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Colorectal cancer (CRC), being one of the most commonly diagnosed cancers worldwide, endangers human health. Because the pathological mechanism of CRC is not fully understood, there are many challenges in the prevention, diagnosis, and treatment of this disease. Long non-coding RNAs (lncRNAs) have recently drawn great attention for their potential roles in the different stages of CRC formation, invasion, and progression, including regulation of molecular signaling pathways, apoptosis, autophagy, angiogenesis, tumor metabolism, immunological responses, cell cycle, and epithelial-mesenchymal transition (EMT). This review aims to discuss the potential mechanisms of several oncogenic lncRNAs, as well as several suppressor lncRNAs, in CRC occurrence and development to aid in the discovery of new methods for CRC diagnosis, treatment, and prognosis assessment.

Summary: Training and experiences are usually required to successfully culture and differentiate human embryonic stem cells (hESCs). Here, we describe a simple but highly efficient protocol to induce endoderm differentiation of hESCs with crotonate, a precursor of crotonyl-CoA for histone crotonylation deposition on endodermal genes. In this protocol, adding crotonate in different endoderm differentiation media significantly increases the differentiation efficiency and substantially reduces the amount of required reagents.For complete details on the use and execution of this protocol, please refer to Fang et al. (2021).

Tumor immune escape refers to the phenomenon in which tumor cells escape the recognition and attack of the body’s immune system through various mechanisms so that they can survive and proliferate in vivo. The imbalance of immune checkpoint protein expression is the primary mechanism for breast cancer to achieve immune escape. Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) are critical immune checkpoints for breast cancer. Immune checkpoint inhibitors block the checkpoint and relieve its inhibition effect on immune cells, reactivate T-cells and destroy cancer cells and restore the body’s ability to resist tumors. At present, immunological checkpoint inhibitors have made significant progress in breast cancer immunotherapy, and it is expected to become a new treatment for breast cancer.

Previous studies have shown that melatonin can mitigate cryopreservation-induced mitochondrial dysfunction in oocytes; however, the underlying molecular mechanism remains unclear. The objective of the present study was to investigate whether melatonin can improve the mitochondrial function during in vitro maturation of vitrified-warmed mouse germinal vesicle (GV) oocytes by modulating phosphorylation of dynamin related protein 1 (Drp1). Vitrification/warming procedures resulted in the following: (1) After cryopreservation of mouse GV oocytes, the phosphorylation level of Drp1 at Ser616 (p-Drp1 Ser616) in metaphase II (MII) oocytes was increased (P < 0.05). Furthermore, the rates of in vitro maturation, cleavage and blastocyst formation after parthenogenetic activation were decreased (P < 0.05). (2) In MII oocytes, the expression levels of translocase of the mitochondrial outer membrane 20 (TOMM20), mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mRNA levels of mitochondrial biogenesis-related genes (Sirt1, Pgc-1α, Tfam) were all decreased (P < 0.05), and (3) Reactive oxygen species (ROS) level, early apoptosis level, Cytochrome C release and mRNA levels of pro-apoptotic related genes (Bax, Caspase9, Caspase3) in MII oocytes were all increased (P < 0.05). The results of this study further revealed that negative impacts of GV oocyte cryopreservation were mitigated by supplementation of warming and in vitro maturation media with 10−7mol /L melatonin or 2 x 10−5mol/L Mdivi-1 (Drp1 inhibitor). Therefore, we concluded that 10−7mol/L melatonin improved mitochondrial function, reduced oxidative stress and inhibited apoptosis by regulating phosphorylation of Drp1, thereby enhancing in vitro development of vitrified-warmed mouse GV oocytes.

Oocyte cryopreservation is widely used in assisted-reproductive technology and animal production. However, cryopreservation not only induces a massive accumulation of reactive oxygen species (ROS) in oocytes, but also leads to oxidative-stress-inflicted damage to mitochondria and the endoplasmic reticulum. These stresses lead to damage to the spindle, DNA, proteins, and lipids, ultimately reducing the developmental potential of oocytes both in vitro and in vivo. Although oocytes can mitigate oxidative stress via intrinsic antioxidant systems, the formation of ribonucleoprotein granules, mitophagy, and the cryopreservation-inflicted oxidative damage cannot be completely eliminated. Therefore, exogenous antioxidants such as melatonin and resveratrol are widely used in oocyte cryopreservation to reduce oxidative damage through direct or indirect scavenging of ROS. In this review, we discuss analysis of various oxidative stresses induced by oocyte cryopreservation, the impact of antioxidants against oxidative damage, and their underlying mechanisms. We hope that this literature review can provide a reference for improving the efficiency of oocyte cryopreservation.

A simple and novel method for the deposition of polypyrrole (PPy) and cellulose nanocrystal (CNC) composites on different fiber substrates by reactive ink-jet printing was proposed. PPy/CNCs composites were successfully prepared, and the surface resistance of conductive layer deposited on different fiber substrates is the least when the monomer concentration is 0.6 M. PPy/CNCs were deposited on polyethylene terephthalate (PET) to form a conductive layer by adding polyvinyl alcohol (PVA), and the optimum sintering temperature is 100 °C (monomer/PVA ratio 4.0, conductivity 0.769 S cm−1). The PPy/CNCs conductive layer deposited on the paper has the lowest surface resistance and the best adhesion, and the surface resistance of PPy/CNCs conductive layer decreases first and then increases with the increase of sulfonate concentration. Moreover, the volume of anion in sulfonate will affect the arrangement and aggregation of PPy molecular chain in composite materials. Appropriate sulfonate doping can improve the conductivity and stability of conductive paper, and the maximum conductivity is 0.813 S cm−1. Three devices based on PPy/CNCs conductive paper were proposed and fabricated. Therefore, this ink-jet printing provides a new method for the preparation of conductive materials, sensors, energy storage and electromagnetic shielding, etc.

