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Since the end of 2019, COVID-19 caused by SARS-CoV-2 has spread worldwide, and the understanding of the new coronavirus is in a preliminary stage. Currently, immunotherapy, cell therapy, antiviral therapy, and Chinese herbal medicine have been applied in the clinical treatment of the new coronavirus; however, more efficient and safe drugs to control the progress of the new coronavirus are needed. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) may provide new therapeutic targets for novel coronavirus treatments. The first aim of this paper is to review research progress on COVID-19 in the respiratory, immune, digestive, circulatory, urinary, reproductive, and nervous systems. The second aim is to review the body systems and potential therapeutic targets of lncRNAs, miRNAs, and circRNAs in patients with COVID-19. The current research on competing endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA) in SARS-CoV-2 is summarized. Finally, we predict the possible therapeutic targets of four lncRNAs, MALAT1, NEAT1, TUG1, and GAS5, in COVID-19. Importantly, the role of PTEN gene in the ceRNA network predicted by lncRNA MALAT1 and lncRNA TUG1 may help in the discovery and clinical treatment of effective drugs for COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang, Chen, Zhao, Shen, Wu, Li, Chen, Li, Sun, Gu, Li, Wang, Yao, Zhang, Xiao and Du.)

Intestinal stem cells (ISCs) play an important role in maintaining intestinal homeostasis via promoting a healthy gut barrier. Within the stem cell niche, gut microbiota linking the crosstalk of dietary influence and host response has been identified as a key regulator of ISCs. Emerging insights from recent research reveal that ISC and gut microbiota interplay regulates epithelial self-renewal. This article reviews the recent knowledge on the key role of ISC in their local environment (stem cell niche) associating with gut microbiota and their metabolites as well as the signaling pathways. The current progress of intestinal organoid culture is further summarized. Subsequently, the key challenges and future directions are discussed., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Intraoperative intraocular pressure (IOP) elevation is a risk factor for postoperative blindness. Surgical position is associated with intraoperative IOP elevation. In China, there are few studies on the effect of various surgical positions on intraoperative IOP. This study was conducted to explore IOP change and its related factors in four common surgical positions in China., Methods: This was a cross-sectional observational study. A total of 325 surgical patients who had non-ocular surgery from January 2019 to December 2019 in the hospital, were enrolled in this study. During their surgeries for general anesthesia, these participants were placed in lithotomy position/lateral position/prone position/supine position according to their surgery requirement. IOP was measured by icareTA03 handheld portable tonometer at 9 different time points from admission to exiting the operation room. And general information, postural position, and surgery information were collected through a uniform questionnaire. Multivariate analysis was performed to explore the related factors of IOP change., Results: IOP of both eyes on lithotomy position, lateral position, and supine position showed statistical differences by ANOVA test at each time point (p < 0.05). IOP of both eyes in the prone position before exit from the operating room was significantly higher than IOP 10-min after anesthesia (p < 0.01). IOP under different postural angles showed statistical differences (F value = 4.85, P < 0.05), and the larger the head-down angle, the higher the IOP. IOP on the compressed side in the lateral position was higher than that on the non-compressed side (p < 0.01). In the multivariate linear regression analysis adjusted by other factors, postural position and baseline IOP were associated with IOP difference between before and after surgery (p < 0.01)., Conclusion: IOP in the four surgical positions showed different change patterns with the surgical process and position change. Nurses should assist the surgeon to reduce the head-down angle without interfering with the surgical operation and strengthen the inspection of IOP on patients with long-time surgery, to avoid intraoperative rapid IOP changes., (© 2022. The Author(s).)

Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Numerous approaches have been developed to improve the resin-dentin bond performance, among which the bio-application of mussel-derived compounds have drawn great attention recently. To assess the performance of N -(3,4-dihydroxyphenethyl)methacrylamide (DMA), a mussel-derived compound, as a functional monomer in dental adhesive, its potential property to cross-link with dentin collagen and polymerize with adhesive will first be evaluated by transmission electron microscopy (TEM), attenuated total reflectance technique of Fourier transform infrared (ATR-FTIR), and atomic force microscopy (AFM) via Peakforce QNM mode. After validating the influence of DMA on collagen and adhesive separately, the overall performance of DMA/ethanol solution as a primer in dentin bonding was examined using micro-tensile bond strength (μTBS) testing, fracture pattern observation, and nanoleakage evaluation both immediately and after 10,000 times thermocycling aging. The inhibitory effect of DMA on endogenous metalloproteinases (MMPs) was evaluated by in situ zymography using confocal laser scanning microscopy (CLSM) and the cytotoxicity of DMA was evaluated using cell counting kit-8. Results demonstrated that DMA successfully cross-linked with dentin collagen via non-covalent bonds and had no influence on the polymerization and mechanical properties of the adhesive. Furthermore, even after 10,000 times thermocycling aging, the μTBS and nanoleakage expression of the DMA-treated groups showed no significant change compared with their immediate values. In situ zymography revealed reduced endogenous proteolytic activities after the application of DMA, and no cytotoxicity effect was observed for DMA concentration up to 25 ​μmol/L. Thus, DMA could be used as a novel, biocompatible functional monomer in dentin bonding., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Ltd.)

Main Conclusion: BnPGIPs interacted with Sclerotinia sclerotiorum PGs to improve rapeseed SSR resistance at different levels; the BnPGIP-overexpression lines did not affect plant morphology or seed quality traits. Plant polygalacturonase-inhibiting proteins (PGIPs) play a crucial role in plant defence against phytopathogenic fungi by inhibiting fungal polygalacturonase (PG) activity. We overexpressed BnPGIP2, BnPGIP5, and BnPGIP10 genes in an inbred line 7492 of rapeseed (Brassica napus). Compared with 7492WT, the overexpression of BnPGIP2 lines significantly increased Sclerotinia sclerotiorum resistance in both seedlings and adult plants. BnPGIP5 overexpression lines exhibited decreased S. sclerotiorum disease symptoms in seedlings only, whereas BnPGIP10 overexpression lines did not improve Sclerotinia resistance for seedlings or adult plants. Quantitative real-time PCR analysis of S. sclerotiorum PG1, SsPG3, SsPG5, and SsPG6 genes in overexpressing BnPGIP lines showed that these pathogenic genes in the Sclerotinia resistance transgenic lines exhibited low expression in stem tissues. Split-luciferase complementation experiments confirmed the following: BnPGIP2 interacts with SsPG1 and SsPG6 but not with SsPG3 or SsPG5; BnPGIP5 interacts with SsPG3 and SsPG6 but not with SsPG1 or SsPG5; and BnPGIP10 interacts with SsPG1 but not SsPG3, SsPG5, or SsPG6. Leaf crude protein extracts from BnPGIP2 and BnPGIP5 transgenic lines displayed high inhibitory activity against the SsPG crude protein. BnPGIP-overexpression lines with Sclerotinia resistance displayed a lower accumulation of H 2 O 2 and higher expression of the H 2 O 2 -removing gene BnAPX (ascorbate peroxidase) than 7492WT, as well as elevated expression of defence response genes including jasmonic acid/ethylene and salicylic acid pathways after S. sclerotiorum infection. The plants overexpressing BnPGIP exhibited no difference in either agronomic traits or grain yield from 7492WT. This study provides potential target genes for developing S. sclerotiorum resistance in rapeseed.

