Stereoselective Construction of the ABCDE Pentacyclic Motif of Phainanoids via Norrish-Yang Photocyclization Reaction.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

Recent Progress of Oral Functional Nanomaterials for Intestinal Microbiota Regulation.

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota.

CRIg+ macrophages deficiency enhanced inflammation damage in IBD due to gut extracellular vesicles containing microbial DNA.

Gut microbiota-derived extracellular vesicles (mEVs) are reported to regulate inflammatory response by delivering bacterial products into host cells. The complement receptor of the immunoglobulin superfamily macrophages (CRIg+ Mφ) could clear invading bacteria and their derivatives. Here, we investigate the role of CRIg+ Mφ and the mechanism by which mEVs regulate intestinal inflammation. We found that it is exacerbated in IBD patients and colitis mice by mEVs' leakage from disturbed gut microbiota, enriching microbial DNA in the intestinal mucosa. CRIg+ Mφ significantly decrease in IBD patients, allowing the spread of mEVs into the mucosa. The microbial DNA within mEVs is the key trigger for inflammation and barrier function damage. The cGAS/STING pathway is crucial in mEVs-mediated inflammatory injury. Blocking cGAS/STING signaling effectively alleviates inflammation caused by mEVs leakage and CRIg+ Mφ deficiency. Microbial DNA-containing mEVs, along with CRIg+ Mφ deficiency, stimulate inflammation in IBD, with the cGAS/STING pathway playing a crucial role.

Circadian rhythm disruption-mediated downregulation of Bmal1 exacerbates DSS-induced colitis by impairing intestinal barrier.

Background: Circadian rhythm disruption (CRD) is thought to increase the risk of inflammatory bowel disease. The deletion of Bmal1, a core transcription factor, leads to a complete loss of the circadian rhythm and exacerbates the severity of dextran sodium sulfate (DSS)-induced colitis in mice. However, the underlying mechanisms by which CRD and Bmal1 mediate IBD are still unclear. Methods: We used a CRD mouse model, a mouse colitis model, and an in vitro model of colonic epithelial cell monolayers. We also knocked down and overexpressed Bmal1 in Caco-2 cells by transfecting lentivirus in vitro. The collected colon tissue and treated cells were assessed and analyzed using immunohistochemistry, immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction, western blot, flow cytometry, transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. Results: We found that CRD mice with downregulated Bmal1 expression were more sensitive to DSS-induced colitis and had more severely impaired intestinal barrier function than wild-type mice. Bmal1-/- mice exhibited more severe colitis, accompanied by decreased tight junction protein levels and increased apoptosis of intestinal epithelial cells compared with wild-type mice, which were alleviated by using the autophagy agonist rapamycin. Bmal1 overexpression attenuated Lipopolysaccharide-induced apoptosis of intestinal epithelial cells and impaired intestinal epithelial cells barrier function in vitro, while inhibition of autophagy reversed this protective effect. Conclusion: This study suggests that CRD leads to the downregulation of Bmal1 expression in the colon, which may exacerbate DSS-induced colitis in mice, and that Bmal1 may serve as a novel target for treating inflammatory bowel disease.

Regioselective Syntheses of 1,4- and 1,6-Dicarbonyl Compounds via Photoredox-Based Oxidative Heterocoupling of Enolsilanes with Oxygen as an Oxidant.

A photoredox-based oxidative heterocoupling of enolsilanes to the corresponding 1,4- and 1,6-dicarbonyl compounds was developed by using Mes-Acr+BF4- as the photocatalyst, and oxygen was used as the oxidant. This newly developed chemistry adheres to the principles of atom economy, step economy, and redox economy, making it a concise and efficient method.

Development of a Strategy for the Total Synthesis of Aspidosperma Alkaloids via the Cyclobutenone-Based PET-Initiated Cationic Radical-Driven [2+2]/Retro-Mannich Reaction.

A novel strategy for the synthesis of Aspidosperma alkaloids has been achieved via a photoredox-initiated [2+2]/retro-Mannich reaction of tryptamine-substituted enaminones as a key step. The developed chemistry has been applied to the construction of the core tetracycle of Aspidosperma alkaloids (±)-aspidospermidine and (±)-limaspermidine.

Composite RISE control for vehicle-mounted servo system with unknown modeling uncertainties and unknown time-varying disturbances.

In light of the problem of trajectory tracking control in vehicle servo systems with system model uncertainty and external time-varying disturbance, an effective trajectory tracking control method that can handle system model uncertainty and external time-varying disturbances is proposed. To achieve this goal, a novel composite robust integral of the sign of the error (RISE) control method is introduced that combines a multi-layer neural network and an extended state observer. Specifically, multi-layer neural networks are utilized to approximate the uncertainty of the system model, while an extended state observer is employed to estimate the fitting near-error and the external time-varying interference, which are used as feedforward compensation. Finally, the RISE controller is implemented as a robust feedback controller. By applying Lyapunov theory for stability analysis and conducting experiments, the results demonstrate that the proposed approach exhibits excellent performance and robustness in addressing the uncertainties and disturbances involved in trajectory tracking control for vehicle servo systems.