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IntroductionCirculating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together.MethodsConcurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method via DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients.ResultsHigher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression.ConclusionsA standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery and the prognosis of AKI worsens with the increase in AKI severity. Syndecan-1(SDC-1) is a biomarker of endothelial glycocalyx degradation. Fluid overload (FO) is associated with poor outcomes in AKI patients and may be related to the damage of endothelial function. This study aimed at demonstrating the association between elevated SDC-1, FO, and AKI progression.Methods: In this prospective study, we screened patients who underwent cardiac surgery and enrolled patients who experienced an AKI within 48 h after surgery from December 1, 2018 to January 31, 2019. Blood and urine samples were collected at the time of AKI diagnosis for plasma SDC-1 (pSDC-1) and urine SDC-1 (uSDC-1) measurements. Fluid balance (FB) = accumulated [fluid intake (L) - fluid output (L)]/body weight (kg) × 100%. FO was defined as FB > 5%. The primary endpoint was progressive AKI, defined as AKI progression from a lower to a higher stage. The patients were divided into progressive AKI group vs. non-progressive AKI group.Results: The quartiles of pSDC-1 concentration (117.3 [67.4, 242.3] ng/mL) showed a graded association with the incidence of progressive AKI, ranging from 5.0, 11.9, 32.6 to 52.4% (p for trend < 0.001). Multivariate logistic regression showed that increased pSDC-1 was an independent risk factor for progressive AKI. The AUC-ROC area of pSDC-1 concentration in predicting AKI progression was 0.847. Linear regression showed a positive correlation between FB and pSDC-1 concentration (R2 = 0.384, p < 0.001). In patients with FO, the progressive AKI incidence was significantly higher in the high pSDC-1 (≥117.3 ng/mL) subgroup than in the low pSDC-1 subgroup (58.3 vs. 17.6%, OR = 9.167, P = 0.005). In patients without FO, the progressive AKI incidence was also significantly higher in the high pSDC-1 subgroup with a lower odds ratio (30.4 vs. 7.4%, OR = 6.714, P = 0.002).Conclusion: Elevated pSDC-1 concentration was associated with progressive AKI after cardiac surgery and showed good predictive ability for progressive AKI. FB was related to the increase of pSDC-1. The interaction between pSDC-1 and FB may further aggravate the progression of AKI.

Background: Success has been reported in PD-1/PD-L1 blockade via pembrolizumab, atezolizumab, or avelumab monotherapy in manifold malignancies including metastatic breast cancer. Due to lack of large-scale study, here we present interim analyses to evaluate the safety and efficacy of these promising strategies in patients with advanced breast cancer.Methods: Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 monotherapy agents before July 1, 2020, were included. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab, land avelumab. Statistics was analyzed by R software and IBM SPSS Statistics 22.Results: Global analysis showed that for this monotherapy, the complete response was 1.26%, partial response was 7.65%, objective response rate (ORR) was 9.85%, and disease control rate (DCR) was 18.33%. 1-year overall survival rate and 6-month progression-free survival rate were 43.34 and 17.24%. Overall incidence of adverse events (AEs) was 64.18% in any grade and 12.94% in severe grade, while the incidence of immune-related AEs (irAEs) was approximately 14.75%: the most common treatment-related AEs of any grade that occurred in at least 5% of patients were arthralgia and asthenia; the most common severe treatment-related AEs occurred in at least 1% of patients were anemia and autoimmune hepatitis; the most common irAEs were hypothyroidism. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06 and 0.31%, respectively. Additionally, by comparing efficacy indicators between PD-L1–positive and PD-L1–negative groups, an implicated correspondence between efficacy and the expression of PD-L1 biomarker was found: the PR was 9.93 vs 2.69%; the ORR was 10.62 vs. 3.07%; the DCR was 17.95 vs. 4.71%.Conclusion: Anti–PD-1/PD-L1 monotherapy showed a manageable safety profile and had a promising and durable anti-tumor efficacy in metastatic breast cancer patients. Higher PD-L1 expression may be closely correlated to a better clinical efficacy.

Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, numerous cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, serves as an alternative inhibitory receptor to be targeted in the clinic. The impacts of LAG3 on immune cell populations and coregulation of immune responses in breast cancer remain largely unknown. To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from 2,994 breast cancer patients. We estimated the landscape of the relationship between LAG3 and 10 types of cell populations of breast cancer. We investigated the correlation pattern between LAG3 and immune modulators in pancancer, particularly the synergistic role of LAG3 with other immune checkpoint members in breast cancer. LAG3 expression was closely related to the malignancy of breast cancer and may serve as a potential biomarker. LAG3 may play an important role in regulating the tumor immune microenvironment of T cells and other immune cells. More important, LAG3 may synergize with CTLA4, PD1/PDL1, and other immune checkpoints, thereby contributing more evidence to improve combination cancer immunotherapy by simultaneously targeting LAG3, PD1/PDL1, and CTLA4.

