bluuebunny/crossref_metadata_2025 huggingface dataset:
Hair sheep in the Americas: economic traits and sustainable production
Authors: Dearborn Lindsey , Abdul-Rahmaan Bakeerah , Pesato Michael , Memili Erdogan , Rios Leyla
Published: December 2023

The relevance of hair sheep and their place in animal agriculture in the United States is expanding. Fueled by the exigency of sustainable agricultural practices, the integration of hair sheep to replace their wool breed counterparts is essential. Approximately 10% of all sheep globally are hair sheep but they are growing in numbers and production each year. Hair sheep breeds are widely diverse but share a common origin in tropical countries. Most of the prominent breeds were mindfully developed and crossed with wool breeds (namely, the Mouflon sheep) to improve the economically important traits of the animal. This genetic development has proven successful; hair sheep are considered highly advantageous in carcass quality, meat taste, litter size, and leather quality. Aside from those economically important traits, hair sheep are also advantageous in production traits, such as parasitic resistance, disease resistance, heat tolerance, sperm quality, and nutritional efficiency. These identified traits of hair sheep are highly desirable and contribute to the hair sheep’s positive reputation. However, hair sheep pose some disadvantages, such as an average or below average scrotal circumference, lower meat yield (although high in quality), meat with higher cholesterol than that of the wool breeds, and the lack of wool leaving the hair sheep susceptible to cold stress. These disadvantages can be mitigated with genetic selection and production techniques. The importance to further developing hair sheep is irrefutable. This review focuses on the fundamental and applied science of the most common hair sheep breeds and is expected to be useful for students, scientists, and producers of hair sheep.
Eu-doped carbon quantum dot as a selective probe for visualizing and monitoring sulfite in biological systems
Authors: Kan Bo , Li Li , Hou Jiaoyu , Liu Shuyan , Tian Zhenwei , Sun Qianchuang
Published: December 2023

The detection of SO32− in complex environments and its visualization at the cellular level are critical for understanding its role in biological processes. In this study, we developed an Eu-doped long-wavelength fluorescent carbon quantum dot (CD2) and investigated the detection mechanism, interference effects and cellular imaging applications of the fluorescent probe CD2. The results show that the addition of SO32− induces an electronic rearrangement that restores CD2 to its original structure, leading to a rapid increase in fluorescence intensity. Selectivity experiments showed that CD2 has excellent selectivity to SO32−, with minimal interference from common anions. In addition, CD2 shows good biocompatibility for cellular imaging applications, as evidenced by the high cell viability observed in HeLa cells. Using confocal microscopy, we detected a significant enhancement of red fluorescence in HeLa cells after addition of exogenous SO32−, demonstrating the potential of CD2 as a probe for monitoring cellular SO32− levels. These findings highlight the promise of CD2 as a selective SO32− detection probe in complex environments and its utility in cellular imaging studies. Further studies are necessary to fully exploit the potential of CD2 in various biological and biomedical applications.
Head-centric computing for vestibular stimulation under head-free conditions
Authors: La Scaleia Barbara , Brunetti Claudia , Lacquaniti Francesco , Zago Myrka
Published: December 2023

Background: The vestibular end organs (semicircular canals, saccule and utricle) monitor head orientation and motion. Vestibular stimulation by means of controlled translations, rotations or tilts of the head represents a routine manoeuvre to test the vestibular apparatus in a laboratory or clinical setting. In diagnostics, it is used to assess oculomotor postural or perceptual responses, whose abnormalities can reveal subclinical vestibular dysfunctions due to pathology, aging or drugs.

Objective: The assessment of the vestibular function requires the alignment of the motion stimuli as close as possible with reference axes of the head, for instance the cardinal axes naso-occipital, interaural, cranio-caudal. This is often achieved by using a head restraint, such as a helmet or strap holding the head tightly in a predefined posture that guarantees the alignment described above. However, such restraints may be quite uncomfortable, especially for elderly or claustrophobic patients. Moreover, it might be desirable to test the vestibular function under the more natural conditions in which the head is free to move, as when subjects are tracking a visual target or they are standing erect on the moving platform. Here, we document algorithms that allow delivering motion stimuli aligned with head-fixed axes under head-free conditions.

Methods: We implemented and validated these algorithms using a MOOG-6DOF motion platform in two different conditions. 1) The participant kept the head in a resting, fully unrestrained posture, while inter-aural, naso-occipital or cranio-caudal translations were applied. 2) The participant moved the head continuously while a naso-occipital translation was applied. Head and platform motion were monitored in real-time using Vicon.

Results: The results for both conditions showed excellent agreement between the theoretical spatio-temporal profile of the motion stimuli and the corresponding profile of actual motion as measured in real-time.

