ABSTRACT
The basal region of maize (Zea mays) kernels, which includes the pedicel, placenta-chalazal, and basal endosperm transfer layers, serves as the maternal/filial interface for nutrient transfer from the mother plant to the developing seed. However, transcriptome dynamics of this maternal/filial interface remain largely unexplored. To address this gap, we conducted high-temporal-resolution RNA sequencing of the basal and upper kernel regions between 4 and 32 days after pollination and deeply analyzed transcriptome dynamics of the maternal/filial interface. Utilizing 790 specifically and highly expressed genes in the basal region, we performed the gene ontology (GO) term and weighted gene co-expression network analyses. In the early-stage basal region, we identified five MADS-box transcription factors (TFs) as hubs. Their homologs have been demonstrated as pivotal regulators at the maternal/filial interface of rice or Arabidopsis, suggesting their potential roles in maize kernel development. In the filling-stage basal region, numerous GO terms associated with transcriptional regulation and transporters are significantly enriched. Furthermore, we investigated the molecular function of three hub TFs. Through genome-wide DNA affinity purification sequencing combined with promoter transactivation assays, we suggested that these three TFs act as regulators of 10 basal-specific transporter genes involved in the transfer of sugars, amino acids, and ions. This study provides insights into transcriptomic dynamic and regulatory modules of the maternal/filial interface. In the future, genetic investigation of these hub regulators must advance our understanding of maternal/filial interface development and function.
Subject(s)
Gene Expression Regulation, Plant , Plant Proteins , Seeds , Transcriptome , Zea mays , Zea mays/genetics , Zea mays/growth & development , Zea mays/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Seeds/genetics , Seeds/growth & development , Seeds/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Endosperm/genetics , Endosperm/growth & development , Endosperm/metabolism , Gene Regulatory Networks , Gene Expression ProfilingABSTRACT
Demographic history and mutational load are of paramount importance for the adaptation of the endangered species. However, the effects of population evolutionary history and genetic load on the adaptive potential in endangered conifers remain unclear. Here, using population transcriptome sequencing, whole chloroplast genomes and mitochondrial DNA markers, combined with niche analysis, we determined the demographic history and mutational load for three threatened whitebark pines having different endangered statuses, Pinus bungeana, P. gerardiana and P. squamata. Demographic inference indicated that severe bottlenecks occurred in all three pines at different times, coinciding with periods of major climate and geological changes; in contrast, while P. bungeana experienced a recent population expansion, P. gerardiana and P. squamata maintained small population sizes after bottlenecking. Abundant homozygous-derived variants accumulated in the three pines, particularly in P. squamata, while the species with most heterozygous variants was P. gerardiana. Abundant moderately and few highly deleterious variants accumulated in the pine species that have experienced the most severe demographic bottlenecks (P. gerardiana and P. squamata), most likely because of purging effects. Finally, niche modeling showed that the distribution of P. bungeana might experience a significant expansion in the future, and the species' identified genetic clusters are also supported by differences in the ecological niche. The integration of genomic, demographic and niche data has allowed us to prove that the three threatened pines have contrasting patterns of demographic history and mutational load, which may have important implications in their adaptive potential and thus are also key for informing conservation planning.
