Poly(l-lactic acid) Janus Shape Memory Membranes with Uniform Vertically Penetrative Channels and Slit Pores for Enhanced Fog Collection: Synergistic Effect of Transport through Membranes and Sequential Sliding Behaviors of Water Droplets.

In this work, poly(l-lactic acid) (PLLA) Janus shape memory membranes with uniform vertically penetrative channels (SMEUVs) with slit pores have been fabricated with the help of template-assisting spray-coating and uniaxial tension at high temperature. During fog collection, superhydrophobic and hydrophilic surfaces act as the front (fog-facing) side and back side, respectively, in which the structural characteristics play essential roles. On one hand, the vertically penetrative channels in SMEUVs and the special pore geometry contribute to lower resistance, accelerating the transport of captured water through membranes (from the superhydrophobic side to the hydrophilic side). On the other hand, the movement of water droplets along the back side has been guided by the oriented structures of slit pores, promoting the detachment of droplets from the hydrophilic surface. Their synergistic effect removes captured water in a timely manner and provides fresh sites for the subsequent nucleation of water, enhancing fog collection performance. As a result, the optimal specimen (Janus SMEUVs with a draw ratio of 2.5, placed in the parallel direction) exhibits a much higher water collection rate (∼6×) relative to references (superhydrophobic and hydrophilic membranes). Our results are significant for sustainable development in view of both fog collection in arid regions and the biodegradability of PLLA.

Benefit of aerosol reduction to winter wheat during China's clean air action: A case study of Henan Province.

A strongly declining aerosol radiative effect has been observed in China since 2013 after implementing the clean air action, yet its impact on wheat (Triticum aestivum L.) production remains unclear. We use satellite measures and a biophysical crop model to assess the impact of aerosol-induced radiative perturbations on winter wheat production in the agricultural belt of Henan province from 2013 to 2018. After calibrating parameters with the extended Fourier Amplitude Sensitivity Test (EFAST) and the generalized likelihood uncertainty estimation (GLUE) method, the DSSAT CERES-Wheat model was able to simulate crop biomass and yield more accurately. We found that the aerosol negatively impacted wheat biomass by 21.87% and yield by 22.48% from 2006 to 2018, and the biomass effects from planting to anthesis were more significant compared to anthesis to maturity. Due to the strict clean air action, under all-sky conditions, the surface solar shortwave radiation (SSR) in 2018 increased by about 7.08% over 2006-2013 during the wheat growing seasons. As a result of the improvement of crop photosynthesis, winter wheat biomass and yield increased by an average of 5.46% and 2.9%, respectively. Our findings show that crop carbon uptake and yield will benefit from the clean air action in China, helping to ensure national food and health security.

Evaluation of semen DNA integrity and related parameters with COVID-19 infection: a prospective cohort study.

BACKGROUND: In the context of Corona Virus Disease 2019 (COVID-19) global pandemic, Its impact on male reproductive function should be concerned. METHODS: Our study is a prospective cohort study that recruited participants infected or uninfected with COVID-19 between December 2022 and March 2023. All laboratory tests and questionnaire data were completed at the First Affiliated Hospital of Nanchang University. A total of 132 participants were enrolled, with 78 COVID-19 positive patients as the positive group and 54 COVID-19 negative participants as the negative group. Semen quality was assessed by the fifth World Health Organization criteria. The general characteristics of semen samples were assessed using CASA (computer-assisted sperm analysis). DNA damage and the high density stainability was assessed by sperm chromatin structure analysis (SCSA) based on flowcytometry. RESULTS: The sperm concentration, progressive motility and motility in COVID-19 negative group were significantly higher than positive group. In the following DNA damage analysis, a remarkably lower sperm DNA fragmentation index (DFI) in the COVID-19 negative group. In the positive group, unhealthy lifestyles had no significant effect on semen parameters, DNA fragmentation and nuclear compaction. CONCLUSIONS: After excluding the interference of unhealthy lifestyle, the COVID-19 infection can have a significant impact on the quality of semen, especially the DFI,. Therefore, it shows that COVID-19 can adversely affects male fertility, and this result provides advisory guidance for clinicians.

