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1.
Nat Immunol ; 18(2): 152-160, 2017 02.
Article in English | MEDLINE | ID: mdl-27992404

ABSTRACT

Autoimmune diseases affect 7.5% of the US population, and they are among the leading causes of death and disability. A notable feature of many autoimmune diseases is their greater prevalence in females than in males, but the underlying mechanisms of this have remained unclear. Through the use of high-resolution global transcriptome analyses, we demonstrated a female-biased molecular signature associated with susceptibility to autoimmune disease and linked this to extensive sex-dependent co-expression networks. This signature was independent of biological age and sex-hormone regulation and was regulated by the transcription factor VGLL3, which also had a strong female-biased expression. On a genome-wide level, VGLL3-regulated genes had a strong association with multiple autoimmune diseases, including lupus, scleroderma and Sjögren's syndrome, and had a prominent transcriptomic overlap with inflammatory processes in cutaneous lupus. These results identified a VGLL3-regulated network as a previously unknown inflammatory pathway that promotes female-biased autoimmunity. They demonstrate the importance of studying immunological processes in females and males separately and suggest new avenues for therapeutic development.


Subject(s)
Gene Regulatory Networks , Keratinocytes/physiology , Lupus Erythematosus, Cutaneous/genetics , Scleroderma, Systemic/genetics , Sex Factors , Sjogren's Syndrome/genetics , Skin/pathology , Transcription Factors/metabolism , Adult , Aged , Aged, 80 and over , Cells, Cultured , Female , Gene Expression Profiling , Genetic Association Studies , Genome-Wide Association Study , Humans , Male , Middle Aged , Quantitative Trait Loci , Transcription Factors/genetics , Transcriptome , Young Adult
2.
Plant J ; 118(5): 1550-1568, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38412303

ABSTRACT

The increased soil salinity is becoming a major challenge to produce more crops and feed the growing population of the world. In this study, we demonstrated that overexpression of OsDIR55 gene enhances rice salt tolerance by altering the root diffusion barrier. OsDIR55 is broadly expressed in all examined tissues and organs with the maximum expression levels at lignified regions in rice roots. Salt stress upregulates the expression of OsDIR55 gene in an abscisic acid (ABA)-dependent manner. Loss-function and overexpression of OsDIR55 compromised and improved the development of CS and root diffusion barrier, manifested with the decreased and increased width of CS, respectively, and ultimately affected the permeability of the apoplastic diffusion barrier in roots. OsDIR55 deficiency resulted in Na+ accumulation, ionic imbalance, and growth arrest, whereas overexpression of OsDIR55 enhances salinity tolerance and provides an overall benefit to plant growth and yield potential. Collectively, we propose that OsDIR55 is crucial for ions balance control and salt stress tolerance through regulating lignification-mediated root barrier modifications in rice.


Subject(s)
Gene Expression Regulation, Plant , Oryza , Plant Proteins , Plant Roots , Salt Tolerance , Oryza/genetics , Oryza/physiology , Oryza/metabolism , Oryza/growth & development , Plant Roots/genetics , Plant Roots/physiology , Plant Roots/growth & development , Plant Roots/metabolism , Salt Tolerance/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Abscisic Acid/metabolism , Sodium/metabolism , Plants, Genetically Modified , Salt Stress/genetics
3.
Plant Cell ; 34(11): 4274-4292, 2022 10 27.
Article in English | MEDLINE | ID: mdl-35929087

