Vision matters for shape representation: Evidence from sculpturing and drawing in the blind.

Shape is a property that could be perceived by vision and touch, and is classically considered to be supramodal. While there is mounting evidence for the shared cognitive and neural representation space between visual and tactile shape, previous research tended to rely on dissimilarity structures between objects and had not examined the detailed properties of shape representation in the absence of vision. To address this gap, we conducted three explicit object shape knowledge production experiments with congenitally blind and sighted participants, who were asked to produce verbal features, 3D clay models, and 2D drawings of familiar objects with varying levels of tactile exposure, including tools, large nonmanipulable objects, and animals. We found that the absence of visual experience (i.e., in the blind group) led to stronger differences in animals than in tools and large objects, suggesting that direct tactile experience of objects is essential for shape representation when vision is unavailable. For tools with rich tactile/manipulation experiences, the blind produced overall good shapes comparable to the sighted, yet also showed intriguing differences. The blind group had more variations and a systematic bias in the geometric property of tools (making them stubbier than the sighted), indicating that visual experience contributes to aligning internal representations and calibrating overall object configurations, at least for tools. Taken together, the object shape representation reflects the intricate orchestration of vision, touch and language.

Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits.

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.

Alterations of the cerebral microstructure in patients with noise-induced hearing loss: A diffusion tensor imaging study.

OBJECTIVE: To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). METHOD: Overall, 122 patients with NIHL (mild [MP, n = 79], relatively severe patients [including moderate and severe; RSP, n = 32], and undetermined [lost to follow-up, n = 11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini-Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract-based spatial statistics and region of interest (ROI) analysis were used for assessment. RESULTS: The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p < .05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p < .05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p < .05), whereas the THI scores were positively correlated with the hearing threshold (p < .05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) for the three groups (p < .05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto-pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C-H) of the MP and RSP than in those of the HCs (p < .05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p < .05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p > .05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C-H for the three groups (p < .05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p < .05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p < .05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p < .05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p < .05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p < .05). CONCLUSION: The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

Tribological Properties of Groove-Textured Ti-6Al-4V Alloys with Solid Lubricants in Dry Sliding against GCr15 Steel Balls.

A nanosecond laser is used to fabricate groove-patterned textures on the upper surface of Ti-6Al-4V alloys, and then molybdic sulfide solid lubricants are filled into the grooves. The treated titanium alloy is subjected to friction and wear tests. The tribological performances of Ti-6Al-4V alloys are evaluated, and the wearing mechanism is analyzed. The combination of solid lubricants and surface texturing can effectively reduce the frictional coefficient and reduce the adhesion of Ti-6Al-4V materials on the steel balls for friction. The main wearing mechanism is the adhesive wear of the Ti-6Al-4V alloy and the adhesion of Ti-6Al-4V alloy materials on the surface of the steel balls. During the friction process, solid lubricants are squeezed from the grooves and coated at the friction interface to form a solid lubrication layer. This is the important reason why the combination of surface texturing and solid lubricants can improve the friction properties of titanium alloys effectively. The combination of solid lubricants and laser surface texturing provides an effective alternative way to improve the tribological properties of titanium alloy materials.

Alternaphenol B2, a new IDH1 inhibitor from the coral-derived fungus Parengyodontium album SCSIO SX7W11.

A new aromatic polyketide, alternaphenol B2 (1), and four known compounds (2-5) were isolated from the coral-derived fungus Parengyodontium album SCSIO SX7W11. Their structures were elucidated by high-resolution mass spectrometry, 1D and 2D NMR spectroscopy and comparison with reported literatures. Compounds 1 and 2 exhibited selective inhibitory activity against isocitrate dehydrogenase mutant R132H (IDH1m), with IC50 values of 41.9 and 27.7 µM, respectively. Our findings thus provide a fresh incentive for investigation on IDH1m inhibitors as lead compounds for cancer treatment.

The value of dual-energy computed tomography (DECT) in the diagnosis of urinary calculi: a systematic review and meta-analysis of retrospective studies.

