ABSTRACT
BACKGROUND: The clinical features of Turner syndrome (TS) involve multiple organ system dysplasia, among which growth retardation and gonadal dysplasia are the most important clinical phenotypes. METHODS: G banding karyotype analysis, chromosome microarray (CMA), and fluorescence in situ hybridization (FISH) were used for prenatal diagnosis of fetal chromosomes. RESULTS: The result of fetal chromosome karyotype analysis was 46,XX. CMA showed arr[GRCh38]Xp22.33 p22.13(251888_18176046)x1,Xq27.1q28(140998347_156003433)x3. FISH indicated that the short arm end fragment of X chromosome was monomer and the long arm end fragment was trisomy. CONCLUSIONS: The fetal chromosome karyotype was normal, but CMA indicated that there was deletion and duplication of X chromosome. FISH verified the CMA results, locating the deletion and duplication fragments. CMA and FISH make up for the shortcomings of chromosome karyotype analysis technique. It is suggested that multiple detection methods should be applied in genetic prenatal diagnosis.
Subject(s)
In Situ Hybridization, Fluorescence , Karyotyping , Prenatal Diagnosis , Turner Syndrome , Humans , Turner Syndrome/diagnosis , Turner Syndrome/genetics , Female , In Situ Hybridization, Fluorescence/methods , Pregnancy , Prenatal Diagnosis/methods , Chromosomes, Human, X/genetics , Adult , Chromosome BandingABSTRACT
Predicting soil heavy metal (SHM) content is crucial for understanding SHM pollution levels in urban residential areas and guide efforts to reduce pollution. However, current research indicates low SHM prediction accuracy in urban areas. Therefore, we employed a deep learning method (fully connected deep neural network) alongside four other methods (muti-layer perceptron, radial basis function neural network, multiple stepwise linear regression, and Kriging interpolation) to predict SHM content in the urban residential areas of Beijing and demonstrated the strength of deep learning in improving prediction accuracy. We found the contents of the evaluated heavy metals (Cd, Cu, Pb, and Zn) exhibited significant correlations with numerous other soil physicochemical properties and environmental factors. The prediction accuracy for Cu, Pb, and Zn contents was relatively high across different methods. Notably, deep learning showed considerable strength in predicting the contents of the four heavy metals, with the R2 for the test set of the model ranging from 0.75 to 0.91. Compared to other methods, deep learning achieved markedly higher prediction accuracy according to different accuracy evaluation indicators (e.g., deep learning showed increases in the cumulative R2 of the four heavy metals ranging from 53.16 % to 187.36 % compared to other methods). Our study indicates that deep learning can significantly improve SHM content prediction accuracy in urban areas and is highly applicable in urban residential areas with complex environmental influences.
ABSTRACT
The high intensity of diverse human activities in urban-rural areas leads to complex soil Pb accumulation processes and high spatiotemporal heterogeneity, making it difficult to reveal the spatiotemporal characteristics of soil Pb accumulation in these areas. This study used a typical urban-rural area in a large city in Central China as the study area, constructed a soil Pb accumulation model, and established a spatiotemporal simulation method for soil Pb accumulation processes combining this model and land use classification and simulation results. Using this method, we simulated the soil Pb content in the study area from 2013 to 2040 and elucidated the future spatiotemporal variation characteristics of soil Pb content. The results showed that the average soil Pb content in the study area in 2013 was approximately 1.77 times the background value of the Pb content in the surface soil of the province where the city is located, indicating significant soil Pb pollution. The soil Pb content was predicted to continue increasing from 2013 to 2040, with relatively low increases (0.53-2.25 mg·kg-1) in the western, northern, and southern parts of the study area, accounting for 25.46 % of the total area, and relatively high increases (3.98-5.70 mg·kg-1) in the eastern part, accounting for 17.14 % of the total area. The increase in the area of forest land and the decrease in the area of water bodies and grassland in the eastern part of the study area led to a substantial rise in soil Pb content in this region; in addition, the spatial distribution of soil Pb content was highly correlated with the distribution of important factories and transportation facilities. This study overcomes the limitations of previous research that treated land use as unchanging and to a certain extent reflects the impact of regional land use changes on the heavy metal accumulation process. It provides a method for simulating the soil Pb accumulation process in urban-rural areas and a basis for controlling soil Pb pollution in the city's urban-rural areas.
