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Background: Breast cancer (BC) is a highly common form of cancer that occurs in many parts of the world. However, early -stage BC is curable. Many patients with BC have poor prognostic outcomes owing to ineffective diagnostic and therapeutic tools. The ubiquitination system and associated proteins were found influencing the outcome of individuals with cancer. Therefore, developing a biomarker associated with ubiquitination genes to forecast BC patient outcomes is a feasible strategy. Objective: The primary goal of this work was to develop a novel risk score signature capable of accurately estimate the future outcome of patients with BC by targeting ubiquitinated genes. Methods: Univariate Cox regression analysis was conducted utilizing the E1, E2, and E3 ubiquitination-related genes in the GSE20685 dataset. Genes with p

Abstract Genotyping‐by‐sequencing (GBS) is a widely used strategy for obtaining large numbers of genetic markers in model and non‐model organisms. In crop plants, GBS‐derived marker datasets are frequently used to perform quantitative trait locus (QTL) mapping. In some plant species, however, high heterozygosity and complex genome structure mean that researchers must use care in handling GBS data to conduct QTL mapping most effectively. Such outbred crops include most of the perennial grass and tree species used for bioenergy. To identify strategies for increasing accuracy and precision of QTL mapping using GBS data in outbred crops, we conducted an empirical study of SNP‐calling and genetic map‐building pipeline parameters in a Miscanthus sinensis population, and a complementary simulation study to estimate the relationship between genome‐wide error rate, read depth, and marker number. The bioenergy grass Miscanthus is an obligate outcrossing species with a recent (diploidized) whole‐genome duplication. For the study of empirical M. sinensis data, we compared two SNP‐calling methods (one non‐reference‐based and one reference‐based), a series of depth filters (12×, 20×, 30×, and 40×) and two map‐construction methods (i.e., marker ordering: linkage‐only and order‐corrected based on a reference genome). We found that correcting the order of markers on a linkage map by using a high‐quality reference genome improved QTL precision (shorter confidence intervals). For typical GBS datasets of between 1000 and 5000 markers to build a genetic map for biparental populations, a depth filter set at 30× to 40× applied to outbred populations provided a genome‐wide genotype‐calling error rate of less than 1%, improved accuracy of QTL point estimates and minimized type I errors for identifying QTL. Based on these results, we recommend using a reference genome to correct the marker order of genetic maps and a robust genotype depth filter to improve QTL mapping for outbred crops.

Toll-like receptors (TLRs) are a key family of pattern recognition receptors (PRRs) in the innate immune system. The activation of TLRs will not only prevent pathogen infection but also respond to damage-induced danger signaling. Increasing evidence suggests that TLRs play a critical role in breast cancer development and treatment. However, the activation of TLRs is a double-edged sword that can induce either pro-tumor activity or anti-tumor effect. The underlying mechanisms of these opposite effects of TLR signaling in cancer are not fully understood. Targeting TLRs is a promising strategy for improving breast cancer treatment, either as monotherapies or by improving other current therapies. Here we provide an update on the role of TLRs in breast cancer immunity and immunotherapy.

Abstract Introduction Demyelination is a key factor in axonal degeneration and neural loss, leading to disability in multiple sclerosis (MS) patients. Transforming growth factor beta activated kinase 1 (TAK1) is a critical molecule involved in immune and inflammatory signaling pathways. Knockout of microglia TAK1 can inhibit autoimmune inflammation of the brain and spinal cord and improve the outcome of MS. However, it is unclear whether inhibiting TAK1 can alleviate demyelination. Methods Eight‐week‐old male c57bl/6j mice were randomly divided into five groups: (a) the control group, (b) the group treated with cuprizone (CPZ) only, (c) the group treated with 5Z‐7‐Oxozaenol (OZ) only, and (d) the group treated with both cuprizone and 15 μg/30 μg OZ. Demyelination in the mice of this study was induced by administration of CPZ (ig) at a daily dose of 400 mg/kg for consecutive 5 weeks. OZ was intraperitoneally administered at mentioned doses twice a week, starting from week 3 after beginning cuprizone treatment. Histology, rotarod test, grasping test, pole test, Western blot, RT‐PCR, and ELISA were used to evaluate corpus callosum demyelination, behavioral impairment, oligodendrocyte differentiation, TAK1 signaling pathway expression, microglia, and related cytokines. Results Our results demonstrated that OZ protected against myelin loss and behavior impairment caused by CPZ. Additionally, OZ rescued the loss of oligodendrocytes in CPZ‐induced mice. OZ inhibited the activation of JNK, p65, and p38 pathways, transformed M1 polarized microglia into M2 phenotype, and increased brain‐derived neurotrophic factor (BDNF) expression to attenuate demyelination in CPZ‐treated mice. Furthermore, OZ reduced the expression of proinflammatory cytokines and increases anti‐inflammatory cytokines in CPZ‐treated mice. Conclusion These findings suggest that inhibiting TAK1 may be an effective approach for treating demyelinating diseases.

Abstract Molecular biomarkers have the potential to predict the recurrence risk of early-stage lung adenocarcinoma (LUAD) after complete resection, but the study results are controversial. We aimed to clarify the association of molecular alterations with disease-free survival (DFS) and recurrence-free survival (RFS) in early-stage LUAD with R0 resection. Comprehensive searches were conducted in PubMed/MEDLINE, Web of Science, and Cochrane Library for this systematic review and meta-analysis with date restrictions from 2012 to 2022. In the 18 included studies, data from a total of 7417 participants in 11 studies and 4167 participants in 9 studies were collected for the EGFR and KRAS meta-analyses, respectively. Two studies were assessed as having a moderate risk of bias, and the others were all assessed as having a high individual risk of bias. The molecular alterations in KRAS rather than EGFR, were associated with a high risk of recurrence for early-stage LUAD patients suffering from R0 resection, especially for those in pStage I, the pooled hazard ratios (HRs) of KRAS were 2.71 (95% CI, 1.81–4.06; I 2 = 22%; P

Background The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC.Methods This study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status.Results We observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules.Conclusion CD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.

