The DEP1 Mutation Improves Stem Lodging Resistance and Biomass Saccharification by Affecting Cell Wall Biosynthesis in Rice.

BACKGROUND: Plant cell walls have evolved precise plasticity in response to environmental stimuli. The plant heterotrimeric G protein complexes could sense and transmit extracellular signals to intracellular signaling systems, and activate a series of downstream responses. dep1 (Dense and Erect Panicles 1), the gain-of-function mutation of DEP1 encoding a G protein γ subunit, confers rice multiple improved agronomic traits. However, the effects of DEP1 on cell wall biosynthesis and wall-related agronomic traits remain largely unknown. RESULTS: In this study, we showed that the DEP1 mutation affects cell wall biosynthesis, leading to improved lodging resistance and biomass saccharification. The DEP1 is ubiquitously expressed with a relatively higher expression level in tissues rich in cell walls. The CRISPR/Cas9 editing mutants of DEP1 (dep1-cs) displayed a significant enhancement in stem mechanical properties relative to the wild-type, leading to a substantial improvement in lodging resistance. Cell wall analyses showed that the DEP1 mutation increased the contents of cellulose, hemicelluloses, and pectin, and reduced lignin content and cellulose crystallinity (CrI). Additionally, the dep1-cs seedlings exhibited higher sensitivity to cellulose biosynthesis inhibitors, 2,6-Dichlorobenzonitrile (DCB) and isoxaben, compared with the wild-type, confirming the role of DEP1 in cellulose deposition. Moreover, the DEP1 mutation-mediated alterations of cell walls lead to increased enzymatic saccharification of biomass after the alkali pretreatment. Furthermore, the comparative transcriptome analysis revealed that the DEP1 mutation substantially altered expression of genes involved in carbohydrate metabolism, and cell wall biosynthesis. CONCLUSIONS: Our findings revealed the roles of DEP1 in cell wall biosynthesis, lodging resistance, and biomass saccharification in rice and suggested genetic modification of DEP1 as a potential strategy to develop energy rice varieties with high lodging resistance.

Bioinformatics analysis and validation of HAUS6 as a key prognostic gene in squamous cell carcinoma of the tongue.

OBJECTIVE: To explore the expression of HAUS6 in squamous cell carcinoma of the tongue (TSCC) and its relationship with the clinicopathological features of patients, and to further provide new ideas and therapeutic targets for curing TSCC. DESIGN: The Cancer Genome Atlas (TCGA) database was used to screen for differentially expressed genes (DEGs) between TSCC and normal tissues and survival analysis. DEGs of HAUS6 were screened and analyzed for GO, KEGG and GSEA enrichment. Exploring the correlation of HAUS6 with immune cell infiltration and immune checkpoint-related genes. The expression of HAUS6 in tumor and paraneoplastic tissues was confirmed by immunohistochemistry and Western Blot. RESULTS: Analysis of the TCGA database results showed that expression of HAUS6 mRNA was significantly enhanced and correlated with overall survival (OS, p < 0.05) in TSCC. HAUS6 expression correlated with the level of immune cell infiltration and immune checkpoint-related genes. Immunohistochemistry and Western Blot confirmed that the expression level of HAUS6 protein was significantly higher in tumor tissues than in paraneoplastic tissues, and that tumor size and hypo-differentiation were higher in the HAUS6 high expression group than in the low expression group in TSCC (p < 0.05). CONCLUSIONS: In conclusion, these analyses suggest that HAUS6 can act as an independent predictor of prognosis (p < 0.05) and high HAUS6 expression is strongly associated with poor prognosis.

Spontaneous blink-related beta power increase and theta phase reset in subthalamic nucleus of Parkinson patients during walking.

