bluuebunny/crossref_metadata_2025 huggingface dataset:
Amount of bird suitable areas under climate change is modulated by morphological, ecological and geographical traits
Authors: Mota Flávio Mariano Machado , Heming Neander Marcel , Morante-Filho José Carlos , Talora Daniela Custódio
Published: September 2022

Biodiversity is already experiencing the effects of climate change through range expansion, retraction, or relocation, potentializing negative effects of other threats. Future projections already indicate richness reduction and composition modifications of bird communities due to global warming, which may disrupt the provision of key ecological services to ecosystem maintenance. Here, we systematically review the effect of morphological, ecological, and geographical traits on the amount of future suitable area for birds worldwide. Specifically, we tested whether body mass, diet, habitat type, movement pattern, range size, and biogeographic realm affect birds' suitable area. Our search returned 75 studies that modeled the effects of climate change on 1,991 bird species. Our analyses included 1,661 species belonging to 128 families, representing 83% of the total, for which we were able to acquire all the six traits. The proportion of birds' suitable area was affected by range size, body mass, habitat type, and biogeographic realm, while diet and movement pattern showed lower relative importance and were not included in our final model. Contrary to expectations, the proportion of birds' suitable area was negatively related to range size, which may be explained by higher climatic stability predicted in certain areas that harbor species with restricted distribution. In contrast, we observed that birds presenting higher body mass will show an increase of the proportion of suitable area in the future. This is expected due to the high exposure of smaller birds to environmental changes and their difficulty to keep thermoregulation. Our results also indicated a low proportion of suitable area to forest-dependent birds, which is in accordance with their higher vulnerability due to specific requirements for reproduction and feeding. Finally, the proportion of suitable area was low for birds from Oceania, which is expected since the region encompasses small islands isolated from continents, preventing their species from reaching new suitable areas. Our study highlights that different traits should be considered when assessing extinction risk of species based on future projections, helping to improve bird conservation, especially the most vulnerable to climate change.
Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation
Authors: Jiang Feng , Zhang Weiwei , Lu Hongdan , Tan Meiling , Zeng Zhicong , Song Yinzhi , Ke Xiao , Lin Fengxia
Published: September 2022

Inflammatory immune response is apparently one of the determinants of progressive exacerbation of valvular atrial fibrillation(VAF). Ferroptosis, an iron-dependent modality of regulated cell death, is involved in the immune regulation of cardiovascular disease. However, the relevant regulatory mechanisms of immune infiltration and ferroptosis in VAF have been less studied. In the current study, a highly efficient system for screening immunity- and ferroptosis-related biomarkers and immunomodulatory ability of herbal ingredients has been developed with the integration of intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. VAF patients showed higher infiltration of neutrophils and resting stage dendritic cells, while VSR patients showed higher infiltration of follicular helper T cells. In addition, six (e.g., PCSK2) and 47 (e.g., TGFBR1) ImmDEGs and one (SLC38A1) and four (TGFBR1, HMGB1, CAV1, and CD44) FerDEGs were highly expressed in patients with valvular sinus rhythm (VSR) and VAF, respectively. We further identified a core subnetwork containing 34 hub genes, which were intersected with ImmDEGs and FerDEGs to obtain the key gene TGFBR1. Based on TGFBR1, 14 herbs (e.g., Fructus zizyphi jujubae, Semen Juglandis, and Polygonum cuspidatum) and six herbal ingredients (curcumin, curcumine, D-glucose, hexose, oleovitamin A, and resveratrol) were predicted. Finally, TGFBR1 was found to dock well with curcumin and resveratrol, and it was further verified that curcumin and resveratrol could significantly reduce myocardial fibrosis. We believe that herbs rich in curcumin and resveratrol such as Rhizoma curcumae longae and Curcuma kwangsiensis, mitigate myocardial fibrosis to improve VAF by modulating the TGFβ/Smad signaling pathway. This strategy provides a prospective approach systemically characterizing phenotype-target-herbs relationships based on the tissue-specific biological functions in VAF and brings us new insights into the searching lead compounds from Chinese herbs.
Double cytoplast embryonic cloning improves in vitro but not in vivo development from mitotic pluripotent cells in cattle
Authors: Appleby Sarah Jane , Misica‐Turner Pavla , Oback Fleur Catherine , Dhali Arindam , McLean Zachariah Louis , Oback Björn
Published: September 2022

