bluuebunny/crossref_metadata_2025 huggingface dataset:
In-silico molecular docking, ADME study, and molecular dynamic simulation of new azetidin-2-one derivatives with antiproliferative activity
Authors: Ahmed Aya , Faisal Monther
Published: July 2024

Over the past two decades, protein kinase has been a heavily studied target in the development of new anti-proliferative medications. Heterocyclic systems have been identified as the preferred scaffold because of their wide range of biological properties. In this research, the objective was to design and develop fifteen novel azetidin-2-one derivatives and assess their cytotoxic potential as inhibitors of the epidermal growth factor receptor, which is considered one of the key factors influencing cell growth and proliferation. The crystal structure of inactive EGFR tyrosine kinase domain ligand erlotinib from protein data bank was retrieved in order to be docked with our proposed azetidine-2-one derivatives to evaluate their activity as anti-proliferative agents. In this article, an in-silico molecular docking approach proposes that these azetidine-2-one derivatives have satisfactory binding contact with the erlotinib binding site. Although, three compounds have been identified as the most powerful as they have PLP fitness scores of (77.79, 76.68 and 71.46), respectively, while the reference ligand’s fitness score was (71.94). Additionally, all of our derivatives have satisfied the Swiss-ADME parameters, indicating that they may be orally active compounds. In conclusion, two compounds (A-2 and A-8) have better PLP fitness, and one (A-14) has a comparable score in comparison to the reference ligand, at the active site of epidermal growth factor receptor. indicating that the novel azetidine-2-one derivatives have shown interesting results and could be used as model compounds to create novel anti-proliferative drugs. However, more pharmacological evaluation is needed.
Writing the Law in Late Medieval and Early Modern Scotland: Regiam maiestatem, the Marchmont Manuscript (now St Andrews MS 39000), and its Scribe Robert Ewyn, Notary
Authors: Connolly Margaret , Hart Rachel
Published: July 2024

This article extends knowledge of sixteenth-century Scottish textual production by exploring the range of writing activities undertaken by Robert Ewyn, scribe, chaplain and notary. Ewyn made a copy of Regiam maiestatem in Scots in 1548. This manuscript was held in a private collection until 2016 and is comparatively unknown: a full codicological description and account of its provenance history is offered here. A biographical profile of Robert Ewyn is constructed from references in wills and other public records, revealing his family connections and his links to the Edinburgh crafts community; his career as a notary, pre- and post-reformation, is investigated and documents prepared by him are identified. Ewyn's scribal hand is traced across three very different writing contexts (literary book production, legal documentation and secretarial note-taking); as a result, evidence emerges of the different kinds of handwriting a professional scribe could produce, and of the multiple forms of employment that pre-modern notaries might undertake.
Effects of electrical stimulation with alternating fields on the osseointegration of titanium implants in the rabbit tibia - a pilot study
Authors: Klinder A. , Möws F. , Ziebart J. , Su Y. , Gabler C. , Jonitz-Heincke A. , van Rienen U. , Ellenrieder M. , Bader R.
Published: July 2024

Introduction: Electrical stimulation has been used as a promising approach in bone repair for several decades. However, the therapeutic use is hampered by inconsistent results due to a lack of standardized application protocols. Recently, electrical stimulation has been considered for the improvement of the osseointegration of dental and endoprosthetic implants.

Methods: In a pilot study, the suitability of a specifically developed device for electrical stimulation in situ was assessed. Here, the impact of alternating electric fields on implant osseointegration was tested in a gap model using New Zealand White Rabbits. Stimulation parameters were transmitted to the device via a radio transceiver, thus allowing for real-time monitoring and, if required, variations of stimulation parameters. The effect of electrical stimulation on implant osseointegration was quantified by the bone-implant contact (BIC) assessed by histomorphometric (2D) and µCT (3D) analysis.

Results: Direct stimulation with an alternating electric potential of 150 mV and 20 Hz for three times a day (45 min per unit) resulted in improved osseointegration of the triangular titanium implants in the tibiae of the rabbits. The ratio of bone area in histomorphometry (2D analysis) and bone volume (3D analysis) around the implant were significantly increased after stimulation compared to the untreated controls at sacrifice 84 days after implantation.

Conclusion: The developed experimental design of an electrical stimulation system, which was directly located in the defect zone of rabbit tibiae, provided feedback regarding the integrity of the stimulation device throughout an experiment and would allow variations in the stimulation parameters in future studies. Within this study, electrical stimulation resulted in enhanced implant osseointegration. However, direct electrical stimulation of bone tissue requires the definition of dose-response curves and optimal duration of treatment, which should be the subject of subsequent studies.
Impact of sodium-glucose cotransporter-2 inhibitor use on peak VO2 in advanced heart failure patients
Authors: Desai A. , Sharma S. , Abuah N. , Jang J. , Desai S. , Paghdhar S. , Goswami R. M.
Published: July 2024

Introduction

Advanced heart failure (HF) is an epidemic that affects multiple organ systems with high morbidity and mortality rates despite optimal medical therapy (OMT) and remains the leading cause of hospitalizations in type 2 diabetes-related cardiovascular disease. The addition of sodium-glucose co-transporter inhibitors (SGLT2i) in treating these patients has seen improved mortality and hospital admission rates. As such, we felt it was important to investigate whether the use of SGLT2i improved functional capacity in patients with HF when compared to OMT by evaluating maximum oxygen consumption (peak VO2) using cardiopulmonary exercise testing (CPET).

