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BACKGROUND: Diabetes can cause chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN). DR and DN can lead to or exacerbate diabetic macular edema (DME). Hemodialysis (HD) is the main treatment method for patients with end-stage kidney disease (ESKD) secondary to DN. PURPOSE: The aim of this prospective cohort study was to determine the immediate effect of single HD session on retinal and choroidal thickness in DR patients with ESKD and the features of DR and the prevalence of DME in these patients who have received long-term HD. METHODS: Eighty-five eyes of 44 DR patients with ESKD who underwent long-term HD were examined by swept-source optical coherence tomography angiography (SS-OCTA). Based on OCTA images, the characteristics of DR and the prevalence of DME in these patients were analyzed. Changes in central retinal thickness (CRT), central retinal volume (CRV), subfoveal choroidal thickness (SFCT) and subfoveal choroidal volume (SFCV) within 30 min before and after single HD session were compared. CRT, CRV, SFCT and SFCV were compared before single HD session and before the next single HD session. RESULTS: There was no significant difference in the average CRT (251.69 ± 39.21 µm vs. 251.46 ± 39.38 µm, P = 0.286) or CRV (0.15 ± 0.62 µm vs. 0.15 ± 0.63 µm, P = 0.324) between before and after single HD session. After single HD session, SFCT (243.11 ± 77.15 µm vs. 219.20 ± 72.84 µm, P < 0.001) and SFCV (0.15 ± 0.10 µm vs. 0.13 ± 0.90 µm, P < 0.001) significantly decreased. There was no statistically significant difference in CRT (251.69 ± 39.21 µm vs. 251.11 ± 38.47 µm, P = 0.206), CRV (0.15 ± 0.62 µm vs. 0.15 ± 0.61 µm, P = 0.154), SFCT (243.11 ± 77.15 µm vs. 245.41 ± 76.23 µm, P = 0.108), or SFCV (0.15 ± 0.10 µm vs. 0.16 ± 0.10 µm, P = 0.174) before HD and before the next single HD session. On en face OCTA images, eighty-five eyes (100%) had retinal nonperfusion areas, foveal avascular zone (FAZ) enlargement, and abnormal retinal microvasculature. Based on cross-sectional OCTA images, retinal neovascularization (RNV) was confirmed in 42 eyes (49.41%), and intraretinal microvascular abnormalities (IRMAs) were detected in 85 eyes (100%). Seventeen eyes (20%) still had DME, all of which were cystoid macular edema (CME). Among eyes with DME, the epiretinal membrane (ERM) was present in 7 eyes (8.24%). CONCLUSIONS: For DR patients with ESKD who have undergone long-term HD, the choroidal thickness still changes significantly before and after single HD session, which may be related to short-term effects such as reduced blood volume and plasma osmotic pressure caused by single HD session. Although macular features seem to have stabilized in DR patients undergoing long-term dialysis, the DR of patients with ESKD should still be given attention.
Subject(s)
Choroid , Diabetic Retinopathy , Fluorescein Angiography , Kidney Failure, Chronic , Renal Dialysis , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Diabetic Retinopathy/diagnosis , Male , Female , Prospective Studies , Middle Aged , Fluorescein Angiography/methods , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/complications , Choroid/blood supply , Choroid/diagnostic imaging , Choroid/pathology , Visual Acuity , Retina/diagnostic imaging , Retina/pathology , Adult , Follow-Up Studies , Fundus Oculi , Macular Edema/etiology , Macular Edema/diagnostic imaging , Macular Edema/diagnosisABSTRACT
This study aims to explore the risk factors associated with frozen shoulder (FS) and develop a predictive model for diagnosing FS, in order to facilitate early detection of the condition. A total of 103 patients diagnosed with FS and admitted to the Department of Joint Surgery at Suining Central Hospital between October 2021 and October 2023 were consecutively included in the study. Additionally, 309 individuals without shoulder joint diseases, matched for age and gender, who visited the department during the same time, were included as the control group.The complete recording of clinical data for all patients was followed by the utilization of statistical tests such as the Mann-Whitney U test, sample t test, and chi-square test to compare different groups. Additionally, multivariate binary logistic regression analysis was employed to identify risk factors associated with the occurrence of FS in patients, leading to the establishment of a prediction model and derivation of a simplified equation. The diagnostic effectiveness of individual indicators and prediction models was assessed through the use of receiver operating characteristic (ROC) curve analysis. In the sample of 103 individuals, 35 were identified as male and 68 as female, with an average age range of 40-70 years (mean age: 54.20 ± 6.82 years). The analysis conducted between different groups revealed that individuals with a low body mass index (BMI), in conjunction with other factors such as diabetes, cervical spondylosis, atherosclerosis, and hyperlipidemia, were more susceptible to developing FS. Logistic regression analysis further indicated that low BMI, diabetes, cervical spondylosis, and hyperlipidemia were significant risk factors for the occurrence of FS. These variables were subsequently incorporated into a predictive model, resulting in the creation of a simplified equation.The ROC curve demonstrated that the combined indicators in the predictive model exhibited superior diagnostic efficacy compared to single indicators, as evidenced by an area under the curve of 0.787, sensitivity of 62.1%, and specificity of 82.2%. Low BMI, diabetes, cervical spondylosis, and hyperlipidemia are significant risk factors associated with the occurrence of FS. Moreover, the utilization of a prediction model has demonstrated superior capability in forecasting the likelihood of FS compared to relying solely on individual indicators. This finding holds potential in offering valuable insights for the early diagnosis of FS.
