RÉSUMÉ
Purpose: The impact of moral beliefs on individuals' moral judgments, particularly within the framework of contrasting cultural values such as collectivism and individualism, continues to be a subject of interest. This research delves into whether individuals with distinct values display differences in moral beliefs, with a specific focus on selflessness. Methods: Through experiment 1 and 2, we scrutinize the moral judgments of individuals with diverse values concerning pro-social behaviors driven by selflessness and in-group favoritism. Experiment 3 investigates the underlying mechanisms by examining reward expectations. Results: The findings from experiments 1 and 2 indicate that collectivists exhibit significantly higher moral judgment levels for selfless pro-social behaviors compared to individualists, highlighting a disparity in moral beliefs between the two value systems. Experimental 2 also found that collectivists' moral judgments rose and fell as rescuers' selflessness increased or decreased. However, individualist moral judgment did not change significantly with behavioral selflessness. The results reveal that collectivists hold higher reward expectations for selfless behavior, which contributes to their heightened moral judgment of selfless behavior. Conclusion: While it may be assumed that collectivists' moral beliefs would be dominated by in-group preferences, aligning with the conceptual in-group preference of collectivism, this study unexpectedly found evidence of collectivists' pursuit of selflessness in their moral beliefs. These findings offer initial evidence of distinct patterns of moral beliefs associated with collectivism and individualism, shedding light on potential reasons that lead collectivists to possess stronger moral beliefs about selflessness.
RÉSUMÉ
BACKGROUND: Our study aims to investigate the mechanisms through which Fc receptor-like A (FCRLA) promotes renal cell carcinoma (RCC) and to examine its significance in relation to tumor immune infiltration. MATERIALS AND METHODS: The correlation between FCRLA and data clinically related to RCC was explored using The Cancer Genome Atlas (TCGA), then validated using Gene Expression Omnibus (GEO) gene chip data. Enrichment and protein-protein interaction (PPI) network analyses were performed for FCRLA and its co-expressed genes. FCRLA was knocked down in RCC cell lines to evaluate its impact on biological behavior. Then the potential downstream regulators of FCRLA were determined by western blotting, and rescue experiments were performed for verification. The relevance between FCRLA and various immune cells was analyzed through GSEA, TIMER, and GEPIA tools. TIDE and ESTIMATE algorithms were used to predict the effect of FCRLA in immunotherapy. RESULTS: Fc receptor-like A was associated with clinical and T stages and could predict the M stage (AUC = 0.692) and 1-3- and 5-year survival rates (AUC = 0.823, 0.834, and 0.862) of RCC patients. Higher expression of FCLRA predicted an unfavorable overall survival (OS) in TCGA-RCC and GSE167573 datasets (p = 0.03, p = 0.04). FCRLA promoted the malignant biological behavior of RCC cells through the pERK1/2/-MMP2 pathway and was associated with tumor immune microenvironment in RCC. CONCLUSION: Fc receptor-like A is positively correlated with poor outcomes in RCC patients and plays an oncogenic role in RCC through the pERK1/2-MMP2 pathway. Patients with RCC might benefit from immunotherapy targeting FCRLA.
Sujet(s)
Néphrocarcinome , Tumeurs du rein , Humains , Néphrocarcinome/génétique , Néphrocarcinome/immunologie , Néphrocarcinome/anatomopathologie , Néphrocarcinome/métabolisme , Tumeurs du rein/génétique , Tumeurs du rein/immunologie , Tumeurs du rein/anatomopathologie , Tumeurs du rein/métabolisme , Lignée cellulaire tumorale , Régulation de l'expression des gènes tumoraux , Récepteur Fc/génétique , Récepteur Fc/métabolisme , Pronostic , Microenvironnement tumoral/immunologie , Mâle , Prolifération cellulaire , Femelle , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Cartes d'interactions protéiques , Lymphocytes TIL/immunologie , Lymphocytes TIL/métabolisme , Matrix metalloproteinase 2/génétique , Matrix metalloproteinase 2/métabolismeRÉSUMÉ
This corrects the article 10.3791/66737.