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OBJECTIVE: Exposure to heavy metals has been reported to be associated with impaired cognitive function, but the underlying mechanisms remain unclear. This pilot study aimed to identify key heavy metal elements associated with cognitive function and further explore the potential mediating role of metal-related DNA methylation. METHODS: Blood levels of arsenic, cadmium, lead, copper, manganese, and zinc and genome-wide DNA methylations were separately detected in peripheral blood in 155 older adults. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Least absolute shrinkage and selection operator penalized regression and Bayesian kernel machine regression were used to identify metals associated with cognitive function. An epigenome-wide association study examined the DNA methylation profile of the identified metal, and mediation analysis investigated its mediating role. RESULTS: The MMSE scores showed a significant decrease of 1.61 (95% confidence interval [CI]: -2.64, -0.59) with each 1 standard deviation increase in ln-transformed arsenic level; this association was significant in multiple-metal models and dominated the overall negative effect of 6 heavy metal mixture on cognitive function. Seventy-three differentially methylated positions were associated with blood arsenic (p < 1.0 × 10-5). The methylation levels at cg05226051 (annotated to TDRD3) and cg18886932 (annotated to GAL3ST3) mediated 24.8% and 25.5% of the association between blood arsenic and cognitive function, respectively (all p < 0.05). INTERPRETATION: Blood arsenic levels displayed a negative association with the cognitive function of older adults. This finding shows that arsenic-related DNA methylation alterations are critical partial mediators that may serve as potential biomarkers for further mechanism-related studies. ANN NEUROL 2024;96:87-98.
Subject(s)
Cognition , DNA Methylation , Epigenome , Mediation Analysis , Metals, Heavy , Humans , DNA Methylation/drug effects , DNA Methylation/genetics , Female , Male , Metals, Heavy/blood , Aged , Cognition/drug effects , Epigenome/genetics , Pilot Projects , Arsenic/blood , Arsenic/toxicity , Genome-Wide Association Study , Middle Aged , Cognitive Dysfunction/genetics , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/blood , Aged, 80 and over , Mental Status and Dementia TestsABSTRACT
Low-dimensional semiconductor-based field-effect transistor (FET) biosensors are promising for label-free detection of biotargets while facing challenges in mass fabrication of devices and reliable reading of small signals. Here, we construct a reliable technology for mass production of semiconducting carbon nanotube (CNT) film and FET biosensors. High-uniformity randomly oriented CNT films were prepared through an improved immersion coating technique, and then, CNT FETs were fabricated with coefficient of performance variations within 6% on 4-in. wafers (within 9% interwafer) based on an industrial standard-level process. The CNT FET-based ion sensors demonstrated threshold voltage standard deviations within 5.1 mV at each ion concentration, enabling direct reading of the concentration information based on the drain current. By integrating bioprobes, we achieved detection of biosignals as low as 100 aM through a plug-and-play portable detection system. The reliable technology will contribute to commercial applications of CNT FET biosensors, especially in point-of-care tests.
ABSTRACT
Variegation and complexity of polarization relaxation loss in many heterostructured materials provide available mechanisms to seek a strong electromagnetic wave (EMW) absorption performance. Here we construct a unique heterostructured compound that bonds α-Fe2O3 nanosheets of the (110) plane on carbon microtubes (CMTs). Through effective alignment between the Fermi energy level of CMTs and the conduction band position of α-Fe2O3 nanosheets at the interface, we attain substantial polarization relaxation loss via novel atomic valence reversal between Fe(III) â Fe(III-) induced with periodic electron injection from conductive CMTs under EMW irradiation to give α-Fe2O3 nanosheets. Such heterostructured materials possess currently reported minimum reflection loss of -84.01 dB centered at 10.99 GHz at a thickness of 3.19 mm and an effective absorption bandwidth (reflection loss ≤ -10 dB) of 7.17 GHz (10.83-18 GHz) at 2.65 mm. This work provides an effective strategy for designing strong EMW absorbers by combining highly efficient electron injection and atomic valence reversal.
ABSTRACT
BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown. METHODS: High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis. RESULTS: In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC. CONCLUSIONS: Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , MicroRNAs , Humans , Carcinoma, Renal Cell/genetics , Alternative Splicing , RNA, Circular/genetics , MicroRNAs/genetics , Kidney Neoplasms/genetics , Heterogeneous-Nuclear Ribonucleoproteins , Polypyrimidine Tract-Binding Protein , Cytochrome P-450 CYP1B1 , Heterogeneous-Nuclear Ribonucleoprotein Group C/geneticsABSTRACT
Platelets and M2 macrophages both play crucial roles in tumorigenesis, but their relationship and the prognosis value of the relative genes in bladder cancer (BLCA) remain obscure. In the present study, we found that platelets stimulated by BLCA cell lines could promote M2 macrophage polarization, and platelets were significantly associated with the infiltration of M2 macrophages in BLCA samples. Through the bioinformatic analyses, A2M, TGFB3, and MYLK, which were associated with platelets and M2 macrophages, were identified and verified in vitro and then included in the predictive model. A platelet and M2 macrophage-related gene signature was constructed to evaluate the prognosis and immunotherapeutic sensitivity, helping to guide personalized treatment and to disclose the underlying mechanisms.
