bluuebunny/crossref_metadata_2025 huggingface dataset:
The “mid”-Cretaceous (Lower Cenomanian) Continental Vertebrates of Gara Samani, Algeria. Sedimentological Framework and Palaeodiversity
Authors: Benyoucef Madani , Pérez-García Adán , Bendella Mohamed , Ortega Francisco , Vullo Romain , Bouchemla Imad , Ferré Bruno
Published: July 2022

Excellent outcrops of the upper part of the “Continental Intercalaire” deposits occur in the Gara Samani area, southern Algeria. These strata are recognised herein as belonging to the Gara Samani Formation, which is composed of the Samani Vertebrate-rich Sand Member, the Samani Sandstone Member and the Méguidène Stratified Sand Member. The first two members are from a fluvial system and the last member corresponds to an aeolian (dune and interdune) system. They have preserved one of the most diverse continental vertebrate faunas of latest Albian–early Cenomanian age yet known from northern Africa. Most of the taxa identified there, cited for the first time for the “mid”-Cretaceous of Algeria, have not been analysed in detail so far; and many of them have never been figured. The faunal list of vertebrates from this locality was supplemented thanks to detailed analysis of new and relatively abundant finds. As a consequence, the Gara Samani vertebrate assemblage is recognised as composed of elasmobranchs (two Hybodontiformes, i.e., Tribodus sp. and Distobatidae indet.; and a Batoidea, Onchopristis numida), actinopterygians (Bawitius sp., Adrianaichthys sp., Obaichthys africanus, and Calamopleurus africanus), sarcopterygians (Mawsoniidae indet. and the Dipnoi, cf. Lavocatodus humei and Neoceratodus africanus), testudines (at least two Pelomedusoides, one of them being a representative of Araripemydidae), crocodyliforms (all remains being compatible with Neosuchia, represented at least by Elosuchus broinae), ornithocheirid pterosaurs, and non-avian dinosaurs (titanosauriform sauropods and at least two theropods, Spinosaurus aegyptiacus and Carcharodontosaurus saharicus). This fauna association displays close similarities to contemporaneous ones from North Africa, especially with that from the Kem Kem beds.
Technology Adoption Model: Is Use/Non-use a Case of Technological Affordances or Psychological Disposition or Pedagogical Reasoning in the Context of Teaching During the COVID-19 Pandemic Period?
Authors: Sadeck Osman
Published: July 2022

The educational implications of COVID-19 have shaken both practitioners and researchers alike. Practitioners were expected to use technologies instantaneously, and this set up trauma in individuals. The ramification of understanding people’s response to why technologies are accepted/not accepted and used/not used has significant implications for education. This conceptual paper sets out the process used to develop a theoretical framework based on the technology acceptance model (TAM). The constructs within the original TAM and extended TAM, were explored to understand “why” practicing teachers would choose to use technologies for educational purposes at primary and secondary school levels during the COVID-19 pandemic period. The TAM has been criticized for being simplistic and narrowly focused. Many researchers criticize TAM because their finding cannot be confirmed or that the constructs don’t fit their needs. This paper challenges these critiques. The theoretical framework suggested in this paper represents a view of reality of the relational and influencing effects of variables that potentially moderate or control affective and cognitive responses. It contributes to the existing literature through a comprehensive reviewing of concepts, constructs and COVID-19 “event” contextual realities. The findings offered are that: contextual realities and application often require a grounded theoretical framework to unravel complex questions and answers; the suggested unidirectional influence of perceived ease of use (PEOU) on perceived usefulness (PU) can be challenged through a dispositional rationale; neglecting non-use as a reality severely hampers TAMs applicability in studies focused on theory testing, and TAM provides sufficient flexibility by leaving the doors open for adaptation, and this flexibility is an asset in social science research.
Stimulatory Effect of Tofacitinib on Bone Marrow Adipocytes Differentiation
Authors: Letarouilly Jean-Guillaume , Paccou Julien , Badr Sammy , Chauveau Christophe , Broux Odile , Clabaut Aline
Published: July 2022

Background

Systemic inflammation is the main factor underlying secondary osteoporosis in patients with rheumatoid arthritis (RA). Janus kinase inhibitors (JAKi), such as tofacitinib (Tofa), can control systemic inflammation and may have beneficial effects on bone in various models. This might be due to direct effects on the bone microenvironment and not exclusively based on their anti-inflammatory function. Bone marrow adipocytes (BMAds) are abundant in the bone microenvironment. The effect of JAKi on BMAds is unknown, but evidence suggests that there is competition between human bone marrow-derived stromal cell (hBMSC) differentiation routes towards BMAds and osteoblasts (Ob) in osteoporosis.

Objectives

The aims of the study are to determine whether Tofa influences BMAds and Ob derived from hBMSCs and to investigate the potential effects of Tofa on bone marrow adiposity in RA patients.

Methods

To determine the effect of Tofa on cellular commitment, hBMSCs were differentiated to BMAds or OBs for 3 days together with Tofa at 200, 400, or 800 nM and TNFα. This study was also conducted using differentiated BMAds. The impact of Tofa was determined by gene and protein expression analysis and cell density monitoring. In parallel, in a pilot study of 9 RA patients treated with Tofa 5 mg twice a day (NCT04175886), the proton density fat fraction (PDFF) was measured using MRI at the lumbar spine at baseline and at 6 months.

