DDAH1 promotes neurogenesis and neural repair in cerebral ischemia.

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

Bioinspired Collective Total Synthesis of (±)-Rhynchines A-E.

Herein, we present the first racemic total synthesis of the structurally complex monoterpene indole alkaloids rhynchines A-E, starting from commercially available methyl nicotinate and 3-(2-bromoethyl)-1H-indole. The success of our synthesis is attributed to the utilization of a bioinspired synthetic strategy, which facilitated the rapid construction of the pentacyclic core skeleton of the target molecules through biomimetic skeletal rearrangement and late-stage C-H oxidative cyclization. Additionally, silica-gel-promoted tautomerization played a crucial role as a strategic element in the chemical synthesis of rhynchines A and B.

Bioinspired Total Synthesis of Cephalotaxus Diterpenoids and Their Structural Analogues.

Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one-carbon introduction and ring expansion operations, we have successfully converted cephalotane-type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid-type C19 norditerpenoids and intact cephalotane-type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13-oxo-cephinoid H, 7-oxo-cephinoid H, fortalpinoid C, 7-epi-fortalpinoid C, cephanolide E, and 13-epi-cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between ß-oxo esters and ß-substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family.

Reduced Volume Expansion of Micron-Sized SiOx via Closed-Nanopore Structure Constructed by Mg-Induced Elemental Segregation.

The inherently huge volume expansion during Li uptake has hindered the use of Si-based anodes in high-energy lithium-ion batteries. While some pore-forming and nano-architecting strategies show promises to effectively buffer the volume change, other parameters essential for practical electrode fabrication, such as compaction density, are often compromised. Here we propose a new in situ Mg doping strategy to form closed-nanopore structure into a micron-sized SiOx particle at a high bulk density. The doped Mg atoms promote the segregation of O, so that high-density magnesium silicates form to generate closed nanopores. By altering the mass content of Mg dopant, the average radii (ranged from 5.4 to 9.7 nm) and porosities (ranged from 1.4 % to 15.9 %) of the closed pores are precisely adjustable, which accounts for volume expansion of SiOx from 77.8 % to 22.2 % at the minimum. Benefited from the small volume variation, the Mg-doped micron-SiOx anode demonstrates improved Li storage performance towards realization of a 700-(dis)charge-cycle, 11-Ah-pouch-type cell at a capacity retention of >80 %. This work offers insights into reasonable design of the internal structure of micron-sized SiOx and other materials that undergo conversion or alloying reactions with drastic volume change, to enable high-energy batteries with stable electrochemistry.

Cryoprotective effect of soluble soybean polysaccharides and enzymatic hydrolysates on the myofibrillar protein of Nemipterus virgatus surimi.

Cryoprotective effect and potential mechanism of soluble soybean polysaccharides (SSPS) and enzymatic hydrolysates on surimi was investigated. After hydrolysis, the molecular weight of SSPS significantly decreased, and the hydrolysates prepared by endo-polygalacturonase (EPG-SSPS) was the lowest (154 kDa). Infrared spectrum analysis revealed that enzymatic hydrolysis didn't alter the functional groups of SSPS, but it did augment the exposure to hydroxyl groups. Surimi containing 5 % EPG-SSPS had the lowest freezable water after 20 days of frozen storage. Furthermore, the 5 % EPG-SSPS group manifested the highest metrics in total sulfhydryl (8.0 × 10-5 mol/g), active sulfhydryl content (6.7 × 10-5 mol/g), Ca2+-ATPase activity, and exhibited the lowest level in carbonyl content, surface hydrophobicity (153 µg). Notably, the 5 % EPG-SSPS maintained the stability of protein structure. Conclusively, SSPS enzymatic hydrolysate using endo-polygalacturonase imparted superior cryoprotective effect on the myofibrillar protein of surimi, and the mechanism might be a decrease in molecular weight and exposure of hydroxyl groups.

Development of a spiropyran-assisted cellulose aerogel with switchable wettability as oil sorbent for oil spill cleanup.

