Single-cell RNA sequencing integrated with bulk RNA sequencing analysis identifies a tumor immune microenvironment-related lncRNA signature in lung adenocarcinoma.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have been demonstrated as essential roles in tumor immune microenvironments (TIME). Nevertheless, researches on the clinical significance of TIME-related lncRNAs are limited in lung adenocarcinoma (LUAD). METHODS: Single-cell RNA sequencing and bulk RNA sequencing data are integrated to identify TIME-related lncRNAs. A total of 1368 LUAD patients are enrolled from 6 independent datasets. An integrative machine learning framework is introduced to develop a TIME-related lncRNA signature (TRLS). RESULTS: This study identified TIME-related lncRNAs from integrated analysis of single­cell and bulk RNA sequencing data. According to these lncRNAs, a TIME-related lncRNA signature was developed and validated from an integrative procedure in six independent cohorts. TRLS exhibited a robust and reliable performance in predicting overall survival. Superior prediction performance barged TRLS to the forefront from comparison with general clinical features, molecular characters, and published signatures. Moreover, patients with low TRLS displayed abundant immune cell infiltration and active lipid metabolism, while patients with high TRLS harbored significant genomic alterations, high PD-L1 expression, and elevated DNA damage repair (DDR) relevance. Notably, subclass mapping analysis of nine immunotherapeutic cohorts demonstrated that patients with high TRLS were more sensitive to immunotherapy. CONCLUSIONS: This study developed a promising tool based on TIME-related lncRNAs, which might contribute to tailored treatment and prognosis management of LUAD patients.

Integrated Exploration of Epigenetic Dysregulation Reveals a Stemness/EMT Subtype and MMP12 Linked to the Progression and Prognosis in Hepatocellular Carcinoma.

Epigenetic dysregulation drives aberrant transcriptional programs playing a critical role in hepatocellular carcinoma (HCC), which may provide novel insights into the heterogeneity of HCC. This study performed an integrated exploration on the epigenetic dysregulation of miRNA and methylation. We discovered and validated three patterns endowed with gene-related transcriptional traits and clinical outcomes. Specially, a stemness/epithelial-mesenchymal transition (EMT) subtype was featured by immune exhaustion and the worst prognosis. Besides, MMP12, a characteristic gene, was highly expressed in the stemness/EMT subtype, which was verified as a pivotal regulator linked to the unfavorable prognosis and further proven to promote tumor proliferation, invasion, and metastasis in vitro experiments. Proteomic analysis by mass spectrometry sequencing also indicated that the overexpression of MMP12 was significantly associated with cell proliferation and adhesion. Taken together, this study unveils innovative insights into epigenetic dysregulation and identifies a stemness/EMT subtype-specific gene, MMP12, correlated with the progression and prognosis of HCC.

Cellular Ligand-Receptor Perturbations Unravel MEIS2 as a Key Factor for the Aggressive Progression and Prognosis in Stage II/III Colorectal Cancer.

Approximately 10-15% of stage II and 25-30% of stage III colorectal cancer (CRC) patients experience recurrence within 5 years after surgery, and existing taxonomies are insufficient to meet the needs of clinical precision treatment. Thus, robust biomarkers and precise management were urgently required to stratify stage II and III CRC and identify potential patients who will benefit from postoperative adjuvant therapy. Alongside, interactions of ligand-receptor pairs point to an emerging direction in tumor signaling with far-reaching implications for CRC, while their impact on tumor subtyping has not been elucidated. Herein, based on multiple large-sample multicenter cohorts and perturbations of the ligand-receptor interaction network, four well-characterized ligand-receptor-driven subtypes (LRDS) were established and further validated. These molecular taxonomies perform with unique heterogeneity in terms of molecular characteristics, immune and mutational landscapes, and clinical features. Specifically, MEIS2, a key LRDS4 factor, performs significant associations with proliferation, invasion, migration, and dismal prognosis of stage II/III CRC, revealing promising directions for prognostic assessment and individualized treatment of CRC patients. Overall, our study sheds novel insights into the implications of intercellular communication on stage II/III CRC from a ligand-receptor interactome perspective and revealed MEIS2 as a key factor in the aggressive progression and prognosis for stage II/III CRC.

