Cotton SNARE complex component GhSYP121 regulates salicylic acid signaling during defense against Verticillium dahliae.

Syntaxin of plant (SYP) plays a crucial role in SNARE-mediated membrane trafficking during endocytic and secretory pathways, contributing to the regulation and execution of plant immunity against pathogens. Verticillium wilt is among the most destructive fungal diseases affecting cotton worldwide. However, information regarding SYP family genes in cotton is scarce. Through genome-wide identification and transcriptome profiling, we identified GhSYP121, a Qa SNARE gene in Gossypium hirsutum. GhSYP121 is notably induced by Verticillium dahliae, the causal agent of Verticillium wilt in cotton, and acts as a negative regulator of defense against V. dahliae. This is evidenced by the reduced resistance of GhSYP121-deficient cotton and the increased susceptibility of GhSYP121-overexpressing lines. Furthermore, the activation of the salicylic acid (SA) pathway by V. dahliae is inversely correlated with the expression level of GhSYP121. GhSYP121 interacts with its cognate SNARE component, GhSNAP33, which is required for the penetration resistance against V. dahliae in cotton. Collectively, GhSYP121, as a member of the cotton SNARE complex, is involved in regulating the SA pathway during plant defense against V. dahliae. This finding enhances our understanding of the potential role of GhSYP121 in these distinct pathways that contribute to plant defense against V. dahliae infection.

Identification of rare variants in PTCH2 associated with non-syndromic orofacial clefts.

Orofacial clefts (OFCs) represent the most prevalent congenital craniofacial anomalies, significantly impacting patients' appearance, oral function, and psychological well-being. Among these, non-syndromic OFCs (NSOFCs) are the most predominant type, with the etiology attributed to a combination of genetic and environmental factors. Rare variants of key genes involved in craniofacial development-related signaling pathway are crucial in the occurrence of NSOFCs, and our recent studies have identified PTCH1, a receptor-coding gene in the Hedgehog signaling pathway, as a causative gene for NSOFCs. However, the role of PTCH2, the paralog of PTCH1, in pathogenesis of NSOFCs remains unclear. Here, we perform whole-exome sequencing to explore the genetic basis of 144 sporadic NSOFC patients. We identify five heterozygous variants of PTCH2 in four patients: p.L104P, p.A131G, p.R557H, p.I927S, and p.V978D, with the latter two co-occurring in a single patient. These variants, all proven to be rare through multiple genomic databases, with p.I927S and p.V978D being novel variants and previously unreported. Sequence alignment suggests that these affected amino acids are evolutionarily conserved across vertebrates. Utilizing predictive structural modeling tools such as AlphaFold and SWISS-MODEL, we propose that these variants may disrupt the protein's structure and function. In summary, our findings suggest that PTCH2 may be a novel candidate gene predicted to be associated with NSOFCs, thereby broadening the spectrum of causative genes implicated in the craniofacial anomalies.

Long-term immune response to Omicron-specific mRNA vaccination in mice, hamsters, and nonhuman primates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (such as BQ.1, XBB and the latest variants, including XBB.1.16, EG.5, and BA.2.86), as the dominant variants, currently account for almost all new infections in the world due to their high transmissibility and immune escape ability. Omicron-specific mRNA vaccines showed great potential to protect against Omicron infections. However, whether the vaccine could provide long-term protection is unknown. Toward this goal, we evaluated the immunogenicity of a preclinical Omicron (BA.1)-specific mRNA vaccine (SOmicron-6P) in different animal models. SOmicron-6P induced the highest levels of antibody titers at 1-2 weeks in different animals after the second dose. Even 9 months after the immunization, we observed modest neutralizing activity against Omicron subvariants in macaques. In addition, immunological memory cells can be rapidly reactivated upon stimulation. SOmicron-6P at concentrations higher than 10 µg effectively protected hamsters from BA.1 challenge 253 days after the first immunization, which could be attributed to the reactivation of immune systems. In addition, the toxicity tests conducted in rats revealed a highly favorable biosafety profile for SOmicron-6P, even at high dosages. Our data suggest that the Omicron-specific mRNA vaccine is highly effective and safe in animal models and provides long-term immunologic protection against SARS-CoV-2 Omicron infections.

