Bi-allelic LoF NRROS Variants Impairing Active TGF-ß1 Delivery Cause a Severe Infantile-Onset Neurodegenerative Condition with Intracranial Calcification.

Negative regulator of reactive oxygen species (NRROS) is a leucine-rich repeat-containing protein that uniquely associates with latent transforming growth factor beta-1 (TGF- ß1) and anchors it on the cell surface; this anchoring is required for activation of TGF-ß1 in macrophages and microglia. We report six individuals from four families with bi-allelic variants in NRROS. All affected individuals had neurodegenerative disease with refractory epilepsy, developmental regression, and reduced white matter volume with delayed myelination. The clinical course in affected individuals began with normal development or mild developmental delay, and the onset of seizures occurred within the first year of life, followed by developmental regression. Intracranial calcification was detected in three individuals. The phenotypic features in affected individuals are consistent with those observed in the Nrros knockout mouse, and they overlap with those seen in the human condition associated with TGF-ß1 deficiency. The disease-causing NRROS variants involve two significant functional NRROS domains. These variants result in aberrant NRROS proteins with impaired ability to anchor latent TGF-ß1 on the cell surface. Using confocal microscopy in HEK293T cells, we demonstrate that wild-type and mutant NRROS proteins co-localize with latent TGF-ß1 intracellularly. However, using flow cytometry, we show that our mutant NRROS proteins fail to anchor latent TGF-ß1 at the cell surface in comparison to wild-type NRROS. Moreover, wild-type NRROS rescues the defect of our disease-associated mutants in presenting latent TGF-ß1 to the cell surface. Taken together, our findings suggest that loss of NRROS function causes a severe childhood-onset neurodegenerative condition with features suggestive of a disordered response to inflammation.

E2F7, EREG, miR-451a and miR-106b-5p are associated with the cervical cancer development.

PURPOSE: We aimed to seek the crucial genes or microRNAs (miRNA) correlated with the cervical cancer development. METHODS: The miRNA profiling GSE30656 and gene expression profiling GSE63514 were obtained from Gene Expression Omnibus database. Differentially expressed microRNAs (DEMiRs) and differentially expressed genes (DEGs) were screened. Then target genes of DEMiRs were obtained and matched with DEGs to obtain interaction pairs between DEMiRs and DEGs. Gene Ontology-biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for DEGs and DEMiRs in the DEMiRs-DEGs pairs. The DEMiRs-DEGs regulatory network, protein-protein interaction network and transcription factor (TF)-target regulatory network were constructed. Ultimately, long non-coding RNAs (lncRNAs) associated with DEMiRs were obtained, and then lncRNA-miRNA-target ceRNA network was established. RESULTS: Total 18 DEMiRs and 620 DEGs were identified. DEMiRs were enriched in 35 KEGG pathways, such as PI3K-Akt signaling pathway (involving miR-451a). DEGs were enriched in various functions, such as DNA replication (involving E2F7) and angiogenesis (involving EREG). There were 120 nodes and 216 interaction pairs in the DEMIR-DEG regulatory network, and miR-106b-5p has the greatest degree. EREG and E2F7 were regulated by miR-451a and miR-148a-3p, respectively. Besides, E2F7 was identified in the TF-target regulatory network, regulating CDC6. There were 15 lncRNAs, 11 miRNAs and 90 DEGs in the ceRNA network. Specially, miR-148a-3p was interacted with lncRNA HOTAIR in the ceRNA network. CONCLUSION: E2F7, EREG, miR-451a and miR-106b-5p were likely to be related to the cervical cancer development.

Simple D-A-D Structural Bisbithiophenyl Diketopyrrolopyrrole as Efficient Bioimaging and Photothermal Agents.