Abstract Background The commonly used recommended criteria for renal recovery are not unequivocal. This study compared five different definitions of renal recovery in order to evaluate long-term outcomes of cardiac surgery associated acute kidney injury (CSA-AKI). Methods Patients who underwent cardiac surgery between April 2009 and April 2013 were enrolled and divided into acute kidney injury (AKI) and non-AKI groups. The primary endpoint was 3-year major adverse events (MAEs) including death, new dialysis and progressive chronic kidney disease (CKD). We compared five criteria for complete renal recovery: Acute Renal Failure Trial Network (ATN): serum creatinine (SCr) at discharge returned to within baseline SCr + 0.5 mg/dL; Acute Dialysis Quality Initiative (ADQI): returned to within 50% above baseline SCr; Pannu: returned to within 25% above baseline SCr; Kidney Disease: Improving Global Outcomes (KDIGO): eGFR at discharge ≥60 mL/min/1.73 m2; Bucaloiu: returned to ≥90% baseline estimated glomerular filtration rate (eGFR). Multivariate regression analysis was used to compare risk factors for 3-year MAEs. Results The rate of complete recovery for ATN, ADQI, Pannu, KDIGO and Bucaloiu were 84.60% (n = 1242), 82.49% (n = 1211), 60.49% (n = 888), 68.60% (n = 1007) and 46.32% (n = 680). After adjusting for confounding factors, AKI with complete renal recovery was a risk factor for 3-year MAEs (OR: 1.69, 95% CI: 1.20–2.38, P 30% or > 0.4 mg/dL above baseline SCr or 30% or > 0.4 mg/dL of baseline, or eGFR

Abstract The current study aimed to evaluate the expression and role of miR‐323a in the progression of bladder cancer (BC), thereby providing a theoretical basis and potential therapy methods for BC patients. Our data showed that miR‐323a levels were significantly reduced in BC tissues compared with those of non‐cancerous tissues. Meanwhile, miR‐323a was significantly decreased in human BC cell lines (T24, J82, TCCSUP, RT‐112) than that in human normal bladder epithelial cell line SV‐HUC‐1. Furthermore, inhibition of miR‐323a markedly enhanced the migration and invasive capacity of T24 and TCCSUP cells. Moreover, overexpression of miR‐323a significantly prompted the apoptosis of BC cells. Dual luciferase reporter assay and western blot analysis confirmed that c‐Met was a target gene of miR‐323a. More importantly, upregulation of c‐Met significantly prompted BC cell proliferation mainly as a result of the enhanced level of phosphorylation of AKT. This effect could be abolished when c‐Met was silenced in BC cells. In summary, reduced miR‐323a expression in BC contributed to enhanced BC cell proliferation and migration mainly by targeting c‐Met.

Abstract Background To study different value of estimated glomerular filtration rate with normal serum creatinine whether is a risk factor for hidden renal function of cardiac surgery outcomes. Methods A total of 1744 cardiac surgery patients with serum creatinine ≤1.2 mg/dL (female)/1.5 mg/dL (male) were divided into 3 groups: estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 (no renal dysfunction, n = 829), 60 ≤ estimated glomerular filtration rate

The wind climate characteristics around the Wuhan Qingshan Yangtze River Highway Bridge are analyzed based on the wind data of the newly built wind tower at the Bridge site, Huangpi and the Provincial Agricultural Exhibition Center automatic weather station. The basic wind speed at the automatic weather station is estimated by the extreme value type Ⅰ distribution. Then, combined with the wind data at the bridge site, the design wind speed is calculated based on the basic wind speed by the ratio method. Finally, the characteristics of atmospheric turbulence are analyzed in the near surface layer around the bridge. Results are as follows. (1) The annual maximum and extreme wind speeds in the bridge area are 17.0 and 20.9 m·s-1, respectively. Mean number of high wind days is 5.8 d, and the most frequent wind direction is NNE. (2) The annual 10min average maximum wind speed (designed wind speed) in the bridge area at 10m height is 25.6 m·s-1 in a hundred years reappearing period. (3) When wind speed is high, the vertical turbulent flux of horizontal momentum is large and the turbulence parameter is small. The turbulence spectral density is higher by 1-2 orders of magnitude at high twind speed than at low wind speed. The wind attack angle in 1 h is 0 to 3 degrees when the extreme wind speed occurs.

Abstract Highly conductive ink with low sintering temperature is important for printed electronics on paper substrate. Silver nanoparticles (Ag NPs) of different average radii ranging from 48 to 176 nm were synthesized by adjusting the Ag+ concentration in the reaction process. The electric resistivity of the Ag NP-based ink film in relation to Ag NP size, sintering temperature, amount of PVP capping agent on Ag NP surface, and morphology evolution of the film during heating process was investigated. It was found that the resistivity of the films reduced very rapidly with increasing particle size due above all to reduced amount of protective agent capping on the Ag NPs. A semi-empirical relationship between the resistivity and the particle size was proposed. With the help of this mathematical expression, one gains both systematic and detailed insight to the resistivity evaluation with regard to the Ag particle size. The optimal electric resistivity of 4.6 μΩ cm was achieved at 140 °C for 10 min which was very close to the resistivity value of bulk Ag (1.58 μΩ cm). Mechanical flexibility of the printed electronics with the Ag NP-based ink on paper substrates was investigated. The prints on the art coated paper exhibited better flexibility compared to that on the photopaper. This might be attributed to the surface coating composition, surface morphology of the paper, and their corresponding ink absorption property.

This paper investigates the decoding performance of channel-coded ship-based satellite communications on-the-move (SSCOTM) between ships and satellites. In practical communications, ship antennas deviated from satellites by wind waves suffer rapid channel degradation with serious burst errors and even losing all the data. To address this issue, we first establish a mathematical model to study the influence of wind waves and derive the effective signal-to-noise ratio (SNR) in SSCOTM. Second, we propose a vertical Reed-Solomon (RS) with cyclic redundancy check (CRC) and low-density parity check (VRC-LDPC) code, where the RS code and LDPC code are treated as the inner code and outer code to correct both burst and random errors, respectively. Moreover, both the encoder and the decoder of the proposed VRC-LDPC can be carried out in parallel implementations. Finally, simulation results show that the proposed VRC-LDPC performs much better than the conventional codes of the Consultative Committee for Space Data Systems (CCSDS) standard. Thus, this paper provides an excellent alternative channel code for reliable error-correction systems of SSCOTM.