Subject(s)
Blood Platelets , Immunotherapy , Macrophages , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/pathology , Humans , Prognosis , Macrophages/immunology , Macrophages/metabolism , Blood Platelets/metabolism , Cell Line, Tumor , Immunotherapy/methods , Male , Female , Gene Expression Regulation, Neoplastic , Computational Biology/methods , Mice , Transcriptome , Middle Aged , Gene Expression Profiling/methodsABSTRACT
PURPOSES: STAT1 is a transduction and transcriptional regulator that functions within the classical JAK/STAT pathway. In addition to chronic mucocutaneous candidiasis, bacterial infections are a common occurrence in patients with STAT1 gain-of-function (GOF) mutations. These patients often exhibit skewing of B cell subsets; however, the impact of STAT1-GOF mutations on B cell-mediated humoral immunity remains largely unexplored. It is also unclear whether these patients with IgG within normal range require regular intravenous immunoglobulin (IVIG) therapy. METHODS: Eleven patients (harboring nine different STAT1-GOF mutations) were enrolled. Reporter assays and immunoblot analyses were performed to confirm STAT1 mutations. Flow cytometry, deep sequencing, ELISA, and ELISpot were conducted to assess the impact of STAT1-GOF on humoral immunity. RESULTS: All patients exhibited increased levels of phospho-STAT1 and total STAT1 protein, with two patients carrying novel mutations. In vitro assays showed that these two novel mutations were GOF mutations. Three patients with normal total IgG levels received regular IVIG infusions, resulting in effective control of bacterial infections. Four cases showed impaired affinity and specificity of pertussis toxin-specific antibodies, accompanied by reduced generation of class-switched memory B cells. Patients also had a disrupted immunoglobulin heavy chain (IGH) repertoire, coupled with a marked reduction in the somatic hypermutation frequency of switched Ig transcripts. CONCLUSION: STAT1-GOF mutations disrupt B cell compartments and skew IGH characteristics, resulting in impaired affinity and antigen-specificity of antibodies and recurrent bacterial infections. Regular IVIG therapy can control these infections in patients, even those with normal total IgG levels.
Subject(s)
B-Lymphocytes , Bacterial Infections , Gain of Function Mutation , Immunoglobulins, Intravenous , STAT1 Transcription Factor , Humans , STAT1 Transcription Factor/genetics , Bacterial Infections/immunology , Bacterial Infections/genetics , Female , Male , Child , Immunoglobulins, Intravenous/therapeutic use , B-Lymphocytes/immunology , Adult , Immunoglobulin G/immunology , Immunoglobulin G/blood , Child, Preschool , Adolescent , Young Adult , Immunity, HumoralABSTRACT
The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igß respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.
Subject(s)
Agammaglobulinemia , Chromosomes, Human, Pair 19 , Fluoxetine , Uniparental Disomy , Humans , Fluoxetine/therapeutic use , Chromosomes, Human, Pair 19/genetics , Agammaglobulinemia/genetics , Agammaglobulinemia/drug therapy , CD79 Antigens/genetics , Male , Enterovirus Infections/drug therapy , Enterovirus Infections/genetics , Mutation/genetics , Immunoglobulins, Intravenous/therapeutic use , FemaleABSTRACT
Estrogen receptor α (ERα) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ERα protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ERα protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ERα-positive from the ERα-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ERα protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ERα protein concentrations, the dissociation constant (Kd) was estimated to be 7.35 ± 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ERα protein. The nanosensor was able to analyze ERα proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ERα-positive and ERα-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ERα protein without antibody labeling.
