bluuebunny/crossref_metadata_2025 huggingface dataset:
Talaromycosis from Wuhan: two-case report and literature review
Authors: Yao Zhiyuan , Pan Zhou , Li Guang , Liao Zhaomin , Yu Zhen , Zhan Liying , Xia Wenfang
Published: March 2024

Background

Talaromycosis is a serious opportunistic infectious disease caused by Talaromyces marneffei, which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical countries and regions of Southeast Asia and South Asia, but non-endemic areas also have patients with Talaromycosis. The disease has no characteristic clinical manifestations and is difficult to diagnose. Delayed diagnosis often leads to death.

Case presentation

Both patients had cellular immunodeficiency. Case 1 had a history of acquired immune deficiency syndrome, and case 2 had a history of renal transplantation and glucose-6-phosphate dehydrogenase deficiency. They all had fever, anemia, fatigue, and skin lesions. Case 1 had gastrointestinal bleeding, enlarged lymph nodes, and hepatosplenomegaly. Case 2 had cough and dyspnea. Both patients had thrombocytopenia and hypoalbuminemia; an increased neutrophil ratio, procalcitonin, and C-reactive protein; and abnormal liver function and coagulation dysfunction. Case 1 sputum culture, blood culture, and bronchoalveolar lavage fluid were positive for T. marneffei. T. marneffei was detected in the blood culture of case 2, with infection of Candida parapsilosis and Pneumocystis jirovecii. Chest computed tomography scan mainly showed pulmonary exudative lesions. Although these two patients were actively treated, they died of poor efficacy.

Conclusion

Talaromycosis has an insidious onset, long course, atypical clinical symptoms, imaging performance and laboratory results, difficult diagnosis, and high mortality. Therefore, it is important to promptly consider and treat Talaromycosis in immunocompromised patients upon infection in order to reduce mortality.
Overlapping action of T3 and T4 during Xenopus laevis development
Authors: Tribondeau Alicia , Du Pasquier David , Benchouaia Médine , Blugeon Corinne , Buisine Nicolas , Sachs Laurent M.
Published: March 2024

Thyroid hormones are involved in many biological processes such as neurogenesis, metabolism, and development. However, compounds called endocrine disruptors can alter thyroid hormone signaling and induce unwanted effects on human and ecosystems health. Regulatory tests have been developed to detect these compounds but need to be significantly improved by proposing novel endpoints and key events. The Xenopus Eleutheroembryonic Thyroid Assay (XETA, OECD test guideline no. 248) is one such test. It is based on Xenopus laevis tadpoles, a particularly sensitive model system for studying the physiology and disruption of thyroid hormone signaling: amphibian metamorphosis is a spectacular (thus easy to monitor) life cycle transition governed by thyroid hormones. With a long-term objective of providing novel molecular markers under XETA settings, we propose first to describe the differential effects of thyroid hormones on gene expression, which, surprisingly, are not known. After thyroid hormones exposure (T3 or T4), whole tadpole RNAs were subjected to transcriptomic analysis. By using standard approaches coupled to system biology, we found similar effects of the two thyroid hormones. They impact the cell cycle and promote the expression of genes involves in cell proliferation. At the level of the whole tadpole, the immune system is also a prime target of thyroid hormone action.
Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses
Authors: Zhang Min , Bai Ye , Wang Yutong , Cui Huijie , Zhang Wenqiang , Zhang Li , Yan Peijing , Tang Mingshuang , Liu Yunjie , Jiang Xia , Zhang Ben
Published: March 2024

Background

General obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD.

Methods

We first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase=43,639, ncontrol=506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649).

Results

Observational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78).

Conclusion

Both observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD.
Does industrialization promote the emission mitigation agenda of East Africa? a pathway toward environmental sustainability
Authors: Yu Yan , Zhao Jingyi , Musah Mohammed , Owusu-Akomeah Michael , Nkyi Joseph Akwasi , Li Jing , Appiagyei Ampong George Oppong , Kumah Emmanuel Attah , Cao Siqi , Xu Yuxiang , Shi Yingfang , Wang Liqi , Hui Can , Li Kaodui
Published: March 2024