OBJECTIVE: Both blinking and walking are altered in Parkinson's disease and both motor outputs have been shown to be linked in healthy subjects. Additionally, studies suggest an involvement of basal ganglia activity and striatal dopamine in blink generation. We investigated the role of the basal ganglia circuitry on spontaneous blinking and if this role is dependent on movement state and striatal dopamine. METHODS: We analysed subthalamic nucleus (STN) activity in seven chronically implanted patients for deep brain stimulation (DBS) with respect to blinks and movement state (resting state and unperturbed walking). Neurophysiological recordings were combined with individual molecular brain imaging assessing the dopamine reuptake transporter (DAT) density for the left and right striatum separately. RESULTS: We found a significantly higher blink rate during walking compared to resting. The blink rate during walking positively correlated with the DAT density of the left caudate nucleus. During walking only, spontaneous blinking was followed by an increase in the right STN beta power and a bilateral subthalamic phase reset in the low frequencies. The right STN blink-related beta power modulation correlated negatively with the DAT density of the contralateral putamen. The left STN blink-related beta power correlated with the DAT density of the putamen in the less dopamine-depleted hemisphere. Both correlations were specific to the walking condition and to beta power following a blink. CONCLUSION: Our findings show that spontaneous blinking is related to striatal dopamine and has a frequency specific deployment in the STN. This correlation depends on the current movement state such as walking. SIGNIFICANCE: This work indicates that subcortical activity following a motor event as well as the relationship between dopamine and motor events can be dependent on the motor state. Accordingly, disease related changes in brain activity should be assessed during natural movement.

PI-RADS v2.1 evaluation of prostate "nodule in nodule" variants: clinical, imaging, and pathological features.

OBJECTIVES: To analyze the correlation among the imaging features of prostate "nodule in nodule," clinical prostate indices, and pathology results. METHODS: We retrospectively analyzed the prostate images from 47 male patients who underwent MRI scans and pathological biopsy from January 2022 to July 2023. Two radiologists (R1/R2) evaluated the morphology and signal intensity of the "nodule in nodule" in a double-blind manner and calculated the PI-RADS v2.1 score, which was compared with clinical prostate indices and pathological results. RESULTS: 34.04% (16/47) of patients were pathologically diagnosed with clinically significant prostate cancer (csPCa). Total prostate-specific antigen (tPSA), free/t PSA, PSA density (PSAD), and prostate gland volume (PGV) were significantly different between csPCa patients and benign prostatic hyperplasia (BPH) patients with prostate "nodule in nodule". R1/R2 detected 17/17 prostate "nodule in nodule" pathologically confirmed as csPCa on MRI; 10.60% (16/151) (R1) and 11.11% (17/153) (R2) had diffusion-weighted imaging (DWI) PI-RADS v2.1 score of 4, and 0.66% (1/151) (R1) had a score of 3. The percentages of encapsulated, circumscribed, and atypical nodules and obscured margins were 0.00% (0/151), 0.00% (0/151), 5.96% (9/151), and 5.30% (8/151), respectively, for R1, and 0.00% (0/153), 0.00% (0/153), 5.88% (9/153), and 4.58% (7/153) for R2. CONCLUSION: When the inner nodules of "nodule in nodule" lesions in PI-RADS v2.1 category 1 in the TZ show incomplete capsulation or obscured margins, they are considered atypical nodules and might be upgraded to PI-RADS v2.1 category 3 if they exhibit marked diffusion restriction. However, further validation is needed. CRITICAL RELEVANCE STATEMENT: This study first analyzed the relationship between clinical and pathological findings and the size, margin, and multimodal MRI manifestations of the prostate "nodule in nodule." These findings could improve the diagnostic accuracy of PI-RADS v2.1 for prostate lesions. KEY POINTS: • The margin of the prostate inner nodules affects the PI-RADS v2.1 score. • The morphology of prostate "nodule in nodule" is related to their pathology. • The PI-RADS v2.1 principle requires consideration of prostate "nodule in nodule" variants.

A spatial-attentional mechanism underlies action-related distortions of time judgment.

