CircORC2 promoted proliferation and inhibited the sensitivity of osteosarcoma cell lines to cisplatin by regulating the miR-485-3p/TRIM2 axis.

Resistance to chemotherapy leads to poor prognosis for osteosarcoma (OS) patients. However, due to the high metastasis of tumor and the decrease in sensitivity of tumor cells to cisplatin (DDP), the 5-year survival rate of OS patients is still unsatisfactory. This study explored a mechanism for improving the sensitivity of OS cells to DDP. A DDP-resistant OS cell model was established, and we have found that circORC2 and TRIM2 were upregulated in DDP-resistant OS cells, but miR-485-3p was downregulated. The cell viability and proliferation of the OS cells decreased gradually with the increase of DDP dose, but a gradual increase in apoptosis was noted. CircORC2 promoted OS cell proliferation and DDP resistance and upregulated TRIM2 expression by targeting miR-485-3p. Functionally, circORC2 downregulated miR-485-3p to promote OS cell proliferation and inhibit DDP sensitivity. Additionally, it promoted cell proliferation and inhibited the sensitivity of DDP by regulating the miR-485-3p/TRIM2 axis. In conclusion, circORC2 promoted cell proliferation and inhibited the DDP sensitivity in OS cells via the miR-485-3p/TRIM2 axis. These findings indicated the role of circORC2 in regulating the sensitivity of OS cells to DDP.

Maternal diseases and congenital anomalies of the kidney and urinary tract in offspring: a cohort study.

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of prenatally diagnosed developmental malformation. This study aimed to assess the relationship between maternal diseases and CAKUT in offspring. METHODS: This retrospective study enrolled all pregnant women registered from January 2020 to December 2022 at one medical center. Medical information on maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease was collected. Based on the records of ultrasound scanning during the third trimester, the diagnosis was classified as isolated urinary tract dilation (UTD) or kidney anomalies. Multivariate logistic regression was performed to establish models to predict antenatal CAKUT. RESULTS: Among the 19,656 pregnant women, perinatal ultrasound detected suspicious CAKUT in 114 (5.8/1000) fetuses, comprising 89 cases with isolated UTD and 25 cases with kidney anomalies. The risk of antenatal CAKUT was increased in the fetuses of mothers who experienced gestational diabetes, thyroid dysfunction, neuropsychiatric disease, anemia, ovarian and uterine disorders. A prediction model for isolated UTD was developed utilizing four confounding factors, namely gestational diabetes, gestational hypertension, maternal thyroid dysfunction, and hepatic disease. Similarly, a separate prediction model for kidney anomalies was established based on four distinct confounding factors, namely maternal thyroid dysfunction, gestational diabetes, disorders of ovarian/uterine, and kidney disease. CONCLUSIONS: Isolated UTD and kidney anomalies were associated with different maternal diseases. The results may inform the clinical management of pregnancy and highlight potential differences in the genesis of various subtypes of CAKUT.

Mechanical rheological model on the assessment of elasticity and viscosity in tissue inflammation: A systematic review.

Understanding the extent of inflammation is crucial for early disease detection, monitoring disease progression, and evaluating treatment responses. Over the past decade, researchers have demonstrated the need to understand the extent of inflammation through qualitative or quantitative characterization of tissue viscoelasticity using different techniques. In this scientific review, an examination of research on the association between elasticity and Viscosity in diseases, particularly as tissue inflammation progresses, is conducted. A review of utilizing mechanical rheological models to characterize quantitative viscoelastic parameters of normal and inflamed tissues is also undertaken. Based on inclusion and exclusion criteria, we identified 14 full-text studies suitable for review out of 290 articles published from January 2000 to January 2024. We used PRISMA guidelines for the systematic review. In the review, three studies demonstrated the criterion used by the researchers in identifying the best rheological model. Eleven studies showed the clinical application of the rheological model in quantifying the viscoelastic properties of normal and pathological tissue. The review quantified viscoelastic parameters for normal and pathological tissue across various soft tissues. It evaluated the effectiveness of each viscoelastic property in distinguishing between normal and pathological tissue stiffness. Furthermore, the review outlined additional viscoelastic-related parameters for researchers to consider in future stiffness classification studies.