ABSTRACT
Demonstrating the temporal changes in PM2.5 pollution risk in regions facing serious PM2.5 pollution problems can provide scientific evidence for the air pollution control of the region. However, research on the variation of PM2.5 pollution risk on a fine temporal scale is very limited. Therefore, we developed a method for quantitative characterizing PM2.5 pollution risk based on the supply and demand of PM2.5 removal services, analyzed the time series characteristics of PM2.5 pollution risk, and explored the reasons for the temporal changes using the urban areas of Beijing as the case study area. The results show that the PM2.5 pollution risk in the urban areas of Beijing was close between 2008 and 2012, decreased by approximately 16.3% in 2016 compared to 2012, and further decreased by approximately 13.2% in 2021 compared to 2016. The temporal variation pattern of the PM2.5 pollution risk in 2016 and 2021 showed significant differences, including an increase in the number of risk-free days, a decrease in the number of heavily polluted days, and an increase in the stability of the risk day sequence. The significant reduction in risk level was mainly attributed to Beijing's air pollution control measures, supplemented by the impact of COVID-19 control measures in 2021. The results of PM2.5 pollution risk decomposition indicate that compared to the previous 2 years, the stability and predictability of the risk variation in 2016 increased, but the overall characteristics of high risk from November to February and low risk from April to September did not change. The high risk from November to February was mainly due to the demand for coal heating during this period, a decrease in PM2.5 removal service supply caused by plant leaf fall, and the common occurrence of temperature inversions in winter, which hinders the diffusion of air pollutants. This study provides a method for the analysis of PM2.5 pollution risk on fine temporal scales and may provide a reference for the PM2.5 pollution control in the urban areas of Beijing.
Subject(s)
Air Pollutants , Air Pollution , Environmental Monitoring , Particulate Matter , Particulate Matter/analysis , Beijing , Air Pollution/statistics & numerical data , Environmental Monitoring/methods , Air Pollutants/analysis , COVID-19/epidemiology , HumansABSTRACT
Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.
ABSTRACT
Excessive cadmium (Cd) concentration in wheat grain is becoming a widespread concern in China. Considering the complexity of Cd transfer in the soil-wheat system, how the Cd risk in wheat grain be accurately predicted from the limited details available is of great significance for the risk management of Cd. Bayes' theory could leverage existing data by combining prior information and observational data, providing a promising strategy with which to calculate a more robust posterior probability of a grain sample exceeding the food safety standard (FSS) for Cd (0.1 mg kg-1). In the current study, a risk prediction model, based on Bayes' theory, was established to achieve a more accurate prediction of the wheat grain Cd risk from a limited number of soil parameters. The risk prediction model could predict the risk probability of wheat grain with a Cd concentration exceeding the FSS under a given soil concentration of either total Cd or diethylenetriaminepentaacetic acid (DTPA)-extractable Cd. Soil total Cd concentration proved to be a better variable for the model with greater predictive accuracy. The model predicted that fewer than 5% of the wheat grain would have a Cd concentration exceeding the FSS when grown in soil with a total Cd concentration of less than 0.299 mg kg-1. The risk probability rose significantly to 50% when the soil total Cd reached 0.778 mg kg-1. The accuracy of the model was greater than the widely applied multiple linear regression model, whereas previously published data from similar soil conditions also confirmed that the Bayesian model could predict wheat Cd risk with minimal error. The proposed model provides an accurate, accessible and cost-effective methodology for predicting Cd risk in wheat grown in alkaline soils before harvest. The wider application to other soil conditions, crops or contaminants using the Bayesian model is also promising for risk management authorities.
