The structure of liquid water is primarily composed of three-dimensional networks of water clusters formed by hydrogen bonds, and dissolved oxygen is one of the most important indicators for assessing water quality. In this work, distilled water with different concentration of dissolved oxygen were prepared, and a clear negative correlation between the size of water clusters and dissolved oxygen concentration was observed. Besides, a phenomenon of rapid absorption and release of oxygen at the water interfaces was unveiled, suggesting that oxygen molecules predominantly exist at the interfaces of water clusters. Oxygen molecules can move rapidly through the interfaces among water clusters, allowing dissolved oxygen to quickly reach a saturation level at certain partial pressure of oxygen and temperature. Further exploration into the mechanism by molecular dynamics simulations of oxygen and water clusters found that oxygen molecules can only exist stably at the interfaces among water clusters. A semi-empirical formula relating the average number of water molecules in a cluster (n) to 17O NMR half-peak width (W) was summarized: n = 0.1 W + 0.85. These findings provide a foundation for exploring the structure and properties of water.
B-cell epitope identification plays a vital role in the development of vaccines, therapies, and diagnostic tools. Currently, molecular docking tools in B-cell epitope prediction are heavily influenced by empirical parameters and require significant computational resources, rendering a great challenge to meet large-scale prediction demands. When predicting epitopes from antigen-antibody complex, current artificial intelligence algorithms cannot accurately implement the prediction due to insufficient protein feature representations, indicating novel algorithm is desperately needed for efficient protein information extraction. In this paper, we introduce a multimodal model called WUREN (Whole-modal Union Representation for Epitope predictioN), which effectively combines sequence, graph, and structural features. It achieved AUC-PR scores of 0.213 and 0.193 on the solved structures and AlphaFold-generated structures, respectively, for the independent test proteins selected from DiscoTope3 benchmark. Our findings indicate that WUREN is an efficient feature extraction model for protein complexes, with the generalizable application potential in the development of protein-based drugs. Moreover, the streamlined framework of WUREN could be readily extended to model similar biomolecules, such as nucleic acids, carbohydrates, and lipids.
OBJECTIVE: To observe the multi-slice spiral CT angiography (MSCTA) imaging features of arteriovenous fistula dysfunction in patients undergoing maintenance hemodialysis and analyze the significance of the imaging examination. METHODS: Altogether 90 patients with end-stage renal disease treated by maintenance hemodialysis in General Hospital of China Resources & Wisco from June 2020 to February 2023 were divided into a normal function group (n=68) and a dysfunction group (n=22) according to the function of autogenous arteriovenous fistula. The clinical data of the two groups were recorded. The MSCTA was performed in each patient, and the manifestations of arteriovenous fistula dysfunction were analyzed. Additionally, the vascular access stenosis, vascular access lumen stenosis, arteriovenous diameter, blood flow, and hemodynamic indices were tested, and the value of MSCTA in predicting arteriovenous fistula function was analyzed by Logistic regression. RESULTS: The degree of vascular access stenosis and vascular access lumen stenosis in the normal group were less than those in the dysfunctional group (P<0.05). The arteriovenous diameter, blood flow, blood flow velocity at anastomotic vein end, dialysis adequacy (spKt/V), and von Willebrand factor (vWF) function in the normal group were larger than those in the dysfunction group, and the radial artery shear force was lower than in the dysfunction group, with statistical significance (P<0.05). Among the arteriovenous fistula dysfunction, there were 3 patients with anastomotic + outflow vein stenosis, 4 patients with outflow vein stenosis, 9 patients with inflow artery + anastomosis + outflow vein stenosis, and 6 patients with superior vena cava stenosis. Logistic regression analysis showed that slow blood flow velocity at the venous end of anastomosis and high shear force of radial artery were influencing factors of arteriovenous fistula dysfunction, and the area under ROC curve of blood flow velocity at the venous end of anastomosis plus shear force of radial artery was 0.93, with a sensitivity of 0.87 and a specificity of 0.85. CONCLUSION: MSCTA can be used to evaluate the dysfunction of autologous arteriovenous fistula in patients undergoing maintenance hemodialysis, and provide important reference information for the formulation of the next best clinical treatment plan.
