Altered epitopes enhance macrophage-mediated anti-tumour immunity to low-immunogenic tumour mutations.

Personalized neoantigen therapy has shown long-term and stable efficacy in specific patient populations. However, not all patients have sufficient levels of neoantigens for treatment. Although somatic mutations are commonly found in tumours, a significant portion of these mutations do not trigger an immune response. Patients with low mutation burdens continue to exhibit unresponsiveness to this treatment. We propose a design paradigm for neoantigen vaccines by utilizing the highly immunogenic unnatural amino acid p-nitrophenylalanine (pNO2Phe) for sequence alteration of somatic mutations that failed to generate neoepitopes. This enhances the immunogenicity of the mutations and transforms it into a suitable candidate for immunotherapy. The nitrated altered epitope vaccines designed according to this paradigm is capable of activating circulating CD8+ T cells and inducing immune cross-reactivity against autologous mutated epitopes in different MHC backgrounds (H-2Kb, H-2Kd, and human HLA-A02:01), leading to the elimination of tumour cells carrying the mutation. After immunization with the altered epitopes, tumour growth was significantly inhibited. It is noteworthy that nitrated epitopes induce tumour-infiltrating macrophages to differentiate into the M1 phenotype, surprisingly enhancing the MHC II molecule presenting pathway of macrophages. Nitrated epitope-treated macrophages have the potential to cross-activate CD4+ and CD8+ T cells, which may explain why pNO2Phe can enhance the immunogenicity of epitopes. Meanwhile, the immunosuppressive microenvironment of the tumour is altered due to the activation of macrophages. The nitrated neoantigen vaccine strategy enables the design of vaccines targeting non-immunogenic tumour mutations, expanding the pool of potential peptides for personalized and shared novel antigen therapy. This approach provides treatment opportunities for patients previously ineligible for new antigen vaccine therapy.

Guidelines for the diagnosis and treatment of neurally mediated syncope in children and adolescents (revised 2024).

BACKGROUND: Significant progress has been made in the diagnosis and treatment of pediatric syncope since the publication of the "2018 Chinese Pediatric Cardiology Society (CPCS) guideline for diagnosis and treatment of syncope in children and adolescents" ("2018 Edition Guidelines"). Therefore, we have revised and updated it to assist pediatricians in effectively managing children with syncope. DATA SOURCES: According to the "2018 Edition Guidelines", the expert groups collected clinical evidence, evaluated preliminary recommendations, and then organized open-ended discussions to form the recommendations. This guideline was developed by reviewing the literature and studies in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to April 2024. Search terms included "syncope", "children", "adolescents", "diagnosis", and "treatment." RESULTS: The guidelines were based on the latest global research progress and were evidence-based. The classification of syncope etiology, diagnostic procedures, postural tests, such as the active standing test, head-up tilt test, and active sitting test, clinical diagnosis, and individualized treatment for neurally mediated syncope in pediatric population were included. CONCLUSIONS: The guidelines were updated based on the latest literature. The concepts of sitting tachycardia syndrome and sitting hypertension were introduced and the comorbidities of neurally mediated syncope were emphasized. Some biomarkers used for individualized treatment were underlined. Specific suggestions were put forward for non-pharmacological therapies as well as the follow-up process. The new guidelines will provide comprehensive guidance and reference for the diagnosis and treatment of neurally mediated syncope in children and adolescents.

Study on the effect of conditioner on NOx precursor control behavior from sewage sludge pyrolysis: Focusing on conditioner assessments and in-situ fixation mechanism.