Introduction: In recent years, with the advancement of life sciences, the theories of Traditional Chinese medicine (TCM) have been scientifically elucidated, particularly the integration of the TCM theory of ''the lung and large intestine are interrelated'' and the modern scientific theory of the ''lung-gut axis''. The theory emphasizes the close relationship between the lung and gut, with the lung-gut microbiota, metabolites and mucosal immunity acting as bridges. Methods: Databases such as the National Center for Biotechnology Information (NCBI), ScienceDirect, Web of Science and China National Knowledge Infrastructure (CNKI) were used for search of literature by keywords such as “Traditional Chinese medicine”, “Gut Microbiota”, ''Metabolites'', “Mucosal Immunity”, and “Respiratory Diseases” and so on, and articles were selected according to their credibility and impact and then reviewed. Results: TCM has made significant progress in the treatment of respiratory diseases based on the lung-gut axis theory. TCM can repair damaged intestinal mucosal barriers, maintain the stability of the lung-gut microbiota and related metabolites, improve mucosal immune function, and thereby reduce the incidence of respiratory system diseases. Discussion: TCM can maintain intestinal homeostasis through multi-target and multi-pathway, thereby improving the clinical symptoms of respiratory diseases. TCM therapy based on the lung-gut axis theory is a new direction for exploring new treatment methods.

In order to gain a deeper understanding of the pressure relief characteristics of shale brittle fracture caused by large-scale tectonic uplift and its impact on shale oil enrichment, this paper, taking the Chang 73 sub-member of Yanchang Formation in Yan'an area of Ordos Basin as the research object, quantitatively analyzes the evolution of different lithological properties from overpressure to underpressure or near normal pressure, and further summarizes its influence on the enrichment of shale oil by utilizing the modified overpressure identification plate and numerical simulation techniques and taking into account the effects of temperature reduction, elastic rebound, and brittle rupture of overpressured shale in the process of tectonic uplift. The results show that the origins of overpressure at the end of the Early Cretaceous in the Chang 73 sub-member in the study area are mainly hydrocarbon generation and disequilibrium compaction, and the overpressure of the sandstone layer mainly originates from the overpressure transference from the neighboring source rocks; elastic rebound and temperature reduction due to tectonic uplift since the Late Cretaceous dominates the formation of underpressure in the Chang 73 sub-member sandstones in the study area, and brittle fracture pressure relief and temperature reduction lead to the formation of weak overpressure or near normal pressure in the Chang 73 sub-member shale. The timing of brittle fracture pressure relief of the top and bottom sets of organic-rich shale in the Chang 73 sub-member of the study area is not synchronized, resulting in large transport dynamics (source-reservoir excess pressure difference) between the top and bottom sets of organic-rich shale and their intercalated sandstones with magnitudes ranging from 16 to 22 MPa. Meanwhile, fractures in the top shale have closed during oil and gas preservation, and there is an excess pressure differential of about 1.42-6.80 MPa between it and the underlying sandstone, which strengthens the hydrocarbon containment capacity of the shale. Differential evolution of formation pressure under different source-reservoir configurations plays an important role in controlling shale oil enrichment.

Abstract Neutrophils, the most prevalent innate immune cells in humans, have garnered significant attention in recent years due to their involvement in cancer progression. This comprehensive review aimed to elucidate the important roles and underlying mechanisms of neutrophils in cancer from the perspective of their whole life cycle, tracking them from development in the bone marrow to circulation and finally to the tumor microenvironment (TME). Based on an understanding of their heterogeneity, we described the relationship between abnormal neutrophils and clinical manifestations in cancer. Specifically, we explored the function, origin, and polarization of neutrophils within the TME. Furthermore, we also undertook an extensive analysis of the intricate relationship between neutrophils and clinical management, including neutrophil-based clinical treatment strategies. In conclusion, we firmly assert that directing future research endeavors towards comprehending the remarkable heterogeneity exhibited by neutrophils is of paramount importance.

Abstract The cGAS-STING signaling pathway has emerged as a promising target for immunotherapy development. Here, we introduce a light-sensitive optogenetic device for control of the cGAS/STING signaling to conditionally modulate innate immunity, called ‘light-inducible SMOC-like repeats’ (LiSmore). We demonstrate that photo-activated LiSmore boosts dendritic cell (DC) maturation and antigen presentation with high spatiotemporal precision. This non-invasive approach photo-sensitizes cytotoxic T lymphocytes to engage tumor antigens, leading to a sustained antitumor immune response. When combined with an immune checkpoint blocker (ICB), LiSmore improves antitumor efficacy in an immunosuppressive lung cancer model that is otherwise unresponsive to conventional ICB treatment. Additionally, LiSmore exhibits an abscopal effect by effectively suppressing tumor growth in a distal site in a bilateral mouse model of melanoma. Collectively, our findings establish the potential of targeted optogenetic activation of the STING signaling pathway for remote immunomodulation in mice.

The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with Olea europaea, and of these, only a relatively small fraction have been characterised. Utilising the OliveNetTM library, phenolic compounds were investigated as potential inhibitors of the epigenetic modifier lysine-specific demethylase 1 (LSD1). Furthermore, the compounds were screened for inhibition of the structurally similar monoamine oxidases (MAOs) which are directly implicated in the pathophysiology of depression. Molecular docking highlighted that olive phenolics interact with the active site of LSD1 and MAOs. Protein–peptide docking was also performed to evaluate the interaction of the histone H3 peptide with LSD1, in the presence of ligands bound to the substrate-binding cavity. To validate the in silico studies, the inhibitory activity of phenolic compounds was compared to the clinically approved inhibitor tranylcypromine. Our findings indicate that olive phenolics inhibit LSD1 and the MAOs in vitro. Using a cell culture model system with corticosteroid-stimulated human BJ fibroblast cells, the results demonstrate the attenuation of dexamethasone- and hydrocortisone-induced MAO activity by phenolic compounds. The findings were further corroborated using human embryonic stem cell (hESC)-derived neurons stimulated with all-trans retinoic acid. Overall, the results indicate the inhibition of flavin adenine dinucleotide (FAD)-dependent amine oxidases by olive phenolics. More generally, our findings further support at least a partial mechanism accounting for the antidepressant effects associated with EVOO and the Mediterranean diet.

