bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Contradictions Between Energy Production and Consumption Along With Economic Development and Environmental Protection in China: Evidence and Policy Implications
Authors: Tang Erzi
Published: June 2022

This paper empirically describes and analyzes the structural contradictions between energy production and consumption in the Chinese local economy. Alongside rapid economic growth, energy usage in China increased gradually and exceeded energy production for a long time. For some particular energy sources such as petroleum, the gap between supply and demand is relatively larger than that of the whole energy sector in the economy. The process of turning fossil fuels into final energy products for use causes a great deal of pollution, especially emitting industrial waste gases, such as particulate matter emission, into the atmospheric environment. Increasing energy production directly and greatly to solve the gap between energy supply and demand in the economy may impact environmental quality and not meet sustainable development needs. It is difficult to coordinate energy production and consumption when considering economic development and environmental protection in economic operation. Importing energy could meet the excess energy consumption in a short period but often fluctuates from foreign energy market changes and global political events. For policy recommendations, some policies which directly lower energy consumption may impact economic development since industry is the main consumer of energy, and industrial production is an important component of GDP in China. Declining the role of the industry sector in the economy and reducing industrial product exports, including some energy-intensive products, could solve the structural contradictions between energy production and consumption under the condition of maintaining economic development and protecting the environment in China, but this is a long-term adjustment process.
Identification of Immune-Related Subtypes and Characterization of Tumor Microenvironment Infiltration in Kidney Renal Clear Cell Carcinoma
Authors: Qin Huisheng , Wang Tiancheng , Zhang Hui
Published: June 2022

Background: Tumor microenvironment (TME) plays indisputable role in the progression of cancers. Immune cell infiltration (ICI) in TME was related to the prognosis of tumor patients. In this paper, we identified the pattern of immune-related ICI subtypes based on the TME immune infiltration pattern.

Methods: The data from kidney renal clear cell carcinoma data (KIRC) was downloaded from the TCGA database. The distinct ICI subtypes were identified using CIBERSORT and ESTIMATE algorithms. The gene subgroups were identified based on DEGs in ICI subtypes. The single sample gene set enrichment analysis (ssGSEA) was used to ascertain the ICI score. Kaplan-Meier curve with log-rank test was conducted to analyze the survival probability of patients with KIRC in different subtypes.

Results: The patients with high ICI scores exhibited a longer survival time and lower expression of checkpoint-related and immune activity-related genes. The high ICI score clusters were positively related to TMB. The patients in the low TMB subgroups have a favorable prognosis. The prediction ICI score did not affect the TMB status, and the low TMB subgroups + low/high ICI score subgroups exhibited better survival.

Conclusion: In all, the tumor immune microenvironment, ICI score, and TMB were important determinants of KIRC patients’ survival outcomes. The TMB + ICI score may be a potential biomarker for predicting the prognosis of patients and for targeted immunotherapies to treating KIRC.
Extracellular Nucleosomes Accelerate Microglial Inflammation via C-Type Lectin Receptor 2D and Toll-Like Receptor 9 in mPFC of Mice With Chronic Stress
Authors: Wu Huanghui , Bao Han , Liu Cong , Zhang Qiao , Huang Ailing , Quan Minxue , Li Chunhui , Xiong Ying , Chen Guozhong , Hou Lichao
Published: June 2022

Damage-associated molecular patterns (DAMPs) are the primary promoter of progressive neuroinflammation and are associated with chronic stress-related emotional disorders. The present study investigated the role and mechanism of extracellular nucleosomes and histones, the newly defined DAMPs, in mice with chronic stress. C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) and corticosterone drinking, respectively, for 4 weeks. Negative emotional behaviors were comprehensively investigated. Microglial morphology, oxidative stress, and inflammation, as well as C-type lectin receptor 2D (Clec2d) and Toll-like receptor 9 (TLR9) expression in medial prefrontal cortex (mPFC) were assessed with flow cytometer and cell sorting. Specifically, microglial pro-inflammatory activation and inflammation were further investigated with stereotactic injection of recombinant nucleosomes and histones in mPFC and further evaluated with AAV-Clec2d knocking-down, DNase I, and activated protein C (APC) pretreatment. Moreover, the rescue effect by AAV-Clec2d knocking-down was observed in mice with chronic stress. Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors and accompanied with significant microglial oxidative stress and inflammation, indicating by reactive oxygen species (ROS) production, primed nuclear factor-κB (NF-κB) signaling pathway, activated NACHT, LRR, and PYD domain–containing protein 3 (NLRP3) inflammasome, and upregulated Clec2d and TLR9 in mPFC, together with histones dictation in cerebrospinal fluid and extracellular trap formation. Stereotactic injection of nucleosomes was contributed to promote microglial inflammation rather than histones in mPFC, indicating that the pro-inflammatory role was derived from extracellular histones-bound DNA but not freely histones. AAV-Clec2d knocking-down, DNase I, and APC were all effective to inhibit nucleosome-induced microglial oxidative stress and inflammation. Moreover, AAV-Clec2d knocking-down in mice with chronic stress exhibited reduced microglial inflammation and improved negative emotional behaviors. Our findings reveal a novel mechanism of DAMP-associated inflammation that extracellular nucleosomes accelerate microglial inflammationviaClec2d and TLR9, and then contribute to chronic stress-induced emotional disorders.
Nutrient Condition in the Microenvironment Determines Essential Metabolisms of CD8+ T Cells for Enhanced IFNγ Production by Metformin
Authors: Chao Ruoyu , Nishida Mikako , Yamashita Nahoko , Tokumasu Miho , Zhao Weiyang , Kudo Ikuru , Udono Heiichiro
Published: June 2022