Subject(s)
Bursitis , Humans , Male , Female , Bursitis/epidemiology , Bursitis/diagnosis , Middle Aged , Risk Factors , Aged , Adult , ROC Curve , Body Mass Index , Logistic ModelsABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.
Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Disease Progression , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Humans , Cell Line, Tumor , Animals , Cell Movement/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Male , Mice, Nude , Mice , Gene Expression Regulation, Neoplastic , Female , Mice, Inbred BALB C , Middle Aged , Phase SeparationABSTRACT
BACKGROUND: Many patients with asthma experience alopecia areata (AA) in their lives. However, it is unclear whether asthma causes or results from AA. Our objective was to investigate the genetic causal relationship between asthma and AA. METHODS: Two-sample Mendelian randomization (MR) was used to assess the causal relationship between asthma and AA based on the largest publicly available genome-wide association study summary statistics. Androgenetic alopecia (AGA) and cicatricial alopecia (CA) were chosen as the control groups for AA. The main estimates were obtained using inverse variance weighting meta-analysis (IVW), Mendelian randomization-Egger (MR-Egger), maximum likelihood estimation, and the weighted median. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger, and leave-one-out methods. Lastly, we conducted a reverse MR analysis to evaluate the possibility of reverse causation. RESULTS: Genetically, asthma is associated with an increased risk of AA, while the association between genetically predicted AGA or CA and asthma was negative. The risk of AA increased by 1.86 times in patients with asthma under the IVW method (OR = 1.86, 95% CI = 1.31-2.629, p < 0.001). The reverse MR analysis did not find evidence supporting reverse causality from three phenotypes of alopecia to asthma. Sensitivity analyses yielded consistent causal estimates. CONCLUSION: This study suggests that asthma is causally associated with AA. The findings deepen our understanding of the role of asthma in the pathology of AA, which emphasizes the potential for opening a new vista for the prevention and diagnosis of AA.
Subject(s)
Alopecia Areata , Asthma , Genetic Predisposition to Disease , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Alopecia Areata/genetics , Asthma/genetics , Asthma/epidemiology , Genetic Predisposition to Disease/genetics , Polymorphism, Single NucleotideABSTRACT
A 2-dimensional (2D) egg-shape equation can be used to construct a 3D egg geometry based on the hypothesis that an egg is a solid of revolution, which helps to calculate egg volume and surface area. The parameters in the 2D egg-shape equation are potentially valuable for providing a clue to the ecology and evolution of avian eggs. In this study, the 5-parameter Preston equation (PE), the 4-parameter Troscianko equation (TE), and another 2 egg-shape equations, were compared in describing real 2D egg-shape data of 300 Gallus gallus domesticus eggs and additional 50 eggs that represented the variation in avian egg geometries. Adjusted root-mean-square error was used to quantify each equation's prediction error. Given that the 4 equations are nonlinear, relative curvature measures of nonlinearity were used to assess the extent of nonlinearity in each equation. PE was found to be the best among the 4 equations in terms of adjusted root-mean-square error and minimizing nonlinearity. The empirically determined egg volumes using a graduated cylinder were compared with the predicted egg volumes using the formula for a solid of revolution based on 2D predictions from the 4 egg-shape equations. There were negligible differences in the predicted egg volumes and surface areas among the 4 equations, indicating that these equations are all valid in calculating egg volume and surface area. In addition, we proposed a 5-parameter TE and found that it outperformed the above 4 equations in describing the 2D egg shape of G. gallus, but was less general than PE for other egg shapes. This work provides statistical evidence to show which equation is the best for describing the geometry of avian eggs and nondestructively calculating their volume and surface area, helping to classify poultry eggs into different grades according to the morphological characteristics of the eggs.
