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Immune composition within the tumor microenvironment (TME) plays a central role in the propensity of cancer cells to metastasize and respond to therapy. Previous studies have suggested that the metastatic TME is immune-suppressed. However, limited accessibility to multiple metastatic sites within patients has made assessing the immune TME difficult in the context of multiorgan metastases. We utilized a rapid postmortem tissue collection protocol to assess the immune composition of numerous sites of breast cancer metastasis and paired tumor-free tissues. Metastases had comparable immune cell densities and compositions to paired tumor-free tissues of the same organ type. In contrast, immune cell densities in both metastatic and tumor-free tissues differed significantly between organ types, with lung immune infiltration being consistently greater than that in the liver. These immune profiling results were consistent between flow cytometry and multiplex immunofluorescence-based spatial analysis. Furthermore, we found that granulocytes were the predominant tumor-infiltrating immune cells in lung and liver metastases, and these granulocytes comprised most PD-L1-expressing cells in many tissue sites. We also identified distinct potential mechanisms of immunosuppression in lung and liver metastases, with the lung having increased expression of PD-L1+ antigen-presenting cells and the liver having higher numbers of activated regulatory T cells and HLA-DRlow monocytes. Together, these results demonstrate that the immune contexture of metastases is dictated by organ type and that immunotherapy strategies may benefit from unique tailoring to the tissue-specific features of the immune TME., (©2024 American Association for Cancer Research.)

This study aimed to systematically review and compare the efficacy and safety of anterior cervical controllable antedisplacement and fusion (ACAF) versus anterior cervical corpectomy and fusion (ACCF) in treating ossification of the cervical posterior longitudinal ligament (OPLL), focusing on surgery-related indicators and postoperative outcomes. This review was conducted and reported in accordance with the Cochrane Handbook for Systematic Reviews of Interventions guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards. The methodological quality of this systematic review was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) checklist. A detailed search strategy was implemented to retrieve literature from electronic databases, including PubMed, EMBASE, and the Cochrane Library, followed by quality assessment and data extraction for eligible studies. A total of 5 studies involving 366 participants were included. ACAF was associated with significantly fewer complications (OR = 0.25, 95% CI [0.12, 0.51], p = 0.000), including a lower incidence of cerebrospinal fluid (CSF) leakage (OR = 0.20, 95% CI [0.08, 0.52], p = 0.000). ACAF also showed better outcomes in postoperative neck disability index (NDI) scores (SMD = -0.48, 95% CI [-0.81, -0.15], p = 0.020), C2-C7 angle (SMD = 1.29, 95% CI [0.56, 2.03], p = 0.000), spinal canal area (SCA) (SMD = 0.93, 95% CI [0.56, 1.29], p = 0.000), and diameter of the spinal cord (DSC) (SMD = 0.38, 95% CI [0.11, 0.66], p = 0.010). Additionally, ACAF improved The Japanese Orthopedic Association (JOA) scores (SMD = 0.29, 95% CI [0.01, 0.57], p = 0.040) but required longer operation time (SMD = 1.08, 95% CI [0.01, 2.15], p = 0.049). No significant differences were found in blood loss (SMD = 0.23, 95% CI [-0.34, 0.79], p = 0.431), hospital stay (SMD = 0.65, 95% CI [-1.46, 2.76], p = 0.547), and improvement rate (IR) (SMD = 0.38, 95% CI [-0.10, 0.86], p = 0.118). The current meta-analysis indicated that ACAF surgery can effectively reduce the incidence of complications, significantly increase the spinal canal area and improve the spatial conditions of the spinal cord compared to those associated with ACCF surgery. This is more advantageous for the postoperative neurological recovery of patients. Nonetheless, it is crucial to approach these findings with a degree of caution., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tumor draining lymph nodes (TDLN) represent a key component of the tumor-immunity cycle. There are few studies describing how TDLNs impact lymphocyte infiltration into tumors. Here we directly compare tumor-free TDLNs draining "cold" and "hot" human triple negative breast cancers (TDLN Cold and TDLN Hot ). Using machine-learning-based self-correlation analysis of immune gene expression, we find unbalanced intranodal regulations within TDLN Cold . Two gene pairs (TBX21/GATA3-CXCR1) with opposite correlations suggest preferential priming of T helper 2 (Th2) cells by mature dendritic cells (DC) within TDLN Cold . This is validated by multiplex immunofluorescent staining, identifying more mature-DC-Th2 spatial clusters within TDLN Cold versus TDLN Hot . Associated with this Th2 priming preference, more IL4 producing mast cells (MC) are found within sinus regions of TDLN Cold . Downstream, Th2-associated fibrotic TME is found in paired cold tumors with increased Th2/T-helper-1-cell (Th1) ratio, upregulated fibrosis growth factors, and stromal enrichment of cancer associated fibroblasts. These findings are further confirmed in a validation cohort and public genomic data. Our results reveal a potential role of IL4 + MCs within TDLNs, associated with Th2 polarization and reduced immune infiltration into tumors., (© 2024. The Author(s).)

