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1.
Int J Gen Med ; 17: 2791-2800, 2024.
Article in English | MEDLINE | ID: mdl-38962174

ABSTRACT

Purpose: Pain is a common yet undertreated symptom of Parkinson's disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD. Patients and Methods: A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I-III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10). Results: The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred. Conclusion: The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.

2.
Sci Rep ; 14(1): 12355, 2024 05 29.
Article in English | MEDLINE | ID: mdl-38811747

ABSTRACT

Time-stamped cross-sectional data, which lack linkage across time points, are commonly generated in single-cell transcriptional profiling. Many previous methods for inferring gene regulatory networks (GRNs) driving cell-state transitions relied on constructing single-cell temporal ordering. Introducing COSLIR (COvariance restricted Sparse LInear Regression), we presented a direct approach to reconstructing GRNs that govern cell-state transitions, utilizing only the first and second moments of samples between two consecutive time points. Simulations validated COSLIR's perfect accuracy in the oracle case and demonstrated its robust performance in real-world scenarios. When applied to single-cell RT-PCR and RNAseq datasets in developmental biology, COSLIR competed favorably with existing methods. Notably, its running time remained nearly independent of the number of cells. Therefore, COSLIR emerges as a promising addition to GRN reconstruction methods under cell-state transitions, bypassing the single-cell temporal ordering to enhance accuracy and efficiency in single-cell transcriptional profiling.


Subject(s)
Gene Regulatory Networks , Single-Cell Analysis , Single-Cell Analysis/methods , Gene Expression Profiling/methods , Humans , Computational Biology/methods , Algorithms
3.
Biochem Biophys Res Commun ; 717: 150028, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38714016

ABSTRACT

Mycoplasma pneumoniae (MP),as the most commonly infected respiratory pathogen in community-acquired pneumonia in preschool children,has becoming a prominent factor affecting children's respiratory health.Currently, there is a lack of easy, rapid, and accurate laboratory testing program for MP infection, which causes comparatively difficulty for clinical diagnostic.Here,we utilize loop-mediated isothermal amplification (LAMP) to amplify and characterize the P1 gene of MP, combined with nucleic acid lateral flow (NALF) for fast and visuallized detection of MP.Furthermore, we evaluated and analyzed the sensitivity, specificity and methodological consistency of the method.The results showed that the limit of detection(LoD) of MP-LAMP-NALF assay was down to 100 copys per reaction and there was no cross-reactivity with other pathogens infected the respiratory system. The concordance rate between MP-LAMP-NALF assay with quantitative real-time PCR was 94.3 %,which exhibiting excellent testing performance.We make superior the turnaround time of the MP-LAMP-NALF assay, which takes only about 50 min. In addition, there is no need for precision instruments and no restriction on the laboratory site.Collectively, LAMP-NALF assay targeting the P1 gene for Mycoplasma pneumoniae detection was a easy, precise and visual test which could be widely applied in outpatient and emergency departments or primary hospitals.When further optimized, it could be used as "point-of-care testing" of pathogens or multiple testing for pathogens.


Subject(s)
Molecular Diagnostic Techniques , Mycoplasma pneumoniae , Nucleic Acid Amplification Techniques , Pneumonia, Mycoplasma , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/isolation & purification , Nucleic Acid Amplification Techniques/methods , Humans , Pneumonia, Mycoplasma/diagnosis , Pneumonia, Mycoplasma/microbiology , Molecular Diagnostic Techniques/methods , Sensitivity and Specificity , Limit of Detection , DNA, Bacterial/genetics
4.
Phys Rev E ; 108(5): L052104, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38115516

ABSTRACT

We investigate the thermodynamics of general nonequilibrium processes stopped at stochastic times. We propose a systematic strategy for constructing fluctuation-theorem-like martingales for each thermodynamic functional, yielding a family of stopping-time fluctuation theorems. We derive second-law-like thermodynamic inequalities for the mean thermodynamic functional at stochastic stopping times, the bounds of which are even stronger than the thermodynamic inequalities resulting from the traditional fluctuation theorems when the stopping time is reduced to a deterministic one. Numerical verification is carried out for three well-known thermodynamic functionals, namely, entropy production, free energy dissipation, and dissipative work. These universal equalities and inequalities are valid for arbitrary stopping strategies, and thus provide a comprehensive framework with insights into the fundamental principles governing nonequilibrium systems.

