bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors and their influence on the indicators of milk productivity of first-born of Ukrainian dairy breeds
Authors: Ladyka V. , Skliarenko Y. , Pavlenko Y. , Malikova A.
Published: January 2024

The article examines the influence of genotypic factors on the formation of milk productivity indicators in first-born cows of various breeds. Genotyping of 744 cows of Ukrainian Brown Dairy, Ukrainian RedAnd White, Ukrainian Black-and-White Dairy breeds and Sumy inbred type of Ukrainian Black-and-White dairy breed, which are kept in breeding farms of State Enterprise "Experimental Farm of Institute of Agriculture of Northern East of NAAS" of Sumy district of Sumy Region and PRAE Ichnyanske and PRAE Khliborob of Chernihiv region. In order to determine the polymorphism of the beta-casein gene, genetic studies were carried out in the laboratory of Institute of Physiology named after Bogomolets of NAS with the help of molecular biological analysis of allele recognition by polymerase chain reaction (PCR) in real time. The study of milk productivity indicators was carried out with the help of generally accepted methods, using the electronic database of SUMS "Orsek". The influence of genotypic factors was determined based on the results of one-factor variance analysis. Between animals of different breeds, there is a significant difference in the influence of genotypic factors on indicators of milk productivity. Linear belonging had a statistically significant effect on milk yield and the content of fat and protein in milk in animals of the Ukrainian black-and-white and redand-white dairy breeds. Whereas in cows of Ukrainian brown dairy breed - only on the amount of milk yield. In first-borns of Sumy intrabreed type, linear belonging did not have a statistically significant effect on the studied indicators. Father's origin has a much greater influence (ή2,=22-62 %). The genotype of the animal according to beta-casein actually does not have a reliable effect on the indicators of milk productivity. However, in animals of Ukrainian red-and-white dairy breed and Sumy inbred type of Ukrainian black-and-white dairy breed, it reliably influenced the formation of milk yield and fat content in milk. Therefore, with the aim of forming the desired value of milk productivity traits in first-born cows, the primary task is to carry out the selection of breeders assessed for the quality of the offspring of the corresponding lineal affiliation.
Key words: genotype, beta-casein, influence, milk productivity, breed
Use of DNA technologies for the examination of foodstuff
Authors: Dyman T. , Dyman N.
Published: January 2024

An integral component of the management system in the field of food safety is the examination of food products, which is based mostly on physical, chemical, physico-chemical and biochemical methods of research. Progress in the mastery of DNA diagnostic methods has become an incentive for the development and introduction into laboratory practice of highly sensitive methods for assessing the safety and quality of foodstuff, based on the polymerase chain reaction (PCR) method. In recent decades, the demand for molecular tools for food examination, authentication and traceability has increased significantly. This is due to the fact that legislation in the food sector is becoming increasingly strict, and market strategies are aimed at evaluating the food chain "from field to table" and ensuring that consumer choices match their expectations. An overview of proven and widely tested molecular approaches for the examination of food products is presented: PCR-RFLP method, RAPD-PCR, SSR-PCR, RTPCR. The potential and prospects of the latest technologies, such as SNP - single nucleotide polymorphisms, isothermal amplification, digital PCR, Whole-Genome Sequencing (WGS), DNA metabarcoding, are also described. The specified methods are characterized by high productivity, speed and scaling, enabling the study of biological systems at a new qualitative level. Examples of successful use of the specified methods for examination of foodstuff of plant and animal origin, their authentication and traceability are given. A broad panel of molecular methods is a powerful tool to protect both producers and consumers, providing consumers with freedom of choice and increasing transparency in food production systems, enabling honest producers to properly promote their products.
Key words: DNA-technologies, polymerase chain reaction, food safety, foodstuff examination.
La caducidad de la prisión preventiva
Authors: Jaramillo Tenenpaguay Eliceo Antonio , Palacios Moreno Diego
Published: January 2024

Introducción: la situación legal de una persona procesada o que está cumpliendo una medida cautelar de prisión preventiva, que sirve como último recurso antes del juicio, es de suma importancia. Esto se debe al aparente contraste entre las disposiciones de la Constitución de la República del Ecuador y el Código Orgánico Integral Penal dentro de nuestro sistema legal. La norma constitucional establece que la prisión preventiva debe quedar sin efecto una vez que se hayan cumplido los plazos de 6 meses para los delitos punibles con prisión y 1 año para los delitos punibles con prisión. Esta disposición establece un plazo para la privación de libertad en relación con distintos delitos. Estos límites no deben superarse. Sin embargo, el Código Orgánico Integral Penal desarrolla aún más la disposición constitucional y aborda específicamente el concepto de la expiración de la prisión preventiva. Presenta la particularidad de que suspende el plazo para la ejecución de la sentencia una vez dictada. Esta suspensión aparentemente contradice la norma constitucional y viola el derecho a la presunción de inocencia. Objetivo: garantizar su coherencia con la norma constitucional e impedir cualquier violación de la presunción de inocencia de las personas procesadas. Metodología: enfoque cualitativo. Implica una revisión exhaustiva de la literatura relevante y la aplicación de criterios, teorías y leyes legales para fundamentar los hallazgos. El nivel de profundidad de esta investigación es descriptivo y explicativo, lo que nos permite describir las principales características y las causas fundamentales de la expiración de la prisión preventiva. Conclusión: este trabajo de investigación establece que el cumplimiento de la ley penal contradice la norma constitucional. Existe una discrepancia entre nuestra constitución y el derecho penal, ya que la suspensión de los plazos al dictarse una sentencia viola el derecho a la libertad y la presunción de inocencia cuando se supera el período de prisión preventiva establecido constitucionalmente. Por lo tanto, se propone una reforma de nuestra legislación penal para abordar esta cuestión.
The Role of Hyperbaric Oxygen Therapy in the Treatment of Sudden Sensorineural Hearing Loss
Authors: Kim Hwabin , Oh Se-Joon
Published: January 2024

