bluuebunny/crossref_metadata_2025 huggingface dataset:
Red meat consumption and risk for dyslipidaemia and inflammation: A systematic review and meta-analysis
Authors: Sun Le , Yuan Jia-Lin , Chen Qiu-Cen , Xiao Wen-Kang , Ma Gui-Ping , Liang Jia-Hua , Chen Xiao-Kun , Wang Song , Zhou Xiao-Xiong , Wu Hui , Hong Chuang-Xiong
Published: September 2022

Aim

The study (PROSPERO: CRD42021240905) aims to reveal the relationships among red meat, serum lipids and inflammatory biomarkers.

Methods and results

PubMed, EMBASE and the Cochrane databases were explored through December 2021 to identify 574 studies about red meat and serum lipids markers including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP) or hypersensitive-CRP (hs-CRP). Finally, 20 randomized controlled trials (RCTs) involving 1001 people were included, red meat and serum lipid markers and their relevant information was extracted. The pooled standard mean difference (SMD) was obtained by applying a random-effects model, and subgroup analyses and meta-regression were employed to explain the heterogeneity. Compared with white meat or grain diets, the gross results showed that the consumption of red meat increased serum lipid concentrations like TG (0.29 mmol/L, 95% CI 0.14, 0.44,P<0.001), but did not significantly influence the TC (0.13 mmol/L, 95% CI −0.07, 0.33, P = 0.21), LDL-C (0.11 mmol/L, 95% CI −0.23, 0.45, P = 0.53), HDL-C (−0.07 mmol/L, 95% CI −0.31, 0.17, P = 0.57),CRP or hs-CRP (0.13 mmol/L, 95% CI −0.10, 0.37,P = 0.273).

Conclusion

Our study provided evidence to the fact that red meat consumption affected serum lipids levels like TG, but almost had no effect on TC, LDL-C, HDL-C and CRP or hs-CRP. Such diets with red meat should be taken seriously to avoid the problem of high lipid profiles.

Systematic review registration

[https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42021240905].
Estimation of porosity and facies distribution through seismic inversion in an unconventional tight sandstone reservoir of Hangjinqi area, Ordos basin
Authors: Ashraf Umar , Anees Aqsa , Shi Wanzhong , Wang Ren , Ali Muhammad , Jiang Ren , Vo Thanh Hung , Iqbal Ibrar , Zhang Xiaonan , Zhang Hucai
Published: September 2022

Precision porosity and facies determinations are critical in reducing drilling uncertainty and increasing hydrocarbon recoveries from heterogeneous sources. The porosity and facies distribution of the Taiyuan-Shanxi Formations (T9c-T9d), and Shihezi-1 Formation (T9d-T9e) within the Hangjinqi area are uncertain and no studies have covered the spatial distribution on a regional scale. The heterogeneous nature of coal, mudstone, and sandstone makes it challenging to comprehend the distribution of porosity and lithofacies. Also, the seismic resolution is not able to resolve the reservoir heterogeneity. Therefore, we have employed regional 3D seismic and well logs by utilizing the advanced acoustic impedance inversion to accomplish our study. Results of petrophysical analysis conducted on the well J32 showed that Shihezi-1 and Shanxi-1 Formations have potential gas-saturated zones. Crossplot analysis distinguished the lowest impedance coal from the highest impedance tight sandstone facies. The outcomes of the constrained sparse spike inversion (CSSI) reliably distinguished the coal facies from the channel-tight sandstone facies. The tight sandstone facies showed the highest impedance values as compared to coal and mudstone facies on the absolute acoustic impedance section. Impedance and porosity maps of T9d and T9e suggested the presence of a maximum porosity (8%–12% for T9d, and 5%–10% for T9e), and maximum distribution of tight sandstone facies, while T9c shows the lowest porosity (0%–6%) and lowest impedance values due to the presence of coal facies. Thick braided fluvial channels are evident on the T9d impedance and porosity maps, making it the most favorable horizon to produce the maximum gas. Whereas, T9c shows the least distribution of sandstone facies making it the least favorable. We propose that the zones of maximum porosity on the T9c, T9d, and T9e horizons can be exploited for future gas explorations.
A comparative study on initial developments between explosive and nonexplosive cyclones off the East Asian coast in winter
Authors: Gao Xiaoyu , Lu Ping , Zhang Shuqin , Hu Yang , Fu Gang , Sun Xiaoyan , Zhang Qiuyang
Published: September 2022

