Long non-coding RNA RP11-283G6.5 confines breast cancer development through modulating miR-188-3p/TMED3/Wnt/ß-catenin signalling.

The contributions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) to breast cancer are critical areas of investigation. In this study, we identified a novel lncRNA RP11-283G6.5 which was lowly expressed in breast cancer and whose low expression was correlated with poor overall survival and disease-free survival of breast cancer patients. Functional experiments revealed that ectopic expression of RP11-283G6.5 confined breast cancer cellular growth, migration, and invasion, and promoted cellular apoptosis. Conversely, RP11-283G6.5 silencing facilitated breast cancer cellular growth, migration, and invasion, and repressed cellular apoptosis. Moreover, RP11-283G6.5 was found to confine breast cancer tumour growth and metastasis in vivo. Mechanistically, RP11-283G6.5 competitively bound to ILF3, reduced the binding of ILF3to primary miR-188 (pri-miR-188), abolished the suppressive effect of ILF3 on pri-miR-188 processing, and therefore promoted pri-miR-188 processing, leading to the reduction of pri-miR-188 and the upregulation of mature miR-188-3p. The expression of RP11-283G6.5 was significantly positively correlated with that of miR-188-3p in breast cancer tissues. Through increasing miR-188-3p, RP11-283G6.5 decreased TMED3, a target of miR-188-3p. RP11-283G6.5 further suppressed Wnt/ß-catenin signalling via decreasing TMED3. Rescue assays revealed that inhibition of miR-188-3p, overexpression of TMED3 or blocking Wnt/ß-catenin signalling all attenuated the roles of RP11-283G6.5 in breast cancer. Collectively, these findings demonstrated that RP11-283G6.5 is a tumour suppressive lncRNA in breast cancer via modulating miR-188-3p/TMED3/Wnt/ß-catenin signalling. This study indicated that RP11-283G6.5 might be a promising prognostic biomarker and therapeutic target for breast cancer.

Effect of posterior cervical expansive open-door laminoplasty on cervical sagittal balance.

PURPOSE: Posterior cervical expansive open-door laminoplasty (LAMP) is a mature surgical procedure for the treatment of cervical spondylotic myelopathy (CSM), but there are few studies on the changes in cervical sagittal balance. This study aimed to analyze the imaging and clinical data of patients who underwent LAMP and to explore the effect of this procedure on the cervical sagittal balance. METHODS: This was a retrospective study of the patients who underwent LAMP between 01/2014 and 12/2017. The C0-C2 Cobb angle, sagittal vertical angle (SVA), C2-C7 Cobb angle, and T1-slope were measured. The Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), and visual analog scale (VAS) were used. RESULTS: There were 69 males and 39 females. The mean age was 61.3 ± 5.3 years. The C0-C2 Cobb angle increased from 11.3 ± 5.5° to 26.8 ± 4.8° (P = 0.186). The C2-C7 Cobb angle decreased from 13.9 ± 8.6° to 10.65 ± 10.7° P = 0.016). SVA increased from 21.0 ± 5.8 mm to 25.4 ± 11.5 mm (P = 0.001). The preoperative average JOA score was 11.1 ± 2.2 points, and the postoperative score was 14.0 ± 2.1 points, with an average improvement rate of JOA of 46.5 ± 3.8%. The NDI score decreased from preoperative 15.6 ± 5.4 points to 11.3 ± 7.9 points, and the VAS score was decreased from 4.6 ± 1.8 points to 3.3 ± 1.6 points (all P < 0.05). CONCLUSION: LAMP improved the neurological function and quality of life of patients with CSM. The cervical vertebrae show a tendency of tilting forward, suggesting that overextension of the upper cervical vertebra might be used to maintain the center of gravity of the skull and horizontal vision.

Gene regulatory network and abundant genetic variation play critical roles in heading stage of polyploidy wheat.

BACKGROUND: The extensive adaptability of polyploidy wheat is attributed to its complex genome, and accurately controlling heading stage is a prime target in wheat breeding process. Wheat heading stage is an essential growth and development processes since it starts at a crucial point in the transition from vegetative phase to reproductive phase. MAIN BODY: Heading stage is mainly decided by vernalization, photoperiod, hormone (like gibberellic acid, GA), and earliness per se (Eps). As a polyploidy species, common wheat possesses the abundant genetic variation, such as allelic variation, copy number variation etc., which have a strong effect on regulation of wheat growth and development. Therefore, understanding genetic manipulation of heading stage is pivotal for controlling the heading stage in wheat. In this review, we summarized the recent advances in the genetic regulatory mechanisms and abundant variation in genetic diversity controlling heading stage in wheat, as well as the interaction mechanism of different signals and the contribution of different genetic variation. We first summarized the genes involved in vernalization, photoperoid and other signals cross-talk with each other to control wheat heading stage, then the abundant genetic variation related to signal components associated with wheat heading stage was also elaborated in detail. CONCLUSION: Our knowledge of the regulatory network of wheat heading can be used to adjust the duration of the growth phase for the purpose of acclimatizing to different geographical environments.