Sudden sensorineural hearing loss (SSNHL) is defined as acute hearing loss of >30 dB at three consecutive frequencies, with an abrupt onset (within 3 days). In most patients with SSNHL, an exact cause is rarely identified. Diverse etiological theories have been proposed, including vascular disease, viral infection, autoimmune disease, inner ear hydrops, and genetic factors. Based on these hypotheses, various treatments have been tried, including corticosteroids (systemic and/or intratympanic), antivirals, vasoactive drugs, and hyperbaric oxygen therapy (HBOT), but the evidence remains inconclusive. The 2019 American Academy of Otolaryngology-Head and Neck Surgery guideline had suggested that HBOT can be provided as either initial or salvage treatment when combined with steroid therapy. HBOT, a noninvasive treatment involving the inhalation of 100% oxygen at a pressure of >1 atmosphere absolute (ATA) is another treatment option as a method to improve oxygen supply after cochlear damage. Although the pressure, frequency, and total time of HBOT remain variable among different studies, a protocol of 2.0-2.5 ATA and 10-20 sessions in total are commonly used. The treatment strategies for SSNHL have been evolving, and recent attempts involved increasing the effectiveness through various combinations of systemic steroid, intratympanic steroid, and HBOT. In this review, we will review various studies about HBOT and discuss the efficacy of HBOT in SSNHL.
Sign Description on “Sausage Party” Movie Directed by Greg Tiernan and Conrad Vernon
Authors: Andika Andika , Putra Ansor , Arman Arman
Published: January 2024

This study analyzes the signs that exist within the scope of cultural representation in the Sausage Party movie using Charles Sanders Peirce's semiotic theoretical approach. The purpose of this study is to analyze how culture is represented in the form of signs in the Sausage Party movie using Charles Sanders Peirce's Semiotic theory approach. The data source is taken from the film Sosis Party. This research uses a descriptive qualitative method. Data collection is done by searching and downloading, watching movies, classifying, and coding data. based on the analysis the researcher managed to find fifteen signs which were divided into several types of signs including, icon, index, symbol, qualisign, legsign, sinsign, rheme, dicent, and argument. Every sign that appears on the characters in this film has a very precise placement and cannot be separated from the rules of the culture that is being represented.
Feminist Consumerism Discourse in Dove Advertisements on Dove US YouTube Channel
Authors: Hermilawanda Hermilawanda , Martisa Ela
Published: January 2024

The objective of this research is to find out how the feminist consumerism discourse described in “Dove” beauty in terms of gender identity, fashion, beauty standards, and feminine beauty ideology by Talbot (2020). Feminist consumerism discourse is an ideology that forms a person or group to carry out the process of using or consuming goods produced sustainably based only on desires, not needs. This research used a descriptive qualitative method. The source of data in this research is Dove advertisements were taken from the Dove US YouTube channel. Data collection was done by downloading, watching, transcribing, selecting, and coding based on Talbot’s theory. Data analysis cam carried out by presenting data, describing the context and situation, interpreting the data, and concluding the results of data analysis. The data for this research are 11 feminist consumerism discourse data in Dove advertisements to support the analytical process that the researcher is conducting. The researcher found that several elements of the feminist consumerism discourse that can be seen in the Dove advertisements video are in four aspects, such as gendered identity, fashion, beauty standards, and feminine beauty ideology. From the several aspects above, the feminist consumerism discourse is found in Dove advertisements and there are also persuasive elements.
The bradykinin-forming cascade in anaphylaxis and ACE-inhibitor induced angioedema/airway obstruction
Authors: Ghebrehiwet Berhane , Joseph Kusumam , Kaplan Allen P.
Published: January 2024

