Prenatal Diagnosis of Cerebellar Cortical Dysplasia: Case Report.

This was a study of 12 cerebellar cortical dysplasias (CCDs) fetuses, these cases were characterized by a disorder of cerebellar fissures. Historically, CCD diagnosis was primarily performed using postnatal imaging. Unique to this study was the case series of CCD for prenatal diagnosis using prenatal ultrasound, as well as we found that AXIN1 and FOXC1 mutations may be related to CCD.

Hydrogen Sulfide Alleviates Oxidative Damage under Chilling Stress through Mitogen-Activated Protein Kinase in Tomato.

Tomato is the vegetable with the largest greenhouse area in China, and low temperature is one of the main factors affecting tomato growth, yield, and quality. Hydrogen sulfide (H2S) plays an important role in regulating plant chilling tolerance, but its downstream cascade reaction and mechanism remain unclear. Mitogen-activated protein kinases (MAPK/MPKs) are closely related to a variety of signaling substances in stress signal transmission. However, whether H2S is related to the MPK cascade pathway in response to low-temperature stress is rarely reported. In this study, NaHS treatment significantly decreased the electrolyte leakage (EL), superoxide anion (O2-) production rate, and hydrogen peroxide (H2O2) content of seedlings at low temperatures. In addition, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were obviously increased; and the photochemical efficiency of PSII (Fv/Fm) was enhanced with treatment with NaHS, indicating that NaHS improved the seedlings' cold tolerance by alleviating the degree of membrane lipid peroxidation and oxidative damage. However, H2S scavenger hypotaurine (HT) treatment showed the opposite effect. We found that H2S content, L-cysteine desulfhydrase (LCD) activity, and mRNA expression were increased by chilling stress but reduced by MPK inhibitor PD98059; PD98059 reversed the alleviating effect of H2S via increasing the EL and H2O2 contents. The expression levels of MPK1-MPK7 at low temperatures showed that SlMPK4 was significantly induced by exogenous NaHS and showed a trend of first increasing and then decreasing, while the expression level of SlMPK4 in HT-treated seedlings was lower than that of the control. After SlMPK4 was silenced by virus-induced gene silencing, the H2S-induced upregulation of C-repeat-Binding Factor (CBF1), inducer of CBF expression 1 (ICE1), respiratory burst oxidase homologs (RBOH1, RBOH2) at low temperatures disappeared, and tomato cold tolerance decreased. In conclusion, H2S improves the cold tolerance of tomato plants by increasing the activity of antioxidant enzymes and reducing reactive oxygen species (ROS) accumulation and membrane lipid peroxidation. MPK4 may act as a downstream signaling molecule in this process.

The effect of GnRH analog treatment on BMI in children treated for precocious puberty: a systematic review and meta-analysis.

INTRODUCTION: The purpose of the present meta-analysis was to systematically evaluate the effect of GnRHa treatment on the BMI of children with precocious puberty after GnRHa treatment as compared to before, and to analyze the effect of GnRHa treatment on the body composition of children with precocious puberty at different BMIs by classifying into normal body mass, overweight, and obese groups according to BMI at the time of initial diagnosis. CONTENT: A meta-analysis was performed using Stata 12.0 software by searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), and Wan fang database for relevant literature on standard deviation score of body mass index (BMI-SDS) after GnRHa treatment as compared to before in children with precocious puberty. SUMMARY: A total of eight studies were included with a total sample size of 715 cases, and the results of meta-analysis showed that BMI-SDS increased in children with precocious puberty after GnRHa treatment as compared to before starting [(weighted mean difference (WMD)=0.23, 95 % CI: 0.14-0.33, p=0.000)] and also increased in children with normal body mass [(WMD=0.37, 95 % CI: 0.28-0.46, p=0.000)], and there was no significant change in BMI-SDS in children in the overweight or obese group [(WMD=0.01, 95 % CI: -0.08-0.10, p=0.775)]. OUTLOOK: Overall, there was an observed increase in BMI-SDS at the conclusion of GnRHa treatment in children with precocious puberty. Additionally, it was found that the effect of GnRHa treatment on body composition varied among children with different BMI status. Clinicians should emphasize the promotion of a healthy lifestyle and personalized dietary management for children.

An Easy and Effective Method for Evaluating the Position of Conus Medullaris: Counting the Number of Vertebral Ossification Center Below the End of Conus Medullaris.

