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1.
BMC Genomics ; 25(1): 658, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956486

ABSTRACT

BACKGROUND: The cashmere goat industry is one of the main pillars of animal husbandry in Inner Mongolia Autonomous Region, and plays an irreplaceable role in local economic development. With the change in feeding methods and environment, the cashmere produced by Inner Mongolia cashmere goats shows a tendency of coarser, and the cashmere yield can not meet the consumption demand of people. However, the genetic basis behind these changes is not fully understood. We measured cashmere traits, including cashmere yield (CY), cashmere diameter (CD), cashmere thickness (CT), and fleece length (FL) traits for four consecutive years, and utilized Genome-wide association study of four cashmere traits in Inner Mongolia cashmere goats was carried out using new genomics tools to infer genomic regions and functional loci associated with cashmere traits and to construct haplotypes that significantly affect cashmere traits. RESULTS: We estimated the genetic parameters of cashmere traits in Inner Mongolia cashmere goats. The heritability of cashmere yield, cashmere diameter, and fleece length traits of Inner Mongolia cashmere goats were 0.229, 0.359, and 0.250, which belonged to the medium heritability traits (0.2 ~ 0.4). The cashmere thickness trait has a low heritability of 0.053. We detected 151 genome-wide significantly associated SNPs with four cashmere traits on different chromosomes, which were very close to the chromosomes of 392 genes (located within the gene or within ± 500 kb). Notch3, BMPR1B, and CCNA2 have direct functional associations with fibroblasts and follicle stem cells, which play important roles in hair follicle growth and development. Based on GO functional annotation and KEGG enrichment analysis, potential candidate genes were associated with pathways of hair follicle genesis and development (Notch, P13K-Akt, TGF-beta, Cell cycle, Wnt, MAPK). We calculated the effective allele number of the Inner Mongolia cashmere goat population to be 1.109-1.998, the dominant genotypes of most SNPs were wild-type, the polymorphic information content of 57 SNPs were low polymorphism (0 < PIC < 0.25), and the polymorphic information content of 79 SNPs were moderate polymorphism (0.25 < PIC < 0.50). We analyzed the association of SNPs with phenotypes and found that the homozygous mutant type of SNP1 and SNP3 was associated with the highest cashmere yield, the heterozygous mutant type of SNP30 was associated with the lowest cashmere thickness, the wild type of SNP76, SNP77, SNP78, SNP80, and SNP81 was associated with the highest cashmere thickness, and the wild type type of SNP137 was associated with the highest fleece length. 21 haplotype blocks and 68 haplotype combinations were constructed. Haplotypes A2A2, B2B2, C2C2, and D4D4 were associated with increased cashmere yield, haplotypes E2E2, F1F1, G5G5, and G1G5 were associated with decreased cashmere fineness, haplotypes H2H2 was associated with increased cashmere thickness, haplotypes I1I1, I1I2, J1J4, L5L3, N3N2, N3N3, O2O1, P2P2, and Q3Q3 were associated with increased cashmere length. We verified the polymorphism of 8 SNPs by KASP, and found that chr7_g.102631194A > G, chr10_g.82715068 T > C, chr1_g.124483769C > T, chr24_g.12811352C > T, chr6_g.114111249A > G, and chr6_g.115606026 T > C were significantly genotyped in verified populations (P < 0.05). CONCLUSIONS: In conclusion, the genetic effect of single SNP on phenotypes is small, and SNPs are more inclined to be inherited as a whole. By constructing haplotypes from SNPs that are significantly associated with cashmere traits, it will help to reveal the complex and potential causal variations in cashmere traits of Inner Mongolia cashmere goats. This will be a valuable resource for genomics and breeding of the cashmere goat.


Subject(s)
Genome-Wide Association Study , Goats , Haplotypes , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Animals , Goats/genetics , Goats/growth & development , Phenotype , China , Quantitative Trait, Heritable
2.
Pathol Res Pract ; 260: 155449, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38981345

