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1.
Nat Rev Cancer ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698126

ABSTRACT

In the past two decades, technological advances have brought unprecedented insights into the paediatric cancer genome revealing characteristics distinct from those of adult cancer. Originating from developing tissues, paediatric cancers generally have low mutation burden and are driven by variants that disrupt the transcriptional activity, chromatin state, non-coding cis-regulatory regions and other biological functions. Within each tumour, there are multiple populations of cells with varying states, and the lineages of some can be tracked to their fetal origins. Genome-wide genetic screening has identified vulnerabilities associated with both the cell of origin and transcription deregulation in paediatric cancer, which have become a valuable resource for designing new therapeutic approaches including those for small molecules, immunotherapy and targeted protein degradation. In this Review, we present recent findings on these facets of paediatric cancer from a pan-cancer perspective and provide an outlook on future investigations.

2.
Nat Commun ; 15(1): 3732, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702309

ABSTRACT

Immunotherapy with chimeric antigen receptor T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify cancer specific exon targets, here we analyze 1532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We find 2933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n = 148) or the alternatively spliced isoform (n = 9) level. Expression of selected alternatively spliced targets, including the EDB domain of fibronectin 1, and gene targets, such as COL11A1, are validated in pediatric patient derived xenograft tumors. We generate T cells expressing chimeric antigen receptors specific for the EDB domain or COL11A1 and demonstrate that these have antitumor activity. The full target list, explorable via an interactive web portal ( https://cseminer.stjude.org/ ), provides a rich resource for developing immunotherapy of pediatric solid and brain tumors using gene or AS targets with high expression specificity in cancer.


Subject(s)
Brain Neoplasms , Exons , Receptors, Chimeric Antigen , Humans , Brain Neoplasms/immunology , Brain Neoplasms/therapy , Brain Neoplasms/genetics , Animals , Exons/genetics , Child , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Mice , Immunotherapy/methods , Alternative Splicing , Fibronectins/genetics , Fibronectins/metabolism , Fibronectins/immunology , Xenograft Model Antitumor Assays , Gene Expression Regulation, Neoplastic , RNA-Seq , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Cell Line, Tumor , Immunotherapy, Adoptive/methods
3.
Res Sq ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38585847

ABSTRACT

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL(ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA-sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription (JUNB), and epigenetic regulators (TET1, KMT2B, KMT2A, KMT2C, KMT2E). Gene expression and methylation profiling consistently subclassified ALK+ ALCLs into two groups characterized by diferential ALK expression levels. The ALK-low group showed enrichment of pathways associated with immune response, cytokine signaling, and a hypermethylated predominant pattern compared to the ALK- high group, which had more frequent copy number changes, and was enriched with pathways associated with cell growth, proliferation, metabolic pathways, and. Taken together, these findings suggest that there is molecular heterogeneity within pediatric ALK+ALCL, predicting distinct biological mechanisms that may provide novel insights into disease pathogenesis and represent prognostic markers.

4.
Front Plant Sci ; 15: 1294895, 2024.
Article in English | MEDLINE | ID: mdl-38645388

ABSTRACT

Livestock presence impacts plant biodiversity (species richness) in grassland ecosystems, yet extent and direction of grazing impacts on biodiversity vary greatly across inter-annual periods. In this study, an 8-year (2014-2021) grazing gradient experiment with sheep was conducted in a semi-arid grassland to investigate the impact of grazing under different precipitation variability on biodiversity. The results suggest no direct impact of grazing on species richness in semi-arid Stipa grassland. However, increased grazing indirectly enhanced species richness by elevating community dominance (increasing the sheltering effect of Stipa grass). Importantly, intensified grazing also regulates excessive community biomass resulting from increased inter-annual wetness (SPEI), amplifying the positive influence of annual humidity index on species richness. Lastly, we emphasize that, in water-constrained grassland ecosystems, intra-annual precipitation variability (PCI) was the most crucial factor driving species richness. Therefore, the water-heat synchrony during the growing season may alleviate physiological constraints on plants, significantly enhancing species richness as a result of multifactorial interactions. Our study provides strong evidence for how to regulate grazing intensity to increase biodiversity under future variable climate patterns. We suggest adapting grazing intensity according to local climate variability to achieve grassland biodiversity conservation.