Methods

We found 94 heart failure patients between August 2020 and August 2021 who underwent CPET before and after treatment at Mayo Clinic in Florida. 50 patients received OMT and 44 received OMT and SGLT2i therapy. CPET results before and after were compared for each group.

Results

The baseline ejection fraction was not significantly different between groups, with the OMT group at 38% and the SGLT2i group at 33%, p = 0.10. OMT patients were found to have a significantly lower hemoglobin A1c of 5.7 (5.4–6.1) compared to those with SGLT2i therapy of 6.4 (5.8–7.1), p = 0.01. The baseline peak VO2 was 17.3 ml/kg/min (13.3–21.6) in the OMT group and 17.3 ml/kg/min (14.4–18.9) in the SGLT2i group, p = 0.18, not significantly different. The interesting finding is that the follow-up peak VO2 at one year for the OMT group was 17 ml/kg/min (13.3–21.6), which was not significantly different from the SGLT2i group peak VO2 of 17 ml/kg/min (14.6–19.6), p = 0.19. Our study is the first to compare before and after peak VO2 values of the OMT+SGLT2i group to the patient's own baseline and we found no significant improvement.

Conclusion

Our single-center data shows no improvement in functional capacity after the addition of SGLT2i therapy to OMT in patients with advanced heart failure. Improved hospitalization and symptoms may be attributed to other numerous effects of SGLT2i such as volume management.
Experimental replication of early human behaviour in bird preparation: a pilot-study focusing on bone surface modification and breakage patterns
Authors: Nabais Mariana , Rufà Anna , Igreja Marina
Published: July 2024

The origin of complex behaviour amongst early humans is a subject of heated debate within the scientific community, and the study of small prey remains has become a significant aspect when examining such modern behaviour. Nonetheless, the consumption of small prey by human populations poses analytical difficulties due to the often negligible, or entirely absent, traces on bone surfaces. To address this difficulty, an experimental study focusing on terrestrial avifauna has been prepared, and here we present a preliminary phase of this research. The aim is to distinguish potential modifications on bird bone surfaces and fracture patterns that might facilitate the recognition of human manipulation of avian skeletal remains. Building upon the challenges encountered in the study of archaeological findings recovered from recent excavations in Iberian Middle Palaeolithic sites, the experimental protocol was formulated to encompass the processing of two uncooked and three roasted birds; and the lithic use-wear analysis of the flint flake used in the processing of raw birds. The results showcase distinct patterns of bone surface modifications and breakage between cooked and uncooked birds. Higher numbers of cut marks and manual disarticulation breaks are found on raw animals, whereas roasted animals show no cut marks, local-specific burns and higher bone loss. This pilot-study provides a baseline for future research to further explore the role of avifauna in Neanderthal subsistence and food processing, which may help highlight cultural choices.
Effect of probiotics at different intervention time on glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Wang Xinghui , Chen Lu , Zhang Chunling , Shi Qing , Zhu Lei , Zhao Sisi , Luo Zhiqin , Long Yirun
Published: July 2024

Background

Type 2 diabetes mellitus(T2DM) is characterized by hyperglycemia. Gut microbiome adjustment plays a positive part in glucose regulation, which has become a hotspot. Probiotics have been studied for their potential to control the gut flora and to treat T2DM. However, the conclusion of its glucose-lowering effect is inconsistent based on different probiotic intervention times.

Objectives

To comprehensively evaluate how various probiotic intervention times affect glycemic control in people with T2DM.

Methods

We retrieved PubMed, Embase, Web of Science, and Cochrane Library on randomized controlled trials(RCTs)regarding the impact of probiotics on glycemic control in patients with T2DM from the inception to November 16, 2023. Separately, two researchers conducted a literature analysis, data extraction, and bias risk assessment of the involved studies. We followed the PRISMA guidelines, used RevMan 5.4 software for meta-analysis, and assessed the risk of bias by applying the Cochrane Handbook for Systematic Reviews 5.1.0.

Results

We included eight RCTs with 507 patients. Meta-analysis revealed that the use of probiotics might considerably reduce levels of glycosylated hemoglobin (HbA1c) {mean deviation (MD) = -0.33, 95% confidence interval (CI) (-0.59, -0.07), p = 0.01}, Insulin {standard mean deviation (SMD) = -0.48, 95% CI (-0.74, -0.22), p = 0.0003} and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR){SMD = -1.36, 95% CI (-2.30, -0.41), p = 0.005} than placebo group. No statistically significant differences were found regarding fasting blood glucose (FBG) and body mass index (BMI) {SMD = -0.39, 95% CI (-0.83, 0.05), p = 0.08}, {SMD = -0.40, 95% CI (-1.07, 0.27), p = 0.25}, respectively. Subgroup analyses, grouped by intervention times, showed that six to eight weeks of intervention improved HbA1c compared to the control group (p < 0.05), both six to eight weeks and 12-24 weeks had a better intervention effect on Insulin, and HOMA-IR (p < 0.05).In contrast, there was no statistically significant variation in the length between FBG and BMI regarding duration.