Subject(s)
Bayes Theorem , Cadmium , Soil Pollutants , Soil , Triticum , Cadmium/analysis , Triticum/chemistry , Triticum/growth & development , Soil Pollutants/analysis , Soil/chemistry , China , Risk Assessment , Edible Grain/chemistry , Food Contamination/analysis , Models, TheoreticalABSTRACT
The incidence and mortality of endometrial carcinoma (EC) are increasing year by year. Although the curative effect of surgery and commonly used drugs is clear, it is accompanied by obvious side effects, and safe and effective means are urgently needed to promote the curative effect and decrease the toxicity of drugs. Traditional Chinese medicine has been passed down for thousands of years in China and has proved to be advantageous in the treatment of various cancers and the auxiliary enhancement and reduction of toxicity. This paper reviewed the role and internal mechanism of Salvia miltiorrhiza in preventing and treating endometrial carcinoma by referring to relevant literature and works, so as to more comprehensively understand and grasp the research status, effective components, curative effect and effective mechanism of S. miltiorrhiza in preventing and treating endometrial carcinoma, and provide ideas and basis for clinical use and basic research.
Subject(s)
Drugs, Chinese Herbal , Endometrial Neoplasms , Salvia miltiorrhiza , Salvia miltiorrhiza/chemistry , Humans , Female , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional/methodsABSTRACT
Sushi domain-containing protein 4 (SUSD4) is a complement regulatory protein whose primary function is to inhibit the complement system, and it is involved in immune regulation. The role of SUSD4 in cancer progression has largely remained elusive. SUSD4 was studied across a variety of cancer types in this study. According to the results, there is an association between the expression level of SUSD4 and prognosis in multiple types of cancer. Further analysis demonstrated that SUSD4 expression level was related to immune cell infiltration, immune-related genes, tumor heterogeneity, and multiple cancer pathways. Additionally, we validated the function of SUSD4 in colorectal cancer cell lines and found that knockdown of SUSD4 inhibited cell growth and impacted the JAK/STAT pathway. By characterizing drug sensitivity in organoids, we found that the expression of SUSD4 showed a positive correlation trend with IC50 of Selumetinib, YK-4-279, and Piperlongumine. In conclusion, SUSD4 is a valuable prognostic indicator for diverse types of cancer, and it has the potential to be a target for cancer therapy.
Subject(s)
Colorectal Neoplasms , Piperidones , Humans , Benzimidazoles/pharmacology , Benzimidazoles/therapeutic use , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Prognosis , Signal TransductionABSTRACT
Predicting chemical flux to soil from industrial point sources accurately at a regional scale has been a significant challenge due to high uncertainty in spatial heterogeneity and quantification. To address this challenge, we developed an innovative approach by combining California Air Resources Board Puff (CALPUFF) and mass balance models, leveraging their complementary strengths in quantitative accuracy and spatial precision. Specifically, CALPUFF was used to predict the polycyclic aromatic hydrocarbons (PAHs) flux to soil due to industrial sources. Additionally, the spatial distribution coefficient of PAHs flux (e.g., si for spatial unit i) was calculated by neural network and combined with the mass balance model to obtain the results of total PAHs fluxes, which were then combined with the results predicted by CALPUFF to effectively estimate the contribution of industrial sources to soil PAHs flux. Taking a petrochemical industry region located in Zhejiang province, China as a case study, results showed the input Phenanthrene (Phe) and Benzo(a)pyrene (BaP) fluxes predicted by CALPUFF were generally lower than those by the mass balance model, with slightly different distribution patterns. CALPUFF results, based on 36 industrial sources, partially represent those of the mass balance model, which includes all sources and pathways. It was suggested that industrial sources contributed 49%-89% and 65%-100% of soil Phe and BaP, respectively across the study area. The average Phe flux from point sources by deposition averaged 2.68 mg m-2âa-1 in 2021, accounting for approximately 60% of the total Phe flux to soil. The average BaP flux from point sources by deposition averaged 0.0755 mg m-2âa-1, accounting for only 0.1%-3.65% of the total BaP flux to soil. Thereby, our approach fills up a gap between the relevance to point sources and the accuracy of deposition quantification in estimating chemical flux from specific point sources to soil at a regional scale.