Investigation and genome-wide association study for Fusarium crown rot resistance in Chinese common wheat.

BACKGROUND: Fusarium crown rot (FCR) is a severe and chronic disease in common wheat and is able to cause serious yield loss and health problems to human and livestock. RESULTS: Here, 234 Chinese wheat cultivars were evaluated in four greenhouse experiments for FCR resistance and genome-wide association studies (GWAS) were performed using the wheat 660 K genotyping assay. The results indicated that most cultivars evaluated showed FCR disease index (DI) of 40-60, while some cultivars showed stably good FCR resistance (DI < 30). GWAS identified 286 SNPs to be significantly associated with FCR resistance, of which 266, 6 and 8 were distributed on chromosomes 6A, 6B and 6D, respectively. The significant SNPs on 6A were located in a 7.0-Mb region containing 51 annotated genes. On the other hand, QTL mapping using a bi-parental population derived from UC1110 and PI610750 detected three QTLs on chromosomes 6A (explaining 7.77-10.17% of phenotypic variation), 2D (7.15-9.29%) and 2A (5.24-6.92%). The 6A QTL in the UC1110/PI610750 population falls into the same chromosomal region as those detected from GWAS, demonstrating its importance in Chinese materials for FCR resistance. CONCLUSION: This study could provide useful information for utilization of FCR-resistant wheat germplasm and further understanding of molecular and genetics basis of FCR resistance in common wheat.

Genome-wide association study of six quality traits reveals the association of the TaRPP13L1 gene with flour colour in Chinese bread wheat.

Flour colour, kernel hardness, grain protein content and wet gluten content are important quality properties that determine end use in bread wheat. Here, a wheat 90K genotyping assay was used for a genome-wide association study (GWAS) of the six quality-related traits in Chinese wheat cultivars in eight environments over four years. A total of 846 significant single nucleotide polymorphisms (SNPs) were identified, explaining approximately 30% of the phenotypic variation on average, and 103 multienvironment-significant SNPs were detected in more than four environments. Quantitative trait loci (QTL) mapping in the biparent population confirmed some important SNP loci. Moreover, it was determined that some important genes were associated with the six quality traits, including some known functional genes and annotated unknown functional genes. Of the annotated unknown functional genes, it was verified that TaRPP13L1 was associated with flour colour. Wheat cultivars or lines with TaRPP13L1-B1a showed extremely significantly higher flour redness and lower yellowness than those with TaRPP13L1-B1b in the Chinese wheat natural population and the doubled haploid (DH) population. Two tetraploid wheat lines with premature stop codons of the TaRPP13L1 gene mutagenized by ethyl methanesulfonate (EMS) showed extremely significantly higher flour redness and lower yellowness than wild type. Our data suggest that the TaRPP13L1 gene plays an important role in modulating wheat flour colour. This study provides useful information for further dissection of the genetic basis of flour colour and also provides valuable genes or genetic loci for marker-assisted selection to improve the process of breeding quality wheat in China.

Sign of Neck Mass as the Chief Complaint: A Case Report and Literature Review About Thyroid Metastasis of Colorectal Cancer.

Background: Commonly, the thyroid gland is regarded as an organ with fewer metastatic diseases, and colorectal metastasis to the thyroid (CMT) is rarely reported, especially, with that the clinical sign of thyroid metastasis nidus is the chief complaint. The CMT occurs in advanced colorectal cancer and is associated with poor prognosis and short survival. Case Report: In this case, we reported a patient with the sign of neck mass as the first manifestation of CMT. The patient underwent a partial thyroidectomy in June 2019, immunohistochemical findings of thyroid carcinoma suggested the possibility of adenocarcinoma of gastrointestinal tract. The patient underwent a colonoscopy in July 2019 and a colonic mass was found. Pathological examination diagnosed rectal adenocarcinoma. The patient underwent neoadjuvant chemotherapy, surgical treatment, postoperative adjuvant chemotherapy and targeted therapy. The patient died in June 2022. Conclusion: The metastasis disease would not be ignored at all, when a patient complains at signs of neck mass. Further, the possibility of metastasis cancer should be considered once thyroid nodules occur in patients with colorectal cancer. Even though the biological characteristics and stage of the primary tumor have an important impact on the prognosis, positive standardized treatments can also be helpful.

ROS-Responsive Fluorescent Sensor Array for Precise Diagnosis of Cancer via pH-Controlled Multicolor Gold Nanoclusters.