Aqueous MXene dispersion suffers from a bottleneck issue of oxidation, leading to its gradual deterioration and ultimately compromised physicochemical characteristics. Herein, Tris-HCl buffer is employed to stabilize the diluted Ti 3 C 2 T x -MXene dispersion (0.05 mg mL -1 ) through the synergy of its potent pH-regulation capability and capping effect toward oxidation-susceptible defects/edges. Tris-HCl functionalized Ti 3 C 2 T x maintained its original morphology, structure, and favorable dispersity even after 150 days of aging under naturally aerated conditions. The pH-regulation nature of Tris-HCl is elucidated through solution monitoring of Ti 3 C 2 T x dispersion, while the adsorption of Tris-HCl onto defects/edges is revealed by spectral analysis and multi-scale simulations. Tris-HCl at the neutral pH can bind to the negatively charged basal plane of Ti 3 C 2 T x via + HTris moiety, while the other moiety (Tris) interacts with the exposed edge-based Ti atoms and/or intrinsic defects, forming a Ti─N bond that prevents MXene from attack by H 2 O and O 2 . Besides, Tris-HCl stabilized Ti 3 C 2 T x exhibited nearly identical capacitive characteristics to its freshly-etched counterpart, indicating the minimal impact of Tris-HCl on electrochemical performance of Ti 3 C 2 T x during long-term storage. This study provides practical guidance for stabilizing MXene in their native aqueous dispersion without compromising the inherent properties., (© 2024 Wiley‐VCH GmbH.)

Four new lignans named cephaliverins A-D (1-4), along with seven known analogues (5-11), were isolated from Cephalotaxus oliveri Mast. Their structures were elucidated on the basis of HR-ESI-MS and NMR analyses, and their absolute configurations were determined by ECD comparison. Cephaliverin A (1), herpetotriol (5) and hedyotol A (6) exhibited moderate antitumor activity against HepG2 and A549 cell lines., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Organoid tumor models have emerged as a powerful tool in the fields of biology and medicine as such 3D structures grown from tumor cells recapitulate better tumor characteristics, making these tumoroids unique for personalized cancer research. Assessment of their functional behavior, particularly protein secretion, is of significant importance to provide comprehensive insights. Here, a label-free spectroscopic imaging platform is presented with advanced integrated optofluidic nanoplasmonic biosensor that enables real-time secretion analysis from single tumoroids. A novel two-layer microwell design isolates tumoroids, preventing signal interference, and the microarray configuration allows concurrent analysis of multiple tumoroids. The dual imaging capability combining time-lapse plasmonic spectroscopy and bright-field microscopy facilitates simultaneous observation of secretion dynamics, motility, and morphology. The integrated biosensor is demonstrated with colorectal tumoroids derived from both cell lines and patient samples to investigate their vascular endothelial growth factor A (VEGF-A) secretion, growth, and movement under various conditions, including normoxia, hypoxia, and drug treatment. This platform, by offering a label-free approach with nanophotonics to monitor tumoroids, can pave the way for new applications in fundamental biological studies, drug screening, and the development of therapies., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Low-carbon alkaline thermal hydrolysis of sewage sludge for the production of high-quality plant-growth-promoting nutrients and biostimulants is a growing concern for sludge resource utilization in agriculture. Thus, this study aims to investigate functional characteristics and soil biochemical effects of sewage sludge-derived nutrients and biostimulants (SS-NB). The content of heavy metals in SS-NB decreased by 47.39-100%, and an increase in soil protease, invertase, and soil nutrient utilization rates are observed in SS-NB groups. SS-NB substituted for chemical fertilizer increased the diversity and evenness of microbial community and reduced the abundance of the soil-borne bacterial genus Arthrobacter. The dominant community of SS-NB100 group is mainly enriched in Microvirga, Ensifer, Novosphingobium, Bosea and Ellin6055, which are principally beneficial symbiotic bacteria of plants and participated in C and N cycles. Moreover, SS-NB reduced the accumulation of Ktedonobacteria and Nitrosospira, which are involved in the production of CO 2 and N 2 O, and also enhanced the coordination of soil microorganisms with enzyme activities and nutrient utilization rate. In conclusion, the results suggest that SS-NB exerts a positive effect on reducing greenhouse gas emissions and preventing soil-borne diseases, and can further enhance collaboration with soil enzyme activity and soil nutrient utilization by stimulating soil microorganisms., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The reduction of the carbon emissions of construction industry is urgent. Therefore, it is essential to accurately predict the carbon emissions of the provincial construction industry, which can support differentiation emission reduction policies in China. This paper proposes a carbon emission prediction model that optimizes the backpropagation (BP) neural network by genetic algorithm (GA) to predict carbon emission of construction industry, or "GA-BP". To begin with, the carbon