Purple Light-Promoted Coupling of Bromopyridines with Grignard Reagents via SET.

Alkyl- and arylpyridines and 2,2'-bipyridines are conventionally prepared by Minisci reactions of pyridines and transition metal-catalyzed coupling reactions of halopyridines. Herein, purple light-promoted radical coupling reactions of 2- or 4-bromopyridines with Grignard reagents in Et2O or a mixture of Et2O and tetrahydrofuran in regular glassware without the need for a transition metal catalyst were disclosed for the first time. Methyl, primary and secondary alkyl, cycloalkyl, aryl, heteroaryl, pyridyl, and alkynyl Grignard reagents were compatible with the protocol. As a result, alkyl- and arylpyridines and 2,2'-bipyridines were easily prepared. Single electron transfer from the Grignard reagent to bromopyridine was stimulated by purple light. An electron extruded from the dimerization of the Grignard reagent worked as the catalyst. Light on/off experiments indicated that constant irradiation was required for product formation. Studies of radical clock substrates verified the involvement of a pyridyl radical from bromopyridine and the noninvolvement of an alkyl or aryl radical from the Grignard reagent. The available proof supports a photoinduced SRN mechanism for the new coupling reactions.

Exploiting Ca2+ signaling in T cells to advance cancer immunotherapy.

Decades of basic research has established the importance of Ca2+ to various T cell functions, such as cytotoxicity, proliferation, differentiation and cytokine secretion. We now have a good understanding of how proximal TCR signaling initiates Ca2+ influx and how this influx subsequently changes transcriptional activities in T cells. As chimeric antigen receptor (CAR)-T therapy has achieved great clinical success, is it possible to harness Ca2+ signaling to further advance CAR-T research? How is CAR signaling different from TCR signaling? How can functional CARs be identified in a high-throughput way? Quantification of various Ca2+ signals downstream of CAR/TCR activation might help answer these questions. Here we first summarized recent studies that used Ca2+ dye, genetically-encoded Ca2+ indicators (GECI) or transcriptional activity reporters to understand CAR activation in vitro and in vivo. We next reviewed several proof-of-concept reports that manipulate Ca2+ signaling by light or ultrasound to achieve precise spatiotemporal control of T cell functions. These efforts, though preliminary, opened up new avenues to solve the on-target/off-tumor problem of therapeutic T cells. Other modalities to regulate Ca2+ signaling, such as radio wave and electrical pulse, were also discussed. Thus, monitoring or manipulating Ca2+ signaling in T cells provides us many opportunities to advance cancer immunotherapy.

The Overexpression of Zea mays Strigolactone Receptor Gene D14 Enhances Drought Resistance in Arabidopsis thaliana L.

Strigolactones (SLs) represent a recently identified class of plant hormones that are crucial for plant tillering and mycorrhizal symbiosis. The D14 gene, an essential receptor within the SLs signaling pathway, has been well-examined in crops, like rice (Oryza sativa L.) and Arabidopsis (Arabidopsis thaliana L.), yet the research on its influence in maize (Zea mays L.) remains scarce. This study successfully clones and establishes Arabidopsis D14 gene overexpression lines (OE lines). When compared with the wild type (WT), the OE lines exhibited significantly longer primary roots during germination. By seven weeks of age, these lines showed reductions in plant height and tillering, alongside slight decreases in rosette and leaf sizes, coupled with early aging symptoms. Fluorescence-based quantitative assays indicated notable hormonal fluctuations in OE lines versus the WT, implying that D14 overexpression disrupts plant hormonal homeostasis. The OE lines, exposed to cold, drought, and sodium chloride stressors during germination, displayed an especially pronounced resistance to drought. The drought resistance of OE lines, as evident from dehydration-rehydration assays, outmatched that of the WT lines. Additionally, under drought conditions, the OE lines accumulated less reactive oxygen species (ROS) as revealed by the assessment of the related physiological and biochemical parameters. Upon confronting the pathogens Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), post-infection, fluorescence quantitative investigations showed a significant boost in the salicylic acid (SA)-related gene expression in OE lines compared to their WT counterparts. Overall, our findings designate the SL receptor D14 as a key upregulator of drought tolerance and a regulator in the biotic stress response, thereby advancing our understanding of the maize SL signaling pathway by elucidating the function of the pivotal D14 gene.

