bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the relationship between urbanization and environment in the Jiulong river basin based on coupling coordination degree model
Authors: Liao Yiping , Liu Guangsheng , Luan Haijun , Deng Guojiang , Zheng Meiduan , Cai Wenhao
Published: May 2023

Rapid urbanization has placed the sustainable development of some watershed ecosystems in jeopardy. In order to achieve sustainable urban development, it is vital to identify the coupling mechanisms between urbanization and the ecological environment quality. This study establishes indicators to evaluate the Jiulong River Basin’s urbanization and ecological environment systems. These are utilized to analyze spatial and temporal changes and build a coupling coordination degree model. This research investigates the level of development coordination between urbanization and the ecological environment quality in the basin. The data sources include nighttime lighting and Landsat data from 2000 to 2020. The findings indicated the following: 1) Urbanization levels in the basin rise annually, and the years 2010–2020 represent a stage of high urbanization growth. In addition, the development levels are spatially heterogeneous, with high levels in the south and low levels in the north. 2) The ecological environment quality category for the basin is generally Excellent; however, many facets of the climate and human activity drastically lowered this grade in 2005. 3) In the basin, there is a basic coordination relationship between urbanization and environmental quality, but the number of cities falling into the moderate imbalance category has grown. 4) Increasing the urbanization level raises the coordination between urbanization and the ecological environment more than improving environmental quality, but antagonistic effects make it necessary to strengthen the protection of the ecological environment alongside economic development. From the viewpoint of counties, this study examines the long-term interactions between the ecological environment and urbanization in Fujian Province, China. Recommendations for balancing urban development and environmental concerns in coastal watersheds are presented, providing references to the fact that the future of this area of China can be sustainable.
Spatio-temporal variation and prediction of ecological quality based on remote sensing ecological index – a case study of Zhanjiang City, China
Authors: Wang Jing , Wang Jia , Xu Jiangqi
Published: May 2023

A significant portion of Zhanjiang City’s ecological land areas have been reduced as a result of the city’s growing urbanization, which has caused the city’s ecological environment quality to decline. In order to monitor the quality of the ecological environment, the remote sensing ecological index (RSEI) is frequently utilized. In this study, the Landsat series satellite images from 2000, 2005, 2009, 2015, and 2020 were used. The Normalized Differential Vegetation Index (NDVI), Wetness (WET), Normalized Differential Build-up and bare Soil Index (NDBSI), and Land Surface Temperature (LST) were the four indicators utilized in the RSEI to quantitatively evaluate the changes in ecological environment quality in Zhanjiang City. The results are as follows. (1) The mean RSEI values for the years 2000, 2005, 2009, 2015, and 2020 are, respectively, 0.579, 0.597, 0.597, 0.607, and 0.601. In addition, the overall ecological environment of Zhanjiang is very good. In terms of spatial differences, the ecological environment quality in the central and southeastern parts of Zhanjiang is significantly higher than that in other areas, while the ecological environment quality in its coastal town areas is much worse. The lower RSEI index of developed land in coastal areas proves that the RSEI index can reflect the deterioration of the urban environment in coastal areas from 2000 to 2020. Therefore, the RSEI can be used to evaluate the ecological environment quality of Zhanjiang City. (2) The ecological environment changes in the study area are “substantially better,” “better,” “no change,” “worse,” and “much worse,” respectively, according to the difference in RSEI processed between 2000 and 2020. These changes were 38.38, 6,047, 13.93, 6.65, and 34.58%. The percentage of ecological environmental quality in Zhanjiang City that has become better is higher than that has become worse. This indicates that the quality of ecological environment in Zhanjiang City has improved between 2000 and 2020. (3) The regression produced the following equation for the association, which was significant at the 0.053 level: 100*Rsei = 154.69–1.18*IS(R = 0.66). The remote sensing ecological index for Zhanjiang in 2035 is 0.488 when the city’s planned population and area are added together.
Computable structured aptamer for targeted treatment of ovarian cancer
Authors: Ruan Luoshan , Han Liting , Li Xin , Chen Xin , Sun Gege , Wang Xinyu , Luo Yan , Gu Chuanqi , Shi Xiaolong
Published: May 2023

Nucleolin protein expression is higher on the ovarian cancer cell surface. AS1411, a DNA aptamer, can bind with nucleolin protein specifically. In this study, we developed HA and ST DNA tiles to assemble six AS1411 aptamers to deliver doxorubicin. In addition, to superior serum stability and drug loading, HA-6AS and ST-6AS outperformed TDN-AS in cellular uptake. HA-6AS and ST-6AS exhibited satisfactory targeted cytotoxicity and achieved resounding lysosomal escape. Moreover, when injected into nude mice subcutaneous xenograft models, HA-6AS reached the peak in tumor more quickly than ST-6AS, and better expressed the active targeting ability of AS1411. Our study suggests that designing appropriate DNA tiles to assemble different aptamers to deliver different chemotherapeutic drugs is a promising treatment for ovarian cancer.
Myo1f has an essential role in γδT intraepithelial lymphocyte adhesion and migration
Authors: Martínez-Vargas Irving Ulises , Sánchez-Bello Maria Elena , Miguel-Rodríguez Carlos Emilio , Hernández-Cázares Felipe , Santos-Argumedo Leopoldo , Talamás-Rohana Patricia
Published: May 2023