Temporal binding has been understood as an illusion in timing judgment. When an action triggers an outcome (e.g. a sound) after a brief delay, the action is reported to occur later than if the outcome does not occur, and the outcome is reported to occur earlier than a similar outcome not caused by an action. We show here that an attention mechanism underlies the seeming illusion of timing judgment. In one method, participants watch a rotating clock hand and report event times by noting the clock hand position when the event occurs. We find that visual spatial attention is critically involved in shaping event time reports made in this way. This occurs because action and outcome events result in shifts of attention around the clock rim, thereby biasing the perceived location of the clock hand. Using a probe detection task to measure attention, we show a difference in the distribution of visual spatial attention between a single-event condition (sound only or action only) and a two-event agency condition (action plus sound). Participants accordingly report the timing of the same event (the sound or the action) differently in the two conditions: spatial attentional shifts masquerading as temporal binding. Furthermore, computational modeling based on the attention measure can reproduce the temporal binding effect. Studies that use time judgment as an implicit marker of voluntary agency should first discount the artefactual changes in event timing reports that actually reflect differences in spatial attention. The study also has important implications for related results in mental chronometry obtained with the clock-like method since Wundt, as attention may well be a critical confounding factor in the interpretation of these studies.

Comprehensive analysis of transcriptome data and experimental identification show that solute carrier 35 member A2 (SLC35A2) is a prognostic marker of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a solid tumor with high morbidity and mortality rates. Accumulating evidence shows that the soluble carrier family 35 member A2 (SLC35A2), a nucleotide sugar transporter, plays a key role in the pathogenesis of various tumors. However, its expression and function in CRC has not been fully elucidated. METHODS: The prognosis-related gene SLC35A2 was obtained using differential analysis, prognosis correlation analysis, and LASSO regression screening. Its expression levels in CRC tissues were analyzed, and so was the relationship of this expression with clinical characteristics of patients. Subsequently, the expression levels were correlated with clinicopathological parameters using immunohistochemical analysis. Analysis based on GO/KEGG databases was used to reveal the potential mechanisms of SLC35A2. Next, we explored the relationship between SLC35A2 and immune cells in CRC tissues. A nomogram was created to help understand the prognosis of CRC patients. Finally, western blotting and qRT-PCR reaction were used to verify the expression of SLC35A2 in CRC cell lines. RESULTS: SLC35A2 expression was upregulated and related to tumor pathological stage and lymph node metastasis, indicating that SLC35A2 is an independent prognostic factor and a potential diagnostic marker for CRC. We verified by IHC, WB and PCR that the expression of SLC35A2 was up-regulated in colorectal cancer tissues and cell lines, and its high expression was related to the tumor pathological stage of CRC clinical samples. CONCLUSIONS: Our study found that SLC35A2 can be used as a biomarker for the diagnosis and prognosis of CRC, providing motivation for further study.

The Fragile culm19 (FC19) mutation largely improves plant lodging resistance, biomass saccharification, and cadmium resistance by remodeling cell walls in rice.

Cell wall is essential for plant upright growth, biomass saccharification, and stress resistance. Although cell wall modification is suggested as an effective means to increase biomass saccharification, it is a challenge to maintain normal plant growth with improved mechanical strength and stress resistance. Here, we reported two independent fragile culm mutants, fc19-1 and fc19-2, resulting from novel mutations of OsIRX10, produced by the CRISPR/Cas9 system. Compared to wild-type, the two mutants exhibited reduced contents of xylose, hemicellulose, and cellulose, and increased arabinose and lignin without significant alteration in levels of pectin and uronic acids. Despite brittleness, the mutants displayed increased breaking force, leading to improved lodging resistance. Furthermore, the altered cell wall and increased biomass porosity in fc19 largely increased biomass saccharification. Notably, the mutants showed enhanced cadmium (Cd) resistance with lower Cd accumulation in roots and shoots. The FC19 mutation impacts transcriptional levels of key genes contributing to Cd uptake, sequestration, and translocation. Moreover, transcriptome analysis revealed that the FC19 mutation resulted in alterations of genes mainly involved in carbohydrate and phenylpropanoid metabolism. Therefore, a hypothetic model was proposed to elucidate that the FC19 mutation-mediated cell wall remodeling leads to improvements in lodging resistance, biomass saccharification, and Cd resistance.

Characterization of SHCBP1 to prognosis and immunological landscape in pan-cancer: novel insights to biomarker and therapeutic targets.