Explosive cyclones (ECs) pose serious challenges for weather forecasting and significant threats to human life and property. In searching for the key points that make a cyclone go through explosive deepening off the East Asian coast, we present a comparative analysis of ECs and nonexplosive cyclones (or ordinary cyclones; OCs) using 10 years of ERA5 reanalysis data with high temporal and spatial resolutions. Their differences in synoptic backgrounds are shown, and mechanisms of the initial developments are compared quantitatively from the perspective of potential vorticity (PV). Among the identified 135 cyclones, 72 went through explosive growth and 37.5/36.1/20.8/5.6% of these ECs are ranked as weak/medium/strong/super ECs. ECs feature stronger low-level baroclinicity and higher PV than OCs. The decomposition of the local PV tendency shows the dominant role of the PV advection (with a correlation coefficient of 0.8). During the initial development, ECs have an average meridional temperature contrast 4 K larger than OCs within 20 latitudes at the low troposphere in the upstream, due to a stronger cold advection. The upstream colder air increases the horizontal temperature gradient and thus produces steeper isentropic surfaces inclining to the west. Since the PV intrusion is mainly along the isentropic surfaces, the increase in their slope significantly enhances the downward transport of PV from upper air. The importance of the horizontal gradient of potential temperature is further proved by numerical experiments with the Weather Research and Forecast (WRF) model on typical winter ECs. In sensitivity experiments, the low troposphere meridional temperature contrast decreasing by the average difference between ECs and OCs significantly decreases PV and stops the cyclones from explosive deepening. Despite the importance of diabatic processes in the deepening of mid-latitude cyclones emphasized by many studies, this study shows that the PV intrusion dominated by cold air mass is the key cause of winter explosive cyclogenesis in this region.
Fragmentation analyses of rocks under high-velocity impacts using the combined finite-discrete element simulation
Authors: Yang Tao , Ma Hui , Weng Lei , Liu Yang , Chu Zhaofei , Zhang Penglin , Jin Gang , Chang Weixue
Published: September 2022

The impact-induced fragmentation of rock blocks is frequently encountered when the natural hazards (e.g., rockfalls, rockslides, and rock avalanches) occur in mountainous areas. To address the progressive damage and cracking characteristics of rock upon impacting, this paper presents a three-dimensional finite-discrete method (3D-FDEM) study on the complex impact-induced fragmentation process of rock. The influences of the impact velocity on the dynamic fragmentation process, damage evolution, fragment characteristics, fragment flying velocity, and angle were systematically investigated. The parameters as input for simulation were first calibrated by the 3D uniaxial compression tests and rock-impact tests. Then, the complex fragmentation process of rock samples subjected to different impact velocities (i.e., 20–80 m/s) was simulated. The numerical results show that the number of cohesive elements following shear-dominated failures gradually increases with increasing the impact velocity. The fractal method can well describe the distribution of the equivalent fragment length, and the variations of the fractal dimension are consistent with that of the damage ratio, increasing with impact velocity. Both the average and maximum flying velocities of the fragments increase linearly with increasing impact velocity. However, the average flying angle of the fragments shows a sharp increase and then slight increase with increasing the impact velocity.
Least-squares reverse time migration based on the viscoacoustic VTI pure qP-wave equation
Authors: Zhang Shanshan , Gu Bingluo , Li Zhenchun
Published: September 2022

With the deepening of oil and gas exploration and the increasing complexity of exploration targets, the influence of anisotropy and anelasticity of subsurface media on seismic imaging cannot be ignored. The least-squares reverse time migration is developed on the idea of linear inversion, which can effectively solve the amplitude imbalance, low resolution, and serious imaging noise problems of RTM. In this paper, based on the viscoacoustic pure qP-wave equation, the corresponding demigration operator, adjoint operator, and gradient-sensitive kernel are derived, and the least-square reverse time migration imaging algorithm of viscoacoustic pure qP-wave in VTI medium is proposed. During iterative inversion, the inverse of Hessian is approximately solved to achieve stable attenuation compensation. Finally, we verify the effectiveness and applicability of the proposed viscoacoustic VTI least-squares reverse time migration imaging algorithm through the model tests and field data. The numerical results show that the method can compensate for the amplitude loss and phase distortion caused by attenuation, and correct the anisotropy-induced misalignment of the reflection interfaces, which improves the accuracy and resolution of the imaging profile.
Analysis of thyroid involvement in children and adult Langerhans cell histiocytosis: An underestimated endocrine manifestation
Authors: Li Yuanmeng , Chang Long , Chai Xiaofeng , Liu He , Yang Hongbo , Xia Yu , Huo Li , Zhang Hui , Li Naishi , Lian Xiaolan
Published: September 2022

Background

Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal expansion of CD1a+/CD207+ LCH cells. The thyroid involvement in LCH has mostly been described in case reports.

Methods

We retrospectively evaluated the clinical characteristics, diagnosis, and treatment of 27 children and adult patients with thyroid LCH in our center between 2010 and 2021.

Results

The incidence of thyroid LCH was 14.00% (7/50) in children and 10.10% (20/198) in adults, respectively. Among patients with thyroid involvement, 81.5% presented with diabetes insipidus (DI) as the first symptom, and 51.9% complained of neck swelling or mass. Children and adults with thyroid LCH had higher frequencies of the hypothalamic-pituitary axis (HPA) (children: 100% vs. 62.8%, P=0.05; adult: 95% vs. 42.1%, P<0.001), the lung (children: 85.7% vs. 25.6%, P=0.004; adult: 70% vs. 50.6%, P=0.099), and a lower frequency of bone (children: 14.3% vs. 55.8%, P=0.049; adult: 45% vs. 73.6%, P=0.008) involvement than patients without thyroid involvement. Patients with thyroid LCH had a higher frequency of primary hypothyroidism and a lower frequency of euthyroidism than patients without it. The two major types of ultrasound imaging were diffuse (55%) and nodular type (45%). The standardized uptake value of thyroid on 18-F-fluorodeoxyglucose positron emission tomography/computed tomography was 5.3–12.8. The diagnoses were confirmed using thyroid aspiration (54.5%) or surgery (45.5%). In addition, thyroid LCH combined with papillary thyroid carcinoma was not rare (2/27).