Anaphylaxis is a potentially life-threatening multi-system allergic reaction to a biological trigger resulting in the release of potent inflammatory mediators from mast cells and basophils and causing symptoms in at least two organ systems that generally include skin, lungs, heart, or gastrointestinal tract in any combination. One exception is profound hypotension as an isolated symptom. There are two types of triggers of anaphylaxis: immunologic and non-Immunologic. Immunologic anaphylaxis is initiated when a foreign antigen directly binds to IgE expressed on mast cells or basophils and induces the release of histamine and other inflammatory substances resulting in vasodilation, vascular leakage, decreased peripheral vascular resistance, and heart muscle depression. If left untreated, death by shock (profound hypotension) or asphyxiation (airway obstruction) can occur. The non-immunologic pathway, on the other hand, can be initiated in many ways. A foreign substance can directly bind to receptors of mast cells and basophils leading to degranulation. There can be immune complex activation of the classical complement cascade with the release of anaphylatoxins C3a and C5a with subsequent recruitment of mast cells and basophils. Finally, hyperosmolar contrast agents can cause blood cell lysis, enzyme release, and complement activation, resulting in anaphylactoid (anaphylactic-like) symptoms. In this report we emphasize the recruitment of the bradykinin-forming cascade in mast cell dependent anaphylactic reactions as a potential mediator of severe hypotension, or airway compromise (asthma, laryngeal edema). We also consider airway obstruction due to inhibition of angiotensin converting enzyme with a diminished rate of endogenous bradykinin metabolism, leading not only to laryngeal edema, but massive tongue swelling with aspiration of secretions.
Application of micro/nanorobot in medicine
Authors: Sun Tianhao , Chen Jingyu , Zhang Jiayang , Zhao Zhihong , Zhao Yiming , Sun Jingxue , Chang Hao
Published: January 2024

The development of micro/nanorobots and their application in medical treatment holds the promise of revolutionizing disease diagnosis and treatment. In comparison to conventional diagnostic and treatment methods, micro/nanorobots exhibit immense potential due to their small size and the ability to penetrate deep tissues. However, the transition of this technology from the laboratory to clinical applications presents significant challenges. This paper provides a comprehensive review of the research progress in micro/nanorobotics, encompassing biosensors, diagnostics, targeted drug delivery, and minimally invasive surgery. It also addresses the key issues and challenges facing this technology. The fusion of micro/nanorobots with medical treatments is poised to have a profound impact on the future of medicine.
Pb-214/Bi-214-TCMC-Trastuzumab inhibited growth of ovarian cancer in preclinical mouse models
Authors: Metebi Abdullah , Kauffman Nathan , Xu Lu , Singh Satyendra Kumar , Nayback Chelsea , Fan Jinda , Johnson Nathan , Diemer John , Grimm Terry , Zamiara Mike , Zinn Kurt R.
Published: January 2024

Introduction: Better treatments for ovarian cancer are needed to eliminate residual peritoneal disease after initial debulking surgery. The present study evaluated Trastuzumab to deliver Pb-214/Bi-214 for targeted alpha therapy (TAT) for HER2-positive ovarian cancer in mouse models of residual disease. This study is the first report of TAT using a novel Radon-222 generator to produce short-lived Lead-214 (Pb-214, t1/2 = 26.8 min) in equilibrium with its daughter Bismuth-214 (Bi-214, t1/2 = 19.7 min); referred to as Pb-214/Bi-214. In this study, Pb-214/Bi-214-TCMC-Trastuzumab was tested.

Methods: Trastuzumab and control IgG antibody were conjugated with TCMC chelator and radiolabeled with Pb-214/Bi-214 to yield Pb-214/Bi-214-TCMC-Trastuzumab and Pb-214/Bi-214-TCMC-IgG1. The decay of Pb-214/Bi-214 yielded α-particles for TAT. SKOV3 and OVAR3 human ovarian cancer cell lines were tested for HER2 levels. The effects of Pb-214/Bi-214-TCMC-Trastuzumab and appropriate controls were compared using clonogenic assays and in mice bearing peritoneal SKOV3 or OVCAR3 tumors. Mice control groups included untreated, Pb-214/Bi-214-TCMC-IgG1, and Trastuzumab only.

Results and discussion: SKOV3 cells had 590,000 ± 5,500 HER2 receptors/cell compared with OVCAR3 cells at 7,900 ± 770. In vitro clonogenic assays with SKOV3 cells showed significantly reduced colony formation after Pb-214/Bi-214-TCMC-Trastuzumab treatment compared with controls. Nude mice bearing luciferase-positive SKOV3 or OVCAR3 tumors were treated with Pb-214/Bi-214-TCMC-Trastuzumab or appropriate controls. Two 0.74 MBq doses of Pb-214/Bi-214-TCMC-Trastuzumab significantly suppressed the growth of SKOV3 tumors for 60 days, without toxicity, compared with three control groups (untreated, Pb-214/Bi-214-TCMC-IgG1, or Trastuzumab only). Mice-bearing OVCAR3 tumors had effective therapy without toxicity with two 0.74 MBq doses of Pb-214/Bi-214-TCMC-trastuzumab or Pb-214/Bi-214-TCMC-IgG1. Together, these data indicated that Pb-214/Bi-214 from a Rn-222 generator system was successfully applied for TAT. Pb-214/Bi-214-TCMC-Trastuzumab was effective to treat mouse xenograft models. Advantages of Pb-214/Bi-214 from the novel generator systems include high purity, short half-life for fractioned therapy, and hourly availability from the Rn-222 generator system. This platform technology can be applied for a variety of cancer treatment strategies.
The value of coordinated analysis of multimodal atherosclerotic plaque imaging in the assessment of cardiovascular and cerebrovascular events
Authors: Yu Shun , Zheng Yonghong , Dai Xiaomin , Chen Huangjing , Yang Shengsheng , Ma Mingping , Huang Feng , Zhu Pengli
Published: January 2024

