TMSCl-Promoted Sulfonylation of Propargylic Alcohols with Sodium Sulfinates for the Construction of (E)-1,3-Disulfonylpropenes and (E)-1-Sulfonylpropenols.

A direct and novel transformation of propargylic alcohols with sodium sulfinates for the regio- and stereoselective synthesis of (E)-1,3-disulfonylpropenes and (E)-1-sulfonylpropenols was successfully developed in the presence of TMSCl under mild conditions. The preliminary mechanistic experiments demonstrated that the reaction underwent an unprecedented dual nucleophilic substitution/radical addition process, in which sodium sulfinates were used not only as nucleophiles but also as a sulfonyl radical source.

TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Non-contrast CT radiomics-clinical machine learning model for futile recanalization after endovascular treatment in anterior circulation acute ischemic stroke.

OBJECTIVE: To establish a machine learning model based on radiomics and clinical features derived from non-contrast CT to predict futile recanalization (FR) in patients with anterior circulation acute ischemic stroke (AIS) undergoing endovascular treatment. METHODS: A retrospective analysis was conducted on 174 patients who underwent endovascular treatment for acute anterior circulation ischemic stroke between January 2020 and December 2023. FR was defined as successful recanalization but poor prognosis at 90 days (modified Rankin Scale, mRS 4-6). Radiomic features were extracted from non-contrast CT and selected using the least absolute shrinkage and selection operator (LASSO) regression method. Logistic regression (LR) model was used to build models based on radiomic and clinical features. A radiomics-clinical nomogram model was developed, and the predictive performance of the models was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 174 patients were included. 2016 radiomic features were extracted from non-contrast CT, and 9 features were selected to build the radiomics model. Univariate and stepwise multivariate analyses identified admission NIHSS score, hemorrhagic transformation, NLR, and admission blood glucose as independent factors for building the clinical model. The AUC of the radiomics-clinical nomogram model in the training and testing cohorts were 0.860 (95%CI 0.801-0.919) and 0.775 (95%CI 0.605-0.945), respectively. CONCLUSION: The radiomics-clinical nomogram model based on non-contrast CT demonstrated satisfactory performance in predicting futile recanalization in patients with anterior circulation acute ischemic stroke.

Chiral Cpx Rhodium(III)-Catalyzed Enantioselective Aziridination of Unactivated Terminal Alkenes.

Chiral cyclopentadienyl-rhodium(III) Cpx Rh(III) catalysis has been demonstrated to be competent for catalyzing highly enantioselective aziridination of challenging unactivated terminal alkenes and nitrene sources. The chiral Cpx Rh(III) catalysis system exhibited outstanding catalytic performance and wide functional group tolerance, yielding synthetically important and highly valuable chiral aziridines with good to excellent yields and enantioselectivities (up to 99 % yield, 93 % ee). This protocol presents a novel and effective strategy for synthesizing enantioenriched aziridines from simple alkenes. Various transformations were performed on the aziridine products, illustrating the versatility and synthetic potential of this protocol for constructing highly functionalized compounds.

Cascade Cyclization of 1,5-Diynols and (RO)2P(O)SH to Construct Benzo[b]fluorenyl S-Alkyl Phosphorothioates under Catalyst-Free Conditions.

An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed. A variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates were successfully constructed in moderate to excellent yields. Furthermore, this protocol exhibited good functional group tolerance, a broad substrate scope, and potential practical applications, with water as the only byproduct. The reaction proceeded with allenyl thiophosphate as a key intermediate, followed by a Schmittel-type cyclization process to produce the target product.

Electrochemically enabled decyanative C(sp3)-H oxygenation of N-cyanomethylamines to formamides.

Selective oxygenation of C(sp3)-H bonds adjacent to nitrogen atoms is a highly attractive strategy for synthesizing various formamide derivatives while preserving the substrate skeletons. Herein, an environmentally benign electrochemically enabled decyanative C(sp3)-H oxygenation of N-cyanomethylamines using H2O as a carbonyl oxygen atom source is described, leading to the synthesis of a large class of formamides in good to excellent yields with a broad substrate scope under metal- and oxidant-free conditions. This electrochemical technology highlights the facile incorporation of N-formyl into some important bioactive molecules.

Electro-/photocatalytic alkene-derived radical cation chemistry: recent advances in synthetic applications.