Africa’s economy continues to be characterized by increasing environmental pollution caused by anthropogenic activities. Despite the implications of environmental pollution in the continent, little attention has been paid to it, although almost all its countries are signatories to the Paris Agreement. One macroeconomic variable that has proven to be a major driver of environmental pollution in the region is industrialization. However, despite the numerous explorations on the connection between industrialization and environmental degradation, limited studies have examined the linkage amidst the series in East Africa. This study was, therefore, conducted to help fill that gap. In accomplishing this goal, econometric techniques that control cross-sectional correlations, heterogeneity, and endogeneity, among others, were employed for the analysis. From the results, the panel under consideration was heterogeneous and cross sectionally correlated. In addition, the studied series were first differenced stationary and co-integrated in the long run. The elasticities of the regressors were explored via the cross sectionally augmented autoregressive distributed lag (CS-ARDL) estimator, the cross sectionally augmented distributed lag (CS-DL) estimator, and the augmented mean group (AMG) estimator. According to the results, industrialization led to a reduction in the environmental quality in the region through high CO2 emissions. In addition, financial development, foreign direct investments, urbanization, and energy consumption were not environmentally friendly in the bloc. On the causal linkages amid the series, bidirectional causalities between industrialization and CO2 emissions, energy consumption and CO2 emissions, and foreign direct investments and CO2 emissions were detected. Finally, one-way causal movements from financial development and urbanization to CO2 emissions were unraveled. These findings are useful in helping stimulate the emission mitigation agenda of the region. Based on the findings, the study recommended, among others, that national policies that can promote energy conservation at the industrial level and can convert the industrial structure of the region to a low carbon-intensive one should be formulated.
Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers
Authors: Bricio-Moreno Laura , Barreto de Albuquerque Juliana , Neary Jake M. , Nguyen Thao , Kuhn Lucy F. , Yeung YeePui , Hastie Kathryn M. , Landeras-Bueno Sara , Olmedillas Eduardo , Hariharan Chitra , Nathan Anusha , Getz Matthew A. , Gayton Alton C. , Khatri Ashok , Gaiha Gaurav D. , Ollmann Saphire Erica , Luster Andrew D. , Moon James J.
Published: March 2024

Understanding adaptive immunity against SARS-CoV-2 is a major requisite for the development of effective vaccines and treatments for COVID-19. CD4+ T cells play an integral role in this process primarily by generating antiviral cytokines and providing help to antibody-producing B cells. To empower detailed studies of SARS-CoV-2-specific CD4+ T cell responses in mouse models, we comprehensively mapped I-Ab-restricted epitopes for the spike and nucleocapsid proteins of the BA.1 variant of concern via IFNγ ELISpot assay. This was followed by the generation of corresponding peptide:MHCII tetramer reagents to directly stain epitope-specific T cells. Using this rigorous validation strategy, we identified 6 immunogenic epitopes in spike and 3 in nucleocapsid, all of which are conserved in the ancestral Wuhan strain. We also validated a previously identified epitope from Wuhan that is absent in BA.1. These epitopes and tetramers will be invaluable tools for SARS-CoV-2 antigen-specific CD4+ T cell studies in mice.
Metabolic profiling of synovial fluid in human temporomandibular joint osteoarthritis
Authors: Zhang Dahe , Zhang Yuxin , Xia Simo , Shen Pei , Yang Chi
Published: March 2024

Introduction

Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level.

Methods

Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging.

Results

A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA.

Discussion

In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.
The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study
Authors: Yang Yujie , Zheng Xuwei , Lv Haiying , Tang Bin , Zhong Yiyuan , Luo Qianqian , Bi Yang , Yang Kexin , Zhong Haixin , Chen Haiming , Lu Chuanjian
Published: March 2024

Objective

To explore the influence of serum metabolites on the risk of psoriasis.

Methods

In the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio’s odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran’s Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages.

Results

In the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism.

Conclusion

Circulating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.
B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1
Authors: Liang Yue , Wang HanChen , Seija Noé , Lin Yun Hsiao , Tung Lin Tze , Di Noia Javier M. , Langlais David , Nijnik Anastasia
Published: March 2024

Introduction

BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored.

Methods and results

In the current study, we demonstrate that a B-cell intrinsic loss of BAP1 in activated B cells in the Bap1fl/flCγ1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression.

Conclusion and discussion

In summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity.
Comparative immunohistochemical analysis of inflammatory cytokines in distinct subtypes of Sweet syndrome
Authors: Chieosilapatham Panjit , Daroontum Teerada , Suwansirikul Songkiet , Chaiwarith Romanee , Phinyo Phichayut , Chaowattanapanit Suteeraporn , Choonhakarn Charoen , Kiratikanon Salin , Rujiwetpongstorn Rujira , Tovanabutra Napatra , Chiewchanvit Siri , Chuamanochan Mati
Published: March 2024

Background

A dysregulated immune response has been implicated in Sweet syndrome (SS) pathogenesis; however, cytokine profiles across different conditions associated with SS — including adult-onset immunodeficiency (AOID) due to anti-interferon (IFN)-γ autoantibodies — remain unknown.