LncRNA GNAS-AS1 knockdown inhibits keloid cells growth by mediating the miR-188-5p/RUNX2 axis.

Keloid is a common dermis tumor, occurring repeatedly, affecting the quality of patients' life. Long non-coding RNAs (lncRNAs) have crucial regulatory capacities in skin scarring formation and subsequent scar carcinogenesis. The intention of this study was to investigate the mechanism and function of GNAS antisense-1 (GNAS-AS1) in keloids. Clinical samples were collected to evaluate the expression of GNAS-AS1, RUNX2, and miR-188-5p by qRT-PCR. The proliferation, migration, and invasion of HKF cells were detected by CCK-8, wound healing, and Transwell assays. The expression levels of mRNA and protein were examined through qRT-PCR and Western blot assay. Luciferase reporter assay was used to identify the binding relationship among GNAS-AS1, miR-188-5p, and Runt-related transcription factor 2 (RUNX2). GNAS-AS1 and RUNX2 expressions were remarkably enhanced, and miR-188-5p expression was decreased in keloid clinical tissues and HKF cells. GNAS-AS1 overexpression promoted cells proliferation, migration, and invasion, while GNAS-AS1 knockdown had the opposite trend. Furthermore, overexpression of GNAS-AS1 reversed the inhibitory effect of 5-FU on cell proliferation, migration, and invasion. MiR-188-5p inhibition or RUNX2 overexpression could enhance the proliferation, migration, and invasion of HKF cells. GNAS-AS1 targeted miR-188-5p to regulate RUNX2 expression. In addition, the inhibition effects of GNAS-AS1 knockdown on HKF cells could be reversed by inhibition of miR-188-5p or overexpression of RUNX2, while RUNX2 overexpression eliminated the suppressive efficaciousness of miR-188-5p mimics on HKF cells growth. GNAS-AS1 knockdown could regulate the miR-188-5p/RUNX2 signaling axis to inhibit the growth and migration in keloid cells. It is suggested that GNAS-AS1 may become a new target for the prevention and treatment of keloid.

Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder.

Hypusine is formed post-translationally from lysine and is found in a single cellular protein, eukaryotic translation initiation factor-5A (eIF5A), and its homolog eIF5A2. Biosynthesis of hypusine is a two-step reaction involving the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). eIF5A is highly conserved throughout eukaryotic evolution and plays a role in mRNA translation, cellular proliferation, cellular differentiation, and inflammation. DHPS is also highly conserved and is essential for life, as Dhps-null mice are embryonic lethal. Using exome sequencing, we identified rare biallelic, recurrent, predicted likely pathogenic variants in DHPS segregating with disease in five affected individuals from four unrelated families. These individuals have similar neurodevelopmental features that include global developmental delay and seizures. Two of four affected females have short stature. All five affected individuals share a recurrent missense variant (c.518A>G [p.Asn173Ser]) in trans with a likely gene disrupting variant (c.1014+1G>A, c.912_917delTTACAT [p.Tyr305_Ile306del], or c.1A>G [p.Met1?]). cDNA studies demonstrated that the c.1014+1G>A variant causes aberrant splicing. Recombinant DHPS enzyme harboring either the p.Asn173Ser or p.Tyr305_Ile306del variant showed reduced (20%) or absent in vitro activity, respectively. We co-transfected constructs overexpressing HA-tagged DHPS (wild-type or mutant) and GFP-tagged eIF5A into HEK293T cells to determine the effect of these variants on hypusine biosynthesis and observed that the p.Tyr305_Ile306del and p.Asn173Ser variants resulted in reduced hypusination of eIF5A compared to wild-type DHPS enzyme. Our data suggest that rare biallelic variants in DHPS result in reduced enzyme activity that limits the hypusination of eIF5A and are associated with a neurodevelopmental disorder.