Conclusion: We propose our approach as a safe, non-intrusive method to test the vestibular system under the natural head-free conditions required by the experiential perspective of the patients.
Microscale tissue engineering of liver lobule models: advancements and applications
Authors: Wang Qi , Liu Juan , Yin Wenzhen , Wang Anqi , Zheng Jingjing , Wang Yunfang , Dong Jiahong
Published: December 2023

The liver, as the body’s primary organ for maintaining internal balance, is composed of numerous hexagonal liver lobules, each sharing a uniform architectural framework. These liver lobules serve as the basic structural and functional units of the liver, comprised of central veins, hepatic plates, hepatic sinusoids, and minute bile ducts. Meanwhile, within liver lobules, distinct regions of hepatocytes carry out diverse functions. The in vitro construction of liver lobule models, faithfully replicating their structure and function, holds paramount significance for research in liver development and diseases. Presently, two primary technologies for constructing liver lobule models dominate the field: 3D bioprinting and microfluidic techniques. 3D bioprinting enables precise deposition of cells and biomaterials, while microfluidics facilitates targeted transport of cells or other culture materials to specified locations, effectively managing culture media input and output through micro-pump control, enabling dynamic simulations of liver lobules. In this comprehensive review, we provide an overview of the biomaterials, cells, and manufacturing methods employed by recent researchers in constructing liver lobule models. Our aim is to explore strategies and technologies that closely emulate the authentic structure and function of liver lobules, offering invaluable insights for research into liver diseases, drug screening, drug toxicity assessment, and cell replacement therapy.
An optimized protocol for expression and purification of monomeric full-length BAX protein for functional interrogations
Authors: Chen Yiyang , Gelles Jesse D. , Mohammed Jarvier N. , Chipuk Jerry Edward
Published: December 2023

Diverse developmental signals and pro-death stresses converge on the regulation of the mitochondrial pathway of apoptosis. BAX, a proapoptotic BCL-2 effector, directly forms proteolipid pores in the outer mitochondrial membrane to activate the mitochondrial pathway of apoptosis. BAX is a viable pharmacological target for various human diseases, and increasing efforts have been made to study the molecular regulation of BAX while identifying small molecules selectively targeting BAX. However, generating large quantities of monomeric and functionally competent BAX has been challenging due to its aggregation-prone nature. Additionally, there is a lack of detailed and instructional protocols available for investigators who are not already familiar with recombinant BAX production. Here, we present a comprehensive protocol for expressing, purifying, and storing functional monomeric recombinant BAX protein. We use an intein-chitin binding domain-tagged BAX-expressing construct and employ a two-step chromatography strategy to capture and purify BAX. We also provide examples of standard assays to observe BAX activation, and highlight the best practices for handling and storing BAX to effectively preserve its quality, shelf life, and function.
Clinical utility of metagenomic next-generation sequencing in pathogen detection for lower respiratory tract infections and impact on clinical outcomes in southernmost China
Authors: Hao Jinxiang , Li Weili , Wang Yaoyao , Zhao Jiangman , Chen Yu
Published: December 2023

Background

Today, metagenomic next-generation sequencing (mNGS) has emerged as a diagnostic tool for infections. However, since Hainan has a complicated pathogen spectrum, the diagnostic value and impact on patient outcomes of mNGS in Hainan are to be explored.

Methods

From April 2020 to October 2021, 266 suspected lower respiratory tract infections (LRTIs) patients in Hainan were enrolled, and specimens were collected before antibiotic treatment. Bronchoalveolar lavage fluid (BALF) samples were subjected to mNGS and culture to compare the diagnostic performance. Other conventional microbiological tests (CMT) were also performed. Patients’ treatments and clinical outcomes were recorded, and the antibiotic resistance genes (ARGs) were detected via mNGS workflow.

Results

The positive rate of mNGS outperformed that of culture (87.55% vs. 39.30%, p<0.001) and CMT (87.12% vs. 52.65%, p<0.001). Specifically, mNGS detected more P. aeruginosa (12.03% vs 9.02%, p<0.05), H. influenzae (9.77% vs 2.26%, p<0.001), Aspergillus fumigatus (3.00% vs 0.75%, p<0.05), Candida albicans (26.32% vs 7.52%, p<0.001) and uncommon pathogens. It also demonstrated great diagnostic advantages in Mycobacterium tuberculosis with 80% sensitivity and 97.4% specificity. Over half of the patients (147, 55.26%) had modified empirical treatment according to mNGS results and 89.12% of them responded well. For three deaths with modified treatment, multiple drug resistance was predicted by mNGS and confirmed by antibiotic susceptibility test.

Conclusions

The application of mNGS can benefit clinics in pathogen identification and antimicrobial treatment stewardship. Physicians should be alert to some emerging uncommon pathogens, including Chlamydia Psittaci, Nocardia otitidiscaviarum, and rare NTM.
A rare bacteremia caused by Fannyhessea vaginae in a pregnant woman: case report and literature review
Authors: Liu Peng , Wang Lina , Li Rongguo , Chen Xiaodi
Published: December 2023