RÉSUMÉ
The molecular editing of ketones represents an appealing strategy due to its ability to maximize the structural diversity of ketone compounds in a straightforward manner. However, developing efficient methods for the arbitrary modification of ketonic molecules, particularly those integrated within complex skeletons, remains a significant challenge. Herein, we present a unique strategy for ketone recasting that involves radical acylation of pre-functionalized ketones facilitated by N-heterocyclic carbene and photo dual catalysis. This protocol features excellent substrate tolerance and can be applied to the convergent synthesis and late-stage functionalization of structurally complex bioactive ketones. Mechanistic investigations, including experimental studies and density functional theory (DFT) calculations, shed light on the reaction mechanism and elucidate the basis of the regioselectivity.
RÉSUMÉ
BACKGROUND: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. METHODS: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. RESULTS: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. CONCLUSIONS: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.
RÉSUMÉ
Menopause-associated mood disorder is characterized by emotional depression, anxiety, and stress, which accompany hypogonadism in women in the menopausal phase. The current treatment for menopause-associated mood disorder provides only symptomatic relief and is associated with many side effects. Supplementation with vitamin E has been shown to be effective in ameliorating anxiety and depression. However, the effects of vitamin E and its underlying mechanism in ameliorating menopause-associated mood disorders remain uncertain. This work evaluated the effects of α-tocopherol and tocotrienol-rich palm oil extract on depressive and anxiety-related phenotypes induced by estrogen deficiency through ovariectomy in mice. Our study revealed that ovariectomized mice exhibited alterations in behavior indicative of depressive- and anxiety-like behaviors. The serum corticosterone level, a glucocorticoid hormone associated with stress, was found to be elevated in ovariectomized mice as compared to the sham group. Oral administration of α-tocopherol (50 and 100 mg/kg) and tocotrienol-rich palm oil extract (100 and 200 mg/kg) for 14 days alleviated these behavioral changes, as observed in open field, social interaction, and tail suspension tests. However, treatment with tocotrienol-rich palm oil extract, but not α-tocopherol, modulated the depressive- and anxiety-like responses in ovariectomized mice subjected to chronic restraint stress. Both treatments suppressed the elevated serum corticosterone level. Our findings suggested that α-tocopherol and tocotrienol-rich palm oil extract alleviated menopause-associated mood disorder, at least in part, by modulating the hypothalamic-pituitary-adrenal (HPA) axis. The findings of this study can provide a new foundation for the treatment of menopause-associated depressive- and anxiety-like phenotypes, for the betterment of psychological wellbeing.
RÉSUMÉ
The transformation of organoboron compounds plays an important role in synthetic chemistry, and recent advancements in boron-migration reactions have garnered considerable attention. Here, we report an unprecedented 1,2-boron migrative acylation upon photocatalysis-facilitated N-heterocyclic carbene catalysis. The design of a redox-active boronic ester substrate, serving as an excellent ß-boron radical precursor, is the linchpin to the success of this chemistry. With the established protocol, a wide spectrum of ß-boryl ketones has been rapidly synthesized, which could further undergo various CâB bond transformations to give multifunctionalized products. The robustness of this catalytic strategy is underscored by its successful application in late-stage modification of drug-derived molecules and natural products. Preliminary mechanistic investigations, including several control experiments, photochemistry measurements, and computational studies, shed light on the catalytic radical reaction mechanism.
