DDIT3 aggravates TMJOA cartilage degradation via Nrf2/HO-1/NLRP3-mediated autophagy.

OBJECTIVE: DNA damage-inducible transcript 3 (DDIT3), as a downstream transcription factor of endoplasmic reticulum stress, is reported to regulate chondrogenic differentiation under physiological and pathological state. However, the specific involvement of DDIT3 in the degradation of condylar cartilage of temporomandibular joint osteoarthritis (TMJOA) is unclarified. DESIGN: The expression patterns of DDIT3 in condylar cartilage from monosodium iodoacetate-induced TMJOA mice were examined to uncover the potential role of DDIT3 in TMJOA. The Ddit3 knockout (Ddit3-/-) mice and their wildtype littermates (Ddit3+/+) were used to clarify the effect of DDIT3 on cartilage degradation. Primary condylar chondrocytes and ATDC5 cells were applied to explore the mechanisms of DDIT3 on autophagy and extracellular matrix (ECM) degradation in chondrocytes. The autophagy inhibitor chloroquine (CQ) was used to determine the effect of DDIT3-inhibited autophagy in vivo. RESULTS: DDIT3 were highly expressed in condylar cartilage from TMJOA mice. Ddit3 knockout alleviated condylar cartilage degradation and subchondral bone loss, compared with their wildtype littermates. In vitro study demonstrated that DDIT3 exacerbated ECM degradation in chondrocytes induced by TNF-α through inhibiting autophagy. The intraperitoneal injection of CQ further confirmed that Ddit3 knockout alleviated cartilage degradation in TMJOA through activating autophagy in vivo. CONCLUSIONS: Our findings identified the crucial role of DDIT3-inhibited autophagy in condylar cartilage degradation during the development of TMJOA.

Promoting effect of lanthanum doping on photovoltaic performance of CZTSSe solar cells.

A large open-circuit voltage (VOC) deficit is the major challenge hindering the efficiency improvement of Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. Cation substitution, or doping, is usually an effective strategy to achieve carrier regulation and improve efficiency. In this work, we developed a rare-earth element lanthanum (La) doped CZTSSe thin-film solar cell by directly introducing La3+ ions into the CZTS precursor solution. Such a proposed La doping approach could effectively enhance light harvesting, adjust the bandgap, and increase the electron diffusion length. Furthermore, appropriate concentrations of La doping can reduce harmful defect cluster. Benefiting from the La doping, the VOC significantly increases from 431 to 497 mV. Consequently, the power conversion efficiency is enhanced significantly from 6.54% (VOC = 431 mV, JSC = 25.50 mA/cm2, FF = 58.28%) for the reference cell to 10.21% (VOC = 497 mV, JSC = 35.20 mA/cm2, FF = 58.41%) for the optimized La-doped cell. This research provides a new direction for enhancing the performance of CZTSSe cells, offering promising prospects for the future of CZTSSe thin-film solar cells.

Versatile Cu2ZnSnS4-based synaptic memristor for multi-field-regulated neuromorphic applications.

Integrating both electrical and light-modulated multi-type neuromorphic functions in a single synaptic memristive device holds the most potential for realizing next-generation neuromorphic systems, but is still challenging yet achievable. Herein, a simple bi-terminal optoelectronic synaptic memristor is newly proposed based on kesterite Cu2ZnSnS4, exhibiting stable nonvolatile resistive switching with excellent spatial uniformity and unique optoelectronic synaptic behaviors. The device demonstrates not only low switching voltage (-0.39 ± 0.08 V), concentrated Set/Reset voltage distribution (<0.08/0.15 V), and long retention time (>104 s) but also continuously modulable conductance by both electric (different width/interval/amplitude) and light (470-808 nm with different intensity) stimulus. These advantages make the device good electrically and optically simulated synaptic functions, including excitatory and inhibitory, paired-pulsed facilitation, short-/long-term plasticity, spike-timing-dependent plasticity, and "memory-forgetting" behavior. Significantly, decimal arithmetic calculation (addition, subtraction, and commutative law) is realized based on the linear conductance regulation, and high precision pattern recognition (>88%) is well achieved with an artificial neural network constructed by 5 × 5 × 4 memristor array. Predictably, such kesterite-based optoelectronic memristors can greatly open the possibility of realizing multi-functional neuromorphic systems.

Attention affects the perception of self-motion direction from optic flow.

