Asymmetric Intramolecular Amination Catalyzed with Cp*Ir-SPDO via Nitrene Transfer for Synthesis of Spiro-Quaternary Indolinone.

An asymmetric intramolecular spiro-amination to high steric hindering α-C-H bond of 1,3-dicarbonyl via nitrene transfer using inactive aryl azides has been carried out by developing a novel Cp*Ir(III)-SPDO (spiro-pyrrolidine oxazoline) catalyst, thereby enabling the first successful construction of structurally rigid spiro-quaternary indolinone cores with moderate to high yields and excellent enantioselectivities. DFT computations support the presence of double bridging H-F bonds between [SbF6]- and both the ligand and substrate, which favors the plane-differentiation of the enol π-bond for nitrenoid attacking. These findings open up numerous opportunities for the development of new asymmetric nitrene transfer systems.

Multi-omic analysis reveals the effects of interspecific hybridization on the synthesis of seed reserve polymers in a Triticum turgidum ssp. durum × Aegilops sharonensis amphidiploid.

BACKGROUND: Wheat grain endosperm is mainly composed of proteins and starch. The contents and the overall composition of seed storage proteins (SSP) markedly affect the processing quality of wheat flour. Polyploidization results in duplicated chromosomes, and the genomes are often unstable and may result in a large number of gene losses and gene rearrangements. However, the instability of the genome itself, as well as the large number of duplicated genes generated during polyploidy, is an important driving force for genetic innovation. In this study, we compared the differences in starch and SSP, and analyzed the transcriptome and metabolome among Aegilops sharonensis (R7), durum wheat (Z636) and amphidiploid (Z636×R7) to reveal the effects of polyploidization on the synthesis of seed reserve polymers. RESULTS: The total starch and amylose content of Z636×R7 was significantly higher than R7 and lower than Z636. The gliadin and glutenin contents of Z636×R7 were higher than those in Z636 and R7. Through transcriptome analysis, there were 21,037, 2197, 15,090 differentially expressed genes (DEGs) in the three comparison groups of R7 vs Z636, Z636 vs Z636×R7, and Z636×R7 vs R7, respectively, which were mainly enriched in carbon metabolism and amino acid biosynthesis pathways. Transcriptome data and qRT-PCR were combined to analyze the expression levels of genes related to storage polymers. It was found that the expression levels of some starch synthase genes, namely AGP-L, AGP-S and GBSSI in Z636×R7 were higher than in R7 and among the 17 DEGs related to storage proteins, the expression levels of 14 genes in R7 were lower than those in Z636 and Z636×R7. According to the classification analysis of all differential metabolites, most belonged to carboxylic acids and derivatives, and fatty acyls were enriched in the biosynthesis of unsaturated fatty acids, niacin and nicotinamide metabolism, one-carbon pool by folate, etc. CONCLUSION: After allopolyploidization, the expression of genes related to starch synthesis was down-regulated in Z636×R7, and the process of starch synthesis was inhibited, resulting in delayed starch accumulation and prolongation of the seed development process. Therefore, at the same development time point, the starch accumulation of Z636×R7 lagged behind that of Z636. In this study, the expression of the GSe2 gene in Z636×R7 was higher than that of the two parents, which was beneficial to protein synthesis, and increased the protein content. These results eventually led to changes in the synthesis of seed reserve polymers. The current study provided a basis for a greater in-depth understanding of the mechanism of wheat allopolyploid formation and its stable preservation, and also promoted the effective exploitation of high-value alleles.

Molecular Biomarkers Affecting Moyamoya Disease.

Although the pathogenetic pathway of moyamoya disease (MMD) remains unknown, studies have indicated that variations in the RING finger protein RNF 213 is the strongest susceptible gene of MMD. In addition to the polymorphism of this gene, many circulating angiogenetic factors such as growth factors, vascular progenitor cells, inflammatory and immune mediators, angiogenesis related cytokines, as well as circulating proteins promoting intimal hyperplasia, excessive collateral formation, smooth muscle migration and atypical migration may also play critical roles in producing this disease. Identification of these circulating molecules biomarkers may be used for the early detection of this disease. In this chapter, how the hypothesized pathophysiology of these factors affect MMD and the interactive modulation between them are summarized.