5.
Cancer Discov ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38593228

ABSTRACT

Childhood cancer survivorship studies generate comprehensive datasets comprising demographic, diagnosis, treatment, outcome, and genomic data from survivors. To broadly share this data, we created the St. Jude Survivorship Portal (https://survivorship.stjude.cloud), the first data portal for sharing, analyzing, and visualizing pediatric cancer survivorship data. Over 1,600 phenotypic variables and 400 million genetic variants from over 7,700 childhood cancer survivors can be explored on this free, open-access portal. Summary statistics of variables are computed on-the-fly and visualized through interactive and customizable charts. Survivor cohorts can be customized and/or divided into groups for comparative analysis. Users can also seamlessly perform cumulative incidence and regression analyses on the stored survivorship data. Using the portal, we explored the ototoxic effects of platinum-based chemotherapy, uncovered a novel association between mental health, age, and limb amputation, and discovered a novel haplotype in MAGI3 strongly associated with cardiomyopathy specifically in survivors of African ancestry.

7.
Cancer Lett ; 589: 216822, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38521200

ABSTRACT

Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP. We analyzed the transcriptomes of 56,225 unsorted single cells, revealing the heterogeneity of each cell type, and compared gene expression among tissues. Then we compared the gene expression with that of sporadic CRC. Furthermore, we analyzed specimens of 26 FAP patients and 40 sporadic CRC patients by immunohistochemistry. Immunosuppressiveness of myeloid cells, fibroblasts, and regulatory T cells was upregulated even in the early stages of carcinogenesis. CD8+ T cells became exhausted only in carcinoma, although the cytotoxicity of CD8+ T cells was gradually increased according to the carcinogenic step. When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP.


Subject(s)
Adenoma , Adenomatous Polyposis Coli , Colorectal Neoplasms , Humans , CD8-Positive T-Lymphocytes/pathology , Adenomatous Polyposis Coli/complications , Adenomatous Polyposis Coli/genetics , Adenomatous Polyposis Coli/pathology , Adenomatous Polyposis Coli Protein/genetics , Carcinogenesis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Tumor Microenvironment
8.
Talanta ; 272: 125838, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38430866

ABSTRACT

In this study, a novel integrated liposome-based microfluidic platform combined with a smartphone was designed for the rapid colorimetric detection of microRNA-21 (miRNA-21) in real samples. The flowing surface-functionalized liposomes were first captured by nucleic acid-functionalized Au nanoparticles in the microfluidic chip. In the presence of miRNA-21, the DNA strand modified on the surface of Au nanoparticles hybridized with the target to form double-stranded products and was cleaved by duplex-specific nuclease (DSN) enzyme, causing the liposomes to be re-released. Then, as the liposomes in the colorimetric module were lysed and the "cellular" contents were released, a step-by-step "glucose-glucose oxidase-3,3',5,5'-tetramethylbenzidine (TMB)" colorimetric reaction process catalyzed by the G-quadruplex/hemin was triggered. The grayscale values were recorded and recognized by the smartphone camera for miRNA-21 analysis. The advantages of the present strategy included the portability of smartphone-based colorimetric assay, the encapsulation and transport of reactants by liposomes and the low solvent usage of microfluidic chip. Under optimal conditions, this assay exhibited a wide linear range from 1 pM to 1 nM (r2 = 0.9981), and the limit of detection of miRNA-21 was as low as 0.27 pM. Moreover, the high specificity of this strategy allowed its successful application to the rapid analysis of miRNA-21 in real blood serum samples of people with type 2 diabetes.


Subject(s)
Biosensing Techniques , Diabetes Mellitus, Type 2 , Metal Nanoparticles , MicroRNAs , Humans , MicroRNAs/analysis , Liposomes , Colorimetry , Microfluidics , Gold , Limit of Detection
9.
Anal Chem ; 96(13): 5195-5204, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38520334

ABSTRACT

The detection of multiple single nucleotide polymorphisms (SNPs) of circulating tumor DNA (ctDNA) is still a great challenge. In this study, we designed enzyme-assisted nucleic acid strand displacement amplification combined with high-performance liquid chromatography (HPLC) for the simultaneous detection of three ctDNA SNPs. First, the trace ctDNA could be hybridized to the specially designed template strand, which initiated the strand displacement nucleic acid amplification process under the synergistic action of DNA polymerase and restriction endonuclease. Then, the targets would be replaced with G-quadruplex fluorescent probes with different tail lengths. Finally, the HPLC-fluorescence assay enabled the separation and quantification of multiple signals. Notably, this method can simultaneously detect both the wild type (WT) and mutant type (MT) of multiple ctDNA SNPs. Within a linear range of 0.1 fM-0.1 nM, the detection limits of BRAF V600E-WT, EGFR T790M-WT, and KRAS 134A-WT and BRAF V600E-MT, EGFR T790M-MT, and KRAS 134A-MT were 29, 31, and 11 aM and 22, 29, and 33 aM, respectively. By using this method, the mutation rates of multiple ctDNA SNPs in blood samples from patients with lung or breast cancer can be obtained in a simple way, providing a convenient and highly sensitive analytical assay for the early screening and monitoring of lung cancer.