Influence of presurgical nasoalveolar molding (PNAM) treatment in maxillary dental arch width and nasolabial symmetry in patients with unilateral complete cleft lip and palate.

Unilateral complete cleft lip and palate (UCCLP) is one of the most severe clinical subphenotypes among nonsyndromic cleft lip and/or palate (NSCL/P), that complicates surgical repair operations. Presurgical nasoalveolar molding (PNAM) is a technique used to reshape the nose, lip and alveolar bone of infants with UCCLP before surgery (the modified Mohler rotation advancement cheiloplasty and two flap palatoplasty), with the potential to facilitate surgical repair. However, the effectiveness of PNAM treatment is still a matter of debate. In this paper, the 3Shape scanning system and 3dMD stereophotography were used to assess the short-term and long-term effects of PNAM treatment on the dental arch morphology and nasolabial features of patients with UCCLP, respectively. The findings indicated that PNAM treatment negatively affects both short-term and long-term dental arch shape compared to the treatment without PNAM, particularly in terms of limiting the transverse width of the maxillary canine-to-midline. Regarding the nasal and labial symmetry, PNAM improves the symmetry of the nasal alae in patients over 7 years old and the symmetry of the lip in patients under 7 years old. Moreover, UCCLP patients who received PNAM treatment exhibited a shorter and wider shape of the nostril on the cleft side compared to those without PNAM treatment. In clinical practice, the multidisciplinary team should carefully consider the advantages and disadvantages of the outcomes of PNAM treatment when treating infants with cleft lip and palate.

Establishment of a novel classification system for alveolar morphology in infants with unilateral complete cleft lip and palate.

OBJECTIVES: Unilateral complete cleft lip and palate (UCCLP) is one of the most severe clinical subtypes among cleft lip and palate (CLP), making repair surgery and subsequent orthodontic treatment particularly challenging. Presurgical nasoalveolar molding (PNAM) has shown conflicting and heterogeneous results in the treatment of UCCLP patients, raising questions about whether the diversity in alveolar anatomical morphology among these patients plays a role in the effectiveness of PNAM treatment. MATERIALS AND METHODS: We collected 90 digital maxillary models of infants with UCCLP and performed mathematical clustering analysis, including principal component analysis (PCA), decision tree modeling, and area under the ROC Curve (AUC) analysis, to classify alveolar morphology and identify key measurements. We also conducted clinical evaluations to assess the association between the alveolar morphology and CLP treatment outcomes. RESULTS: Using mathematical clustering analysis, we classified the alveolar morphology into three distinct types: average form, horizontal form, and longitudinal form. The decision tree model, AUC analysis, and comparison analysis revealed that four measurements (Trans ACG-ACL, ML length, MG length and Inc length) were essential for clustering the alveolar morphology of infants with UCCLP. Furthermore, the blinded clinical evaluation indicated that UCCLP patients with alveolar segments of horizontal form had the lowest treatment outcomes. CONCLUSION: Overall, our findings establish a novel quantitative classification system for the morphology of alveolar bone in infants with UCCLP and suggest that this classification may be associated with the outcomes of CLP treatment. CLINICAL RELEVANCE: The multidisciplinary CLP team should thoroughly evaluate and classify the specific alveolar morphology when administering PNAM to infants with UCCLP.

ERK1-mediated immunomodulation of mesenchymal stem cells ameliorates inflammatory disorders.

Immune system disorders, especially T cell disorders, are important therapeutic targets of mesenchymal stem cells (MSCs) in many autoimmune diseases (ADs). Although extracellular regulated protein kinases (ERKs) play a role in MSC therapy by promoting T cell apoptosis, the mechanism remains unclear. Our findings indicate that ERK1-/- bone marrow MSCs (BMMSCs), but not ERK2-/- BMMSCs, failed to promote T cell apoptosis due to incapacity to activate the ETS2/AURKA/NF-κB/Fas/MCP-1 cascade. Moreover, ERK1-/- BMMSCs were unable to upregulate regulatory T cells and suppress T helper 17 cells. Licochalcone A (LA), which promotes ERK pathway activation, enhanced the therapeutic efficacy of MSC therapy in ulcerative colitis and collagen-induced arthritis mice. Our findings suggest that ERK1, but not ERK2, plays a crucial role in regulating T cells in MSCs. LA-treated MSCs provide a strategy to improve the efficacy of MSC-based treatments for ADs.