Cereal and legume proteins, pivotal for human health, significantly influence the quality and stability of processed foods. Despite their importance, the inherent limited functional properties of these natural proteins constrain their utility across various sectors, including the food, packaging, and pharmaceutical industries. Enhancing functional attributes of cereal and legume proteins through scientific and technological interventions is essential to broadening their application. Cold plasma (CP) technology, characterized by its non-toxic, non-thermal nature, presents numerous benefits such as low operational temperatures, lack of external chemical reagents, and cost-effectiveness. It holds the promise of improving proteins’ functionality while maximally retaining their nutritional content. This review delves into the pros and cons of different cold plasma generation techniques, elucidates the underlying mechanisms of protein modification via CP, and thoroughly examines research on the application of cold plasma in augmenting the functional properties of proteins. The aim is to furnish theoretical foundations for leveraging CP technology in the modification of cereal and legume proteins, thereby enhancing their practical applicability in diverse industries.

PurposeTOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been shown an essential role in tumorigenesis by accelerating the DNA replication of tumor cells.MethodsRT-qPCR was used to detect the mRNA expression of TICRR in LUAD tumors and adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the critical role of TICRR expression in survival prognosis and clinicopathology characters in LUAD. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR expression with immune cell infiltration, RNA epigenetic modification, DNA damage repair (DDR) pathway, and cell metabolism of LUAD was further explored to verify significant conclusions.ResultsTICRR was significantly upregulated in most cancer types, including LUAD, lung squamous cell carcinoma (LUSC), and others. Cox regression analysis indicated the overexpression of TICRR was associated with poor survival in several cancers. In LUAD, TICRR expression was positively correlated with tumor stage and was increased in smoking, male, and high tumor mutational burden (TMB) patients. Enrichment analysis revealed that TICRR could influence tumor proliferation and prognosis via activating pathways involving cell cycle, DNA repair, DNA replication, cysteine metabolism, oxidative phosphorylation, and ubiquitin-mediated proteolysis pathways. Interestingly, high TICRR expression correlated with DDR pathway signature (34 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Silencing the TICRR gene affects cysteine metabolism and modifies cancer-related pathways, with decreased cell cycle and increased B/T cell receptor signaling. Our TICRR risk model accurately predicts LUAD patient prognosis, validated across GEO datasets, and is integrated with clinical characteristics via a nomogram, facilitating personalized treatment strategies and enhancing patient management.ConclusionsTaken together, TICRR has emerged as a promising prognostic biomarker in lung adenocarcinoma (LUAD), with implications in immune activation, cell cycle regulation, RNA modification, and tumor energy metabolism. These findings suggest that TICRR could serve as a viable therapeutic target and a reliable prognostic indicator for LUAD.

BackgroundColorectal cancer (CRC) is a prevalent malignancy with diverse molecular characteristics. The NGS-based approach enhances our comprehension of genomic landscape of CRC and may guide future advancements in precision oncology for CRC patients.MethodIn this research, we conducted an analysis using Next-Generation Sequencing (NGS) on samples collected from 111 individuals who had been diagnosed with CRC. We identified somatic and germline mutations and structural variants across the tumor genomes through comprehensive genomic profiling. Furthermore, we investigated the landscape of driver mutations and their potential clinical implications.ResultsOur findings underscore the intricate heterogeneity of genetic alterations within CRC. Notably, BRAF, ARID2, KMT2C, and GNAQ were associated with CRC prognosis. Patients harboring BRAF, ARID2, or KMT2C mutations exhibited shorter progression-free survival (PFS), whereas those with BRAF, ARID2, or GNAQ mutations experienced worse overall survival (OS). We unveiled 80 co-occurring and three mutually exclusive significant gene pairs, enriched primarily in pathways such as TP53, HIPPO, RTK/RAS, NOTCH, WNT, TGF-Beta, MYC, and PI3K. Notably, co-mutations of BRAF/ALK, BRAF/NOTCH2, BRAF/CREBBP, and BRAF/FAT1 correlated with worse PFS. Furthermore, germline AR mutations were identified in 37 (33.33%) CRC patients, and carriers of these variants displayed diminished PFS and OS. Decreased AR protein expression was observed in cases with AR germline mutations. A four-gene mutation signature was established, incorporating the aforementioned prognostic genes, which emerged as an independent prognostic determinant in CRC via univariate and multivariate Cox regression analyses. Noteworthy BRAF and ARID2 protein expression decreases detected in patients with their respective mutations.ConclusionThe integration of our analyses furnishes crucial insights into CRC’s molecular characteristics, drug responsiveness, and the construction of a four-gene mutation signature for predicting CRC prognosis.

Herein, the effect of current on the solidification microstructure and properties of 35CrMo structural steel has been studied. The effect of an electric field on the solidification structure of an ingot was investigated by immersing two parallel electrodes into the free surface of molten steel. Using the interaction between the current and melt as well as the Lorentz force generated by its own induced magnetic field, the whole region of the melt was covered with an eddy current. The numerical simulation of the ingot solidification process has been carried out and its influence on the inner flow field during the ingot solidification control process discussed. The results showed that an applied electric field caused turbulence inside the ingot, which drove the molten alloys to rotate and stir, refined the solidification structure, reduced the solidification defects, such as shrinkage cavity and segregation, and increased from 549.9 MPa at the top edge of the ingot and 411.4 MPa at the middle edge to 560.2 and 510.2 MPa, respectively. In addition, the electric field made the hardness and strength of each part of the ingot more uniform and improved the quality of its rigidity for the steel production process.

Enzyme inactivation is crucial for enhancing the shelf life of lightly milled rice (LMR), yet the impact of diverse superheated steam (SS) treatment conditions on lipolytic enzyme efficiency, physicochemical properties, and volatile profiles of LMR remains unclear. This study investigated varying SS conditions, employing temperatures of 120 °C, 140 °C, and 160 °C and exposure times of 2, 4, 6, and 8 min. The research aimed to discern the influence of these conditions on enzyme activities, physicochemical characteristics, and quality attributes of LMR. Results indicated a significant rise in the inactivation rate with increased treatment temperature or duration, achieving a notable 70% reduction in enzyme activities at 120 °C for 6 min. Prolonged exposure to higher temperatures also induced pronounced fissures on LMR surfaces. Furthermore, intensive SS treatment led to a noteworthy 5.52% reduction in the relative crystallinity of LMR starch. GC/MS analysis revealed a consequential decrease, ranging from 44.7% to 65.7%, in undesirable odor ketones post-SS treatment. These findings underscore the potential of SS treatment in enhancing the commercial attributes of LMR.