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Helicity-dependent photocurrent (HDPC) and its modulation in topological insulator Bi2Te3 nanowires have been investigated. It is revealed that when the incident plane of a laser is perpendicular to the nanowire, the HDPC is an odd function of the incident angle, which is mainly contributed by the circular photogalvanic effect originating from the surface states of Bi2Te3 nanowire. When the incident plane of a laser is parallel to the nanowire, the HDPC is approximately an even function of the incident angle, which is due to the circular photon drag effect coming from the surface states. It is found that the HDPC can be effectively tuned by the back gate and the ionic liquid top gate. By analyzing the substrate dependence of the HDPC, we find that the HDPC of the Bi2Te3 nanowire on the Si substrate is an order of magnitude larger than that on SiO2, which may be due to the spin injection from the Si substrate to the Bi2Te3 nanowire. In addition, by applying different biases, the Stokes parameters of a polarized light can be extracted by arithmetic operation of the photocurrents measured in the Bi2Te3 nanowire. This work suggests that topological insulator Bi2Te3 nanowires may provide a good platform for opto-spintronic devices, especially in chirality and polarimtry detection.
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There is a lack of research on whether tree size affects lamina and petiole biomass allocation patterns, whereas the trade-off between leaf biomass allocated to the lamina and the petiole is of significance when considering the hydraulic and mechanical function of the leaf as a whole. Here, Camptotheca acuminata Decne was selected for study because of the availability of trees differing in size growing under the same conditions. A total of 600 leaves for two tree size groups and 300 leaves per group differing in height and trunk diameter were collected. The lamina fresh mass (LFM), lamina dry mass (LDM), lamina area (LA), petiole fresh mass (PFM), and petiole length (PL) of each leaf was measured, and reduced major axis regression protocols were used to determine the scaling relationships among the five functional traits. The bootstrap percentile method was used to determine if the scaling exponents of the traits differed significantly between the two tree size groups. The results indicated that (i) there was a significant difference in the LFM, LDM, PFM, PL, LMA, LFMA and PFM/LFM between large and small trees, but no significant difference in LA; (ii) the LA versus LFM, LA versus LDM, LFM versus PFM, LA versus PFM, and PL versus PFM scaling relationships of the two groups were allometric (i.e., not isometric); (iii) there were significant differences in the scaling exponents of LA versus LFM, LA versus PFM, PL versus PFM between the two groups, but there was no significant difference in the LFM versus PFM scaling relationship between the two groups of trees. The data were also consistent with the phenomenon known as "diminishing returns". These data indicate that tree size influences leaf biomass allocation patterns in ways that can potentially influence overall plant growth, and therefore have an important bearing on life-history strategies.
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Background: This research explores the causal association between circulating inflammatory markers and the development of sciatica, a common and debilitating condition. While previous studies have indicated that inflammation may be a factor in sciatica, but a thorough genetic investigation to determine a cause-and-effect relationship has not yet been carried out. Gaining insight into these interactions may uncover novel treatment targets. Methods: We utilized data from the OpenGWAS database, incorporating a large European cohort of 484,598 individuals, including 4,549 sciatica patients. Our study focused on 91 distinct circulating inflammatory markers. Genetic variations were employed as instrumental variables (IVs) for these markers. The analysis was conducted using inverse variance weighting (IVW) as the primary method, supplemented by weighted median-based estimation. Validation of the findings was conducted by sensitivity studies, utilizing the R software for statistical computations. Results: The analysis revealed that 52 out of the 91 inflammatory markers studied showed a significant causal association with the risk of developing sciatica. Key markers like CCL2, monocyte chemotactic protein-4, and protein S100-A12 demonstrated a positive correlation. In addition, there was no heterogeneity or horizontal pleiotropy in these results. Interestingly, a reverse Mendelian randomization analysis also indicated potential causative effects of sciatica on certain inflammatory markers, notably Fms-related tyrosine kinase 3 ligands. Discussion: The study provides robust evidence linking specific circulating inflammatory markers with the risk of sciatica, highlighting the role of inflammation in its pathogenesis. These findings could inform future research into targeted treatments and enhance our understanding of the biological mechanisms underlying sciatica.
