ABSTRACT
Endometrial injury is a major cause of infertility and recurrent miscarriage. However, no clinically available methods currently exist to effectively repair the damaged endometrium. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for promoting tissue regeneration, yet a biocompatible scaffold capable of delivering MSCs and supporting their growth is needed. Herein, the study reports a peptide hydrogel scaffold, self-assembled from a peptide IVK8-RGD consisting of an ionic complementary peptide sequence IEVEIRVK and a bioactive sequence RGD, to load umbilical cord-derived mesenchymal stem cells (UC-MSCs). This peptide forms a hydrogel under the physiological condition through self-assembly, and the peptide hydrogel exhibits injectability and adhesiveness to uterus, making it suitable for endometrial repair. Importantly, this hydrogel supports the adhesion and proliferation of UC-MSCs in a 3D environment. In vivo experiments using rats with endometrial injury have shown that treatment with IVK8-RGD hydrogel loaded with UC-MSCs effectively restores endometrial thickness, inhibits fibrosis, and facilitates angiogenesis through activating Raf/MEK/ERK pathway, leading to significantly improved fertility and live birth rate. These findings demonstrate the potential of the UC-MSCs-loaded hydrogel in repairing damaged endometrium and may address the unmet clinical needs of treating recurrent miscarriage and infertility induced by endometrial damage.
ABSTRACT
Background: Unfortunately, the morphologic magnetic resonance imaging (MRI) is unable to determine perineural invasion (PNI) status. This study applied histogram analysis of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the assessment of PNI status of rectal cancer (RC). Methods: The retrospective analysis enrolled 175 patients with RC confirmed by postoperative pathology in The First Affiliated Hospital of Shandong First Medical University from January 2019 to December 2021. All patients underwent preoperative rectal MRI. Whole-tumor volume histogram features from IVIM-DWI were extracted using open-source software. Univariate analysis and multivariate logistic regression analysis were used to compare the differences in histogram parameters and clinical features between the PNI-positive group and PNI-negative group. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance, while the Delong test was used to compare the area under the curve of the models. Results: The interobserver agreement of the histogram features derived from DWI, including apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), water molecular diffusion heterogeneity index (α), and distributed diffusion coefficient (DDC) were good to excellent. A total of eight histogram features including DWI_maximum, DWI_skewness, D_kurtosis, D_minimum, D_skewness, D*_energy, D*_skewness, and f_minimum were significantly different between the PNI-positive and PNI-negative groups in the univariate analysis (P<0.05); among the clinicoradiologic factors, percentage of rectal wall circumference invasion (PCI) was significantly different between the two groups (P<0.05). Multivariate analysis demonstrated that the values of D*_energy, D*_skewness, and f_minimum differed significantly between the PNI-positive patients and PNI-negative patients (P<0.05), with the independent risk factors being D*_skewness [odds ratio (OR) =1.157; 95% confidence interval (CI): 1.050-1.276; P=0.003] and PCI (OR =11.108, 95% CI: 1.767-69.838; P=0.0002). The area under the curve of the model combining the three histogram features and PCI to assess PNI status in RC was 0.807 (95% CI: 0.741-0.863). The results of the Delong test showed that the combined model was significantly different from each single-parameter model (P<0.05). Conclusions: The combined model constructed on the basis of IVIM-DWI histogram features may help to assess the status of RC PNI.
ABSTRACT
The rapid development of electronic communication technology has led to an undeniable issue of electromagnetic pollution, prompting widespread attention from researchers to the study of electromagnetic shielding materials. Herein, a simple and feasible method of melt blending was applied to prepare iPP/TPU/MWCNT nanocomposites with excellent electromagnetic shielding performance. The addition of maleic anhydride-grafted polypropylene (PP-g-MAH) effectively improved the interface compatibility of iPP and TPU. A double continuous structure within the matrix was achieved by controlling the iPP/TPU ratio at 4:6, while the incorporation of multi-walled carbon nanotubes endowed the composites with improved electromagnetic shielding properties. Furthermore, by regulating the addition sequence of raw materials during the melt-blending process, a selective distribution of carbon nanotubes in the TPU matrix was achieved, thereby constructing interconnected conductive networks within the composites, significantly enhancing the electromagnetic shielding performance of iPP/TPU/MWCNTs, which achieved a maximum EMI shielding efficiency of 37.8 dB at an iPP/TPU ratio of 4:6 and an MWCNT concentration of 10 wt.%.