[Establishment and Validation of a Predictive Model for Gallstone Disease in the General Population: A Multicenter Study]. / èƒ†ç»“çŸ³æ‚£ç— é£Žé™©é¢„æµ‹æ¨¡åž‹çš„æž„å»ºå’Œå¤šä¸­å¿ƒéªŒè¯ç ”ç©¶.

Objective: Gallstone disease (GSD) is one of the common digestive tract diseases with a high worldwide prevalence. The effects of GSD on patients include but are not limited to the symptoms of nausea, vomiting, and biliary colic directly caused by GSD. In addition, there is mounting evidence from cohort studies connecting GSD to other conditions, such as cardiovascular diseases, biliary tract cancer, and colorectal cancer. Early identification of patients at a high risk of GSD may help improve the prevention and control of the disease. A series of studies have attempted to establish prediction models for GSD, but these models could not be fully applied in the general population due to incomplete prediction factors, small sample sizes, and limitations in external validation. It is crucial to design a universally applicable GSD risk prediction model for the general population and to take individualized intervention measures to prevent the occurrence of GSD. This study aims to conduct a multicenter investigation involving more than 90000 people to construct and validate a complete and simplified GSD risk prediction model. Methods: A total of 123634 participants were included in the study between January 2015 and December 2020, of whom 43929 were from the First Affiliated Hospital of Chongqing Medical University (Chongqing, China), 11907 were from the First People's Hospital of Jining City (Shandong, China), 1538 were from the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China), and 66260 were from the People's Hospital of Kaizhou District (Chongqing, China). After excluding patients with incomplete clinical medical data, 35976 patients from the First Affiliated Hospital of Chongqing Medical University were divided into a training data set (n=28781, 80%) and a validation data set (n=7195, 20%). Logistic regression analyses were performed to investigate the relevant risk factors of GSD, and a complete risk prediction model was constructed. Factors with high scores, mainly according to the nomograms of the complete model, were retained to simplify the model. In the validation data set, the diagnostic accuracy and clinical performance of these models were validated using the calibration curve, area under the curve (AUC) of the receiver operating characteristic curve, and decision curve analysis (DCA). Moreover, the diagnostic accuracy of these two models was validated in three other hospitals. Finally, we established an online website for using the prediction model (The complete model is accessible at https://wenqianyu.shinyapps.io/Completemodel/, while the simplified model is accessible at https://wenqianyu.shinyapps.io/Simplified/). Results: After excluding patients with incomplete clinical medical data, a total of 96426 participants were finally included in this study (35876 from the First Affiliated Hospital of the Chongqing Medical University, 9289 from the First People's Hospital of Jining City, 1522 from the Tianjin Medical University Cancer Institute, and 49639 from the People's Hospital of Kaizhou District). Female sex, advanced age, higher body mass index, fasting plasma glucose, uric acid, total bilirubin, gamma-glutamyl transpeptidase, and fatty liver disease were positively associated with risks for GSD. Furthermore, gallbladder polyps, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and aspartate aminotransferase were negatively correlated to risks for GSD. According to the nomograms of the complete model, a simplified model including sex, age, body mass index, gallbladder polyps, and fatty liver disease was constructed. All the calibration curves exhibited good consistency between the predicted and observed probabilities. In addition, DCA indicated that both the complete model and the simplified model showed better net benefits than treat-all and treat-none. Based on the calibration plots, DCA, and AUCs of the complete model (AUC in the internal validation data set=74.1% [95% CI: 72.9%-75.3%], AUC in Shandong=71.7% [95% CI: 70.6%-72.8%], AUC in Tianjin=75.3% [95% CI: 72.7%-77.9%], and AUC in Kaizhou=72.9% [95% CI: 72.5%-73.3%]) and the simplified model (AUC in the internal validation data set=73.7% [95% CI: 72.5%-75.0%], AUC in Shandong=71.5% [95% CI: 70.4%-72.5%], AUC in Tianjin=75.4% [95% CI: 72.9%-78.0%], and AUC in Kaizhou=72.4% [95% CI: 72.0%-72.8%]), we concluded that the complete and simplified risk prediction models for GSD exhibited excellent performance. Moreover, we detected no significant differences between the performance of the two models (P>0.05). We also established two online websites based on the results of this study for GSD risk prediction. Conclusions: This study innovatively used the data from 96426 patients from four hospitals to establish a GSD risk prediction model and to perform risk prediction analyses of internal and external validation data sets in four cohorts. A simplified model of GSD risk prediction, which included the variables of sex, age, body mass index, gallbladder polyps, and fatty liver disease, also exhibited good discrimination and clinical performance. Nonetheless, further studies are needed to explore the role of low-density lipoprotein cholesterol and aspartate aminotransferase in gallstone formation. Although the validation results of the complete model were better than those of the simplified model to a certain extent, the difference was not significant even in large samples. Compared with the complete model, the simplified model uses fewer variables and yields similar prediction and clinical impact. Hence, we recommend the application of the simplified model to improve the efficiency of screening high-risk groups in practice. The use of the simplified model is conducive to enhancing the self-awareness of prevention and control in the general population and early intervention for GSD.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.

Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care. Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed. Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens. Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.

Functional analysis of transgenic cry1Ah-1 maize.

Maize is an important food crop in the world, but the yield and quality of maize have been significantly reduced due to the impact of insect pests. In order to address this issue, the cry1Ah gene was subjected to error-prone PCR for mutagenesis, and subsequently, the mutant cry1Ah-1 gene was introduced into maize inbred line GSH9901 callus using the Agrobacterium-mediated method. The T2 generation transformed plants were obtained by subculture, and 9 transgenic positive plants were obtained by molecular detection which was carried out by PCR, qRT-PCR, Bt gold-labeled immunoassay test strips, Western blot and ELISA. It was found that the Cry1Ah-1 gene could be transcribed normally in maize leaves, of which OE1 and OE3 had higher relative expression levels and could successfully express proteins of 71.94 KD size. They were expressed in different tissues at the 6-leaf stage, heading stage and grain-filling stage, and could ensure the protection of maize from corn borer throughout the growth period. The biological activities of OE1 and OE3 were tested indoors and in the field, and the results showed that in indoors, the corn borer that fed on OE1 and OE3 corn leaves had a mortality rate of 100 % after 3 days; in the field, OE1 and OE3 had strong insecticidal activity against corn borer, reaching a high resistance level. In conclusion, the transgenic cry1Ah-1 maize has a strong insecticidal effect on corn borer, and has a good prospect of commercialization.

gem-Bromonitroalkane Involved Radical 1,2-Aryl Migration of α,α-Diaryl Allyl Alcohol TMS Ether via Visible-Light Photoredox Catalysis.

A mild and efficient coupling method concerning the reactions of gem-bromonitroalkanes with α,α-diaryl allyl alcohol trimethylsilyl ethers was reported. A cascade consisting of visible-light-induced generation of an α-nitroalkyl radical and a subsequent neophyl-type rearrangement was key to realize the coupling reactions. Structurally diverse α-aryl-γ-nitro ketones, especially those bearing a nitrocyclobutyl structure, were prepared in moderate to high yields, which could be converted into spirocyclic nitrones and imines.

Ultrahigh-performance liquid chromatography-high-resolution mass spectrometry-based plasma metabolomics study of thymoma and thymic hyperplasia.

RATIONALE: Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problems, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma. METHODS: Metabolic profiling of plasma from thymoma and thymic hyperplasia patients was performed using ultrahigh-performance liquid chromatography combined with high-resolution mass spectrometry in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental tandem mass spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence. RESULTS: A total of 47 differential metabolites were identified in thymoma. Significantly higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significantly lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG(-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma. CONCLUSIONS: Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma.

