Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data.

BACKGROUND: Colorectal cancer is a malignant tumor of the digestive system originating from abnormal cell proliferation in the colon or rectum, often leading to gastrointestinal symptoms and severe health issues. Nucleotide metabolism, which encompasses the synthesis of DNA and RNA, is a pivotal cellular biochemical process that significantly impacts both the progression and therapeutic strategies of colorectal cancer METHODS: For single-cell RNA sequencing (scRNA-seq), five functions were employed to calculate scores related to nucleotide metabolism. Cell developmental trajectory analysis and intercellular interaction analysis were utilized to explore the metabolic characteristics and communication patterns of different epithelial cells. These findings were further validated using spatial transcriptome RNA sequencing (stRNA-seq). A risk model was constructed using expression profile data from TCGA and GEO cohorts to optimize clinical decision-making. Key nucleotide metabolism-related genes (NMRGs) were functionally validated by further in vitro experiments. RESULTS: In both scRNA-seq and stRNA-seq, colorectal cancer (CRC) exhibited unique cellular heterogeneity, with myeloid cells and epithelial cells in tumor samples displaying higher nucleotide metabolism scores. Analysis of intercellular communication revealed enhanced signaling pathways and ligand-receptor interactions between epithelial cells with high nucleotide metabolism and fibroblasts. Spatial transcriptome sequencing confirmed elevated nucleotide metabolism states in the core region of tumor tissue. After identifying differentially expressed NMRGs in epithelial cells, a risk prognostic model based on four genes effectively predicted overall survival and immunotherapy outcomes in patients. High-risk group patients exhibited an immunosuppressive microenvironment and relatively poorer prognosis and responses to chemotherapy and immunotherapy. Finally, based on data analysis and a series of cellular functional experiments, ACOX1 and CPT2 were identified as novel therapeutic targets for CRC. CONCLUSION: In this study, a comprehensive analysis of NMRGs in CRC was conducted using a combination of single-cell sequencing, spatial transcriptome sequencing, and high-throughput data. The prognostic model constructed with NMRGs shows potential as a standalone prognostic marker for colorectal cancer patients and may significantly influence the development of personalized treatment approaches for CRC.

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single-cell RNA sequencing.

Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome-wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, ß-receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse-variance-weighted method. Mendelian randomization analysis showed that BBs with the ß1-adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267-0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422-0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single-cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1-targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.

Parasitic Reflection Eliminating for Planar Elements Based on Multi-Frequency Phase-Shifting in Phase Measuring Deflectometry.

Phase measuring deflectometry (PMD) stands as an extremely important technique for specular surface measurement. However, the parasitic reflection from the rear surface poses a challenge for PMD. To solve this problem, this paper proposes an effective method based on multi-frequency and phase-shifting to search for the correct phase. Firstly, the relationship between the phase error and fringe frequency is adequately investigated. Subsequently, an auxiliary function is established to find the special frequency at which the phase error is zero theoretically and the unwrapped phase is the phase of the top surface exactly. Then, the shape of the top surface can be reconstructed correctly. A standard plane element with a thickness of 40 mm and a flat glass with 19 mm were measured. The experimental results verify the feasibility of the proposed method. Considering the result of the interferometer as a reference, the RMSE of the error map is up to 20 nm for the standard plane element. The experimental results demonstrate that the proposed method can successfully untangle the superposed reflections and reliably reconstruct the top surface of the object under test.

Model-independent nonlinearity rectification algorithm using a phase-probability-equalization-based look-up table.

In the fringe projection system, nonlinearities often result in severe artifacts, such as the gamma effect and the phase-shifting error. Most previous methods can only eliminate the nonlinearity of a particular model. Additionally, the problems of coupling nonlinearities are difficult to solve. Therefore, this paper proposes a model-independent nonlinear rectification algorithm. By applying phase probability equalization (PPE) on several complete periods of a flat area, we built a look-up table (LUT) between the phase error and the wrapped phase, and retrieved an accurate phase with the subtraction of a searched phase error. The simulation and experimental results show that, compared with the traditional full-field PPE algorithm, the proposed algorithm is more robust to the object height distributions and has better rectification on incomplete fringe periods. Besides, the proposed algorithm also has higher efficiency because of the characteristics of local processing and noniterative characteristics.

Core Microbiota in the Rhizosphere of Heavy Metal Accumulators and Its Contribution to Plant Performance.