OBJECTIVE: This study aimed to ascertain the conus medullaris position by counting the number of ossification centers in the vertebral bodies below the conus medullaris endpoint (N) and assess its utility in screening for closed spinal dysraphism and tethered cord syndrome. METHODS: A total of 900 normal fetuses and 146 fetuses with closed spinal dysraphism or tethered cord syndrome were included in this study. The N values were tallied and compared along the spinal longitudinal plane. The receiver operating characteristic curve was utilized, and the cut-off value of N was analyzed. RESULTS: The counting of N was successfully performed in 856 normal and 146 abnormal fetuses. In the normal group, an increase in N with gestational age was observed. Specifically, in the subgroup of 17-20 wk fetuses, N was ≥6 in 117 out of 131 cases. This figure increased to 211 out of 213 in 21-24 wk and 512 out of 512 in 25-41 wk, respectively. Cases with N ≥7 accounted for 715 out of 856 fetuses in the 17-41 wk range. In the abnormal group, N was less than 7 in 152 out of 163 fetuses, showing statistical differences between the two groups. With a cut-off value of 6.5, specificity and sensitivity reached 93.3% and 83.5%. CONCLUSIONS: The counting of N was found to be a straightforward and efficient method for evaluating the position of the conus medullaris.

Noncanonical translation of circRNAs drive antitumor immunity.

Identifying tumor-specific antigenic peptides beyond mutational events is essential for developing effective antitumor immunotherapies. In a recent study, Huang et al. identified an immunogenic cryptic peptide encoded by the circular RNA circFAM53B, through integrating mass spectrometry and ribosome sequencing data from breast cancer samples, and demonstrated its antitumor immunogenicity.

MLMSeg: A multi-view learning model for ultrasound thyroid nodule segmentation.

Accurate segmentation of the thyroid gland in ultrasound images is an essential initial step in distinguishing between benign and malignant nodules, thus facilitating early diagnosis. Most existing deep learning-based methods to segment thyroid nodules are learned from only a single view or two views, which limits the performance of segmenting nodules at different scales in complex ultrasound scanning environments. To address this limitation, this study proposes a multi-view learning model, abbreviated as MLMSeg. First, a deep convolutional neural network is introduced to encode the features of the local view. Second, a multi-channel transformer module is designed to capture long-range dependency correlations of global view between different nodules. Third, there are semantic relationships of structural view between features of different layers. For example, low-level features and high-level features are endowed with hidden relationships in the feature space. To this end, a cross-layer graph convolutional module is proposed to adaptively learn the correlations of high-level and low-level features by constructing graphs across different layers. In addition, in the view fusion, a channel-aware graph attention block is devised to fuse the features from the aforementioned views for accurate segmentation of thyroid nodules. To demonstrate the effectiveness of the proposed method, extensive comparative experiments were conducted with 14 baseline methods. MLMSeg achieved higher Dice coefficients (92.10% and 83.84%) and Intersection over Union scores (86.60% and 73.52%) on two different thyroid datasets. The exceptional segmentation capability of MLMSeg for thyroid nodules can greatly assist in localizing thyroid nodules and facilitating more precise measurements of their transverse and longitudinal diameters, which is of significant clinical relevance for the diagnosis of thyroid nodules.

Single-cell transcriptomics enable the characterization of local extension in retinoblastoma.

Retinoblastoma (RB) is the most prevalent ocular tumor of childhood, and its extraocular invasion significantly increases the risk of metastasis. Nevertheless, a single-cell characterization of RB local extension has been lacking. Here, we perform single-cell RNA sequencing on four RB samples (two from intraocular and two from extraocular RB patients), and integrate public datasets of five normal retina samples, four intraocular samples, and three extraocular RB samples to characterize RB local extension at the single-cell level. A total of 128,454 qualified cells are obtained in nine major cell types. Copy number variation inference reveals chromosome 6p amplification in cells derived from extraocular RB samples. In cellular heterogeneity analysis, we identified 10, 8, and 7 cell subpopulations in cone precursor like cells, retinoma like cells, and MKI67+ photoreceptorness decreased (MKI67+ PhrD) cells, respectively. A high expression level of SOX4 was detected in cells from extraocular samples, especially in MKI67+ PhrD cells, which was verified in additional clinical RB samples. These results suggest that SOX4 might drive RB local extension. Our study presents a single-cell transcriptomic landscape of intraocular and extraocular RB samples, improving our understanding of RB local extension at the single-cell resolution and providing potential therapeutic targets for RB patients.