Metformin (Met), a first-line drug for type 2 diabetes, lowers blood glucose levels by suppressing gluconeogenesis in the liver, presumably through the liver kinase B1-dependent activation of AMP-activated protein kinase (AMPK) after inhibiting respiratory chain complex I. Met is also implicated as a drug to be repurposed for cancers; its mechanism is believed identical to that of gluconeogenesis inhibition. However, AMPK activation requires high Met concentrations at more than 1 mM, which are unachievable in vivo. The immune-mediated antitumor response might be the case in a low dose Met. Thus, we proposed activating or expanding tumor-infiltrating CD8+ T cells (CD8TILs) in a mouse model by orally administering Met in free drinking water. Here we showed that Met, at around 10 μM and a physiologically relevant concentration, enhanced production of IFNγ,TNFα and expression of CD25 of CD8+ T cells upon TCR stimulation. Under a glucose-rich condition, glycolysis was exclusively involved in enhancing IFNγ production. Under a low-glucose condition, fatty acid oxidation or autophagy-dependent glutaminolysis, or both, was also involved. Moreover, phosphoenolpyruvate carboxykinase 1 (PCK1), converting oxaloacetate to phosphoenolpyruvate, became essential. Importantly, the enhanced IFNγ production was blocked by a mitochondrial ROS scavenger and not by an inhibitor of AMPK. In addition, IFNγ production by CD8TILs relied on pyruvate translocation to the mitochondria and PCK1. Our results revealed a direct effect of Met on IFNγ production of CD8+ T cells that was dependent on differential metabolic pathways and determined by nutrient conditions in the microenvironment.
Allele and Haplotype Frequencies of HLA-A, -B, -C, and -DRB1 Genes in 3,750 Cord Blood Units From a Kinh Vietnamese Population
Authors: Que Tran Ngoc , Khanh Nguyen Ba , Khanh Bach Quoc , Van Son Chu , Van Anh Nguyen Thi , Anh Tran Thi Thuy , Tung Pham Dinh , Thang Nguyen Dinh
Published: June 2022

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A–B, HLA-A–C, HLA-A–DRB1, HLA-B–C, HLA-B–DRB1, and HLA-C–DRB1 haplotypes were A*11:01–B*15:02 (7.63%), A*11:01–C*08:01 (7.98%), A*11:01–DRB1*12:02 (10.56%), B*15:02–C*08:01 (14.0%), B*15:02–DRB1*12:02 (10.47%), and C*08:01–DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A–B–C, HLA-A–B–DRB1, HLA-A–C–DRB1, HLA-B–C–DRB1, and HLA-A–B–C–DRB1 were A*11:01–B*15:02–C*08:01 (7.57%), A*11:01–B*15:02–DRB1*12:02 (5.39%), A*11:01–C*08:01–DRB1*12:02 (5.54%), B*15:02–C*08:01–DRB1*12:02 (10.21%), and A*11:01–B*15:02–C*08:01–DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam.
CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation
Authors: Aviles-Padilla Kevin , Angelo Laura S. , Fan Dwight , Paust Silke
Published: June 2022

