ATAD3B is a mitophagy receptor mediating clearance of oxidative stress-induced damaged mitochondrial DNA.

Mitochondrial DNA (mtDNA) encodes several key components of respiratory chain complexes that produce cellular energy through oxidative phosphorylation. mtDNA is vulnerable to damage under various physiological stresses, especially oxidative stress. mtDNA damage leads to mitochondrial dysfunction, and dysfunctional mitochondria can be removed by mitophagy, an essential process in cellular homeostasis. However, how damaged mtDNA is selectively cleared from the cell, and how damaged mtDNA triggers mitophagy, remain mostly unknown. Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates. ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. Our findings uncover a new pathway to selectively remove damaged mtDNA and reveal that increasing ATAD3B activity is a potential therapeutic approach for mitochondrial diseases.

Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.

BACKGROUND: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. METHODS: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. RESULTS: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. CONCLUSIONS: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.

Rhodium-Catalyzed Asymmetric C-H Functionalization Reactions.

This review summarizes the advancements in rhodium-catalyzed asymmetric C-H functionalization reactions during the last two decades. Parallel to the rapidly developed palladium catalysis, rhodium catalysis has attracted extensive attention because of its unique reactivity and selectivity in asymmetric C-H functionalization reactions. In recent years, Rh-catalyzed asymmetric C-H functionalization reactions have been significantly developed in many respects, including catalyst design, reaction development, mechanistic investigation, and application in the synthesis of complex functional molecules. This review presents an explicit outline of catalysts and ligands, mechanism, the scope of coupling reagents, and applications.

Z-Retentive Asymmetric Allylic Substitution Reactions of Aldimine Esters under Ru/Cu Dual Catalysis.

Ru/Cu dual catalysis has been applied for Z-retentive asymmetric allylic substitution reactions of aldimine esters. This reaction provides an enantioselective synthesis of chiral Z-olefins in high yields (up to 91% yield) with excellent enantioselectivity (up to 98% ee) under mild conditions. The previously unreacted trisubstituted allylic electrophiles under Ir catalytic system are found to be compatible, affording the stereoretentive products in either Z- or E-form. Both linear and branched allylic electrophiles are suitable substrates with excellent reaction outcomes. Notably, Ru and Cu complexes are added in one-pot and simplifies the manipulation of this protocol and self-sorting phenomena could be observed in this Ru/Cu dual catalytic system.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Novel dominant and recessive variants in human ROBO1 cause distinct neurodevelopmental defects through different mechanisms.

The Roundabout (Robo) receptors, located on growth cones of neurons, induce axon repulsion in response to the extracellular ligand Slit. The Robo family of proteins controls midline crossing of commissural neurons during development in flies. Mono- and bi-allelic variants in human ROBO1 (HGNC: 10249) have been associated with incomplete penetrance and variable expressivity for a breath of phenotypes, including neurodevelopmental defects such as strabismus, pituitary defects, intellectual impairment, as well as defects in heart and kidney. Here, we report two novel ROBO1 variants associated with very distinct phenotypes. A homozygous missense p.S1522L variant in three affected siblings with nystagmus; and a monoallelic de novo p.D422G variant in a proband who presented with early-onset epileptic encephalopathy. We modeled these variants in Drosophila and first generated a null allele by inserting a CRIMIC T2A-GAL4 in an intron. Flies that lack robo1 exhibit reduced viability but have very severe midline crossing defects in the central nervous system. The fly wild-type cDNA driven by T2A-Gal4 partially rescues both defects. Overexpression of the human reference ROBO1 with T2A-GAL4 is toxic and reduces viability, whereas the recessive p.S1522L variant is less toxic, suggesting that it is a partial loss-of-function allele. In contrast, the dominant variant in fly robo1 (p.D413G) affects protein localization, impairs axonal guidance activity and induces mild phototransduction defects, suggesting that it is a neomorphic allele. In summary, our studies expand the phenotypic spectrum associated with ROBO1 variant alleles.

Site-Specific Anchoring a Luminescent Tag in a Protein with Non-Emissive Iridium(III) Complex.

Site-specific modification of proteins with synthetic fluorescent tag effectively improves the resolution of imaging, and such a labeling method with negligible three-dimensional structural perturbations and minimal impact on the biological functions of proteins is of high interest to dissect the high-resolution activities of biomolecules in complex systems. To this end, several non-emissive iridium(III) complexes [Ir(C-N)2 (H2 O)2 ]+ OTF- (C-N denotes various cyclometalated ligands) were designed and synthesized. These complexes were tested for attaching a protein by coordinating to H/X (HisMet, HisHis, and HisCys) that are separated by i and i+4 in α-helix. Replacement of the two labile water ligands in the iridium(III) complex by a protein HisHis pair increases the luminescent intensity up to over 100 folds. This labeling approach has been demonstrated in a highly specific and efficient manner in a number of proteins, and it is also feasible for labeling target proteins in cell lysates.

Novel intertypic recombination of Echovirus 11 in the Enterovirus species B.

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.

Glucose metabolism disorder related to follicular fluid exosomal miR-122-5p in cumulus cells of endometriosis patients.