Cloning multiple animals from genomically selected donor embryos is inefficient but would accelerate genetic gain in dairy cattle breeding. To improve embryo cloning efficiency, we explored the idea that epigenetic reprogramming improves when donor cells are in mitosis. We derived primary cultures from bovine inner cell mass (ICM) cells of in vitro fertilized (IVF) embryos. Cells were grown feeder-free in a chemically defined medium with increased double kinase inhibition (2i+). Adding recombinant bovine interleukin 6 to 2i+ medium improved plating efficiency, outgrowth expansion, and expression of pluripotency-associated epiblast marker genes (NANOG, FGF4, SOX2, and DPPA3). For genotype multiplication by embryonic cell transfer (ECT) cloning, primary colonies were treated with nocodazole, and single mitotic donors were harvested by mechanical shake-off. Immunofluorescence against phosphorylated histone 3 (P-H3) showed 37% of nocodazole-treated cells in metaphase compared to 6% in DMSO controls (P < 1 × 10−5), with an average of 53% of P-H3-positive cells expressing the pluripotency marker SOX2. We optimized several parameters (fusion buffer, pronase treatment, and activation timing) for ECT with mitotic embryonic donors. Sequential double cytoplast ECT, whereby another cytoplast was fused to the first cloned reconstruct, doubled cloned blastocyst development and improved morphological embryo quality. However, in situ karyotyping revealed that over 90% of mitotic ECT-derived blastocysts were tetraploid or aneuploid with extra chromosomes, compared to less than 2% in the original ICM donor cells. Following the transfer of single vs. double cytoplast embryos, there was no difference between the two methods in pregnancy establishment at D35 (1/22 = 5% vs. 4/53 = 8% for single vs. double ECT, respectively). Overall, post-implantation development was drastically reduced from embryonic mitotic clones when compared to somatic interphase clones and IVF controls. We conclude that mitotic donors cause ploidy errors during in vitro development that cannot be rescued by enhanced epigenetic reprogramming through double cytoplast cloning.
A novel diagnostic four-gene signature for hepatocellular carcinoma based on artificial neural network: Development, validation, and drug screening
Authors: Chen Min , Wu Guang-Bo , Xie Zhi-Wen , Shi Dan-Li , Luo Meng
Published: September 2022

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers with high mortality in the world. HCC screening and diagnostic models are becoming effective strategies to reduce mortality and improve the overall survival (OS) of patients. Here, we expected to establish an effective novel diagnostic model based on new genes and explore potential drugs for HCC therapy.

Methods: The gene expression data of HCC and normal samples (GSE14811, GSE60502, GSE84402, GSE101685, GSE102079, GSE113996, and GSE45436) were downloaded from the Gene Expression Omnibus (GEO) dataset. Bioinformatics analysis was performed to distinguish two differentially expressed genes (DEGs), diagnostic candidate genes, and functional enrichment pathways. QRT-PCR was used to validate the expression of diagnostic candidate genes. A diagnostic model based on candidate genes was established by an artificial neural network (ANN). Drug sensitivity analysis was used to explore potential drugs for HCC. CCK-8 assay was used to detect the viability of HepG2 under various presentative chemotherapy drugs.

Results: There were 82 DEGs in cancer tissues compared to normal tissue. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and infiltrating immune cell analysis were administered and analyzed. Diagnostic-related genes of MT1M, SPINK1, AKR1B10, and SLCO1B3 were selected from DEGs and used to construct a diagnostic model. The receiver operating characteristic (ROC) curves were 0.910 and 0.953 in the training and testing cohorts, respectively. Potential drugs, including vemurafenib, LOXO-101, dabrafenib, selumetinib, Arry-162, and NMS-E628, were found as well. Vemurafenib, dabrafenib, and selumetinib were observed to significantly affect HepG2 cell viability.

Conclusion: The diagnostic model based on the four diagnostic-related genes by the ANN could provide predictive significance for diagnosis of HCC patients, which would be worthy of clinical application. Also, potential chemotherapy drugs might be effective for HCC therapy.
Cuproptosis-Related genes in the prognosis of colorectal cancer and their correlation with the tumor microenvironment
Authors: Wu Weiqiang , Dong Jingqing , Lv Yang , Chang Dongmin
Published: September 2022

Colorectal cancer (CRC) is a common tumor disease of the digestive system with high incidence and mortality. Cuproptosis has recently been found to be a new form of cell death. The clinical significance of cuproptosis-related genes (CRGs) in CRC is not clear. In this study, The Cancer Genome Atlas Colon and Rectal Cancer dataset was used to analyze the relationship between CRGs and clinical characteristics of CRC by differential expression analysis and Kaplan–Meier survival (K-M) analysis. Based on CRGs, prognosis model and risk score of CRC was constructed in COADREAD by multivariate Cox analysis. Receiver operating curves (ROC) analysis, K-M analysis and calibration analysis in GDC TCGA Colon Cancer dataset were applied to validating model. Subsequently, the relationship between risk score of CRC and immune microenvironment was analyzed by multiple immune score algorithms. Finally, we found that most CRGs were differentially expressed between tumors and normal tissues. Some CRGs were differentially expressed among different clinical characteristics. K-M analysis showed that the CRGs were related to overall survival (OS), disease-specific survival, and progression-free survival. Subsequently, DLAT and CDKN2A were identified as risk factors for OS in CRC by multivariate Cox analysis, and the risk score was established. K–M analysis showed that there was a significant difference in OS between the high-risk and low-risk groups, which were grouped by risk score median. ROC analysis showed that the risk score performs well in predicting the 1-year, 3-year and 5-year OS. Enrichment analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immune-related signaling pathways. Further analysis showed that there were significant differences in the levels of immune cells and stromal cells between the high- and low-risk groups. The high-risk group had higher levels of immune cells and interstitial cells. At the same time, the high-risk group had a higher immune escape ability, and the predicted immune treatment response in the high-risk group was poor. In conclusion, CRGs can be used as prognostic factors in CRC and are closely related to the levels of immune cells and stromal cells in the tumor microenvironment.
Drug repositioning for esophageal squamous cell carcinoma
Authors: Bennett Adam N. , Huang Rui Xuan , He Qian , Lee Nikki P. , Sung Wing-Kin , Chan Kei Hang Katie
Published: September 2022