5.
Life Sci ; 334: 122241, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37944639

ABSTRACT

AIMS: TAFA2, a cytokine specifically expressed in the central nervous system, plays a vital role in neuronal cell survival. TAFA2 deficiency has been correlated to various neurological disorders in mice and humans. However, the underlying mechanism remains elusive, especially its membrane-binding receptor through which TAFA2 functions. This study aimed to identify the specific binding receptor responsible for the anti-apoptotic effects of TAFA2. MAIN METHOD: Co-immunoprecipitation (Co-IP) and quantitative mass spectrometry-based proteomic analysis were employed to identify potential TAFA2 binding proteins in V5 knockin mouse brain lysates. Subsequent validation involved in vitro and in vivo Co-IP and pull-down using specific antibodies. The functional analysis included evaluating the effects of ADGRL1 knockout, overexpression, and Lectin-like domain (Lec) deletion mutant on TAFA2's anti-apoptotic activity and analyzing the intracellular signaling pathways mediated by TAFA2 through ADGRL1. KEY FINDINGS: Our study identified ADGRL1 as a potential receptor for TAFA2, which directly binds to TAFA2 through its lectin-like domain. Overexpression ADGRL1, but not ADGRL1ΔLec, induced apoptosis, which could be effectively suppressed by recombinant TAFA2 (rTAFA2). In ADGRL1-/- cells or re-introducing with ADGRL1ΔLec, responses to rTAFA2 in suppressing cell apoptosis were compromised. Increased cAMP, p-PKA, p-CREB, and BCL2 levels were also observed in response to rTAFA2 treatment, with these responses attenuated in ADGRL1-/- or ADGRL1ΔLec-expressing cells. SIGNIFICANCE: Our results demonstrated that TAFA2 directly binds to the lectin-like domain of ADGRL1, activating cAMP/PKA/CREB/BCL2 signaling pathway, which is crucial in preventing cell death. These results implicate TAFA2 and its receptor ADGRL1 as potential therapeutic targets for neurological disorders.


Subject(s)
Nervous System Diseases , Proteomics , Animals , Humans , Mice , Apoptosis , Cell Survival , Cyclic AMP Response Element-Binding Protein/metabolism , Lectins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction
6.
Front Plant Sci ; 14: 1220921, 2023.
Article in English | MEDLINE | ID: mdl-38023919

ABSTRACT

Verticillium wilt is one of the most crucial diseases caused by Verticillium dahliae that threatens the cotton industry. Statistical results showed that the return of cotton plants infected with V. dahliae to the field might be an essential cause of the continuous aggravation of cotton Verticillium wilt. The correlation among the cotton plants infected with V. dahliae returning to the field, the occurrence of Verticillium wilt, and the number of microsclerotia in rhizosphere soil need further investigation. A potted experiment was carried out to explore the effects of the direct return of cotton plants infected with Verticillium dahliae to the field on the subsequent growth and Verticillium wilt occurrence in cotton. As a risk response plan, we investigated the feasibility of returning dung-sand (i.e., insect excreta) to the field, the dung-sand was from the larvae of Protaetia brevitarsis (Coleoptera: Cetoniidea) that were fed with the V. dahliae-infected cotton plants. The results demonstrated that the return of the entire cotton plants to the field presented a promotional effect on the growth and development of cotton, whereas the return of a single root stubble or cotton stalks had an inhibitive effect. The return of cotton stalks and root stubble infected with V. dahliae increased the risk and degree of Verticillium wilt occurrence. The disease index of Verticillium wilt occurrence in cotton was positively correlated with the number of microsclerotia in the rhizosphere soil. The disease index increased by 20.00%, and the number of soil microsclerotia increased by 8.37 fold in the treatment of returning root stubble infected with V. dahliae to the field. No Verticillium wilt microsclerotia were detected in the feed prepared from cotton stalks and root stubble fermented for more than 5 days or in the transformed dung-sand. There was no risk of inoculation with Verticillium wilt microsclerotia when the dung-sand was returned to the field. The indirect return of cotton plants infected with V. dahliae to the field by microorganism-insect systems is worthy of further exploration plan of the green prevention and control for Verticillium wilt and the sustainable development of the cotton industry.