Objective: Dual-energy computed tomography (DECT) imaging technology opens a new idea and method for analyzing stone composition, which can obtain several quantitative parameters reflecting tissue-related information and energy images different from traditional images. However, the application of DECT in diagnosing urinary calculi remains unknown. This study aims to evaluate the value of DECT in diagnosing urinary calculi by meta-analysis. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to articles published from the establishment of the databases to April 18, 2023. We reviewed the articles on the diagnosis of urinary calculi detected by DECT, established standards, screened the articles, and extracted data. Two researchers carried out data extraction and the Cohen's unweighted kappa was estimated for inter-investigator reliability. The quality of the literature was evaluated by the diagnostic test accuracy quality evaluation tool (QUADAS-2). The heterogeneity and threshold effects were analyzed by Meta-Disc 1.4 software, and the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic ratio were calculated. The combined receiver-operating characteristic (ROC) curve was drawn, and the value of DECT in the diagnosis of urinary calculi was evaluated by the area under the curve (AUC). The meta-analysis was registered at PROSPERO (CRD42023418204). Results: One thousand and twenty-seven stones were detected in 1,223 samples from 10 diagnostic tests. The analyzed kappa alternated between 0.78-0.85 for the document's retrieval and detection procedure. The sensitivity of DECT in the diagnosis of urinary calculi was 0.94 (95% CI [0.92-0.96]). The positive likelihood ratio (PLR) of DECT in the diagnosis of urinary stones was 0.91 (95% CI [0.88-0.94]), and the negative likelihood ratio (NLR) was 0.08 (95% CI [0.05-0.11]). The specificity of DECT for detecting urinary calculi was 0.91 (95% CI [0.88-0.94]). The area under the curve of the summary receiver operator characteristic (SROC) was 0.9875. The sensitivity of dual-energy CT in the diagnosis of urinary calculi diameter <3 mm was 0.94 (95% CI [0.91-0.96]). The PLR of DECT in the diagnosis of urinary stones diameter <3 mm was 10.79 (95% CI [5.25 to 22.17]), and the NLR was 0.08 (95% CI [0.05-0.13]). The specificity of DECT for detecting urinary calculi <3 mm was 0.91 (95% CI [0.87-0.94]). The SROC was 0.9772. Conclusion: The DECT has noble application value in detecting urinary calculi.

T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

Spontaneous acute epidural hematoma secondary to skull and dural metastasis of hepatocellular carcinoma: A case report.

BACKGROUND: The skull and dura are uncommon sites for the metastasis of hepatocellular carcinoma (HCC). Spontaneous acute epidural hematoma (AEDH) is also very rare. We report here a spontaneous AEDH secondary to skull and dural metastasis of HCC. This case is extremely rare. CASE SUMMARY: A 48-year-old male patient with a history of HCC developed unconsciousness spontaneously. Head computed tomography showed "a huge AEDH in the left parietal and occipital region with osteolytic destruction of the left parietal bone. Emergent operation was performed to evacuate the hematoma and resect the lesion. Pathological study revealed that the lesion was the metastases from HCC. The patient died of lung infection, anemia, and liver failure 3 wk after operation. CONCLUSION: Spontaneous AEDH caused by hepatocellular carcinoma (HCC) dural and skull metastases is extremely rare, the outcome is poor. So, early diagnosis is important. If the level of AFP does not decrease with the shrinkage of intrahepatic lesions after treatment, it is necessary to be alert to the existence of extrahepatic metastases. Since most of the patients had scalp and bone masses, physicians should pay attention to the patient's head palpation. Once a patient with the history of HCC had sudden neurological dysfunction, the possibility of spontaneous AEDH caused by the skull and dura mater metastases should be considered. Since hemorrhage is common in the skull HCC metastases, for patients with spontaneous AEDH accompanied by skull osteolytic lesions, it is also necessary to be alert to the possibility of HCC. For AEDH secondary to HCC metastases, early diagnosis and timely treatment are critical to improve the patients' outcomes.

miR-223-3p contributes to suppressing NLRP3 inflammasome activation in Streptococcus equi ssp. zooepidemicus infection.