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Previous studies have validated a performance equation (PE) and its generalized version (GPE) in describing the rotated and right-shifted Lorenz curves of organ size (e.g., leaf area and fruit volume) distributions of herbaceous plants. Nevertheless, there are still two questions that have not been adequately addressed by prior work: (i) whether the PE and GPE apply to woody plant species and (ii) how do the PE and GPE perform in comparison with other Lorenz equations when fitting data. To address these deficiencies, we measured the lamina length and width of each leaf on 60 Alangium chinense saplings to compare the performance of the PE and GPE with three other Lorenz equations in quantifying the inequality of leaf area distributions across individual trees. Leaf area is shown to be the product of a proportionality coefficient (k) and leaf length and width. To determine the numerical value of k, we scanned 540 leaves to obtain the leaf area empirically. Using the estimated k, the leaf areas of 60 A. chinense saplings were calculated. Using these data, the two performance equations and three other Lorenz equations were then compared and assessed using the root-mean-square error (RMSE) and Akaike information criterion (AIC). The PE and GPE were found to be valid in describing the rotated and right-shifted Lorenz curves of the A. chinense leaf area distributions, and GPE has the lowest RMSE and AIC values. This work validates the GPE as the best model in gauging variations in leaf area of the woody species.
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Although the pencilfish is a globally popular economic fish in the aquarium market, its taxonomic classification could be further refined. In order to understand the taxonomy of species of the genus Nannostomus (Characiformes, Lebiasinidae) and their phylogenetic position within the order Characiformes, in this study, we characterized mitochondrial genomes (mitogenomes) from four Nannostomus species for the first time. The four mitogenomes exhibited the typical circular structure, with overall sizes varying from 16,661 bp to 16,690 bp. They contained 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and 1 control region (CR). Nucleotide composition analysis suggested that the mitochondrial sequences were biased toward A and T. Bayesian inference and maximum likelihood analyses based on PCGs support the family Lebiasinidae classification, described using four Nannostomus species, clustering together with Lebiasina multimaculata from the same family. The results of this study support the current taxonomic classification of the family Lebiasinidae. Phylogenetic analysis also suggested that gene rearrangement would not significantly impact the phylogenetic relationships within the order Characiformes. These results might provide new data regarding the phylogeny and classification of the order Characiformes, thus providing a theoretical basis for the economic development of aquarium fish markets.
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Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.
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BACKGROUND: Unhealthy diets significantly contribute to stomach, colorectal and esophageal cancer burden globally. Western diets high in processed and red meats promote carcinogenesis in these gastrointestinal cancers. However, adolescent and young adult (AYA) patients' unique needs regarding these cancers have been neglected. METHODS: Data from the 2019 Global Burden of Disease study was used to quantify stomach, colorectal and esophageal cancer burden among AYAs from 1990 to 2040 across 204 countries. Correlations between the burden of these cancers and the Socio-demographic Index were examined. RESULTS: High SDI locations experienced the largest reduction in cancer DALY rate change from 1990 to 2019 (-22% [-12 to -33]), compared to a small increase in low-middle SDI regions. Middle SDI areas saw the largest reduction in DALY rate change from 1990 to 2019 (-62% [-32 to -75]), compared to a small decrease in low-middle SDI locations (-9% [-27 to 10]) in esophageal cancer. From 1990-2019, stomach cancer deaths and DALYs declined across all SDI regions, with the largest reductions in high SDI locations (-61% [-57 to -69]) and smallest in low-middle SDI areas (-25% [-13 to -34]). Colorectal cancer deaths and DALYs rose across all SDI regions except high SDI locations, which showed a slight decrease. CONCLUSION: This study demonstrates the evolving global burden of stomach, colorectal and esophageal cancers among AYAs. The highest burden was in high-middle and high SDI regions, underscoring the need to prioritize initiatives targeting these gastrointestinal malignancies in youth.