Intracellular reactive oxygen species (ROS) are closely associated with cancer cell types. Therefore, ROS-based pattern recognition is a promising strategy for precise diagnosis of cancer, but such a possibility has never been reported yet. Herein, we proposed an ROS-responsive fluorescent sensor array based on pH-controlled histidine-templated gold nanoclusters (AuNCs@His) to distinguish cancer cell types and their proliferation states. In this strategy, three types of AuNCs@His with diverse fluorescence profiles were first synthesized by only adjusting the pH value. Upon the addition of various ROS, fluorescence quenching of three types of AuNCs@His occurred with different degrees, thereby forming unique optical "fingerprints", which were well-clustered into several separated groups without overlap by principal component analysis (PCA). The sensing mechanism was attributable to the oxidation of AuNCs@His by ROS, as revealed by X-ray photoemission spectroscopy, Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry. Based on the ROS-responsive sensing pattern, cancer cell types were successfully differentiated via PCA with 100% accuracy. Additionally, the proposed sensor array exhibited excellent performance in distinguishing the proliferation states of cancer cells, which was supported by the results of the Ki-67 immunohistochemistry assay. Overall, the ROS-responsive fluorescent sensor array can serve as a promising tool for precise diagnosis of cancer, indicating great potential for clinical application.

Epigenetic regulator KDM4A activates Notch1-NICD-dependent signaling to drive tumorigenesis and metastasis in breast cancer.

BACKGROUND: Altered epigenetic reprogramming and events contribute to breast cancer (Bca) progression and metastasis. How the epigenetic histone demethylases modulate breast cancer progression remains poorly defined. We aimed to elucidate the biological roles of KDM4A in driving Notch1 activation and Bca progression. METHODS: The KDM4A expression in Bca specimens was analyzed using quantitative PCR and immunohistochemical assays. The biological roles of KDM4A were evaluated using wound-healing assays and an in vivo metastasis model. The Chromatin Immunoprecipitation (ChIP)-qPCR assay was used to determine the role of KDM4A in Notch1 regulation. RESULTS: Here, we screened that targeting KDM4A could induce notable cell growth suppression. KDM4A is required for the growth and progression of Bca cells. High KDM4A enhances tumor migration abilities and in vivo lung metastasis. Bioinformatic analysis suggested that KDM4A was highly expressed in tumors and high KDM4A correlates with poor survival outcomes. KDM4A activates Notch1 expressions via directly binding to the promoters and demethylating H3K9me3 modifications. KDM4A inhibition reduces expressions of a list of Notch1 downstream targets, and ectopic expressions of ICN1 could restore the corresponding levels. KDM4A relies on Notch1 signaling to maintain cell growth, migration and self-renewal capacities. Lastly, we divided a panel of cell lines into KDM4Ahigh and KDM4Alow groups. Targeting Notch1 using specific LY3039478 could efficiently suppress cell growth and colony formation abilities of KDM4Ahigh Bca. CONCLUSION: Taken together, KDM4A could drive Bca progression via triggering the activation of Notch1 pathway by decreasing H3K9me3 levels, highlighting a promising therapeutic target for Bca.

Assessing the decision quality of artificial intelligence and oncologists of different experience in different regions in breast cancer treatment.

Background: AI-based clinical decision support system (CDSS) has important prospects in overcoming the current informational challenges that cancer diseases faced, promoting the homogeneous development of standardized treatment among different geographical regions, and reforming the medical model. However, there are still a lack of relevant indicators to comprehensively assess its decision-making quality and clinical impact, which greatly limits the development of its clinical research and clinical application. This study aims to develop and application an assessment system that can comprehensively assess the decision-making quality and clinical impacts of physicians and CDSS. Methods: Enrolled adjuvant treatment decision stage early breast cancer cases were randomly assigned to different decision-making physician panels (each panel consisted of three different seniority physicians in different grades hospitals), each physician made an independent "Initial Decision" and then reviewed the CDSS report online and made a "Final Decision". In addition, the CDSS and guideline expert groups independently review all cases and generate "CDSS Recommendations" and "Guideline Recommendations" respectively. Based on the design framework, a multi-level multi-indicator system including "Decision Concordance", "Calibrated Concordance", " Decision Concordance with High-level Physician", "Consensus Rate", "Decision Stability", "Guideline Conformity", and "Calibrated Conformity" were constructed. Results: 531 cases containing 2124 decision points were enrolled; 27 different seniority physicians from 10 different grades hospitals have generated 6372 decision opinions before and after referring to the "CDSS Recommendations" report respectively. Overall, the calibrated decision concordance was significantly higher for CDSS and provincial-senior physicians (80.9%) than other physicians. At the same time, CDSS has a higher " decision concordance with high-level physician" (76.3%-91.5%) than all physicians. The CDSS had significantly higher guideline conformity than all decision-making physicians and less internal variation, with an overall guideline conformity variance of 17.5% (97.5% vs. 80.0%), a standard deviation variance of 6.6% (1.3% vs. 7.9%), and a mean difference variance of 7.8% (1.5% vs. 9.3%). In addition, provincial-middle seniority physicians had the highest decision stability (54.5%). The overall consensus rate among physicians was 64.2%. Conclusions: There are significant internal variation in the standardization treatment level of different seniority physicians in different geographical regions in the adjuvant treatment of early breast cancer. CDSS has a higher standardization treatment level than all physicians and has the potential to provide immediate decision support to physicians and have a positive impact on standardizing physicians' treatment behaviors.