ABSTRACT

Parathyroid carcinoma(PC) is an extremely rare malignant tumor of the parathyroid glands. The lung is the most common target organ for PC distant metastases. In this study, twelve patients diagnosed with PC with lung metastases were enrolled in the study. Hematoxylin and Eosin(H&E) stained, immunohistochemical stained and next-generation sequencing (NGS) of a 425-gene panel were performed on tumor tissue samples. At the same time, we also evaluated its histopathologic characteristics. The results indicate that the microscopic examination of metastatic lesions reveals the same structure and characteristics as PC; the tumor was composed of relatively uniform cells organized in nests and separated by thin fibrous bands and abundant blood vessels. Immunohistochemical evaluation of Ki67, CyclinD1, PTH, SYN, CgA, and CD56 was useful in diagnosing PC with lung metastases. The most frequently genetic alterations were mutations of CDC73 and copy number variation (CNV) of MCL1, with a mutation rate of 25 %. In addition, the mutations of CDC73, ATM, TP53, ALK, ERBB2, MAP3K4, TSC1, CCND1 and CNV of CDK4, MCL1, SMARCB1 overlap between metastatic lesions and primary lesions. In conclusions, PC is a rare endocrine malignant tumor that is very difficult to diagnose preoperatively and prone to clinical recurrence or distant metastasis. Genetic mutations, presentation and histological characteristic were the basis for diagnosing PC with lung metastases.

3.
BMC Genomics ; 25(1): 698, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014331

ABSTRACT

BACKGROUND: Inner Mongolia cashmere goat (IMCG), renowned for its superior cashmere quality, is a Chinese indigenous goat breed that has been developed through natural and artificial selection over a long period. However, recently, the genetic resources of IMCGs have been significantly threatened by the introduction of cosmopolitan goat breeds and the absence of adequate breed protection systems. RESULTS: In order to assess the conservation effectiveness of IMCGs and efficiently preserve and utilize the purebred germplasm resources, this study analyzed the genetic diversity, kinship, family structure, and inbreeding of IMCGs utilizing resequencing data from 225 randomly selected individuals analyzed using the Plink (v.1.90), GCTA (v.1.94.1), and R (v.4.2.1) software. A total of 12,700,178 high-quality SNPs were selected through quality control from 34,248,064 SNP sites obtained from 225 individuals. The average minor allele frequency (MAF), polymorphic information content (PIC), and Shannon information index (SHI) were 0.253, 0.284, and 0.530, respectively. The average observed heterozygosity (Ho) and the average expected heterozygosity (He) were 0.355 and 0.351, respectively. The analysis of the identity by state distance matrix and genomic relationship matrix has shown that most individuals' genetic distance and genetic relationship are far away, and the inbreeding coefficient is low. The family structure analysis identified 10 families among the 23 rams. A total of 14,109 runs of homozygosity (ROH) were identified in the 225 individuals, with an average ROH length of 1014.547 kb. The average inbreeding coefficient, calculated from ROH, was 0.026 for the overall population and 0.027 specifically among the 23 rams, indicating a low level of inbreeding within the conserved population. CONCLUSIONS: The IMCGs exhibited moderate polymorphism and a low level of kinship with inbreeding occurring among a limited number of individuals. Simultaneously, it is necessary to prevent the loss of bloodline to guarantee the perpetuation of the IMCGs' germplasm resources.


Subject(s)
Genetic Variation , Goats , Polymorphism, Single Nucleotide , Animals , Goats/genetics , Whole Genome Sequencing , Gene Frequency , Inbreeding , China
4.
Front Microbiol ; 15: 1331656, 2024.
Article in English | MEDLINE | ID: mdl-38841074

ABSTRACT

Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), is one of the urgent clinical problems and public health challenges. Culture-based phenotypic drug susceptibility testing (pDST) is time-consuming, and PCR-based assays are limited to hotspot mutations. In this study, we developed and validated a convenient and efficient approach based on high-throughput nanopore sequencing technology combined with multiplex PCR, namely nanopore targeted sequencing (NTS), to simultaneously sequence 18 genes associated with antibiotic resistance in Mycobacterium tuberculosis (MTB). The analytical performance of NTS was evaluated, and 99 clinical samples were collected to assess its clinical performance. The NTS results showed that MTB and its drug resistance were successfully identified in approximately 7.5 h. Furthermore, compared to the pDST and Xpert MTB/RIF assays, NTS provided much more drug resistance information, covering 14 anti-TB drugs, and it identified 20 clinical cases of drug-resistant MTB. The mutations underlying these drug-resistant cases were all verified using Sanger sequencing. Our approach for this TB drug resistance assay offers several advantages, including being culture-free, efficient, high-throughput, and highly accurate, which would be very helpful for clinical patient management and TB infection control.