BACKGROUND: Previous studies have revealed the significant roles of SHC SH2 domain-binding protein 1 (SHCBP1) in occurrence and progression of cancers, but there is no pan-cancer analysis of SHCBP1. METHODS: In this study, we explored the potential carcinogenic role of SHCBP1 across 33 tumors from the TCGA and GTEx databases. We investigated SHCBP1 expression, prognosis, genetic alterations, tumor mutational burden (TMB) score, microsatellite instability (MSI) and tumor microenvironment from TIMER2, GEPIA2, UALCAN and cBioPortal databases. Moreover, the cellular functions and potential mechanisms were evaluated by GO and KEGG analysis. Besides, the mRNA expression of SHCBP1 was examined using qRT-PCR assay in gastrointestinal cancers. RESULTS: SHCBP1 was significantly upregulated in various cancers, and apparent relationship existed between SHCBP1 and survival prognosis in patients. The TMB, MSI, and tumor microenvironment analysis indicated that SHCBP1 was closely related to immune checkpoints, immune targets, as well as CD4+ naive T cell, CD8+ T cell, and neutrophil. Moreover, the cellular functions of SHCBP1 were mainly in regulating cell cycle motor protein activity. In addition, we validated that SHCBP1 mRNA expression was over-expressed in gastrointestinal cancers. CONCLUSIONS: This study was the first to systematically determine the prognostic value of SHCBP1, providing a forward-looking perspective on immunotherapy and cellular processes in pan-cancer.

Human visual processing during walking: Dissociable pre- and post-stimulus influences.

Walking influences visual processing but the underlying mechanism remains poorly understood. In this study, we investigated the influence of walking on pre-stimulus and stimulus-induced visual neural activity and behavioural performance in a discrimination task while participants were standing or freely walking. The results showed dissociable pre- and post-stimulus influences by the movement state. Walking was associated with a reduced pre-stimulus alpha power, which predicted enhanced N1 and decreased P3 components during walking. This pre-stimulus alpha activity was additionally modulated by time on the task, which was paralleled by a similar behavioural modulation. In contrast, the post-stimulus alpha power was reduced in its modulation due to stimulus onset during walking but showed no evidence of modulation by time on the task. Additionally, stimulus parameters (eccentricity, laterality, distractor presence significantly influenced post-stimulus alpha power, whereas the visually evoked components showed no evidence of such an influence. There was further no evidence of a correlation between pre-stimulus and post stimulus alpha power. We conclude that walking has two dissociable influences on visual processing: while the walking induced reduction in alpha power suggests an attentional state change that relates to visual awareness, the post-stimulus influence on alpha power modulation indicates changed spatial visual processing during walking.

OsUGE3-mediated cell wall polysaccharides accumulation improves biomass production, mechanical strength, and salt tolerance.

Cell walls constitute the majority of plant biomass and are essential for plant resistance to environmental stresses. It is promising to improve both plant biomass production and stress resistance simultaneously by genetic modification of cell walls. Here, we report the functions of a UDP-galactose/glucose epimerase 3 (OsUGE3) in rice growth and salt tolerance by characterizing its overexpressing plants (OsUGE3-OX) and loss-of-function mutants (uge3). The OsUGE3-OX plants showed improvements in biomass production and mechanical strength, whereas uge3 mutants displayed growth defects. The OsUGE3 exhibits UDP-galactose/glucose epimerase activity that provides substrates for polysaccharides polymerization, consistent with the increased biosynthesis of cellulose and hemicelluloses and strengthened walls in OsUGE3-OX plants. Notably, the OsUGE3 is ubiquitously expressed and induced by salt treatment. The uge3 mutants were hypersensitive to salt and osmotic stresses, whereas the OsUGE3-OX plants showed improved tolerance to salt and osmotic stresses. Moreover, OsUGE3 overexpression improves the homeostasis of Na+ and K+ and induces a higher accumulation of hemicelluloses and soluble sugars during salt stress. Our results suggest that OsUGE3 improves biomass production, mechanical strength, and salt stress tolerance by reinforcement of cell walls with polysaccharides and it could be targeted for genetic modification to improve rice growth under salt stress.

Restoration of Attention by Rest in a Multitasking World: Theory, Methodology, and Empirical Evidence.