The Oncolytic virus VT1092M and an Anti-PD-L1 antibody synergize to induce systemic antitumor immunity in a murine bilateral tumor model.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

1,4-Disubstituted Piperazin-2-Ones as Selective Late Sodium Current Inhibitors with QT Interval Shortening Properties in Isolated Rabbit Hearts.

Late sodium current (INa) inhibitors are a new subclass of antiarrhythmic agents. To overcome the drawbacks, e.g., low efficacy and inhibition effect on K+ current, of the FDA-approved late INa inhibitor ranolazine, chain amide 6a-6q, 1,4-disubstituted piperazin-2-ones 7a-7s, and their derivatives 8a-8n were successively designed, synthesized, and evaluated in vitro on the NaV1.5-transfected HEK293T cells by the whole-cell patch clamp recording assay at the concentration of 40 µM. Among the new skeleton compounds, 7d showed the highest efficacy (IC50 = 2.7 µM) and good selectivity (peak/late ratio >30 folds), as well as excellent pharmacokinetics properties in mice (T1/2 of 3.5 h, F = 90%, 3 mg/kg, po). It exhibited low hERG inhibition and was able to reverse the ATX-II-induced augmentation of late INa phenotype of LQT3 model in isolated rabbit hearts. These results suggest the application potentials of 7d in the treatments of arrhythmias related to the enhancement of late INa.

DDID: a comprehensive resource for visualization and analysis of diet-drug interactions.

Diet-drug interactions (DDIs) are pivotal in drug discovery and pharmacovigilance. DDIs can modify the systemic bioavailability/pharmacokinetics of drugs, posing a threat to public health and patient safety. Therefore, it is crucial to establish a platform to reveal the correlation between diets and drugs. Accordingly, we have established a publicly accessible online platform, known as Diet-Drug Interactions Database (DDID, https://bddg.hznu.edu.cn/ddid/), to systematically detail the correlation and corresponding mechanisms of DDIs. The platform comprises 1338 foods/herbs, encompassing flora and fauna, alongside 1516 widely used drugs and 23 950 interaction records. All interactions are meticulously scrutinized and segmented into five categories, thereby resulting in evaluations (positive, negative, no effect, harmful and possible). Besides, cross-linkages between foods/herbs, drugs and other databases are furnished. In conclusion, DDID is a useful resource for comprehending the correlation between foods, herbs and drugs and holds a promise to enhance drug utilization and research on drug combinations.

The genetic architecture of dog ownership: large-scale genome-wide association study in 97,552 European-ancestry individuals.

Dog ownership has been associated with several complex traits and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through meta-analysis of 31,566 Swedish twins in five discovery cohorts and additional 65,986 European-ancestry individuals in three replication cohorts from Sweden, Norway, and the UK. Association test with >7.4 million single-nucleotide polymorphisms were meta-analyzed using a fixed effect model after controlling for population structure and relatedness. We identified two suggestive loci using discovery cohorts, which did not reach genome-wide significance after meta-analysis with replication cohorts. Single-nucleotide polymorphisms-based heritability of dog ownership using linkage disequilibrium score regression was estimated at 0.123 (CI 0.038-0.207) using the discovery cohorts and 0.018 (CI -0.002, 0.039) when adding in replication cohorts. Negative genetic correlation with complex traits including type 2 diabetes, depression, neuroticism and asthma was only found using discovery summary data. Furthermore, we did not identify any genes/gene-sets reaching even suggestive level of significance. This genome-wide association study does not, by itself, provide clear evidence on common genetic variants that influence the dog ownership among European-ancestry individuals.

Prophylactic Effects of n-Acethylcysteine on Inflammation-induced Depression-like Behaviors in Mice.