Background

Although atherosclerosis (AS) can affect multiple vascular beds, previous studies have focused on the analysis of single-site AS plaques.

Objective

The aim of this study is to explore the differences or similarities in the characteristics of atherosclerotic plaque found in the internal carotid artery, cerebral artery, and coronary artery between patients with atherosclerotic cardiovascular disease (ASCVD) and those without events.

Methods

Patients aged ≥ 18 years who underwent both high-resolution vessel wall imaging (HR-VWI) and coronary computed tomography angiography (CCTA) were retrospectively collected and categorized into the ASCVD group and the non-event group. The plaques were then categorized into culprit plaques, non-culprit plaques, and non-event plaques. Plaque morphological data such as stenosis, stenosis grades, plaque length (PL), plaque volume (PV), minimal lumen area (MLA), enhancement grade, and plaque composition data such as calcified plaque volume (CPV), fibrotic plaque volume (FPV), fibro-lipid plaque volume (FLPV), lipid plaque volume (LPV), calcified plaque volume ratio (CPR), fibrotic plaque volume ratio (FPR), fibro-lipid plaque ratio (FLPR), lipid plaque volume ratio (LPR), intraplaque hemorrhage volume (IPHV), and intraplaque hemorrhage volume ratio (IPHR)were recorded and analyzed.

Results

A total of 44 patients (mean age 66 years, SD 9 years, 28 men) were included. In cervicocephalic plaques, the ASCVD group had more severe stenosis grades (p = 0.030) and demonstrated significant differences in LPV, LPR, and CPV (p = 0.044, 0.030, 0.020) compared with the non-event group. In coronary plaques, the ASCVD group had plaques with greater stenosis (p < 0.001), more severe stenosis grades (p < 0.001), larger volumes (p = 0.001), longer length (p = 0.008), larger FLPV (p = 0.012), larger FPV (p = 0.002), and higher FPR (p = 0.043) compared with the non-event group. There were significant differences observed in stenosis (HR-VWI, CCTA: p < 0.001, p < 0.001), stenosis grades (HR-VWI, CCTA: p < 0.001, p < 0.001), plaque length (HR-VWI, CCTA: p = 0.028, p < 0.001), and plaque volume (HR-VWI, CCTA: p = 0.013, p = 0.018) between the non-event plaque, non-culprit plaque, and culprit plaque. In the image analysis of HR-VWI, there were differences observed between IPHR (p < 0.001), LPR (p = 0.001), FPV (p = 0.011), and CPV (p = 0.015) among the three groups of plaques. FLPV and FPV were significantly different among the three different plaque types from the coronary artery (p = 0.043, p = 0.022).

Conclusion

There is a consistent pattern of change in plaque characteristics between the cervicocephalic and coronary arteries in the same patient.
Identification of first active compounds in drug discovery. how to proceed?
Authors: Giraud Stéphane
Published: January 2024

In the quest for the discovery of new therapies, the identification of the initial active molecules is a major challenge. Although significant progress in chemistry and biology has been made in recent years, the process remains difficult. In this mini-review, we will explain the major approaches and experimental methods that can be used to identify these molecules. Two main approaches are described, target-based and phenotypic-based and a focus is made on some high throughput technologies and biophysical methods.
Incorporating vertical collaboration to address sustainable development goals: the Monarch Route Project
Authors: Cuevas-Cancino Maria de la O , Peña-Becerril Maritza , Mondragon-Estrada Enrique , Camacho-Zuñiga Claudia
Published: January 2024

