bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferroptosis and metabolic syndrome and complications: association, mechanism, and translational applications
Authors: Zhou Dongmei , Lu Peipei , Mo Xianglai , Yang Bing , Chen Ting , Yao You , Xiong Tian , Yue Lin , Yang Xi
Published: January 2024

Metabolic syndrome is a medical condition characterized by several metabolic disorders in the body. Long-term metabolic disorders raise the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Therefore, it is essential to actively explore the aetiology of metabolic syndrome (MetS) and its comorbidities to provide effective treatment options. Ferroptosis is a new form of cell death that is characterized by iron overload, lipid peroxide accumulation, and decreased glutathione peroxidase 4(GPX4) activity, and it involves the pathological processes of a variety of diseases. Lipid deposition caused by lipid diseases and iron overload is significant in metabolic syndrome, providing the theoretical conditions for developing ferroptosis. Recent studies have found that the major molecules of ferroptosis are linked to common metabolic syndrome consequences, such as T2DM and atherosclerosis. In this review, we first discussed the mechanics of ferroptosis, the regulatory function of inducers and inhibitors of ferroptosis, and the significance of iron loading in MetS. Next, we summarized the role of ferroptosis in the pathogenesis of MetS, such as obesity, type 2 diabetes, and atherosclerosis. Finally, we discussed relevant ferroptosis-targeted therapies and raised some crucial issues of concern to provide directions for future Mets-related treatments and research.
Lipopolysaccharide-induced chronic inflammation increases female serum gonadotropins and shifts the pituitary transcriptomic landscape
Authors: Garcia Christopher , Velez Leandro M. , Ujagar Naveena , Del Mundo Zena , Nguyen Thu , Fox Chelsea , Mark Adam , Fisch Kathleen M. , Lawson Mark A. , Duleba Antoni J. , Seldin Marcus M. , Nicholas Dequina A.
Published: January 2024

Introduction

Female reproductive function depends on a choreographed sequence of hormonal secretion and action, where specific stresses such as inflammation exert profound disruptions. Specifically, acute LPS-induced inflammation inhibits gonadotropin production and secretion from the pituitary, thereby impacting the downstream production of sex hormones. These outcomes have only been observed in acute inflammatory stress and little is known about the mechanisms by which chronic inflammation affects reproduction. In this study we seek to understand the chronic effects of LPS on pituitary function and consequent luteinizing and follicle stimulating hormone secretion.

Methods

A chronic inflammatory state was induced in female mice by twice weekly injections with LPS over 6 weeks. Serum gonadotropins were measured and bulk RNAseq was performed on the pituitaries from these mice, along with basic measurements of reproductive biology.

Results

Surprisingly, serum luteinizing and follicle stimulating hormone was not inhibited and instead we found it was increased with repeated LPS treatments.

Discussion

Analysis of bulk RNA-sequencing of murine pituitary revealed paracrine activation of TGFβ pathways as a potential mechanism regulating FSH secretion in response to chronic LPS. These results provide a framework with which to begin dissecting the impacts of chronic inflammation on reproductive physiology.
Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients
Authors: Li Renshi , Zheng Fengjie , Xu Peichen , Lv Li , Mu Yapeng , Zhuang Xianghua , Chen Shihong
Published: January 2024

Background

Cognitive Impairment arising from type 2 diabetes mellitus (T2DM) has garnered significant attention in recent times. However, there are few studies on the identification and diagnosis of markers of cognitive impairment. Notably, alterations in the Retinal Nerve Fiber Layer’s (RNFL) thickness can potentially serve as an indicative measure of central nervous system changes. Further investigations have indicated that the decline in cognitive function within T2DM patients is intricately linked to persistent systemic inflammation and the accumulation of advanced glycosylation end products. Comprehensive studies are warranted to unveil these complex associations.

Objective

This study aims to explore the potential of utilizing the RNFL thickness and serological concentrations of IL-18, irisin, CML, and RAGE as diagnostic indicators for Mild Cognitive Impairment (MCI) among individuals with T2DM.

Methods

The thickness of RNFL were determined in all patients and controls using optical coherence tomography (OCT). The serum levels of IL-18, irisin, CML and RAGE were detected by ELISA kit. In addition, Cognitive assessment was performed by the Mini-Mental State Examination (MMSE) and the Montreal Cognitive assessment (MoCA).

Results

The average RNFL thickness in the right eye were decreased in T2DM and T2DM combined with MCI (T2DM-MCI) patients and were positively correlated with MoCA and MMSE scores. The serum levels of IL-18, CML and RAGE in T2DM and T2DM-MCI increased significantly (p<0.05) and were negative correlated with MoCA and MMSE scores. The level of irisin in T2DM and T2DM-MCI decreased significantly (p<0.05) and were positively correlated with MoCA and MMSE scores. The area under the ROC curve of T2DM-MCI predicted by the average RNFL thickness in the right eye, CML and RAGE were 0.853, 0.874 and 0.815. The diagnostic efficacy of the combination of average RNFL thickness in the right eye, CML, and RAGE for the diagnosis of T2DM-MCI was 0.969.