Conclusion

This meta-analysis found probiotics at different intervention times play a positive role in modulating glucose in T2DM, specifically for HbA1c in six to eight weeks, Insulin and HOMA-IR in six to eight weeks, and 12-24 weeks. To confirm our findings, further excellent large-sample research is still required.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42023483325.
Analysis of beta-cell maturity and mitochondrial morphology in juvenile non-human primates exposed to maternal Western-style diet during development
Authors: Carroll Darian T. , Miller Allie , Fuhr Jennifer , Elsakr Joseph M. , Ricciardi Valerie , Del Bene Alexa N. , Stephens Stedman , Krystofiak Evan , Lindsley Sarah R. , Kirigiti Melissa , Takahashi Diana L. , Dean Tyler A. , Wesolowski Stephanie R. , McCurdy Carrie E. , Friedman Jacob E. , Aagaard Kjersti M. , Kievit Paul , Gannon Maureen
Published: July 2024

Introduction

Using a non-human primate (NHP) model of maternal Western-style diet (mWSD) feeding during pregnancy and lactation, we previously reported altered offspring beta:alpha cell ratio in vivo and insulin hyper-secretion ex vivo. Mitochondria are known to maintain beta-cell function by producing ATP for insulin secretion. In response to nutrient stress, the mitochondrial network within beta cells undergoes morphological changes to maintain respiration and metabolic adaptability. Given that mitochondrial dynamics have also been associated with cellular fate transitions, we assessed whether mWSD exposure was associated with changes in markers of beta-cell maturity and/or mitochondrial morphology that might explain the offspring islet phenotype.

Methods

We evaluated the expression of beta-cell identity/maturity markers (NKX6.1, MAFB, UCN3) via florescence microscopy in islets of Japanese macaque pre-adolescent (1 year old) and peri-adolescent (3-year-old) offspring born to dams fed either a control diet or WSD during pregnancy and lactation and weaned onto WSD. Mitochondrial morphology in NHP offspring beta cells was analyzed in 2D by transmission electron microscopy and in 3D using super resolution microscopy to deconvolve the beta-cell mitochondrial network.

Results

There was no difference in the percent of beta cells expressing key maturity markers in NHP offspring from WSD-fed dams at 1 or 3 years of age; however, beta cells of WSD-exposed 3 year old offspring showed increased levels of NKX6.1 per beta cell at 3 years of age. Regardless of maternal diet, the beta-cell mitochondrial network was found to be primarily short and fragmented at both ages in NHP; overall mitochondrial volume increased with age. In utero and lactational exposure to maternal WSD consumption may increase mitochondrial fragmentation.

Discussion

Despite mWSD consumption having clear developmental effects on offspring beta:alpha cell ratio and insulin secretory response to glucose, this does not appear to be mediated by changes to beta-cell maturity or the beta-cell mitochondrial network. In general, the more fragmented mitochondrial network in NHP beta cells suggests greater ability for metabolic flexibility.
Research on large-signal stability of SOFC-lithium battery ship DC microgrid
Authors: Fang Yibin , Yu Wanneng , Liao Weiqiang , Yang Rongfeng , Luo Chenghan , Zhang Changkun , Dong Xin
Published: July 2024

Aiming at the solid oxide fuel cell (SOFC) applied to the ship DC microgrid in the face of pulse load disturbance is prone to make the SOFC voltage drop too large leading to the DC grid oscillation problem. In this paper, a stability criterion method for SOFC-Li battery DC system based on hybrid potential function is proposed. Firstly, a mathematical model of shipboard DC microgrid with SOFC-Li battery is established and the accuracy of the model is verified. Then, the stability criterion of the system based on the hybrid potential function under large disturbances is constructed. Subsequently, the effects of system stability under impulse load conditions were analysed under different parameters. Based on the constructed criterion, simulation verification of the stability boundary conditions of the SOFC system operating independently or jointly with a lithium battery system is carried out. The experimental results show that the proposed stability criterion and control strategy are effective in accurately predicting the system stability boundary. The experimental results verify the effectiveness of the proposed method in improving the stability of the system and provide a theoretical basis for further research on the dynamic characteristics of SOFC systems under complex load conditions.
China’s foreign direct investment: driving green growth or seeking pollution havens? Based on the perspective of green total factor productivity
Authors: Pan Zijian , Hu Yufeng , Xu Rongrong
Published: July 2024

