MUSCLE: multi-view and multi-scale attentional feature fusion for microRNA-disease associations prediction.

MicroRNAs (miRNAs) synergize with various biomolecules in human cells resulting in diverse functions in regulating a wide range of biological processes. Predicting potential disease-associated miRNAs as valuable biomarkers contributes to the treatment of human diseases. However, few previous methods take a holistic perspective and only concentrate on isolated miRNA and disease objects, thereby ignoring that human cells are responsible for multiple relationships. In this work, we first constructed a multi-view graph based on the relationships between miRNAs and various biomolecules, and then utilized graph attention neural network to learn the graph topology features of miRNAs and diseases for each view. Next, we added an attention mechanism again, and developed a multi-scale feature fusion module, aiming to determine the optimal fusion results for the multi-view topology features of miRNAs and diseases. In addition, the prior attribute knowledge of miRNAs and diseases was simultaneously added to achieve better prediction results and solve the cold start problem. Finally, the learned miRNA and disease representations were then concatenated and fed into a multi-layer perceptron for end-to-end training and predicting potential miRNA-disease associations. To assess the efficacy of our model (called MUSCLE), we performed 5- and 10-fold cross-validation (CV), which got average the Area under ROC curves of 0.966${\pm }$0.0102 and 0.973${\pm }$0.0135, respectively, outperforming most current state-of-the-art models. We then examined the impact of crucial parameters on prediction performance and performed ablation experiments on the feature combination and model architecture. Furthermore, the case studies about colon cancer, lung cancer and breast cancer also fully demonstrate the good inductive capability of MUSCLE. Our data and code are free available at a public GitHub repository: https://github.com/zht-code/MUSCLE.git.

Revealing the contribution of somatic gene mutations to shaping tumor immune microenvironment.

Interaction between tumor cells and immune cells determined highly heterogeneous microenvironments across patients, leading to substantial variation in clinical benefits from immunotherapy. Somatic gene mutations were found not only to elicit adaptive immunity but also to influence the composition of tumor immune microenvironment and various processes of antitumor immunity. However, due to an incomplete view of associations between gene mutations and immunophenotypes, how tumor cells shape the immune microenvironment and further determine the clinical benefit of immunotherapy is still unclear. To address this, we proposed a computational approach, inference of mutation effect on immunophenotype by integrated gene set enrichment analysis (MEIGSEA), for tracing back the genomic factor responsible for differences in immunophenotypes. MEIGSEA was demonstrated to accurately identify the previous confirmed immune-associated gene mutations, and systematic evaluation in simulation data further supported its performance. We used MEIGSEA to investigate the influence of driver gene mutations on the infiltration of 22 immune cell types across 19 cancers from The Cancer Genome Atlas. The top associated gene mutations with infiltration of CD8 T cells, such as CASP8, KRAS and EGFR, also showed extensive impact on other immune components; meanwhile, immune effector cells shared critical gene mutations that collaboratively contribute to shaping distinct tumor immune microenvironment. Furthermore, we highlighted the predictive capacity of gene mutations that are positively associated with CD8 T cells for the clinical benefit of immunotherapy. Taken together, we present a computational framework to help illustrate the potential of somatic gene mutations in shaping the tumor immune microenvironment.

Catalytic Synthesis of Silanols by Hydroxylation of Hydrosilanes: From Chemoselectivity to Enantioselectivity.

As a crucial class of functional molecules in organosilicon chemistry, silanols are found valuable applications in the fields of modern science and will be a potentially powerful framework for biologically active compounds or functional materials. It has witnessed an increasing demand for non-natural organosilanols, as well as the progress in the synthesis of these structural features. From the classic preparative methods to the catalytic selective oxidation of hydrosilanes, electrochemical hydrolysis of hydrosilanes, and then the construction of the most challenging silicon-stereogenic silanols. This review summarized the progress in the catalyzed synthesis of silanols via hydroxylation of hydrosilanes in the last decade, with a particular emphasis on the latest elegant developments in the desymmetrization strategy for the enantioselective synthesis of silicon-stereogenic silanols from dihydrosilanes.

Intramolecular Hosomi-Sakurai Reaction for the Synthesis of Benzoxasiloles.