Streptococcus equi subsp. zooepidemicus (SEZ) is an essential pathogen in a range of species, causing a worldwide variety of diseases, such as meningitis, endocarditis, and septicaemia. Studies have shown that microRNAs (miRNAs), which regulate target genes at the post-transcriptional level, play an important regulatory role in the organism. In this study, the infection of J774A.1 murine macrophages with SEZ up-regulated NLRP3 inflammasome and downstream pathways accompanied by miR-223-3p down-regulation. Through computational prediction and experimental confirmation, we have shown that miR-223-3p directly targets the NLRP3 mRNA. Consequently, overexpression of miR-223-3p suppressed NLRP3 inflammasome activation and downstream pathways in response to SEZ infection. The miR-223-3p inhibitor exhibited the opposite effect, causing hyperactivation of NLRP3 inflammation activation and downstream pathways. Additionally, we further demonstrated that miRNA-223-3p inhibited the secretion of IL-1ß and IL-18 by regulating the NLRP3/caspase-1 pathway. Furthermore, intravenous administration of miR-223-3p significantly decreased inflammation in mice in response to SEZ. In conclusion, our results demonstrated that miR-223-3p contributes to suppressing the NLRP3 inflammasome activation in SEZ infection, contributing novel evidence to identify a therapeutic target for treating SEZ.

RID serve as a more appropriate measure than phenol sulfuric acid method for natural water-soluble polysaccharides quantification.

With structural diversity of water-soluble polysaccharides, their precise quantitative analysis by phenol­sulfuric acid method becomes more difficult and challenging. In this study, the quantification analysis of dextran and glucose in phenol sulfuric acid method was compared in this paper. When the concentration is below 90 µg/mL, the quantification of glucose is close to theoretical value, however, glucose derivatives have significantly different absorption. Later, quantitative factors of water-soluble polysaccharide in RID measurement were investigated. The optimum temperature was 40 °C and linear range was 0.3125-10.0 mg/mL in RID for dextrans (1.0-500 kDa) and glucose derivatives. Method validation studies of the RID method were further performed and compared to conventional phenol sulfuric acid method, which demonstrated that RID measurement is more reliable and satisfactory method. The intervention of water-soluble impurity in RID response should be well control below 6% (w/w). By comparison, the RID measurement could well alleviate drawbacks in phenol­sulfuric acid method.

Study on Preparation and Grinding Performance of Vitrified Bond CBN Grinding Wheel with Controllable Porosity.

Vitrified bond cubic boron nitride (CBN) grinding wheel specimens with controllable porosity were prepared by regulating the pore former dextrin content and varying the forming pressure, and the performance of the grinding camshaft was studied. The porosity of the specimens increases with the increase in dextrin content, and decreases first and then increases with the increase in the forming pressure. The grinding experiments show that the dextrin content is negatively correlated with the grinding force and grinding temperature, while the grinding force and grinding temperature of the specimens increase and then decrease with the increase in the forming pressure. When we observe and measure the grinding surface of the specimen and workpiece, we see that the surface roughness of the specimen after grinding is smaller than that before grinding. In addition, the greater the porosity of the specimen, the rougher the surface of the workpiece after grinding.

Social and emotion dimensional organizations in the abstract semantic space: the neuropsychological evidence.

An essential aspect of human cognition is supported by a rich reservoir of abstract concepts without tangible external referents (e.g., "honor", "relationship", "direction"). While decades of research showed that the neural organization of conceptual knowledge referring to concrete words respects domains of evolutionary salience and sensorimotor attributes, the organization principles of abstract word meanings are poorly understood. Here, we provide neuropsychological evidence for a domain (sociality) and attribute (emotion) structure in abstract word processing. Testing 34 brain-damaged patients on a word-semantic judgment task, we observed double dissociations between social and nonsocial words and a single dissociation of sparing of emotional (relative to non-emotional) words. The lesion profiles of patients with specific dissociations suggest potential neural correlates positively or negatively associated with each dimension. These results unravel a general domain-attribute architecture of word meanings and highlight the roles of the social domain and the emotional attribute in the non-object semantic space.

