The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making ...this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing vascular wilt disease is one of the most devastating pathogens of banana (Musa spp.). To understand the molecular underpinning of ...pathogenicity in Foc, the genomes and transcriptomes of two Foc isolates were sequenced.
Genome analysis revealed that the genome structures of race 1 and race 4 isolates were highly syntenic with those of F. oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence associated genes were identified in both Foc genomes, including genes putatively involved in root attachment, cell degradation, detoxification of toxin, transport, secondary metabolites biosynthesis and signal transductions. Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate (Foc4) has evolved with some expanded gene families of transporters and transcription factors for transport of toxins and nutrients that may facilitate its ability to adapt to host environments and contribute to pathogenicity to banana. Transcriptome analysis disclosed a significant difference in transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the banana 'Brazil' in comparison with the vegetative growth stage. Of particular note, more virulence-associated genes were up regulated in Foc4 than in Foc1. Several signaling pathways like the mitogen-activated protein kinase Fmk1 mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway and a pathogenicity associated two-component system were activated in Foc4 rather than in Foc1. Together, these differences in gene content and transcription response between Foc1 and Foc4 might account for variation in their virulence during infection of the banana variety 'Brazil'.
Foc genome sequences will facilitate us to identify pathogenicity mechanism involved in the banana vascular wilt disease development. These will thus advance us develop effective methods for managing the banana vascular wilt disease, including improvement of disease resistance in banana.
Noninvasive prenatal screening (NIPS) based on cell-free fetal DNA (cffDNA) has rapidly been applied into clinic. However, the reliability of this method largely depends on the concentration of ...cffDNA in the maternal plasma. The chance of test failure results or false negative results would increase when cffDNA fraction is low. In this study, we set out to develop a method to enrich the cffDNA for NIPS based on the size difference between cell-free DNA (cfDNA) of fetal origin and maternal origin, and to evaluate whether the new NIPS method can improve the test quality.
We utilized 10,000 previous NIPS data to optimize a size-selection strategy for enrichment. Then, we retrospectively performed our new NIPS method with cffDNA enrichment on the 1415 NIPS samples, including 1404 routine cases and 11 false negative cases, and compared the results to the original NIPS results.
The 10,000 NIPS data revealed the fetal fraction in short cfDNA fragments (< 160 bp) is significantly higher. By using our new NIPS strategy on the 1404 routine cases, the fetal fraction increased from 11.3 ± 4.2 to 22.6 ± 6.6%, and the new method performed a significant decrease of test-failure rate (0.1% vs 0.7%, P < 0.01). Moreover, in 45.5% (5/11) of the false negative cases, fetal trisomies were successfully detected by our new NIPS method.
We developed an effective method to enrich cffDNA for NIPS, which shows an increased success rate and a reduced chance of false negative comparing to the ordinary NIPS method.
Receptor‐like cytoplasmic kinases (RLCKs) represent a large family of proteins in plants. However, few RLCKs have been well characterized. Here, we report the functional characterization of four rice ...RLCKs – OsRLCK57, OsRLCK107, OsRLCK118 and OsRLCK176 from subfamily VII. These OsRLCKs interact with the rice brassinosteroid receptor, OsBRI1 in yeast cell, but not the XA21 immune receptor. Transgenic lines silenced for each of these genes have enlarged leaf angles and are hypersensitive to brassinolide treatment compared to wild type rice. Transgenic plants silenced for OsRLCK57 had significantly fewer tillers and reduced panicle secondary branching, and lines silenced for OsRLCK107 and OsRLCK118 produce fewer seeds. Silencing of these genes decreased Xa21 gene expression and compromised XA21‐mediated immunity to Xanthomonas oryzae pv. oryzae. Our study demonstrates that these OsRLCKs negatively regulate BR signalling, while positively regulating immune responses by contributing to the expression of the immune receptor XA21.