5.
Front Public Health ; 12: 1392224, 2024.
Article in English | MEDLINE | ID: mdl-38939568

ABSTRACT

Aim: This study aims to assess the extent of social alienation in patients undergoing peritoneal dialysis and examine how personal mastery and perceived social support mediate the association between emotional intelligence and social alienation in this patient population. Methods: This study adopts a cross-sectional survey design. A total of 192 patients were recruited from a tertiary hospital located in Henan Province, China, using a convenience sampling method. We have developed a structural equation model to investigate the mediating influence of personal mastery and perceived social support on the emotional intelligence and social alienation of patients undergoing Peritoneal dialysis. Results: Peritoneal patients exhibited an social alienation score of 42.01 ± 3.15. Elevated EI levels (coefficient = -0.616, p < 0.001) were significantly correlated with reduced social alienation. The mediation model demonstrated that personal mastery and perceived social support fully mediated the impact of emotional intelligence on social alienation. Conclusion: The social alienation of peritoneal dialysis patients is serious, and healthcare professionals should pay attention to patients' social alienation, improve patients' emotional intelligence through relevant interventions, increase personal mastery and perceived social support, and finally reduce social alienation.


Subject(s)
Emotional Intelligence , Peritoneal Dialysis , Social Support , Humans , Male , Female , Peritoneal Dialysis/psychology , Middle Aged , Cross-Sectional Studies , China , Adult , Surveys and Questionnaires , Aged
6.
Article in English | MEDLINE | ID: mdl-38862354

ABSTRACT

BACKGROUND AND AIMS: To investigate causal relationships of lung function with risks microvascular diseases among participants with diabetes, type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), respectively, in prospective and Mendelian randomization (MR) study. METHODS AND RESULTS: 14,617 participants with diabetes and without microvascular diseases at baseline from the UK Biobank were included in the prospective analysis. Of these, 13,421 had T2DM and 1196 had T1DM. The linear MR analyses were conducted in the UK Biobank with 6838 cases of microvascular diseases and 10,755 controls. Lung function measurements included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The study outcome was microvascular diseases, a composite outcome including chronic kidney diseases, retinopathy and peripheral neuropathy. During a median follow-up of 12.1 years, 2668 new-onset microvascular diseases were recorded. FVC (%predicted) was inversely associated with the risk of new-onset microvascular diseases in participants with diabetes (Per SD increment, adjusted HR = 0.86; 95%CI:0.83-0.89), T2DM (Per SD increment, adjusted HR = 0.86; 95%CI:0.82-0.90) and T1DM (Per SD increment, adjusted HR = 0.87; 95%CI: 0.79-0.97), respectively. Similar results were found for FEV1 (%predicted). In MR analyses, genetically predicted FVC (adjusted RR = 0.55, 95%CI:0.39-0.77) and FEV1 (adjusted RR = 0.48, 95%CI:0.28-0.83) were both inversely associated with microvascular diseases in participants with T1DM. No significant association was found in those with T2DM. Similar findings were found for each component of microvascular diseases. CONCLUSION: There was a causal inverse association between lung function and risks of microvascular diseases in participants with T1DM, but not in those with T2DM.

7.
Ther Adv Med Oncol ; 16: 17588359241260985, 2024.
Article in English | MEDLINE | ID: mdl-38882443

ABSTRACT

Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis. Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors. Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study. Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 109/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 109/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles. Results: Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, n = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) versus 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); p value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) versus 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) versus 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo. Conclusion: Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors. Trial registration: ClinicalTrials.gov identifier: NCT03976882.

8.
Mol Divers ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900333

ABSTRACT

Through the approach of molecular hybridization, this study rationally designed and synthesized new trifluoromethyl-1,3,4-oxadiazole amide derivatives, denoted as 1a-1n. The findings reveal that these novel molecules exhibit potent inhibitory effects against various bacterial strains. Thereinto, compounds 1c, 1d, 1i, 1j and 1n, demonstrate relatively superior antimicrobial performance against B. cereus FM314, with a minimum inhibitory concentration (MIC) of 0.03907 µg/mL. Molecular docking analysis suggests the potential importance of the Ser57 and Thr125 amino acid residues (PDB ID: 4EI9) in contributing to the inhibitory activity against B. cereus. The consistency of these results was further corroborated through subsequent molecular dynamics simulations and MMPBSA validations. The insights gained from this study serve to facilitate the rational design and efficient development of novel eco-friendly antimicrobial inhibitors based on the trifluoromethyl-1,3,4-oxadiazole amide scaffold.