Conclusion

Thyroid involvement in LCH is not rare. Furthermore, identifying thyroid involvement can facilitate the pathological diagnosis of LCH. Therefore, the possibility of thyroid LCH should be fully investigated in patients with DI, primary hypothyroidism, abnormal thyroid ultrasound results, and multi-system disease. In addition, thyroid aspiration can confirm suspected thyroid LCH. Finally, special attention should be paid to evaluating HPA and pulmonary involvement in thyroid LCH.
Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
Authors: Ferré Sergi , Belcher Annabelle M. , Bonaventura Jordi , Quiroz César , Sánchez-Soto Marta , Casadó-Anguera Verònica , Cai Ning-Sheng , Moreno Estefanía , Boateng Comfort A. , Keck Thomas M. , Florán Benjamín , Earley Christopher J. , Ciruela Francisco , Casadó Vicent , Rubinstein Marcelo , Volkow Nora D.
Published: September 2022

The functional and pharmacological significance of the dopamine D4 receptor (D4R) has remained the least well understood of all the dopamine receptor subtypes. Even more enigmatic has been the role of the very prevalent human DRD4 gene polymorphisms in the region that encodes the third intracellular loop of the receptor. The most common polymorphisms encode a D4R with 4 or 7 repeats of a proline-rich sequence of 16 amino acids (D4.4R and D4.7R). DRD4 polymorphisms have been associated with individual differences linked to impulse control-related neuropsychiatric disorders, with the most consistent associations established between the gene encoding D4.7R and attention-deficit hyperactivity disorder (ADHD) and substance use disorders. The function of D4R and its polymorphic variants is being revealed by addressing the role of receptor heteromerization and the relatively avidity of norepinephrine for D4R. We review the evidence conveying a significant and differential role of D4.4R and D4.7R in the dopaminergic and noradrenergic modulation of the frontal cortico-striatal pyramidal neuron, with implications for the moderation of constructs of impulsivity as personality traits. This differential role depends on their ability to confer different properties to adrenergic α2A receptor (α2AR)-D4R heteromers and dopamine D2 receptor (D2R)-D4R heteromers, preferentially localized in the perisomatic region of the frontal cortical pyramidal neuron and its striatal terminals, respectively. We also review the evidence to support the D4R as a therapeutic target for ADHD and other impulse-control disorders, as well as for restless legs syndrome.
Concentration and inorganic elemental analysis of particulate matter in a road tunnel environment (Žilina, Slovakia): Contribution of non-exhaust sources
Authors: Jandacka Dusan , Durcanska Daniela , Cibula Robert
Published: September 2022

Particulate matter (PM) is present in the surrounding air. The tunnel environment is no exception, where the PM source is road traffic. In a broader sense, the tunnel can be described as a separate point source of air pollution from which PM pollutants spread to the portal parts and the external environment. PM originates from the exhaust and non-exhaust processes of road traffic (brake wear, tire wear, road surface wear, and road dust re-suspension). This study deals with the specification of non-exhaust PM emissions in a tunnel environment where the primary source is road traffic. PM measurements took place in the “Považský Chlmec” highway tunnel with a length of 2,118 m directly in the tunnel tube and near the tunnel portal. PM measurements were performed using gravimetric and optical methods. PM chemical analyses were performed using energy-dispersive X-ray fluorescence (EDXRF). The concentration of PM in the tunnel was on average: PM10 = 30.76 μg/m3 and PM2.5 = 15.66 μg/m3 and near the tunnel portal PM10 = 14.38 μg/m3 and PM2.5 = 8.74 μg/m3. The average traffic volume in the tunnel tube was 2,274 veh/24 h. Using EDXRF, the main chemical elements Al, Br, Ca, Cl, Cr, Cu, Fe, K, Mg, Mn, Na, P, Si, S, Ti, and Zn were identified in the PM. Chemical element concentrations in PM10 and PM2.5 were subjected to factor analysis (FA) and principal component analysis (PCA) to determine the origin of PM. Two sources were identified for PM10 and three for PM2.5. Absolute principal component scores (APCS) in conjunction with multiple regression analysis (MRA) were used to determine the source contribution to the production of PM10 and PM2.5.
Morphometric analysis of forewing venation does not consistently differentiate the leafhopper tribes Typhlocybini and Zyginellini
Authors: Wen Hui , Zhou Xian , Dietrich Christopher H. , Huang Min
Published: September 2022

Tribes of the leafhopper subfamily Typhlocybinae have traditionally been defined based on differences in hind wing venation, but the forewing venation also differs among some tribes. Here we used geometric morphometric analysis to determine whether previously recognized tribes can be distinguished based on the configuration of forewing veins. Focusing on the apical area of the male right forewing, 76 semi-landmarks in six curves corresponding to individual wing veins were measured for representatives of four previously recognized tribes and the data were analyzed using principal component analysis (PCA), canonical variable analysis (CVA), and UPGMA clustering analysis. The study showed that differences in the apical area of the forewing mainly occur in RP, MP′, and MP″ + CuA′. PCA, CVA, and cluster analysis showed three distinct clusters representing tribes Empoascini, Erythroneurini, and Typhlocybini (sensu lato) but failed to distinguish Typhlocybini (sensu stricto) from Zyginellini, which has been considered as either separate tribe or a synonym of Typhlocybini by recent authors. The results show that the forewing venation differs among tribes of Typhlocybinae, but also agree with recent molecular phylogenetic analyses, indicating that Zyginellini is derived from within Typhlocybini.
Advances and challenges of immunocheckpoint inhibitors in the treatment of primary liver cancer
Authors: Hu Meng , Yao Weirong , Shen Qinglin
Published: September 2022