Conclusion

The average RNFL thickness in the right eye, CML and RAGE have possible diagnostic value in T2DM-MCI patients.
Survival analysis of palliative radiotherapy in patients with HER-2+ metastatic breast cancer
Authors: Li Xueting , Zhong Xiaorong , Xu Hongyu , Wang Jun , Liu Xianguo , Wang Yang , He Liang , Ma Jiayu , Li Guanghua , Liu Lei
Published: January 2024

Background

Whether radiotherapy can improve the long-term survival of HER-2+ metastatic breast cancer remains unclear. We launched this study to explore the effect of HER-2+ metastatic breast cancer patients through anti-HER-2 targeted therapy + radiotherapy.

Methods

488 HER-2 + metastatic breast cancer patients who received anti-HER2 targeted ± local radiotherapy from March 2006 to September 2021 were retrospectively collected. Patients were divided into a radiotherapy group (n=207) and a non-radiotherapy group (n=281) based on whether they received radiotherapy or not. 1: 1 propensity matching analysis was used to determine two groups of patients with similar baselines.

Results

Before matching, the radiotherapy group (n=207) had a median overall survival (mOS) of 51.7 months (48.8-63.8), which was superior to the non-radiotherapy group’s (n=281) mOS of 33.9 months (27.9-39.9) (P < 0.0001). Moreover, the radiotherapy group exhibited better 1-year (94.6% vs 83.9%), 3-year (70.8% vs 45.5%), and 5-year (43.3% vs 25.0%) survival rates compared to the control group. Propensity score matching analysis identified 135 pairs of baseline-matched patients. In the matched groups, the mOS was 57.2 (44.5-69.8) months in the radiotherapy group (n=135) and 34.1 (27.5-40.6) months in the non-radiotherapy group (n=135), showing a statistically significant difference (P < 0.0001). Additionally, the radiotherapy group demonstrated 1-, 3-, and 5-year survival rates of 93.2%, 71.5%, and 46.9%, respectively, while those in the non-radiotherapy group were 89.4%, 45.8%, and 22.2%, respectively. Multivariate Cox analysis revealed that the presence of brain metastasis, liver metastasis, and radiotherapy were identified as independent predictive factors significantly associated with OS.

Conclusion

In patients with HER-2 positive metastatic breast cancer, radiotherapy was associated with better survival benefits compared to those who did not receive radiotherapy.
Natural desiccated thyroid for the treatment of hypothyroidism?
Authors: Heald Adrian H. , Taylor Peter , Premawardhana Lakdasa , Stedman Mike , Dayan Colin
Published: January 2024

Primary hypothyroidism affects about 3% of the general population in Europe. Early treatments in the late 19th Century involved subcutaneous as well as oral administration of thyroid extract. Until the early 1970s, the majority of people across the world with hypothyroidism were treated with natural desiccated thyroid (NDT) (derived from pig thyroid glands) in various formulations, with the majority of people since then being treated with levothyroxine (L-thyroxine). There is emerging evidence that may account for the efficacy of liothyronine (NDT contains a mixture of levothyroxine and liothyronine) in people who are symptomatically unresponsive to levothyroxine. While this is a highly selected group of people, the severity and chronicity of their symptoms and the fact that many patients have found their symptoms to be alleviated, can be viewed as valid evidence for the potential benefit of NDT when given after careful consideration of other differential diagnoses and other treatment options.
Maternal plasma angiotensin 1-7 concentration is related to twin pregnancy chorionicity in the third trimester of pregnancy
Authors: Pietruski Paweł , Kosińska-Kaczyńska Katarzyna , Osińska Agnieszka , Zgliczyńska Magdalena , Żebrowska Kinga , Popko Katarzyna , Stelmaszczyk-Emmel Anna
Published: January 2024

Introduction

Twin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to differences in plasma renin-angiotensin-aldosterone components between monochorionic and dichorionic twin pregnancies. The study aimed to analyze the plasma ANG II and ANG 1-7 concentrations in women with monochorionic and dichorionic twin gestation.

Methods

A prospective observational study included 79 women between 32 and 34 weeks of gestation with twin pregnancy (31 with monochorionic gestation and 48 with dichorionic gestation). Angiotensin II and angiotensin 1-7 concentrations were measured in the collected blood samples.

Results

No significant differences were observed in angiotensin II concentrations between the dichorionic and monochorionic group with significantly higher levels of angiotensin 1-7 being observed in the dichorionic group. Angiotensin 1-7 level was higher than angiotensin II in 20 women (64.5%) in the monochorionic group and in 42 women (87.5%, p=0.01) in the dichorionic group. Higher plasma concentrations of angiotensin II and lower concentrations of angiotensin 1-7 were found in 5 women with gestational hypertension and in 3 with preeclampsia compared to normotensive women.