Non-Small Cell Lung Cancer Detection and Subtyping by UPLC-HRMS-Based Tissue Metabolomics.

Non-small cell lung cancer (NSCLC) is the prevalent histological subtype of lung cancer. In this study, we performed ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS)-based metabolic profiling of 227 tissue samples from 79 lung cancer patients with adenocarcinoma (AC) or squamous cell carcinoma (SCC). Orthogonal partial least squares-discriminant analysis (oPLS-DA) analyses showed that AC, SCC, and NSCLC tumors were discriminated from adjacent noncancerous tissue (ANT) and distant noncancerous tissue (DNT) samples with good accuracies (91.3, 100, and 88.3%), sensitivities (85.7, 100, and 83.9%), and specificities (94.3, 100, and 90.7%), using 12, 4, and 7 discriminant metabolites, respectively. The discriminant panel for AC detection included valine, sphingosine, glutamic acid γ-methyl ester, and lysophosphatidylcholine (LPC) (16:0), levels of which in tumor tissues were significantly altered. Valine, sphingosine, LPC (18:1), and leucine derivatives were used for SCC detection. The discrimination between AC and SCC had 96.8% accuracy, 98.2% sensitivity, and 85.7% specificity using a five-metabolite panel, of which valine and creatine had significant differences. The classification models were further verified with external validation sets, showing a promising prospect for NSCLC tissue detection and subtyping.

Formation mechanism of blemishes in a fiber-optic imaging element.

A rigid fiber-optic imaging element with high fidelity, high resolution, and high contrast is applied in low-level-light night vision and particle detection devices. Any optical fiber in elements is an image transmission unit. However, the independence and integrity of image transmission are disturbed constantly, resulting in blemishes. This paper studies the formation mechanism of the blemishes of rigid fiber-optic imaging elements. The existence of defects with different sizes in or among the optical fibers, and fiber deformation decreasing light transmission ability are simulated theoretically. Then experiments are carried out to verify the simulation results. It is theoretically concluded that a blemish forms when the equivalent sphere radius (RES) of a stone defect is greater than 1.2 µm in a normal fiber, and 1.1 µm in a taper fiber. The RES of a bubble defect is greater than 1.3 µm in the fiber, which can form blemishes. Excessive deformation of fibers behaving as a clad layer with thickness less than 0.3 µm also results in the formation of blemishes. When fiber deformation and the existence of stone are considered, blemishes can occur as long as the size of the stone defect among the fibers is greater than 0.823 µm. The results provide data support and theoretical guidance in solving blemishes and other fixed pattern noises, and significantly improve the engineering and application level of fiber-optic imaging elements.

Two-Stage Stochastic Optimization for the Pre-Position and Reconfiguration of Microgrid Defense Resources against Natural Disasters.

With the aggravation and evolution of global warming, natural disasters such as hurricanes occur more frequently, posing a great challenge to large-scale power systems. Therefore, the pre-position and reconfiguration of the microgrid defense resources by means of Mobile Energy Storage Vehicles (MEVs) and tie lines in damaged scenarios have attracted more and more attention. This paper proposes a novel two-stage optimization model with the consideration of MEVs and tie lines to minimize the shed loads and the outage duration of loads according to their proportional priorities. In the first stage, tie lines addition and MEVs pre-position are decided prior to a natural disaster; in the second stage, the switches of tie lines and original lines are operated and MEVs are allocated from staging locations to allocation nodes according to the specific damaged scenarios after the natural disaster strikes. The proposed load restoration method exploits the benefits of MEVs and ties lines by microgrid formation to pick up more critical loads. The progressive hedging algorithm is employed to solve the proposed scenario-based two-stage stochastic optimization problem. Finally, the effectiveness and superiority of the proposed model and applied algorithm are validated on an IEEE 33-bus test case.