Primary liver cancer (PLC) is one of the most common malignant tumors, which clinically characterized by occult onset, rapid development, easy recurrence and poor prognosis. With the rapid development of tumor immunotherapy research, tumor immunotherapy has also achieved remarkable clinical efficacy, and jointly promoted the overall improvement of tumor immunology from mechanism research to clinical transformation, from single discipline to multi-disciplinary integration. Immunotherapy has obvious advantages in treatment-related toxicity and efficacy compared with traditional therapy. In hepatocellular carcinoma (HCC), immunotherapy alone or in combination with other therapies may help to control tumor progression, and there are many immune checkpoint inhibitors (ICIs) widely used in clinical or ongoing clinical trials. However, tumor immunology research is still facing many challenges. How to effectively evaluate the efficacy, whether there are related biomarkers, the generation of immune tolerance and the lack of clinical trials to objectively evaluate the efficacy are still urgent problems to be solved, but it also brings new research opportunities for basic and clinical immunology researchers. The study of treatment of ICIs of PLC has become a hot spot in clinical research field. This paper summarizes and prospects the research progress and challenges of ICIs for PLC.
Low expression of the metabolism-related gene SLC25A21 predicts unfavourable prognosis in patients with acute myeloid leukaemia
Authors: Wang Wenjun , Liang Qian , Zhao Jingyu , Pan Hong , Gao Zhen , Fang Liwei , Zhou Yuan , Shi Jun
Published: September 2022

Acute myeloid leukaemia (AML) is a heterogeneous disease associated with poor outcomes. To identify AML-specific genes with prognostic value, we analysed transcriptome and clinical information from The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) datasets, and Genotype-Tissue Expression (GTEx) project. The metabolism-related gene, SLC25A21 was found to be significantly downregulated in AML, and was associated with high white blood cell (WBC) counts, high pretrial blood (PB) and bone marrow (BM) blast abundance, FLT3 mutation, NPM1 mutation, and death events (all p value <0.05). We validated the expression of SLC25A21 in our clinical cohort, and found that SLC25A21 was downregulated in AML. Moreover, we identified low expression of SLC25A21 as an independent prognostic factor by univariate Cox regression (hazard ratio [HR]: 0.550; 95% Confidence interval [CI]: 0.358–0.845; p value = 0.006) and multivariate Cox regression analysis (HR: 0.341; 95% CI: 0.209–0.557; p value <0.05). A survival prediction nomogram was established with a C-index of 0.735, which indicated reliable prognostic prediction. Subsequently, based on the median SLC25A21 expression level, patients in the TCGA-LAML cohort were divided into low- and high-expression groups. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs highlighted growth factor binding, extracellular structure organization, cytokine‒cytokine receptor interaction, etc. The results of gene set enrichment analysis (GSEA) indicated that the epithelial-mesenchymal transition, KRAS signalling, oxidative phosphorylation, and reactive oxygen species pathways were enriched. Through gene coexpression and protein‒protein interaction (PPI) network analysis, we identified two hub genes, EGFR and COL1A2, which were linked to worse clinical outcomes. Furthermore, we found that lower SLC25A21 expression was closely associated with a significant reduction in the levels of infiltrating immune cells, which might be associated with immune escape of AML cells. A similar trend was observed for the expression of checkpoint genes (CTLA4, LAG3, TIGIT, and HAVCR2). Finally, drug sensitivity testing suggested that the low-expression SLC25A21 group is sensitive to doxorubicin, mitomycin C, linifanib but resistant to JQ1, belinostat, and dasatinib. Hence, our study demonstrated that a low expression level of SLC25A21 predicts an unfavourable prognosis in patients with AML.
Identification of a novel m5C/m6A-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma
Authors: Ma Yiming , Yang Jun , Ji Tiantai , Wen Fengyun
Published: September 2022

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer (NSCLC) and is associated with high mortality rates. However, effective methods to guide clinical therapeutic strategies for LUAD are still lacking. The goals of this study were to analyze the relationship between an m5C/m6A-related signature and LUAD and construct a novel model for evaluating prognosis and predicting drug resistance and immunotherapy efficacy. We obtained data from LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Based on the differentially expressed m5C/m6A-related genes, we identified distinct m5C/m6A-related modification subtypes in LUAD by unsupervised clustering and compared the differences in functions and pathways between different clusters. In addition, a risk model was constructed using multivariate Cox regression analysis based on prognostic m5C/m6A-related genes to predict prognosis and immunotherapy response. We showed the landscape of 36 m5C/m6A regulators in TCGA-LUAD samples and identified 29 differentially expressed m5C/m6A regulators between the normal and LUAD groups. Two m5C/m6A-related subtypes were identified in 29 genes. Compared to cluster 2, cluster 1 had lower m5C/m6A regulator expression, higher OS (overall survival), higher immune activity, and an abundance of infiltrating immune cells. Four m5C/m6A-related gene signatures consisting of HNRNPA2B1, IGF2BP2, NSUN4, and ALYREF were used to construct a prognostic risk model, and the high-risk group had a worse prognosis, higher immune checkpoint expression, and tumor mutational burden (TMB). In patients treated with immunotherapy, samples with high-risk scores had higher expression of immune checkpoint genes and better immunotherapeutic efficacy than those with low-risk scores. We concluded that the m5C/m6A regulator-related risk model could serve as an effective prognostic biomarker and predict the therapeutic sensitivity of chemotherapy and immunotherapy.
Identification of CD161 expression as a novel prognostic biomarker in breast cancer correlated with immune infiltration
Authors: Weng Miaomiao , Xie Hui , Zheng Mingjie , Hou Xinwen , Wang Shui , Huang Yue
Published: September 2022