Esophageal cancer (EC) remains a significant challenge globally, having the 8th highest incidence and 6th highest mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common form of EC in Asia. Crucially, more than 90% of EC cases in China are ESCC. The high mortality rate of EC is likely due to the limited number of effective therapeutic options. To increase patient survival, novel therapeutic strategies for EC patients must be devised. Unfortunately, the development of novel drugs also presents its own significant challenges as most novel drugs do not make it to market due to lack of efficacy or safety concerns. A more time and cost-effective strategy is to identify existing drugs, that have already been approved for treatment of other diseases, which can be repurposed to treat EC patients, with drug repositioning. This can be achieved by comparing the gene expression profiles of disease-states with the effect on gene-expression by a given drug. In our analysis, we used previously published microarray data and identified 167 differentially expressed genes (DEGs). Using weighted key driver analysis, 39 key driver genes were then identified. These driver genes were then used in Overlap Analysis and Network Analysis in Pharmomics. By extracting drugs common to both analyses, 24 drugs are predicted to demonstrate therapeutic effect in EC patients. Several of which have already been shown to demonstrate a therapeutic effect in EC, most notably Doxorubicin, which is commonly used to treat EC patients, and Ixazomib, which was recently shown to induce apoptosis and supress growth of EC cell lines. Additionally, our analysis predicts multiple psychiatric drugs, including Venlafaxine, as repositioned drugs. This is in line with recent research which suggests that psychiatric drugs should be investigated for use in gastrointestinal cancers such as EC. Our study shows that a drug repositioning approach is a feasible strategy for identifying novel ESCC therapies and can also improve the understanding of the mechanisms underlying the drug targets.
Case report: A novel case of parental mosaicism in SMC1A gene causes inherited Cornelia de Lange syndrome
Authors: Gil-Salvador Marta , Latorre-Pellicer Ana , Lucia-Campos Cristina , Arnedo María , Darnaude María Teresa , Díaz de Bustamante Aránzazu , Villares Rebeca , Palma Milla Carmen , Puisac Beatriz , Musio Antonio , Ramos Feliciano J. , Pié Juan
Published: September 2022

Ultimate advances in genetic technologies have permitted the detection of transmitted cases of congenital diseases due to parental gonadosomatic mosaicism. Regarding Cornelia de Lange syndrome (CdLS), up to date, only a few cases are known to follow this inheritance pattern. However, the high prevalence of somatic mosaicism recently reported in this syndrome (∼13%), together with the disparity observed in tissue distribution of the causal variant, suggests that its prevalence in this disorder could be underestimated. Here, we report a new case of parental gonadosomatic mosaicism in SMC1A gene that causes inherited CdLS, in which the mother of the patient carries the causative variant in very low allele frequencies in buccal swab and blood. While the affected child presents with typical CdLS phenotype, his mother does not show any clinical manifestations. As regards SMC1A, the difficulty of clinical identification of carrier females has been already recognized, as well as the gender differences observed in CdLS expressivity when the causal variant is found in this gene. Currently, the use of DNA deep-sequencing techniques is highly recommended when it comes to molecular diagnosis of patients, as well as in co-segregation studies. These enable us to uncover gonadosomatic mosaic events in asymptomatic or oligosymptomatic parents that had been overlooked so far, which might have great implications regarding genetic counseling for recurrence risk.
Central role of PD-L1 in cardioprotection resulting from P2Y4 nucleotide receptor loss
Authors: Horckmans Michael , Diaz Villamil Esteban , Bianchini Mariaelvy , De Roeck Lucas , Communi Didier
Published: September 2022

A better understanding of the immune function of pericardial adipose tissue is essential to adapt treatments after myocardial infarction. We showed previously that inactivation of mouse P2Y4 nucleotide receptor induces adiponectin overexpression and protection against myocardial infarction. We investigated here the inflammatory state of pericardial adipose tissue in ischemic P2Y4-deficient mice. We demonstrated that P2Y4-deficient mice displayed adipocyte beiging with increased PD-L1 expression and a higher number of regulatory leukocytes in their pericardial adipose tissue after left anterior descending artery ligation, compared to wild type mice. Effectively, a higher level of anti-inflammatory M2c macrophages and regulatory T cells was observed in pericardial adipose tissue of P2Y4 KO mice and correlated with reduced post-ischemic expansion of fat-associated lymphoid clusters. Interestingly, the anti-inflammatory effects observed in P2Y4 KO mice, were no more observed in P2Y4/adiponectin double KO ischemic mice. Finally, the reduction of T cell infiltration and cardiac fibrosis observed in P2Y4-deficient heart was lost after injection of anti-PD-L1 blocking antibody in ischemic mice. The present study defines P2Y4 as a regulator of PD-L1 and adiponectin, and as a potential target for anti-inflammatory therapies to improve myocardial infarction outcome. The combined effect of P2Y4 loss on adipocyte beiging and regulatory leukocyte increase highlights this nucleotide receptor as an important player in post-ischemic cardiac response.
SLE classification criteria: Science-based icons or algorithmic distractions – an intellectually demanding dilemma
Authors: Rekvig Ole Petter
Published: September 2022