Objective

To investigate alterations in inflammatory cytokines in skin lesions of distinct subtypes of SS.

Methods

Skin biopsies were collected from 42 AOID- and 52 non-AOID-associated SS patients and 18 healthy controls. The comparative immunohistochemical study was conducted using monoclonal antibodies against interleukin (IL)-1β, IL-6, IL-17, IFN-γ, and tumor necrosis factor-α on paraffin-embedded sections. The quantitative percentage positivity and intensity were calculated using computer-based image analysis.

Results

The results showed stronger and more diffuse dermal immunoreactivity for IFN-γ and IL-17 in the AOID-associated (p < 0.001 and p < 0.001, respectively) and non-AOID-associated SS (p < 0.001 and p < 0.001, respectively) groups. However, no significant differences in the levels of these two cytokines were observed between the AOID- and non-AOID-associated SS groups. Increased expression of IFN-γ together with IL-17 was also noted in almost all subtypes among non-AOID-associated SS.

Conclusions

These results demonstrate that IFN-γ and IL-17 are implicated in immunopathology of all SS subtypes, including AOID-associated SS, despite the presence of anti-IFN-γ autoantibodies.
Oxidative phosphorylation in HIV-1 infection: impacts on cellular metabolism and immune function
Authors: Rodriguez Natalia Rodriguez , Fortune Trinisia , Hegde Esha , Weinstein Matthew Paltiel , Keane Aislinn M. , Mangold Jesse F. , Swartz Talia H.
Published: March 2024

Human Immunodeficiency Virus Type 1 (HIV-1) presents significant challenges to the immune system, predominantly characterized by CD4+ T cell depletion, leading to Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) effectively suppresses the viral load in people with HIV (PWH), leading to a state of chronic infection that is associated with inflammation. This review explores the complex relationship between oxidative phosphorylation, a crucial metabolic pathway for cellular energy production, and HIV-1, emphasizing the dual impact of HIV-1 infection and the metabolic and mitochondrial effects of ART. The review highlights how HIV-1 infection disrupts oxidative phosphorylation, promoting glycolysis and fatty acid synthesis to facilitate viral replication. ART can exacerbate metabolic dysregulation despite controlling viral replication, impacting mitochondrial DNA synthesis and enhancing reactive oxygen species production. These effects collectively contribute to significant changes in oxidative phosphorylation, influencing immune cell metabolism and function. Adenosine triphosphate (ATP) generated through oxidative phosphorylation can influence the metabolic landscape of infected cells through ATP-detected purinergic signaling and contributes to immunometabolic dysfunction. Future research should focus on identifying specific targets within this pathway and exploring the role of purinergic signaling in HIV-1 pathogenesis to enhance HIV-1 treatment modalities, addressing both viral infection and its metabolic consequences.
Novel prognostic biomarker TBC1D1 is associated with immunotherapy resistance in gliomas
Authors: Song Daqiang , Yang Qian , Li Liuying , Wei Yuxian , Zhang Chong , Du Huimin , Ren Guosheng , Li Hongzhong
Published: March 2024

Background

Glioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy.

Methods

We identified genes associated with immunotherapy resistance through an analysis of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Subsequently, qRT-PCR and western blot analyses were conducted to measure the mRNA and protein levels of TBC1 Domain Family Member 1 (TBC1D1), respectively. Additionally, Gene Set Enrichment Analysis (GSEA) was employed to reveal relevant signaling pathways, and the expression of TBC1D1 in immune cells was analyzed using single-cell RNA sequencing (scRNA-seq) data from GEO database. Tumor Immune Dysfunction and Exclusion (TIDE) database was utilized to assess T-cell function, while Tumor Immunotherapy Gene Expression Resource (TIGER) database was employed to evaluate immunotherapy resistance in relation to TBC1D1. Furthermore, the predictive performance of molecules on prognosis was assessed using Kaplan-Meier plots, nomograms, and ROC curves.

Results

The levels of TBC1D1 were significantly elevated in tumor tissue from glioma patients. Furthermore, high TBC1D1 expression was observed in macrophages compared to other cells, which negatively impacted T cell function, impaired immunotherapy response, promoted treatment tolerance, and led to poor prognosis. Inhibition of TBC1D1 was found to potentially synergistically enhance the efficacy of immunotherapy and prolong the survival of cancer patients with gliomas.