Background: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. In pediatric gliomas, abnormal expression of Homeobox (HOX) family genes (HFGs) has been observed and is associated with the development and progression of the disease. Studies have found that overexpression or underexpression of certain HOX genes is linked to the occurrence and prognosis of gliomas. This aberrant expression may contribute to the dysregulation of important pathological processes such as cell proliferation, differentiation, and metastasis. This study aimed to propose a novel HOX-related signature to predict patients’ prognosis and immune infiltrate characteristics in PGs.Methods: The data of PGs obtained from publicly available databases were utilized to reveal the relationship among abnormal expression of HOX family genes (HFGs), prognosis, tumor immune infiltration, clinical features, and genomic features in PGs. The HFGs were utilized to identify heterogeneous subtypes using consensus clustering. Then random forest-supervised classification algorithm and nearest shrunken centroid algorithm were performed to develop a prognostic signature in the training set. Finally, the signature was validated in an internal testing set and an external independent cohort.Results: Firstly, we identified HFGs significantly differentially expressed in PGs compared to normal tissues. The individuals with PGs were then divided into two heterogeneous subtypes (HOX-SI and HOX-SII) based on HFGs expression profiles. HOX-SII showed higher total mutation counts, lower immune infiltration, and worse prognosis than HOX-SI. Then, we constructed a HOX-related gene signature (including HOXA6, HOXC4, HOXC5, HOXC6, and HOXA-AS3) based on the cluster for subtype prediction utilizing random forest supervised classification and nearest shrunken centroid algorithm. The signature was revealed to be an independent prognostic factor for patients with PGs by multivariable Cox regression analysis.Conclusion: Our study provides a novel method for the prognosis classification of PGs. The findings also suggest that the HOX-related signature is a new biomarker for the diagnosis and prognosis of patients with PGs, allowing for more accurate survival prediction.

Abstract Cellular immunotherapy harnesses the body's own immune system to fight cancer by using engineered T cells, macrophages, or natural killer (NK) cells. Compared to chimeric antigen receptor T (CAR‐T) cells that are commonly used to treat hematological malignancies, CAR‐NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety, reduced risk of graft‐versus‐host disease, fewer side effects, and amplified antitumor efficacy. Preclinical trials have unveiled the high potential of adoptive CAR‐NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models. We brought forth herein the design principle of CAR‐NK cells, highlighted the latest progress in the preclinical testing and clinical trials of CAR‐NK cells, briefly delved into discussed major roadblocks in CAR‐NK therapy, and discussed potential solutions to surmount these challenges. Given the accelerated progress in both basic and translational studies on immune cell engineering, CAR‐NK cell therapy promises to become a serious contender and important addition to the next‐generation cell‐based immunotherapy.

Abstract Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of Invasive Ductal Carcinoma (IDC) and thus the identification of features that may predict DCIS progression would be of potential clinical value. Experimental mouse models can be used to address this challenge by studying DCIS-to-IDC biology. Here we utilize single cell RNA sequencing (scRNAseq) on the C3Tag genetically engineered mouse model that forms DCIS-like precursor lesions and for which many lesions progress into end-stage basal-like molecular subtype IDC. We also perform bulk RNAseq analysis on 10 human synchronous DCIS-IDC pairs comprised of estrogen receptor (ER) positive and ER-negative subsets and utilize 2 additional public human DCIS data sets for comparison to our mouse model. By identifying malignant cells using inferred DNA copy number changes from the murine C3Tag scRNAseq data, we show the existence of cancer cells within the C3Tag pre-DCIS, DCIS, and IDC-like tumor specimens. These cancer cells were further classified into proliferative, hypoxic, and inflammatory subpopulations, which change in frequency in DCIS versus IDC. The C3Tag tumor progression model was also associated with increase in Cancer-Associated Fibroblasts and decrease in activated T cells in IDC. Importantly, we translate the C3Tag murine genomic findings into human DCIS where we find common features only with human basal-like DCIS, suggesting there are intrinsic subtype unique DCIS features. This study identifies several tumor and microenvironmental features associated with DCIS progression and may also provide genomic signatures that can identify progression-prone DCIS within the context of human basal-like breast cancers.

BackgroundColorectal cancer (CRC) is the third most prevalent malignancy and the one of most lethal cancer. Metastatic CRC (mCRC) is the third most common cause of cancer deaths worldwide. DNA damage response (DDR) genes are closely associated with the tumorigenesis and development of CRC. In this study, we aimed to construct a DDR-related gene signature for predicting the prognosis of mCRC patients.MethodsThe gene expression and corresponding clinical information data of CRC/mCRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed for patients between the high-DDRscore and low-DDRscore groups.ResultsWe constructed a prognostic model consisting of four DDR-related genes (EME2, MSH4, MLH3, and SPO11). Survival analysis showed that patients in the high-DDRscore group had a significantly worse OS than those in the low-DDRscore group. The area under the curve (AUC) value of the ROC curve of the predictive model is 0.763 in the training cohort GSE72970, 0.659 in the stage III/IV colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) data portal, and 0.639 in another validation cohort GSE39582, respectively. GSEA functional analysis revealed that the most significantly enriched pathways focused on nucleotide excision repair, base excision repair, homologous recombination, cytokine receptor interaction, chemokine signal pathway, cell adhesion molecules cams, ECM-receptor interaction, and focal adhesion.ConclusionThe DDRscore was identified as an independent prognostic and therapy response predictor, and the DDR-related genes may be potential diagnosis or prognosis biomarkers for mCRC patients.

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition of tumor tissues. The differently expressed genes among each cluster were identified by EdgeR. GO enrichment analysis was used to understand the roles of genes within the clusters. Pseudotime cell trajectory was used to reveal the molecular pathways underlying cell fate decisions and identify genes whose expression changed as the cells underwent transition. We applied CellPhoneDB to identify cell-cell interactions among the epithelial and neural cells in PNI-PCa.Results: Analysis of the ∼17,000 single-cell transcriptomes in three PNI prostate cancer tissues, we identified 12 major cell clusters, including neural cells and two epithelial subtypes with different expression profiles. We found that basal/intermediate epithelial cell subtypes highly expressed PCa progression-related genes, including PIGR, MMP7, and AGR2. Pseudotime trajectory analysis showed that luminal epithelial cells could be the initiating cells and transition to based/intermediate cells. Gene ontology (GO) enrichment analysis showed that pathways related to cancer progressions, such as lipid catabolic and fatty acid metabolic processes, were significantly enriched in basal/intermediate cells. Our analysis also suggested that basal/intermediate cells communicate closely with neural cells played a potential role in PNI-PCa progression.Conclusion: These results provide our understanding of PNI-PCa cellular heterogeneity and characterize the potential role of basal/intermediate cells in the PNI-PCa progression.