Background: A few studies have shown that urinary kidney injury molecule-1 (uKIM-1) levels are increased in acute kidney injury (AKI); however, the correlation between uKIM-1 and histological tubular injury, which is considered to be the gold standard for evaluating renal damage and predicting prognosis, is still unclear. We performed this study to determine whether the predicted value of uKIM-1 is correlated with renal KIM-1 (tKIM-1) expression and tissue damage in AKI patients. Methods: This retrospective study recruited 14 healthy individuals and 27 biopsy-proven acute tubular injury (ATI) patients. uKIM-1 and plasma KIM-1 (sKIM-1) levels were measured by ELISA, and tKIM-1 expression was evaluated by immunohistochemistry. Results: Elevated levels of urinary, plasma, and renal KIM-1 were found in ATI patients. The uKIM-1 concentration was positively correlated with tKIM-1 expression and reflected the severity of renal histological injury. The outcome of ATI was associated with uKIM-1 expression: the ATI patients with higher uKIM-1 levels had an increased potential for an incomplete recovery of renal function during follow-up. Additionally, the level of KIM-1, regardless of source, was negatively related to the eGFR, and ROC curve analysis revealed that the ROC-AUC was 0.923 (p = 0.000) for the diagnosis of ATI based on a combination of high uKIM-1 and sKIM-1 levels. Conclusion: The uKIM-1 level corresponds with the severity of renal histological damage and can be a potential reliable predictor of adverse renal outcomes in ATI patients. Moreover, combining uKIM-1 and sKIM-1 can increase the sensitivity and specificity of the diagnosis of severe ATI.

Abstract Inflammatory breast cancer (IBC) is an infrequent but aggressive manifestation of breast cancer, which accounts for 2–4% of all breast cancer cases but responsible for 7–10% of breast cancer-related deaths, and with a 20–30% 10-year overall survival compared with 80% for patients with non-IBC with an unordinary phenotype, whose molecular mechanisms are still largely unknown to date. Discovering and identifying novel bio-markers responsible for diagnosis and therapeutic targets is a pressing need. MicroRNAs are a class of small non-coding RNAs that are capable to post-transcriptionally regulate gene expression of genes by targeting mRNAs, exerting vital and tremendous affects in numerous malignancy-related biological processes, including cell apoptosis, metabolism, proliferation and differentiation. In this study, we review present and high-quality evidences regarding the potential applications of inflammatory breast cancer associated microRNAs for diagnosis and prognosis of this lethal disease.

With the development and upgrading of intelligent mines, research on the unmanned walking of intelligent electric shovels (ES) has been carried out to improve the moving efficiency of extra-large excavators. This paper first introduces an electric shovel’s primary moving condition in an open-pit mine. According to the moving characteristics of the heavy-duty crawler, the artificial potential field (APF) algorithm is improved to plan the moving trajectory of the electric shovel and carry out simulation verification. A dynamic model of an electric shovel is established. A fuzzy control tracking method is proposed based on preview displacement and centroid displacement deviation. The robustness of the tracking algorithm is verified by multi-condition simulation. Finally, the electric shovel prototype is tested through path planning and tracking experiments. The experimental results show that the improved artificial potential field algorithm can plan an obstacle-free path that satisfies the movement of an electric shovel, and the electric shovel can quickly track the preset trajectory. The maximum deviation of the track tracking center of mass is no more than 10 cm, and the deviation of the heading angle when the shovel reaches the endpoint is within 2°.

The high-value utilization of sulfate-rich tailings (SRCTs) can accelerate their mass consumption, so the many problems caused by the massive accumulation of SRCTs can be alleviated, such as environmental pollution, land occupation, security risk, etc. This study proposes using SRCTs to replace fine natural aggregates in MgO-activated slag materials (MASMs) and investigate the influence of the sulfur content in SRCTs on the properties of MASMs. The experimental results showed that the 28 d compressive strength of MASM mortars was increased by up to 83% using SRCT composites. Two major mechanisms were discovered: additional hydration product formation and pore structure refinement. The results of XRD suggested that incorporating SRCT composite into MASMs increased the production of expansive sulfate-containing hydration products, such as ettringite, gypsum, and hydroxyl-Afm. The results of element mapping showed that the oxidation of pyrite in SRCTs could release sulfates into the surrounding area and participate in the hydration of MASM, indicating that SRCTs can work as an auxiliary activator for MASMs. Furthermore, the addition of SRCT significantly refined the pore structure of MASMs, leading to the reduction in porosity by up to 37.77%. These findings confirm a synergistic effect on activating the slag between SRCTs and MgO, promoting the mass utilization of SRCTs. As a result, the additional expansive hydration products contribute to the enhanced compressive strength and refined pore structure.

With high pozzolanic reactivity, metakaolin (MK) is a popular supplementary cementitious material (SCM), which can be used to partially replace Portland cement in concretes. Due to its small particle size, however, MK can agglomerate, resulting in a nonuniform matrix and underperformance of the produced concrete. To address this issue, this paper exploits a low-cost, bio-based admixture—black tea extract (BTE)—to replace the traditional petroleum-based chemical admixture to enhance the dispersion and workability of MK blended cement mortars. Major biomolecules in the BTE such as caffeine, catechin, theanine, and theaflavin are rich in polyphenol, hydroxyl, and carboxylic acid groups, which can interact with cement particles and have profound effects on the hydration process and microstructure of the hydration products. Experimental studies showed that BTE does improve the workability of the MK blended cement mortar. More importantly, the BTE introduces significant change on the microstructure of the hardened pastes. Both the pores with size less than 50 nm and the total porosity of the hardened paste were significantly reduced, leading to a significant improvement in the micro- and macro-mechanical properties of the hardened paste. Experimental results suggest that up to 35% greater improvement in the compressive strength at 28 days was achieved using the proposed bio-admixture. Economic and environmental advantages of using the BTE as a renewable admixture were also illustrated through analyzing the cost–benefit, embodied carbon, and eco-efficiency of the MK blended mortars.