Higher Education Institutions in their societal transformative role need to effectively integrate the UN‘s Sustainable Development Goals (SDGs) and the 2030 Agenda into their curricula. Our goal is to inspire and trigger the discussion in the academic community on learning environments for education for sustainable development. We report The Monarch Route (MRP), a project conducted at Tecnologico de Monterrey and awarded with the 2018 Premios Latinoamerica Verde. Engaging all the students enrolled in the different semesters of the Sustainable Development Engineering (SDE) program, it adopted a research-based learning methodology, which is highly flexible at setting the final deliverables and due dates. It also implemented horizontal (intraclass), vertical (interclass), and interdisciplinary (multiple courses) student collaboration. In partnership with a non-governmental organization, the MRP aimed to reverse the extinction threat to the monarch butterfly while benefiting rural communities along the butterfly’s migratory route. With an exploratory action research approach, we analyzed the data gathered 2 months after the end of the courses: A survey on the perceived learning outcomes (87% confidence level) and a letter for future classes sharing their experience on the MRP, both optional. The analysis included a mixed methodology, i.e., quantitative and qualitative, including text mining, which evidenced that the participants strengthened both, transverse competences (collaboration, citizenship, communication, and critical thinking) and disciplinary competences (subject matter). The MRP is innovative for its dynamic structure that resembles the interconnectedness of real professional practice, scientific research, and environmental conservation efforts. In addition to the disciplinary application and societal relevance, the instructional design of MRP reflects that contributing to 2030 Agenda requires a multi-faceted approach, involving educational institutions, community partnerships, and interdisciplinary collaboration. Traditional education no longer fulfills our needs to face environmental challenges; academics, institutions, and governments are encouraged to implement policies and strategies to educate for a sustainable and better future for humanity and the planet.
CHST12: a potential prognostic biomarker related to the immunotherapy response in pancreatic adenocarcinoma
Authors: Liu Kun , Li Lu , Han Guang
Published: January 2024

Background

Pancreatic adenocarcinoma (PAAD) is characterized by lower immunogenicity with a poor response rate to immune checkpoint inhibitors (ICIs) and exhibits the poorest prognosis of all solid tumors, which results in the highest tumor-related mortality among malignancies. However, the underlying mechanisms are poorly understood. In addition, diverse carbohydrate sulfotransferases (CHSTs), which are involved in the sulfation process of these structures, play an important role in the metastatic spread of tumor cells. Aberrant glycosylation is beginning to emerge as an influencing factor in tumor immunity and immunotherapy. Therefore, it might serve as a biomarker of the immunotherapeutic response in tumors. The purpose of the study was to evaluate the role of CHST12 in PAAD prognosis and its relevance to the immunotherapeutic response.

Methods

A comprehensive investigation of the interactions between CHST12 expression and the immune microenvironment as well as the clinical significance of CHST12 in PAAD was conducted. Data derived from the Cancer Genome Atlas (TCGA) database were analyzed using univariate and multivariate approaches, the Tumor Immune Estimation Resource (TIMER), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. Publicly available datasets were analyzed in this study. These data can be found on websites such as http://www.xiantao.love and https://www.proteinatlas.org. An assessment of the predictive value of CHST12 for PAAD prognosis was conducted using univariate and multivariate Cox regression analysis, Kaplan–Meier analysis, and nomograms. The TIMER algorithm calculates the proportions of six types of immune cells. The TIDE algorithm was used to indicate the characteristics of tumors that respond to ICI therapy.

Results

The mRNA and protein levels of CHST12 showed the opposite trend. CHST12 mRNA expression was significantly upregulated in PAAD. According to Cox regression analysis, CHST12 RNA expression acts as a protective factor for overall survival [hazard ratio (HR), 0.617, P < 0.04]. Functional annotation indicated that CHST12-associated differentially expressed genes (DEGs) were related to the signaling activity of receptor tyrosine kinases and the regulation of ubiquitin-protein transferase. These are usually involved in tumor development and may be related to the treatment responses of immune checkpoint inhibitors (ICIs). There was significantly higher CHST12 mRNA expression in PAAD samples than in non-malignant samples.

Conclusions

In PAAD, elevated CHST12 mRNA expression might regulate immune cell infiltration into the tumor microenvironment (TME) and may predict clinical outcomes.
Development and validation of machine learning-augmented algorithm for insulin sensitivity assessment in the community and primary care settings: a population-based study in China
Authors: Zhang Hao , Zeng Tianshu , Zhang Jiaoyue , Zheng Juan , Min Jie , Peng Miaomiao , Liu Geng , Zhong Xueyu , Wang Ying , Qiu Kangli , Tian Shenghua , Liu Xiaohuan , Huang Hantao , Surmach Marina , Wang Ping , Hu Xiang , Chen Lulu
Published: January 2024

Objective

Insulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the “common soil” of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings.

Methods

We analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models.

Results

The LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc.

Conclusion

The ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.
Exploration and countermeasures for the development of low-carbon agriculture: a study from Chongming District, Shanghai
Authors: Song Xuemei , Dou Yibo
Published: January 2024

To achieve the goals of carbon peaking and carbon neutrality, China is actively promoting carbon reduction in many areas. Agriculture is one of the main sources of greenhouse gas emissions, and promoting the development of low-carbon agriculture is a critical way to achieve carbon reduction targets. Taking Chongming District in Shanghai as an example, this study summarizes the experience of low-carbon agricultural development in Chongming and analyzes the problems and challenges faced during its development. Finally, based on the system dynamics method, the causal relationship of carbon emission in Chongming’s agricultural development is constructed, and feasible loop optimization suggestions are put forward.
Galectin-3 and prohibitin 1 are autoantigens in IgG4-related cholangitis without clear-cut protective effects against toxic bile acids
Authors: Kersten Remco , Trampert David C. , Hubers Lowiek M. , Tolenaars Dagmar , Vos Harmjan R. , van de Graaf Stan F. J. , Beuers Ulrich
Published: January 2024