A Lewis acid-catalyzed intramolecular Hosomi-Sakurai reaction of o-(allylsilyl)benzaldehyde/ketone has been developed. The reaction proceeds through simultaneous C-Si bond cleavage and C-C bond reconstruction. This protocol provides a rapid approach for the synthesis of allyl-substituted benzoxasiloles under mild conditions.

Patterns of peripartum depression and anxiety during the pre-vaccine COVID-19 pandemic.

BACKGROUND: Pregnant people are vulnerable to new or worsening mental health conditions. This study aims to describe prevalence and course of depression and anxiety symptoms in pregnancy during the pre-vaccine COVID-19 pandemic. METHODS: This is a prospective cohort study of pregnant individuals with known or suspected COVID-19. Participants completed Edinburgh Postnatal Depression Scale (EPDS) and Generalized-Anxiety Disorder-7 (GAD-7) questionnaires, screening tools for depression and anxiety, at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum. Prevalence of elevated depressive and anxiety symptoms at each visit was described. Univariable logistic regression analysis was used to determine the association between demographic and clinical factors and those with elevated depression or anxiety symptoms. RESULTS: 317 participants were included. The prevalence of elevated antepartum depression symptoms was 14.6%, 10.3%, and 20.6% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. The rate of elevated anxiety symptoms was 15.1%, 10.0%, and 17.3% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. A prior history of depression and/or anxiety (p's < 0.03), as well as higher EPDS and GAD-7 scores at enrollment (p's < 0.04) associated with elevated depression and anxiety symptoms throughout pregnancy and the postpartum period. Quarantining during pregnancy was associated with elevated anxiety symptoms at 34weeks gestational age in univariate (P = 0.027) analyses. COVID-19 diagnosis and hospitalization were not associated with elevated depression or anxiety symptoms. CONCLUSIONS: Elevated depression and anxiety symptoms were prevalent throughout pregnancy and the postpartum period, particularly in those with prior depression and/or anxiety and who quarantined. Strategies that target social isolation may mitigate potential adverse consequences for pregnant people, and continued vigilance in recognition of depression and anxiety in pregnancy should be considered.

Evaluation of the immunoprotective effect of the recombinant Eimeria intestinalis rhoptry protein 25 and rhoptry protein 30 on New Zealand rabbits.

BACKGROUND: Rabbit coccidiosis is a parasitism caused by either one or multiple co-infections of Eimeria species. Among them, Eimeria intestinalis is the primary pathogen responsible for diarrhea, growth retardation, and potential mortality in rabbits. Concerns regarding drug resistance and drug residues have led to the development of recombinant subunit vaccines targeting Eimeria species as a promising preventive measure. The aim of this study was to assess the immunoprotective efficacy of recombinant subunit vaccines comprising EiROP25 and EiROP30 (rhoptry proteins (ROPs)) against E. intestinalis infection in rabbits. METHODS: Cloning, prokaryotic expression, and protein purification were performed to obtain EiROP25 and EiROP30. Five groups of fifty 35-day-old Eimeria-free rabbits were created (unchallenged control group, challenged control group, vector protein control group, rEiROP25 group, and rEiROP30 group), with 10 rabbits in each group. Rabbits in the rEiROP25 and rEiROP30 groups were immunized with the recombinant proteins (100 µg per rabbit) for primary and booster immunization (100 µg per rabbit) at a two-week intervals, and challenged with 7 × 104 oocysts per rabbit after an additional two-week interval. Two weeks after the challenge, the rabbits were euthanized for analysis. Weekly collections of rabbit sera were made to measure changes in specific IgG and cytokine level. Clinical symptoms and pathological changes after challenge were observed and recorded. At the conclusion of the animal experiment, lesion scores, the relative weight increase ratio, the oocyst reduction rate, and the anticoccidial index were computed. RESULTS: Rabbits immunized with rEiROP25 and rEiROP30 exhibited relative weight gain ratios of 56.57% and 72.36%, respectively. Oocysts decreased by 78.14% and 84.06% for the rEiROP25 and rEiROP30 groups, respectively. The anticoccidial indexes were 140 and 155. Furthermore, there was a noticeable drop in intestinal lesions. After the primary immunization with rEiROP25 and rEiROP30, a week later, there was a notable rise in specific IgG levels, which remained elevated for two weeks following challenge (P < 0.05). Interleukin (IL)-2 levels increased markedly in the rEiROP25 group, whereas IL-2, interferon gamma (IFN-γ), and IL-4 levels increased substantially in the rEiROP30 group (P < 0.05). CONCLUSION: Immunization of rabbits indicated that both rEiROP25 and rEiROP30 are capable of inducing an increase in specific antibody levels. rEiROP25 triggered a Th1-type immune protection response, while rEiROP30 elicited a Th1/Th2 mixed response. EiROP25 and EiROP30 can generate a moderate level of immune protection, with better efficacy observed for EiROP30. This study provides valuable insights for the promotion of recombinant subunit vaccines targeting rabbit E. intestinalis infection.