Identification and validation of SOCS1/2/3/4 as potential prognostic biomarkers and correlate with immune infiltration in glioblastoma.

Suppressor of cytokine signalling (SOCS) 1/2/3/4 are involved in the occurrence and progression of multiple malignancies; however, their prognostic and developmental value in patients with glioblastoma (GBM) remains unclear. The present study used TCGA, ONCOMINE, SangerBox3.0, UALCAN, TIMER2.0, GENEMANIA, TISDB, The Human Protein Atlas (HPA) and other databases to analyse the expression profile, clinical value and prognosis of SOCS1/2/3/4 in GBM, and to explore the potential development mechanism of action of SOCS1/2/3/4 in GBM. The majority of analyses showed that SOCS1/2/3/4 transcription and translation levels in GBM tissues were significantly higher than those in normal tissues. qRT-PCR, western blotting (WB) and immunohistochemical staining were used to verify that SOCS3 was expressed at higher mRNA and protein levels in GBM than in normal tissues or cells. High SOCS1/2/3/4 mRNA expression was associated with poor prognosis in patients with GBM, especially SOCS3. SOCS1/2/3/4 were highly contraindicated, which had few mutations, and were not associated with clinical prognosis. Furthermore, SOCS1/2/3/4 were associated with the infiltration of specific immune cell types. In addition, SOCS3 may affect the prognosis of patients with GBM through JAK/STAT signalling pathway. Analysis of the GBM-specific protein interaction (PPI) network showed that SOCS1/2/3/4 were involved in multiple potential carcinogenic mechanisms of GBM. In addition, colony formation, Transwell, wound healing and western blotting assays revealed that inhibition of SOCS3 decreased the proliferation, migration and invasion of GBM cells. In conclusion, the present study elucidated the expression profile and prognostic value of SOCS1/2/3/4 in GBM, which may provide potential prognostic biomarkers and therapeutic targets for GBM, especially SOCS3.

Machine learning algorithm-generated and multi-center validated melanoma prognostic signature with inspiration for treatment management.

BACKGROUND: Although immunotherapy and targeted treatments have dramatically improved the survival of melanoma patients, the intra- or intertumoral heterogeneity and drug resistance have hindered the further expansion of clinical benefits. METHODS: The 96 combination frames constructed by ten machine learning algorithms identified a prognostic consensus signature based on 1002 melanoma samples from nine independent cohorts. Clinical features and 26 published signatures were employed to compare the predictive performance of our model. RESULTS: A machine learning-based prognostic signature (MLPS) with the highest average C-index was developed via 96 algorithm combinations. The MLPS has a stable and excellent predictive performance for overall survival, superior to common clinical traits and 26 collected signatures. The low MLPS group with a better prognosis had significantly enriched immune-related pathways, tending to be an immune-hot phenotype and possessing potential immunotherapeutic responses to anti-PD-1, anti-CTLA-4, and MAGE-A3. On the contrary, the high MLPS group with more complex genomic alterations and poorer prognoses is more sensitive to the BRAF inhibitor dabrafenib, confirmed in patients with BRAF mutations. CONCLUSION: MLPS could independently and stably predict the prognosis of melanoma, considered a promising biomarker to identify patients suitable for immunotherapy and those with BRAF mutations who would benefit from dabrafenib.

Multi-omics analyses of CD276 in pan-cancer reveals its clinical prognostic value in glioblastoma and other major cancer types.