Reliability optimization of process parameters for marine diesel engine block hole system machining using improved PSO.

The processing quality of the block hole system affects the working performance of the marine diesel engine block directly. Choosing an appropriate combination of process parameters is a prerequisite to improving the accuracy of the block hole system. Uncertain fluctuations of process parameters during the machining process would affect the process reliability of the block hole system, resulting in an ultra-poor accuracy. For this reason, the RBF method is used to establish the relationship between the verticality of the cylinder hole and process parameters, including cutting speed, depth of cut, and feed rate. The minimum cylinder hole verticality is taken as the goal and the process reliability constraints of the cylinder hole are set based on Monte Carlo, a reliability optimization model of processing parameters for cylinder hole is established in this paper. Meanwhile, an improved particle swarm algorithm was designed to solve the model, and eventually, the global optimal combination of process parameters for the cylinder hole processing of the diesel engine block in the reliability stable region was obtained.

Lumbar Disc Herniation is a Nonnegligible Factor for the Degeneration of Sacroiliac Joints.

BACKGROUND: Sacroiliac joint (SIJ) abnormality is a potential source of low back pain (LBP), therefore numerous patients receive various treatments because of the degenerative changes of SIJ. However, the outcome is unfavorable for patients because these morphologic alterations are common but not the origins of LBP. Previous studies revealed lumbar fusion and transitional vertebra increased the prevalence of degeneration of SIJ. Lumbar disc herniation (LDH) is one of the most common lumbar diseases, but there is no study regarding the relationship between LDH and SIJ degradation. OBJECTIVES: The aim of this study was to investigate the severity of SIJ degeneration in patients with LBP with LDH. The relationship between degenerative changes of SIJ and LDH was also assessed. STUDY DESIGN: Retrospective observational study. SETTING: This study was conducted in 2 medical centers located in southeast and midwest China, respectively. METHODS: Lumbar and pelvic computed tomography (CT) scans of patients with LDH (LDH group) from January 2016 to May 2020 were reviewed using a picture archiving and communication system. The control group was age, gender, and body mass index-matched patients with LBP without LDH. Patients underwent whole abdomen and pelvic CT examinations due to non-musculoskeletal disorders. Scores of SIJ degeneration were compared between patients with LDH and the control group. Differences in SIJ degeneration among patients with LDH with diverse characteristics, symptoms, and complications were also evaluated. Univariate and multivariate linear mixed model (LMM) was chosen to identify the factors associated with SIJ degeneration. RESULTS: CT examinations of 782 patients with LDH were assessed, whereas 223 patients were in the control group. The SIJ degeneration score of the LDH group and control group were 6.00 (5.00) and 3.00 (4.00) (P < 0.05). Age and whether patients suffered from LDH were included in the LMM, which involved all reviewed patients (P < 0.05). Regarding the characteristics of LDH, the patients with more herniated discs had more severe SIJ degeneration. The score of SIJ degradation in patients with upper LDH was significantly higher than the other patients with LDH (12.00 [4.00] vs. 6.00 [4.00]; P < 0.05). Similarly, more significant SIJ degeneration was observed in patients with LDH who had secondary lumbar spinal stenosis (10.00 [4.00] vs. 5.00 [4.00]; P < 0.05). The scores of SIJ degradation were significantly greater in patients with LDH with sciatica, numbness, weakness, and/or cauda equina syndrome. Age and LDH were identified as associated factors for more serious degeneration of SIJ among patients with LDH. LIMITATIONS: The main limitation of this study was the retrospective observational nature. Hence our study described that SIJ degeneration was relevant to LDH, but the causal relationship was uncertain. Magnetic resonance imaging was not chosen in this study. CONCLUSIONS: The SIJ degeneration in patients with LDH was more serious than in individuals without LDH. SIJ degeneration was more significant in patients with LDH with more pathological alterations, symptoms, and complications. Age and LDH relate to SIJ degeneration. Therefore the diagnosis and selection of treatment for SIJ changes should comprehensively consider the coexistence of LDH.

