Nagendran , Xu Shi , Felix Lewis Oscar , Roy Biswajit , Xian Ming , Mylonakis Eleftherios , Fuchs Beth Burgwyn
Published: August 2023

Introduction

There is a significant need for new antimicrobial compounds that are effective against drug-resistant microbes. Thioredoxin reductase (TrxR) is critical in redox homeostasis and was identified as a potential drug target and confirmed through inhibition by compounds auranofin and Bay11-7085.

Methods

Additional TrxR inhibitors were designed and found to exhibit antimicrobial activity against Gram-positive (Enterococcus faecium and Staphylococcus aureus) and glutathione-deficient bacteria (Helicobacter pylori). Investigational compounds were tested for antimicrobial activity, anti-biofilm efficacy, target impact, and cytotoxicity.

Results

The first-generation molecules AU1 and AU5 inhibited TrxR activity and inhibited methicillin-resistant S. aureus strain MW2 with minimal inhibitory concentrations (MIC) of 0.125 and 0.5 μg/mL, respectively. In an S. aureus enzymatic assay, AU1 inhibited TrxR enzymatic activity in a dose-dependent manner causing a decrease in intracellular free thiols. In addition, biofilm studies demonstrated that AU1 and AU5 reduced biofilm formation at 1X MIC and disrupted mature biofilms at 4X MIC. Cytotoxicity profiles were created using human cell lines and primary cells with LD50 exceeding MICs by at least 12X.

Discussion

Thus, AU1 and AU5 were TrxR inhibitors that yielded low-concentration antimicrobial activity impacting S. aureus in planktonic and biofilm forms with limited toxic liability.
Improving data use in decision-making and utilization of maternal healthcare services through a data-informed platform for health approaches in districts of the Gedeo Zone, southern Ethiopia, 2023: a cluster-randomized control trial
Authors: Zenebe Getachew Assefa , Alemu Wagaye , Yehualashet Daniel , Nakachew Mequanint
Published: August 2023

Background

In low-resource countries such as Ethiopia, the utilization of local data for planning and decision-making health systems was frequently constrained. In addition, despite several government initiatives, maternal health services were not completely utilized. On the other hand, efforts to effectively utilize the local data available to improve the utilization level of maternal healthcare services were insufficient, necessitating the need for a different approach.

Objective

This implementation study aims to test and validate the effectiveness of a data-informed platform for health (DIPH) strategies on data use for decision-making and utilization of maternal health services in districts of the Gedeo Zone, southern Ethiopia.

Methods

A two-arm parallel group, type II hybrid, cluster-randomized control trial design has been implemented to conduct the study between 1 September 2022 and 29 February 2024. Six woredas/districts have been assigned to the intervention arm and the other six to the control arm. Baseline and end-line data have been collected from 120 eligible health management staff (from both intervention arm and control arm). In the intervention arm, district health management staff have been given specialized training and continuous technical assistance as a package called the DIPH strategy by embedding it with the district's current decision-making platform such as Performance Review Team meetings. The DIPH strategy has mainly focused on five-step approaches such as situational assessment, stakeholder engagement, defining/setting priorities, planning, and follow-up. Health management staff in the control arm have performed their regular daily activities. The χ2 and t-tests have been used to check the effect of the intervention. In addition, difference-in-differences estimates have been calculated because the change may inherently occur over time. A P-value of <0.05 and a 95% confidence interval have been used to declare the significance of the intervention.

Discussion

The findings of this study were supposed to give insights into implementation strategies that improve data use in decision-making and utilization of maternal healthcare services at the woreda level and uncover contextual factors that boost the response of these strategies.
Development of in vitro methods to model the impact of vaginal lactobacilli on Staphylococcus aureus biofilm formation on menstrual cups as well as validation of recommended cleaning directions
Authors: Friberg Maria , Woeller Kara , Iberi Vighter , Mancheno Paolo Palacio , Riedeman James , Bohman Lisa , Davis Catherine C.
Published: August 2023

Introduction

Menstrual cups (MC) are a reusable feminine hygiene product. A recent publication suggested that Staphylococcus aureus (S. aureus) biofilms can form on MCs which may lead to increased risk of menstrual Toxic Shock Syndrome (mTSS). Additionally, there is concern that buildup of residual menses may contribute to microbial growth and biofilm formation further increasing mTSS risk. Quantitative and qualitative analysis of in vitro tests were utilized to determine if S. aureus biofilm could form on MC in the presence of the keystone species Lactobacillus after 12 h of incubation. The methodology was based on a modification of an anaerobic in vitro method that harnesses the keystone species hypothesis by including a representative of vaginal lactic acid bacteria.

Methods

MCs were incubated anaerobically for 12 h in Vaginal Defined Media (VDM) with the two morphologically distinct bacteria, Lactobacillus gasseri (L. gasseri) and S. aureus. Colony Forming Units (CFU) for each organism from the VDM broth and sonicated MC were estimated. In addition, a separate experiment was conducted where S. aureus was grown for 12 h in the absence of L. gasseri. Qualitative analysis for biofilm formation utilized micro-CT (µ-CT) and cryogenic scanning electron microscopy (Cryo-SEM).

Results

Samples collected from the media control had expected growth of both organisms after 12 h of incubation. Samples collected from VDM broth were similar to media control at the end of the 12-h study. Total S. aureus cell density on MC following sonication/rinsing was minimal. Results when using a monoculture of S. aureus demonstrated that there was a significant growth of the organism in the media control and broth as well as the sonicated cups indicating that the presence of L. gasseri was important for controlling growth and adherence of S. aureus. Few rod-shaped bacteria (L. gasseri) and cocci (S. aureus) could be identified on the MCs when grown in a dual species culture inoculum and no biofilm was noted via µ-CT and cryo-SEM. Additionally, efforts to model and understand the validity of the current labeled recommendations for MC cleaning in-between uses are supported.

Discussion

The data support continued safe use of the Tampax® cup when used and maintained as recommended.