Discussion

It is the first study investigating angiotensin II and angiotensin 1-7 in twin pregnancies regarding chorionicity. Our results showed that plasma angiotensin 1-7 concentration was related to chorionicity, while plasma angiotensin II level was not. In most women with twin gestation angiotensin 1-7 concentration exceeded the concentration of angiotensin II. A switch in the relation between angiotensin II and angiotensin 1-7 was observed in hypertensive pregnant women.
Experimental evaluation of the performance and power output enhancement of a divergent solar chimney power plant by increasing the chimney height
Authors: Prasad Reemal , Ahmed M. Rafiuddin
Published: January 2024

Solar energy is an attractive renewable energy option for countries located in the tropical region. Harvesting this energy using simple yet innovative technologies such as solar chimney power plants (SCPP) will help the developing countries in meeting their sustainable development goals. In an SCPP, air is heated under a greenhouse collector and the hot air is passed to a chimney, where it drives a turbine while rising up. Research efforts have been directed in the past at improving the performance and power output of an SCPP by varying its geometric parameters. The chimney height of a previously optimized solar chimney power plant, having a divergent chimney, was increased from 4 to 6 m and then to 8 m in this first experimental work of this kind. The temperature variations inside the collector, along the chimney height, the velocity at the turbine section, the power available and the output power of an air turbine, estimated by applying mechanical load, are compared for the three chimney heights. The temperature rise of the air inside the collector was the highest for the 4 m tall SCPP and reduced as the chimney height was increased to 6 and 8 m due to the lower time of stay of air in the collector for greater chimney heights. Along the height of the divergent chimney, the temperature dropped with the maximum drop occurring for the 8 m tall SCPP indicating a lower enthalpy loss at the chimney exit. The air velocity at the turbine section was found to increase with chimney height for given solar insolation/time of the day due to the higher driving force which is the buoyancy effect produced by the hot air. The maximum turbine output power for the 8 m tall SCPP increased by 252% compared to the 4 m tall SCPP indicating that significant improvement in the power output can be achieved by increasing the height of a divergent chimney SCPP. An average power of about 40 kW will be available for a chimney height of 100 m which will be extremely beneficial for the sustainable development of small islands.
Influence of the vertically arranged front injector system on the performance and operational stability of the short jet pump
Authors: Ma Xiaogang , Yang Jun , Dai Tingting , Wang Jun , Tang Lei , Yang Yang
Published: January 2024

As the core component of a water conservancy sprinkler irrigation system, the self-priming jet pump is required not only to meet performance criteria for self-priming but also to align with the growing trend toward compactness in sprinkler irrigation systems. This paper takes the short compact self-priming jet pump as the research object whose injector is perpendicular to the main flow direction of the impeller inlet in order to reduce the volume of the jet pump and adopts the method of numerical simulation combined with experimental validation to study the effect of vertical arrangement of the injector on the hydraulic characteristics and operational instability of the self-priming jet pump. The results show that compared with the traditional hydraulic structure, the front injector leads to a significant reduction in the applicable flow range of the short jet pump. The hydraulic efficiency of the jet pump is notably inferior to that of traditional pumps across various flow conditions. This discrepancy arises from the eccentric rotation induced by the front-mounted injector, leading to pronounced circumferential asymmetry in the media flow within the individual impeller channels. Consequently, this asymmetry contributes to increased hydraulic losses in the flow channel. At the same time, the smaller overflow area within the injector enhances the turbulent flow characteristics of the medium, leading to increased instability of the subsequent flow field. This induces the generation of unwieldy low-frequency pressure pulsation signals within the flow channel, which are more readily propagated throughout the sprinkler system. In the practical application of short jet pumps, the circumferentially asymmetric distribution of the media flow in the impeller channel may result in the eccentric rotation of the rotor, thereby diminishing the service life of the pump. Furthermore, the complicated low-frequency signals will induce low-frequency vibration of the hydraulic sprinkler system, reducing the operational stability of the sprinkler system.
Research on the hydration process of solid waste–based cementitious materials and application in roadbase
Authors: Chu Feng , Li Chuanhai , Wu Chuanshan , Wang Yansheng
Published: January 2024

In order to improve the high-value utilization of industrial solid waste materials, this study prepared a solid waste–based cementitious material (SWCM) using slag, fly ash, desulfurization gypsum, and gangue. The mechanical strength and hydration process of the SWCM and an ordinary Portland cement (OPC) were studied. The results showed that the compressive strength of the SWCM was lower than that of OPC at 3 d, but the compressive strength exceeded that of OPC after 7 d. The isothermal calorimetry results showed that the induction period of the SWCM was five times that of OPC, and the total 4 d exothermic amount of OPC was 1.7 times that of the SWCM. XRD and SEM showed that the hydration products of the SWCM were mainly ettringite (AFt) and hydrated calcium silicate gel (C-S-H). The unconfined compressive strength and dry shrinkage of stabilized macadam were also studied by using the SWCM to replace OPC. The results indicated that the unconfined compressive strength of the SWCM-stabilized macadam is comparable to that of the OPC-stabilized macadam. The dry shrinkage strain was only 79.7% of the OPC-stabilized macadam.
In situ, high-resolution evidence for the release of heavy metals from lake sediments during ice-covered and free periods
Authors: Zhu Xiaoyan , Wu Zhong , Han Xuhang , Yang Zihao , Dong Xiangqian , Yuan Yuxiang , Wang Nannan , Qu Zhi , Wang Chunqing
Published: January 2024