MiR-122-5p, high expression in follicular fluid exosomes of patients with endometriosis, impairs the glucose metabolism function of cumulus cells and may further impair oocyte quality. Endometriosis (EMs) affects fertility in women of childbearing age in many ways. However, the mechanisms are complex, including the decrease in oocyte quality, which still needs to be studied. Exosomes, small vesicles responsible for intercellular information exchange, have been found to be involved in many biological events, such as follicle development and oocyte meiosis recovery. From the perspective of follicular fluid exosomes, this study aims to elucidate the mechanism of EMs-related oocyte quality decline. Follicular fluid was collected from three groups of women: the untreated EMs group (EMs_UT), the satisfactorily treated EMs group (EMs_ST) and the control group (Ctrl). Mouse cumulus oocyte complexes (COCs) were cocultured with exosomes extracted from follicular fluid during in vitro maturation. Oocyte quality and cumulus cell function were assessed. High-throughput sequencing of miRNA in exosomes was conducted. The function of differentially expressed miRNAs was studied by using SVOG cells (human ovarian granulosa cell line) transfected with miRNA mimic and inhibitor. Our date suggest that follicular fluid exosomes from patients with untreated EMs reduce the maturation rate and damage the quality of mouse oocytes. MiR-122-5p, overexpressed in untreated EMs, inhibits the translation of key aldolase enzymes related to glucose metabolism and partially impairs cumulus cells of endometriosis patients.

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 µg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 µg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

Developing a Predictive Model for Minimal or Mild Endometriosis as a Clinical Screening Tool in Infertile Women: Uterosacral Tenderness as a Key Predictor.

STUDY OBJECTIVE: To develop a noninvasive predictive model based on patients with infertility for identifying minimal or mild endometriosis. DESIGN: A retrospective cohort study. SETTING: This study was conducted at a tertiary referral center. PATIENTS: A total of consecutive 1365 patients with infertility who underwent laparoscopy between January 2013 and August 2020 were divided into a training set (n = 910) for developing the predictive model and a validation set (n = 455) to confirm the model's prediction efficiency. The patients were randomly assigned in a 2:1 ratio. INTERVENTIONS: Sensitivities, specificities, area under the curve, the Hosmer-Lemeshow goodness of fit test, Net Reclassification Improvement index, and Integrated Discrimination Improvement index were evaluated in the training set to select the optimum model. In the validation set, the model's discriminations, calibrations, and clinical use were tested for validation. MEASUREMENTS AND MAIN RESULTS: In the training set, there were 587 patients with minimal or mild endometriosis and 323 patients without endometriosis. The combination of clinical parameters in the model was evaluated for both statistical and clinical significance. The best-performing model ultimately included body mass index, dysmenorrhea, dyspareunia, uterosacral tenderness, and serum cancer antigen 125 (CA-125). The nomogram based on this model demonstrated sensitivities of 87.7% and 93.3%, specificities of 68.6% and 66.4%, and area under the curve of 0.84 (95% confidence interval 0.81-0.87) and 0.85 (95% confidence interval 0.80-0.89) for the training and validation sets, respectively. Calibration curves and decision curve analyses also indicated that the model had good calibration and clinical value. Uterosacral tenderness emerged as the most valuable predictor. CONCLUSION: This study successfully developed a predictive model with high accuracy in identifying infertile women with minimal or mild endometriosis based on clinical characteristics, signs, and cost-effective blood tests. This model would assist clinicians in screening infertile women for minimal or mild endometriosis, thereby facilitating early diagnosis and treatment.

Prophylactic use of vancomycin powder on postoperative infection after total joint arthroplasty.

OBJECTIVE: By reviewing the literature analyzing vancomycin powder for preventive surgery, the effect of this method on reducing the infection rate after TJA was systematically evaluated to provide a basis for future clinical work. METHODS: Using PubMed, Medline, Elsevier, and CNKI, with the following mesh words: "vancomycin", "local / intraoperative / topical / intrawound", "TJA", "TKA", "THA", "total joint arthroplasty", "total knee arthroplasty", "total hip arthroplasty", "infection", and "SSI", to search for case-control research papers on the impact of prophylactic application of vancomycin powder on the incidence of postoperative infection, we compared the overall infection rate in the literature by using RevMan 5.3 meta-analysis software and analyzed the impact of vancomycin on the infection rate of different parts and types of TJA according to different subgroups. RESULTS: A total of 22 qualified studies were selected; twenty-five studies compared the effect of prophylactic use of vancomycin powder on infection rates after TJA. There were 23,363 cases in total, including 9545 cases in the vancomycin group and 13,818 cases in the control group. The results of the meta-analysis showed that the possibility of postoperative infection after prophylactic use of vancomycin powder was significantly lower than that without vancomycin risk ratio: 0.38 [0.23,0.59], P < 0.01). However, a meta-analysis of randomized controlled trials (RCTs) showed no significant effect of vancomycin on postoperative infection (P = 0.52). CONCLUSION: Based on the retrospective studies, local prophylactic use of vancomycin powder in TJA can significantly reduce the incidence of postoperative infection. High-quality RCTs should be carried out to further evaluate these results.