Reactivation of human cytomegalovirus (HCMV) is a life-threatening complication in transplant patients. Natural Killer (NK) cells are the first lymphocyte lineage to reconstitute following an allogeneic hematopoietic stem cell transplant (HSCT). Amongst them, NK cell Group 2 isoform C/Killer cell lectin-like receptor subfamily C, member 2 (NKG2C)-expressing NK cells contribute significantly to patient protection upon HCMV reactivation. NKG2C+NK cells are capable of immunological memory, albeit NK cell memory is not restricted to them. Hepatic C-X-C Motif Chemokine Receptor 6 (CXCR6)-expressing NK cells also mediate memory responses in mice and humans. Small numbers of them circulate and can thus be studied in peripheral blood samples. We hypothesize that NKG2C+and CXCR6+NK cell subsets are distinct. To test our hypothesis, we used multi-parametric flow cytometry to determine the phenotypes and effector functions of CD56brightvs. CD56dimand NKG2C+vs. CXCR6+human NK cell subsets in the peripheral blood (PB) of pediatric transplant recipients monthly while monitoring patients for HCMV reactivation. Interestingly, we did not find any NKG2C+CXCR6+NK cells in the transplant recipients’ peripheral blood, suggesting that NKG2C+and CXCR6+NK cells are distinct. Also, NKG2C–CXCR6– NK cells, rather than NKG2C+NK cells, made up most NK cells post-transplant, even in transplant recipients with HCMV viremia. In contrast to NKG2C+NK cells, CXCR6+NK cells appeared phenotypically less differentiated but were highly proliferative and produced IFN-γ and TNFα. Our findings contribute to our understanding of post-transplant NK cell development and its implications for human health.
Octanoate Alleviates Dietary Soybean Oil-Induced Intestinal Physical Barrier Damage, Oxidative Stress, Inflammatory Response and Microbial Dysbiosis in Large Yellow Croaker (Larimichthys Crocea)
Authors: Zhang Zhou , Tang Yuhang , Fang Wei , Cui Kun , Xu Dan , Liu Guobin , Chi Shuyan , Tan Beiping , Mai Kangsen , Ai Qinghui
Published: June 2022

Octanoate is a type of classical medium-chain fatty acids, which is widely used to treat neurological and metabolic syndrome. However, the specific role of octanoate in repairing intestinal health impairment is currently unknown. Therefore, we investigated whether dietary octanoate repaired the intestinal damage induced by surplus soybean oil in Larimichthys crocea. In this study, dietary octanoate alleviated abnormal morphology of the intestine and enhanced expression of ZO-1 and ZO-2 to improve intestinal physical barrier. Further, dietary octanoate increased antioxidant enzymic activities and decreased the level of ROS to alleviate the intestinal oxidative stress. Dietary octanoate also attenuated the expression of proinflammatory cytokines and the polarity of macrophage to reduce the intestinal inflammatory response. Moreover, the result of intestinal microbial 16S rRNA sequence showed that dietary octanoate repaired the intestinal mucosal microbial dysbiosis, and increased the relative abundance of Lactobacillus. Dietary octanoate supplementation also increased the level of acetic acid in intestinal content and serum through increasing the abundance of acetate-producing strains. Overall, in Larimichthys crocea, dietary octanoate might alleviated oxidative stress, inflammatory response and microbial dysbiosis to repair the intestinal damage induced by surplus soybean oil. This work provides vital insights into the underlying mechanisms and treatment strategies for intestinal damage in vertebrates.
A Massive Number of Extracellular Tropheryma whipplei in Infective Endocarditis: A Case Report and Literature Review
Authors: Hannachi Nadji , Arregle Florent , Lepidi Hubert , Baudoin Jean-Pierre , Gouriet Frédérique , Martel Hélène , Hubert Sandrine , Desnues Benoit , Riberi Alberto , Casalta Jean-Paul , Habib Gilbert , Camoin-Jau Laurence
Published: June 2022

Whipple’s disease (WD) is a chronic multisystemic infection caused by Tropheryma whipplei. If this bacterium presents an intracellular localization, associated with rare diseases and without pathognomonic signs, it is often subject to a misunderstanding of its physiopathology, often a misdiagnosis or simply an oversight. Here, we report the case of a patient treated for presumed rheumatoid arthritis. Recently, this patient presented to the hospital with infectious endocarditis. After surgery and histological analysis, we discovered the presence of T. whipplei. Electron microscopy allowed us to discover an atypical bacterial organization with a very large number of bacteria present in the extracellular medium in vegetation and valvular tissue. This atypical presentation we report here might be explained by the anti-inflammatory treatment administrated for our patient’s initial diagnosis of rheumatoid arthritis.
Extracellular CIRP Promotes GPX4-Mediated Ferroptosis in Sepsis
Authors: Shimizu Junji , Murao Atsushi , Nofi Colleen , Wang Ping , Aziz Monowar
Published: June 2022

Sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern (DAMP) that promotes inflammation and induces cell death via apoptosis, NETosis, and/or pyroptosis. Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxide on cellular membranes. We hypothesize that eCIRP induces ferroptosis in macrophages and lung tissue during sepsis. RAW 264.7 cells stimulated with recombinant murine (rm) CIRP significantly decreased the expression of glutathione peroxidase 4 (GPX4), a negative regulator of ferroptosis, and increased lipid reactive oxygen species (ROS) in a TLR4 dependent manner. In TLR4-/- peritoneal macrophages, depression of GPX4 expression and increase in lipid ROS levels were attenuated after rmCIRP-treatment compared to WT macrophages. rmCIRP also induced cell death in RAW 264.7 cells which was corrected by the ferroptosis inhibitor, ferrostatin-1 (Fer-1). Intraperitoneal injection of rmCIRP decreased GPX4 expression and increased lipid ROS in lung tissue, whereas the increase of lipid ROS was reduced by Fer-1 treatment. GPX4 expression was significantly decreased, while malondialdehyde (MDA), iron levels, and injury scores were significantly increased in lungs of WT mice after cecal ligation and puncture (CLP)-induced sepsis compared to CIRP-/- mice. Treatment with C23, a specific eCIRP inhibitor, in CLP mice alleviated the decrease in GPX4 and increase in MDA levels of lung tissue. These findings suggest that eCIRP induces ferroptosis in septic lungs by decreasing GPX4 and increasing lipid ROS. Therefore, regulation of ferroptosis by targeting eCIRP may provide a new therapeutic approach in sepsis and other inflammatory diseases.
Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Acute Myocardial Infarction
Authors: Qian Jun , Gao Yanhua , Lai Yan , Ye Zi , Yao Yian , Ding Keke , Tong Jing , Lin Hao , Zhu Guoqi , Yu Yunan , Ding Haoran , Yuan Deqiang , Chu Jiapeng , Chen Fei , Liu Xuebo
Published: June 2022

Background

Acute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive.

Methods

Ten AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells.

Results

We identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell–cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture.

Conclusions

Our studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.
Transcriptional and Epigenetic Regulation of Monocyte and Macrophage Dysfunction by Chronic Alcohol Consumption
Authors: Malherbe Delphine C. , Messaoudi Ilhem
Published: June 2022

Drinking alcohol, even in moderation, can affect the immune system. Studies have shown disproportionate effects of alcohol on circulating and tissue-resident myeloid cells (granulocytes, monocytes, macrophages, dendritic cells). These cells orchestrate the body’s first line of defense against microbial challenges as well as maintain tissue homeostasis and repair. Alcohol’s effects on these cells are dependent on exposure pattern, with acute drinking dampening but chronic drinking enhancing production of inflammatory mediators. Although chronic drinking is associated with heightened systemic inflammation, studies on tissue resident macrophage populations in several organs including the spleen, liver, brain, and lung have also shown compromised functional and metabolic capacities of these cells. Many of these effects are thought to be mediated by oxidative stress caused by alcohol and its metabolites which can directly impact the cellular epigenetic landscapes. In addition, since myeloid cells are relatively short-lived in circulation and are under constant repopulation from the bone marrow compartment, alcohol’s effects on bone marrow progenitors and hematopoiesis are important for understanding the impact of alcohol systemically on these myeloid populations. Alcohol-induced disruption of progenitor, circulating, and tissue resident myeloid populations contribute to the increased susceptibility of patients with alcohol use disorders to viral and bacterial infections. In this review, we provide an overview of the impact of chronic alcohol consumption on the function of monocytes and macrophages in host defense, tissue repair and inflammation. We then summarize our current understanding of the mechanisms underlying alcohol-induced disruption and examine changes in transcriptome and epigenome of monocytes and mcrophages. Overall, chronic alcohol consumption leads to hyper-inflammation concomitant with decreased microbial and wound healing responses by monocytes/macrophages due to a rewiring of the epigentic and transcriptional landscape. However, in advanced alcoholic liver disease, myeloid cells become immunosuppressed as a response to the surrounding hyper-inflammatory milieu. Therefore, the effect of chronic alcohol on the inflammatory response depends on disease state and the immune cell population.
Efficient T Cell Migration and Activation Require L-Plastin
Authors: Joshi Hemant , Morley Sharon Celeste
Published: June 2022

Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T cells. LPL- deficient T cells migrate slowly in response to chemo-attractants such as CXCL12, CCL19, and poorly polarize towards ICAM-1. Loss of LPL impairs thymic egress and intranodal motility. LPL is also required for T-cell IS maturation with APCs, and therefore for efficient cytokine production and proliferation. LPL-/-mice are less susceptible to T-cell mediated pathologies, such as allograft rejection and experimental autoimmune encephalomyelitis (EAE). LPL activity is regulated by its N-terminal “headpiece”, which contains serine and threonine phosphorylation and calcium- and calmodulin-binding sites. LPL phosphorylation is required for lamellipodia formation during adhesion and migration, and also for LFA-1 clustering during IS formation. However, the precise molecular interactions by which LPL supports T-cell functional responses remain unclear. Future studies elucidating LPL-mediated regulation of T-cell migration and/or activation may illuminate pathways for therapeutic targeting in T-cell-mediated diseases.
The Association Between Psoriasis and Risk of Cardiovascular Disease: A Mendelian Randomization Analysis
Authors: Gao Ning , Kong Minjian , Li Xuebiao , Zhu Xian , Wei Dongdong , Ni Ming , Wang Yifan , Hong Ze , Dong Aiqiang
Published: June 2022

Background

A large number of observational studies showed that patients with psoriasis have a higher risk of cardiovascular disease (CVD), but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis. We used Mendelian randomization (MR) to evaluate the potential causal relationship between psoriasis and CVD.