Heavy metal dynamics at the sediment-water interface (SWI) has attracted plenty of attention due to their meticulous depiction for metal sorption-release processes. However, little is known about their concentration, migration and release characteristics underneath the ice, especially at the millimeter scale. Here we investigated dynamics of labile As, Cd, Cu, Mn, Pb and Zn by the diffusive gradients in thin-films (DGT) technique during ice-covered and ice-free periods in the Lake Xingkai basin. The concentrations of metals were relatively high at the SWI and ranged for As: 0.001~13.42 μg L−1, Cd: 0.01~0.45 μg L−1, Cu: 0.001~2.75 μg L−1, Mn: 5.31~2958.29 μg L−1, Pb: 0.06~1.43 μg L−1, and Zn: 2.92~112.96 μg L−1. Particularly, concentration of Mn was extremely higher than other studies, possibly due to diagenetic process. Labile concentrations of heavy metals in January were significantly lower than those in May, suggesting that elevated temperatures lead to the release of heavy metals from the sediment to the overlying water. Based on the Fick’s first law, the diffusive fluxes as a source of Mn (413.82-1163.25 mg·m-2·d-1) and As (3.53 -8.12 mg·m-2·d-1) indicated that heavy metals were released from sediments to the overlying water. While the diffusive fluxes as a sink of Zn (-1.80-(-2.36) mg·m-2·d-1) and Pb (-0.02-(-0.46) mg·m-2·d-1) to sediments. Redundancy Analysis (RDA) revealed that the main factors influencing the heavy metal migration were dissolved oxygen (45.6% of total explanation, P=0.01) in January, and water temperature (52.9%, P=0.006) in May. This study extends theoretical scope for understanding metal migration and release process, and provides valuable suggestions for lake management during the freezing period.
Natural and artificial selection of multiple alleles revealed through genomic analyses
Authors: Biová Jana , Kaňovská Ivana , Chan Yen On , Immadi Manish Sridhar , Joshi Trupti , Bilyeu Kristin , Škrabišová Mária
Published: January 2024

Genome-to-phenome research in agriculture aims to improve crops through in silico predictions. Genome-wide association study (GWAS) is potent in identifying genomic loci that underlie important traits. As a statistical method, increasing the sample quantity, data quality, or diversity of the GWAS dataset positively impacts GWAS power. For more precise breeding, concrete candidate genes with exact functional variants must be discovered. Many post-GWAS methods have been developed to narrow down the associated genomic regions and, ideally, to predict candidate genes and causative mutations (CMs). Historical natural selection and breeding-related artificial selection both act to change the frequencies of different alleles of genes that control phenotypes. With higher diversity and more extensive GWAS datasets, there is an increased chance of multiple alleles with independent CMs in a single causal gene. This can be caused by the presence of samples from geographically isolated regions that arose during natural or artificial selection. This simple fact is a complicating factor in GWAS-driven discoveries. Currently, none of the existing association methods address this issue and need to identify multiple alleles and, more specifically, the actual CMs. Therefore, we developed a tool that computes a score for a combination of variant positions in a single candidate gene and, based on the highest score, identifies the best number and combination of CMs. The tool is publicly available as a Python package on GitHub, and we further created a web-based Multiple Alleles discovery (MADis) tool that supports soybean and is hosted in SoyKB (https://soykb.org/SoybeanMADisTool/). We tested and validated the algorithm and presented the utilization of MADis in a pod pigmentation L1 gene case study with multiple CMs from natural or artificial selection. Finally, we identified a candidate gene for the pod color L2 locus and predicted the existence of multiple alleles that potentially cause loss of pod pigmentation. In this work, we show how a genomic analysis can be employed to explore the natural and artificial selection of multiple alleles and, thus, improve and accelerate crop breeding in agriculture.
An Anguillid lens: how Eels reconnect people and waterways
Authors: Gansworth Kristi Leora , Bowser Christopher H.
Published: January 2024

The population decline of American Eels (Anguilla rostrata) in North America represents multiple crises: ecosystem destruction, industrial impact, forced relocation, cultural disenfranchisement, water degradation, and biodiversity loss. Once a key component of Indigenous societies, trade routes, economies, and ceremonial cycles, today Eels experience migration barriers and habitat degradation stemming from waterway abuse and land use alteration. The development of agricultural and industrial social norms has led to dramatic reductions in Eel populations across North America. Fishery agencies familiar with Eel life cycles often list species as depleted, and disappearance of Eels is well-accepted in all sectors. Related species of Anguillid Eels are in decline globally. Yet, in some areas, American Eels continue to migrate, grow, and even thrive. This article proposes Eel continuity as powerful survivorship in troubled times, a counter-narrative to overwhelming stories of environmental pessimism. Although Eels are often discredited, reviled, and disrespected by Americans and Canadians alike, their contributions to marine and aquatic zones are underestimated and poorly understood. This article employs a reflexive method of dialogue and commentary from two Eel advocates with interdisciplinary training and backgrounds, who envision relational, wisdom-based practices that meaningfully integrate Indigenous, community, academic, and other forms of knowledge about Eels and about water.
Single‐cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms
Authors: Yoon Hyundong , Dean Logan S. , Jiyarom Boonyanudh , Khadka Vedbar S. , Deng Youping , Nerurkar Vivek R. , Chow Dominic C. , Shikuma Cecilia M. , Devendra Gehan , Koh Youngil , Park Juwon
Published: January 2024