Subject(s)
Phenanthrenes , Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Soil , Polycyclic Aromatic Hydrocarbons/analysis , Phenanthrenes/analysis , Soil Pollutants/analysis , China , Environmental Monitoring/methodsABSTRACT
The tea pest, Basilepta melanopus Lefèvre 1893 (Chrysomelidae), belongs to the subfamily Eumolpinae. In this study, the complete mitochondrial genome sequence of B. melanopus from southern China was sequenced using the next-generation sequencing technique, assembled, and annotated using bioinformatics tools. The complete mitochondrial genome was 15,905 bp in length. The overall GC content was 22.51%, in which the percentages for the bases A, T, C, and G were 41.23%, 36.26%, 8.92%, and 13.59%, respectively. Thirty-seven genes were predicted, including 13 protein-coding, 22 transfer RNA, and two ribosomal RNA genes. Phylogenetic analysis based on the complete mitochondrial genome sequences of 18 Chrysomelidae taxa revealed that B. melanopus was closely related to Basilepta fulvipes.
ABSTRACT
Background: Many studies have investigated the efficacy of acupuncture in treating depression, but the mechanism of acupuncture for depression is still controversial and there is a lack of meta-analysis of mechanisms. Consequently, we investigated acupuncture's efficacy and mechanism of depression. Methods: We searched the Cochrane Library, PubMed, EMBASE, Web of Science. The SYRCLE Risk of Bias Tool was used to assess bias risk. Meta-analysis was performed using Stata 15.0 for indicators of depression mechanisms, body weight and behavioral tests. Results: A total of 22 studies with 497 animals with depressive-like behaviors were included. Meta-analysis showed that acupuncture significantly increased BDNF [SMD = 2.40, 95% CI (1.33, 3.46); I2 = 86.6%], 5-HT [SMD = 2.28, 95% CI (1.08, 3.47); I2 = 87.7%] compared to the control group (p < 0.05), and significantly reduced IL-1ß [SMD = -2.33, 95% CI (-3.43, -1.23); I2 = 69.6%], CORT [SMD = -2.81, 95% CI (-4.74, -0.87); I2 = 86.8%] (p < 0.05). Acupuncture improved body weight [SMD = 1.35, 95% CI (0.58, 2.11); I2 = 84.5%], forced swimming test [SMD = -1.89, 95% CI (-2.55, -1.24); I2 = 76.3%], open field test (crossing number [SMD = 3.08, 95% CI (1.98, 4.17); I2 = 86.7%], rearing number [SMD = 2.53, 95% CI (1.49, 3.57); I2 = 87.0%]) (p < 0.05) compared to the control group. Conclusion: Acupuncture may treat animals of depressive-like behaviors by regulating neurotrophic factors, neurotransmitters, inflammatory cytokines, neuroendocrine system. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403318, identifier (CRD42023403318).
ABSTRACT
Background: Alzheimer's disease (AD) is characterized by neuroinflammation, which is frequently accompanied by immune system dysfunction. Although the mechanism of neurodegenerative lesions is unclear, various clinical trials have highlighted that early intervention in AD is crucial to the success of treatment. In order to explore the potential of immunotherapy in the early period of AD, the present study evaluated whether application of glatiramer acetate (GA), an immunomodulatory agent approved for remitting-relapsing multiple sclerosis (RRMS), in the early stages of AD prior to amyloid beta (Aß) deposition altered the Aß pathology and cognitive impairments in APPswe/PSEN1dE9 (APP/PS1) transgenic mice. Methods: We treated two cohorts of pre-depositing and amyloid-depositing (2- and 6-month-old) APP/PS1 mice with weekly-GA subcutaneous injection over a 12-week period. We then tested spatial learning and memory using the Morris water maze (MWM) and the Y maze. Immunohistochemistry staining was utilized to analyze Aß burden in the brain as well as activated microglia. Furthermore, the inflammatory cytokine milieu within brains was estimated by quantitative real-time polymerase chain reaction, and the peripheral CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleen were measured by flow cytometry. Results: We found that early GA administration reduced Aß burden and ameliorated cognitive decline. Meanwhile, the immune microenvironment had changed in the brain, with an increase in the production of anti-inflammatory cytokines and a decrease in microglial activation. Interestingly, early GA administration also modulated the peripheral immune system through the amplification of Tregs in the spleen. Conclusion: Overall, our findings revealed that GA treatment might enhance the central and peripheral immune systems' protective capabilities in the early stages of AD, eventually improving cognitive deficits. Our research supports the advantages of immunomodulatory treatments for AD at an early stage.