Exons as units of phenotypic impact for truncating mutations in autism.

Autism spectrum disorders (ASD) are a group of related neurodevelopmental diseases displaying significant genetic and phenotypic heterogeneity. Despite recent progress in understanding ASD genetics, the nature of phenotypic heterogeneity across probands remains unclear. Notably, likely gene-disrupting (LGD) de novo mutations affecting the same gene often result in substantially different ASD phenotypes. Nevertheless, we find that truncating mutations affecting the same exon frequently lead to strikingly similar intellectual phenotypes in unrelated ASD probands. Analogous patterns are observed for two independent proband cohorts and several other important ASD-associated phenotypes. We find that exons biased toward prenatal and postnatal expression preferentially contribute to ASD cases with lower and higher IQ phenotypes, respectively. These results suggest that exons, rather than genes, often represent a unit of effective phenotypic impact for truncating mutations in autism. The observed phenotypic patterns are likely mediated by nonsense-mediated decay (NMD) of splicing isoforms, with autism phenotypes usually triggered by relatively mild (15-30%) decreases in overall gene dosage. We find that each ASD gene with recurrent mutations can be characterized by a parameter, phenotype dosage sensitivity (PDS), which quantifies the relationship between changes in a gene's dosage and changes in a given disease phenotype. We further demonstrate analogous relationships between exon LGDs and gene expression changes in multiple human tissues. Therefore, similar phenotypic patterns may be also observed in other human genetic disorders.

Machine learning revealed molecular classification of colorectal cancer with negative lymph node metastasis.

Purpose: Accurate preoperative staging directly affects the treatment decision of patients with rectal cancer. However, our understanding of the immune subclasses of CRC without lymph node metastasis is still incomplete.Materials and methods: Here, we first analyzed the subclasses of CRC without lymph node metastasis on the Cancer Genome Atlas (TCGA) and verified its stability in the GSE39582 dataset. Four immune subclasses (C1-C4) were identified and verified by non-negative matrix factorization (NMF) of gene expression profiles. Then, ICI scores of six genes were constructed to characterize subclasses.Results: There were significant differences in metabolic and progression-associated signatures, immune characteristics, and clinical characteristics among subclasses. C3 represented a good prognosis with high TMB. C4 showed unique immune characteristics. We believe that C3 is the initial stage of CRC. After the C1 and C2 stages, it progresses to the C4 stage, and finally, lymph node metastasis occurs.Conclusions: This work may help to provide a basis for immunotherapy decision-making in early CRC and may guide personalized methods of cancer immunotherapy.

Comprehensive Eco-Environment Quality Index Model with Spatiotemporal Characteristics.

Ecological environment assessment, which forms the basis for the survival and development of human society, is a crucial measure for the sustainable development of society and economy. However, current quantitative assessment models such as EI, EQI, RSEI et al. are insufficient to meet the requirements of dynamic research in large areas, long time series and dense time intervals. Therefore, in this paper, we constructed the comprehensive ecological environment quality index model SCEQI that can meet these needs by applying the remote sensing big data as the data source. The SCEQI aggregated the ecological indices NDVI, NDBSI, Lst and Wet by full-sequence dynamic dimensionless, automated principal component analysis and multi-temporal average method. In order to verify the spatial and temporal accuracy of the model, we took Henan Province as an example to compare the result of SCEQI with that of EI, EQI, RSEI and proved that SCEQI performed better in both time and space. Also, we verified the superiority of time, space, and precision of SCEQI with profiles, samples, and cluster analysis.