Atroposelective synthesis of biaxial bridged eight-membered terphenyls via a Co/SPDO-catalyzed aerobic oxidative coupling/desymmetrization of phenols.

Bridged chiral biaryls are axially chiral compounds with a medium-sized ring connecting the two arenes. Compared with plentiful methods for the enantioselective synthesis of biaryl compounds, synthetic approaches for this subclass of bridged atropisomers are limited. Here we show an atroposelective synthesis of 1,3-diaxial bridged eight-membered terphenyl atropisomers through an Co/SPDO (spirocyclic pyrrolidine oxazoline)-catalyzed aerobic oxidative coupling/desymmetrization reaction of prochiral phenols. This catalytic desymmetric process is enabled by combination of an earth-abundant Co(OAc)2 and a unique SPDO ligand in the presence of DABCO (1,4-diaza[2.2.2]bicyclooctane). An array of diaxial bridged terphenyls embedded in an azocane can be accessed in high yields (up to 99%) with excellent enantio- (>99% ee) and diastereoselectivities (>20:1 dr).

Effects of nitrate reduction on the biotransformation of 1H-1,2,4-triazole: Mechanism and community evolution.

Due to the refractory of 1 H-1,2,4-triazole (TZ), conventional anaerobic biological treatment technology is usually restricted by low removal efficiency and poor system stability. In this study, TZ biodegradation and nitrate reduction was coupled to improve the removal efficiency of TZ from polluted wastewater. Batch assay was performed with pure culture strain Raoultella sp. NJUST42, which was reported to have the capability to degrade TZ in our previous study. Based on batch assay result, complete removal of TZ could be achieved in the presence of nitrate, whereas only 50% of TZ could be removed in the control system. Long-term stability experiment indicated that the relative abundance of microorganisms (Bacteroidetes_vadinHA17, Georgenia, Anaerolinea, etc) was obviously enhanced under nitrate reduction condition. During long-term period, major intermediates for TZ biodegradation such as [1,2,4]Triazolidine-3,5-diol, hydrazine dibasic carboxylic acid and carbamic acid were detected. A novel TZ biotransformation approach via hydration, TZ-ring cleavage, deamination and oxidation was speculated. PICRUSt1 and KEGG pathway analyses indicated that hydration (dch), oxidation (adhD, oah, pucG, fdhA) of TZ and nitrate reduction (Nar, napA, nrfA, nirBK, norB, nosZ) were significantly enhanced in the presence of nitrate. Moreover, the significant enrichment of TCA cycle (gab, sdh, fum, etc.) indicated that carbon and energy metabolism were facilitated with the addition of nitrate, thus improved TZ catabolism. The proposed mechanism demonstrated that TZ biodegradation coupled with nitrate reduction would be a promising approach for efficient treatment of wastewater contaminated by TZ.

[Research progress of PD-L1 in inflammatory lung diseases].

Programmed death-ligand 1 (PD-L1) is important in maintaining central and peripheral immune tolerance in normal tissues, mediating tumor immune escape and keeping the balance between anti- and pro-inflammatory responses. Inflammation plays an important role in inflammatory lung diseases. This article reviews the research progress and potential clinical value of PD-L1 in inflammatory lung diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma and idiopathic pulmonary fibrosis.

Catalytic Asymmetric Synthesis of Vicinal Quaternary Stereocenters Enabled by Alkylation of α,α-Disubstituted Aldehydes with 3-Bromooxindoles.

An organocatalytic enantioselective alkylation of α,α-disubstituted aldehydes with 3-bromooxindoles is reported. Enantioenriched oxindoles with vicinal quaternary stereocenters are accessed by an asymmetric conjugate addition process of branched aldehydes with o-azaxylylene intermediates (indol-2-ones). Key to the success of highly diastereo- and enantioselective transformations is the combined use of a triphenylsilyl-protected ß-amino alcohol catalyst derived from the spiropyrrolidine scaffold and 3,5-dinitrobenzoic acid. This study also presents a rare example of aldehyde alkylation with the formation of consecutive quaternary stereocenters.