The nitrogen transformation during sludge pyrolysis is affected by the dewater conditioner. However, the comparative analysis of the conditioner under identical pyrolysis conditions has been previously absent. In this study, Ca-, Fe- and Al-based conditioners were selected as the representatives. A comprehensive evaluation considering the cost of the conditioners and the product characteristics was conducted. Additionally, the in-situ fixation mechanism of the conditioner on nitrogen-containing gas was concurrently revealed. Among the six conditioners, CaO and AlCl3 were identified as the top performers, ranking first and second, respectively. Furthermore, Fe/Ca-based conditioners reduced NH3 and HCN release by 1.5 âˆ¼ 5.53 % and 0 âˆ¼ 1.55 %, respectively, by facilitating the conversion of amine-N to a more stable form in condensable fraction. Fe promoted volatile amine-N cyclization, while Ca encouraged its dehydrogenation. Both Fe/Ca-based conditioners increased 7.5 âˆ¼ 14.8 % nitrogen retention in char, by inhibiting the decomposition of protein-N. Al-based conditioners had little effect on NH3 and HCN, but contributed to 2.3 âˆ¼ 2.8 % production of stabilized nitrogen in char. The introduction of Cl in Fe/Ca/Al chloride conditioners would promote the decomposition of inorganic ammonium salts to produce NH3 at 30 âˆ¼ 185 °C. And Cl also reacted with volatiles through electrophilic substitution reaction, leading to the formation of halogenated hydrocarbons in condensable fraction and the release of more NH3, HCN, and HNCO at 30 âˆ¼ 465 °C. The findings of this study provide a detailed comparative analysis of various conditioners under uniform conditions and reveal the in-situ fixation mechanism of nitrogen-containing gas. This will provide guidance for the sludge conditioning-dewatering-drying integrated treatment and disposal.

Dual-Vacancy-Engineered ZnIn2S4 Nanosheets for Harnessing Low-Frequency Vibration Induced Piezoelectric Polarization Coupled with Static Dipole Field to Enhance Photocatalytic H2 Evolution.

This study investigates the impact of In- and S-vacancy concentrations on the photocatalytic activity of non-centrosymmetric zinc indium sulfide (ZIS) nanosheets for the hydrogen evolution reaction (HER). A positive correlation between the concentrations of dual In and S vacancies and the photocatalytic HER rate over ZIS nanosheets is observed. The piezoelectric polarization, stimulated by low-frequency vortex vibration to ensure the well-dispersion of ZIS nanosheets in solution, plays a crucial role in enhancing photocatalytic HER over the dual-vacancy engineered ZIS nanosheets. The piezoelectric characteristic of the defective ZIS nanosheets is confirmed through the piezopotential response measured using piezoelectric force microscopy. Piezophotocatalytic H2 evolution over the ZIS nanosheets is boosted under accelerated vortex vibrations. The research explores how vacancies alter ZIS's dipole moment and piezoelectric properties, thereby increasing electric potential gradient and improving charge-separation efficiency, through multi-scale simulations, including Density Functional Theory and Finite Element Analysis, and a machine-learning interatomic potential for defect identification. Increased In and S vacancies lead to higher electric potential gradients in ZIS along [100] and [010] directions, attributing to dipole moment and the piezoelectric effect. This research provides a comprehensive exploration of vacancy engineering in ZIS nanosheets, leveraging the piezopotential and dipole field to enhance photocatalytic performances.

The Natural History of Crohn's Disease Leading to Intestinal Failure: A Longitudinal Cohort Study from 1973 to 2018.