ABSTRACT
With the surge in the human coastal population and the increasing frequency of human activities along the coast, cases of marine envenomation, particularly jellyfish envenomation, have notably risen. Jellyfish stings can induce a spectrum of symptoms that vary in severity, encompassing skin injuries, acute systemic venom effects, delayed indirect sequelae, and even fatality, causing significant distress to patients. Among these manifestations, the occurrence of skin lesions following jellyfish stings is prevalent and substantial. These lesions are characterized by evident blister formation, development of bullae, subcutaneous hemorrhage, erythema, papules, wheal, ecchymosis, and ulceration or skin necrosis. Local cutaneous manifestations may persist for several weeks or even months after the initial sting. Despite aggressive treatment, many skin injuries still result in significant pigmentation or scarring after recovery. To address this issue effectively, it is imperative to conduct comprehensive evidence-based medical research, elucidate various components within jellyfish venom, and elucidate its pathogenic mechanism to develop targeted treatment programs. This article aims to review the skin symptoms, pathophysiology, and management of jellyfish stings. Such considerations can provide comprehensive guidance to medical professionals and the public and minimize the harm caused by jellyfish stings.
Subject(s)
Bites and Stings , Cnidarian Venoms , Skin , Humans , Bites and Stings/therapy , Bites and Stings/physiopathology , Bites and Stings/complications , Animals , Skin/pathology , Skin/physiopathology , Cnidaria , Skin Diseases/therapy , Skin Diseases/physiopathology , Skin Diseases/etiology , ScyphozoaABSTRACT
Objective: Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women with normal blood pressure during pregnancy, revealing a potential association between hyperandrogenism in women and PE. To explore the causal relationship between hyperandrogenism and PE, this study selected total testosterone (TT), bioavailable testosterone (BIOT), and sex hormone binding globulin (SHBG) as exposure factors and PE and chronic hypertension with superimposed PE as disease outcomes. Two-sample Mendelian randomization (MR) analyses were used to genetically dissect the causal relationships between the three exposure factors (TT, BIOT, and SHBG) and the outcomes of PE and chronic hypertension with superimposed PE. Methods: Two independent genome-wide association study (GWAS) databases were used for the two-sample MR analysis. In the GWAS data of female participants from the UK Biobank cohort, single nucleotide polymorphisms (SNPs) associated with TT, BIOT, and SHBG were analyzed, involving 230454, 188507, and 188908 samples, respectively. GWAS data on PE and chronic hypertension with superimposed PE from the Finnish database were used to calculate SNP, involving 3556 PE cases and 114735 controls, as well as 38 cases of chronic hypertension with superimposed PE and 114735 controls. To meet the assumptions of instrumental relevance and independence in MR analysis, SNPs associated with exposure were identified at the genome-wide level (P<5.0×10-8), and those in linkage disequilibrium interference were excluded based on clustering thresholds of R 2<0.001 and an allele distance greater than 10000 kb. Known confounding factors, including previous PE, chronic kidney disease, chronic hypertension, diabetes, systemic lupus erythematosus, or antiphospholipid syndrome, were also identified and the relevant SNPs were removed. Finally, we extracted the outcome data based on the exposure-related SNPs in the outcome GWAS, integrating exposure and outcome data, and removing palindromic