Genome-Wide Identification and Expression Analysis of RLCK-VII Subfamily Genes Reveal Their Roles in Stress Responses of Upland Cotton.

Receptor-like cytoplasmic kinase VII (RLCK-VII) subfamily members are vital players in plant innate immunity and are also involved in plant development and abiotic stress tolerance. As a widely cultivated textile crop, upland cotton (Gossypium hirsutum) attaches great importance to the cotton industry worldwide. To obtain details of the composition, phylogeny, and putative function of RLCK-VII genes in upland cotton, genome-wide identification, evolutionary event analysis, and expression pattern examination of RLCK-VII subfamily genes in G. hirsutum were performed. There are 129 RLCK-VII members in upland cotton (GhRLCKs) and they were divided into nine groups based on their phylogenetic relationships. The gene structure and sequence features are relatively conserved within each group, which were divided based on their phylogenetic relationships, and consistent with those in Arabidopsis. The phylogenetic analysis results showed that RLCK-VII subfamily genes evolved in plants before the speciation of Arabidopsis and cotton, and segmental duplication was the major factor that caused the expansion of GhRLCKs. The diverse expression patterns of GhRLCKs in response to abiotic stresses (temperature, salt, and drought) and V. dahliae infection were observed. The candidates that may be involved in cotton's response to these stresses are highlighted. GhRLCK7 (GhRLCK7A and D), which is notably induced by V. dahliae infection, was demonstrated to positively regulate cotton defense against V. dahliae by the loss-of-function assay in cotton. These findings shed light on the details of the RLCK-VII subfamily in cotton and provide a scaffold for the further function elucidation and application of GhRLCKs for the germplasm innovation of cotton.

GhERF.B4-15D: A Member of ERF Subfamily B4 Group Positively Regulates the Resistance against Verticillium dahliae in Upland Cotton.

Verticillium wilt is a fungal disease in upland cotton and exerts a significant effect on growth and potential productivity. This disease is mainly caused by V. dahliae Kleb. Ethylene response factor (ERF) is one of the superfamilies of transcription factors that is involved in the development and environmental adaption of crops. A total of 30 ERF.B4 group members were detected in upland cotton and divided into 6 subgroups. Gene structures, conserved motifs, and domain analysis revealed that members in each subgroup are highly conserved. Further, the 30 GhERF.B4 group members were distributed on 18 chromosomes, and 36 gene synteny relationships were found among them. GhERF.B4 genes were ubiquitously expressed in various tissues and developmental stages of cotton. Amongst them, GhERF.B4-15D was predominantly expressed in roots, and its expression was induced by V. dahliae infection. In addition, GhERF.B4-15D responded to methyl jasmonate (MeJA), methyl salicylate (MeSA), and ethylene (ET) phytohormones. It was also found that the V. dahliae resistance was enhanced due to overexpression of GhERF.B4-15D in Arabidopsis thaliana. On the contrary, interference of GhERF.B4-15D by virus-induced gene silencing (VIGS) technology decreased the V. dahliae resistance level in upland cotton. The subcellular localization experiment showed that GhERF.B4-15D was located in the nucleus. Yeast two-hybrid (Y2H) and luciferase complementation (LUC) approaches demonstrated that GhERF.B4-15D interacted with GhDREB1B. Additionally, the V. dahliae resistance was significantly decreased in GhDREB1B knockdowns. Our results showed that GhERF.B4-15D plays a role during V. dahliae infection in cotton.