Background

Although our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complications in COVID-19 infection remains unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequelae of SARS-CoV-2 infection (PASC) with persistent pulmonary symptoms. The dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown.

Results

To characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing (scRNA-seq) to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from a participant naïve to SARS-CoV-2 (Control) (n=1) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC) (n=2). After integrating scRNA-seq data with a naïve participant from a published dataset, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14+/CD16+monocytes, and dendritic cells) was increased in PPASC (n=2) compared to controls (n=2). MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis-related (VEGF, WNT, and SMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. Further comparison of PPASC with scRNA-seq data with Severe COVID-19 (n=4) data demonstrated enrichment of fibrotic transcriptional signatures. In PPASC, we observed interactive VEGF ligand-receptor pairs among MLCs, and network modules in CD14+ (cluster 4) and CD16+ (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID-19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS-CoV-2 naïve samples.

Conclusion

Analysis of a small scRNA-seq dataset demonstrated alterations in the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests a potential role in PPASC development.
Dupilumab and the potential risk of eosinophilic pneumonia: case report, literature review, and FAERS database analysis
Authors: Zhou Xiyuan , Yang Ge , Zeng Xuemei , Wang Lan , Xiang Jing , Zhao Jinyu , Chen Xuejun , Zhang Lixia
Published: January 2024

Eosinophilic pneumonia (EP) is a rare but noteworthy adverse effect linked to dupilumab, an interleukin-4 (IL-4) and IL-13 inhibitor used in the managing atopic diseases. The underlying mechanisms, potential predisposing factors, clinical characteristics, and optimal management strategies for dupilumab-induced EP remain unclear. We report a 71-year-old patient who developed acute EP after the first 600-mg dose of dupilumab. Eosinophils (EOSs) were also transiently increased (up to 1,600 cells/μl). After the acute EP was effectively treated with glucocorticoids, dupilumab treatment was continued. Rash, itching, and immunoglobulin E levels continued to decrease in the patient, and no further pulmonary adverse events occurred. We combined this case with a literature review of nine articles and analyzed data from 93 cases reported in the FDA Adverse Event Reporting System (FAERS) database of patients developing EP after dupilumab use. Our findings imply that dupilumab may induce EP, particularly in individuals over 45 years old, those with a history of respiratory diseases, and those who have previously used inhaled or systemic steroids. Vigilance is required, especially when there is a persistent elevation in peripheral blood EOSs during treatment. Although steroid treatment can effectively manage EP, more data are needed to determine the safety of resuming dupilumab treatment after controlling pneumonia.
Single-cell profiling of CD11c+ B cells in atherosclerosis
Authors: Pattarabanjird Tanyaporn , Srikakulapu Prasad , Ransegnola Brett , Marshall Melissa A. , Ghosheh Yanal , Gulati Rishab , Durant Chistopher , Drago Fabrizio , Taylor Angela M. , Ley Klaus , McNamara Coleen A.
Published: January 2024

Circulating CD11c+ B cells, a novel subset of activated B cells, have been linked to autoimmunity and shown to expand with age. Atherosclerosis is an age-associated disease that involves innate and adaptive immune responses to modified self-antigens. Yet, the expression of CD11c on specific B-cell subtypes and its link to atherosclerosis are poorly understood. In this study, we characterized the frequency of CD11c+ B cells in tissues in mice with aging. We observed an age-associated increase in CD11c+ B cells in the spleen and bone marrow of ApoE−/− mice, and this was associated with an increase in aortic plaque. In addition, we also utilized single-cell multi-omics profiling of 60 human subjects undergoing advanced imaging for coronary artery disease (CAD) to subtype CD11c+ B cells and determine their frequency in subjects with high and low severity of CAD. Using unsupervised clustering, we identified four distinct clusters of CD11c+ B cells, which include CD27 and IgD double negative 2 (DN2), age-associated (ABC), CD11c+ unswitched memory (USWM), and activated Naïve (aNav) B cells. We observed an increase in the frequency of both ABC B cells and DN2 B cells in patients with high CAD severity. Pathway analysis further demonstrated augmentation of autophagy, IFNg signaling, and TLR signaling in DN2 cells in high-severity CAD patients. On the other hand, an increase in the negative regulator of BCR signaling through CD72 was found in ABC cells in low-severity CAD patients. Through investigating scRNAseq of atheroma, these DN2 cells were also found to infiltrate human coronary atheroma.
Case report: Approaches to treatment-refractory and super-refractory glutamic acid decarboxylase antibody-spectrum disorders
Authors: Rajmohan Ravi , Baveja Shivali , Nguyen Dai , Shah Eshita , Sy Michael , Attaripour Sanaz , Swope David
Published: January 2024

Background

Glutamic acid decarboxylase antibody-spectrum disorders (GAD-SDs) include a group of autoimmune neurological diseases associated with neuronal excitability, most noticeably stiff person syndrome. Immune modulators are the mainstay of treatment, but a significant number of patients remain refractory.