Stromal Vascular Fraction Gel (SVF-Gel) Combined with Nanofat for Tear Trough Deformity.

BACKGROUND: Tear trough deformity makes patients appear tired. Patients with less severe tear trough deformity prefer a less invasive method to correct the deformity. The infraorbital area is a multilayered tissue, and the aging of various components leads to tear trough deformity. To this end, we utilized the different characteristics of different fat derivatives to correct tear trough deformity. METHODS: Thirty-two patients with Barton Grade I/II tear trough deformity were enrolled in this study between September 2020 and March 2021. We injected Stromal Vascular Fraction Gel (SVF-Gel) into the suborbicularis oculi fat layer and Nanofat into the subcutaneous. After 12 months of follow-up, we evaluated the changes using standardized clinical photogrammetric techniques, volume, global aesthetic improvement scale, and patient self-evaluation. RESULTS: There were no major complications in any of the 32 patients. The measured data points demonstrated improvements in all aesthetic parameters. The width of the tear trough and the distance from the pupil to the tear trough improved. The Global Aesthetic Improvement Scale (GAIS) showed a high score (2.45±0.64 points), with patient self-assessment showing satisfactory results. CONCLUSION: SVF-Gel combined with Nanofat injection can effectively correct tear trough deformities. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prediction Model for Unfavorable Outcome in Spontaneous Intracerebral Hemorrhage Based on Machine Learning.

OBJECTIVE: The spontaneous intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. The purpose of this retrospective study is to develop multiple models for predicting ICH outcomes using machine learning (ML). METHODS: Between January 2014 and October 2021, we included ICH patients identified by computed tomography or magnetic resonance imaging and treated with surgery. At the 6-month check-up, outcomes were assessed using the modified Rankin Scale. In this study, four ML models, including Support Vector Machine (SVM), Decision Tree C5.0, Artificial Neural Network, Logistic Regression were used to build ICH prediction models. In order to evaluate the reliability and the ML models, we calculated the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR). RESULTS: We identified 71 patients who had favorable outcomes and 156 who had unfavorable outcomes. The results showed that the SVM model achieved the best comprehensive prediction efficiency. For the SVM model, the AUC, accuracy, specificity, sensitivity, PLR, NLR, and DOR were 0.91, 0.92, 0.92, 0.93, 11.63, 0.076, and 153.03, respectively. For the SVM model, we found the importance value of time to operating room (TOR) was higher significantly than other variables. CONCLUSION: The analysis of clinical reliability showed that the SVM model achieved the best comprehensive prediction efficiency and the importance value of TOR was higher significantly than other variables.

Cisplatin-induced PANDAR-Chemo-EVs contribute to a more aggressive and chemoresistant ovarian cancer phenotype through the SRSF9-SIRT4/SIRT6 axis.

OBJECTIVE: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. METHODS: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatin-resistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich pre-mRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. RESULTS: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. CONCLUSION: Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

A knowledge-interpretable multi-task learning framework for automated thyroid nodule diagnosis in ultrasound videos.

Ultrasound has become the most widely used modality for thyroid nodule diagnosis, due to its portability, real-time feedback, lack of toxicity, and low cost. Recently, the computer-aided diagnosis (CAD) of thyroid nodules has attracted significant attention. However, most existing techniques can only be applied to either static images with prominent features (manually selected from scanning videos) or rely on 'black boxes' that cannot provide interpretable results. In this study, we develop a user-friendly framework for the automated diagnosis of thyroid nodules in ultrasound videos, by simulating the typical diagnostic workflow used by radiologists. This process consists of two orderly part-to-whole tasks. The first interprets the characteristics of each image using prior knowledge, to obtain corresponding frame-wise TI-RADS scores. Associated embedded representations not only provide diagnostic information for radiologists but also reduce computational costs. The second task models temporal contextual information in an embedding vector sequence and selectively enhances important information to distinguish benign and malignant thyroid nodules, thereby improving the efficiency and generalizability of the proposed framework. Experimental results demonstrated this approach outperformed other state-of-the-art video classification methods. In addition to assisting radiologists in understanding model predictions, these CAD results could further ease diagnostic workloads and improve patient care.

Irisin protected hemopoietic stem cells and improved outcome of severe bone marrow failure.