China has significantly increased its foreign direct investment (FDI). Although these investments help to boost global development, their impacts on the environment are still controversial and deserve careful investigation. This paper uses the super-efficiency SBM model to measure the green total factor productivity (GTFP) of 123 host countries of China’s FDI. On this basis, we adopt the two-step system GMM and dynamic panel threshold effect model to analyze the impact of China’s FDI on the GTFP of host countries. The research results show that: 1) The impact of China’s FDI on the GTFP of host countries is mainly through green technology efficiency. Its impact is inhibitory, followed by a promotional one, with the latter being significantly larger than the former. 2) There is no evidence of the “pollution haven effect” associated with China’s FDI. In fact, for countries with lower environmental regulations, China’s FDI promotes the growth of GTFP more effectively. 3) The innovation level of host countries moderates the relationship between China’s FDI and GTFP growth. For host countries with stronger innovation level, their GTFP growth can be enhanced to a greater extent by China’s FDI.
Evaluation of the potential food allergy risks of human lactoferrin expressed in Komagataella phaffii
Authors: Anaya Yanisa , Rosario Martinez Raysa , Goodman Richard E. , Johnson Philip , Vajpeyi Shashwat , Lu Xiaoning , Peterson Ross , Weyers Sarah M. , Breen Bella , Newsham Kahler , Scottoline Brian , Clark Anthony J. , Malinczak Carrie-Anne
Published: July 2024

Introduction

Prior to the introduction of novel food ingredients into the food supply, safety risk assessments are required, and numerous prediction models have been developed and validated to evaluate safety.

Methods

The allergenic risk potential of Helaina recombinant human lactoferrin (rhLF, Effera™), produced in Komagataella phaffii (K. phaffii) was assessed by literature search, bioinformatics sequence comparisons to known allergens, glycan allergenicity assessment, and a simulated pepsin digestion model.

Results

The literature search identified no allergenic risk for Helaina rhLF, K. phaffii, or its glycans. Bioinformatics search strategies showed no significant risk for cross-reactivity or allergenicity between rhLF or the 36 residual host proteins and known human allergens. Helaina rhLF was also rapidly digested in simulated gastric fluid and its digestibility profile was comparable to human milk lactoferrin (hmLF), further demonstrating a low allergenic risk and similarity to the hmLF protein.

Conclusion

Collectively, these results demonstrate a low allergenic risk potential of Helaina rhLF and do not indicate the need for further clinical testing or serum IgE binding to evaluate Helaina rhLF for risk of food allergy prior to introduction into the food supply.
A common secretomic signature across epithelial cancers metastatic to the pleura supports IL-6 axis therapeutic targeting
Authors: Donnenberg Vera S. , Luketich James D. , Popov Bosko , Bartlett David L. , Donnenberg Albert D.
Published: July 2024

Background

Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy.

Method

We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology.

Results

Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor.

Conclusion

The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.
Systematic computer-aided disulfide design as a general strategy to stabilize prefusion class I fusion proteins
Authors: Gonzalez Karen J. , Yim Kevin C. , Blanco Jorge C. G. , Boukhvalova Marina S. , Strauch Eva-Maria
Published: July 2024

Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricate task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric constraints of disulfide bonds and introduces a ranking system to estimate their potential in stabilizing the prefusion conformation. We hypothesized that disulfides restricting the initial stages of the conformational switch could offer higher stability to the prefusion state than those preventing unfolding at a later stage. The implementation of our algorithm on the RSV F protein led to the discovery of prefusion-stabilizing disulfides that supported our hypothesis. Furthermore, the evaluation of our top design as a vaccine candidate in a cotton rat model demonstrated robust protection against RSV infection, highlighting the potential of our approach for vaccine development.
Machine learning-based derivation and validation of three immune phenotypes for risk stratification and prognosis in community-acquired pneumonia: a retrospective cohort study
Authors: Qin Qiangqiang , Yu Haiyang , Zhao Jie , Xu Xue , Li Qingxuan , Gu Wen , Guo Xuejun
Published: July 2024

Background

The clinical presentation of Community-acquired pneumonia (CAP) in hospitalized patients exhibits heterogeneity. Inflammation and immune responses play significant roles in CAP development. However, research on immunophenotypes in CAP patients is limited, with few machine learning (ML) models analyzing immune indicators.

Methods

A retrospective cohort study was conducted at Xinhua Hospital, affiliated with Shanghai Jiaotong University. Patients meeting predefined criteria were included and unsupervised clustering was used to identify phenotypes. Patients with distinct phenotypes were also compared in different outcomes. By machine learning methods, we comprehensively assess the disease severity of CAP patients.

Results

A total of 1156 CAP patients were included in this research. In the training cohort (n=809), we identified three immune phenotypes among patients: Phenotype A (42.0%), Phenotype B (40.2%), and Phenotype C (17.8%), with Phenotype C corresponding to more severe disease. Similar results can be observed in the validation cohort. The optimal prognostic model, SuperPC, achieved the highest average C-index of 0.859. For predicting CAP severity, the random forest model was highly accurate, with C-index of 0.998 and 0.794 in training and validation cohorts, respectively.