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BACKGROUND AND AIMS: Leaf area (A) is a crucial indicator of the photosynthetic capacity of plants. The Montgomery equation (ME), which hypothesizes that A is proportional to the product of leaf length (L) and width (W), is a valid tool for nondestructively measuring A for many broad-leaved plants. At present, the methods used to compute L and W for ME can be broadly divided into two kinds: using computer recognition, and measuring manually. However, the potential difference in the prediction accuracy using either method has not been thoroughly examined in prior studies. METHODS: In the present study, we measured 540 Alangium chinense leaves, 489 Liquidambar formosana leaves, and 215 Liriodendron × sinoamericanum leaves, utilizing computer recognition and manual measurement methods to determine L and W. ME was used to fit the data determined by the two methods, and the goodness of fits were compared. The prediction errors of A were analyzed by examining the correlations with two leaf symmetry indices (areal ratio of the left side to the right side, and standardized index for bilateral asymmetry), as well as the leaf shape complexity index (the leaf dissection index). KEY RESULTS: The results indicate that there is a neglectable difference in the estimation of A between both methods. This further validates that ME is an effective method for estimating A in broad-leaved tree species, including those with lobes. Additionally, leaf shape complexity significantly influenced the estimation of A. CONCLUSIONS: These results show that the use of computer recognition and manual measurement in the field are both effective and feasible, although the influence of leaf shape complexity should be considered when applying ME to estimate A in the future.
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Skin cutaneous melanoma (SKCM) is a highly malignant form of skin cancer, known for its unfavorable prognosis and elevated mortality rate. RARRES1, a gene responsive to retinoic acid receptors, displays varied functions in various cancer types. However, the specific role and underlying mechanisms of RARRES1 in SKCM are still unclear. GSE15605 was utilized to analyze the expression of RARRES1 in SKCM. Subsequently, the TCGA and GEO databases were employed to investigate the relationships between RARRES1 and clinicopathological parameters, as well as the prognostic implications and diagnostic efficacy of RARRES1 in SKCM. GO, KEGG, and GSEA analyses were conducted to explore the potential functions of RARRES1. Furthermore, the associations between RARRES1 and immune infiltration were examined. Genomic alterations and promoter methylation levels of RARRES1 in SKCM were assessed using cBioPortal, UALCAN, and the GEO database. Finally, RARRES1 expression in SKCM was validated through immunohistochemistry, and its functional role in SKCM progression was elucidated via in vivo and in vitro experiments. We found that RARRES1 was downregulated in SKCM compared with normal tissues, and this low expression was associated with worse clinicopathological features and poor prognosis of SKCM. The diagnostic efficacy of RARRES1, as determined by ROC analysis, was 0.732. Through GO, KEGG, and GSEA enrichment analysis, we identified 30 correlated genes and pathways that were mainly enriched in the tumor immune microenvironment, proliferation, apoptosis, and autophagy. Additionally, RARRES1 expression was found to be positively related to the infiltration of various immune cells in SKCM, particularly macrophages and T helper cells, among others. Analysis of genomic alterations and promoter methylation revealed that shallow deletion and hypermethylation of the RARRES1 promoter could lead to reduced RARRES1 expression. IHC validation confirmed the downregulation of RARRES1 in SKCM. Moreover, overexpression of RARRES1 inhibited the proliferation and migration of A375 cells, promoted apoptosis, and inhibited autophagic flux. In the mouse xenograft model, RARRES1 overexpression also suppressed SKCM tumor growth. Collectively, these findings suggest that RARRES1 may function as a suppressor and could potentially serve as a prognostic biomarker and therapeutic target for SKCM.
Subject(s)
Biomarkers, Tumor , Computational Biology , Gene Expression Regulation, Neoplastic , Melanoma, Cutaneous Malignant , Melanoma , Skin Neoplasms , Humans , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Skin Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Computational Biology/methods , Animals , Cell Line, Tumor , Mice , Prognosis , DNA Methylation , Female , Cell Proliferation , Male , Tumor Microenvironment/genetics , Promoter Regions, Genetic , Middle Aged , Apoptosis/genetics , Membrane ProteinsABSTRACT
Degeneracy and symmetry have a profound relation in quantum systems. Here, we report gate-tunable subband degeneracy in PbTe nanowires with a nearly symmetric cross-sectional shape. The degeneracy is revealed in electron transport by the absence of a quantized plateau. Utilizing a dual gate design, we can apply an electric field to lift the degeneracy, reflected as emergence of the plateau. This degeneracy and its tunable lifting were challenging to observe in previous nanowire experiments, possibly due to disorder. Numerical simulations can qualitatively capture our observation, shedding light on device parameters for future applications.