Pericoronary adipose tissue attenuation in patients with acute aortic dissection based on coronary computed tomography angiography.

Background: Periaortic fat is associated with coronary disease. Thus, it was hypothesized that the inflammation associated with acute aortic dissection (AAD) spreads to pericoronary adipose tissue (PCAT) via thoracic periaortic fat. Pericoronary adipose tissue attenuation (PCATa) serves as a marker for inflammation of perivascular adipose tissue (PVAT). This study sought to examine PCATa in individuals diagnosed with AAD. Methods: Consecutive patients with chest pain from May 2020 to September 2022 were prospectively enrolled in this study and underwent coronary computed tomography angiography (CCTA) and/or aorta computed tomography angiography (CTA). Based on the results of the CTA, the patients were divided into the following two groups: (I) the AAD group; and (II) the non-AAD group. PCATa of the right coronary angiography (RCA), left anterior descending (LAD), and left circumflex (LCx) was quantified for each patient using semi-automated software. The PCATa values were compared between the AAD and non-AAD patients according to the atherosclerosis of the coronary arteries. Similarly, the PCATa values of the AAD patients were compared between the preoperative and postoperative steady states. Results: A total of 136 patients (42 female, 94 male; mean age: 63.3±11.9 years) were divided into the two groups according to the presence of aortic dissection on CTA. The RCAPCATa, LADPCATa, and LCxPCATa values were significantly higher in the AAD subjects than the non-AAD subjects, regardless of the presence or absence of atherosclerosis in the coronary arteries [-85.1±9.3 vs. -92.9±10.0 Hounsfield unit (HU); -83.2±7.4 vs. -89.9±9.1 HU; -77.5±8.4 vs. -85.6±7.9 HU, all P<0.001). The preoperative RCAPCATa, LADPCATa, and LCxPCATa values were higher in the AAD patients than the postoperative steady-state patients (-82.9±8.7 vs. -97.6±8.8 HU; -79.8±7.6 vs. -92.8±6.8 HU; -74.6±7.1 vs. -87.7±6.9 HU, all P<0.001). According to the multivariable logistic regression analysis, high RCAPCATa and LADPCATa values were associated with AAD regardless of the degree of stenosis [odds ratio (OR) =0.014; 95% confidence interval (CI): 0.001-0.177; P=0.001 and OR =0.010; 95% CI: 0.001-0.189; P=0.002]. Conclusions: PCATa on computed tomography was increased in patients with AAD regardless of the presence or absence of coronary artery disease (CAD). This suggests that vascular inflammation is present in AAD independent of CAD. Further research should be conducted to investigate the potential of this imaging biomarker to predict AAD and monitor patients' responses to therapies for AAD.

Risk, Predictive, and Preventive Factors for Noninfectious Ventriculitis and External Ventricular Drain Infection.

BACKGROUND: External ventricular drain (EVD) is used for monitoring intracranial pressure or diverting cerebrospinal fluid. However, confirmation of an infection is not immediate and requires obtaining culture results, often leading to the excessive use of antibiotics. This study aimed to compare noninfectious ventriculitis and EVD infection in terms of the risk factors, predictors, prognosis, and effectiveness of care bundle interventions. METHODS: This retrospective study was conducted at a medical center with 1,006 beds in northern Taiwan between January 2018 and July 2022. Standard EVD insertion protocols and care bundles have been implemented since 2018, along with the initiation of chlorhexidine. RESULTS: In total, 742 EVD cases were identified. Noninfectious ventriculitis typically presents with fever approximately 8 days following EVD placement, whereas EVD infection typically manifests as fever after 20 days. Aneurysmal subarachnoid hemorrhage was strongly associated with the development of noninfectious ventriculitis (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.4). Alcoholism (adjusted OR 3.5, 95% CI 1.1-12.3) and arteriovenous malformation (adjusted OR 13.1, 95% CI 2.9-58.2) significantly increased the risk of EVD infection. The EVD infection rate significantly decreased from 3.6% (14 of 446) to 1.0% (3 of 219) (p = 0.03) after the implementation of chlorhexidine gluconate bathing. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage or fever with neuroinflammation within 2 weeks of EVD placement is indicative of a higher likelihood of noninfectious ventriculitis. Conversely, patients with arteriovenous malformation, alcoholism, or fever with neuroinflammation occurring after more than 3 weeks of EVD placement are more likely to necessitate antibiotic treatment for EVD infection. Chlorhexidine gluconate bathing decreases EVD infection.