Methods

We present our single-center experience of eight cases of GAD-SD, two of which were refractory to immune modulatory treatments.

Results

Of the two cases that were refractory to immunomodulation, one showed significant improvement with bilateral globus pallidus interna deep brain stimulation (GPi DBS) placement, and the other showed significant improvement with autologous hematopoietic stem cell transplant (aHSCT).

Discussion

To our knowledge, this is the first instance of GPi DBS placement being noted to improve GAD-SD movements.
Plexin B1 controls Treg numbers, limits allergic airway inflammation, and regulates mucins
Authors: Chapoval Svetlana P. , Gao Hongjuan , Fanaroff Rachel , Keegan Achsah D.
Published: January 2024

We investigated the effect of global Plexin B1 deficiency on allergic airway responses to house dust mite (HDM) or ovalbumin (OVA). In the HDM model, there were higher Th2 cytokine levels in the BALF of Plexin B1 knock-out (KO) mice compared to wild type (WT), and tissue inflammation and mucus production were modestly enhanced. In the OVA model, Plexin B1 deficiency led to increases in lung inflammation, mucus production, and lung Th2 cytokines accompanied by dysregulated mucin gene expression without affecting anti-OVA IgE/IgG1 levels. Spleen cells from Plexin B1 KO mice proliferated more robustly than WT cells in vitro to a variety of stimuli. Plexin B1 KO CD4+ T cells from spleens expressed higher levels of Ki-67 and CD69 compared to WT cells. Spleen cells from naïve Plexin B1 KO mice secreted increased amounts of IL-4 and IL-6 when pulsed in vitro with OVA whereas in vivo OVA-primed spleen cells produced IL-4/IL-5 when subjected to in vitro OVA restimulation. The upregulated allergic inflammatory response in Plexin B1 KO mice was associated with a lower number of Tregs in the lung tissues. Moreover, these mice displayed lower numbers of Treg cells in the lymphoid tissues at the baseline. These results demonstrate a previously unrecognized link between Plexin B1, Treg cells, and mucus in allergic lung inflammation.
ANCA-associated glomerulonephritis and lupus nephritis following COVID-19 vaccination: a case report and literature review
Authors: Campos Marcos Adriano Garcia , Valois Tiago de Oliveira , Magalhães Luís Eduardo , Vasques Lucas Fernandes , de Medeiros Rafael Goulart , Costa Denise Maria do Nascimento , Salgado Filho Natalino , Nogueira Raquel Moraes da Rocha , Neves Precil Diego Miranda de Menezes , Silva Gyl Eanes Barros
Published: January 2024

With the coverage of COVID-19 vaccination, it has been possible to observe the potential side effects of SARS-CoV-2 vaccines, with the most common ones being fever, myalgia, headache, and fatigue. However, an association has been observed between new and recurrent kidney injuries, mainly glomerulonephritis and lupus nephritis associated with ANCA, with the Pfizer-BioNTech, Moderna, Sinovac, and AstraZeneca vaccines, although the relationship between them is not clear. We report a case of ANCA-related vasculitis and lupus glomerulonephritis after the second dose of the AstraZeneca vaccine. The elderly patient presented significant worsening of kidney function after immunosuppression and complications after a new onset COVID-19 infection that led to death. We provide a literature review about kidney damage related to ANCA vasculitis after COVID-19 vaccine, aiming for a better understanding of the pathophysiological mechanism of kidney injury, its presentation, and treatment.
A Mendelian randomization study of the effect of serum 25-hydroxyvitamin D levels on autoimmune thyroid disease
Authors: Yu Yunfeng , Yang Xinyu , Wu Jingyi , Shangguan Xueli , Bai Siyang , Yu Rong
Published: January 2024

Objective

The influence of vitamin D on autoimmune thyroid disease (AITD) remains a subject of ongoing debate. This study employs Mendelian randomization (MR) to investigate the causal correlations of serum 25-hydroxyvitamin D (25[OH]D) levels with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves disease (GD).

Methods

Data on single nucleotide polymorphisms related to serum 25(OH)D levels, AIT, AIH, and GD were sourced from UK Biobank and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were employed to test the exposure-outcome causal relationship. Assessments of horizontal pleiotropy, heterogeneity, and stability were performed using the MR-Egger intercept, Cochran’s Q test, and leave-one-out sensitivity analysis, respectively.

