Influential factors on urine EV DNA methylation detection and its diagnostic potential in prostate cancer

The value of Extracellular vesicles (EVs) diagnostic markers is widely recognized. However, current research on EV DNA remains limited. This study investigates the biological properties, preprocessing factors, and diagnostic potential of EV DNA. We found that DNA positive vesicles account for 23.3% ± 6.7% of the urine total EV, with a large amount of DNA attached to the outside. EV DNA fragments are large, there is no significant effect on uEV DNA when store urine less than 6 h at 4°C. In addition, the influence of different EV extraction methods on methylation detection is also minor. More importantly, RASSF1A methylation in urine total EV DNA can distinguish between PCa and BPH, with an AUC of 0.874. Our results suggest the potential of urine EV DNA as a novel marker for PCa diagnosis. This provides a new idea for the study of urinary tumor markers

CRISPR-Cas9-Based Functional Interrogation of Unconventional Translatome Reveals Human Cancer Dependency on Cryptic Non-Canonical Open Reading Frames

Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. To fill this gap and systematically identify colorectal cancer (CRC) dependency on non-canonical ORFs, we apply an integrative multiomic strategy, combining ribosome profiling and a CRISPR-Cas9 knockout screen with large-scale analysis of molecular and clinical data. Many such ORFs are upregulated in CRC compared to normal tissues and are associated with clinically relevant molecular subtypes. We confirm the in vivo tumor-promoting function of the microprotein SMIMP, encoded by a primate-specific, long noncoding RNA, the expression of which is associated with poor prognosis in CRC, is low in normal tissues and is specifically elevated in CRC and several other cancer types. Mechanistically, SMIMP interacts with the ATPase-forming domains of SMC1A, the core subunit of the cohesin complex, and facilitates SMC1A binding to cis-regulatory elements to promote epigenetic repression of the tumor-suppressive cell cycle regulators encoded by CDKN1A and CDKN2B. Thus, our study reveals a cryptic microprotein as an important component of cohesin-mediated gene regulation and suggests that the \u27dark\u27 proteome, encoded by cryptic non-canonical ORFs, may contain potential therapeutic or diagnostic targets

Diurnal microstructural variations in healthy adult brain revealed by diffusion tensor imaging.

Biorhythm is a fundamental property of human physiology. Changes in the extracellular space induced by cell swelling in response to the neural activity enable the in vivo characterization of cerebral microstructure by measuring the water diffusivity using diffusion tensor imaging (DTI). To study the diurnal microstructural alterations of human brain, fifteen right-handed healthy adult subjects were recruited for DTI studies in two repeated sessions (8∶30 AM and 8∶30 PM) within a 24-hour interval. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial (λ//) and radial diffusivity (λ⊥) were compared pixel by pixel between the sessions for each subject. Significant increased morning measurements in FA, ADC, λ// and λ⊥ were seen in a wide range of brain areas involving frontal, parietal, temporal and occipital lobes. Prominent evening dominant λ⊥ (18.58%) was detected in the right inferior temporal and ventral fusiform gyri. AM-PM variation of λ⊥ was substantially left side hemisphere dominant (p<0.05), while no hemispheric preference was observed for the same analysis for ADC (p = 0.77), λ// (p = 0.08) or FA (p = 0.25). The percentage change of ADC, λ//, λ⊥, and FA were 1.59%, 2.15%, 1.20% and 2.84%, respectively, for brain areas without diurnal diffusivity contrast. Microstructural variations may function as the substrates of the phasic neural activities in correspondence to the environment adaptation in a light-dark cycle. This research provided a baseline for researches in neuroscience, sleep medicine, psychological and psychiatric disorders, and necessitates that diurnal effect should be taken into account in following up studies using diffusion tensor quantities

A De Novo sSMC (22) Characterized by High-Resolution Chromosome Microarray Analysis in a Chinese Boy with Cat-Eye Syndrome