Results

In non-inflammatory conditions, the gene expression of Runx2 and Dlx5 decreased in Ob treated with Tofa (p <0.05). The gene expression of PPARγ2, C/EBPα, and Perilipin 1 were increased compared to controls (p <0.05) in BMAds treated with Tofa. Under inflammatory conditions, Tofa did not change the expression profiles of Ob compared to TNFα controls. In contrast, Tofa limited the negative effect of TNFα on BMAd differentiation (p <0.05). An increase in the density of differentiated BMAds treated with Tofa under TNFα was noted (p <0.001). These findings were consolidated by an increase in PDFF at 6 months of treatment with Tofa in RA patients (46.3 ± 7.0% versus 53.2 ± 9.2% p <0.01).

Conclusion

Together, these results suggest a stimulatory effect of Tofa on BMAd commitment and differentiation, which does not support a positive effect of Tofa on bone.
Pollution Load Estimation and Control Countermeasures of Zhangze Reservoir
Authors: Yang Long , Zhang Min , Wei Jia , Qi Jun
Published: July 2022

Raising the water pollution control countermeasures on the basis of rational pollution load estimation is significant for improving water quality. Zhangze Reservoir, the largest water body in Changzhi city, China, was selected for this study. Considering the information constraints of the reservoir basin, the pollution load estimation method system covering point sources, non-point sources, and internal sources is systematically constructed using an export coefficient model, an sediment pore water diffusion model, and other methods, with the aim of estimating the discharge of pollutants into the Zhangze Reservoir from domestic sources, industrial sources, agricultural sources, sediment release, and urban runoff. The findings indicate the following: 1) the pollution loads of COD, NH3-N, TN, and TP are 3,157.82t, 177.62t, 760.72t, and 42.29t, respectively; 2) in terms of the distribution of pollution sources, urban domestic sources top the rest, accounting for 65.47% of COD, 82.83% of NH3-N, 79.00% of TN, and 60.65% of TP, followed by the agricultural source; 3) the total discharge of the main water pollutants exceeds the water environmental capacity, characterized as the dominating existence of domestic point source, the coexistence of point sources and non-point sources, and the coexistence of exogenous sources and endogenous sources. Finally, control countermeasures are raised to minimize the total discharge of pollutants for improving the water quality.
ENSO Teleconnection to Interannual Variability in Carbon Monoxide Over the North Atlantic European Region in Spring
Authors: Liu Yi , Liu Jane , Xie Min , Fang Keyan , Tarasick David W. , Wang Honglei , Meng Lingyun , Cheng Xugeng , Han Han , Zhang Xun
Published: July 2022

Carbon monoxide (CO) is an important trace gas in the troposphere, while the El Niño-Southern Oscillation (ENSO) phenomenon is the most important tropical climate variability. ENSO is known to influence interannual variation in meteorological variables on the global scale but its influence on atmospheric CO over large areas in a long term is uncertain. Here we report a strong positive teleconnection between the El Niño–Southern Oscillation (ENSO) in winter (November to February) to tropospheric CO over the North Atlantic European region (NAE) in the following spring (March to May). This ENSO teleconnection is evident in trajectory-mapped airborne CO data (In-service Aircraft for a Global Observing System, IAGOS) over 2002–2019. CO concentrations in El Niño years are 5–20 ppbv higher than those in La Niña years over the NAE troposphere. The regional mean difference from the surface to 300 hPa is 9.4 ppbv (7.6% of the mean). The correlation coefficient (r) between the ENSO index and detrended CO concentrations in the NAE is 0.67 at 400 hPa and 0.63 near the surface, both statistically significant at the 95% level. Such a teleconnection is also observed in independent surface observations, withrranging from 0.57 to 0.74, all at 95% significance level. From analysis of fire emissions and atmospheric conditions, combined with tagged CO simulations using a chemical transport model, GEOS-Chem, we conclude that this teleconnection results from the combined effects of ENSO on both biomass burning and atmospheric transport. We find that in El Niño years, CO emissions from biomass burning are significantly enhanced in Northern Hemispheric South America, Southeast Asia, and North America due to warmer air temperatures and lowered precipitation. In addition, ENSO enhances CO transport from these regions to the NAE by enhancing upward and northeastward motions in the fire regions, accelerating westerlies over 20°N–40°N, and prompting ascents over the Atlantic and descents over Europe, while reducing CO outflow at the eastern boundary of Europe. The combined effect of ENSO on both CO emissions and CO transport leads to interannual variability in tropospheric CO over the NAE.
Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia
Authors: Wang Yuye , Lv Shuang , Zhou Xiao , Niu Xiaoqian , Chen Leian , Yang Ziyuan , Peng Dantao
Published: July 2022

