Single-Cell Analysis in Blood Reveals Distinct Immune Cell Profiles in Gouty Arthritis.

Gout is a chronic disease caused by monosodium urate crystal deposition. Previous studies have focused on the resident macrophage, infiltrating monocyte, and neutrophil responses to monosodium urate crystal, yet the mechanisms of the potential involvement of other immune cells remain largely unknown. In this study, we enrolled seven gout patients and five age-matched healthy individuals and applied single-cell mass cytometry to study the distribution of immune cell subsets in peripheral blood. To our knowledge, our study reveals the immune cell profiles of gout at different stages for the first time. We identified many immune cell subsets that are dysregulated in gout and promote gouty inflammation, especially those highly expressing CCR4 and OX40 (TNFR superfamily member 4), including CCR4+OX40+ monocytes, CCR4+OX40+CD56high NK cells, CCR4+OX40+CD4+ NK T cells, and CCR4+CD38+CD4+ naïve T cells. Notably, the plasma levels of CCL17 and CCL22, measured by ELISA, increased in the acute phase of gout and declined in the interval. We also found a clue that Th2-type immune responses may participate in gout pathology. Moreover, the subset of granzyme B+ (GZMB+) CD38+ NK cells is positively correlated with serum urea acid level, and another two γδT subsets, GZMB+CD161+ γδT cells and GZMB+CCR5+ γδT cells, are negatively correlated with erythrocyte sedimentation rate. In sum, gouty arthritis is not a disease simply mediated by macrophages; multiple types of immune cell may be involved in the pathogenesis of the disease. Future research needs to shift attention to other immune cell subsets, such as NK cells and T cells, which will facilitate the identification of novel therapeutic targets.

Isolation and Identification of Salinity-Tolerant Rhizobia and Nodulation Phenotype Analysis in Different Soybean Germplasms.

Increasing the soybean-planting area and increasing the soybean yield per unit area are two effective solutions to improve the overall soybean yield. Northeast China has a large saline soil area, and if soybeans could be grown there with the help of isolated saline-tolerant rhizobia, the soybean cultivation area in China could be effectively expanded. In this study, soybeans were planted in soils at different latitudes in China, and four strains of rhizobia were isolated and identified from the soybean nodules. According to the latitudes of the soil-sampling sites from high to low, the four isolated strains were identified as HLNEAU1, HLNEAU2, HLNEAU3, and HLNEAU4. In this study, the isolated strains were identified for their resistances, and their acid and saline tolerances and nitrogen fixation capacities were preliminarily identified. Ten representative soybean germplasm resources in Northeast China were inoculated with these four strains, and the compatibilities of these four rhizobium strains with the soybean germplasm resources were analyzed. All four isolates were able to establish different extents of compatibility with 10 soybean resources. Hefeng 50 had good compatibility with the four isolated strains, while Suinong 14 showed the best compatibility with HLNEAU2. The isolated rhizobacteria could successfully establish symbiosis with the soybeans, but host specificity was also present. This study was a preliminary exploration of the use of salinity-tolerant rhizobacteria to help the soybean nitrogen fixation in saline soils in order to increase the soybean acreage, and it provides a valuable theoretical basis for the application of saline-tolerant rhizobia.

Unlocking the Potential of Amorphous Prussian Blue with Highly Active Mn Sites at Room Temperature for Impressive Oxygen Evolution Reaction and Super Capacitor Electrochemical Performance.

The key to increasing the rate of oxygen evolution reaction (OER) lies in accelerated four-electron dynamics, while the key to facilitating the development of supercapacitors lies in the design of electrode materials. This paper synthesized manganese-iron Prussian blue (MnFe-PBA@IF) at room temperature, and hexagonal concave structures w ere prepared using a fast-reducing matrix. Interestingly, MnFe-PBA@IF has an amorphous structure favorable to exposing more active surfaces. According to Gibbs free energy calculations on MnFe-PBA, charge depletion of manganese atoms can greatly enhance the adsorption of electron-rich oxygen-containing groups on the surface. Furthermore, the overpotential in 1 m KOH is 280 mV. Also, it can be used as a supercapacitor with a stable operating voltage range of -0.9-0 V and a specific capacity of 1260 F g-1 . This work provides new insights into the synthesis of OER catalysts for Prussian blue ferromanganese at room temperature. Non-gold-bonded adsorption, highly active metal centers and active surfaces are the underlying reasons for the superior performance of supercapacitors. Therefore, Prussian blue with good energy storage performance and high active surface can be used as multifunctional energy storage and conversion electrodes.