7.
BMC Musculoskelet Disord ; 24(1): 673, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620829

ABSTRACT

INTRODUCTION: This study aimed to compare the Forgotten Joint Score-12(FJS) outcomes and the minimum clinically important difference (MCID) of the FJS after high tibial osteotomy (HTO), unicompartmental knee arthroplasty (UKA), and total knee arthroplasty (TKA) with short-term follow-up (at least 2 years). Another objective of the study is to investigate the factors influencing FJS. It is hypothesized that there are differences in FJS outcomes among the three procedures. METHODS: Patients who underwent HTO, UKA, and TKA from January 2016 to December 2020 and were followed up for a minimum of 2 years were included in the study. The FJS were analyses from a cohort of people who submitted data to two years. The preoperative and postoperative clinical outcomes were compared and evaluated the patient-related factor. The FJS scores were predicted using multiple linear regression analysis. Additionally, Patient's Joint Perception (PJP) questions were used as anchors to determine the achievement of the forgotten joint, and FJS MCID were calculated using the receiver operating characteristic curve (ROC). RESULTS: Three hundred eighty-nine patients were included in the final study, and there were 111 patients in HTO groups,128patients in UKA groups, and 150 patients in TKA groups. The mean follow-up was 47.0 months. There was a significant difference in the total FJS, between the HTO, UKA, and TKA groups (FJS:59.38 ± 7.25, 66.69 ± 7.44 and 56.90 ± 6.85, p < 0.001. We found the MCID of the FJS of HTO, UKA, and TKA were 63.54, 69.79, and 61.45, respectively. In multiple linear regression, younger age, and higher FS were significant predictors of better FJS. CONCLUSION: Medial UKA demonstrated lower patient awareness in comparison to HTO and TKA, as assessed by the FJS. Younger age and higher FS were identified as significant predictors of improved FJS, providing valuable guidance for surgical decision-making.


Subject(s)
Arthroplasty, Replacement, Knee , Humans , Arthroplasty, Replacement, Knee/adverse effects , Retrospective Studies , Linear Models , Minimal Clinically Important Difference , Osteotomy/adverse effects
8.
Sensors (Basel) ; 23(16)2023 Aug 11.
Article in English | MEDLINE | ID: mdl-37631652

ABSTRACT

Spherical robots have fully wrapped shells, which enables them to walk well on complex terrains, such as swamps, grasslands and deserts. At present, path planning algorithms for spherical robots mainly focus on finding the shortest path between the initial position and the target position. In this paper, an improved A* algorithm considering energy consumption is proposed for the path planning of spherical robots. The optimization objective of this algorithm is to minimize both the energy consumption and path length of a spherical robot. A heuristic function constructed with the energy consumption estimation model (ECEM) and the distance estimation model (DEM) is used to determine the path cost of the A* algorithm. ECEM and DCM are established based on the force analysis of the spherical robot and the improved Euclidean distance of the grid map, respectively. The effectiveness of the proposed algorithm is verified by simulation analysis based on a 3D grid map and a spherical robot moving with uniform velocity. The results show that compared with traditional path planning algorithms, the proposed algorithm can minimize the energy consumption and path length of the spherical robot as much as possible.