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BACKGROUND: Phosphatidylinositol-4-phosphate 5-kinase type 1 alpha (PIP5K1A) acts upstream of the Akt regulatory pathway and is abnormally expressed in many types of malignancies. However, the role and mechanism of PIP5K1A in colorectal cancer (CRC) have not yet been reported. In this study, we aimed to determine the association between PIP5K1A and progression of CRC and assess the efficacy and mechanism by which rupatadine targets PIP5K1A. METHODS: Firstly, expression and function of PIP5K1A in CRC were investigated by human colon cancer tissue chip analysis and cell proliferation assay. Next, rupatadine was screened by computational screening and cytotoxicity assay and interactions between PIP5K1A and rupatadine assessed by kinase activity detection assay and bio-layer interferometry analysis. Next, rupatadine's anti-tumor effect was evaluated by in vivo and in vitro pharmacodynamic assays. Finally, rupatadine's anti-tumor mechanism was explored by quantitative real-time reverse-transcription polymerase chain reaction, western blot, and immunofluorescence. RESULTS: We found that PIP5K1A exerts tumor-promoting effects as a proto-oncogene in CRC and aberrant PIP5K1A expression correlates with CRC malignancy. We also found that rupatadine down-regulates cyclin-dependent kinase 2 and cyclin D1 protein expression by inhibiting the PIP5K1A/Akt/GSK-3ß pathway, induces cell cycle arrest, and inhibits CRC cell proliferation in vitro and in vivo. CONCLUSIONS: PIP5K1A is a potential drug target for treating CRC. Rupatadine, which targets PIP5K1A, could serve as a new option for treating CRC, its therapeutic mechanism being related to regulation of the Akt/GSK-3ß signaling pathway.
Subject(s)
Cell Proliferation , Colorectal Neoplasms , Cyproheptadine , Phosphotransferases (Alcohol Group Acceptor) , Proto-Oncogene Proteins c-akt , Signal Transduction , Humans , Cell Proliferation/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Signal Transduction/drug effects , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Cyproheptadine/pharmacology , Cyproheptadine/analogs & derivatives , Mice, Nude , Cell Line, Tumor , Mice, Inbred BALB C , Male , Proto-Oncogene Mas , Xenograft Model Antitumor Assays , Mice , Antineoplastic Agents/pharmacologyABSTRACT
Perfluorooctane sulfonate (PFOS), one of the most frequently detected per- and polyfluoroalkyl substances (PFAS) occurring in soil, surface water, and groundwater near sites contaminated with aqueous film-forming foam (AFFF), has proven to be recalcitrant to many destructive remedies, including chemical oxidation. We investigated the potential to utilize microbially mediated reduction (bioreduction) to degrade PFOS and other PFAS through addition of a known dehalogenating culture, WBC-2, to soil obtained from an AFFF-contaminated site. A substantial decrease in total mass of PFOS (soil and water) was observed in microcosms amended with WBC-2 and chlorinated volatile organic compound (cVOC) co-contaminants - 46.4 ± 11.0 % removal of PFOS over the 45-day experiment. In contrast, perfluorooctanoate (PFOA) and 6:2 fluorotelomer sulfonate (6:2 FTS) concentrations did not decrease in the same microcosms. The low or non-detectable concentrations of potential metabolites in full PFAS analyses, including after application of the total oxidizable precursor assay, indicated that defluorination occurred to non-fluorinated compounds or ultrashort-chain PFAS. Nevertheless, additional research on the metabolites and degradation pathways is needed. Population abundances of known dehalorespirers did not change with PFOS removal during the experiment, making their association with PFOS removal unclear. An increased abundance of sulfate reducers in the genus Desulfosporosinus (Firmicutes) and Sulfurospirillum (Campilobacterota) was observed with PFOS removal, most likely linked to initiation of biodegradation by desulfonation. These results have important implications for development of in situ bioremediation methods for PFAS and advancing knowledge of natural attenuation processes.
