Temporal-spatial cross attention network for recognizing imagined characters.

Previous research has primarily employed deep learning models such as Convolutional Neural Networks (CNNs), and Recurrent Neural Networks (RNNs) for decoding imagined character signals. These approaches have treated the temporal and spatial features of the signals in a sequential, parallel, or single-feature manner. However, there has been limited research on the cross-relationships between temporal and spatial features, despite the inherent association between channels and sampling points in Brain-Computer Interface (BCI) signal acquisition, which holds significant information about brain activity. To address the limited research on the relationships between temporal and spatial features, we proposed a Temporal-Spatial Cross-Attention Network model, named TSCA-Net. The TSCA-Net is comprised of four modules: the Temporal Feature (TF), the Spatial Feature (SF), the Temporal-Spatial Cross (TSCross), and the Classifier. The TF combines LSTM and Transformer to extract temporal features from BCI signals, while the SF captures spatial features. The TSCross is introduced to learn the correlations between the temporal and spatial features. The Classifier predicts the label of BCI data based on its characteristics. We validated the TSCA-Net model using publicly available datasets of handwritten characters, which recorded the spiking activity from two micro-electrode arrays (MEAs). The results showed that our proposed TSCA-Net outperformed other comparison models (EEG-Net, EEG-TCNet, S3T, GRU, LSTM, R-Transformer, and ViT) in terms of accuracy, precision, recall, and F1 score, achieving 92.66 % , 92.77 % , 92.70 % , and 92.58 % , respectively. The TSCA-Net model demonstrated a 3.65 % to 7.49 % improvement in accuracy over the comparison models.

Characterization, evolution, and abiotic stress responses of leucine-rich repeat receptor-like protein kinases (LRR-RLK) in Liriodendron chinense.

BACKGROUND: Liriodendron chinense is susceptible to extinction due to the increasing severity of abiotic stresses resulting from global climate change, consequently impacting its growth, development, and geographic distribution. However, the L. chinense remains pivotal in both socio-economic and ecological realms. The LRR-RLK (leucine-rich repeat receptor-like protein kinase) genes, constituting a substantial cluster of receptor-like kinases in plants, are crucial for plant growth and stress regulation and are unexplored in the L. chinense. RESULT: 233 LchiLRR-RLK genes were discovered, unevenly distributed across 17 chromosomes and 24 contigs. Among these, 67 pairs of paralogous genes demonstrated gene linkages, facilitating the expansion of the LchiLRR-RLK gene family through tandem (35.82%) and segmental (64.18%) duplications. The synonymous and nonsynonymous ratios showed that the LchiLRR-RLK genes underwent a purifying or stabilizing selection during evolution. Investigations in the conserved domain and protein structures revealed that the LchiLRR-RLKs are highly conserved, carrying conserved protein kinase and leucine-rich repeat-like domians that promote clustering in different groups implicating gene evolutionary conservation. A deeper analysis of LchiLRR-RLK full protein sequences phylogeny showed 13 groups with a common ancestor protein. Interspecies gene collinearity showed more orthologous gene pairs between L. chinense and P. trichocarpa, suggesting various similar biological functions between the two plant species. Analysis of the functional roles of the LchiLRR-RLK genes using the qPCR demonstrated that they are involved in cold, heat, and salt stress regulation, especially, members of subgroups VIII, III, and Xa. CONCLUSION: Conclusively, the LRR-RLK genes are conserved in L. chinense and function to regulate the temperature and salt stresses, and this research provides new insights into understanding LchiLRR-RLK genes and their regulatory effects in abiotic stresses.

Plasma Asprosin Concentrations are Associated with Progression of Diabetic Kidney Disease.

Purpose: To explore the expression of asprosin in subjects with pre-DKD and DKD and to analyze its relationship with kidney injury, inflammation, and glucose and lipid metabolism. Methods: Based on urine albumin:creatinine ratio (UACr), participants were divided into DM, pre-DKD, and DKD groups. Relevant human physiological and biochemical parameters were detected in the three groups. Results: We found relatively higher levels of asprosin in both pre-DKD and DKD groups than the DM group. Moreover, data from the Nephroseq database support increased gene expression of asprosin in kidney tissue from DKD patients. Further correlation analysis revealed that the plasma asprosin level was positively correlated with age, waist circumference, waist:hip ratio, systolic blood pressure, creatinine, UACr, triglycerides, HDL-c, fasting insulin, HOMA-IR, and the inflammatory marker G3P and negatively associated with eGFR. Multiple logistical regression analysis showed that asprosin concentration was significantly associated with pre-DKD and DKD after adjusting for sex, age, BMI, WHR, and HOMA-IR, while this correlation was lost after controlling for G3P. Conclusion: Plasma asprosin is associated with kidney injury in diabetic conditions, and this association might be connected through inflammatory response. Further studies are needed to assess the role and mechanism of asprosin in DKD.