In this work, we evaluate the status of both theory and empirical evidence in the field of experimental rest-break research based on a framework that combines mental-chronometry and psychometric-measurement theory. To this end, we (1) provide a taxonomy of rest breaks according to which empirical studies can be classified (e.g., by differentiating between long, short, and micro-rest breaks based on context and temporal properties). Then, we (2) evaluate the theorizing in both the basic and applied fields of research and explain how popular concepts (e.g., ego depletion model, opportunity cost theory, attention restoration theory, action readiness, etc.) relate to each other in contemporary theoretical debates. Here, we highlight differences between all these models in the light of two symbolic categories, termed the resource-based and satiation-based model, including aspects related to the dynamics and the control (strategic or non-strategic) mechanisms at work. Based on a critical assessment of existing methodological and theoretical approaches, we finally (3) provide a set of guidelines for both theory building and future empirical approaches to the experimental study of rest breaks. We conclude that a psychometrically advanced and theoretically focused research of rest and recovery has the potential to finally provide a sound scientific basis to eventually mitigate the adverse effects of ever increasing task demands on performance and well-being in a multitasking world at work and leisure.

FRAGILE CULM 18 encodes a UDP-glucuronic acid decarboxylase required for xylan biosynthesis and plant growth in rice.

Although UDP-glucuronic acid decarboxylases (UXSs) have been well studied with regard to catalysing the conversion of UDP-glucuronic acid into UDP-xylose, their biological roles in grasses remain largely unknown. The rice (Oryza sativa) genome contains six UXSs, but none of them has been genetically characterized. Here, we reported on the characterization of a novel rice fragile culm mutant, fc18, which exhibited brittleness with altered cell wall and pleiotropic defects in growth. Map-based cloning and transgenic analyses revealed that the FC18 gene encodes a cytosol-localized OsUXS3 and is widely expressed with higher expression in xylan-rich tissues. Monosaccharide analysis showed that the xylose level was decreased in fc18, and cell wall fraction determinations confirmed that the xylan content in fc18 was lower, suggesting that UDP-xylose from FC18 participates in xylan biosynthesis. Moreover, the fc18 mutant displayed defective cellulose properties, which led to an enhancement in biomass saccharification. Furthermore, expression of genes involved in sugar metabolism and phytohormone signal transduction was largely altered in fc18. Consistent with this, the fc18 mutant exhibited significantly reduced free auxin (indole-3-acetic acid) content and lower expression levels of PIN family genes compared with wild type. Our work reveals the physiological roles of FC18/UXS3 in xylan biosynthesis, cellulose deposition, and plant growth in rice.

Differential effects of walking across visual cortical processing stages.

Perceptual processes are almost exclusively investigated and understood under marked movement restriction, while natural behaviour includes pronounced movements. Recent human studies have indicated a profound influence of body movement on early visual responses (e.g., evoked components around 100 msec in EEG, electroencephalogram). However, very little is known about the influence of free walking on later visual responses (e.g., responses related to visual selective attention in a later time window than the stimulus evoked N1 component). In the current study, we measured neural signals (EEG) and behavioural performance in a visual selective attention task while participants were standing or freely walking. The results showed that walking was associated with an amplification of early sensory-evoked potential as indicated by the N1 component. Interestingly, neural indexes of the succeeding processing stages of stimulus discrimination and identification, namely the N2pc component and alpha oscillations, and the eventual behavioural measures were comparable between standing and walking. Additionally, in both standing and walking conditions, an overall advantage in target processing for the right visual field was observed. Our work provides evidence that the early sensory processing is enhanced during locomotion while the succeeding processing steps in a later time window are not modulated by locomotion. We conclude that walking has differential effects across visual cortical processing stages.

ANXA1 (Annexin A1) regulated by MYC (MYC proto-oncogene) promotes the growth of papillary thyroid carcinoma.