BACKGROUND AND AIMS: The natural history of Crohn's disease leading to intestinal failure is not well characterised. This study aims to describe the clinical course of Crohn's disease preceding intestinal failure and compare disease course and burden between Crohn's disease patients with and without intestinal failure. METHODS: Patients with Crohn's disease complicated by intestinal failure from Rigshospitalet, Copenhagen (n=182) and a nationwide Danish Crohn's disease cohort without intestinal failure (n=22,845) were included. Using nationwide registries in Denmark, disease course was determined from hospitalisations, surgeries and outpatient medications, and disease burden was determined from employment and mortality data. RESULTS: The 10-year cumulative incidence of intestinal failure following Crohn's disease diagnosis declined from 2.7% prior to 1980 to 0.2% after 2000. Compared to Crohn's disease patients without intestinal failure, those with intestinal failure experienced significantly longer duration of severe disease (50 vs. 19 years per 100 patient-years, p<0.01), secondary to greater corticosteroid use (71% vs. 60%, p=0.02), inpatient contacts (98% vs. 55%, p<0.01), and abdominal surgeries (99% vs. 48%, p<0.01). However, exposure to biologics was not different between the two groups (20.4% vs. 21%, p=0.95), and duration on biologics was shorter in Crohn's disease patients with intestinal failure (2,068 vs. 4,126 days per 100 patient-years, p=0.02). Standard mortality ratio in Crohn's disease patients with intestinal failure was 3.66 [97.5% CI 2.79,4.72]. CONCLUSION: Patients with Crohn's disease complicated by intestinal failure experienced a more persistently severe preceding course of Crohn's disease but were not more likely to be treated with biological therapy.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Synergistic Catalytic Effects on Nitrogen Transformation during Biomass Pyrolysis: A Focus on Proline as a Model Compound.

To investigate the control mechanisms of NOx precursors and the synergistic effects of composite catalysts during proline pyrolysis, a systematic series of experiments was conducted utilizing composite catalysts with varying Fe-Ca ratios. Product distribution analysis was employed to elucidate the catalysts' mechanisms in reducing NOx precursor emissions. The synergistic interactions between Fe and Ca were quantitatively assessed through comparative theoretical and experimental release calculations. The results indicate that an increase in the Fe content in the catalyst led to a rise in amine concentrations from 0.9% to 2.95%, implying that Fe facilitates the generation of amine-N through ring-opening and substitution reactions. When the Fe to Ca ratio was balanced at 1:1, nitrogen predominantly participated in the formation of purines via cyclization and substitution reactions. Additionally, all composite catalysts exhibited a suppressive effect on the release of NOx precursors, attributed to their significant enhancement of solid product retention. Fe-Ca composite catalyst synergistically inhibits the release of gaseous nitrogen. Notably, the strongest synergistic effect was observed with a 1:3 Fe to Ca ratio, which reduced the release of NH3 by 38.7% and HCN by 53.6% during proline pyrolysis. This study offers valuable insights into the control of NOx precursors and the optimization of nitrogen-rich biomass pyrolysis processes.

Two-Dimensional Metal-Organic Frameworks/Epoxy Composite Coatings with Superior O2/H2O Resistance for Anticorrosion Applications.

Corrosion protection technology plays a crucial role in preserving infrastructure, ensuring safety and reliability, and promoting long-term sustainability. In this study, we combined experiments and various analyses to investigate the mechanism of corrosion occurring on the epoxy-based anticorrosive coating containing the additive of two-dimensional (2D) and water-stable zirconium-based metal-organic frameworks (Zr-MOFs). By using benzoic acid as the modulator for the growth of the MOF, a 2D MOF constructed from hexazirconium clusters and BTB linkers (BTB = 1,3,5-tri(4-carboxyphenyl)benzene) with coordinated benzoate (BA-ZrBTB) can be synthesized. By coating the BA-ZrBTB/epoxy composite film (BA-ZrBTB/EP) on the surface of cold-rolled steel (CRS), we found the lowest coating roughness (RMS) of BA-ZrBTB/EP is 2.83 nm with the highest water contact angle as 99.8°, which represents the hydrophobic coating surface. Notably, the corrosion rate of the BA-ZrBTB/EP coating is 2.28 × 10-3 mpy, which is 4 orders of magnitude lower than that of the CRS substrate. Moreover, the energy barrier for oxygen diffusion through BA-ZrBTB/EP coating is larger than that for epoxy coating (EP), indicating improved oxygen resistance for adding 2D Zr-MOFs as the additive. These results underscore the high efficiency and potential of BA-ZrBTB as a highly promising agent for corrosion prevention in various commercial applications. Furthermore, this study represents the first instance of applying 2D Zr-MOF materials in anticorrosion applications, opening up new possibilities for advanced corrosion-resistant coatings.