RÉSUMÉ
Atopic dermatitis (AD) is a chronic, allergic inflammatory skin disorder that lacks a definite cure. Using a mouse DNCB-induced AD-like skin lesions model, this study evaluated the potential therapeutic utility of tHGA as an oral and topical treatment for AD. Male BALB/c mice were sensitised and challenged with 1% and 0.5% DNCB on their shaved dorsal skin. Mice in the treatment group were administered tHGA (20, 40, and 80 mg/kg) orally three times per week for 2 weeks, or tHGA (0.2%, 1%, and 5%) topically once daily for 12 days. On day 34, the mice were euthanized, and blood and dorsal skin samples were obtained for analysis. All doses of orally and topically administered tHGA significantly improved scratching, epidermal thickness, blood eosinophilia and mast cell infiltration. There was a minor discrepancy between the two routes of administration, with orally treated tHGA showing significant reductions in Scoring of Atopic Dermatitis (SCORAD), tissue eosinophil infiltration, serum IgE and skin IL-4 levels with treatment of 40 and 80 mg/kg tHGA, whereas topically applied tHGA showed significant reductions in all dosages. These findings suggest that tHGA exhibited therapeutic potential for AD as both oral and topical treatment ameliorates AD-like symptoms in the murine model.
Sujet(s)
Administration par voie topique , Eczéma atopique , 1-Chloro-2,4-dinitro-benzène , Immunoglobuline E , Souris de lignée BALB C , Peau , Animaux , Eczéma atopique/traitement médicamenteux , Eczéma atopique/induit chimiquement , Eczéma atopique/anatomopathologie , Administration par voie orale , Mâle , Souris , Immunoglobuline E/sang , Peau/effets des médicaments et des substances chimiques , Peau/anatomopathologie , Peau/métabolisme , Modèles animaux de maladie humaine , Acétophénones/administration et posologie , Acétophénones/pharmacologie , Acétophénones/usage thérapeutique , Granulocytes éosinophiles/effets des médicaments et des substances chimiques , Interleukine-4/métabolisme , Mastocytes/effets des médicaments et des substances chimiquesRÉSUMÉ
Background: The gut microbiota (GM) has been implicated in neurological disorders, but the relationship with hydrocephalus, especially the underlying mechanistic pathways, is unclear. Using Mendelian randomization (MR), we aim to discover the mediating role of inflammatory factors in the relationship between GM and hydrocephalus. Methods: After removing confounders, univariable and multivariable MR analyses were performed using summary statistics to assess the causal relationships between GM, inflammatory factors (IL-17A and IL-27), and types of hydrocephalus. Meta-analyses were used to reconcile the differences in MR results between different hydrocephalus sources. Finally, mediator MR analyses were applied to determine the mediating effect of inflammatory factors. Various sensitivity analysis methods were employed to ensure the reliability and stability of the results. Results: After correction for P-values, Firmicutes (phylum) (OR, 0.34; 95%CI, 0.17-0.69; P = 2.71E-03, P FDR = 2.44E-02) significantly reduced the risk of obstructive hydrocephalus. The remaining 18 different taxa of GM had potential causal relationships for different types of hydrocephalus. In addition, Firmicutes (phylum) decreased the risk of obstructive hydrocephalus by increasing levels of IL-17A (mediating effect = 21.01%), while Eubacterium ruminantium group (genus) increased the risk of normal-pressure hydrocephalus by decreasing levels of IL-27 (mediating effect = 7.48%). Conclusion: We reveal the connection between GM, inflammatory factors (IL-17A and IL-27), and hydrocephalus, which lays the foundation for unraveling the mechanism between GM and hydrocephalus.
Sujet(s)
Microbiome gastro-intestinal , Hydrocéphalie , Interleukine-17 , Analyse de randomisation mendélienne , Humains , Microbiome gastro-intestinal/immunologie , Hydrocéphalie/microbiologie , Hydrocéphalie/étiologie , Hydrocéphalie/immunologie , Inflammation/microbiologie , Interleukine-17/génétique , Interleukine-27/génétiqueRÉSUMÉ
We herein reported a novel photoredox-catalyzed three-component alkylarylation of vinyl arenes with alkylboronic pinacol esters (APEs) and cyanoarenes via radical addition/cross-coupling to construct 1,1-diarylalkanes. In this transformation, alkyl radicals were easily available by visible-light-induced oxidative N-H cleavage of morpholine, which used APEs as a radical precursor. Furthermore, this protocol exhibited a broad substrate scope, enabling various styrenes, APEs, and cyanoarenes, as well as bioactive molecule derivatives.