Subject(s)
Biosensing Techniques , Graphite , Limit of Detection , Estrogen Receptor alpha , Transistors, Electronic , Biomarkers , Biosensing Techniques/methodsABSTRACT
Aligned carbon nanotube (A-CNT) with high semiconducting purity and high-density have been considered as one of the most promising active channels for field-effect transistors (FETs), but conjugated polymer dispersant residues on the surface of A-CNT have become the main obstacle for its further development in electronics applications. In this work, a series of removable conjugated polymers (CPs) are designed and synthesized to achieve favorable purification and alignment for CNT arrays with a high density of ≈360 CNTs/µm. Furthermore, a removal process of CPs on the CNT array film is developed. Raman spectra show that the CNTs in array film are almost not damaged after the removal process, and the G/D ratio is as high as 35. The field-effect transistors (FETs) are fabricated with a saturation current density up to 600 µA µm-1 and a current on-off ratio of ≈105, even with a relatively long channel length of ≈3 µm.
ABSTRACT
In this work, multi-layer Ti3C2 - carbon nanotubes - gold nanoparticles (Ti3C2-CNTs-Au) and cyclodextrin metal-organic framework - carbon nanotubes (CD-MOF-CNTs) have been prepared by in situ growth method and used to construct the ultra-sensitive rutin electrochemical sensor for the first time. Among them, the large number of metal active sites of Ti3C2, the high electron transfer efficiency of CNTS, and the good catalytic properties of AuNPs significantly enhance the electrochemical properties of the composite carbon nanomaterials. Interestingly, CD-MOF has a unique host-guest recognition and a large number of cavities, molecular gaps, and surface reactive groups, which gives the composite outstanding accumulation properties and selectivity for rutin. Under the optimized conditions, the constructed novel sensor has satisfactory detection performance for rutin in the range of 2 × 10-9 to 8 × 10-7 M with a limit of detection of 6.5 × 10-10 M. In addition, the sensor exhibits amazing anti-interference performance against rutin in some flavonoid compounds and can be used to test natural plant samples (buckwheat, Cymbopogon distans, and flos sophorae immaturus). This work has promising applications in the field of environmental and food analysis, and exploring new directions for the application of Mxene-based composites.
Subject(s)
Cyclodextrins , Gold , Nanotubes, Carbon , Rutin , Titanium , Rutin/chemistry , Rutin/analysis , Gold/chemistry , Cyclodextrins/chemistry , Nanotubes, Carbon/chemistry , Titanium/chemistry , Metal-Organic Frameworks/chemistry , Metal Nanoparticles/chemistry , Electrochemical Techniques/methodsABSTRACT
To manufacture flexible batteries, it can be a challenge for silicon base anode materials to maintain structural integrity and electrical connectivity under bending and torsion conditions. In this work, 1D silicon nanowire array structures combined with flexible carbon chains consisting of short carbon nanofibers (CNFs) and long carbon nanotubes (CNTs) are proposed. The CNFs and CNTs serve as chain joints and separate chain units, respectively, weaving the well-ordered Si nanowire array into a robust and integrated configuration. The prepared flexible and stretchable silicon array anode exhibits excellent electrochemical performance during dynamic operation. A high initial specific capacity of 2856 mAh g-1 is achieved. After 1000 cycles, a capacity retention of 60% (1602 mAh g-1) is maintained. Additionally, the capacity attenuation is less than 1% after 100 bending cycles. This excellent cycling stability is obtained with a high Si loading of 6.92 mg cm-2. This novel approach offers great promise for the development of high-loading flexible energy-storage devices.