Vascular dementia (VaD) is the second most common cause of dementia. At present, precise molecular processes of VaD are unclear. We attempted to discover the VaD relevant candidate genes, enrichment biological processes and pathways, key targets, and the underlying mechanism by microarray bioinformatic analysis. We selected GSE122063 related to the autopsy samples of VaD for analysis. We first took use of Weighted Gene Co-expression Network Analysis (WGCNA) to achieve modules related to VaD and hub genes. Second, we filtered out significant differentially expressed genes (DEGs). Third, significant DEGs then went through Geno Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Fourth, Gene Set Enrichment Analysis (GSEA) was performed. At last, we constructed the protein–protein interaction (PPI) network. The results showed that the yellow module had the strongest correlation with VaD, and we finally identified 21 hub genes. Toll-like receptor 2 (TLR2) was the top hub gene and was strongly correlated with other possible candidate genes. In total, 456 significant DEGs were filtered out and these genes were found to be enriched in the Toll receptor signaling pathway and several other immune-related pathways. In addition, Gene Set Enrichment Analysis results showed that similar pathways were significantly over-represented in TLR2-high samples. In the PPI network, TLR2 was still an important node with high weight and combined scores. We concluded that the TLR2 acts as a key target in neuroinflammation which may participate in the pathophysiological process of VaD.
RNA Sequencing Reveals the Expression Profiles of circRNAs and Indicates Hsa_circ_0070562 as a Pro-osteogenic Factor in Bone Marrow-Derived Mesenchymal Stem Cells of Patients With Ankylosing Spondylitis
Authors: Wang Shan , Chen Fenglei , Zeng Chenying , Gu Huimin , Wang Ziming , Yu Wenhui , Wu Yanfeng , Shen Huiyong
Published: July 2022

Recent studies have reported that circular RNAs (circRNAs) play a crucial regulatory role in a variety of human diseases. However, the roles of circRNAs in pathological osteogenesis in ankylosing spondylitis (AS) remain unclear. We conducted circRNA and miRNA expression profiling of osteogenically differentiated bone marrow-derived mesenchymal stem cells (BMSCs) of patients with AS compared with those of healthy donors (HDs) by RNA sequencing (RNA-seq). Results showed that a total of 31806 circRNAs were detected in the BMSC samples, of which 418 circRNAs were significantly differentially expressed (DE) with a fold change ≥2 and p value <0.05. Among these, 204 circRNAs were upregulated, and 214 were downregulated. GO and KEGG analyses demonstrated that the DE circRNAs were mainly involved in the regulation of biological processes of the cell matrix adhesion and the TGF-beta signaling pathway, which are closely related to AS. circRNA-miRNA interaction networks related to the TGF-beta signaling pathway were established. The results of qRT-PCR showed that has_circ_0070562 was significantly up-regulated in AS-MSCs. In vitro experiments showed that silencing of has_circ_0070562 weakened osteogenesis of AS-BMSCs. In conclusion, we identified numerous circRNAs that were dysregulated in AS-BMSCs compared with HD-BMSCs. Bioinformatic analyses suggested that these dysregulated circRNAs might play important functional roles in AS-BMSCs osteogenesis. Circ_0070562 functioned as a pro-ostegenic factor and might serve as a potential biomarker and a therapeutic target for AS.
Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine
Authors: Nakahashi-Ouchida Rika , Mori Hiromi , Yuki Yoshikazu , Umemoto Shingo , Hirano Takashi , Uchida Yohei , Machita Tomonori , Yamanoue Tomoyuki , Sawada Shin-ichi , Suzuki Masashi , Fujihashi Kohtaro , Akiyoshi Kazunari , Kurono Yuichi , Kiyono Hiroshi
Published: July 2022

Nontypeable Haemophilus influenzae (NTHi) strains form a major group of pathogenic bacteria that colonizes the nasopharynx and causes otitis media in young children. At present, there is no licensed vaccine for NTHi. Because NTHi colonizes the upper respiratory tract and forms biofilms that cause subsequent infectious events, a nasal vaccine that induces NTHi-specific secretory IgA capable of preventing biofilm formation in the respiratory tract is desirable. Here, we developed a cationic cholesteryl pullulan–based (cCHP nanogel) nasal vaccine containing the NTHi surface antigen P6 (cCHP-P6) as a universal vaccine antigen, because P6 expression is conserved among 90% of NTHi strains. Nasal immunization of mice with cCHP-P6 effectively induced P6-specific IgA in mucosal fluids, including nasal and middle ear washes. The vaccine-induced P6-specific IgA showed direct binding to the NTHi via the surface P6 proteins, resulting in the inhibition of NTHi biofilm formation. cCHP-P6 nasal vaccine thus protected mice from intranasal NTHi challenge by reducing NTHi colonization of nasal tissues and eventually eliminated the bacteria. In addition, the vaccine-induced IgA bound to different NTHi clinical isolates from patients with otitis media and inhibited NTHi attachment in a three-dimensional in vitro model of the human nasal epithelial surface. Therefore, the cCHP-P6 nanogel nasal vaccine induced effective protection in the airway mucosa, making it a strong vaccine candidate for preventing NTHi-induced infectious diseases, such as otitis media, sinusitis, and pneumonia.
Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing via Mechanotransduction
Authors: Skibber Max A. , Olson Scott D. , Prabhakara Karthik S. , Gill Brijesh S. , Cox Charles S.
Published: July 2022

Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation via cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of classical pro-inflammatory cytokines. A dose-dependent effect of WSS on potency is evidenced by production of prostaglandin E2 (PGE2) and indoleamine 2,3 dioxygenase 1 (IDO1), as well as suppression of tumor necrosis factor-α (TNF- α) and interferon-γ (IFN-γ) production by activated immune cells. Consistent, reproducible licensing is demonstrated in adipose tissue and bone marrow human derived MSC without significant impact on cell viability, cellular yield, or identity. Transcriptome analysis of WSS-conditioned BM-MSC elucidates the broader phenotypic implications on the differential expression of immunomodulatory factors. These results suggest mechanotransduction as a viable, scalable pre-conditioning alternative to pro-inflammatory cytokines. Enhancing the immunomodulatory capacity of MSC via biomechanical conditioning represents a novel cell therapy manufacturing approach.
MSC-Derived Small Extracellular Vesicles Attenuate Autoimmune Dacryoadenitis by Promoting M2 Macrophage Polarization and Inducing Tregs via miR-100-5p
Authors: Li Na , Gao Zhiqi , Zhao Lu , Du Bei , Ma Binyun , Nian Hong , Wei Ruihua
Published: July 2022

Background

Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and the underlying mechanism of MSC-sEVs in autoimmune dry eye have been rarely studied.