Genetic regulation of organisms involves complicated RNA–RNA interactions (RRIs) among messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA). Detecting RRIs is beneficial for discovering biological mechanisms as well as designing new drugs. In recent years, with more and more experimentally verified RNA–RNA interactions being deposited into databases, statistical machine learning, especially recent deep-learning-based automatic algorithms, have been widely applied to RRI prediction with remarkable success. This paper first gives a brief introduction to the traditional machine learning methods applied on RRI prediction and benchmark databases for training the models, and then provides a recent methodology overview of deep learning models in the prediction of microRNA (miRNA)–mRNA interactions and long non-coding RNA (lncRNA)–miRNA interactions.

Acute kidney injury (AKI) is increasingly recognized as a cumulative risk factor for chronic kidney disease (CKD) progression. However, the underlying mechanisms remain unclear. Using an aristolochic acid (AA)-induced mouse model of AKI-to-CKD transition, we found that the development of tubulointerstitial fibrosis following AKI was accompanied with a strong activation of miR-21 and canonical Wnt signaling, whereas inhibition of miR-21 or selective silencing of Wnt ligands partially attenuated AKI-to-CKD transition. To explore the interaction between miR-21 and Wnt/β-catenin signaling, we examined the effects of genetic absence or pharmacologic inhibition of miR-21 on Wnt/β-catenin pathway expression. In miR-21−/− mice and in wild-type mice treated with anti-miR21 oligos, Wnt1 and Wnt4 canonical signaling in the renal tissue was significantly reduced, with partial reversal of renal interstitial fibrosis. Although the renal abundance of miR-21 remained unchanged after inhibition or activation of Wnt/β-catenin signaling, early intervention with ICG-001, a β-catenin inhibitor, significantly attenuated renal interstitial fibrosis. Moreover, early (within 24 h), but not late β-catenin inhibition after AA administration attenuated AA-induced apoptosis and inflammation. In conclusion, inhibition of miR-21 or β-catenin signaling may be an effective approach to prevent AKI-to-CKD progression.

Sphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here, we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD+-dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of Smpdl3b through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation in vitro and in vivo. Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.

Molecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperone CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2). CCT2 is a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). Through the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2,994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer. We found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype. In summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.

BackgroundUrinary tract infections (UTIs) are one the most common infections. The rapid and accurate identification of uropathogens, and the determination of antimicrobial susceptibility, are essential aspects of the management of UTIs. However, existing detection methods are associated with certain limitations. In this study, a new urinary tract infection high-throughput multiplex genetic detection system (UTI-HMGS) was developed for the semi-quantitative detection of 18 pathogens and the simultaneously screening of nine resistance genes directly from the clinical urine sample within 4 hours.MethodsWe designed and optimized a multiplex polymerase chain reaction (PCR) involving fluorescent dye-labeled specific primers to detect 18 pathogens and nine resistance genes. The specificity of the UTI-HMGS was tested using standard strains or plasmids for each gene target. The sensitivity of the UTI-HMGS assay was tested by the detection of serial tenfold dilutions of plasmids or simulated positive urine samples. We also collected clinical urine samples and used these to perform urine culture and antimicrobial susceptibility testing (AST). Finally, all urine samples were detected by UTI-HMGS and the results were compared with both urine culture and Sanger sequencing.ResultsUTI-HMGS showed high levels of sensitivity and specificity for the detection of uropathogens when compared with culture and sequencing. In addition, ten species of bacteria and three species of fungi were detected semi-quantitatively to allow accurate discrimination of significant bacteriuria and candiduria. The sensitivity of the UTI-HMGS for the all the target genes could reach 50 copies per reaction. In total, 531 urine samples were collected and analyzed by UTI-HMGS, which exhibited high levels of sensitivity and specificity for the detection of uropathogens and resistance genes when compared with Sanger sequencing. The results from UTI-HMGS showed that the detection rates of 15 pathogens were significantly higher (P

Purpose: Nomogram prognostic models could greatly facilitate risk stratification and treatment strategies for cancer patients. We developed and validated a new nomogram prognostic model, named NCCBM, for breast cancer patients with brain metastasis (BCBM) using a large BCBM cohort from the SEER (Surveillance, Epidemiology, and End Results) database.Patients and Methods: Clinical data for 975 patients diagnosed from 2011 to 2014 were used to develop the nomogram prognostic model. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using an independent cohort of 542 BCBM patients diagnosed from 2014 to 2015.Results: The following variables were selected in the final prognostic model: age, race, surgery, radiation therapy, chemotherapy, laterality, grade, molecular subtype, and extracranial metastatic sites. The C-index for the model described here was 0.69 (95% CI, 0.67 to 0.71). The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The model was validated in an independent validation cohort with a C-index of 0.70 (95% CI, 0.68 to 0.73).Conclusion: We developed and validated a nomogram prognostic model for BCBM patients, and the proposed nomogram resulted in good performance.

This study aims to investigate the prognostic significance of p-JNK in breast cancer patients receiving neoadjuvant chemotherapy (NACT) and analyze the relationship between anisomycin, p-JNK. A total of 104 breast cancer patients had NACT were enrolled in this study. The western blot and immunohistochemistry assays were used to determine the protein expressions of p-JNK in human breast cancer cell lines and patients’ cancer tissues. The chi-square test and Fisher’s exact test were adopted to gauge the associations between breast cancer and clinicopathological variables by p-JNK expression, whereas the univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of p-JNK expression. The Kaplan-Meier plots and the log-rank test were adopted to determine patients’ disease-free survival (DFS) and overall survival (OS). Findings indicated that the p-JNK expression had prognostic significance in univariate and multivariate Cox regression survival analyses. Results of log-rank methods showed that: (1) the mean DFS and OS times in patients with high p-JNK expression were significantly longer than those in patients with low p-JNK expression (χ2 = 5.908, P = 0.015 and χ2 = 6.593, P = 0.010, respectively). p-JNK expression is a significant prognostic factor that can effectively predict the survival in breast cancer patients receiving NACT. Treatment with the JNK agonist anisomycin can induce apoptosis, lead to increased p-JNK expression and decreased p-STAT3 expression. Moreover, the p-JNK expression was inversely correlated with p-STAT3 expression.

