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Molecular Plant Jun 2024Maize develops separate ear and tassel inflorescences with initially similar morphology but finally different architecture and sexuality. The detailed regulatory...
Maize develops separate ear and tassel inflorescences with initially similar morphology but finally different architecture and sexuality. The detailed regulatory mechanisms underlying these changes still remain largely unclear. In this study, through analyzing the time-course meristem transcriptomes and floret single-cell transcriptomes of ear and tassel, we revealed the regulatory dynamics and pathways underlying inflorescence development and sex differentiation. We identified 16 diverse gene clusters with differential spatiotemporal expression patterns and revealed biased regulation of redox, programmed cell death and hormone signals on meristem differentiation between ear and tassel. Particularly, based on their dynamic patterns, we revealed the roles of two RNA binding proteins in regulating inflorescence meristem activity and axillary meristem formation. Moreover, using the transcriptional profiles of 53,910 single cells, we uncovered the cellular heterogeneity between ear and tassel florets. We found that multiple signals associated with either enhanced cell death or reduced growth are responsible for tassel pistil suppression, while part of GA signal may act non-cell-autonomously to regulate ear stamen arrest during sex differentiation. We further showed that the pistil protection gene SILKLESS 1 (SK1) functions antagonistically to the known pistil suppression genes through regulating common molecular pathways, and constructed a regulatory model for pistil fate determination. Collectively, our study provides a deep understanding of the regulatory mechanisms underlying inflorescence development and sex differentiation in maize, laying the foundation to identify new regulators and pathways for maize hybrid breeding and improvement.
PubMed: 38877701
DOI: 10.1016/j.molp.2024.06.007 -
Frontiers in Plant Science 2024Though used as the model liverwort in culture for several decades, the biology of Marchantia polymorpha subsp. ruderalis in nature has never been documented in detail in...
INTRODUCTION
Though used as the model liverwort in culture for several decades, the biology of Marchantia polymorpha subsp. ruderalis in nature has never been documented in detail in a single account.
METHODS
Here we synthesize routine field observations documented with hundreds of images of M. ruderalis colonies (or groups) showing sex differentiation over 3 years on two populations of M. ruderalis after major heathland fires in 2020.
RESULTS
Initial post-fire establishment is from airborne spores rather than a spore bank but thereafter spread is via gemmae which have less exacting germination requirements. Young sporelings are highly gemmiferous but gemmae production becomes less frequent after sex organ formation. Over the course of a year there are up to three waves of carpocephalum production with the overwhelming majority of antheridiophores appearing 2-3 months ahead of the archegoniophores though no differences in growth rates were apparent between male and female thalli. Spermatozoids are produced almost continuously throughout the year, whilst sporophyte maturation is restricted to the summer months.
DISCUSSION
Because of the asynchrony between antheridiophore and archegoniophore production a 1:1 sex ratio is only apparent over this period. The spring months see an excess of males with more females in the summer. An almost 100% fertilization rate, with fertilization distances of up to 19 m far exceeding those in all other bryophytes, is attributed to vast spermatozoid production for most of the year, dispersal on surface oil films between thalli and highly effective intra-thallus spermatozoid transport via the pegged-rhizoid water-conducting system. Archegoniophores do develop on female-only populations but have shorter stalks than those where fertilization has occurred. Eventual disappearance post fires is attributed to a fall in topsoil nutrient levels preventing new sporeling establishment and competition from Ceratodon purpureus and Polytrichum spp. A major drought in the summer of 2022 almost wiped out the heathland Marchantia populations but all the other bryophytes survived.
PubMed: 38872896
DOI: 10.3389/fpls.2024.1339832 -
Cancer Medicine Jun 2024Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of...
BACKGROUND
Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) METHODS: Plasma cSFRP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64).
RESULTS
Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II-III CRC (univariate: HR 1.82, 95% CI: 1.02-3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12-4.88, p = 0.015).
CONCLUSION
This study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II-III disease.