ABSTRACT
Graphene nanoribbons (GNRs) are promising in nanoelectronics for their quasi-1D structures with tunable bandgaps. The methods for controllable fabrication of high-quality GNRs are still limited. Here a way to generate sub-5-nm GNRs by annealing single-walled carbon nanotubes (SWCNTs) on Cu(111) is demonstrated. The structural evolution process is characterized by low-temperature scanning tunneling microscopy. Substrate-dependent measurements on Au(111) and Ru(0001) reveal that the intermediate strong SWCNT-surface interaction plays a pivotal role in the formation of GNRs.
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PURPOSE: Demonstrate the potential of spatiotemporal encoding (SPEN) MRI to deliver largely undistorted 2D, 3D, and diffusion weighted images on a 110 mT portable system. METHODS: SPEN's quadratic phase modulation was used to subsample the low-bandwidth dimension of echo planar acquisitions, delivering alias-free images with an enhanced immunity to image distortions in a laboratory-built, low-field, portable MRI system lacking multiple receivers. RESULTS: Healthy brain images with different SPEN time-bandwidth products and subsampling factors were collected. These compared favorably to EPI acquisitions including topup corrections. Robust 3D and diffusion weighted SPEN images of diagnostic value were demonstrated, with 2.5 mm isotropic resolutions achieved in 3 min scans. This performance took advantage of the low specific absorption rate and relative long TEs associated with low-field MRI. CONCLUSION: SPEN MRI provides a robust and advantageous fast acquisition approach to obtain faithful 3D images and DWI data in low-cost, portable, low-field systems without parallel acceleration.
Subject(s)
Brain , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Humans , Brain/diagnostic imaging , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Equipment Design , Reproducibility of Results , Algorithms , Image Enhancement/methods , Sensitivity and Specificity , Spatio-Temporal Analysis , Signal Processing, Computer-Assisted , Echo-Planar Imaging , Equipment Failure Analysis , Image Interpretation, Computer-Assisted/methods , Diffusion Magnetic Resonance ImagingABSTRACT
BACKGROUND: Caspase Recruitment Domain-containing protein 9 (CARD9) expressed in myeloid cells has been demonstrated to play an antifungal immunity role in protecting against disseminated candidiasis. Hereditary CARD9 ablation leads to fatal disseminated candidiasis. However, the myeloid cell types and molecular mechanisms implicated in CARD9 protecting against disseminated candidiasis remain wholly elusive. METHODS: The role of CARD9 ablation in exacerbating disseminated candidiasis was determined in vivo and in vitro. The molecular mechanism by which CARD9 ablation promotes acute kidney injury in disseminated candidiasis was identified by RNA-sequencing analysis. The expression of mitochondrial proteins and ferroptosis-associated proteins were measured by Quantitative real-time PCR and western blot. RESULTS: CARD9 ablation resulted in a reduced proportion of myeloid-derived suppressor cells (MDSCs) and a substantially lower expression of solute carrier family 7 member 11 (SLC7A11) in the kidneys, which increased susceptibility to acute kidney injury and renal ferroptosis during disseminated Candida tropicalis (C. tropicalis) infection. Moreover, CARD9-deficient MDSCs were susceptible to ferroptosis upon stimulation with C. tropicalis, which was attributed to augmented mitochondrial oxidative phosphorylation (OXPHOS) caused by reduced SLC7A11 expression. Mechanistically, C-type lectin receptors (CLRs)-mediated recognition of C. tropicalis promoted the expression of SLC7A11 which was transcriptionally manipulated by the Syk-PKCδ-CARD9-FosB signaling axis in MDSCs. FosB enhanced SLC7A11 transcription by binding to the promoter of SLC7A11 in MDSCs stimulated with C. tropicalis. Mitochondrial OXPHOS, which was negatively regulated by SLC7A11, was responsible for inducing ferroptosis of MDSCs upon C. tropicalis stimulation. Finally, pharmacological inhibition of mitochondrial OXPHOS or ferroptosis significantly increased the number of MDSCs in the kidneys to augment host antifungal immunity, thereby attenuating ferroptosis and acute kidney injury exacerbated by CARD9 ablation during disseminated candidiasis. CONCLUSIONS: Collectively, our findings show that CARD9 ablation enhances mitochondria-mediated ferroptosis in MDSCs, which negatively regulates antifungal immunity. We also identify mitochondria-mediated ferroptosis in MDSCs as a new molecular mechanism of CARD9 ablation-exacerbated acute kidney injury during disseminated candidiasis, thus targeting mitochondria-mediated ferroptosis is a novel therapeutic strategy for acute kidney injury in disseminated candidiasis.
