Application of conventional IVF during preimplantation genetic testing for aneuploidies: a feasibility study.

RESEARCH QUESTION: Is it feasible to apply conventional IVF to couples undergoing preimplantation genetic testing for aneuploidies (PGT-A) with non-severe male infertility? DESIGN: The last wash fluid of biopsied trophectoderm (TE) cells was collected for whole genome amplification (WGA). A method was developed to determine parental contamination. Using single-nucleotide polymorphism (SNP) analysis, two standard curves were established; further mixtures were used for verification. Finally, 29 WGA products from couples undergoing conventional IVF were used to evaluate parental contamination. RESULTS: The WGA results of the last wash fluid of biopsied TE cells revealed almost no free DNA. By adopting two strategies based on maternally and paternally biased SNP in the mixture, data from bioinformatics analysis were analysed to determine the relationship between maternal (Index M) and paternal (Index F) bias statistics. Two standard curves were successfully established based on these indices that allowed the prediction of maternal and parental contamination, which correlated well with actual ratios of known composition mixtures during validation. The average contamination level was 10.6% determined from 10 WGA products that featured maternal contamination, whereas that of the other 19 products that featured paternal contamination was less than 10%. CONCLUSIONS: This study confirmed the feasibility of applying conventional IVF to couples undergoing PGT-A with non-severe male infertility.

Resveratrol Enhances the Radiosensitivity by Inducing DNA Damage and Antitumor Immunity in a Glioblastoma Rat Model under 3 T MRI Monitoring.

Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3+CD8+T cells and IFN-γ +CD8+T cells were enhanced, while (CD4+CD25+Foxp3)/CD4+T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN-γ levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.

Perceptual confidence of visual stimulus features is associated with duration perception.

It has been shown that the perceived duration of an object in the subsecond range is closely associated with its nontemporal perceptual properties, the mechanism under which remains unclear. Previous studies have revealed a modulatory effect of early visual feature processing on the apparent duration. Here, we further examined the relationship between perceptual confidence and subjective time by asking participants to simultaneously perform temporal and nontemporal perceptual judgments. The results revealed a significant effect on confidence levels. When participants' confidence in judging the coherent motion direction or relative dot numerosity increases, their perceived duration of the stimulus also appears longer. These results are discussed in the context of perceptual evidence accumulation and evaluation for the decision-making of perceptual properties. They suggest a profound contribution of object processing to the computation of subjective time and provide further insights into the mechanism of event timing.

Factors influencing mosaicism: a retrospective analysis.

RESEARCH QUESTION: What factors affect the incidence of mosaic embryos resulting from assisted reproductive technology? DESIGN: A retrospective analysis of data from preimplantation genetic testing for aneuploidies in 544 couples was conducted using data from an electronic medical record database. RESULTS: Of 1910 embryos studied, 127 (6.6%) were mosaic. In multivariable logistic regression analysis, mosaicism incidence increased in embryos from IVF versus intracytoplasmic sperm injection (ICSI) (odds ratio [OR] 4.560, 95% confidence interval [CI] 2.800-7.424, P < 0.001), and in embryos from abnormal versus normal semen (OR 3.496, 95% CI 2.455-4.979, P < 0.001). Embryos tested using SurePlex 24Sure had lower mosaicism percentages than those tested using MALBAC-NGS and PicoPLEX GenetiSure (OR 2.726, 95% CI 1.532-4.852, P = 0.001; OR 2.389, 95% CI 1.537-3.711, P < 0.001, respectively). CONCLUSIONS: Semen quality, fertilization method and detection system are independent factors associated with embryonic mosaicism.

Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome.

Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advanced CRC and explore possible new therapeutic strategies, we herein conducted integrated proteomics and metabolomics analyses of 40 serum samples collected from 20 advanced CRC patients before and after treatment. The mass spectrometry-based proteomics analysis was performed under data-independent acquisition (DIA), and the metabolomics analysis was performed by ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). Trace elements including Mg, Zn, and Fe were measured by inductively coupled plasma spectrometry (ICP-MS) analysis. Four of the 20 patients had progressive disease (PD) after treatment, and clinical test results indicated that they all had impaired liver functions. In the proteomics analysis, 64 proteins were discovered to be significantly altered after treatment. These proteins were enriched in cancer-related pathways and pathways participating immune responses, such as MAPK signaling pathway and complement/coagulation cascades. In the metabolomics analysis, 128 metabolites were found to be significantly changed after treatment, and most of them are enriched in pathways associated with lipid metabolism. The cholesterol metabolism pathway was significantly enriched in both the proteomics and metabolomics pathway enrichment analyses. The concentrations of Mg in the serums of CRC patients were significantly lower than those in healthy individuals, which returned to the normal range after treatment. Correlation analysis linked key lipids, proteins, and Mg as immune modulators in the development of advanced CRC. The results of this study not only extended our knowledge on the molecular basis of advanced CRC but also provided potential novel therapeutic targets for CRC treatment.

[Application of mapping allele with resolved carrier status technique for preimplantation genetic testing in carriers with balanced chromosomal translocations].

OBJECTIVE: To assess the application value of mapping allele with resolved carrier status (MaReCs) technique for preimplantation genetic testing (PGT). METHODS: The characteristics of MaReCs for PGT and outcome of patients were retrospectively analyzed. RESULTS: Compared with those who could not use the technique, carriers who have used the MaReCs technique were younger, had significantly higher level of anti-Mullerian hormone, more antral follicles, occytes, mature occytes, biopsied embryos and euploid embryos, and lower risks for de novo chromosomal abnormality (P<0.05). It was necessary for couples with fewer oocytes, mature oocytes and balstocyst to preserve discarded embryos to facilitate the test. Carriers who have used the MaReCs technique had higher clinical pregnancy rate and abortion rate compared with those undergoing routine PGT, albeit no significant difference was found between the two groups (P> 0.05). Carriers undergoing MaReCs test could preferentially select embryos with normal chromosome structures for the transfer. CONCLUSION: Application of MaReCs has a prerequisite for having a minimum number of occytes and biopsied embryos and using discarded embryos sometimes. MaReCs is efficient for the detection of carrier status of embryos and attaining higher rate of pregnancy and live birth, which can significantly improve the outcome for couples carrying chromosomal translocations.

Integration of quantitative diffusion kurtosis imaging and prostate specific antigen in differential diagnostic of prostate cancer.

ABSTRACT: This study aimed to evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) and prostate-specific antigen (PSA) biomarkers in differentiating prostate cancer (PCa) and benign prostatic hyperplasia (BPH).A total of 43 cases of prostate diseases verified by pathology were enrolled in the present study. These cases were assigned to the BPH group (n = 20, 68.85±10.81 years old) and PCa group (n = 23, 74.13 ±â€Š7.37 years old). All patients underwent routine prostate magnetic resonance imaging and DKI examinations, and the mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA) values were calculated. Three serum indicators (PSA, free PSA [fPSA], and f/t PSA) were collected. We used univariate logistic regression to analyze the above quantitative parameters between the 2 groups, and the independent factors were further incorporated into the multivariate logistic regression model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacy of the single indicator and combined model.The difference in PSA, f/t PSA, MK, and FA between PCa and BPH was statistically significant (P < .05). The AUC for the combined model (f/t PSA, MK, and FA) of 0.972 (95% confidence interval [CI]: 0.928, 1.000) was higher than the AUC of 0.902 (95% CI: 0.801, 1.000) for f/t PSA, 0.833 (95% CI: 0.707, 0.958) for MK, and 0.807 (95% CI: 0.679, 0.934) for FA.The MK and FA values for DKI and f/t PSA effectively identify PCa and BPH, compared to the PSA indicators. Combining DKI and PSA derivatives can further improve the diagnosis efficiency and might help in the clinical setting.