Conclusion

CAP patients can be categorized into three distinct immune phenotypes, each with prognostic relevance. Machine learning exhibits potential in predicting mortality and disease severity in CAP patients by leveraging clinical immunological data. Further external validation studies are crucial to confirm applicability.
Chronicles of Kyphosus in the Mediterranean Sea: new records and complete mitogenomes support the scenario of one expanding fish species
Authors: Nota Alessandro , Tiralongo Francesco , Santovito Alfredo , Torroni Antonio , Olivieri Anna
Published: July 2024

The Mediterranean Sea is a biodiversity hotspot, being home to a vast array of marine species. Furthermore, seawater warming is facilitating the arrival and spread of new thermophilic species, posing a severe threat to biodiversity. Among the species currently extending their range and increasing in abundance in Mediterranean waters, sea chubs (genus Kyphosus) are one of the most enigmatic. One challenge arises from the high phenotypic similarity between the two congeneric species documented in the basin: Kyphosus vaigiensis and Kyphosus sectatrix. Their resemblance has often led to identification challenges, resulting in incorrect or omitted species-level classifications. Therefore, despite the growing presence of these fish in the Mediterranean, it remains unclear whether only one or both species are experiencing a demographic increase and range extension. To date, there have been 26 reports of Kyphosus individuals in the Mediterranean Sea, documented in 24 separate papers. Here, we reviewed the history of the genus in the basin and provided 13 new records of these fish from multiple localities along Mediterranean coasts. In addition, we sequenced the entire mitogenomes of two specimens, assessed their phylogenetic relationships with published Kyphosus mitochondrial DNAs from around the world, and conducted detailed morphological and meristic analyses on one of them, allowing us to provide accurate species-level identifications. Our results indicate that K. vaigiensis is the species currently expanding its range in the Mediterranean Sea, while K. sectatrix is still very rare and only sporadically reported. Notably, our mitogenome data indicate that Mediterranean K. vaigiensis individuals most likely came from Atlantic waters, while there is no evidence to support an entrance through the Red Sea or any other anthropogenic vector. Finally, the potential ecological and fishing impacts associated with the proliferation of these fish in the region are discussed.
Nutritional composition and transcriptome analysis of the newly hatched Anguilla japonica from embryo to preleptocephali obtained from artificial reproduction
Authors: Li Kang , Li Yuangu , Li Tiezhu , Cui Rongfeng , Liu Liping
Published: July 2024

The starter diet for Japanese eel (Anguilla japonica) has always been a difficult problem for the realization of total artificial reproduction. Therefore, this research analyzed the nutritional composition of artificially fertilized eggs, and transcriptome of samples from early hatchlings of fry to better understand nutrients requirements. The composition of crude lipid and crude protein in fertilized eggs was 7.24% ± 0.32% and 10.56% ± 0.41%, respectively. Seven kinds of essential amino acids (EAA) were detected but took a comparable lower content (3.19%) than other marine fish eggs. We randomly assembled 265.74 million clean reads and identified 1751 differentially expressed genes (DEGs) (P < 0.01) from pre-leptocephalus larvae. A total of 23 KEGG pathways related to the digestive and metabolic system were detected. Genes related to the secretion pathway of saliva, pancreatic juice and other digestive juices were significantly changed. Transcriptome analysis showed that as larvae aged, glycolytic metabolism and the transcription level of hexokinase (HK) increased significantly (day 0 to 12). This study will facilitate future studies on the nutrition of A. japonica larvae and other biological traits to reproductive research.
A deep neural network-based approach for seizure activity recognition of epilepsy sufferers
Authors: Khurshid Danial , Wahid Fazli , Ali Sikandar , Gumaei Abdu H. , Alzanin Samah M. , Mosleh Mogeeb A. A.
Published: July 2024

Epilepsy is one of the most frequent neurological illnesses caused by epileptic seizures and the second most prevalent neurological ailment after stroke, affecting millions of people worldwide. People with epileptic disease are considered a category of people with disabilities. It significantly impairs a person’s capacity to perform daily tasks, especially those requiring focusing or remembering. Electroencephalogram (EEG) signals are commonly used to diagnose people with epilepsy. However, it is tedious, time-consuming, and subjected to human errors. Several machine learning techniques have been applied to recognize epilepsy previously, but they have some limitations. This study proposes a deep neural network (DNN) machine learning model to determine the existing limitations of previous studies by improving the recognition efficiency of epileptic disease. A public dataset is used in this study and classified into training and testing sets. Experiments were performed to evaluate the DNN model with different dataset classification ratios (80:20), (70:30), (60:40), and (50:50) for training and testing, respectively. Results were evaluated by using different performance metrics including validations, and comparison processes that allow the assessment of the model’s effectiveness. The experimental results showed that the overall efficiency of the proposed model is the highest compared with previous works, with an accuracy rate of 97%. Thus, this study is more accurate and efficient than the existing seizure detection approaches. DNN model has great potential for recognizing epileptic patient activity using a numerical EEG dataset offering a data-driven approach to improve the accuracy and reliability of seizure detection systems for the betterment of patient care and management of epilepsy.
The acetyltransferase SCO0988 controls positively specialized metabolism and morphological differentiation in the model strains Streptomyces coelicolor and Streptomyces lividans
Authors: Bi Yunwen , An Hao , Chi Zhewei , Xu Zhongheng , Deng Yuan , Ren Yuxian , Wang Rui , Lu Xinyi , Guo Jia , Hu Ren , Virolle Marie-Joelle , Xu Delin
Published: July 2024