9.
Phys Rev Lett ; 131(1): 014001, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37478448

ABSTRACT

Recently, the discovery of optical spatiotemporal (ST) vortex beams with transverse orbital angular momentum (OAM) has attracted increasing attention and is expected to extend the research scope and open new opportunities for practical applications of OAM states. The ST vortex beams are also applicable to other physical fields that involve wave phenomena, and here we develop the ST vortex concept in the field of acoustics and report the generation of Bessel-type ST acoustic vortex beams. The ST vortex beams are fully characterized using the scalar approach for the pressure field and the vector approach for the velocity field. We further investigate the transverse spreading effect and construct ST vortex beams with an ellipse-shaped spectrum to reduce the spreading effect. We also experimentally demonstrated the orthogonality relations between ST vortex beams with different charges. Our study successfully demonstrates the versatility of the acoustic system for exploring and discovering spatiotemporally structured waves, inspiring further investigation of exotic wave physics.

10.
Sensors (Basel) ; 23(12)2023 Jun 17.
Article in English | MEDLINE | ID: mdl-37420840

ABSTRACT

Cable-stayed bridges have been commonly used on high-speed railways. The design, construction, and maintenance of cable-stayed bridges necessitate an accurate assessment of the cable temperature field. However, the temperature fields of cables have not been well established. Therefore, this research aims to investigate the distribution of the temperature field, the time variability of temperatures, and the representative value of temperature actions in stayed cables. A cable segment experiment, spanning over one year, is conducted near the bridge site. Based on the monitoring temperatures and meteorological data, the distribution of the temperature field is studied, and the time variability of cable temperatures is investigated. The findings show that the temperature distribution is generally uniform along the cross-section without a significant temperature gradient, while the amplitudes of the annual cycle variation and daily cycle variation in temperatures are significant. To accurately determine the temperature deformation of a cable, it is necessary to consider both the daily temperature fluctuations and the annual cycle of uniform temperatures. Then, using the gradient boosted regression trees method, the relationship between the cable temperature and multiple environmental variables is explored, and representative cable uniform temperatures for design are obtained by the extreme value analysis. The presented data and results provide a good basis for the operation and maintenance of in-service long-span cable-stayed bridges.


Subject(s)
Temperature , Regression Analysis
11.
J Orthop Surg Res ; 18(1): 486, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37415243

ABSTRACT

OBJECTIVE: This study aims to investigate the efficacy and outcomes of different surgical procedures, namely unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO), for the treatment of bilateral medial compartment knee osteoarthritis in the same patient. The joint awareness and function of these two surgical methods were evaluated. METHODS: A total of 15 patients with bilateral medial compartment knee osteoarthritis who underwent either UKA or HTO between 2012 and 2020 were included in the study. Patient data, including age, gender, body mass index and length of hospital stay, were collected. Pre- and post-operative measurements were conducted, including tibiofemoral angle, tibial plateau posterior inclination angle, proximal tibial medial angle, distance from mechanical axis to knee joint center, hip-knee-ankle angle, pre- and post-operative knee joint scores, knee joint range of motion, and FIS-12 scores at 3, 6, 12, and 24 months postoperatively. The latest follow-up was used for evaluating the outcomes of osteoarthritis treatment. Normality of continuous variables was assessed using the Shapiro-Wilk test. Between-group comparisons were performed using the paired sample t-test or Wilcoxon rank-sum test. Repeated measures analysis of variance was utilized to analyze FJS-12 measurements at different time points, and the correlation between FJS-12 and postoperative clinical results was examined using Pearson's correlation coefficient. Statistical significance was set at P < 0.05. RESULTS: Significant differences were observed in FJS between the UKA and HTO groups at 3 and 6 months postoperatively, but no significant difference was found at 1 and 2 years postoperatively. FJS in the UKA group demonstrated a significant increase from 3 to 6 months postoperatively, but no significant difference was observed from 6 to 24 months postoperatively. In contrast, FJS in the HTO group showed a significant increase from 3 to 24 months postoperatively. CONCLUSIONS: Patients who underwent UKA exhibited superior joint awareness compared to those who underwent HTO during the early postoperative period. Furthermore, the rate of joint awareness in UKA patients was faster than in HTO patients.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Treatment Outcome , Knee Joint/diagnostic imaging , Knee Joint/surgery , Arthroplasty, Replacement, Knee/methods , Osteotomy/methods , Tibia/surgery , Proprioception , Retrospective Studies
12.
BMC Musculoskelet Disord ; 24(1): 434, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37254116