Background As an integral part of the tumor microenvironment (TME), tumor-associated neutrophils play a crucial role in tumor development. The objective of this study was to investigate the plasticity of tumor-associated N1 and N2 neutrophils in the TME of pancreatic ductal adenocarcinoma (PDAC), along with its impact on survival and association with immune infiltrations.Methods The primary and validation cohorts including 90 radical resection patients from September 2012 to May 2016 and 29 radical resection patients from September 2018 to October 2019, respectively, with complete survival data, were enrolled. Immunofluorescence staining was used to identify tumor-associated N1 and N2 neutrophils, and the N1/N2 ratio was used to evaluate N1 and N2 plasticity. Thereafter, the association between tumor-associated N1/N2 neutrophil plasticity, clinical features, and immune infiltrations was investigated.Results There was a significant increase in tumor-associated N2 neutrophils compared with tumor-associated N1 neutrophils. Low N1/N2 ratios were associated with the poorer differentiation of tumors, easier lymph node metastases, and a higher TNM stage. The median overall survival (OS) and recurrence-free survival (RFS) of the high tumor-associated N1 neutrophil group were significantly longer than those of the low group, while the tumor-associated N2 neutrophils played an opposite role. The multivariable analysis revealed that a high N1/N2 ratio was a significant prognostic indicator for OS and RFS. In addition, tumor-associated N1/N2 neutrophils showed an opposite correlation with tumor-infiltrating CD8+ T cells and Tregs.Conclusion The plasticity of tumor-associated N1/N2 neutrophils was identified as a crucial prognostic indicator that might reflect the TME and immune escape in patients with PDAC. On further investigation and validation, our findings may be used to further stratify patients with varying prognoses to optimize treatment.

Diverticulosis is a commonly acquired disease of the lower gastrointestinal tract, which may be associated with significant morbidity and adverse effects on quality of life. Although several national guidelines focused on the treatment of diverticulosis, multiple controversies remained regarding the disease management of diverticulosis. For some controversial issues, such as the role of antibiotics in mild diverticulitis, when and how to operate on patients with acute diverticulitis, there is no conclusion yet. To our knowledge, this is the first report of endoscopic therapy for anastomotic diverticulitis caused by stercorolith incarceration. In the current case, a 49-year-old woman complained of recurrent subumbilical pain without obvious inducement for half a year. Colonoscopy showed anastomotic diverticulum combined with stercorolith incarceration. After local inflammation relieved by conservative treatment, the patients received endoscopic mucosal incision and lithotomy. Then the diverticulum was closed with titanium clips. The abdominal pain of patient was completely relieved, and the reexamination of colonoscopy showed that the wound healed well after 1 year of follow-up. This case suggests that for anastomotic diverticulitis caused by stercorolith incarceration, endoscopic therapy can remove the stimulation factors better and avoid the recurrence and progression of the disease compared with conservative treatment. Moreover, endoscopic therapy achieves the maximum in minimally invasive surgery and reduces complications and surgical costs compared with radical surgery.

Abstract Single-cell RNA sequencing (scRNA-seq) provides new opportunities to characterize cell populations, typically accomplished through some type of clustering analysis. Estimation of the optimal cluster number (K) is a crucial step but often ignored. Our approach improves most current scRNA-seq cluster methods by providing an objective estimation of the number of groups using a multi-resolution perspective. MultiK is a tool for objective selection of insightful Ks and achieves high robustness through a consensus clustering approach. We demonstrate that MultiK identifies reproducible groups in scRNA-seq data, thus providing an objective means to estimating the number of possible groups or cell-type populations present.

Antibiotic resistance is a severe global problem afflicting the field of public health in recent years. Antibiotic-resistant bacteria (ARB) and their antibiotic resistance genes (ARGs) can spread into the environment via various sources like hospital wastewater, domestic wastewater, agricultural runoff, and animal feeding operations. However, it is difficult to track or predict pollutant origins for antibiotic resistance in the environment. In this study, whole-genome sequencing (WGS) analysis was used to determine the origins (host animals) and molecular epidemiology of antibiotic resistant E. coli in the watersheds of Lake Biwa in Japan, by examining the influent and discharge from large, centralized wastewater treatment plants (WWTPs), WWTP discharged directly into Lake Biwa, and inflow rivers of Lake Biwa, with respect to non-selective, ampicillin-resistant, and tetracycline-resistant E. coli. By using WGS, the molecular characterization of non-selective E. coli from various water samples revealed a difference in phylogenetic group and host source distribution between WWTP discharges and Lake Biwa samples. This finding suggests that the WWTP discharges are not the major source of fecal pollution in Lake Biwa. Contrastingly, ampicillin-resistant E. coli isolates from WWTP discharge and Lake Biwa showed similar phylogroup and host source composition, indicating a relationship between antibiotic resistance spread from WWTP discharge into Lake Biwa. On the other hand, the difference between the WWTP discharge and river samples in the E. coli phylogroup and host source was observed in tetracycline-resistant E. coli isolates, implying that the inflow rivers of Lake Biwa received antibiotic resistance pollution apart from WWTP discharges. These results contribute to improving the current state of knowledge regarding potential antibiotic resistance pollution sources in the aquatic environment and the possible ramifications of antibiotic resistance dissemination by WWTP discharge and other sources in Japan.

Lymphatic metastasis influences clinical treatment and prognosis of patients with non-small-cell lung cancer (NSCLC). There is an urgency to understand the molecular features and mechanisms of lymph node metastasis. We analyzed the molecular features on pairs of the primary tumor and lymphatic metastasis tissue samples from 15 NSCLC patients using targeted next-generation sequencing. The potential metastasis-related genes were screened from our cohort based on cancer cell fraction. After filtering with gene functions, candidate metastasis-related events were validated in the MSK cohort with Fisher’s exact test. The molecular signature and tumor mutational burden were similar in paired samples, and the average mutational concordance was 42.0% ± 28.9%. Its metastatic mechanism is potentially a linear progression based on the metastatic seeding theory. Furthermore, mutated ataxia telangiectasia mutated and Rad3-related (ATR) and tet methylcytosine dioxygenase 2 (TET2) genes were significantly enriched in lymphatic metastases (p ≤ 0.05). Alterations in these two genes could be considered metastasis-related driving events. Mutated ATR and TET2 might play an active role in the metastasis of lymph nodes with NSCLC. More case enrollment and long-term follow-up will further verify the clinical significance of these two genes.