Cervical squamous cell carcinoma develops through a series of stages, including low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), microinvasive squamous cell carcinoma (MISCC), and invasive squamous cell carcinoma (ISCC). The difference between HSIL and MISCC is the appearance of microinvasion, which determines the treatment for patients. However, sometimes it is difficult to differentiate HSIL from MISCC in morphology, and no effective markers are available to help determine microinvasion. Here, we evaluated the expression patterns of podoplanin in cervical tissues by immunohistochemistry staining. Results showed that podoplanin was specifically expressed in a continuous or discontinuous linear pattern within the basal layer of cells from normal cervical squamous epithelium (NS) (100%, 96/96) and HSIL (81%, 57/70). However, its expression was completely absent in microinvasive lesions (0%, 72/72), and the location of podoplanin expression loss was consistent with that of microinvasive lesions. Thus, for HSIL with positive podoplanin expression, the sudden loss of podoplanin represents the occurrence of early invasion. Furthermore, podoplanin was expressed in 3.4% (4/118) of ISCC, and its expression was not correlated with the age of the patient, tumor size, differentiation, FIGO stage, depth of invasion, lymph node, or distant metastasis. The prognosis of patients with positive podoplanin was slightly better than those without it (p > 0.05). Therefore, we found that podoplanin, as a new specific marker for the basal layer cells of cervical squamous epithelium, could assist the diagnosis of microinvasion in cervical squamous cell carcinoma. The specific staining pattern of podoplanin provides the possibility of clinical application in the future., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. PE increases the risk of poor outcomes for both the mother and the baby. Methylation-mediated transcriptional dysregulation motifs (methTDMs) could contribute the PE development. However, precise functional roles of methTDMs in PE have not been globally described., Methods: Here, we develop a comprehensive and computational pipeline to identify PE-specific methTDMs following TF, gene, methylation expression profile, and experimentally verified TF-gene interactions., Results: The regulation patterns of methTDMs are multiple and complex in PE and contain relax inhibition, intensify inhibition, relax activation, intensify activation, reverse activation, and reverse inhibition. A core module is extracted from global methTDM network to further depict the mechanism of methTDMs in PE. The common and specific features of any two kinds of regulation pattern are also analyzed in PE. Some key methylation sites, TFs, and genes such as IL2RG are identified in PE. Functional analysis shows that methTDMs are associated with immune-, insulin-, and NK cell-related functions. Drug-related network identifies some key drug repurposing candidates such as NADH., Conclusion: Collectively, the study highlighted the effect of methylation on the transcription process in PE. MethTDMs could contribute to identify specific biomarkers and drug repurposing candidates for PE.

Cisplatin yields significant efficacy and is generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, acquired resistance strongly limits its application. Here, we identified that a novel histone deacetylase (HDAC) inhibitor S11, with P-glycoprotein inhibitory activity, could obviously suppress cell growth in cisplatin-resistant NSCLC cell lines. In addition, S11 could increase the expression of Ac-H4 and p21, which confirmed its HDAC inhibitory action, suppress colony formation, and block cell migration of cisplatin-resistant NSCLC cells. Notably, co-treatment with S11 and cisplatin exhibited synergistically inhibitory efficacy in cisplatin-resistant NSCLC cells. Gene microarray data showed that OAZ1 was downregulated in resistant cells but upregulated after S11 treatment. Further study indicated that knockdown of OAZ1 by siRNA resulted in the decrease of sensitivity of resistant cells to cisplatin treatment and contributed to the increase of resistant cell migration. Additionally, ChIP assay data demonstrated that HDAC inhibitor S11 could increase the accumulation of Ac-H4 in OAZ1 promoter region, suggesting the direct regulation of OAZ1 by HDAC. Importantly, the combination of S11 and cisplatin overcome resistance through inhibiting HDAC activity and subsequently increasing the OAZ1 expression in preclinical model. Moreover, we observed that positive expression of HDAC1 was associated with the downregulation of OAZ1 in NSCLC patients with platinum-based treatment, and predicted drug resistance and poor prognosis. In summary, we demonstrated a role of HDAC/OAZ1 axis in cisplatin-resistant NSCLC and identified a promising compound to overcome cisplatin resistance.