Thyroid carcinoma is one of the most common endocrine malignancies, in which papillary thyroid carcinoma (PTC) is the main pathotype. ANXA1 plays a significant role in many cancer types, but how it works in PTC has not been identified. MYC is a common transcript factor involved in tumorigenesis, development, invasion, and metastasis. The relation between ANXA1 and MYC has not been proved in PTC. In this study, firstly, we analyzed the expression and prognostic value of ANXA1 in pan-cancer using the data from the UCSC database. Then we explore the role of ANXA1 in PTC, including expression, prognostic value, and immune infiltration. In addition, we evaluated the relation between ANXA1 and the transcription factor MYC. Finally, we identified the expression of ANXA1 and MYC and then evaluated their function associated with proliferation and apoptosis in PTC cell lines by CCK8 proliferation and flow cytometry apoptosis experiment. We found that ANXA1 is up-regulated in PTC comparing with normal patients. High expression of ANXA1 was associated with adverse overall survival of PTC. ANXA1 may be regulated by MYC to promote the proliferation of PTC. MYC may regulate the expression of ANXA and thus affect the proliferation of PTC.

Delusional thinking and action binding in healthy individuals.

Action binding is the effect that the perceived time of an action is shifted towards the action related feedback. A much larger action binding effect in schizophrenia compared to normal controls has been shown, which might be due to positive symptoms like delusions. Here we investigated the relationship between delusional thinking and action binding in healthy individuals, predicting a positive correlation between them. The action binding effect was evaluated by comparing the perceived time of a keypress between an operant (keypress triggering a sound) and a baseline condition (keypress alone), with a novel testing method that massively improved the precision of the subjective timing measurement. A positive correlation was found between the tendency of delusional thinking (measured by the 21-item Peters et al. delusions inventory) and action binding across participants after controlling for the effect of testing order between operant and baseline conditions. The results indicate that delusional thinking in particular influences action time perception and support the notion of a continuous distribution of schizotypal traits with normal controls at one end and clinical patients at the other end.

Effects of YAP1 and SFRP2 overexpression on the biological behavior of colorectal cancer cells and their molecular mechanisms.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide and has a high mortality rate. With the development of tumor molecular biology, more and more attention is being paid to the mechanisms of cell pathways in colorectal carcinogenesis, such as the Hippo/Yes-associated protein 1 (YAP1) and Wnt/ß-catenin signaling pathways. The abnormal expression of YAP1 and ß-catenin have been reported in CRC, and can lead to excessive cell proliferation, and eventually, tumor formation. Secreted frizzled-related protein 2 (SFRP2) levels have been found to be decreased in a variety of cancers, and SFRP2 is an antagonist that binds directly to Wnt signal. At present, the molecular basis of colorectal tumors is still not fully understood. In the present study, we sought to identify the molecular mechanisms underlying YAP1 and SFRP2 in the development of CRC. METHODS: We constructed CRC cell lines that stably overexpressed YAP1 and SFRP2 using lentivirus packaging and cell infection. The levels of expression of the proteins were evaluated by western blot and immunofluorescence assays. Protein complex immunoprecipitation (Co-IP) was used to detect the interaction between YAP1, SFRP2, and ß-catenin. The functional roles of YAP1 and SFRP2 in CRC was determined by a Cell Counting Kit-8 (CCK8) proliferation assay and flow cytometric apoptosis assay. RESULTS: The data of the present study showed that the overexpression of SFRP2 promoted the expression of YAP1 and ß-catenin protein, and the overexpression of YAP1 promoted the expression of ß-catenin protein. YAP1 overexpression promoted cell proliferation, while SFRP2 overexpression inhibited cell proliferation and promoted cell apoptosis. CONCLUSIONS: Our findings showed that the expression of YAP1, SFRP2, and ß-catenin is correlated in CRC cells. The Hippo pathway and Wnt pathway interact with each other in the pathogenesis of CRC, and YAP1 and SFRP2 are involved in the formation and development of CRC.