ABSTRACT

Lipid droplets (LDs) are evolutionarily conserved organelles that serve as hubs of cellular lipid and energy metabolism in virtually all organisms. Mobilization of LDs is important in light-induced stomatal opening. However, whether and how LDs are involved in stomatal development remains unknown. We show here that Arabidopsis thaliana LIPID DROPLETS AND STOMATA 1 (LDS1)/RABC1 (At1g43890) encodes a member of the Rab GTPase family that is involved in regulating LD dynamics and stomatal morphogenesis. The expression of RABC1 is coordinated with the different phases of stomatal development. RABC1 targets to the surface of LDs in response to oleic acid application in a RABC1GEF1-dependent manner. RABC1 physically interacts with SEIPIN2/3, two orthologues of mammalian seipin, which function in the formation of LDs. Disruption of RABC1, RABC1GEF1, or SEIPIN2/3 resulted in aberrantly large LDs, severe defects in guard cell vacuole morphology, and stomatal function. In conclusion, these findings reveal an aspect of LD function and uncover a role for lipid metabolism in stomatal development in plants.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Animals , Arabidopsis/metabolism , Lipid Droplets/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Lipid Metabolism/genetics , Mammals/metabolism
4.
Cell ; 140(3): 372-83, 2010 Feb 05.
Article in English | MEDLINE | ID: mdl-20144761

ABSTRACT

Nuclear pore complexes have recently been shown to play roles in gene activation; however their potential involvement in metazoan transcription remains unclear. Here we show that the nucleoporins Sec13, Nup98, and Nup88, as well as a group of FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct loci that often do not represent nuclear envelope contact sites. Whereas Nup88 localizes to silent loci, Sec13, Nup98, and a subset of FG-repeat nucleoporins bind to developmentally regulated genes undergoing transcription induction. Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically inhibits transcription of their target genes and prevents efficient reactivation of transcription after heat shock, suggesting an essential role of NPC components in regulating complex gene expression programs of multicellular organisms.


Subject(s)
Chromatin/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Gene Expression Regulation , Nuclear Pore Complex Proteins/metabolism , Animals , Drosophila melanogaster/genetics , Heat-Shock Response , RNA Polymerase II/metabolism , Transcription, Genetic
5.
Nano Lett ; 24(15): 4415-4422, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38577835

ABSTRACT

The increasing demand for personal protective equipment such as single-use masks has led to large amounts of nondegradable plastic waste, aggravating economic and environmental burdens. This study reports a simple and scalable approach for upcycling waste masks via a chemical vapor deposition technique, realizing a trichome-like biomimetic (TLB) N95 respirator with superhydrophobicity (water contact angle ≥150°), N95-level protection, and reusability. The TLB N95 respirator comprising templated silicone nanofilaments with an average diameter of ∼150 nm offers N95-level protection and breathability comparable to those of commercial N95 respirators. The TLB N95 respirator can still maintain its N95-level protection against particulate matter and viruses after 10 disinfection treatment cycles (i.e., ultraviolet irradiation, microwave irradiation, dry heating, and autoclaving), demonstrating durable reusability. The proposed strategy provides new insight into upcycle waste masks, breaking the existing design and preparation concept of reusable masks.


Subject(s)
COVID-19 , Respiratory Protective Devices , Humans , N95 Respirators , Masks , SARS-CoV-2
6.
Small ; : e2301074, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38659180

ABSTRACT

The coating of filter media with silver is typically achieved by chemical deposition and aerosol processes. Whilst useful, such approaches struggle to provide uniform coating and are prone to blockage. To address these issues, an in situ method for coating glass fibers is presented via the dopamine-mediated electroless metallization method, yielding filters with low air resistance and excellent antibacterial performance. It is found that the filtration efficiency of the filters is between 94 and 97% and much higher than that of silver-coated filters produced using conventional dipping methods (85%). Additionally, measured pressure drops ranged between 100 and 150 Pa, which are lower than those associated with dipped filters (171.1 Pa). Survival rates of Escherichia coli and Bacillus subtilis bacteria exposed to the filters decreased to 0 and 15.7%±1.49, respectively after 2 h, with no bacteria surviving after 6 h. In contrast, survival rates of E. coli and B. subtilis bacteria on the uncoated filters are 92.5% and 89.5% after 6 h. Taken together, these results confirm that the in situ deposition of silver onto fiber surfaces effectively reduces pore clogging, yielding low air resistance filters that can be applied for microbial filtration and inhibition in a range of environments.