ABSTRACT
The A3 adenosine receptor (AR) is an important inflammatory and immunological target. However, the underlying mechanisms are not fully understood. Here, we report the gene regulation in HL-60 cells treated acutely with highly selective A3AR agonist MRS5698, positive allosteric modulator (PAM) LUF6000, or both. Both pro- and anti-inflammatory genes, such as IL-1a, IL-1ß, and NFκBIZ, are significantly upregulated. During our observations, LUF6000 alone produced a lesser effect, while the MRS5698 + LUF6000 group demonstrated generally greater effects than MRS5698 alone, consistent with allosteric enhancement. The number of genes up- and down-regulated are similar. Pathway analysis highlighted the critical involvement of signaling molecules, including IL-6 and IL-17. Important upstream regulators include IL-1a, IL-1ß, TNF-α, NF-κB, etc. PPAR, which modulates eicosanoid metabolism, was highly downregulated by the A3AR agonist. Considering previous pharmacological results and mathematical modeling, LUF6000's small enhancement of genetic upregulation suggested that MRS5698 is a nearly full agonist, which we demonstrated in both cAMP and calcium assays. The smaller effect of LUF6000 on MRS5698 in comparison to its effect on Cl-IB-MECA was shown in both HL-60 cells endogenously expressing the human (h) A3AR and in recombinant hA3AR-expressing CHO cells, consistent with its HL-60 cell genetic regulation patterns. In summary, by using both selective agonists and PAM, we identified genes that are closely relevant to immunity and inflammation to be regulated by A3AR in differentiated HL-60 cells, a cell model of neutrophil function. In addition, we demonstrated the previously uncharacterized allosteric signaling-enhancing effect of LUF6000 in cells endogenously expressing the hA3AR.
ABSTRACT
Disease-associated variants identified from genome-wide association studies (GWASs) frequently map to non-coding areas of the genome such as introns and intergenic regions. An exclusive reliance on gene-agnostic methods of genomic investigation could limit the identification of relevant genes associated with polygenic diseases such as Alzheimer disease (AD). To overcome such potential restriction, we developed a gene-constrained analytical method that considers only moderate- and high-risk variants that affect gene coding sequences. We report here the application of this approach to publicly available datasets containing 181,388 individuals without and with AD and the resulting identification of 660 genes potentially linked to the higher AD prevalence among Africans/African Americans. By integration with transcriptome analysis of 23 brain regions from 2,728 AD case-control samples, we concentrated on nine genes that potentially enhance the risk of AD: AACS, GNB5, GNS, HIPK3, MED13, SHC2, SLC22A5, VPS35, and ZNF398. GNB5, the fifth member of the heterotrimeric G protein beta family encoding Gß5, is primarily expressed in neurons and is essential for normal neuronal development in mouse brain. Homozygous or compound heterozygous loss of function of GNB5 in humans has previously been associated with a syndrome of developmental delay, cognitive impairment, and cardiac arrhythmia. In validation experiments, we confirmed that Gnb5 heterozygosity enhanced the formation of both amyloid plaques and neurofibrillary tangles in the brains of AD model mice. These results suggest that gene-constrained analysis can complement the power of GWASs in the identification of AD-associated genes and may be more broadly applicable to other polygenic diseases.