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis.

BACKGROUND: Overexpression of solute carrier family 7 member 8 (SLC7A8) has been shown to relate to the survival time and tumor progression in cancer patients. However, the role of SLC7A8 in lung adenocarcinoma (LUAD) is still obscure. METHOD: The relationships between SLC7A8 expression in LUAD tissues and clinical values as well as immune infiltration were explored through bioinformatics. The functions and pathways of SLC7A8 in LUAD were investigated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, Western blotting, and other methods. RESULTS: We found that the expression of SLC7A8 was decreased significantly in LUAD tissues compared with normal tissues, which was related to the dismal survival time and disease progression. Moreover, it carried diagnostic value in LUAD and was a risk factor for dismal prognosis. Receiver operating characteristic curve analysis indicated that the expression level of SLC7A8 carried significant diagnostic value in LUAD. Overexpression of SLC7A8 inhibited the proliferation, invasion, and migration of LUAD cells, likely through a mechanism involving the cell cycle. SLC7A8 expression in LUAD was significantly correlated with the infiltration of immune cells, especially B cells, interstitial dendritic cells, mast cells, CD56 bright cells, natural killer cells, plasmacytoid dendritic cells, T follicular helper cells, T helper 2 and 17 cells, and immune factors. CONCLUSION: The downregulation of SLC7A8 was related to a dismal prognosis and immune cell infiltration in LUAD. Increasing the expression of SLC7A8 inhibited the growth and migration of LUAD cells, thereby improving the prognosis of patients.

Comprehensive Analysis of Sideroflexin 4 in Hepatocellular Carcinoma by Bioinformatics and Experiments.

Background: Sideroflexins (SFXNs) are a family of highly conserved mitochondrial transporters which regulate iron homeostasis and mitochondrial respiratory chain. However, the roles and mechanisms of SFXNs in HCC remain unknown. Methods: SFXNs expression and prognostic value in HCC was comprehensively analyzed. Proteins interacting with SFXN4 were analyzed in STRING database. The co-expression genes of SFXN4 were analyzed in cBioPortal database, and function of SFXN4 co-expression genes were annotated. The putative transcription factors and miRNA targeting SFXN4 were analyzed in NetworkAnalyst. The correlation between SFXN4 expression and immune infiltration was analyzed by ssGSEA. Cancer pathway activity and drug sensitivity related to SFXN4 were explored in GSCALite. The roles of SFXN4 in proliferation, migration and invasion of HCC were assessed in vitro and in vivo. Results: SFXN4 was consistently elevated in HCC, positively correlated with clinicopathological characteristics and predicted poor outcome. Functional enrichment showed SFXN4 was mainly related to oxidative phosphorylation, reactive oxygen species and metabolic pathways. SFXN4 expression was regulated by multiple transcription factors and miRNAs, and SFXN4 expression in HCC was associated with several cancer pathways and drug sensitivity. SFXN4 expression correlated with immune infiltration in HCC. In vitro, knockdown of SFXN4 inhibited HCC proliferation, migration and invasion, and decreased the expression of cyclin D1 and MMP2. In vivo, knockdown of SFXN4 inhibited the growth of tumor xenografts in mice. Conclusion: SFXN4 was upregulated in HCC, predicted poor prognosis, and may facilitate HCC development and progression via various mechanisms. For HCC, SFXN4 may provide both prognostic information and therapeutic potential.

Total Synthesis of (+)-Haperforin G.

(+)-Haperforin G was synthesized in 20 steps from commercially available starting materials. A Co-catalyzed intramolecular Pauson-Khand reaction was used for stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position. Light-initiated photocatalysis was used for convergent and asymmetric cross-coupling of the unstabilized C(sp3) radical with an enone. The developed chemistry paves the way to the synthesis of structurally diverse analogs of haperforin G (6).

Regioselective Hydroxylation of Flavonoids by Transition-Metal-Catalyzed C-H Bond Oxidation.

Regioselective synthesis of 5,6,7-trihydroxyl and 5,7,8-trihydroxyl flavones has been achieved via a transition-metal-catalyzed C-H oxidation as the key step using naturally enriched 5,7-dihydroxyl flavone. The developed chemistry was applied to the synthesis of the naturally occurring and biologically active flavonoids wogonin (2), oroxylin A (3), and their glycosylated derivatives (4 and 5) as potential carnitine palmitoyltransferase 1 activators.

Concise Synthesis of 7-Deoxypsammaplysins K and O and 7-Deoxyceratinamide A by 1,3-Dipole Cycloaddition.