Alkaloids from Fritillaria przewalskii Bulbs and Their Anti-Alzheimer's Disease Activities.

Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1 µM, AChE activity with IC50 value of 6.9 µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6 µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.

Cross-cultural translation and validation of the Chinese version Distress Tolerance Scale for adolescents with chronic physical disease.

INTRODUCTION: Chronic physical disease (CPD) makes life filled with many negative events in adolescents, but not all adolescents experiencing negative life events proceed to develop emotional distress, only those with low emotional distress tolerance (EDT). A valid and reliable scale to measure EDT in CPD adolescents is important for caring for their emotional distress. Therefore, the purpose of this study is to translate the 15-item English version Distress Tolerance Scale (DTS) into a Chinese version and then validate the scale for measuring EDT of adolescents with CPD. METHODS: The 15-item English version DTS was translated into a Chinese version using the translation guidelines for cross-cultural research. Two cohorts of adolescents with CPD were recruited from four hospitals in southern Taiwan, with the first cohort including 124 adolescents with CPD employed to conduct exploratory factor analysis, corrected item-total correlation and reliability testing, while the second cohort, consisting of 238 adolescents with CPD, was utilized to examine confirmatory factor analysis and concurrent validity. RESULTS: The two-factor nine-item Chinese version DTS for Adolescents with CPD (C-DTS-A) was developed. Lower scores of the C-DTS-A were significantly associated with higher diabetes distress, poorer self-management, and worse glycaemic control; their correlation coefficients sequentially were -.40, .17 and -.23. Cronbach's α and the test-retest reliability of the two-factor C-DTS-A ranged from .81 to .87 and from .79 to .89, respectively. CONCLUSION: The two-factor nine-item C-DTS-A with good cross-cultural translation quality was a reliable and valid scale to assess EDT for adolescents with CPD.

Sulfur in Waste-Free Sustainable Synthesis: Advancing Carbon-Carbon Coupling Techniques.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.

Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

Epigenetic regulation of papillary thyroid carcinoma by long non-coding RNAs.

Thyroid cancer is the most common primary endocrine malignancy with papillary thyroid carcinoma (PTC) its most common subtype. The jump in diagnoses over last many years has prompted re-assessment of molecularly targeted therapies and the discovery of novel targets. Long non-coding RNAs (lncRNAs) are increasingly being assessed for their expression in various PTC models. Interestingly, in addition to cell line models, a large proportion of the reported studies have evaluated lncRNA levels in PTC patient samples providing an immediate clinical relevance of their findings. While most lncRNAs either promote or suppress PTC pathogenesis, data on individual lncRNAs is not very clear. As expected, lncRNAs function in PTC through sponging of microRNAs as well as modulation of several signaling pathways. The process of epithelial-mesenchymal transition and the PI3K/Akt and wnt signaling pathways have emerged as the primary targets of lncRNAs in PTC. This comprehensive review discusses all the information that is available on lncRNAs in PTC, ranging from in vitro and in vivo findings to the possible role of lncRNAs as diagnostic and/or prognostic biomarkers.

Enantioselective Dearomatization of Indoles via SmI2-Mediated Intermolecular Reductive Coupling with Ketones.

Samarium diiodide (SmI2) mediated reductive coupling reactions are powerful methods for the construction of carbon-carbon bond in organic synthesis. Despite the extensive development in recent decades, successful examples of the corresponding asymmetric reactions remained scarce, probably due to the involvement of highly reactive radical intermediates. In this Article, we report an enantioselective dearomatization of indoles via SmI2-mediated intermolecular reductive coupling with ketones. The utilization of samarium reductant supported by chiral tridentate aminodiol ligands allows the facile synthesis of indoline molecules bearing two contiguous stereogenic centers in high yields (up to 99%) and stereoselectivity (up to 99:1 er and >20:1 dr). Combined experimental and computational investigations suggested that parallel single-electron transfer to each substrate from the chiral samarium reductant allows the radical-radical recombination in an enantioselective manner, which is a unique mechanistic scenario in SmI2-mediated reductive coupling reactions.

Asymmetric Dearomatization of Indoles with Azodicarboxylates via Cascade Electrophilic Amination/Aza-Prins Cyclization/Phenonium-like Rearrangement.

Herein, we report a highly efficient synthesis of enantioenriched aza-[3.3.1]-bicyclic enamines and ketones, a class of structural cores in many natural products, via asymmetric dearomatization of indoles with azodicarboxylates. The reaction is initiated by electrophilic amination and followed by aza-Prins cyclization/phenonium-like rearrangement. A newly developed fluorine-containing chiral phosphoric acid displays excellent activity in promoting this cascade reaction. The absence or presence of water as the additive directs the reaction pathway toward either enamine or ketone products in high yields (up to 93%) with high enantiopurity (up to 98% ee). Comprehensive density functional theory (DFT) calculations reveal the energy profile of the reaction and the origins of enantioselectivity and water-induced chemoselectivity.

Enantioselective Synthesis of Cyclobutane Derivatives via Cascade Asymmetric Allylic Etherification/[2 + 2] Photocycloaddition.

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.