Persistent microbial symbioses can confer greater fitness to their host under unfavorable conditions, but manipulating such beneficial interactions necessitates a mechanistic understanding of the consistently important microbiomes for the plant. Here, we examined the phylogenetic profiles and plant-beneficial traits of the core microbiota that consistently inhabits the rhizosphere of four divergent Cd hyperaccumulators and an accumulator. We evidenced the existence of a conserved core rhizosphere microbiota in each plant distinct from that in the non-hyperaccumulating plant. Members of Burkholderiaceae and Sphingomonas were the shared cores across hyperaccumulators and accumulators. Several keystone taxa in the rhizosphere networks were part of the core microbiota, the abundance of which was an important predictor of plant Cd accumulation. Furthermore, an inoculation experiment with synthetic communities comprising isolates belonging to the shared cores indicated that core microorganisms could facilitate plant growth and metal tolerance. Using RNA-based stable isotope probing, we discovered that abundant core taxa overlapped with active rhizobacteria utilizing root exudates, implying that the core rhizosphere microbiota assimilating plant-derived carbon may provide benefits to plant growth and host phenotype such as Cd accumulation. Our study suggests common principles underpinning hyperaccumulator-microbiome interactions, where plants consistently interact with a core set of microbes contributing to host fitness and plant performance. These findings lay the foundation for harnessing the persistent root microbiomes to accelerate the restoration of metal-disturbed soils.

End-to-end computational optics with a singlet lens for large depth-of-field imaging.

Large depth-of-field (DOF) imaging with a high resolution is useful for applications ranging from robot vision to bio-imaging. However, it is challenging to construct an optical system with both a high resolution and large DOF. The common solution is to design relatively complex optical systems, but the setup of such systems is often bulky and expensive. In this paper, we propose a novel, compact, and low-cost method for large-DOF imaging. The core concept is to (1) design an aspherical lens with a depth-invariant point spread function to enable uniform image blurring over the whole depth range and (2) construct a deep learning network to reconstruct images with high fidelity computationally. The raw images captured by the aspherical lens are deblurred by the trained network, which enables large-DOF imaging at a smaller F number. Experimental results demonstrate that our end-to-end computational imager can achieve enhanced imaging performance. It can reduce loss by up to 46.5% compared to inherited raw images. With the capabilities of high-resolution and large-DOF imaging, the proposed method is promising for applications such as microscopic pathological diagnosis, virtual/augmented reality displays, and smartphone photography.

High-speed 3D shape measurement using a rotary mechanical projector.

In this paper, a fast rotary mechanical projector (RMP) is designed and manufactured for high-speed 3D shape measurement. Compared with the common high-speed projectors, RMP has a good performance in high-speed projection, which can obtain high quality projected fringes with shorter camera exposure time by using the error diffusion binary coding method and chrome plating technology. The magnitude, acceptability of systemic projection error is analyzed and quantified in detail. For the quantified error, the probability distribution function (PDF) algorithm is introduced to correct the error. Corrected projection error is reduced to more than one third of the original error. Subsequently, a monocular measurement system composed of the RMP and a single camera is constructed. The combination of the RMP device and PDF algorithm ensure the accuracy of a corresponding 3D shape measurement system. Experiments have demonstrated that the proposed solution has a good performance for the 3D measurement of high-speed scenes.

Uniaxial 3D Measurement with Auto-Synchronous Phase-Shifting and Defocusing Based on a Tilted Grating.

Conventional uniaxial techniques generally require shifting objects or projection grating with the assistance of a high-precision mechanical moving component. To overcome this limitation, we propose a novel uniaxial 3-D shape measurement system with auto-synchronous phase-shifting and defocusing by using a tilted and fixed projection grating. The tilted focused image plane (FIP), which is reflected by a mirror at about 90 degrees, could be shifted across the measured surface by slightly rotating the mirror within a small angle range. This procedure will simultaneously introduce the change in defocusing and phase-shifting of the fringe. The modulation curve of each point can be deciphered by Fourier fringe analysis after a sequence of fringe intensities is acquired. Since both the measured object and projection grating are fixed, the proposed method could make the measurement system more compact and flexible. Both computer simulation and experiments are carried out to demonstrate the validity of this proposed system.

Umbilical cord-derived mesenchymal stromal/stem cells expressing IL-24 induce apoptosis in gliomas.