Broadband Visible Light-Absorbing [70]Fullerene-BODIPY-Triphenylamine Triad: Synthesis and Application as Heavy Atom-Free Organic Triplet Photosensitizer for Photooxidation.

A broadband visible light-absorbing [70]fullerene-BODIPY-triphenylamine triad (C70-B-T) has been synthesized and applied as a heavy atom-free organic triplet photosensitizer for photooxidation. By attaching two triphenylmethyl amine units (TPAs) to the π-core of BODIPY via ethynyl linkers, the absorption range of the antenna is extended to 700 nm with a peak at 600 nm. Thus, the absorption spectrum of C70-B-T almost covers the entire UV-visible region (270-700 nm). The photophysical processes are investigated by means of steady-state and transient spectroscopies. Upon photoexcitation at 339 nm, an efficient energy transfer (ET) from TPA to BODIPY occurs both in C70-B-T and B-T, resulting in the appearance of the BODIPY emission at 664 nm. Direct or indirect (via ET) excitation of the BODIPY-part of C70-B-T is followed by photoinduced ET from the antenna to C70, thus the singlet excited state of C70 (1C70*) is populated. Subsequently, the triplet excited state of C70 (3C70*) is produced via the intrinsic intersystem crossing of C70. The photooxidation ability of C70-B-T was studied using 1,5-dihydroxy naphthalene (DHN) as a chemical sensor. The photooxidation efficiency of C70-B-T is higher than that of the individual components of C70-1 and B-T, and even higher than that of methylene blue (MB). The photooxidation rate constant of C70-B-T is 1.47 and 1.51 times as that of C70-1 and MB, respectively. The results indicate that the C70-antenna systems can be used as another structure motif for a heavy atom-free organic triplet photosensitizer.

Funny or Angry? Neural Correlates of Individual Differences in Aggressive Humor Processing.

Humor has been a hot topic for social cognition in recent years. The present study focused on the social attribute of humor and showed different stories to participants, which were divided into four types according to the model of humor style, to explore the underlying neural mechanism of point-to-self aggressive humor and how individual differences modulated it. Measuring the degree of anger and funniness, results suggested that aggressive humor helped us in social communication by reducing the degree of anger. The neural activities showed that bilateral temporal lobes and frontal lobes played a synergistic role in the point-to-self aggressive humor processing, while point-to-self non-aggressive humor was dominant in the left-side brain. Results from the region of interest (ROI) analysis showed that the individual differences of the self-control level and the self-construal level may influence the neural processing of point-to-self aggressive humor by modulating the activated levels and patterns of the right inferior orbital frontal gyrus, the right superior temporal lobe, and the right superior frontal lobe.

Long noncoding RNA GIHCG functions as an oncogene and serves as a serum diagnostic biomarker for cervical cancer.

Cervical cancer is the most common and lethal gynaecological tumor. Long noncoding RNAs (lncRNAs) have critical roles in various cancers, including cervical cancer. However, few studies investigated the diagnostic value of lncRNAs for cervical cancer. In this study, we investigated the expression pattern of a recently identified lncRNA GIHCG in cervical cancer tissues, cell lines, and serums by qRT-PCR. Furthermore, we explored the roles of GIHCG in cervical cancer using gain-of-function and loss-of-function assays. Our results revealed that GIHCG is up-regulated in cervical cancer tissues and cell lines compared with adjacent normal tissues and normal cervical epithelial cell line, respectively. Furthermore, serum GIHCG is significantly up-regulated in cervical cancer patients compared with healthy controls. ROC curve analysis revealed that serum GIHCG could accurately discriminate cervical cancer patients from healthy controls. Functionally, we found that overexpression of GIHCG promotes cell proliferation, inhibits cell apoptosis, and promotes cell migration of cervical cancer cells. Conversely, depletion of GIHCG inhibits cell proliferation, induces cell apoptosis, and inhibits cell migration of cervical cancer cells. Mechanistically, we found that GIHCG represses the expression of miR-200b. The expression of miR-200b is inversely correlated with the expression of GIHCG in cervical cancer tissues. Moreover, overexpression of miR-200b attenuates the roles of GIHCG in promoting cervical cancer tumor growth in vivo. In summary, this study demonstrated that GIHCG functions as an oncogene in cervical cancer via repressing miR-200b. This study also suggested that GIHCG may be a non-invasive diagnostic biomarker and a potential therapeutic target for cervical cancer.