9.
Chemistry ; : e202401589, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872250

ABSTRACT

Chemotherapy is one of the most employed strategies in clinical treatment of cancer. However, reducing medication adverse effects and improving the biological activity remains a significant issue for chemotherapy. We developed a pH and Ca2+-responsive pillar[5]arene-based supramolecular nanodrug delivery system (NDDS) WP5⊃EV@DOX to address the aforementioned challenges. The formation of this NDDS began with the spontaneous formation of supramolecular nanodrug carrier WP5⊃EV in water from PEG-modified pillar[5]arene and the bipyridilium salt derivative EV through simple host-guest interaction. Then the antitumor drug doxorubicin DOX was efficiently loaded with a high encapsulation rate of 84.6%. Cytotoxicity results indicated that the constructed nanoplatform not only reduced DOX toxicity and side effects on normal cell (293T), but also significantly enhanced the antitumor activity on cancer cell (HepG2). Moreover, in vivo experiments showed that WP5⊃EV@DOX had a longer half-life and higher bioavailability in the blood of mice compared to the nake drug DOX, with increases to 212% and 179%, respectively. Therefore, WP5⊃EV@DOX has great potential in tumor therapy and provides a new idea for host-guest drug delivery system.

10.
World J Clin Cases ; 12(17): 3235-3242, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38898830

ABSTRACT

BACKGROUND: This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion (UBE-LIF), utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment, and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw placement. The advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies, and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients, and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for reference. CASE SUMMARY: A 44-year-old patient presented to our hospital. Combining various clinical data, we diagnosed the patient with lumbar disc herniation with radiculopathy, lumbar spondylolisthesis, and lumbar spinal stenosis. We developed a surgical plan of "UBE decompression + UBE-LIF + orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation". The results were satisfactory. CONCLUSION: We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good results. Therefore, the technique is worthy of clinical promotion.

11.
J Genet Genomics ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38723744

ABSTRACT

Drought is a natural disaster that has a profound impact on global agricultural production, significantly reduces crop yields and thereby poses a severe threat to worldwide food security. Addressing the challenge of effectively improving crop drought resistance (DR) to mitigate yield loss under drought conditions is a global issue. An optimal root system architecture (RSA) plays a pivotal role in enhancing crops' capacity to efficiently uptake water and nutrients, which consequently strengthens their resilience against environmental stresses. In this review, we discuss the compositions and roles of crop RSA and summarize the most recent developments in augmenting drought tolerance in crops by manipulating RSA-related genes. Based on current research, we propose the potential optimal RSA configuration that could be helpful in enhancing crop DR. Lastly, we discussed the existing challenges and future directions for breeding crops with enhanced DR capabilities through genetic improvements targeting RSA.

13.
Environ Manage ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38713413

ABSTRACT

Scientific assessment of urban ecological security (ES) is an important prerequisite to realize regional sustainable development. Previous studies lack the consideration of quality and poor systematic correlation, which could not reflect the internal dynamic relationship. On the basis of considering the time lag, this study divided the research process into the natural operation stage and the management feedback stage based on the driving forces, pressures, state, impacts, responses, management (DPSIRM) framework model and DEA theory, so as to effectively overcome the above shortcomings. Finally, we analyzed the spatio-temporal characteristics and influencing factors of the ES level of 108 cities in the Yangtze River Economic Belt (YREB) during 2005-2019. The results showed that: (a) both two stages showed a slow and fluctuating upward trend in time series, and the level of urban ES in the management feedback stage was significantly higher than that in the natural operation stage; (b) with the passage of time, the spatial distribution of ES in the natural operation stage gradually developed towards the middle and downstream of the YREB, while the management feedback stage mainly evolved from the midstream to the edge area; (c) the level of urban ES presented a different degree of spatial agglomeration phenomenon, and showed an increasing trend over time; and (d) the key influencing factors gradually changed from pressure to response during 2005-2019. This research aims to provide an innovative perspective for the measurement of urban ES, and provide scientific reference for improving urban ecological sustainable development.