Streptomycetes are well-known antibiotic producers possessing in their genomes numerous silent biosynthetic pathways that might direct the biosynthesis of novel bio-active specialized metabolites. It is thus of great interest to find ways to enhance the expression of these pathways to discover most needed novel antibiotics. In this study, we demonstrated that the over-expression of acetyltransferase SCO0988 up-regulated the production of specialized metabolites and accelerated sporulation of the weak antibiotic producer, Streptomyces lividans and that the deletion of this gene had opposite effects in the strong antibiotic producer, Streptomyces coelicolor. The comparative analysis of the acetylome of a S. lividans strain over-expressing sco0988 with that of the original strain revealed that SCO0988 acetylates a broad range of proteins of various pathways including BldKB/SCO5113, the extracellular solute-binding protein of an ABC-transporter involved in the up-take of a signal oligopeptide of the quorum sensing pathway. The up-take of this oligopeptide triggers the “bald cascade” that regulates positively specialized metabolism, aerial mycelium formation and sporulation in S. coelicolor. Interestingly, BldKB/SCO5113 was over-acetylated on four Lysine residues, including Lys425, upon SCO0988 over-expression. The bald phenotype of a bldKB mutant could be complemented by native bldKB but not by variant of bldKB in which the Lys425 was replaced by arginine, an amino acid that could not be acetylated or by glutamine, an amino acid that is expected to mimic acetylated lysine. Our study demonstrated that Lys425 was a critical residue for BldKB function but was inconclusive concerning the impact of acetylation of Lys425 on BldKB function.
Evaluation of fecal microbiota of late gestation sows in relation to pelvic organ prolapse risk
Authors: Kiefer Zoë E. , Koester Lucas R. , Studer Jamie M. , Schmitz-Esser Stephan , Ross Jason W.
Published: July 2024

Introduction

Sow mortality in the U.S. swine industry has increased in recent years, for which pelvic organ prolapse (POP) is a major contributor, accounting for 21% of all sow mortality. Dysbiosis of microbial communities has been associated with disease and reproductive dysfunction in several species, and previous studies have shown changes in vaginal microbiota in sows with increased risk for POP during late gestation. However, there is insufficient knowledge surrounding the potential relationship between fecal microbiota and POP in sows. Therefore, the study objective was to identify differences in sow fecal microbiota and determine if fecal and vaginal microbial communities are correlated in relation to POP risk.

Methods

Sows were evaluated for POP risk using an established perineal scoring system, with a perineal score (PS) of 1 (PS1) presuming little to no risk of POP to a PS of 3 (PS3) presuming high risk of POP. In the current study, 2,864 sows were scored during gestation week 15, and 1.0%, 2.7%, and 23.4% of PS1, PS2, and PS3 sows, respectively, subsequently experienced POP. Fecal swabs (n = 215) were collected between gestation days 108-115, DNA was extracted, and 16S rRNA gene amplicon sequencing libraries were analyzed using mothur, phyloseq and SAS in reference to PS and POP outcome. Additionally, co-occurrence networks were constructed using CoNet to compare fecal and vaginal microbiota from the same cohort of sows and identify correlations between different taxa.

Results

Differences in fecal community composition (PERMANOVA; P < 0.05), structure (alpha diversity measurements; P < 0.05), and 13 individual operational taxonomic units (OTUs) were revealed between PS1 and PS3 assigned sows. No differences in fecal microbiota were detected as a result of POP outcome. However, the abundances of several taxa were correlated across sample collection sites, suggesting the fecal and vaginal microbial communities may be related to one another.

Discussion

Collectively, fewer differences in the fecal microbiota exist in sows with differing risk for POP compared to the vaginal microbiota, suggesting the vaginal microbiome may be more relevant in relation to POP outcome, although correlations between fecal and vaginal communities may provide insight for strategies to combat POP.
Rumen microbiota helps Tibetan sheep obtain energy more efficiently to survive in the extreme environment of the Qinghai–Tibet Plateau
Authors: Wu Xiukun , Zhang Gaosen , Zhang Wei , Zhou Jianwei , Cong Haitao , Yang Guo , Liu Guangxiu
Published: July 2024

Introduction

T-sheep and H-sheep exhibit different environmental adaptability and production performance. The rumen microbiome has co-evolved with hosts and plays a vital role in nutrient digestion and energy metabolism. In our previous study, we found that T-sheep have a higher efficiency in energy metabolism than H-sheep, but the rumen microbial community remains unclear.