Results

The results of MR analysis showed increased serum 25(OH)D levels was associated with a reduced risk of AIT (OR 0.499, 95% CI 0.289 to 0.860, p = 0.012) but not causal associated with AIH (OR 0.935, 95% CI 0.695 to 1.256, p = 0.654) and GD (OR 0.813, 95% CI 0.635 to 1.040, p = 0.100). Intercept analysis showed no horizontal pleiotropy (p > 0.05), and Cochran’s Q test showed no heterogeneity (p > 0.05). Sensitivity analysis suggested that these results were robust.

Conclusion

An increased serum 25(OH)D level is associated with AIT risk reduction but unrelated to AIH and GD. This finding suggests that vitamin D supplementation can be valuable for preventing and treating AIT.
Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression
Authors: Fornari Laurindo Lucas , Aparecido Dias Jefferson , Cressoni Araújo Adriano , Torres Pomini Karina , Machado Galhardi Cristiano , Rucco Penteado Detregiachi Claudia , Santos de Argollo Haber Luíza , Donizeti Roque Domingos , Dib Bechara Marcelo , Vialogo Marques de Castro Marcela , de Souza Bastos Mazuqueli Pereira Eliana , José Tofano Ricardo , Jasmin Santos German Borgo Iris , Maria Barbalho Sandra
Published: January 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as a significant contributing factor. It involves the activation of microglia and astrocytes, leading to the release of pro-inflammatory cytokines and chemokines and the infiltration of peripheral leukocytes into the central nervous system (CNS). These instances result in neuronal damage and neurodegeneration through activated nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain containing protein 3 (NLRP3) and nuclear factor kappa B (NF-kB) pathways and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Due to limited effectiveness regarding the inhibition of neuroinflammatory targets using conventional drugs, there is challenging growth in the search for innovative therapies for alleviating neuroinflammation in CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling and Expression, Cold Exposure, and Fibrin-Targeted strategies significantly promise to mitigate neuroinflammatory processes. These approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such as Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, and Alzheimer’s Disease. While the findings are promising, immunomodulatory therapies often face limitations due to Immune-Related Adverse Events. Therefore, the conduction of randomized clinical trials in this matter is mandatory, and will pave the way for a promising future in the development of new medicines with specific therapeutic targets.
Zinc intake ameliorates intestinal morphology and oxidative stress of broiler chickens under heat stress
Authors: Hu Ping , Li Kaiqi , Peng Xiaoxu , Yao Tongjia , Zhu Chuyang , Gu Haotian , Liu Hao-Yu , Sun Ming-an , Hu Yun , Ennab Wael , Luo Xugang , Cai Demin
Published: January 2024

Zinc (Zn), an essential trace element for poultry, plays a crucial role in promoting growth, improving feed conversion efficiency, enhancing antioxidant activity, and preventing disease. This study investigated the impact of different levels and sources of dietary Zn supplementation on the growth performance, intestinal morphology and antioxidant activity of broiler chickens under heat stress conditions. In this experiment, 1024 Xueshan chickens were divided into eight groups and subjected to heat stress conditions with different levels of Zn supplementation (30 mg/kg, 60 mg/kg, and 90 mg/kg) using organic or inorganic sources. Our findings indicated that dietary Zn supplementation significantly increased the feed-to-weight ratio of broilers during the experimental period under heat stress. Moreover, Zn supplementation positively increased the villus height and villus width in the jejunum and ileum at 74 and 88 days old, with the 60 and 90 mg/kg groups outperforming other groups, and organic Zn was more effective than inorganic Zn. Furthermore, Zn supplementation significantly increased serum antioxidant levels, with higher superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-px) activities, and organic Zn was more effective than inorganic Zn. This study concludes that Zn supplementation is beneficial in mitigating the detrimental impacts of heat stress on broilers. The findings suggest that employing Zn as a strategy can enhance productivity in the poultry industry by positively influencing intestinal morphology and bolstering antioxidant activity to counteract potential stress.
Lipid peroxidation of immune cells in cancer
Authors: Xiao Liuling , Xian Miao , Zhang Chuanchao , Guo Qi , Yi Qing
Published: January 2024

Growing evidence indicates that cellular metabolism is a critical determinant of immune cell viability and function in antitumor immunity and lipid metabolism is important for immune cell activation and adaptation to the tumor microenvironment (TME). Lipid peroxidation is a process in which oxidants attack lipid-containing carbon-carbon double bonds and is an important part of lipid metabolism. In the past decades, studies have shown that lipid peroxidation participates in signal transduction to control cell proliferation, differentiation, and cell death, which is essential for cell function execution and human health. More importantly, recent studies have shown that lipid peroxidation affects immune cell function to modulate tumor immunity and antitumor ability. In this review, we briefly overview the effect of lipid peroxidation on the adaptive and innate immune cell activation and function in TME and discuss the effectiveness and sensitivity of the antitumor ability of immune cells by regulating lipid peroxidation.
Case report: Overlapping anti-AMPAR encephalitis with anti-IgLON5 disease post herpes simplex virus encephalitis
Authors: Sun Shihui , Ren Jiafeng , Zhong Zhao , Ma Xuxia , Shang Danqing , Su Changjun , Zhao Xianchao
Published: January 2024