Background:CD161 has been identified as a prognostic biomarker in many neoplasms, but its role in breast cancer (BC) has not been fully explained. We aimed to investigate the molecular mechanism and prognostic value of CD161 in BC.

Methods:CD161 expression profile was extracted from TIMER, Oncomine, UALCAN databases, and verified by the Gene Expression Omnibus (GEO) database and quantitative real-time polymerase chain reaction (qRT-PCR). The prognostic value of CD161 was assessed via GEPIA, Kaplan–Meier plotter and PrognoScan databases. The Cox regression and nomogram analyses were conducted to further validate the association between CD161 expression and survival. Gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, and KEGG pathway enrichment analysis were performed to probe the tumor-associated annotations of CD161. CIBERSORT and ssGSEA were employed to investigate the correlation between CD161 expression and immune cell infiltration in BC, and the result was verified by TIMER and TISIDB.

Results: Multiple BC cohorts showed that CD161 expression was decreased in BC, and a high CD161 expression was associated with a preferable prognosis. Therefore, we identified the combined model including CD161, age and PR status to predict the survival (C index = 0.78) of BC patients. Functional enrichment analysis indicated that CD161 and its co-expressed genes were closely related to several cancerous and immune signaling pathways, suggesting its involvement in immune response during cancer development. Moreover, immune infiltration analysis revealed that CD161 expression was correlated with immune infiltration.

Conclusion: Collectively, our findings revealed that CD161 may serve as a potential biomarker for favorable prognosis and a promising immune therapeutic target in BC.
Impact of adjuvant: Trivalent vaccine with quadrivalent-like protection against heterologous Yamagata-lineage influenza B virus
Authors: Myers Mallory L. , Gallagher John R. , Woolfork De’Marcus D. , Stradtmann-Carvalho Regan K. , Maldonado-Puga Samantha , Bock Kevin W. , Boyoglu-Barnum Seyhan , Syeda Hubza , Creanga Adrian , Alves Derron A. , Kanekiyo Masaru , Harris Audray K.
Published: September 2022

As new vaccine technologies and platforms, such as nanoparticles and novel adjuvants, are developed to aid in the establishment of a universal influenza vaccine, studying traditional influenza split/subunit vaccines should not be overlooked. Commercially available vaccines are typically studied in terms of influenza A H1 and H3 viruses but influenza B viruses need to be examined as well. Thus, there is a need to both understand the limitations of split/subunit vaccines and develop strategies to overcome those limitations, particularly their ability to elicit cross-reactive antibodies to the co-circulating Victoria (B-V) and Yamagata (B-Y) lineages of human influenza B viruses. In this study, we compared three commercial influenza hemagglutinin (HA) split/subunit vaccines, one quadrivalent (H1, H3, B-V, B-Y HAs) and two trivalent (H1, H3, B-V HAs), to characterize potential differences in their antibody responses and protection against a B-Y challenge. We found that the trivalent adjuvanted vaccine Fluad, formulated without B-Y HA, was able to produce antibodies to B-Y (cross-lineage) on a similar level to those elicited from a quadrivalent vaccine (Flucelvax) containing both B-V and B-Y HAs. Interestingly, Fluad protected mice from a lethal cross-lineage B-Y viral challenge, while another trivalent vaccine, Fluzone HD, failed to elicit antibodies or full protection following challenge. Fluad immunization also diminished viral burden in the lungs compared to Fluzone and saline groups. The success of a trivalent vaccine to provide protection from a cross-lineage influenza B challenge, similar to a quadrivalent vaccine, suggests that further analysis of different split/subunit vaccine formulations could identify mechanisms for vaccines to target antigenically different viruses. Understanding how to increase the breadth of the immune response following immunization will be needed for universal influenza vaccine development.
The OSE complotype and its clinical potential
Authors: Alic Lejla , Binder Christoph J. , Papac-Milicevic Nikolina
Published: September 2022