Bloodstream infection caused by anaerobic microorganisms continues to be associated with a high mortality risk, necessitating a rapid diagnosis and an appropriate treatment. As an anaerobic gram-positive organism associated with vaginal infections, Fannyhessea vaginae is a rare cause of invasive infections. In this case, a 32-year-old pregnant woman with bacterial vaginosis presented with bacteremia. The microbiological analysis of the blood cultures identified F. vaginae. The patient was treated empirically with 5 days of cefoperazone/sulbactam and recovered well. Here, we provide a review of the literature on F. vaginae infections, and the reported cases demonstrate the need for awareness of the different anaerobic species found in the vaginal tract and adaptation of empirical therapies, especially in pregnant women.
Case Report: Fluoroless implantation of left branch bundle pacing in a pregnant patient
Authors: Li Jun , Li Xiaofang , Zhang Anxin , Li Fanqi , Wang Haixiong
Published: December 2023

A pregnant patient had symptomatic atrial standstill and indications for pacing therapy with an expected high ventricular pacing ratio. With the consideration of potential pacing-induced cardiomyopathy in the future we conducted zero-fluoro left bundle branch pacing (zLBBP) implantation for heart failure prevention. An ex vivo 3D cardiac model (Medtronic, USA) was used preoperatively to simulate the zLBBP implantation to improve procedure safety and efficiency. Intraoperatively, the simulation steps were followed, and a combination of electroanatomic navigation systems (EANS) and intracardiac echocariography (ICE) were used to ensure that the procedure was performed efficiently and safely.
Promoting systems thinking through perspective taking when using an online modeling tool
Authors: Jordan Rebecca C. , Gray Steven , Boyse-Peacor Alita , Sorensen Amanda E. , Frantz Cynthia McPherson , Jauernig Johanna , Brehm Paul , Shammin Md Rumi , Petersen John
Published: December 2023

Introduction

Disagreements between people on different sides of popular issues in STEM are often rooted in differences in “mental models,” which include both rational and emotional cognitive associations about the issue; especially given these issues are systemic in nature.

Methods

In the research described here, we employ the fuzzy cognitive mapping software MentalModeler (developed by one of the authors)1 as a tool for articulating implicit and explicit assumptions about one’s knowledge of both the environmental and social science and values underpinning complex system related issues. More specifically, we test the assumption that this pedagogical approach will foster certain aspects of perspective taking that can be traced with cognitive development and systems thinking as students not only articulate their own understanding of an issue, but also articulate the view of others.

Results and discussion

Results are discussed with respect to systems thinking that is developed through this type of modeling.
Children’s multisensory experiences in museums: how olfaction interacts with color
Authors: Kucirkova Natalia I. , Speed Laura J.
Published: December 2023

This case study was designed to engage children’s sense of smell through a story-related museum exhibition. Children’s responses to the exhibition, with particular attention to their olfactory perceptions of the odors at the exhibition, were solicited through researcher-child interviews and children’s drawings. Responses from 28 children (girlsN = 14, boysN = 14) aged between 4.5–8 years were analyzed after they visited the exhibition using the cross-modal association and multisensory theories. Interview data showed that dark (brown and black) colors elicited children’s negative olfactory associations for both positive and negative odors. Children’s drawings did not seem to make references to the odors at the exhibitions but rather their preferences for the different story characters. We theorize about the associations between smell and colors in children’s responses and distil some key learnings for multisensory museology.
Association of trajectory of body shape index with all-cause and cause-specific mortality: 18 years follow-up
Authors: Kazemian Elham , Mehran Ladan , Masoumi Safdar , Amouzegar Atieh , Azizi Fereidoun
Published: December 2023

Objectives

The current study aimed to examine how the trajectory of a body shape index (ABSI) could predict mortality in a prospective cohort of 5587 participants.

Methods

A Growth Mixture Model (GMM) was employed to identify ABSI and body shape trajectories spanning from 2000 to 2018. Multivariate Cox regression models with hazard ratio (HR) and 95% confidence intervals (CIs) were built to assess the association of death from all-cause and cardiovascular disease (CVD) with ABSI and body shape trajectories.

Results

We found that individuals with a low ABSI–marked increase (Class II) and high ABSI–marked increase trajectory (Class III) had a higher risk of all-cause (adjusted HR for Class II, 1.37; 95%CI, 1.04-1.79; adjusted HR for Class III, 1.42; 95%CI, 1.05-1.91) and non- CVD mortality (adjusted HR for Class II, 1.38; 95%CI, 1.00-1.91; adjusted HR for Class III, 1.42; 95%CI, 1.00-2.05) as well as an increased risk of CVD (adjusted HR for Class II, 1.40; 95%CI, 1.14-1.71; adjusted HR for Class III, 1.42; 95%CI, 1.13-1.78) and coronary heart disease (CHD) (adjusted HR for Class II, 1.52; 95%CI, 1.18-1.96; adjusted HR for Class III, 1.47; 95%CI, 1.11-1.95. The trajectories of body shape phenotypes did not show any significant associations with mortality, CVD, or CHD events.

Conclusions

ABSI trajectories might be associated with subsequent risk of mortality and CVD events.
Estrobolome dysregulation is associated with altered immunometabolism in a mouse model of endometriosis
Authors: Alghetaa Hasan , Mohammed Amira , Singh Narendra P. , Bloomquist Ryan F. , Chatzistamou Ioulia , Nagarkatti Mitzi , Nagarkatti Prakash
Published: December 2023

Introduction

Endometriosis is a painful disease that affects around 5% of women of reproductive age. In endometriosis, ectopic endometrial cells or seeded endometrial debris grow in abnormal locations including the peritoneal cavity. Common manifestations of endometriosis include dyspareunia, dysmenorrhea, chronic pelvic pain and often infertility and symptomatic relief or surgical removal are mainstays of treatment. Endometriosis both promotes and responds to estrogen imbalance, leading to intestinal bacterial estrobolome dysregulation and a subsequent induction of inflammation.