Strain Effects in Ru-Au Bimetallic Aerogels Boost Electrocatalytic Hydrogen Evolution.

To improve the sluggish kinetics of the hydrogen evolution reaction (HER), a key component in water-splitting applications, there is an urgent desire to develop efficient, cost-effective, and stable electrocatalysts. Strain engineering is proving an efficient strategy for increasing the catalytic activity of electrocatalysts. This work presents the development of Ru-Au bimetallic aerogels by a simple one-step in situ reduction-gelation approach, which exhibits strain effects and electron transfer to create a remarkable HER activity and stability in an alkaline environment. The surface strain induced by the bimetallic segregated structure shifts the d-band center downward, enhancing catalysis by balancing the processes of water dissociation, OH* adsorption, and H* adsorption. Specifically, the optimized catalyst shows low overpotentials of only 24.1 mV at a current density of 10 mA cm-2 in alkaline electrolytes, surpassing commercial Pt/C. This study can contribute to the understanding of strain engineering in bimetallic electrocatalysts for HER at the atomic scale.

Diagnostic strategy of metagenomic next-generation sequencing for gram negative bacteria in respiratory infections.

OBJECTIVE: This study aims to identify the most effective diagnostic method for distinguishing pathogenic and non-pathogenic Gram-negative bacteria (GNB) in suspected pneumonia cases using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples. METHODS: The effectiveness of mNGS was assessed on BALF samples collected from 583 patients, and the results were compared with those from microbiological culture and final clinical diagnosis. Three interpretational approaches were evaluated for diagnostic accuracy. RESULTS: mNGS outperformed culture significantly. Among the interpretational approaches, Clinical Interpretation (CI) demonstrated the best diagnostic performance with a sensitivity of 87.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98.3%. CI's specificity was significantly higher than Simple Interpretation (SI) at 37.9%. Additionally, CI excluded some microorganisms identified as putative pathogens by SI, including Haemophilus parainfluenzae, Haemophilus parahaemolyticus, and Klebsiella aerogenes. CONCLUSION: Proper interpretation of mNGS data is crucial for accurately diagnosing respiratory infections caused by GNB. CI is recommended for this purpose.

Association of sleep quality on the night of operative day with postoperative delirium in elderly patients: A prospective cohort study.

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.

Instability in a carbon pool driven by multiple dissolved organic matter sources in a eutrophic lake basin: Potential factors for increased greenhouse gas emissions.

Lakes serve as vital reservoirs of dissolved organic matter (DOM) and play pivotal roles in biogeochemical carbon cycles. However, the sources and compositions of DOM in freshwater lakes and their potential effects on lake sediment carbon pools remain unclear. In this study, seven inflowing rivers in the Lake Taihu basin were selected to explore the potential effects of multi-source DOM inputs on the stability of the lake sediment carbon pool. The results showed the high concentrations of dissolved organic carbon in the Lake Taihu basin, accompanied by a high complexity level. Lignins constituted the majority of DOM compounds, surpassing 40% of the total, while the organic carbon content was predominantly composed of humic acids (1.02-3.01 g kg-1). The high amounts of lignin oxidative cleavage led to CHO being the main molecular structure in the DOM of the seven rivers. The carbon constituents within the sediment carbon reservoir exhibited a positive correlation with dissolved CH4 and CO2, with a notable emphasis on humic acid and dissolved CH4 (R2 = 0.86). The elevated concentration of DOM, coupled with its intricate composition, contributed to the increases in dissolved greenhouse gases (GHGs). Experiments showed that the mixing of multi-source DOM can accelerate the organic carbon mineralization processes. The unit carbon emission efficiency was highest in the mixed group, reaching reached 160.9 µmol∙Cg-1, which also exhibited a significantly different carbon pool. The mixed decomposition of DOM from different sources influenced the roles of the lake carbon pool as source and sink, indicating that the multi-source DOM of this lake basin was a potential driving factor for increased carbon emissions. These findings have improved our understanding of the sources and compositions of DOM in lake basins and revealed their impacts on carbon emissions, thereby providing a theoretical basis for improving assessments of lake carbon emissions.

Cost-effective In Vivo and In Vitro Mouse Models for Evaluating Anticryptosporidial Drug Efficacy: Assessing Vorinostat, Docetaxel, and Baicalein.