Methods

Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit dry eye model, and their preventive or therapeutical effects were assessed by recording the clinical and histological scores. Quantitative real-time PCR (Q-PCR), western blot and flow cytometry were performed to evaluate the immunomodulatory effects of hUC-MSC-sEVs on macrophages and T regulatory cells (Tregs) both in vivo and in vitro, and the in vitro T cell proliferation was detected by Bromodeoxyuridine (BrdU) assay. In addition, high expression of miR-100-5p in hUC-MSC-sEVs was identified by Q-PCR, and the functional role of sEVs-miR-100-5p on macrophages was explored by a series of co-culture experiments using sEVs derived from hUC-MSCs transfected with miR-100-5p inhibitor.

Results

We firstly demonstrated that hUC-MSC-sEVs had the preventive and therapeutical effects on rabbit autoimmune dacryoadenitis, an animal model of Sjögren’s syndrome (SS) dry eye. Further investigation revealed that hUC-MSC-sEVs administration effectively elicited macrophages into an anti-inflammatory M2 phenotype and elevated the proportion of Tregs both in vivo and in vitro, which contributed to reduced inflammation and improved tissue damage. Importantly, hUC-MSC-sEVs-educated macrophages with M2-like phenotype exhibited strong capacity to inhibit CD4+ T cell proliferation and promote Treg generation in vitro. Mechanistically, miR-100-5p was highly enriched in hUC-MSC-sEVs, and knockdown of miR-100-5p in hUC-MSC-sEVs partially blunted the promotion of hUC-MSC-sEVs on M2 macrophage polarization and even attenuated the effect of hUC-MSC-sEVs-educated macrophages on T cell suppression and Treg expansion.

Conclusion

Our data indicated that hUC-MSC-sEVs alleviated autoimmune dacryoadenitis by promoting M2 macrophage polarization and Treg generation possibly through shuttling miR-100-5p. This study sheds new light on the application of MSC-sEVs as a promising therapeutic method for SS dry eye.
Chemotherapy and Physical Therapeutics Modulate Antigens on Cancer Cells
Authors: Szlasa Wojciech , Janicka Natalia , Sauer Natalia , Michel Olga , Nowak Bernadetta , Saczko Jolanta , Kulbacka Julita
Published: July 2022

Cancer cells possess specific properties, such as multidrug resistance or unlimited proliferation potential, due to the presence of specific proteins on their cell membranes. The release of proliferation-related proteins from the membrane can evoke a loss of adaptive ability in cancer cells and thus enhance the effects of anticancer therapy. The upregulation of cancer-specific membrane antigens results in a better outcome of immunotherapy. Moreover, cytotoxic T-cells may also become more effective when stimulated ex-vivo toward the anticancer response. Therefore, the modulation of membrane proteins may serve as an interesting attempt in anticancer therapy. The presence of membrane antigens relies on various physical factors such as temperature, exposure to radiation, or drugs. Therefore, changing the tumor microenvironment conditions may lead to cancer cells becoming sensitized to subsequent therapy. This paper focuses on the therapeutic approaches modulating membrane antigens and enzymes in anticancer therapy. It aims to analyze the possible methods for modulating the antigens, such as pharmacological treatment, electric field treatment, photodynamic reaction, treatment with magnetic field or X-ray radiation. Besides, an overview of the effects of chemotherapy and immunotherapy on the immunophenotype of cancer cells is presented. Finally, the authors review the clinical trials that involved the modulation of cell immunophenotype in anticancer therapy.
A Human CD68 Promoter-Driven Inducible Cre-Recombinase Mouse Line Allows Specific Targeting of Tissue Resident Macrophages
Authors: Rumianek Agata N. , Davies Ben , Channon Keith M. , Greaves David R. , Purvis Gareth S. D.
Published: July 2022

Current genetic tools designed to target macrophages in vivo often target cells from all myeloid lineages. Therefore, we sought to generate a novel transgenic mouse which has a tamoxifen inducible Cre-recombinase under the control of the human CD68 promoter (hCD68-CreERT2). To test the efficiency and specificity of the of Cre-recombinase activity we crossed the hCD68-CreERT2 mice with a loxP-flanked STOP cassette red fluorescent protein variant (tdTomato) mouse. We established that orally dosing mice with 2 mg of tamoxifen for 5 consecutive days followed by a 5-day induction period resulted in robust expression of tdTomato in CD11b+ F4/80+ tissue resident macrophages. Using this induction protocol, we demonstrated tdTomato expression within peritoneal, liver and spleen macrophages and blood Ly6Clow monocytes. Importantly there was limited or no inducible tdTomato expression within other myeloid cells (neutrophils, monocytes, dendritic cells and eosinophils), T cells (CD4+ and CD8+) and B cells (CD19+). We also demonstrated that the level of tdTomato expression can be used as a marker to identify different populations of peritoneal and liver macrophages. We next assessed the longevity of tdTomato expression in peritoneal macrophages, liver and splenic macrophages and demonstrated high levels of tdTomato expression as long as 6 weeks after the last tamoxifen dose. Importantly, hCD68-CreERT2 expression is more restricted than that of LysM-Cre which has significant expression in major myeloid cell types (monocytes and neutrophils). To demonstrate the utility of this novel macrophage-specific Cre driver line we demonstrated tdTomato expression in recruited CD11b+CD64+F4/80+ monocyte-derived macrophages within the atherosclerotic lesions of AAV8-mPCSK9 treated mice, with limited expression in recruited neutrophils. In developing this new hCD68-CreERT2 mouse we have a tool that allows us to target tissue resident macrophages, with the advantage of not targeting other myeloid cells namely neutrophils and inflammatory monocytes.
The Road Less Taken: Less Appreciated Pathways for Manipulating CD8+ T Cell Exhaustion
Authors: Pichler Andrea C. , Cannons Jennifer L. , Schwartzberg Pamela L.
Published: July 2022