emissions of construction industry in Sichuan Province from 2000 to 2020 are calculated by the emission factor method. Further, the electricity correction factor is introduced to eliminate the regional difference in electricity carbon emission coefficient. Finally, four factors are selected by the grey correlation analysis method to predict the carbon emission of construction industry in Sichuan Province from 2021 to 2025. The results show that the carbon emissions of construction industry in Sichuan Province have been trending up in the past two decades, with an average increase rate of 10.51%. The GA-BP model is a high-precision prediction model to predict carbon emissions of construction industry. The mean absolute percentage error (MAPE) of the model is only 6.303%, and its coefficient of determination is 0.853. Moreover, the carbon emissions of construction industry in Sichuan Province will reach 8891.97 million tons of CO 2 in 2025. The GA-BP model can effectively predict the future carbon emissions of construction industry in Sichuan Province, which provides a new idea for the green and sustainable development of construction industry in Sichuan Province., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The production of high quality liquid nitrogen fertilizer with both nutrient comprehensive and biostimulant properties by alkaline thermal hydrolysis of sewage sludge has shown great potential in agricultural production. However, little is known about the effects of sewage sludge-derived nutrients, and biostimulants (SS-NB) on leaf photosynthesis and root growth in rice. Phenotypic, metabolic and microbial analyses were used to reveal the mechanism of SS-NB on rice. Compared to NF treatment, phenotypic parameters (fresh/dry weight, soluble sugar, amino acid, protein) were increased by SS-NB in rice. SS-NB can enhance the photosynthesis of rice leaves by improving the photoconversion efficiency, chlorophyll content, ATP synthase activity, Rubisco and NADPH production. Meanwhile, SS-NB also increased antioxidant capacity (SOD, POD, CAT and proline) in rice leaf and root tissues. Metabolomics revealed that SS-NB application increased the expression levels of metabolites in root and leaf tissues, including carbohydrate, nitrogen and sulfur metabolism, amino acid metabolism, antioxidants, and phytohormone. Most importantly, the regulation of metabolites in rice root tissues is more sensitive than in leaf tissues, especially to the higher levels of antioxidants and phytohormones (IAA and GA) in rice root tissues. Furthermore, SS-NB increased the abundance of photosynthetic autotrophic, organic acids-degrading and denitrifying functional bacteria in rice roots and recruited plant growth-promoting bacteria (Azospirillum and norank_f_JG30-KF-CM45), while the NF treatment group resulted in an imbalance of the microbial community, leading to the dominance of pathogenic bacteria. The results showed that SS-NB had great application potential in crop growth and stress resistance improvement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: While mutation-derived neoantigens are well recognized in generating anti-tumour T cell response, increasing evidences highlight the complex association between tumour mutation burden (TMB) and tumour infiltrating lymphocytes (TILs). The exploration of non-TMB determinants of active immune response could improve the prognosis prediction and provide guidance for current immunotherapy., Methods: The transcriptomic and whole exome sequence data in The Cancer Genome Atlas were used to examine the relationship between TMB and exhausted CD8+ T cells (Tex), as an indicator of tumour antigen-specific T cells across nine major cancer types. Computational clustering analysis was performed on 4510 tumours to identify different immune profiles. NanoString gene expression analysis and single cell RNA-seq analysis using fresh human breast cancer were performed for finding validation., Findings: TMB was found to be poorly correlated with active immune response in various cancer types. Patient clustering analysis revealed a group of tumours with abundant Tex but low TMB. In those tumours, we observed significantly higher expression of the stimulator of interferon genes (STING) signalling. Dendritic cells, particularly those of BATF3+ lineage, were also found to be essential for accumulation of Tex within tumours. Mechanistically, loss of genomic and cellular integrity, marked by decreased DNA damage repair, defective replication stress response, and increased apoptosis were shown to drive STING activation., Interpretation: These results highlight that TMB alone does not fully predict tumour immune profiles, with STING signalling compensating for low TMB in non-hypermutated tumours to enhance anti-tumour immunity. Translating these results, STING agonists may benefit patients with non-hypermutated tumours. STING activation may serve as an additional biomarker to predict response to immune checkpoint blockades alongside TMB. Our research also unravelled the interplay between genomic instability and STING activation, informing potential combined chemotherapy targeting the axis of genomic integrity and immunotherapy., Funding: City of Hope Christopher Family Endowed Innovation Fund for Alzheimer's Disease and Breast Cancer Research in honor of Vineta Christopher; Breast Cancer Alliance Early Career Investigator Award; National