Pyroptosis patterns influence the clinical outcome and immune microenvironment characterization in HPV-positive head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor with diverse molecular pathological profiles. Recent studies have suggested the vital role of pyroptosis in tumor microenvironment. However, the expression patterns of pyroptosis in HPV-positive HNSCC are still unclear. METHODS: Unsupervised clustering analysis was used to identify the pyroptosis patterns based on the RNA-sequencing data of 27 pyroptosis-related genes (PRGs) in HPV-positive HNSCC samples. Random forest classifier and artificial neural network were performed to screen the signature genes associated with pyroptosis, which were verified in two independent external cohorts and qRT-PCR experiment. Principal component analysis was used to develop a scoring system, namely Pyroscore. RESULTS: The expression variations of 27 PRGs in HPV-positive HNSCC patients were analyzed from genomic and transcriptional domains. Two pyroptosis-related subtypes with distinct clinical outcomes, enrichment pathways and immune characteristics were identified. Next, six signature genes (GZMB, LAG3, NKG7, PRF1, GZMA and GZMH) associated with pyroptosis were selected for prognostic prediction. Further, a Pyroscore system was constructed to determine the level of pyroptosis in each patient. A low Pyroscore was featured by better survival time, increased immune cell infiltration, higher expression of immune checkpoint molecules and T cell-inflamed genes, as well as elevated mutational burden. The Pyroscore was also related to the sensitivity of chemotherapeutic agents. CONCLUSIONS: The pyroptosis-related signature genes and Pyroscore system may be reliable predictors of prognosis and serve as mediators of immune microenvironment in patients with HPV-positive HNSCC.

Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion.

The Lassa virus (LASV) is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 â€‹N-glycosylation sites. All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. Meanwhile, the pseudotype virus bearing GPCN79Q was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence. Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection.

Identification of rare loss-of-function variants in FAM3B associated with non-syndromic orofacial clefts.

Orofacial clefts (OFCs) are the most common congenital craniofacial disorders and cause serious problems with the appearance, orofacial function and mental health of the patients. The fibroblast growth factor (FGF) signaling pathway is critical for several aspects of craniofacial development and loss-of-function mutations of coding genes for multiple FGFs and FGFRs can lead to OFCs. We recently characterized FAM3B as a novel ligand of FGF signaling, which, through binding to FGFRs and activating downstream ERK, regulates craniofacial development in Xenopus. In this study, we identify two rare variants in FAM3B (p.Q61R and p.D128G) via target region sequencing of FAM3B on 144 unrelated sporadic patients with non-syndromic OFCs (NSOFCs). Bioinformatic analysis predict that these two variants are likely to be damaging and biochemical experiments show that these two variants weaken the FGF ligand activity of FAM3B by decreasing its expression and thus secretion. In summary, our results indicate that FAM3B is a novel candidate gene for NSOFCs in humans.

Reductive Deuteration of Acyl Chlorides for the Synthesis of α,α-Dideuterio Alcohols Using SmI2 and D2O.

The synthesis of α,α-dideuterio alcohols has been achieved via single electron transfer reductive deuteration of acyl chlorides using SmI2 and D2O. This method is distinguished by its remarkable functional group tolerance and exquisite deuterium incorporation, which has also been applied to the synthesis of valuable deuterated agrochemicals and their building blocks.

Analysis of PAT1 subfamily members in the GRAS family of upland cotton and functional characterization of GhSCL13-2A in Verticillium dahliae resistance.

KEY MESSAGE: GhSCL13-2A, a member of the PAT1 subfamily in the GRAS family, positively regulates cotton resistance to Verticillium dahliae by mediating the jasmonic acid and salicylic acid signaling pathways and accumulation of reactive oxygen species. Verticillium wilt (VW) is a devastating disease of upland cotton (Gossypium hirsutum) that is primarily caused by the soil-borne fungus Verticillium dahliae. Scarecrow-like (SCL) proteins are known to be involved in plant abiotic and biotic stress responses, but their roles in cotton defense responses are still unclear. In this study, a total of 25 GhPAT1 subfamily members in the GRAS family were identified in upland cotton. Gene organization and protein domain analysis showed that GhPAT1 members were highly conserved. GhPAT1 genes were widely expressed in various tissues and at multiple developmental stages, and they were responsive to jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) signals. Furthermore, GhSCL13-2A was induced by V. dahliae infection. V. dahliae resistance was enhanced in Arabidopsis thaliana by ectopic overexpression of GhSCL13-2A, whereas cotton GhSCL13-2A knockdowns showed increased susceptibility. Levels of reactive oxygen species (ROS) and JA were also increased and SA content was decreased in GhSCL13-2A knockdowns. At the gene expression level, PR genes and SA signaling marker genes were down-regulated and JA signaling marker genes were upregulated in GhSCL13-2A knockdowns. GhSCL13-2A was shown to be localized to the cell membrane and the nucleus. Yeast two-hybrid and luciferase complementation assays indicated that GhSCL13-2A interacted with GhERF5. In Arabidopsis, V. dahliae resistance was enhanced by GhERF5 overexpression; in cotton, resistance was reduced in GhERF5 knockdowns. This study revealed a positive role of GhSCL13-2A in V. dahliae resistance, establishing it as a strong candidate gene for future breeding of V. dahliae-resistant cotton cultivars.