Many studies have demonstrated that attention affects the perception of many visual features. However, previous studies show conflicting results regarding the effect of attention on the perception of self-motion direction (i.e., heading) from optic flow. To address this question, we conducted three behavioral experiments and found that estimation accuracies of large headings (>14°) decreased with attention load, discrimination thresholds of these headings increased with attention load, and heading estimates were systematically compressed toward the focus of attention. Therefore, the current study demonstrated that attention affected heading perception from optic flow, showing that the perception is both information-driven and cognitive.

Alum/CpG adjuvant promotes immunogenicity of inactivated SARS-CoV-2 Omicron vaccine through enhanced humoral and cellular immunity.

The SARS-CoV-2 Omicron variant, which was classified as a variant of concern (VOC) by the World Health Organization on 26 November 2021, has attracted worldwide attention for its high transmissibility and immune evasion ability. The existing COVID-19 vaccine has been shown to be less effective in preventing Omicron variant infection and symptomatic infection, which brings new challenges to vaccine development and application. Here, we evaluated the immunogenicity and safety of an Omicron variant COVID-19 inactivated vaccine containing aluminum and CpG adjuvants in a variety of animal models. The results showed that the vaccine candidate could induce high levels of neutralizing antibodies against the Omicron variant virus and binding antibodies, and significantly promoted cellular immune response. Meanwhile, the vaccine candidate was safe. Therefore, it provided more foundation for the development of aluminum and CpG as a combination adjuvant in human vaccines.

MoOx Synaptic Memristor with Programmable Multilevel Conductance for Reliable Neuromorphic Hardware.

Memristor holds great potential for enabling next-generation neuromorphic computing hardware. Controlling the interfacial characteristics of the device is critical for seamlessly integrating and replicating the synaptic dynamic behaviors; however, it is commonly overlooked. Herein, we report the straightforward oxidation of a Mo electrode in air to design MoOx memristors that exhibit nonvolatile ultrafast switching (0.6-0.8 mV/decade, <1 mV/decade) with a high on/off ratio (>104), a long durability (>104 s), a low power consumption (17.9 µW), excellent device-to-device uniformity, ingeniously synaptic behavior, and finely programmable multilevel analog switching. The analyzed physical mechanism of the observed resistive switching behavior might be the conductive filaments formed by the oxygen vacancies. Intriguingly, upon organization into memristor-based crossbar arrays, in addition to simulated multipattern memorization, edge detection on random images can be implemented well by parallel processing of pixels using a 3 × 3 × 2 array of Prewitt filter groups. These are vital functions for neural system hardware in efficient in-memory computing neural systems with massive parallelism beyond a von Neumann architecture.

Enhancing Inactivated Yellow Fever 17D Vaccine-Induced Immune Responses in Balb/C Mice Using Alum/CpG.

There are some concerns about the safety of live attenuated yellow fever vaccines (YF-live), particularly viscerotropic adverse events, which have a high mortality rate. The cellular production of the vaccine will not cause these adverse effects and has the potential to extend applicability to those who have allergic reactions, immunosuppression, and age. In this study, inactivated yellow fever (YF) was prepared and adsorbed with Alum/CpG. The cellular and humoral immunities were investigated in a mouse model. The results showed that Alum/CpG (20 µg/mL) could significantly increase the binding and neutralizing activities of the antibodies against YF. Moreover, the antibody level at day 28 after one dose was similar to that of the attenuated vaccine, but significantly higher after two doses. At the same time, Alum/CpG significantly increased the levels of IFN-γ and IL-4 cytokines.

The cross-linking and protective effect of artemisinin and its derivatives on collagen fibers of demineralized dentin surface.

OBJECTIVE: To investigate the cross-linking and protective effect of artemisinin (ART), dihydroartemisinin (DHA), and artesunate (AST) on collagen fibers of demineralized dentin surface. METHODS: Molecular docking was used to predict potential interactions of ART, DHA, and AST with dentin type I collagen. Human third molars without caries were completely demineralized and treated with different solutions for 1 min. The molecular interactions and cross-linking degree of ART and its derivatives with dentin collagen were evaluated by FTIR spectroscopy, total extractable protein content, and a ninhydrin assay. Scanning electron microscopy, hydroxyproline release, and ultimate microtensile strength tests (µUTS) were employed to confirm the mechanical properties and anti-collagenase degradation properties of dentin collagen fibers. RESULTS: ART, DHA, and AST combined with dentin type I collagen mainly through hydrogen bonding and hydrophobic interactions, and the cross-linking reaction sites were mainly C=O and CN functional groups. Compared to the control group, ART and its derivatives significantly increased the degree of cross-linking. Additionally, significant increases were observed in resistance to enzymatic digestion and mechanical properties of the artemisinin and its derivatives group. CONCLUSION: ART, DHA, and AST could cross-link with demineralized dentin collagen, through improving the mechanical properties and anti-collagenase degradation properties. CLINICAL SIGNIFICANCE: The study endorses the potential use of ART and its derivatives as a prospective collagen cross-linking agent for degradation-resistant and long-period dentin bonding in composite resin restorations.