ObjectiveThe purpose of our study was to analyze the clinicopathologic features and surgical and oncological outcomes of adenoid cystic carcinoma (ACC) of the breast and to provide the basis for a clinical therapeutic schedule.MethodsA total of 14 patients with primary breast adenoid cystic carcinoma treated at Cancer Hospital of the Chinese Academy of Medical Sciences from January 2000 to December 2017 were included. Data on clinical presentation, treatment strategy, and outcome, as well as the pathological features of ACC, were reviewed and analyzed.ResultsFourteen patients were diagnosed with ACC of the breast, out of 23205 total patients treated for breast cancer (0.06%). All but three patients were postmenopausal, with a median age at diagnosis of 60.5 years (range, 39–73 years). The most common clinical presentation was a palpable mass (85.7%), and the imaging characteristics of all patients on color Doppler ultrasound and mammography were nonspecific. Six patients (42.9%) were suspected of having ACC by fine-needle aspiration cytology (FNAC) and were confirmed by postoperative histology and immunohistochemistry. All 14 patients underwent surgery, and no patient had a positive lymph node status. Median tumor size was 1.75 cm (range, 1–3 cm). Eight/14 (57.1%) patients were hormone receptor negative (HR−) and HER-2/neu (−) (HER2−). The remaining patients were hormone receptor positive (HR+). There was no significant difference in clinicopathological characteristics between the HR+ group and the HR- group (P>0.05). The mean follow-up period was 57 months. Local recurrence occurred in 14.3% of patients, 1.7% of patients had distant metastasis, all patients with local recurrence or distant metastasis were in the HR (-) group, and all patients were alive at the last follow-up.ConclusionACC of the breast cannot be simply summarized as triple-negative breast cancer because it also includes a small number of hormone receptor-positive breast cancers. Establishing a preoperative diagnosis is difficult on the basis of clinical imaging examination, FNAC may be useful tool in the diagnosis. the final diagnosis can only be assessed based on the results of the histopathological and immunohistochemical examination. Breast-conserving surgery may be an alternative treatment strategy, and axillary lymph node dissection or sentinel node biopsy may not be necessary in some cases.

ObjectivePrognostic nutritional index (PNI), calculated as serum albumin (ALB) (g/L) + 5 × total lymphocyte count (109/L), is initially used to evaluate nutritional status in patients undergoing surgery and may evaluate the therapeutic effects and predict the survival of various solid tumors. The present study aimed to evaluate the potential prognostic significance of PNI in breast cancer patients receiving neoadjuvant chemotherapy (NACT).MethodsA total of 785 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of PNI by receiver operating characteristic curve stratified patients into a low-PNI group (

Summary: Interferon (IFN)-induced activation of the signal transducer and activator of transcription (STAT) family is an important event in antiviral immunity. Here, we show that the nonreceptor kinases c-Abl and Arg directly interact with STAT1 and potentiate the phosphorylation of STAT1 on Y701. c-Abl/Arg could mediate STAT1 phosphorylation independent of Janus kinases in the absence of IFNγ and potentiate IFNγ-mediated STAT1 phosphorylation. Moreover, STAT1 dimerization, nuclear translocation, and downstream gene transcription are regulated by c-Abl/Arg. c-Abl/Arg (abl1/abl2) deficiency significantly suppresses antiviral responses in vesicular stomatitis virus-infected cells. Compared to vehicle, administration of the c-Abl/Arg selective inhibitor AMN107 resulted in significantly increased mortality in mice infected with human influenza virus. Our study demonstrates that c-Abl plays an essential role in the STAT1 activation signaling pathway and provides an important approach for antiviral immunity regulation.

Although various immunotherapies have exerted promising effects on cancer treatment, many patients with cancer continue to exhibit poor responses. Because of its negative regulatory effects on T cells and its biological functions related to immune and inflammatory responses, there has been considerable emphasis on a protein-coding gene named lymphocyte-activation gene 3 (LAG3). Recently, evidence demonstrated marked synergy in its targeted therapy with programmed death-1 and programmed death-1 ligand-1 (PD-1/PD-L1) blockade, and a variety of LAG3 targeted agents are in clinical trials, indicating the important role of LAG3 in immunotherapy. This mini-review discusses preclinical and clinical studies investigating PD-1 pathway blockade in combination with LAG3 inhibition as a potentially more effective immunotherapy strategy for further development in the clinic. This strategy might provide a new approach for the design of more effective and precise cancer immune checkpoint therapies.

The structural engineering codes dictate the design criteria of the facility. Given that different countries use different parameters to design a facility, different codes are followed. Current code comparison focus on the clauses analysis in the code gives theoretical guideline. When the US facility design team needs to make a decision to follow which code to in China, the current study cannot provide a business decision input. This study evaluates the design process to illustrate when and where the codes will be applied and calculated through a design process where the loading and coefficient factors of different codes are analyzed. Software programs built-in codes are then used to design the structure to obtain the structure result in terms of volume of the concrete and weight of the rebar being calculated. The study also presents a case study and calculates that the United States code uses 8–10% more rebar compared to the Chinese code. The study result can be a reference for the project management team who has to make a business decision over which code to be followed at what cost. The paper also identifies the choice of the seismic coefficient factor has a significant impact on the usage of the rebar and might be justified for the future study.