sequences. Five genetic causal analysis methods, including inverse variance-weighted method (IVW), MR-Egger regression, weighted median method, simple mode method, and weighted mode method, were used to infer causal relationships. In the IVW, it was assumed that the selected SNPs satisfied the three assumptions and provided the most ideal estimate of the effect. IVW was consequently used as the primary analysis method in this study. Considering the potential heterogeneity among the instrumental variables, random-effects IVW was used for MR analysis. The results were interpreted using odds ratios (OR) and the corresponding 95% confidence interval (CI) to explain the impact of exposure factors on PE and chronic hypertension with superimposed PE. If the CI did not include 1 and had a P value less than 0.05, the difference was considered statistically significant. Sensitivity analysis was conducted to assess heterogeneity and pleiotropy. Heterogeneity was examined using Cochran's Q test, and pleiotropy was assessed using MR-Egger intercept analysis. Additionally, leave-one-out analysis was conducted to examine whether individual SNPs were driving the causal associations. To further validate the findings, MR analyses were performed using the same methods and outcome variables, but with different exposure factors, including waist-to-hip ratio adjusted for BMI (WHRadjBMI) and 25-hydroxyvitamin D levels, with MR results for WHRadjBMI and PE serving as the positive controls and MR results for 25-hydroxyvitamin D levels and PE as the negative controls. Results: According to the criteria for selecting genetic instrumental variables, 186, 127, and 262 SNPs were identified as genetic instrumental variables significantly associated with testosterone indicators TT, BIOT, and SHBG. MR analysis did not find a causal relationship between the TT, BIOT, and SHBG levels and the risk of developing PE and chronic hypertension with superimposed PE. The IVW method predicted that genetically predicted TT (OR [95% CI]=1.018 [0.897-1.156], P=0.78), BIOT (OR [95% CI]=1.11 [0.874-1.408], P=0.392), and SHBG (OR [95% CI]=0.855 [0.659-1.109], P=0.239) were not associated with PE. Similarly, genetically predicted TT (OR [95% CI]=1.222 [0.548-2.722], P=0.624), BIOT (OR [95% CI]=1.066 [0.242-4.695], P=0.933), and SHBG (OR [95% CI]=0.529 [0.119-2.343], P=0.402) were not significantly associated with chronic hypertension with superimposed PE. Additionally, MR analysis using the MR-Egger method, weighted median method, simple mode method, and weighted mode method yielded consistent results, indicating no significant causal relationship between elevated testosterone levels and PE or chronic hypertension with superimposed PE. Heterogeneity was observed for SHBG in the analysis with PE (Cochran's Q test, P=0.01), and pleiotropy was detected for BIOT in the analysis with PE (MR-Egger intercept analysis, P=0.014), suggesting that the instrumental variables did not affect PE through BIOT. Other instrumental variables did not show significant heterogeneity or pleiotropy. Leave-one-out analysis confirmed that the results of the MR analysis were not driven by individual instrumental variables. Consistent with previous MR studies, the results of the control MR analyses using WHRadjBMI and 25-hydroxyvitamin D levels supported the accuracy of the MR analysis approach and the methods used in this study. Conclusion: The MR analysis results suggest that current genetic evidence does not support a causal relationship between TT, BIOT, and SHBG levels and the development of PE and chronic hypertension with superimposed PE. This study suggests that elevated testosterone may be a risk factor for PE but not a direct cause.