It is, so to say, not a prerogative authority assigned to SLE classification criteria that allow them to declare something definitively important about SLE. This is particularly true as criteria-based classification processes overrule the highly needed evolution of concise diagnostic criteria. It is classification criteria that allocate SLE patients into cohorts intended to describe the nature of their disease. Therefore, all major SLE classification criteria since the 1971 preliminary criteria usurp the role of diagnostic criteria. Today´s practice silently accept that the SLE classification process “diagnose” SLE patients despite the fact that classification criteria are not accepted as diagnostic criteria! This is a central paradox in contemporary SLE research strategies. Contemporary SLE cohorts are designed to investigate SLE´s etiological features. However, each cohort that is categorized by classification criteria has one central inherent problem. From theoretical and practical arguments, they embody multiple distinct clinical phenotypes. This raises the critical and principal question if phenotypically heterogenic SLE cohorts are useful to identify basic SLE-specific etiology(ies) and disease process(es). In times to come, we must prioritize development of firm diagnostic criteria for SLE, as the classification criteria have not contributed to reduce the enigmatic character of the syndrome. No radical improvements are visible in the horizon that may lead to concise investigations of SLE in well-defined homogenous SLE cohorts. We must develop new strategies where studies of phenotypically standardized cohorts of SLE must be central elements. Problems related to contemporary SLE classification criteria are contemplated, analyzed, and critically discussed in this study.
The effect of tai chi intervention on NLRP3 and its related antiviral inflammatory factors in the serum of patients with pre-diabetes
Authors: Hu Shujuan , Hu Yingxing , Long Peilin , Li Peixiong , Chen Ping , Wang Xianwang
Published: September 2022

Background

NLRP3 inflammasome and its related antiviral inflammatory factors have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, but its contribution to pre-diabetes remains poorly understood.

Objective

To investigate the effects and the potential mechanism of Tai Chi intervention on NLRP3 inflammasome and its related inflammatory factors in the serum of middle-aged and older people with pre-diabetes mellitus (PDM).

Methods

40 pre-diabetic subjects were divided into a pre-diabetic control group (PDM-C group, N=20) and a Tai Chi group (PDM-TC group, N=20) by random number table. 10 normoglycemic subjects (NG) were selected as controls. We measured clinical metabolic parameters and collected blood samples before and after the 12 weeks of Tai Chi intervention. Antiviral inflammatory factors in serum were detected by enzyme-linked immunosorbent assay.

Results

The blood glucose, insulin resistance, and inflammation in PDM groups were higher than those in the NG group (P<0.05 and P<0.01, respectively). The results also suggested that 12 weeks of Tai Chi intervention could reduce body weight, blood pressure, blood glucose, insulin resistance, blood lipid, and the expressions of serum inflammatory factors in the pre-diabetic population.

Conclusion

Tai Chi intervention may improve blood glucose, lipid levels, and insulin resistance in middle-aged and elderly pre-diabetic patients by reducing the level of NLRP3 inflammasome and its related inflammatory factors.
Metabolomics-based investigation of SARS-CoV-2 vaccination (Sinovac) reveals an immune-dependent metabolite biomarker
Authors: He Maozhang , Huang Yixuan , Wang Yun , Liu Jiling , Han Maozhen , Xiao Yixuan , Zhang Na , Gui Hongya , Qiu Huan , Cao Liqing , Jia Weihua , Huang Shenghai
Published: September 2022

SARS-CoV-2 and its mutant strains continue to rapidly spread with high infection and fatality. Large-scale SARS-CoV-2 vaccination provides an important guarantee for effective resistance to existing or mutated SARS-CoV-2 virus infection. However, whether the host metabolite levels respond to SARS-CoV-2 vaccine-influenced host immunity remains unclear. To help delineate the serum metabolome profile of SARS-CoV-2 vaccinated volunteers and determine that the metabolites tightly respond to host immune antibodies and cytokines, in this study, a total of 59 sera samples were collected from 30 individuals before SARS-CoV-2 vaccination and from 29 COVID-19 vaccines 2 weeks after the two-dose vaccination. Next, untargeted metabolomics was performed and a distinct metabolic composition was revealed between the pre-vaccination (VB) group and two-dose vaccination (SV) group by partial least squares-discriminant and principal component analyses. Based on the criteria: FDR < 0.05, absolute log2 fold change greater than 0.25, and VIP >1, we found that L-glutamic acid, gamma-aminobutyric acid (GABA), succinic acid, and taurine showed increasing trends from SV to VB. Furthermore, SV-associated metabolites were mainly annotated to butanoate metabolism and glutamate metabolism pathways. Moreover, two metabolite biomarkers classified SV from VB individuals with an area under the curve (AUC) of 0.96. Correlation analysis identified a positive association between four metabolites enriched in glutamate metabolism and serum antibodies in relation to IgG, IgM, and IgA. These results suggest that the contents of gamma-aminobutyric acid and indole in serum could be applied as biomarkers in distinguishing vaccinated volunteers from the unvaccinated. What’s more, metabolites such as GABA and taurine may serve as a metabolic target for adjuvant vaccines to boost the ability of the individuals to improve immunity.
Unravelling soluble immune checkpoints in chronic lymphocytic leukemia: Physiological immunomodulators or immune dysfunction
Authors: Landeira-Viñuela Alicia , Arias-Hidalgo Carlota , Juanes-Velasco Pablo , Alcoceba Miguel , Navarro-Bailón Almudena , Pedreira Carlos Eduardo , Lecrevisse Quentin , Díaz-Muñoz Laura , Sánchez-Santos José Manuel , Hernández Ángela-Patricia , García-Vaquero Marina L. , Góngora Rafael , De Las Rivas Javier , González Marcos , Orfao Alberto , Fuentes Manuel
Published: September 2022

Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasm characterized by the accumulation of mature B cells. The diagnosis is established by the detection of monoclonal B lymphocytes in peripheral blood, even in early stages [monoclonal B-cell lymphocytosis (MBLhi)], and its clinical course is highly heterogeneous. In fact, there are well-characterized multiple prognostic factors that are also related to the observed genetic heterogenicity, such as immunoglobulin heavy chain variable region (IGHV) mutational status, del17p, andTP53mutations, among others. Moreover, a dysregulation of the immune system (innate and adaptive immunity) has been observed in CLL patients, with strong impact on immune surveillance and consequently on the onset, evolution, and therapy response. In addition, the tumor microenvironment is highly complex and heterogeneous (i.e., matrix, fibroblast, endothelial cells, and immune cells), playing a critical role in the evolution of CLL. In this study, a quantitative profile of 103 proteins (cytokines, chemokines, growth/regulatory factors, immune checkpoints, and soluble receptors) in 67 serum samples (57 CLL and 10 MBLhi) has been systematically evaluated. Also, differential profiles of soluble immune factors that discriminate between MBLhiand CLL (sCD47, sCD27, sTIMD-4, sIL-2R, and sULBP-1), disease progression (sCD48, sCD27, sArginase-1, sLAG-3, IL-4, and sIL-2R), or among profiles correlated with other prognostic factors, such as IGHV mutational status (CXCL11/I-TAC, CXCL10/IP-10, sHEVM, and sLAG-3), were deciphered. These results pave the way to explore the role of soluble immune checkpoints as a promising source of biomarkers in CLL, to provide novel insights into the immune suppression process and/or dysfunction, mostly on T cells, in combination with cellular balance disruption and microenvironment polarization leading to tumor escape.
Single-cell sequencing reveals effects of chemotherapy on the immune landscape and TCR/BCR clonal expansion in a relapsed ovarian cancer patient
Authors: Ren Yanyu , Li Runrong , Feng Hanxiao , Xie Jieying , Gao Lin , Chu Shuai , Li Yan , Meng Fanliang , Ning Yunshan
Published: September 2022

Cancer recurrence and chemoresistance are the leading causes of death in high-grade serous ovarian cancer (HGSOC) patients. However, the unique role of the immune environment in tumor progression for relapsed chemo-resistant patients remains elusive. In single-cell resolution, we characterized a comprehensive multi-dimensional cellular and immunological atlas from tumor, ascites, and peripheral blood of a chemo-resistant patient at different stages of treatment. Our results highlight a role in recurrence and chemoresistance of the immunosuppressive microenvironment in ascites, including MDSC-like myeloid and hypo-metabolic γδT cells, and of peripheral CD8+ effector T cells with chemotherapy-induced senescent/exhaustive. Importantly, paired TCR/BCR sequencing demonstrated relative conservation of TCR clonal expansion in hyper-expanded CD8+ T cells and extensive BCR clonal expansion without usage bias of V(D)J genes after chemotherapy. Thus, our study suggests strategies for ameliorating chemotherapy-induced immune impairment to improve the clinical outcome of HGSOC.
Prognostic value of programmed cell death ligand-1 expression in patients with bladder urothelial carcinoma undergoing radical cystectomy: A meta-analysis
Authors: Zhang Jindong , Song Liangdong , Zhu Huixuan , Liu Qinyuan , Wang Delin
Published: September 2022

Background

Radical cystectomy and removal of pelvic lymph nodes (RC-PLND) is a recommended treatment for high-risk non-muscle-invasive and muscle-invasive non-metastatic bladder cancer (BC). However, 50% of patients relapse after RC-PLND. This study aimed to evaluate the effect of programmed cell death ligand-1 (PD-L1) on the prognosis of bladder urothelial carcinoma (BUC) after RC-PLND.

Methods

We present this meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Guidelines. The main outcomes were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) of 3 and 5 years after RC-PLND.

Results

Overall, 11 studies and 1393 BUC cases were included in our meta-analysis. In tumor cells (TCs), the PD-L1 negative group had statistically significant advantage in 5-year OS (risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.74–0.97, P = 0.02), RFS (RR: 0.76, 95% CI: 0.58–0.99, P = 0.04), and CSS (RR: 0.73, 95% CI: 0.58–0.92, P = 0.009) compared with the PD-L1 positive group. But, no statistically significant difference in 5-year OS and RFS was observed between the PD-L1 negative and positive groups in tumor-infiltrating immune cells.

Conclusions

Our study found that patients with BUC who tested positive for PD-L1 in TCs had a poor prognosis after RC-PLND. PD-1 or PD-L1 inhibitors could be used as a adjuvant medication for patients with BUC after RC-PLND who exhibit PD-L1 overexpression in TCs.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022301424.
Signature construction and molecular subtype identification based on cuproptosis-related genes to predict the prognosis and immune activity of patients with hepatocellular carcinoma
Authors: Peng Xingyu , Zhu Jinfeng , Liu Sicheng , Luo Chen , Wu Xun , Liu Zitao , Li Yanzhen , Yuan Rongfa
Published: September 2022

Background

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with high incidence, high malignancy, and low survival rate. Cuproptosis is a novel form of cell death mediated by lipoylated TCA cycle proteins-mediated novel cell death pathway and is highly associated with mitochondrial metabolism. However, the relationship between the expression level of cuproptosis-related genes (CRGs) and the prognosis of HCC is still unclear.