Synergistic effect of adsorptive photocatalytic oxidation and degradation mechanism of cyanides and Cu/Zn complexes over TiO2/ZSM-5 in real wastewater.

The treatment of cyanide wastewater from the gold industry is essential. Photocatalytic oxidation is an effective method for the elimination of cyanides and metal cyanide complexes. TiO2/ZSM-5 composite photocatalysts with different SiO2/Al2O3 ratios were prepared using the solid-state dispersion (SSD) method. The composite catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), N2 adsorption-desorption, and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS). The catalytic efficiency of different SiO2/Al2O3 ratios and the synergistic effect of adsorptive photocatalytic oxidation for the degradation of cyanide wastewater was investigated under different adsorption and illumination times. With the extension of the photocatalytic time (>2.0 h), the composite catalyst with a high SiO2/Al2O3 ratio had better photocatalytic performance. A 93.97% degradation efficiency of total cyanides was observed after adsorption for 3.0 h and illumination for 4.0 h under room temperature with air as the oxidant. The removal efficiencies of the copper and zinc ions were 81.67% and 100%, respectively. The degradation of cyanide followed pseudo-first-order kinetics. Energy dispersive spectroscopy (EDS) results showed that the generally irregular surface of the catalyst with a high SiO2/Al2O3 ratio contains more nano-TiO2. The adsorption capacities of copper and zinc were relatively high. X-ray photoelectron spectroscopy (XPS) suggested that cyanide was eventually degraded to CO2 and NO3-. Copper and zinc were removed in the form of Cu(II) and Zn(II).

Real-Time In Situ Navigation System With Indocyanine Green Fluorescence for Sentinel Lymph Node Biopsy in Patients With Breast Cancer.

BACKGROUND: The naked-eye invisibility of indocyanine green fluorescence limits the application of near-infrared fluorescence imaging (NIR) systems for real-time navigation during sentinel lymph node biopsy (SLNB) in patients with breast cancer undergoing surgery. This study aims to evaluate the effectiveness and safety of a novel NIR system in visualizing indocyanine green fluorescence images in the surgical field and the application value of combined methylene blue (MB) and the novel NIR system in SLNB. METHODS: Sixty patients with clinical node-negative breast cancer received indocyanine green (ICG) and MB as tracers. Two NIR system instruments, namely, lymphatic fluorescence imaging system (LFIS) designed by the University of Science and Technology of China and vascular imager by Langfang Mingde Medical Biotechnology Co., Ltd. (Langfang vascular imager), were used as navigation assistance to locate sentinel lymph nodes (SLNs). Excising the lymph nodes developed by both MB and ICG by two NIR systems or palpably suspicious as SLNs and undergoing rapid pathological examination. RESULTS: Both instruments exhibited 95% (57/60) success for real-time lymphatic fluorescent images. A total of 186 SLNs were identified, of which two were pathologically confirmed as lacking any lymph node tissue. SLN identification rate was 100% (184/184) for MB plus LFIS and 86.96% (160/184) for MB alone. The median number of SLNs identified by LFIS combined with MB was 3 (range of 1-8), which was significantly higher than that by MB alone at 2 (range 1-7) (P<0.05). CONCLUSION: LFIS effectively detects SLNs in breast cancer, projects the fluorescence signals during surgery, and provides a continuous surgical navigation system without the need for a remote monitor. The ICG method navigated by combined LFIS and MB may be a promising alternative tracer for radioisotope in SLN mapping. CLINICAL TRIAL REGISTRATION: This clinical trial was registered with the China Clinical Trial Center, registration number ChiCTR2000039542.

Turning Pore Size of Silica-Based Nano-TiO2 for Treating Cyanide Wastewater.

Cyanide wastewater is a very highly toxic substance. In this study, a kind of silicon-based nano-TiO2 material by turning pore size accurately is prepared to treat cyanide wastewater. The materials are characterized by XRD, TG analysis, N2 adsorption/desorption test, UVAS analysis and TEM. Results show that adding NaCl to the synthesis of silica supports can change the size of pores. It emerges that pore size can affect the catalytic performance of the material. Catalytic experiments confirm that cyanide has the best catalytic effect when it has a pore size of 16.47 nm. UVAS spectrum demonstrate that the cyanide has been broken down rather than adsorbed onto the material.