Subject(s)
Genome-Wide Association Study , Hyperandrogenism , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Pre-Eclampsia , Sex Hormone-Binding Globulin , Testosterone , Humans , Female , Pregnancy , Pre-Eclampsia/genetics , Hyperandrogenism/genetics , Sex Hormone-Binding Globulin/genetics , Sex Hormone-Binding Globulin/analysis , Testosterone/blood , Hypertension/geneticsABSTRACT
Grasslands, the largest carbon pool in China, possess enormous potential for carbon sequestration. Increasing the stomatal aperture to increase the CO2 absorption capacity is a potential method to improve plant photosynthetic efficiency and ultimately enhance the carbon sequestration capacity of grass plants. Research on stomatal aperture regulation has focused mostly on Arabidopsis or crops, while research on grass plants in these areas is scarce, which seriously restricts the implementation of this grassland carbon sequestration strategy. Here, a widely used ecological grass, centipedegrass, was used as the experimental material. First, a convenient method for observing the stomatal aperture was developed. The leaves were floated in a potassium ion-containing open solution (67 mM KCl, pH 6.0) with the adaxial surface rather than the abaxial surface in contact with the solution and were cultivated under light for 1.5 h. Then, nail polish was applied on the adaxial surface, and a large number of open stomata were imprinted. Second, with the help of this improved method, the concentrationâresponse characteristics of the stomatal aperture to eleven environmental stimuli were tested. The stomatal aperture is dependent on these environmental stimuli in a concentration-dependent manner. The addition of 100 µM brassinolide led to the maximal stomatal aperture. This study provided a technical basis for manipulating stomatal opening to increase the carbon sequestration capacity of centipedegrass.
Subject(s)
Plant Stomata , Poaceae , Plant Stomata/physiology , Poaceae/physiology , Poaceae/metabolism , Plant Leaves/physiology , Plant Leaves/metabolism , Brassinosteroids/metabolismABSTRACT
The proliferation of toxic organisms caused by changes in the marine environment, coupled with the rising human activities along the coastal lines, has resulted in an increasing number of stinging incidents, posing a serious threat to public health. Here, we evaluated the systemic toxicity of the venom in jellyfish Chrysaora quinquecirrha at both cellular and animal levels, and found that jellyfish tentacle extract (TE) has strong lethality accompanied by abnormal elevation of blood biochemical indicators and pathological changes. Joint analysis of transcriptome and proteome indicated that metalloproteinases are the predominant toxins in jellyfish. Specially, two key metalloproteinases DN6695_c0_g3 and DN8184_c0_g7 were identified by mass spectrometry of the red blood cell membrane and tetracycline hydrochloride (Tch) inhibition models. Structurally, molecular docking and kinetic analysis are employed and observed that Tch could inhibit the enzyme activity by binding to the hydrophobic pocket of the catalytic center. In this study, we demonstrated that Tch impedes the metalloproteinase activity thereby reducing the lethal effect of jellyfish, which suggests a potential strategy for combating the health threat of marine toxic jellyfish.
Subject(s)
Cnidarian Venoms , Metalloproteases , Molecular Docking Simulation , Scyphozoa , Animals , Metalloproteases/chemistry , Metalloproteases/metabolism , Cnidarian Venoms/chemistry , Tetracycline/toxicity , Transcriptome/drug effectsABSTRACT
Background: Hyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Methods: The "limma" and "GSVA" packages in R were used to perform differential expression analysis and to assess the activity of signalling pathways, respectively. InferCNV was used to infer copy number variation (CNV) for each hepatocyte and "CellChat" was used to analyse intercellular communication networks. Recursive partitioning analysis (RPA) was used to re-stage HCC patients. The IC50 values of various drugs were evaluated using the "pRRophetic" package. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumour. Results: Multiple cohort studies and qRT-PCR demonstrated that HMMR was overexpressed in HCC tissue compared with normal tissue. In addition, HMMR had excellent diagnostic performance. HMMR knockdown inhibited the proliferation and migration of HCC cells in vitro. Moreover, high HMMR expression was associated with "G2M checkpoint" and "E2F targets" in bulk RNA and scRNA-seq, and FCM confirmed that HMMR could regulate the cell cycle. In addition, HMMR was involved in the regulation of the tumour immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively associated with genomic heterogeneity with patients with high HMMR expression potentially benefitting more from immunotherapy. Moreover, HMMR was associated with poor prognosis in patients with HCC and the re-staging by recursive partitioning analysis (RPA) gave a good prognosis prediction value and could guide chemotherapy and targeted therapy. Conclusion: The results of the present study show that HMMR could play a role in the diagnosis, prognosis, and treatments of patients with HCC based on bulk RNA-seq and scRAN-seq analyses and is a promising molecular marker for HCC.