Effects of patient decision aids in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIMS: This study aimed to systematically evaluate the effectiveness of patient decision aids on knowledge, decisional conflict and decisional self-efficacy outcomes in patients with diabetes. METHODS: A comprehensive database search was performed using the Web of Science, Cochrane Library, PubMed, Embase, PsycINFO (Ovid), CINAHL (EBASCO), CNKI, VIP, Wan Fang Database and the Ottawa Decision Aid Library Inventory (http://decisionaid.ohri.ca/index.html) from inception to 13 October 2019. Two reviewers independently searched databases, screened articles, extracted data and evaluated the risk bias of included studies. Then Rev Man 5.3 software was adopted for statistical analysis. RESULTS: Ten articles containing 1,452 people with diabetes were selected. The results of meta-analysis showed that patient decision aids had a positive effect on reducing decisional conflict and improving decisional self-efficacy among patients with type 2 diabetes. Meanwhile, this article also revealed that patient decision aids have beneficial short-term effects on improving knowledge, but there was no significant long-term effect. CONCLUSION: Patient decision aids are capable of becoming support tools to improve shared decision making. Further implementation studies are required to transform patient decision aids tools into clinical practice.

An enhanced adaptive non-local means algorithm for Rician noise reduction in magnetic resonance brain images.

BACKGROUND: The Rician noise formed in magnetic resonance (MR) imaging greatly reduced the accuracy and reliability of subsequent analysis, and most of the existing denoising methods are suitable for Gaussian noise rather than Rician noise. Aiming to solve this problem, we proposed fuzzy c-means and adaptive non-local means (FANLM), which combined the adaptive non-local means (NLM) with fuzzy c-means (FCM), as a novel method to reduce noise in the study. METHOD: The algorithm chose the optimal size of search window automatically based on the noise variance which was estimated by the improved estimator of the median absolute deviation (MAD) for Rician noise. Meanwhile, it solved the problem that the traditional NLM algorithm had to use a fixed size of search window. Considering the distribution characteristics for each pixel, we designed three types of search window sizes as large, medium and small instead of using a fixed size. In addition, the combination with the FCM algorithm helped to achieve better denoising effect since the improved the FCM algorithm divided the membership degrees of images and introduced the morphological reconstruction to preserve the image details. RESULTS: The experimental results showed that the proposed algorithm (FANLM) can effectively remove the noise. Moreover, it had the highest peak signal-noise ratio (PSNR) and structural similarity (SSIM), compared with other three methods: non-local means (NLM), linear minimum mean square error (LMMSE) and undecimated wavelet transform (UWT). Using the FANLM method, the image details can be well preserved with the noise being mostly removed. CONCLUSION: Compared with the traditional denoising methods, the experimental results showed that the proposed approach effectively suppressed the noise and the edge details were well retained. However, the FANLM method took an average of 13 s throughout the experiment, and its computational cost was not the shortest. Addressing these can be part of our future research.

Effectiveness of cognitive behavioural therapy for perinatal depression: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To systematically review the efficacy of cognitive behavioural therapy for improving mood in perinatal depression. BACKGROUND: The impact of cognitive behavioural therapy on perinatal depression has been evaluated in various studies, but there is uncertainty about their impact. DESIGN: Systematic review and meta-analysis. METHODS: Nine electronic literature databases were searched to retrieve eligible randomised controlled trials: CNKI, VIP digital database, Chinese Wanfang database, the Cochrane library, PubMed, Web of science, EMBASE, PsycINFO, CINAHL from the inception of the databases up to 15 November 2019. The eligible studies were screened and extracted, and then, the methodological quality was evaluated independently by two researchers. The meta-analyst software (Rev Man 5.3) was used to conduct the meta-analysis. Checklist of Preferred Reporting Items for Systematic Reviews and Meta-analyses has been followed. RESULTS: Thirteen RCTs with 966 participants were included. The results showed that the CBT group was superior to the usual care group in reducing depression symptoms of pregnant women after treatment immediately, and the difference was statistically significant. Similarly, at postpartum (<4 months), the results showed that the CBT group was superior to the usual care group in improving depression symptoms of pregnant women. However, there was no statistical difference at postpartum (>4 months). CONCLUSIONS: Cognitive behavioural therapy can effectively relieve the symptoms of depression at short-term effect. However, its long-term effect need to be verified by further clinical studies. RELEVANCE TO CLINICAL PRACTICE: This meta-analysis suggested that cognitive behavioural therapy should be considered as a complementary programme for patients with perinatal depression. Medical workers could apply cognitive behavioural therapy into daily routine cares for perinatal depression.