Methods

Combining the HCC transcriptomic data from The Cancer Genome Atlas(TCGA) and Gene Expression Omnibus (GEO) databases, we identified the differentially expressed cuproptosis-related genes (DECRGs) and obtained the prognosis-related DECRGs through univariate regression analysis.LASSO and multivariate COX regression analyses of these DECRGs yielded four genes that were used to construct the signature. Next, we use ROC curves to evaluate the performance of signatures. The tumor microenvironment, immune infiltration, tumor mutation load, half-maximum suppression concentration, and immunotherapy effects were also compared between the low-risk and high-risk groups. Finally, we analyzed the expression level, prognosis, and immune infiltration correlation on the four genes that constructed the model.

Results

Four DECRGs s were used to construct the signature. The ROC curves indicated that signature can better assess the prognosis of HCC patients. Patients were grouped according to the signature risk score. Patients in the low-risk group had a significantly longer survival time than those in the high-risk group. Furthermore, the tumor mutation burden (TMB) values were associated with the risk score and the higher-risk group had a higher proportion of TP53 mutations than the low-risk group.ESTIMATE analysis showed significant differences in stromal scores between the two groups.N6-methyladenosine (m6A) and multiple immune checkpoints were expressed at higher levels in the high-risk group. Then, we found that signature score correlated with chemotherapeutic drug sensitivity and immunotherapy efficacy in HCC patients. Finally, we further confirmed that the four DECRGs genes were associated with the prognosis of HCC through external validation.

Conclusions

We studied from the cuproptosis perspective and developed a new prognostic feature to predict the prognosis of HCC patients. This signature with good performance will help physicians to evaluate the overall prognosis of patients and may provide new ideas for clinical decision-making and treatment strategies.
Transcriptional states of CAR-T infusion relate to neurotoxicity – lessons from high-resolution single-cell SOM expression portraying
Authors: Loeffler-Wirth Henry , Rade Michael , Arakelyan Arsen , Kreuz Markus , Loeffler Markus , Koehl Ulrike , Reiche Kristin , Binder Hans
Published: September 2022

Anti-CD19 CAR-T cell immunotherapy is a hopeful treatment option for patients with B cell lymphomas, however it copes with partly severe adverse effects like neurotoxicity. Single-cell resolved molecular data sets in combination with clinical parametrization allow for comprehensive characterization of cellular subpopulations, their transcriptomic states, and their relation to the adverse effects. We here present a re-analysis of single-cell RNA sequencing data of 24 patients comprising more than 130,000 cells with focus on cellular states and their association to immune cell related neurotoxicity. For this, we developed a single-cell data portraying workflow to disentangle the transcriptional state space with single-cell resolution and its analysis in terms of modularly-composed cellular programs. We demonstrated capabilities of single-cell data portraying to disentangle transcriptional states using intuitive visualization, functional mining, molecular cell stratification, and variability analyses. Our analysis revealed that the T cell composition of the patient’s infusion product as well as the spectrum of their transcriptional states of cells derived from patients with low ICANS grade do not markedly differ from those of cells from high ICANS patients, while the relative abundancies, particularly that of cycling cells, of LAG3-mediated exhaustion and of CAR positive cells, vary. Our study provides molecular details of the transcriptomic landscape with possible impact to overcome neurotoxicity.
Comparative anatomical outcomes of high-flow vs. low-flow phacoemulsification cataract surgery: A systematic review and meta-analysis
Authors: Kuo Po-Chin , Hung Jia-Horung , Su Yu-Chen , Fang Ching-Ju , Lee Chaw-Ning , Huang Yi-Hsun , Shao Shih-Chieh , Lai Edward Chia-Cheng
Published: September 2022

Background

Phacoemulsification is an effective and widely performed technique in cataract surgery, but the comparative anatomical outcomes, including endothelial cell loss (ECL), central corneal thickness (CCT), and central macular thickness (CMT), between high-flow and low-flow phacoemulsification cataract surgery remain unclear.

Methods

This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Random-effects models were applied to measure pooled mean differences (MD) with 95% confidence intervals (CI) of anatomical outcomes between high-flow and low-flow phacoemulsification cataract surgery. We judged overall certainty of evidence (CoE) based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.

Results

We included six randomized controlled trials (RCTs) totaling 477 participants. The meta-analysis showed similar changes associated with these two surgery types in both ECL at postoperative days 2–14 (MD: −1.63%; 95% CI: −3.73 to 0.47%; CoE: very low), days 15–42 (MD: −0.65%; 95% CI −2.96 to 1.65%; CoE: very low) and day 43 to month 18 (MD: −0.35%; 95% CI: −1.48 to 0.78%; CoE: very low), and CCT at postoperative day 1 (MD: −16.37 μm; 95% CI: −56.91 to 24.17 μm; CoE: very low), days 2–14 (MD: −10.92 μm; 95% CI: −30.00 to 8.16 μm; CoE: very low) and days 15–42 (MD: −2.76 μm; 95% CI: −5.75 to 0.24 μm; CoE: low). By contrast, low-flow phacoemulsification showed less increase in CMT at postoperative days 15–42 (MD, −4.58 μm; 95% CI: −6.3 to −2.86 μm; CoE: low).