Design and synthesis of biocompatible and multifunctional photothermal agents is crucial for effective cancer phototherapy. In order to achieve this ambition, simple D-A-D structural bisbithiophenyl diketopyrrolopyrrole (TDPP) was fabricated. In this molecule, the donor, 2-thiophenylboric acid, was conjugated via Suzuki coupling reaction, which could expand the emission wavelength to the red region of the spectrum. TDPP could self-assemble into stable and uniform nanoparticles (TDPP NPs) in assistant of amphiphilic Pluronic F-127 polymer. Exposing TDPP NPs (100 µg/mL) aqueous dispersion to 638 nm (0.61 W/cm2) laser irradiation resulted in a temperature elevation of approximately 30 °C within 5 min, which is high enough for inducing the cytotoxicity and tumor inhibition. Because of the bathochromic shift absorption of TDPP NPs in water, TDPP NPs could also act as a contrast agent for near-infrared fluorescence imaging (NIRF) to visualize the drug distribution in vivo. Coupled with the infrared thermal imaging properties of the photothermal agent, TDPP NPs were proven to be a multifunctional theranostic agent for dual-modal imaging-guided phototherapy.

Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination.

Long non-coding RNAs (lncRNAs) (> 200 bp) play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS) development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF) occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC) differentiation from Neural Stem Cells (NSCs) and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE) mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation)-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and analysis results via the interactive genome browser at our laboratory website that is freely accessible to the research community. This is the first lncRNA expression database of collective populations of glia, vascular cells, and neurons. We anticipate that these studies will advance the knowledge of this major class of non-coding genes and their potential roles in neurological development and diseases.

The Latest Advancements in Selective Neck Dissection for Early Stage Oral Squamous Cell Carcinoma.

OPINION STATEMENT: The management of cervical lymph node metastasis remains a crucial component of the treatment of head and neck cancers. However, the proper management of clinical N 0 cases with early-stage oral squamous cell carcinoma (OSCC) remains undefined. In the advent of minimally invasive techniques in the 1980s, these techniques have gained popularity among numerous surgeons in all fields of surgery. Although there are no randomized controlled trial data comparing the outcomes of minimally invasive techniques (endoscopically assisted selective neck dissection (SND), robot-assisted SND) with conventional techniques, encouraging evidence from several studies suggests that both endoscopically assisted SND and robot-assisted SND are safe, minimally invasive techniques with achieved short-term oncologic outcomes and can reach a better cosmetic outcome than conventional SND. In this review, we also compare the indications, surgical approaches, and relative advantages and disadvantages of conventional SND, endoscopically assisted SND, and robot-assisted SND to provide surgeons with a means to better consider these techniques for the treatment of early-stage OSCC.

[Genome-wide identification and expression analysis of the WRKY gene family in peach].

The WRKY transcription factors are one of the largest families of transcriptional regulators and play diverse regulatory roles in biotic and abiotic stresses, plant growth and development processes. In this study, the WRKY DNA-binding domain (Pfam Database number: PF03106) downloaded from Pfam protein families database was exploited to identify WRKY genes from the peach (Prunus persica 'Lovell') genome using HMMER 3.0. The obtained amino acid sequences were analyzed with DNAMAN 5.0, WebLogo 3, MEGA 5.1, MapInspect and MEME bioinformatics softwares. Totally 61 peach WRKY genes were found in the peach genome. Our phylogenetic analysis revealed that peach WRKY genes were classified into three Groups: Ⅰ, Ⅱ and Ⅲ. The WRKY N-terminal and C-terminal domains of Group Ⅰ (group I-N and group I-C) were monophyletic. The Group Ⅱ was sub-divided into five distinct clades (groupⅡ-a, Ⅱ-b, Ⅱ-c, Ⅱ-d and Ⅱ-e). Our domain analysis indicated that the WRKY regions contained a highly conserved heptapeptide stretch WRKYGQK at its N-terminus followed by a zinc-finger motif. The chromosome mapping analysis showed that peach WRKY genes were distributed with different densities over 8 chromosomes. The intron-exon structure analysis revealed that structures of the WRKY gene were highly conserved in the peach. The conserved motif analysis showed that the conserved motifs 1, 2 and 3, which specify the WRKY domain, were observed in all peach WRKY proteins, motif 5 as the unknown domain was observed in group Ⅱ-d, two WRKY domains were assigned to GroupⅠ. SqRT-PCR and qRT-PCR results indicated that 16 PpWRKY genes were expressed in roots, stems, leaves, flowers and fruits at various expression levels. Our analysis thus identified the PpWRKY gene families, and future functional studies are needed to reveal its specific roles.