Topics: Humans; Colorectal Neoplasms; Male; Female; Prognosis; Middle Aged; Aged; Biomarkers, Tumor; Adaptor Proteins, Signal Transducing; Adult; Neoplasm Staging; ROC Curve; Aged, 80 and over; Case-Control Studies
PubMed: 38872420
DOI: 10.1002/cam4.7352 -
World Journal of Surgical Oncology Jun 2024The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and...
BACKGROUND
The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood.
METHODS
This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the "limma" package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration.
RESULTS
Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment.
CONCLUSIONS
The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value.
Topics: Humans; Male; Female; Colorectal Neoplasms; Retrospective Studies; Lymph Nodes; Middle Aged; Neoplasm Staging; Survival Rate; Prognosis; Aged; Follow-Up Studies; SEER Program; Lymphatic Metastasis; Predictive Value of Tests
PubMed: 38872183
DOI: 10.1186/s12957-024-03404-7 -
BJS Open May 2024Endoscopic resection of T1 colon cancer (CC) is currently limited by guidelines related to risk of lymph node metastases. However, clinical outcome following endoscopic...
BACKGROUND
Endoscopic resection of T1 colon cancer (CC) is currently limited by guidelines related to risk of lymph node metastases. However, clinical outcome following endoscopic and surgical resection is poorly investigated.
METHOD
A retrospective multicentre national cohort study was conducted on prospectively collected data from the Swedish colorectal cancer registry on all non-pedunculated T1 CC patients undergoing surgical and endoscopic resection between 2009 and 2021. Patients were categorized on the basis of deep submucosal invasion (Sm2-3), lymphovascular invasion (LVI), poor tumour differentiation, and R1/Rx into low- and high-risk cases. The primary outcomes of interest were recurrence rates and disease-free interval (DFI, defined as time from treatment to date of recurrence) according to resection methods and risk factors (sex, age at diagnosis, histologic grade, LVI, perineural invasion, mucinous subtype, submucosal invasion, tumour location, resection margin and nodal positivity in the surgical group).
RESULTS
In total, 1805 patients undergoing endoscopic (488) and surgical (1317) resection with 60.0 months median follow-up were included. Recurrence occurred in 18 (3.7%) endoscopically and 48 (3.6%) surgically resected patients. Adjuvant treatment was administered in 7.4% and 0.2% of the cases respectively in the surgical and endoscopically treated patients. Five-year DFI was 95.6% after endoscopic and 96.2% after surgical resection, with no significant difference when adjusting for confounding factors (HR 1.03, 95% c.i. 0.56 to 1.91, P = 0.920). There were no statistically significant differences in recurrence comparing endoscopic (1.7%) versus surgical (3.6%) low-risk and endoscopic (5.4%) versus surgical (3.8%) high-risk cases. LVI was the only significant risk factor for recurrence in multivariate Cox regression (HR 3.73, 95% c.i. 1.76 to 7.92, P < 0.001).
CONCLUSIONS
This study shows no difference in recurrence after endoscopic and surgical resection in high-risk T1 CC. Although it was not possible to match groups according to treatment, the multivariate analysis showed that lymphovascular invasion was the only independent risk factor for recurrence.
Topics: Humans; Male; Female; Neoplasm Recurrence, Local; Aged; Registries; Colonic Neoplasms; Retrospective Studies; Middle Aged; Sweden; Risk Factors; Aged, 80 and over; Lymphatic Metastasis; Colonoscopy; Neoplasm Staging; Neoplasm Invasiveness; Colectomy
PubMed: 38869239
DOI: 10.1093/bjsopen/zrae053 -
Cancer Control : Journal of the Moffitt... 2024The purpose of this study is to employ a competing risk model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for...
BACKGROUND
The purpose of this study is to employ a competing risk model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for elderly individuals with sigmoid colon adenocarcinoma (SCA) and compare them with the classic Cox proportional hazards model.
METHODS
We extracted data from elderly patients diagnosed with SCA registered in the SEER database between 2010 and 2015. Univariate analysis was conducted using cumulative incidence functions and Gray's test, while multivariate analysis was performed using both the Fine-Gray and Cox proportional hazards models.