Conclusions

We found similar anatomical outcomes, except in CMT, for both high-flow and low-flow phacoemulsification cataract surgery. Future head-to-head RCTs on visual outcomes should confirm our findings.

Systematic review registration

PROSPERO, identifier: CRD42022297036.
Indications for diagnostic use of nuclear medicine in rheumatology: A mini-review
Authors: Wenger Martin , Schirmer Michael
Published: September 2022

Nuclear medicine techniques allow important insights not only into oncologic, neurologic, and infectious conditions, but also for the assessment of rheumatic diseases. This review provides a brief, update on the potential role of nuclear imaging in rheumatology, especially on 18F-fluorodeoxyglucose (FDG) positron emission tomography for the diagnosis of giant cell arteritis and other large vessel arteritis according to international recommendations. Besides, the potential role of this and other nuclear imaging techniques for the rheumatologic practice are summarized. With 18F-fluoride as tracer for positron emission tomography, a new option for bone scintigraphy comes up, whereas the use of a semiquantitative sialoscintigraphy is no more supported for classification of Sjögren's syndrome according to current recommendations. Other techniques are used for different organ manifestations in systemic rheumatic diseases like for myocardial infarction and apoplectic insult.
Integrative analysis of the mouse fecal microbiome and metabolome reveal dynamic phenotypes in the development of colorectal cancer
Authors: Liu Jingjing , Qi Mingyang , Qiu Chengchao , Wang Feng , Xie Shaofei , Zhao Jian , Wu Jing , Song Xiaofeng
Published: September 2022

The gut microbiome and its interaction with host have been implicated as the causes and regulators of colorectal cancer (CRC) pathogenesis. However, few studies comprehensively investigate the compositions of gut bacteria and their interactions with host at the early inflammatory and cancerous stages of CRC. In this study, mouse fecal samples collected at inflammation and CRC were subjected to microbiome and metabolome analyses. The datasets were analyzed individually and integratedly using various bioinformatics approaches. Great variations in gut microbiota abundance and composition were observed in inflammation and CRC. The abundances of Bacteroides, S24-7_group_unidifineted, and Allobaculum were significantly changed in inflammation and CRC. The abundances of Bacteroides and Allobaculum were significantly different between inflammation and CRC. Furthermore, strong excluding and appealing microbial interactions were found in the gut microbiota. CRC and inflammation presented specific fecal metabolome profiling. Fecal metabolomic analysis led to the identification and quantification of 1,138 metabolites with 32 metabolites significantly changed in CRC and inflammation. 1,17-Heptadecanediol and 24,25,26,27-Tetranor-23-oxo-hydroxyvitamin D3 were potential biomarkers for CRC. 3α,7β,12α-Trihydroxy-6-oxo-5α-cholan-24-oic Acid and NNAL-N-glucuronide were potential biomarkers for inflammation. The significantly changed bacterial species and metabolites contribute to inflammation and CRC diagnosis. Integrated microbiome and metabolomic analysis correlated microbes with host metabolites, and the variated microbe-metabolite association in inflammation and CRC suggest that microbes facilitate tumorigenesis of CRC through interfering host metabolism.
Enterovirus A71 utilizes host cell lipid β-oxidation to promote its replication
Authors: Yang Xiuwen , Chen Jiayi , Lu Zixin , Huang Shan , Zhang Shihao , Cai Jintai , Zhou Yezhen , Cao Guanhua , Yu Jianhai , Qin Zhiran , Zhao Wei , Zhang Bao , Zhu Li
Published: September 2022

Enterovirus A71 (EV-A71) is a major pathogen that causes severe and fatal cases of hand-foot-and-mouth disease (HFMD), which is an infectious disease that endangers children’s health. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Metabolism and stress are known to play critical roles in multiple stages of the replication of viruses. Lipid metabolism and ER stress is an important characterization post viral infection. EV-A71 infection alters the perturbations of intracellular lipid homeostasis and induces ER stress. The characterizations induced by viral infections are essential for optimal virus replication and may be potential antiviral targets. In this study, we found that the addition of the chemical drug of ER stress, PKR IN, an inhibitor, or Tunicamycin, an activator, could significantly reduce viral replication with the decrease of lipid. The replication of viruses was reduced by Chemical reagent TOFA, an inhibitor of acetyl-CoA carboxylase (ACC) or C75, an inhibitor of fatty acid synthase (FASN), while enhanced by oleic acid (OA), which is a kind of exogenous supplement of triacylglycerol. The pharmacochemical reagent of carnitine palmitoyltransferase 1 (CPT1) called Etomoxir could knock down CPT1 to induce EV-A71 replication to decrease. This suggests that lipid, rather than ER stress, is the main factor affecting EV-A71 replication. In conclusion, this study revealed that it is the β-oxidation of lipid that plays a core role, not ER stress, which is only a concomitant change without restrictive effect, on virus replication.
Lacticaseibacillus rhamnosus R0011 secretome attenuates Salmonella enterica serovar Typhimurium secretome-induced intestinal epithelial cell monolayer damage and pro-inflammatory mediator production in intestinal epithelial cell and antigen-presenting cell co-cultures
Authors: Jeffrey Michael P. , MacPherson Chad W. , Tompkins Thomas A. , Green-Johnson Julia M.
Published: September 2022