Acquired aplastic anemia (AA) is a bone marrow failure (BMF) disease, characterized by fatty bone marrow (BM) and BM hypocellularity resulted from auto-immune dysregulated T cells-mediated destruction of BM haemopoietic stem cells (HPSC). The objective of this study was to investigate potential therapeutic effect of irisin, a molecule involved in adipose tissue transition, on AA mouse model. Our results showed that the concentration of irisin in serum was lower in AA patients than in healthy controls, suggesting a role of irisin in the pathogenesis of AA. In the AA mice, irisin administration prolonged the survival rate, prevented or attenuated peripheral pancytopenia, and preserved HPSC in the BM. Moreover, irisin also markedly reduced BM adipogenesis. In vitro results showed that irisin increased both cell proliferation and colony numbers of HPSC. Furthermore, our results demonstrated that irisin upregulated the expression of mitochondrial ATPase Inhibitory Factor 1 (IF1) in HPSC, inhibited the activation of mitochondrial fission protein (DRP1) and enhanced aerobic glycolysis. Taken together, our findings indicate novel roles of irisin in the pathogenesis of AA, and in the protection of HPSC through stimulation of proliferation and regulation of mitochondria function, which provides a proof-of-concept for the application of irisin in AA therapy.

Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging.

Fibroblast activation protein (FAP) is closely related to central nervous system diseases such as stroke and brain tumors, but PET tracers that can be used for brain imaging have not been reported. Here, we designed, synthesized, and evaluated 18F-labeled UAMC1110 derivatives suitable for brain imaging targeting FAP. By substituting the F atom for the H atom on the aromatic ring of compound UAMC1110, 1a-c were designed and prepared. 1a-c were confirmed to have a high affinity for FAP through molecular docking and enzyme assay. [18F]1a-c were successfully prepared and confirmed to have high affinity. The stability in vivo indicates that no obvious metabolites of [18F]1a,b were found in the plasma 1 h after injection, which is beneficial for brain imaging. In vitro cell uptake experiments showed that [18F]1a,b and [68Ga]FAPI04 exhibited similar uptake and internalization rates. PET imaging of U87MG subcutaneous tumor showed that [18F]1a,b could penetrate the blood-brain barrier with higher uptake and longer retention time than [68Ga]FAPI04 (uptake at 62.5 min, 1.06 ± 0.23, 1.09 ± 0.25% ID/g vs 0.21 ± 0.10% ID/g, respectively). The brain-to-blood ratios of [18F]1a,b were better than [68Ga]FAPI04. Biodistribution and PET imaging showed that [18F]1a had better uptake on tumors and a higher tumor-to-muscle ratio than [18F]1b and [68Ga]FAPI04. Further imaging of U87MG intracranial glioma showed that [18F]1a outlined high-contrast gliomas in a short period of time compared to [18F]1b. Therefore, [18F]1a is expected to be useful in the diagnosis of FAP-related brain diseases.

Unlocking the potential of milk whey protein components in colorectal cancer prevention and therapy.

Extensive research from large prospective cohort studies and meta-analytical investigations over recent decades have consistently indicated that dairy foods have protective effects, reducing the risk of colorectal cancer. Most of the literature has explored the potential role of milk minerals and vitamins in managing colorectal cancer. Yet, there is a paucity of a comprehensive summary of the anticancer attributes of milk protein components and their underlying mechanisms of action. Recent advancements have spotlighted the potential of whey proteins, including ß-lactoglobulin, α-lactalbumin, serum albumin, and lactoferrin, as promising candidates for both the prevention and treatment of colorectal cancer. Notably, whey proteins have demonstrated a more pronounced capacity for suppressing carcinogen-induced tumors when compared to casein. Their strong binding affinity enables them to serve as effective carriers for small molecules or drugs targeting colon cancer therapy. Furthermore, numerous studies have underscored the anti-inflammatory and antioxidant prowess of whey proteins in cancer prevention. Additionally, whey proteins have been shown to trigger apoptosis, hinder tumor cell proliferation, and impede metastasis. This comprehensive review, therefore, not only substantiates the significance of incorporating whey protein components into a balanced daily diet but also underscores their potential in safeguarding against the onset and progression of colorectal cancer.

Dairy products have consistently had protective effects in reducing the risk of colorectal cancer.Whey proteins have shown promise as candidates for the prevention and treatment of colorectal cancer.Whey proteins have a strong binding ability, enabling them to act as carriers of small molecules or drugs targeting colon cancer therapy.Their anti-inflammatory and anti-oxidant capacity may play a role in cancer prevention.Whey proteins could induce apoptosis and inhibit the proliferation and metastasis of tumor cells.