14.
Thromb Haemost ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38729191

ABSTRACT

OBJECTIVE: The association between tea consumption and venous thromboembolism (VTE) remains unknown. We aimed to evaluate the association between tea consumption with different additives (milk and/or sweeteners) and incident VTE, and the modifying effects of genetic variation in caffeine metabolism on the association. METHODS: A total of 190,189 participants with complete dietary information and free of VTE at baseline in the UK Biobank were included. The primary outcome was incident VTE, including incident deep vein thrombosis and pulmonary embolism. RESULTS: During a median follow-up of 12.1 years, 4,485 (2.4%) participants developed incident VTE. Compared with non-tea drinkers, tea drinkers who added neither milk nor sweeteners (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.76-0.94), only milk (HR: 0.86; 95% CI: 0.80-0.93), and both milk and sweeteners to their tea (HR: 0.90; 95% CI: 0.81-0.99) had a lower risk of VTE, while those who added only sweeteners to their tea did not (HR: 0.94; 95% CI: 0.75-1.17). Moreover, there was an L-shaped relationship between tea consumption and incident VTE among tea drinkers who added neither milk nor sweeteners, only milk, and both milk and sweeteners to their tea, respectively. However, a nonsignificant association was found among tea drinkers who added only sweeteners to their tea. Genetic variation in caffeine metabolism did not significantly modify the association (p-interaction = 0.659). CONCLUSION: Drinking unsweetened tea, with or without added milk, was associated with a lower risk of VTE. However, there was no significant association between drinking tea with sweeteners and incident VTE.

15.
Sci Rep ; 14(1): 10339, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710719

ABSTRACT

Reservoir temperature estimation is crucial for geothermal studies, but traditional methods are complex and uncertain. To address this, we collected 83 sets of water chemistry and reservoir temperature data and applied four machine learning algorithms. These models considered various input factors and underwent data preprocessing steps like null value imputation, normalization, and Pearson coefficient calculation. Cross-validation addressed data volume issues, and performance metrics were used for model evaluation. The results revealed that our machine learning models outperformed traditional fluid geothermometers. All machine learning models surpassed traditional methods. The XGBoost model, based on the F-3 combination, demonstrated the best prediction accuracy with an R2 of 0.9732, while the Bayesian ridge regression model using the F-4 combination had the lowest performance with an R2 of 0.8302. This study highlights the potential of machine learning for accurate reservoir temperature prediction, offering geothermal professionals a reliable tool for model selection and advancing our understanding of geothermal resources.

16.
Vaccine ; 42(18): 3751-3755, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38714449

ABSTRACT

To assess the levels of and neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its mutants in serum samples from patients with breakthrough infection. Sixty-four patients with breakthrough infections were recruited for this cross-sectional study. All samples were used to neutralizing antibodies (nAbs) against SARS-CoV-2 and its mutants using a focused reduction neutralization assay. A total of 512 serum samples were obtained from unvaccinated patients who received one dose of vaccine (n = 12), received two doses of vaccine (n = 15), and received three doses of vaccine (n = 37). The geometric mean titer (GMT) of neutralizing antibodies against the Omicron subvariant was significantly lower (GMT 66.8 and 56.1) compared to the original strain, regardless of whether two or three doses of vaccine were administered. This result highlights that sera from breakthrough infections induce broad neutralization, but Omicron XBB.1.16 exhibits high immune evasion potential.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Neutralization Tests , SARS-CoV-2 , Humans , SARS-CoV-2/immunology , SARS-CoV-2/genetics , COVID-19/immunology , COVID-19/prevention & control , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Cross-Sectional Studies , Female , Male , Middle Aged , Adult , Immunization, Secondary , Aged , Immune Evasion , Breakthrough Infections
17.
BMC Cancer ; 24(1): 573, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724951

ABSTRACT

BACKGROUND: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. METHODS: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. RESULTS: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. CONCLUSION: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Disease Progression , Microsatellite Instability , Phosphopyruvate Hydratase , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Prognosis , Female , Male , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition/genetics , Middle Aged , Nomograms , Single-Cell Analysis , DNA Copy Number Variations
18.
Int J Biol Macromol ; 271(Pt 2): 132593, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38788865