Alkene-derived radical cations are versatile reactive intermediates and have been widely applied in the construction of complex functionalized molecules and cyclic systems for chemical synthesis. Therefore, the synthetic application of these alkene-derived radical cations represents a powerful and green tool that can be used to achieve the functionalization of alkenes partially because the necessity of stoichiometric external chemical oxidants and/or hazardous reaction conditions is eliminated. This review summarizes the recent advances in the synthetic applications of the electro-/photochemical alkene-derived radical cations, emphasizing the key single-electron oxidation steps of the alkenes, the scope and limitations of the substrates, and the related reaction mechanisms. Using electrocatalysis and/or photocatalysis, single electron transfer (SET) oxidation of the CC bonds in the alkenes occurs, generating the alkene-derived radical cations, which sequentially enables the functionalization of translocated radical cations to occur in two ways: the first involves direct reaction with a nucleophile/radical or two molecules of nucleophiles to realize hydrofunctionalization, difunctionalization and cyclization; and the second involves the transformation of the alkene-derived radical cations into carbon-centered radicals using a base followed by radical coupling or oxidative nucleophilic coupling.

Electrochemical 1,2-Diarylation of Alkenes Enabled by Direct Dual C-H Functionalizations of Electron-Rich Aromatic Hydrocarbons.

A cobalt-promoted electrochemical 1,2-diarylation of alkenes with electron-rich aromatic hydrocarbons via direct dual C-H functionalizations is described, which employs a radical relay strategy to produce polyaryl-functionalized alkanes. Simply by using graphite rod cathode instead of platinum plate cathode, chemoselectivity of this radical relay strategy is shifted to the dehydrogenative [2+2+2] cycloaddition via 1,2-diarylation, annulation, and dehydrogenation cascades leading to complex 11,12-dihydroindolo[2,3-a]carbazoles. Mechanistical studies indicate that a key step for the radical relay processes is transformations of the aromatic hydrocarbons to the aryl sp2 -hybridized carbon-centered radicals via deprotonation of the corresponding aryl radical cation intermediates with bases.

Chemical Composition of Essential Oil from Flower of 'Shanzhizi' (Gardenia jasminoides Ellis) and Involvement of Serotonergic System in Its Anxiolytic Effect.

Gardenia jasminoides Ellis is a famous fragrant flower in China. Previous pharmacological research mainly focuses on its fruit. In this study, the essential oil of the flower of 'Shanzhizi', which was a major variety for traditional Chinese medicine use, was extracted by hydro distillation and analyzed by GC-MS. Mouse anxiety models included open field, elevated plus maze (EPM), and light and dark box (LDB), which were used to evaluate its anxiolytic effect via inhalation. The involvement of monoamine system was studied by pretreatment with neurotransmitter receptor antagonists WAY100635, flumazenil and sulpiride. The monoamine neurotransmitters contents in the prefrontal cortex (PFC) and hippocampus after aroma inhalation were also analyzed. The results showed that inhalation of G. jasminoides essential oil could significantly elevated the time and entries into open arms in EPM tests and the time explored in the light chamber in LDB tests with no sedative effect. WAY100635 and sulpiride, but not flumazenil, blocked its anxiolytic effect. Inhalation of G. jasminoides essential oil significantly down-regulated the 5-HIAA/5-HT in the PFC and reduced the 5-HIAA content in hippocampus compared to the control treatment. In conclusion, inhalation of gardenia essential oil showed an anxiolytic effect in mice. Monoamine, especially the serotonergic system, was involved in its anxiolytic effect.

ALPL regulates the aggressive potential of high grade serous ovarian cancer cells via a non-canonical WNT pathway.

The ALPL gene is linked to hypophosphatasia, a rare genetic disease. Owing to the inverse relationships between ALPL expression and both the International Federation of Gynecology and Obstetrics (FIGO) stages and histological grades assigned to patients with serous ovarian cancer (SOC), this study was designed to explore the role and possible mechanisms of ALPL in cell motility of high grade SOC (HGSOC). The effects of ALPL overexpression on migration and invasion were detected in HGSOC cell lines SKOV3 and HEY. Gene ontology analysis for differential genes with ALPL overexpression identified several biological processes, including EMT, correlated with cell motility. Genes potentially implicated in EMT and associated with ALPL were screened using The Cancer Genome Atlas (TCGA) database. The WNT receptor Frizzled2 (FZD2) was identified and its role in HGSOC cell motility and survival was investigated. It was found that forced expression of ALPL could inhibit migration, invasion, and EMT in HGSOC cells. It also reduced the expression of FZD2 and its ligand WNT5A, accompanied by suppressed expression of their downstream target phosphorylated-STAT3 (pSTAT3). These effects were initiated via the FZD2 knockdown using siRNA and reversed by recombinant WNT5A protein. The relationship between FZD2 expression and poor HGSOC patient survival was also investigated. This data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis, a non-canonical WNT pathway for promoting EMT progression, which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.