[Radial growth response of Populus euphratica to climate change in the Cele desert oasis ecotone, China]. / ç­–å‹’æ²™æ¼ ç»¿æ´²è¿‡æ¸¡å¸¦èƒ¡æ¨å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Populus euphratica is an important tree species in the arid regions of Northwest China, which is sensitive to climate changes. Climate of the Northwest China is changing to be "warm and humid", but how it would affect the regional forest growth is not clear. In this study, the radial growth response of P. euphratica to major climatic factors and their temporal changes during 1984-2021 were analyzed by using dendrochronology method in the desert oasis ecotone of Cele in the southern Tarim basin. The results showed that tree-ring width index of P. euphratica had a significant negative correlation with temperature in September of the previous year, and in February and May of current year, had significant positive correlation with precipitation in September of previous year and March and May of current year, and had significant positive correlations with SPEI in February and May of current year. The relationships between tree-ring width index and combined month climatic factors were more obvious. The results of moving correlation analysis showed that the correlation between tree-ring width index and temperature in the growing season tended to be strengthened in recent years, while the correlation between tree-ring width index and precipitation, SPEI tended to be declined or remain stable. The variations of the relationships between tree-ring width index and combined month climatic factors were more obvious compared that with single month. Current regional climate is conducive to the growth and development, as well as the improvement of ecological shelter function of P. euphratica forest in the desert oasis ecotone of Cele.

Post-hysterectomy vaginal cuff cancer secondary to HPV infection and CIN: A case report.

We present a case report of secondary vaginal cancer after complete hysterectomy due to myoma that was complicated by low-grade cervical intraepithelial neoplasia (CIN I) and human papilloma virus (HPV) infection. After complete hysterectomy, the HPV DNA level in the vaginal tissue was obviously increased, and vaginal cancer was diagnosed 6 months later. We conclude that HPV infection can cause vaginal cancer after complete hysterectomy in cases complicated by CIN. Therefore, HPV should be regularly assessed during the postoperative follow-up period.

A review on surgical treatment options in gliomas.

Gliomas are one of the most common primary central nervous system tumors, and surgical treatment remains the principal role in the management of any grade of gliomas. In this study, based on the introduction of gliomas, we review the novel surgical techniques and technologies in support of the extent of resection to achieve long-term disease control and summarize the findings on how to keep the balance between cytoreduction and neurological morbidity from a list of literature searched. With modern neurosurgical techniques, gliomas resection can be safely performed with low morbidity and extraordinary long-term functional outcomes.

SARS-CoV-2 Nsp8 induces mitophagy by damaging mitochondria.

Autophagy plays an important role in the interaction between viruses and host cells. SARS-CoV-2 infection can disrupt the autophagy process in target cells. However, the precise molecular mechanism is still unknown. In this study, we discovered that the Nsp8 of SARS-CoV-2 could cause an increasing accumulation of autophagosomes by preventing the fusion of autophagosomes and lysosomes. From further investigation, we found that Nsp8 was present on mitochondria and can damage mitochondria to initiate mitophagy. The results of experiments with immunofluorescence revealed that Nsp8 induced incomplete mitophagy. Moreover, both domains of Nsp8 orchestrated their function during Nsp8-induced mitophagy, in which the N-terminal domain colocalized with mitochondria and the C-terminal domain induced auto/mitophagy. This novel finding expands our understanding of the function of Nsp8 in promoting mitochondrial damage and inducing incomplete mitophagy, which helps us to understand the etiology of COVID-19 as well as open up new pathways for creating SARS-CoV-2 treatment methods.

Two Resveratrol Oligomers Inhibit Cathepsin L Activity to Suppress SARS-CoV-2 Entry.