Optoelectronic bio-synaptic plasticity on neotype kesterite memristor with switching ratio >104.

Optoelectronic memristors hold the most potential for realizing next-generation neuromorphic computation; however, memristive devices that can integrate excellent resistive switching and both electrical-/light-induced bio-synaptic behaviors are still challenging to develop. In this study, an artificial optoelectronic synapse is proposed and realized using a kesterite-based memristor with Cu2ZnSn(S,Se)4 (CZTSSe) as the switching material and Mo/Ag as the back/top electrode. Benefiting from unique electrical features and a bi-layered structure of CZTSSe, the memristor exhibits highly stable nonvolatile resistive switching with excellent spatial uniformity, concentrated Set/Reset voltage distribution (variation <0.08/0.02 V), high On/Off ratio (>104), and long retention time (>104 s). A possible mechanism of the switching behavior in such a device is proposed. Furthermore, these memristors successfully achieve essential bio-synaptic functions under both electrical and various visible light (470-655 nm) stimulations, including electrical-induced excitatory postsynaptic current, paired pulse facilitation, long-term potentiation, long-term depression, spike-timing-dependent plasticity, as well as light-stimulated short-/long-term plasticity and learning-forgetting-relearning process. As such, the proposed neotype kesterite-based memristor demonstrates significant potential in facilitating artificial optoelectronic synapses and enabling neuromorphic computation.

Neotype kuramite optoelectronic memristor for bio-synaptic plasticity simulations.

Memristive devices with both electrically and optically induced synaptic dynamic behaviors will be crucial to the accomplishment of brain-inspired neuromorphic computing systems, in which the resistive materials and device architectures are two of the most important cornerstones, but still under challenge. Herein, kuramite Cu3SnS4 is newly introduced into poly-methacrylate as the switching medium to construct memristive devices, and the expected high-performance bio-mimicry of diverse optoelectronic synaptic plasticity is demonstrated. In addition to the excellent basic performances, such as stable bipolar resistive switching with On/Off ratio of ∼486, Set/Reset voltage of ∼-0.88/+0.96 V, and good retention feature of up to 104 s, the new designs of memristors possess not only the multi-level controllable resistive-switching memory property but also the capability of mimicking optoelectronic synaptic plasticity, including electrically and visible/near-infrared light-induced excitatory postsynaptic currents, short-/long-term memory, spike-timing-dependent plasticity, long-term plasticity/depression, short-term plasticity, paired-pulse facilitation, and "learning-forgetting-learning" behavior as well. Predictably, as a new class of switching medium material, such proposed kuramite-based artificial optoelectronic synaptic device has great potential to be applied to construct neuromorphic architectures in simulating human brain functions.

Optoelectronic Memristive Synapse Behavior for the Architecture of Cu2ZnSnS4@BiOBr Embedded in Poly(methyl methacrylate).

The great potential of artificial optoelectronic devices that are capable of mimicking biosynapse functions in brain-like neuromorphic computing applications has aroused extensive interest, and the architecture design is decisive yet challenging. Herein, a new architecture of p-type Cu2ZnSnS4@BiOBr nanosheets embedded in poly(methyl methacrylate) (PMMA) films (CZTS@BOB-PMMA) is presented acting as a switching layer, which not only shows the bipolar resistive switching features (SET/RESET voltages, ∼ -0.93/+1.35 V; retention, >104 s) and electrical- and near-infrared light-induced synapse plasticity but also demonstrates electrical-driven excitatory postsynaptic current, spiking-time-dependent plasticity, paired pulse facilitation, long-term plasticity, long- and short-term memory, and "learning-forgetting-learning" behaviors. The approach is a rewarding attempt to broaden the research of optoelectric controllable memristive devices for building neuromorphic architectures mimicking human brain functionalities.

Trait anxiety is related to an impaired attention model for controllable threat cues: Evidence from ERPs.