The Integration of Metabolomics and Transcriptomics Provides New Insights for the Identification of Genes Key to Auxin Synthesis at Different Growth Stages of Maize.

As a staple food crop, maize is widely cultivated worldwide. Sex differentiation and kernel development are regulated by auxin, but the mechanism regulating its synthesis remains unclear. This study explored the influence of the growth stage of maize on the secondary metabolite accumulation and gene expression associated with auxin synthesis. Transcriptomics and metabonomics were used to investigate the changes in secondary metabolite accumulation and gene expression in maize leaves at the jointing, tasseling, and pollen-release stages of plant growth. In total, 1221 differentially accumulated metabolites (DAMs) and 4843 differentially expressed genes (DEGs) were screened. KEGG pathway enrichment analyses of the DEGs and DAMs revealed that plant hormone signal transduction, tryptophan metabolism, and phenylpropanoid biosynthesis were highly enriched. We summarized the key genes and regulatory effects of the tryptophan-dependent auxin biosynthesis pathways, giving new insights into this type of biosynthesis. Potential MSTRG.11063 and MSTRG.35270 and MSTRG.21978 genes in auxin synthesis pathways were obtained. A weighted gene co-expression network analysis identified five candidate genes, namely TSB (Zm00001d046676 and Zm00001d049610), IGS (Zm00001d020008), AUX2 (Zm00001d006283), TAR (Zm00001d039691), and YUC (Zm00001d025005 and Zm00001d008255), which were important in the biosynthesis of both tryptophan and auxin. This study provides new insights for understanding the regulatory mechanism of auxin synthesis in maize.

Overexpression of ZmDHN15 Enhances Cold Tolerance in Yeast and Arabidopsis.

Maize (Zea mays L.) originates from the subtropical region and is a warm-loving crop affected by low-temperature stress. Dehydrin (DHN) protein, a member of the Group 2 LEA (late embryogenesis abundant proteins) family, plays an important role in plant abiotic stress. In this study, five maize DHN genes were screened based on the previous transcriptome sequencing data in our laboratory, and we performed sequence analysis and promoter analysis on these five DHN genes. The results showed that the promoter region has many cis-acting elements related to cold stress. The significantly upregulated ZmDHN15 gene has been further screened by expression pattern analysis. The subcellular localization results show that ZmDHN15 fusion protein is localized in the cytoplasm. To verify the role of ZmDHN15 in cold stress, we overexpressed ZmDHN15 in yeast and Arabidopsis. We found that the expression of ZmDHN15 can significantly improve the cold resistance of yeast. Under cold stress, ZmDHN15-overexpressing Arabidopsis showed lower MDA content, lower relative electrolyte leakage, and less ROS (reactive oxygen species) when compared to wild-type plants, as well as higher seed germination rate, seedling survival rate, and chlorophyll content. Furthermore, analysis of the expression patterns of ROS-associated marker genes and cold-response-related genes indicated that ZmDHN15 genes play an important role in the expression of these genes. In conclusion, the overexpression of the ZmDHN15 gene can effectively improve the tolerance to cold stress in yeast and Arabidopsis. This study is important for maize germplasm innovation and the genetic improvement of crops.

Overexpression of ZmSRG7 Improves Drought and Salt Tolerance in Maize (Zea mays L.).

Osmotic stress caused by drought and high salinity is the key factor limiting plant growth. However, its underlying molecular regulatory mechanism remains unclear. In this study, we found the stress-related gene Zm00001d019704 (ZmSRG7) based on transcriptome sequencing results previously obtained in the laboratory and determined its biological function in maize. We found that ZmSRG7 was significantly expressed in both roots and leaves under 10% PEG6000 or 150 mM NaCl. Subcellular localization showed that the gene was localized in the nucleus. The germination rate and root length of the ZmSRG7 overexpressing lines were significantly increased under drought or salt stress compared with the control. However, after drought stress, the survival rate and relative water content of maize were increased, while the water loss rate was slowed down. Under salt stress, the Na+ concentration and Na+: K+ ratio of maize was increased. In addition, the contents of antioxidant enzymes and proline in maize under drought or salt stress were higher than those in the control, while the contents of MDA, H2O2 and O2- were lower than those in the control. The results showed that the ZmSRG7 gene played its biological function by regulating the ROS signaling pathway. An interaction between ZmSRG7 and the Zmdhn1 protein was found using a yeast two-hybrid experiment. These results suggest that the ZmSRG7 gene can improve maize tolerance to drought or salt by regulating hydrogen peroxide homeostasis.