Cancer Institute of the National Institutes of Health under award number R01CA256989 and R01CA240392., Competing Interests: Declaration of interests All authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Tumor-associated macrophages (TAMs) are the predominant cells that express programmed cell death ligand 1 (PD-L1) within human tumors in addition to cancer cells, and PD-L1 + TAMs are generally thought to be immunosuppressive within the tumor immune microenvironment (TIME). Using single-cell transcriptomic and spatial multiplex immunofluorescence analyses, we show that PD-L1 + TAMs are mature and immunostimulatory with spatial preference to T cells. In contrast, PD-L1 - TAMs are immunosuppressive and spatially co-localize with cancer cells. Either higher density of PD-L1 + TAMs alone or ratio of PD-L1 + /PD-L1 - TAMs correlate with favorable clinical outcome in two independent cohorts of patients with breast cancer. Mechanistically, we show that PD-L1 is upregulated during the monocyte-to-macrophage maturation and differentiation process and does not require external IFN-γ stimulus. Functionally, PD-L1 + TAMs are more mature/activated and promote CD8 + T cells proliferation and cytotoxic capacity. Together, our findings reveal insights into the immunological significance of PD-L1 within the TIME., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

At present, percutaneous surgery is widely used to treat thoracolumbar fractures. However, the actual safety, feasibility, and effectiveness of percutaneous surgery are not clear. Through systematic review and meta-analysis, we compared the efficacies of percutaneous pedicle screw fixation and open pedicle screw fixation in the treatment of thoracolumbar fractures without nerve root symptoms. We systematically searched the PubMed, Embase, and Cochrane libraries for articles published on or before June 2023. All results were evaluated by standard methods recommended for meta-analysis, continuous data were expressed by standard mean differences (SMDs), and binary variables were analyzed by odds ratios (ORs) and 95% confidence intervals (95% CIs). We also explored the main sources of heterogeneity and the stability of the results through sensitivity analysis, Begg's funnel plots, and Egger's test. Thirty-five cohort studies with a total of 3039 patients were included. The study found that patients who undergo percutaneous approaches have less intraoperative blood loss (IBL), shorter length of hospital stay (LOS), shorter operation time, and shorter incision. Moreover, percutaneous approaches had more advantages in terms of visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, and infection rates. However, there was no significant difference in anterior vertebral body height (AVB), Cobb angle (CA), or screw errors between the two groups. In the long run, the clinical and surgical results of the percutaneous approach are better than those of the open approach, but the radiological results of both operations do not seem to show an advantage for any specific approach. Because of publication bias and heterogeneity, our findings must be interpreted with caution. However, this paper will provide some support for clinicians to choose suitable surgical methods for the treatment of thoracolumbar fractures., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Four undescribed naturally diterpenolignans, and two cephalotane diterpenoids, along with seven known compounds, including two pairs of enantiomers, were isolated from the twigs and leaves of Cephalotaxus oliveri Mast. Their structures were elucidated via spectroscopic data interpretation, chiral-phase HPLC analysis, NMR calculations, and electronic circular dichroism analysis. All the isolated compounds were evaluated for their cytotoxic activities against three kinds of human tumor cell lines. Among them, compound 8 exhibited the most potent activities against MCF-7, HepG2 and A549 cell lines with IC 50 values of 2.83, 4.75 and 2.77 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Emotional labor has been a focal point in occupational well-being literature, but studies have long overlooked an important group of emotional laborers: performers. This research represents a pioneering effort to examine dancers' adoption of emotional labor strategies, their antecedent of self-consciousness, and the outcome of flow experience. We explored these elements both in the traditional setting of stage dancing and in the novel context of online dance classes without on-site spectators during the COVID-19 pandemic. The results revealed that dancers employed all three common emotional labor strategies: surface acting, deep acting, and expression of naturally felt emotions, with deep acting being the most frequent. In the traditional setting, only the expression of naturally felt emotions mediated the positive effect of private self-consciousness and the negative effect of public self-consciousness on flow experience. In contrast, in the online setting, only private self-consciousness impacted flow through the mediation of deep acting and expression of naturally felt emotions. This exploratory study bridges dramaturgy-originated theories of emotional labor with empirical performing arts research, preliminarily advancing knowledge in the relevant fields of dance education, self-presentation, and flow studies., (© 2023. Springer Nature Limited.)

