Low-Surface-Area Nitrogen-Doped Carbon Submicrospheres as High-Coulombic-Efficiency and High-Capacity Anodes for Practical Sodium-Ion Batteries.

Nitrogen-doped carbon submicrospheres (NCSMs) are synthesized via an efficient and environmentally friendly one-pot polymerization reaction at room temperature, in which dopamine hydrochloride serves as the source for both carbon and nitrogen. Through leverage of its distinctive structure characterized by minimal surface area, fewer oxygen-containing functional groups, and a heightened presence of active nitrogen-doping sites, the synthesized NCSM showcases a noteworthy initial Coulombic efficiency (ICE) of 84.8%, a remarkable sodium storage capacity of 384 mAh g-1, an impressive rate capability of 215 mAh g-1 at 10 A g-1, and a superior cyclic performance, maintaining 83.0% of its capacity after 2000 cycles. The submicron spherical structure, with its limited surface area and scarce oxygen-containing moieties, effectively curtails the irreversible sodium-ion loss in solid-electrolyte interphase film formation, resulting in heightened ICE. The abundant nitrogen doping can expand carbon-layer spacing as well as improve the electron/ion-transport dynamics, guaranteeing a high sodium storage capacity and a strong rate capability. Crucially, the synthesis method presented here is straightforward, effective, and amenable to scaling, offering a novel avenue for the commercialization of sodium-ion batteries.

Nonlinear Conductivity and Thermal Stability of Anti-Corona Epoxy Resin Nanocomposites.

The long-term operation of motors induces substantial alterations in the surface conductivity and nonlinear coefficient of anti-corona paint, diminishing its efficacy and jeopardizing the longevity of large motors. Hence, the development of high-performance anti-corona paint holds paramount importance in ensuring motor safety. In this study, we integrate two nano-fillers, namely silicon carbide (SiC) and organic montmorillonite (O-MMT), into a composite matrix comprising micron silicon carbide and epoxy resin (SiC/EP). Subsequently, three distinct types of anti-corona paint are formulated: SiC/EP, Nano-SiC/EP, and O-MMT/SiC/EP. Remarkably, O-MMT/SiC/EP exhibits a glass transition temperature about 25 °C higher than that of SiC/EP, underscoring its superior thermal properties. Moreover, the introduction of nano-fillers markedly augments the surface conductivity of the anti-corona paint. Aging tests, conducted across varying temperatures, unveil a notable reduction in the fluctuation range of surface conductivity post-aging. Initially, the nonlinear coefficients exhibit a declining trend, succeeded by an ascending trajectory. The O-MMT/SiC/EP composite displays a maximum nonlinearity coefficient of 1.465 and a minimum of 1.382. Furthermore, the incorporation of nanofillers amplifies the dielectric thermal stability of epoxy resin composites, with O-MMT/SiC/EP showcasing the pinnacle of thermal endurance. Overall, our findings elucidate the efficacy of nano-fillers in enhancing the performance and longevity of anti-corona paint, particularly highlighting the exceptional attributes of the O-MMT/SiC/EP composite in bolstering motor safety through improved thermal stability and electrical properties.

Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice.

The COVID-19 pandemic has raised the standard regarding the current vaccine development pace, as several messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines have proved their ability to induce strong immunogenicity and protective efficacy. We developed 1-methylpseudouridine-containing mRNA-LNP vaccines, expressing either the more conserved SARS-CoV-2 nucleoprotein (mRNA-N) or spike protein (mRNA-S), both based on the prototypic viral sequences. When combining both mRNA-S and mRNA-N together (mRNA-S+N), the vaccine showed high immunogenicity and broad protection against different SARS-CoV-2 variants, including wildtype, Delta, BA.1, BA.5, and BQ.1. To better understand the mechanisms behind this broad protection obtained by mRNA-S+N, we analyzed innate and adaptive immune parameters following vaccination in mice. Compared to either mRNA-S or mRNA-N alone, mice vaccinated with mRNA-S+N exhibited an increase in the innate immune response, as depicted by the higher cytokine (IL-6 and chemokine (MCP-1) levels. In addition, lymph node immunophenotyping showed the maturation and activation of dendritic cells and natural killer cells, respectively. To understand the adaptive immune response, RNA-Seq analyses of the lung and spleen samples of the vaccinated mice were performed in parallel and revealed a stronger immune gene-expression profile in the lung than that in the spleen. Compared to mRNA-S alone, mRNA-S+N vaccination elicited higher levels of expression for genes involved in multiple immune pathways, including T cells, cytokine signaling, antigen presentation, B cells, and innate immunity. Together, our studies provide immunological insights into the mechanisms of broad protection conferred by dual mRNA vaccination against SARS-CoV-2 variants.