A New Data Fusion Algorithm for Wireless Sensor Networks Inspired by Hesitant Fuzzy Entropy.

The wireless sensor network (WSN) is mainly composed of a large number of sensor nodes that are equipped with limited energy and resources. Therefore, energy consumption in wireless sensor networks is one of the most challenging problems in practice. On the other hand, data fusion can effectively decrease data redundancy, reduce the amount of data transmission and energy consumption in the network, extend the network life cycle, improve the utilization of bandwidth, and thus overcome the bottleneck on energy and bandwidth consumption. This paper proposes a new data fusion algorithm based on Hesitant Fuzzy Entropy (DFHFE). The new algorithm aims to reduce the collection of repeated data on sensor nodes from the source, and strives to utilize the information provided by redundant data to improve the data reliability. Hesitant fuzzy entropy is exploited to fuse the original data from sensor nodes in the cluster at the sink node to obtain higher quality data and make local decisions on the events of interest. The sink nodes periodically send local decisions to the base station that aggregates the local decisions and makes the final judgment, in which process the burden for the base station to process all the data is significantly released. According to our experiments, the proposed data fusion algorithm greatly improves the robustness, accuracy, and real-time performance of the entire network. The simulation results demonstrate that the new algorithm is more efficient than the state-of-the-art in terms of both energy consumption and real-time performance.

TrmFO, a Fibronectin-Binding Adhesin of Mycoplasma bovis.

Mycoplasma bovis is an important pathogenic mycoplasma, causing the cattle industry serious economic losses. Adhesion is a crucial step in the mycoplasmas' infection and colonization process; fibronectin (Fn), an extracellular matrix glycoprotein, is a molecular bridge between the bacterial adhesins and host cell receptors. The present study was designed to characterize the Fn-binding ability of methylenetetrahydrofolate-tRNA-(uracil-5-)-methyltransferase (TrmFO) and its role in M. bovis cytoadherence. The trmFO (MBOV_RS00785) gene was cloned and expressed in E. coli BL21, and polyclonal antibodies against the recombinant TrmFO (rTrmFO) were raised in rabbits. Immunoblotting demonstrated that TrmFO was an immunogenic component, and the TrmFO expression was conserved in different M. bovis isolates. The mycoplasmacidal assay further showed that in the presence of complement, rabbit anti-recombinant TrmFO serum exhibited remarkable mycoplasmacidal efficacy. TrmFO was detected in both the M. bovis membrane and cytoplasm. By ligand dot blot and enzyme-linked immunosorbent assay (ELISA) binding assay, we found that rTrmFO bound Fn in a dose-dependent manner. Immunostaining visualized by confocal laser scanning microscopy showed that rTrmFO had capacity to adhere to the embryonic bovine lung (EBL) cells. In addition, the adhesion of M. bovis and rTrmFO to EBL cells could be inhibited by anti-rTrmFO antibodies. To the best of our knowledge, this is the first report to characterize the Fn-binding ability of TrmFO and its role in the bacterial adhesion to host cells.

Hyaluronic acid/chitosan microcapsules capped with hollow CuS nanoparticles for NIR/pH dual-responsive drug release.

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.

Switchable surface and loading/release of target molecules in hierarchically porous PLA nonwovens based on shape memory effect.