Subject(s)
Carcinoma, Hepatocellular , Hyaluronan Receptors , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , DNA Copy Number Variations , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Single-Cell Gene Expression Analysis , Tumor Microenvironment/geneticsABSTRACT
Exosomes, extracellular vesicles released by cells, hold potential as diagnostic markers for the early detection of lung cancer. Despite their clinical promise, current technologies lack rapid and effective means to discriminate between exosomes derived from adenocarcinoma in situ (AIS) and early-stage invasive adenocarcinoma (IAC). This challenge arises from the intrinsic structural heterogeneity of exosomes, necessitating the development of advanced methodologies for precise differentiation. Here, we demonstrate a novel approach for plasma exosome detection utilizing multi-receptor surface-enhanced Raman spectroscopy (SERS) technology to differentiate between AIS and early-stage IAC. To accomplish this, we synthesized a stable and uniform two-dimensional SERS substrate (BC/Au NPs film) by fabricating gold nanoparticles onto bacterial cellulose. We then enhanced its capabilities by introducing multi-receptor SERS functionality via modifying the substrate with both low-specificity and physicochemical-selective molecules. Furthermore, by strategically combining all capturer-exosome SERS spectra, comprehensive "combined-SERS spectra" are reconstructed to enhance spectral variations of the exosome. Combining these features with partial least squares regression-discriminant analysis (PLS-DA) modeling significantly improved discriminatory accuracy, achieving 90% sensitivity and 95% specificity in distinguishing AIS from early-stage IAC. Our developed SERS sensor provides an effective method for early detection of lung cancer, thereby paving a new way for innovative advancements in diagnosing lung cancer.
Subject(s)
Adenocarcinoma in Situ , Adenocarcinoma , Exosomes , Lung Neoplasms , Metal Nanoparticles , Humans , Exosomes/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Spectrum Analysis, Raman/methods , Lung Neoplasms/diagnosisABSTRACT
Perennial grasses seasonal nitrogen (N) cycle extends the residence and reuse time of N within the plant system, thereby enhancing N use efficiency. Currently, the mechanism of N metabolism has been extensively examined in model plants and annual grasses, and although perennial grasses exhibit similarities, they also possess distinct characteristics. Apart from assimilating and utilizing N throughout the growing season, perennial grasses also translocate N from aerial parts to perennial tissues, such as rhizomes, after autumn senescence. Subsequently, they remobilize the N from these perennial tissues to support new growth in the subsequent year, thereby ensuring their persistence. Previous studies indicate that the seasonal storage and remobilization of N in perennial grasses are not significantly associated with winter survival despite some amino acids and proteins associated with low temperature tolerance accumulating, but primarily with regrowth during the subsequent spring green-up stage. Further investigation can be conducted in perennial grasses to explore the correlation between stored N and dormant bud outgrowth in perennial tissues, such as rhizomes, during the spring green-up stage, building upon previous research on the relationship between N and axillary bud outgrowth in annual grasses. This exploration on seasonal N cycling in perennial grasses can offer valuable theoretical insights for new perennial grasses varieties with high N use efficiency through the application of gene editing and other advanced technologies.