Methods

In the current study, we investigated the linkage between gut dysbiosis and immune metabolic response in endometriotic mice. Ovariectomized BALB/c mice received intraperitoneal transplantation of endometrial tissue from OVX donors (OVX+END). Control groups included naïve mice (Naïve), naïve mice that received endometrial transplants (Naive+END) and OVX mice that received the vehicle (OVX+VEH). Colonic content was collected 2 weeks post-transplantation for 16s rRNA pyrosequencing and peritoneal fluid was collected to determine the phenotype of inflammatory cells by flow cytometry.

Results

We noted a significant increase in the number of peritoneal fluid cells, specifically, T cells, natural killer (NK) cells, and NKT cells in OVX+END mice. Phylogenetic taxonomy analysis showed significant dysbiosis in OVX+END mice, with an increase in abundance of Phylum Tenericutes, Class Mollicutes, Order Aneroplasmatales, and Genus Aneroplasma, and a decrease in Order Clostridiales, and Genus Dehalobacterium, when compared to OVX+VEH controls. The metabolomic profile showed an increase in some tricarboxylic acid cycle (TCA)-related metabolites accompanied by a reduction in short-chain fatty acids (SCFA) such as butyric acid in OVX+END mice. Additionally, the mitochondrial and ATP production of immune cells was enforced to a maximal rate in OVX+END mice when compared to OVX+VEH mice.

Conclusion

The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.
Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver
Authors: Fernández-Pérez Leandro , Guerra Borja , Recio Carlota , Cabrera-Galván Juan José , García Irma , De La Rosa Juan Vladimir , Castrillo Antonio , Iglesias-Gato Diego , Díaz Mario
Published: December 2023

Preclinical and clinical studies suggest that hypothyroidism might cause hepatic endocrine and metabolic disturbances with features that mimic deficiencies of testosterone and/or GH. The absence of physiological interactions between testosterone and GH can be linked to male differentiated liver diseases. Testosterone plays relevant physiological effects on somatotropic-liver axis and liver composition and the liver is a primary organ of interactions between testosterone and GH. However, testosterone exerts many effects on liver through complex and poorly understood mechanisms. Testosterone impacts liver functions by binding to the Androgen Receptor, and, indirectly, through its conversion to estradiol, and cooperation with GH. However, the role of testosterone, and its interaction with GH, in the hypothyroid liver, remains unclear. In the present work, the effects of testosterone, and how they impact on GH-regulated whole transcriptome and lipid composition in the liver, were studied in the context of adult hypothyroid-orchiectomized rats. Testosterone replacement positively modulated somatotropic-liver axis and impacted liver transcriptome involved in lipid and glucose metabolism. In addition, testosterone enhanced the effects of GH on the transcriptome linked to lipid biosynthesis, oxidation-reduction, and metabolism of unsaturated and long-chain fatty acids (FA). However, testosterone decreased the hepatic content of cholesterol esters and triacylglycerols and increased fatty acids whereas GH increased neutral lipids and decreased polar lipids. Biological network analysis of the effects of testosterone on GH-regulated transcriptome confirmed a close connection with crucial proteins involved in steroid and fatty acid metabolism. Taken together, this comprehensive analysis of gene expression and lipid profiling in hypothyroid male liver reveals a functional interplay between testosterone and pulsed GH administration.
Protective role of perivascular adipose tissue in the cardiovascular system
Authors: Tong Yi , Zuo Zheng , Li Xinqi , Li Minghua , Wang Zhenggui , Guo Xiaoxue , Wang Xishu , Sun Ying , Chen Dongmei , Zhang Zhiguo
Published: December 2023

This review provides an overview of the key role played by perivascular adipose tissue (PVAT) in the protection of cardiovascular health. PVAT is a specific type of adipose tissue that wraps around blood vessels and has recently emerged as a critical factor for maintenance of vascular health. Through a profound exploration of existing research, this review sheds light on the intricate structural composition and cellular origins of PVAT, with a particular emphasis on combining its regulatory functions for vascular tone, inflammation, oxidative stress, and endothelial function. The review then delves into the intricate mechanisms by which PVAT exerts its protective effects, including the secretion of diverse adipokines and manipulation of the renin-angiotensin complex. The review further examines the alterations in PVAT function and phenotype observed in several cardiovascular diseases, including atherosclerosis, hypertension, and heart failure. Recognizing the complex interactions of PVAT with the cardiovascular system is critical for pursuing breakthrough therapeutic strategies that can target cardiovascular disease. Therefore, this review aims to augment present understanding of the protective role of PVAT in cardiovascular health, with a special emphasis on elucidating potential mechanisms and paving the way for future research directions in this evolving field.
Can environmental supervision improve air quality? Quasi-experimental evidence from China
Authors: Zou Xuan , He Yao , Zhang Jincheng
Published: December 2023