7.
New Phytol ; 241(1): 227-242, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37853545

ABSTRACT

As a key regulator of plant photosynthesis, water use efficiency and immunity, stomata are specialized cellular structures that adopt defined shapes. However, our knowledge about the genetic players of stomatal pore formation and stomatal morphogenesis remains limited. Forward genetic screening, positional cloning, confocal and electron microscopy, physiological and pharmacological assays were employed for isolation and characterization of mutants and genes. We identified a mutant, dsm1, with impaired cytokinesis and deformed stomata. DSM1 is highly expressed in guard mother cells and guard cells, and encodes COBRA-LIKE 7 (COBL7), a plant-specific glycosylphosphatidylinositol (GPI)-anchored protein. COBRA-LIKE 7 and its closest homologue, COBL8, are first enriched on the forming cell plates during cytokinesis, and then their subcellular distribution and abundance change are correlated with the progressive stages of stomatal pore formation. Both COBL7 and COBL8 possess an ability to bind cellulose. Perturbing the expression of COBL7 and COBL8 leads to a decrease in cellulose content and inhibition of stomatal pore development. Moreover, we found that COBL7, COBL8 and CSLD5 have synergistic effects on stomatal development and plant growth. Our findings reveal that COBL7 plays a predominant and functionally redundant role with COBL8 in stomatal formation through regulating cellulose deposition and ventral wall modification in Arabidopsis.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cellulose/metabolism , Gene Expression Regulation, Plant , Photosynthesis , Plant Stomata/metabolism
8.
Hematol Oncol ; 42(3): e3268, 2024 May.
Article in English | MEDLINE | ID: mdl-38676394

ABSTRACT

Mantle cell lymphoma (MCL) is an uncommon and incurable B-cell lymphoma subtype that has an aggressive course. Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas, and is characterized by distinct clinical and genetic features. Here, we showed that 9.5% of MCL Chinese patients were hepatitis B surface antigen positive (HBsAg+). Compared to HBsAg-negative (HBsAg-) patients, HBsAg+ MCL patients had a greater incidence of elevated lactate dehydrogenase (LDH), but no difference was observed in the other clinical characteristics, including sex, age, ECOG ps, Ann Arbor stage, MIPI, extranodal involvement and Ki-67. The HD-AraC (high-dose cytarabine) regimen was the main first-line induction regimen for younger HBsAg+ patients, and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were used for elderly patients. HBsAg seropositivity was associated with a significantly shorter PFS than HBsAg seronegativity when patients were treated with rituximab or CHOP-based regimens. Compared with CHOP, the HD-AraC regimen was associated with longer PFS in HBsAg+ patients. Treatment with a Bruton tyrosine kinase inhibitor (BTKi) alone can also cause HBV reactivation. Among the 74 patients who underwent targeted deep sequencing (TDS), the nonsynonymous mutation load of HBsAg+ MCL patients was greater than that of HBsAg- MCL patients. HDAC1, TRAF5, FGFR4, SMAD2, JAK3, SMC1A, ZAP70, BLM, CDK12, PLCG2, SMO, TP63, NF1, PTPR, EPHA2, RPTOR and FIP1L1 were significantly enriched in HBsAg+ MCL patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Hepatitis B virus , Hepatitis B , Lymphoma, Mantle-Cell , Mutation , Humans , Male , Female , Middle Aged , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/genetics , Aged , Hepatitis B virus/genetics , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B/virology , Hepatitis B/pathology , Aged, 80 and over , Hepatitis B Surface Antigens/blood , Vincristine/therapeutic use , Vincristine/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Treatment Outcome
9.
Inflamm Res ; 73(6): 897-913, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38625657