Exhausted CD8+T (Tex) cells are a distinct cell population that arise during persistent antigen exposure in the context of chronic infections and cancers. Although characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression and distinct transcriptional and epigenetic programs, Tex cells are heterogeneous. Among these, a self-renewing TCF-1+ Tex population, having unique characteristics and the ability to respond to immune-checkpoint blockade, gives rise to TCF-1-terminally Tex cells. These TCF-1+ cells have stem cell-like properties similar to memory T cell populations, but the signals that regulate the developmental pathways and relationships among exhausted cell populations are still unclear. Here, we review our current understanding of Tex cell biology, and discuss some less appreciated molecules and pathways affecting T cell exhaustion. We highlight two co-stimulatory receptors, CD226 and CD137, and their role in inducing or restraining T cell exhaustion, as well as signaling pathways that may be amenable to pharmacological inhibition with a focus on Phosphoinositide-3 Kinase and IL-2 partial agonists. Finally, we discuss novel methods that may increase TCF-1+populations and therefore improve immunotherapy responsiveness. Understanding features of and pathways to exhaustion has important implications for the success of immunotherapy, including checkpoint blockade and adoptive T-cell transfer therapies.
Orally Administered Brain Protein Combined With Probiotics Increases Treg Differentiation to Reduce Secondary Inflammatory Damage Following Craniocerebral Trauma
Authors: Cui Yang , Xu Lixia , Wang Fanchen , Wang Zhengang , Tong Xiaoguang , Yan Hua
Published: July 2022

Craniocerebral trauma is caused by external forces that can have detrimental effects on the vasculature and adjacent nerve cells at the site. After the mechanical and structural primary injury, a complex series of secondary cascades of injury exacerbates brain damage and cognitive dysfunction following mechanical and structural primary injury. Disruption of the blood-brain barrier and exposure of brain proteins following craniocerebral trauma, recognition by the immune system triggering autoimmune attack, and excessive secondary inflammatory responses causing malignant brain swelling, cerebral edema, and subsequent brain cell apoptosis provide a new direction for the suppression of brain inflammatory responses in the treatment of craniocerebral trauma. We observed that CD4+T/CD8+T in peripheral blood T cells of craniocerebral trauma rats were significantly higher than those of normal rats, and the ratio of CD4+CD25+Foxp3 (Foxp3)+Regulatory T cell (Treg) was significantly lower than that of normal rats and caused increased secondary inflammation. We constructed a rat model of post-surgical brain injury and orally administered brain protein combined with probiotics, which was observed to significantly reduce CD4+T/CD8+T and induce T-cell differentiation into CD4+CD25+Foxp3+Treg, thus, reducing secondary inflammatory responses following craniocerebral trauma. However, collecting intestinal stool and small intestinal tissues for broad target metabolomics, 16s rRNA bacteriomics, and the combined analysis of intestinal tissue proteomics revealed that oral administration of brain protein combined with probiotics activates glycerophospholipid and vitamin B6 metabolic pathways to promote the production of CD4+CD25+Foxp3+Treg. Therefore, we propose the novel idea that oral administration of brain protein combined with probiotics can induce immune tolerance by increasing Treg differentiation, thus, reducing secondary inflammatory injury following craniocerebral trauma.
RETRACTED: Lactobacillus paracasei X11 Ameliorates Hyperuricemia and Modulates Gut Microbiota in Mice
Authors: Cao Jiayuan , Liu Qiqi , Hao Haining , Bu Yushan , Tian Xiaoying , Wang Ting , Yi Huaxi
Published: July 2022

Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the potential effect of alleviating HUA. The purpose of this study was to screen probiotics with UA-lowering activity and explore the underlying mechanism. The UA-lowering activity of 20 lactic acid bacteria strains was investigated in vitro, and the effect of candidate probiotics on UA metabolism was evaluated using the HUA Balb/c mouse model. The results showed that Lactobacillus paracasei X11 had excellent UA-lowering activity in vitro, which could degrade nucleotides and nucleosides completely within 30 min, and the degradation rates of purine and trioxypurine could reach 83.25% and 80.42%, respectively. In addition, oral administration of L. paracasei X11 could reduce serum UA by 52.45% and inhibit renal proinflammatory cytokine IL-1β by 50.69%, regulating adenosine deaminase (ADA), xanthine oxidase (XOD), and transporter expression (GLUT9, NPT1, and URAT1) to a normal level. Moreover, it could restore the ratio of Bacteroidetes to Firmicutes (Bac/Firm ratio) and showed a positive effect on the recovery of the intestinal microbiota. These findings provided fundamental information about the UA-lowering properties of probiotics, which suggested that L. paracasei X11 had the potential to be developed as a novel probiotic strain to ameliorate HUA.
Long-Term Warm–Cold Phase Shifts in the Gerlache Strait, Western Antarctic Peninsula
Authors: Su Zhiqiang , Zhang Zhaoru , Zhu Yiwu , Zhou Meng
Published: July 2022