RÉSUMÉ
α-Amylases and glucoamylases play a crucial role in starch degradation for various industrial applications. Further exploration of novel α-amylases and glucoamylases with diverse enzymatic characteristics is necessary. In this study, metagenomics analysis revealed a high abundance of these enzymes in the microorganisms of Daqu and Pu-erh tea, identifying 271 glucoamylases and 232 α-amylases with significant sequence identity to known enzymes. Functional studies indicated that these enzymes have broad optimal temperatures (30 °C to 70 °C) and acidic or neutral pH optima. Additionally, two novel low-temperature glucoamylases and one novel low-temperature α-amylases were characterized, demonstrating potential for use in industries operating under low temperature conditions. Further analysis suggested that fewer molecular interactions and more flexible coli regions may contribute to their high activity at low temperatures. In summary, this study not only highlights the feasibility of exploring enzymes through metagenomic approaches, but also presents a library of novel and diverse α-amylases and glucoamylases for potential industrial applications.
RÉSUMÉ
Gynostemma pentaphyllum (Thunb.) Makino is a perennial creeping herb belonging to the Cucurbitaceae family that has a long history of usage in traditional oriental medicine. Gypenosides are the primary bioactive compounds in Gynostemma pentaphyllum. Because of the medicinal value of gypenosides, functional food and supplements containing gypenosides have been promoted and consumed with popularity, especially among Asian communities. This review presented the progress made in the research of pharmacological properties of gypenosides on diseases of the nervous system and their possible mechanism of action. To date, preclinical studies have demonstrated the therapeutic effects of gypenosides in alleviating neuropsychiatric disorders like depression, Parkinson's disease, Alzheimer's disease, secondary dementia, stroke, optic neuritis, etc. Pharmacological studies have discovered that gypenosides can modulate various major signaling pathways like NF-κB, Nrf2, AKT, ERK1/2, contributing to the neuroprotective properties. However, there is a dearth of clinical research on gypenosides, with current investigations on the compounds being mainly conducted in vitro and on animals. Future studies focusing on isolating and purifying novel gypenosides and investigations on exploring the potential molecular mechanism underlying their biological activities are warranted, which may serve as a foundation for further clinical trials for the betterment of human health.
Sujet(s)
Gynostemma , Neuroprotecteurs , Extraits de plantes , Gynostemma/composition chimique , Neuroprotecteurs/pharmacologie , Neuroprotecteurs/usage thérapeutique , Animaux , Humains , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutique , Troubles mentaux/traitement médicamenteux , Évaluation préclinique de médicament , Transduction du signal/effets des médicaments et des substances chimiquesRÉSUMÉ
Background: The coexistence of heart failure and diabetes is prevalent, particularly in Intensive Care Units (ICU). However, the relationship between the triglyceride-glucose (TyG) index, heart failure, diabetes, and the length of hospital stay (LHS) in patients with cerebrovascular disease in the ICU remains uncertain. This study aims to investigate the association between the TyG index and LHS in patients with heart failure and diabetes. Methods: This retrospective study utilized the Medical Information Mart for Intensive Care (MIMIC)-IV database to analyze patients with diabetes and heart failure. Participants were categorized into quartiles based on the TyG index, and the primary outcome was LHS. The association between the TyG index at ICU admission and LHS was examined through multivariable logistic regression models, restricted cubic spline regression, and subgroup analysis. Results: The study included 635 patients with concurrent diabetes and heart failure. The fully adjusted model demonstrated a positive association between the TyG index and LHS. As a tertile variable (Q2 and Q3 vs Q1), the beta (ß) values were 0.88 and 2.04, with a 95% confidence interval (95%CI) of -0.68 to 2.44 and 0.33 to 3.74, respectively. As a continuous variable, per 1 unit increment, the ß (95% CI) was 1.13 (0.18 to 2.08). The TyG index's relationship with LHS showed linearity (non-linear p = 0.751). Stratified analyses further confirmed the robustness of this correlation. Conclusion: The TyG index exhibited a linearly positive association with the LHS in patients with both heart failure and diabetes. Nevertheless, prospective, randomized, controlled studies are imperative to substantiate and validate the findings presented in this investigation.