Subject(s)
Circulating Tumor DNA , Lung Neoplasms , Humans , Circulating Tumor DNA/genetics , Mutation , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins B-raf/genetics , ErbB Receptors/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Protein Kinase Inhibitors , Chromatography, Liquid
10.
J Natl Cancer Inst ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38445706

ABSTRACT

BACKGROUND: Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related-quality-of-life (HRQOL). However, associations between DNA methylation (DNAm)-based aging biomarkers and HRQOL have not been evaluated. METHODS: DNAm was generated with Infinium EPIC BeadChip on blood-derived DNA (median[range] for age at blood draw = 34.5[18.5-66.6] years) and HRQOL was assessed with age at survey (32.3[18.4-64.5] years) from 2,206 survivors in the St Jude Lifetime Cohort. DNAm-based aging biomarkers, including epigenetic age using multiple clocks (eg, GrimAge) and others (eg, DNAmB2M beta-2-microglobulin; DNAmADM: adrenomedullin), were derived from the DNAm Age Calculator (https://dnamage.genetics.ucla.edu). HRQOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey to capture eight domains, and physical and mental component summaries (PCS and MCS). General linear models evaluated associations between HRQOL and epigenetic age acceleration (EAA, eg, EAA_GrimAge) or other age-adjusted DNAm-based biomarkers (eg, ageadj_DNAmB2M) after adjusting for age at blood draw, sex, cancer treatments, and DNAm-based surrogate for smoking pack-years. All P values were 2-sided. RESULTS: Worse HRQOL was associated with greater EAA_GrimAge (PCS ß[95%CI]=-0.18[-0.251,-0.11] years, P = 1.85 × 10-5; and four individual HRQOL domains), followed by ageadj_DNAmB2M (PCS: -0.08[-0.124,-0.037], P = .003; and three individual HRQOL domains), and ageadj_DNAmADM (PCS: -0.082[-0.125,-0.039], P = .002; and two HRQOL domains). EAA_Hannum (Hannum clock) was not associated with any HRQOL. CONCLUSIONS: Overall and domain-specific measures of HRQOL are associated with DNAm measures of biological aging. Future longitudinal studies should test biological aging as a potential mechanism underlying the association between poor HRQOL and increased risk of clinically assessed adverse health outcomes.

11.
Risk Manag Healthc Policy ; 17: 423-433, 2024.
Article in English | MEDLINE | ID: mdl-38481393

ABSTRACT

Background: Medical personnel contact with the patient closely, and their knowledge of vascular catheter-associated infections (VCAIs) is closely related to the prevention of VCAIs. Researchers mainly pay attention to the VCAIs knowledge of doctors and nurses but rarely pay attention to the nursing students in the hospital internship stage. Purpose: To investigate the current situation of knowledge of intern-nursing students in VCAIs, and analyze its influencing factors. Patients and Methods: 843 intern-nursing students were selected from 10 hospitals in five regions of eastern, western, southern, northern, and central China from June 26 to July 31, 2023, using a two-stage random sampling method. A self-designed questionnaire with good reliability and validity was used to investigate their knowledge of VCAIs, and t-test, multiple linear regression analysis, and Welch t-test were used to analyze the collected data by using SPSS Statistics 26.0 (IBM Corp., Armonk, NY). Results: Intern nursing students' mean score of VCAIs knowledge was 48.66 (SD=15.77), with a score below 60 (unqualified) accounting for 75.4%, a score of 60-79 (qualified) accounting for 19.7%, a score of 80-89 (good) accounting for 3.6%, and a score of above 90 accounting for 1.3%. Students who attended VCAIs training three or more times had higher scores than those who did not attend training (B: 4.706, p=0.001), knowledge scores of students with a bachelor's degree or above were higher than those with junior college degree or below (B: 8.479, p<0.001), students who interned in tertiary hospitals had higher scores than those practicing in secondary hospitals (B:12.381, p<0.001) and scores of students in hospital training were significantly higher than study independently (B:4.116, p=0.007). Conclusion: Intern-nursing students have a relatively low level of knowledge about VCAIs. It is recommended to strengthen clinical systematic and standardized training, improve the knowledge mastery level of intern-nursing students, and enhance their ability to handle VCAIs.