This research presents the successful development and optimization of a spiropyran-assisted cellulose aerogel (CNF-SP) aerogel with UV-induced switchable wettability, and the evaluation of its performance as an effective oil sorbent for oil spill cleanup. The aerogel initially exhibited strong hydrophobicity (124°) and showed UV-induced switchable wettability due to the photo-response structure of spiropyran. Upon UV irradiation, the hydrophobicity of the aerogel could be switched to hydrophilicity (31°), while visible light irradiation could restore its hydrophobicity. The three-dimensional (3D) porous structure of the CNF-SP aerogel combined with the hydrophobic properties of spiropyranol led to its great oil adsorption performance (27-30 g/g of oil adsorption ratio). The central composite design (CCD) was applied to optimize the aerogel and investigate the effects of raw material ratio (i.e., carboxymethyl cellulose, carboxyethyl spiropyran, polyvinyl alcohol, and nano zinc oxide) on the oil sorption performance of the aerogel. The optimized CNF-SP aerogel demonstrated a high oil sorption efficiency, particularly in acid and cold environments. Moreover, the switchable function indicated that the aerogel exhibited reusability and renewability, with the added benefit of UV-induced oil recovery.

Computational identification of DNA damage-relevant lncRNAs for predicting therapeutic efficacy and clinical outcomes in cancer.

OBJECTIVES: The role of long non-coding RNAs (lncRNAs) in cancer treatment, particularly in modulating DNA repair programs, is an emerging field that warrants systematic exploration. This study aimed to systematically identify the lncRNA regulators that potentially regulate DNA damage response (DDR). METHODS: Using genome-wide mRNA and lncRNA expression profiles of the same tumor patients, we proposed a novel computational framework. This framework performed Gene Set Variation Analysis to calculate DDR pathway enrichment score, which relies on weighting by tumor purity to obtain DDR activity score for each patient. Then, an in-depth differential expression profiling was conducted to identify pathway activity lncRNAs between high- and low-activity groups, utilizing a bootstrap-based randomization method. RESULTS: We comprehensively charted the landscape of DDR-relevant lncRNAs across 23 epithelial-based cancer types. Its effectiveness was validated by assessing the consistency of these lncRNAs within various datasets of the same cancer type (hypergeometric test P < 0.001), examining the expression perturbation of these lncRNAs in response to treatment and demonstrating its application in prioritizing clinically-related lncRNAs. Furthermore, leveraging 820 epithelial ovarian cancer patients from four public datasets, we applied these lncRNAs identified by DDRLnc to establish and validate a risk stratification model to evaluate the benefits of platinum-based adjuvant chemotherapy for the improvement of clinical treatment outcomes. CONCLUSIONS: Comprehensive pan-cancer analysis illustrates the utility of computational framework in identifying potentially lncRNAs involved in DDR, thereby offering novel insights into the complex realm of cancer research, and it will become a valuable tool for identifying potential therapeutic targets for cancer.

Electron-donating arene-substituted pentacenedione derivatives: a study of structural, electronic, and electrochemical properties.

A new series of redox-active tetraryl-substituted pentacenedione derivatives, namely Ar4-PDs, was prepared through Suzuki-Miyaura coupling reactions between a bis(dibromomethane)pentacenedione and various arene boronic acids. Single-crystal X-ray diffraction analysis and density functional theory (DFT) calculations have confirmed that these Ar4-PDs possess highly twisted conformations due to the significant steric encumbrance between the Ar substituents and the anthraquinodimethane moiety. Cyclic voltammetric analysis revealed that the nature of the Ar group critically influences the redox properties of Ar4-PDs. In the case where the Ar group is a strong electron donor, triphenylamino (TPA), the Ar4-PD derivative exhibits an amphoteric redox behavior with a narrowed electrochemical band gap (1.38 eV) and a noticeable intramolecular charge transfer (ICT) band in the visible region of the spectrum. The twisted molecular conformation is believed to facilitate through-space interactions between the donor (TPA) and acceptor (anthraquinone) groups, while protonation of this compound with a strong organic acid can further enhance the ICT effect.

Meta-analysis of selenium effects on the meat quality of broilers.

The effects of sodium selenite or selenium yeast on the meat quality of broilers were searched in the literature published in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), PubMed, Web of Science, and Science Direct databases from January 1, 2010 to December 31, 2022. Meta-analysis was performed with Stata software (StataCorp. 2011), and the standardized mean difference (SMD) and its 95% confidence interval (CI) were calculated using a random effects model. Twenty of the identified 846 literature sources, which included 791 broilers, were screened. The meat quality indices considered were shear force, drip loss, cooking loss, water holding capacity (WHC), pH, and color. The source of heterogeneity was studied using sensitivity and subgroup analyses, and publication bias was evaluated using funnel plots. The results showed that the supplementation of selenium in the broiler diet significantly reduced the shear force (SMD = -0.67, 95% CI [-1.12, -0.22], P < 0.05) and drip loss (SMD = -0.84, 95% CI [-1.39, -0.30], P < 0.05) and increased the pH (SMD = 0.38, 95% CI [0.01, 0.75], P < 0.05) of broiler breast muscle; however, it had no significant effects on other indices. Funnel plots revealed a slight publication bias in the shear force and pH of breast muscle but none in the drip loss of breast muscle. The sensitivity analysis showed that the results were stable and reliable. In conclusion, selenium supplementation in broiler feed can improve some indices of broiler meat quality, and its inclusion in broiler diets is recommended, in conjunction with other minerals, which is of great significance to improve the quality, preservation time and economic benefits of chicken products.