Cellular death, aging, and tissue damage trigger inflammation that leads to enzymatic and non-enzymatic lipid peroxidation of polyunsaturated fatty acids present on cellular membranes and lipoproteins. This results in the generation of highly reactive degradation products, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), that covalently modify free amino groups of proteins and lipids in their vicinity. These newly generated neoepitopes represent a unique set of damage-associated molecular patterns (DAMPs) associated with oxidative stress termed oxidation-specific epitopes (OSEs). OSEs are enriched on oxidized lipoproteins, microvesicles, and dying cells, and can trigger sterile inflammation. Therefore, prompt recognition and removal of OSEs is required to maintain the homeostatic balance. This is partially achieved by various humoral components of the innate immune system, such as natural IgM antibodies, pentraxins and complement components that not only bind OSEs but in some cases modulate their pro-inflammatory potential. Natural IgM antibodies are potent complement activators, and 30% of them recognize OSEs such as oxidized phosphocholine (OxPC-), 4-HNE-, and MDA-epitopes. Furthermore, OxPC-epitopes can bind the complement-activating pentraxin C-reactive protein, while MDA-epitopes are bound by C1q, C3a, complement factor H (CFH), and complement factor H-related proteins 1, 3, 5 (FHR-1, FHR-3, FHR-5). In addition, CFH and FHR-3 are recruited to 2-(ω-carboxyethyl)pyrrole (CEP), and full-length CFH also possesses the ability to attenuate 4-HNE-induced oxidative stress. Consequently, alterations in the innate humoral defense against OSEs predispose to the development of diseases associated with oxidative stress, as shown for the prototypical OSE, MDA-epitopes. In this mini-review, we focus on the mechanisms of the accumulation of OSEs, the pathophysiological consequences, and the interactions between different OSEs and complement components. Additionally, we will discuss the clinical potential of genetic variants in OSE-recognizing complement proteins – the OSE complotype - in the risk estimation of diseases associated with oxidative stress.
Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages
Authors: Royzman Dmytro , Peckert-Maier Katrin , Stich Lena , König Christina , Wild Andreas B. , Tauchi Miyuki , Ostalecki Christian , Kiesewetter Franklin , Seyferth Stefan , Lee Geoffrey , Eming Sabine A. , Fuchs Maximilian , Kunz Meik , Stürmer Ewa K. , Peters Eva M. J. , Berking Carola , Zinser Elisabeth , Steinkasserer Alexander
Published: September 2022

To facilitate the recovery process of chronic and hard-to-heal wounds novel pro-resolving treatment options are urgently needed. We investigated the pro-regenerative properties of soluble CD83 (sCD83) on cutaneous wound healing, where sCD83 accelerated wound healing not only after systemic but also after topical application, which is of high therapeutic interest. Cytokine profile analyses revealed an initial upregulation of inflammatory mediators such as TNFα and IL-1β, followed by a switch towards pro-resolving factors, including YM-1 and IL-10, both expressed by tissue repair macrophages. These cells are known to mediate resolution of inflammation and stimulate wound healing processes by secretion of growth factors such as epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), which promote vascularization as well as fibroblast and keratinocyte differentiation. In conclusion, we have found strong wound healing capacities of sCD83 beyond the previously described role in transplantation and autoimmunity. This makes sCD83 a promising candidate for the treatment of chronic- and hard-to-heal wounds.
Sustained Infiltration of Neutrophils Into the CNS Results in Increased Demyelination in a Viral-Induced Model of Multiple Sclerosis
Authors: Skinner Dominic D. , Syage Amber R. , Olivarria Gema M. , Stone Colleen , Hoglin Bailey , Lane Thomas E.
Published: September 2022

Intracranial inoculation of the neuroadapted JHM strain of mouse hepatitis virus (JHMV) into susceptible strains of mice results in acute encephalomyelitis followed by a cimmune-mediated demyelination similar to the human demyelinating disease multiple sclerosis (MS). JHMV infection of transgenic mice in which expression of the neutrophil chemoattractant chemokine CXCL1 is under the control of a tetracycline-inducible promoter active within GFAP-positive cells results in sustained neutrophil infiltration in the central nervous system (CNS) that correlates with an increase in spinal cord demyelination. We used single cell RNA sequencing (scRNAseq) and flow cytometry to characterize molecular and cellular changes within the CNS associated with increased demyelination in transgenic mice compared to control animals. These approaches revealed the presence of activated neutrophils as determined by expression of mRNA transcripts associated with neutrophil effector functions, includingCD63,MMP9,S100a8, S100a9, andASPRV1, as well as altered neutrophil morphology and protein expression. Collectively, these findings reveal insight into changes in the profile of neutrophils associated with increased white matter damage in mice persistently infected with a neurotropic coronavirus.
Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial
Authors: Tang Xiaofeng , Deng Biaolong , Zang Aiping , He Xiaowen , Zhou Ye , Wang Daimeng , Li Dan , Dai Xueyu , Chen Jieqiong , Zhang Xuhua , Liu Ye , Xu Yonghua , Chen Jingjing , Zheng Weijie , Zhang Luding , Gao Constance , Yang Huanfeng , Li Bin , Wang Xueqi
Published: September 2022

Background

Aging is usually accompanied by functional declines of the immune system, especially in T-cell responses. However, little is known about ways to alleviate this.

Methods

Here, 37 middle-aged healthy participants were recruited, among which 32 were intravenously administrated with expanded NK cells and 5 with normal saline. Then, we monitored changes of peripheral senescent and exhausted T cells within 4 weeks after infusion by flow cytometry, as well as serum levels of senescence-associated secretory phenotype (SASP)-related factors. In vitro co-culture assays were performed to study NK-mediated cytotoxic activity against senescent or exhausted T cells. Functional and phenotypic alteration of NK cells before and after expansion was finally characterized.