12.
Urology ; 185: 49-53, 2024 03.
Article in English | MEDLINE | ID: mdl-38309594

ABSTRACT

Renal agenesis represents the most severe form of congenital anomalies of the kidney and urinary tract. Bilateral renal agenesis is almost invariably fatal at birth and has high genetic heterogeneity. Here we report on a Chinese family with two pregnancies affected by a prenatal form of bilateral renal agenesis. Trio-WES was conducted to explore the underlying genetic cause and identified a novel nonsense variant (c .2621G>A: p. Trp874Ter) in the GREB1L gene. Based on previous research, pathogenic mutations in GREB1L can cause renal hypodysplasia/aplasia-3 (RHDA3) with autosomal dominant inheritance. Sanger sequencing performed on the family members revealed that the variant was vertically transmitted from the maternal grandfather through the unaffected mother to the two affected fetuses, fully demonstrating the incomplete dominance of the disease. Our study extends the mutational spectrum associated with RHDA3 and contributes to a more general understanding for the complex genetic inheritance of GREB1L.


Subject(s)
Congenital Abnormalities , Kidney Diseases/congenital , Kidney/abnormalities , Urogenital Abnormalities , Infant, Newborn , Pregnancy , Female , Humans , Penetrance , China , Pedigree
13.
Cell Death Discov ; 10(1): 101, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38413579

ABSTRACT

Pancreatic ductal adenocarcinoma (PDA) mortality is primarily attributed to metastasis and chemotherapy resistance. In this research, the long non-coding RNA MACC1-AS1 was studied, playing a significant role in regulating lipid oxidation processes. This regulation could further lead to the inhibition of ferroptosis induced by chemotherapeutic drugs, making it a contributing factor to gemcitabine resistance in PDA. In both gemcitabine-resistant PDA patients and mouse models, the elevated expression level of MACC1-AS1 in the tumors was noted. Additionally, overexpression of MACC1-AS1 in pancreatic cancer cells was found to enhance tolerance to gemcitabine and suppress ferroptosis. Proteomic analysis of drug-resistant pancreatic cells revealed that overexpressed MACC1-AS1 inhibited the ubiquitination degradation of residues in the protein kinase STK33 by MDM4. Furthermore, its accumulation in the cytoplasm activated STK33, further activating the ferroptosis-suppressing proteins GPX4, thereby counteracting gemcitabine-induced cellular oxidative damage. These findings suggested that the long non-coding RNA MACC1-AS1 could play a significant role in the ability of pancreatic cancer cells to evade iron-mediated ferroptosis induced by gemcitabine. This discovery holds promise for developing clinical therapeutic strategies to combat chemotherapy resistance in pancreatic cancer.

14.
Res Sq ; 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38260279

ABSTRACT

Immunotherapy with CAR T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons (CSE) present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify CSE targets, we analyzed 1,532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We found 2,933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n=148) or the alternatively spliced (AS) isoform (n=9) level. Expression of selected AS targets, including the EDB domain of FN1 (EDB), and gene targets, such as COL11A1, were validated in pediatric PDX tumors. We generated CAR T cells specific to EDB or COL11A1 and demonstrated that COL11A1-CAR T-cells have potent antitumor activity. The full target list, explorable via an interactive web portal (https://cseminer.stjude.org/), provides a rich resource for developing immunotherapy of pediatric solid and brain tumors using gene or AS targets with high expression specificity in cancer.