ABSTRACT

OBJECTIVES AND DESIGN: As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control Mycobacterium tuberculosis (Mtb) infection. METHODS: We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection. RESULTS: Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival. Further insight into the mechanisms of Viperin-mediated regulation of IFN-γ production revealed the role of TANK-binding kinase 1 (TBK1), the TAK1-dependent inhibition of NF-kappa B kinase-epsilon (IKKε), and interferon regulatory factor 3 (IRF3). Inhibition of the TBK1-IKKε-IRF3 axis restored IFN-γ production reduced by Viperin knockout in BMDM and suppressed intracellular Mtb survival. Moreover, Viperin deficiency activated the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which promoted IFN-γ production and inhibited Mtb infection in BMDM. Additionally, a combination of the anti-TB drug INH treatment in the absence of Viperin resulted in further IFN-γ production and anti-TB effect. CONCLUSIONS: This study highlights the involvement of TBK1-IKKε-IRF3 axis and JAK-STAT signaling pathways in Viperin-suppressed IFN-γ production in Mtb infected macrophages, and identifies a novel mechanism of Viperin on negatively regulating host immune response to Mtb infection.


Subject(s)
Interferon Regulatory Factor-3 , Interferon-gamma , Macrophages , Mice, Inbred C57BL , Mycobacterium tuberculosis , Protein Serine-Threonine Kinases , Proteins , Signal Transduction , Animals , Interferon-gamma/metabolism , Interferon-gamma/immunology , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Mycobacterium tuberculosis/immunology , Macrophages/immunology , Macrophages/metabolism , Interferon Regulatory Factor-3/metabolism , Mice , Proteins/genetics , Proteins/metabolism , I-kappa B Kinase/metabolism , Janus Kinases/metabolism , Oxidoreductases Acting on CH-CH Group Donors , Mice, Knockout , Tuberculosis/immunology , Lung/immunology , Lung/microbiology , Viperin Protein
10.
J Immunol ; 209(5): 907-915, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35922063

ABSTRACT

The PD-L1/2-PD-1 immune checkpoint is essential for the proper induction of peripheral tolerance and limits autoimmunity, whereas tumor cells exploit their expression to promote immune evasion. Many different cell types express PD-L1/2, either constitutively or upon stimulation, but the factors driving this expression are often poorly defined. In this study, using genome-wide CRISPR activation screening, we identified three factors that upregulate PD-L1 expression: GATA2, MBD6, and transcription cofactor vestigial-like protein 3 (VGLL3). VGLL3 acts as a transcriptional regulator, and its expression induced PD-L1 in many different cell types. Conversely, loss of VGLL3 impaired IFN-γ-induced PD-L1/2 expression in human keratinocytes. Mechanistically, by performing a second screen to identify proteins acting in concert with VGLL3, we found that VGLL3 forms a complex with TEAD1 and RUNX1/3 to drive expression of PD-L1/2. Collectively, our work identified a new transcriptional complex controlling PD-L1/2 expression and suggests that VGLL3, in addition to its known role in the expression of proinflammatory genes, can balance inflammation by upregulating the anti-inflammatory factors PD-L1 and PD-L2.


Subject(s)
B7-H1 Antigen , Programmed Cell Death 1 Receptor , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Core Binding Factor Alpha 2 Subunit/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Immune Evasion , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Programmed Cell Death 1 Receptor/genetics , TEA Domain Transcription Factors , Transcription Factors/genetics
11.
Acta Pharmacol Sin ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992121

ABSTRACT

Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.