Autoimmune encephalitis (AE) is the result of an autoimmune process that occurs as a rapidly advancing encephalopathy. Autoimmune encephalitis was commonly linked to herpes simplex virus 1 (HSV-1) as the most frequently identified virus. The main areas affected by this invasion are the temporal lobe, frontal lobe, and limbic system. Limbic encephalitis is a highly uncommon occurrence involving anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and anti-IgLON family member 5 (IgLON5) disease, both belonging to the rare category. As far as we know, this is the first report showing that a patient diagnosed with AMPAR encephalitis overlapped with anti-IgLON5 disease post herpes simplex virus encephalitis (HSE), which helps to broaden the range of this uncommon autoimmune disease. We recommend autoantibody testing in all patients with HSE, particularly those involving neurological relapses or progression.
Spatial analysis of demersal food webs through integration of eDNA metabarcoding with fishing activities
Authors: Cicala Davide , Maiello Giulia , Fiorentino Fabio , Garofalo Germana , Massi Daniela , Sbrana Alice , Mariani Stefano , D’Alessandro Simone , Stefani Matteo , Perrodin Lucie , Russo Tommaso
Published: January 2024

The evaluation of the status of marine communities, and especially the monitoring of those heavily exploited by fisheries, is a key, challenging task in marine sciences. Fishing activities are a major source of disruption to marine food webs, both directly, by selectively removing components at specific trophic levels (TL), and indirectly, by altering habitats and production cycles. Food web analysis can be very useful in the context of an Ecosystem Approach to Fisheries, but food web reconstructions demand large and expensive data sets, which are typically available only for a small fraction of marine ecosystems. Recently, new technologies have been developed to easily, quickly and cost-effectively collect environmental DNA (eDNA) during fishing activities. By generating large, multi-marker metabarcoding data from eDNA samples obtained from commercial trawlers, it is possible to produce exhaustive taxonomic inventories for the exploited ecosystems, which are suitable for food-web reconstructions. Here, we integrate and re-analyse the data of a recent study in which the α diversity was investigated using the eDNA opportunistically collected during fishing operations. Indeed, we collect highly resolved information on species feeding relationships to reconstruct the food webs at different sites in the Strait of Sicily (Mediterranean Sea) from eDNA and catch data. After observing that the trophic networks obtained from eDNA metabarcoding data are more consistent with the available knowledge, a set of food web indicators (species richness, number of links, direct connectance and generality) is computed and analysed to unravel differences in food webs structure through different areas (spatial variations). Species richness, number of links and generality (positively) and direct connectance (negatively) are correlated with increasing distance from the coast and fishing effort intensity. The combined effects of environmental gradients and fishing effort on food web structure at different study sites are then examined and modelled. Taken together, these findings indicate the suitability of eDNA metabarcoding to assist and food web analysis, obtain several food web-related ecological indicators, and tease out the effect of fishing intensity from the environmental gradients of marine ecosystems.
Potentialities of the combined use of underwater fluorescence imagery and photogrammetry for the detection of fine-scale changes in marine bioconstructors
Authors: Castagnetti Cristina , Rossi Paolo , Righi Sara , Cattini Stefano , Simonini Roberto , Rovati Luigi , Capra Alessandro
Published: January 2024

Marine communities are facing both natural disturbances and anthropogenic stressors. Bioconstructor species are endangered by multiple large-scale and local pressures and the early identification of impacts and damages is a primary goal for preserving coral reefs. Taking advantage of the recent development in underwater photogrammetry, the use of photogrammetry and fluorimetry was coupled to design, test and validate in laboratory a multi-sensor measuring system that could be potentially exploited in open water by SCUBA divers for assessing the health status of corals and detecting relevant biometric parameters with high accuracy and resolution. The approach was tested with fragments of the endemic coral Cladocora caespitosa, the sole zooxanthellate scleractinian reef-builder in the Mediterranean. The most significant results contributing to the scientific advancement of knowledge were: 1) the development of a cost-effective, flexible and easy-to-use approach based on emerging technologies; 2) the achievement of a sub-centimetric resolution for measuring relevant biometric parameters (polyp counting, colony surface areas and volumes); 3) set up of a reliable and repeatable strategy for multi-temporal analyses capable of quantifying changes in coral morphology with sub-centimeter accuracy; 4) detect changes in coral health status at a fine scale and under natural lighting through autofluorescence analysis. The novelty of the present research lies in the coupling of emerging techniques that could be applied to a wide range of 3D morphometrics, different habitats and species, thus paving the way to innovative opportunities in ecological research and more effective results than traditional in-situ measurements. Moreover, the possibility to easily modify the developed system to be installed on an underwater remotely operated vehicle further highlights the possible concrete impact of the research for ecological monitoring and protection purposes.