Certain lactic acid bacteria (LAB) are associated with immune modulatory activities including down-regulation of pro-inflammatory gene transcription and expression. While host antigen-presenting cells (APCs) and intestinal epithelial cells (IEC) can interact directly with both pathogenic and commensal bacteria through innate immune pattern recognition receptors, recent evidence indicates indirect communication through secreted molecules is an important inter-domain communication mechanism. This communication route may be especially important in the context of IEC and APC interactions which shape host immune responses within the gut environment. We have previously shown that the Lacticaseibacillus rhamnosus R0011 secretome (LrS) dampens pro-inflammatory gene transcription and mediator production from Tumor Necrosis Factor-α and Salmonella enterica serovar Typhimurium secretome (STS)-challenged HT-29 IECs through the induction of negative regulators of innate immunity. However, many questions remain about interactions mediated through these bacterial-derived soluble components and the resulting host immune outcomes in the context of IEC and APC interactions. In the present study, we examined the ability of the LrS to down-regulate pro-inflammatory gene transcription and cytokine production from STS-challenged T84 human IEC and THP-1 human monocyte co-cultures. Cytokine and chemokine profiling revealed that apically delivered LrS induces apical secretion of macrophage inhibitory factor (MIF) and down-regulates STS-induced pro-inflammatory mediator secretion into the apical and basolateral chambers of the T84/THP-1 co-culture. Transcriptional profiling confirmed these results, as the LrS attenuated STS challenge-induced CXCL8 and NFκB1 expression in T84 IECs and THP-1 APCs. Interestingly, the LrS also reversed STS-induced damage to monolayer transepithelial resistance (TER) and permeability, results which were confirmed by ZO-1 gene expression and immunofluorescence visualization of ZO-1 expression in T84 IEC monolayers. The addition of a MIF-neutralizing antibody abrogated the ability of the LrS to reverse STS-induced damage to T84 IEC monolayer integrity, suggesting a novel role for MIF in maintaining IEC barrier function and integrity in response to soluble components derived from LAB. The results presented here provide mechanistic evidence for indirect communication mechanisms used by LAB to modulate immune responses to pathogen challenge, using in vitro approaches which allow for IEC and APC cell communication in a context which more closely mimics that which occurs in vivo.
Complete genome sequence, metabolic model construction, and huangjiu application of Saccharopolyspora rosea A22, a thermophilic, high amylase and glucoamylase actinomycetes
Authors: Ma Donglin , Liu Shuangping , Han Xiao , Nan Mujia , Xu Yuezheng , Qian Bin , Wang Lan , Mao Jian
Published: September 2022

Saccharopolysporais an important microorganism in the fermentation process of wheatquandhuangjiu, yet the mechanisms by which it performs specific functions inhuangjiuremain unclear. A strain with high amylase and glucoamylase activities was isolated from wheatquand identified asSaccharopolyspora rosea(S. rosea) A22. We initially reported the whole genome sequence ofS. roseaA22, which comprised a circular chromosome 6,562,638 bp in size with a GC content of 71.71%, and 6,118 protein-coding genes. A functional genomic analysis highlighted regulatory genes involved in adaptive mechanisms to harsh conditions, andin vitroexperiments revealed that the growth ofS. roseaA22 could be regulated in response to the stress condition. Based on whole-genome sequencing, the first genome-scale metabolic model ofS. roseaA22 namediSR1310 was constructed to predict the growth ability on different media with 91% accuracy. Finally,S. roseaA22 was applied tohuangjiufermentation by inoculating raw wheatqu, and the results showed that the total higher alcohol content was reduced by 12.64% compared with the control group. This study has elucidated the tolerance mechanisms and enzyme-producing properties ofS. roseaA22 at the genetic level, providing new insights into its application tohuangjiu.
Plant traits and community composition drive the assembly processes of abundant and rare fungi across deserts
Authors: Wang Jianming , Qu Mengjun , Wang Yin , He Nianpeng , Li Jingwen
Published: September 2022

The difference in community assembly mechanisms between rare and abundant fungi in deserts remains unknown. Hence, we compared the distribution patterns of abundant and rare fungi, and assessed the factors driving their assembly mechanisms across major vegetation types (shrubby desert, semi-shrubby and dwarf semi-shrubby desert, dwarf semi-arboreous desert, and shrubby steppe desert) of Chinese deserts. We assessed abundant and rare fungal subcommunities base on the sequencing data of fungal ITS data. Abundant fungal assembly was more affected by neutral processes than the rare. Null model and VPA analysis indicated that heterogeneous selection dominated rare sub-communities, whereas abundant fungal assembly was mainly determined by heterogeneous selection, dispersal limitation and other, unknown processes together. As a result, abundant sub-communities exhibited a higher species turnover rate than the rare. Hierarchical partitioning analysis indicated that soil conditions and plant attributes drove the assembly processes of abundant and rare fungi, respectively. Meanwhile, the relative strength of different assembly processes differed significantly among four vegetation types. In addition, we found that plant functional traits and composition played more critical roles in shaping the assembly processes of rare fungi than those of abundant fungi. Taken together, our findings collectively suggest that rare and abundant fungi exhibit differential ecological patterns that are driven by distinct assembly processes in deserts. We emphasize that the assembly processes of abundant and rare fungi are dependent on different abiotic and biotic factors in desert ecosystems.