12.
Plant Cell Rep ; 43(7): 188, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960994

ABSTRACT

KEY MESSAGE: BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance in Arabidopsis roots. The formative divisions of cortex/endodermis initials (CEIs) and CEI daughter cells (CEIDs) in Arabidopsis roots are coordinately controlled by the longitudinal auxin gradient and the radial SHORT ROOT (SHR) abundance. However, the mechanism underlying this coordination remains poorly understood. In this study, we demonstrate that BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance. Mutations in BIG gene repressed cell cycle progression, delaying the formative divisions within the ground tissues and impairing the establishment of endodermal and cortical identities. In addition, we uncovered auxin's suppressive effect on BIG expression, triggering CYCLIND6;1 (CYCD6;1) activation in an SHR-dependent fashion. Moreover, the degradation of RETINOBLASTOMA-RELATED (RBR) is jointly regulated by BIG and CYCD6;1. The loss of BIG function led to RBR protein accumulation, detrimentally impacting the SHR/SCARECROW (SCR) protein complex and the CEI/CEID formative divisions. Collectively, these findings shed light on a fundamental mechanism wherein BIG intricately coordinates the interplay between SHR/SCR and auxin, steering ground tissue patterning within Arabidopsis root tissue.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Gene Expression Regulation, Plant , Indoleacetic Acids , Plant Roots , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/cytology , Indoleacetic Acids/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Plant Roots/cytology , Plant Roots/growth & development , Plant Roots/metabolism , Plant Roots/genetics , Asymmetric Cell Division , Mutation/genetics , Stem Cells/metabolism , Stem Cells/cytology , Cyclins/metabolism , Cyclins/genetics , Calmodulin-Binding Proteins , Transcription Factors
13.
J Am Chem Soc ; 145(28): 15303-15312, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37402130

ABSTRACT

Transition-metal-catalyzed intermolecular annulation of silicon reagents with organic molecules is still underdeveloped due to the scarcity of silicon reagent types and their diverse reactivity. Herein, a readily accessible silicon reagent (octamethyl-1,4-dioxacyclohexasilane) has been developed for divergent synthesis of silacycles via time-controlled palladium-catalyzed cascade C-H silacyclization. This protocol enables the rapid and selective transformation of acrylamides into spirosilacycles with different ring sizes, including benzodioxatetrasilecines, benzooxadisilepines, and benzosiloles, in moderate to good yields through a time switch. Notably, the tetrasilane reagent can also be utilized for C-H silacyclization of 2-halo-N-methacryloylbenzamides and 2-iodobiphenyls, leading to diverse fused silacycles. Furthermore, several synthetic transformations of products are achieved. A series of mechanistic studies demonstrate the transformation relationships and possible pathways among ten-, seven-, and five-membered silacycles.

14.
Int J Cancer ; 153(5): 1016-1025, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37204683

ABSTRACT

Regimens based on Bruton's tyrosine kinase inhibitors (BTKi) have been increasingly used to treat mantle cell lymphoma (MCL). A real-world multicenter study was conducted to characterize treatment patterns and outcomes in patients with newly diagnosed MCL by Chinese Hematologist and Oncologist Innovation Cooperation of the Excellent (CHOICE). The final analysis included 1261 patients. Immunochemotherapy was the most common first-line treatment, including R-CHOP in 34%, cytarabine-containing regimens in 21% and BR in 3% of the patients. Eleven percent (n = 145) of the patients received BTKi-based frontline therapy. Seventeen percent of the patients received maintenance rituximab. Autologous hematopoietic stem cell transplantation (AHCT) was conducted in 12% of the younger (<65 years) patients. In younger patients, propensity score matching analysis did not show significant difference in 2-year progression-free survival and 5-year overall survival rate in patients receiving standard high-dose immunochemotherapy followed by AHCT than induction therapy with BTKi-based regimens without subsequent AHCT (72% vs 70%, P = .476 and 91% vs 84%, P = .255). In older patients, BTKi combined with bendamustine plus rituximab (BR) was associated with the lowest POD24 rate (17%) compared with BR and other BTKi-containing regimens. In patients with resolved hepatitis B at the baseline, HBV reactivation rate was 2.3% vs 5.3% in those receiving anti-HBV prophylaxis vs not; BTKi treatment was not associated with higher risk of HBV reactivation. In conclusion, non-HD-AraC chemotherapy combined with BTKi may be a viable therapeutic strategy for younger patients. Anti-HBV prophylaxis should be implemented in patients with resolved hepatitis B.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatitis B , Lymphoma, Mantle-Cell , Adult , Humans , Aged , Lymphoma, Mantle-Cell/drug therapy , Rituximab/therapeutic use , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols , Cytarabine/therapeutic use
15.
Radiology ; 307(4): e222729, 2023 05.
Article in English | MEDLINE | ID: mdl-37097141