BACKGROUND: Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and specialized breeding/housing requirements limit in vivo drug testing. Numerous anticryptosporidial lead compounds identified in vitro remain untested in vivo. METHODS: Cryptosporidium tyzzeri, a natural mouse parasite closely related to Cryptosporidium parvum and Cryptosporidium hominis, was isolated to establish an infection model in immunocompetent mice. The model was validated using classic anticryptosporidial drugs (paromomycin and nitazoxanide) and then employed to assess the efficacy of 3 new leads (vorinostat, docetaxel, and baicalein). An in vitro culture of C. tyzzeri was also developed to complement the animal model. RESULTS: Chronic C. tyzzeri infection was established in chemically immunosuppressed wild-type mice. Paromomycin (1000 mg/kg/d) and nitazoxanide (100 mg/kg/d) demonstrated efficacy against C. tyzzeri. Vorinostat (30 mg/kg/d), docetaxel (25 mg/kg/d), and baicalein (50 mg/kg/d) were highly effective against C. tyzzeri infection. In vitro, nitazoxanide, vorinostat, docetaxel, and baicalein exhibited low to submicromolar efficacy against C. tyzzeri. CONCLUSIONS: Novel in vivo and in vitro models have been developed for cost-effective anticryptosporidial drug testing. Vorinostat, docetaxel, and baicalein show potential for repurposing and/or optimization for developing new anticryptosporidial drugs.

Synergetic Monitoring of both Physiological Pressure and Epidermal Biopotential Based on a Simplified on-Skin-Printed Sensor Modality.

Flexible electronic sensors show great potential for health monitoring but are usually limited to single sensing functionality. To enrich their functions, complicated device configurations, sophisticated material systems, and preparation processes are typically involved, obstructing their large-scale deployment and widespread application. Herein, to achieve a good balance between simplicity and multifunctionality, a new paradigm of sensor modality for both mechanical sensing and bioelectrical sensing is presented based on a single material system and a simple solution processing approach. The whole multifunctional sensors are constructed with a pair of highly conductive ultrathin electrodes (WPU/MXene-1) and an elastic micro-structured mechanical sensing layer (WPU/MXene-2), with the human skin serving as the substrate for the whole sensors. The resultant sensors show high pressure sensitivity and low skin-electrode interfacial impedance, enabling to synergetically monitor both physiological pressure (e.g., arterial pulse signals) and epidermal bioelectrical signals (including electrocardiograph and electromyography). The universality and extensibility of this methodology to construct multifunctional sensors with different material systems are also verified. This simplified sensor modality with enhanced multifunctionality provides a novel design concept to construct future smart wearables for health monitoring and medical diagnosis.

Modulating Electronic Structure and Atomic Insights into the Novel Hierarchically Porous PdCuFe Trimetallic Alloy Aerogel for Efficient Oxygen Reduction.

The high cost of noble Pd/Pt required for the oxygen reduction reaction (ORR) in the cathode restricts the wide applications of fuel cells. In this study, the synthesis of a novel Pd3 CuFe0.5 aerogel electrocatalyst is successfully demonstrated using self-assembly and lyophilization techniques, employing a mild reducing agent. The resulting aerogel electrocatalyst exhibits a distinctive 3D network structure, possessing a substantial BET-specific surface area of 75.19 m2  g-1 . It is worth noting that the optimized Pd3 CuFe0.5 aerogel demonstrates exceptional ORR performance with a high half-wave potential of 0.92 V versus RHE, a significant limiting current density of 7.6 mA cm-2 , and the excellent electrocatalytic stability, superior to the reported noble metal electrocatalysts, with the ORR activity decays only 4.9% after 16 000 s. In addition, the Pd3 CuFe0.5 aerogel electrocatalyst shows superior cycling stability for ≈120 h at a charge/discharge current density of 10 mA cm-2 , indicating its promising application in fuel cells. Furthermore, the resulting composite aerogel possesses excellent hydrogen evolution reaction and ethanol oxidation reaction activity. The density functional theory calculations show that the partial oxidation of Pd3 CuFe0.5 aerogel leads to a negative shift of the d-band center, which energetically optimizes the binding strength of *O intermediates, therefore accelerating the ORR activity.

Generalized Rapid Synthesis of Supported Nanocluster Catalyst for Mild Hydrogenation of Phenol toward KA Oil.