Subject(s)
Alkanesulfonic Acids , Biodegradation, Environmental , Fluorocarbons , Soil Microbiology , Soil Pollutants , Fluorocarbons/metabolism , Alkanesulfonic Acids/metabolism , Soil Pollutants/metabolism , Anaerobiosis , Halogenation , Solvents , Soil/chemistry , MicrobiotaABSTRACT
Single cell RNA sequencing (scRNA-seq), a powerful tool for studying the tumor microenvironment (TME), does not preserve/provide spatial information on tissue morphology and cellular interactions. To understand the crosstalk between diverse cellular components in proximity in the TME, we performed scRNA-seq coupled with spatial transcriptomic (ST) assay to profile 41,700 cells from three colorectal cancer (CRC) tumor-normal-blood pairs. Standalone scRNA-seq analyses revealed eight major cell populations, including B cells, T cells, Monocytes, NK cells, Epithelial cells, Fibroblasts, Mast cells, Endothelial cells. After the identification of malignant cells from epithelial cells, we observed seven subtypes of malignant cells that reflect heterogeneous status in tumor, including tumor_CAV1, tumor_ATF3_JUN | FOS, tumor_ZEB2, tumor_VIM, tumor_WSB1, tumor_LXN, and tumor_PGM1. By transferring the cellular annotations obtained by scRNA-seq to ST spots, we annotated four regions in a cryosection from CRC patients, including tumor, stroma, immune infiltration, and colon epithelium regions. Furthermore, we observed intensive intercellular interactions between stroma and tumor regions which were extremely proximal in the cryosection. In particular, one pair of ligands and receptors (C5AR1 and RPS19) was inferred to play key roles in the crosstalk of stroma and tumor regions. For the tumor region, a typical feature of TMSB4X-high expression was identified, which could be a potential marker of CRC. The stroma region was found to be characterized by VIM-high expression, suggesting it fostered a stromal niche in the TME. Collectively, single cell and spatial analysis in our study reveal the tumor heterogeneity and molecular interactions in CRC TME, which provides insights into the mechanisms underlying CRC progression and may contribute to the development of anticancer therapies targeting on non-tumor components, such as the extracellular matrix (ECM) in CRC. The typical genes we identified may facilitate to new molecular subtypes of CRC.
Subject(s)
Colorectal Neoplasms , Single-Cell Analysis , Transcriptome , Tumor Microenvironment , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Tumor Microenvironment/genetics , Transcriptome/genetics , Gene Expression Regulation, Neoplastic , Genetic Heterogeneity , Gene Expression Profiling , Male , FemaleABSTRACT
The thymus-derived lymphocytes of jawed vertebrates have four T-cell receptor (TCR) chains that play a significant role in immunity. As chickens have commercial value, their immune systems require a great deal of attention. Local chicken breeds are an essential part of poultry genetic resources in China. Here, we used high-throughput sequencing to analyze the TCRα and TCRß repertoires and their relative expression levels in the native chicken breeds Baier Buff, Longyou Partridge, Xiaoshan, and Xianju. We found that TCR Vα and TCR Vß were expressed and included 17, 19, 17, and six segments of the Vα2, Vα3, Vß1, and Vß2 subgroups, respectively. V-J pairing was biased; Jα11 was utilized by nearly all Vα segments and was the most commonly used. Breed-specific V segments and V-J pairings were detected as well. The results of the principal coordinate analysis (PCoA) as well as the V-J pairing and CDR3 diversity analyses suggested that the four local chicken breeds did not significantly differ in terms of TCR diversity. Hence, they expressed not significant differentiation, and they are rich genetic resources for the development and utilization of immune-related poultry breeding.
Subject(s)
Chickens , Receptors, Antigen, T-Cell, alpha-beta , Animals , Chickens/immunology , Chickens/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/metabolism , High-Throughput Nucleotide Sequencing , Breeding , Genetic Variation , China , Complementarity Determining Regions/geneticsABSTRACT
One-unit-cell FeSe films on SrTiO3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( Δ 1 ~15 meV vs. Δ 2 ~10 meV) and pairing temperatures (Tp1~52.0 K vs. Tp2~37.3 K), and correspondingly two-step nonlinear V ~ I α behavior but a concurrent Berezinskii-Kosterlitz-Thouless (BKT)-like transition occurring at T BKT ~28.7 K. Moreover, the onset transition temperature T c onset ~54 K and zero-resistivity temperature T c zero ~31 K are consistent with Tp1 and T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity.