In-Depth Serum Proteomics Reveals the Trajectory of Hallmarks of Cancer in Hepatitis B Virus-Related Liver Diseases.

Hepatocellular carcinoma (HCC) is a prevalent cancer in China, with chronic hepatitis B (CHB) and liver cirrhosis (LC) being high-risk factors for developing HCC. Here, we determined the serum proteomes (762 proteins) of 125 healthy controls and Hepatitis B virus-infected CHB, LC, and HCC patients and constructed the first cancerous trajectory of liver diseases. The results not only reveal that the majority of altered biological processes were involved in the hallmarks of cancer (inflammation, metastasis, metabolism, vasculature, and coagulation) but also identify potential therapeutic targets in cancerous pathways (i.e., IL17 signaling pathway). Notably, the biomarker panels for detecting HCC in CHB and LC high-risk populations were further developed using machine learning in two cohorts comprised of 200 samples (discovery cohort = 125 and validation cohort = 75). The protein signatures significantly improved the area under the receiver operating characteristic curve of HCC (CHB discovery and validation cohort = 0.953 and 0.891, respectively; LC discovery and validation cohort = 0.966 and 0.818, respectively) compared to using the traditional biomarker, alpha-fetoprotein, alone. Finally, selected biomarkers were validated with parallel reaction monitoring mass spectrometry in an additional cohort (n = 120). Altogether, our results provide fundamental insights into the continuous changes of cancer biology processes in liver diseases and identify candidate protein targets for early detection and intervention.

Programmable living assembly of materials by bacterial adhesion.

The field of engineered living materials aims to construct functional materials with desirable properties of natural living systems. A recent study demonstrated the programmed self-assembly of bacterial populations by engineered adhesion. Here we use this strategy to engineer self-healing living materials with versatile functions. Bacteria displaying outer membrane-anchored nanobody-antigen pairs are cultured separately and, when mixed, adhere to each other to enable processing into functional materials, which we term living assembled material by bacterial adhesion (LAMBA). LAMBA is programmable and can be functionalized with extracellular moieties up to 545 amino acids. Notably, the adhesion between nanobody-antigen pairs in LAMBA leads to fast recovery under stretching or bending. By exploiting this feature, we fabricated wearable LAMBA sensors that can detect bioelectrical or biomechanical signals. Our work establishes a scalable approach to produce genetically editable and self-healable living functional materials that can be applied in biomanufacturing, bioremediation and soft bioelectronics assembly.

Anionic oxyl radical formed on CrVI-oxo anchored on the defect site of the UiO-66 node facilitates methane to methanol conversion.

The direct conversion of methane to methanol has attracted increasing interest due to abundant and low-cost natural gas resources. Herein, by anchoring Cr-oxo/-oxyhydroxides on UiO-66 metal-organic frameworks, we demonstrate that reactive anionic oxyl radicals can be formed by controlling the coordination environment based on the results of density functional theory calculations. The anionic oxyl radicals produced at the completely oxidized CrVI site acted as the active species for facile methane activation. The thermodynamically stable CrVI-oxo/-oxyhydroxides with the anionic oxyl radicals catalyze the activation of the methane C-H bond through a homolytic mechanism. An analysis of the results showed that the catalytic performance of the active oxyl species correlates with the reaction energy of methane activation and H adsorption energies. Following methanol formation, N2O can regenerate the active sites on the most stable CrVI oxyhydroxides, i.e., the Cr(O)4Hf species. The present study demonstrated that the anionic oxyl radicals formed on the anchored CrVI oxyhydroxides by tuning the coordination environment enabled facile methane activation and facilitated methanol production.

The features associated with mammography-occult MRI-detected newly diagnosed breast cancer analysed by comparing machine learning models with a logistic regression model.

PURPOSE: To compare machine learning (ML) models with logistic regression model in order to identify the optimal factors associated with mammography-occult (i.e. false-negative mammographic findings) magnetic resonance imaging (MRI)-detected newly diagnosed breast cancer (BC). MATERIAL AND METHODS: The present single-centre retrospective study included consecutive women with BC who underwent mammography and MRI (no more than 45 days apart) for breast cancer between January 2018 and May 2023. Various ML algorithms and binary logistic regression analysis were utilized to extract features linked to mammography-occult BC. These features were subsequently employed to create different models. The predictive value of these models was assessed using receiver operating characteristic curve analysis. RESULTS: This study included 1957 malignant lesions from 1914 patients, with an average age of 51.64 ± 9.92 years and a range of 20-86 years. Among these lesions, there were 485 mammography-occult BCs. The optimal features of mammography-occult BC included calcification status, tumour size, mammographic density, age, lesion enhancement type on MRI, and histological type. Among the different ML models (ANN, L1-LR, RF, and SVM) and the LR-based combined model, the ANN model with RF features was found to be the optimal model. It demonstrated the best discriminative performance in predicting mammography false- negative findings, with an AUC of 0.912, an accuracy of 86.90%, a sensitivity of 85.85%, and a specificity of 84.18%. CONCLUSION: Mammography-occult MRI-detected breast cancers have features that should be considered when performing breast MRI to improve the detection rate for breast cancer and aid in clinician management.

S100A11 Promotes Metastasis via AKT and ERK Signaling Pathways and Has a Diagnostic Role in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common and malignant liver tumor worldwide, although the treatment approaches for HCC continue to evolve, metastasis is the main reason for high mortality rates. S100 calcium-binding protein A11 (S100A11), an important member of the S100 family of small calcium-binding proteins, is overexpressed in various cells and regulates tumor development and metastasis. However, few studies report the role and underlying regulatory mechanisms of S100A11 in HCC development and metastasis. Herein, we discovered that S100A11 is overexpressed and associated with poor clinical outcomes in HCC cohorts, and we provided the first demonstration that S100A11 could serve as a novel diagnostic biomarker used in conjunction with AFP for HCC. Further analysis implied that S100A11 outperforms AFP in determining whether HCC patients have hematogenous metastasis or not. Using in vitro cell culture model, we demonstrated that S100A11 is overexpressed in metastatic hepatoma cells, knockdown of S100A11 decreases hepatoma cells proliferation, migration, invasion, and epithelial-mesenchymal transition process by inhibiting AKT and ERK signaling pathways. Altogether, our study provides new sights into the biological function and mechanisms underlying S100A11 in promoting metastasis of HCC and explores a novel target for HCC diagnosis and treatment.

Coupled oxygen desorption and structural reconstruction accompanying reduction of copper oxide.

Understanding structural transformation and phase transition accompanying reactions in a solid as a catalyst or oxygen carrier is important to the design and optimization of many catalytic or chemical looping reaction processes. Herein, we combined density functional theory calculation with the stochastic surface walking global optimization approach to track the structural transformation accompanying the reduction of CuO upon releasing oxygen. We then used machine learning (ML) methods to correlate the structural properties of CuOx with varying x. By decomposing a reduction step into oxygen detachment and structural reconstruction, we identified two types of pathways: (1) uniform reduction with minimal structural changes; (2) segregated reduction with significant reconstruction. The results of ML analysis showed that the most important feature is the radial distribution functions of Cu-O at a percentage of oxygen vacancy [C(OV)] < 50% and Cu-Cu at C(OV) > 50% for CuOx formation. These features reflect the underlying physicochemical origin, i.e., Cu-O breaking and Cu-Cu formation in the respective stage of reduction. Phase diagram analysis indicates that CuO will be reduced to Cu2O under a typical oxygen uncoupling condition. This work demonstrates the complexity of solid structural transformation and the potential of ML methods in studying solid state materials involved in many chemical processes.

MolMiner: You Only Look Once for Chemical Structure Recognition.

Molecular structures are commonly depicted in 2D printed forms in scientific documents such as journal papers and patents. However, these 2D depictions are not machine readable. Due to a backlog of decades and an increasing amount of printed literatures, there is a high demand for translating printed depictions into machine-readable formats, which is known as Optical Chemical Structure Recognition (OCSR). Most OCSR systems developed over the last three decades use a rule-based approach, which vectorizes the depiction based on the interpretation of vectors and nodes as bonds and atoms. Here, we present a practical software called MolMiner, which is primarily built using deep neural networks originally developed for semantic segmentation and object detection to recognize atom and bond elements from documents. These recognized elements can be easily connected as a molecular graph with a distance-based construction algorithm. MolMiner gave state-of-the-art performance on four benchmark data sets and a self-collected external data set from scientific papers. As MolMiner performed similarly well in real-world OCSR tasks with a user-friendly interface, it is a useful and valuable tool for daily applications. The free download links of Mac and Windows versions are available at https://github.com/iipharma/pharmamind-molminer.

The association between several autophagy-related genes and their prognostic values in hepatocellular carcinoma: a study on the foundation of TCGA, GEPIA and HPA databases.

BACKGROUND: The purpose of this study was to investigate the relationship between the expression of autophagy-related genes and prognosis in hepatocellular carcinoma (HCC). METHODS AND RESULTS: We selected three autophagy-related genes (ATG3, ATG7, and ATG9A) from gene expression data of liver cancer patients in The Cancer Genome Atlas (TCGA) database by Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis, and Gene Set Enrichment Analysis (GSEA). Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were applied to testify the credibility of our results. The expression levels of ATG3, ATG7, and ATG9A were verified by real-time quantitative PCR (RT-qPCR) in normal liver cells (L02) and three HCC cell lines (HepG2, Hep3b, and Li-7). Data analysis results from TCGA showed high ATG3, ATG7, ATG9A expression in HCC tumor tissues. Kaplan-Meier survival analysis showed that the survival rate of the high expression group of ATG3, ATG7, and ATG9A was all significantly lower than the low expression group. GSEA analysis showed that many signaling pathways (such as the regulation of autophagy, glycine serine and threonine metabolism, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, mammalian target of rapamycin (mTOR) signaling pathway, as well as P53 signaling pathway) were differentially enriched in HCCs with ATG3, ATG7, and ATG9A expression. GEPIA and RT-qPCR also identified that the mRNA expression level of ATG3, ATG7, and ATG9A in normal liver cells were significantly lower than in HCC cells. High protein expression of ATG3, ATG7, and ATG9A was displayed in HCCs from the HPA database. CONCLUSIONS: The ATG3, ATG7, ATG9A might be utilized as prognostic biomarkers for liver cancer.

A critical assessment of provincial-level variation in agricultural GHG emissions in China.

China is a world leader on agriculture production; with only 8% of global cropland it feeds 20% of the world's population. However, the increasing production capacity comes with the cost of greenhouse gas (GHG) emissions. As a populous country with the highest GHG emissions in the world, determining how to achieve the dual goals of mitigating climate change and ensuring food security is of great significance for the agricultural sector. This requires assessing the spatial variation in agricultural greenhouse gases (GHGs) and their drivers. In this study, we conduct a spatial assessment of agricultural GHGs at the provincial level in China for the years 1997-2017, and then explore the effects of related factors on GHG emissions using a geographically weighted regression (GWR) model. The results suggest the following. 1) There have always been significant interprovincial variations, whether in the total amount, structure, intensity, or per capita level of agricultural GHG emissions. 2) The directions of the effects of selected factors on GHG intensity fall broadly into three categories: negative effects (urbanization, intensity of agricultural practices, and agricultural structure), positive effects (agricultural investment and cropland endowments), and mixed effects, with factors leading to reductions in some provinces and increases in others (economic level, frequency and intensity of disasters, and the level of mechanization). 3) The magnitude of the effects varies by factor and also by province. The results suggest synergetic province- or state-specific reduction policies in agricultural GHG for China, as well as for other developing and emerging economies.

R-spondin3 promotes the tumor growth of choriocarcinoma JEG-3 cells.

R-spondin3 (RSPO3), an activator of Wnt/ß-catenin signaling, plays a key role in tumorigenesis of various cancers, but its role in choriocarcinoma remains unknown. To investigate the effect of RSPO3 on the tumor growth of choriocarcinoma JEG-3 cells, the expression of RSPO3 in human term placenta was detected, and a stable RSPO3-overexpressing JEG-3 cell line was established via lentivirus-mediated transduction. The expression of biomarkers involved in tumorigenicity was detected in the RSPO3-overexpressing JEG-3 cells, and cell proliferation, invasion, migration, and apoptosis were investigated. Moreover, soft agar clonogenic assays and xenograft tumorigenicity assays were performed to assess the effect of RSPO3 on tumor growth in vitro and in vivo. The results showed that RSPO3 was widely expressed in human term placenta and overexpression of RSPO3 promoted the proliferation and inhibited the migration, invasion, and apoptosis of the JEG-3 cells. Meanwhile, RSPO3 overexpression promoted tumor growth both in vivo and in vitro. Further investigation showed that the phosphorylation levels of Akt, phosphatidylinositol 3-kinase (PI3K), and ERK as well the expression of ß-catenin and proliferating cell nuclear antigen (PCNA) were increased in the RSPO3-overexpressing JEG-3 cells and tumor xenograft. Taken together, these data indicate that RSPO3 promotes the tumor growth of choriocarcinoma via Akt/PI3K/ERK signaling, which supports RSPO3 as an oncogenic driver promoting the progression of choriocarcinoma.

A potential downstream platform approach for WuXiBody-based IgG-like bispecific antibodies.

WuXiBody is a novel bispecific antibody (bsAb) platform developed by WuXi Biologics. It enables almost any monoclonal antibody (mAb) sequence pair to be assembled into a bispecific construct. BsAbs based on WuXiBody can adopt either asymmetric or symmetric format. WuXiBody's unique design not only ensures desired chain pairing but also facilitates removal of potential product-related impurities. In this work, demonstrated with four WuXiBody-based bsAbs (two asymmetric and two symmetric ones), we showed that Protein A followed by anion exchange (AEX) and mixed-mode chromatography (i.e., Capto MMC ImpRes or Capto adhere ImpRes) can be a potential platform approach for WuXiBody purification.

A density functional theory study on reduction-induced structural transformation of copper-oxide-based oxygen carrier.

A clear understanding of the structural transformation of copper-oxide-based oxygen carriers accompanying their reduction by fuels helps to design more efficient oxygen carriers for chemical looping combustion. Herein, density functional theory calculations have been performed on the bulk CuO, CuO(111) surface, and (CuO)32 cluster models with the same number of CuO molecular units to investigate structural transformation accompanying the reduction. The results showed that the averaged reaction energies of desorbing an oxygen molecule from the bulk and surface models are roughly the same [246.2 kJ/(mol O2) and 245.9 kJ/(mol O2), respectively]. The slab model does not significantly lower the overall reaction energy compared to the bulk model. In contrast, the averaged reaction energy using the cluster model is significantly lower [127.5 kJ/(mol O2)] than that of bulk and slab models. The key structural difference is the obvious Cu-Cu bond formation in the cluster model, which would result in nucleation of a metallic Cu phase. The results also showed that different states can be reached by desorbing different number oxygen atoms in a single step, corresponding to different reaction rates, when the system reaches the same level of reduction. These results demonstrate the complexity of reactions involving solid state materials and are consistent with the structural diversity observed experimentally. This study illustrates the importance of particle sizes and reaction conditions in the formation of suboxides during CuO reduction.

The adequate amount of sodium chloride in Protein A wash buffer for effective host cell protein clearance.

Post-load column wash in Protein A chromatography can effectively improve host cell protein (HCP) clearance. A commonly used wash additive for this purpose is sodium chloride. However, the adequate amount of sodium chloride required for effective HCP clearance is less consistent in literature. In this study we investigated the impact of different amounts of sodium chloride on HCP clearance with five monoclonal antibodies (mAbs). For each mAb, elution pool HCP levels from runs under different wash conditions are compared. For all five mAbs, the data suggested that 250 mM would be an adequate amount for the salt to largely achieve its HCP reducing effect. The same conclusion is also reached for calcium chloride, a less commonly used but equally effective Protein A wash additive for HCP clearance.

Monitoring removal of hole-hole homodimer by analytical hydrophobic interaction chromatography in purifying a bispecific antibody.

Despite the use of knobs-into-holes (KiH) strategy to promote heterodimerization in recombinant production of bispecific antibody (bsAb), homodimer (especially the hole-hole homodimer) can still be generated in small amount. This by-product needs to be removed by downstream process. However, as homodimer and the target bsAb are usually very close in size, these two species may not be readily differentiated using size-exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Thus, method other than SEC-HPLC needs to be developed to monitor removal of this by-product. Here, through a case study we demonstrate that analytical hydrophobic interaction chromatography (HIC) is a powerful tool for quantitatively monitoring removal of hole-hole homodimer in bsAb purification.

Targeted Delivery Prodigiosin to Choriocarcinoma by Peptide-Guided Dendrigraft Poly-l-lysines Nanoparticles.

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, in vivo, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from Serratia marcescens subsp. lawsoniana was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.

Enhancing Mucosal Immune Response of Newcastle Disease Virus DNA Vaccine Using N-2-Hydroxypropyl Trimethylammonium Chloride Chitosan and N,O-Carboxymethyl Chitosan Nanoparticles as Delivery Carrier.

Because mucosal sites are the entry ports of pathogens, immunization via mucosal routes can extremely enhance the immunity. To elevate the potential of N-2-hydroxypropyl trimethylammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMC) nanoparticles as a mucosal immune delivery carrier for DNA vaccines, we prepared the NDV F gene plasmid DNA with C3d6 molecular adjuvant (pVAX I-F(o)-C3d6) encapsulated in the N-2-HACC-CMC nanoparticles (N-2-HACC-CMC/pFDNA-C3d6 NPs). The N-2-HACC-CMC/pFDNA-C3d6 NPs had regular spherical morphology and low toxicity with a mean diameter of 309.7 ± 6.52 nm, zeta potential of 49.9 ± 4.93 mV, encapsulation efficiency of 92.27 ± 1.48%, and loading capacity of 50.75 ± 1.35%. The N-2-HACC-CMC had high stability and safety. The pVAX I-F(o)-C3d6 could be sustainably released from the N-2-HACC-CMC/pFDNA-C3d6 NPs after an initial burst release. Immunization intranasally of chickens with N-2-HACC-CMC/pFDNA-C3d6 NPs not only produced higher anti-NDV IgG and sIgA antibody than chickens in other groups did, but also significantly stimulated lymphocyte proliferation and triggered higher the IL-2, IL-4, and IFN-γ levels. These findings indicated that the N-2-HACC-CMC could be used as an efficient delivery carrier for the mucosal immunity of Newcastle disease virus DNA vaccine. The work laid a basis for the quaternized chitosan nanoparticles as efficient mucosal immunity delivery carrier for DNA vaccines and had immense application promise and potential for vaccines and drugs.

Direct C-C Coupling of CO2 and the Methyl Group from CH4 Activation through Facile Insertion of CO2 into Zn-CH3 σ-Bond.

Conversion of CO2 and CH4 to value-added products will contribute to alleviating the green-house gas effect but is a challenge both scientifically and practically. Stabilization of the methyl group through CH4 activation and facile CO2 insertion ensure the realization of C-C coupling. In the present study, we demonstrate the ready C-C coupling reaction on a Zn-doped ceria catalyst. The detailed mechanism of this direct C-C coupling reaction was examined based on the results from density functional theory calculations. The results show that the Zn dopant stabilizes the methyl group by forming a Zn-C bond, thus hindering subsequent dehydrogenation of CH4. CO2 can be inserted into the Zn-C bond in an activated bent configuration, with the transition state in the form of a three-centered Zn-C-C moiety and an activation barrier of 0.51 eV. The C-C coupling reaction resulted in the acetate species, which could desorb as acetic acid by combining with a surface proton. The formation of acetic acid from CO2 and CH4 is a reaction with 100% atom economy, and the implementation of the reaction on a heterogeneous catalyst is of great importance to the utilization of the greenhouse gases. We tested other possible dopants including Al, Ga, Cd, In, and Ni and found a positive correlation between the activation barrier of C-C coupling and the electronegativity of the dopant, although C-H bond activation is likely the dominant reaction on the Ni-doped ceria catalyst.

Elimination of hepatitis C in a hospital characterized by infectious diseases.

Background: The World Health Organization has proposed to eliminate hepatitis C by 2030, yet there is still a large gap to the goal. Screening for hepatitis C is cost-effective and efficient in medical institutions. The aim of this study was to identify the key populations for HCV antibody screening in hospital characterized by infectious diseases, and provide estimates of the proportion of HCV-infected persons in the Beijing Ditan hospital completing each step along a proposed HCV treatment cascade. Methods: A total of 105,112 patients who underwent HCV antibody testing in Beijing Ditan hospital between 2017 and 2020 were included in this study. HCV antibody and HCV RNA positivity rate were calculated and compared by chi-square test. Results: The positivity rate of HCV antibody was 6.78%. The HCV antibody positivity rate and the proportion of positive patients showed an upward trend along with age in the five groups between 10-59 years. In the contrary, a decreasing trend was observed in the three groups above 60 years. Patients with positive HCV antibody were mainly from the Liver Disease Center (36.53%), the Department of Integrative Medicine (16.10%), the Department of Infectious Diseases (15.93%) and the Department of Obstetrics and Gynecology (9.44%). Among HCV antibody positive patients, 6,129 (85.95%) underwent further HCV RNA testing, of whom 2097 were HCV RNA positive, the positivity rate was 34.21%. Of the patients who were HCV RNA positive, 64.33% did not continue with HCV RNA testing. The cure rate for HCV antibody positive patients was 64.98%. Besides, there was a significant positive correlation between HCV RNA positivity rate and HCV antibody level (r = 0.992, P < 0.001). The detection rate of HCV antibody among inpatients showed an upward trend (Z = 5.567, P < 0.001), while the positivity rate showed a downward trend (Z = 2.2926, P = 0.0219). Conclusions: We found that even in hospitals characterized by infectious diseases, a large proportion of patients did not complete each step along a proposed HCV treatment cascade. Besides, we identified key populations for HCV antibody screening, namely: (1) patients over 40 years of age, especially those aged 50-59 years; (2) the Department of Infectious Diseases and the Department of Obstetrics and Gynecology patients. In addition, HCV RNA testing was highly recommended for patients with HCV antibody levels above 8 S/CO.

Intron-capture RNA-seq reveals the landscape of intronic RNAs in Arabidopsis.

Intronic RNAs have been overlooked for a long time: They are functional, but treated as "junk." In this work, we designed a new sequencing strategy to investigate intronic RNAs. By using intron-capture RNA-seq, we systematically analyzed the intronic RNAs in Arabidopsis by zooming into the intronic regions an order of magnitude deeper than in previous work. Our key findings include: (1) Intron-capture RNA-seq is a much more efficient approach to analyze intronic RNAs than total RNA-seq and mRNA-seq. (2) We identified three types of intronic RNAs, and found that the GC pattern differs significantly between the introns with and without intronic RNAs. (3) We detected many hidden elements in introns, including circular RNAs, splice junctions, and transcripts that have previously been overlooked. (4) The expression of these intronic RNAs varies during the time course of pathogen infection, which indicates that an unknown mechanism may exist for these RNAs. (5) We also demonstrated that most of intronic RNAs are detectable in both Arabidopsis and rice, suggesting that these non-coding molecules are conserved. Taken together, this work proposes an efficient strategy to analyze intronic RNAs, and provides an unprecedented view of this essential component in biological pathways.

Ni-Catalyzed Asymmetric Hydrogenation of α-Substituted α,ß-Unsaturated Phosphine Oxides/Phosphonates/Phosphoric Acids.

Efficient Ni/(S,S)-Ph-BPE-catalyzed asymmetric hydrogenation of α-substituted α,ß-unsaturated phosphine oxides/phosphonates/phosphoric acids has been successfully developed, and a wide range of chiral α-substituted phosphines hydrogenation products were obtained in generally high yields with excellent enantioselective control (92%-99% yields, 84%->99% ee). This method features a cheap transition metal nickel catalytic system, high functional group tolerance, wide substrate scope generality, and excellent enantioselectivity. A plausible catalytic cycle was proposed for this asymmetric hydrogenation according to the results of deuterium-labeling experiments.