Methods

In this study, we determined the rumen bacterial profile and rumen fermentation parameters to reveal the bacterial profiles and predictive functions among breeds and diets with four different energy levels, as well as the correlation between bacterial profiles and rumen fermentation characteristics.

Results

The results showed that the rumen total volatile fatty acids (VFAs), acetate, butyrate, total branched-chain VFAs, iso-butyrate, and iso-valerate were higher in T-sheep than H-sheep. The alpha diversity of ruminal bacteria is not affected by dietary energy, but it shows a distinction between the sheep breeds. Specifically, T-sheep rumen bacteria exhibit higher alpha diversity than H-sheep. The beta diversity of ruminal bacteria is not influenced by dietary energy or sheep breeds, indicating similar communities of ruminal bacteria between different diets and sheep breeds. The phyla of Bacteroidetes and Firmicutes predominate in the rumen, with a higher relative abundance of Firmicutes observed in T-sheep than H-sheep. The two most abundant genera in the rumen were Prevotella 1 and Rikenellaceae RC9 gut group. Prevotella 1 is the predominant bacterial genus in the rumen of H-sheep, while the Rikenellaceae RC9 gut group dominates in the rumen of T-sheep. Microbial co-occurrence network analysis reveals that variations in rumen fermentation characteristics result from differences in module abundance, with a higher abundance of VFA-producing modules observed in the rumen of T-sheep. Microbial function prediction analysis showed that dietary energy rarely alters the functional composition of rumen bacteria. However, there were differences in the functions of rumen bacteria between sheep breeds, with T-sheep showing a greater emphasis on energy metabolism-related functions, while H-sheep showed a greater emphasis on protein metabolism-related functions.

Discussion

These findings provide evidence of the special rumen microbial community that helps T-sheep efficiently obtain energy from low-protein and low-energy diets, enabling them to survive in the extreme environment of the Qinghai–Tibet Plateau.
Genetic approaches to elucidating cortical and hippocampal GABAergic interneuron diversity
Authors: Machold Robert , Rudy Bernardo
Published: July 2024

GABAergic interneurons (INs) in the mammalian forebrain represent a diverse population of cells that provide specialized forms of local inhibition to regulate neural circuit activity. Over the last few decades, the development of a palette of genetic tools along with the generation of single-cell transcriptomic data has begun to reveal the molecular basis of IN diversity, thereby providing deep insights into how different IN subtypes function in the forebrain. In this review, we outline the emerging picture of cortical and hippocampal IN speciation as defined by transcriptomics and developmental origin and summarize the genetic strategies that have been utilized to target specific IN subtypes, along with the technical considerations inherent to each approach. Collectively, these methods have greatly facilitated our understanding of how IN subtypes regulate forebrain circuitry via cell type and compartment-specific inhibition and thus have illuminated a path toward potential therapeutic interventions for a variety of neurocognitive disorders.
Feasibility of noninvasive near-infrared spectroscopy monitoring in predicting the prognosis of spontaneous intracerebral hemorrhage
Authors: Sun Zhen , Liu Jing , Wang Kunpeng , Zhang Jiandang , Liu Sujie , Xue Fei
Published: July 2024

Objective

This study aimed to assess the impact of multimodal monitoring on predicting the prognosis of patients with spontaneous intracerebral hemorrhage (SICH) and to examine the feasibility of using noninvasive near-infrared spectroscopy (NIRS) for monitoring clinical prognosis.

Methods

Clinical data of 38 patients with SICH who underwent surgery in the Department of Neurosurgery of Shaanxi Provincial People’s Hospital from May 2022 to December 2022 were retrospectively analyzed. The patients were categorized into two groups based on the Glasgow Outcome Scale (GOS) 3 months after operation: poor outcome group (GOSI-III) and good outcome group (GOSIV and V). Multimodal monitoring included invasive intracranial pressure (ICP), brain temperature (BT), internal jugular venous oxygen saturation (SjvO2), and noninvasive NIRS. NIRS monitoring comprised the assessment of brain tissue oxygen saturation (StO2), blood volume index (BVI), and tissue hemoglobin index (THI). The prognostic differences between the two groups were compared. The predictive values were evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC).

Results

ICP, BT, BVI, and THI in the good prognosis group were lower than those in the poor prognosis group. The SjvO2 and StO2 in the group with a good prognosis were higher than those in the group with a poor prognosis.

Conclusion

The levels of ICP, BT, SjvO2, StO2, BVI, and THI reflect the changes in brain function and cerebral blood flow and significantly correlate with the prognosis of patients with SICH. NIRS monitoring has a high clinical utility in assessing the prognosis.
Nutritional knowledge and practice among antiretroviral therapy user adults in Bule Hora hospital, southern Oromia, Ethiopia
Authors: Gemede Habtamu Fekadu , Yazew Tamiru
Published: July 2024

Introduction

Nutrition is the necessary basis for life, health, and human development over the entire lifespan. Poor nutritional knowledge, poor nutritional practices, and malnutrition among HIV-positive adults can contribute to accelerating the progression of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) and related diseases. Therefore, this study aimed to assess the dietary knowledge, practices and associated factors of HIV-positive adults participating in antiretroviral therapy (ART) at Bule Hora Hospital, West Guji Zone, South Oromia, Ethiopia.