BACKGROUND: CD276 (also known as B7-H3) is one of the most important immune checkpoints of the CD28 and B7 superfamily, and its abnormal expression is closely associated with various types of cancer. It has been shown that CD276 is able to inhibit the function of T cells, and that this gene may potentially be a promising immunotherapy target for different types of cancer. METHODS: Since few systematic studies have been published on the role of CD276 in cancer to date, the present study has employed single-cell sequencing and bioinformatics methods to analyze the expression patterns, clinical significance, prognostic value, epigenetic alterations, DNA methylation level, tumor immune cell infiltration and immune functions of CD276 in different types of cancer. In order to analyze the potential underlying mechanism of CD276 in glioblastoma (GBM) to assess its prognostic value, the LinkedOmics database was used to explore the biological function and co-expression pattern of CD276 in GBM, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In addition, a simple validation of the above analyses was performed using reverse transcription-quantitative (RT-q)PCR assay. RESULTS: The results revealed that CD276 was highly expressed, and was often associated with poorer survival and prognosis, in the majority of different types of cancer. In addition, CD276 expression was found to be closely associated with T cell infiltration, immune checkpoint genes and immunoregulatory interactions between lymphoid and a non-lymphoid cell. It was also shown that the CD276 expression network exerts a wide influence on the immune activation of GBM. The expression of CD276 was found to be positively correlated with neutrophil-mediated immunity, although it was negatively correlated with the level of neurotransmitters, neurotransmitter transport and the regulation of neuropeptide signaling pathways in GBM. It is noteworthy that CD276 expression was found to be significantly higher in GBM compared with normal controls according to the RT-qPCR analysis, and the co-expression network, biological function and chemotherapeutic drug sensitivity of CD276 in GBM were further explored. In conclusion, the findings of the present study have revealed that CD276 is strongly expressed and associated with poor prognosis in most types of cancer, including GBM, and its expression is strongly associated with T-cell infiltration, immune checkpoint genes, and immunomodulatory interactions between lymphocytes and non-lymphoid cells. CONCLUSIONS: Taken together, based on our systematic analysis, our findings have revealed important roles for CD276 in different types of cancers, especially GBM, and CD276 may potentially serve as a biomarker for cancer.

TFF3 mediates the NF-κB/COX2 pathway to regulate PMN-MDSCs activation and protect against necrotizing enterocolitis.

Intestinal trefoil factor 3 (TFF3) plays an important role in repairing the intestinal mucosa. However, the detailed mechanism regarding immune regulation by TFF3 is not well defined. Here, we reported that treatment of mouse BM cells and human peripheral blood mononuclear cells from healthy volunteers with TFF3 activated polymorphnuclear myeloid-derived suppressor cells (PMN-MDSCs) in vitro. We also found that prostaglandin E2 is a major TFF3-mediated MDSC target, and that NF-κB/COX2 signaling was involved in this process. Moreover, TFF3 treatment or transfer of TFF3-derived PMN-MDSCs (TFF3-MDSCs) to experimental necrotizing enterocolitis (NEC) mice caused PMN-MDSC accumulation in the lamina propria (LP), which was associated with decreased intestinal inflammation, permeability, bacterial loading, and prolonged survival. Interestingly, no NEC severity remission was observed in Rag1 KO mice that were given TFF3-MDSCs, but coinjection with CD4+ T cells significantly relieved NEC inflammation. Overall, TFF3 mediates the NF-κB/COX2 pathway to regulate PMN-MDSC activation and attenuates NEC in a T-cell-dependent manner, which suggests a novel mechanism in preventing NEC occurrence.

An updated review of the effects of eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins on bone preservation.

Resolvins are biosynthesized from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in vivo by means of enzymatic activities, and these factors can attenuate inflammation and promote tissue regeneration. Inflammatory bone disorders can lead to bone loss and thereby be harmful to human health. The link between bone preservation and resolvins has been discussed in some experimental studies. Significant evidence has shown that resolvins benefit bone health and bone preservation by promoting the resolution of inflammation and directly regulating osteoclasts and osteoblasts. Therefore, this review highlights the role and beneficial impact of resolvins derived from EPA and DHA on inflammatory bone disorders, such as rheumatoid arthritis and periodontitis. In addition, the mechanisms by which resolvins exert their beneficial effects on bone preservation have also been summarized based on the available literature.

Impact of Resolvin D1 on the inflammatory phenotype of periodontal ligament cell response to hypoxia.

