[Application of mRNA nano-delivery system in CAR-T tumor immunotherapy].

Chimeric antigen receptor T cells (CAR-T) immunotherapy, which activates immunity specific to the system in order to achieve antitumor effects, has experienced exciting progress in recent years. mRNA nano-delivery systems, which encapsulate tumor immunotherapy-related antigen mRNA with nanoparticles, have shown great potential in CAR-T tumor immunotherapy. On one hand, these systems can directly target T cells to generate CAR-T cells that directly act upon the corresponding tumor cells. On the other hand, they can be delivered to antigen-presenting cells through targeting, thereby enhancing the function of CAR-T cells and further inducing specific immune responses against tumor cells. This review summarizes the synthesis of mRNA nano-delivery systems and their application in CAR-T tumor immunotherapy.

LncRNA MACC1-AS1 induces gemcitabine resistance in pancreatic cancer cells through suppressing ferroptosis.

Pancreatic ductal adenocarcinoma (PDA) mortality is primarily attributed to metastasis and chemotherapy resistance. In this research, the long non-coding RNA MACC1-AS1 was studied, playing a significant role in regulating lipid oxidation processes. This regulation could further lead to the inhibition of ferroptosis induced by chemotherapeutic drugs, making it a contributing factor to gemcitabine resistance in PDA. In both gemcitabine-resistant PDA patients and mouse models, the elevated expression level of MACC1-AS1 in the tumors was noted. Additionally, overexpression of MACC1-AS1 in pancreatic cancer cells was found to enhance tolerance to gemcitabine and suppress ferroptosis. Proteomic analysis of drug-resistant pancreatic cells revealed that overexpressed MACC1-AS1 inhibited the ubiquitination degradation of residues in the protein kinase STK33 by MDM4. Furthermore, its accumulation in the cytoplasm activated STK33, further activating the ferroptosis-suppressing proteins GPX4, thereby counteracting gemcitabine-induced cellular oxidative damage. These findings suggested that the long non-coding RNA MACC1-AS1 could play a significant role in the ability of pancreatic cancer cells to evade iron-mediated ferroptosis induced by gemcitabine. This discovery holds promise for developing clinical therapeutic strategies to combat chemotherapy resistance in pancreatic cancer.

The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement.

OBJECTIVE: Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. METHODS: A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. RESULTS: IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. CONCLUSION: sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

Effects of Different Forms and Proportions of Nitrogen on the Growth, Photosynthetic Characteristics, and Carbon and Nitrogen Metabolism in Tomato.

Optimal plant growth in many species is achieved when the two major forms of N are supplied at a particular ratio. This study investigated optimal nitrogen forms and ratios for tomato growth using the 'Jingfan 502' tomato variety. Thirteen treatments were applied with varying proportions of nitrate nitrogen (NN), ammonium nitrogen (AN), and urea nitrogen (UN). Results revealed that the combination of AN and UN inhibited tomato growth and photosynthetic capacity. Conversely, the joint application of NN and UN or NN and AN led to a significant enhancement in tomato plant growth. Notably, the T12 (75%UN:25%NN) and T4 (75%NN:25%AN) treatments significantly increased the gas exchange and chlorophyll fluorescence parameters, thereby promoting the accumulation of photosynthetic products. The contents of fructose, glucose, and sucrose were significantly increased by 121.07%, 206.26%, and 94.64% and by 104.39%, 156.42%, and 61.40%, respectively, compared with those in the control. Additionally, AN favored starch accumulation, while NN and UN favored fructose, sucrose, and glucose accumulation. Gene expression related to nitrogen and sugar metabolism increased significantly in T12 and T4, with T12 showing greater upregulation. Key enzyme activity in metabolism also increased notably. In summary, T12 enhanced tomato growth by upregulating gene expression, increasing enzyme activity, and boosting photosynthesis and sugar accumulation. Growers should consider using NN and UN to reduce AN application in tomato fertilization.

Controlling water deficiency as an abiotic stress factor to improve tomato nutritional and flavour quality.