A spiro-oxepin isoxazoline skeleton was constructed via 1,3-dipole cycloaddition as a key step, which enabled the total syntheses of 7-deoxyceratinamide A and 7-deoxypsammaplysins K and O. The developed chemistry could be applied to total synthesis of structurally diverse spiro-oxepin isoxazoline-based marine natural products.

Semisynthesis of (-)-Bufospirostenin A Enabled by Photosantonin Rearrangement Reaction.

An enantioselective semisynthesis of (-)-bufospirostenin A is described. The key steps in the synthesis involve use of our proposed biomimetic and diastereoselective photosantonin rearrangement reaction for construction of the 5/7 bicyclic motif, and a Co-catalyzed reversible double-bond isomerization reaction for installing the double bond in the seven-membered ring.

Total Synthesis of (+)-Cyclobutastellettolide B.

A convenient enantioselective total synthesis of (+)-cyclobutastellettolide B via a strategy that involves a diastereoselective Johnson-Claisen rearrangement, a regioselective cyclopropoxytrimethylsilane ring-opening reaction, and a Norrish-Yang cyclization is described. The results of computational and experimental studies indicate that the regio- and stereoselectivity of the Norrish-Yang reaction are controlled by the C-H bond dissociation energy and restricted rotation of the C13-C14 bond.

Stereoselective Synthesis of trans-Decalin-Based Spirocarbocycles via Photocyclization of 1,2-Diketones.

Diastereoselective synthesis of the trans-decalin-based α-hydroxyl butanone spirocarbocycles bearing all-carbon quaternary stereogenic centers has been achieved via Norrish-Yang photocyclization of trans-decalin-substituted-2,3-butanediones using daylight. Density functional theory (DFT) calculations suggest that this diastereoselective reaction is affected by both substrate conformation and intramolecular hydrogen bonds. The developed chemistry could be applied to synthesizing the derivatives of the trans-decalin-based biologically important natural products.

Synthetic Strategy for Construction of Highly Congested Tetracyclic Core (6-5-7-4) of Harziane Diterpenoids.

The structurally intriguing tetracyclic core of complex harziane diterpenoid was constructed in 14 steps from commercially available 3-ethoxycyclohex-2-en-1-one. The key steps were a Mn/Cu-mediated oxidative 1,3-dicarbonyl radical cascade cyclization reaction, which diastereoselectively formed the core of dimethylbicyclo[3.2.1]octane structure, and a Au-catalyzed diastereoselective formal [2 + 2] cycloaddition for construction of the harziane diterpenoid tetracyclic framework. The developed method paves the way for achieving total synthesis of this type of complex natural product.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 2: The Final Phase and Completion.

The final phase of the total synthesis of (-)-spirochensilide A is described. A tungsten-mediated cyclopropene-based Pauson-Khand reaction was developed to form the spiral CD ring system with desired stereochemistry at the C13 quaternary center. Other important steps enabling completion of this synthesis included an intermolecular aldol condensation to link the ABCD core with the EF fragment and a Cu-mediated 1,4-addition to stereoselectively install the C21 stereogenic center. The chemistry developed for this total synthesis of (-)-spirochensilide A (1) will aid the synthesis of polycyclic natural products bearing this unique spiral ring system.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A.

A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson-Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13(R)-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.

A Machining State-Based Approach to Tool Remaining Useful Life Adaptive Prediction.

The traditional predictive model for remaining useful life predictions cannot achieve adaptiveness, which is one of the main problems of said predictions. This paper proposes a LightGBM-based Remaining useful life (RUL) prediction method which considers the process and machining state. Firstly, a multi-information fusion strategy that can effectively reduce the model error and improve the generalization ability of the model is proposed. Secondly, a preprocessing method for improving the time precision and small-time granularity of feature extraction while avoiding dimensional explosion is proposed. Thirdly, an importance coefficient and a custom loss function related to the process and machining state are proposed. Finally, using the processing data of actual tool life cycle, through five evaluation indexes and 25 sets of contrast experiments, the superiority and effectiveness of the proposed method are verified.

Photoredox-Catalyzed Isomerization of Highly Substituted Allylic Alcohols by C-H Bond Activation.

Photoredox-catalyzed isomerization of γ-carbonyl-substituted allylic alcohols to their corresponding carbonyl compounds was achieved for the first time by C-H bond activation. This catalytic redox-neutral process resulted in the synthesis of 1,4-dicarbonyl compounds. Notably, allylic alcohols bearing tetrasubstituted olefins can also be transformed into their corresponding carbonyl compounds. Density functional theory calculations show that the carbonyl group at the γ-position of allylic alcohols are beneficial to the formation of their corresponding allylic alcohol radicals with high vertical electron affinity, which contributes to the completion of the photoredox catalytic cycle.