OBJECTIVE: Periodontal ligament cells (PDLCs) are critical for wound healing and regenerative capacity of periodontal diseases. Within an inflammatory periodontal pocket, a hypoxic environment can aggravate periodontal inflammation, where PDLCs response to the inflammation would change. Resolvin D1 (RvD1) is an endogenous lipid mediator, which can impact intracellular inflammatory pathways of periodontal/oral cells and periodontal regeneration. It is not clear how hypoxia and RvD1 impact the inflammatory responses of pro-inflammatory PDLCs phenotype. Therefore, this study aimed to test hypoxia could induce changes in pro-inflammatory phenotype of PDLCs and RvD1 could reverse it. METHODS: Human PDLCs were cultured from periodontal tissues from eight healthy individuals and were characterized by immunofluorescence staining of vimentin and cytokeratin. Cell viability was examined by Methyl-thiazolyl-tetrazolium (MTT) assay. To examine the effects of hypoxia and RvD1 on the inflammatory responses of pro-inflammatory PDLCs phenotype, protein levels and gene expressions of inflammatory cytokines and signal transduction molecules were measured by enzyme-linked immunosorbent assay (ELISA), western blotting (WB), and real-time quantitative reverse transcription PCR (real-time qRT-PCR). Alizarin red S staining and real-time qRT-PCR were employed to study the effects of hypoxia and RvD1 on the osteogenic differentiation of pro-inflammatory PDLCs phenotype. RESULTS: It was found that hypoxia increases the expression of inflammatory factors at the gene level (p < .05). RvD1 reduced the expression of IL-1ß (p < .05) in PDLCs under hypoxia both at the protein and RNA levels. There were increases in the expression of p38 mitogen-activated protein kinase (p38 MAPK, p < .01) and protein kinase B (Akt, p < .05) in response to RvD1. Also, a significantly higher density of calcified nodules was observed after treatment with RvD1 for 21 days under hypoxia. CONCLUSION: Our results indicate that hypoxia up-regulated the inflammatory level of PDLCs. RvD1 can reduce under-hypoxia-induced pro-inflammatory cytokines in the inflammatory phenotype of PDLCs. Moreover, RvD1 promotes the calcium nodules in PDLCs, possibly by affecting the p38 MAPK signaling pathway through Akt and HIF-1α.

Adipose-specific knockout of Protein Kinase D1 suppresses de novo lipogenesis in mice via SREBP1c-dependent signaling.

Having healthy adipose tissue is essential for metabolic health, as excessive adipose tissue in the body can cause its dysregulation and driving chronic metabolic diseases. Protein kinase D1 (PKD1) is considered to be a key kinase in signal transduction, which regulates multiple cellular functions, but its physiological functions in adipose are still not fully understood. This study aimed at elucidating the function of adipocyte PKD1 on lipogenesis. From RNA-Sequencing data, we found that the fatty acid biosynthesis pathway in white adipose tissue lacking PKD1 was significantly affected. Critical rate-limiting enzymes for de novo lipogenesis in adipocytes, such as FASN, ACCα, and SCD1, were significantly repressed after deleting PKD1 in vivo and in vitro. Further studies revealed that blockade of PKD1 significantly increased phosphorylation of SREBP1c at serine 372 site. Co-immunoprecipitation analysis showed that PKD1 interacts with SREBP1c in vitro and in vivo. Importantly, overexpression of SREBP1c reversed the inhibition of FASN and ACCα expression caused by PKD1 silencing. Together, adipocyte PKD1 promotes de novo lipogenesis via SREBP1c-dependent manner in visceral white adipose tissue and might provide a new target for the development of anti-obesity therapies.

Excessive phosphorus inputs dominate soil legacy phosphorus accumulation and its potential loss under intensive greenhouse vegetable production system.

Phosphorus (P) is an essential element for crop growth and it plays a critical role in agricultural production. Excessive P applications has become a serious concern in Chinese greenhouse vegetable production (GVP) systems. Nevertheless, P accumulation (legacy P) in GVP profile soils and its potential loss remain poorly documented. Hence, this study aimed to response this issue via paired collection of 136 soil samples (0-30, 30-60 and 60-90 cm depth) and 41 vegetable samples from both plastic greenhouses (PG) and solar greenhouses (SG) in Shouguang, Shandong province. Results showed that the annual input of P ranged from 772 to 2458 kg ha-1 for different vegetables through the whole growing season versus little vegetable P uptake (ranging from 47.8 to 155 kg ha-1). Results also revealed significant P accumulation in both SG and PG profile soils. Compared to arable soils (background soils), legacy P to the depth of 90 cm in PG and SG soils were 3.28 and 11.16 Mg P ha-1, respectively. The content of total P in PG and SG soils significantly increased with cultivation duration. The maximum environmental capacity of P in SG soils was 187 Mg ha-1, and the maximum number of years for safe planting was 38 yrs. After four years of cultivation, P loss would occur in these soils and the loss rate of P increased with cultivation duration. Opposite to PG soils, a potentially higher risk of P losses took place in SG soils. Our results also demonstrated that excessive P inputs driven by intensive agricultural practices dominated legacy P accumulation within the profile soils and its losses in GVP systems. Site-specific P managements, including improving P use efficiency, reducing further P surplus and reusing legacy P in soils, are urgently needed to minimize P loss. At the same time, the potential loss of subsoil P could not be neglected.