ABSTRACT

BACKGROUND AND OBJECTIVE: At present, the influence of the internal metallic endoskeleton of Spacer on the biomechanical strength of Spacer remains unclear. The aim of this study was to analyze the mechanical stability of a novel Spacer applying a annular skeleton that mimics the structure of trabecular bone using finite element methods. METHEDS: The femur models of three healthy individuals and skeletonless Spacer, K-Spacer, and AD-Spacer were assembled to create 15 3D models. Finite element analysis was performed in an Ansys Bench2022R1. Biomechanical parameters such as stress and strain of the Spacer, internal skeleton and femur were evaluated under three loads, which were applied with the maximum force borne by the hip joint (2100 N), standing on one leg (700 N), and standing on two legs (350 N). The mechanical properties of the new hip Spacer were evaluated. RESULT: The stresses on the medial and lateral surfaces of the AD-Spacer and K-Spacer were smaller than the stresses in the state without skeletal support. The maximum stresses on the medial and lateral surfaces of the AD-Spacer were smaller than those of the inserted K-Spacer, and the difference gradually increased with the increase of force intensity. When the skeleton diameter was increased from 3 to 4 mm, the stresses in the medial and lateral sides of the AD-Spacer and K-Spacer necks decreased. The stress of both skeletons was concentrated at the neck, but the stress of the annular skeleton was evenly distributed on the medial and lateral sides of the skeleton. The mean stress in the proximal femur was higher in femurs with K-Spacer than in femurs with AD-Spacer. CONCLUSIONS: AD-Spacer has lower stress and higher load-bearing capacity than K-Spacer, and the advantages of AD-Spacer are more obvious under the maximum load state of hip joint.


Subject(s)
Femur , Hip Joint , Humans , Finite Element Analysis , Stress, Mechanical , Femur/surgery , Weight-Bearing , Biomechanical Phenomena
13.
Polymers (Basel) ; 15(9)2023 Apr 23.
Article in English | MEDLINE | ID: mdl-37177150

ABSTRACT

Styrene-based thermoplastic elastomers (TPEs) demonstrate excellent overall performance and account for the largest industrial output. The traditional methods of preparation styrene-based thermoplastic elastomers mainly focused on anionic polymerization, and strict equipment conditions were required. In recent years, controlled/living radical polymerization (CRP) has developed rapidly, enabling the synthesis of polymers with various complex topologies while controlling their molecular weight. Herein, a series of core crosslinked star-shaped poly(styrene-b-isoprene-b-styrene)s (SISs) was synthesized for the first time via reversible addition-fragmentation chain transfer (RAFT) polymerization. Meanwhile, linear triblock SISs with a similar molecular weight were synthesized as a control. We achieved not only the controlled/living radical polymerization of isoprene but also investigated the factors influencing the star-forming process. By testing the mechanical and thermal properties and characterizing the microscopic fractional phase structure, we found that both the linear and star-shaped SISs possessed good tensile properties and a certain phase separation structure, demonstrating the characteristics of thermoplastic elastomers.

