SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment

BACKGROUND: SHON nuclear expression (SHON-Nuc+) was previously reported to predict clinical outcomes to tamoxifen therapy in ERα+ breast cancer (BC). Herein we determined if SHON expression detected by specific monoclonal antibodies could provide a more accurate prediction and serve as a biomarker for anthracycline-based combination chemotherapy (ACT).METHODS: SHON expression was determined by immunohistochemistry in the Nottingham early-stage-BC cohort (n=1,650) who, if eligible, received adjuvant tamoxifen; the Nottingham ERα- early-stage-BC (n=697) patients who received adjuvant ACT; and the Nottingham locally advanced-BC cohort who received pre- operative ACT with/without taxanes (Neo-ACT, n=120) and if eligible, 5-year adjuvant tamoxifen treatment. Prognostic significance of SHON and its relationship with the clinical outcome of treatments were analysed.RESULTS: As previously reported, SHON-Nuc+ in high risk/ERα+ patients was significantly associated with a 48% death risk reduction after exclusive adjuvant tamoxifen treatment compared with SHON-Nuc- [HR(95%CI)=0.52(0.34-0.78), p=0.002]. Meanwhile, in ERα- patients treated with adjuvant ACT, SHON cytoplasmic expression (SHON-Cyto+) was significantly associated with a 50% death risk reduction compared with SHON-Cyto- [HR(95%CI)=0.50(0.34-0.73), p=0.0003]. Moreover, in patients received Neo-ACT, SHON-Nuc- or SHON-Cyto+ was associated with an increased pathological complete response (pCR) compared with SHON-Nuc+ [21% vs 4%; OR(95%CI)=5.88(1.28-27.03), p=0.012], or SHON-Cyto- [20.5% vs 4.5%; OR(95%CI)=5.43(1.18-25.03), p=0.017], respectively. After receiving Neo-ACT, patients with SHON-Nuc+ had a significantly lower distant relapse risk compared to those with SHON-Nuc- [HR(95%CI)=0.41(0.19-0.87), p=0.038], whereas SHON-Cyto+ patients had a significantly higher distant relapse risk compared to SHON-Cyto- patients [HR(95%CI)=4.63(1.05-20.39), p=0.043]. Furthermore, multivariate Cox regression analyses revealed that SHON-Cyto+ was independently associated with a higher risk of distant relapse after Neo-ACT and 5- year tamoxifen treatment [HR(95%CI)=5.08(1.13-44.52), p=0.037]. The interaction term between ERα status and SHON-Nuc+ (p=0.005), and between SHON-Nuc+ and tamoxifen therapy (p=0.007), were both statistically significant.CONCLUSION: SHON-Nuc+ in tumours predicts response to tamoxifen in ERα+ BC while SHON-Cyto+ predicts response to ACT

Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model

BackgroundThe prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients’ leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients.MethodsPatients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model.ResultsThere are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts.ConclusionsThe CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management

Terpinen-4-ol Improves Lipopolysaccharide-Induced Macrophage Inflammation by Regulating Glutamine Metabolism

Terpinen-4-ol (T-4-O) is an important component of tea tree oil and has anti-inflammatory effects. Currently, there are very few studies on the mechanisms by which T-4-O improves lipopolysaccharide (LPS)-induced macrophage inflammation. In this study, LPS-stimulated mouse RAW264.7 macrophages were used as a model to analyze the effects of T-4-O on macrophage inflammatory factors and related metabolic pathways in an inflammatory environment. The results showed that T-4-O significantly decreased the expression levels of inflammatory cytokines induced by LPS. Cellular metabolism results showed that T-4-O significantly decreased the ratio of the extracellular acidification rate and oxygen consumption rate. Non-targeted metabolomics results showed that T-4-O mainly affected glutamine and glutamate metabolism and glycine, serine, and threonine metabolic pathways. qPCR results showed that T-4-O increased the transcript levels of GLS and GDH and promoted glutamine catabolism. Western blotting results showed that T-4-O inhibited the mTOR and IκB, thereby decreasing NF-κB activity. The overall results showed that T-4-O inhibited mTOR phosphorylation to promote glutamine metabolism and increased cell oxidative phosphorylation levels, thereby inhibiting the expression of LPS-induced inflammatory cytokines