In 2016, Wears defined and studied algebraic T-solitons. In this paper, we define algebraic Schouten solitons as a special T-soliton and classify the algebraic Schouten solitons associated with Levi-Civita connections, canonical connections, and Kobayashi–Nomizu connections on three-dimensional Lorentzian Lie groups that have some product structure.

Based on a comprehensive introduction of the development history, application situation, advantages and disadvantages of China's airborne cloud detection systems, this paper gives a detailed description of the system composition, detection principle, detection method and detection range of the new generation of airborne cloud detection system SPEC and discusses the recent domestic and foreign research progresses. With the increasing requirements by scientific community on the precision and accuracy of cloud detection, cloud detection systems such as particle measurement system (PMS) used in the past have been unable to meet the needs of some scientific experiments. Compared to many other cloud detection systems, SPEC has great detection advantages in terms of precision, information amount and resolution of detected particles. This is very important for more in-depth research on cloud physics. The SPEC system has been developed and applied abroad for decades, and China has introduced it recently and applied this detection system more and more to explore the macro- and microphysical cloud characteristics, which will definitely help us better understand the cloud physics.

Abstract Background Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy. Methods 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance. Results BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735–34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305–97.300), P = 0.005]. Conclusions This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.

Abstract Background The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression. Methods In this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA). Results Seven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored. Conclusion The ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.

Abstract Background To compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the treatment of breast cancer. Methods We systematically searched the PubMed, Embase, and Cochrane Central Register databases. Randomized controlled trials (RCTs) and cohort studies, published in English, about the comparison between nab-paclitaxel and sb-taxanes as neoadjuvant therapy in patients with breast cancer were searched up to September 2019. Results The primary outcome was the proportion of patients with pathological complete response (pCR, defined as ypT0 ypN0 or ypT0/is ypN0). Other main outcomes included long-term survival and adverse events (AEs). Seven studies (five RCTs and two cohorts) and 2949 patients were included. Neoadjuvant nab-paclitaxel improved pCR compared with sb-taxanes (ypT0 ypN0: OR = 1.52, 95%CI: 1.27–1.83, P 20% (OR = 1.63, 95%CI: 1.26–2.12, P 3 AEs between nab-paclitaxel and sb-taxanes (all P > 0.05), besides of any grade hypersensitivity (OR = 0.29, 95%CI: 0.11–0.72, P = 0.008), any grade (OR = 2.10, 95%CI: 1.37–3.23, P = 0.001) and grade > 3 (OR = 4.01, 95%CI: 2.51–6.41, P

Millet Huangjiu is a national alcoholic beverage in China. The quality of Chinese millet Huangjiu is significantly influenced by the protein components in the raw materials of millet. Therefore, in this study, the impact of different protein components on the quality of millet Huangjiu was investigated by adding exogenous proteins glutelin and albumin either individually or in combination. The study commenced with the determination of the oenological parameters of different millet Huangjiu samples, followed by the assessment of free amino acids and organic acids. In addition, the volatile profiles of millet Huangjiu were characterized by employing HS-SPME-GC/MS. Finally, a sensory evaluation was conducted to evaluate the overall aroma profiles of millet Huangjiu. The results showed that adding glutelin significantly increased the contents of total soluble solids, amino acid nitrogen, and ethanol in millet Huangjiu by 32.2%, 41.5%, and 17.7%, respectively. Furthermore, the fortification of the fermentation substrate with glutelin protein was found to significantly enhance the umami (aspartic and glutamic acids) and sweet-tasting (alanine and proline) amino acids in the final product. Gas chromatography-quadrupole mass spectrometry coupled with multivariate statistical analysis revealed distinct impacts of protein composition on the volatile organic compound (VOC) profiles of millet Huangjiu. Excessive glutelin led to an over-accumulation of alcohol aroma, while the addition of albumin protein proved to be a viable approach for enhancing the ester and fruity fragrances. Sensory analysis suggested that the proper amount of protein fortification using a Glu + Alb combination could enhance the sensory attributes of millet Huangjiu while maintaining its unique flavor characteristics. These findings suggest that reasonable adjustment of the glutelin and albumin contents in millet could effectively regulate the chemical composition and improve the sensory quality of millet Huangjiu.

The perennial grass Miscanthus is a promising biomass crop. Here, via genomics and transcriptomics, the authors reveal its allotetraploid origin, characterize gene expression associated with rhizome development and nutrient recycling, and describe the hybrid origin of the triploid M. x giganteus.

This paper provides the concept of import dependence between countries, which is a relative quantity. In order to reveal the evolutionary characteristics of the import dependence between countries in energy trade and its influencing factors, firstly, based on the network analysis method, this paper constructs a model of energy import dependence network (EIDN) among countries and regions along the Belt and Road (B&R countries). Crude oil and natural gas are taken as empirical objects, and the evolution characteristics of the two kinds of EIDNs are analysed. The result showed that most of the B&R countries had a small number of crude oil and natural gas trade partners. However, the import dependence in crude oil and natural gas trade between countries is relatively large, indicating that the risk of oil and gas security in B&R countries is high. Moreover, based on the QAP method, spatial distance, economic differences, the signing of free trade agreements, and the differences in energy consumption between countries have a significant impact on the import dependence in crude oil and natural gas trade among B&R countries. First published online 30 November 2021

Financial crisis, rooted in a lack of system resilience and robustness, is a particular type of critical transition that may cause grievous economic and social losses and should be warned against as early as possible. Regarding the financial system as a time-varying network, researchers have identified early warning signals from the changing dynamics of network motifs. In addition, network motifs have many different morphologies that unveil high-order correlation patterns of a financial system, whose synchronous change represents the dramatic shift in the financial system’s functionality and may indicate a financial crisis; however, it is less studied. This paper proposes motif transition intensity as a novel method that quantifies the synchronous change of network motifs in detail. Applying this method to stock networks, we developed three early warning indicators. Empirically, we conducted a horse race to predict ten global crises during 1991–2020. The results show evidence that the proposed indicators are more efficient than the VIX and the other 39 network-based indicators. In a detailed analysis, the proposed indicators send sensitive and comprehensible warning signals, especially for the U.S. subprime mortgage crisis and the European sovereign debt crisis. Furthermore, the proposed method provides a new perspective to detect critical signals and may be extended to predict other crisis events in natural and social systems.