Conclusion

Heightened expression of TBC1D1 may facilitate an immunosuppressive microenvironment and predict a poor prognosis. Blocking TBC1D1 could minimize immunotherapy resistance in cancer patients with gliomas.
The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications
Authors: Zhao Hui , Song Jialin , Li Xiujun , Xia Zhaoyi , Wang Qian , Fu Jiaqi , Miao Yuqing , Wang Dapeng , Wang Xuguang
Published: March 2024

Pulmonary hypertension (PH) is a malignant disease with progressive increase of pulmonary vascular pressure, which eventually leads to right heart failure. More and more evidences show that immune cells and inflammation play an important role in the occurrence and development of PH. In the context of pulmonary vascular diseases, immune cells migrate into the walls of the pulmonary vascular system. This leads to an increase in the levels of cytokines and chemokines in both the bloodstream and the surrounding tissues of the pulmonary vessels. As a result, new approaches such as immunotherapy and anti-inflammatory treatments are being considered as potential strategies to halt or potentially reverse the progression of PH. We reviewed the potential mechanisms of immune cells, cytokines and chemokines in PH development. The potential relationship of vascular cells or bone morphogenetic protein receptor 2 (BMPR2) in immune regulation was also expounded. The clinical application and future prospect of immunotherapy were further discussed.
Fungal endophytes from Thalassia testudinum show bioactivity against the seagrass pathogen, Labyrinthula spp.
Authors: Ugarelli Kelly , Jagels Annika , Choi Chang Jae , Loesgen Sandra , Stingl Ulrich
Published: March 2024

Thalassia testudinum has undergone die-offs in the past century due to seagrass wasting disease caused by Labyrinthula sp. Little is known about how seagrasses resist Labyrinthula infections, but metabolites that inhibit Labyrinthula were previously extracted from seagrass leaves. Furthermore, leaf fungal endophytes from seagrasses possess antipathogenic potential, but their activity against Labyrinthula is unknown. Here, we aimed to identify whether fungal endophytes of T. testudinum can aid in disease defense against Labyrinthula. Through Illumina amplicon sequencing of the leaves’ mycobiome, we identified fungi that are known to produce antimicrobials. We also isolated and extracted organic compounds from endophytes to test their anti-Labyrinthula potential using disk diffusion assays. There were 22 isolates that inhibited Labyrinthula, from which two isolates, Trichoderma sp. P1a and Diaporthe sp. M14, displayed strong inhibition. LC-HRMS/MS analysis determined the likely bioactive compounds of Trichoderma as peptaibols and of Diaporthe as cytosporone B. Cytosporone B was confirmed bioactive against Labyrinthula via disk diffusion assays. While these organisms are low in abundance in the mycobiome, this study demonstrates that seagrass endophytes have the potential to play an important role in defense against Labyrinthula.
Unraveling the shift in bacterial communities profile grown in sediments co-contaminated with chlorolignin waste of pulp-paper mill by metagenomics approach
Authors: Kumar Vineet , Ameen Fuad , Verma Pradeep
Published: March 2024

Pulp-paper mills (PPMs) are known for consistently generating a wide variety of pollutants, that are often unidentified and highly resistant to environmental degradation. The current study aims to investigate the changes in the indigenous bacterial communities profile grown in the sediment co-contaminated with organic and inorganic pollutants discharged from the PPMs. The two sediment samples, designated PPS-1 and PPS-2, were collected from two different sites. Physico-chemical characterization of PPS-1 and PPS-2 revealed the presence of heavy metals (mg kg−1) like Cu (0.009–0.01), Ni (0.005–0.002), Mn (0.078–0.056), Cr (0.015–0.009), Pb (0.008–0.006), Zn (0.225–0.086), Fe (2.124–0.764), Al (3.477–22.277), and Ti (99.792–45.012) along with high content of chlorophenol, and lignin. The comparative analysis of organic pollutants in sediment samples using gas chromatography–mass spectrometry (GC–MS) revealed the presence of major highly refractory compounds, such as stigmasterol, β-sitosterol, hexadecanoic acid, octadecanoic acid; 2,4-di-tert-butylphenol; heptacosane; dimethyl phthalate; hexachlorobenzene; 1-decanol,2-hexyl; furane 2,5-dimethyl, etc in sediment samples which are reported as a potential toxic compounds. Simultaneously, high-throughput sequencing targeting the V3–V4 hypervariable region of the 16S rRNA genes, resulted in the identification of 1,249 and 1,345 operational taxonomic units (OTUs) derived from a total of 115,665 and 119,386 sequences read, in PPS-1 and PPS-2, respectively. Analysis of rarefaction curves indicated a diversity in OTU abundance between PPS-1 (1,249 OTUs) and PPS-2 (1,345 OTUs). Furthermore, taxonomic assignment of metagenomics sequence data showed that Proteobacteria (55.40%; 56.30%), Bacteoidetes (11.30%; 12.20%), and Planctomycetes (5.40%; 4.70%) were the most abundant phyla; Alphproteobacteria (20.50%; 23.50%), Betaproteobacteria (16.00%; 12.30%), and Gammaproteobacteria were the most recorded classes in PPS-1 and PPS-2, respectively. At the genus level, Thiobacillus (7.60%; 4.50%) was the most abundant genera grown in sediment samples. The results indicate significant differences in both the diversity and relative abundance of taxa in the bacterial communities associated with PPS-2 when compared to PPS-1. This study unveils key insights into contaminant characteristics and shifts in bacterial communities within contaminated environments. It highlights the potential for developing efficient bioremediation techniques to restore ecological balance in pulp-paper mill waste-polluted areas, stressing the importance of identifying a significant percentage of unclassified genera and species to explore novel genes.
Treatment strategies and treatment-related adverse events in MG according to the age of onset
Authors: Moura João , Fernandes Joana , Lima Maria João , Sousa Ana Paula , Samões Raquel , Martins Silva Ana , Santos Ernestina
Published: March 2024