Oxygen Vacancies of Cr-Doped CeO2 Nanorods That Efficiently Enhance the Performance of Electrocatalytic N2 Fixation to NH3 under Ambient Conditions.

Producing ammonia (NH3) by electrocatalytic N2 fixation is a promising and environmentally friendly strategy, in comparison to the Haber-Bosch process with high consumption of energy and CO2 emissions. Because of the extremely high bond energy, it is indispensable to explore valid catalysts to activate the triple bond. In this paper, Cr-doped CeO2 nanorods are developed to serve as non-noble-metal electrocatalysts for an electrocatalytic N2 reduction reaction. Introducing Cr into the catalyst leads to an increase of the oxygen vacancies. In a 0.1 M Na2SO4 solution, the Cr0.1CeO2 nanorods achieve a high Faradaic efficiency (3.84%) and a large NH3 yield (16.82 µg h-1 mgcat.-1) at -0.7 V versus reversible hydrogen electrode. The Cr0.1CeO2 nanorods also exhibit high stability during the reaction.

Greatly Improving Electrochemical N2 Reduction over TiO2 Nanoparticles by Iron Doping.

Titanium-based catalysts are needed to achieve electrocatalytic N2 reduction to NH3 with a large NH3 yield and a high Faradaic efficiency (FE). One of the cheapest and most abundant metals on earth, iron, is an effective dopant for greatly improving the nitrogen reduction reaction (NRR) performance of TiO2 nanoparticles in ambient N2 -to-NH3 conversion. In 0.5 m LiClO4 , Fe-doped TiO2 catalyst attains a high FE of 25.6 % and a large NH3 yield of 25.47 µg h-1 mgcat -1 at -0.40 V versus a reversible hydrogen electrode. This performance compares favorably to those of all previously reported titanium- and iron-based NRR electrocatalysts in aqueous media. The catalytic mechanism is further probed with theoretical calculations.

Phosphate-Based Ultrahigh Molecular Weight Polyethylene Fibers for Efficient Removal of Uranium from Carbonate Solution Containing Fluoride Ions.

This work provides a cost-effective approach for preparing functional polymeric fibers used for removing uranium (U(VI)) from carbonate solution containing NaF. Phosphate-based ultrahigh molecular weight polyethylene (UHMWPE-g-PO4) fibers were developed by grafting of glycidyl methacrylate, and ring-opening reaction using phosphoric acid. Uranium (U(VI)) adsorption capacity of UHMWPE-g-PO4 fibers was dependent on the density of phosphate groups (DPO, mmol∙g−1). UHMWPE-g-PO4 fibers with a DPO of 2.01 mmol∙g−1 removed 99.5% of U(VI) from a Na2CO3 solution without the presence of NaF. In addition, when NaF concentration was 3 g∙L−1, 150 times larger than that of U(VI), the U(VI) removal ratio was still able to reach 92%. The adsorption process was proved to follow pseudo-second-order kinetics and Langmuir isotherm model. The experimental maximum U(VI) adsorption capacity (Qmax) of UHMWPE-g-PO4 fibers reached 110.7 mg∙g−1, which is close to the calculated Qmax (117.1 mg∙g−1) by Langmuir equation. Compared to F−, Cl−, NO3−, and SO4²− did not influence U(VI) removal ratio, but, H2PO4− and CO3²− significantly reduced U(VI) removal ratio in the order of F− > H2PO4− > CO3²−. Cyclic U(VI) sorption-desorption tests suggested that UHMWPE-g-PO4 fibers were reusable. These results support that UHMWPE-g-PO4 fibers can efficiently remove U(VI) from carbonate solutions containing NaF.

Supercritical CO2 Foaming of Radiation Cross-Linked Isotactic Polypropylene in the Presence of TAIC.