ABSTRACT

Background Prediction of microvascular invasion (MVI) may help determine treatment strategies for hepatocellular carcinoma (HCC). Purpose To develop a radiomics approach for predicting MVI status based on preoperative multiphase CT images and to identify MVI-associated differentially expressed genes. Materials and Methods Patients with pathologically proven HCC from May 2012 to September 2020 were retrospectively included from four medical centers. Radiomics features were extracted from tumors and peritumor regions on preoperative registration or subtraction CT images. In the training set, these features were used to build five radiomics models via logistic regression after feature reduction. The models were tested using internal and external test sets against a pathologic reference standard to calculate area under the receiver operating characteristic curve (AUC). The optimal AUC radiomics model and clinical-radiologic characteristics were combined to build the hybrid model. The log-rank test was used in the outcome cohort (Kunming center) to analyze early recurrence-free survival and overall survival based on high versus low model-derived score. RNA sequencing data from The Cancer Image Archive were used for gene expression analysis. Results A total of 773 patients (median age, 59 years; IQR, 49-64 years; 633 men) were divided into the training set (n = 334), internal test set (n = 142), external test set (n = 141), outcome cohort (n = 121), and RNA sequencing analysis set (n = 35). The AUCs from the radiomics and hybrid models, respectively, were 0.76 and 0.86 for the internal test set and 0.72 and 0.84 for the external test set. Early recurrence-free survival (P < .01) and overall survival (P < .007) can be categorized using the hybrid model. Differentially expressed genes in patients with findings positive for MVI were involved in glucose metabolism. Conclusion The hybrid model showed the best performance in prediction of MVI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Summers in this issue.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Male , Humans , Middle Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/genetics , Retrospective Studies , Neoplasm Invasiveness/pathology , Tomography, X-Ray Computed/methods
16.
Cancer Cell Int ; 23(1): 103, 2023 May 27.
Article in English | MEDLINE | ID: mdl-37245016

ABSTRACT

BACKGROUND: Oxaliplatin-based chemotherapy is the first-line treatment for colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been implicated in chemotherapy sensitivity. This study aimed to identify lncRNAs related to oxaliplatin sensitivity and predict the prognosis of CRC patients underwent oxaliplatin-based chemotherapy. METHODS: Data from the Genomics of Drug Sensitivity in Cancer (GDSC) was used to screen for lncRNAs related to oxaliplatin sensitivity. Four machine learning algorithms (LASSO, Decision tree, Random-forest, and support vector machine) were applied to identify the key lncRNAs. A predictive model for oxaliplatin sensitivity and a prognostic model based on key lncRNAs were established. The published datasets, and cell experiments were used to verify the predictive value. RESULTS: A total of 805 tumor cell lines from GDSC were divided into oxaliplatin sensitive (top 1/3) and resistant (bottom 1/3) groups based on their IC50 values, and 113 lncRNAs, which were differentially expressed between the two groups, were selected and incorporated into four machine learning algorithms, and seven key lncRNAs were identified. The predictive model exhibited good predictions for oxaliplatin sensitivity. The prognostic model exhibited high performance in patients with CRC who underwent oxaliplatin-based chemotherapies. Four lncRNAs, including C20orf197, UCA1, MIR17HG, and MIR22HG, displayed consistent responses to oxaliplatin treatment in the validation analysis. CONCLUSION: Certain lncRNAs were associated with oxaliplatin sensitivity and predicted the response to oxaliplatin treatment. The prognostic models established based on the key lncRNAs could predict the prognosis of patients given oxaliplatin-based chemotherapy.