A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study.

Background: Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors. Methods: This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use. Results: Patients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/. Conclusion: We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.

Elasticity-controlled jamming criticality in soft composite solids.

Soft composite solids are made of inclusions dispersed within soft matrices. They are ubiquitous in nature and form the basis of many biological tissues. In the field of materials science, synthetic soft composites are promising candidates for building various engineering devices due to their highly programmable features. However, when the volume fraction of the inclusions increases, predicting the mechanical properties of these materials poses a significant challenge for the classical theories of composite mechanics. The difficulty arises from the inherently disordered, multi-scale interactions between the inclusions and the matrix. To address this challenge, we systematically investigated the mechanics of densely filled soft elastomers containing stiff microspheres. We experimentally demonstrate how the strain-stiffening response of the soft composites is governed by the critical scalings in the vicinity of a shear-jamming transition of the included particles. The proposed criticality framework quantitatively connects the overall mechanics of a soft composite with the elasticity of the matrix and the particles, and captures the diverse mechanical responses observed across a wide range of material parameters. The findings uncover a novel design paradigm of composite mechanics that relies on engineering the jamming properties of the embedded inclusions.

SynergyX: a multi-modality mutual attention network for interpretable drug synergy prediction.

Discovering effective anti-tumor drug combinations is crucial for advancing cancer therapy. Taking full account of intricate biological interactions is highly important in accurately predicting drug synergy. However, the extremely limited prior knowledge poses great challenges in developing current computational methods. To address this, we introduce SynergyX, a multi-modality mutual attention network to improve anti-tumor drug synergy prediction. It dynamically captures cross-modal interactions, allowing for the modeling of complex biological networks and drug interactions. A convolution-augmented attention structure is adopted to integrate multi-omic data in this framework effectively. Compared with other state-of-the-art models, SynergyX demonstrates superior predictive accuracy in both the General Test and Blind Test and cross-dataset validation. By exhaustively screening combinations of approved drugs, SynergyX reveals its ability to identify promising drug combination candidates for potential lung cancer treatment. Another notable advantage lies in its multidimensional interpretability. Taking Sorafenib and Vorinostat as an example, SynergyX serves as a powerful tool for uncovering drug-gene interactions and deciphering cell selectivity mechanisms. In summary, SynergyX provides an illuminating and interpretable framework, poised to catalyze the expedition of drug synergy discovery and deepen our comprehension of rational combination therapy.

Large-Scale Production and Integrated Application of Micro-Supercapacitors.

Micro-supercapacitors, emerging as promising micro-energy storage devices, have attracted significant attention due to their unique features. This comprehensive review focuses on two key aspects: the scalable fabrication of MSCs and their diverse applications. The review begins by elucidating the energy storage mechanisms and guiding principles for designing high-performance devices. It subsequently explores recent advancements in scalable fabrication techniques for electrode materials and micro-nano fabrication technologies for micro-devices. The discussion encompasses critical application domains, including multifunctional MSCs, energy storage integration, integrated power generation, and integrated applications. Despite notable progress, there are still some challenges such as large-scale production of electrode material, well-controlled fabrication technology, and scalable integrated manufacture. The summary concludes by emphasizing the need for future research to enhance micro-supercapacitor performance, reduce production costs, achieve large-scale production, and explore synergies with other energy storage technologies. This collective effort aims to propel MSCs from laboratory innovation to market viability, providing robust energy storage solutions for MEMS and portable electronics.

Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.

pH Sensitive Quercetin Nanoparticles Ameliorate DSS-Induced Colitis in Mice by Colon-Specific Delivery.

SCOPE: Ulcerative colitis (UC) is a classic inflammatory bowel disease (IBD) that represents a serious threat to human health. As a natural flavonoid with multiple biological activities, quercetin (QCT) suffers from low bioavailability through limitations in chemical stability. Here, the study investigates the regulatory effects of quercetin nanoparticles (QCT NPs) on dextran sulfate sodium (DSS) induced colitis mice. METHODS AND RESULTS: Chitosan is modified to obtain N-succinyl chitosan (NSC) with superior water solubility. Nanoparticles composed of sodium alginate (SA) and NSC can encapsulate QCT after cross-linking, forming QCT NPs. In vitro drug release assays demonstrate the pH sensitivity of QCT NPs. Compared with free quercetin, QCT NPs have better therapeutic efficacy in modulating gut microbiota and its metabolites short chain fatty acid (SCFAs) to relieve DSS-induced colitis in mice, thereby alleviating colon inflammatory infiltration, increasing goblet cells density and mucus protein, ameliorating TNF-α, IL-1ß, IL-6, IL-10, and Myeloperoxidase (MPO) levels, and recovering intestinal barrier integrity. CONCLUSION: pH sensitive QCT nanoparticles can reduce inflammatory reaction, improve gut microbiota, and repair intestinal barrier by targeting colon, thus improving DSS induced colitis in mice, providing reference for the treatment of colitis.