BACKGROUND: Telitacicept, an innovative drug used for the treatment of systemic lupus erythematosus (SLE), can effectively control disease progression and achieve favorable outcomes. While case reports have mentioned the use of Telitacicept in lupus nephritis (LN) treatment, its safety and efficacy in treating patients with LN have not been explored. Therefore, in this study, we aimed to evaluate the safety and efficacy of Telitacicept in managing patients with LN. METHODS: In a single-center, real-world retrospective study, 30 LN patients with poor response or adverse reactions to conventional glucocorticoids at our Hospital were enrolled to receive Telitacicept. Patients were administered 160 mg of Telitacicept subcutaneously once a week for at least 24 weeks in addition to standard treatment. We assessed the SLE responder index-4 (SRI-4) at the beginning and the end of the treatment period, measured laboratory test indicators at 3, 6, and 9 months, and observed the occurrence of adverse events in these patients. RESULTS: The SRI-4 response rate was 86.67% (n = 26), with a significantly lower systemic lupus erythematosus disease activity index (SLEDAI) score compared to the baseline. Post Telitacicept treatment, glucocorticoid intake of patients with LN significantly reduced from 50 (IQR:40, 51.25) at baseline to 10 (IQR:5,10) at the endpoint (Z = - 6.547, p < 0.001). Patients with LN showed significantly improved urine occult blood levels after Telitacicept therapy. While the complement (C3 and C4) contents increased, immunoglobulins (IgG, IgA and IgM) reduced markedly (p < 0.001). The negative rate of dsDNA reached 26.67% and adverse events were alleviated post treatment. Only two cases of LN-related adverse reactions were reported, including herpes and infectious fever, respectively. Telitacicept primarily serves as an agent for the induction of remission therapy, with an attainment of complete remission rate standing at a commendable 73.3%. CONCLUSIONS: Telitacicept treatment reduced disease severity in patients with LN. The initial clinical trial provided supportive evidence for the effectiveness and safety of Telitacicept as a viable treatment option for LN, allowing a reduction in the daily glucocorticoid intake while maintaining a good safety profile, and improving hypocomplementation in LN management.
Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine. This study proposes the use of diamond-like carbon (DLC) deposited on polylactic acid (PLA) membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats. The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane, with histological score decreasing from 3.12 ± 0.27 to 2.20 ± 0.22 and anti-adhesion effectiveness increasing from 21.61% to 44.72%. Mechanistically, the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively; thus, the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited. Consequently, excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) is largely reduced. For biocompatibility evaluation, PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes. Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds, which further delays the fibrosis process. It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.
The Chinese chestnut, Castanea mollissima Blume, a nut-bearing tree native to China and North Korea, belongs to the Fagaceae family. As an important genetic resource, C. mollissima is vital in enhancing edible chestnut varieties and offers significant insights into the origin and evolution of chestnut species. While the chloroplast genome of C. mollissima has been sequenced, its mitochondrial genome (mitogenome) remains largely uncharted. In this study, we have characterized the C. mollissima mitogenome, assembling it utilizing reads from both BGI and Nanopore sequencing platforms, and conducted a comparative analysis with the mitochondrial genomes of closely related species. The mitogenome of C. mollissima manifests a polycyclic structure consisting of two circular molecules measuring 363,232 bp and 24,806 bp, respectively. This genome encompasses 35 unique protein-coding genes, 19 tRNA genes, and three rRNA genes. A total of 139 SSRs were identified throughout the entire C. mollissima mitogenome. Furthermore, the combined length of homologous fragments between the chloroplast and mitochondrial genomes was 5766 bp, constituting 1.49% of the mitogenome. We also predicted 484 RNA editing sites in C. mollissima, demonstrating C-to-U RNA editing. Phylogenetic analysis of related species' mitogenomes showed that C. mollissima was closely related to Lithocarpus litseifolius (Hance) Chun and Quercus acutissima Carruth. Interestingly, the mitogenome sequences of C. mollissima, L. litseifolius, Q. acutissima, Fagus sylvatica L., and Juglans mandshurica Maxim did not show conservation in their alignments, indicating frequent genome reorganization. This report marks the inaugural study of the C. mollissima mitogenome, serving as a benchmark genome for economically significant plants within the Castanea genus. Moreover, it supplies invaluable information that can guide future molecular breeding efforts and contribute to the broader understanding of chestnut genomics.