The Gerlache Strait plays an important role for the transports of heat, nutrients, and primary producers between the northern West Antarctic Peninsula (WAP) and the continental shelf in the southern WAP. The means, seasonal variations, and long-term trends of currents in the Gerlache Strait are analyzed based on Acoustic Doppler Current Profiler (ADCP) data between 1999 and 2016 available from the Joint Archive for Shipboard ADCP (JASADCP) dataset. The results revealed that the mean currents between the sea surface and 300 m in the Gerlache Strait (known as the Gerlache Strait Current) were predominantly northeastward, associated with the northeastward intrusion of Modified Circumpolar Deep Water (MCDW). The variance ellipses of currents were in parallel to the principal axis of the strait. The currents reached the maximum during austral spring and summer and were minimum during austral winter. The long-term trends revealed that the mean currents were southwestward during austral fall or winter before 2005, and the northeastward currents increased between 1999 and 2011, weakened, and reversed between 2011 and 2016. The long-term shifts between warm and cold phases in the Gerlache Strait were associated with shifts between the dominance of northeastward and southwestward currents in the strait, which are respectively associated with the intrusion of warm MCDW in the south and the transport of cold water from the Bransfield Strait in the north.
Oyster and Barnacle Recruitment Dynamics on and Near a Natural Reef in China: Implications for Oyster Reef Restoration
Authors: Jiang Wei , Shi Wen-Jing , Li Nan-Nan , Fan Rui-Liang , Zhang Wen-Kao , Quan Wei-Min
Published: July 2022

Oysters and barnacles are dominant inhabitants of natural and restored oyster reefs around the world, and high areal coverage of barnacles at natural or restored reefs commonly decreases substrate accessibility for oyster settlement. The overall understanding of oyster and barnacle recruitment dynamics provides invaluable information on site selection and strategies employed for oyster reef restoration. This study documented the temporal and spatial patterns of oyster and barnacle recruitment on and near the largest natural intertidal oyster reef (Liyashan) in China during 2019–2020. The oyster Crassostrea sikamea recruitment appeared as a continuous process from June through late November or early December, with the peak in August. Greater recruits of oyster spat occurred on the sheltered inshore at the upstream of the natural oyster reef than on the reef and the nearby open coast (p < 0.05). The barnacle recruitment extended from spring to early winter, with mid-spring and mid-summer peaks. Conversely, higher barnacle recruitment appeared on the natural oyster reef and the nearby open coast than on the sheltered inshore. Across all the monitoring sites, the cumulative recruits of oysters in each of 2019 and 2020 was negatively correlated with those of barnacles (p < 0.05). The inshore sites (SH1 and SH2) with high oyster recruitment and low barnacle recruitment should be recognized as the natural spatfall sites for the natural oyster reef restoration. The separation in the recruitment peak between the oyster and the barnacle indicated that August was the most favorable window for capturing oyster spat through substratum addition to the water around the natural reef.
Inner Retinal Layer Hyperreflectivity Is an Early Biomarker for Acute Central Retinal Artery Occlusion
Authors: Wenzel Daniel A. , Poli Sven , Casagrande Maria , Druchkiv Vasyl , Spitzer Martin S. , Bartz-Schmidt Karl Ulrich , Grohmann Carsten , Schultheiss Maximilian
Published: July 2022

Purpose

To investigate inner retinal hyperreflectivity on optical coherence tomography (OCT) as a potential biomarker indicating acute central retinal artery occlusion (CRAO).

Methods

A total of 56 patients at two university hospitals with acute CRAO (symptom onset ≤48 h) were included in this retrospective study. The optical intensity of the inner retinal layers was determined in both eyes and the relationship between symptom onset and inner retinal layer optical intensity in OCT scans compared to the unaffected fellow eye was analyzed. Several differential diagnoses [central retinal vein occlusion, anterior ischemic optic neuropathy, diabetic macular edema, and subretinal fibrosis/disciform scar (Junius-Kuhnt)] served as controls to validate optical intensity-based diagnosis of CRAO.

Results

CRAO strongly correlated with an increased inner retinal layer hyperreflectivity in this cohort with acute CRAO with a time since symptom onset ranging from 1.1 to 48.0 h. Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.99 to confirm CRAO with a true positive rate of 0.93 and a false positive rate of 0.02. No correlation between optical intensity and time since symptom onset was noticeable. None of the differential diagnoses did show an elevated optical intensity of the inner retinal layers as it was detectable in CRAO.