Impact of Removal of Lymph Nodes on Survival in Stage I-III Gastric Signet-Ring Cell Cancer: The More, the Better?

BACKGROUND: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. METHODS: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). RESULTS: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. CONCLUSIONS: A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.

BRD4 as a potential target for human papillomaviruses associated cancer.

Around 99% of cervical cancer and 5%-10% of human cancer are associated with human papillomaviruses (HPV). Notably, the life-cycle of HPV begins by low-level infection of the basal cells of the stratified epithelium, where the viral genomes are replicated and passed on to the daughter proliferating basal cells. The production of new viral particles remains restricted to eventually differentiated cells. HPVs support their persistent infectious cycle by hijacking pivotal pathways and cellular processes. Bromodomain-containing protein 4 (BRD4) is one of the essential cellular factors involved in multiple stages of viral transcription and replication. In this review, we demonstrate the role of BRD4 in the multiple stages of HPV infectious cycle. Also, we provide an overview of the intense research about the cellular functions of BRD4, the mechanism of action of bromodomain and extra terminal inhibitors, and how it could lead to the development of antiviral/anticancer therapies.

Monovalent SARS-COV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants.

The emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that are resistant to the current COVID-19 vaccines highlights the need for continued development of broadly protective vaccines for the future. Here, we developed two messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines, TU88mCSA and ALCmCSA, using the ancestral SARS-CoV-2 spike sequence, optimized 5' and 3' untranslated regions (UTRs), and LNP combinations. Our data showed that these nanocomplexes effectively activate CD4+ and CD8+ T cell responses and humoral immune response and provide complete protection against WA1/2020, Omicron BA.1 and BQ.1 infection in hamsters. Critically, in Omicron BQ.1 challenge hamster models, TU88mCSA and ALCmCSA not only induced robust control of virus load in the lungs but also enhanced protective efficacy in the upper respiratory airways. Antigen-specific immune analysis in mice revealed that the observed cross-protection is associated with superior UTRs [Carboxylesterase 1d (Ces1d)/adaptor protein-3ß (AP3B1)] and LNP formulations that elicit robust lung tissue-resident memory T cells. Strong protective effects of TU88mCSA or ALCmCSA against both WA1/2020 and VOCs suggest that this mRNA-LNP combination can be a broadly protective vaccine platform in which mRNA cargo uses the ancestral antigen sequence regardless of the antigenic drift. This approach could be rapidly adapted for clinical use and timely deployment of vaccines against emerging and reemerging VOCs.

Lonidamine liposomes to enhance photodynamic and photothermal therapy of hepatocellular carcinoma by inhibiting glycolysis.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.

Next-Generation Vaccines Against COVID-19 Variants: Beyond the Spike Protein.

Vaccines are among the most effective medical countermeasures against infectious diseases. The current Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred the scientific strategies to fight against the disease. Since 2020, a great number of vaccines based on different platforms have been in development in response to the pandemic, among which mRNA, adenoviral vector, and subunit vaccines have been clinically approved for use in humans. These first-generation COVID-19 vaccines largely target the viral spike (S) protein and aim for eliciting potent neutralizing antibodies. With the emergence of SARS-CoV-2 variants, especially the highly transmissible Omicron strains, the S-based vaccine strategies have been faced constant challenges due to strong immune escape by the variants. The coronavirus nucleocapsid (N) is one of the viral proteins that induces strong T-cell immunity and is more conserved across different SARS-CoV-2 variants. Inclusion of N in the development of COVID-19 vaccines has been reported. Here, we briefly reviewed and discussed COVID-19 disease, current S-based vaccine strategies, and focused on the immunobiology of N protein in SARS-CoV-2 host immunity, as well as the next-generation vaccine strategies involving N protein, to combat current and emerging SARS-CoV-2 variants.

Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours (HOPE): protocol for a randomised, controlled, multicentre study.