Subject(s)
Alzheimer Disease , GTP-Binding Protein beta Subunits , Mice , Humans , Animals , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Genome-Wide Association Study , Neurofibrillary Tangles/metabolism , Phenotype , Genomics , Amyloid beta-Peptides/genetics , Brain/metabolism , Solute Carrier Family 22 Member 5/genetics , Solute Carrier Family 22 Member 5/metabolism , GTP-Binding Protein beta Subunits/genetics , GTP-Binding Protein beta Subunits/metabolismABSTRACT
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic contaminants in urban soils. The accumulation and source identifications of PAHs within a city have been frequently studied. However, impacts of urbanization development modes on PAHs accumulation patterns by taking a city as a whole have been seldom reported. Four cities with two development modes in Hebei province, Chengde and Zhangjiakou (tourist cities) and Handan and Tangshan (industrial cities), were selected. The concentrations of 16 priority PAHs in soils in the study areas were investigated. The results showed that the average concentrations of Σ16PAHs in Handan (2517 µg/kg) and Tangshan (2256 µg/kg) were more than twice of those in Chengde (696 µg/kg) and Zhangjiakou (926 µg/kg) approximately. Lines of evidence, provided by a combination of diagnostic ratios, pairwise correlation, and PMF methods, revealed that the dominant sources of PAHs in either city were industrial emission, vehicle emission, and petrogenic/biogenic process but with different proportions. Linear fittings based on Bayesian kernel machine regression analysis (BKMR) were constructed to illustrate the impact of industrialization on PAHs accumulation. The probability of excessing the 10 % (376 µg/kg) and 50 % (1138 µg/kg) of current ∑16PAHs would be higher than 90 % given the gross industrial production per unit area >5.00 × 106 and 20.5 × 106 CNY/km2, respectively. The proposed threshold values of industrialization are of significance for determining industrial structure and proportion in urban management.
ABSTRACT
Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer and other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, PCR-capillary electrophoresis is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline mismatch repair (MMR) mutations, the functional redundancy of the MMR system, and abnormal methylation of MutL Homolog 1 promoter. Therefore, this study aimed to develop new biomarkers for dMMR based on artificial intelligence (AI) and pathologic images, which may help to improve the detection accuracy. To screen for the differential expression genes (DEGs) in dMMR patients and validate their diagnostic and prognostic efficiency, we used the expression profile data from the Cancer Genome Atlas (TCGA). The results showed that the expression of Immunoglobulin Lambda Joining 3 in dMMR patients was significantly downregulated and negatively correlated with the prognosis. Meanwhile, our diagnostic models based on pathologic image features showed good performance with area under the curves (AUCs) of 0.73, 0.86, and 0.81 in the training, test, and external validation sets (Jiangsu Traditional Chinese Medicine Hospital cohort). Based on gene expression and pathologic characteristics, we developed an effective prognosis model for dMMR patients through multiple Cox regression analysis (with AUC values of 0.88, 0.89, and 0.88 at 1-, 3-, and 5-year intervals, respectively). In conclusion, our results showed that Immunoglobulin Lambda Joining 3 and nucleus shape-related parameters (such as nuclear texture, nuclear eccentricity, nuclear size, and nuclear pixel intensity) were independent diagnostic and prognostic factors, suggesting that they could be used as new biomarkers for dMMR patients.
Subject(s)
Adenocarcinoma , Brain Neoplasms , Colonic Neoplasms , Colorectal Neoplasms , Neoplastic Syndromes, Hereditary , Humans , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/pathology , DNA Mismatch Repair/genetics , Artificial Intelligence , Multiomics , Colorectal Neoplasms/pathology , Biomarkers , Immunoglobulins/geneticsABSTRACT
Phenylboronic acid (PBA) groups are effective in building glucose-responsive drug delivery systems. Chitosan (CS) offers distinct advantages in the construction of PBA-based biomaterials, such as biodegradability and biocompatibility. However, challenges still persist due to the limited solubility of CS. This study proposes an efficient approach to introduce PBA groups into CS chains within 1 h via the O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)-mediated amidation between 3-carboxyphenylboronic acid (CPBA) and O-hydroxypropyl chitosan (HPCS). The results showed that a wide range of substitution degrees, from 0.15 to 0.78, could be finely controlled by the amount of CPBA added. Furthermore, the obtained novel carboxyphenylboronic acid-grafted hydroxypropyl chitosan (PBA-HPCS) derivative showed enhanced crystallinity and thermostability compared to HPCS, and it demonstrated solubility in an alkaline solution. Based on the reversible bonding between the boronic acid group and cis-1,2/1,3-diols, PBA-HPCS was successfully used as an efficient crosslinker for the preparation of hydrogels incorporating sorbitol and polyhydroxy polymers, such as guar gum and polyvinyl alcohol. These hydrogels exhibited rapid gelation, rapid self-healing, injectability, and responsiveness to glucose and pH. These findings suggest that PBA-HPCS holds promise for advancing the development of PBA-based biomaterials.