Conclusion

OCT-based determination of inner retinal layer hyperreflectivity is a very promising biomarker for a prompt diagnosis of CRAO in an emergency setting. This may be of major interest to speed up the administration of a possible thrombolytic treatment.
Resection of Thymic Neuroendocrine Carcinoma Guided by Three-Dimensional Reconstruction: A Case Report
Authors: Liu Fang , Lu Hengxiao , Chen Liqian , Geng Junfeng , Xu Tongzhen
Published: July 2022

Primary thymic small cell neuroendocrine carcinoma (SCNEC), which possesses a more aggressive biological behaviour, including invasion of proximal structures, local recurrence, and distant metastasis, is extremely rare. According to a previous literature report, only a few patients with this disease have been reported, compared to patients with distant metastasis of bones, lungs, spleen, liver, and adrenal glands (1, 2). The report data suggest that SCNEC is a highly malignant tumour compared to most other tumours of the human body. In this study, we presented the case of a patient who underwent surgery guided by three-dimensional reconstruction modelling before the operation. We were fully prepared for the resection of this tumour using three-dimensional reconstruction modelling, even after reading the computed tomography (CT) images that showed a closed relationship with the pericardium, the vein of the right middle lung lobe, and the phrenic nerve. All these features demonstrate that SCNEC is highly malignant. To date, there are no procedural reports for three-dimensional reconstruction modelling in malignant thymus tumours.
Diffusion Tensor Imaging Profiles Can Distinguish Diffusivity and Neural Properties of White Matter Injury in Hydrocephalus vs. Non-hydrocephalus Using a Strategy of a Periodic Table of DTI Elements
Authors: Keong Nicole C. , Lock Christine , Soon Shereen , Hernowo Aditya Tri , Czosnyka Zofia , Czosnyka Marek , Pickard John D. , Narayanan Vairavan
Published: July 2022

Background:

The aim of this study was to create a simplistic taxonomy to improve transparency and consistency in, and reduce complexity of, interpreting diffusion tensor imaging (DTI) profiles in white matter disruption. Using a novel strategy of a periodic table of DTI elements, we examined if DTI profiles could demonstrate neural properties of disruption sufficient to characterize white matter changes specific for hydrocephalus vs. non-hydrocephalus, and to distinguish between cohorts of neural injury by their differing potential for reversibility.

Methods

DTI datasets from three clinical cohorts representing pathological milestones from reversible to irreversible brain injury were compared to those of healthy controls at baseline, over time and with interventions. The final dataset comprised patients vs. controls in the following groupings: mild traumatic brain injury (mTBI), n = 24 vs. 27, normal pressure hydrocephalus (NPH), n = 16 vs. 9 and Alzheimer's disease (AD), n = 27 vs. 47. We generated DTI profiles from fractional anisotropy (FA) and mean, axial and radial diffusivity measures (MD, L1 and L2 and 3 respectively), and constructed an algorithm to map changes consistently to a periodic table of elements, which fully described their diffusivity and neural properties.

Results

Mapping tissue signatures to a periodic table of DTI elements rapidly characterized cohorts by their differing patterns of injury. At baseline, patients with mTBI displayed the most preserved tracts. In NPH, the magnitude of changes was dependent on “familial” DTI neuroanatomy, i.e., potential for neural distortion from risk of ventriculomegaly. With time, patients with Alzheimer's disease were significantly different to controls across multiple measures. By contrast, patients with mTBI showed both loss of integrity and pathophysiological processes of neural repair. In NPH, some patterns of injury, such as “stretch/compression” and “compression” were more reversible following intervention than others; these neural profile properties suggested “microstructural resilience” to injury.

Conclusion

Using the novel strategy of a periodic table of DTI elements, our study has demonstrated it is possible to distinguish between different cohorts along the spectrum of brain injury by describing neural profile properties of white matter disruption. Further work to contribute datasets of disease toward this proposed taxonomic framework would enhance the translatability of DTI profiles to the clinical-research interface.
How to Promote Urban Intelligent Transportation: A Fuzzy Cognitive Map Study
Authors: Zhao Luwei , Wang Qing’e , Hwang Bon-Gang
Published: July 2022

As an important part of smart city, intelligent transportation is an critical breakthrough to solve urban traffic congestion, build an integrated transportation system, realize the intelligence of traffic infrastructure and promote sustainable development of traffic. In order to investigate the construction of intelligent transportation in cities, 20 initial affecting variables were determined in this study based on literature analysis. A questionnaire collected from professionals in intelligent transportation was conducted, and a total of 188 valid responses were received. Then the potential grouping was revealed through exploratory factor analysis. Finally, a causal model containing seven concepts was established using the practical experience and knowledge of the experts. A root cause analysis method based on fuzzy cognitive map (FCM) was also proposed to simulate intelligent transportation construction (ITC). The results indicate:(1) The 20 variables can be divided into six dimensions: policy support (PS), traffic sector control (TSC), technical support (TS), communication foundation (CF), residents’ recognition (RR), and talent quality (TQ); and (2) In the FCM model, all six concept nodes (PS, TSC, TS, CF, RR, and TQ) have a significant positive correlation with the target concept node ITC. The rank of the six dimensions according to correlation strength is TS, CF, PS, TSC, RR, and TQ. The findings of this paper can help academics and practitioners understand the deep-seated determinants of urban intelligent transportation construction more comprehensively, and provide valuable suggestions for policy makers. And thus, the efficiency of intelligent transportation construction can be improved.
Abnormal Cerebral Blood Flow and Volumetric Brain Morphometry in Patients With Obstructive Sleep Apnea
Authors: Xiao Ping , Hua Kelei , Chen Feng , Yin Yi , Wang Jurong , Fu Xiangjun , Yang Jiasheng , Liu Qingfeng , Chan Queenie , Jiang Guihua
Published: July 2022

