Formation of cyclopenta[c]quinolines through visible-light-induced photoredox cascade bis-annulations of 1,7-enynes with sulfoxonium ylides.

A novel visible-light-driven photoredox-catalyzed cascade bicyclization of 1,7-enynes with aqueous sulfoxonium ylides is reported. The reaction is highly chemoselective with three new C-C bonds, two new rings, and an all-carbon quaternary stereocenter constructed in a one-pot fashion. This mild protocol features a remarkably broad substrate scope with good functional group tolerance, providing a general and practical approach to access various cyclopenta[c]quinolines.

Efficient unsymmetric disulfide formation by molecular-scale tailoring of ortho-polyquinone-based polymer photocatalyst.

Disulfide bonds, especially unsymmetric disulfide bonds, have important applications in bioactivity and drug molecules, but the synthesis of unsymmetric disulfide bonds remains challenging due to efficiency and selectivity issues. Herein, this work utilizes anthraquinone (AQ) and cyclictriphosphonononitrile through a nucleophilic substitution reaction to synthesize an organic polymer (ANTH-AMI) that incorporates an ortho-polyquinone (o-polyquinone) redox center. The anthraquinone molecule functions as a redox center, capable of accepting photoinduced electrons and subsequently transferring them to initiate an electron-coupled hydrogenation reaction (AQ to AQH). Moreover, the proximity of the o-polyquinone redox sites facilitates the catalysis of unsymmetric disulfide bond formation. Consequently, the ANTH-AMI photocatalysts demonstrate exceptional yields (up to 82 %), substrate versatility, cycling stability, and scalable preparation in promoting unsymmetric coupling reactions of thiol. This work offers a solution for designing organic polymer photocatalysts with adjacent multiple redox centers for cross-coupling reactions.

Acid-Promoted Amination of Cyclohexenone for the Divergent Synthesis of p-Aminophenols and Tertiary Amines.

A tunable method for the selective preparation of p-aminophenol and tertiary amines from a secondary amine and cyclohexenone has been described. Nonaromatic cyclohexenones were used as an aryl source. The desired tertiary amine products were generated when using I2 as the catalyst. This approach yields single-site-selective p-aminophenol without using I2, and the 18O labeling experiments demonstrated that hydroxyl oxygen originates from O2.

Augmented photocatalytic NO removal by the S-scheme Bi7O9I3/Bi2S3 heterojunctions with surface oxygen vacancies: Experimental analyses and theoretical calculations.

The establishment of S-scheme heterojunctions represents an effective strategy for enhancing the transfer and separation of charge carriers, thereby bolstering redox capacities and consequently benefiting subsequent photocatalytic reactions. In this study, the pristine Bi7O9I3 underwent a facile vulcanization process to in-situ produce various composites. Systematical characterizations confirmed the simultaneous generation of Bi7O9I3/Bi2S3 (BI-BS) heterojunctions with surface oxygen vacancies (OVs). Under visible light, these BI-BS composites exhibited improved NO removal efficiencies with reduced NO2 generation compared to bare Bi7O9I3. Particularly, the best candidate BI-BS2 possesses the highest NO removal (43.02%) and lowest NO2 generation (5.44%) among all tested samples. The improvement was primarily attributed to synergetic effects of heterojunction and surface OVs, including enhanced charge separation, heightened light responsiveness, and improved generation of reactive oxygen-containing species through an S-scheme mode. Furthermore, the Density Functional Theory (DFT) calculations had demonstrated that the establishment of BI-BS heterojunctions with surface OVs not only optimized the electronic structure to facilitate the transfer and separation of charge carriers, but also significantly enhanced the adsorption of NO, H2O, and O2 molecules, ultimately favoring the generation of NO3- species. These as-synthesized composites indicated sufficient structural stability and hold potential for the photocatalytic removal of NO at ppb levels.

Chemoselective Hydroheteroarylation of Alkenes via Photoredox-Neutral Proton- and BF3-Mediated Electron Transfer.

Herein, we have developed a complementary entry to enable hydroheteroarylation of alkenes involving basically photoredox dearomatizative heterocyclic carbon radical formation through acid-coupled electron transfer followed by Giese addition. While protonic solvent and thiophenol additive enabled two molecular hydroheteroarylations of alkenes, the nonproton environment with BF3 altered the chemoselectivity over cascade hydroheteroarylation of alkenes by radical addition of heteroaromatics with two molecular alkenes. This chemoselectivity can be mechanistically attributed to the dynamically favored hydrogen atom transfer via the cyclic transition state.