Subject(s)
Acute Kidney Injury , Candidiasis , Ferroptosis , Myeloid-Derived Suppressor Cells , Mice , Animals , Antifungal Agents , Mice, KnockoutABSTRACT
BACKGROUND: There is increasing evidence that gut fungi dysbiosis plays a crucial role in the development and progression of colorectal cancer (CRC). It has been reported that gut fungi exacerbate the severity of CRC by regulating tumor immunity. Our previous studies have shown that the opportunistic pathogenic fungal pathogen, Candida tropicalis (C. tropicalis) promotes CRC progression by enhancing the immunosuppressive function of MDSCs and activating the NLRP3 inflammasome of MDSCs. However, the relationship between IL-1ß produced by NLRP3 inflammasome activation and the immunosuppressive function of MDSCs enhanced by C. tropicalis in CRC remains unclear. METHODS: The TCGA database was used to analyze the relationship between IL-1ß and genes related to immunosuppressive function of MDSCs in human CRC. The expression of IL-1ß in human CRC tissues was detected by immunofluorescence staining. The proteomic analysis was performed on the culture supernatant of C. tropicalis-stimulated MDSCs. The experiments of supplementing and blocking IL-1ß as well as inhibiting the NLRP3 inflammasome activation were conducted. A mouse colon cancer xenograft model was established by using MC38 colon cancer cell line. RESULTS: Analysis of CRC clinical samples showed that the high expression of IL-1ß was closely related to the immunosuppressive function of tumor-infiltrated MDSCs. The results of in vitro experiments revealed that IL-1ß was the most secreted cytokine of MDSCs stimulated by C. tropicalis. In vitro supplementation of IL-1ß further enhanced the immunosuppressive function of C. tropicalis-stimulated MDSCs and NLRP3-IL-1ß axis mediated the immunosuppressive function of MDSCs enhanced by C. tropicalis. Finally, blockade of IL-1ß secreted by MDSCs augmented antitumor immunity and mitigated C. tropicalis-associated colon cancer. CONCLUSIONS: C. tropicalis promotes excessive secretion of IL-1ß from MDSCs via the NLRP3 inflammasome. IL-1ß further enhances the immunosuppressive function of MDSCs to inhibit antitumor immunity, thus promoting the progression of CRC. Therefore, targeting IL-1ß secreted by MDSCs may be a potential immunotherapeutic strategy for the treatment of CRC.