Cell entry of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) depends on specific host cell proteases, which are the key targets for preventing and treating viral infections. Herein, we describe miyabenol C and trans-ε-viniferin, two resveratrol oligomers that specifically inhibit SARS-CoV-2 entry by targeting host protease cathepsin L. Several cell-based assays were used to demonstrate the effect of resveratrol oligomers, and their target was identified via screening of antiviral targets. Molecular docking analysis suggested that the oligomers could occupy the active cavity of cathepsin L. The surface plasmon resonance assay showed that the equilibrium dissociation constant (KD) values of miyabenol C-cathepsin L and trans-ε-viniferin-cathepsin L were 5.54 and 8.54 µM, respectively, indicating their excellent binding ability for cathepsin L. Our study demonstrated the potential application of resveratrol oligomers as lead compounds in controlling SARS-CoV-2 infection by targeting cathepsin L.

Adenovirus vector-based in vitro neuronal cell model for Huntington's disease with human disease-like differential aggregation and degeneration.

BACKGROUND: Neuronal degeneration, in particular in the striatum, and the formation of nuclear and cytoplasmic inclusions are characteristics of Huntington's disease (HD) as a result of the expansion of a polyglutamine tract located close to the N-terminus of huntingtin (htt). Because of the large (10-kb) size of the htt cDNA, expression of full-length htt in primary neurons has proved difficult in the past. METHODS: We generated a new chronic in vitro model that is based on high-capacity adenovirus vector-mediated transduction of primary murine striatal and cortical neurons. Because the vector has a large capacity for transport of foreign DNA, it was possible to quantitatively express in these primary cells normal and mutant full-length htt (designed as fusion proteins with enhanced green fluorescent protein) in addition to its truncated versions. Pathological changes caused by mutant htt were characterized. RESULTS: The model mimicked several features observed in HD patients: prominent nuclear inclusions in cortical but not in striatal neurons, preferential neuronal degeneration of striatal neurons and neurofilament fragmentation in this cell type. Compared with expressed truncated mutant htt, the expression of full-length mutant htt in neurons resulted in a much slower appearance of pathological changes. Different from cortical neurons, the vast majority of nuclei in striatal cells contained only diffusely distributed N-terminal htt fragments. Cytoplasmic inclusions in both cell types contained full-length mutant htt. CONCLUSIONS: This model and the adenovirus vectors used will be valuable for studying the function of htt and the pathogenesis of HD at molecular and cellular levels in different neuronal cell types.

Detection and imaging of Carbon monoxide releasing Molecule-2 in HeLa cells and zebrafish using a Metal-Free Near-Infrared fluorescent off-on probe.

By incorporating 4-nitrobenzene as the recognition unit into a stable hemicyanine skeleton based on IR 780, a designed near-infrared fluorescent off-on probe DNXI shows excellent analytical performance in real-time monitoring of carbon monoxide releasing molecule-2 (CORM-2) in living HeLa cells and zebrafish without transition metals. The response mechanism of CORM-2 with DNXI may reduce the nitro group to an amino group, followed by 1,6-rearrangement elimination reaction, resulting in the recovery of both color and fluorescence signal. As a result, DNXI shows very low background signal, which is rather desired for achieving sensitive detection of CORM-2. Compared with the existing CORM-2 probes, DNXI shows excellent optical performance in vitro and in vivo, high selectivity and sensitivity to CORM-2, as well as near-infrared fluorescence emission 712 nm, with a low detection limit of 103 nM. More importantly, DNXI is low cytotoxic, cell membrane permeable, and its applicability has been demonstrated for monitoring CORM-2 in living HeLa cells and zebrafish. These superior properties of the probe enable it have great potential to be used in biological systems or in vivo related studies.

[Spatial-temporal variation of vegetation water use efficiency and its relationship with climate factors over the Qinghai-Tibet Plateau, China]. / é’è—é«˜åŽŸæ¤è¢«æ°´åˆ†åˆ©ç”¨æ•ˆçŽ‡æ—¶ç©ºå˜åŒ–åŠä¸Žæ°”å€™å› å­çš„å ³ç³».