Introduction

Early-onset (EOMG) and late-onset (LOMG) are distinct groups of MG patients. It is unclear if treatment strategies and treatment-related adverse events may differ according to the age of MG onset.

Methods

This single-center retrospective study includes all MG patients followed at a tertiary center since 2007. We reviewed the electronic clinical records.

Results

In total, 212 patients were identified, 142 (67.0%) females, with a median disease duration of 10 years. The median age of symptom onset was 42.0 (26.0–64.5) years, with 130 (61.3%) EOMG cases and 82 (38.7%) LOMG. EOMG were more frequently female, had longer disease duration and often more generalized MG (p < 0.001). Comorbidities were significantly more frequent in LOMG (67.1%) compared to EOMG (53.1%) (p = 0.002). Steroid-related adverse effects motivating the switch to steroid-sparing agents (82.0%) were different between groups, with hypertension, hypercholesterolemia, diabetes mellitus and malignancies being more common in LOMG. At the same time, osteoporosis and dyspepsia were more frequent in EOMG (p < 0.001). The most common first-line choice was azathioprine (45.8%), and rituximab was used in 4 patients (1.9%).

Conclusion

Our study shows that treatment modalities are similar between EOMG and LOMG, while steroid-related adverse events appear to be distinct.
Age and duration of hypertension are associated with carotid artery tortuosity
Authors: Huang Huan , Fu Jian-Jiong , Yao Pi-Guang , Wang Meng-Yao , Wang Xue , Guo An-Na , Li Wei , Chen Shao-Huai , Li Dan-Dong
Published: March 2024

Objective

Tortuosity of the carotid artery is a common angiographic finding that may impact blood flow and neuronal function. However, information on its prevalence and risk factors remains limited. In this study, we determined to explore the factors affecting carotid artery tortuosity.

Methods

The head and neck computed tomography angiography (CTA) imaging and cerebral angiography data performed at the Second Affiliated Hospital of Wenzhou Medical University between January 2019 and September 2021 were collected, and a total of 356 cases were enrolled in the study after screening. Carotid artery tortuosity refers to the angle between the two adjacent segments of the carotid artery, from the opening of the aortic arch on either side to the external orifice of the carotid canal, being less than 150°. A retrospective analysis was performed to compare the general information, laboratory indicators, personal history, and medical history between the two groups. The χ2 test, t-test, and Mann–Whitney U-test were performed to compare the parameters between the two groups. If there were significant differences between the groups, multivariate logistic regression was performed to analyze the factors affecting carotid artery tortuosity.

Results

A total of 222 of the 356 cases were determined to have carotid artery tortuosity, accounting for 63.6%. There were statistically significant differences in age, body mass index (BMI), duration of diabetes and hypertension, levels of low-density lipoprotein cholesterol (LDL-C), diastolic blood pressure, history of ischemic and hemorrhagic stroke, and the usage of antihypertensive drugs between the two groups. Multivariate logistic regression analysis of the above factors showed that age (OR = 5.063, 95% CI 2.963–10.26, p < 0.001) and duration of hypertension (OR = 2.356, 95% CI 1.353–8.625, p = 0.021) were associated with a higher incidence of carotid artery tortuosity. Compared to patients who did not consume antihypertensive drugs, the incidence of carotid artery tortuosity was significantly less (OR = 0.094, 95% CI 0.002–0.713, p = 0.019) in those consuming antihypertensive drugs.