Background and aims

IgG4-related cholangitis (IRC) is the hepatobiliary manifestation of IgG4-related disease, a systemic B cell-driven fibro-inflammatory disorder. Four autoantigens have recently been described in IgG4-RD: annexin A11, galectin-3, laminin 511-E8, and prohibitin 1. We have previously reported a protective role of annexin A11 and laminin 511-E8 in human cholangiocytes against toxic bile acids. Here, we explored the potentially protective role of the carbohydrate-binding lectin galectin-3 and the scaffold proteins prohibitins 1 and 2.

Methods

Anti-galectin-3, anti-prohibitin 1 and 2 autoantibody positivity in IRC and healthy and disease (primary sclerosing cholangitis (PSC)) control sera was assessed by ELISA/liquid chromatography–tandem mass spectrometry (LC-MS/MS). Human H69 cholangiocytes were subjected to short hairpin RNA (shRNA) knockdown targeting galectin-3 (LGALS3), prohibitin 1 (PHB1), and prohibitin 2 (PHB2). H69 cholangiocytes were also exposed to recombinant galectin-3, the inhibitor GB1107, recombinant prohibitin 1, and the pan-prohibitin inhibitor rocaglamide. Protection against bile acid toxicity was assessed by intracellular pH (pHi) measurements using BCECF-AM, 22,23-3H-glycochenodeoxycholic acid (3H-GCDC) influx, and GCDC-induced apoptosis using Caspase-3/7 assays.

Results

Anti-galectin-3 autoantibodies were detected in 13.5% of individuals with IRC but not in PSC. Knockdown of LGALS3 and galectin-3 inhibition with GB1107 did not affect pHi, whereas recombinant galectin-3 incubation lowered pHi. LGALS3 knockdown increased GCDC-influx but not GCDC-induced apoptosis. GB1107 reduced GCDC-influx and GCDC-induced apoptosis. Recombinant galectin-3 tended to decrease GCDC-influx and GCDC-induced apoptosis. Anti-prohibitin 1 autoantibodies were detected in 61.5% and 35.7% of individuals with IRC and PSC, respectively. Knockdown of PHB1, combined PHB1/2 KD, treatment with rocaglamide, and recombinant prohibitin 1 all lowered pHi. Knockdown of PHB1, PHB2, or combined PHB1/2 did not alter GCDC-influx, yet knockdown of PHB1 increased GCDC-induced apoptosis. Conversely, rocaglamide reduced GCDC-influx but did not attenuate GCDC-induced apoptosis. Recombinant prohibitin 1 did not affect GCDC-influx or GCDC-induced apoptosis. Finally, anti-galectin-3 and anti-prohibitin 1 autoantibody pretreatment did not lead to increased GCDC-influx.

Conclusions

A subset of individuals with IRC have autoantibodies against galectin-3 and prohibitin 1. Gene-specific knockdown, pharmacological inhibition, and recombinant protein substitution did not clearly disclose a protective role of these autoantigens in human cholangiocytes against toxic bile acids. The involvement of these autoantibodies in processes surpassing epithelial secretion remains to be elucidated.
Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment
Authors: Muñoz-Grajales Carolina , Barraclough Michelle L. , Diaz-Martinez Juan P. , Su Jiandong , Bingham Kathleen , Kakvan Mahta , Kretzmann Roberta Pozzi , Tartaglia Maria Carmela , Ruttan Lesley , Choi May Y. , Appenzeller Simone , Marzouk Sherief , Bonilla Dennisse , Katz Patricia , Beaton Dorcas , Green Robin , Gladman Dafna D. , Wither Joan , Touma Zahi
Published: January 2024

Objective

Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI.

Methods

Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated.

Results

Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI.

Conclusion

In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.
Innate immune responses to RNA: sensing and signaling
Authors: Luan Xiaohan , Wang Lei , Song Guangji , Zhou Wen
Published: January 2024