When the poor excel: Poverty facilitates procedural learning.

Recent research has shown that poverty directly impeded cognitive functions because the poor could be easily distracted by monetary concerns. We argue that this effect may be limited to functions relying on working memory. For functions that rely on proceduralized processes however, monetary concerns elicited by reminding of financial demands would be conducive rather than harmful. Our results supported this hypothesis by showing that participants with lower income reached the learning criterion of the information-integration categorization task faster than their more affluent counterparts after reminding of financial demands.

Relationship between diagonal earlobe creases and coronary artery disease as determined via angiography.

OBJECTIVE: This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD). METHODS: A total of 558 consecutive participants (402 males and 156 females) aged 36-91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system. RESULTS: In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively. CONCLUSIONS: The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study.

Individual differences in dopamine level modulate the ego depletion effect.

Initial exertion of self-control impairs subsequent self-regulatory performance, which is referred to as the ego depletion effect. The current study examined how individual differences in dopamine level, as indexed by eye blink rate (EBR), would moderate ego depletion. An inverted-U-shaped relationship between EBR and subsequent self-regulatory performance was found when participants initially engaged in self-control but such relationship was absent in the control condition where there was no initial exertion, suggesting individuals with a medium dopamine level may be protected from the typical ego depletion effect. These findings are consistent with a cognitive explanation which considers ego depletion as a phenomenon similar to "switch costs" that would be neutralized by factors promoting flexible switching.

Situational context is important: perceptual grouping modulates temporal perception.

Subjective time of an event in the sub-second range is often compressed or dilated by the situational context created by preceding and succeeding stimuli. How such context distorts psychological time is still an open question. Here, we pursued this issue by examining whether the perceptual grouping among successive visual stimuli modulates the perceived duration. Using a duration comparison task, we asked observers to judge the relative duration of a target and a comparison item, and estimated the apparent duration of the target from the corresponding psychometric function. The target was temporally flanked by a preceding item and a succeeding item. In different conditions, the target was more similar to either the preceding or the succeeding item. Results showed that perceptual grouping based on similarity modulated perceived duration. Specifically, when the target was grouped with the preceding item, its subjective duration was shorter than when it was grouped with the succeeding item. Interestingly, this pattern was observed when the preceding and target items were kept constant while the succeeding item was manipulated, suggesting that the effect depends, to some degree, on the holistic perceptual grouping rather than on fragmented processes. These results demonstrate that the situational context is an important factor in shaping temporal codes, thus bridging the seemingly independent perceptual feature processes and temporal representation.

Temporal perception in visual processing as a research tool.

Accumulated evidence has shown that the subjective time in the sub-second range can be altered by different factors; some are related to stimulus features such as luminance contrast and spatial frequency, others are processes like perceptual grouping and contextual modulation. These findings indicate that temporal perception uses neural signals involved in non-temporal feature processes and that perceptual organization plays an important role in shaping the experience of elapsed time. We suggest that the temporal representation of objects can be treated as a feature of objects. This new concept implies that psychological time can serve as a tool to study the principles of neural codes in the perception of objects like "reaction time (RT)." Whereas "RT" usually reflects the state of transient signals crossing decision thresholds, "apparent time" in addition reveals the dynamics of sustained signals, thus providing complementary information of what has been obtained from "RT" studies.