Very few receptor‐like cytoplasmic kinases (RLCKs) in rice have been well characterized. We found that four rice RLCKs – OsRLCK57, OsRLCK107, OsRLCK118 and OsRLCK176 from subfamily VII interact with the rice brassinosteroid receptor, OsBRI1, and negatively regulate BL‐mediated signalling. Silencing each of the four OsRLCK genes leads to a decrease in Xa21 gene expression and compromises XA21‐mediated immunity to Xoo. Our findings proved that the four OsRLCKs regulate both development and immunity in rice.
The brassinosteroid-SIGNALING KINASE (BSK) belongs to the receptor-like cytoplasmic kinase XII subgroup. BSK1 regulates development and immunity in
. However, the function of rice (
) BSK1 is largely ...unknown. Here, we report that the expression level of
is induced after a chitin or fagellin22 (flg22) treatment. Silencing
in rice results in compromised responses to chitin- or flg22-triggered immunity and resistance to
, but does not alter the plant's architecture nor reduce plant responses to brassinosteroid signaling. Our study reveals that OsBSK1-2 functions as a major regulator in rice plant immunity.
This study aimed to determine the correlation between fetal fraction (FF) of cell-free DNA (cf-DNA) and pregnancy complications related to placental dysfunction in Twin Pregnancy.
This retrospective ...cohort study analyzed twin pregnant women who underwent non-invasive prenatal testing (NIPT) at 12
-26
weeks of gestation from April 2017 to April 2021. Low fetal fraction (LFF) was defined individually as less than the 25th, 10th, 5th, and 2.5th percentile among all fetal fractions in the cohort. Primary outcomes included gestational hypertension (GH), preeclampsia (PE), gestational diabetes mellitus (GDM), and small for gestational age (SGA). Logistic regression analysis was used to assess the relationship between LFF and pregnancy complications.
A total of 500 twin pregnancies (male-male twins, 245; female-female twins, 255) were included in this study. In LFF group (FF < 25th percentiles), maternal BMI was significantly higher than FF > 75th percentiles (23.6 kg/m
vs. 21.3 kg/m
;
< 0.001). The risk of SGA increased gradually from FF < 25th percentiles adjusted odds ratio (OR), 1.71; 95% confidence interval (CI), 1.07-2.99;
= 0.016 to FF < 2.5th percentiles (adjusted OR, 4.44; 95% CI,1.33-14.82;
< 0.015). In addition, the risks of SGA in both fetuses were higher than the risks of at least one fetus SGA in LFF group. LFF had no correlation with GH, PE, and GDM in twin pregnancy.
LFF has a strong association with increased risk of SGA in twin pregnancy. Moreover, FF of cf-DNA may provide a new idea for the early screening of diseases related to placental dysfunction in twin pregnancy.
The identification of lymph node metastases is important for the diagnosis, treatment and prognosis of patients with lung cancer. We found DDX49 was associated with the lymph node metastases in lung ...cancer by the Akt/β‐catenin pathway. Transcriptome sequencing, bioinformatics analysis, quantitative RT‐PCR, cell transfection and the Cancer Genome Atlas (TCGA) data set were used to identify DDX49 responsible for lymph node metastases. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to explore the possible molecular mechanism in experimental cell. The DDX49 gene was correlated significantly with lymph node metastases of lung cancer. The knockdown of DDX49 inhibited the cell proliferation and migration in PC‐9 and H460 cells. The mechanism research found downexpression of DDX49 decreased the Akt/β‐catenin pathway in lung cancer cell. In vivo experiments showed that DDX49 promoted the proliferation and metastases of lung cancer cells by increasing the Akt/β‐catenin pathway. These findings suggested that DDX49 may be useful as a novel biomarker of lymph node metastases and therapeutic target for lung cancer metastasis.
Cancer metastasis and recurrence are major causes of poor survival in patients with colorectal cancer (CRC). Therefore, the biological behavior of microRNA (miR)‑451 in CRC deserves further ...investigation. Reverse transcription‑quantitative PCR was applied to measure the relative expression of miR‑451 in blood serum specimens from patients with CRC and CRC cells.