Water deficit (WD) irrigation techniques to improve water use efficiency have been rapidly developed. However, the effect of WD irrigation on tomato quality has not been sufficiently studied. Here, we investigated the effects of varying water irrigation levels [T1-T4: 80%, 65%, 55%, and 45% of maximum field moisture capacity (FMC)] and full irrigation (CK: 90% of maximum FMC) on tomato fruits from the mature-green to red-ripening stages, to compare the nutritional and flavour qualities of the resulting tomatoes. The proline, aspartic, malic, citric, and ascorbic acid contents increased, phenylalanine and glutamic acid contents decreased, and the total amino and organic acid contents increased by 18.91% and 26.12%, respectively, in T2-treated fruits. Furthermore, the T2-treated fruits exhibited higher K and P contents alongside improved characteristic aromas. These findings provide novel insights for further improvements in tomato quality while also developing water-saving irrigation techniques.

Are couple-based psychological interventions beneficial for the mental health of prostate cancer patients and their spouses? A systematic review and meta-analysis.

As the survival rates for prostate cancer (PCa) have improved, there has been an increasing focus on the mental health of couples affected by this condition. There have been several couple-based psychological interventions, and yet the impact of this treatment modality on the mental health of PCa patients and their spouses is unclear. Consequently, a systematic search was conducted in PubMed, Embase, Cochrane, LILACS, and Web of Science up to March 2023 for randomized controlled trials (RCTs) addressing the impacts of couple-based psychological interventions on both PCa patients and their spouses. Besides, the Cochrane Risk of Bias Assessment Tool was employed to evaluate the methodological quality and potential bias of the included studies. Moreover, statistical analysis and meta-analysis were performed utilizing Revman 5.4, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was employed to assess the certainty of evidence. A total of nine RCTs were included, utilizing anxiety, depression, distress, communication, and self-efficacy as outcome indicators to assess mental health. Results demonstrated that couple-based psychological interventions increased spouses' self-efficacy (WMD, 0.21; 95% CI: -0.00 ~ 0.42; P = 0.05) and communication (SMD, 0.34; 95% CI: 0.09 ~ 0.59; P = 0.009), while reducing their distress (SMD, -0.21; 95% CI: -0.40 ~ -0.02; P = 0.03). Nonetheless, there is a need for additional research on the effect of couple-based psychological interventions on the mental health of PCa-affected couples given the limited evidence supporting this conclusion.

GNA13 inhibits glioblastoma metastasis via the ERKs/FOXO3 signaling pathway.

Glioblastoma (GBM) is a malignant tumor characterized by poor prognosis and low overall survival (OS) rate. Identification of novel biological markers for the diagnosis and treatment of GBM is crucial to developing interventions to improve patient survival. GNA13, a member of the G12 family, has been reported to play important roles in a variety of biological processes involved in tumorigenesis and development. However, its role in GBM is currently unknown. Here, we explored the expression patterns and functions of GNA13 in GBM, as wells its impact on metastasis process. Results showed that GNA13 was downregulated in GBM tissues and correlated with poor prognosis of GBM. Downregulation of GNA13 promoted the migration, invasion and proliferation of GBM cells; whereas its overexpression abolished these effects. Western blots revealed that GNA13 knockdown and overexpression upregulated and inhibited the phosphorylation of ERKs, respectively. Moreover, GNA13 was the upstream of ERKs signaling to regulating ERKs phosphorylation level. Furthermore, U0126 alleviated the metastasis effect induced by GNA13 knockdown. Bioinformatics analyses and qRT-PCR experiments demonstrated that GNA13 could regulate FOXO3, a downstream signaling molecule of ERKs pathway. Overall, our results demonstrate that GNA13 expression is negatively correlated with GBM and can suppress tumor metastasis by inhibiting the ERKs signaling pathway and upregulating FOXO3 expression.

Middle-shallow feature aggregation in multimodality for face anti-spoofing.