Antibiotic use during radical surgery in stage I-III colorectal cancer: correlation with outcomes?

AIMS: Accumulating evidence indicates that the use of antibiotics (ATBs) in cancer patients is potentially correlated with patient prognosis. Interestingly, the use of these agents is not uncommon in colorectal cancer (CRC) patients during surgery; however, their prognostic value in the clinic has never been addressed. MATERIALS AND METHODS: Data on ATB use during surgery, including the cumulative defined daily dose (cDDD) and the number of categories, were collected. Differences in the clinical data between the low and high cDDD subgroups and between subgroups with ≤ 4 and >4 categories. Additionally, the disease-free survival (DFS) and overall survival (OS) among these subgroups and the specific categories were compared. Finally, a Cox proportional hazard model was used to validate the risk factors for the outcome. RESULTS: The number of categories, rather than the cDDD, was a significant predictor of both DFS (P = 0.043) and OS (P = 0.039). Patients with obstruction are more likely to have a high cDDD, whereas older patients are more likely to have multiple categories. There were no significant differences in the DFS (log rank = 1.36, P = 0.244) or OS (log rank = 0.40, P = 0.528) between patients in the low- and high-cDDD subgroups, whereas patients with ≤ 4 categories had superior DFS (log rank = 9.92, P = 0.002) and OS (log rank = 8.30, P = 0.004) compared with those with >4 categories. Specifically, the use of quinolones was harmful to survival (DFS: log rank = 3.67, P = 0.055; OS: log rank = 5.10, P = 0.024), whereas the use of macrolides was beneficial to survival (DFS: log rank = 12.26, P < 0.001; OS: log rank = 9.77, P = 0.002). Finally, the number of categories was identified as an independent risk factor for both DFS (HR = 2.05, 95% CI: 1.35-3.11, P = 0.001) and OS (HR = 1.82, 95% CI: 1.14-2.90, P = 0.012). CONCLUSIONS: The cDDD of ATBs during surgery in stage I-III CRC patients did not correlate with outcome; however, patients in multiple categories or a specific category are likely to have inferior survival. These results suggest that particular caution should be taken when selecting ATBs for these patients in the clinic.

Subcutaneous fat thickness predicts postoperative seroma following laparoscopic total extra-peritoneal hernioplasty.

PURPOSE: Seroma formation is the most common cause of morbidity associated with laparoscopic inguinal hernia repair. This study aimed to examine the relationship between the thickness of subcutaneous fat (TSF) and the risk of postoperative seroma. METHODS: We reviewed data from a prospective cohort of 229 male patients who underwent laparoscopic total extra-peritoneal (TEP) hernioplasty for indirect inguinal hernia between August 2018 and July 2021. The TSF was assessed using preoperative ultrasound images. The risk factors for postoperative seroma were determined using univariate and multivariate logistic regression models. RESULTS: Postoperative seromas occurred in 26 patients (11.4%). The factors associated with postoperative seroma included longer hernia duration, larger hernia defects, extension into the scrotum, and greater TSF (P < 0.05). In multivariate analysis, a greater TSF was independently associated with a greater risk of postoperative seroma (per 1 mm: odd ratio [OR] 1.105, 95% confidence interval [CI] 1.048-1.165, P < 0.001; TSF ≥ 26.0 mm: OR 7.033, 95% CI 2.485-19.901, P < 0.001). Similar results were obtained in the subgroup analysis. The area under the curve of TSF for predicting seroma formation was 0.703 (95% CI 0.601-0.806). CONCLUSION: Ultrasound-derived TSF may be a promising prognostic factor for postoperative seroma in patients undergoing laparoscopic TEP repair. Further validation is required and then this parameter can be used to improve decision-making process.

Case report: BTK inhibitors is effective in type II mixed cryoglobulinemia with wild-type MyD88.