Obstructive sleep apnea (OSA) is a serious breathing disorder, leading to myocardial infarction, high blood pressure, and stroke. Brain morphological changes have been widely reported in patients with OSA. The pathophysiological mechanisms of cerebral blood flow (CBF) changes associated with OSA are not clear. In this study, 20 patients with OSA and 36 healthy controls (HCs) were recruited, and then pseudo-continuous arterial spin labeling (pCASL) and voxel-based morphometry (VBM) methods were utilized to explore blood perfusion and morphological changes in the patients with OSA. Compared with the HC group, the OSA group showed increased CBF values in the right medial prefrontal cortex (mPFC), left precentral gyrus, and right insula and showed decreased CBF values in the right temporal pole (TP) and the right cerebellum_Crus2. Compared with the HC group, the patients with OSA showed decreased gray matter volume (GMV) in the right dorsal lateral prefrontal cortex (DLPFC), the right occipital pole, and the vermis. There were no significantly increased GMV brain regions found in patients with OSA. Pearson correlation analysis showed that the reduced GMV in the right DLPFC and the right occipital pole was both positively correlated with Mini-Mental State Examination (MMSE) (r = 0.755, p < 0.001; r = 0.686, p = 0.002) and Montreal Cognitive Assessment (MoCA) scores (r = 0.716, p = 0.001; r = 0.601, p = 0.008), and the reduced GMV in the right occipital pole was negatively correlated with duration of illness (r = −0.497, p = 0.036). Patients with OSA have abnormal blood perfusion metabolism and morphological changes in brain regions including the frontal lobe and the cerebellum and were closely related to abnormal behavior, psychology, and cognitive function, which play an important role in the pathophysiological mechanism of OSA.
Interleukin-17A Mediates Hippocampal Damage and Aberrant Neurogenesis Contributing to Epilepsy-Associated Anxiety
Authors: Choi In-Young , Cho Mi-La , Cho Kyung-Ok
Published: July 2022

Anxiety disorder is one of the most common comorbidities in temporal lobe epilepsy (TLE), but its neurobiological mechanisms remain unclear. Here we identified a novel target, interleukin-17A (IL-17A), which can contribute to TLE-associated anxiety. Epileptic seizures were induced in 6-week-old IL-17A wild-type (WT) and knockout (KO) mice by pilocarpine injection. To evaluate anxiety level, we subjected mice to open field and elevated plus maze (EPM) tests and measured the time animals spent in center zone or open arms. Epileptic IL-17A WT mice showed thigmotaxis and reluctance to stay in open arms, whereas IL-17A KO mice spent more time in the center area and open arms, suggesting alleviated anxiety in epilepsy. Histological assessments revealed that hippocampal neuronal death as evaluated by Fluoro-Jade B staining was significantly reduced in IL-17A KO mice. Moreover, at 6 weeks after pilocarpine-induced status epilepticus, the number of hilar ectopic granule cells was also markedly decreased by IL-17A deficiency without a difference in the proliferation of neural progenitors or the generation of newborn neurons in the dentate gyrus. Taken together, our data demonstrated that IL-17A deletion mitigates TLE-associated anxiety behavior, possibly via the hippocampal neuroprotection and the reduction of seizure-induced aberrant neurogenesis.
Breast Milk Lipidome Is Associated With Maternal Diet and Infants' Growth
Authors: Calvo-Lerma Joaquim , Selma-Royo Marta , Hervas David , Yang Baoru , Intonen Linda , González Sonia , Martínez-Costa Cecilia , Linderborg Kaisa M. , Collado Maria Carmen
Published: July 2022

Objectives

The fatty acid (FA) composition of breast milk is a relevant aspect related to the development of the lactating infant. The present study aimed at exploring correlations between dietary intake of macro- and micronutrients with the FA profile in breast milk, and the possible implication for infants' growth.

Study Design

Breast milk samples from a cohort of lactating women were collected 7–15 days postpartum. The FA profiles in triacylglycerol (TAG) and phospholipid (PL)-rich fractions were analyzed by gas chromatography. Diet was registered during the third trimester of pregnancy by means of a food frequency questionnaire (FFQ). In addition, anthropometric measurements of infants were collected from gestation and up to 12 months postpartum.

Results

The FA profile in breast milk was characterized by a median of 37.4, 41.3 and 16.8% of saturated, monounsaturated, and polyunsaturated FAs, respectively. From the dietary components, zinc, iron, and B group vitamins were correlated positively with the proportion of total n-3 FAs in TAG and C20:5 n-3 in PL. Lycopene, vitamin E, zinc, and vitamin B2 showed a similar correlation with total polyunsaturated fatty acid (PUFA), total n-6 FAs, C20:4 n-6, and C18:2 n-6 in TAG. Regarding food groups, nuts showed the strongest association with several PUFA both in TAG and PL, while the vegetable group was also positively associated with C18:3 n-3. Furthermore, the concentration of linolenic acid (C18:3 n-3) and palmitic acid (C16:0) were positively associated with increased length for age (LFA) and weight for age (WFA) at 12 months compared with birth [ΔLFA −0.16 (−0.85, 0.37); ΔWFA −0.26 (−0.77, 0.21)].

Conclusions

Mothers' intake of nuts, dietary sources of zinc, iron, and B group vitamins were identified as potential predictors of a high-unsaturated FA profile in breast milk. In addition, linolenic and palmitic acids in breast milk were positively associated with infants' growth in the first year of life.