General Defluoroalkylation of Trifluoromethylarenes with Both Electron-Donating and -Withdrawing Alkenes.

The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.

Copper-Catalyzed Four-Component Domino Cyclization for the Synthesis of 2-Methylpyridines.

A convenient protocol for synthesis of unsymmetrical 2-methylpyridines from acetyl ketones, ammonium salts and tertiary amines is described. The construction of two C-C bonds and two C-N bonds via [2 + 2 + 1 + 1] four-component domino cyclization reaction is achieved using Cu(OTf) as catalyst in one pot. This cyclization reaction shows good selectivity and produces multisubstituted 2-methylpyridine derivatives in good yields with various functional groups.

Analysis of the associations between moderate-to-vigorous physical activity and screen time on psychological symptoms among university students: a cross-sectional survey based on six geographic regions in China.

BACKGROUND: Declining physical activity and increasing screen time (ST) among Chinese adolescents have become major concerns shared by scholars, while mental health issues are also on the rise. Previous studies have confirmed the association between physical activity and screen time and psychological symptoms, but it is unclear how their psychological symptoms, especially for Chinese university students who have a high proportion of psychological symptoms, and no research evidence has been found. METHODS: This study investigated physical activity, screen time, and psychological symptoms in 11,173 university students aged 19-22 years in six regions of China. A binary logistic regression analysis was used to analyze the association between moderate-to-vigorous physical activity (MVPA) and screen time and psychological symptoms. And the generalize linear model (GLM) analysis was used to further analyze the association between MVPA and screen time and psychological symptoms. RESULTS: The detection rate of psychological symptoms among Chinese university students was 16.3%, with a higher percentage of female students (17.5%) than male students (14.7%). The proportion of male students (8.2%) with MVPA > 60 min/d was higher than that of female students (2.3%), and the proportion of male students (33.8%) and female students (34.5%) with screen time > 2 h/d was basically the same. The generalize linear model (GLM) analysis showed that university students with MVPA < 30 min/d and screen time > 2 h/d (OR = 1.59, 95% CI: 1.10-2.31) had the highest risk of psychological symptoms (OR = 1.59, 95% CI: 1.10-2.31) compared to university students with MVPA > 60 min/d and screen time < 1 h/d as the reference group. The risk of psychological symptoms was the highest among those with MVPA < 30 min/d and screen time > 2 h/d (OR = 1.59,95% CI: 1.10-2.31). In addition, university students with MVPA > 60 min/d and a screen time of 1-2 h/d (OR = 0.09, 95% CI: 0.03-0.25) had the lowest risk of psychological symptoms (P < 0.001). The same trend was observed for both male and female students. CONCLUSION: Chinese university students have a certain proportion of psychological symptom problems, and there is a significant between MVPA and screen time and psychological symptoms, and the same trend exists for both male and female students. Chinese university students should perform MVPA for not less than 60 min a day, and at the same time control the duration of screen time, and screen time should be controlled between 1 and 2 h a day, which has a better promotion effect on psychological health.

Stereoselective Three-Component Carbocyclization of 1,7-Enynes with Sulfoxonium Ylides and Water under Photoredox Catalysis.

A visible-light-induced photoredox three-component carbocyclization reaction of 1,7-enynes with sulfoxonium ylides and water is reported. The protocol provides a facile entry to structurally valuable highly functionalized cyclopenta[c]quinoline scaffolds in a highly chemoselective and stereoselective manner. Salient features of this method include facile redox-neutral conditions, no requirement of base or other additive, and good functional-group tolerance.

Copper-Catalyzed Three-Component Synthesis of ß-Hydroxysulfides from Styrene Oxide, Aryl Iodide, and Carbon Disulfide.

A copper-catalyzed three-component coupling reaction of styrene oxide, aryl iodide, and carbon disulfide for the construction of ß-hydroxysulfides has been developed. In this process, readily available CS2 was used as the sulfur source to construct C-S bonds for the synthesis of phenyl-ß-hydroxysulfides and (benzo[d]thiazol)-ß-hydroxysulfides. This process features mild reaction conditions, simple operation, and wide substrate scope (>50 examples).