Attentional bias to threat cues is maladaptive for individuals with high trait anxiety (HTA), but may become adaptive when the dangers signaled by these cues can be controlled by timely actions. However, it remains unclear how HTA individuals allocate attention to controllable threat cues. The current study examined whether trait anxiety is associated with an impaired attention model for controllable threat cues and explored the related underlying neural mechanisms. A sample of 21 participants with low trait anxiety (LTA) and 21 with HTA completed a modified cued anticipation task which allowed participants to control the appearance of threatening pictures associated with controllable threat cues. Results revealed that HTA individuals had no difference in N1 amplitude among controllable threat cues, uncontrollable threat cues, and neutral cues, while LTA individuals showed the greatest N1 amplitude on controllable cues. HTA individuals also exhibited lower N2 amplitude than LTA individuals. The current study provides electrophysiological evidence showing that HTA individuals have impaired attention for processing controllable threat cues and weak inhibitory control. Deficient attention to controllable threat cues may be crucial in the mechanisms underlying trait anxiety.

Overexpression of the key genes in the biosynthetic pathways of lipid A and peptidoglycan in Escherichia coli.

Gram-negative bacterium Escherichia coli has a tripartite cell envelope with a cytoplasmic membrane, a peptidoglycan layer, and an asymmetric outer membrane containing lipopolysaccharide in its outer leaflet. The biogenesis of peptidoglycan and lipopolysaccharide shares the same substrate UDP-GlcNAc. From UDP-GlcNAc, MurA catalyzes the first reaction for peptidoglycan biosynthesis, while LpxA catalyzes the first reaction for lipopolysaccharide biosynthesis. This study demonstrates that murA overexpression in E. coli MG1655 inhibited the cell growth and increased the cell length, whereas lpxA overexpression in MG1655 neither inhibited the cell growth nor increased the cell length. Further study showed that individual overexpression of the other eight genes encoding the enzymes to catalyze the initial reactions in the biosynthetic pathway of lipopolysaccharide did not inhibit the cell growth. When MG1655/pBad-lpxA, MG1655/pBad-lpxD, and MG1655/pBad-lpxH were transformed with pFW01-thrA*BC-rhtC that contains the key genes for L-threonine biosynthesis and transport, the L-threonine production was increased. The L-threonine production in MG1655/pFW01-thrA*BC-rhtC/pBad-lpxH increased 46.1% as compared to the control MG1655/pFW01-thrA*BC-rhtC/pBad.

(NH4)2S-induced improvement of interfacial wettability for high-quality heterojunctions to boost the chloride-assembled CZTSSe solar cells.

Concernin the crucial interfacial issues in multi-layered kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells, (NH4)2S treatment has been proven to be effective in eliminating surface secondary phases. While for the CZTSSe absorbers without impurity phases, what can the low-temperature (NH4)2S treatment do to the absorbers, thus to the device performance? Herein, the chloride-fabricated CZTSSe absorbers are surface treated with the (NH4)2S solution at room temperature, and its influence on the device performance is investigated in detail. Surprisingly, such treatment can make the absorbers' surface become nearly super-hydrophilicity, greatly decreasing the surface wetting angle from 63.1° ± 3.4° to 7.3° ± 0.6° after 50 min-treating, and thus lead to marked differences in the interfacial properties of the CdS/CZTSSe heterojunctions deposited in a chemical bath. Consequently, for the best-performing CZTSSe cells, combining the passivated interfacial defects, increased carrier concentration, reduced carrier recombination, and prolonged minority lifetime, the efficiency is improved from 6.54% to 9.88%, together with the 37 mV and 7.9% increase in VOC and FF, respectively. This study confirms the newfound results that the (NH4)2S treatment can effectively adjust the wettability of the absorbers to form high-quality heterojunctions to boost the device efficiency, which would be valuable for an in-depth understanding of the intrinsic mechanisms of interfacial processing.

Alum/CpG Adjuvanted Inactivated COVID-19 Vaccine with Protective Efficacy against SARS-CoV-2 and Variants.