15.
Insects ; 13(12)2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36554993

ABSTRACT

Cotton stalks (CS) are a potential agricultural biomass resource. We investigated the use of CS as a feed for Proteatia brevitarsis Lewis larvae and the resulting frass (larvae dung-sand) as a fertilizer. Based on a three-factor experiment (decomposition inoculant, fermentation duration, and cattle manure ratio), the optimal parameters for the transformation of CS using P. brevitarsis larvae were determined as 40-50% of cattle manure, the use of VT inoculant and a fermentation duration of 25-30 days. Regarding the products of the transformation, the protein content of the larval body was as high as 52.49%, and the fat content was 11.7%, which is a suitable-quality insect protein source. The organic matter content of larvae dung-sand was 54.8%, and the content of total nitrogen, phosphorus, and potassium (TNPK) was 9.04%, which is twice more than that of the organic fertilizer standard (NY525-2021, Beijing, China, TNPK ≥ 4.0%), and larvae dung-sand has the potential of fertilizer application. Therefore, CS as a feed and fertilizer based on the transformation of P. brevitarsis larvae is feasible, and it is a highly efficient way to promote the utilization of both CS and cattle manure.

16.
Front Neurorobot ; 16: 999658, 2022.
Article in English | MEDLINE | ID: mdl-36213147

ABSTRACT

For a learning automaton, a proper configuration of the learning parameters is crucial. To ensure stable and reliable performance in stochastic environments, manual parameter tuning is necessary for existing LA schemes, but the tuning procedure is time-consuming and interaction-costing. It is a fatal limitation for LA-based applications, especially for those environments where the interactions are expensive. In this paper, we propose a parameter-free learning automaton (PFLA) scheme to avoid parameter tuning by a Bayesian inference method. In contrast to existing schemes where the parameters must be carefully tuned according to the environment, PFLA works well with a set of consistent parameters in various environments. This intriguing property dramatically reduces the difficulty of applying a learning automaton to an unknown stochastic environment. A rigorous proof of ϵ-optimality for the proposed scheme is provided and numeric experiments are carried out on benchmark environments to verify its effectiveness. The results show that, without any parameter tuning cost, the proposed PFLA can achieve a competitive performance compared with other well-tuned schemes and outperform untuned schemes on the consistency of performance.

17.
Angew Chem Int Ed Engl ; 61(50): e202213640, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36282184

ABSTRACT

Exploring the pathways for photocatalytic dissolution of precious metals (PMs) is crucial for optimizing recovery. In this work, we systematically investigated the selectivity and solvation effects observed for dissolution by focusing on photocatalysis, precious metals and solvents. By combining transient characterization, reaction kinetics, and density functional theory, we determined that the radicals generated in photocatalysis were the key active species in the entire reaction. The cyano functional group in the solvent was the driving factor for dissolution of gold, and the importance of chlorine radicals for dissolution of platinum group precious metals was further confirmed. In addition, the catalytic properties of different precious metals can promote different transformations of functional groups, leading to selective dissolution. The structures of photocatalytic precious metal leaches also precisely explains the special coordination forms of precious metals and functional group ligands.

18.
JASA Express Lett ; 2(4): 044001, 2022 Apr.
Article in English | MEDLINE | ID: mdl-36154228

ABSTRACT

An acoustic vector sensor can directly detect acoustic particle velocity based on the measured temperature difference between closely spaced heated wires. For the detection of velocity in three dimensions, an integrated three-dimensional (3 D) sensor is desired, but it remains challenging in MEMS (Micro-Electro-Mechanical System) manufacturing. Here, a novel monolithic 3 D acoustic vector sensor is proposed, which is constructed using in-plane distributed wires assembled with acoustically transparent heat sink. The planar MEMS structure of the proposed sensor makes it easy to be fabricated and packaged. This work offers a new method for the design of acoustic vector sensors and other thermal convection-based MEMS sensors.