MUC4 O-GlcNAcylation Regulates the Epithelial Phenotype in Conjunctival Epithelial Cells.

In the present study, our aim was to explore the role of MUC4 in IL-4-stimulated conjunctival epithelial cells and the underlying mechanisms. Human recombinant IL-4 was employed in human conjunctival epithelial cells (HConEpic) cells, and MUC4 shRNA (sh-MUC4) was constructed to explore the functional role of MUC4. The protein level of MUC4, O-GlcNAc transferase (OGT), O-GlcNAc hydrolase (OGA), zonula occludens 1 (ZO-1), gap junction protein beta 2 (GJB2), claudin-8 (CLDN8), and E-cadherin were detected by Western blot in HConEpic cells, the interaction between MUC4 and OGT/OGA was assessed by co-immunoprecipitation (IP) and Western blot in 293T cells. Our results showed that IL-4 significantly up-regulated MUC4 and OGT protein levels in HConEpic cells, while down-regulated OGA protein level. Also, IL-4 down-regulated ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, while which was markedly reversed by sh-MUC4. Additionally, OGT inhibitor significantly reduced MUC4 protein level, and elevated ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, while OGA inhibitor resulted in the opposite results. Furthermore, in addition to the interaction between OGT/OGA and MUC4, Co-IP and Western blot also revealed the alteration of MUC4 O-GlcNAcylation in 293T cells treated with OGT/OGA inhibitor. Above findings suggested that OGT/OGA inhibitor regulated MUC4 protein level by affecting MUC4 O-GlcNAcylation to regulate ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, which was achieved via inhibiting the interaction between OGT/OGA and MUC4. This study may provide a better understanding of the pathogenesis of allergic conjunctivitis (AC).

Effect of GnRH Active Immunisation on Reproductive Performance of Male Sprague Dawley Rats.

To investigate the effect of active immunisation with gonadotropin-releasing hormone (GnRH) on the reproductive function in male Sprague Dawley (SD) rats, 24 42-day-old rats were randomly assigned to treatment with GnRH6-MAP, GnRH-OVA, a surgical castration group, and a blank control group. Each rat in the treatment groups was intramuscularly injected at 6, 8, and 10 weeks of age. The serum concentrations of testosterone (T), follicle-stimulating hormone (FSH), luteinising hormone (LH), and anti-GnRH antibodies were determined using enzyme-linked immunosorbent assays. The results showed that active immunisation with recombinant GnRH6-MBP and GnRH-OVA significantly increased the serum levels of anti-GnRH antibodies and reduced the serum concentrations of testosterone compared to the black control. Eight weeks after immunisation, the rats' testes were surgically removed for morphological evaluation, showing atrophy of the convoluted vasculature, relative emptying of the lumen, and insignificant differentiation of spermatogonial cells, which were increased in weight and volume compared with the blank control group. These findings indicated that active immunisation with GnRH can lead to testicular atrophy and reduce gonadal hormone concentrations, suggesting that GnRH is a highly effective immunogen.

Copper-Catalyzed Asymmetric Synthesis of Silicon-Stereogenic Benzoxasiloles.

A Cu-catalyzed asymmetric synthesis of silicon-stereogenic benzoxasiloles has been realized via intramolecular Si-O coupling of [2-(hydroxymethyl)phenyl]silanes. Cu(I)/difluorphos is found to be an efficient catalytic system for enantioselective Si-C bond cleavage and Si-O bond formation. In addition, kinetic resolution of racemic substituted [2-(hydroxymethyl)phenyl]silanes using Cu(I)/ PyrOx (pyridine-oxazoline ligands) as the catalytic system is developed to afford carbon- and silicon-stereogenic benzoxasiloles. Ring-opening reactions of chiral benzoxasiloles with organolithiums and Grignard reagents yield various enantioenriched functionalized tetraorganosilanes.