Animal models of studying the pathogenesis of multi-organ tissue damage in lupus.

Moderate-to-severe systemic lupus erythematosus (SLE) is characterized by extensive autoantibody deposition and persistent autoinflammation. As the existing animal models are limited in accurately reproducing the pathological characteristics of human SLE, we introduced a novel animal model simulating multi-organ autoinflammation through intra-organ injections. The model closely mimicked key features of SLE, including IgG deposition, inflammation, and tissue damage. The model could be used to assess the roles of IgG, immune cells, cytokines, and Fc gamma receptor (FcγR) in the pathogenesis of autoinflammation. The results obtained from this model could be confirmed by lupus MRL/lpr mice. The review suggested that the diagnostic criteria should be reconsidered to incorporate IgG deposition in tissues and highlighted the limitations of current T-cell and B-cell-focused treatments. To summarize, the IgG deposition model can be used to investigate the pathogenesis and treatment of multi-organ tissue damage associated with SLE.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Photoselectively modulating main products by changing the wavelength of visible light over D-π-A-D conjugated polymers.

The diversity of catalytic products determines the difficulty of selective product modulation, which usually relies on adjusting the catalyst and reaction conditions to obtain different main products selectively. Herein, we synthesized D-π-A-D conjugated organic polymers (TH-COP) using cyclotriphosphonitrile, alkyne, 2H-benzimidazole, and sulfur units as electron donors, π bridges, electron acceptors, and electron donors, respectively. TH-COP exhibited excellent photoinduced carrier separation and redox ability under different visible light wavelengths, and the main products of its CO2 reduction are CH4 (1000.0 µmol g-1) and CO (837.0 µmol g-1) under 400-420 nm and 420-560 nm, respectively. In addition, TH-COP could completely convert phenylmethyl sulfide to methyl phenyl sulfone at 400-420 nm and diphenyl disulfide at 480-485 nm in yields up to 95 %. This study presents a novel strategy for the targeted fabrication of various main products using conjugated polymers by simply changing the wavelength range of visible light.

Copper-Catalyzed 1,2-Sulfonyletherification of 1,3-Dienes.

A selective three-component 1,2-sulfonyl etherification of aryl 1,3-dienes enabled by copper catalysis to afford biologically interesting alkenyl 1,2-sulfone ether derivatives through C-S and C-O bond formation is described. The protocol proceeds with the sulfonyl chloride and alcohols under simple, mild, and base-free conditions, providing a straightforward route to sulfonylated allyl ether compounds with broad functional group tolerance and excellent chemo- and regioselectivity. Mechanistic studies indicate that the selective alkene difunctionalization includes a key copper-mediated single-electron transfer process.

Accessing pyrrolo[1,2-a]indole derivatives via visible-light-induced dearomatizative cyclization of indoles.

Pyrrolo[1,2-a]indoles are structurally important scaffolds in many natural products and bioactive compounds. Herein, we report a novel synthetic method for pyrrolo[1,2-a]indole derivatives through visible-light-induced cascade dearomatizative cyclization of indoles with external nucleophiles. Moderate yields, good diastereoselectivities, and excellent regioselectivities were generally observed with the resultant indole-fused polycyclic compounds.

Synthesis of Spiro Polycyclic N-Heterocycles and Indolecarbazoles via Merging Oxidative Coupling and Cascade Palladium-Catalyzed Intramolecular Oxidative Cyclization.

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis.

BACKGROUND: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes. AIM: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. METHODS: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort (n = 309) and validation cohort (n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year. RESULTS: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development. CONCLUSION: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

Accessing 3,4-Dihydroquinolinone from N-Arylacrylamides via Tetralone-Mediated Energy Transfer and 1,3-Hydrogen Shift.

Herein, we introduce a tetralone-mediated photocyclization method of N-arylacrylamides. The protocol proceeds smoothly to deliver a diverse set of 3,4-dihydroquinolinones in moderate to good yields with excellent functional group compatibility and readily allows for late-stage modifications of a number of complex drug molecules. Mechanistic studies reveal that the present systems with ultraviolet light irradiation enable the cyclization via energy transfer and exclusive 1,3-hydrogen shift.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.