Conclusion

Carotid artery tortuosity is a relatively common carotid artery disease. The incidence of carotid artery tortuosity may increase with age and the duration of hypertension. The consumption of antihypertensive drugs may reduce the incidence of carotid artery tortuosity.
Individual and group-level optimization of electric field in deep brain region during multichannel transcranial electrical stimulation
Authors: Nishimoto Hidetaka , Kodera Sachiko , Otsuru Naofumi , Hirata Akimasa
Published: March 2024

Electrode montage optimization for transcranial electric stimulation (tES) is a challenging topic for targeting a specific brain region. Targeting the deep brain region is difficult due to tissue inhomogeneity, resulting in complex current flow. In this study, a simplified protocol for montage optimization is proposed for multichannel tES (mc-tES). The purpose of this study was to reduce the computational cost for mc-tES optimization and to evaluate the mc-tES for deep brain regions. Optimization was performed using a simplified protocol for montages under safety constraints with 20 anatomical head models. The optimization procedure is simplified using the surface EF of the deep brain target region, considering its small volume and non-concentric distribution of the electrodes. Our proposal demonstrated that the computational cost was reduced by >90%. A total of six–ten electrodes were necessary for robust EF in the target region. The optimization with surface EF is comparable to or marginally better than using conventional volumetric EF for deep brain tissues. An electrode montage with a mean injection current amplitude derived from individual analysis was demonstrated to be useful for targeting the deep region at the group level. The optimized montage and injection current were derived at the group level. Our proposal at individual and group levels showed great potential for clinical application.
On decoding of rapid motor imagery in a diverse population using a high-density NIRS device
Authors: Kothe Christian , Hanada Grant , Mullen Sean , Mullen Tim
Published: March 2024

Introduction

Functional near-infrared spectroscopy (fNIRS) aims to infer cognitive states such as the type of movement imagined by a study participant in a given trial using an optical method that can differentiate between oxygenation states of blood in the brain and thereby indirectly between neuronal activity levels. We present findings from an fNIRS study that aimed to test the applicability of a high-density (>3000 channels) NIRS device for use in short-duration (2 s) left/right hand motor imagery decoding in a diverse, but not explicitly balanced, subject population. A side aim was to assess relationships between data quality, self-reported demographic characteristics, and brain-computer interface (BCI) performance, with no subjects rejected from recruitment or analysis.

Methods

BCI performance was quantified using several published methods, including subject-specific and subject-independent approaches, along with a high-density fNIRS decoder previously validated in a separate study.

Results

We found that decoding of motor imagery on this population proved extremely challenging across all tested methods. Overall accuracy of the best-performing method (the high-density decoder) was 59.1 +/– 6.7% after excluding subjects where almost no optode-scalp contact was made over motor cortex and 54.7 +/– 7.6% when all recorded sessions were included. Deeper investigation revealed that signal quality, hemodynamic responses, and BCI performance were all strongly impacted by the hair phenotypical and demographic factors under investigation, with over half of variance in signal quality explained by demographic factors alone.

Discussion

Our results contribute to the literature reporting on challenges in using current-generation NIRS devices on subjects with long, dense, dark, and less pliable hair types along with the resulting potential for bias. Our findings confirm the need for increased focus on these populations, accurate reporting of data rejection choices across subject intake, curation, and final analysis in general, and signal a need for NIRS optode designs better optimized for the general population to facilitate more robust and inclusive research outcomes.
A rare huge bladder inflammatory myofibroblastic tumor treated by en bloc resection with diode laser: a case report and literature review
Authors: Yuan Huisheng , Wang Zilong , Sun Jiaxing , Chu Junhao , Duan Shishuai , Wang Muwen
Published: March 2024

Background

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with malignant potential. Bladder IMT is even rarer and mainly treated by surgical resection However, partial or radical cystectomy would affect the quality of life of patients due to major surgical trauma, and classical TURBT is hard to avoid intraoperative complications including obturator nerve reflex and bleeding etc. Therefore, the safe and effective better choice of surgical approaches become critical to bladder IMT.