Protection against Eimeria intestinalis infection in rabbits immunized with the recombinant elongation factors EF1α and EFG.

Eimeria intestinalis is the most pathogenic species of rabbit coccidiosis, causing weight loss, diarrhea, and even acute death. The currently used anticoccidial drugs against E. intestinalis in rabbits are associated with drug resistance and residues. Immunological control might be a potential alternative. We cloned and expressed the E. intestinalis recombinant EF1α and EFG (rEi-EF1α and rEi-EFG, respectively). Rabbits were immunized subcutaneously every 14 days with 100 µg of rEi-EF1α and rEi-EFG and followed by 5 × 104 E. intestinalis sporulated oocysts orally challenge. Serum samples were collected every 7 days to measure the levels of specific antibodies and cytokines. On post-challenge day 14, rabbits were sacrificed and the anticoccidial index was evaluated. The rabbits of PBS challenged groups exhibited anorexia, diarrhea, marked intestinal wall thickening, and white nodules that formed patches, while rabbits from the rEi-EF1α or rEi-EFG challenged group exhibited milder symptoms. The rEi-EF1α group showed a 75.18% oocyst reduction and 89.01%wt gain; the rEi-EFG group had a 60.58% oocyst reduction and 56.04%wt gain. After vaccination, specific IgG levels increased and stayed high (P < 0.05). The IL-4 and IL-2 levels of rEi-EF1α immunized groups showed a significant increase after immunization (P < 0.05). Both rEi-EF1α and rEi-EFG could induce humoral and cellular immune responses. In contrast, rabbits immunized with rEi-EF1α were better protected from challenge by E. intestinalis than rEi-EFG.

Atropisomers with Axial and Point Chirality: Synthesis and Applications.

Enantiopure atropisomers have become increasingly important in asymmetric synthesis and catalysis, pharmaceutical science, and material science since the discovery of inherent features of axial chirality originating from rotational restriction. Despite the advances made in this field to date, it remains highly desirable to construct structurally diverse atropisomers with potentially useful functions. We propose superposition to match axial and point chirality as a potentially useful strategy to access structurally complex and diverse building blocks for organic synthesis and pharmaceutical science because merging atropisomeric backbones with one or more extra chiral elements can topologically broaden three-dimensional environments to create complex scaffolds with multiple tunable parameters. Over the past decade, we have successfully implemented a strategic design for the superposition of axial and point chirality to develop a series of enantiopure atropisomers and have utilized the synergistic functions of these molecules to enhance chirality transfer in various catalytic asymmetric transformations.In this Account, we present several novel atropisomers with superposed axial and point chirality developed in our laboratory. In our studies, this superposition strategy was used to design and synthesize both biaryl and non-biaryl atropisomers from commercially available chiral sources. Consequently, these atropisomers were used to demonstrate the importance of the synergetic functions of axial and point chirality in specific enantioselective reactions. For example, aromatic amide-derived atropisomers, simplified as Xing-Phos arrays, were broadly employed in Ag-catalyzed [3 + 2] cycloaddition by a series of reactions of aldiminoesters with activated alkenes and imines, as well as being used as chiral solvating agents for the discrimination of optically active mandelic acid derivatives. Considering the powerful potential of non-biaryl atropisomers for asymmetric catalysis, we also explored the transition-metal-catalyzed enantioselective construction of a novel backbone of non-biaryl atropisomers (Ar-alkene, Ar-N axis) bearing both axial and point chirality for the design and synthesis of chiral ligands and functional molecules.The studies presented herein are expected to stimulate further research efforts on the development of functional atropisomers by superposition of matching axial and point chirality. In addition to tunable electron and stereohindrance effects, the synergy between matching chiral elements of axial/point chirality and functional groups is proven to be a special function that cannot be ignored for promoting reactivity and chirality-transfer efficiency in enantioselective synthesis. Consequently, our novel types of scaffolds with superposed axial and point chirality that are capable of versatile coordination with various metal catalysts in asymmetric catalysis highlight the power of the superposition of matching axial and point chirality for the construction of synthetically useful atropisomers.

13-8-13-Membered Tricyclic Ladder-Type Siloxanes Hybridized with BINOLs: Synthesis, Characterization, and Fluorescence Sensing of Fluorides.