In this work, hierarchically porous PLA (polylactic acid) shape memory nonwovens were prepared by electrospinning its blend solution with PEO (polyethylene oxide) and subsequent water etching. Based on shape memory effect resulting from tiny crystals and the amorphous matrix of PLA, the switch between compact and porous surfaces has been achieved via cyclical hot-pressing and recovery in a hot water bath. After hot-pressing, the disappearance of hierarchical pores contributes to compact surface, enabling embedding of the target molecule in PLA nonwoven (i.e., CLOSE state). Upon exposure to heat, PLA nonwoven recovers to its permanent shape and exhibits a porous surface, providing a penetrative diffusion pathway for small molecules (i.e., OPEN state). The hierarchically porous structure and shape memory effect endow PLA nonwoven with the capability of rapid release. Our results provide a good candidate for some potential applications, such as temperature-controlled quick-release of catalysts and drugs.

Lipidomic and transcriptomic characteristics of boar seminal plasma extracellular vesicles associated with sperm motility.

Seminal plasma extracellular vesicles (SPEVs) play an important role in regulating sperm motility by delivering various cargoes, such as miRNAs, mRNAs, proteins and metabolites. However, information on the lipid compositions of SPEVs and their roles in semen quality is limited. Here, we performed high-throughput transcriptomic and lipidomic analysis on SPEVs isolated from 20 boars with high or low sperm motility. Then, we evaluated the lipid composition and gene expression characteristics of SPEVs and identified the specific lipids and genes related to sperm motility. As a result, a total of 26 lipid classes were identified in SPEVs, and five subclasses, CerG2, CerG3, LPE, LPS and TG, were significantly different in boars with high and low sperm motility. In addition, 195 important lipids and 334 important genes were identified by weighted gene coexpression analysis (WGCNA) and differential expression analysis. We observed that several important genes and lipids in SPEVs potentially influence sperm motility via glycerophospholipid metabolism, glycerolipid metabolism, the sphingolipid signaling pathway and the ferroptosis pathway. Furthermore, we found a significant correlation between the content of 22 lipids and the expression levels of 67 genes (|cor| > 0.8, P < 0.05). Moreover, we observed that three important gene-lipid linkages (CerG1 (d22:0/24:0) - RCAN3, Cer (d18:1/24:0) - SCFD2 and CerG1 (d18:0/24:1) - SCFD2) were strongly correlated with sperm motility. Based on the results, some genes and lipids in SPEVs may play important roles in sperm motility by interacting with sperm through important pathways.

Raspberry Ketone Prevents LPS-Induced Depression-Like Behaviors in Mice by Inhibiting TLR-4/NF-κB Signaling Pathway via the Gut-Brain Axis.

SCOPE: Depression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food-derived phenolics. Raspberries, renowned globally for their delectable flavor, harbor a phenolic compound known as raspberry ketone (RK). However, the impact of RK on depressive symptoms remains ambiguous. This study aims to investigate the impact of RK on lipopolysaccharide (LPS)-induced depressed mice and elucidates its potential mechanisms, focusing on the gut-brain axis. METHODS AND RESULTS: Through behavioral tests, RK exerts a notable preventive effect on LPS-induced depression-like behaviors in mice. RK proves capable of attenuating gut inflammation, repairing gut barrier impairment, modulating the composition of the gut microbiome (Muribaculaceae, Streptococcus, Lachnospiraceae, and Akkermansia), and promoting the production of short-chain fatty acids. Furthermore, RK alleviates neuroinflammation by suppressing the TLR-4/NF-κB pathway and bolsters synaptic function by elevating levels of neurotrophic factors and synapse-associated proteins. CONCLUSION: The current study provides compelling evidence that RK effectively inhibits the TLR-4/NF-κB pathway via the gut-brain axis, leading to the improvement of LPS-induced depression-like behaviors in mice. This study addresses the research gap in understanding the antidepressant effects of RK and illuminates the potential of utilizing RK as a functional food for preventing depression.

N6-methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer.