The clinical efficacy of periodontally accelerated osteogenic orthodontics in patients with bone fenestration and dehiscence: a retrospective study.

PURPOSE: The objective of the study was to explore the effect of periodontally accelerated osteogenic orthodontics (PAOO) in orthodontic patients with bone dehiscence and fenestration in the anterior alveolar region of the mandible. METHODS: A retrospective study was performed in 42 patients with bone dehiscence and fenestrations in the anterior alveolar region of the mandible who underwent the PAOO technique. The bleeding index (BI), probing depth (PD), keratinized gingiva width (KGW), gingival recession level (GRL), and gingival phenotype were recorded and assessed at baseline and 6 and 12 months postoperatively. Cone-beam computerized tomography was used to measure bone volume in terms of root length (RL), horizontal bone thickness at different levels, and vertical bone height at baseline and 6 months and 12 months after surgery. RESULTS: The sample was composed of 42 patients (22 males and 20 females; mean age, aged 25.6 ± 4.8 years) with 81 teeth showing dehiscence/fenestrations and 36 sites presenting gingival recessions. There was no significant difference in BI, PD, or KGW (between baseline and 6 or 12 months postoperatively) based on the clinical evaluations (P > 0.05). Gingival recession sites demonstrated a significant reduction in the GRL after surgery (P < 0.05). Furthermore, the proportion of teeth with a thick gingival phenotype increased from 33.61% at baseline to 53.13% at the end of the follow-up. In addition, the bone thickness measurements at the mid-root and crestal levels were markedly increased compared with the baseline values (P < 0.05), although the increase in thickness at the apical level was not statistically significant (P > 0.05). CONCLUSIONS: Within the limitations of the study, the results show that the PAOO technique is beneficial to periodontal conditions in terms of soft and hard tissue augmentation. The PAOO procedure may represent a safe and efficient treatment for orthodontic patients with bone dehiscence and fenestration. TRIAL REGISTRATION: This study was approved by the ethics committee of the stomatological hospital affiliated with Xi'an Jiaotong University (xjkqll [2019] No. 016) and registered in the Chinese Clinical Trial Registry (ChiCTR2100053092).

Screening and Identification of Lassa Virus Entry Inhibitors from a Fragment-Based Drug Discovery Library.

Lassa virus (LASV) is a highly pathogenic virus that is categorized as a biosafety level-4 pathogen. Currently, there are no approved drugs or vaccines specific to LASV. In this study, high-throughput screening of a fragment-based drug discovery library was performed against LASV entry using a pseudotype virus bearing the LASV envelope glycoprotein complex (GPC). Two compounds, F1920 and F1965, were identified as LASV entry inhibitors that block GPC-mediated membrane fusion. Analysis of adaptive mutants demonstrated that the transient mutants L442F and I445S, as well as the constant mutant F446L, were located on the same side on the transmembrane domain of the subunit GP2 of GPC, and all the mutants conferred resistance to both F1920 and F1965. Furthermore, F1920 antiviral activity extended to other highly pathogenic mammarenaviruses, whereas F1965 was LASV-specific. Our study showed that both F1920 and F1965 provide a potential backbone for the development of lead drugs for preventing LASV infection.

A392V and R945X mutations cause orofacial clefts via impairing PTCH1 function.