Sujet(s)
Glycémie , Diabète de type 2 , Défaillance cardiaque , Unités de soins intensifs , Durée du séjour , Triglycéride , Humains , Défaillance cardiaque/sang , Défaillance cardiaque/épidémiologie , Femelle , Mâle , Études rétrospectives , Diabète de type 2/sang , Diabète de type 2/complications , Unités de soins intensifs/statistiques et données numériques , Triglycéride/sang , Sujet âgé , Durée du séjour/statistiques et données numériques , Glycémie/analyse , Glycémie/métabolisme , Adulte d'âge moyen , Sujet âgé de 80 ans ou plusRÉSUMÉ
(1) Background: Crop yields in China's arid and semi-arid regions are limited by water shortages. Exploring the interactions and resource utilization among agroforestry species is key to maintaining diversified agricultural production. (2) Objective: An apple-watermelon agroforestry system and watermelon sole-cropping system were compared to quantify how resource availability (light, water) and watermelon performance (leaf photosynthetic rate, growth, and yield) change with irrigation strategies. (3) Methods: A three-year apple and watermelon field experiment was conducted in a young apple orchard in the arid area of central Ningxia to test the effect of light competition and irrigation systems on light environment, leaf photosynthetic rate, plant growth, and yield in watermelon. The experiment encompassed two planting patterns: (i) apple-watermelon agroforestry (AF) and watermelon sole-cropping (SC) and (ii) three irrigation quotas (W1: 105 mm, W2: 210 mm, and W3: 315 mm). (4) Results: The results show that the agroforestry planting pattern extended the growth period of watermelon and increased the leaf area index. Mean daily shade intensity increased by 16.02% from 2020 to 2022. The land equivalent ratio (LER) was >1 in 2021 and 2022. The SWC, leaf photosynthetic rate, LAI, and yield of watermelon in an agroforestry planting pattern were lower than when in a sole-cropping planting pattern. However, under the W1 irrigation strategy, the total soluble solids of the agroforestry planting pattern were 2.27% higher than those of the sole-cropping pattern, and the yield of the agroforestry planting pattern was 2.59% higher than that of the sole-cropping pattern. Under the W3 irrigation strategy, the average watermelon weight in the agroforestry planting pattern was 2.85% higher than that of the sole-cropping pattern. A path analysis showed that the agroforestry planting pattern can increase the yield by increasing soil water content, which is different from the sole-cropping pattern. (5) Conclusions: The results confirm that the apple-watermelon agroforestry planting pattern reduced watermelon yields. However, the LER of the agroforestry system was greater than 1.0. It is reasonable to plant watermelons in young apple forests.
RÉSUMÉ
A total of five samples of Chrysomya megacephala samples - three fresh samples, one sample stored in alcohol for 2 years, and one sample stored in dry sealed storage for 2 years protected from light only - were selected to investigate whether a blood DNA extraction kit could extract DNA from necrophilous flies and to determine whether alcohol could prolong the preservation of necrophilous flies' DNA. First, the blood DNA extraction kit was used to extract DNA from their thorax tissues. Then, the DNA purity and concentration were examined using a microplate reader and a fluorometer. Finally, PCR amplification and electrophoresis of the extracted DNA were done with necrophilic fly-specific primers located in the mitochondrial CO I gene sequence. The results showed that the DNA purity of all samples was greater than 2.0. The DNA concentration was observed to be of the following order: fresh samples > alcohol-preserved old samples > untreated, old samples. All samples had specific electrophoretic bands after PCR amplification. In conclusion, a blood DNA extraction kit can be used to extract DNA from necrophilic flies successfully, and the DNA concentration of fresh fly samples is greater than that of old fly samples. The flies can be stored in alcohol for a long time.
Sujet(s)
ADN , Réaction de polymérisation en chaîne , Animaux , ADN/isolement et purification , ADN/génétique , Réaction de polymérisation en chaîne/méthodes , Calliphoridae/génétique , Calliphoridae/composition chimiqueRÉSUMÉ
Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.