Long noncoding RNAs (lncRNAs) have increasingly been shown to be important biological regulators involved in numerous diseases. Further, increasing evidence demonstrates that circulating lncRNAs can be used as diagnostic biomarkers. Therefore, the purpose of this study was to evaluate the potential for circulating lncRNAs as novel biomarkers for the diagnosis of preeclampsia. In the present study, we measured the expression of five lncRNAs known to be relevant to the uterus in whole blood samples from 48 preeclampsia patients and 24 non-preeclampsia healthy subjects using qRT-PCR. We found that circulating levels of lncRNA BC030099 were significantly higher in patients with preeclampsia (1.232 ± 0.4870) than in non-preeclampsia healthy subjects (0.9928 ± 0.2008, p < 0.05). The area under the receiver operating characteristic (ROC) curve for lncRNA BC030099 was 0.713. Univariate and multivariate analyses identified lncRNA BC030099 as an independent predictor for preeclampsia. In brief, our results suggest that increased plasma levels of lncRNA BC030099 are associated with an increased risk of preeclampsia and may be considered a novel biomarker., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder with the highest incidence in the world. Dysfunction of the blood-brain barrier (BBB) may be responsible for the pathogenesis and pathology of AD for abnormally transporting amyloid-β (Aβ, the main component of the senile plaques) from the sera into the central nervous system. Aβ peptides induce apoptosis in human brain microvascular endothelial cells (hBMECs), the main component of BBB. Apoptosis in neuronal cells plays a critical role in the pathogenesis of AD. Asiaticoside, a natural glycoside extracted from Centella asiatica (L.) Urban, has an anti-apoptotic effect on hBMECs but the molecule mechanism remains unclear. Therefore, we investigate the protective effect of asiaticoside on Aβ 1-42 -induced cytotoxicity and apoptosis as well as associated mechanism in hBMECs with commonly used in vitro methods for clinical development of asiaticoside as a novel anti-AD agent. In the present study, we investigated the effects of asiaticoside on cytotoxicity by Cell Counting Kit-8 assay, mitochondrial membrane potential by JC-1 fluorescence analysis, anti-apoptosis by Hoechst 33258 staining and Annexin V-FITC (fluorescein isothiocyanate) and propidium iodide (PI) analyses, the expressions of TNF-α and IL-6 by enzyme-linked immunosorbent assay (ELISA) and TLR4, MyD88, TRAF6, p-NF-κB p65, and total NF-κB p65 by Western blotting, and nuclear translocation of NF-κB p65 by immunofluorescence analysis in hBMECs. The results showed that pretreatment of asiaticoside (25, 50, and 100 μM) for 12 h significantly attenuated cell growth inhibition and apoptosis, and restored declined mitochondrial membrane potential induced by Aβ 1-42 (50 μM) in hBMECs. Asiaticoside also significantly downregulated the elevated expressions of TNF-α, IL-6, TLR4, MyD88, TRAF6, and p-NF-κB p65, as well as inhibited NF-κB p65 translocation from cytoplasm to nucleus induced by Aβ 1-42 in hBMECs in a concentration-dependent manner. The possible underlying molecular mechanism of asiaticoside may be through inhibiting the TLR4/NF-κB signaling pathway. Therefore, asiaticoside may be developed as a novel agent for the prevention and/or treatment of AD clinically.

The early auxin responsive SAUR family is an important gene family in auxin signal transduction. We here present the first report of a genome-wide identification of SAUR genes in watermelon genome. We successfully identified 65 ClaSAURs and provide a genomic framework for future study on these genes. Phylogenetic result revealed a Cucurbitaceae-specific SAUR subfamily and contribute to understanding of the evolutionary pattern of SAUR genes in plants. Quantitative RT-PCR analysis demonstrates the existed expression of 11 randomly selected SAUR genes in watermelon tissues. ClaSAUR36 was highly expressed in fruit, for which further study might bring a new prospective for watermelon fruit development. Moreover, correlation analysis revealed the similar expression profiles of SAUR genes between watermelon and Arabidopsis during shoot organogenesis. This work gives us a new support for the conserved auxin machinery in plants.