Subject(s)
Candida tropicalis , Colorectal Neoplasms , Interleukin-1beta , Myeloid-Derived Suppressor Cells , NLR Family, Pyrin Domain-Containing 3 Protein , Interleukin-1beta/metabolism , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/microbiology , Animals , Myeloid-Derived Suppressor Cells/metabolism , Myeloid-Derived Suppressor Cells/immunology , Humans , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Cell Line, Tumor , Inflammasomes/metabolism , Male , Mice, Inbred C57BL , FemaleABSTRACT
BACKGROUND: Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is caused by UNC13D variants. The clinical manifestations of FHL3 are highly diverse and complex. Some patients exhibit atypical or incomplete phenotypes, making accurate diagnosis difficult. Our study aimed to broaden the understanding of the atypical FHL3 clinical spectrum. METHODS: In our study, we analyzed in detail the clinical features of four Chinese patients with UNC13D variants. Additionally, we conducted a comprehensive review of the existing literature on previously reported atypical manifestations and summarized the findings. RESULTS: Two of our patients presented with muscle involvement, while the other two had hematological involvement; none of them met the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). However, protein expression and functional analysis ultimately confirmed diagnostic criteria for FHL3 in all patients. From the literature we reviewed, many atypical FHL3 patients had neurological involvement, especially isolated neurological manifestations. At the same time, arthritis and hypogammaglobulinemia were also prone to occur. CONCLUSION: Our study highlights that the expression of the Munc13-4 protein may not fully indicate the pathogenicity of UNC13D variants, whereas CD107a analysis could be more sensitive for disease diagnosis. These findings contribute to a broader understanding of the FHL3 clinical spectrum and may offer new insights into the underlying pathogenesis of UNC13D variants. It is crucial to prioritize the timely and accurate diagnosis of atypical patients, as they may often be overlooked among individuals with rheumatic or hematological diseases.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Membrane Proteins , Child , Female , Humans , Infant , Male , China/epidemiology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/genetics , Membrane Proteins/genetics , Mutation , Phenotype , AdolescentABSTRACT
Root phenes are associated with the absorptive efficiency of water and fertilizers. However, there are few reports on the genetic variation and stability of peanut (Arachis hypogaea L.) root architecture under different environments. In this study, the diversity, variance and stability of root phenes of 89 peanut varieties were investigated with shovelomics (high throughput phenotyping of root system architecture) for two years in both field and laboratory experiments. The root phenes of these peanut genotypes presented rich diversity; for example, the value of total root length (TRL) ranged from 347.84 cm to 1013.80 cm in the field in 2018, and from 55.14 cm to 206.22 cm in the laboratory tests. The root phenes of different genotypes varied differently; for example, the coefficient of variation (CV) of TRL ranged from 24.0 to 83.5 across the two-year field test. Field and laboratory evaluations were highly correlated, especially on lateral root density (LRD) and root angle (RA), and the quadrant graph analysis of LRD and RA implied that 69.7% of the roots belong to the same type. These not only further reflect root phenes stability through different environment but also demonstrate that some root phenes identified at early stage can indicate their status at later growth stage. In addition, root phenes showed a strong correlation with shoot growth, especially root dry weight (RDW), TRL andï¼nodule numberï¼NN. Thus, laboratory tests in combination with field shovelomics can efficiently screen and select genotypes with contrasting root phenes to optimize water and nutrient management.
Subject(s)
Arachis , Fabaceae , Arachis/genetics , Plant Roots/genetics , Genotype , WaterABSTRACT
BACKGROUND AND AIM: To explore the feasibility of a standardized training and assessment system for magnetically controlled capsule gastroscopy (MCCG). METHODS: The results of 90 trainees who underwent the standardized training and assessment system of the MCCG at the First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to November 2023 was retrospectively analyzed. The trainees were divided into three groups according to their medical backgrounds: doctor, nurse, and non-medical groups. The training and assessment system adopted the '7 + 2' mode, seven days of training plus two days of theoretical and operational assessment. The passing rates of theoretical, operational, and total assessment were the primary outcomes. Satisfaction and mastery of the MCCG was checked. RESULTS: Ninety trainees were assessed; theoretical assessment's passing rates in the three groups were 100%. The operational and total assessment passing rates were 100% (25/25), 97.92% (47/48), and 94.12% (16/17), for the doctor, nurse, and non-doctor groups respectively, with no significant difference (χ2 = 1.741, p = 0.419). No bleeding or perforation occurred during the procedure. Approximately, 96.00% (24/25), 95.83% (46/48), and 94.12% (16/17) of the doctor, nurse and non-medical groups anonymously expressed great satisfaction, respectively, without statistically significant difference (χ2 = 0.565, p = 1.000). The average follow-up time was 4-36 months, and 87 trainees (96.67%) had mastered the operation of the MCCG in daily work. CONCLUSIONS: Standardized training and assessment of magnetically controlled capsule endoscopists is effective and feasible. Additionally, a strict assessment system and long-term communication and learning can improve teaching effects.