Nucleic acids are among the most essential PAMPs (pathogen-associated molecular patterns). Animals have evolved numerous sensors to recognize nucleic acids and trigger immune signaling against pathogen replication, cellular stress and cancer. Many sensor proteins (e.g., cGAS, AIM2, and TLR9) recognize the molecular signature of infection or stress and are responsible for the innate immune response to DNA. Remarkably, recent evidence demonstrates that cGAS-like receptors acquire the ability to sense RNA in some forms of life. Compared with the nucleic-acid sensing by cGAS, innate immune responses to RNA are based on various RNA sensors, including RIG-I, MDA5, ADAR1, TLR3/7/8, OAS1, PKR, NLRP1/6, and ZBP1, via a broad-spectrum signaling axis. Importantly, new advances have brought to light the potential clinical application of targeting these signaling pathways. Here, we highlight the latest discoveries in the field. We also summarize the activation and regulatory mechanisms of RNA-sensing signaling. In addition, we discuss how RNA sensing is tightly controlled in cells and why the disruption of immune homeostasis is linked to disease.
Complement C7 and clusterin form a complex in circulation
Authors: Massri Mariam , Toonen Erik J.M. , Sarg Bettina , Kremser Leopold , Grasse Marco , Fleischer Verena , Torres-Quesada Omar , Hengst Ludger , Skjoedt Mikkel-Ole , Bayarri-Olmos Rafael , Rosbjerg Anne , Garred Peter , Orth-Höller Dorothea , Prohászka Zoltán , Würzner Reinhard
Published: January 2024

Introduction

The complement system is part of innate immunity and is comprised of an intricate network of proteins that are vital for host defense and host homeostasis. A distinct mechanism by which complement defends against invading pathogens is through the membrane attack complex (MAC), a lytic structure that forms on target surfaces. The MAC is made up of several complement components, and one indispensable component of the MAC is C7. The role of C7 in MAC assembly is well documented, however, inherent characteristics of C7 are yet to be investigated.

Methods

To shed light on the molecular characteristics of C7, we examined the properties of serum-purified C7 acquired using polyclonal and novel monoclonal antibodies. The properties of serum‑purified C7 were investigated through a series of proteolytic analyses, encompassing Western blot and mass spectrometry. The nature of C7 protein-protein interactions were further examined by a novel enzyme-linked immunosorbent assay (ELISA), as well as size‑exclusion chromatography.

Results

Protein analyses showcased an association between C7 and clusterin, an inhibitory complement regulator. The distinct association between C7 and clusterin was also demonstrated in serum-purified clusterin. Further assessment revealed that a complex between C7 and clusterin (C7-CLU) was detected. The C7-CLU complex was also identified in healthy serum and plasma donors, highlighting the presence of the complex in circulation.

Discussion

Clusterin is known to dissociate the MAC structure by binding to polymerized C9, nevertheless, here we show clusterin binding to the native form of a terminal complement protein in vivo. The presented data reveal that C7 exhibits characteristics beyond that of MAC assembly, instigating further investigation of the effector role that the C7-CLU complex plays in the complement cascade.
DAMPs and radiation injury
Authors: Yamaga Satoshi , Aziz Monowar , Murao Atsushi , Brenner Max , Wang Ping
Published: January 2024

The heightened risk of ionizing radiation exposure, stemming from radiation accidents and potential acts of terrorism, has spurred growing interests in devising effective countermeasures against radiation injury. High-dose ionizing radiation exposure triggers acute radiation syndrome (ARS), manifesting as hematopoietic, gastrointestinal, and neurovascular ARS. Hematopoietic ARS typically presents with neutropenia and thrombocytopenia, while gastrointestinal ARS results in intestinal mucosal injury, often culminating in lethal sepsis and gastrointestinal bleeding. This deleterious impact can be attributed to radiation-induced DNA damage and oxidative stress, leading to various forms of cell death, such as apoptosis, necrosis and ferroptosis. Damage-associated molecular patterns (DAMPs) are intrinsic molecules released by cells undergoing injury or in the process of dying, either through passive or active pathways. These molecules then interact with pattern recognition receptors, triggering inflammatory responses. Such a cascade of events ultimately results in further tissue and organ damage, contributing to the elevated mortality rate. Notably, infection and sepsis often develop in ARS cases, further increasing the release of DAMPs. Given that lethal sepsis stands as a major contributor to the mortality in ARS, DAMPs hold the potential to function as mediators, exacerbating radiation-induced organ injury and consequently worsening overall survival. This review describes the intricate mechanisms underlying radiation-induced release of DAMPs. Furthermore, it discusses the detrimental effects of DAMPs on the immune system and explores potential DAMP-targeting therapeutic strategies to alleviate radiation-induced injury.
Apoptosis activation during Lagovirus europaeus/GI.2 infection in rabbits
Authors: Bębnowska Dominika , Hrynkiewicz Rafał , Wiśniewska Karolina , Żabińska Magdalena , Rintz Estera , Pierzynowska Karolina , Niedźwiedzka-Rystwej Paulina
Published: January 2024