Design, Synthesis, and Biological Evaluation of a Novel [18F]-Labeled Arginine Derivative for Tumor Imaging.

To better diagnose and treat tumors related to arginine metabolism, (2S,4S)-2-amino-4-(4-(2-(fluoro-18F)ethoxy)benzyl)-5-guanidinopentanoic acid ([18F]7) was designed and prepared by introducing [18F]fluoroethoxy benzyl on carbon-4 of arginine. [18F]7 and 7 were successfully prepared using synthesis methods similar to those used for (2S,4S)-4-[18F]FEBGln and (2S,4S)-4-FEBGln, respectively. In vitro experiments on cell transport mechanisms showed that [18F]7 was similar to (2S,4S)4-[18F]FPArg and was transported into tumor cells by cationic amino acid transporters. However, [18F]7 can also enter MCF-7 cells via ASC and ASC2 amino acid transporters. Further microPET-CT imaging showed that the initial uptake and retention properties of [18F]7 in MCF-7 subcutaneous tumors were good (2.29 ± 0.09%ID/g at 2.5 min and 1.71 ± 0.09%ID/g at 60 min after administration), without significant defluorination in vivo. However, compared to (2S,4S)4-[18F]FPArg (3.06 ± 0.59%ID/g at 60 min after administration), [18F]7 exhibited lower tumor uptake and higher nonspecific uptake. When further applied to U87MG imaging, [18F]7 can quickly visualize brain gliomas (tumor-to-brain, 1.85 at 60 min after administration). Therefore, based on the above results, [18F]7 will likely be applied for the diagnosis of arginine nutrition-deficient tumors and efficacy evaluations.

AUF1-induced circular RNA hsa_circ_0010467 promotes platinum resistance of ovarian cancer through miR-637/LIF/STAT3 axis.

BACKGROUND: Increasing evidences has indicated that primary and acquired resistance of ovarian cancer (OC) to platinum is mediated by multiple molecular and cellular factors. Understanding these mechanisms could promote the therapeutic efficiency for patients with OC. METHODS: Here, we screened the expression pattern of circRNAs in samples derived from platinum-resistant and platinum-sensitive OC patients using RNA-sequencing (RNA-seq). The expression of hsa_circ_0010467 was validated by Sanger sequencing, RT-qPCR, and fluorescence in situ hybridization (FISH) assays. Overexpression and knockdown experiments were performed to explore the function of hsa_circ_0010467. The effects of hsa_circ_0010467 on enhancing platinum treatment were validated in OC cells, mouse model and patient-derived organoid (PDO). RNA pull-down, RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were performed to investigate the interaction between hsa_circ_0010467 and proteins. RESULTS: Increased expression of hsa_circ_0010467 is observed in platinum-resistant OC cells, tissues and serum exosomes, which is positively correlated with advanced tumor stage and poor prognosis of OC patients. Hsa_circ_0010467 is found to maintain the platinum resistance via inducing tumor cell stemness, and silencing hsa_circ_0010467 substantially increases the efficacy of platinum treatment on inhibiting OC cell proliferation. Further investigation reveals that hsa_circ_0010467 acts as a miR-637 sponge to mediate the repressive effect of miR-637 on leukemia inhibitory factor (LIF) and activates the LIF/STAT3 signaling pathway. We further discover that AUF1 could promote the biogenesis of hsa_circ_0010467 in OC. CONCLUSION: Our study uncovers the mechanism that hsa_circ_0010467 mediates the platinum resistance of OC through AUF1/hsa_circ_0010467/miR-637/LIF/STAT3 axis, and provides potential targets for the treatment of platinum-resistant OC patients.

Single-cell characterization of tumor evolution from precursor diseases.

Elucidating the characteristics of precursor diseases is important to the understanding of malignant transformation during tumor progression. In a recent study, Dang et al. characterized the cellular and molecular evolution from precursor conditions to multiple myeloma (MM) by integrating single-cell RNA sequencing (scRNA-seq) and B cell-receptor sequencing (scBCR-seq).

A New Parameter to Evaluate Fetal Sylvian Fissure by Transabdominal 2-D Ultrasound.