Determining intracellular lipid content of different oleaginous yeasts by one simple and accurate Nile Red fluorescent method.

A simple and accurate Nile Red fluorescent method was built to evaluate the lipid content of three different oleaginous yeasts by one standard curve. The staining of cells can be observed clearly by laser scanning confocal microscope, showing that Nile Red can enter into the cells of oleaginous yeasts easily. A series of conditions such as pretreating temperature, cell suspension concentration (OD600), staining time, Nile Red concentration and the type of suspension solvent were learnt systematically to obtain the optimal process parameters for Nile Red staining. After optimization, the fitting curve of Nile Red fluorescent method was established under suitable conditions (pretreating temperature: 50 °C, OD600: 1.0; staining time: 5 mins; Nile Red concentration: 1.0 µg/mL; suspension solvent: PBS) and it had a suitable correlation coefficient (R2 = 0.95) for lipid content measurement of different oleaginous yeasts. By this study, the possibility of lipid content determination of different oleaginous yeasts by one fitting curve can be proven and this will improve the efficiency of researches related to microbial lipid production.

Efficient bioconversion from acid hydrolysate of waste oleaginous yeast biomass after microbial oil extraction to bacterial cellulose by Komagataeibacter xylinus.

Biomass acid hydrolysate of oleaginous yeast Trichosporon cutaneum after microbial oil extraction was applied as substrate for bacterial cellulose (BC) production by Komagataeibacter xylinus (also named as Gluconacetobacter xylinus previously) for the first time. BC was synthesized in static culture for 10 days, and the maximum BC yield (2.9 g/L) was got at the 4th day of fermentation. Most carbon sources in the substrate (glucose, mannose, formic acid, acetic acid) can be utilized by K. xylinus. The highest chemical oxygen demand (COD) removal (40.7 ± 3.0%) was obtained at the 6th day of fermentation, and then the COD increased possibly due to the degradation of BC. The highest BC yield on COD consumption was 38.7 ± 4.0% (w/w), suggesting that this is one efficient bioconversion for BC production. The BC structure was affected little by the substrate by comparison with that generated in classical HS medium using field-emission scanning electron microscope (FE-SEM), Fourier transform infrared, and X-ray diffraction. Overall, this technology can both solve the issue of waste oleaginous yeast biomass and produce valuable biopolymer (BC).

Efficient Using Durian Shell Hydrolysate as Low-Cost Substrate for Bacterial Cellulose Production by Gluconacetobacter xylinus.

Durian is one important tropical fruit with high nutritional value, but its shell is usually useless and considered as waste. To explore the efficient and high-value utilization of this agricultural and food waste, in this study, durian shell was simply hydrolyzed by dilute sulfuric acid, and the durian shell hydrolysate after detoxification was used for bacterial cellulose (BC) production by Gluconacetobacter xylinus for the first time. BC was synthesized in static culture for 10 days and the highest BC yield (2.67 g/L) was obtained at the 8th day. The typical carbon sources in the substrate including glucose, xylose, formic acid, acetic acid, etc. can be utilized by G. xylinus. The highest chemical oxygen demand (COD) removal (16.40%) was obtained at the 8th day. The highest BC yield on COD consumption and the highest BC yield on sugar consumption were 93.51% and 22.98% (w/w), respectively, suggesting this is one efficient bioconversion for BC production. Durian shell hydrolysate showed small influence on the BC structure by comparison with the structure of BC generated in traditional Hestrin-Schramm medium detected by FE-SEM, FTIR, and XRD. Overall, this technology can both solve the issue of waste durian shell and produce valuable bio-polymer (BC).

Photocatalytic Enantioselective Radical Cascade Multicomponent Minisci Reaction of ß-Carbolines Using Diazo Compounds as Radical Precursors.

Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of ß-carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of ß-carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo-/enantio-selective control, and good functional group tolerance, allowing access to a variety of valuable chiral ß-carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions. Moreover, the efficiency and practicality of this approach are demonstrated by the asymmetric synthesis of bioactive compounds and natural products.