Attention mechanism-enhanced graph convolutional neural network for unbalanced lithology identification.

In this study, we propose a novel method for identifying lithology using an attention mechanism-enhanced graph convolutional neural network (AGCN). The aim of this method is to address the limitations of traditional approaches that evaluate unbalanced lithology by improving the identification of thin layers and small samples, while providing reliable data support for reservoir evaluation. To achieve this goal, we begin by using Principal Component Analysis (PCA) with maximum and minimum distance clustering (Max-min-distance) to correct the logging curves, which compensates for the low resolution of thin layers and enhances the accuracy of stratigraphic representation. Subsequently, we transform the logging data into graph-structured data by connecting distance similarity points and feature similarity points of the logging samples. We then use the graph convolutional network (GCN) to identify lithology, leveraging both labeled and unlabeled data to enhance the ability to identify lithology in small sample datasets. Additionally, our model incorporates a channel and spatial attention mechanism that assigns weights to the graph structure during lithology identification, improving the model's capability to discern differences across samples. To evaluate the performance of our model, we constructed a lithology dataset comprising five wells and conducted experiments. The results indicate that our approach achieves a maximum accuracy of 97.67%, surpassing the performance of a singlestructure model in lithology identification. In conclusion, our proposed method provides a promising and effective approach for unbalanced lithology identification, significantly improving accuracy levels.

RNA-binding protein AZGP1 inhibits epithelial cell proliferation by regulating the genes of alternative splicing in COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity, disability, and mortality rates worldwide. RNA-binding proteins (RBPs) might regulate genes involved in oxidative stress and inflammation in COPD patients. Single-cell transcriptome sequencing (scRNA-seq) offers an accurate tool for identifying intercellular heterogeneity and the diversity of immune cells. However, the role of RBPs in the regulation of various cells, especially AT2 cells, remains elusive. MATERIALS AND METHODS: A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out. RESULTS: RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD. CONCLUSION: RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.

Sensitivity analysis of RT-qPCR and RT-ddPCR for SARS-CoV-2 detection with mutations on N1 and E primer-probe region.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that undergoes rapid mutation. Based on viral whole genome sequencing analysis in Hebei Province, China, we identified several essential single nucleotide variants (SNVs) on primer-probe regions accumulating within some Omicron variants' genomes. In this study, we focused on three SNVs, C28290T, T28297C, and C28311T emerging on 2019-nCoV-N1 (CDC-N1) primer-probe regions, recommended by CDC in 2020, and two SNVs, C26270T, A26275G emerging on E (Charité-E) primer-probe regions recommended by Charité, Germany. Our findings revealed that the presence of one or two SNVs in the primer or probe region affected the sensitivity of reverse transcription-quantitative polymerase chain reaction and droplet digital PCR to varying extents. This discovery underscores the importance of continuously monitoring the whole genome sequences of SARS-CoV-2 variants, especially the primer-probe targeting regions, and correspondingly updating commercial test kits or recommended primer-probe sequence sets. IMPORTANCE: The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has resulted in a growing number of mutations in its genome, presenting new challenges for the diagnosis of SARS-CoV-2 using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and droplet digital PCR (RT-ddPCR) methods. There is an urgent need to develop refined methods for modifying primers and probes to improve the detection of these emerging variants. In this study, our focus was on the SNVs that have emerged in the CDC-N1 and Charité-E primer-probe regions. Our research has confirmed that the presence of these SNVs in the primer or probe region can significantly affect the results of coronavirus disease 2019 tests. we have developed and validated a modified detection method that can provide higher sensitivity and specificity. This study emphasizes the importance of refining the primer-probe sets to ensure the diagnostic accuracy of RT-qPCR and RT-ddPCR detection.