This study presents two cases of type II mixed cryoglobulinemia. One case is essential, while the other is presumably associated with hepatitis B virus (HBV) infection. Both patients tested positive for monoclonal IgMκ, but negative for MyD88 mutation. They showed resistance to rituximab combined with a glucosteroid regimen, but responded positively to BTK inhibitors. These cases highlight the remarkable effectiveness of BTK inhibitors in treating refractory type II cryoglobulinemia without MyD88 mutation. The first patient achieved rapid complete remission of nephrotic syndrome within one month of starting ibrutinib, along with a significant reduction in cryoglobulin levels and abnormal clonal cells. The second patient had a rapid disappearance of rash within three days and accelerated wound healing within one week of initiating orelabrutinib, accompanied by a reduction in C-reactive protein. However, there was no reduction in cryoglobulin levels during the 12-month follow-up. These findings suggest varied mechanisms of action of BTK inhibitors in type II cryoglobulinemia through different mechanisms.

Disrupted de novo pyrimidine biosynthesis impairs adult hippocampal neurogenesis and cognition in pyridoxine-dependent epilepsy.

Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. It points to a need for additional therapeutic interventions for PDE beyond pyridoxine treatment, which provokes us to investigate the mechanisms underlying the impairment of brain hemostasis by ALDH7A1 deficiency. In this study, we show that ALDH7A1-deficient mice with seizure control exhibit altered adult hippocampal neurogenesis and impaired cognitive functions. Mechanistically, ALDH7A1 deficiency leads to the accumulation of toxic lysine catabolism intermediates, α-aminoadipic-δ-semialdehyde and its cyclic form, δ-1-piperideine-6-carboxylate, which in turn impair de novo pyrimidine biosynthesis and inhibit NSC proliferation and differentiation. Notably, supplementation of pyrimidines rescues abnormal neurogenesis and cognitive impairment in ALDH7A1-deficient adult mice. Therefore, our findings not only define the important role of ALDH7A1 in the regulation of adult hippocampal neurogenesis but also provide a potential therapeutic intervention to ameliorate the defective mental capacities in PDE patients with seizure control.

Improving Anti-HIV activity and pharmacokinetics of enfuvirtide (T20) by modification with oligomannose.

Dendritic cells (DCs) play a pivotal role in controlling HIV-1 infections of CD4+ T cells. DC-SIGN, which is expressed on the surface of DCs, efficiently captures HIV-1 virions by binding to the highly mannosylated membrane protein, gp120, and then the DCs transport the virus to target T cells in lymphoid organs. This study explored the modification of T20, a peptide inhibitor of HIV-1 fusion, by conjugation of the N-terminus with varying sizes of oligomannose, which are DC-SIGN-specific carbohydrates, aiming to create dual-targeting HIV inhibitors. Mechanistic studies indicated the dual-target binding of the conjugates. Antiviral assays demonstrated that N-terminal mannosylation of T20 resulted in increased inhibition of the viral infection of TZM-b1 cells (EC50 = 0.3-0.8 vs. 1.4 nM). Pentamannosylated T20 (M5-T20) exhibited a stronger inhibitory effect on virus entry into DC-SIGN+ 293T cells compared with T20 (67% vs. 50% inhibition at 500 µM). M5-T20 displayed an extended half-life in rats relative to T20 (T1/2: 8.56 vs. 1.64 h, respectively). These conjugates represent a potential new treatment for HIV infections with improved antiviral activity and pharmacokinetics, and this strategy may prove useful in developing dual-target inhibitors for other pathogens that require DC-SIGN involvement for infection.

Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells.

The circadian clock throughout the day organizes the activity of neural stem cells (NSCs) in the dentate gyrus (DG) of adult hippocampus temporally. However, it is still unclear whether and how circadian signals from the niches contribute to daily rhythmic variation of NSC activation. Here, we show that norepinephrinergic (NEergic) projections from the locus coeruleus (LC), a brain arousal system, innervate into adult DG, where daily rhythmic release of norepinephrine (NE) from the LC NEergic neurons controlled circadian variation of NSC activation through ß3-adrenoceptors. Disrupted circadian rhythmicity by acute sleep deprivation leads to transient NSC overactivation and NSC pool exhaustion over time, which is effectively ameliorated by the inhibition of the LC NEergic neuronal activity or ß3-adrenoceptors-mediated signaling. Finally, we demonstrate that NE/ß3-adrenoceptors-mediated signaling regulates NSC activation through molecular clock BMAL1. Therefore, our study unravels that adult NSCs precisely coordinate circadian neural circuit and intrinsic molecular circadian clock to adapt their cellular behavior across the day.