Most of the coastal beach zone in the world is rich in wind energy reserves and has great potential for offshore wind power development. However, the sedimentary environment in the coastal area is complex and changeable, and the nature of the foundation soil of offshore wind power platforms is weak and complex, which is quite different from that in the land areas. In order to systematically study the mechanical properties of marine foundation soils, a series of geotechnical tests are carried out on representative undisturbed seabed soils, such as basic laboratory geotechnical tests, bender element tests, undrained triaxial shear tests, and resonance column tests. The test results show that shear wave velocity (Vs) of marine silt and silty clay increases linearly with the buried depth; the stress-strain relationship curves of silty clay and silt present two different modes of development: strain hardening and strain softening, the undrained shear strength (Sd) of the two types of marine soils decreases with the increase of the void ratio (e), and both present a good single correlation. Based on the relationship between Sd and Vs from the laboratory test of disturbed seabed soils, an undrained strength evaluation method of undisturbed seabed soils under the current stratum conditions incorporating in situ shear wave velocity is established. The dynamic shear modulus (G) in the various strain ranges of undisturbed silty clay and silt increases regularly with the buried depth (H). Meanwhile, the maximum dynamic shear modulus (Gmax) linearly increases with the increase of H, whereas the attenuation relationship of G decreases with the increase of H. The prediction method of G based on buried depth is established with high accuracy.

The effects of marine and continental sedimentary environments and geological ages on the dynamic shear modulus ratio and damping ratio of the Quaternary sedimentary soils in the offshore areas of the Yellow Sea were analyzed by using a resonant column device (GCTS, USA). The results show the following: (1) The Gmax of various marine soils increases with the depth and shows a typical linear relationship. (2) The marine transgression has significantly different effects on the dynamic shear modulus ratio versus the shear strain amplitude curves (i.e., G/Gmax~γa curves) and the damping ratio versus the shear strain amplitude curves (i.e., λ~γa curves) of the different soil types in the offshore areas of the Yellow Sea. The effects of marine transgression were strong on clays, moderate on silty clays, and minor on silts. (3) The geological ages have noticeable effects on the G/Gmax~γa curves of the tested marine silty clays, marine silts, and continental silty clays, but the effects of geological ages on the λ~γa curves are minimal. The fitting parameters and recommended empirical equations of the G/Gmax~γa and λ~γa curves for each type of the tested soils (silty clay, clay, and silt) were obtained mirroring the effects of sedimentary environments and geological ages.

Renal ischemia-reperfusion (I/R) can induce oxidative stress and injury via the generation of reactive oxygen species (ROS). Renal proximal tubular cells are susceptible to oxidative stress, and the dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways. A recent study showed that the generation of ROS can increase perilipin 2 (Plin2) expression in HepG2 cells. Some evidence has also demonstrated the association between Plin2 expression and renal tumors. However, the underlying mechanism of Plin2 in I/R-induced acute kidney injury (AKI) remains elusive. Here, using a mouse model of I/R-induced AKI, we found that ROS generation was increased and the expression of Plin2 was significantly upregulated. An in vitro study further revealed that the expression of Plin2, and the generation of ROS were significantly upregulated in primary tubular cells treated with hydrogen peroxide. Accordingly, Plin2 knockdown decreased apoptosis in renal proximal tubular epithelial cells treated with hydrogen peroxide, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). Overall, the present study demonstrated that Plin2 is involved in AKI; knockdown of this marker might limit apoptosis via the activation of PPARα. Consequently, the downregulation of Plin2 could be a novel therapeutic strategy for AKI.

IntroductionMutations in the teneurin transmembrane protein 4 (TENM4) gene, known to be involved in neuropsychiatric disorders, have been identified in three pedigree of essential tremor (ET) from Spain. ET has overlapping clinical manifestations and epidemiological symptoms with Parkinson’s disease (PD), suggesting these two disorders may reflect common genetic risk factors. In this study, we investigated clinical and genetic manifestations in four unrelated pedigrees with both ET and PD in which TENM4 variants were identified.MethodsWe subsequently explored whether TENM4 variants contributed to the risk of developing PD. The frequency of TENM4 variants was evaluated from four PD pedigrees and other 407 subjects.ResultsThe results revealed 12 different novel heterozygous variants, all at low frequency. A clear general enrichment of TENM4 variants was detected in early onset PD patients (p < 0.001, OR = 5.264, 95% CI = 1.957–14.158).ConclusionThe results indicate that rare TENM4 variants may be associated with an increased risk of PD.

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers.

We designed a high electron mobility transistor (HEMT) epitaxial structure based on an AlGaN/GaN heterojunction, utilizing Silvaco TCAD, and selected AlGaN with an aluminum composition of 0.1 as the back-barrier of the AlGaN/GaN heterojunction. We enhanced the confinement of the two-dimensional electron gas (2DEG) by optimizing the structural parameters of the back barrier, so that the leakage current of the buffer layer is reduced. Through these optimization methods, a lower drain leakage current and a good radio frequency performance were obtained. The device has a cut-off frequency of 48.9 GHz, a maximum oscillation frequency of 73.20 GHz, and a radio frequency loss of 0.239 dB/mm (at 6 GHz). This work provides a basis for the preparation of radio frequency devices with excellent frequency characteristics and low RF loss.

We report here the purification of a novel metal-binding protein from Oratosquilla oratoria (O. oratoria MT-1) by gel and ion-exchange chromatography. SDS-PAGE and MALDI-TOF analyses demonstrated that isolated O. oratoria MT-1 was of high purity with a molecular weight of 12.4 kDa. The fluorescence response to SBD-F derivatives revealed that O. oratoria MT-1 contained a large number of sulfhydryl groups, which is a general property of metallothioneins. Zn and Cu metal stoichiometries for O. oratoria MT-1 were 3.97:1 and 0.55:1, respectively. The proportion of cysteine (Cys) residues in the amino acid composition was 32.69%, and aromatic amino acids were absent. The peptide sequence coverage with Macrobrachium rosenbergii calmodulin (accession AOA3S8FSK5) was 60%. Infrared spectroscopy of O. oratoria MT-1 revealed two obvious peaks at absorption frequencies for the amide I band and the amide II band. CD spectra revealed that the secondary structure was mainly composed of random coil (57.6%) and β-sheet (39.9%). An evaluation of in vitro antioxidant activity revealed that isolated O. oratoria MT-1 has strong reducing activities, exhibiting scavenging rates for DPPH and OH of 77.8% and 75.8%, respectively (IC50 values 0.57 mg/mL and 1.1 mg/mL). O. oratoria MT-1 may be used as a functional additive in cosmetics, health foods, and medical products, as well as a reference material for quantitative analysis of metallothionein in such products.