DBPboost:A method of classification of DNA-binding proteins based on improved differential evolution algorithm and feature extraction.

DNA-binding proteins are a class of proteins that can interact with DNA molecules through physical and chemical interactions. Their main functions include regulating gene expression, maintaining chromosome structure and stability, and more. DNA-binding proteins play a crucial role in cellular and molecular biology, as they are essential for maintaining normal cellular physiological functions and adapting to environmental changes. The prediction of DNA-binding proteins has been a hot topic in the field of bioinformatics. The key to accurately classifying DNA-binding proteins is to find suitable feature sources and explore the information they contain. Although there are already many models for predicting DNA-binding proteins, there is still room for improvement in mining feature source information and calculation methods. In this study, we created a model called DBPboost to better identify DNA-binding proteins. The innovation of this study lies in the use of eight feature extraction methods, the improvement of the feature selection step, which involves selecting some features first and then performing feature selection again after feature fusion, and the optimization of the differential evolution algorithm in feature fusion, which improves the performance of feature fusion. The experimental results show that the prediction accuracy of the model on the UniSwiss dataset is 89.32%, and the sensitivity is 89.01%, which is better than most existing models.

NOTUM plays a bidirectionally modulatory role in the odontoblastic differentiation of human stem cells from the apical papilla through the WNT/ß-catenin signaling pathway.

OBJECTIVE: Notum is a secreted deacylase, which is crucial for tooth dentin development in mice. This study aimed to investigate the effect of NOTUM on the odontoblastic differentiation of human stem cells from the apical papilla (hSCAPs), to reveal the potential value of NOTUM in pulp-dentin complex regeneration. DESIGN: The expression pattern of NOTUM in human tooth germs and during in vitro odontoblastic differentiation of hSCAPs was evaluated by immunohistochemical staining, and quantitative polymerase chain reaction, respectively. To manipulate the extracellular NOTUM level, ABC99 or small interfering RNA was used to down-regulate it, while recombinant NOTUM protein was added to up-regulate it. The effects of changing NOTUM level on the odontoblastic differentiation of hSCAPs and its interaction with the WNT/ß-catenin signaling pathway were studied using alkaline phosphatase staining, alizarin red staining, quantitative polymerase chain reaction, and western blot. RESULTS: NOTUM was observed in the apical papilla of human tooth germs. During in vitro odontoblastic differentiation of hSCAPs, NOTUM expression initially increased, while the WNT/ß-catenin pathway was activated. Downregulation of NOTUM hindered odontoblastic differentiation. Recombinant NOTUM protein had varying effects on odontoblastic differentiation depending on exposure duration. Continuous addition of the protein inhibited both odontoblastic differentiation and the WNT/ß-catenin pathway. However, applying the protein solely in the first 3 days enhanced odontoblastic differentiation and up-regulated the WNT/ß-catenin pathway. CONCLUSION: NOTUM demonstrated a bidirectional impact on in vitro odontoblastic differentiation of hSCAPs, potentially mediated by the WNT/ß-catenin pathway. These findings suggest its promising potential for pulp-dentin complex regeneration.

Thematic analysis to explore patients' experiences with long COVID-19: a conceptual model of symptoms and impacts on daily lives.

OBJECTIVES: There is limited qualitative research on patients' experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients' lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life. SETTING: Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews. PARTICIPANTS: Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals's clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed. PRIMARY AND SECONDARY OUTCOMES: Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model. RESULTS: Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months. CONCLUSION: The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients' physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.

Total Synthesis of Ganoderma Meroterpenoids Cochlearol B and Its Congeners Driven by Structural Similarity and Biological Homology.