Since the maximum foaming temperature window is only about 4 °C for supercritical CO2 (scCO2) foaming of pristine polypropylene, it is important to raise the melt strength of polypropylene in order to more easily achieve scCO2 foaming. In this work, radiation cross-linked isotactic polypropylene, assisted by the addition of a polyfunctional monomer (triallylisocyanurate, TAIC), was employed in the scCO2 foaming process in order to understand the benefits of radiation cross-linking. Due to significantly enhanced melt strength and the decreased degree of crystallinity caused by cross-linking, the scCO2 foaming behavior of polypropylene was dramatically changed. The cell size distribution, cell diameter, cell density, volume expansion ratio, and foaming rate of radiation-cross-linked polypropylene under different foaming conditions were analyzed and compared. It was found that radiation cross-linking favors the foamability and formation of well-defined cell structures. The optimal absorbed dose with the addition of 2 wt % TAIC was 30 kGy. Additionally, the foaming temperature window was expanded to about 8 °C, making the handling of scCO2 foaming of isotactic polypropylene much easier.

Association of rs712 polymorphism in Kras gene 3'-luntranslated region and cancer risk: a meta-analysis.

PURPOSE: Mutation and polymorphism of Kras oncogene are considered as candidate risk factor and drug response predictor for cancer. However, the conclusions of accumulating reports related to the relationship of rs712 of Kras gene and risk of cancer remain nuclear. METHODS: We performed a meta-analysis including 6 eligible studies containing 1661 cases and 2139 controls to explore the role of rs712 in the risk of cancer development. RESULTS: Meta-analysis results showed that rs712 allele T (P(H)=0.08, odds ratio/OR=1.35, 95% confidence interval/ CI=1.17-1.55) and genotype TT (P(H)=0.174, OR=2.32, 95% CI=1.60-3.37), and allele T carrier genotype (GT/TT) (P(H)=0.14, OR=1.30, 95% CI=1.10-1.55) were strongly associated with cancer in Chinese population. No evidence of association was observed between rs712 and risk of cancer in overall population. CONCLUSION: The findings suggested that allele T, genotype TT and allele T carrier (GT/TT) of rs712 may increase susceptibility to cancer risk in Chinese population, and can be used as a genetic factor for evaluating risk of cancer.

Surfactant as a critical factor when tuning the hydrophilicity in three-dimensional polyester-based scaffolds: impact of hydrophilicity on their mechanical properties and the cellular response of human osteoblast-like cells.

In tissue engineering, the hydrophilicity of porous scaffolds is essential and influences protein and cell adhesion as well as nutrient diffusion into the scaffold. The relative low hydrophilicity of degradable polyesters, which limits diffusion of nutrients, is a major drawback in large porous scaffolds of these materials when used for bone tissue engineering and repair of critical size defects. Designing porous biodegradable polymer scaffolds with improved hydrophilicity, while maintaining their mechanical, thermal, and degradation properties is therefore of clinical interest. Here, surfactants were used to tune the hydrophilicity and material properties. A total of 3-20% (w/w) of surfactant, polysorbate 80 (Tween 80), was used as an additive in poly(l-lactide-co-1,5-dioxepan-2-one) [poly(LLA-co-DXO)] and poly(l-lactide)-co-(ε-caprolactone) [poly(LLA-co-CL)] scaffolds. A significantly decreased water contact angle was recorded for all the blends and the crystallinity, glass transition temperature and crystallization temperature were reduced with increased amounts of surfactant. Copolymers with the addition of 3% Tween 80 had comparable mechanical properties as the pristine copolymers. However, the E-modulus and tensile stress of copolymers decreased significantly with the addition of 10 and 20% Tween 80. Initial cell response of the material was evaluated by seeding human osteoblast-like cells (HOB) on the scaffolds. The addition of 3% Tween 80 did not significantly influence cell attachment or proliferation, while 20% Tween 80 significantly inhibited osteoblast proliferation. RT-PCR results showed that 3% Tween 80 stimulated mRNA expression of alkaline phosphatase (ALP), osteoprotegerin (OPG), and bone morphogenetic protein-2 (BMP-2).

Monitoring of Sweat Ions and Physiological Parameters via a Reconfigurable Modular System.

In recent years, wearable sensors have revolutionized health monitoring by enabling continuous, real-time tracking of human health and performance. These noninvasive devices are usually designed to monitor human physical state and biochemical markers. However, enhancing their functionalities often demands intricate customization by designers and additional expenses for users. Here, we present a strategy using assembled modular circuits to customize health monitoring wearables. The modular circuits can be effortlessly reconfigured to meet various specific requirements, facilitating the incorporation of diverse functions at a lower cost. To validate this approach, modular circuits were employed to develop four distinct systems for in vitro evaluations. These systems enabled the detection of sweat biomarkers and physical signals under various scenarios, including sedentary state, exercise, and daily activities with or without incorporating iontophoresis to induce sweat. Four key sweat markers (K+, Ca2+, Na+, and pH) and three essential physical indicators (heart rate, blood oxygen levels, and skin temperature) are selected as the detection targets. Commercial methods were also used to evaluate the potential for effective health monitoring with our technique. This reconfigurable modular wearable (ReModuWear) system promises to provide more easy-to-use and comprehensive health assessments. Additionally, it may contribute to environmental sustainability by reusing modules.

Crosstalk of cell death pathways unveils an autophagy-related gene AOC3 as a critical prognostic marker in colorectal cancer.

The intricate crosstalk of various cell death forms was recently implicated in cancers, laying a foundation for exploring the association between cell death and cancers. Recent evidence has demonstrated that biological networks outperform snapshot gene expression profiles at discovering promising biomarkers or heterogenous molecular subtypes across different cancer types. In order to investigate the behavioral patterns of cell death-related interaction perturbation in colorectal cancer (CRC), this study constructed the interaction-perturbation network with 11 cell death pathways and delineated four cell death network (CDN) derived heterogeneous subtypes (CDN1-4) with distinct molecular characteristics and clinical outcomes. Specifically, we identified a subtype (CDN4) endowed with high autophagy activity and the worst prognosis. Furthermore, AOC3 was identified as a potential autophagy-related biomarker, which demonstrated exceptional predictive performance for CDN4 and significant prognostic value. Overall, this study sheds light on the complex interplay of various cell death forms and reveals an autophagy-related gene AOC3 as a critical prognostic marker in CRC.

Establishment and validation of a bad outcomes prediction model based on EEG and clinical parameters in prolonged disorder of consciousness.

Objective: This study aimed to explore the electroencephalogram (EEG) indicators and clinical factors that may lead to poor prognosis in patients with prolonged disorder of consciousness (pDOC), and establish and verify a clinical predictive model based on these factors. Methods: This study included 134 patients suffering from prolonged disorder of consciousness enrolled in our department of neurosurgery. We collected the data of sex, age, etiology, coma recovery scales (CRS-R) score, complications, blood routine, liver function, coagulation and other laboratory tests, resting EEG data and follow-up after discharge. These patients were divided into two groups: training set (n = 107) and verification set (n = 27). These patients were divided into a training set of 107 and a validation set of 27 for this study. Univariate and multivariate regression analysis were used to determine the factors affecting the poor prognosis of pDOC and to establish nomogram model. We use the receiver operating characteristic (ROC) and calibration curves to quantitatively test the effectiveness of the training set and the verification set. In order to further verify the clinical practical value of the model, we use decision curve analysis (DCA) to evaluate the model. Result: The results from univariate and multivariate logistic regression analyses suggested that an increased frequency of occurrence microstate A, reduced CRS-R scores at the time of admission, the presence of episodes associated with paroxysmal sympathetic hyperactivity (PSH), and decreased fibrinogen levels all function as independent prognostic factors. These factors were used to construct the nomogram. The training and verification sets had areas under the curve of 0.854 and 0.920, respectively. Calibration curves and DCA demonstrated good model performance and significant clinical benefits in both sets. Conclusion: This study is based on the use of clinically available and low-cost clinical indicators combined with EEG to construct a highly applicable and accurate model for predicting the adverse prognosis of patients with prolonged disorder of consciousness. It provides an objective and reliable tool for clinicians to evaluate the prognosis of prolonged disorder of consciousness, and helps clinicians to provide personalized clinical care and decision-making for patients with prolonged disorder of consciousness and their families.