Alkaline thermal hydrolysis of sewage sludge to produce high-quality liquid fertilizer that contains protein, amino acid, organic acid and biostimulants is receiving wide attention, however, the impact on plants and environmental risks must be evaluated for sustainable use. In this study, the interactions between sewage sludge-derived nutrients, biostimulants (SS-NB), and pakchoi cabbage were investigated by a combination of phenotypic and metabolic approaches. Compared with SS-NB0 (single chemical fertilizer), SS-NB100, SS-NB50, and SS-NB25 had no effect on crop yield, but the net photosynthetic rate increased from 1.13 % to 9.82 %. In addition, the antioxidant enzyme activity (SOD) increased from 29.60 % to 71.42 %, with decreasing malondialdehyde (MDA) and H 2 O 2 levels by 84.62-92.93 % and 8.62-18.97 %, respectively, indicating positive effects on photosynthetic and antioxidant capacities. Leaf metabolomics revealed that SS-NB100, SS-NB50, and SS-NB25 resulted in up-regulation of amino acid and alkaloid metabolites, down-regulation of carbohydrate metabolites, and up-regulation and down-regulation of organic acid metabolites, which were involved in carbon and nitrogen redistribution. Galactose metabolism was inactivated by SS-NB100, SS-NB50, and SS-NB25, indicating the protective role of SS-NB in oxidative damage in cells. Furthermore, the application of SS-NB also resulted in a significant reduction in heavy metal contents (Cr, Ni, and Pb) and the target hazard quotient (THQ). The THQ values of Cd, Cr, Ni and Pb were <1.0 in SS-NB50, and may be considered as an optimal fertilization strategy. The result provided better understanding of the phenotypic and metabolic changes imposed by SS-NB-replaced chemical fertilizer nitrogen in pakchoi cabbage leaves., Competing Interests: Declaration of competing interest All the authors listed have approved the manuscript and agreed to authorship and submission of the manuscript for peer review., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Transplantation of mesenchymal stem cells (MSCs) holds promise to repair severe traumatic injuries. However, current transplantation practices limit the potential of this technique, either by losing the viable MSCs or reducing the performance of resident MSCs. Herein, we design a "bead-jet" printer, specialized for high-throughput intra-operative formulation and printing of MSCs-laden Matrigel beads. We show that high-density encapsulation of MSCs in Matrigel beads is able to augment MSC function, increasing MSC proliferation, migration, and extracellular vesicle production, compared with low-density bead or high-density bulk encapsulation of the equivalent number of MSCs. We find that the high-density MSCs-laden beads in sparse patterns demonstrate significantly improved therapeutic performance, by regenerating skeletal muscles approaching native-like cell density with reduced fibrosis, and regenerating skin with hair follicle growth and increased dermis thickness. MSC proliferation within 1-week post-transplantation and differentiation at 3 - 4 weeks post-transplantation are suggested to contribute therapy augmentation. We expect this "bead-jet" printing system to strengthen the potential of MSC transplantation., (© 2022. The Author(s).)