Results

After NK cell infusion, senescent CD28-, CD57+, CD28-CD57+, and CD28-KLRG1+ CD4+ and CD8+ T-cell populations decreased significantly, so did PD-1+ and TIM-3+ T cells. These changes were continuously observed for 4 weeks. Nevertheless, no significant changes were observed in the normal saline group. Moreover, SASP-related factors including IL-6, IL-8, IL-1α, IL-17, MIP-1α, MIP-1β, and MMP1 were significantly decreased after NK cell infusion. Further co-culture assays showed that expanded NK cells specifically and dramatically eliminated senescent CD4+ T cells other than CD28+CD4+ T cells. They also showed improved cytotoxic activity, with different expression patterns of activating and inhibitory receptors including NKG2C, NKG2A, KLRG1, LAG3, CD57, and TIM3.

Conclusion

Our findings imply that T-cell senescence and exhaustion is a reversible process in healthy individuals, and autologous NK cell administration can be introduced to alleviate the aging.

Clinical Trial Registration

ClinicalTrials.gov, ChiCTR-OOh-17011878.
Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis
Authors: Zeng Liuting , Deng Ying , Yang Kailin , Chen Junpeng , He Qi , Chen Hua
Published: September 2022

Objective

To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases.

Methods

Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis.

Results

Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn’s disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn’s disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups.

Conclusion

Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.
The causal relationship between neuromyelitis optica spectrum disorder and other autoimmune diseases
Authors: Wang Xiaofei , Shi Ziyan , Zhao Zhengyang , Chen Hongxi , Lang Yanlin , Kong Lingyao , Lin Xue , Du Qin , Wang Jiancheng , Zhou Hongyu
Published: September 2022

Objectives

The coexistence of neuromyelitis optica spectrum disorder (NMOSD) with other autoimmune diseases has been well recognized. However, the causal association between these two conditions has not been fully studied. The etiology and therapies of NMOSD coexisting with autoimmune diseases also need to be elucidated.

Methods

We performed two-sample Mendelian randomization (MR) analysis to examine the causality. Genome-wide association (GWAS) summary data from NMOSD, autoimmune thyroid disease (AITD), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SS) were used to identify genetic instruments. Causal single-nucleotide polymorphisms (SNPs) were annotated and searched for cis-expression quantitative trait loci (cis-eQTL) data. Pathway enrichment analysis was performed to identify the mechanism of NMOSD coexisting with AITD, SLE, and SS. Potential therapeutic chemicals were searched using the Comparative Toxicogenomics Database.

Results

The MR analysis found that AITD, SLE, and SS were causally associated with NMOSD susceptibility, but not vice versa. Gene Ontology (GO) enrichment analysis revealed that MHC class I-related biological processes and the interferon-gamma-mediated signaling pathway may be involved in the pathogenesis of NMOSD coexisting with AITD, SLE, and SS. A total of 30 chemicals were found which could inhibit the biological function of cis-eQTL genes.

Conclusions

Our findings could help better understand the etiology of NMOSD and provide potential therapeutic targets for patients with coexisting conditions.
Bio-products from Serratia marcescens isolated from Ghanaian Anopheles gambiae reduce Plasmodium falciparum burden in vector mosquitoes
Authors: Akorli Esinam Abla , Ubiaru Prince Chigozirim , Pradhan Sabyasachi , Akorli Jewelna , Ranford-Cartwright Lisa
Published: September 2022

Novel ideas for control of mosquito-borne disease include the use of bacterial symbionts to reduce transmission. Bacteria belonging to the family Enterobacteriaceae isolated from mosquito midgut have shown promise in limiting Plasmodium intensity in the Anopheles vector. However, the mechanism of interaction between bacteria and parasite remains unclear. This study aimed at screening bio-products of two bacteria candidates for their anti-Plasmodial effects on mosquito stages of P. falciparum. Enterobacter cloacae and Serratia marcescens were isolated from field-caught Anopheles gambiae s.l. Spent media from liquid cultures of these bacteria were filtered, lyophilized and dissolved in sterile phosphate buffered saline (PBS). The re-dissolved bacterial products were added to gametocytaemic blood meals and fed to An. gambiae mosquitoes via membrane feeders. Control groups were fed on infected blood with or without lyophilized LB medium. The effect of the products on the infection prevalence and intensity of P. falciparum in mosquitoes was assessed by dissecting mosquito midguts and counting oocysts 10-11 days post-infection. S. marcescens bio-products elicited significant reduction in the number of mosquitoes infected (P=4.02 x10-5) with P. falciparum and the oocyst intensity (P<2 x 10-16) than E. cloacae products (P>0.05 for both prevalence and intensity) compared to the control (lyophilized LB medium). These data support the use of bioproducts released by S. marcescens for malaria control based on transmission blocking in the vector.
Characterization of the “gut microbiota-immunity axis” and microbial lipid metabolites in atrophic and potential celiac disease
Authors: Ricci Federica , Russo Edda , Renzi Daniela , Baldi Simone , Nannini Giulia , Lami Gabriele , Menicatti Marta , Pallecchi Marco , Bartolucci Gianluca , Niccolai Elena , Cerboneschi Matteo , Smeazzetto Serena , Ramazzotti Matteo , Amedei Amedeo , Calabrò Antonino Salvatore
Published: September 2022

Introduction

Potential celiac disease (pCD) is characterized by genetic predisposition, positive anti-endomysial and anti-tissue transglutaminase antibodies, but a normal or almost normal jejunal mucosa (e.g., minor histological abnormalities without villous atrophy). To gain further insights into basic mechanisms involved in the development of intestinal villous atrophy, we evaluated and compared the microbial, lipid, and immunological signatures of pCD and atrophic CD (aCD).