A Novel Senescence-Specific Gene (ZmSAG39) Negatively Regulates Darkness and Drought Responses in Maize.

The papain-like cysteine proteases (PLCPs) is a subfamily of cysteine proteases that plays an important role in leaf senescence, and some of its members are involved in the regulation of plant growth and development under stress. In this study, we cloned a new gene, ZmSAG39, from maize. Expression profile analysis showed that ZmSAG39 was induced by darkness and drought treatments. In addition, the ZmSAG39 overexpression in maize accelerated the senescence of maize leaves under darkness and drought treatments. However, the knockout of ZmSAG39 in maize enhanced the resistance of maize to darkness and drought stresses and reduced the degree of senescence of maize leaves. Under drought stress, compared with WT plants, the knockout lines had a higher seed germination rate, seedling survival rate and chlorophyll content, and lower reactive oxygen species (ROS) level and malondialdehyde (MDA) content. In addition, quantitative real-time PCR (qRT-PCR) analysis showed that ZmSAG39 negatively regulated some stress-related genes but positively regulated senescence-related genes under darkness and drought stress conditions. To summarize, these results indicate that ZmSAG39 is a senescence-related gene and plays a negative role in response to darkness and drought stresses. This study laid a theoretical foundation for the innovation of maize germplasm resources with high quality, high yield and strong stress resistance.

Crystal Structure of African Swine Fever Virus pS273R Protease and Implications for Inhibitor Design.

African swine fever (ASF) is a highly contagious hemorrhagic viral disease of domestic and wild pigs that is responsible for serious economic and production losses. It is caused by the African swine fever virus (ASFV), a large and complex icosahedral DNA virus of the Asfarviridae family. Currently, there is no effective treatment or approved vaccine against the ASFV. pS273R, a specific SUMO-1 cysteine protease, catalyzes the maturation of the pp220 and pp62 polyprotein precursors into core-shell proteins. Here, we present the crystal structure of the ASFV pS273R protease at a resolution of 2.3 Å. The overall structure of the pS273R protease is represented by two domains named the "core domain" and the N-terminal "arm domain." The "arm domain" contains the residues from M1 to N83, and the "core domain" contains the residues from N84 to A273. A structure analysis reveals that the "core domain" shares a high degree of structural similarity with chlamydial deubiquitinating enzyme, sentrin-specific protease, and adenovirus protease, while the "arm domain" is unique to ASFV. Further, experiments indicated that the "arm domain" plays an important role in maintaining the enzyme activity of ASFV pS273R. Moreover, based on the structural information of pS273R, we designed and synthesized several peptidomimetic aldehyde compounds at a submolar 50% inhibitory concentration, which paves the way for the design of inhibitors to target this severe pathogen.IMPORTANCE African swine fever virus, a large and complex icosahedral DNA virus, causes a deadly infection in domestic pigs. In addition to Africa and Europe, countries in Asia, including China, Vietnam, and Mongolia, were negatively affected by the hazards posed by ASFV outbreaks in 2018 and 2019, at which time more than 30 million pigs were culled. Until now, there has been no vaccine for protection against ASFV infection or effective treatments to cure ASF. Here, we solved the high-resolution crystal structure of the ASFV pS273R protease. The pS273R protease has a two-domain structure that distinguishes it from other members of the SUMO protease family, while the unique "arm domain" has been proven to be essential for its hydrolytic activity. Moreover, the peptidomimetic aldehyde compounds designed to target the substrate binding pocket exert prominent inhibitory effects and can thus be used in a potential lead for anti-ASFV drug development.