Case presentation

A 42-year-old male patient was admitted to the department of urology with persistent painless gross hematuria for more than 10 days without the presentation of hypertension. Preoperative routine urine examination of red blood cells was 7738.9/HPF (normal range ≤ 3/HPF). CTU indicated a space occupying lesion (6.0 cm×5.0 cm) in the left posterior wall of the bladder with heterogeneous enhancement in the excretory phase. MRI also indicated bladder tumor with slightly equal SI on T1WI and mixed high SI on T2WI (6.0 cm×5.1cm×3.5cm) in the left posterior wall of the bladder. En bloc resection of bladder IMT with 1470 nm diode laser in combination of removing the enucleated tumor by the morcellator system was performed. Postoperative pathological examination revealed bladder IMT, with IHC positive for Ki-67 (15-20%), CK AE1/AE3, SMA, and Desmin of bladder IMT and negative for ALK of bladder IMT as well as FISH negative for ALK gene rearrangement. Second TUR with 1470 nm diode laser was performed within 6 weeks to reduce postoperative risk of recurrence due to highly malignant potential for the high expression of Ki-67 (15-20%) and negative ALK in IHC staining. The second postoperative pathology report showed chronic inflammation concomitant with edema of the bladder mucosa without bladder IMT, furthermore no tumor was observed in muscularis propria layer of bladder. No recurrence occurred during the period of 24-month follow-up.

Conclusion

En bloc resection of bladder IMT in combination of the following second transurethral resection with 1470 nm diode laser is a safe and effective surgical approach for the huge bladder IMT with highly malignant potential.
Establishment of a pharmacokinetics and pharmacodynamics model of Schisandra lignans against hippocampal neurotransmitters in AD rats based on microdi-alysis liquid chromatography-mass spectrometry
Authors: Zhang Jinpeng , Cui Xinyuan , Zhao Shuo , Chang Zenghui , Zhang Junshuo , Chen Yufeng , Liu Jiale , Sun Guohao , Wang Yiyuan , Liu Yuanyuan
Published: March 2024

Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer’s disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model.

Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group.

Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.
Antibacterial activity of cinnamon essential oil and its main component of cinnamaldehyde and the underlying mechanism
Authors: Shu Chengjie , Ge Ling , Li Zhuohang , Chen Bin , Liao Shengliang , Lu Lu , Wu Qinlin , Jiang Xinyi , An Yuhan , Wang Zongde , Qu Man
Published: March 2024

Background: Plant essential oils have long been regarded as repositories of antimicrobial agents. In recent years, they have emerged as potential alternatives or supplements to antimicrobial drugs. Although literature reviews and previous studies have indicated that cinnamon essential oil (CIEO) and its major component, cinnamaldehyde (CID), possess potent antibacterial activities, their antibacterial mechanisms, especially the in vivo antibacterial mechanisms, remain elusive.

Methods: In this study, we utilized the in vivo assessment system of Caenorhabditis elegans (C. elegans) to investigate the effects and mechanisms of high dose (100 mg/L) and low dose (10 mg/L) CIEO and CID in inhibiting Pseudomonas aeruginosa (P. aeruginosa). In addition, we also examined the in vitro antibacterial abilities of CIEO and CID against other common pathogens including P. aeruginosa and 4 other strains.

Results: Our research revealed that both high (100 mg/L) and low doses (10 mg/L) of CIEO and CID treatment significantly alleviated the reduction in locomotion behavior, lifespan, and accumulation of P. aeruginosa in C. elegans infected with the bacteria. During P. aeruginosa infection, the transcriptional expression of antimicrobial peptide-related genes (lys-1 and lys-8) in C. elegans was upregulated with low-dose CIEO and CID treatment, while this trend was suppressed at high doses. Further investigation suggested that the PMK-1 mediated p38 signaling pathway may be involved in the regulation of CIEO and CID during nematode defense against P. aeruginosa infection. Furthermore, in vitro experimental results also revealed that CIEO and CID exhibit good antibacterial effects, which may be associated with their antioxidant properties.

Conclusion: Our results indicated that low-dose CIEO and CID treatment could activate the p38 signaling pathway in C. elegans, thereby regulating antimicrobial peptides, and achieving antimicrobial effects. Meanwhile, high doses of CIEO and CID might directly participate in the internal antimicrobial processes of C. elegans. Our study provides research basis for the antibacterial properties of CIEO and CID both in vivo and in vitro.
Formation of field-induced breakdown precursors on metallic electrode surfaces
Authors: Bagchi Soumendu , Simakov Evgenya , Perez Danny
Published: March 2024