17.
BMC Cancer ; 23(1): 773, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37596528

ABSTRACT

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in tumorigenesis, progression, and therapeutic response in many cancers. This study aimed to comprehensively investigate the role of TME in colorectal cancer (CRC) by generating a TMEscore based on gene expression. METHODS: The TME patterns of CRC datasets were investigated, and the TMEscores were calculated. An unsupervised clustering method was used to divide samples into clusters. The associations between TMEscores and clinical features, prognosis, immune score, gene mutations, and immune checkpoint inhibitors were analyzed. A TME signature was constructed using the TMEscore-related genes. The results were validated using external and clinical cohorts. RESULTS: The TME pattern landscape was for CRC was examined using 960 samples, and then the TMEscore pattern of CRC datasets was evaluated. Two TMEscore clusters were identified, and the high TMEscore cluster was associated with early-stage CRC and better prognosis in patients with CRC when compared with the low TMEscore clusters. The high TMEscore cluster indicated elevated tumor cell scores and tumor gene mutation burden, and decreased tumor purity, when compared with the low TMEscore cluster. Patients with high TMEscore were more likely to respond to immune checkpoint therapy than those with low TMEscore. A TME signature was constructed using the TMEscore-related genes superimposing the results of two machine learning methods (LASSO and XGBoost algorithms), and a TMEscore-related four-gene signature was established, which had a high predictive value for discriminating patients from different TMEscore clusters. The prognostic value of the TMEscore was validated in two independent cohorts, and the expression of TME signature genes was verified in four external cohorts and clinical samples. CONCLUSION: Our study provides a comprehensive description of TME characteristics in CRC and demonstrates that the TMEscore is a reliable prognostic biomarker and predictive indicator for patients with CRC undergoing immunotherapy.


Subject(s)
Colorectal Neoplasms , Tumor Microenvironment , Humans , Prognosis , Tumor Microenvironment/genetics , Immunotherapy , Algorithms , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy
18.
BMC Geriatr ; 23(1): 617, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37784045

ABSTRACT

BACKGROUND: Pre-traumatic frailty in geriatric trauma patients has caught attention from emergency medical workers and the assessment of it thus become one of the important aspects of risk management. Several tools are available to identify frailty, but limited tools have been validated for geriatric trauma patients in China to assess pre-traumatic frailty.The aim of this study is to translate the Trauma-Specific Frailty Index(TSFI) into Chinese, and to evaluate the reliability and validity of the translated version in geriatric trauma patients. METHODS: A cross-sectional study was conducted. The TSFI was translated with using the Brislin model, that included forward and backward translation. A total of 184 geriatric trauma patients were recruited by a convenience sampling between October and December 2020 in Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan. Using reliability or internal consistency tests assessed with Cronbach's alpha coefficient, split-half reliability and test-retest reliability. Content validity and construct validity analysis were both performed. Sensitivity, specificity and maximum Youden index(YI) were used to determine the optimal cut-off value. The screening performance was examined by Kappa value. RESULTS: The total study population included 184 subjects, of which 8 participants were excluded, resulting in a study sample size of 176 elderly trauma patients (the completion rate was 95.7%). The Chinese version of Trauma-Specific Frailty Index(C-TSFI) have 15 items with 5 dimensions. Cronbach's alpha coefficient of the C-TSFI was 0.861, Cronbach's alpha coefficient of dimensions ranged from 0.837 to 0.875, the split-half reliability of the C-TSFI were 0.894 and 0.880 respectively, test-retest reliability ranged from 0.692 to 0.862. The correlation coefficient between items and the C-TSFI ranged from 0.439 to 0.761. The content validity index for items (I-CVI) of the C-TSFI scale was 0.86~1.00, and the scale of content validity index (S-CVI) was 0.93. The area under curve (AUC) of the C-TSFI was 0.932 (95%CI 0.904-0.96, P < 0.05), the maximum YI was 0.725, the sensitivity was 80.2%, the specificity was 92.3%, and the critical value was 0.31. Kappa value was 0.682 (P < 0.05). CONCLUSIONS: The Chinese version of TSFI could be used as a general assessment tool in geriatric trauma patients, and both its reliability and validity have been demonstrated.