Out-of-plane displacement measurement for an optical fiber image transmission element using optical flow.

To realize the industrial in-situ deformation detection of an optical fiber image transmission element, a method for out-of-plane displacement detection based on the combination of optical flow and an image spherizing algorithm is presented. After capturing the 2D deformation images, the out-of-plane displacement can be extracted from the in-plane displacement estimated by the optical flow method, which means that the out-of-plane displacement information contained in a 2D image is fully used. The principle of the Brox optical flow method is introduced and the accuracy of the method is proven by comparing test results with the digital image correlation method. Experimental results show that the relative errors and the absolute errors of the measurement are less than 2% and 0.1 µm. Because the optical flow algorithm introduces a time parameter and the smoothness assumption, the new method is more appropriate for dynamic and microscale out-of-plane displacement measurement. Unlike conventional methods, it does not need phase unwrapping or frequency domain conversion during detection and has many attractive characteristics such as nondestructive testing, a simple arrangement, and low errors. This method has been applied to the industrial in-situ monitoring of an optical fiber image transmission element.

Protective effect of vitamin C and lycopene on the in vitro fertilization capacity of sex-sorted bull sperm by inhibiting the oxidative stress.

The fertilization capacity of sex-sorted sperms is seriously decreased, which inhibits its wide application. However, little information is still available about the effect of vitamin C (VC) and lycopene (Lyc) on the fertilization capacity of sex-sorted bull sperm. In this study, the washing medium and fertilization medium of sex-sorted sperm from three bull individuals were supplemented with different concentrations of VC (0, 1 × 10-3 , 1 × 10-4 , 1 × 10-5 , 1 × 10-6  M) or Lyc (0, 1 × 10-4 , 1 × 10-5 , 1 × 10-6 , 1 × 10-7 ). After washing twice and incubation for 1.5 hr, the malondialdehyde (MDA) level, phosphatidylserine (PS) translocation, membrane potential (Δψm) and IVF (in vitro fertilization) ability of sex-sorted sperm were investigated. For the sex-sorted sperm of bulls A, B and C, 1 × 10-3  M VC or 1 × 10-4  M Lyc treatment significantly decreased their MDA levels and PS translocation and increased their Δψm levels and cleavage rates after IVF. When blastocysts were concerned, 1 × 10-4  M Lyc significantly improved the blastocyst rates and their IFN-tau expression of bulls A and C. In conclusion, supplementation of 1 × 10-3  M VC or 1 × 10-4  M Lyc in washing and fertilization medium contributed greatly to improving the fertilization capacity of sex-sorted bull sperm during IVF procedure.

The Proton Dissociation of Bio-Protic Ionic Liquids: [AAE]X Amino Acid Ionic Liquids.

[AAE]X composed of amino acid ester cations is a sort of typically "bio-based" protic ionic liquids (PILs). They possess potential Brønsted acidity due to the active hydrogens on their cations. The Brønsted acidity of [AAE]X PILs in green solvents (water and ethanol) at room temperature was systematically studied. Various frameworks of amino acid ester cations and four anions were investigated in this work from the viewpoint of structure-property relationship. Four different ways were used to study the acidity. Acid dissociation constants (pKa) of [AAE]X determined by the OIM (overlapping indicator method) were from 7.10 to 7.73 in water and from 8.54 to 9.05 in ethanol. The pKa values determined by the PTM (potential titration method) were from 7.12 to 7.82 in water. Their Hammett acidity function (H0) values (0.05 mol·L-1) were about 4.6 in water. In addition, the pKa values obtained by the DFT (proton-transfer reactions) were from 7.11 to 7.83 in water and from 8.54 to 9.34 in ethanol, respectively. The data revealed that the cationic structures of [AAE]X had little effect and the anions had no effect on the acidity of [AAE]X. At the same time, the OIM, PTM, Hammett method and DFT method were reliable for determining the acidic strength of [AAE]X in this study.