Comparison of trait and state mind wandering among schizotypal, subclinically depressed, and control individuals.

BACKGROUND: Mind wandering is a common phenomenon in daily life. However, the manifestations and cognitive correlates of mind wandering in different subclinical populations remain unclear. In this study, these aspects were examined in individuals with schizotypal traits and individuals with depressive symptoms, i.e., subclinical populations of patients with schizophrenia and depression. METHODS: Forty-two individuals with schizotypal traits, 42 individuals with subclinical depression, and 42 controls were recruited to complete a mind wandering thought sampling task (state level) and a mind wandering questionnaire (trait level). Measures of rumination and cognitive functions (attention, inhibition, and working memory) were also completed by participants. RESULTS: Both subclinical groups exhibited more state and trait mind wandering than did the control group. Furthermore, individuals with schizotypal traits demonstrated more trait mind wandering than individuals with subclinical depression. Rumination, sustained attention, and working memory were associated with mind wandering. In addition, mind wandering in individuals with subclinical depression can be accounted for by rumination or attention, while mind wandering in individuals with high schizotypal traits cannot be accounted for by rumination, attention, or working memory. CONCLUSIONS: The results suggest that individuals with high schizotypal traits and subclinical depression have different patterns of mind wandering and mechanisms. These findings have implications for understanding the unique profile of mind wandering in subclinical individuals.

Social risk to infant: The role of kin for maternal visual monitoring in Tibetan macaques.

Maternal monitoring of conspecifics is a crucial anti-predator strategy that also protects infants against risks within the social group. This study examines how maternal characteristics, infant characteristics, mother-infant distance, and the social environment affect maternal monitoring behaviors in free-ranging Tibetan macaques (Macaca thibetana). We observed 12 females with infants and analyzed their visual monitoring patterns. Our findings indicate that maternal rank significantly influences the time allocated to maternal visual monitoring, higher-ranking mothers spending less time than lower-ranking mothers. Maternal experience also played a role in monitoring strategies. Differences in monitoring strategies were observed based on maternal experience: first-time mothers (primiparity) engaged in longer but less frequent monitoring sessions compared to experienced mothers (multiparity). The time and frequency of maternal monitoring decreased as infants aged, and mothers with male infants showed higher levels of monitoring than those with female infants. The distance between mother and infant also affected visual monitoring behavior, with mothers increasing their monitoring levels when infants were nearby (1-5 m), rather than within reach (0-1 m) or beyond nearby (>5 m). Additionally, the presence of kin and non-kin influenced monitoring: as the number of nearby kin increased, monitoring levels decreased, while the presence of more non-kin males led to an increase in monitoring time, and higher-ranking non-kin neighbors increased the frequency of monitoring. These results suggest that Tibetan macaque mothers can adapt their visual monitoring to the social risks faced by their infants, adjusting their strategies to their status and the needs of their offspring.

Impaired interferon response in senecavirus A infection and identification of 3Cpro as an antagonist.