Methods

We used genetic instruments from the genome-wide association study (GWAS) of European descent for psoriasis to investigate its relationship with CVD. Inverse variance-weighted (IVW) MR analyses were used for the primary analysis. In addition, a variety of other methods were used to replicate the analysis.

Results

The fixed-effects IVW method indicated that genetic susceptibility to psoriasis was associated with a higher risk of heart failure (HF) [odds ratio (OR) = 1.04; 95% CI, 1.01–1.06, P = 2.72E-03], atrial fibrillation (AF) (OR = 1.04; 95% CI, 1.02–1.07, P = 3.27E-04), myocardial infarction (MI) (OR = 1.07; 95% CI, 1.01–1.12, P = 0.01), valvular heart disease (VHD) (OR = 1.001; 95% CI, 1.000–1.002, P = 1.85E-03), and large artery stroke (LAS) (OR = 1.11; 95% CI, 1.05–1.18, P = 5.37E-04) but not with the other two subtypes of ischemic stroke (IS) [cardioembolic stroke (CES) (OR = 1.03; 95% CI, 0.98–1.07, P = 0.27) and small vessel stroke (SVS) (OR = 1.00; 95% CI, 0.95–1.07), P = 0.88)]. Sensitivity analysis found weak evidence of horizontal diversity and heterogeneity to ensure the stability of the results.

Conclusion

Our study provided evidence for a potential causal link between psoriasis and CVD. These findings partly suggest that early monitoring of cardiovascular risk in patients with psoriasis is intentional.
Claudin-1 Mediated Tight Junction Dysfunction as a Contributor to Atopic March
Authors: Xia Yuhan , Cao Han , Zheng Jie , Chen Lihong
Published: June 2022

Atopic march refers to the phenomenon wherein the occurrence of asthma and food allergy tends to increase after atopic dermatitis. The mechanism underlying the progression of allergic inflammation from the skin to gastrointestinal (GI) tract and airways has still remained elusive. Impaired skin barrier was proposed as a risk factor for allergic sensitization. Claudin-1 protein forms tight junctions and is highly expressed in the epithelium of the skin, airways, and GI tract, thus, the downregulation of claudin-1 expression level caused by CLDN-1 gene polymorphism can mediate common dysregulation of epithelial barrier function in these organs, potentially leading to allergic sensitization at various sites. Importantly, in patients with atopic dermatitis, asthma, and food allergy, claudin-1 expression level was significantly downregulated in the skin, bronchial and intestinal epithelium, respectively. Knockdown of claudin-1 expression level in mouse models of atopic dermatitis and allergic asthma exacerbated allergic inflammation, proving that downregulation of claudin-1 expression level contributes to the pathogenesis of allergic diseases. Therefore, we hypothesized that the tight junction dysfunction mediated by downregulation of claudin-1 expression level contributes to atopic march. Further validation with clinical data from patients with atopic march or mouse models of atopic march is needed. If this hypothesis can be fully confirmed, impaired claudin-1 expression level may be a risk factor and likely a diagnostic marker for atopic march. Claudin-1 may serve as a valuable target to slowdown or block the progression of atopic march.
Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β
Authors: Colarusso Chiara , Terlizzi Michela , Maglio Angelantonio , Molino Antonio , Candia Claudio , Vitale Carolina , Hansbro Philip M. , Vatrella Alessandro , Pinto Aldo , Sorrentino Rosalinda
Published: June 2022

Severe acute respiratory syndrome-coronavirus-2 (SARS‐CoV‐2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1α, IFN-α and TGF-β. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-α was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1α and pro-fibrogenic TGF-β were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.
Ecological Responses of Core Phytoplankton by Latitudinal Differences in the Arctic Ocean in Late Summer Revealed by 18S rDNA Metabarcoding
Authors: Joo Hyoung Min , Kim Kang Eun , Park Joon Sang , Kim Hyun-Jung , Yang Eun Jin , Lee Taek-Kyun , Cho Kyoung-Ho , Jung Jinyoung , Lee Youngju , Kang Sung-Ho , Jung Seung Won
Published: June 2022