Yes-associated protein expression is associated with poor prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. The aim of the present study was to investigate the expression of yes-associated protein (YAP) in CRC tissues, and to determine the relationship between the expression levels of YAP and the clinicopathological characteristics and prognosis of patients with CRC. Bioinformatics analysis was conducted to examine the expression of YAP and its correlation with clinicopathological characteristics and key genes, using functional enrichment analysis. Immunohistochemistry was used to detect YAP expression in 181 CRC tissue samples and 30 normal colorectal mucosa samples. Western blotting and reverse transcription-quantitative PCR were performed to detect the expression of YAP and ß-catenin in CRC cells, and cellular proliferation was assessed using a Cell Counting Kit-8 assay. Finally, apoptosis was analyzed using flow cytometry. Immunohistochemical staining indicated that the positive expression rate of YAP in CRC tissues was 73.5%, which was significantly higher than that in normal colorectal mucosa samples. The expression of YAP in CRC was associated with histological differentiation, lymph node metastasis and Duke's stage. However, no significant associations were observed between YAP expression and age, sex and T stage. Downregulation of YAP promoted the proliferation and the inhibited apoptosis of CRC cells, and YAP expression was positively correlated with that of ß-catenin in both CRC tissues and cells. Furthermore, YAP expression was upregulated in CRC tissues, which was correlated with tumor progression and prognosis. Therefore, YAP expression may be used as an independent predictor of poor prognosis in patients with CRC, and the underling molecular mechanism may be associated with the combined effect of Hippo and Wnt/ß-catenin signaling.

Breast metastasis from EGFR/ALK negative lung adenocarcinoma: A case report.

INTRODUCTION: Lung adenocarcinoma is the most common type of lung cancer. Distant metastasis of lung adenocarcinoma often occurs in multiple organs. The common metastasis sites of lung cancer include the lungs, brain, bones, adrenal glands, and lymph nodes; however, breast metastasis is rare. PATIENT CONCERNS: In this report, we describe a case of breast metastasis from lung adenocarcinoma. A 55-year-old woman reported left breast pain for more than 1 month. DIAGNOSIS: Based on imaging, pathological examination, and immunohistochemical examination, the diagnosis of breast metastasis from lung adenocarcinoma was confirmed. Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement were not detected by next-generation sequencing. INTERVENTIONS: The patient was treated with six courses of a combination of albumin-bound paclitaxel, cisplatin, and bevacizumab over 21 days. OUTCOMES: After six cycles of palliative chemotherapy, her left breast pain and swelling subsided; in addition, her serum CA12-5, CYFRA, and CEA levels normalized by April 2019. PR status was evaluated as per the RECIST 1.1 criteria. The patient developed brain metastases 3 months later and died due to multiple organ failure. CONCLUSION: The possibility of breast metastasis should be considered in patients with existing malignant tumors and breast pain. Clinical and imaging examinations are helpful for diagnosis, and pathological and immunohistochemical analyses are the most important diagnostic tools.

FoxM1 is Upregulated in Osteosarcoma and Inhibition of FoxM1 Decreases Osteosarcoma Cell Proliferation, Migration, and Invasion.

BACKGROUND: Osteosarcoma (OS) is a highly aggressive bone malignancy that is mostly diagnosed in children and young adults. Increasing evidence indicates that the transcription factor Forkhead Box M1 (FoxM1) plays a key role in the pathogenesis of various tumors. However, the function of FoxM1 in OS has not been clearly elucidated. METHODS: In the present study, we first analyzed the expressions of FoxM1 in human OS and myositis ossificans (MO, included as a control) tissues by immunohistochemistry. To investigate the functional significance of FoxM1 in OS tumorigenesis, we examined the effects of FoxM1 downregulation in MG-63 and HOS-MNNG cells by either short hairpin RNA (shRNA)-mediated gene silencing or treatment with thiostrepton, a specific FoxM1 inhibitor. RESULTS: FoxM1 was detected in 82.1% (55/67) of OS vs only 10% (2/20) of MO samples. High expressions of FoxM1 were also detected in three human OS cell lines (HOS-MNNG, MG-63, and U-2OS). FoxM1 downregulation significantly reduced MG-63 and HOS-MNNG cell proliferation, migration, and invasion as well as cell cycle arrest in the G2/M phase and increased apoptotic cell death. CONCLUSION: The present study demonstrated the critical role of FoxM1 in the pathogenesis of OS. Therefore, FoxM1 may serve as a potential therapeutic target for the treatment of OS.