Introduction: Lung cancer is the leading cause of cancer deaths in the world and is usually divided into non-small cell lung cancer (NSCLC) and small cell lung cancer. NSCLC is dominant and accounts for 85% of the total cases. Currently, the therapeutic method of NSCLC is not so satisfactory, and thus identification of new biomarkers is critical for new clinical therapy for this disease., Methods: Datasets of miRNA and gene expression were obtained from the NCBI database. The differentially expressed genes (DEGs) and miRNAs (DEMs) were analyzed by GEO2R tools. The DEG-DEM interaction was built via miRNA-targeted genes by miRWalk. Several hub genes were selected via network topological analysis in Cytoscape., Results: A set of 276 genes were found to be significantly differentially expressed in the three datasets. Functional enrichment by the DAVID tool showed that these 276 DEGs were significantly enriched in the term "cancer", with a statistic p -value of 1.9 × 10 -5 . The subdivision analysis of the specific cancer types indicated that "lung cancer" occupies the largest category with a p -value of 2 × 10 -3 . Furthermore, 75 miRNAs were shown to be differentially expressed in three representative datasets. A group of 13 DEGs was selected by analysis of the miRNA-gene interaction of these DEGs and DEMs. The investigation of these 13 genes by GEPIA tools showed that eight of them had consistent results with NSCLC samples in the TCGA database. In addition, we applied the KMplot to conduct the survival analysis of these eight genes and found that seven of them have a significant effect on the prognosis survival of patients. We believe that this study could provide effective research clues for the prevention and treatment of non-small cell lung cancer.

Objective To investigate whether swelling stress exists in lung cancer cells by comparing water content and nucleus size as well as mitogen activated protein kinase (MAPK) phosphorylation activation between lung cancer tissues and corresponding paracancerous tissues. Methods Differences in water content between fresh specimens of 10 human lung adenocarcinoma, 12 lung squamous cell carcinoma, and corresponding paracancerous normal lung tissues were examined through "dry and wet" mass comparison. The expressions and phosphorylation activation of mitogen activated protein kinases JNK, ERK1/2, and p38 in 30 lung adenocarcinoma samples, 32 lung squamous cell carcinoma samples, and alveolar epithelial cells and lung bronchial epithelial cells of 10 paracancerous normal tissues samples were detected with their phosphorylated and non-phosphorylated antibodies and by immunohistochemical staining. Nucleus size differences between cancer cells from lung adenocarcinoma and lung squamous cell carcinoma samples and corresponding paracancerous normal lung alveolar epithelial cells or bronchial epithelial cells were estimated by HE staining and analyzed with image analysis software. Results The average water content of lung squamous cell carcinoma and lung adenocarcinoma samples were significantly higher than that of their corresponding paracancerous normal tissues. Immunohistochemistry showed that p38 was highly expressed in all samples of lung adenocarcinoma, lung squamous cell carcinoma, and paracancerous tissues. ERK was weakly expressed in lung adenocarcinoma and squamous cell carcinoma samples, but highly expressed in paracancerous tissues. JNK was weakly expressed in lung adenocarcinoma and paracancerous tissues. JNK, p38 MAPK, and ERK1/2 were not activated through phosphorylation in alveolar or bronchial epithelial tissues. However, JNK, not p38 or ERK1/2, was phosphorylated in lung adenocarcinoma and lung squamous cell carcinoma tissues. The average nucleus size of lung cancer cells was significantly larger than those of their corresponding paracancerous normal lung epithelial cells. Conclusion There is swelling stress in lung cancer cells, and different types of human lung cancer cells have different swelling stress signaling pathways.

CD8+ tumor-infiltrating lymphocytes (TILs) are associated with improved survival in triple-negative breast cancer (TNBC) yet have no association with survival in estrogen receptor-positive (ER+) BC. The basis for these contrasting findings remains elusive. We identified subsets of BC tumors infiltrated by CD8+ T cells with characteristic features of exhausted T cells (TEX). Tumors with abundant CD8+ TEX exhibited a distinct tumor microenvironment marked by amplified interferon-γ signaling-related pathways and higher programmed death ligand 1 expression. Paradoxically, higher levels of tumor-infiltrating CD8+ TEX associated with decreased overall survival of patients with ER+ BC but not patients with TNBC. Moreover, high tumor expression of a CD8+ TEX signature identified dramatically reduced survival in premenopausal, but not postmenopausal, patients with ER+ BC. Finally, we demonstrated the value of a tumor TEX signature score in identifying high-risk premenopausal ER+ BC patients among those with intermediate Oncotype DX Breast Recurrence Scores. Our data highlight the complex relationship between CD8+ TILs, interferon-γ signaling, and ER status in BC patient survival. This work identifies tumor-infiltrating CD8+ TEX as a key feature of reduced survival outcomes in premenopausal patients with early-stage ER+ BC.