Senecavirus A (SVA), a picornavirus, causes vesicular diseases and epidemic transient neonatal losses in swine, resulting in a multifaceted economic impact on the swine industry. SVA counteracts host antiviral response through multiple strategies facilitatng viral infection and transmission. However, the mechanism of how SVA modulates interferon (IFN) response remains elusive. Here, we demonstrate that SVA 3C protease (3Cpro) blocks the transduction of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway to antagonize type I IFN response. Mechanistically, 3Cpro selectively cleaves and degrades STAT1 and STAT2 while does not target JAK1, JAK2, and IRF9, through its protease activity. Notably, SVA 3Cpro cleaves human and porcine STAT1 on a Leucine (L)-Aspartic acid (D) motif, specifically L693/D694. In the case of STAT2, two cleavage sites were identified: glutamine (Q) 707 was identified in both human and porcine, while the second cleavage pattern differed, with residues 754-757 (Valine-Leucine-Glutamine-Serine motifs) in human STAT2 and Q758 in porcine STAT2. These cleavage patterns by SVA 3Cpro partially differ from previously reported classical motifs recognized by other picornaviral 3Cpro, highlighting the distinct characteristics of SVA 3Cpro. Together, these results reveal a mechanism by which SVA 3Cpro antagonizes IFN-induced antiviral response but also expands our knowledge about the substrate recognition patterns for picornaviral 3Cpro.IMPORTANCESenecavirus A (SVA), the only member in the Senecavirus genus within the Picornaviridae family, causes vesicular diseases in pigs that are clinically indistinguishable from foot-and-mouth disease (FMD), a highly contagious viral disease listed by the World Organization for Animal Health (WOAH). Interferon (IFN)-mediated antiviral response plays a pivotal role in restricting and controlling viral infection. Picornaviruses evolved numerous strategies to antagonize host antiviral response. However, how SVA modulates the JAK-STAT signaling pathway, influencing the type I IFN response, remains elusive. Here, we identify that 3Cpro, a protease of SVA, functions as an antagonist for the IFN response. 3Cpro utilizes its protease activity to cleave STAT1 and STAT2, thereby diminishing the host IFN response to promote SVA infection. Our findings underscore the significance of 3Cpro as a key virulence factor in the antagonism of the type I signaling pathway during SVA infection.

Unraveling the role of C1GALT1 in abnormal glycosylation and colorectal cancer progression.

C1GALT1 plays a pivotal role in colorectal cancer (CRC) development and progression through its involvement in various molecular mechanisms. This enzyme is central to the O-glycosylation process, producing tumor-associated carbohydrate antigens (TACA) like Tn and sTn, which are linked to cancer metastasis and poor prognosis. The interaction between C1GALT1 and core 3 synthase is crucial for the synthesis of core 3 O-glycans, essential for gastrointestinal health and mucosal barrier integrity. Aberrations in this pathway can lead to CRC development. Furthermore, C1GALT1's function is significantly influenced by its molecular chaperone, Cosmc, which is necessary for the proper folding of T-synthase. Dysregulation in this complex interaction contributes to abnormal O-glycan regulation, facilitating cancer progression. Moreover, C1GALT1 affects downstream signaling pathways and cellular behaviors, such as the epithelial-mesenchymal transition (EMT), by modifying O-glycans on key receptors like FGFR2, enhancing cancer cell invasiveness and metastatic potential. Additionally, the enzyme's relationship with MUC1, a mucin protein with abnormal glycosylation in CRC, highlights its role in cancer cell immune evasion and metastasis. Given these insights, targeting C1GALT1 presents a promising therapeutic strategy for CRC, necessitating further research to develop targeted inhibitors or activators. Future efforts should also explore C1GALT1's potential as a biomarker for early diagnosis, prognosis, and treatment response monitoring in CRC, alongside investigating combination therapies to improve patient outcomes.

Controllable Fabrication of Hydrophilic Surface Micro/Nanostructures of CFRP by Femtosecond Laser.

Carbon fiber reinforced polymer (CFRP), a highly engineered lightweight material with superior properties, is widely used in industrial fields, such as aerospace, automobile, and railway transportation, as well as medical implants and supercapacitor. This work presents an effective surface treatment method for the controllable fabrication of hydrophilic surface micro/nanostructures of CFRP through femtosecond laser processing. Selective removal of the epoxy resin and leaving the carbon fibers exposed are achieved when CFRP is weakly ablated by a femtosecond laser. The diameters and structures of the carbon fibers can be controlled by adjusting the laser processing parameters. Three-dimensional surface micro/nanostructures are processed when CFRP is strongly ablated by a femtosecond laser. Meanwhile, the transformation of the sp2 orbitals to sp3 orbitals of graphitic carbons of carbon fibers is induced by a femtosecond laser. Moreover, the investigation of surface roughness and wettability of femtosecond laser-processed CFRP indicates increased roughness and excellent hydrophilicity (a contact angle of 28.1°). This work reveals the effect of femtosecond laser processing on the regulation of the physicochemical properties of CFRP, which can be applicable to surface treatment and performance control of other fiber-resin composites. The excellent hydrophilicity will be conducive to the combination of CFRP with other materials or to reducing the friction resistance of CFRP used in medical implants.