RESULTS
Among the 10,712 eligible elderly patients diagnosed with SCA, 5595 individuals passed away: 2987 due to sigmoid colon adenocarcinoma and 2608 from other causes. The results of one-way Gray's test showed that age, race, marital status, AJCC stage, differentiation grade, tumor size, surgical status, liver metastasis status, lung metastasis status, brain metastasis status, radiotherapy status, and chemotherapy status all affected the prognosis of SCA ( < .05). Multivariate analysis showed that sex, age, race, marital status, and surgical status affected the prognosis of SCA ( < .05). Multifactorial Fine-Gray analysis revealed that key factors influencing the prognosis of SCA patients include age, race, marital status, AJCC stage, grade classification, surgical status, tumor size, liver metastasis, lung metastasis, and chemotherapy status ( < .05).
CONCLUSION
Data from the SEER database were used to more accurately estimate CIFs for sigmoid colon adenocarcinoma-specific mortality and prognostic factors using competing risk models.
Topics: Humans; Male; Female; Aged; Adenocarcinoma; Prognosis; SEER Program; Sigmoid Neoplasms; Risk Assessment; Aged, 80 and over; Proportional Hazards Models; Risk Factors
PubMed: 38868954
DOI: 10.1177/10732748241262184 -
Oncology Letters Aug 2024The aim of the present study was to develop and evaluate a clinical-imaging-radiomic nomogram based on pre-enhanced computed tomography (CT) for pre-operative...
Clinical‑imaging‑radiomic nomogram based on unenhanced CT effectively predicts adrenal metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas.
The aim of the present study was to develop and evaluate a clinical-imaging-radiomic nomogram based on pre-enhanced computed tomography (CT) for pre-operative differentiation lipid-poor adenomas (LPAs) from metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas (AIs). A total of 196 consecutive patients with lung cancer, who underwent initial chest or abdominal pre-enhanced CT scan with small hyperattenuating AIs, were included. The patients were randomly divided into a training cohort with 71 cases of LPAs and 66 cases of metastases, and a testing cohort with 31 cases of LPAs and 28 cases of metastases. Plain CT radiological and clinical features were evaluated, including sex, age, size, pre-enhanced CT value (CT), shape, homogeneity and border. A total of 1,316 radiomic features were extracted from the plain CT images of the AIs, and the significant features selected by the least absolute shrinkage and selection operator were used to establish a Radscore. Subsequently, a clinical-imaging-radiomic model was developed by multivariable logistic regression incorporating the Radscore with significant clinical and imaging features. This model was then presented as a nomogram. The performance of the nomogram was assessed by calibration curves and decision curve analysis (DCA). A total of 4 significant radiomic features were incorporated in the Radscore, which yielded notable area under the receiver operating characteristic curves (AUCs) of 0.920 in the training dataset and 0.888 in the testing dataset. The clinical-imaging-radiomic nomogram incorporating the Radscore, CT, sex and age revealed favourable differential diagnostic performance (AUC: Training, 0.968; testing, 0.915) and favourable calibration curves. The nomogram was revealed to be more useful than the Radscore and the clinical-imaging model in clinical practice by DCA. The clinical-imaging-radiomics nomogram based on initial plain CT images by integrating the Radscore and clinical-imaging factors provided a potential tool to effectively differentiate LPAs from metastases in patients with lung cancer with small hyperattenuating AIs.
PubMed: 38855505
DOI: 10.3892/ol.2024.14472 -
Scientific Reports Jun 2024The enzyme dUTPase has an essential role in maintaining genomic integrity. In mouse, nuclear and mitochondrial isoforms of the enzyme have been described. Here we...
The enzyme dUTPase has an essential role in maintaining genomic integrity. In mouse, nuclear and mitochondrial isoforms of the enzyme have been described. Here we present the isoform-specific mRNA expression levels in different murine organs during development using RT-qPCR. In this study, we analyzed organs of 14.5-day embryos and of postnatal 2-, 4-, 10-week- and 13-month-old mice. We demonstrate organ-, sex- and developmental stage-specific differences in the mRNA expression levels of both isoforms. We found high mRNA expression level of the nuclear isoform in the embryo brain, and the expression level remained relatively high in the adult brain as well. This was surprising, since dUTPase is known to play an important role in proliferating cells, and mass production of neural cells is completed by adulthood. Thus, we investigated the pattern of the dUTPase protein expression specifically in the adult brain with immunostaining and found that dUTPase is present in the germinative zones, the subventricular and the subgranular zones, where neurogenesis occurs and in the rostral migratory stream where neuroblasts migrate to the olfactory bulb. These novel findings suggest that dUTPase may have a role in cell differentiation and indicate that accurate dTTP biosynthesis can be vital, especially in neurogenesis.