γδT intraepithelial lymphocyte represents up to 60% of the small intestine intraepithelial compartment. They are highly migrating cells and constantly interact with the epithelial cell layer and lamina propria cells. This migratory phenotype is related to the homeostasis of the small intestine, the control of bacterial and parasitic infections, and the epithelial shedding induced by LPS. Here, we demonstrate that Myo1f participates in the adhesion and migration of intraepithelial lymphocytes. Using long-tailed class I myosins KO mice, we identified the requirement of Myo1f for their migration to the small intestine intraepithelial compartment. The absence of Myo1f affects intraepithelial lymphocytes’ homing due to reduced CCR9 and α4β7 surface expression. In vitro, we confirm that adhesion to integrin ligands and CCL25-dependent and independent migration of intraepithelial lymphocytes are Myo1f-dependent. Mechanistically, Myo1f deficiency prevents correct chemokine receptor and integrin polarization, leading to reduced tyrosine phosphorylation which could impact in signal transduction. Overall, we demonstrate that Myo1f has an essential role in the adhesion and migration in γδT intraepithelial lymphocytes.
Analysis of immunogenic cell death in ascending thoracic aortic aneurysms based on single-cell sequencing data
Authors: Tian Zemin , Zhang Peng , Li Xinyang , Jiang Delong
Published: May 2023

Background

At present, research on immunogenic cell death (ICD) is mainly associated with cancer therapy. Little is known about the role of ICD in cardiovascular disease, especially in ascending thoracic aortic aneurysms (ATAA).

Method

ATAA single-cell RNA (scRNA) sequencing data were analyzed to identify the involved cell types and determine their transcriptomic characteristics. The chi-square test, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Gene Set Enrichment Analysis (GSEA), and CellChat for cell-to-cell communication analysis from the Gene Expression Omnibus (GEO) database were used.

Result

A total of 10 cell types were identified, namely, monocytes, macrophages, CD4 T/NK (CD4+ T cells and natural killer T cells), mast cells, B/Plasma B cells, fibroblasts, endothelial cells, cytotoxic T cells (CD8+ T cells, CTLs), vascular smooth muscle cells (vSMCs), and mature dendritic cells (mDCs). A large number of inflammation-related pathways were present in the GSEA results. A large number of ICD-related pathways were found in the KEGG enrichment analysis of differentially expressed genes in endothelial cells. The number of mDCs and CTLs in the ATAA group was significantly different from that in the control group. A total of 44 pathway networks were obtained, of which 9 were associated with ICD in endothelial cells (CCL, CXCL, ANNEXIN, CD40, IL1, IL6, TNF, IFN-II, GALECTIN). The most important ligand−receptor pair by which endothelial cells act on CD4 T/NK cells, CTLs and mDCs is CXCL12-CXCR4. The most important ligand−receptor pair by which endothelial cells act on monocytes and macrophages is ANXA1-FPR1. The most important ligand−receptor pair by which CD4 T/NK cells and CTLs act on endothelial cells is CCL5-ACKR1. The most important ligand−receptor pair that myeloid cells (macrophages, monocytes and mDCs) act on endothelial cells is CXCL8-ACKR1. Moreover, vSMCs and fibroblasts mainly promote inflammatory responses through the MIF signaling pathway.

Conclusion

ICD is present in ATAA and plays an important role in the development of ATAA. The target cells of ICD may be mainly endothelial cells, in which the aortic endothelial cell ACKR1 receptor can not only promote T-cell infiltration through the CCL5 ligand but also promote myeloid cell infiltration through the CXCL8 ligand. ACKR1 and CXCL12 may become target genes for ATAA drug therapy in the future.
Case Report: Interindividual variability and possible role of heterozygous variants in a family with deficiency of adenosine deaminase 2: are all heterozygous born equals?
Authors: Pulvirenti Federica , Cinicola Bianca Laura , Ferrari Simona , Guadagnolo Daniele , Sculco Eleonora , Capponi Martina , Loffredo Lorenzo , Sciannamea Maddalena , Insalaco Antonella , Quinti Isabella , De Benedetti Fabrizio , Zicari Anna Maria
Published: May 2023

Deficiency of adenosine deaminase 2 (DADA2) is a rare systemic autoinflammatory disease, typically with autosomal recessive inheritance, usually caused by biallelic loss of function mutations in the ADA2 gene. The phenotypic spectrum is broad, generally including fever, early-onset vasculitis, stroke, and hematologic dysfunction. Heterozygous carriers may show related signs and symptoms, usually milder and at an older age. Here we describe the case of two relatives, the proband and his mother, bearing an ADA2 homozygous pathogenic variant, and a heterozygous son. The proband was a 17-year-old boy with intermittent fever, lymphadenopathies, and mild hypogammaglobulinemia. He also had sporadic episodes of aphthosis, livedo reticularis and abdominal pain. Hypogammaglobulinemia was documented when he was 10 years old, and symptoms appeared in his late adolescence. The mother demonstrated mild hypogammaglobulinemia, chronic pericarditis since she was 30 years old and two transient episodes of diplopia without lacunar lesions on MRI. ADA2 (NM_001282225.2) sequencing identified both mother and son as homozygous for the c.1358A>G, p.(Tyr453Cys) variant. ADA2 activity in the proband and the mother was 80-fold lower than in the controls. Clinical features in both patients improved on anti-tumor necrosis factor therapy. An older son was found to be heterozygous for the same mutation post-mortem. He died at the age of 12 years due to a clinical picture of fever, lymphadenitis, skin rash and hypogammaglobulinemia evolving toward fatal multiorgan failure. Biopsies of skin, lymph nodes, and bone marrow excluded lymphomas and vasculitis. Despite being suspected of symptomatic carrier, the contribution of an additional variant in compound heterozygosity, or further genetic could not be ruled out, due to poor quality of DNA samples available. In conclusion, this familiar case demonstrated the wide range of phenotypic variability in DADA2. The search for ADA2 mutations and the assessment of ADA2 activity should be considered also in patients with the association of hypogammaglobulinemia and inflammatory conditions, also with late presentation and in absence of vasculitis. Furthermore, the clinical picture of the deceased carrier suggests a possible contribution of heterozygous pathogenic variants to inflammation.
Leptin deficiency in CD8+ T cells ameliorates non-segmental vitiligo by reducing interferon-γ and Granzyme B
Authors: Wu Meiyu , Wang Lu , Wu Haijing , Yang Ming , He Zhenghao , Chen Yiran , Zhang Huiming
Published: May 2023