Depression, affecting individuals worldwide, is a prevalent mental disease, with an increasing incidence. Numerous studies have been conducted on depression, yet its pathogenesis remains elusive. Recent advancements in research indicate that disturbances in synaptic transmission, synaptic plasticity, and reduced neurotrophic factor expression significantly contribute to depression's pathogenesis. In our study, we utilized adult male C57BL/6J mice. Lipopolysaccharide (LPS) can induce both chronic and acute depression-like symptoms in mice, a widely used model for studying depression associated with inflammation. N-acetylcysteine (NAC) exhibits anti-inflammatory and ameliorative effects on depressive symptoms. This study sought to determine whether NAC use could mitigate inflammatory depressive behavior through the enhancement of synaptic transmission, synaptic plasticity, and increasing levels of brain-derived neurotrophic factor (BDNF). In this study, we discovered that in mice modeled with depression-like symptoms, the expression levels of dendrites, BDNF, and miniature excitatory postsynaptic potential (mEPSC) in glutamatergic neurons, as well as the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPARs) GluA1 and GluA2 subunits, were significantly decreased. These findings suggest an impairment in the synaptic transmission of glutamatergic neurons. Following treatment with NAC, the previously mentioned levels improved, indicating an enhancement in both synaptic transmission and synaptic plasticity. Our results suggest that NAC exerts a protective effect on mouse models of inflammatory depression, potentially through the enhancement of synaptic transmission and plasticity, as well as the restoration of neurotrophic factor expression. These findings offer vital animal experimental evidence supporting NAC's role in mitigating inflammatory depressive behaviors.

The value of urinary exosomal microRNA-21 in the early diagnosis and prognosis of bladder cancer.

Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)-21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR-21, prognostic value of miR-21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR-21, miR-4454, and urine cytology for Ta-T1 and T2-T4 stage BC were analyzed. Urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 were highly expressed in BC patients. miR-146a-5p, miR-93-5p, miR-663b, miR-21, miR-4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR-21, miR-4454, and miRNA co-diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR-21 was closely related to Tumor-Node-Metastasis staging and grading in BC patients. Urinary exosomal miR-21 had high diagnostic value for BC and Ta-T1 and T2-T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.

Sub-Nyquist sampling-based high-frequency photoacoustic computed tomography.

High-frequency (greater than 30 MHz) photoacoustic computed tomography (PACT) provides the opportunity to reveal finer details of biological tissues with high spatial resolution. To record photoacoustic signals above 30 MHz, sampling rates higher than 60 MHz are required according to the Nyquist sampling criterion. However, the highest sampling rates supported by existing PACT systems are typically within the range of 40-60 MHz. Herein, we propose a novel PACT imaging method based on sub-Nyquist sampling. The results of numerical simulation, phantom experiment, and in vivo experiment demonstrate that the proposed imaging method can achieve high-frequency PACT imaging with a relatively low sampling rate. An axial resolution of 22 µm is achieved with a 30-MHz transducer and a 41.67-MHz sampling rate. To the best of our knowledge, this is the highest axial resolution ever achieved in PACT based on a sampling rate of not greater than 60 MHz. This work is expected to provide a practical way for high-frequency PACT imaging with limited sampling rates.

Image restoration for ring-array photoacoustic tomography system based on blind spatially rotational deconvolution.

Ring-array photoacoustic tomography (PAT) system has been widely used in noninvasive biomedical imaging. However, the reconstructed image usually suffers from spatially rotational blur and streak artifacts due to the non-ideal imaging conditions. To improve the reconstructed image towards higher quality, we propose a concept of spatially rotational convolution to formulate the image blur process, then we build a regularized restoration problem model accordingly and design an alternating minimization algorithm which is called blind spatially rotational deconvolution to achieve the restored image. Besides, we also present an image preprocessing method based on the proposed algorithm to remove the streak artifacts. We take experiments on phantoms and in vivo biological tissues for evaluation, the results show that our approach can significantly enhance the resolution of the image obtained from ring-array PAT system and remove the streak artifacts effectively.

Effects of different types of Ringer's solution on patients with traumatic haemorrhagic shock: a prospective cohort study.

OBJECTIVE: To compare the fluid resuscitation effect of sodium acetate Ringer's solution and sodium bicarbonate Ringer's solution on patients with traumatic haemorrhagic shock. METHOD: We conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer's solution group and sodium acetate Ringer's solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients' vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3-), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation. RESULTS: The post-resuscitation heart rate of the sodium bicarbonate Ringer's solution group was significantly lower than that of the sodium acetate Ringer's solution group (p < 0.05), and the MAP was also significantly lower (p < 0.05). The patients in the sodium bicarbonate Ringer's solution group had significantly higher pH, cHCO3- and PaO2 values and lower pCO2 and CLac values (p < 0.05) than those in the sodium acetate Ringer's solution group, and the post-resuscitation peripheral platelet counts and fibrinogen levels were significantly higher, with shorter plasma prothrombin times and smaller shock indices (p < 0.001). CONCLUSION: Sodium bicarbonate Ringer's solution is beneficial for maintaining MAP at a low level after resuscitation. The use of sodium bicarbonate Ringer's solution in limited fluid resuscitation has positive results and is of high clinical value.