At present, most advanced algorithms for face anti-spoofing use stacked convolutions and residual structure to obtain complex characteristics of deep networks, and then distinguish liveness and deception. These methods ignore the shallow features that contain more detailed information. As a result, the model lacks sufficient fine-grained information, which affects the accuracy and robustness of the algorithm. In this paper, we use the simple features of the shallow network to increase the fine-grained information of the model, so as to improve the performance of the algorithm. First of all, the shallow features are spliced to the middle layer by "shortcut" structure to reserve more details for the middle layer features and improve their detail representation ability. Secondly, the network is initialized with the best pre-trained model parameters under unbalanced samples, and then trained on the balanced samples to improve the classification ability of the model. Finally, RS Block based on depthwise separable convolution is used to replace res module, and model parameters and floating point operations are reduced from 18G and 61 M to 1.9 M and 347 M. The algorithm is simulated on CASIA-SURF dataset, and the results show that the average classification error rate (ACER) is only 0.0008, TPR@FPR = 10E-4 reaches 0.9990, which is better than the previous face anti deception methods.

The diagnostic value of urinary N-terminal fragment of titin for skeletal muscle damage in idiopathic inflammatory myopathy.

OBJECTIVES: N-terminal fragment of titin (N-titin) is a marker of sarcomere damage in striated muscles; however, its value in patients with IIM (idiopathic inflammatory myopathy) is unclear. This study aimed to investigate the diagnostic value of N-titin for skeletal muscle damage in patients with IIM. METHODS: Urine samples from 62 patients with IIM, 59 patients with other CTD diseases, and 29 healthy controls were collected to detect N-titin by ELISA assays. Clinical features and laboratory data were all included in logistic regression analysis to obtain the independent predictive factor for skeletal muscle damage. RESULTS: Urinary N-titin level of the IIM group [168.3 (19.0, 1279.0) pmol/mg cr] was significantly higher than that in CTD controls [2.80 (1.53, 3.60)] and healthy controls [1.83 (1.09, 2.95)] (P < 0.001). IIM patients with skeletal muscle injury had a significantly higher level of urinary N-titin [1001.0, (181.8, 1977.0)] than those without [9.3, (5.8, 23.9)] (P < 0.001). The N-titin level was strongly correlated with CK (r = 0.907, P < 0.001) and muscle disease activity assessment scores by Spearman correlation analysis. After adjusting for the anti-MDA5 antibody and cardiac troponin T, N-titin was shown to independently predict skeletal muscle damage in patients with IIM (odds ratio = 1.035, 95% CI: 1.002, 1.069, P = 0.039). The cut-off value of urinary N-titin to diagnose skeletal muscle damage was 89.9 pmol/mg Cr, with a sensitivity of 87.8% and a specificity of 100% (AUC = 0.971, 95% CI: 0.938, 1.000, P < 0.001). CONCLUSION: Urinary N-titin is a non-invasive and independent predictive factor for determining skeletal muscle damage in patients with IIM.

MTHFD2 suppresses glioblastoma progression via the inhibition of ERK1/2 phosphorylation.

Glioblastoma (GBM) is a WHO grade 4 tumor and is the most malignant form of glioma. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme involved in folate metabolism, has been reported to be highly expressed in several human tumors. However, little is known about the role of MTHFD2 in GBM. In this study, we aimed to explore the biological functions of MTHFD2 in GBM and identify the associated mechanisms. We performed experiments such as immunohistochemistry, Western blot, and transwell assays and found that MTHFD2 expression was lower in high-grade glioma than in low-grade glioma. Furthermore, a high expression of MTHFD2 was associated with a favorable prognosis, and MTHFD2 levels showed good prognostic accuracy for glioma patients. The overexpression of MTHFD2 could inhibit the migration, invasion, and proliferation of GBM cells, whereas its knockdown induced the opposite effect. Mechanistically, our findings revealed that MTHFD2 suppressed GBM progression independent of its enzymatic activity, likely by inducing cytoskeletal remodeling through the regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, thereby influencing GBM malignance. Collectively, these findings uncover a potential tumor-suppressor role of MTHFD2 in GBM cells. MTHFD2 may act as a promising diagnostic and therapeutic target for GBM treatment.

Exogenous application of ALA enhanced sugar, acid and aroma qualities in tomato fruit.