Environmental supervision is significantly disrupted by local economic development and typically characterized by a lack of independence in China. This paper investigates the impacts and mechanisms of the vertical management reform of environmental protection department in China on urban air quality. We construct a principal–agent model suitable for explaining the interactions between the central and local governments and elaborate the intrinsic mechanism of EVM on strengthening environmental supervision. Using manually collected data, we conduct EVM as a quasi-experiment and construct a time-varying difference-in-difference (DID) model. Our empirical results show that the EVM significantly strengthens regional environmental supervision and reduces urban air pollution, bringing abatement in the PM2.5 concentration. The mechanism shows that EVM increases enterprises’ green innovation and attracts new entrants, further promoting industrial upgrading. Our study provides a new perspective on environmental governance and urban air quality in emerging countries such as China.
Average phenotype but not plasticity in two metabolic hormones covary in wild female bonobos (Pan paniscus)
Authors: Sonnweber Ruth , Hohmann Gottfried , Stevens Jeroen M. G. , Deschner Tobias , Fruth Barbara , Fiedler Anna-Lena , Nurmi Niina O. , Behringer Verena
Published: December 2023

Each individual is equipped with a distinct genetic disposition and ontogenetic history and experiences environmental conditions in a unique way. As a result, individuals vary in terms of phenotypic differences regarding their responses to internal and external conditions. By modulating hormone secretion, an individual can react to changing conditions, thus maintaining homeostasis. Cortisol and triiodothyronine (T3) are involved in mediating energy homeostasis. The secretion of metabolic hormones enables individuals to respond flexibly to internal and external conditions. However, this flexibility may be constrained by tradeoffs between average hormone levels and the degree of hormonal plasticity and the impact of the HPA axis on T3 secretion and effects. Like many other species, bonobos (Pan paniscus) are confronted with rapid ecological and climatic perturbations, resulting in challenges to energetic homeostasis. Due to their limited genetic diversity, K-strategist and stenoecious species characteristics, they are predicted to have only limited potential for adaptation. Therefore, it is important to quantify individual cortisol and T3 reaction norms and examine their relationship with each other to understand the level of flexibility of metabolic hormone phenotypes. Using a multivariate random slope model, we found that diurnal urinary excretion patterns of cortisol and T3 in wild female bonobos have (i) no relationship between average phenotype and plasticity within the reaction norms of both hormones. (ii) We also found a negative correlation between the intercepts of the two metabolic hormones, but (iii) no relationship between their slopes. (iv) Standard deviations of cortisol and T3 intercepts and slopes between females indicate little variation among females. Our data show that plasticity within and between the two metabolic hormones is not related to overall low or high hormone levels, but there is a linear negative relationship between cortisol and T3 average phenotypes. Thus, individuals with high average cortisol levels, investing in restoring energy depots, have low average T3 levels, reducing energy expenditure, and vice versa. From this we conclude that the plasticity of diurnal hormone excretion is not affected by average metabolic hormone phenotypes. Evaluations of cortisol and T3 plasticity along ecological gradients can enhance our understanding of the adaptive potential of a given species to environmental changes.
The unresolved ecological and evolutionary role of fungal fruit body coloration
Authors: Krah Franz-Sebastian
Published: December 2023

Fruit body-forming fungi are hyperdiverse and of central importance for the functioning of ecosystems worldwide. They provide habitat and resources for other organisms and perform critical roles in carbon and nutrient cycling. Like in animals and plants, fungal coloration is expected to play a fundamental role in response to biotic and abiotic environments, thus providing invaluable information to predict fungal and associated diversity in the Anthropocene. Despite centuries of plant and animal coloration research, the role of fruit body colors in fungal ecology remains mostly obscure. Essential questions are unresolved, such as: How do fruit body colors function to cope with abiotic stress? Do fruit body colors function to attract dispersal vectors or prevent predation via camouflage or aposematism? What is the significance of fruit body colors for fungal fitness? What are the implications of climate change-induced fruit body color change on fungal and associated biodiversity? Here, I review existing knowledge and outline several research trajectories to better understand the ecological role of fruit body colors. Revealing climate-driven adaptations and interactions with other organisms will improve forecasts under climate change for fungal diversity and interrelated biodiversity and inform cross-taxonomic conservation strategies.
Monitoring the reduction of UO3 thin film by hydrogen atoms using valence-level spectroscopy: correlating the U5f1 signal to surface hydroxyls
Authors: El Jamal G. , Gouder T. , Eloirdi R. , Jonsson M. , Idriss H.
Published: December 2023