Developing fluorescent chemosensors with sensitivity and high specificity for recognizing fluorides is still challenging. Herein, four innovative compounds based on 13-8-13-membered tricyclic ladder-type siloxanes hybridized with BINOLs (abbreviated as TLS-BINOLs) were prepared through the B(C6F5)3-catalyzed Piers-Rubinsztajn reaction. The well-defined ladder-type structure of the TLS-BINOLs was determined by X-ray crystallographic analysis. Additionally, the fluorescent sensing ability of the TLS-BINOLs toward anions was studied. Our finding revealed that all four ladder-type compounds (TLS-BINOLs) exhibited high specificity in recognizing fluorides through fluoride-triggered structural decomposition. The detection limits for fluorides were determined to be 0.37, 0.35, 0.39, and 0.48 µM for the respective TLS-BINOLs. The nonemissive product induced by the fluorides was also determined using single-crystal X-ray diffraction analysis.

Systematic investigation of the prognostic impact of clonal status of somatic mutations across multiple cancer types.

Tumors are genetically heterogeneous and many mutations are actually present in subclonal populations. The clonal status of mutations is valuable for accurate prognosis, clinical management. The aim of this study was to identify the clonal status of somatic mutations and systematically evaluate their prognostic values across various cancer types. We totally identified 227 clonal and 432 subclonal mutations contributed to prognosis and demonstrated the importance of clonal status in improving mutation-related clinical guidance. We further developed a customized multi-step approach to identify gene-specific prognostic patterns of clonal status at pan-cancer level and found some cancer-specific prognostic patterns. The 'subclonal-dependent risk' subpattern was one of the most common subpatterns, it usually accompanied by high genomic in-stability and high extent of intra-tumor heterogeneity and could be used to improve the accuracy of prognostic analysis. Our results revealed the importance of clonal status, especially subclonal mutation in clinical survival.

Assessment of the Immunoprotective Efficacy of Recombinant 14-3-3 Protein and Dense Granule Protein 10 (GRA10) as Candidate Antigens for Rabbit Vaccines against Eimeria intestinalis.

Eimeria intestinalis infects rabbits, causing severe intestinal coccidiosis. Prolonged anticoccidial drug use might lead to coccidia resistance and drug residues in food. Thus, vaccines are required to control rabbit coccidiosis. In this study, recombinant E. intestinalis 14-3-3 and GRA10 proteins (rEi-14-3-3 and rEi-GRA10) were obtained via prokaryotic expression and used as recombinant subunit vaccines. Fifty 30-day-old rabbits were randomly grouped as follows: PBS-uninfected group, PBS-infected group, Trx-His-S control group, and rEi-14-3-3 and rEi-GRA10 immunized groups. The rabbits were subcutaneously immunized twice at 2-week intervals, challenged with 7 × 104 sporulated oocysts, and sacrificed 14 days later. The protective effects were assessed via clinical signs, relative weight gain, oocyst reduction, mean intestinal lesion score, ACI (anticoccidial index), cytokine, and specific antibody levels in sera. The rEi-14-3-3 and rEi-GRA10 groups had higher relative weight gain rates of 81.94% and 73.61% (p < 0.05), and higher oocyst reduction rates of 86.13% and 84.87% (p < 0.05), respectively. The two immunized groups had fewer intestinal lesions (p < 0.05) and higher IgG levels (p < 0.05). Higher levels of IL-2, IL-4, and IFN-γ cytokines in the rEi-14-3-3 group (p < 0.05) and a higher level of IFN-γ in the rEi-GRA10 group (p < 0.05) were observed. The ACI values of the rEi-14-3-3 and rEi-GRA10 groups were 168.24 and 159.91, with good and moderate protective effects, respectively. Both rEi-14-3-3 and rEi-GRA10 induced humoral immunity in the rabbits. In addition, rEi-14-3-3 induced Th1- and Th2-type immune responses. Both recombinant proteins were protective against E. intestinalis infection in rabbits, with rEi-14-3-3 showing a better protective effect.

Myxobolus dumerilii sp. n. (Myxozoa: Myxobolidae) infecting the brain of Chinese longsnout catfish Tachysurus dumerili (Bleeker) in China.