Subject(s)
Nitrogen , Poaceae , Poaceae/metabolism , Seasons , Nitrogen/metabolism , Cold Temperature , Amino Acids/metabolismABSTRACT
OBJECTIVE: To identify the predictive factors of intestinal ischaemia in adhesive small bowel obstruction (ASBO) and develop an intestinal ischaemia risk score. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China, from January 2017 to February 2022. METHODOLOGY: ASBO was determined by findings at laparotomy. The assessment of small bowel's viability was conducted through surgical inspection and subsequent histological examination of the surgical specimen. Univariate and multivariate analyses were conducted to ascertain the risk factors associated with intestinal ischaemia. RESULTS: In total, 79 patients were included. Factors entered into multivariate analysis associated with intestinal ischaemia were; rebound tenderness (odds ratio (OR): 7.8, 95% confidence interval (CI):1.7-35.3; p=0.008), procalcitonin (PCT) >0.5 ng/mL (OR: 11.7, 95% CI: 2.3-58.1; p=0.003), and reduced bowel wall enhancement on computerised tomography (CT) scan (OR: 12.2, 95% CI:2.4-61.5; p=0.003). Among patients with 0, 1, 2, and 3 factors, the rate of intestinal ischaemia increased from 0% to 49%, 72%, and 100%, respectively. According to the number of risk factors, the area under the receiver operating characteristic curve for the determination of intestinal ischaemia was 0.848 (95% CI: 0.764-0.932). CONCLUSION: Rebound tenderness, PCT levels >0.5 ng/mL, and reduced bowel wall enhancement are risk factors of intestinal ischemic injury that require surgery within the context of ASBO. These factors need to be closely monitored that could assist clinicians in avoiding unnecessary laparotomies and selecting patients eligible for surgery. KEY WORDS: Intestinal obstruction, Ischaemia, Adhesions.
Subject(s)
Intestinal Obstruction , Mesenteric Ischemia , Tissue Adhesions , Vascular System Injuries , Humans , Abdominal Pain/etiology , Intestinal Obstruction/complications , Intestinal Obstruction/pathology , Intestinal Obstruction/surgery , Laparotomy , Mesenteric Ischemia/etiology , Mesenteric Ischemia/surgery , Procalcitonin , Retrospective Studies , Tissue Adhesions/complications , Tissue Adhesions/surgery , Vascular System Injuries/etiology , Vascular System Injuries/surgeryABSTRACT
Centipedegrass (Eremochloa ophiuroides) is an important warm-season grass plant used as a turfgrass as well as pasture grass in tropical and subtropical regions, with wide application in land surface greening and soil conservation in South China and southern United States. In this study, the complete cp genome of E. ophiuroides was assembled using high-throughput Illumina sequencing technology. The circle pseudomolecule for E. ophiuroides cp genome is 139,107 bp in length, with a quadripartite structure consisting of a large single copyregion of 82,081 bp and a small single copy region of 12,566 bp separated by a pair of inverted repeat regions of 22,230 bp each. The overall A + T content of the whole genome is 61.60%, showing an asymmetric nucleotide composition. The genome encodes a total of 131 gene species, composed of 20 duplicated genes within the IR regions and 111 unique genes comprising 77 protein-coding genes, 30 transfer RNA genes, and 4 ribosome RNA genes. The complete cp genome sequence contains 51 long repeats and 197 simple sequence repeats, and a high degree of collinearity among E. ophiuroide and other Gramineae plants was disclosed. Phylogenetic analysis showed E. ophiuroides, together with the other two Eremochloa species, is closely related to Mnesithea helferi within the subtribe Rottboelliinae. These findings will be beneficial for the classification and identification of the Eremochloa taxa, phylogenetic resolution, novel gene discovery, and functional genomic studies for the genus Eremochloa.
ABSTRACT
The isothermal melting behaviors of ultra-high molecular weight polyethylene (UHMWPE) with different entangled states (i.e., nascent and melt-crystallized samples) are studied. For two kinds of UHMWPE samples, the result shows that the relative content of survived crystals (Xs) exponentially decreases with time and reaches a constant value. It is suggested that such a melting behavior is related to the observed nonlinear growth of crystals induced by the kinetically rejected entanglements accumulated at the growth front. Additionally, the exponential decay of Xs with time provides a characteristic melting time (τ) for the melting process. Compared to the melt-crystallized UHMWPE, the τ value of nascent UHMWPE is generally longer even in a higher temperature range, which is mainly because the former has a larger entanglement density difference. Furthermore, these observations demonstrate that UHMWPEs with different entangled states have an analogous melting mechanism since they exhibit a similar melting activation energy (≈1300 kJ mol-1).