Understanding the underlying factors responsible for higher-than-anticipated local field enhancements required to trigger vacuum breakdown on pristine metal surfaces is crucial for the development of devices capable of withstanding intense operational fields. In this study, we investigate the behavior of nominally flat copper electrode surfaces exposed to electric fields of hundreds of MV/m. Our novel approach considers curvature-driven diffusion processes to elucidate the formation of sharp breakdown precursors. To do so, we develop a mesoscale finite element model that accounts for driving forces arising from both electrostatic and surface-tension-induced contributions to the free energy. Our findings reveal a dual influence: surface tension tends to mitigate local curvature, while the electric field drives mass transport toward regions of high local field density. This phenomenon can trigger the growth of sharper protrusions, ultimately leading to a rapid enhancement of local fields and, consequently, to a runaway growth instability. We delineate supercritical and subcritical regimes across a range of initial surface roughness. Our numerical results are in qualitative agreement with experimentally reported data, indicating the potential practical relevance of field-driven diffusion in the formation of breakdown precursors.
High-intensity interval training improves respiratory and cardiovascular adjustments before and after initiation of exercise
Authors: Ito Go , Feeley Marina , Sawai Toru , Nakata Hideomi , Otsuki Shingo , Nakahara Hidehiro , Miyamoto Tadayoshi
Published: March 2024

Purpose: High-intensity interval training (HIIT) may induce training-specific physiological adaptations such as improved respiratory and cardiovascular adjustments before and after the onset of high-intensity exercise, leading to improved exercise performance during high-intensity exercise. The present study investigated the effects of HIIT on time-dependent cardiorespiratory adjustment during maximal exercise and before and after initiation of high-intensity exercise, as well as on maximal exercise performance.

Methods: 21 healthy male college students were randomly assigned to HIIT group (n = 11) or control group (n = 10). HIIT group performed training on a cycle ergometer once a week for 8 weeks. The training consisted of three bouts of exercise at 95% maximal work rate (WRmax) until exhaustion. Before and after the HIIT program, dynamic cardiorespiratory function was investigated by ramp and step exercise tests, and HIIT-induced cardiac morphological changes were assessed using echocardiography.

Results: HIIT significantly improved not only maximal oxygen uptake and minute ventilation, but also maximal heart rate (HR), systolic blood pressure (SBP), and time to exhaustion in both exercise tests (p < 0.05). Time-dependent increases in minute ventilation (VE) and HR before and at the start of exercise were significantly enhanced after HIIT. During high-intensity exercise, there was a strong correlation between percent change (from before to after HIIT program) in time to exhaustion and percent change in HRmax (r = 0.932, p < 0.001). Furthermore, HIIT-induced cardiac morphological changes such as ventricular wall hypertrophy was observed (p < 0.001).

Conclusion: We have demonstrated that HIIT at 95% WRmax induces training-specific adaptations such as improved cardiorespiratory adjustments, not only during maximal exercise but also before and after the onset of high-intensity exercise, improvement of exercise performance mainly associated with circulatory systems.
Phylogeographic analysis reveals extensive genetic variation of native grass Elymus nutans (Poaceae) on the Qinghai-Tibetan plateau
Authors: Li Jin , Li Xinda , Zhang Changbing , Zhou Qingping , Chen Shiyong
Published: March 2024

Introduction

Elymus nutans holds ecological and pastoral significance due to its adaptability and nutritional value, the Qinghai-Tibet Plateau (QTP) is a key hub for its genetic diversity. To conserve and harness its genetic resources in highland ecosystems, a thorough assessment is vital. However, a comprehensive phylogeographic exploration of E. nutans is lacking. The objective of this study was to unravel the genetic diversity, adaptation, and phylogenetics of E. nutans populations.

Methods

Encompassing 361 individuals across 35 populations, the species' genetic landscape and dynamic responses to diverse environments were decoded by using four chloroplast DNA (cpDNA) sequences and nine microsatellite markers derived from the transcriptome.

Results and discussion

This study unveiled a notable degree of genetic diversity in E. nutans populations at nuclear (I = 0.46, He = 0.32) and plastid DNA levels (Hd = 0.805, π = 0.67). Analysis via AMOVA highlighted genetic variation predominantly within populations. Despite limited isolation by distance (IBD), the Mekong-Salween Divide (MSD) emerged as a significant factor influencing genetic differentiation and conserving diversity. Furthermore, correlations were established between external environmental factors and effective alleles of three EST-SSRs (EN5, EN57 and EN80), potentially linked to glutathione S-transferases T1 or hypothetical proteins, affecting adaptation. This study deepens the understanding of the intricate relationship between genetic diversity, adaptation, and environmental factors within E. nutans populations on the QTP. The findings shed light on the species' evolutionary responses to diverse ecological conditions and contribute to a broader comprehension of plant adaptation mechanisms.