Secondary metabolites that have the same biological origin must share some relationship in their biosynthesis. Exploring this relationship has always been a significant task for synthetic biologists. However, from the perspective of synthetic chemists, it is equally important to propose, prove, or refute potential biosynthetic pathways in order to elucidate and understand the biosynthesis of homologous secondary metabolites. In this study, driven by the high structural similarity between the homologous Ganoderma meroterpenoids cochlearol B and ganocin B, two chemically synthetic strategies were designed and investigated sequentially for the synthesis of cochlearol B from ganocin B. These strategies include intramolecular metal-catalyzed hydrogen atom transfer (MHAT) and intramolecular photochemical [2+2] cycloaddition. The aim was to reveal their potential biosynthetic conversion relationship using chemical synthesis methods. As a result, a highly efficient total synthesis of cochlearol B, cochlearol T, cochlearol F, as well as the formal total synthesis of ganocins A-B, and ganocochlearins C-D, has been achieved. Additionally, a novel synthetic approach for the synthesis of 6,6-disubstituted 6H-dibenzo[b,d]pyran and its analogues has been developed through palladium(II)-catalyzed Wacker-type/cross-coupling cascade reactions.

Digenic inheritance accounts for phenotypic variability in amelogenesis imperfecta.

Amelogenesis imperfecta (AI) represents a group of clinically and genetically heterogeneous disorders that affect enamel formation and mineralization. Although AI is commonly considered a monogenic disorder, digenic inheritance is rarely reported. In this study, we recruited two nonconsanguineous Chinese families exhibiting diverse phenotypes of enamel defects among affected family members. Digenic variants were discovered in both probands. In family 1, the proband inherited a paternal frameshift variant in LAMA3 (NM_198129.4:c.3712dup) and a maternal deletion encompassing the entire AMELX gene. This resulted in a combined hypoplastic and hypomineralized AI phenotype, which was distinct from the parents' manifestations. In family 2, whole-exome sequencing analysis revealed the proband carried a maternal heterozygous splicing variant in COL17A1 (NC_000010.11 (NM_000494.3): c.4156 + 2dup) and compound heterozygous variants in RELT (paternal: NM_032871.4:c.260A > T; maternal: NM_032871.4:c.521 T > G). These genetic changes caused the abundant irregular enamel defects observed in the proband, whereas other affected family members carrying heterozygous variants in both COL17A1 and RELT displayed only horizontal grooves as their phenotype. The pathogenicity of the novel COL17A1 splice site variant was confirmed through RT-PCR and minigene assay. This study enhances our understanding by highlighting the potential association between the co-occurrence of variants in two genes and variable phenotypes observed in AI patients.

Using TransR to enhance drug repurposing knowledge graph for COVID-19 and its complications.

MOTIVATION: The COVID-19 pandemic has been spreading globally for four years, yet specific drugs that effectively suppress the virus remain elusive. Furthermore, the emergence of complications associated with COVID-19 presents significant challenges, making the development of therapeutics for COVID-19 and its complications an urgent task. However, traditional drug development processes are time-consuming. Drug repurposing, which involves identifying new therapeutic applications for existing drugs, presents a viable alternative. RESULT: In this study, we construct a knowledge graph by retrieving information on genes, drugs, and diseases from databases such as DRUGBANK and GNBR. Next, we employ the TransR knowledge representation learning approach to embed entities and relationships into the knowledge graph. Subsequently, we train the knowledge graph using a graph neural network model based on TransR scoring. This trained knowledge graph is then utilized to predict drugs for the treatment of COVID-19 and its complications. Based on experimental results, we have identified 15 drugs out of the top 30 with the highest success rates associated with treating COVID-19 and its complications. Notably, out of these 15 drugs, 10 specifically aimed at treating COVID-19, such as Torcetrapib and Tocopherol, has not been previously identified in the knowledge graph. This finding highlights the potential of our model in aiding healthcare professionals in drug development and research related to this disease.

GwasWA: A GWAS one-stop analysis platform from WGS data to variant effect assessment.

Using the accumulated whole-genome sequencing (WGS) data and assessing the functional effects of genetic variants, particularly non-coding variants, help identify new and rare variants and decipher the molecular mechanisms underlying diseases and traits but presents significant challenges. GwasWA is a comprehensive and efficient platform to identify causal variants and assess their functional effects based on WGS data. It covers the entire workflow from downloading and processing WGS data to detecting associated variants and assessing their functional effects with optimized configurations, standardized input/output formats, personalized analysis options, data visualization, and parallel processing capability that is crucial for large-scale studies. Applying GwasWA to real datasets identified three novel genes related to seed size and revealed the regulatory mechanism underlying the linkage between a human non-coding variant, rs80067372, and tumor necrosis factor levels. These results highlight the capability of GwasWA to detect novel variants based on WGS data and provide comprehensive insights into the molecular mechanisms underlying the association of variants with diseases and traits, thus contributing to medicine and biology. GwasWA and its documentation are freely available at https://github.com/unicorn-23/GwasWA.