Action orientation overcomes the ego depletion effect.

It has been consistently demonstrated that initial exertion of self-control had negative influence on people's performance on subsequent self-control tasks. This phenomenon is referred to as the ego depletion effect. Based on action control theory, the current research investigated whether the ego depletion effect could be moderated by individuals' action versus state orientation. Our results showed that only state-oriented individuals exhibited ego depletion. For individuals with action orientation, however, their performance was not influenced by initial exertion of self-control. The beneficial effect of action orientation against ego depletion in our experiment results from its facilitation for adapting to the depleting task.

Visual feature processing in the early visual cortex affects duration perception.

Event timing engages a distributed neural network including cortical and subcortical structures. However, it remains unclear whether the early visual cortex contributes to event timing. Here we showed that the processes of nontemporal visual features such as orientation and spatial location, which are coded by the early visual cortex, contribute to the temporal representation of a visual stimulus. Participants were presented with 2 successive Gabor patches (a prime and a target) with different orientations or spatial locations. The subjective duration of the target was significantly reduced when it was preceded by the prime compared with when presented alone. More important, this duration-compression effect varied systematically as a function of orientation similarity or spatial proximity between the prime and the target and was influenced by how the prime and the target were perceptually grouped. Our results suggest that repetition suppression of neural activity in response to orientation may contribute to the observed duration distortion and that neurons in the early visual cortex with small receptive fields and orientation selectivity may be involved in visual temporal perception. Our findings help to understand the functional role of early visual cortex in event timing in humans.

Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-κB-induced matrix metalloproteinase 2 expression.

Calpain small subunit 1 (Capn4) plays a key role in tumor migration or invasion. In this study, expression and function of Capn4 was investigated in human nasopharyngeal carcinoma (NPC). Here we report that both mRNA and protein levels of Capn4 were elevated in NPC tissues when compared to normal NP tissues. Similarly, Capn4 was also highly expressed in multiple NPC cell lines, compared to immortalized human nasopharyngeal epithelial cell line NP69. Moreover, expression of Capn4 was significantly correlated with Epstein-Barr virus infection, advanced stages, and lymph node or distant metastasis (P < 0.001). The patients with NPC displaying higher Capn4 had a significantly shorter overall survival (P = 0.002) and progression-free survival (P = 0.003). Furthermore, siRNA knockdown of Capn4 suppressed cell migration and invasion in vitro and in vivo. These events resulted from Capn4 downregulation were associated with reduced expression of matrix metalloproteinase 2 (MMP2), Snail, and Vimentin. Finally, we demonstrated that Capn4 upregulated MMP2 via nuclear factor-κB (NF-κB) activation, manifested by increased phosphorylation of p65, a subunit of NF-κB. Together, these findings argue a novel function of Capn4 in invasion and metastasis of NPC, and thereby suggest that Capn4 may represent an independent prognostic factor and a potential therapeutic target in NPC.

The activation of theory of mind network differentiates between point-to-self and point-to-other verbal jokes: an fMRI study.

The mind-reading hypothesis of humor and the inner eye theory of laughter both claim that readers' mentalizing about characters in jokes is essential for perceiving humor. On the basis of this notion, we hypothesized that point-to-other verbal jokes (in which one character said funny things about the other character) induced more theory of mind (ToM) processing than point-to-self verbal jokes (in which one character said funny things about him/herself to the other character). Our hypothesis was tested by comparing percent signal changes of these two conditions in six core components of the ToM neural network. A whole-brain analysis was also conducted. Results from both the region of interest (ROI) analysis and the whole-brain analysis show that theory of mind network is more activated when subjects read point-to-other jokes than when they read point-to-self jokes. Moreover, the whole-brain results provide support for the viewpoint that the right hemisphere, especially the right frontal lobe, is important in ToM and humor processing.