Subject(s)
Frailty , Humans , Aged , Frailty/diagnosis , Reproducibility of Results , Cross-Sectional Studies , Patients , Hospitals , China/epidemiology , Psychometrics/methods , Surveys and Questionnaires
19.
Chem Biodivers ; 20(10): e202300648, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37615232

ABSTRACT

Polysaccharides are rich in Panax notoginseng residue after extraction. This study aims to explore the structural characteristics of PNP-20, which is a homogeneous polysaccharide, separated from P. notoginseng residue by fractional precipitation and evaluate the anti-enteritis effect of PNP-20. The structure of PNP-20 was determined by spectroscopic analyses. A mouse model with enteritis induced by restraint stress (RS) and lipopolysaccharide (LPS) was used to evaluate the pharmacological effect of PNP-20. The results indicated that PNP-20 consisted of glucose (Glc), galactose (Gal), Mannose (Man) and Rhamnose (Rha). PNP-20 was composed of Glcp-(1→, →4)-α-Glcp-(1→, →4)-α-Galp-(1→, →4,6)-α-Glcp-(1→, →4)-Manp-(1→ and →3)-Rhap-(1→, and contained two backbone fragments of →4)-α-Glcp-(1→4)- α-Glcp-(1→ and →4)-α-Galp-(1→4)-α-Glcp-(1→. PNP-20 reduced intestinal injury and inflammatory cell infiltration in RS- and LPS-induced enteritis in mice. PNP-20 decreased the expression of intestinal tumor necrosis factor-α, NOD-like receptor family pyrin domain containing 3, and nuclear factor-κB and increased the expression of intestinal superoxide dismutase 2. In conclusion, PNP-20 may be a promising material basis of P. Notoginseng for the treatment of inflammatory bowel disease.

20.
J Craniofac Surg ; 34(2): 602-606, 2023.
Article in English | MEDLINE | ID: mdl-36731109

ABSTRACT

Children with cleft lip/palate are usually faced with upper airway problems after surgical repair. The severity of upper airway obstruction is more likely associated with the age and preoperative diagnosis of obstructive sleep apnea (OSA). This study aimed to investigate the severity of OSA in toddlers before palatoplasty from the perspective of polysomnography. In this retrospective cohort study, 97 children with unrepaired cleft palate and habitual prone sleeping were identified with a mean age of 1.6 years (SD 0.6) and divided into 2 age groups (1.5 year or younger and older than 1.5 year). Detailed information was collected including demographics, sleep parameters, and respiratory disturbances. Polysomnography results showed these children were at high risks of OSA with averagely moderate severity at night during their early childhood [apnea-hypopnea index 7.2±3.2 events/hour; obstructive apnea index (OAI) 6.5±2.8 events/hour]. Positional OAI was greatly lower in prone than that in laterals or in supine. Far more sleep time was spent in prone than in supine (42.9%±42.2% versus 8.5%±15.7%), which were consistent with parental reporting of prone sleeping habits. There were no significant differences found between the 2 age groups in respiratory disturbances such as apnea-hypopnea index, OAI, mean oxygen saturation, and nadir oxygen saturation ( P =0.097-0.988). Thus, prone sleeping with a history of snoring might be indicators for early screening for OSA in the cleft population. Adequate attention should be paid to their upper airway and, if available, overnight polysomnography should be performed to ascertain their potential respiratory problems before repair surgery.


Subject(s)
Cleft Lip , Cleft Palate , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Child, Preschool , Infant , Cleft Palate/surgery , Cleft Lip/complications , Retrospective Studies , Sleep
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