The content and proportion of sugars and acids in tomato fruit directly affect its flavor quality. Previous studies have shown that 5-aminolevulinic acid (ALA) could promote fruit ripening and improve its aroma quality. In order to explore the effect of ALA on sugar and acid quality during tomato fruit development, 0, 100, and 200 mg L-1 ALA solutions were sprayed on the fruit surface 10 days after pollination of the fourth inflorescence, and the regulation of ALA on sugar, acid metabolism and flavor quality of tomato fruit was analyzed. The results showed that ALA treatment could enhance the activities of acid invertase (AI), neutral invertase (NI), and sucrose synthase (SS), reduce the activity of sucrose phosphate synthase (SPS), up-regulate the expression of SlAI, SlNI and SlSS, change the composition and content of sugar in tomato fruit at three stages, significantly increase the content of sugars in fruit, and promote the accumulation of sugars into flesh. Secondly, ALA treatments increased the activities of phosphoenolpyruvate carboxykinase (PEPC), malic enzyme (ME), and citrate synthase (CS), up-regulated the expression of SlPPC2, SlME1, and SlCS, and reduced the citric acid content at maturity stage, thereby reducing the total organic acid content. In addition, ALA could also increase the number and mass fraction of volatile components in mature tomato fruits. These results indicated that exogenous application of ALA during tomato fruit development could promote the formation of fruit aroma quality and were also conducive to the formation of fruit sugar and acid quality.

Enhanced efficiency of enzymatic hydrolysis of wheat straw via freeze-thaw pretreatment.

This research investigated enhancing the efficiency of enzymatic hydrolysis of wheat straw via freeze-thaw pretreatment and assessed the physicochemical structural changes after this pretreatment. The enzymatic hydrolysis efficiency of cellulose and hemicellulose was enhanced, and hemicellulose was more susceptible to pretreatment. The highest enzymatic hydrolysis efficiency of cellulose and hemicellulose was 57.06 and 70.66%, respectively, at - 80 ℃ for 24 h and - 10 ℃ for 24 h, respectively, which were 2.23 and 3.13-fold higher than the control levels, respectively. Scanning electron microscopy images indicated that transverse cracks appeared before longitudinal cracks with stronger pretreatment conditions, and holes were found in every sample after this pretreatment. Fourier transform infrared spectroscopy and X-ray diffraction analysis indicated that freeze-thaw pretreatment affected both the crystalline and amorphous regions and disrupted the hydrogen bonds within them. This study provides a physical pretreatment method to improve the efficiency of enzymatic hydrolysis of wheat straw.

Effects of dexmedetomidine on glucose-related hormones and lactate in non-diabetic patients under general anesthesia: a randomized controlled trial.

BACKGROUND: The aim of this study was to explore the effects of dexmedetomidine on glucose-related hormones and lactate levels in non-diabetic patients undergoing malignant gastrointestinal tumor radical resection. METHODS: Groups D1 and D2 received dexmedetomidine loading dose 1 µg/kg and maintenance dose 0.25 and 0.5 µg/kg/h, respectively. Group C received saline solution. Glucose, lactate, insulin, glucagon, cortisol, epinephrine, norepinephrine and dopamine levels were measured before dexmedetomidine infusion (T1), 1 h after surgery beginning (T2), at surgery ending (T3), and 1 h after transfer to the postanesthesia care unit (T4). RESULTS: Compared with group C, glucose levels increased in group D2 at T2 and reduced in groups D1 and D2 at T4. Lactate levels reduced in groups D1 and D2 at T4. A positive correlation between glucose and lactate levels was found in all groups. Compared with group C, insulin level reduced in group D2 at T2; glucagon levels reduced in groups D1 and D2 at T4; cortisol levels reduced in group D1 at T4 and in group D2 at T3 and T4; epinephrine and norepinephrine levels reduced in group D1 at T4 and in group D2 at T2 and T4; and dopamine level reduced in group D2 at T4. CONCLUSIONS: Dexmedetomidine loading dose 1 µg/kg and maintenance dose 0.25 µg/kg/h produces a stable insulin level and significant postoperative decreases in glucagon, cortisol, epinephrine and norepinephrine secretion with stable maintenance of intraoperative and postoperative blood glucose levels and decreased postoperative lactate levels in non-diabetic patients under general anesthesia.