Teacher-student guided knowledge distillation for unsupervised convolutional neural network-based speckle tracking in ultrasound strain elastography.

Accurate and efficient motion estimation is a crucial component of real-time ultrasound elastography (USE). However, obtaining radiofrequency ultrasound (RF) data in clinical practice can be challenging. In contrast, although B-mode (BM) data is readily available, elastographic data derived from BM data results in sub-optimal elastographic images. Furthermore, existing conventional ultrasound devices (e.g., portable devices) cannot provide elastography modes, which has become a significant obstacle to the widespread use of traditional ultrasound devices. To address the challenges above, we developed a teacher-student guided knowledge distillation for an unsupervised convolutional neural network (TSGUPWC-Net) to improve the accuracy of BM motion estimation by employing a well-established convolutional neural network (CNN) named modified pyramid warping and cost volume network (MPWC-Net). A pre-trained teacher model based on RF is utilized to guide the training of a student model using BM data. Innovations outlined below include employing spatial attention transfer at intermediate layers to enhance the guidance effect of the model. The loss function consists of smoothness of the displacement field, knowledge distillation loss, and intermediate layer loss. We evaluated our method on simulated data, phantoms, and in vivo ultrasound data. The results indicate that our method has higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values in axial strain estimation than the model trained on BM. The model is unsupervised and requires no ground truth labels during training, making it highly promising for motion estimation applications.

Development of a colloidal gold immunochromatographic strip for rapid detection of avian coronavirus infectious bronchitis virus.

Avian infectious bronchitis virus (IBV) still causes serious economic losses in the poultry industry. Currently, there are multiple prevalent genotypes and serotypes of IBVs. It is imperative to develop a new diagnosis method that is fast, sensitive, specific, simple, and broad-spectrum. A monoclonal hybridoma cell, N2D5, against the IBV N protein was obtained after fusion of myeloma SP2/0 cells with spleen cells isolated from the immunized Balb/c mice. The N2D5 monoclonal antibody (mAb) and the previously prepared mouse polyclonal antibody against the IBV N protein were used to target IBV as a colloidal gold-mAb conjugate and a captured antibody, respectively, in order to develop an immunochromatographic strip. The optimal pH and minimum antibody concentration in the reaction system for colloidal gold-mAb N2D5 conjugation were pH 6.5 and 30 µg/mL, respectively. Common avian pathogens were tested to evaluate the specificity of the strip and no cross-reaction was observed. The sensitivity of the strip for detecting IBV was 10-1.4522 EID50/mL. The strip showed a broad-spectrum cross-reactive capacity for detecting IBV antigens, including multiple IBV genotypes in China and all of the seven serotypes of IBV that are currently prevalent in southern China. Additionally, the result can be observed within 2 min without any equipment. The throat and cloacal swab samples of chickens that were artificially infected with three IBV strains were tested using the developed strip and the qPCR method; the strip test demonstrated a high consistency in detecting IBV via qPCR gene detection. In conclusion, the immunochromatographic strip that was established is rapid, sensitive, specific, simple, practical, and broad-spectrum; additionally, it has the potential to serve as an on-site rapid detection method of IBV and can facilitate the surveillance and control of the disease, especially in resource-limited areas.

Blind multi-Poissonian image deconvolution with sparse log-step gradient prior.

Blind image deconvolution plays a very important role in the fields such as astronomical observation and fluorescence microscopy imaging, in which the noise follows Poisson distribution. However, due to the ill-posedness, it is a very challenging task to reach a satisfactory result from a single blurred image especially when the power of the Poisson noise is at a high level. Therefore, in this paper, we try to achieve high-quality restoration results with multi-blurred images which are contaminated by Poisson noise. Firstly, we design a novel sparse log-step gradient prior which adopts a mixture of logarithm and step functions to regularize the image gradients and combine it with the Poisson distribution to formulate the blind multi-image deconvolution problem. Secondly, we incorporate the methods of variable splitting and Lagrange multiplier to convert the original problem into sub-problems, then we alternately solve them to achieve the estimation of all the blur kernels of corresponding blurred images. Besides, we also design a non-blind multi-image deconvolution algorithm which is based on the log-step gradient prior to reach the final restored image. Experimental results on both synthetic and real-world blurred images show that the proposed prior is very capable of suppressing negative artifacts caused by ill-posedness. The algorithm can achieve restored image of very high quality which is competitive with some state-of-the-art methods.