Water use efficiency (WUE) is an effective index to study the coupling of land carbon and water cycle. The Qinghai-Tibet Plateau is the most important ecological security barrier in China. Understanding the characteristics and mechanism of WUE is important for the carbon cycle and water resources rational utilization in the plateau. Based on MODIS data of gross primary productivity (GPP) and evapotranspiration (ET), we analyzed the spatial-temporal variations of WUE over the Qinghai-Tibet Plateau and the effects of climate factors. The results showed that WUE in the Qinghai-Tibet Plateau had an upward trend under the combined action of GPP and ET during 2001-2020. The southeast and northeast of the Plateau had the highest WUE value, while the central part had the lowest WUE value. WUE of grassland, marsh and alpine vegetation showed an increasing trend, while that of shrub land, broadleaved forest and coniferous forest showed a decreasing trend. There was a significant positive correlation between WUE and annual air temperature, and the sensitivity increased with the increases of air temperature. The relationship between WUE and annual precipitation was non-linear. When precipitation was less than 700 mm, the sensitivity of WUE to precipitation decreased with the increases of precipitation. When precipitation was more than 700 mm, the sensitivity of precipitation increased with the increases of precipitation. However, WUE was negatively correlated with precipitation in more than 75% of regions, and was affected by precipitation in a larger area. In the future, warm and humid climate would lead to a decrease in WUE.

[Research advances in shrub dendroecology]. / çŒæœ¨å¹´è½®ç”Ÿæ€å­¦ç ”ç©¶è¿›å±•.

The ecological value of shrub-ring data has received more and more attention. The tree-ring data of shrub species have been increasingly used to reveal growth dynamics of regional shrub vegetation and its sensitivity to climate change. Up to now, nearly 70 species of shrubs have been used in the studies of shrub dendrochronology, which considerably broadened the traditional tree-ring research network, enriched the research scope and object of dendrochronology, and certainly with great significance in revealing the characteristics of regional climate fluctuation and annual dynamics of structure, function and service for shrubland ecosystems. In this study, we systematically collected dendrochronological studies based on shrub species during the 1996-2021, and reviewed research progress in four main subfields (physiology, climatology, ecology and hydrology) in dendrochronology for shrub species. The characteristics of shrub growth and xylem anatomy under different environmental stresses were expounded. The main limiting factors for shrub growth in different climatic conditions and the history of regional climate fluctuations based on shrub-ring data were revealed. The individual growth and population dynamics of shrub species driven by climate and the changes in ecosystems caused by non-climatic factors were assessed, and the reconstructions of regional hydrological histories were compiled using tree-ring data of shrub species. Under the context of global warming, dendrochronological studies of shrub species in China should pay more attention to the responses of shrub species radial growth to drought stress under different moisture conditions in the semi-arid and arid regions and the transforming feature of distribution pattern and climate response sensitivity for shrub species under the background of climate change.

ΔE1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum.

BACKGROUND: The merozoite surface protein (MSP)-1 of Plasmodium falciparum, the causative agent of malaria tropica, is considered to be a promising vaccine candidate. Although its stable cloning and expression has been difficult in the past, adenoviral vectors expressing the complex protein are described in the present study. METHODS: Codon-optimized msp-1 was used to construct a set of first generation (ΔE1Ad) and high-capacity adenovirus (HC-Ad) vectors, and cellular and humoral immune responses induced by the vectors were characterized in detail in mice. RESULTS: Generation of stable ΔE1Ad and HC-Ad vectors expressing full-length MSP-1 and their production to high vector titers was found to be feasible. Epitope identification and analysis of frequencies of specific CD8 T-cells revealed that MSP-1 expressing HC-Ad vectors induced higher frequencies of interferon-γ + CD8 T-cells than ΔE1 vectors. Irrespective of the vector format, higher titers of MSP-1 specific antibodies were generated by Ad vectors expressing MSP-1 from a chicken ß-actin (CAG) promoter comprising the cytomegalovirus early enhancer element and the chicken ß-actin promoter. CONCLUSIONS: The findings of the present study suggest that Ad vectors expressing full-length codon-optimized MSP-1 are promising candidate vaccines against P. falciparum infections. Use of the HC-Ad vector type for delivery, as well as the CAG promoter to control MSP-1 expression, may further increase the efficacy of this vaccine candidate.