Subject(s)
Crystallization , Polyethylenes , Kinetics , Polyethylenes/chemistry , Transition Temperature , TemperatureABSTRACT
α-Enolase (ENO1) is a crucial molecular target for tumor therapy and has emerged as a research hotspot in recent decades. Here, we aimed to explore the role of ENO1 in bladder cancer (BLCA) and then construct a signature to predict the prognosis and treatment response of BLCA. Firstly, we found ENO1 was highly expressed in BLCA tissues, as verified by IHC, and was associated with poor prognosis. The analysis of the tumor immune microenvironment by bulk RNA-seq and scRNA-seq showed that ENO1 was associated with CD8+ T-cell exhaustion. Additionally, the results in vitro showed that ENO1 could promote the proliferation and invasion of BLCA cells. Then, the analysis of epithelial cells (ECs) revealed that ENO1 might promote BLCA progression by metabolism, the cell cycle and some carcinogenic pathways. A total of 249 hub genes were obtained from differentially expressed genes between ENO1-related ECs, and we used LASSO analysis to construct a novel signature that not only accurately predicted the prognosis of BLCA patients but also predicted the response to treatment for BLCA. Finally, we constructed a nomogram to better guide clinical application. In conclusion, through multi-omics analysis, we found that ENO1 was overexpressed in bladder cancer and associated with poor prognosis, CD8+ T-cell exhaustion and epithelial heterogeneity. Moreover, the prognosis and treatment of patients can be well predicted by constructing an epithelial-related prognostic signature.
Subject(s)
Multiomics , Urinary Bladder Neoplasms , Humans , Prognosis , Urinary Bladder Neoplasms/genetics , Nomograms , Urinary Bladder , Tumor Microenvironment/genetics , DNA-Binding Proteins/genetics , Phosphopyruvate Hydratase/genetics , Biomarkers, Tumor/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
Reservoir construction increasingly alters the natural transport of riverine water and sediment to the sea, including the trace metals and other pollutants. In 2018, an intensive flood event and 412 million tons of sediment were released from the Xiaolangdi dam during the water-sediment regulation of Yellow River, one of the world's largest sediment releases. During the artificial flood event, the surface sediments in Xiaolangdi Reservoir (XLD) and the Yellow River estuary, suspended sediments at Lijin Station were collected. The concentration and speciation of particulate Cr, Ni, Cu, Zn, Cd and Pb, as well as the major geochemical composition were analyzed, to characterize the behaviors of the metals from the reservoir to estuary mixing zone, and elucidate the controlling mechanisms. The results showed that for exogenous phases, Cr, Ni, Cu and Zn were likely bound to the FeMn oxides, whereas Pb and Cd were mainly adsorbed in the carbonates. The trace metals in XLD were stably combined with fine-grained bottom sediments at high concentrations before dam release. During the delivery from reservoir to downstream channel, the binding of Cr, Ni and Cu with FeMn oxides was markedly enhanced. Pb and Cu showed obvious migration from carbonates to FeMn oxides, and Cd and Pb were even released into the water. The accumulation and migration of trace metals were controlled by the adsorption of fine-grained components, especially FeMn oxides and carbonates, and influenced by the oxidizing processes. After entering the estuary, the trace metals were greatly scavenged by reservoir-sourced fine particles, tended to bound to organic matter affected by the reducing environment. Our results suggest that dam regulation and artificial flood events will likely alter the existing forms and redox state of trace metals and the potential environmental effects should be considered.