Methods

A cross-sectional institutional study was conducted among 418 HIV-positive adults by systematic sampling technique. Semi-structured questionnaires were used for data collection and analyzed with SPSS version 21.0. Logistic regression analyses were used to identify factors associated with dependent variables using adjusted odds ratio (AOR), with 95% CI (confidence interval) at p < 0.05.

Results

The result of this study showed that the prevalence of poor nutritional knowledge and poor nutritional practices among (HIV) positive adults was 74.9 and 69.1%, respectively. In the multivariate analysis, adult age (AOR = 2.37, 95% CI: 1.30, 4.32), marital status (AOR = 2.46, 95% CI: 1.29, 4, 69), educational level (AOR = 1.83, 95% CI: 1.01, 3.30) and occupational status (AOR = 0.55, 95% CI: 0.25, 0.94) were significantly associated with the nutritional knowledge. Educational level (AOR = 2.58, 95% CI: 1.48, 4.50), monthly income (AOR = 2.80, 95% CI: 1.68, 4.69), and adult occupational status (AOR = 0.48, 95% CI: 0.26, 0.89) were also significantly associated with the level of dietary practice.

Conclusion

It was concluded that the respondents’ nutritional knowledge and practices in the city of Bule Hora were poor compared to other national findings. The identified factors related to nutritional knowledge and practices were educational level, monthly income, adult occupation, and marital status of respondents in the study area. Therefore, each concerned agency should address the above gaps in nutritional knowledge and practices of HIV-positive adults in the study area.
In silico and in vitro chemometrics, cell toxicity and permeability of naringenin 8-sulphonate and derivatives
Authors: Macedo Tiago , Paiva-Martins Fátima , Valentão Patrícia , Pereira David M.
Published: July 2024

Background

Sulphur containing natural compounds are among the most biologically relevant metabolites in vivo. Naringenin 8-sulphonate from Parinari excelsa Sabine was evaluated in a previous work, demonstrating ability to act as a natural anti-inflammatory. Although the interference of this molecule against different inflammatory mediators was described, there is no information regarding its potential toxicity and pharmacokinetics, which are essential for its capacity to reach its therapeutic targets. In fact, despite the existence of reports on naringenin ADMET properties, the influence of sulphation patterns on them remains unknown.

Objectives

This work aims to assess the in vitro pharmacokinetic and toxicological behavior of naringenin 8-sulphonate, as well as to understand the importance of the presence and position of the sulphur containing group for that.

Methods

Naringenin 8-sulphonate physicochemical and ADMET properties were investigated using in silico tools and cell-based in vitro models. At the same time, naringenin and naringenin 4’-O-sulphate were investigated to evaluate the impact of the sulphonate group on the results. ADMETlab 2.0 in silico tool was used to predict the compounds’ physicochemical descriptors. Pharmacokinetic properties were determined experimentally in vitro. While MRC-5 lung fibroblasts and HaCaT keratinocytes were used to evaluate the cytotoxicity of samples through MTT and LDH assays, Caco-2 human intestinal epithelial cells were used for the determination of genotoxicity, through alkaline comet assay, and as a permeability model to assess the ability of compounds to cross biological barriers.

Results

Experimental determinations showed that none of the compounds was cytotoxic. In terms of genotoxicity, naringenin 8-sulphonate and naringenin caused significant DNA fragmentation, whereas naringenin 4’-O-sulphate did not. When it comes to permeability, the two sulphur-containing compounds with a sulphur containing group were clearly less capable to cross the Caco-2 cell barrier than naringenin.

Conclusion

In this study, we conclude that the sulphur containing group from naringenin 8-sulphonate is disadvantageous for the molecule in terms of ADMET properties, being particularly impactful in the permeability in intestinal barrier models. Thus, this work provides important insights regarding the role of flavonoids sulphation and sulphonation upon pharmacokinetics and toxicity.
Supportive care of female hormones in brain health: what and how?
Authors: Zhu Afang , Song Shujia , Pei Lijian , Huang Yuguang
Published: July 2024

Female hormones, functioning as neuroactive steroids, are utilized beyond menopausal hormone therapy. The rapid onset of allopregnanolone analogs, such as brexanolone and zuranolone, in treating depression, and the effectiveness of megestrol acetate in addressing appetite and weight gain, prompted the Food and Drug Administration to authorize the use of progesterone for treating postpartum depression and cancer-related cachexia. Progesterone has also been found to alleviate neuropathic pain in animal studies. These off-label applications offer a promising option for patients with advanced cancer who often experience various mood disorders such as depression, persistent pain, social isolation, and physical complications like cachexia. These patients have shown low tolerance to opioids and mood-regulating medications. However, the potential risks and uncertainties associated with hormone therapy treatment modalities can be daunting for both patients and medical professionals. This review aims to offer a comprehensive understanding of the non-reproductive functions and mechanisms of female hormones in brain health.