Rabbit Haemorrhagic Disease (RHD) is a severe disease caused by Lagovirus europaeus/GI.1 and GI.2. Immunological processes such as apoptosis are important factors involved in the pathogenesis of Rabbit Haemorrhagic Disease (RHD). The process of programmed cell death has been quite well characterized in infection with GI.1 strains, but apoptosis in infection with GI.2 strains has not been widely studied. This is particularly important as several studies have shown that significant differences in the host immune response are observed during infection with different strains of Lagovirus europaeus. In this study, we analyzed the gene expression, protein levels and activity of key apoptotic cell death factors in the spleen, kidney, lung, and heart of rabbits. As a result, we showed that there is a significant increase in caspase-3, Bax, Bcl2 and Bax/Bcl2 mRNA gene expression ratio in organs of infected animals. Our results show also increased levels of cleaved caspase-3, caspase-6 and PARP. Moreover, significant activity of caspase-3 was also detected. Our results indicate that caspase-3, caspase-6 and genes coding Bcl2 family proteins play a key role in the apoptotic response in Lagovirus europaeus/GI.2 infection in organs that are not the target of virus replication.
Transcriptomic and metabolomic analysis reveals the influence of carbohydrates on lignin degradation mediated by Bacillus amyloliquefaciens
Authors: Li Xiaodan , Li Zhuofan , Li Ming , Li Jingwen , Wang Quan , Wang Shuxiang , Li Shuna , Li Hongya
Published: January 2024

Introduction

Ligninolytic bacteria can secrete extracellular enzymes to depolymerize lignin into small-molecular aromatics that are subsequently metabolized and funneled into the TCA cycle. Carbohydrates, which are the preferred carbon sources of bacteria, influence the metabolism of lignin-derived aromatics through bacteria.

Methods

In this study, untargeted metabolomics and transcriptomics analyses were performed to investigate the effect of carbohydrates on lignin degradation mediated by Bacillus amyloliquefaciens MN-13, a strain with lignin-degrading activity that was isolated in our previous work.

Results

The results demonstrated that the cell growth of the MN-13 strain and lignin removal were promoted when carbohydrates such as glucose and sodium carboxymethyl cellulose were added to an alkaline lignin-minimal salt medium (AL-MSM) culture. Metabolomics analysis showed that lignin depolymerization took place outside the cells, and the addition of glucose regulated the uptake and metabolism of lignin-derived monomers and activated the downstream metabolism process in cells. In the transcriptomics analysis, 299 DEGs were screened after 24 h of inoculation in AL-MSM with free glucose and 2 g/L glucose, respectively, accounting for 8.3% of the total amount of annotated genes. These DEGs were primarily assigned to 30 subcategories, including flagellar assembly, the PTS system, RNA degradation, glycolysis/gluconeogenesis, the TCA cycle, pyruvate metabolism, and tryptophan metabolism. These subcategories were closely associated with the cell structure, generation of cellular energy, and precursors for biosynthetic pathways, based on a − log 10 (P adjust) value in the KEGG pathway analysis.

Conclusion

In summary, the addition of glucose increased lignin degradation mediated by the MN-13 strain through regulating glycolysis, TCA cycle, and central carbon metabolism.
Oral treatment of human gut microbiota associated IL-10−/− mice suffering from acute campylobacteriosis with carvacrol, deferoxamine, deoxycholic acid, and 2-fucosyl-lactose
Authors: Mousavi Soraya , Foote Minnja S. , Du Ke , Bandick Rasmus , Bereswill Stefan , Heimesaat Markus M.
Published: January 2024

Food-borne Campylobacter jejuni infections constitute serious threats to human health worldwide. Since antibiotic treatment is usually not indicated in infected immune-competent patients, antibiotic-independent treatment approaches are needed to tackle campylobacteriosis. To address this, we orally applied carvacrol, deferoxamine, deoxycholate, and 2-fucosyl-lactose either alone or all in combination to human microbiota-associated IL-10−/− mice from day 2 until day 6 following oral C. jejuni infection. Neither treatment regimen affected C. jejuni loads in the colon, whereas carvacrol lowered the pathogen numbers in the ileum on day 6 post-infection (p.i.). The carvacrol and combination treatment regimens resulted in alleviated diarrheal symptoms, less distinct histopathological and apoptotic epithelial cell responses in the colon, as well as diminished numbers of colonic neutrophils and T lymphocytes on day 6 p.i., whereas the latter cells were also decreased upon deferoxamine, deoxycholate, or 2-fucosyl-lactose application. Remarkably, the carvacrol, deferoxamine, and combination treatment regimens dampened ex-vivo IFN-γ secretion in the colon, the kidneys, and even in the serum to basal concentrations on day 6 p.i. In conclusion, carvacrol alone and its combination with deferoxamine, deoxycholate, and 2-fucosyl-lactose constitute promising antibiotics-independent treatment options to fight acute campylobacteriosis.
Eutypellaolides A–J, Sesquiterpene diversity expansion of the polar fungus Eutypella sp. D-1
Authors: Ning Zhe , Hu Bo , Sun Yuan-Yuan , Ding Jin-Feng , Han Xiang-Ying , Lu Xiao-Ling , Yin Zi-Fei , He Ying , Jiao Bing-Hua , Yu Hao-Bing , Liu Xiao-Yu
Published: January 2024

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A–H (1–8), and two new eudesmane-type sesquiterpenes, eutypellaolides I–J (9–10), along with four known 12,8-eudesmanolide compounds 11–14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 μg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 μM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 μM, respectively.