Characteristic Analysis and Risk Control of Syngas Explosion during Underground Coal Gasification.

Gas explosion is one of the main accident risks during underground coal gasification (UCG). There are significant differences in the gas composition and explosive environment between UCG syngas and other gases. Previous research on the explosion characteristics of UCG syngas is not comprehensive enough, especially without considering the influence of the initial temperature on various characteristic parameters. A set of calculation methods for explosion characteristic parameters of UCG syngas based on existing research was proposed, which was applied to analyze explosion characteristics of syngas produced by different gasifying processes in the Huating UCG industrial test. The results showed that with the initial temperature improving, the maximum temperature and upper explosion limit of different gases increased, while the maximum pressure, lower explosion limit, and oxygen content safety limit decreased. However, the explosion thermal effect, pressure rise rate, and explosion characteristic values showed small changes. When the initial temperature increased from 298 to 1473 K, the explosion temperature of different gas explosions increased from 1645-2286 to 2652-3238 K, the maximum pressure dropped from 0.59-0.81 MPa (absolute pressure) to 0.19-0.23 MPa, the lower explosion limit dropped from 12.34-29.79% to 0.58-1.77%, the upper explosion limit increased from 55.68-83.35% to 70.89-93.73%, and the safety limit of oxygen content dropped from 4.86-6.37% to 0.26-0.34%. In addition, the gas calorific value also affected the values of various explosion characteristic parameters, among which the explosive thermal effect, maximum temperature, maximum pressure, pressure rise rate, explosion characteristic value, and safety limit of oxygen content in the syngas were all proportional to the calorific value of gas, while the lower and upper limits of explosion were inversely proportional to it. Based on the above research, syngas explosion-prone stages and causes of each potential risk area in the Huating UCG project were analyzed, the explosion characteristic parameters were determined, and targeted prevention and control measures were proposed accordingly. This study can lay a theoretical foundation for the study of syngas explosion characteristics and risk control for the UCG project.

Epitope mapping and establishment of a blocking ELISA for mAb targeting the p72 protein of African swine fever virus.

The African swine fever virus (ASFV) has the ability to infect pigs and cause a highly contagious acute fever that can result in a mortality rate as high as 100%. Due to the viral epidemic, the pig industry worldwide has suffered significant financial setbacks. The absence of a proven vaccine for ASFV necessitates the development of a sensitive and reliable serological diagnostic method, enabling laboratories to effectively and expeditiously detect ASFV infection. In this study, four strains of monoclonal antibodies (mAbs) against p72, namely, 5A1, 4C4, 8A9, and 5E10, were generated through recombinant expression of p72, the main capsid protein of ASFV, and immunized mice with it. Epitope localization was performed by truncated overlapping polypeptides. The results indicate that 5A1 and 4C4 recognized the amino acid 20-39 aa, 8A9 and 5E10 are recognized at 263-282 aa, which is consistent with the reported 265-280 aa epitopes. Conserved analysis revealed 20-39 aa is a high conservation of the epitopes in the ASFV genotypes. Moreover, a blocking ELISA assay for detection ASFV antibody based on 4C4 monoclonal antibody was developed and assessed. The receiver-operating characteristic (ROC) was performed to identify the best threshold value using 87 negative and 67 positive samples. The established test exhibited an area under the curve (AUC) of 0.9997, with a 95% confidence interval ranging from 99.87 to 100%. Furthermore, the test achieved a diagnostic sensitivity of 100% (with a 95% confidence interval of 95.72 to 100%) and a specificity of 98.51% (with a 95% confidence interval of 92.02 to 99.92%) when the threshold was set at 41.97%. The inter- and intra-batch coefficient of variation were below 10%, demonstrating the exceptional repeatability of the method. This method can detect the positive standard serum at a dilution as high as 1:512. Subsequently, an exceptional blocking ELISA assay was established with high diagnostic sensitivity and specificity, providing a novel tool for detecting ASFV antibodies. KEY POINTS: • Four strains of ASFV monoclonal antibodies against p72 were prepared and their epitopes were identified. • Blocking ELISA method was established based on monoclonal antibody 4C4 with an identified conservative epitope. • The established blocking ELISA method has a good effect on the detection of ASFV antibody.