The Hedgehog (HH) signaling plays key roles in embryogenesis and organogenesis, and its dysfunction causes a variety of human birth defects. Orofacial cleft (OFC) is one of the most common congenital craniofacial defects, and its etiology is closely related to mutations in multiple components in the HH pathway, including the PTCH1 receptor. A quantity of PTCH1 variants have been associated with OFC, but the pathogenicity and underlying mechanism of these variants have not been functionally validated. In our previous studies, we identified two PTCH1 variants (A392V and R945X) in two families with hereditary OFC. Here we explore the functional consequences of these two variants. In zebrafish embryos, microinjection of wild type PTCH1 mRNA causes curved body axis and craniofacial anomalies. In contrast, microinjection of A392V and R945X PTCH1 mRNAs results in much milder phenotypes, suggesting these two variants are loss-of-function mutations. In mammalian cells, A392V and R945X mutations reverse the inhibitory effect of PTCH1 on HH signaling. Biochemically, the two mutants PTCH1 show lower expression levels and shortened half-life, indicting these mutations decrease the stability of PTCH1. A392V and R945X mutations also appear to cause PTCH1 to localize away from vesicles. Taken together, our findings indicate that A392V and R945X variants are loss-of-function mutations that disrupt the function of PTCH1 and thus cause dysregulation of HH signaling, leading to the pathogenesis of OFC.

Porphyrin-based conjugated organic polymer with dual metal sites for highly active and selective visible-light-driven reduction of CO2 to CO.

A porphyrin-based conjugated organic polymer (COP) was constructed from 5,10,15,20-tetrakis(4-bromophenyl)porphyrin copper (CuTBPP) and 5,5'-bis-ethynyl-2,2'-bipyridine (BPY) via Sonogashira coupling. Its complex Co/CuTBPP-BPY-COP (with dual metal sites composed of copper porphyrin and a cobalt BPY unit) was prepared by coordination with Co2+. All of the prepared CuTBPP-BPY-COP and Co/CuTBPP-BPY-COP compounds exhibited excellent photocatalytic performance toward CO2 reduction under visible-light irradiation without another sacrificial reagent but only H2O. Co/CuTBPP-BPY-COP (dual metal sites) exhibited better photocatalytic activity than CuTBPP-BPY-COP (a single metal site). Co/CuTBPP-BPY-COP retained a higher photocatalysis capacity for CO2 reduction after 10 consecutive cycles. The total quantity of CO product was 263.2 µmol g-1 after 10 h of irradiation. Theoretical studies indicate that introducing Co metal centers and nitro groups are more favorable for the photoreduction catalysis of CO2 compared with that using CuTBPP-BPY-COP.

Cu Nanoparticles Modified Step-Scheme Cu2O/WO3 Heterojunction Nanoflakes for Visible-Light-Driven Conversion of CO2 to CH4.

In this study, Cu and Cu2O hybrid nanoparticles were synthesized onto the WO3 nanoflake film using a one-step electrodeposition method. The critical advance is the use of a heterojunction consisting of WO3 flakes and Cu2O as an innovative stack design, thereby achieving excellent performance for CO2 photoreduction with water vapor under visible light irradiation. Notably, with the modified Cu nanoparticles, the selectivity of CH4 increased from nearly 0% to 96.7%, while that of CO fell down from 94.5% to 0%. The yields of CH4, H2 and O2 reached 2.43, 0.32 and 3.45 mmol/gcat after 24 h of visible light irradiation, respectively. The boosted photocatalytic performance primarily originated from effective charge-transfer in the heterojunction and acceleration of electron-proton transfer in the presence of Cu nanoparticles. The S-scheme charge transfer mode was further proposed by the in situ-XPS measurement. In this regard, the heterojunction construction showed great significance in the design of efficient catalysts for CO2 photoreduction application.

One-Pot Sequential Hydrogen Isotope Exchange/Reductive Deuteration for the Preparation of α,ß-Deuterated Alcohols using Deuterium Oxide.

An efficient one-pot sequential hydrogen isotope exchange (HIE)/reductive deuteration approach was developed for the preparation of α,ß-deuterated alcohols using ketones as the precursors. The HIE step can also be used for the synthesis of α-deuterated ketones. This method has been applied in the synthesis of four deuterated drug and MS internal standards.