The potential influence of seasonal climate variables on the net primary production of forests in eastern China.

Knowledge of the effects of climate factors on net primary production (NPP) is pivotal to understanding ecosystem processes in the terrestrial carbon cycle. Our goal was to evaluate four different categories of effects (physical, climatic, NDVI, and all effects[global]) as predictors of forest NPP in eastern China. We developed regression models with data from 221 NPP in eastern China and identified the best model with each of the four categories of effects. Models explained a large part of the variability in NPP, ranging from 46.8% in global model to 36.5% in NDVI model. In the most supported global model, winter temperature and sunshine duration negatively affected NPP, while winter precipitation positively affected NPP. Thus, winter climate conditions play an important role in modulating forest NPP of eastern China. Spring temperature had a positive affect on NPP, which was likely because a favorable warm climate in the early growing season promotes forest growth. Forest NPP was also negatively affected by summer and autumn temperatures, possibly because these are related to temperature induced drought stress. In the NDVI model, forest NPP was affected by NDVI in spring (positive), summer (negative) and winter (negative) seasons. Our study provides insight into seasonal effects of climate and NPP of forest in China, as well as useful knowledge for the development of climate-vegetation models.

Detection of Tyrosinase in Real Food Samples and Living Cells by a Novel Near-Infrared Fluorescence Probe.

A new near-infrared fluorescence probe was developed and applied to the fluorescence detection of tyrosinase in real food samples and living cells. The probe (E)-2-(2-(6-((3-hydroxybenzyloxy)carbonylamino)-2,3-dihydro-1H-xanthen-4-yl)vinyl)-3,3-dimethyl-1-propyl-3H-indolium (1) was designed and synthesized by coupling 3-hydroxybenzyl alcohol via carbamate bond with an amino hemicyanine skeleton, based on the high anti-interference ability of 3-hydroxybenzyl alcohol to reactive oxygen species and its binding affinity to tyrosinase. Compared with the existing tyrosinase probes, the proposed probe exhibits superior analytical performance, such as high selectivity, high sensitivity, superior spatiotemporal sampling ability, fluorescence signal switching at 706 nm, and low detection limit of 0.36 U mL-1. More importantly, the probe has been successfully used to monitor tyrosinase in the browning of apple slices for the first time, and the results indicated that the strongest fluorescence intensity could be achieved at 2.5 h to realize precise visual recognition of tyrosinase. Notably, the probe determined tyrosinase in real food samples (apple, banana, cheese, and red wine) with a stable average recovery range of 95.7-108.3% and has been successfully used to monitor tyrosinase in the living B16 cells. The superior properties of the probe make it of great potential use in food nutritional value evaluation and clinical diagnosis of melanin-related diseases.

SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS.

The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is still unclear. In this study, we found that SARS-CoV-2 Nsp5 can induce the expression of cytokines IL-1ß, IL-6, TNF-α, and IL-2 in Calu-3 and THP1 cells. Further research found that Nsp5 enhances cytokine expression through activating the NF-κB signaling pathway. Subsequently, we investigated the upstream effectors of the NF-κB signal pathway on Nsp5 overexpression and discovered that Nsp5 increases the protein level of MAVS. Moreover, Nsp5 can promote the SUMOylation of MAVS to increase its stability and lead to increasing levels of MAVS protein, finally triggering activation of NF-κB signaling. The knockdown of MAVS and the inhibitor of SUMOylation treatment can attenuate Nsp5-mediated NF-κB activation and cytokine induction. We identified a novel role of SARS-CoV-2 Nsp5 to enhance cytokine production by activating the NF-κB signaling pathway.