During an investigation of Myxobolus diversity in the Chinese longsnout catfish Tachysurus dumerili (Bleeker), a new species infecting the intracranial epidermis of the host was discovered. Upon opening the cranial cavity, several round whitish plasmodia measuring 0.55-0.80 mm in diameter were observed. Fresh spores (n= 50) were pyriform in the frontal view and fusiform in the sutural view, with a length of 15.4±0.6 (13.9-16.5) µm, width of 9.1±0.4 (8.3-9.8) µm, and thickness of 7.0±0.4 (6.3-7.9) µm. The spores had smooth shell surfaces and transparent membrane sheaths in the posterior. No folds, intercapsular appendix, and caudal appendages were observed. Two equal polar capsules were pyriform and measured 7.5±0.5 (6.7-8.7) µm in length and 3.2±0.3 (2.5-3.6) µm in width. The polar filaments were coiled with five to six turns and perpendicular to the polar capsule length. A BLAST search indicated M. dumerilii sp. n. was closely related to five Myxobolus species (with sequences similarities ranging from 90.54% to 96.52%) found in different organs of yellow catfish Tachysurus fulvidraco (Richardson), rather than the T. dumerili-infecting species M. branchiola Dong and Zhao, 2014 (with 90.5% sequence similarity). Phylogenetic analysis showed that M. dumerilii sp. n. didn't form sister clade with brain-infecting Myxobolus spp, but clustered with M. jianlinensis Gao et Zhao, 2020 and M. voremkhai Akhmerov, 1960 within the Siluriformes-clade with highly supported values, indicating that the host specificity may play a stronger signal than site infections during the evolution of Myxobolus species. Based on the morphological, ecological, and molecular differences observed between the newly discovered species and other available Myxobolus species, M. dumerilii sp. n., is proposed and described in this study.

New resources for genetic studies in maize (Zea mays L.): a genome-wide Maize6H-60K single nucleotide polymorphism array and its application.

Despite the availability of numerous molecular markers in maize, effective evaluation of all types of germplasm resources, accurate identification of varieties and analysis of a large number of materials in a timely, low-cost manner is challenging. Here, we present Maize6H-60K, a genome-wide single nucleotide polymorphism (SNP) array to facilitate maize genotyping. We first identified 160 million variants by sequencing data of 388 representative inbreds and then tiled 200 000 high-quality variants on a screening array. These variants were further narrowed down to 61 282 using stringent filtering criteria. Among the 60 000 markers, 21 460 SNPs (35%) were within genic regions and 12 835 (21%) were located in coding regions. To assess their effectiveness, 329 inbreds, 221 hybrids, 34 parent-offspring sets and six breeding samples were genotyped. Overall, 48 972 SNPs (80%) were categorized into the highest quality class, that of 'poly high resolution'. A total of 54 658 (89.29%) and 53 091 (86.73%) SNPs had minor allele frequency values ≥ 0.20 in inbreds and hybrids respectively. A linkage disequilibrium (LD) analysis revealed that LD decline was in equilibrium when r2 was between 0.10 and 0.15, which corresponds to a physical distance of 400-600 kb. UPGMA clustering analysis divided the 329 inbred lines into nine groups that were consistent with known pedigrees. A background analysis of breeding materials indicated that the 60 000 markers were suitable for evaluation of breeding populations constructed by materials between or within heterotic groups. The developed Maize6H-60K array should be an important tool in maize genetic studies, variety identification and molecular breeding.

The Discovery of Multifunctional Chiral P Ligands for the Catalytic Construction of Quaternary Carbon/Silicon and Multiple Stereogenic Centers.