BACKGROUND: Chemoresistance is a major cause of treatment failure in gastric cancer (GC). Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an N6-methyladenosine (m6A)-binding protein involved in a variety of cancers. However, whether m6A modification and hnRNPA2B1 play a role in GC chemoresistance is largely unknown. In this study, we aimed to investigate the role of hnRNPA2B1 and the downstream mechanism in GC chemoresistance. METHODS: The expression of hnRNPA2B1 among public datasets were analyzed and validated by quantitative PCR (qPCR), Western blotting, immunofluorescence, and immunohistochemical staining. The biological functions of hnRNPA2B1 in GC chemoresistance were investigated both in vitro and in vivo. RNA sequencing, methylated RNA immunoprecipitation, RNA immunoprecipitation, and RNA stability assay were performed to assess the association between hnRNPA2B1 and the binding RNA. The role of hnRNPA2B1 in maintenance of GC stemness was evaluated by bioinformatic analysis, qPCR, Western blotting, immunofluorescence, and sphere formation assays. The expression patterns of hnRNPA2B1 and downstream regulators in GC specimens from patients who received adjuvant chemotherapy were analyzed by RNAscope and multiplex immunohistochemistry. RESULTS: Elevated expression of hnRNPA2B1 was found in GC cells and tissues, especially in multidrug-resistant (MDR) GC cell lines. The expression of hnRNPA2B1 was associated with poor outcomes of GC patients, especially in those who received 5-fluorouracil treatment. Silencing hnRNPA2B1 effectively sensitized GC cells to chemotherapy by inhibiting cell proliferation and inducing apoptosis both in vitro and in vivo. Mechanically, hnRNPA2B1 interacted with and stabilized long noncoding RNA NEAT1 in an m6A-dependent manner. Furthermore, hnRNPA2B1 and NEAT1 worked together to enhance the stemness properties of GC cells via Wnt/ß-catenin signaling pathway. In clinical specimens from GC patients subjected to chemotherapy, the expression levels of hnRNPA2B1, NEAT1, CD133, and CD44 were markedly elevated in non-responders compared with responders. CONCLUSION: Our findings indicated that hnRNPA2B1 interacts with and stabilizes lncRNA NEAT1, which contribute to the maintenance of stemness property via Wnt/ß-catenin pathway and exacerbate chemoresistance in GC.

Hsa_circ_0015382 is involved in the pathogenesis of preeclampsia by mediating THBS2 expression.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy that causes significant maternal and perinatal morbidity and mortality. Circular RNA (circRNA) hsa_circ_0015382 is associated with the pathogenesis of PE, but its underlying regulatory mechanism remains to be explored. METHODS: Relative RNA levels of hsa_circ_0015382, microRNA-616-3p and thrombospondin-2 (THBS2) were detected by quantitative reverse transcription-polymerase chain reaction. In vitro regulatory effects of hsa_circ_0015382 on the proliferation, migration, invasion and angiogenesis of trophoblasts were evaluated by CCK-8, flow cytometry for cell cycle, EdU, transwell, wound healing and HUVEC tube formation assays, respectively. Targeting interaction was verified by dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: Hsa_circ_0015382 was highly expressed in placental tissues from PE patients. Upregulation of hsa_circ_0015382 repressed trophoblast proliferation, migration, invasion and lowered trophoblast-induced HUVEC tube formation. Hsa_circ_0015382 was validated as a miR-616-3p sponge and miR-616-3p targeted THBS2. Hsa_circ_0015382 could mediate trophoblast proliferation, migration, invasion and regulate trophoblast-induced HUVEC tube formation by sponging miR-616-3p and regulating THBS2 expression. CONCLUSION: Hsa_circ_0015382 is associated with the pathogenesis of PPE by regulating the miR-616-3p/THBS2 axis. HIGHLIGHTS: Hsa_circ_0015382 is overexpressed in preeclampsia patients. Hsa_circ_0015382 inhibits trophoblast proliferation, migration, invasion and decreases trophoblast-induced HUVEC tube formation. Hsa_circ_0015382 interacts with miR-616-3p to regulate THBS2 expression.