19.
Genome Med ; 14(1): 93, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35974387

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) ranks as the second-leading cause of cancer-related death worldwide with metastases being the main cause of cancer-related death. Here, we investigated the genomic and transcriptomic alterations in matching adjacent normal tissues, primary tumors, and metastatic tumors of CRC patients. METHODS: We performed whole genome sequencing (WGS), multi-region whole exome sequencing (WES), simultaneous single-cell RNA-Seq, and single-cell targeted cDNA Sanger sequencing on matching adjacent normal tissues, primary tumors, and metastatic tumors from 12 metastatic colorectal cancer patients (n=84 for genomes, n=81 for exomes, n=9120 for single cells). Patient-derived tumor organoids were used to estimate the anti-tumor effects of a PPAR inhibitor, and self-renewal and differentiation ability of stem cell-like tumor cells. RESULTS: We found that the PPAR signaling pathway was prevalently and aberrantly activated in CRC tumors. Blocking of PPAR pathway both suppressed the growth and promoted the apoptosis of CRC organoids in vitro, indicating that aberrant activation of the PPAR signaling pathway plays a critical role in CRC tumorigenesis. Using matched samples from the same patient, distinct origins of the metastasized tumors between lymph node and liver were revealed, which was further verified by both copy number variation and mitochondrial mutation profiles at single-cell resolution. By combining single-cell RNA-Seq and single-cell point mutation identification by targeted cDNA Sanger sequencing, we revealed important phenotypic differences between cancer cells with and without critical point mutations (KRAS and TP53) in the same patient in vivo at single-cell resolution. CONCLUSIONS: Our data provides deep insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution. Our findings offer novel knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy. The high-precision single-cell RNA-seq dataset of matched adjacent normal tissues, primary tumors, and metastases from CRCs may serve as a rich resource for further studies.


Subject(s)
Colorectal Neoplasms , Neoplasm Metastasis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Copy Number Variations , DNA, Complementary , Genomics , Humans , Mutation , Peroxisome Proliferator-Activated Receptors/antagonists & inhibitors , Peroxisome Proliferator-Activated Receptors/genetics , Transcriptome
20.
BMC Plant Biol ; 22(1): 416, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36038835

ABSTRACT

BACKGROUND: Asian cotton (Gossypium arboreum L.), as a precious germplasm resource of cotton with insect resistance and stress tolerance, possesses a broad spectrum of phenotypic variation related to pigmentation. Flower color affects insect pollination and the ornamental value of plants. Studying flower color of Asian cotton varieties improves the rate of hybridization and thus enriches the diversity of germplasm resources. Meanwhile, it also impacts the development of the horticultural industry. Unfortunately, there is a clear lack of studies concerning intricate mechanisms of cotton flower-color differentiation. Hereby, we report an integrative approach utilizing transcriptome and metabolome concerning flower color variation in three Gossypium arboreum cultivars. RESULTS: A total of 215 differentially accumulated metabolites (DAMs) were identified, including 83 differentially accumulated flavonoids (DAFs). Colorless kaempferol was more abundant in white flowers, while gossypetin-fer showed specificity in white flowers. Quercetin and gossypetin were the main contributors to yellow petal formation. Pelargonidin 3-O-beta-D-glucoside and cyanidin-3-O-(6''-Malonylglucoside) showed high accumulation levels in purple petals. Quercetin and gossypetin pigments also promoted purple flower coloration. Moreover, 8178 differentially expressed genes (DEGs) were identified by RNA sequencing. The correlation results between total anthocyanins and DEGs were explored, indicating that 10 key structural genes and 29 transcription factors promoted anthocyanin biosynthesis and could be candidates for anthocyanin accumulation. Ultimately, we constructed co-expression networks of key DAFs and DEGs and demonstrated the interactions between specific metabolites and transcripts in different color flowers. CONCLUSION: This study provides new insights into elucidating the regulatory mechanisms of cotton flower color and lays a potential foundation for generate cotton varieties with highly attractive flowers for pollinators.


Subject(s)
Anthocyanins , Transcriptome , Anthocyanins/metabolism , Flavonoids/metabolism , Flowers , Gene Expression Regulation, Plant , Gossypium/genetics , Gossypium/metabolism , Pigmentation/genetics , Quercetin/metabolism
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