The reaction of a UO3 thin film with atomic hydrogen was studied by He(II) ultraviolet photoelectron spectroscopy (UPS) in the temperature range 190–300 K. UO3 reduction was instantaneously observed once it contacted H atoms at 10–7 torr. The reduction was manifested by the presence of U5f1 electrons in He(II) UPS at approximately 1.5 eV below the Fermi level. Based on the peak characteristics, the valence band shape (composed largely of O2p orbitals in addition to some contribution from U6d and U5f orbitals), and X-ray photoelectron spectroscopy (XPS) U4f lines, the reduction of U6+ in UO3 only results in the formation of U5+ cations and was largely limited to those on the surface. Associated with the reduction was the formation of surface hydroxyls (-OH species) due to the transfer of a proton of the H atom (H.) to surface oxygen ions, while the electron of H. is transferred to a U5f orbital. The pseudo-first-order rate constant of the initial rate of reduction at 10–7 torr and 190 K was found to be approximately 0.01 s–1. Qualitative analysis of the valence band before and after reduction indicates that O2p hybridization with U6d and U5f orbitals leads to well-distinguished features that are characteristic of UO3, U2O5, and UO2. These features, which were quantitatively reversed during the redox process, furthers the assessment of the stoichiometry of a given binary uranium oxide.
Exploring the involvement of the alternative complement pathway in non-infectious uveitis pathogenesis
Authors: Kulshrestha Prerna , Goel Pallavi , Murthy Somasheila , Tyagi Mudit , Basu Soumvaya , Gogri Pratik , Kaur Inderjeet
Published: December 2023

Purpose

Non-infectious uveitis is a complex disease characterized by intraocular inflammation of the uveal area and the leading cause of vision impairment and blindness in young people globally. However, what triggers inflammation and contributes to its recurrence remains unclear. The complement system has been linked to various immunological and inflammatory conditions. In the present study, we have systematically evaluated the role of the alternative complement pathway in the pathogenesis of non-infectious uveitis.

Methodology

Quantitative PCR was done in the peripheral leukocytes to study the expression of genes and regulatory miRNA in both anterior and posterior uveitis (n=28 in each category). Multiplex ELISA was performed to measure alternative pathway complement components, such as C3b, factor B, and CFH, and aqueous humor of infectious and non-infectious uveitis patients and non-inflammatory controls (n=10 each). Western blotting was done to validate the ELISA findings in a subset of patients and controls.

Results

Downregulation of C3 and CFH mRNA in the peripheral blood was shown by quantitative PCR in the group of anterior uveiits (AU), while the opposite result was found in the group of posterior uveitis (PU). ELISA levels of C3b and CFH proteins were significantly higher in aqueous humor of infectious and non-infectious uveitis (*p = 0.03 and **p = 0.0007 respectively) as compared to the control group. Western blotting further validated (VitH) the activation of the complement cascade in the aqueous (AH) and vitreous humor of patients with non-infectious uveitis, with an increased level of C3b (n=6) and CFH (n=4) in aqueous humor. C3b level was significantly increased while CFH was reduced relative to controls in the vitreous humor (VitH) of posterior uveitis patients compared to controls (n=27 in each category). A C3b to CFH ratio was computed to assess the regulation of complement activation and this index was several folds higher in both anterior and posterior uveitis (n=10 each). The expression of miRNA-hsa-miR-146a and miRNA-hsa-miR-155-5p that regulates CFH was downregulated and nicely correlated with the increased complement proteins in both anterior and posterior uveitis (n=10 each).

Conclusion

Our results demonstrate a clear role of CFH and the activation of the alternative complement pathway in the pathogenesis of non-infectious uveitis; however, its therapeutic potential warrants further investigations.
Correlation of endoplasmic reticulum stress patterns with the immune microenvironment in hepatocellular carcinoma: a prognostic signature analysis
Authors: Zhan Ke , Yang Xin , Li Shuang , Bai Yang
Published: December 2023

Backgrounds

The extended duration of endoplasmic reticulum stress (ERS) can impact the progression of hepatocellular carcinoma (HCC) and the efficacy of immunotherapies by interacting with immune cells that have infiltrated the tumor microenvironment (TME).

Methods and results

The study utilized a training cohort of 364 HCC patients with complete information from The Cancer Genome Atlas Program (TCGA) database, and a validation cohort of 231 HCC patients from the International Cancer Genome Consortium (ICGC) database. The genes related to ERS exhibiting a strong correlation with overall survival (OS) were identified using univariate Cox regression analysis. A 13-gene predictive signature was then produced through the least absolute shrinkage and selection operator (LASSO) regression approach. The data revealed that the ERS-associated gene signature effectively stratified patients into high- or low-risk groups regarding OS in both the training and validation cohorts (P < 0.0001 and P = 0.00029, respectively). Using the multivariate method, it is still an independent prognostic factor in both the training and validation cohorts (P < 0.001 and P = 0.008, respectively). Moreover, several metabolic pathways were identified to be enriched among the 13 genes in the predictive signature. When the ERS-associated gene signature was combined with the tumor-node-metastasis (TNM) stage, the ERS nomogram performed better than either the gene signature or the TNM stage alone (C-index values: 0.731, 0.729, and 0.573, respectively). Further analysis revealed that patients in the high-risk group exhibited increased infiltration of immune cells. Additionally, GP6 was downregulated in HCC tissues among these signature genes (P < 0.05), which was related to poor OS.