We report a 15-year-old boy with cat-eye syndrome (CES) without short stature or intellectual disorder. The boy was confirmed by cytogenetic and high-resolution chromosome microarray analysis (CMA). The G-banding karyotype confirmed the de novo of the patient. Also, the CMA result showed 1.76 Mb tetrasomy of proximal 22Q11.1 ⟶ 22Q11.21 consistent with CES {arr22q11.1q11.21 (16,888,899–18,644,241) X4}, a typical small type I CES chromosome. The patient has many of the basic characteristics of CES; however, he is taller than his peers instead of shorter. It is rarely reported in the past since short stature is a common feature of this syndrome. Furthermore, the boy has no intellectual disorder and attends a normal school since he was six-year-old. What bothered him most were recurrent respiratory infections, retromicrognathia, and heart defects

DataSheet1_Influential factors on urine EV DNA methylation detection and its diagnostic potential in prostate cancer.zip

The value of Extracellular vesicles (EVs) diagnostic markers is widely recognized. However, current research on EV DNA remains limited. This study investigates the biological properties, preprocessing factors, and diagnostic potential of EV DNA. We found that DNA positive vesicles account for 23.3% ± 6.7% of the urine total EV, with a large amount of DNA attached to the outside. EV DNA fragments are large, there is no significant effect on uEV DNA when store urine less than 6 h at 4°C. In addition, the influence of different EV extraction methods on methylation detection is also minor. More importantly, RASSF1A methylation in urine total EV DNA can distinguish between PCa and BPH, with an AUC of 0.874. Our results suggest the potential of urine EV DNA as a novel marker for PCa diagnosis. This provides a new idea for the study of urinary tumor markers.</p

Functional MRI Investigation of Ultrasound Stimulation at ST 36

Background. Clinical and experimental data suggest that ultrasound stimulation (US) at acupoints can produce similar effective treatment compared to manual acupuncture (MA). Although the brain activation to MA at acupoints is investigated by numerous studies, the brain activation to US at acupoints remains unclear. Methods. In the present work, we employed task state functional magnetic resonance imaging (fMRI) to explore the human brain’s activation to US and MA at ST 36 (Zusanli) which is one of the most commonly used acupoints in acupuncture-related studies. 16 healthy subjects underwent US and MA procedures in an interval of more than one week. On-off block design stimulation was used for the recording of fMRI-related brain patterns. Results. Both US and MA at ST 36 produced activations in somatosensory and limbic/paralimbic regions (postcentral gyrus, insula, middle prefrontal cortex, and anterior cingulate cortex). Only US at ST 36 produced a significant signal increase in the inferior parietal lobule and decrease in the posterior cingulate cortex, whereas MA at ST 36 produced a significant signal increase in the lentiform nucleus and cerebellum. Conclusions. Our results indicate that US may be a possible noninvasive alternative method to MA due to its similar activation patterns

DataSheet2_Influential factors on urine EV DNA methylation detection and its diagnostic potential in prostate cancer.ZIP

The value of Extracellular vesicles (EVs) diagnostic markers is widely recognized. However, current research on EV DNA remains limited. This study investigates the biological properties, preprocessing factors, and diagnostic potential of EV DNA. We found that DNA positive vesicles account for 23.3% ± 6.7% of the urine total EV, with a large amount of DNA attached to the outside. EV DNA fragments are large, there is no significant effect on uEV DNA when store urine less than 6 h at 4°C. In addition, the influence of different EV extraction methods on methylation detection is also minor. More importantly, RASSF1A methylation in urine total EV DNA can distinguish between PCa and BPH, with an AUC of 0.874. Our results suggest the potential of urine EV DNA as a novel marker for PCa diagnosis. This provides a new idea for the study of urinary tumor markers.</p

Diurnal variations of λ_⊥ map.

<p>Brain regions with significant diurnal variations of λ_⊥ between AM and PM (P<0.05, cluster size >168 voxels). The results are projected on the Ch2.nii template. The left side of the image is the right side of the brain (radiological representation). Color bar indicates t value (Red-yellow, AM >PM, blue-green, AM</p

Diurnal variations of FA map.

<p>Parametric map superimposed on the Ch2.nii template locates the neuroanatomical regions with significantly increased morning fractional anisotropy (FA) relative to the evening measurement (P<0.05, cluster size >168 voxels). The left hand side of the image is the right side of the brain (radiological representation). Color bar indicates t value scale (Red-yellow, AM >PM, blue-green, AM</p