Occurrence, physicochemical properties and environmental behavior of polychlorinated dibenzothiophenes: A comprehensive review and future perspectives.

Polychlorinated dibenzothiophenes (PCDTs) are a form of emerging pollutant that has attracted great attention due to their structural resemblance to dioxins, which cast detrimental influence on the ecosystem and human health. This review shows the current status of research on PCDTs, focusing on their environmental occurrence, physicochemical properties, environmental behavior, and toxicity. Studies have suggested that the steps leading to the formation of PCDTs resemble those generating polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs), indicating their probable origin from the same sources. Furthermore, they may undergo a dechlorination process as a result of their photodegradation in the environment and metabolic reaction occurring within organisms, which could result in the conversion of these substances into additional pollutants like dibenzothiophene. PCDTs exist widely in the environmental media and have high logKOW values (>4.0), indicating their tendency to bioaccumulate. Moreover, the prediction results of EPI (Estimation Program Interface) Suite demonstrated a strong accumulation capacity for tetra-CDTs in fish compared to other chlorinated PCDTs. The biotransformation half-life of PCDTs would prolong with an increasing number of substituted Cl atoms in fish. A limited number of studies have also suggested that PCDTs can cause damage to the liver and immune system in living organisms, and the toxicity of PCDTs depends on the number and position of substituted Cl atoms. Future studies should be conducted on processes causing PCDT toxicity as well as their behavior and fate in actual environments.

Photoinduced reductive Reformatsky reaction of α-haloesters and aldehydes or ketones by cooperative dual-metal catalysis.

A photoinduced reductive Reformatsky reaction by cooperative dual-metal catalysis is described. This methodology enables the implementation of this venerable reaction in environmentally friendly conditions, obviating the need for a stoichiometric amount of metals. A broad range of synthetically useful ß-hydroxy esters can be efficiently prepared in moderate to high yields using this protocol.

Catalytic Asymmetric Polycyclization of Tertiary Enamides with Silyl Enol Ethers: Total Synthesis of (-)-Cephalocyclidin A.

A catalytic enantioselective polycyclization of tertiary enamides with terminal silyl enol ethers has been developed by virtue of Cu(OTf)2 catalysis with a novel spiropyrroline-derived oxazole (SPDO) ligand. This tandem reaction offers an effective approach to assemble bicyclic and tricyclic N-heterocycles bearing both aza- and oxa-quaternary stereogenic centers, which are primal subunits in a range of natural alkaloids. Strategic application of this methodology and a late-stage radical cyclization as key steps have been showcased in the concise total synthesis of (-)-cephalocyclidin A.

Enantioselective Synthesis of 2,3,3a,8a-Tetrahydrofuro[2,3-b]benzofuran Scaffolds Enabled by Cu(II)/SPDO-Catalyzed [3+2] Cycloaddition of 2,3-Dihydrofuran and Quinone Esters.

An asymmetric [3+2] cycloaddition of quinone esters with 2,3-dihydrofuran has been realized via a newly developed Cu(II)/SPDO complex. It provides straightforward access to 2,3,3a,8a-tetrahydrofuro[2,3-b]benzofurans (TFB) with high enantioselectivity (up to 97.5:2.5 er) and diastereoselectivity (all >20:1 dr). The resulting adducts contain two adjacent stereocenters and a continuously functionalized benzene ring. Additionally, this transformation could be easily performed on a gram scale, allowing for expedient synthesis of natural dihydroaflatoxin D2 and aflatoxin B2.

Cross-Electrophile C-PIII Coupling of Chlorophosphines with Organic Halides: Photoinduced PIII and Aminoalkyl Radical Generation Enabled by Pnictogen Bonding.