15.
Adv Mater ; : e2312275, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38277492

ABSTRACT

Patients diagnosed with inflammatory bowel disease (IBD) exhibit a notable prevalence of psychiatric disorders, such as anxiety and depression. Nevertheless, the etiology of psychiatric disorders associated with IBD remains uncertain, and an efficacious treatment approach has yet to be established. Herein, an oral hydrogel strategy (SP@Rh-gel) is proposed for co-delivery of Spirulina platensis and rhein to treat IBD and IBD-associated anxiety and depression by modulating the microbiota-gut-brain axis. SP@Rh-gel improves the solubility, release characteristics and intestinal retention capacity of the drug, leading to a significant improvement in the oral therapeutic efficacy. Oral administration of SP@Rh-gel can reduce intestinal inflammation and rebalance the disrupted intestinal microbial community. Furthermore, SP@Rh-gel maintains intestinal barrier integrity and reduces the release of pro-inflammatory factors and their entry into the hippocampus through the blood-brain barrier, thereby inhibiting neuroinflammation and maintaining neuroplasticity. SP@Rh-gel significantly alleviates the colitis symptoms, as well as anxiety- and depression-like behaviors, in a chronic colitis mouse model. This study demonstrates the significant involvement of the microbiota-gut-brain axis in the development of IBD with psychiatric disorders and proposes a safe, simple, and highly efficient therapeutic approach for managing IBD and comorbid psychiatric disorders.

16.
Int J Nurs Stud ; 151: 104676, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38241817

ABSTRACT

BACKGROUND: Central venous catheters are widely used in clinical practice, and the incidence of central venous catheter occlusion is between 25 % and 38 %. The turbulence caused by the pulsatile flushing technique is harmful to the vascular endothelium and may lead to phlebitis. The low-speed continuous infusion catheter technique is a new type of continuous infusion that ensures that the catheter is always in a keep-vein-open state by continuous low-speed flushing; hence, avoiding the problem of catheter occlusion. OBJECTIVE: To investigate the effectiveness of the low-speed continuous infusion catheter technique and the routine care of double-lumen central venous catheters. DESIGN: This was a prospective, randomized, controlled, open-label trial. SETTING: Patients were recruited from 14 medical institutions in China between February and June 2023. PARTICIPANTS: In total, 251 patients were recruited, with 125 in the intervention group and 126 in the control group. METHODS: Patients who used double-lumen central venous catheters for infusion treatment were selected, and those who met the sampling criteria were randomly divided into intervention and control groups using the random envelope method. The intervention group used the low-speed continuous infusion catheter technique to maintain catheter patency, whereas the control group used routine care with a trial period of 7 days. The primary outcome was the occlusion rate. The secondary outcomes included nursing satisfaction and complication rates of the two groups. RESULTS: After 7 days, the rate of catheter occlusion was 28.0 % (35/125, 95 % confidence interval (CI):0.203, 0.367) in the intervention group and 53.97 % (68/126, 95 % CI: 0.449-0.629) in the control group, with a statistically significant difference (χ2 = 17.488, p < 0.001); at 3 days of intervention, the rate of catheter blockage was 8.0 % (10/125, 95 % CI: 0.039-0.142) in the intervention group and 23.8 % (30/126, 0.167-0.322) in the control group, with a statistically significant difference (χ2 = 11.707, p < 0.001). Nurse satisfaction was significantly higher in the intervention group (115/125, 92.0 %, 95 % CI: 0.858-0.961) than in the control group (104/126, 82.54 %, 95 % CI: 0.748-0.887) (χ2 = 5.049, p = 0.025). There were no statistically significant complication rates in either group (p = 0.622). CONCLUSION: The low-speed continuous infusion catheter technique helps maintain catheter patency, improves nurse satisfaction, and provides a high level of safety. REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200064007, www.chictr.org.cn). The first recruitment was conducted in February. https://www.chictr.org.cn/showproj.html?proj=177311.


Subject(s)
Catheterization, Central Venous , Central Venous Catheters , Phlebitis , Humans , Prospective Studies , Catheterization, Central Venous/adverse effects , Incidence
17.
Anal Chem ; 96(3): 1054-1063, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38190445

ABSTRACT

In this work, an integrated strategy with excellent accuracy and high throughput is proposed for the precise indication of single nucleotide polymorphism (SNP) in nonsmall cell lung cancer diseases. Two types of point mutations (L858R and T790M) and the corresponding wild types could be identified together in a single high-performance liquid chromatographic run. Signal amplification was achieved through a series of enzyme ligation, primer extension, and enzyme cleavage strategies, and a large number of DNA probes with different fluorescence signals were finally generated. The factors affecting the spatiotemporal separation efficiency of four DNA probes were systematically investigated. The limits of detection of wild types (WTs) or mutant types (MTs) abbreviated as L858R-MT, L858R-WT, T790M-MT, and T790M-WT were 26, 24, 19, and 22 aM, respectively. In addition, the levels of mutant types and wild types in the serum of 40 nonsmall cell lung cancer patients at different stages were detected using the method, and the correlation between the mutation ratios and cancer stages was preliminarily verified. The proposed highly selective and sensitive method may serve as an alternative approach for early diagnosis and staging of nonsmall cell lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , ErbB Receptors/metabolism , Polymorphism, Single Nucleotide , Mutation , Protein Kinase Inhibitors , Chromatography, Liquid , DNA Probes
18.
J Med Chem ; 67(2): 971-987, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38217860