Since the beginning of the COVID-19 pandemic, numerous variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, including five variants of concern (VOC) strains listed by the WHO: Alpha, Beta, Gamma, Delta and Omicron. Extensive studies have shown that most of these VOC strains, especially the currently dominant variant Omicron, can escape the host immune response induced by existing COVID-19 vaccines to different extents, which poses considerable risk to the health of human beings around the world. In the present study, we developed a vaccine based on inactivated SARS-CoV-2 and an adjuvant consisting of aluminum hydroxide (alum) and CpG. The immunogenicity and safety of the vaccine were investigated in rats. The candidate vaccine elicited high titers of SARS-CoV-2-spike-specific IgG antibody and neutralizing antibody in immunized rats, which not only neutralize the original SARS-CoV-2, but also showed great cross-neutralization activity against the Beta, Delta and Omicron variants.

Risk of anxiety and depression in patients with uveitis: a Meta-analysis.

AIM: To quantitatively evaluate the risk of anxiety and depression in patients with uveitis via performing a Meta-analysis. METHODS: Three electronic database (PubMed, Embase, and Cochrane Library databases) were searched for studies recording data about uveitis and anxiety as well as depression simultaneously up to January 2021. The incidence rate and standard mean difference (SMD) with a 95% confidence interval (95%CI) were calculated to analyse the association using random-effects models based on heterogeneity tests. RESULTS: In total, 12 observational studies containing 874 patients with uveitis were included. The results showed that there was a significant association between uveitis and anxiety (SMD=0.97, 95%CI: 0.39 to 1.54, P=0.0009) and depression (SMD=0.79, 95%CI: 0.51 to 1.07, P<0.00001). The overall morbidities of anxiety and depression in patients with uveitis were 39% and 17%, respectively. With subgroup analysis, the heterogeneity actually came from different kinds of uveitis. Specifically, the incidence rates of both anxiety and depression were relatively low in patients with anterior uveitis (33% and 15%), moderate in patients with infectious uveitis (46% and 22%), and high in patients with unspecified uveitis (59% and 35%). CONCLUSION: It is preliminarily indicated that patients with uveitis may have a high risk of anxiety and depression. Ophthalmologists and psychologists should pay more attention to the psychological state when dealing with patients with uveitis. Further high-quality studies with detailed direct data are needed to draw more precise conclusions.

Metabolic Engineering for Overproduction of Colanic Acid in Escherichia coli Mutant with Short Lipopolysaccharide.

Colanic acid is a major exopolysaccharide existing in most Enterobacteriaceae when exposed to an extreme environment. Colanic acid possesses excellent physical properties and biological activities, which makes it a candidate in the food and healthcare market. Previous strategies for colanic acid overproduction in E. coli mainly focus on removing the negative regulator on colanic acid biosynthesis or overexpressing the rcsA gene to up-regulate the cps operon. In this study, modifications in metabolic pathways were implemented in E. coli mutant strains with shortened lipopolysaccharides to improve colanic acid production. First, ackA was deleted to remove the byproduct acetate and the effect of accumulated acetyl-phosphate on colanic acid production was investigated. Second, 11 genes responsible for O-antigen synthesis were deleted to reduce its competition for glucose-1-phosphate and UDP-galactose with colanic acid production. Third, uppS was overexpressed to supply lipid carriers for synthesizing a colanic acid repeat unit. Colanic acid production in the final engineered strain WZM008/pTrcS reached 11.68 g/L in a 2.0 L bioreactor, 3.54 times the colanic acid production by the WQM001 strain. The results provide insights for further engineering E. coli to maximize CA production.

USP7 Attenuates Endoplasmic Reticulum Stress and NF-κB Signaling to Modulate Chondrocyte Proliferation, Apoptosis, and Inflammatory Response under Inflammation.

The purpose of this research was to observe the functions and mechanisms of ubiquitin-specific peptidase 7 (USP7) on chondrocytes under tumor necrosis factor alpha- (TNF-α-) induced inflammation. Knee osteoarthritis (OA) models of mice were constructed by anterior cruciate ligament transection. The knee joint of mice was observed by histological staining, and the expression of USP7 was measured by immunohistochemistry staining. After knocking down or inhibiting USP7, chondrocyte proliferation was measured by histological staining and the CCK-8 assay; apoptosis was measured by western blot, flow cytometry, Caspase-3 activity, and TUNEL staining; and inflammatory response was measured by qRT-PCR and ELISA. The 4-phenylbutyric acid (4-PBA), siRNA of CHOP (si-CHOP), and QNZ were used to verify the signaling pathways. It was found that USP7 was reduced in the knee joint cartilage of OA mice. The knockdown of USP7 or its inhibitor decreased chondrocyte proliferation and accelerated apoptosis and inflammatory response under inflammation. The USP7 inhibitor exacerbated cartilage destruction in mice with OA. The knockdown of USP7 or its inhibitor activated the BiP-eIF2α-ATF4-CHOP signaling of endoplasmic reticulum stress (ERS) and NF-κB/p65 signaling. 4-PBA, si-CHOP, and QNZ partly reversed chondrocyte proliferation, apoptosis, and inflammatory response caused by USP7 knockdown. In conclusion, through inhibiting the BiP-eIF2α-ATF4-CHOP signaling of ERS and NF-κB/p65 signaling, USP7 promotes chondrocyte proliferation and suppresses the apoptosis and inflammatory response under TNF-α-induced inflammation.