Materials and methods

This study included 17 aCD patients, 10 pCD patients, and 12 healthy controls (HC). Serum samples from all participants were collected to analyze free fatty acids (FFAs). Duodenal mucosa samples of aCD and pCD patients were taken to evaluate histology, tissue microbiota composition, and mucosal immune response.

Results

We found no significant differences in the mucosa-associated microbiota composition of pCD and aCD patients. On the other hand, in pCD patients, the overall abundance of serum FFAs showed relevant and significant differences in comparison with aCD patients and HC. In detail, compared to HC, pCD patients displayed higher levels of propionic, butyric, valeric, 2-ethylhexanoic, tetradecanoic, hexadecanoic, and octadecanoic acids. Instead, aCD patients showed increased levels of propionic, isohexanoic, and 2-ethylhexanoic acids, and a lower abundance of isovaleric and 2-methylbutyricacids when compared to HC. In addition, compared to aCD patients, pCD patients showed a higher abundance of isobutyric and octadecanoic acid. Finally, the immunological analysis of duodenal biopsy revealed a lower percentage of CD4+ T lymphocytes in pCD infiltrate compared to that observed in aCD patients. The functional characterization of T cells documented a pro-inflammatory immune response in both aCD and pCD patients, but the pCD patients showed a higher percentage of Th0/Th17 and a lower percentage of Th1/Th17.

Conclusion

The results of the present study show, for the first time, that the duodenal microbiota of patients with pCD does not differ substantially from that of aCD; however, serum FFAs and local T cells displayed a distinctive profile between pCD, aCD, and HC. In conclusion, our result may help to shed new light on the “gut microbiota-immunity axis,” lipid metabolites, and duodenal immune response in overt CD and pCD patients, opening new paradigms in understanding the pathogenesis behind CD progression.
The effects of Clostridium butyricum on Ira rabbit growth performance, cecal microbiota and plasma metabolome
Authors: Ye Xiao Xing , Li Ke Yao , Li Ya Fei , Lu Jia Ning , Guo Ping Ting , Liu Hao Yu , Zhou Li Wen , Xue Shuai Shuai , Huang Cai Yun , Fang Shao Ming , Gan Qian Fu
Published: September 2022

Clostridium butyricum (C. butyricum) can provide many benefits for animals’ growth performance and gut health. In this study, we investigated the effects of C. butyricum on the growth performance, cecal microbiota, and plasma metabolome in Ira rabbits. A total of 216 Ira rabbits at 32 days of age were randomly assigned to four treatments supplemented with basal diets containing 0 (CG), 200 (LC), 400 (MC), and 600 mg/kg (HC) C. butyricum for 35 days, respectively. In comparison with the CG group, C. butyricum supplementation significantly improved the average daily gain (ADG) and feed conversion rate (FCR) at 53 and 67 days of age (P < 0.05) and digestibilities of crude protein (CP) and crude fiber (CF) at 67 days of age (P < 0.05). The cellulase activity in the HC group was higher respectively by 50.14 and 90.13% at 53 and 67 days of age, than those in the CG groups (P < 0.05). Moreover, at 67 days of age, the diet supplemented with C. butyricum significantly increased the relative abundance of Verrucomicrobia at the phylum level (P < 0.05). Meanwhile, the concentrations of different metabolites, such as amino acids and purine, were significantly altered by C. butyricum (P < 0.05). In addition, 10 different genera were highly correlated with 52 different metabolites at 53-day-old and 6 different genera were highly correlated with 18 different metabolites at 67-day-old Ira rabbits. These findings indicated that the C. butyricum supplementation could significantly improve the growth performance by modifying the cecal microbiota structure and plasma metabolome of weaned Ira rabbits.
The impact of single-cell genomics on the field of mycobacterial infection
Authors: Geraldes Inês , Fernandes Mónica , Fraga Alexandra G. , Osório Nuno S.
Published: September 2022

Genome sequencing projects of humans and other organisms reinforced that the complexity of biological systems is largely attributed to the tight regulation of gene expression at the epigenome and RNA levels. As a consequence, plenty of technological developments arose to increase the sequencing resolution to the cell dimension creating the single-cell genomics research field. Single-cell RNA sequencing (scRNA-seq) is leading the advances in this topic and comprises a vast array of different methodologies. scRNA-seq and its variants are more and more used in life science and biomedical research since they provide unbiased transcriptomic sequencing of large populations of individual cells. These methods go beyond the previous “bulk” methodologies and sculpt the biological understanding of cellular heterogeneity and dynamic transcriptomic states of cellular populations in immunology, oncology, and developmental biology fields. Despite the large burden caused by mycobacterial infections, advances in this field obtained via single-cell genomics had been comparatively modest. Nonetheless, seminal research publications using single-cell transcriptomics to study host cells infected by mycobacteria have become recently available. Here, we review these works summarizing the most impactful findings and emphasizing the different and recent single-cell methodologies used, potential issues, and problems. In addition, we aim at providing insights into current research gaps and potential future developments related to the use of single-cell genomics to study mycobacterial infection.