Limited information is available regarding the phytoplankton communities in the Arctic Ocean, especially in the Chukchi Sea. We conducted research cruises in the Arctic Ocean in the late summers of 2015, 2016, 2018, and 2019, and used 18S ribosomal DNA metabarcoding to examine the dynamic changes in core phytoplankton. Environmental factors were divided into three Groups: “surface layers in low latitude”, “subsurface chlorophyll maximum layers in low latitude”, and “high latitude.” The phytoplankton community was divided into two Groups. One Group, “the phytoplankton community in lower latitudes affected by the Pacific Influx “, comprised Dinophyta (56.33%), Bacillariophyta (22.28%), and Chlorophyta (20.77%), while the other Group, “the phytoplankton community in higher latitudes affected by the Arctic Sea “, comprised Dinophyta (57.51%), Bacillariophyta (10.71%), and Chlorophyta (27.57%). The common phytoplankton taxa in Group of lower latitudes included 33 operational taxonomic units (OTUs) (99.04%), while the other Group included nine OTUs (98.80%). In these groups, OTUs #005 (Heterocapsa rotundata), #001 (Micromonas pusilla), and #003 (Chaetoceros gelidus) were core OTUs (>5%). These core OTUs were significantly different between the two Groups; OTU #001 and #003 were distributed at high relative abundance and rapidly increased at higher latitudes. OTU #005 showed a relatively high abundance at lower latitudes. Analysis of the indicator species revealed that 34 OTUs in lower latitudes and only one OTU (#003) in higher latitudes were observed to have a strong value of >0.8. Our results indicate that core phytoplankton taxa and community structures by latitudinal differences are highly dependent on different water masses and show their dynamic ecological responses to extreme environmental conditions.
Sub-Nano Pt/β-FeOOH Quantum Dots for Photocatalytic Removal of Toluene: Catalyst Design, Preparation, and Benefits
Authors: Pei Mengxi , Lv Shangchun , Liu Yishui , Si Zhichun , Wu Xiaodong , Ran Rui , Weng Duan , Kang Feiyu
Published: June 2022

Photocatalytic removal of organic pollutants under solar irradiation at room temperature is considered an energy-saving technique of environmental remediation. However, photocatalysis is impeded by the poor response to visible light and fast charge recombination. In this work, sub-nano Pt/β-FeOOH quantum dots (QDs) were designed to shorten the charge migration path and obtain wide light harvesting. Interestingly, the crystalline β-FeOOH QDs can be obtained by loading sub-nano Pt particles via a reconstruction mechanism of amorphous FeOOH induced by H2 spillover, which facilitates the fast kinetics of charge transition and benefits the oxygen-rich surface of the catalyst for photocatalytic oxidation reactions. Moreover, the Pt-VO-Fe interfaces were proved to be the most active sites for the activation of O2. As a result, the catalyst exhibits a predominant photocatalytic performance in toluene oxidation, achieving a TOFPt of 0.591 min−1 at room temperature under visible light irradiation. This work provides a new perspective on the design and preparation of nanocatalysts for high-efficient photocatalysis under visible light irradiation.
Balancing Benefits and Risks of Indomethacin in the Management of Antenatal Bartter Syndrome: A Case Report
Authors: Alajjuri Omar Ala' , Samaha Mayar Essam , Honemeyer Ulrich , Mohammed Ghada , Mousa Noha A.
Published: June 2022

Background

Bartter syndrome, a very rare inherited renal tubular disorder, characterized by urinary salt wastage, hypokalemia, polyuria, and metabolic alkalosis, may manifest antenatally as severe isolated polyhydramnios. Indomethacin is known to reduce salt wastage and subsequent polyhydramnios during pregnancy; however, it reduces the Ductus Arteriosus diameter among other potential complications, such as inhibition of gastrointestinal perfusion and increasing the risk of renal toxicity.

Case

A 36-year-old multigravida presented with severe isolated polyhydramnios at 30 weeks of gestation. Based on a history of a previous pregnancy affected with Bartter syndrome, indomethacin was initiated. Amniotic fluid volume and Ductus Arteriosus diameter were monitored. As evidence lacks on optimal dose and duration of indomethacin, multiple-dose adjustments were made to reduce the amniotic fluid volume while maintaining normal Ductus Arteriosus diameter. Progressive polyhydramnios led to Cesarean section at 34+ weeks of gestation resulting in a healthy fetus diagnosed with Bartter syndrome in the early neonatal period.