The development of highly effective chiral ligands is a key topic in enhancing the catalytic activity and selectivity in metal-catalyzed asymmetric synthesis. Traditionally, the difficulty of ligand synthesis, insufficient accuracy in controlling the stereoselectivity, and poor universality of the systems often become obstacles in this field. Using the concept of nonequivalent coordination to the metal, our group has designed and synthesized a series of new chiral catalysts to access various carbon/silicon and/or multiple stereogenic centers containing products with excellent chemo-, diastereo-, and enantioselectivity.In this Account, we summarize a series of new phosphine ligands with multiple stereogenic centers that have been developed in our laboratory. These ligands exhibited good to excellent performance in the transition-metal-catalyzed enantioselective construction of quaternary carbon/silicon and multiple stereogenic centers. In the first section, notable examples of the design and synthesis of new chiral ligands by non-covalent interaction-based multisite activation are described. The integrations of axial chirality, atom-centered chirality, and chiral anions and multifunctional groups into a single scaffold are individually highlighted, as represented by Ar-BINMOLs and their derivative ligands, HZNU-Phos, Fei-Phos, and Xing-Phos. In the second, third, and fourth sections, the enantioselective construction of quaternary carbon stereocenters, multiple stereogenic centers, and silicon stereogenic centers using our newly developed chiral ligands is summarized. These sections refer to detailed reaction information in the chiral-ligand-controlled asymmetric catalysis based on the concept of nonequivalent coordination with multisite activation. Accordingly, a wide array of transition metal and main-group metal catalysts has been applied to the enantioselective synthesis of chiral heterocycles, amino acid derivatives, cyclic ketones, alkenes, and organosilicon compounds bearing one to five stereocenters.This Account shows that this new model of multifunctional ligand-controlled catalysts exhibits excellent stereocontrol and catalytic efficiency, especially in a stereodivergent and atom-economical fashion. Furthermore, a brief mechanistic understanding of the origin of enantioselectivity from our newly developed chiral catalyst systems could inspire further development of new ligands and enhancement of enantioselective synthesis by asymmetric metal catalysis.

3-Alkyl-2-pyridyl Directing Group-Enabled C2 Selective C-H Silylation of Indoles and Pyrroles via an Iridium Catalyst.

An iridium-catalyzed, directing group-enabled site selective intra- and intermolecular silylation of indoles and pyrroles with hydrosilanes has been developed under ligand-free conditions. Fine-tuning of the removable 3-alkyl-2-pyridyl directing group was found to be crucial for achieving high yields for C2-silylated indole and pyrrole products. Moreover, the scalability was demonstrated, and further transformations of the silylation products were achieved.

Mass mortalities associated with viral nervous necrosis in Murray cod in China.

In December 2019, a mass mortality among cultured Murray cod (Maccullochella peelii peelii) fry occurred on a freshwater farm located at Foshan city of Guangdong province, China. The cumulative mortality was up to 45% within 15 days. The diseased fish showed clinical signs, including abnormal swimming behaviour, loss of appetite and dark body colouration before mass mortality. Samples of brain and retina tissues were collected from affected fish and subjected to reverse transcriptase polymerase chain reaction detection and virus isolation in cell culture. Approximately 430 bp product was detected from the brain and retina tissues and culture supernatant of betanodavirus-infected SSN-1 cells. The typical cytopathic effect of betanodavirus infection, which is characterized by vacuolation, was observed in SSN-1 cells at three days after inoculating with the tissue filtrate of diseased Murry cod fry, and the TCID50 of the infected SSN-1 cell supernatant was 107.8 . Histopathological examinations revealed vacuolation and necrosis in the brain and retina of naturally and experimentally infected Murray cod fry. Electron microscopic observation also showed the aggregation of numerous spherical, non-enveloped viral particles measuring 22-28 nm in diameter in the cytoplasm of betanodavirus-infected SSN-1 cells. Sequence and phylogenetic analysis based on RdRp and Cp genes further indicated that the betanodavirus isolated from Murray cod belonged to the RGNNV genotype. Much higher mortality was obtained in challenged Murray cod fry compared with the controls through immersion challenge. This study is the first report of the natural infection of betanodavirus in freshwater fish in China.

Application of aromatic amide-derived atropisomers as chiral solvating agents for discrimination of optically active mandelic acid derivatives in 1 H nuclear magnetic resonance spectroscopy.

Non-biaryl atropisomers and their stereochemistry have attracted much attentions in the past years. However, application of the non-biaryl atropisomers as chiral solvating agents is yet to be explored. In this work, four aromatic amide-derived atropisomeric phosphine ligands (hosts) were used as chiral solvating agents to recognize various mandelic acid derivatives (guests) in 1 H nuclear magnetic resonance (NMR) spectroscopy. It is found that chiral center configurations of the four hosts have different effects on the enantiorecognition to the used guests. In addition, the host and guest interaction was further investigated by determination of the host-guest complex stoichiometry using the Job's method and density functional theory calculation, respectively. Moreover, chiral analysis accuracy of these hosts was evaluated through relationship between enantiomeric excess values of 4-chloromandelic acid provided by NMR and gravimetry, respectively.