ABSTRACT

This study delves into the effects of curdlan integration and thermal sterilization on the rheological properties, structure, and quality attributes of concentrated rice starch gel. Acting as a heat-set polysaccharide, curdlan established a dual-network gel structure with rice starch gel, displaying strong interactions with rice starch, as confirmed by confocal laser scanning microscopy and Fourier-transform infrared spectroscopy. The addition of curdlan expedited the gel formation of rice starch, yielding a denser gel structure. Consequently, this enhanced G', solid-like behavior, textural properties, and cooking quality while reducing frequency-dependence. Given the cooling-induced gelation behavior of pure rice starch, thermal treatment disrupted inter-chain hydrogen bonding, compromising the structural integrity of the gel. This disruption manifested in a softer texture and diminished mechanical properties and cooking quality. Notably, this decline in mechanical properties and cooking quality of rice starch gel was markedly ameliorated with the incorporation of curdlan, particularly at a content of ≥1.0 %. Compared with pure RS, 1.0 % CD inclusion showed a reduction in cooking breakage rate by 30.69 % and an increase in hardness by 38.04 %. This work provides valuable insights for the advancement of fresh starch gel-based foods that exhibit exceptional quality and an extended shelf life.


Subject(s)
Gels , Oryza , Rheology , Starch , beta-Glucans , Oryza/chemistry , beta-Glucans/chemistry , Starch/chemistry , Gels/chemistry , Sterilization/methods , Hot Temperature , Spectroscopy, Fourier Transform Infrared , Cooking/methods
19.
J Ethnopharmacol ; 331: 118337, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38740110

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Microthrombosis is commonly seen in sepsis and COVID-19. Zixue Powder (ZXP) is a traditional Chinese herbal formula with the potential to treat microvascular and infectious diseases. However, the role and mechanism of ZXP in sepsis-associated thrombosis remain unclear. AIM OF THE STUDY: Investigating the therapeutic effectiveness and underlying mechanisms of ZXP in septic thrombosis. MATERIALS AND METHODS: ZXP's compositions were examined with UPLC-QTOF-MS. The efficacy of ZXP on sepsis-induced thrombosis was assessed through various methods: liver tissue pathology was examined using hematoxylin-eosin staining, platelet count was determined by a blood cell analyzer, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum tissue factor (TF), thromboxane B2 (TXB2), D-Dimer, and plasminogen activator inhibitor-1 (PAI-1). Neutrophil extracellular traps (NETs) were localized and expressed in liver tissues by immunofluorescence, and the number of NETs in peripheral blood was evaluated by ELISA, which measured the quantity of cf-DNA and MPO-DNA in serum. Platelet P-selectin expression and platelet-neutrophil aggregation were measured by flow cytometry, and plasma P-selectin expression was measured by ELISA. Furthermore, the mechanism of the stimulator of interferon genes (STING) signaling pathway in ZXP's anti-sepsis thrombosis effect was investigated using the STING agonist, Western blot experiments, and immunoprecipitation experiments. RESULTS: UPLC-QTOF-MS identified 40 chemical compositions of ZXP. Administration of ZXP resulted in significant improvements in liver thrombosis, platelet counts, and levels of TXB2, TF, PAI-1, and D-Dimer in septic rats. Moreover, ZXP inhibited NETs formation in both liver tissue and peripheral blood. Additionally, ZXP decreased the levels of P-selectin in both platelets and plasma, as well as the formation of platelet-neutrophil aggregates, thereby suppressing P-selectin-mediated NETs release. Immunoprecipitation and immunofluorescence staining experiments revealed that ZXP attenuated P-selectin secretion by inhibiting STING-mediated assembly of platelet soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) complex, ultimately preventing inhibition of NETs formation. CONCLUSION: Our study showed that ZXP effectively mitigates platelet granule secretion primarily through modulation of the STING pathway, consequently impeding NET-associated thrombosis in sepsis. These findings offer valuable insights for future research on the development and application of ZXP.


Subject(s)
Drugs, Chinese Herbal , Extracellular Traps , Membrane Proteins , Sepsis , Thrombosis , Animals , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Drugs, Chinese Herbal/pharmacology , Male , Sepsis/drug therapy , Thrombosis/drug therapy , Membrane Proteins/metabolism , Blood Platelets/drug effects , Blood Platelets/metabolism , Rats , Neutrophils/drug effects , Neutrophils/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Rats, Sprague-Dawley , Mice
20.
Yi Chuan ; 46(5): 421-430, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38763776

ABSTRACT

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.


Subject(s)
Breeding , Goats , Animals , Goats/genetics , Goats/growth & development , Phenotype , Genomics/methods , Female , Male , Birth Weight/genetics , Models, Genetic
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