Changes of uterocervical angle and cervical length in early and mid-pregnancy and their value in predicting spontaneous preterm birth.

Objective: To explore the feasibility of transvaginal ultrasound measurement of uterocervical angle (UCA) and cervical length (CL) in early and mid-pregnancy and evaluate their combined prediction of spontaneous preterm birth (sPTB) in singleton pregnancies. Patients and Methods: This retrospective study comprised 274 pregnant women who underwent transvaginal ultrasound measurement of CL in mid-pregnancy (15-23+6 weeks); in 75 among them, CL also had been measured in early-pregnancy (<14 weeks). These 274 pregnant women were further divided into a preterm group (n = 149, <37 weeks gestation) and a control group (n = 125, >37 weeks gestation) according to delivery before or after 37 weeks, respectively. In the preterm group, 35 patients delivered before 34 weeks and the remaining 114 delivered between 34 and 37 weeks. Results: The optimal threshold of CL to predict preterm birth risk in women with <37 weeks gestation was 3.38 cm, and the optimal threshold of the UCA to predict preterm birth risk in the same group of women was 96°. The optimal threshold of CL to predict preterm birth risk in women with <34 weeks gestation was 2.54 cm, while that of the UCA in the same group of patients was 106°. The area under the curve for predicting preterm birth by combining the UCA and CL measurements was greater than that by using the UCA or CL alone (p < 0.01). The sensitivity and specificity for predicting preterm birth at <34 weeks gestation was 71.7% and 86.4%, respectively; and the sensitivity and specificity for predicting preterm birth at <37 weeks gestation was 87.6% and 80.6%, respectively. The difference between the two groups in CL and UCA were not significant in early pregnancy (p > 0.01), but only in mid-pregnancy (p < 0.01). There was a negative correlation between UCA and gestational week at delivery (r = -0.361, p < 0.001) and a positive correlation between CL and gestational week at delivery (r = 0.346, p < 0.001) in mid-pregnancy. The proportion of deliveries at <34 weeks was highest when the UCA was >105°, and the proportion of deliveries between 35 and 37 weeks was highest when the UCA was between 95° and 105°. The proportion of deliveries at <34 weeks was highest when the CL was <2.5 cm. Conclusion: The combination of UCA and CL has a better ability to predict preterm birth than either measurement alone. A more obtuse UCA or a shorter CL is associated with an earlier spontaneous preterm birth. The UCA increases from early to mid-pregnancy, while the CL decreases from early to mid-pregnancy.

Fibroblasts/three-dimensional scaffolds complexes promote wound healing in rats with skin defects.

We aim to construct a three-dimensional nano-skin scaffold material in vitro and study its promoting effect on wound healing in vivo. In this study, hybrid constructs of three-dimensional (3D) scaffolds were successfully fabricated by combination of type I collagen (COL-1) and polylactic-glycolic acid (PLGA). Fibroblasts and human umbilical cord mesenchymal stem cells (hUCMSCs) were used to implanted into 3D scaffolds and constructed into SD skin scaffolds in vitro. Finally, the fibroblasts/scaffolds complexes were inoculated on the surface of rat wound skin to study the promoting effect of the complex on wound healing. In our study, we successfully built a 3D scaffold, which had a certain porosity. Meanwhile, the content of COL-1 in the cell supernatant of fibroblast/scaffold complexes was increased. Furthermore, the expression of F-actin, CD105, integrin ß, VEGF, and COL-1 was up-regulated in hUCMSC/scaffold complexes compared with the control group. In vivo, fibroblast/scaffold complexes promoted wound healing in rats. Our data suggested that the collagen Ⅳ and vimentin were elevated and collagen fibers were neatly arranged in the fibroblast/scaffold complex group was significantly higher than that in the scaffold group. Taken together, fibroblast/scaffold complexes were expected to be novel materials for treating skin defects.

Genome-wide association study identifies new loci associated with OCD.