Homogeneous and nanometric metal clusters with unique electronic structures are promising for catalysis, however, common synthesis techniques for metal clusters suffer from large size and even metal nanocrystals attributing to their high surface energy and unsaturated configurations. Herein, a generalized rapid annealing strategy for synthesizing a series of supported metal clusters as superior catalysts is developed. Remarkably, TiO2 supported platinum nanoclusters (Pt NC/TiO2 ) exhibits the excellent catalytic activity to realize phenol hydrogenation under mild conditions. The complete phenol conversion rate and 100% selectivity toward KA oil are achieved in aqueous solution at room temperature and normal pressure. Semi-continuous scale up production of KA oil is successfully performed under mild conditions. Such excellent performance mainly originates from the partial reconstruction of Pt NC/TiO2 in aqueous phenol solution. Considering that the phenol can be produced from lignin, this study underpins a facile, sustainable, and economical route to synthesize nylon from biomass.

High-Energy-Density Lithium Metal Batteries with Impressive Li+ Transport Dynamic and Wide-Temperature Performance from -60 to 60 °C.

High-energy-density Li metal batteries (LMBs) with Nickel (Ni)-rich cathode and Li-metal anode have attracted extensive attention in recent years. However, commercial carbonate electrolytes bring severe challenges including poor cycling stability, severe Li dendrite growth and cathode cracks, and narrow operating temperature window, especially hardly work at below -40 °C. In this work, a 2.4 m lithium difluoro(oxalato)borate (LiDFOB) in ethyl acetate (EA) solvent with 20 wt% fluorocarbonate (FEC) (named 2.4m-DEF) is designed to solve Li+ transport dynamic at low temperature and improve interfacial stability between electrolyte with Li anode or Ni-rich cathode. Beneficial lower freezing point, lower viscosity, and higher dielectric constant of EA solvent, the electrolyte exhibits excellent Li+ transport dynamic. Relying on the unique Li+ solvation structure, more DFOB- anions and FEC solvents are decomposed to establish a stable solid electrolyte interface at electrolyte/electrode. Therefore, LiNi0.9 Co0.05 Mn0.05 O2 (NCM90)/Li LMB with 2.4m-DEF enables excellent rate capability (184 mA h g-1 at 30 C) and stable cycling performance with ≈93.7% of capacity retention after 200 cycles at 20 C and room temperature. Moreover, the NCM90/Li LMB with 2.4m-DEF exhibits surprising ultra-low-temperature performance, showing 173 mA h g-1 at -40 °C and 152 mA h g-1 at -60 °C, respectively.

Molecular dynamics simulation study on the structures of fascin mutants.

Fascin is a filamentous actin (F-actin) bundling protein, which cross-links F-actin into bundles and becomes an important component of filopodia on the cell surface. Fascin is overexpressed in many types of cancers. The mutation of fascin affects its ability to bind to F-actin and the progress of cancer. In this paper, we have studied the effects of residues of K22, K41, K43, K241, K358, K399, and K471 using molecular dynamics (MD) simulation. For the strong-effect residues, that is, K22, K41, K43, K358, and K471, our results show that the mutation of K to A leads to large values of root mean square fluctuation (RMSF) around the mutated residues, indicating those residues are important for the flexibility and thermal stability. On the other hand, based on residue cross-correlation analysis, alanine mutations of these residues reinforce the correlation between residues. Together with the RMSF data, the local flexibility is extended to the entire protein by the strong correlations to influence the dynamics and function of fascin. By contrast, for the mutants of K241A and K399A those do not affect the function of fascin, the RMSF data do not show significant differences compared with wild-type fascin. These findings are in a good agreement with experimental studies.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

ECM1 controls T(H)2 cell egress from lymph nodes through re-expression of S1P(1).

Type 2 helper T cells (T(H)2) are critically involved in allergies and asthma. Here we demonstrate that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in T(H)2 cells. ECM1 deficiency caused impaired T(H)2 responses and reduced allergic airway inflammation in vivo. Functional analysis demonstrated that although the T(H)2 polarization of ECM1-deficient cells was unimpaired, these cells had a defect in migration and were retained in peripheral lymphoid organs. This was associated with reduced expression of KLF2 and S1P(1). We also found that ECM1 could directly bind the interleukin-2 (IL-2) receptor to inhibit IL-2 signaling and activate S1P(1) expression. Our data identify a previously unknown function of ECM1 in regulating T(H)2 cell migration through control of KLF2 and S1P(1) expression.

Graphene-based Pancharatnam-Berry phase metasurface in the terahertz domain for dynamically independent amplitude and phase manipulation.