BACKGROUND: While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke (AIS) within 4.5 hours of symptom onset, there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic window. AIM: To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on CT perfusion at 4.5-24 hours after stroke onset (for stroke with unknown onset time, the midpoint of the time last known to be well and symptom recognition time; for wake-up stroke, the midpoint of the time last known to be well or sleep onset and wake up time) will benefit from intravenous thrombolysis. DESIGN: HOPE is a prospective, multicentre, randomised, open-label blinded endpoint trial with the stage of phase III. The treatment allocation employs 1:1 randomisation. The treatment arm under investigation is alteplase with standard therapy, the control arm is standard therapy. Eligibility imaging criteria include ischaemic core volume ≤70 mL, penumbra ≥10 mL and mismatch ≥20%. STUDY OUTCOMES: The primary outcome is non-disabled functional outcome (assessed as modified Rankin Scale score of 0-1 at 90 days). DISCUSSION: HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5-24 hours, which has the potential to extend time window and expand eligible population for thrombolysis therapy.

Development of an automatic sample changer with variable temperature for small-angle neutron scattering at China Spallation Neutron Source.

A small-angle neutron scattering (SANS) instrument at the China Spallation Neutron Source (CSNS) is an operating instrument for studying structures and inhomogeneities with dimensions ranging from 1 to 100 nm. Preparing multiple samples at once and measuring them sequentially is a common approach in SANS experiments to reduce neutron beamline wastes and increase experimental efficiency. We present the development of an automatic sample changer for the SANS instrument, including system design, thermal simulation, optimization analysis, structure design details, and temperature control test results. It features a two-row construction that can hold 18 samples on each row. The controllable temperature range is -30 to 300 °C. Furthermore, neutron scattering experiments on SANS at CSNS proved that this instrument has good temperature control performance and low background. This automatic sample changer is optimized for usage at SANS and will be offered to other researchers through the user program.

Total Lymph Node Yield Is Associated with Prolonged Survival after Neoadjuvant Chemotherapy in ypN0 Gastric Cancer Patients.

INTRODUCTION: Lymph node status after neoadjuvant chemotherapy (NAC) plays the main role in predicting the survival of gastric cancer (GC) patients who underwent curative gastrectomy after NAC. NAC can reduce the number of involved lymph nodes. However, it is unknown whether other variables are associated with the survival outcomes for ypN0 GC patients. It is unknown whether lymph node yield (LNY) has prognostic value in ypN0 GC patients treated with NAC plus surgery. METHODS: In this retrospective study, we reviewed the data of patients treated with NAC plus gastrectomy and identified those with ypN0 disease. The LNY cut-off was calculated using the X-tile program to determine the greatest actuarial survival difference. Patients were categorized into the downstaged N0 (cN+/ypN0) and natural N0 (cN0/ypN0) groups based on nodal status. Multivariate analysis was used to identify the prognostic factors and the association between LNY and prognosis. RESULTS: A total of 211 GC patients with ypN0 status were included. The optimal LNY cut-off was 23. Kaplan-Meier analysis revealed no significant difference in overall survival between the natural and downstaged N0 groups, while ypN0 GC patients with an LNY of ≥24 had significantly longer overall survival than those with an LNY of ≤23. Univariate analysis identified that LNY, cT stage, tumor location, ypT stage, perineural invasion, lymphovascular invasion, tumor size, Mandard tumor regression grade, and extent of gastrectomy were significantly associated with overall survival. Multivariate analysis confirmed that perineural invasion (hazard ratio, 4.246; p < 0.001), lymphovascular invasion (hazard ratio, 2.694; p = 0.048), and an LNY of ≥24 (hazard ratio, 0.394; p = 0.011) were independent prognostic factors. CONCLUSIONS: Patients with natural and downstaged ypN0 GC had similar overall survival after NAC. LNY was an independent prognostic factor in these patients, and an LNY of ≥24 predicted prolonged overall survival.

Metformin restrains ZIKV replication and alleviates virus-induced inflammatory responses in microglia.

The re-emergence of Zika virus (ZIKV) remains a major public health threat that has raised worldwide attention. Accumulating evidence suggests that ZIKV can cause serious pathological changes to the human nervous system, including microcephaly in newborns. Recent studies suggest that metformin, an established treatment for diabetes may play a role in viral infection; however, little is known about the interactions between ZIKV infection and metformin administration. Using fluorescent ZIKV by flow cytometry and immunofluorescence imaging, we found that ZIKV can infect microglia in a dose-dependent manner. Metformin diminished ZIKV replication without the alteration of viral entry and phagocytosis. Our study demonstrated that metformin downregulated ZIKV-induced inflammatory response in microglia in a time- and dose-dependent manner. Our RNA-Seq and qRT-PCR analysis found that type I and III interferons (IFN), such as IFNα2, IFNß1 and IFNλ3 were upregulated in ZIKV-infected cells by metformin treatment, accompanied with the downregulation of GBP4, OAS1, MX1 and ISG15. Together, our results suggest that metformin-mediated modulation in multiple pathways may attribute to restraining ZIKV infection in microglia, which may provide a potential tool to consider for use in unique clinical circumstances.