Conclusions

The data suggest that this novel ERS-associated gene signature could contribute to personalized cancer management for HCC. Moreover, targeting GP6 inhibition might be a potential method for HCC therapy.
Case report: Differential diagnosis of highly amplified anti-CD5 CAR T cells and relapsed lymphoma cells in a patient with refractory ALK positive anaplastic large cell lymphoma
Authors: Mu Wei , Zhang Meilan , Hu Guang , Han Yunfeng , Mao Xia , Chen Caixia , Shen Kefeng , Dai Zhenyu , Zhu Xiaojian , Zhou Xiaoxi , Huang Liang , Ao Qilin , Xiao Min
Published: December 2023

Background

Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment.

Case presentation

The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023.

Conclusion

Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment.

Trial registration number

NCT04767308.
Hepatitis D infection induces IFN-β-mediated NK cell activation and TRAIL-dependent cytotoxicity
Authors: Groth Christopher , Maric Jovana , Garcés Lázaro Irene , Hofman Tomáš , Zhang Zhenfeng , Ni Yi , Keller Franziska , Seufert Isabelle , Hofmann Maike , Neumann-Haefelin Christoph , Sticht Carsten , Rippe Karsten , Urban Stephan , Cerwenka Adelheid
Published: December 2023

Background and aims

The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of the disease. Therapy options for HBV/HDV patients are still limited. Here, we investigated the potential of natural killer (NK) cells that are crucial drivers of the innate immune response against viruses to target HDV-infected hepatocytes.

Methods

We established in vitro co-culture models using HDV-infected hepatoma cell lines and human peripheral blood NK cells. We determined NK cell activation by flow cytometry, transcriptome analysis, bead-based cytokine immunoassays, and NK cell-mediated effects on T cells by flow cytometry. We validated the mechanisms using CRISPR/Cas9-mediated gene deletions. Moreover, we assessed the frequencies and phenotype of NK cells in peripheral blood of HBV and HDV superinfected patients.

Results

Upon co-culture with HDV-infected hepatic cell lines, NK cells upregulated activation markers, interferon-stimulated genes (ISGs) including the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), produced interferon (IFN)-γ and eliminated HDV-infected cells via the TRAIL-TRAIL-R2 axis. We identified IFN-β released by HDV-infected cells as an important enhancer of NK cell activity. In line with our in vitro data, we observed activation of peripheral blood NK cells from HBV/HDV co-infected, but not HBV mono-infected patients.

Conclusion

Our data demonstrate NK cell activation in HDV infection and their potential to eliminate HDV-infected hepatoma cells via the TRAIL/TRAIL-R2 axis which implies a high relevance of NK cells for the design of novel anti-viral therapies.
Pro-angiogenic changes of T-helper lymphocytes in hereditary hemorrhagic telangiectasia
Authors: Guilhem Alexandre , Ciudad Marion , Aubriot-Lorton Marie-Hélène , Greigert Hélène , Cladière Claudie , Leguy-Seguin Vanessa , Audia Sylvain , Samson Maxime , Bonnotte Bernard
Published: December 2023

Hereditary hemorrhagic telangiectasia (HHT) is a rare inherited disease due to heterozygous loss-of-function mutations on the BMP9/10 pathway (ENG, ACVRL1 or MADH4 mainly). HHT endothelial cells are prone to lose their quiescence, leading to progressive appearance of numerous telangiectases on skin and mucosa (complicated by epistaxis and anemia), and to larger arteriovenous malformations in lungs, liver and brain. HHT is also associated with T lymphocyte abnormalities, which are currently poorly understood. We quantified by flow-cytometry the main T lymphocyte circulating subsets in 40 HHT patients and 20 matched healthy controls. Immunostaining was done on 2 HHT skin telangiectases. Disruptions in T lymphocyte homeostasis was observed, characterized by increases in subsets known to promote angiogenesis: Th2 (1.38% vs 1.15%, p=0.021), Th17 (0.32% vs 0.22%, p=0.019 2) and Treg (4.94% vs 3.51%, p= 0.027). T angiogenic lymphocytes (Tang), defined as CD3+CD31+CXCR4+ T cells, were at similar levels in both groups, but the proportion of VEGF-A+ Tang after stimulation was higher in the HHT group compared to controls (68.2% vs 44.9%, p=0.012). The global HHT T lymphopenia predominantly affected the effector memory T-helper cells (200 vs 270 cells/mm3, p=0.017), and the lymphocytic infiltrate around HHT telangiectases consisted of memory T-helper cells. The Th17 circulating subset was positively correlated with the monthly epistaxis duration (r coefficient: +0,431, p=0.042), prospectively assessed. HHT T-helper lymphocytes are affected by several pro-angiogenic changes, potentially resulting from their recruitment by abnormal endothelial cells. They could constitute a biologically relevant source of VEGF-A and a valuable therapeutic target in HHT.
Manifestation of subacute cutaneous lupus erythematosus during treatment with anti-PD-1 antibody cemiplimab – a case report
Authors: Fietz Simon , Fröhlich Anne , Mauch Cornelia , de Vos-Hillebrand Luka , Fetter Tanja , Landsberg Jennifer , Hoffmann Friederike , Sirokay Judith
Published: December 2023

Introduction

The anti-programmed cell death protein 1 (PD-1) antibody cemiplimab has shown promising results in the treatment of unresectable or metastatic squamous cell carcinoma, however, frequently leads to immune-related adverse events limiting therapy efficacy. Although cutaneous side effects are common, only very few cases of cutaneous lupus erythematosus have been reported under anti-PD-1 immunotherapy. So far, no case of cutaneous lupus has been described under treatment with cemiplimab.