A recombinant IL-1ß vaccine attenuates bleomycin-induced pulmonary fibrosis in mice.

Interleukin-1ß (IL-1ß) contributes to interstitial lung disease (ILD) and pulmonary fibrosis (PF), thus representing a potential therapeutic target for PF. In this study, we first verified the increased expression of IL-1ß in human fibrotic lung specimens and mouse lung tissues after intratracheal (i.t.) instillation of bleomycin (BLM), after which the pro-inflammatory and pro-fibrotic effects of recombinant IL-1ß were tested in mice. The results above suggested that vaccination against IL-1ß could be an effective strategy for managing PF. An anti-IL-1ß vaccine (PfTrx-IL-1ß) was designed by incorporating two IL-1ß-derived polypeptides, which have been verified as the key domains that mediate the binding of IL-1ß to its type I receptor, into Pyrococcus furiosus thioredoxin (PfTrx). The fusion protein PfTrx-IL-1ß was prepared by using E. coli expression system. The vaccine was well tolerated; it induced robust and long-lasting antibody responses in mice and neutralized the biological activity of IL-1ß, as shown in cellular assays. Pre-immunization with PfTrx-IL-1ß effectively protected mice from BLM-induced lung injury, inflammation, and fibrosis. In vitro experiments further showed that anti-PfTrx-IL-1ß antibodies counteracted the effects of IL-1ß concerning pro-inflammatory and pro-fibrotic cytokine production by primary mouse lung fibroblast, macrophages (RAW264.7), and type II alveolar epithelial cell (A549), primary mouse lung fibroblast activation and epithelial-mesenchymal transition (EMT) of alveolar epithelial cells. In addition, the vaccination did not compromise the anti-infection immunity in mice, as validated by a sepsis model. Our preliminary study suggests that the anti-IL-1ß vaccine we prepared has the potential to be developed as a therapeutic measure for PF. Further experiments are warranted to evaluate whether IL-1ß vaccination has the capacity of inhibiting chronic progressive PF and reversing established PF.

[Prokaryotic expression of N protein of akabane disease virus and preparation of monoclonal antibody].

In order to generate monoclonal antibodies against the akabane virus (AKAV) N protein, this study employed a prokaryotic expression system to express the AKAV N protein. Following purification, BALB/c mice were immunized, and their splenocytes were fused with mouse myeloma cells (SP2/0) to produce hybridoma cells. The indirect ELISA method was used to screen for positive hybridoma cells. Two specific hybridoma cell lines targeting AKAV N protein, designated as 2C9 and 5E9, were isolated after three rounds of subcloning. Further characterization was conducted through ELISA, Western blotting, and indirect immunofluorescence assay (IFA). The results confirmed that the monoclonal antibodies specifically target AKAV N protein, exhibiting strong reactivity in IFA. Subtype analysis identified the heavy chain of the 2C9 mAb's as IgG2b and its light chain as κ-type; the 5E9 mAb's heavy chain was determined to be IgG1, with a κ-type light chain. Their ELISA titers reached 1:4 096 000. This study successfully developed two monoclonal antibodies targeting AKAV N protein, which lays a crucial foundation for advancing diagnostic methods for akabane disease prevention and control, as well as for studying the function of the AKAV N protein.