PTX3 promotes osteogenic differentiation by triggering HA/CD44/FAK/AKT positive feedback loop in an inflammatory environment.

The treatment of periodontitis-induced alveolar bone defects remains a clinical challenge. The secreted protein pentraxin 3 (PTX3) protects tissue during inflammation and maintains bone homeostasis in physiological conditions. However, the effects of PTX3 on osteoblast differentiation and bone regeneration after periodontitis remain unclear. Here, we found that MC3T3-E1 mouse pre-osteoblast cells secreted increased PTX3 under TNF-α-induced inflammatory conditions in vitro. Gain-of-function and loss-of-function experiments revealed that PTX3 overexpression promoted osteogenic potential in an inflammatory environment and vice versa. The promoting effect was attributed to the regulatory role of PTX3 on the hyaluronan (HA)-dependent pericellular matrix (PCM). PTX3 was found in the HA-dependent PCM of MC3T3-E1 cells, where it promoted HA synthesis and the expression of CD44 (main HA receptor), enhancing the HA-CD44 interaction. The HA-CD44 interaction further activated focal adhesion kinase (FAK)/protein kinase B (AKT) signaling cascade. FAK/AKT activation promoted the expression of HA synthases 1/2/3 (HAS1/2/3) and CD44 in MC3T3-E1 cells under inflammatory condition, forming a positive feedback loop that activated by PTX3. Importantly, when HA was digested or any one of these molecules in the positive feedback loop was blocked, PTX3 partially lost the ability to promote osteogenic differentiation in an inflammatory environment. Ligatures were removed after seven days of periodontitis induction in vivo, to investigate alveolar bone regeneration after periodontitis. Histological and Micro-CT evaluation after seven and 14 days of local PTX3 treatment showed that alveolar bone healing was significantly improved compared to the vehicle control group. These findings suggested that PTX3 can induce osteogenic differentiation in an in vitro inflammatory environment by triggering the HA/CD44/FAK/AKT positive feedback loop, and promote bone regeneration after periodontitis.

Structure of Rift Valley Fever Virus RNA-Dependent RNA Polymerase.

Rift Valley fever virus (RVFV) belongs to the order Bunyavirales and is the type species of genus Phlebovirus, which accounts for over 50% of family Phenuiviridae species. RVFV is mosquito-borne and causes severe diseases in both humans and livestock, and consists of three segments (S, M, L) in the genome. The L segment encodes an RNA-dependent RNA polymerase (RdRp, L protein) that is responsible for facilitating the replication and transcription of the virus. It is essential for the virus and has multiple drug targets. Here, we established an expression system and purification procedures for full-length L protein, which is composed of an endonuclease domain, RdRp domain, and cap-binding domain. A cryo-EM L protein structure was reported at 3.6 Å resolution. In this first L protein structure of genus Phlebovirus, the priming loop of RVFV L protein is distinctly different from those of other L proteins and undergoes large movements related to its replication role. Structural and biochemical analyses indicate that a single template can induce initiation of RNA synthesis, which is notably enhanced by 5' viral RNA. These findings help advance our understanding of the mechanism of RNA synthesis and provide an important basis for developing antiviral inhibitors. IMPORTANCE The zoonosis RVF virus (RVFV) is one of the most serious arbovirus threats to both human and animal health. RNA-dependent RNA polymerase (RdRp) is a multifunctional enzyme catalyzing genome replication as well as viral transcription, so the RdRp is essential for studying the virus and has multiple drug targets. In our study, we report the structure of RVFV L protein at 3.6 Å resolution by cryo-EM. This is the first L protein structure of genus Phlebovirus. Strikingly, a single template can initiate RNA replication. The structure and assays provide a comprehensive and in-depth understanding of the catalytic and substrate recognition mechanism of RdRp.