Conclusion

We share our experience in the adjustment of the dose and duration of Indomethacin therapy in the treatment of severe polyhydramnios associated with antenatal Bartter syndrome. Amniotic fluid index, Ductus Arteriosus diameter, and umbilical artery doppler work together as key indicators to guide the success and safety of the therapy.
Sentinel Lymph Node Mapping: Current Applications and Future Perspectives in Gynecology Malignant Tumors
Authors: Wang Tianyou , Xu Yan , Shao Wenyu , Wang Chao
Published: June 2022

The sentinel lymph nodes (SLNs) is a group of lymph nodes initially involved in the metastatic spread of cancer cells. SLN mapping refers to intraoperative localization and biopsy of SLNs with specific tracers to assess lymph node metastases. It is widely used in a variety of tumor surgeries for its high sensitivity and high negative predictive value. In the evaluation of the status of lymph node metastases in gynecological malignancies, it has received increasingly more attention due to its minor invasiveness, few complications, and high diagnosis rate. The National Comprehensive Cancer Network (NCCN) guidelines provide an excellent introduction to the indications and methods of SLN techniques in vulvar, cervical, and endometrial cancers, but they provide little explanation about some specific issues. In this review, we summarize different dyes and injection methods and discuss the indications of application and the clinical trials of SLN mapping in gynecological malignant tumors, aiming to provide a reference for the rational application of sentinel techniques in gynecology malignant tumors before relevant guidelines are updated.
Integrated Analysis of the Alterations in Gut Microbiota and Metabolites of Mice Induced After Long-Term Intervention With Different Antibiotics
Authors: Zhang Nan , Liu Jun , Chen Zhiyun , Chen Ning , Gu Fangyan , He Qiushui
Published: June 2022

Objectives

We aimed to study the effect of antibiotic-induced disruption of gut microbiome on host metabolomes and inflammatory responses after long-term use of antibiotics.

Methods

A total of three groups of 3-week-old female C57BL/6 mice (n = 44) were continuously treated with vancomycin (VAN), polymyxin B (PMB), or water, respectively, for up to 28 weeks. Fecal samples collected at different time points were analyzed by bacterial 16S rRNA gene sequencing and untargeted metabolomics by ultraperformance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS). Serum cytokines (IFN-γ, IL-2, IL-10, IL-13, IL-17A, and TNF-α) were determined by multiplex immunoassay.

Results

Treatment by VAN or PMB did not affect the average body weight of mice. However, a heavier caecum observed in VAN-treated mice. Compared with PMB-treated and control mice, VAN treatment induced more rapid dysbiosis of gut microbiota and dysmetabolism. Instead of Bacteroides, VAN-treated mice had a compositional shift to Proteobacteria and its species Escherichia coli and Verrucomicrobia and its species Akkermansia muciniphila. The shift was accompanied by decreased richness and diversity in microbiota. PMB-treated mice had an increased Firmicutes, and the diversity was shortly increased and further decreased to the baseline. Decreased levels of short-chain and long-chain fatty acids, bile acids, L-arginine, dopamine, L-tyrosine, and phosphatidylcholine (all p < 0.05) were observed in VAN-treated mice. In contrast, significantly increased levels of amino acids including L-aspartic acid, beta-alanine, 5-hydroxy-L-tryptophan, L-glutamic acid, and lysophosphatidylcholines (all p < 0.05) were found. These changes occurred after 3-week treatment and remained unchanged up to 28 weeks. For PMB-treated mice, metabolites involved in the metabolic pathway of vitamin B6 were decreased, whereas glycocholic acid and chenodeoxycholic acid were increased (all p < 0.05). After 8-week treatment, VAN-treated mice had significantly higher levels of serum IFN-γ, IL-13, and IL-17A, and PMB-treated mice had higher levels of IL-13 and IL-17 compared to control mice. At 28-week treatment, only IL-17A remained high in PMB-treated mice.

Conclusion

This study showed that the antibiotic-induced alterations in gut microbiota contribute to host inflammatory responses through the change in metabolic status, which are likely related to the type, rather than timing of antibiotic used.
Bacteriophage Cocktail Can Effectively Control Salmonella Biofilm in Poultry Housing
Authors: Korzeniowski Paweł , Śliwka Paulina , Kuczkowski Maciej , Mišić Dušan , Milcarz Agata , Kuźmińska-Bajor Marta
Published: June 2022

Salmonella enterica serovar Enteritidis (S. Enteritidis) is the major contaminant of poultry products, and its ability to form biofilms on produced food and poultry farm processing surfaces contributes to Salmonella transmission to humans. Bacteriophages have come under increasing interest for anti-Salmonella biofilm control. In this study, we used the three previously sequenced and described phages UPWr_S1, UPWr_S3, and UPWr_S4 and a phage cocktail, UPWr_S134, containing these three phages to degrade biofilms formed by two S. Enteritidis strains, 327 lux and ATCC 13076, in vitro. It was found that treatment with bacteriophages significantly reduced biofilm on a 96-well microplate (32–69%) and a stainless steel surface (52–98%) formed by S. Enteritidis 327 lux. The reduction of biofilm formed by S. Enteritidis ATCC 13076 in the 96-well microplate and on a stainless steel surface for bacteriophage treatment was in the range of 73–87% and 60–97%, respectively. Under laboratory conditions, an experimental model utilizing poultry drinkers artificially contaminated with S. Enteritidis 327 lux and treated with UPWr_S134 phage cocktail was applied. In in vitro trials, the phage cocktail significantly decreased the number of Salmonella on the surface of poultry drinkers. Moreover, the phage cocktail completely eradicated Salmonella from the abundant bacterial load on poultry drinkers in an experimentally infected chickens. Therefore, the UPWr_S134 phage cocktail is a promising candidate for Salmonella biocontrol at the farm level.
Dynamic Profile of S-Layer Proteins Controls Surface Properties of Emetic Bacillus cereus AH187 Strain
Authors: Boutonnet Cécile , Lyonnais Sébastien , Alpha-Bazin Beatrice , Armengaud Jean , Château Alice , Duport Catherine
Published: June 2022