Background

Vitiligo is an autoimmune skin disease mainly mediated by CD8+ T cells, which affects about 0.1%-2% population of the world. Leptin plays a critical role in regulating the activation of CD8+ T cells. However, the effect of Leptin on vitiligo remains unclear.

Objectives

To explore the effect of leptin on CD8+ T cells and its influence on vitiligo.

Methods

RNA sequencing and Quantitative Real-time PCR (RT-qPCR) were used to explore the differentially expressed genes. Immunofluorescence staining was performed on skin lesions. Leptin in serum was detected by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells were detected by flow cytometry after leptin stimulation for 72 hours. A vitiligo model was established by monobenzone on Leptin KO mice.

Results

557 differentially expressed genes were found, including 154 up-regulated and 403 down-regulated genes. Lipid metabolism pathways showed a close relationship to the pathogenesis of vitiligo, especially the PPAR signaling pathway. RT-qPCR (p = 0.013) and immunofluorescence staining (p = 0.0053) verified that LEPR expressed significantly higher in vitiligo. The serum leptin level of vitiligo patients was significantly lower than that of healthy controls (p = 0.0245). The interferon-γ subset of CD8+LEPR+ T cells from vitiligo patients was significantly higher (p = 0.0189). The protein level of interferon-γ was significantly increased after leptin stimulation in vitro (p = 0.0217). In mice, Leptin deficiency resulted in less severe hair depigmentation. Leptin deficiency also resulted in significantly lower expressed vitiligo-related genes, such as Cxcl9 (p = 0.0497), Gzmb (p < 0.001), Ifng (p = 0.0159), and Mx1 (p < 0.001) after modeling.

Conclusion

Leptin could promote the progression of vitiligo by enhancing the cytotoxic function of CD8+ T cells. Leptin may become a new target for vitiligo treatment.
Knowledge mapping of immune thrombocytopenia: a bibliometric study
Authors: Wu Feifeng , Li Cuifang , Mao Jueyi , Zhu Junquan , Wang Yang , Wen Chuan
Published: May 2023

Background

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. Recently, the pathophysiology and novel drugs of ITP have been the focus of researchers with plenty of publications emerging. Bibliometrics is the process of extracting measurable data through statistical analysis of published research studies to provide an insight into the trends and hotspots.

Objective

This study aimed to provide an insight into developing trends and hotspots in the field of ITP by bibliometric analysis.

Methods

By using three bibliometric mapping tools (bibliometrix R package, VOSviewer, CiteSpace), we summarized the overview information of retrieved publications, as well as the analysis of keyword co-occurrence and reference co-citation.

Results

A total of 3299 publications with 78066 citations on ITP research were included in the analysis. The keyword co-occurrence network identified 4 clusters relating to the diagnosis, pathophysiology, and treatment of ITP respectively. Then the reference co-citation analysis produced 12 clusters with a well-structured and highly credible clustering model, and they can be divided into 5 trends: second-line treatment, chronic ITP, novel therapy and pathogenesis, COVID-19 vaccine. Treg cells, spleen tyrosine kinase, and mesenchymal stem cells were the latest hotspots with strong burstness.

Conclusion

This bibliometric analysis provided a comprehensive insight into research hotspots and trends on ITP, which would enrich the review of the ITP research.
Integrating machine learning and single-cell trajectories to analyze T-cell exhaustion to predict prognosis and immunotherapy in colon cancer patients
Authors: Shen Xiaogang , Zuo Xiaofei , Liang Liang , Wang Lin , Luo Bin
Published: May 2023

Introduction

The incidence of colon adenocarcinoma (COAD) has recently increased, and patients with advanced COAD have a poor prognosis due to treatment resistance. Combining conventional treatment with targeted therapy and immunotherapy has shown unexpectedly positive results in improving the prognosis of patients with COAD. More study is needed to determine the prognosis for patients with COAD and establish the appropriate course of treatment.

Methods

This study aimed to explore the trajectory of T-cell exhaustion in COAD to predict the overall survival and treatment outcome of COAD patients. Clinical data were derived from the TCGA-COAD cohort through "UCSC", as well as the whole genome data. Prognostic genes driving T-cell trajectory differentiation were identified on the basis of single-cell trajectories and univariate Cox regression. Subsequently, T-cell exhaustion score (TES) was created by iterative LASSO regression. The potential biological logic associated with TES was explored through functional analysis, immune microenvironment assessment, immunotherapy response prediction, and in vitro experiments.