, HCT116 cells were transfected with miR‑451 mimics, a miR‑451 inhibitor, or SAMD4B plasmids. Proliferation, migration and apoptosis were measured using CCK‑8, Transwell assays and flow cytometry, respectively. Luciferase reporter assay was used to identify targets of miR‑451 and western blotting performed to explore the internal mechanisms of miR‑451 regulation.
, the effect of miR‑451 and SAMD4B plasmids on tumor growth was analyzed using a nude mouse xenograft model. Results indicated that serum miR‑451 expression was lower in patients with CRC compared with healthy controls. Patients with elevated expression of miR‑451 had longer survival times compared with those with low expression. Overexpression of miR‑451 inhibited proliferation and migration, promoted apoptosis and enhanced the sensitivity of CRC cells to chemotherapy. SAMD4B was identified as a direct target of miR‑451 using miRNA target prediction programs and dual luciferase reporter assay validated the binding site of miR‑451 in the 3‑'UTR region of SAMD4B. Further studies confirmed that miR‑451 inhibited CRC progression via targeting SAMD4B. Results indicated that miR‑451 is essential for blocking tumor growth via targeting SAMD4B
and
. The miR‑451/SAMD4B axis may serve as a novel therapeutic target in patients with CRC.
Disease progression after curative surgery is still the main challenge for colorectal cancer (CRC). Identifying biomarkers and precise mechanisms in CRC disease progression is necessary for ...therapeutic improvement. As a transcription factor, ZEB1 promotes malignancy, but the precise mechanism by which ZEB1-dependent transcriptional regulation remains largely undefined. In this study, the transcriptional regulation of lysyl oxidase-like 2 (LOXL2) by ZEB1 in CRC was investigated. Our data show that ZEB1 enhanced LOXL2 transcription through direct binding to its promoter. The gain of function assays of ZEB1 showed increased cell proliferation, migration, and invasion. The inhibition of LOXL2 impaired the invasion and migratory ability of CRC cells, but had no effect on cell proliferation
and
. Immunohistochemical staining of tumor tissues indicated that elevated ZEB1/LOXL2 expression was significantly associated with lymph node metastasis and TNM stage. More importantly, elevated ZEB1/LOXL2 expression was an independent prognostic factor in CRC patients. These findings provide a molecular basis for the promotion of an invasive cancer phenotype by ZEB1-LOXL2 overexpression. Our results identify ZEB1/LOXL2 as a prognostic biomarker and potential therapeutic target against progression of CRC.
Advanced non-small-cell lung cancer (NSCLC) is a huge challenge for physicians. Traditional chemoradiotherapy is associated with high rates of toxicities, especially when treating gerontal patients. ...Our study was focused on investigating the safety and efficacy of permanent iodine-125 seed implantation and chemotherapy for the treatment of advanced NSCLC in the elderly.
Fifty elderly patients with stage III or IV NSCLC at our hospital from January 2011 to June 2017 were treated with the chemotherapy regimens (paclitaxel/cisplatin) and computed tomography (CT)-guided iodine-125 brachytherapy (group A), 50 patients who received chemotherapy consisting of paclitaxel and cisplatin only (group B) were matched-up with the patients in group A. The local response rate was evaluated by CT. Progression-free survival (PFS) and overall survival (OS) data were obtained through clinical follow-up.
The patients were followed-up for 3-46 months. With a median follow-up time of 20 months, the OS and PFS were 20 months (95% CI: 19.09-20.90 months) vs 15 months (95% CI: 14.48-15.51 months) (
<0.05) and 13 months (95% CI: 11.96-14.04 months) vs 8 months (95% CI: 7.63-8.37 months) (
<0.05) in group A and group B, respectively. The symptoms of patients in group A were significantly relieved when compared with group B. Severe complications were not observed in either of the groups.
The combination of iodine-125 seed brachytherapy and chemotherapy is an effective and safe therapy and is superior to chemotherapy alone for advanced NSCLC in the elderly.
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