Genome, Mitochondrial , Quercus , Phylogeny , Genomics , China
BACKGROUND: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy. METHODS: We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results. RESULTS: A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7-48.7%) for hypertension, 31.3% (95% CI, 19.3-43.3%) for proteinuria, 27.3% (95%CI, 21.2-33.4%) for epistaxis, 22.5% (95%CI, 7.8-37.3%) for hemorrhage events, 8.0% (95%CI, 2.0-14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1-26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2-8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49-11.36), proteinuria (OR:4.12, 95%CI: 1.25-13.61), epistaxis (OR:3.71, 95%CI: 2.84-4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23-9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13-8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials). CONCLUSION: The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials.
Antineoplastic Combined Chemotherapy Protocols , Colonic Neoplasms , Hypertension , Humans , Epistaxis , Proteinuria/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects
Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, including lung adenocarcinoma (LUAD). However, the functional and regulatory mechanisms of lncRNAs in LUAD remain poorly understood. In this study, we investigated the role of lncRNA ZBED5-AS1 in LUAD. We found that ZBED5-AS1 was upregulated in LUAD specimens and overexpressed in LUAD cell lines. ZBED5-AS1 promoted LUAD cell proliferation, migration, and invasion in vitro and promoted LUAD cell growth in vivo. ZBED5-AS1 promoted ZNF146 expression, activating the ATR/Chk1 pathway and leading to LUAD progression. We observed that exosomes from LUAD cells have a higher expression of ZBED5-AS1 compared with exosomes from the normal cell line BEAS-2B. Coculture experiments with exosomes showed that ZBED5-AS1 expression was downregulated after coculture with Si-ZBED5-AS1 exosomes, and coculture with exosomes with low ZBED5-AS1 expression inhibited proliferation and invasion of LUAD cells. Our results indicate that ZBED5-AS1 functions as an oncogenic factor in LUAD cells by targeting the ZNF146/ATR/Chk1 axis.
Adenocarcinoma , RNA, Long Noncoding , Humans , Adenocarcinoma/genetics , Ataxia Telangiectasia Mutated Proteins , Carcinogenesis , Cell Transformation, Neoplastic , Lung , RNA, Long Noncoding/genetics
Polysaccharide decolorization has a major effect on polysaccharide function. In the present study, the decolorization of Rehmannia glutinosa polysaccharides (RGP) is optimized using two methods-the AB-8 macroporous resin (RGP-1) method and the H2O2 (RGP-2) method. The optimal decolorization parameters for the AB-8 macroporous resin method were as follows: temperature, 50 °C; macroporous resin addition, 8.4%; decolorization duration, 64 min; and pH, 5. Under these conditions, the overall score was 65.29 ± 3.4%. The optimal decolorization conditions for the H2O2 method were as follows: temperature, 51 °C; H2O2 addition, 9.5%; decolorization duration, 2 h; and pH, 8.6. Under these conditions, the overall score was 79.29 ± 4.8%. Two pure polysaccharides (RGP-1-A and RGP-2-A) were isolated from RGP-1 and RGP-2. Subsequently, their antioxidant and anti-inflammatory effects and mechanisms were evaluated. RGP treatment activated the Nrf2/Keap1 pathway and significantly increased the activity of antioxidant enzymes (p < 0.05). It also inhibited the expression of pro-inflammatory factors and suppressed the TLR4/NF-κB pathway (p < 0.05). RGP-1-A had a significantly better protective effect than RGP-2-A, likely owing to the sulfate and uronic groups it contains. Together, the findings indicate that RGP can act as a natural agent for the prevention of oxidation and inflammation-related diseases.