Objectives: The incidence of stroke is on the rise among younger adults. Stroke educational campaigns are often used to raise public knowledge of stroke warning signs and response actions, but their effectiveness in non-elderly adults is unclear. This study investigated the effectiveness of stroke campaigns in improving stroke symptom recognition and intention to call emergency medical services in adults aged < 65 years, and described the characteristics of public stroke education in this demographic group., Materials and Methods: Seven databases (Cochrane Library, CINAHL, Embase, Medline, PsycINFO, Scopus, and ProQuest Dissertations and Theses) were searched from inception to 24 January 2021. A meta-analysis was conducted to synthesize the effects of stroke education campaigns on stroke symptom recognition and intention to call emergency medical services in adults < 65 years. A narrative synthesis approach was used to explore the types of educational content and campaign best suited to this demographic group., Results: Thirteen studies from 2001 to 2019 were included in this review. Out of the thirteen studies, five were included in the meta-analysis to synthesize the effects of stroke education campaigns on symptom recognition and four were included for synthesizing the effects on intention to call emergency medical services. The estimated pooled risk ratio for post-campaign compared with pre-campaign in stroke symptom recognition and intention to call emergency medical services was 1.20 (95% CI: 1.07-1.36, p = 0.002) and 1.19 (95% CI: 1.11-1.28, p < 0.00001), respectively. Usage of acronyms in broadcast and digital media campaigns appears promising in enhancing recognition of and responsiveness to stroke symptoms., Conclusions: Public stroke education campaigns were found to have a significant impact on stroke symptom recognition and intention to call emergency medical services. The evidence generated from this review could be applied to inform future campaigns targeted at younger adults., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT. Compared with the high-thermogenic brown adipocytes, these low-thermogenic brown adipocytes had substantially lower Ucp1 and Adipoq expression, larger lipid droplets, and lower mitochondrial content. Functional analyses showed that, unlike the high-thermogenic brown adipocytes, the low-thermogenic brown adipocytes have markedly lower basal mitochondrial respiration, and they are specialized in fatty acid uptake. Upon changes in environmental temperature, the 2 brown adipocyte subpopulations underwent dynamic interconversions. Cold exposure converted low-thermogenic brown adipocytes into high-thermogenic cells. A thermoneutral environment had the opposite effect. The recruitment of high-thermogenic brown adipocytes by cold stimulation is not affected by high-fat diet feeding, but it does substantially decline with age. Our results revealed a high degree of functional heterogeneity of brown adipocytes.

We report a paper-based surface-enhanced Raman spectroscopy (SERS) biosensor integrating the enrichment capability, namely enPSERS biosensor, for the sensitive, label-free detection of free bilirubin in blood serum for the accurate diagnosis of jaundice and its related diseases. This biosensor comprises multifunctional graphene oxide-plasmonic gold nanostar (GO-GNS) hybrids decorated on the filter paper, which integrates the high sensitivity of SERS detection, enrichment for serum bilirubin and fluorescence superquenching capability of GO-GNS hybrids for sensitive detection of serum bilirubin. The study of adsorption kinetics reveals that both electrostatic and π-π interactions between the GO-GNS hybrids and targets are responsible for the enrichment of bilirubin, and the adsorption process follows the pseudo-second-order kinetic model. The results of SERS detection of bilirubin in blood serum show two differential linear response ranges from 5.0 to 150 μM and 150-500 μM with the detection limit as low as 0.436 μM. The comparison of the results obtained from our present enPSERS biosensor with the commercial diazo reaction method for determination of free bilirubin in blood serum reveals the clinical effectiveness and suitability of the developed paper-based SERS biosensor. We believe that this sensitive and label-free SERS biosensor holds considerable promise for clinical translation in accurate diagnosis of jaundice., (Copyright © 2019 Elsevier B.V. All rights reserved.)