ABSTRACT
Advances in immune checkpoint inhibitors (ICIs) have enabled more effective treatment for individuals with various types of solid tumors. Given the improved survival benefit and acceptable safety profile of ICIs in advanced gastric cancer, there is plenty of interest in the use of ICIs in the neoadjuvant setting with curative intent. Theoretically, immunoneoadjuvant with ICIs could boost the levels of endogenous tumor antigen present in the tumor to enhance T-cell priming and further enhance systemic immunity. This systemic immune response may improve the detection and elimination of the disseminated micrometastatic tumors beyond the resected tumor, which are sources of postsurgical relapse. Numerous clinical studies have begun to explore the application of ICIs in neoadjuvant treatment of gastric cancer. This article reviews the progress in the use of ICI monotherapy and in combination with alternative therapies for the treatment of gastric cancer to aid in the development of gastric cancer immunoneoadjuvant therapy and improve the overall therapeutic benefit.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Neoadjuvant TherapyABSTRACT
Flexible silver substrates were made by in situ reduction of silver nanoparticles in bacterial cellulose membranes using the unique advantage of dopamine. Subsequently, we modified the substrate with 4-mercaptophenol (4-MP), a molecule capable of specifically recognizing ClO-, and its corresponding SERS signal changes with the concentration of hypochlorite, thus allowing the quantitative detection of ClO- content. The method showed a negative linear correlation (R2 = 0.9567) with the SERS intensity at 1077 cm-1 over the concentration range 0.5-100 µM, and the detection limit was 0.15 µM. The RSD of the SERS intensity at 1077 cm-1 under five batches was 4.2%, which proved the good reproducibility of P-BCM-Ag NP-MP. Finally, the P-BCM-Ag NPs were used for the detection of hypochlorite in cell contents, artificial urine, and clinical serum samples, utilizing spike experiments in all three environments. The recoveries were in the range 90-110% indicating the accuracy of the method for the detection of hypochlorite and validating the promising application of this assay for practical detection in intricate biological samples.
Subject(s)
Cellulose , Metal Nanoparticles , Dopamine , Hypochlorous Acid , Silver/chemistry , Metal Nanoparticles/chemistry , Reproducibility of Results , Spectrum Analysis, Raman/methodsABSTRACT
Compared to traditional methods, three/four-dimensional (3D/4D) printing technologies allow rapid prototyping and mass customization, which are ideal for preparing nano/microstructures of soft polymer materials. Poly (lactic acid) (PLA) is a biopolymer material widely used in additive manufacturing (AM) because of its biocompatibility and biodegradability. Unfortunately, owing to its intrinsically poor nucleation ability, a PLA product is usually in an amorphous state after industrial processing, leading to some undesirable properties such as a barrier property and low thermal resistance. Crystallization mediation offers a most practical way to improve the properties of PLA products. Herein, we summarize and discuss 3D/4D printing technologies in the processing of PLA nano/microstructures, focusing on crystallization principles and practical applications including bio-inspired structures, flexible electronics and biomedical engineering mainly reported in the last five years. Moreover, the challenges and prospects of 3D/4D printing technologies in the fabrication of high-performance PLA materials nano/microstructures will also be discussed.
Subject(s)
Bioengineering , Biomedical Engineering , Crystallization , Commerce , PolyestersABSTRACT
To explore an appropriate time interval between oocyte retrieval and intracytoplasmic sperm injection (ICSI) for optimal embryological and clinical outcomes in ICSI cycles over 40 years of maternal age. A retrospective analysis of 1476 ICSI fresh cycles from women aged over 40 years, was performed at the Reproduction Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University, between December 2013 and August 2020. The fertilization rate and clinical pregnancy rate were the main outcomes. Multivariate linear regression and logistic regression analysis of factors showed that fertilization rate (P = 0.024) and clinical pregnancy rate (P = 0.011) were significantly associated with oocyte pick up (OPU)-ICSI interval. A longer OPU-ICSI interval (no more than 6 h) was associated with a higher fertilization rate but significantly decreased the clinical pregnancy rate when the OPU-ICSI interval was over 4 h (P < 0.05). The optimal OPU-ICSI interval is between 3 and 4 h for excellent embryological and clinical outcomes in ICSI cycles over 40 years of maternal age.