Results

Data showed that patients with significant TES had fewer favorable outcomes. Expression, proliferation, and invasion of COAD cells treated with TXK siRNA were also examined by cellular experiments. Both univariate and multivariate Cox regression indicated that TES was an independent prognostic factor in patients with COAD; in addition, subgroup analysis supported this finding. Functional assay revealed that immune response and cytotoxicity pathways are associated with TES, as the subgroup with low TES has an active immune microenvironment. Furthermore, patients with low TES responded better to chemotherapy and immunotherapy.

Conclusion

In this study, we systematically explored the T-cell exhaustion trajectory in COAD and developed a TES model to assess prognosis and provide guidelines for the treatment decision. This discovery gave rise to a fresh concept for novel therapeutic procedures for the clinical treatment of COAD.
Effects of HLA single chain trimer design on peptide presentation and stability
Authors: Finton Kathryn A. K. , Rupert Peter B. , Friend Della J. , Dinca Ana , Lovelace Erica S. , Buerger Matthew , Rusnac Domnita V. , Foote-McNabb Ulysses , Chour William , Heath James R. , Campbell Jean S. , Pierce Robert H. , Strong Roland K.
Published: May 2023

MHC class I “single-chain trimer” molecules, coupling MHC heavy chain, β2-microglobulin, and a specific peptide into a single polypeptide chain, are widely used in research. To more fully understand caveats associated with this design that may affect its use for basic and translational studies, we evaluated a set of engineered single-chain trimers with combinations of stabilizing mutations across eight different classical and non-classical human class I alleles with 44 different peptides, including a novel human/murine chimeric design. While, overall, single-chain trimers accurately recapitulate native molecules, care was needed in selecting designs for studying peptides longer or shorter than 9-mers, as single-chain trimer design could affect peptide conformation. In the process, we observed that predictions of peptide binding were often discordant with experiment and that yields and stabilities varied widely with construct design. We also developed novel reagents to improve the crystallizability of these proteins and confirmed novel modes of peptide presentation.
Bivalent binding of staphylococcal superantigens to the TCR and CD28 triggers inflammatory signals independently of antigen presenting cells
Authors: Kunkl Martina , Amormino Carola , Spallotta Francesco , Caristi Silvana , Fiorillo Maria Teresa , Paiardini Alessandro , Kaempfer Raymond , Tuosto Loretta
Published: May 2023

Staphylococcus aureus superantigens (SAgs) such as staphylococcal enterotoxin A (SEA) and B (SEB) are potent toxins stimulating T cells to produce high levels of inflammatory cytokines, thus causing toxic shock and sepsis. Here we used a recently released artificial intelligence-based algorithm to better elucidate the interaction between staphylococcal SAgs and their ligands on T cells, the TCR and CD28. The obtained computational models together with functional data show that SEB and SEA are able to bind to the TCR and CD28 stimulating T cells to activate inflammatory signals independently of MHC class II- and B7-expressing antigen presenting cells. These data reveal a novel mode of action of staphylococcal SAgs. By binding to the TCR and CD28 in a bivalent way, staphylococcal SAgs trigger both the early and late signalling events, which lead to massive inflammatory cytokine secretion.
Algorithm to improve the diagnosis of paraneoplastic neurological syndromes associated with SOX1 antibodies
Authors: Arnaldos-Pérez Cristina , Vilaseca Andreu , Naranjo Laura , Sabater Lidia , Dalmau Josep , Ruiz-García Raquel , Graus Francesc
Published: May 2023

SOX1 antibodies (SOX1-abs) are associated with paraneoplastic neurological syndromes (PNS) and small cell lung cancer (SCLC). In many clinical laboratories SOX1-abs are determined by commercial line blots without confirmation by cell-based assay (CBA) with HEK293 cells expressing SOX1. However, the diagnostic yield of commercial line blots is low and the accessibility to the CBA, that is not commercially available, limited. Here, we evaluated if the addition of the band intensity data of the line blot and the immunoreactivity in a tissue-based assay (TBA) improve the diagnostic performance of the line blot. We examined serum of 34 consecutive patients with adequate clinical information that tested positive for SOX1-abs in a commercial line blot. Samples were also assessed by TBA and CBA. SOX1-abs were confirmed by CBA in 17 (50%) patients, all (100%) had lung cancer (SCLC in 16) and 15/17 (88%) had a PNS. In the remaining 17 patients the CBA was negative and none had PNS associated with lung cancer. TBA was assessable in 30/34 patients and SOX1-abs reactivity was detected in 15/17 (88%) with positive and in 0/13 (0%) with negative CBA. Only 2 (13%) of the 15 TBA-negative patients were CBA-positive. The frequency of TBA-negative but CBA-positive increased from 10% (1/10) when the band intensity of the line blot was weak to 20% (1/5) in patients with a moderate or strong intensity band. Confirmation by CBA should be mandatory for samples (56% in this series) not assessable (4/34; 12%) or negative in the TBA (15/34; 44%).
Clinically practical pharmacometrics computer model to evaluate and personalize pharmacotherapy in pediatric rare diseases: application to Graves' disease
Authors: Steffens Britta , Koch Gilbert , Gächter Pascal , Claude Fabien , Gotta Verena , Bachmann Freya , Schropp Johannes , Janner Marco , l'Allemand Dagmar , Konrad Daniel , Welzel Tatjana , Szinnai Gabor , Pfister Marc
Published: May 2023

Objectives

Graves' disease (GD) with onset in childhood or adolescence is a rare disease (ORPHA:525731). Current pharmacotherapeutic approaches use antithyroid drugs, such as carbimazole, as monotherapy or in combination with thyroxine hormone substitutes, such as levothyroxine, as block-and-replace therapy to normalize thyroid function and improve patients' quality of life. However, in the context of fluctuating disease activity, especially during puberty, a considerable proportion of pediatric patients with GD is suffering from thyroid hormone concentrations outside the therapeutic reference ranges. Our main goal was to develop a clinically practical pharmacometrics computer model that characterizes and predicts individual disease activity in children with various severity of GD under pharmacotherapy.