Topics: Animals; Neurogenesis; Pyrophosphatases; Mice; Female; Male; Brain; Gene Expression Regulation, Developmental; RNA, Messenger
PubMed: 38849394
DOI: 10.1038/s41598-024-63405-0 -
Frontiers in Endocrinology 2024The term 'differences of sex development' (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, and/or... (Review)
Review
46,XX Differences of Sex Development outside congenital adrenal hyperplasia: pathogenesis, clinical aspects, puberty, sex hormone replacement therapy and fertility outcomes.
The term 'differences of sex development' (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, and/or anatomical sex. DSD in individuals with a 46,XX karyotype can occur due to fetal or postnatal exposure to elevated amount of androgens or maldevelopment of internal genitalia. Clinical phenotype could be quite variable and for this reason these conditions could be diagnosed at birth, in newborns with atypical genitalia, but also even later in life, due to progressive virilization during adolescence, or pubertal delay. Understand the physiological development and the molecular bases of gonadal and adrenal structures is crucial to determine the diagnosis and best management and treatment for these patients. The most common cause of DSD in 46,XX newborns is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, determining primary adrenal insufficiency and androgen excess. In this review we will focus on the other rare causes of 46,XX DSD, outside CAH, summarizing the most relevant data on genetic, clinical aspects, puberty and fertility outcomes of these rare diseases.
Topics: Humans; Adrenal Hyperplasia, Congenital; Puberty; Hormone Replacement Therapy; Fertility; Female; Male; Disorders of Sex Development; Sexual Development
PubMed: 38841305
DOI: 10.3389/fendo.2024.1402579 -
Indian Journal of Dermatology 2024Pattern recognition receptors (PRRs), which are found in microorganisms but not in hosts, allow Leprae bacilli to be recognized as foreign. Several kinds of pattern...
A Cross-Sectional Study to Evaluate the Role of the Nuclear Factor Kappa B (Nf-κB) Pathway in Regulating the Cytokine Cascade and as a Potential Therapeutic Target in Leprosy.
Pattern recognition receptors (PRRs), which are found in microorganisms but not in hosts, allow Leprae bacilli to be recognized as foreign. Several kinds of pattern recognition receptors, such as toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-1-like receptors (RLRs), are present in the innate immune system. Sen and Baltimore (1986) discovered the transcription factor nuclear factor kappa-B (NF-B), employed by eukaryotic cells to regulate immunity, cell differentiation and proliferation. This study aimed to evaluate the role of the nuclear factor kappa B (NF-B) pathway in controlling the cytokine cascade in leprosy due to a lack of understanding of the link between cytokines and the severity of leprosy. Clinically suspected Hansen's patients were analysed for 4 years. Newly diagnosed leprosy patients were considered to have leprosy disease control (LDC). The cases with active or new lesions and an increase in BI by at least 2+, 12 months after completion of MDT were considered leprosy disease relapse (LDR) cases. Age- and sex-matched healthy individuals served as our control group (HC). An ELISA was performed to measure the concentration of five human cytokines. By qRT-PCR, the quantitative expression of receptor genes (NOD1 and NOD2), cytokine genes and the expression of the transcription factor NFκβ were evaluated. This was followed by a transcription factor NFκβ assay to see its expression in the monocytes of study subjects. Nuclear factor NF-κβ was found to have a pronounced response in monocytes of HC and LDC patients and LDR cases when treated with NOD1 and NOD2 ligands. Our study concludes that the NF-kB pathway is involved in the induction and regulation of the cytokine cascade that contributes to chronic inflammation in leprosy.
PubMed: 38841230
DOI: 10.4103/ijd.ijd_443_23