Although much progress has been made in the treatment of gliomas, the prognosis for patients with gliomas is still very poor. Stem cell-based therapies may be promising options for glioma treatment. Recently, many studies have reported that umbilical cord-derived mesenchymal stromal/stem cells (UC-MSCs) are ideal gene vehicles for tumor gene therapy. Interleukin 24 (IL-24) is a pleiotropic immunoregulatory cytokine that has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. In this study, we investigated UC-MSCs as a vehicle for the targeted delivery of IL-24 to tumor sites. UC-MSCs were transduced with lentiviral vectors carrying green fluorescent protein (GFP) or IL-24 complementary DNA. The results indicated that UC-MSCs could selectively migrate to glioma cells in vitro and in vivo. Injection of IL-24-UC-MSCs significantly suppressed tumor growth of glioma xenografts. The restrictive efficacy of IL-24-UC-MSCs was associated with the inhibition of proliferation as well as the induction of apoptosis in tumor cells. These findings indicate that UC-MSC-based IL-24 gene therapy may be able to suppress the growth of glioma xenografts, thereby suggesting possible future therapeutic use in the treatment of gliomas.

Growth and Photosynthetic Inhibition of Cerium Oxide Nanoparticles on Soybean (Glycine max).

Cerium oxide nanoparticles (CeO2 NPs) are widely used in industries and have caused environmental problems. However, the phytotoxicity induced by CeO2 NPs lacks detailed information on phytotoxicity. In this research, the effect of CeO2 NPs on soybean plants (Glycine max) was studied. Scanning electron microscopy with the energy dispersion spectroscopy was used to characterize the NPs form in soybean. The growth of the root was increased, whereas the growth of shoot was inhibited. Besides, Chlorophyll Fluorescence Imager (CF Imager) showed that chlorophyll synthesis was inhibited: the maximum quantum yield of Photosystem II complex (PSII) (Fv/Fm) and photochemical quenching (qP) decreased. Moreover, transmission electron microscopy revealed that the chloroplast thylakoid structure was changed, and thus reduced the energy conversion in the Calvin cycle from C5 to C3. Our work suggests that CeO2 NPs will cause growth changes as well as irreversible damage to soybean plants. Our findings will provide evidence for estimation of plant toxicity induced by CeO2 NPs.

Abscisic acid-mediated modifications of radial apoplastic transport pathway play a key role in cadmium uptake in hyperaccumulator Sedum alfredii.

Abscisic acid (ABA) is a key phytohormone underlying plant resistance to toxic metals. However, regulatory effects of ABA on apoplastic transport in roots and consequences for uptake of metal ions are poorly understood. Here, we demonstrate how ABA regulates development of apoplastic barriers in roots of two ecotypes of Sedum alfredii and assess effects on cadmium (Cd) uptake. Under Cd treatment, increased endogenous ABA level was detected in roots of nonhyperaccumulating ecotype (NHE) due to up-regulated expressions of ABA biosynthesis genes (SaABA2, SaNCED), but no change was observed in hyperaccumulating ecotype (HE). Simultaneously, endodermal Casparian strips (CSs) and suberin lamellae (SL) were deposited closer to root tips of NHE compared with HE. Interestingly, the vessel-to-CSs overlap was identified as an ABA-driven anatomical trait. Results of correlation analyses and exogenous applications of ABA/Abamine indicate that ABA regulates development of both types of apoplastic barriers through promoting activities of phenylalanine ammonialyase, peroxidase, and expressions of suberin-related genes (SaCYP86A1, SaGPAT5, and SaKCS20). Using scanning ion-selected electrode technique and PTS tracer confirmed that ABA-promoted deposition of CSs and SL significantly reduced Cd entrance into root stele. Therefore, maintenance of low ABA levels in HE minimized deposition of apoplastic barriers and allowed maximization of Cd uptake via apoplastic pathway.

Flexible gamma calculation algorithm based on probability distribution function in digital fringe projection system.

The gamma effect of phase-measuring profilometry systems yields nonlinear errors, which will substantially reduce the 3D shape measurement accuracy. Here, a robust and flexible gamma correction method based on the probability distribution function (PDF) of the wrapped phase is presented. First, a series of PDF curves are generated from the simulated wrapped phase distributions with different gamma values. Second, an experimental PDF curve will be produced after obtaining the wrapped phase from the captured three-step phase-shift fringe images. Then, a correlation procedure will be used to find the most similar PDF curve from the simulated PDF curves, and the gamma value of the matched PDF curve is that of the current system. Note that the gamma value detected by this method will be smaller than the true value due to the defocusing effect of the projection system with a large aperture. Therefore, an improved PDF-based algorithm, which projects two sets of three-step phase-shifting sinusoidal fringe patterns with different pre-coded gamma values and produces two PDF curves, is also added. Then after one more correlation procedure, a more accurate systematic gamma value could be calculated. It does not need large-step phase-shift images and 2×3 fringe images are quite enough. The experimental results show that the technique is very fast, easy to use and quite accurate.

Role of Vertical Transmission of Shoot Endophytes in Root-Associated Microbiome Assembly and Heavy Metal Hyperaccumulation in Sedum alfredii.