Methods

Retrospectively collected clinical data from children and adolescents with GD under up to two years of treatment at four different pediatric hospitals in Switzerland were analyzed. Development of the pharmacometrics computer model is based on the non-linear mixed effects approach accounting for inter-individual variability and incorporating individual patient characteristics. Disease severity groups were defined based on free thyroxine (FT4) measurements at diagnosis.

Results

Data from 44 children with GD (75% female, median age 11 years, 62% receiving monotherapy) were analyzed. FT4 measurements were collected in 13, 15, and 16 pediatric patients with mild, moderate, or severe GD, with a median FT4 at diagnosis of 59.9 pmol/l (IQR 48.4, 76.8), and a total of 494 FT4 measurements during a median follow-up of 1.89 years (IQR 1.69, 1.97). We observed no notable difference between severity groups in terms of patient characteristics, daily carbimazole starting doses, and patient years. The final pharmacometrics computer model was developed based on FT4 measurements and on carbimazole or on carbimazole and levothyroxine doses involving two clinically relevant covariate effects: age at diagnosis and disease severity.

Discussion

We present a tailored pharmacometrics computer model that is able to describe individual FT4 dynamics under both, carbimazole monotherapy and carbimazole/levothyroxine block-and-replace therapy accounting for inter-individual disease progression and treatment response in children and adolescents with GD. Such clinically practical and predictive computer model has the potential to facilitate and enhance personalized pharmacotherapy in pediatric GD, reducing over- and underdosing and avoiding negative short- and long-term consequences. Prospective randomized validation trials are warranted to further validate and fine-tune computer-supported personalized dosing in pediatric GD and other rare pediatric diseases.
Trichoderma and its role in biological control of plant fungal and nematode disease
Authors: Yao Xin , Guo Hailin , Zhang Kaixuan , Zhao Mengyu , Ruan Jingjun , Chen Jie
Published: May 2023

Trichoderma is mainly used to control soil-borne diseases as well as some leaf and panicle diseases of various plants. Trichoderma can not only prevent diseases but also promotes plant growth, improves nutrient utilization efficiency, enhances plant resistance, and improves agrochemical pollution environment. Trichoderma spp. also behaves as a safe, low-cost, effective, eco-friendly biocontrol agent for different crop species. In this study, we introduced the biological control mechanism of Trichoderma in plant fungal and nematode disease, including competition, antibiosis, antagonism, and mycoparasitism, as well as the mechanism of promoting plant growth and inducing plant systemic resistance between Trichoderma and plants, and expounded on the application and control effects of Trichoderma in the control of various plant fungal and nematode diseases. From an applicative point of view, establishing a diversified application technology for Trichoderma is an important development direction for its role in the sustainable development of agriculture.
Alteration of gastric microbiota and transcriptome in a rat with gastric intestinal metaplasia induced by deoxycholic acid
Authors: Xu Zijing , Xiao Ling , Wang Shuaishuai , Cheng Yuqin , Wu Jianping , Meng Yufen , Bao Kaifan , Zhang Junfeng , Cheng Chun
Published: May 2023

Objective

Bile reflux plays a key role in the development of gastric intestinal metaplasia (GIM), an independent risk factor of gastric cancer. Here, we aimed to explore the biological mechanism of GIM induced by bile reflux in a rat model.

Methods

Rats were treated with 2% sodium salicylate and allowed to freely drink 20 mmol/L sodium deoxycholate for 12 weeks, and GIM was confirmed by histopathological analysis. Gastric microbiota was profiled according to the 16S rDNA V3–V4 region, gastric transcriptome was sequenced, and serum bile acids (BAs) were analyzed by targeted metabolomics. Spearman's correlation analysis was used in constructing the network among gastric microbiota, serum BAs, and gene profiles. Real-time polymerase chain reaction (RT-PCR) measured the expression levels of nine genes in the gastric transcriptome.

Results

In the stomach, deoxycholic acid (DCA) decreased the microbial diversity but promoted the abundances of several bacterial genera, such as Limosilactobacillus, Burkholderia–Caballeronia–Paraburkholderia, and Rikenellaceae RC9 gut group. Gastric transcriptome showed that the genes enriched in gastric acid secretion were significantly downregulated, whereas the genes enriched in fat digestion and absorption were obviously upregulated in GIM rats. The GIM rats had four promoted serum BAs, namely cholic acid (CA), DCA, taurocholic acid, and taurodeoxycholic acid. Further correlation analysis showed that the Rikenellaceae RC9 gut group was significantly positively correlated with DCA and RGD1311575 (capping protein-inhibiting regulator of actin dynamics), and RGD1311575 was positively correlated with Fabp1 (fatty acid-binding protein, liver), a key gene involved in fat digestion and absorption. Finally, the upregulated expression of Dgat1 (diacylglycerol acyltransferase 1) and Fabp1 related to fat digestion and absorption was identified by RT-PCR and IHC.

Conclusion

DCA-induced GIM enhanced gastric fat digestion and absorption function and impaired gastric acid secretion function. The DCA–Rikenellaceae RC9 gut group–RGD1311575/Fabp1 axis might play a key role in the mechanism of bile reflux-related GIM.
Role of piRNA biogenesis and its neuronal function in the development of neurodegenerative diseases
Authors: Sato Kaoru , Takayama Ken-ichi , Inoue Satoshi
Published: May 2023

Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by neuronal loss and dysfunction. Despite remarkable improvements in our understanding of these pathogeneses, serious worldwide problems with significant public health burdens are remained. Therefore, new efficient diagnostic and therapeutic strategies are urgently required. PIWI-interacting RNAs (piRNAs) are a major class of small non-coding RNAs that silence gene expression through transcriptional and post-transcriptional processes. Recent studies have demonstrated that piRNAs, originally found in the germ line, are also produced in non-gonadal somatic cells, including neurons, and further revealed the emerging roles of piRNAs, including their roles in neurodevelopment, aging, and neurodegenerative diseases. In this review, we aimed to summarize the current knowledge regarding the piRNA roles in the pathophysiology of neurodegenerative diseases. In this context, we first reviewed on recent updates on neuronal piRNA functions, including biogenesis, axon regeneration, behavior, and memory formation, in humans and mice. We also discuss the aberrant expression and dysregulation of neuronal piRNAs in neurodegenerative diseases, such as AD, PD, and ALS. Moreover, we review pioneering preclinical studies on piRNAs as biomarkers and therapeutic targets. Elucidation of the mechanisms underlying piRNA biogenesis and their functions in the brain would provide new perspectives for the clinical diagnosis and treatment of AD and various neurodegenerative diseases.
Multimodal monitoring: practical recommendations (dos and don'ts) in challenging situations and uncertainty
Authors: Sharma Rohan , Tsikvadze Mariam , Peel Jeffrey , Howard Levi , Kapoor Nidhi , Freeman William D.
Published: May 2023

With the advancements in modern medicine, new methods are being developed to monitor patients in the intensive care unit. Different modalities evaluate different aspects of the patient's physiology and clinical status. The complexity of these modalities often restricts their use to the realm of clinical research, thereby limiting their use in the real world. Understanding their salient features and their limitations can aid physicians in interpreting the concomitant information provided by multiple modalities to make informed decisions that may affect clinical care and outcomes. Here, we present a review of the commonly used methods in the neurological intensive care unit with practical recommendations for their use.
Surface electromyography in the assessment of masticatory muscle activity in patients with pain-related temporomandibular disorders: a systematic review
Authors: Szyszka-Sommerfeld Liliana , Sycińska-Dziarnowska Magdalena , Spagnuolo Gianrico , Woźniak Krzysztof
Published: May 2023

Background

Temporomandibular disorders (TMD) are a set of painful conditions affecting the orofacial region that are prevalent and constitute the most frequent type of non-dental pain complaint in the maxillofacial area. Pain-related TMD (TMD-P) is characterized by ongoing pain in the masticatory muscles, the temporomandibular joint, or surrounding structures. Due to the multiple factors that contribute to the development of this condition, it can be challenging to accurately diagnose. One of the useful method for assessing patients with TMD-P is surface electromyography (sEMG). The aim of this systematic review was to provide a comprehensive overview of the current scientific literature on the evaluation of masticatory muscle activity (MMA) in individuals diagnosed with TMD-P, through the utilization of sEMG.

Methods

To gather relevant information, electronic databases such as PubMed, Web of Science, Scopus, and Embase were searched using specific keywords including: “pain” AND (“temporomandibular disorder*” OR “temporomandibular dysfunction*”) AND “surface electromyography” AND “masticatory muscle activity.” The inclusion criteria were studies assessing MMA in patients with TMD-P using sEMG. The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies was utilized to evaluate the quality of the studies that were included in the review.

Results

The search strategy identified 450 potential articles. Fourteen papers met the inclusion criteria. Global quality rating for significant part of the articles was weak. Most studies showed greater sEMG activity of the masseter (MM) and temporal anterior (TA) muscles at rest in TMD-P subjects than in the asymptomatic controls, while the MM and TA muscles were less active in the pain-related TMD group compared to the non-TMD group during maximal voluntary clenching (MVC).

Conclusion

There were differences in MMA in the TMD-pain population compared to a healthy control group during various tasks. The diagnostic efficacy of surface electromyography in assessing individuals with TMD-P remains unclear.
The regulations on cortical activation and functional connectivity of the dorsolateral prefrontal cortex-primary somatosensory cortex elicited by acupuncture with reinforcing-reducing manipulation
Authors: Cao Jingya , Qu Yuzhu , Chen Li , Liu Tianyu , Guo Jing , Gong Yulai , Tian Zilei , Xiong Jing , Lin Zhenfang , Yang Xin , Yin Tao , Zeng Fang
Published: May 2023

Introduction

Traditional acupuncture with reinforcing-reducing manipulation is essential for clinical effectiveness, whereas the underlying central mechanism of it remains unknown. This study with multiple-channels functional near-infrared spectroscopy (fNIRS) aims to explore cerebral-response modes during acupuncture with reinforcing-reducing manipulations.

Materials and methods

Functional near-infrared spectroscopy data were recorded from 35 healthy participants during the lifting-thrusting reinforcing manipulation, the lifting-thrusting reducing manipulation, and the even reinforcing-reducing manipulation with lifting-thrusting. The general linear model based (GLM) cortical activation analysis and the functional connectivity (FC) based on region of interest (ROI) analysis were combined to be conducted.

Results

In comparison with the baseline, the results showed that three acupuncture with reinforcing-reducing manipulations similarly induced the hemodynamic responses in the bilateral dorsolateral prefrontal cortex (DLPFC) and increased FC between the DLPFC and primary somatosensory cortex (S1). Specifically, the even reinforcing-reducing manipulation deactivated the bilateral DLPFC, the frontopolar area (FP), the right primary motor cortex (M1), the bilateral S1, and the bilateral secondary somatosensory cortex (S2); The reducing manipulation deactivated the bilateral DLPFC; The reinforcing manipulation activated the bilateral DLPFC, the left S1, and the right S2. The between-group comparisons indicated that the reinforcing-reducing manipulation induced opposite hemodynamic responses in the bilateral DLPFC and the left S1 and exhibited different FC patterns in the left DLPFC-S1, within the right DLPFC, and between the left S1 and the left orbitofrontal cortex (OFC).

Conclusion

These findings verified the feasibility of fNIRS for investigating cerebral functional activities of acupuncture manipulations, suggesting that the regulations on the DLPFC-S1 cortex may be the potential central mechanism for the realization of acupuncture with reinforcing-reducing manipulation’s effect.

Clinical trial registration

ClinicalTrials.gov, identifier, ChiCTR2100051893.
Association between serum cystatin C level and cognition in older adults: a cross-sectional analysis
Authors: Wang Shuli , Lin Xuechun , Zhou Jie , Li Meng , Song Dan
Published: May 2023

Introduction

Serum Cystatin C level, an indication of kidney function, has been implicated in the pathogenesis of Alzheimer’s disease and cognitive impairment. In this cross-sectional study, we looked into the relation between serum Cystatin C levels and cognition in a group of U.S. older adults.

Method

The data of this study were from the National Health and Nutrition Examination Survey (NHANES) 1999–2002. A total of 4,832 older adults aged ≥60 who met the inclusion criteria were included. The Dade Behring N Latex Cystatin C assay, which is a particle-enhanced nephelometric assay (PENIA), was utilized to assess Cystatin C levels in participants’ blood samples. Participants’ cognition was examined using the digit symbol substitution test (DSST). Z-scores of the DSST were calculated based on sample means and standard deviations (SD). To investigate the relationships between the quartiles of serum Cystatin C level and DSST z scores, multiple linear regression models were developed while controlling for age, sex, race/ethnicity, and education.

Results

The average age of the participants was 71.1 (SD 7.8). The participants were about half female (50.5%), non-Hispanic White (61.2%), and (36.1%) who had completed at least some college. They had an average serum Cystatin C level of 1.0 mg/dl (SD 0.44). After performing multiple linear regression with a reference group consisting of participants in quartile one of plasma Cystatin C levels, we found that serum Cystatin C levels in quartiles three and four were independently associated with lower DSST z scores (β = −0.059, 95% CI −0.200 to −0.074 and β = −0.108, 95% CI −0.319 to −0.184, respectively).

Conclusion

Higher serum Cystatin C level is associated with worse processing speed, sustained attention, and working memory in older adults. Cystatin C level may be a biomarker for cognitive decline in older adults.
FDXR drives primary and endocrine-resistant tumor cell growth in ER+ breast cancer via CPT1A-mediated fatty acid oxidation
Authors: Yan Chaojun , Gao Ronghui , Gao Chuan , Hong Kai , Cheng Meng , Liu Xiaojing , Zhang Qing , Zhang Jing
Published: May 2023

Background

The majority of breast cancers (BCs) expressing estrogen receptor (ER) have shown endocrine resistance. Our previous study demonstrated that ferredoxin reductase (FDXR) promoted mitochondrial function and ER+ breast tumorigenesis. But the underlying mechanism is not clear.

Methods

Liquid chromatography (LC) tandem mass spectrometry (MS/MS)-based metabolite profiling was utilized to reveal the metabolites regulated by FDXR. RNA microarray was utilized to determine the potential downstream targets of FDXR. Seahorse XF24 analyzer was performed to analyze the FAO-mediated oxygen consumption rate (OCR). Q-PCR and western blotting assays were used to measure expression levels of FDXR and CPT1A. MTS, 2D colony formation and anchorage-independent growth assays were used to evaluate the effects of FDXR or drug treatments on tumor cell growth of primary or endocrine-resistant breast cancer cells.

Results

We found that depletion of FDXR inhibited fatty acid oxidation (FAO) by suppressing CPT1A expression. Endocrine treatment increased the expression levels of both FDXR and CPT1A. Further, we showed that depletion of FDXR or FAO inhibitor etomoxir treatment reduced primary and endocrine-resistant breast cancer cell growth. Therapeutically, combining endocrine therapy with FAO inhibitor etomoxir synergistically inhibits primary and endocrine-resistant breast cancer cell growth.

Discussion

We reveal that the FDXR-CPT1A-FAO signaling axis is essential for primary and endocrine-resistant breast cancer cell growth, thus providing a potential combinatory therapy against endocrine resistance in ER+ breast cancer.
Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles
Authors: Soltys Bohdan J. , Grausam Katie B. , Messerli Shanta M. , Hsia Carleton J. C. , Zhao Haotian
Published: May 2023

Medulloblastoma is a tumor of the cerebellum that metastasizes to the leptomeninges of the central nervous system (CNS), including to forebrain and to spinal cord. The inhibitory effect of polynitroxylated albumin (PNA), a caged nitroxide nanoparticle, on leptomeningeal dissemination and metastatic tumor growth was studied in a Sonic Hedgehog transgenic mouse model. PNA treated mice showed an increased lifespan with a mean survival of 95 days (n = 6, P<0.05) compared with 71 days in controls. In primary tumors, proliferation was significantly reduced and differentiation was significantly increased (P<0.001) as shown by Ki-67+ and NeuN+ immunohistochemistry, while cells in spinal cord tumors appeared unaffected. Yet, histochemical analysis of metastatic tumor in spinal cord showed that the mean total number of cells in spinal cord was significantly reduced in mice treated with PNA compared to albumin vehicle (P<0.05). Examination of various levels of the spinal cord showed that PNA treated mice had significantly reduced metastatic cell density in the thoracic, lumbar and sacral spinal cord levels (P<0.05), while cell density in the cervical region was not significantly changed. The mechanism by which PNA may exert these effects on CNS tumors is discussed.
Preoperative computed tomography-based tumoral radiomic features prediction for overall survival in resectable non-small cell lung cancer
Authors: Peng Bo , Wang Kaiyu , Xu Ran , Guo Congying , Lu Tong , Li Yongchao , Wang Yiqiao , Wang Chenghao , Chang Xiaoyan , Shen Zhiping , Shi Jiaxin , Xu Chengyu , Zhang Linyou
Published: May 2023

Objectives

The purpose of this study was to evaluate whether preoperative radiomics features could meliorate risk stratification for the overall survival (OS) of non-small cell lung cancer (NSCLC) patients.

Methods

After rigorous screening, the 208 NSCLC patients without any pre-operative adjuvant therapy were eventually enrolled. We segmented the 3D volume of interest (VOI) based on malignant lesion of computed tomography (CT) imaging and extracted 1542 radiomics features. Interclass correlation coefficients (ICC) and LASSO Cox regression analysis were utilized to perform feature selection and radiomics model building. In the model evaluation phase, we carried out stratified analysis, receiver operating characteristic (ROC) curve, concordance index (C-index), and decision curve analysis (DCA). In addition, integrating the clinicopathological trait and radiomics score, we developed a nomogram to predict the OS at 1 year, 2 years, and 3 years, respectively.

Results

Six radiomics features, including gradient_glcm_InverseVariance, logarithm_firstorder_Median, logarithm_firstorder_RobustMeanAbsoluteDeviation, square_gldm_LargeDependenceEmphasis, wavelet_HLL_firstorder_Kurtosis, and wavelet_LLL_firstorder_Maximum, were selected to construct the radiomics signature, whose areas under the curve (AUCs) for 3-year prediction reached 0.857 in the training set (n=146) and 0.871 in the testing set (n=62). The results of multivariate analysis revealed that the radiomics score, radiological sign, and N stage were independent prognostic factors in NSCLC. Moreover, compared with clinical factors and the separate radiomics model, the established nomogram exhibited a better performance in predicting 3-year OS.

Conclusions

Our radiomics model may provide a promising non-invasive approach for preoperative risk stratification and personalized postoperative surveillance for resectable NSCLC patients.
Young patients show poor efficacy for immune checkpoint inhibitor combined therapy in metastatic gastrointestinal cancers
Authors: Wang Yingnan , Zhang Shasha , Zhang Fengbin , Wang Lei , Wu Chensi , Zhang Xiaoyun , Zhang Ruixing , Guo Zhanjun
Published: May 2023

Background

The impact of age on the efficacy and safety of immunotherapy remains controversial. The previous studies simply classified patients into younger and older groups, which might not reflect the real impact of young age on immunotherapy efficacy. The current study aimed to explore the efficacy and safety of immune checkpoint inhibitor (ICI) combined therapy in young (aged 18–44 years), middle-aged (aged 45–65 years), and old (aged >65 years) patients with metastatic gastrointestinal cancers (GICs), and further determine the role of immunotherapy in young patients.

Methods

Patients with metastatic GIC including esophageal cancer (EC), gastric cancer (GC), hepatocellular cancer (HCC), and biliary tract cancer (BTC) who received ICI combination therapy were enrolled, divided into young (aged 18–44 years), middle-aged (aged 45–65 years), and old (aged >65 years) groups. The clinical characteristics, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared among three groups.

Results

A total of 254 patients were finally included, with 18, 139, and 97 cases in the young (aged 18–44 years), middle-aged (aged 45–65 years), and old (aged >65 years) groups, respectively. Compared to middle-aged and old patients, young patients had lower DCR (all p < 0.05) and also had inferior PFS (p < 0.001) and OS (p = 0.017). The multivariate analyses showed that young age was an independent prognostic factor for PFS [hazard ratio (HR) 3.474, 95% confidence interval (CI) 1.962–6.150, p < 0.001] and OS (HR 2.740, 95% CI 1.348–5.570, p = 0.005). Subsequent safety analyses referring to irAEs demonstrated no significant differences for distribution frequency among each age group (all p > 0.05), whereas patients with irAEs displayed better DCR (p = 0.035) and PFS (p = 0.037).

Conclusion

Younger GIC patients (aged 18–44 years) showed poor efficacy for ICI combined therapy, and irAEs could be used as a clinical biomarker to predict ICI efficacy in metastatic GIC patients.