Many prokaryotes are covered by a two-dimensional array of proteinaceous subunits. This surface layers (S-layer) is incompletely characterized for many microorganisms. Here, we studied Bacillus cereus AH187. A genome analysis identified two genes encoding the S-layer proteins SL2 and EA1, which we experimentally confirmed to encode the two protein components of the S-layer covering the surface of B. cereus. Shotgun proteomics analysis indicated that SL2 is the major component of the B. cereus S-layer at the beginning of exponential growth, whereas EA1 becomes more abundant than SL2 during later stages of stationary growth. Microscopy analysis revealed the spatial organization of SL2 and EA1 at the surface of B. cereus to depend on their temporal-dynamics during growth. Our results also show that a mutant strain lacking functional SL2 and EA1 proteins has distinct surface properties compared to its parental strain, in terms of stiffness and hydrophilicity during the stationary growth phase. Surface properties, self-aggregation capacity, and bacterial adhesion were observed to correlate. We conclude that the dynamics of SL2 and EA1 expression is a key determinant of the surface properties of B. cereus AH187, and that the S-layer could contribute to B. cereus survival in starvation conditions.
An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease
Authors: Roberts Reno , Wall Mark J. , Braren Ingke , Dhillon Karendeep , Evans Amy , Dunne Jack , Nyakupinda Simbarashe , Huckstepp Robert T. R.
Published: June 2022

Sleep apnoea is a highly prevalent disease that often goes undetected and is associated with poor clinical prognosis, especially as it exacerbates many different disease states. However, most animal models of sleep apnoea (e.g., intermittent hypoxia) have recently been dispelled as physiologically unrealistic and are often unduly severe. Owing to a lack of appropriate models, little is known about the causative link between sleep apnoea and its comorbidities. To overcome these problems, we have created a more realistic animal model of moderate sleep apnoea by reducing the excitability of the respiratory network. This has been achieved through controlled genetically mediated lesions of the preBötzinger complex (preBötC), the inspiratory oscillator. This novel model shows increases in sleep disordered breathing with alterations in breathing during wakefulness (decreased frequency and increased tidal volume) as observed clinically. The increase in dyspnoeic episodes leads to reduction in REM sleep, with all lost active sleep being spent in the awake state. The increase in hypoxic and hypercapnic insults induces both systemic and neural inflammation. Alterations in neurophysiology, an inhibition of hippocampal long-term potentiation (LTP), is reflected in deficits in both long- and short-term spatial memory. This improved model of moderate sleep apnoea may be the key to understanding why this disorder has such far-reaching and often fatal effects on end-organ function.
Brain Network Alterations in Rectal Cancer Survivors With Depression Tendency: Evaluation With Multimodal Magnetic Resonance Imaging
Authors: Zhang Wenwen , Zou Ying , Zhao Feng , Yang Yongqing , Mao Ning , Li Yuan , Huang Gang , Yao Zhijun , Hu Bin
Published: June 2022

Surgery and chemotherapy may increase depression tendency in patients with rectal cancer (RC). Nevertheless, few comprehensive studies are conducted on alterations of brain network induced by depression tendency in patients with RC. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data were collected from 42 patients with RC with surgery and chemotherapy and 38 healthy controls (HCs). Functional network (FN) was constructed from extracting average time courses in brain regions, and structural network (SN) was established by deterministic tractography. Graph theoretical analysis was used to calculate network properties. Networks resilient of two networks were assessed. Clinical correlation analysis was explored between altered network parameters and Hamilton depression scale (HAMD) score. This study revealed impaired FN and SN at both local and global levels and changed nodal efficiency and abnormal small-worldness property in patients with RC. On the whole, all FNs are more robust than SN. Moreover, compared with HC, patients with RC show less robustness in both networks. Regions with decreased nodal efficiency were associated with HAMD score. These cognitive dysfunctions are mainly attributable to depression-related brain functional and structural network alterations. Brain network reorganization is to prevent patients with RC from more serious depression after surgery and chemotherapy.