PURPOSE: Existing biomarkers for diagnosing and predicting metastasis of lung adenocarcinoma (LUAD) may not meet the demands of clinical practice. Risk prediction models with multiple markers may provide better prognostic factors for accurate diagnosis and prediction of metastatic LUAD. METHODS: An animal model of LUAD metastasis was constructed using CRISPR technology, and genes related to LUAD metastasis were screened by mRNA sequencing of normal and metastatic tissues. The immune characteristics of different subtypes were analyzed, and differentially expressed genes were subjected to survival and Cox regression analyses to identify the specific genes involved in metastasis for constructing a prediction model. The biological function of RFLNA was verified by analyzing CCK-8, migration, invasion, and apoptosis in LUAD cell lines. RESULTS: We identified 108 differentially expressed genes related to metastasis and classified LUAD samples into two subtypes according to gene expression. Subsequently, a prediction model composed of eight metastasis-related genes (RHOBTB2, KIAA1524, CENPW, DEPDC1, RFLNA, COL7A1, MMP12, and HOXB9) was constructed. The areas under the curves of the logistic regression and neural network were 0.946 and 0.856, respectively. The model effectively classified patients into low- and high-risk groups. The low-risk group had a better prognosis in both the training and test cohorts, indicating that the prediction model had good diagnostic and predictive power. Upregulation of RFLNA successfully promoted cell proliferation, migration, invasion, and attenuated apoptosis, suggesting that RFLNA plays a role in promoting LUAD development and metastasis. CONCLUSION: The model has important diagnostic and prognostic value for metastatic LUAD and may be useful in clinical applications.
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Animals , Clustered Regularly Interspaced Short Palindromic Repeats , Adenocarcinoma of Lung/genetics , Prognosis , Lung Neoplasms/genetics
Two-dimensional (2D) gas chromatography (GC) provides enhanced vapor separation capabilities in contrast to conventional one-dimensional GC and is useful for the analysis of highly complex chemical samples. We developed a microfabricated flow-restricted pneumatic modulator (FRPM) for portable comprehensive 2D micro-GC (µGC), which enables rapid 2D injection and separation without compromising the 1D separation speed and eluent peak profiles. 2D injection characteristics such as injection peak width and peak height were fully characterized by using flow-through micro-photoionization detectors (µPIDs) at the FRPM inlet and outlet. A 2D injection peak width of ~25 ms could be achieved with a 2D/1D flow rate ratio over 10. The FRPM was further integrated with a 0.5-m long 2D µcolumn on the same chip, and its performance was characterized. Finally, we developed an automated portable comprehensive 2D µGC consisting of a 10 m OV-1 1D µcolumn, an integrated FRPM with a built-in 0.5 m polyethylene glycol 2D µcolumn, and two µPIDs. Rapid separation of 40 volatile organic compounds in ~5 min was demonstrated. A hybrid 2D contour plot was constructed by using both 1D and 2D chromatograms obtained with the two µPIDs at the end of the 1D and 2D µcolumns, which was enabled by the presence of the flow resistor in the FRPM.
Objective: Cigarettes have become the the biggest killer of contemporary female's health and beauty. What kind of health information is suitable for the general public is an important issue to be discussed globally. The purpose of this study is to generate systematic, rigorous, public-demand-oriented and appropriate core information relevant to tobacco control based on the best available evidence, combined with audience preferences and pre-dissemination content review from multidisciplinary expertise in order to improve the effectiveness of health communication of tobacco control. Methods: Relevant systematic reviews meta-analysis that reported smoking on risks of female disease were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Clinical Trials.gov, and the International Clinical Trial Registry Platform. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was applied to assess the evidence in order to make rigorous core information. The audience prevalence survey was conducted to ensure that core information was targeted and tailored. Finally, the expert assessment was used for a pre-dissemination content review and to evaluate whether the core information was appropriate or not. Results: The final core information consisted of eight parts concerning the effects of smoking and female cardiovascular disease, diabetes, rheumatoid arthritis, respiratory disease, digestive system disease, mental disease, non-pregnant female reproductive system disease, as well as pregnant women and their fetuses. A total of 35 items of core information suitable for dissemination was included and the quality of evidence, the degree of public demand and the outcome of pre-dissemination content review were reported. Conclusion: The core information related to female cardiovascular system diseases, as well as liver cancer and upper gastrointestinal cancer is the preferred content for health communication of tobacco control. The quality of evidence for core information related to pregnant women and their infants, as well as diseases of reproductive system, respiratory system, and diabetes needs to be improved to meet high public demand. The core information related to mental disease is more suitable for dissemination to patients with mental illness than to the general public. Besides, dissemination of core information should be individualized. Evidence-based Core Information for Health Communication of Tobacco Control would be helpful to provide evidence support for health communication related to tobacco control and enhance public health literacy for international communities that have high smoking prevalence and related disease burden.