Glycan-Modified Peptides for Dual Inhibition of Human Immunodeficiency Virus Entry into Dendritic Cells and T Cells.

Dendritic cells (DCs) play a crucial role in HIV-1 infection of CD4+ T cells. DC-SIGN, a lectin expressed on the surface of DCs, binds to the highly mannosylated viral membrane protein gp120 to capture HIV-1 virions and then transport them to target T cells. In this study, we modified peptide C34, an HIV-1 fusion inhibitor, at different sites using different sizes of the DC-SIGN-specific carbohydrates to provide dual-targeted HIV inhibition. The dual-target binding was confirmed by mechanistic studies. Pentamannose-modified C34 inhibited virus entry into both DC-SIGN+ 293T cells (52%-71% inhibition at 500 µM) and CD4+ TZM-b1 cells (EC50 = 0.7-1.7 nM). One conjugate, NC-M5, showed an extended half-life relative to C34 in rats (T1/2: 7.8 vs 1.02 h). These improvements in antiviral activity and pharmacokinetics have potential for HIV treatment and the development of dual-target inhibitors for pathogens that require the involvement of DC-SIGN for infection.

Adult neurogenesis research in China.

Neural stem cells are multipotent stem cells that generate functional newborn neurons through a process called neurogenesis. Neurogenesis in the adult brain is tightly regulated and plays a pivotal role in the maintenance of brain function. Disruption of adult neurogenesis impairs cognitive function and is correlated with numerous neurologic disorders. Deciphering the mechanisms underlying adult neurogenesis not only advances our understanding of how the brain functions, but also offers new insight into neurologic diseases and potentially contributes to the development of effective treatments. The field of adult neurogenesis is experiencing significant growth in China. Chinese researchers have demonstrated a multitude of factors governing adult neurogenesis and revealed the underlying mechanisms of and correlations between adult neurogenesis and neurologic disorders. Here, we provide an overview of recent advancements in the field of adult neurogenesis due to Chinese scientists.

Serum Isthmin-1 is negatively correlated with HDL-C in type 2 diabetes mellitus.

BACKGROUND: Isthmin-1 (Ism-1) is a newly identified insulin-like adipokine that increases glucose uptake by adipocytes and inhibits hepatic lipid synthesis. Recent studies have shown that Ism-1 can improve the metabolic disorders associated with type 2 diabetes mellitus (T2DM) and improve lipid metabolism. The classic function of high-density lipoprotein cholesterol (HDL-C) is to transport cholesterol from extra-hepatic tissues to the liver for metabolism. In contrast, disorders of lipid metabolism and inflammation are the leading causes of atherosclerosis (As). Atherosclerosis often manifests as loss of elasticity, lipid accumulation, fibrous tissue proliferation and calcium deposits in the affected arteries, eventually forming plaques. AIM: To illustrate the correlation between HDL-C and Ism-1 in T2DM, and the relationship between lipoprotein cholesterol and carotid plaque. METHODS: A total of 128 patients with T2DM were enrolled in the study and basic information was collected. HDL-C levels were measured chemically. Serum Ism-1 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Linear regression analysis was used to assess the correlation between serum Ism-1 levels and HDL-C in patients with T2DM. Basic information was again collected from 226 patients with T2DM. Independent sample t-tests were performed to explore the relationship between carotid plaque formation and lipids. RESULTS: HDL-C was divided into four groups according to quartiles and there was a between-group difference in Ism-1 (p = 0.040). Multivariable linear regression showed a negative association between Ism-1 and HDL-C in T2DM (ß = -0.235, p < 0.001), even after adjusting for related factors (ß = -0.165, p = 0.009). Low-density lipoprotein cholesterol (LDL-C) and HDL-C showed significant differences between the carotid plaque group and the non-carotid plaque group (pLDL-C = 0.007, pHDL-C = 0.003). CONCLUSION: Serum Ism-1 and HDL-C are negatively correlated in T2DM. LDL-C is significantly higher in carotid plaque group than non-carotid plaque group, while HDL-C is significantly lower than in the non-carotid plaque group.