The Role of Fecal Fusobacterium nucleatum and pks+ Escherichia coli as Early Diagnostic Markers of Colorectal Cancer.

BACKGROUND: Accurate analysis of intestinal microbiota will facilitate establishment of an evaluating system for assessing colorectal cancer (CRC) risk and prognosis. This study evaluates the potential role of Fusobacterium nucleatum (F. nucleatum) and Escherichia coli with a pks gene (pks+ E. coli) in early CRC diagnosis. METHODS: We recruited 139 patients, including CRC (n = 60), colorectal adenomatous polyposis (CAP) (n = 37), and healthy individuals (n = 42) based on their colonoscopy examinations. We collected stool and serum samples from the participants and measured the relative abundance of F. nucleatum and pks+ E. coli in fecal samples by quantitative PCR. Receiver operating characteristic curve (ROC) analyses were used to analyze the diagnostic value of single or combined biomarkers. RESULTS: Fecal F. nucleatum and pks+ E. coli levels were higher in the CRC group in either the CAP group or healthy controls (P = 0.02; 0.01). There was no statistical difference in the distribution of F. nucleatum and pks+ E. coli in patients with different tumor sites (P > 0.05). The combination of F. nucleatum+pks+ E. coli+CEA+CA19-9+FOBT was chosen as the optimal panel in differentiating both CRC and CAP from the controls. The combination of F. nucleatum, pks+ E. coli, and FOBT improved diagnostic efficiency. However, there was difficulty in differentiating CRC from CAP. CONCLUSION: Our results suggested that combining bacterial markers with conventional tumor markers improves the diagnostic efficiency for noninvasive diagnosis of CRC.

Genotype I African swine fever viruses emerged in domestic pigs in China and caused chronic infection.

The Georgia-07-like genotype II African swine fever virus (ASFV) with high virulence has been prevalent in China since 2018. Here, we report that genotype I ASFVs have now also emerged in China. Two non-haemadsorbing genotype I ASFVs, HeN/ZZ-P1/21 and SD/DY-I/21, were isolated from pig farms in Henan and Shandong province, respectively. Phylogenetic analysis of the whole genome sequences suggested that both isolates share high similarity with NH/P68 and OURT88/3, two genotype I ASFVs isolated in Portugal in the last century. Animal challenge testing revealed that SD/DY-I/21 shows low virulence and efficient transmissibility in pigs, and causes mild onset of infection and chronic disease. SD/DY-I/21 was found to cause necrotic skin lesions and joint swelling. The emergence of genotype I ASFVs will present more problems and challenges for the control and prevention of African swine fever in China.

Recovery of a Far-Eastern Strain of Tick-Borne Encephalitis Virus with a Full-Length Infectious cDNA Clone.

Tick-borne encephalitis virus (TBEV) is a pathogenic virus known to cause central nervous system (CNS) diseases in humans, and has become an increasing public health threat nowadays. The rates of TBEV infection in the endemic countries are increasing. However, there is no effective antiviral against the disease. This underscores the urgent need for tools to study the emergence and pathogenesis of TBEV and to accelerate the development of vaccines and antivirals. In this study, we reported an infectious cDNA clone of TBEV that was isolated in China (the WH2012 strain). A beta-globin intron was inserted in the coding region of nonstructural protein 1 (NS1) gene to improve the stability of viral genome in bacteria. In mammalian cells, the inserted intron was excised and spliced precisely, which did not lead to the generation of inserted mutants. High titers of infectious progeny viruses were generated after the transfection of the infectious clone. The cDNA-derived TBEV replicated efficiently, and caused typical cytopathic effect (CPE) and plaques in BHK-21 cells. In addition, the CPE and growth curve of cDNA-derived virus were similar to that of its parental isolate in cells. Together, we have constructed the first infectious TBEV cDNA clone in China, and the clone can be used to investigate the genetic determinants of TBEV virulence and disease pathogenesis, and to develop countermeasures against the virus.