Diabetes Mellitus , Health Communication , Smoking Cessation , Infant , Female , Humans , Pregnancy , Smoking/epidemiology , Nicotiana
BACKGROUND: Lung adenocarcinoma (LUAD) is a highly malignant tumor with a very low five-year survival rate. In this study, we aimed to identify differentially expressed long-chain non-coding RNA (lncRNAs) and mRNAs from benign and malignant pleural effusion exosomes. METHODS: We used gene microassay and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect and verify differentially expressed mRNAs and lncRNAs in benign and malignant pleural effusion exosomes. Gene Ontology (GO) functional significance and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway significance enrichment analyses were performed to identify the difference in biological processes and functions between different mRNAs. We selected the lncRNA ZBED5-AS1 with an upregulated differential fold of 3.003 and conducted a preliminary study on its cellular function. RESULTS: Gene microassay results revealed that 177 differentially expressed lncRNAs were upregulated, and 215 were downregulated. The top 10 upregulated were FMN1, AL118505.1, LINC00452, AL109811.2, CATG00000040683.1, AC137932.1, AC008619.1, AL450344.1, AC092718.6, and ZBED5-AS1. The top 10 downregulated were TEX41, G067726, JAZF1-AS1, AC027328.1, AL445645.1, AL022345.4, AC008572.1, AC123777.1, AC093714.1, and PHKG1. For the mRNAs, 79 were upregulated, and 123 were notably downregulated. GO analysis revealed that the upregulated differential mRNAs were mainly involved in "cellular response to acidic pH" (biological processes), "endoplasmic reticulum part" (cellular components), and "at DNA binding, cyclase activity" (molecular functions). KEGG pathways were found to be related to V. cholerae infection, Parkinson's disease, and cell adhesion molecules. RT-qPCR showed that ZBED5-AS1 was highly expressed in LUAD tissues, cells, and benign and malignant pleural fluid exosomes. Overexpression of ZBED5-AS1 could significantly promote the proliferation, migration, invasion, and colony formation of LUAD cells, and knockdown had the opposite consequence. CONCLUSION: The pleural effusion exosomes from patients with LUAD include several improperly expressed genes, and lncRNA-ZBED5-AS1 is a new biomarker that aids in our understanding of the occurrence and progression of LUAD.
Adenocarcinoma of Lung , Lung Neoplasms , Pleural Effusion, Malignant , RNA, Long Noncoding , Humans , Gene Expression Profiling/methods , Lung/metabolism , Pleural Effusion, Malignant/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Adenocarcinoma of Lung/genetics , Lung Neoplasms/genetics
Aberrant expression of the gene encoding the Ndc80 kinetochore complex component (NUF2) reportedly contributes to the progression of several human cancers. However, the functional roles of NUF2 and their underlying mechanisms in lung adenocarcinoma (LUAD) are largely unknown. The current study aimed to investigate the role of NUF2 in LUAD tumorigenesis. Here, TCGA, ONCOMINE, the Human Protein Atlas, UALCAN, and the results of our cohort were used to analyze the expression of NUF2 in LUAD. A Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were performed to estimate the prognostic values of NUF2 expression in the Cancer Genome Atlas cohort. We studied the effects of NUF2 expression on proliferation, migration, invasion, and tumor growth using LUAD cell lines. Gene set enrichment analysis (GSEA) was used to analyze the pathways and biological function enrichment of NUF2 in LUAD. The ssGSEA database was used to analyze the relationship between NUF2 expression and immune cell infiltration in LUAD. Results revealed elevated expression of NUF2 in LUAD specimens. Patients overexpressing NUF2 had poor prognoses relative to those with low NUF2 expression. Knockdown of NUF2 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition, and colony formation of LUAD cells. Moreover, NUF2 knockdown induced cell cycle arrest at the G0/G1 phase. Gene Ontology and GSEA analyses suggested that NUF2 may be involved in immunity, proliferation, and apoptosis-related pathways. NUF2 overexpression was positively correlated with differential immune cell infiltration. In conclusion, NUF2 expression was associated with the clinical phenotype of LUAD and hence has potential implications in LUAD treatment.