Proteomic Profiling and Tumor Microenvironment Characterization Reveal Molecular and Immunological Hallmarks of Left-Sided and Right-Sided Colon Cancer Tumorigenesis.

Left-sided and right-sided colon cancer (LSCC and RSCC) display different biological and clinical characteristics. However, the differences in their tumorigenesis and tumor microenvironment remain unclear. In this study, we profiled the proteomic landscapes of LSCC and RSCC with data-independent acquisition mass spectrometry (DIA-MS) using fresh tumor and adjacent normal tissues from 24 patients. A total of 7403 proteingroups were primarily identified with DIA-MS. After quality control, 7212 proteingroups were used for further analysis. Through comparing the difference in proteomic profiles between LSCC and RSCC samples, 2556 commonly and 1982 region-type-specific regulated proteingroups were characterized. During the development of LSCC and RSCC, metabolic, growth, cell division, cell adhesion, and migration pathways were found to be significantly dysregulated (P < 0.05), which was further confirmed by transcriptome data from TCGA. Compared to RSCC, most parts of the immune-related signatures, immune cell infiltration scores, and overall immune scores of LSCC were higher. The systematic elucidation of proteomic and transcriptomic profiles in this work improves our understanding of tumorigenesis and immune microenvironment characteristics of LSCC and RSCC.

Glomerular filtration rate in patients with type 2 diabetes mellitus: is serum isthmin-1 level a possible link?

INTRODUCTION: Isthmin-1 (Ism-1) is a novel adipokine. However, little is known regarding the association between Ism-1 and type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between serum Ism-1 levels and glomerular filtration rate (GFR) in patients with T2DM. RESEARCH DESIGN AND METHODS: A total of 209 patients with T2DM were recruited into this retrospective study. Clinical data were collected. Fasting blood samples were collected for serum Ism-1 testing using ELISA kits. Based on the estimated glomerular filtration rate (eGFR), participants were divided into the normal eGFR group (n=167) and the decreased eGFR group (n=42). The relationship between Ism-1 and eGFR was assessed using linear and binary logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was employed to examine the predictive efficacy of Ism-1 for distinguishing patients with eGFR <60 mL/min/1.73 m2. RESULTS: Compared with patients with normal eGFR, serum Ism-1 levels were increased in patients with decreased eGFR (p<0.001). Serum Ism-1 levels were negatively correlated with eGFR in patients with T2DM even after multiple adjustments (p<0.001). For each 0.1 ng/mL increment of Ism-1, the odds of having an eGFR <60 mL/min/1.73 m2 increased by 54.5% (OR=1.545; p<0.001) in patients with T2DM. ROC analysis showed that higher serum Ism-1 levels (>1.297 ng/mL) had predictive efficacy in patients with eGFR <60 mL/min/1.73 m2, with an area under the curve of 0.908. CONCLUSIONS: Serum Ism-1 levels were inversely associated with eGFR, and high Ism-1 levels may be used as a potential biomarker for predicting kidney function impairment in patients with T2DM.

Technological Development and Application of Plant Genetic Transformation.

Genetic transformation is an important strategy for enhancing plant biomass or resistance in response to adverse environments and population growth by imparting desirable genetic characteristics. Research on plant genetic transformation technology can promote the functional analysis of plant genes, the utilization of excellent traits, and precise breeding. Various technologies of genetic transformation have been continuously discovered and developed for convenient manipulation and high efficiency, mainly involving the delivery of exogenous genes and regeneration of transformed plants. Here, currently developed genetic transformation technologies were expounded and compared. Agrobacterium-mediated gene delivery methods are commonly used as direct genetic transformation, as well as external force-mediated ways such as particle bombardment, electroporation, silicon carbide whiskers, and pollen tubes as indirect ones. The regeneration of transformed plants usually involves the de novo organogenesis or somatic embryogenesis pathway of the explants. Ectopic expression of morphogenetic transcription factors (Bbm, Wus2, and GRF-GIF) can significantly improve plant regeneration efficiency and enable the transformation of some hard-to-transform plant genotypes. Meanwhile, some limitations in these gene transfer methods were compared including genotype dependence, low transformation efficiency, and plant tissue damage, and recently developed flexible approaches for plant genotype transformation are discussed regarding how gene delivery and regeneration strategies can be optimized to overcome species and genotype dependence. This review summarizes the principles of various techniques for plant genetic transformation and discusses their application scope and limiting factors, which can provide a reference for plant transgenic breeding.

Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke.

BACKGROUND: Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined. METHODS: We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1CreER. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3-5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry. RESULTS: STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice. CONCLUSIONS: Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.

Effect of biodrying of lignocellulosic biomass on humification and microbial diversity.

By optimizing the carbon to nitrogen (C/N) ratio, this study accomplished an improved level of humification and microbial diversity in the biodrying process of lignocellulosic biomass. The results demonstrated that C/N ratio of 20 accelerated the decomposition of refractory lignocellulose, resulting in lower greenhouse gas emissions and the production of highly mature fertilizer with a germination index of 119.0% and a humic index of 3.2. Moreover, C/N ratio of 20 was found to diversify microbial communities, including Pseudogracilibacillus, Sinibacillus, and Georgenia, which contributed to the decomposition of lignocellulosic biomass and the production of humic acid. Hence, it is recommended to regulate the C/N ratio to 20:1 during the biodrying of biogas residue and wood chips to promote the economic feasibility and bioresource recycling.

Construction and Characterization of Severe Fever with Thrombocytopenia Syndrome Virus with a Fluorescent Reporter for Antiviral Drug Screening.

Severe fever with thrombocytopenia syndrome (SFTS) caused by a novel bunyavirus (SFTSV) is an emerging infectious disease with up to 30% case fatality. Currently, there are no specific antiviral drugs or vaccines for SFTS. Here, we constructed a reporter SFTSV in which the virulent factor nonstructural protein (NSs) was replaced by eGFP for drug screening. First, we developed a reverse genetics system based on the SFTSV HBMC5 strain. Then, the reporter virus SFTSV-delNSs-eGFP was constructed, rescued, and characterized in vitro. SFTSV-delNSs-eGFP showed similar growth kinetics with the wild-type virus in Vero cells. We further detected the antiviral efficacy of favipiravir and chloroquine against wild-type and recombinant SFTSV by the quantification of viral RNA, and compared the results with that of fluorescent assay using high-content screening. The results showed that SFTSV-delNSs-eGFP could be used as a reporter virus for antiviral drug screening in vitro. In addition, we analyzed the pathogenesis of SFTSV-delNSs-eGFP in interferon receptor-deficient (IFNAR-/-) C57BL/6J mice and found that unlike the fatal infection of the wild-type virus, no obvious pathological change or viral replication were observed in SFTSV-delNSs-eGFP-infected mice. Taken together, the green fluorescence and attenuated pathogenicity make SFTSV-delNSs-eGFP a potent tool for the future high-throughput screening of antiviral drugs.

lncRNA RMST suppresses the progression of colorectal cancer by competitively binding to miR-27a-3p/RXRα axis and inactivating Wnt signaling pathway.

Colorectal cancer (CRC) ranks the 3rd in cancer types globally. Long noncoding RNAs (lncRNAs) are related to the initiation and progression of CRC. The current study plans to reveal the action of rhabdomyosarcoma 2-associated transcript (RMST) in CRC. The results show that RMST is downregulated in CRC specimens and cell lines relative to normal specimens and a fetal normal colon cell line (FHC), respectively. Elevation of RMST represses cell proliferation and colony formation and induces cell apoptosis in CRC cells. Bioinformatic analysis reveals a binding site in RMST for miR-27a-3p. The direct association between RMST and miR-27a-3p is confirmed by dual luciferase reporter assay, RNA pull-down assay, and real time-quantitative polymerase chain reaction (RT-qPCR). miR-27a-3p is upregulated in CRC tumor specimens relative to normal specimens, and there is a negative correlation between RMST and miR-27a-3p in CRC tumor specimens. In addition, the effects of RMST overexpression are weakened by the elevation of miR-27a-3p. RMST and retinoid X receptor (RXRα) share the same complementary site with miR-27a-3p. The direct association between RXRα and miR-27a-3p is confirmed by RNA pull-down assay, RT-qPCR and western blot analysis. Overexpression of RMST induces RXRα expression and inactivates the Wnt signaling pathway by decreasing ß-catenin levels in CRC cells. Collectively, our findings reveal a pivotal role of RMST in regulating miR-27a-3p/RXRα axis and counteracting Wnt signaling pathway during the progression of CRC.