Gut microbiota mediates cognitive impairment in young mice after multiple neonatal exposures to sevoflurane.

Multiple exposures to anesthesia may increase the risk of cognitive impairment in young children. However, the mechanisms underlying this neurodevelopmental disorder remain elusive. In this study, we investigated alteration of the gut microbiota after multiple neonatal exposures to the anesthetic sevoflurane and the potential role of microbiota alteration on cognitive impairment using a young mice model. Multiple neonatal sevoflurane exposures resulted in obvious cognitive impairment symptoms and altered gut microbiota composition. Fecal transplantation experiments confirmed that alteration of the microbiota was responsible for the cognitive disorders in young mice. Microbiota profiling analysis identified microbial taxa that showed consistent differential abundance before and after fecal microbiota transplantation. Several of the differentially abundant taxa are associated with memory and/or health of the host, such as species of Streptococcus, Lachnospiraceae, and Pseudoflavonifractor. The results reveal that abnormal composition of the gut microbiota is a risk factor for cognitive impairment in young mice after multiple neonatal exposures to sevoflurane and provide insight into a potential therapeutic strategy for sevoflurane-related neurotoxicity.

Prediction of stroke-associated pneumonia by the A2DS2, AIS-APS, and ISAN scores: a systematic review and meta-analysis.

Background: Different scoring systems (A2DS2, AISAPS, ISAN) have been designed to predict the risk of in-hospital stroke-associated pneumonia (SAP). Studies have assessed the accuracy of these scores for predicting SAP. We performed this meta-analysis to consolidate the evidence on the predictive accuracies for SAP of the A2DS2, AISAPS, and ISAN scores.Materials and methods: We conducted a systematic search for all studies reporting the SAP predictive accuracy of A2DS2, AISAPS, or ISAN scores in the databases of PubMed Central, SCOPUS, MEDLINE, Embase, and Cochrane from inception until December 2020. We used the STATA software for the meta-analysis.Results: We included 19 studies with 35 849 patients. The pooled score sensitivities were 78% (95% CI, 71%-83%) for A2DS2, 79% (95% CI, 77%-81%) for AISAPS, and 79% (95% CI, 77%-81%) for ISAN. The pooled score specificities were 73% (95% CI, 65%-80%) for A2DS2, 74% (95% CI, 69%-79%) for AISAPS, and 74% (95% CI, 69%-79%) for ISAN. We found significant heterogeneity for all the scoring systems based on the chi-square test results and an I2 statistic > 75%. We performed meta-regression to explore the source of heterogeneity and found that patient selection (p< 0.05) and reference standards (p< 0.05) in the sensitivity model, index test standards (p< 0.05), flow and timing of tests (p< 0.01) in the specificity model, and mean age (p < 0.001) in the joint model were the source of heterogeneity.Conclusions: To summarize, we found that A2S2, AISAPS and ISAN have moderate predictive accuracy for SAP with A2S2 having a stable cutoff value.

Emergence and prevalence of naturally occurring lower virulent African swine fever viruses in domestic pigs in China in 2020.

African swine fever virus (ASFV) has been circulating in China for more than two years, and it is not clear whether the biological properties of the virus have changed. Here, we report on our surveillance of ASFVs in seven provinces of China, from June to December, 2020. A total of 22 viruses were isolated and characterized as genotype II ASFVs, with mutations, deletions, insertions, or short-fragment replacement occurring in all isolates compared with Pig/HLJ/2018 (HLJ/18), the earliest isolate in China. Eleven isolates had four different types of natural mutations or deletion in the EP402R gene and displayed a non-hemadsorbing (non-HAD) phenotype. Four isolates were tested for virulence in pigs; two were found to be as highly lethal as HLJ/18. However, two non-HAD isolates showed lower virulence but were highly transmissible; infection with 106 TCID50 dose was partially lethal and caused acute or sub-acute disease, whereas 103 TCID50 dose caused non-lethal, sub-acute or chronic disease, and persistent infection. The emergence of lower virulent natural mutants brings greater difficulty to the early diagnosis of ASF and creates new challenges for ASFV control.