Tissue expansion is a commonly performed therapy to grow extra skin in vivo for reconstruction. While mechanical stretch-induced epidermal changes have been extensively studied in rodents and cell culture, little is known about the mechanobiology of the human epidermis in vivo. Here, we employed single-cell RNA sequencing to interrogate the changes in the human epidermis during long-term tissue expansion therapy in clinical settings. We also verified the main findings at the protein level by immunofluorescence analysis of independent clinical samples. Our data show that the expanding human skin epidermis maintained a cellular composition and lineage trajectory that are similar to its non-expanding neighbor, suggesting the cellular heterogeneity of long-term expanded samples differs from the early response to the expansion. Also, a decrease in proliferative cells due to the decayed regenerative competency was detected. On the other hand, profound transcriptional changes are detected for epidermal stem cells in the expanding skin versus their non-expanding peers. These include significantly enriched signatures of C-FOS, EMT, and mTOR pathways and upregulation of AREG and SERPINB2 genes. CellChat associated ligand-receptor pairs and signaling pathways were revealed. Together, our data present a single-cell atlas of human epidermal changes in long-term tissue expansion therapy, suggesting that transcriptional change in epidermal stem cells is the major mechanism underlying long-term human skin expansion therapy. We also identified novel therapeutic targets to promote human skin expansion efficiency in the future.
The moving magnet voice coil actuator (MMVCA) is a promising choice for the long stroke nanopositioning stage with the advantage of low moving mass. However, the hysteresis observed in MMVCA limits further improvement on tracking performance. The hysteresis is cascading with the linear dynamic of the positioning stage, which makes common hysteresis identification inapplicable. In this paper, the cause and influence of hysteresis in MMVCA are analyzed, which reveal that the magnetic hysteresis leads to a hysteresis of force and causes motion accuracy to degrade. A modified rate-dependent Prandtl-Ishlinskii (P-I) model is proposed to describe the hysteresis in MMVCA. The decoupled method is implemented to identify the parameters of the linear dynamic model and nonlinear hysteresis model. The experimental results validate the feasibility of the proposed P-I model. Based on the hysteresis compensation, the peak-to-peak tracking errors are reduced by 30% and the root-mean-square (rms) tracking errors are decreased by 41% on average for the trajectories with amplitudes from 1 to 3 mm and frequencies from 1 to 5 Hz.
Lung adenocarcinoma (LAD) is a common malignancy; however, its underlying molecular mechanism is unclear. Circular RNAs (circRNAs) serve as significant cancer regulators. The overexpression of circRAPGEF5 in LAD tissues and cells indicated that it may be involved in promoting LAD progression. Analysis of 61 LAD tissues revealed that circRAPGEF5 was related to lymph node metastasis. Functionally, circRAPGEF5 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition of LAD cells in vitro and promoted LAD cells growth in vivo. Mechanistically, dual-luciferase reporter assays confirmed direct interaction of circRAPGEF5, miR-1236-3p, and ZEB1. miR-1236-3p was upregulated and ZEB1 expression reduced after circRAPGEF5 knockdown, and the proliferation, migration, and invasion of LAD cells was inhibited. circRAPGEF5 was significantly overexpressed in LAD cell exosomes, and co-culture experiments showed that exosomal circRAPGEF5 enhanced the metastatic ability of LAD cells. Further experiments found that serum exosomal circRAPGEF5 was overexpressed in LAD; moreover, the area under the receiver operator characteristic curve of exosomal circRAPGEF5 was superior to that of serum carcinoembryonic antigen (CEA). Jointly detected serum exosomal circRAPGEF5 and serum CEA had better diagnostic performance than when detected individually. Thus, exosomal circRAPGEF5 could promote the proliferation and metastasis of LAD via the miR-1236-3p/ZEB1 axis and serum exosomal circRAPGEF5 may serve as a promising biomarker for LAD.