DFT investigations of phenyldithiafulvene dimers at different oxidation states.

Oxidative dimerization of aryl-substituted dithiafulvenes (Ar-DTFs) presents an efficient C-C bond forming method for the preparation of diverse redox-active π-conjugated molecules and conductive polymers. Previous experimental data indicated a reaction pathway in which direct combination of two Ar-DTF radical cations is a key step. However, mechanistic details about how Ar-DTF dimers are formed under different oxidation states have not yet been clearly established prior to this work. The assembly of two Ar-DTF molecules generates a vast conformational and configurational landscape, which is quite complex but fundamentally important for understanding the dimerization mechanism. To cast a deep insight into this aspect, we have performed density functional theory (DFT) calculations at the M06-2X/Def2-SVP level of theory to thoroughly investigate the potential energy surfaces (PESs) of various dimers of a phenyl-substituted dithiafulvene (Ph-DTF) in the mixed-valence radical cation and dication states. Key stationary points in these PESs, including minimum-energy conformers (π-dimers and σ-dimers) as well as the transition states connected to them, were examined and compared. We have also calculated the binding energies of these dimers to evaluate the energetic driving forces for their formation. Based on our computational results, the roles that various Ph-DTF dimers play in different pathways of oxidative dimerization have been clarified.

Tailoring chemical composition of solid electrolyte interphase by selective dissolution for long-life micron-sized silicon anode.

Micron-sized Si anode promises a much higher theoretical capacity than the traditional graphite anode and more attractive application prospect compared to its nanoscale counterpart. However, its severe volume expansion during lithiation requires solid electrolyte interphase (SEI) with reinforced mechanical stability. Here, we propose a solvent-induced selective dissolution strategy to in situ regulate the mechanical properties of SEI. By introducing a high-donor-number solvent, gamma-butyrolactone, into conventional electrolytes, low-modulus components of the SEI, such as Li alkyl carbonates, can be selectively dissolved upon cycling, leaving a robust SEI mainly consisting of lithium fluoride and polycarbonates. With this strategy, raw micron-sized Si anode retains 87.5% capacity after 100 cycles at 0.5 C (1500 mA g-1, 25°C), which can be improved to >300 cycles with carbon-coated micron-sized Si anode. Furthermore, the Si||LiNi0.8Co0.1Mn0.1O2 battery using the raw micron-sized Si anode with the selectively dissolved SEI retains 83.7% capacity after 150 cycles at 0.5 C (90 mA g-1). The selective dissolution effect for tailoring the SEI, as well as the corresponding cycling life of the Si anodes, is positively related to the donor number of the solvents, which highlights designing high-donor-number electrolytes as a guideline to tailor the SEI for stabilizing volume-changing alloying-type anodes in high-energy rechargeable batteries.

Long-range Through-space Charge Transfer in a pH-responsive Mixed Cyclophane of Pyridine and Teropyrene.

A large, strained (SE=44.2 kcal/mol) and conformationally flexible mixed cyclophane of pyridine and teropyrene was synthesized using two intramolecular Wurtz coupling reactions and an unprecedented Scholl reaction between the unreactive 2 positions of the pyrene systems in a triply bridged pyrenophane. Protonation of the pyridine unit results in a greatly enhanced preference for nesting in the cavity of the highly bent teropyrene system (θcalc =162.6°) and emergence of a charge transfer absorption band (λmax =592 nm) due to a long range (5.0-5.5 Å), through-space intramolecular transition between the teropyrene and pyridinium units, which does not exist in the neutral cyclophane.

Total Synthesis of Metaphanine and Oxoepistephamiersine.

Herein, we report a concise and divergent synthesis of the complex hasubanan alkaloids metaphanine and oxoepistephamiersine from commercially available and inexpensive cyclohexanedione monoethylene acetal. Our synthesis features a palladium-catalyzed cascade cyclization reaction to set the tricyclic carbon framework of the desired molecules, a regioselective Baeyer-Villiger oxidation followed by a MeNH2 triggered skeletal reorganization cascade to construct the benzannulated aza[4.4.3]propellane, and a strategically late-stage regio-/diastereoselective oxidative annulation of sp3 C-H bond to form the challenging THF ring system and hemiketal moiety in a single step. In addition, a highly enantioselective alkylation of cyclohexanedione monoethylene acetal paved the way for the asymmetric synthesis of target molecular.