Handmade cloned transgenic sheep rich in omega-3 fatty acids

Technology of somatic cell nuclear transfer (SCNT) has been adapted worldwide to generate transgenic animals, although the traditional procedure relies largely on instrumental micromanipulation. In this study, we used the modified handmade cloning (HMC) established in cattle and pig to produce transgenic sheep with elevated levels of omega-3 (n-3) fatty acids. Codon-optimized nematode mfat-1 was inserted into a eukaryotic expression vector and was transferred into the genome of primary ovine fibroblast cells from a male Chinese merino sheep. Reverse transcriptase PCR, gas chromatography, and chromosome analyses were performed to select nuclear donor cells capable of converting omega-6 (n-6) into n-3 fatty acids. Blastocysts developed after 7 days of in vitro culture were surgically transplanted into the uterus of female ovine recipients of a local sheep breed in Xinjiang. For the HMC, approximately 8.9% (n = 925) of reconstructed embryos developed to the blastocyst stage. Four recipients became pregnant after 53 blastocysts were transplanted into 29 naturally cycling females, and a total of 3 live transgenic lambs were produced. Detailed analyses on one of the transgenic lambs revealed a single integration of the modified nematode mfat-1 gene at sheep chromosome 5. The transgenic sheep expressed functional n23 fatty acid desaturase, accompanied by more than 2-folds reduction of n-6/n-3 ratio in the muscle (p<0.01) and other major organs/tissues (p<0.05). To our knowledge, this is the first report of transgenic sheep produced by the HMC. Compared to the traditional SCNT method, HMC showed an equivalent efficiency but proved cheaper and easier in operation

Estimating Relative Chlorophyll Content in Rice Leaves Using Unmanned Aerial Vehicle Multi-Spectral Images and Spectral–Textural Analysis

Leaf chlorophyll content is crucial for monitoring plant growth and photosynthetic capacity. The Soil and Plant Analysis Development (SPAD) values are widely utilized as a relative chlorophyll content index in ecological agricultural surveys and vegetation remote sensing applications. Multi-spectral cameras are a cost-effective alternative to hyperspectral cameras for agricultural monitoring. However, the limited spectral bands of multi-spectral cameras restrict the number of vegetation indices (VIs) that can be synthesized, necessitating the exploration of other options for SPAD estimation. This study evaluated the impact of using texture indices (TIs) and VIs, alone or in combination, for estimating rice SPAD values during different growth stages. A multi-spectral camera was attached to an unmanned aerial vehicle (UAV) to collect remote sensing images of the rice canopy, with manual SPAD measurements taken immediately after each flight. Random forest (RF) was employed as the regression method, and evaluation metrics included coefficient of determination (R2) and root mean squared error (RMSE). The study found that textural information extracted from multi-spectral images could effectively assess the SPAD values of rice. Constructing TIs by combining two textural feature values (TFVs) further improved the correlation of textural information with SPAD. Utilizing both VIs and TIs demonstrated superior performance throughout all growth stages. The model works well in estimating the rice SPAD in an independent experiment in 2022, proving that the model has good generalization ability. The results suggest that incorporating both spectral and textural data can enhance the precision of rice SPAD estimation throughout all growth stages, compared to using spectral data alone. These findings are of significant importance in the fields of precision agriculture and environmental protection

Production of transgenic lambs by handmade cloning.

<p>(<b>A</b>) The recipient #0907 and the transgenic lamb (PP-01). (<b>B</b>) Detection of the <i>mfat-1</i> gene in umbilical cord samples of three cloned lambs by PCR and RT-qPCR. (<b>C</b>) Insertion site of <i>mfat-1</i> vector in the sheep genome. Arrows indicate the <i>mfat-1</i> transcriptional direction, which is identical with the endogenous putative sheep <i>Cep120</i> gene. PCR fragment obtained in this study are shown by black bars. (<b>D</b>) Southern blot using the ³²P-labled <i>mfat-1</i> specific sequence as a probe to hybridize the genomic DNA from the transgenic donor cells and the cloned lambs. The genomic DNA was digested with <i>Bam</i>HI before the gel electrophoresis. (<b>E</b>) Northern blot analysis. Total RNAs were loaded on each lane (15 µg per sample) and the coding region of <i>mfat-1</i> was used as a probe. Shown below is the gel electrophoresis of rRNA as control. (<b>F</b>) Quantitative PCR analysis of <i>mfat-1</i> expression in major tissues from the transgenic lambs (PP-02). Compared with the mRNA expression level normalized to the donor cell, the highest level of <i>mfat-1</i> expression was observed in transgenic muscle sample.</p

Microsatellite analysis of three transgenic cloned lambs, donor cell, and recipient.

<p>Microsatellite analysis of three transgenic cloned lambs, donor cell, and recipient.</p

Subgenome-aware analyses suggest a reticulate allopolyploidization origin in three Papaver genomes

Section "Matters arising". Original article: Yang, X., Gao, S., Guo, L. et al. Three chromosome-scale Papaver genomes reveal punctuated patchwork evolution of the morphinan and noscapine biosynthesis pathway. Nat Commun 12, 6030 (2021). DOI: 10.1038/s41467-021-26330-8</p