RÉSUMÉ
Recurrence of a lung tumor invading the subclavian artery, causing stenosis and leading to finger ulcers as the initial symptom, is rare. We employed endovascular techniques, inserting a Viabahn® VBX covered stent (W. L. Gore & Associates, Flagstaff, Arizona) to aid in ulcer healing and improve the patient's quality of life. The patient, a 73-year-old male, had a history of lung adenocarcinoma resection two years prior but had not undergone follow-up examinations or cancer-specific treatments. Clinical examination revealed an invasion of the right subclavian artery by the recurrent tumor, resulting in severe stenosis and ischemic symptoms in the right upper limb. Given the patient's advanced cancer stage and the decline of further tumor-specific treatments, an endovascular intervention using a Viabahn VBX covered stent was performed to improve blood flow and promote ulcer healing. The stent demonstrated exceptional stability and patency during the six-month follow-up, greatly improving the patient's quality of life. This case highlights the importance of recognizing atypical symptoms as potential indicators of tumor recurrence or progression and demonstrates the promising role of covered stents in managing vascular complications in selected patients with advanced-stage malignancies.
RÉSUMÉ
The rhizosphere and phyllosphere of plants are home to a diverse range of microorganisms that play pivotal roles in ecosystem services. Consequently, plant growth-promoting bacteria (PGPB) are extensively utilized as inoculants to enhance plant growth and boost productivity. Despite this, the interactions between the rhizosphere and phyllosphere, which are influenced by PGPB inoculation, have not been thoroughly studied to date. In this study, we inoculated Bacillus velezensis SQR9, a PGPB, into the bulk soil, rhizosphere or phyllosphere, and subsequently examined the bacterial communities in the rhizosphere and phyllosphere using amplicon sequencing. Our results revealed that PGPB inoculation increased its abundance in the corresponding compartment, and all treatments demonstrated plant growth promotion effects. Further analysis of the sequencing data indicated that the presence of PGPB exerted a more significant impact on bacterial communities in both the rhizosphere and phyllosphere than in the inoculation compartment. Notably, the PGPB stimulated similar rhizosphere-beneficial microbes regardless of the inoculation site. We, therefore, conclude that PGPB can promote plant growth both directly and indirectly through the interaction between the rhizosphere and phyllosphere, leading to the enrichment of beneficial microorganisms.
Sujet(s)
Bacillus , Écosystème , Rhizosphère , Racines de plante/microbiologie , Bactéries/génétique , Microbiologie du solRÉSUMÉ
Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.
RÉSUMÉ
Background: In May-June 2023, an unprecedented outbreak of human respiratory syncytial virus (HRSV) infections occurred in a kindergarten, Zhejiang Province, China. National, provincial, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. Methods: We interviewed patients with the respiratory symptoms by questionnaire. Respiratory samples were screened for six respiratory pathogens by real-time quantitative polymerase chain reaction (RT-PCR). The confirmed cases were further sequenced of G gene to confirm the HRSV genotype. A phylogenetic tree was reconstructed by maximum likelihood method. Results: Of the 103 children in the kindergarten, 45 were classified as suspected cases, and 25 cases were confirmed by RT-PCR. All confirmed cases were identified from half of classes. 36% (9/25) were admitted to hospital, none died. The attack rate was 53.19%. The median ages of suspected and confirmed cases were 32.7 months and 35.8 months, respectively. Nine of 27 confirmed cases lived in one community. Only two-family clusters among 88 household contacts were HRSV positive. A total of 18 of the G gene were obtained from the confirmed cases. Phylogenetic analyses revealed that 16 of the sequences belonged to the HRSV B/BA9 genotype, and the other 2 sequences belonged to the HRSV A/ON1 genotype. The school were closed on June 9 and the outbreak ended on June 15. Conclusion: These findings suggest the need for an increased awareness of HRSV coinfections outbreak in the kindergarten, when HRSV resurges in the community after COVID-19 pandemic.