Photocatalytic enantioselective Minisci reaction of ß-carbolines and application to natural product synthesis.

A highly efficient enantioselective direct C-H functionalization of ß-carbolines via a Minisci-type radical process under a photo-redox and chiral phosphoric acid cooperative catalytic system has been disclosed. Through this protocol, a wide range of C1 aminoalkylated ß-carbolines were constructed directly with high levels of enantioselectivities from readily available ß-carbolines and alanine-derived redox-active esters. This transformation allows straightforward access to highly valuable enantioenriched ß-carbolines, which are an intriguing structural motif in valuable natural products and synthetic bio-active compounds. This protocol has been utilized as a highly efficient synthetic strategy for the concise asymmetric total synthesis of marine alkaloids eudistomin X, (+)-eudistomidin B and (+)-eudistomidin I.

Deferoxamine in intracerebral hemorrhage: Systematic review and meta-analysis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX. METHODS: We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS: After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups. CONCLUSIONS: DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.

Electrochemical 1,3-Alkyloxylimidation of Arylcyclopropane Radical Cations: Four-Component Access to Imide Derivatives.

Herein, a general electrochemical radical-cation-mediated four-component ring-opening 1,3-alkyloxylimidation of arylcyclopropanes, acetonitrile, carboxylic acids, and alcohols is described, providing a facile and sustainable approach to quickly construct structurally diverse imide derivatives from easily available raw materials in an operationally simple undivided cell. This metal-catalyst- and oxidant-free single-electron oxidation strategy offers a green alternative for the formation of highly reactive cyclopropane-derived radical cations, and this protocol features a broad functional group tolerance.

Electrochemical Arene Radical Cation Promoted Spirocyclization of Biaryl Ynones: Access to Alkoxylated Spiro[5,5]trienones.

Herein, a novel electrochemical arene radical cation promoted dearomative spirocyclization of biaryl ynones with alcohols is described, providing a conceptually novel transformation mode for producing diverse alkoxylated spiro[5,5]trienones. The catalyst- and chemical-oxidant-free spirocyclization protocol features broad substrate scope and high functional group tolerance. Mechanistic studies reveal that the generation of arene radical cation via anodic single-electron oxidation is crucial, with sequential 6-endo-dig cyclization, dissociation of hemiketal, anodic oxidation, and nucleophilic attack of alcohols.

The Symptoms of Benign Prostatic Hyperplasia Patients with Stromal-Dominated Hyperplasia Nodules May Be Associated with Prostate Fibrosis.

Objective: The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules. Methods: Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis. Results: The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis. Conclusion: These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules.

Alterations in the balance of sex hormones may affect rat prostatic inflammation and fibrosis, and osteopontin might be involved in this process.

OBJECTIVE: This study aimed to investigate the effects of sex hormone imbalance on rat prostatic inflammation and fibrosis and identify the key molecules involved. METHODS: Castrated Sprague-Dawley (SD) rats were treated with a constant dose of oestradiol (E2) and different doses of dihydrotestosterone (DHT) to achieve different oestrogen/androgen ratios. After 8 weeks, serum E2 and DHT concentrations, relative seminal vesicle weights, histopathological changes and inflammation were measured, collagen fiber content and oestrogen receptor (ER) and androgen receptor (AR) expression were detected, mRNA sequencing and bioinformatics analysis were performed to identify differentially expressed genes (DEGs). RESULTS: The severity of inflammation in the rat dorsolateral prostate (DLP) was higher, collagen fibre content and ER expression in the rat DLP and prostatic urethra were increased and AR expression in the rat DLP was decreased in the 1:1 E2/DHT-treated group than that in the 1:10 E2/DHT-treated group. RNA-seq analysis identified 487 DEGs, and striking increases in the expression of mRNAs encoding collagen, collagen synthesis and degradation enzymes, growth factors and binding proteins, cytokines and chemokines, and cell-surface molecules were confirmed in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group. mRNA expression of secreted phosphoprotein 1 (Spp1) and protein expression of osteopontin (OPN, encoded by Spp1) were increased in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group, and Spp1 expression correlated positively with Mmp7, Cxcl6 and Igfn1 expression. CONCLUSIONS: The imbalance in the oestrogen/androgen ratio may affect rat prostatic inflammation and fibrosis, and OPN might be involved in this process.