ABSTRACT

Pain severely affects the physical and mental health of patients. The need to develop nonopioid analgesic drugs to meet medical demands is urgent. In this study, we designed a truncated analogue of αO-conotoxin, named GeX-2, based on disulfide-bond deletion and sequence truncation. GeX-2 retained the potency of its parent peptide at the human α9α10 nAChR and exhibited potent inhibitory activity at CaV2.2 channels via activation of the GABAB receptor (GABABR). Importantly, GeX-2 significantly alleviated pain in the rat model of chronic constriction injury. The dual inhibition of GeX-2 at both α9α10 nAChRs and CaV2.2 channels is speculated to synergistically mediate the potent analgesic effects. Results from site-directed mutagenesis assay and computational modeling suggest that GeX-2 preferentially interacts with the α10(+)α10(-) binding site of α9α10 nAChR and favorably binds to the top region of the GABABR2 subunit. The study offers vital insights into the molecular action mechanism of GeX-2, demonstrating its potential as a novel nonopioid analgesic.


Subject(s)
Analgesics, Non-Narcotic , Conotoxins , Receptors, Nicotinic , Rats , Humans , Animals , Conotoxins/chemistry , Receptors, GABA-B/metabolism , Analgesics/pharmacology , Analgesics/therapeutic use , Analgesics/chemistry , Pain/drug therapy , Receptors, Nicotinic/metabolism , gamma-Aminobutyric Acid , Nicotinic Antagonists/pharmacology , Nicotinic Antagonists/chemistry
19.
Sensors (Basel) ; 24(2)2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38257436

ABSTRACT

Laser scanning 3D imaging technology, because it can obtain accurate three-dimensional surface data, has been widely used in the search for wrecks and rescue operations, underwater resource development, and other fields. At present, the conventional underwater spinning laser scanning imaging system maintains a relatively fixed light window. However, in low-light situations underwater, the rotation of the scanning device causes some degree of water fluctuation, which warps the light strip data that the system sensor receives about the object's surface. To solve this problem, this research studies an underwater 3D scanning and imaging system that makes use of a fixed light window and a spinning laser (FWLS). A refraction error compensation algorithm is investigated that is based on the fundamentals of linear laser scanning imaging, and a dynamic refraction mathematical model is established based on the motion of the imaging device. The results of the experiment on error analysis in an optimal underwater environment indicate that the error in reconstructing the radius is decreased by 60% (from 2.5 mm to around 1 mm) when compensating for the measurement data of a standard sphere with a radius of 20 mm. Moreover, the compensated point cloud data exhibit a higher degree of correspondence with the model of the standard spherical point cloud. Furthermore, we examine the impact of physical noise, measurement distance, and partial occlusion of the object on the imaging system inside an authentic underwater setting. This study is a good starting point for looking at the refractive error of an underwater laser scanning imaging system. It also provides to us some ideas for future research on the refractive error of other scanning imaging methods.

20.
Mater Horiz ; 11(4): 1098-1107, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38112000

ABSTRACT

Vanadium dioxide (VO2) has received widespread attention for application in energy-efficient smart windows because of its distinct thermochromic property in the near-infrared region during the reversible metal-insulator phase transition. In this study, lepidocrocite VOOH ultrafine nanoparticles (NPs) with a diameter less than 30 nm were prepared by a mild and efficient hydrothermal method, and the Kirkendall effect played a vital role in the growth of the VOOH NPs. It was found that VOOH could be transformed into VO2via a subsequent annealing treatment during which the size and morphology of VOOH are well preserved even though the annealing temperature is up to 500 °C. The ultrafine VO2 NPs are crucial for achieving excellent nanothermochromic performance with a luminous transmittance (Tlum) up to 56.45% and solar modulation ability (ΔTsol) up to 14.95%. The environmental durability is well improved by coating VO2 NPs with an SiO2 shell as confirmed via progressive oxidation and acid corrosion experiments. Meanwhile, the Tlum of the VO2@SiO2 film is further increased from 56.45% to 62.29% while the ΔTsol remained unchanged. This integrated thermochromic performance presents great potential for the development of VO2-based smart windows.

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