The transmission mode of shoot-associated endophytes in hyperaccumulators and their roles in root microbiome assembly and heavy metal accumulation remain unclear. Using 16S rRNA gene profiling, we investigated the vertical transmission of shoot-associated endophytes in relation to growth and Cd/Zn accumulation of Sedum alfredii ( Crassulaceae). Endophytes were transmitted from shoot cuttings to the rhizocompartment of new plants in both sterilized (γ-irradiated) and native soils. Vertical transmission was far more efficient in the sterile soil, and the transmitted endophytes have become a dominant component of the newly established root-associated microbiome. Based on 16S rRNA genes, the vertically transmitted taxa were identified as the families of Streptomycetaceae, Nocardioidaceae, Pseudonocardiaceae, and Rhizobiaceae. Abundances of Streptomycetaceae, Nocardioidaceae, and Pseudonocardiaceae were strongly correlated with increased shoot biomass and total Cd/Zn accumulation. Inoculation of S. alfredii with the synthetic bacterial community sharing the same phylogenetic relatedness with the vertically transmitted endophytes resulted in significant improvements in plant biomass, root morphology, and Cd/Zn accumulation. Our results demonstrate that successful vertical transmission of endophytes from shoots of S. alfredii to its rhizocompartments is possible, particularly in soils with attenuated microbiomes. Furthermore, the endophyte-derived microbiome plays an important role in metal hyperaccumulation.

Up-regulation of MCM3 Relates to Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats.

Minichromosome maintenance complex component 3, one of the minichromosome maintenance proteins, functions as a part of pre-replication complex to initiate DNA replication in eukaryotes. Minichromosome maintenance complex component 3 (MCM3) was mainly implied in cell proliferation and tumorigenesis. In addition, MCM3 might play an important role in neuronal apoptosis. However, the functions of MCM3 in central nervous system are still with limited acquaintance. In this study, we performed a traumatic brain injury (TBI) model in adult rats. Western blot and immunohistochemistry staining showed up-regulation of MCM3 in the peritrauma brain cortex. The expression patterns of active caspase-3 and Bax, Bcl-2 were parallel with that of MCM3. Immunofluorescent staining and terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling suggested that MCM3 was involved in neuronal apoptosis. In conclusion, our data indicated that MCM3 might play an important role in neuronal apoptosis following TBI. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against TBI.

Radiation-induced removal of sulphadiazine antibiotics from wastewater.

The radiation-induced removal of sulphadiazine (SD) belonging to the heterocyclic sulphonamides pharmaceuticals was investigated by gamma irradiation at different conditions in laboratory scale. The influence of initial SD concentrations, pH values, 02 and N2 on SD degradation was determined. The experimental results showed that gamma-ray irradiation was efficient for removing SD from wastewater. SD could be completely removed at an absorbed dose of 10 kGy. The degradation kinetics of SD conformed to the first-order kinetic equation. When SD concentration was in the range of 10-30 mg/L, the dose constant (d) decreased with an increasing initial SD concentration. The mineralization of SD, in terms of total organic carbon removal, was not obvious at a low absorbed dose, but it increased to more than 75% at 100 kGy. The biodegradability of SD was improved after irradiation, suggesting that irradiation could be used as a pretreatment technology for treating SD-containing wastewater. The possible degradation pathway of SD was tentatively proposed based on the analysis of intermediate products during gamma irradiation.

Genome-Wide Association Study Uncovers Genomic Regions Associated with Coleoptile Length in a Worldwide Collection of Oat.

The length of coleoptile is crucial for determining the sowing depth of oats in low-precipitation regions, which is significant for oat breeding programs. In this study, a diverse panel of 243 oat accessions was used to explore coleoptile length in two independent experiments. The panel exhibited significant variation in coleoptile length, ranging from 4.66 to 8.76 cm. Accessions from Africa, America, and the Mediterranean region displayed longer coleoptile lengths than those from Asia and Europe. Genome-wide association studies (GWASs) using 26,196 SNPs identified 34 SNPs, representing 32 quantitative trait loci (QTLs) significantly associated with coleoptile length. Among these QTLs, six were consistently detected in both experiments, explaining 6.43% to 10.07% of the phenotypic variation. The favorable alleles at these stable loci additively increased coleoptile length, offering insights for pyramid breeding. Gene Ontology (GO) analysis of the 350 candidate genes underlying the six stable QTLs revealed significant enrichment in cell development-related processes. Several phytochrome-related genes, including auxin transporter-like protein 1 and cytochrome P450 proteins, were found within these QTLs. Further validation of these loci will enhance our understanding of coleoptile length regulation. This study provides new insights into the genetic architecture of coleoptile length in oats.