Subject(s)
Chitosan , Chitosan/chemistry , Hydrogen-Ion Concentration , Hydrogels/chemistry , Boronic Acids/chemistry , Glucose/chemistry , Biocompatible Materials , Hypromellose DerivativesABSTRACT
AIM: The purpose of this meta-analysis is to compare the long-term efficacy of transanal local excision (TLE) versus total mesorectal excision (TME) following neoadjuvant therapy for rectal cancer. METHOD: The Web of Science, Pubmed, Medline, Embase, and the Cochrane Library were systematically searched for correlational research. The Newcastle-Ottawa Scale and the Cochrane risk of bias tool were used to assess the quality of cohort studies (CSs) and randomized controlled trials (RCTs), respectively. Statistically analyzed using RevMan5.4. RESULT: A total of 13 studies, including 3 randomized controlled trials (RCTs) and 10 cohort studies (CSs), involving 1402 patients, were included in the analysis. Of these, 570 patients (40.66%) underwent TLE, while 832 patients (59.34%) underwent TME. In the meta-analysis of CSs, no significant difference was observed between the TLE group and TME group regarding 5-year overall survival (OS) and 5-year disease-free survival (DFS) (P > 0.05). However, the TLE group had a higher rates of local recurrence (LR) [risk ratio (RR) = 1.93, 95%CI (1.18, 3.14), P = 0.008] and a lower rates of 5-years local recurrence-free survival (LRFS) [hazard ratio (HR) = 2.79, 95%CI (1.04, 7.50), P = 0.04] compared to the TME group. In the meta-analysis of RCTs, there was no significant difference observed between the TLE group and TME group in terms of LR, 5-year OS, 5-year DFS, and 5-year disease-specific survival (P > 0.05). CONCLUSION: After undergoing neoadjuvant therapy, TLE may provide comparable 5-year OS and DFS to TME for rectal cancer. However, neoadjuvant therapy followed by TLE may has a higher LR and lower 5-year LRFS compared to neoadjuvant therapy followed by TME, so patients should be carefully selected. Neoadjuvant therapy followed by TLE may be a suitable option for patients who prioritize postoperative quality of life. However, the effectiveness of this approach requires further research to draw a definitive conclusion.
Subject(s)
Digestive System Surgical Procedures , Rectal Neoplasms , Humans , Disease-Free Survival , Neoadjuvant Therapy , Neoplasm Recurrence, Local/surgery , Rectal Neoplasms/surgery , Treatment OutcomeABSTRACT
This work presents the first example of acid/base-responsive and near-infrared (NIR)-absorbing photocatalysts based on imidazole-anion-fused perylene diimide chromophores. The photocatalysts were in situ generated by deprotonation of imidazole-fused perylene diimide under an alkaline environment. NIR (λ = 730 nm, 128 mW/cm2) photoinduced atom transfer radical polymerization (ATRP) was implemented, exhibiting high efficiency and excellent livingness under ppm level of photocatalysts (15 ppm relative to monomer) and Cu(II) complex (10 ppm relative to monomer) concentrations. The method showed capabilities to polymerize behind opaque barriers (i.e., paper and pig skin) and under aerobic condition. Notably, this work demonstrated a dual temporal control of polymerization by adding weak base/acid and switching NIR light on/off. The polymerization can even be halted by bubbling CO2 and was then fully recovered by adding triethylamine. The NIR photoATRP of acrylamide monomers in aqueous solution was also performed, which can be regulated by the change of pH.