A new species of the genus Euthystiroides Zhang, Zheng amp; Ren, 1995 fromHeilongjiang, China (Orthoptera, Acridoidea, Acrididae).

A new species of the genus Euthystiroides Zhang, Zheng Ren, 1995 i.e. Euthystiroides heilongjiangensis sp. nov is described from Heilongjiang, China. The new species is allied to E. dalianensis Zhang, Zheng Ren, 1995, but differs from latter by head shorter than pronotum distinctly and without black stripe in the middle, tegmina of male narrower, length 4.0 times width; length of interspace 1.9 times minimum width in mesosternum and width of epiphallus almost equal to high.

The Influence of Tool Rake Surface Geometry on the Hard Turning Process of AISI52100 Hardened Steel.

The hard turning process has been widely used in the field of hard material precision machining because of its high efficiency, low processing residual stress, and low environmental pollution. Due to its undesirably processing quality, it is still not a substitute for traditional grinding, so many studies have reported that the process has been optimized. However, there has been little research on the geometry optimization of hard cutting tools, which have a great influence on the traditional machining process. In this paper, two tools with different rake face shapes are designed. The finite element analysis method is used to compare their performance with a conventional plane tool while turning hardened steel. The results show that the cutting performance of the designed tool T1 and T2 (chip morphology, cutting force, and cutting temperature) and the quality of the machined surface are improved compared with the tool. The cutting force decreased by 12.72% and 14.74%, the cutting temperature decreased by 7.56% and 9.01%, respectively, and the surface residual stress decreased by 26.56% and 28.66%.

Finding the vanished self: Perspective modulates neural substrates of self-reflection in Buddhists.

Asians' self-views are flexible and influenced by short-term situational and long-term cultural factors. Due to the long-term religious cultural influence of Chinese Buddhism, Buddhists showed no self-advantage in behavioral and neural level in many previous studies. However, it is unclear whether Chinese Buddhists really have no self-awareness or self-concept. The beliefs of illusionary self and thinking of others first might suggest that the self of Buddhists comes from others' perspective. The present study examined the self of Buddhists in first- and third-person perspective through the self-referential processing paradigm, comparing the behavioral and neural difference when they make self-, friend- and famous-judgment. The behavioral data showed that there were no different recognition ratios between self-, friend-, and famous-processing for participants in first- and third-person perspective. However, the neural results showed that people in third-person perspective group showed significant difference between self- and famous-processing in ventral medial prefrontal cortex, whereas people in first-person perspective group did not show any significant difference in activation between self-, friend-, and famous-processing in these regions. These findings suggested that Buddhists have self-referential processing only in third-person perspective, not in first-person perspective. This study provides neuroimaging evidence for the influence of perspective on Buddhists' self-reflection, and provide empirical evidence supporting and extending culture as situated cognition model of Asia by considering perspective factor.

Lower genomic stability of induced pluripotent stem cells reflects increased non-homologous end joining.

BACKGROUND: Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) share many common features, including similar morphology, gene expression and in vitro differentiation profiles. However, genomic stability is much lower in iPSCs than in ESCs. In the current study, we examined whether changes in DNA damage repair in iPSCs are responsible for their greater tendency towards mutagenesis. METHODS: Mouse iPSCs, ESCs and embryonic fibroblasts were exposed to ionizing radiation (4 Gy) to introduce double-strand DNA breaks. At 4 h later, fidelity of DNA damage repair was assessed using whole-genome re-sequencing. We also analyzed genomic stability in mice derived from iPSCs versus ESCs. RESULTS: In comparison to ESCs and embryonic fibroblasts, iPSCs had lower DNA damage repair capacity, more somatic mutations and short indels after irradiation. iPSCs showed greater non-homologous end joining DNA repair and less homologous recombination DNA repair. Mice derived from iPSCs had lower DNA damage repair capacity than ESC-derived mice as well as C57 control mice. CONCLUSIONS: The relatively low genomic stability of iPSCs and their high rate of tumorigenesis in vivo appear to be due, at least in part, to low fidelity of DNA damage repair.