It is well-known that the presence of the delamination in a plant fiber-reinforced composite is difficult to detect. However, the delamination introduces a local flexibility, which changes the dynamic characteristics of the composite structure. This paper presents a new methodology for composite laminate delamination detection, which is based on dynamic mechanical analysis. A noticeable delamination-induced storage modulus reduction and loss factor enhancement have been observed when the delaminated laminate was subjected to a forced oscillation compared to the intact composite laminate. For delamination area of 12.8% of the whole area of the composite laminate, loss factor of approximately 12% increase was observed. For near-to-surface delamination position, loss factor of approximately an 18% increment was observed. The results indicate that the delamination can be reliably detected with this method, and delamination position shows greater influence on the loss factor than that of the delamination size. Further investigations on different frequencies and amplitudes configurations show that the variation of loss factor is more apparently with low frequency as well as the low amplitude.

Gene expression is regulated at the transcription and translation levels; thus, both transcription factors (TFs) and microRNAs (miRNA) play roles in regulation of gene expression. This study profiled differentially expressed mRNAs and miRNAs in gastric cancer tissues to construct a TF and miRNA co-regulatory network in order to identify altered genes in gastric cancer progression. A total of 70 cases gastric cancer and paired adjacent normal tissues were subjected to cDNA and miRNA microarray analyses. We obtained 887 up-regulated and 93 down-regulated genes and 41 down-regulated and 4 up-regulated miRNAs in gastric cancer tissues. Using the Transcriptional Regulatory Element Database, we obtained 105 genes that are regulated by the E2F family of genes and using Targetscan, miRanda, miRDB and miRWalk tools, we predicted potential targeting genes of these 45 miRNAs. We then built up the E2F-related TF and miRNA co-regulatory gene network and identified 9 hub-genes. Furthermore, we found that levels of E2F1, 2, 3, 4, 5, and 7 mRNAs associated with gastric cancer cell invasion capacity, and has associated with tumor differentiation. These data showed Overexpression of E2F mRNAs associated with gastric cancer progression.

Deep brain stimulation (DBS) is an established therapy for movement disorders such as Parkinson's disease (PD). Although the efficacy of DBS is clear, its precise molecular mechanism remains unknown. The glial cell line derived factor (GDNF) family of ligands has been shown to confer neuroprotective effects on dopaminergic neurons, and putaminal infusion of GDNF have been investigated in PD patients with promising results. Despite the potential therapeutic role of GDNF in alleviating motor symptoms, there is no data on the effects of electrical stimulation on GDNF-family receptor (GFR) expression in the basal ganglia structures. Here, we report the effects of electrical stimulation on GFRα1 isoforms, particularly GFRα1a and GFRα1b. Wistar rats underwent 2 hours of high frequency stimulation (HFS) at the globus pallidus interna nucleus. A control group was subjected to a similar procedure but without stimulation. The HFS group, sacrificed 24 hours after treatment, had a threefold decrease in mRNA expression level of GFRα1b (p=0.037), but the expression level reverted to normal 72 hours after stimulation. Our preliminary data reveal the acute effects of HFS on splice isoforms of GFRα1, and suggest that HFS may modulate the splice isoforms of GFRα1a and GFRα1b to varying degrees. Going forward, elucidating the interactions between HFS and GFR may shed new insights into the complexity of GDNF signaling in the nervous system and lead to better design of clinical trials using these signaling pathways to halt disease progression in PD and other neurodegenerative diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A method for the determination of three phenoxyalkanoic acid herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D), 2-(2,4-dichlorophenoxy)-propanoic acid (2,4-DP), and 4-chloro-2-methylphenoxy-acetic acid (MCPA), in blood was developed. The blood sample was diluted with 0.1 mol/L hydrochloric acid, and extracted by solid-phase extraction using porous resin GDX401 as adsorbent and ethyl ether as eluent. The extract was esterified with dichloropropanol in the presence of sulfuric acid as catalyst. The derivatives were analysed by gas chromatography with electron-capture detection. The detection limits of 2,4-D, 2,4-DP and MCPA were 20, 8 and 40 ng/mL, respectively. In quantitative analysis, 2,4-dichlorophenylacetic acid was used as an internal standard. The linear relationships and recoveries were satisfactory. The derivatization of the three herbicides with methanol, ethanol, n-propanol, n-butanol, and trifluoroethanol were also studied, and the analytical methods of these derivatization were compared with that of dichloropropanol as esterifying agent. The method is sensitive enough for the examination of the poison samples in actual.