OBJECTIVE: Evaluation of the inclination direction and degree of the Sylvian fissure plateau has not been reported. We aimed to evaluate the Sylvian fissure plateau by Sylvian fissure plateau angle (SFPA) in axial views at 23-28 wk gestation. METHODS: A prospective ultrasound evaluation of 180 normal and 3 abnormal singleton pregnant women was conducted at 23-28 wk gestation. All cases were assessed in three axial planes of the fetal brain (the transthalamic, transventricular and transcerebellar plane) using transabdominal 2-D images. The SFPAs of all cases were measured between the brain midline and a line drawn along the Sylvian fissure plateau. Intraclass correlation coefficients (ICCs) were used to assess the intra- and inter-observer repeatability of SFPA measurements. RESULTS: The SFPAs in normal cases in the transthalamic, transventricular and transcerebellar planes were all above y = 0, while in abnormal cases were below y = 0. However, there was no major difference between the angles measured on the transthalamic and transventricular planes (p = 0.365). There was a major difference between the SFPAs on the transcerebellar plane and transthalamic/transventricular plane (p < 0.05). The intra- and inter-observer ICCs were excellent at 0.971 (95% confidence interval [CI]: 0.945-0.984) and 0.936 (95% CI: 0.819-0.979), respectively. CONCLUSION: The SFPAs of the normal cases in three axial views were stable at 23-28 wk gestation, suggesting that 0° may be a good cut-off value for evaluating abnormal SFPA. Findings offer a potential method by which the SFPA < 0°, as shown in three abnormal cases described herein, can be evaluated prenatally and thus serve as another tool for malformations of cortical development assessment, especially for frontoobitalopercula dysplasia. We recommend use of SFPA of the transthalamic plane to evaluate the Sylvian fissure in clinical work.

Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy.

Circular RNAs (circRNAs) play important roles in the regulation of cancer. However, the clinical implications and regulatory networks of circRNAs in cancer patients receiving immune checkpoint blockades (ICB) have not been fully elucidated. Here, we characterize circRNA expression profiles in two independent cohorts of 157 ICB-treated advanced melanoma patients and reveal overall overexpression of circRNAs in ICB non-responders in both pre-treatment and early during therapy. Then, we construct circRNA-miRNA-mRNA regulatory networks to reveal circRNA-related signaling pathways in the context of ICB treatment. Further, we construct an ICB-related circRNA signature (ICBcircSig) score model based on progression-free survival-related circRNAs to predict immunotherapy efficacy. Mechanistically, the overexpression of ICBcircSig circTMTC3 and circFAM117B could increase PD-L1 expression via the miR-142-5p/PD-L1 axis, thus reducing T cell activity and leading to immune escape. Overall, our study characterizes circRNA profiles and regulatory networks in ICB-treated patients, and highlights the clinical utility of circRNAs as predictive biomarkers of immunotherapy.

Medium chain fatty acid supplementation improves animal metabolic and immune status during the transition period: A study on dairy cattle.

The transition period is the stage of the high incidence of metabolic and infectious diseases in dairy cows. Improving transition dairy cows' health is crucial for the industry. This study aimed to determine the effects of dietary supplementation medium-chain fatty acids (MCFAs) on immune function, metabolic status, performance of transition dairy cows. Twenty multiparous Holstein cows randomly assigned to two treatments at 35 d before calving. 1) CON (fed the basal 2) MCFA treatment (basal diet was supplemented at an additional 20 g MCFAs mixture every day) until 70 d after calving. The results showed that the serum amyloid A myeloperoxidase concentrations in the blood of cows in MCFA treatment significantly decreased during the early lactation (from 1 d to 28 d after calving) 0.03, 0.04, respectively) compared with the CON, while the tumor necrosis factor concentration was significantly decreased at 56 d after calving (P = 0.02). In addition, the concentration of insulin in the pre-calving (from 21 d before calving to calving) blood of cows in MCFA treatment was significantly decreased (P = 0.04), and concentration of triglyceride also showed a downward trend at 28 d after calving 0.07). Meanwhile, MCFAs supplementation significantly decreased the concentrations of lithocholic acid, hyodeoxycholic acid, and hyocholic acid in the blood at 1 d calving (P = 0.02, < 0.01, < 0.01, respectively), and the level of hyocholic acid taurocholic acid concentrations (P < 0.01, = 0.01, respectively) decreased dramatically at 14 d after calving. However, compared with the CON, the pre-calving dry matter intake and the early lactation milk yield in MCFA treatment were significantly decreased (P = 0.05, 0.02, respectively). In conclusion, MCFAs supplementation transition diet could improve the immune function and metabolic status of dairy cows, and the health of transition cows might be beneficial from the endocrine status.