Application value of intraoperative electrophysiological monitoring in cerebral eloquent area glioma surgery: a retrospective cohort study.

INTRODUCTION: Surgery for gliomas involving eloquent areas is a very challenging microsurgical procedure. Maximizing both the extent of resection (EOR) and preservation of neurological function have always been the focus of attention. Intraoperative neurophysiological monitoring (IONM) is widely used in this kind of surgery. The purpose of this study was to evaluate the efficacy of IONM in eloquent area glioma surgery. METHODS: Sixty-eight glioma patients who underwent surgical treatment from 2014 to 2019 were included in this retrospective cohort study, which focused on eloquent areas. Clinical indicators and IONM data were analysed preoperatively, two weeks after surgery, and at the final follow-up. Logistic regression, Cox regression, and Kaplan‒Meier analyses were performed, and nomograms were then established for predicting prognosis. The diagnostic value of the IONM indicator was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: IONM had no effect on the postoperative outcomes, including EOR, intraoperative bleeding volume, duration of surgery, length of hospital stay, and neurological function status. However, at the three-month follow-up, the percentage of patients who had deteriorated function in the monitored group was significantly lower than that in the unmonitored group (23.3% vs. 52.6%; P < 0.05). Logistic regression analysis showed that IONM was a significant factor in long-term neurological function (OR = 0.23, 95% CI (0.07-0.70). In the survival analysis, long-term neurological deterioration indicated worsened overall survival (OS) and progression-free survival (PFS). A prognostic nomogram was established through Cox regression model analysis, which could predict the probability 3-year survival rate. The concordance index was 0.761 (95% CI 0.734-0.788). The sensitivity and specificity of IONM evoked potential (SSEP and TCeMEP) were 0.875 and 0.909, respectively. In the ROC curve analysis, the area under the curve (AUC) for the SSEP and TCeMEP curves was 0.892 (P < 0.05). CONCLUSIONS: The application of IONM could improve long-term neurological function, which is closely related to prognosis and can be used as an independent prognostic factor. IONM is practical and widely available for predicting postoperative functional deficits in patients with eloquent area glioma.

Microecology of aerobic denitrification system construction driven by cyclic stress of sulfamethoxazole.

The construction of aerobic denitrification (AD) systems in an antibiotic-stressed environment is a serious challenge. This study investigated strategy of cyclic stress with concentration gradient (5-30 mg/L) of sulfamethoxazole (SMX) in a sequencing batch reactor (SBR), to achieve operation of AD. Total nitrogen removal efficiency of system increased from about 10 % to 95 %. Original response of abundant-rare genera to antibiotics was changed by SMX stress, particularly conditionally rare or abundant taxa (CRAT). AD process depends on synergistic effect of heterotrophic nitrifying aerobic denitrification bacteria (Paracoccus, Thauera, Hypomicrobium, etc). AmoABC, napA, and nirK were functionally co-expressed with multiple antibiotic resistance genes (ARGs) (acrR, ereAB, and mdtO), facilitating AD process. ARGs and TCA cycling synergistically enhance the antioxidant and electron transport capacities of AD process. Antibiotic efflux pump mechanism played an important role in operation of AD. The study provides strong support for regulating activated sludge to achieve in situ AD function.

Removal of typical pollutant ciprofloxacin using iron-nitrogen co-doped modified corncob in the presence of hydrogen peroxide.

Iron-nitrogen co-doped modified corncob (Fe-N-BC) was synthesized using a hydrothermal and calcination method. The material shows excellent oxidation performance and environmental friendliness. When the dosage of Fe-N-BC was 0.6 g L-1, the concentration of H2O2 was 12 mM and pH was 4, ciprofloxacin (CIP) was virtually totally eliminated in 240 min under Fe-N-BC/H2O2 conditions. The TOC removal efficiency was 54.6%, and the effects of various reaction parameters on the catalytic activity of Fe-N-BC were thoroughly assessed. Through electron paramagnetic resonance (EPR) analyses and free radical quenching experiments, it was established that the reactive oxygen species (˙OH, ˙O2-, 1O2) were crucial in the elimination of CIP. Furthermore, the degradation of CIP was accelerated by the synergistic interaction between the transition metal and PFRs. A thorough evaluation was conducted to assess the respective contributions of adsorption and catalytic oxidation in the system. The degradation mechanism of CIP was proposed under Fe-N-BC/H2O2 conditions. Meanwhile, the possible degradation intermediates and pathways were proposed, and the toxicity of the degradation products of CIP was also meticulously investigated in the study. These findings offered the elimination of CIP in water a theoretical foundation and technical support.