Adenocarcinoma of Lung , Exosomes , Lung Neoplasms , MicroRNAs , Adenocarcinoma of Lung/metabolism , Carcinoembryonic Antigen/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation/genetics , Exosomes/metabolism , Gene Expression Regulation, Neoplastic/genetics , Humans , Lung Neoplasms/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism
Cisplatin (DDP) resistance has become the major obstacle in the therapy of malignant tumors, including lung adenocarcinoma (LAD). Long non-coding RNAs (lncRNAs) were confirmed to be related to DDP-resistance. Studies have shown that RP3-326I13.1 (also known as PINCR) could promote the progression of colorectal cancer, and RP3-326I13.1 knockdown could induce hypersensitivity to chemotherapy drugs. While the function of RP3-326I13.1 in LAD is unclear, therefore, this study aimed to research the biological function and related molecular mechanisms of RP3-326I13.1 in DDP-resistance of LAD. QPCR analysis found that RP3-326I13.1 was highly expressed in A549/DDP cells and LAD tissues. Cytological assays found that RP3-326I13.1 pro-moted the proliferation, migration, invasion, and DDP-resistance of LAD cell lines. Moreover, knock-down of RP3-326I13.1 could induce G1 phase arrest. Nude mouse xenograft assay confirmed that RP3-326I13.1 could promote tumor growth and DDP-resistance in vivo. Mechanically, RNA pull-down and mass spectrometry analysis indicated that heat shock protein HSP 90-beta (HSP90B) could be combined with RP3-326I13.1. HSP90B knockdown inhibited the effect of RP3-326I13.1 on proliferation, invasion, and promoted LAD cell lines apoptosis. Transcriptome sequencing analysis found that MMP13 was the downstream mRNA of RP3-326I13.1. In conclusion, RP3-326I13.1 could promote DDP-resistance of LAD by binding to HSP90B and upregulating human matrix metalloproteinase-13 (MMP-13) and may serve as a therapeutic target, as well as a biomarker for predicting DDP-resistance in LAD.Abbreviations:DDP: Cisplatin; LAD: Lung adenocarcinoma; LncRNAs: Long non-coding RNAs; qPCR: real-time fluorescent quantitative PCR; HSP90B: Heat shock protein HSP 90-beta; RPMI: Roswell Park Memorial Institute; FBS: Fetal bovine serum; CT: computed tomography; MRI: magnetic resonance imaging; RECIST: Response evaluation criteria in solid tumors; NC: Negative control; OE: overexpression; shRNA: short hairpin RNA; siRNA: small interfering RNA; CCK-8: Cell Counting Kit-8; IC50: The half maximal inhibitory concentration; PBS: Phosphate buffer saline; PI: propidium iodide; SDS-PAGE: sodiumdodecylsulfate-polyacrylamide gel electrophoresis; ceRNA: Competing endogenous RNA; HE: hematoxylin-eosin; ns: no significance.
Adenocarcinoma , Lung Neoplasms , RNA, Long Noncoding , Adenocarcinoma/pathology , Animals , Cell Line, Tumor , Cell Proliferation , Cisplatin/therapeutic use , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Humans , Lung/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 13/pharmacology , Membrane Glycoproteins , Mice , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Small Interfering/metabolism
Pancreatic cancer (PC) is a common cause of cancer-related deaths. Current research shows that prognostic biomarkers play a key role in the treatment of PC. This study aimed to identify prognostic genes through bioinformatics research. We combined data from 175 cases of PC from the cancer genome atlas (TCGA) database with gene mutation expression, level distribution of methylation, mRNA expression, and through weighted correlation network analysis to nine hub genes. Subsequently, these genes were verified on TCGA and Gene Expression Profiling Interactive Analysis (GEPIA) platforms. Reverse transcription quantitative PCR (RT-qPCR) was performed to investigate the expression levels of 9 genes in PC cells and cancerous and 30 PC cases and corresponding adjacent tissues. CIBERSORT database analysis was conducted for hub genes. Our findings demonstrated that the 9 genes (MST1R, TMPRSS4, PTK6, KLF5, CGN, ABHD17C, MUC1, CAPN8, and B3GNT3) were prognostic biomarkers of PC identified from the top 10 genes of the 2 coexpression modules. The nine genes were then used to divide early PC cases into two subgroups with significant differences in prognosis and differences in function (digestion, extracellular cell adhesion). Further analysis revealed that the nine genes were highly expressed in PC tissues. In addition, MST1R, PTK6, ABHD17C, and CGN mRNA were expressed high in PC cells and clinical tissues. CIBERSORT analysis indicated that the expression of these genes was closely correlated with naive B cells, CD8+ T cells, and M0 macrophages. This suggests that these genes could play a carcinogenic role in the preservation of immune-dominant status for the tumor microenvironment. The nine key genes identified in this study could enhance our understanding of the molecular mechanisms associated with PC.
Biomarkers, Tumor/genetics , Pancreatic Neoplasms/genetics , Aged , Computational Biology , Databases, Genetic/statistics & numerical data , Female , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Genomics , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Prognosis , RNA, Messenger/genetics