Dynamic and independent amplitude and phase manipulation are the paramount demand for many advanced wavefronts engineering applications. Currently, the coupling issue between the amplitude and phase hinders the efficient modulation wavefront's further implementation. This paper proposes and numerically demonstrates the bi-layer stacked graphene Pancharatnam-Berry (P-B) phase metasurface and mono-layer graphene P-B phase metasurface to address the above problem. The simulation results show that the proposed models can achieve the independent control amplitude and phase and significantly reduce their coupling strength. Our findings offer a flexible and straightforward method for precise wave reconstruction applications such as holography, optical tweezers, and high-resolution imaging.

High carbon emissions from thermokarst lakes and their determinants in the Tibet Plateau.

Thermokarst lakes are potentially important sources of methane (CH4 ) and carbon dioxide (CO2 ). However, considerable uncertainty exists regarding carbon emissions from thermokarst lakes owing to a limited understanding of their patterns and motivators. In this study, we measured CH4 and CO2 diffusive fluxes in 163 thermokarst lakes in the Qinghai-Tibet Plateau (QTP) over 3 years from May to October. The median carbon emissions from the QTP thermokarst lakes were 1440 mg CO2 m-2 day-1 and 60 mg CH4 m-2 day-1 , respectively. The diffusive rates of CO2 and CH4 are related to the catchment land cover type. Sediment microbial abundance and hydrochemistry explain 51.9% and 38.3% of the total variance in CH4 diffusive emissions, respectively, while CO2 emissions show no significant relationship with environmental factors. When upscaling carbon emissions from the QTP thermokarst lakes, the annual average CH4 release per lake area is equal to that of the pan-Arctic region. Our findings highlight the importance of incorporating in situ observation data with different emission pathways for different land cover types in predicting carbon emissions from thermokarst lakes in the future.

Study on the Superlubricity Behavior of Ions under External Electric Fields at Steel Interfaces.

Realizing macroscopic superlubricity in the presence of external electric fields (EEFs) at the steel interfaces is still challenging. In this work, macroscopic superlubricity with a coefficient of friction value of approximately 0.008 was realized under EEFs with the lubrication of LiPF6-based ionic liquids at steel interfaces. The roles of cations and anions in the superlubricity realization under EEFs were studied. Based on the experimental results, the macroscopic superlubricity behavior of Li(PEG)PF6 under EEFs at steel interfaces is attributed to the strong hydration effect of Li+ cations and the complete reactions of anions that contributed to the formation of a boundary film on the appropriate surface. Moreover, the reduction in the number of iron oxides in the boundary film on the disc was beneficial for friction reduction. We also provide a calculation model to describe the relationship between the hydration effect and the optimal voltage position, at which the lowest friction might occur. Ultimately, this work proves that macroscopic superlubricity can be realized under EEFs at steel interfaces and provides a foundation for engineering applications of superlubricity in an electrical environment.

Use of compressed sensing to expedite high-throughput diagnostic testing for COVID-19 and beyond.

The rapid spread of SARS-CoV-2 has placed a significant burden on public health systems to provide swift and accurate diagnostic testing highlighting the critical need for innovative testing approaches for future pandemics. In this study, we present a novel sample pooling procedure based on compressed sensing theory to accurately identify virally infected patients at high prevalence rates utilizing an innovative viral RNA extraction process to minimize sample dilution. At prevalence rates ranging from 0-14.3%, the number of tests required to identify the infection status of all patients was reduced by 69.26% as compared to conventional testing in primary human SARS-CoV-2 nasopharyngeal swabs and a coronavirus model system. Our method provided quantification of individual sample viral load within a pool as well as a binary positive-negative result. Additionally, our modified pooling and RNA extraction process minimized sample dilution which remained constant as pool sizes increased. Compressed sensing can be adapted to a wide variety of diagnostic testing applications to increase throughput for routine laboratory testing as well as a means to increase testing capacity to combat future pandemics.

Attenuated African swine fever virus through serial passaging of viruses in cell culture: a brief review on the knowledge gathered during 60 years of research.

African swine fever virus (ASFV) is a highly pathogenic double-stranded DNA virus. It affects various breeds of pigs, causing serious economic losses and health threats because of its rapid spread and high pathogenicity and infectivity. This situation is not helped by the lack of a validated vaccine or effective therapies. Since the 1960s, different strains of ASFV have been subjected to serial passage in a variety of cell lines. The attenuated ASFV strains obtained through serial passage are not only candidates for ASF vaccine research, but also are useful to study the molecular genetic characteristics and pathogenic mechanism of the virus. This review summarizes related studies on the attenuated strains of ASFV acquired through cell passage over the last 60 years, with the aim of providing inspiration for the rational design of vaccines in future.