Renal tubule-interstitial fibrosis is related to chronic kidney disease progression and a typical feature of the aging kidney. Epigenetic modifications of fibrosis-prone genes regulate the development of renal fibrosis. As a kind of “epigenetic diet”, soy isoflavone genistein was reported to have renal protective action and epigenetic-modulating effects. However, its renal protection role and underlying mechanisms are yet to be fully clarified. Herein, we showed that genistein exhibits a demonstrable anti-fibrotic effect on kidney in vivo UUO (unilateral ureteral occlusion) model and renal epithelial cells in vitro model. The mechanism is strongly associated with epithelial-to-mesenchymal transition and m6A RNA demethylase ALKBH5. Mouse fibrotic kidneys induced by UUO exhibited adverse expression of renal fibrosis-related proteins and significant increases in the total m6A level. As an eraser, ALKBH5 showed severer suppression in the renal fibrosis process. However, genistein pretreatment restored ALKBH5 loss remarkably and reduced renal fibrosis, abnormal protein, and inflammatory markers. The examination of possible mechanisms revealed that genistein promoted ALKBH5 and maybe induced the level of mRNA m6A methylation in some epithelial-to-mesenchymal transition-related transcription factors. We found snail was the critical regulator and critical for the protective role of genistein. To verify the relationship between ALKBH5 and snail, we generated knockdown and overexpression of ALKBH5 cells in vitro. ALKBH5 knockdown enhanced the mesenchymal phenotype marker α-smooth muscle actin and snail expression. In agreement, overexpression ALKBH5 increased epithelial adhesion molecule E-cadherin and reduced snail expression. In conclusion, genistein increased renal ALKBH5 expression in UUO-induced renal fibrosis and reduced RNA m6A levels and ameliorates renal damages.

Introduction Psoriasis is a life-long, immune-mediated disease that greatly reduces the quality of life of patients. Plaque psoriasis is the most common form of psoriasis. Treatment options for plaque psoriasis with good tolerance and sufficient response remain profoundly limited. Based on mechanistic findings that suggest the key pathogenic role of interleukin (IL)-17 in plaque psoriasis, we hypothesise that GR1501, a new monoclonal antibody (IL-17A targeted), will be an efficacious treatment for plaque psoriasis. This phase I/II trial aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of GR1501.Methods and analysis A multicentre, randomised, double-blind, phase I/II dose escalation and expansion trial will be conducted at four hospitals in China. In total, 226 patients with plaque psoriasis will be enrolled in the study, with 46 cases in the dose-escalation stage and 180 cases randomised to GR1501 or the placebo in a 3:1 ratio in the expansion cohort. The primary outcomes are safety and tolerability; the secondary outcomes include pharmacokinetics, immunogenicity and efficacy.Ethics and dissemination The study is in accordance with the Declaration of Helsinki, and the ethics approvals of the protocol have been obtained from the ethics committees of all participating centres, including Peking University People’s Hospital, Chinese PLA General Hospital, The First Affiliated Hospital, College of Medicine, Zhejiang University and the Second Xiangya Hospital of Central South University. The findings of the study will be presented in published journals or at scientific conferences or meetings.Trial registration number ChiCTR1800017956.

BackgroundExcessive aggregation of α-synuclein is the key pathophysiological feature of Parkinson’s disease (PD). Rapid eye movement sleep behavior disorder (RBD) is also associated with synucleinopathies and considered as a powerful predictor of PD. Growing evidence suggests the diminished clearance of α-synuclein may be partly attributable to poor interstitial fluid drainage, which can be reflected by magnetic resonance imaging (MRI)-visible enlarged perivascular space (EPVS). However, the effect of MRI-visible EPVS on iRBD and PD, and their correlation with clinical characteristics remain unclear.ObjectiveTo evaluate the clinical and neuroimaging significance of MRI-visible EPVS in iRBD and PD patients.MethodsWe enrolled 33 iRBD patients, 82 PD (with and without RBD) patients, and 35 healthy controls (HCs), who underwent clinical evaluation and 3.0 Tesla MRI. Two neurologists assessed MRI-visible EPVS in centrum semiovale (CSO), basal ganglia (BG), substantia nigra (SN), and brainstem (BS). Independent risk factors for iRBD and PD were investigated using multivariable logistic regression analysis. Spearman analysis was used to test the correlation of MRI-visible EPVS with clinical characteristics of patients.ResultsiRBD patients had significantly higher EPVS burdens (CSO, BG, SN, and BS) than PD patients. Higher CSO-EPVS and BS-EPVS burdens were independent risk factors for iRBD. Furthermore, higher CSO-EPVS and SN-EPVS burdens were positively correlated with the severity of clinical symptom in iRBD patients, and higher BG-EPVS burden was positively correlated with the severity of cognitive impairment in PD patients.ConclusioniRBD and PD patients have different MRI-visible EPVS burdens, which may be related with a compensatory mechanism in glymphatic system. Lower MRI-visible EPVS burden in PD patients may be a manifestation of severe brain waste drainage dysfunction. These findings shed light on the pathophysiologic relationship between iRBD and PD with respect to neuroimaging marker of PD.