Pnictogen bonding (PnB) has gained recognition as an appealing strategy for constructing novel architectures and unlocking new properties. Within the synthetic community, the development of a straightforward and much simpler protocol for cross-electrophile C-PIII coupling remains an ongoing challenge with organic halides. In this study, we present a simple strategy for photoinduced PnB-enabled cross-electrophile C-PIII couplings using readily available chlorophosphines and organic halides via merging single electron transfer (SET) and halogen atom transfer (XAT) processes. In this photomediated transformation, the PnB formed between chlorophosphines and alkyl amines facilitates the photogeneration of PIII radicals and α-aminoalkyl radicals through SET. Subsequently, the resulting α-aminoalkyl radicals activate C-X bonds via XAT, leading to the formation of carbon radicals. This methodology offers operational simplicity and compatibility with both aliphatic and aromatic chlorophosphines and organic halides.

NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of ß- or γ-Branched Chiral Aromatic N-Heterocycles.

A nickel hydride-catalyzed regio- and enantioselective hydroalkylation reaction was developed to give access to a library of chiral ß- or γ-branched aromatic N-heterocycles. This intriguing asymmetric transformation features excellent selectivities, step- and atom-economies, and generating two kinds of chiral products through one synthetic strategy. Furthermore, the possible reaction mechanism was extensively investigated using numerous control experiments and density functional theory calculations.

Catalytic Enantioselective Alkylation of Aldehydes with 3-Bromooxindoles.

An asymmetric conjugate addition of aldehydes with o-azaxylylene intermediates (indol-2-ones) from 3-bromooxindoles has been developed. The use of a novel spiro-pyrrolidine (SPD)-derived bifunctional N-sulfonylated amide catalyst is essential for a highly diastereo- and enantioselective transformation to provide a wide array of enantioenriched C3 quaternary oxindoles with structurally diverse ß-aldehyde appendages. Further application of this synthetic methodology enables the construction of the tricyclic cores of akuammiline-type alkaloids.

Total Syntheses of Polycyclic Diterpenes Phomopsene, Methyl Phomopsenonate, and iso-Phomopsene via Reorganization of C-C Single Bonds.

The first total syntheses of polycyclic diterpenes phomopsene (1), methyl phomopsenonate (2), and iso-phomopsene (3) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1-3. This work enables us to determine that the correct structure of iso-phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.

Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems.

An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD-NH2 ) and PdII complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ6 -protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD-NH2 catalyst and the branched chain of the substrate, hydrogen-bonding interactions between the N-H of the enamine motif and the C=O of the directing group MQ, and the counterion of the PdII complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.

Photocatalytic Charge-Transfer Complex Enables Hydroarylation of Alkenes for Heterocycle Synthesis.

Here, we report a photocatalytic charge-transfer complex (CTC) strategy for one electron reduction of alkenes using thiolate as a catalytic electron donor. This catalytic CTC system could engage hydroarylation of both activated and unactivated alkenes for the synthesis of various heterocycles. The reactions do not require any photocatalysts or acids and are easy to perform. Mechanistic studies revealed the formation of a CTC between catalytic thiolate and alkene.

Endothelial Dysfunction in Neurodegenerative Diseases.

The cerebral vascular system stringently regulates cerebral blood flow (CBF). The components of the blood-brain barrier (BBB) protect the brain from pathogenic infections and harmful substances, efflux waste, and exchange substances; however, diseases develop in cases of blood vessel injuries and BBB dysregulation. Vascular pathology is concurrent with the mechanisms underlying aging, Alzheimer's disease (AD), and vascular dementia (VaD), which suggests its involvement in these mechanisms. Therefore, in the present study, we reviewed the role of vascular dysfunction in aging and neurodegenerative diseases, particularly AD and VaD. During the development of the aforementioned diseases, changes occur in the cerebral blood vessel morphology and local cells, which, in turn, alter CBF, fluid dynamics, and vascular integrity. Chronic vascular inflammation and blood vessel dysregulation further exacerbate vascular dysfunction. Multitudinous pathogenic processes affect the cerebrovascular system, whose dysfunction causes cognitive impairment. Knowledge regarding the pathophysiology of vascular dysfunction in neurodegenerative diseases and the underlying molecular mechanisms may lead to the discovery of clinically relevant vascular biomarkers, which may facilitate vascular imaging for disease prevention and treatment.