Case report

For the first time, we report the case of a patient with advanced squamous cell carcinoma, who developed clinical and histological findings in sun-exposed skin that were consistent with anti-SS-A/Ro antibody-positive subacute cutaneous lupus erythematosus (SCLE) under treatment with cemiplimab. Additionally, laboratory chemical analyses revealed a severe immune-related hepatitis without clinical symptoms. Both, the SCLE and the hepatitis, resolved after the administration of topical and systemic steroids and the discontinuation of anti-PD-1 therapy.

Conclusion

Treatment with cemiplimab can be associated with the appearance of cutaneous lupus erythematosus in sun-exposed areas. Application of topical and systemic glucocorticoids can lead to a rapid resolution of the skin eruptions. Moreover, our case illustrates the possibility of simultaneously occurring severe immune-related adverse events. This highlights the importance of additional diagnostics to avoid overlooking additional immune-related adverse events.
Nematode communities along a bathymetric transect in the deep eastern Fram Strait (Arctic Ocean): interrelations between diversity, function and environment
Authors: Schnier Jannik , Hasemann Christiane , Mokievsky Vadim , Martínez Arbizu Pedro , Soltwedel Thomas
Published: December 2023

As an expansion of a time-series study on meiobenthos in the Arctic deep sea, the diversity of free-living nematode communities along nine stations along a bathymetric transect was investigated morphologically in taxonomic and functional regards (feeding-type composition, life-history traits, tail-shape composition) and compared with previous studies of the same transect to investigate possible changes in the nematode community composition. Special emphasis was given on the analysis of sedimentary environmental parameters, which are used as proxies for food availability and sediment porosity. Multivariate statistics performed on nematode abundance data revealed a bathymetric zonation into four bathymetric zones: upper bathyal (1300 – 2000 m), lower bathyal (2500 - 3500 m), abyssal (5100 – 5600 m) and an additional ‘outgroup’ consisting of two stations with low nematode densities. Nematode densities generally decreased with increasing depth. Taxonomic diversity (EG(50), H’(log2), J’) decreased in a unimodal pattern peaking in the lower bathyal zone. A distance-based linear model revealed that 44% of the total variation in nematode abundances could be explained by the measured environmental parameters. Microbial feeders are the dominant feeding type along the transect with increasing dominance in the abyssal zone. The maturity index, a measure of environmental disturbance, decreased with depth, indicating a more colonizer-dominated community in the abyssal zone. Nematodes with long conico-cylindrical tails also become more dominant in the abyssal zone. A previous study of the same transect conducted in 2005 found a similar bathymetric zonation, but with a strikingly different dominant feeding type, i.e. epistrate feeders. Between the 2005 study and the year 2010 we conducted our study, the composition of the plankton community in the Fram Strait changed significantly due to a warm water anomaly in the region. We argue that through bentho-pelagic coupling, effects of this warm water anomaly on plankton communities could be a reason for the drastic change in dominant nematode feeding types.
Enhancement of dieckol extraction yield from Ecklonia cava through optimization of major variables in generally recognized as safe solvent-based process
Authors: Shin Hyeonmi , Lee Jeongho , Bae Jihyun , Lee Kang Hyun , Yoo Hah Young , Park Chulhwan
Published: December 2023

Ecklonia cava (EC), an edible brown macroalga abundant in intertidal areas of East Asia (Korea, Japan, and China), contains high-value bioactive compounds such as dieckol, which has antifungal, anti-inflammatory, antitumor, and antihyperlipidemic activities. However, no studies have been reported on the utilization of EC as a biorefinery feedstock, and the design of a more economical and high-yield process is required for the utilization of dieckol for the human healthcare industry. In this study, we designed a bioprocess for the high-yield recovery of dieckol from EC in a generally recognized as safe (GRAS) solvent to facilitate its application in the food and healthcare industries. Preliminary studies identified ethanol as an efficient solvent with the highest dieckol extraction yield (2.9 mg/g biomass). In order to maximize the recovery of dieckol from EC, the major extraction variables (solvent concentration, reaction temperature, and reaction time) were optimized based on statistical methods. Based on the predictive model, the numerical optimization determined that the solution with the highest dieckol content per weight of extract (62.6 vol% ethanol concentration, 54.2°C temperature, 13.2 min) was the optimal extraction condition. Under the determined conditions, the dieckol yield from EC achieved 6.4 mg dieckol/g EC (95.5% agreement with the predicted value). The designed process offers several advantages, including improving the utilization feasibility of EC, utilizing GRAS solvents with potential human applications, short extraction time (13.2 min), maximized process yield, and the highest dieckol recovery compared to previous reports.