Abstract Background Preventing breast cancer-related lymphedema (BCRL) by preserving upper lymphatic drainage is still controversial. Our study aimed to use the axillary reverse mapping (ARM) technique in patients who underwent axillary surgery to analyse the correlation between postoperative residual ARM nodes and the occurrence of lymphedema, select candidates at high risk of developing lymphedema, and analyse the oncologic safety of ARM nodes. Methods Patients undergoing sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) from October 2015 to February 2016 at the Peking University People’s Hospital Breast Center were prospectively recruited for the study. ARM was performed in all patients before surgery. ARM nodes were separated from SLNB and ALND specimens. Data were collected on the identification of ARM nodes before surgery, number of residual ARM nodes after surgery, nodal status, crossover rate, and correlation between residual ARM nodes and the occurrence of lymphedema. Results The analysis included 78 patients. Of the 53 patients who underwent SLNB, crossover between ARM nodes and breast sentinel lymph nodes (SLNs) was seen in 22 specimens. The incidence of ARM node metastasis was 1.89% (1/53) and 25% (9/36) in the SLNB and ALND groups, respectively. The number of positive axillary lymph nodes was associated with the involvement of ARM nodes (P = 0.036). The incidence of residual ARM nodes was significantly higher in the SLNB group than in the ALND group (67.6% vs. 37.9%, P = 0.016). The incidence of lymphedema was significantly higher in the ALND group than in the SLNB group (33.3% vs. 5.4%, P = 0.003). Conclusions For SLNB, the ARM technique can help to resect SLNs more accurately. However, we do not recommend using the ARM technique to preserve ARM nodes in patients undergoing ALND due to oncologic safety issues. Nevertheless, we can predict patients undergoing axillary surgery who are more likely to have a high risk of lymphedema by assessing residual ARM nodes. Trial registration This study was registered on ClinicalTrials.gov in February 2016. The clinical trial registration number is NCT02691624 .

Due to the speed, efficiency, relative risk, and lower costs compared to traditional drug discovery, the prioritization of candidate drugs for repurposing against cancers of interest has attracted the attention of experts in recent years. Herein, we present a powerful computational approach, termed prioritization of candidate drugs (PriorCD), for the prioritization of candidate cancer drugs based on a global network propagation algorithm and a drug–drug functional similarity network constructed by integrating pathway activity profiles and drug activity profiles. This provides a new approach to drug repurposing by first considering the drug functional similarities at the pathway level. The performance of PriorCD in drug repurposing was evaluated by using drug datasets of breast cancer and ovarian cancer. Cross‐validation tests on the drugs approved for the treatment of these cancers indicated that our approach can achieve area under receiver‐operating characteristic curve (AUROC) values greater than 0.82. Furthermore, literature searches validated our results, and comparison with other classical gene‐based repurposing methods indicated that our pathway‐level PriorCD is comparatively more effective at prioritizing candidate drugs with similar therapeutic effects. We hope that our study will be of benefit to the field of drug discovery. In order to expand the usage of PriorCD, a freely available R‐based package, PriorCD, has been developed to prioritize candidate anticancer drugs for drug repurposing.

Next-generation sequencing (NGS) has drastically enhanced human cancer research, but diverse sequencing strategies, complicated open-source software, and the identification of massive numbers of mutations have limited the clinical application of NGS. Here, we first presented GPyFlow, a lightweight tool that flexibly customizes, executes, and shares workflows. We then introduced DIVIS, a customizable pipeline based on GPyFlow that integrates read preprocessing, alignment, variant detection, and annotation of whole-genome sequencing, whole-exome sequencing, and gene-panel sequencing. By default, DIVIS screens variants from multiple callers and generates a standard variant-detection format list containing caller evidence for each sample, which is compatible with advanced analyses. Lastly, DIVIS generates a statistical report, including command lines, parameters, quality-control indicators, and mutation summary. DIVIS substantially facilitates complex cancer genome sequencing analyses by means of a single powerful and easy-to-use command. The DIVIS code is freely available at https://github.com/niu-lab/DIVIS, and the docker image can be downloaded from https://hub.docker.com/repository/docker/sunshinerain/divis.

With the increasing incidence of colorectal cancer (CRC) and continued difficulty in treating it using immunotherapy, there is an urgent need to identify an effective immune-related biomarker associated with the survival and prognosis of patients with this disease. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of autoimmunity, aging, and cancer. In this study, we aimed to identify a novel immune-related methylated signature to aid in predicting the prognosis of patients with CRC. We investigated DNA methylation patterns in patients with stage II/III CRC using datasets from The cancer genome atlas (TCGA). Overall, 182 patients were randomly divided into training (n = 127) and test groups (n = 55). In the training group, five immune-related methylated CG sites (cg11621464, cg13565656, cg18976437, cg20505223, and cg20528583) were identified, and CG site-based risk scores were calculated using univariate Cox proportional hazards regression in patients with stage II/III CRC. Multivariate Cox regression analysis indicated that methylated signature was independent of other clinical parameters. The Kaplan–Meier analysis results showed that CG site-based risk scores could significantly help distinguish between high- and low-risk patients in both the training (P = 0.000296) and test groups (P = 0.022). The area under the receiver operating characteristic curve in the training and test groups were estimated to be 0.771 and 0.724, respectively, for prognosis prediction. Finally, stratified analysis results suggested the remarkable prognostic value of CG site-based risk scores in CRC subtypes. We identified five methylated CG sites that could be used as an efficient overall survival (OS)-related biomarker for stage II/III CRC patients.