To date, four genome-wide association studies (GWAS) of obsessive-compulsive disorder (OCD) have been published, reporting a high single-nucleotide polymorphism (SNP)-heritability of 28% but finding only one significant SNP. A substantial increase in sample size will likely lead to further identification of SNPs, genes, and biological pathways mediating the susceptibility to OCD. We conducted a GWAS meta-analysis with a 2-3-fold increase in case sample size (OCD cases: N = 37,015, controls: N = 948,616) compared to the last OCD GWAS, including six previously published cohorts (OCGAS, IOCDF-GC, IOCDF-GC-trio, NORDiC-nor, NORDiC-swe, and iPSYCH) and unpublished self-report data from 23andMe Inc. We explored the genetic architecture of OCD by conducting gene-based tests, tissue and celltype enrichment analyses, and estimating heritability and genetic correlations with 74 phenotypes. To examine a potential heterogeneity in our data, we conducted multivariable GWASs with MTAG. We found support for 15 independent genome-wide significant loci (14 new) and 79 protein-coding genes. Tissue enrichment analyses implicate multiple cortical regions, the amygdala, and hypothalamus, while cell type analyses yielded 12 cell types linked to OCD (all neurons). The SNP-based heritability of OCD was estimated to be 0.08. Using MTAG we found evidence for specific genetic underpinnings characteristic of different cohort-ascertainment and identified additional significant SNPs. OCD was genetically correlated with 40 disorders or traits-positively with all psychiatric disorders and negatively with BMI, age at first birth and multiple autoimmune diseases. The GWAS meta-analysis identified several biologically informative genes as important contributors to the aetiology of OCD. Overall, we have begun laying the groundwork through which the biology of OCD will be understood and described.

Decreased plasma miR-140-3p is associated with coronary artery disease.

Background: Although many circulating miRNAs (c-miRNAs) are associated with coronary artery disease (CAD), they are far from being the biomarker for CAD diagnosis or risk prediction. Therefore, novel c-miRNAs discovery and validation are still required, especially evaluating their prediction capacity. Objectives: Identify novel CAD-related c-miRNAs and evaluate its risk prediction capacity for CAD. Methods: miRNAs associated with CAD were preliminarily investigated in three paired samples representing pre-CAD stage and CAD stage of three female individuals using the Applied Biosystems miRNA TaqMan® Low-Density Array (TLDA). Then, the candidate miRNAs were further verified in an independent case-control study including 129 CAD patients and 76 controls, and their potential practical value in prediction for CAD was evaluated using a machine learning (ML) algorithm. The accuracy of classification and prediction was assessed with the area under the receiver operating characteristic curve (AUC). Results: TLDA analysis shows that miR-140-3p decreased significantly in CAD-stage (FC = -3.01, P = 0.007). Further study shows that miR-140-3p was significantly lower in CAD group [1.26 (0.68, 2.01)] than in control group [2.07 (1.19, 3.21)] (P < 0.001) and independently associated with CAD (P < 0.001). The addition of miR-140-3p to the variables including smoking history, HDL-c, and APOA1 improved the accuracy of classification by logistic regression and of prediction for CAD by ML models. The ML models built with miR-140-3p and HDL-c, respectively, had a similar prediction accuracy. The feature importance of miR-140-3p and HDL-c in the ML models was also similar. Decision curve analysis showed that miR-140-3p and HDL-c had almost identical net benefits. Conclusion: Reduced levels of miR-140-3p is linked to CAD, and it is possible to use the plasma level of miR-140-3p as a means of evaluating the risk of CAD.

On the imaging depth limit of photoacoustic tomography in the visible and first near-infrared windows.

It is well known that photoacoustic tomography (PAT) can circumvent the photon scattering problem in optical imaging and achieve high-contrast and high-resolution imaging at centimeter depths. However, after two decades of development, the long-standing question of the imaging depth limit of PAT in biological tissues remains unclear. Here we propose a numerical framework for evaluating the imaging depth limit of PAT in the visible and the first near-infrared windows. The established framework simulates the physical process of PAT and consists of seven modules, including tissue modelling, photon transportation, photon to ultrasound conversion, sound field propagation, signal reception, image reconstruction, and imaging depth evaluation. The framework can simulate the imaging depth limits in general tissues, such as the human breast, the human abdomen-liver tissues, and the rodent whole body and provide accurate evaluation results. The study elucidates the fundamental imaging depth limit of PAT in biological tissues and can provide useful guidance for practical experiments.