Background: Indocyanine green (ICG) lymphography is a newer technique for diagnosing lymphedema. Our study aimed to find whether the abnormality of ICG lymphography can predict the occurrence of early lymphedema and then select candidates at high risk of developing lymphedema. Methods: Postoperative breast cancer patients who visited the lymphedema clinic of Peking University People’s Hospital from December 2016 to September 2019 were consecutively enrolled and received ICG lymphography and circumference measurement. Data were collected on the patients’ characteristics and correlation between ICG lymphography and the occurrence of lymphedema. Results: The analysis included 179 patients. There were 91 patients in the lymphedema group and 88 patients in the non-lymphedema group. By multivariate analysis, age, axillary surgery, radiotherapy, and time since breast cancer surgery were regarded as risk factors for lymphedema (p < 0.05). According to the results of ICG lymphography, patients in the non-lymphedema group (n = 88) were divided into ICG-positive (n = 47) and ICG-negative (n = 41) groups. The incidence of lymphedema in the ICG-positive group was significantly higher than that in the ICG-negative group (19.1% vs. 2.4%, p = 0.027). Conclusion: Lymphatic disorder can be detected before circumference change using ICG lymphography. Abnormal ICG lymphography is an independent risk factor for lymphedema. Patients with abnormal dermal backflow patterns are considered to be a high-risk group for lymphedema and should undergo early interventions to prevent lymphedema.

Abstract Background H2S can also protect nerve cells. The objective of the study is to investigate the effects of hydrogen sulfide (H2S) on the expressions of brain-derived neurotrophic factor (BDNF) and its receptors, tyrosine protein kinase B (TrkB) and p75 neurotrophin receptor (p75NTR), in brain tissues of rats with cardiac arrest and cardiopulmonary resuscitation (CA/CPR) following the restoration of spontaneous circulation (ROSC). Methods Rats (n = 240) with CA/CPR were divided into three groups: Intervention (n = 80) that received sodium hydrosulfide (NaHS, 14 μmoL/kg·d) intervention after ROSC; Inhibition (n = 80) that received hydroxylamine (40 μmoL/kg·d) intervention after ROSC; and Control (n = 80) that received saline after ROSC. Kaplan-Meyer analysis was used to analyze the survival data. Quantitative real-time PCR (q-PCR), Western blot, immunohistochemistry and IODs (integrated optical density) were performed to determine the mRNA and protein expressions of BDNF, TrkB and p75NTR in rat brain tissues. Results Survival rate of the three groups had significant difference (χ2 = 28.376, p = 0.000). The Intervention group had the highest survival rate (82.5%), while the Inhibition group had the lowest survival rate (62.5%). The mRNA and protein levels of BDNF and TrkB in the Intervention group were significantly higher compared to the Control group (p

In this work, rotating disk electrodes (RDEs) and surface-enhanced Raman spectroscopy (SERS) have been integrated and used to reveal the mechanism of electrochemical reduction of 4-nitrothiophenol. The electrochemistry of 4-nitrothiophenol was studied in situ on Au@Ag nanoparticles at different potentials using SERS. These spectra together with the RDE results clearly reveal the reduction mechanism of 4-nitrothiophenol to 4-aminothiophenol. This in situ technique offers a new approach in modern electrochemistry that can be used to clarify the reaction mechanisms of different nitrobenzenes at a molecular level.

This paper analyses the evolutionary characteristics of the interprovincial population mobility network structure in China and explores the roles of provinces from 2010 to 2015. By constructing the interprovincial population mobility network, we examine the provinces’ functions during periods of population mobility through population mobility diversity, population mobility, and population mobility intermediation. The results show that the coverage and tightness of the interprovincial population mobility network were influenced by national economic development, increasing steadily from 2010 to 2014 and then suddenly falling in 2015. The regions that played essential roles in the province’s mobility diversity and intermediation showed a dispersion trend. In contrast, areas that played a vital role in the inflows or outflows were relatively concentrated and stable. Additionally, this work further explores how economic factors, e.g., GDP, residents’ consumption levels, total population, unemployment rate, and consumer price index, are used as independent variables to analyse the provinces’ roles in the interprovincial population mobility network. The analysis shows that the inflow or outflow volumes are easily affected by the five indices. These five indices are significantly related to network role indicators to different extents.

We used a grand canonical Monte Carlo simulation to study the influence of impurities including water vapor, SO2, and O2 in the flue gas on the adsorption of CO2/N2 mixture in carbon nanotubes (CNTs) and carboxyl doped CNT arrays. In the presence of single impure gas, SO2 yielded the most inhibitions on CO2 adsorption, while the influence of water only occurred at low pressure limit (0.1 bar), where a one-dimensional chain of hydrogen-bonded molecules was formed. Further, O2 was found to hardly affect the adsorption and separation of CO2. With three impurities in flue gas, SO2 still played a major role to suppress the adsorption of CO2 by reducing the adsorption amount significantly. This was mainly because SO2 had a stronger interaction with carbon walls in comparison with CO2. The presence of three impurities in flue gas enhanced the adsorption complexity due to the interactions between different species. Modified by hydrophilic carboxyl groups, a large amount of H2O occupied the adsorption space outside the tube in the carbon nanotube arrays, and SO2 produced competitive adsorption for CO2 in the tube. Both of the two effects inhibited the adsorption of CO2, but improved the selectivity of CO2/N2, and the competition between the two determined the adsorption distribution of CO2 inside and outside the tube. In addition, it was found that (7, 7) CNT always maintained the best CO2/N2 adsorption and separation performance in the presence of impurity gas, for both the cases of single CNT and CNT array.

This study investigates the size distribution, the mean diameter, and the concentration of ice particles within stratiform clouds by using in situ observations from 29 flights in Hebei, China. Furthermore, it examines the empirical fitting of ice particle size distributions at different temperatures using Gamma and exponential functions. Without considering the first three bins of ice particles, the mean diameter of ice particles (size range 100–1550 µm) is found to increase with temperature from −15 to −9 °C but decrease with temperature from −9 to 0 °C. By considering the first three bins of ice particles using the empirical Gamma fitting relationship found in this study, the mean diameter of ice particles (size range 25–1550 µm) shows a similar variation trend with temperature, while the turning point changes from −9 to −10 °C. The ice particle number concentration increases from 13.37 to 50.23 L−1 with an average of 31.27 L−1 when temperature decreases from 0 to −9 °C. Differently, the ice concentration decreases from 50.23 to about 22.4 L−1 when temperature decreases from −9 to −12 °C. The largest mean diameter of ice particles at temperatures around −9 and −10 °C is most likely associated with the maximum difference of ice and water supersaturation at that temperature, making the ice particles grow the fastest. These findings provide valuable information for future physical parameterization development of ice crystals within stratiform clouds.