Divergent Synthesis of Scabrolide A and Havellockate via an exo-exo-endo Radical Cascade.

Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo-exo-endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6-endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.

Kinetics of H· Transfer from CpCr(CO)3H to Various Enamides: Application to Construction of Pyrrolidines.

The rate constants kH (kD) have been determined at 27 °C for H· (D·) transfer from CpCr(CO)3H(D) to the C=C bonds of various enamides. This process leads to the formation of α-amino radicals. Vinyl enamides with N-alkyl and N-phenyl substituents have proven to be good H· acceptors, with rate constants close to those of styrene and methyl methacrylate. A methyl substituent on the incipient radical site decreases kH by a factor of 4; a methyl substituent on the carbon that will receive the H· decreases kH by a factor of 380. The measured kH values indicate that these α-amino radicals can be used for the cyclization of enamides to pyrrolidines. A vanadium hydride, HV(CO)4(dppe), has proven more effective at the cyclization of enamides than Cr or Co hydrides-presumably because the weakness of the V-H bond leads to faster H· transfer. The use of the vanadium hydride is operationally simple, employs mild reaction conditions, and has a broad substrate scope. Calculations have confirmed that H· transfer is the slowest step in these cyclization reactions.

Dual Suture Versus Suture and Plug Closure Devices for Large Bore Access Haemostasis During Percutaneous Access Endovascular Aneurysm Repair.

PURPOSE: This study aimed to compare a dual Proglide strategy versus a combination of one Proglide and dual Exoseal for large-bore access closure during percutaneous access endovascular aneurysm repair (pEVAR). MATERIALS AND METHODS: We retrospectively analyzed 97 patients who underwent pEVAR at our center between January 2021 and February 2023. The patients were divided into two groups: dual Proglide (P + P) and one Proglide with dual Exoseal (P + E). The primary outcome measures were technical success and access-related vascular complications. Technical success was defined as achieving complete hemostasis without a bailout strategy. Postprocedural follow-up for access-related vascular complications was evaluated at 30 and 60 days using computed tomography angiography and ultrasonography. Severity was graded according to the Cardiovascular Interventional Radiological Society of Europe (CIRSE) Classification. RESULTS: Overall, a dual Proglide strategy was used in 46 patients (47.4%) with 65 groins (46.4%), and a combination of one Proglide and dual Exoseal was used in 51 patients (52.6%) with 75 groins (53.6%). The baseline characteristics were similar between the groups. The total technical success rate was 96.4%, and no significant differences were observed (95.4% vs. 97.3%; p = 0.870). Minor bleeding treatable through compression occurred significantly more often in the P group (CIRSE 1, 10.8% vs. 1.3%, p = 0.042). Hemostasis time, procedural time, length of stay in the hospital, closure device failure, and incidence of unplanned intervention did not differ significantly between the groups. CONCLUSIONS: A combined Proglide and Exoseal strategy is safe and effective for large-bore access closure during pEVAR and can be considered an alternative. However, it should be supported by larger prospective studies.

Acute Pancreatitis After Percutaneous Metallic Stent Insertion for Malignant Biliary Obstruction: A Retrospective 2-Center Study.

BACKGROUND/AIMS: The current study investigated the incidence, risk factors, and outcomes of acute pancreatitis after percutaneous transhepatic biliary stenting for malignant biliary obstruction. MATERIALS AND METHODS: From March 2016 to May 2020, a total of 425 patients who underwent percutaneous transhepatic biliary stent- ing for malignant biliary obstruction were included in this 2-center study. After the procedure, we analyzed the incidence, risk factors, and outcomes of acute pancreatitis. RESULTS: On follow-up, 79 (18.6%) patients showed increased serum amylase levels, of whom 41 (9.6%) developed pancreatitis. On binary logistic regression analysis, stent across the duodenal papilla (odds ratio = 8.54; 95% CI = 3.54-20.62; P < .001) and visualization of the pancreatic duct (odds ratio = 9.87; 95% CI = 4.67-20.86; P < .001) were significant risk factors of pancreatitis after the procedure. Using conservative therapy, all patients were successfully managed at a mean of 3.5 days (range 1-6 days), and no severe pancreatitis happened. CONCLUSION: Acute pancreatitis is a relatively common complication after percutaneous transhepatic biliary stenting. Stent across the duodenal papilla and visualization of the pancreatic duct are independent risk factors.

Safety and Effectiveness of a Sequential Suture and Plug Vascular Closure Devices Technique for Large-Bore Access Closure after Percutaneous Endovascular Aneurysm Repair.

PURPOSE: To evaluate the safety and effectiveness of sequential sutures and plugged vascular closure devices (VCDs) for large-bore access closure during percutaneous access endovascular aneurysm repair (PEVAR). MATERIALS AND METHODS: Data on 16 patients who underwent PEVAR at the authors' center from January 2022 to May 2022 were retrospectively reviewed. The median age was 72 years (interquartile range [IQR], 59-75 years), with a male-to-female ratio of 3:1. All patients received sequential suture and plug VCDs using dual Exoseal after 1 Proglide for access closure. Success was defined as the ability to achieve complete hemostasis and was confirmed by ultrasonography. The patients were followed up for access-related adverse events at 30 and 90 days after the procedure, and the severity was graded according to the Society of Interventional Radiology (SIR) classification. RESULTS: Overall, 24 access sites were included. The median sheath size was 21 F (IQR, 18-23 F). The median hemostasis time was 11.0 minutes (IQR, 9.3-13.0 minutes), the median procedural time was 133.5 minutes (IQR, 102.5-151.0 minutes), and the median length of stay was 5 days (IQR, 4.0-6.8 days). The success rate was 95.8%, and a pseudoaneurysm (SIR Grade 2) developed in 1 patient, which was treated by a percutaneous injection of thrombin. No other access-related adverse events occurred, and the total adverse event rate was 4.2%. CONCLUSIONS: Placement of sequential suture and plug VCDs using 1 Proglide and dual Exoseal is a safe and effective method and may be an option for access closure during PEVAR.

Cu-catalysed enantioselective radical heteroatomic S-O cross-coupling.

The transition-metal-catalysed cross-coupling reaction has established itself as one of the most reliable and practical synthetic tools for the efficient construction of carbon-carbon/heteroatom (p-block elements other than carbon) bonds in both racemic and enantioselective manners. In contrast, development of the corresponding heteroatom-heteroatom cross-couplings has so far remained elusive, probably due to the under-investigated and often challenging heteroatom-heteroatom reductive elimination. Here we demonstrate the use of single-electron reductive elimination as a strategy for developing enantioselective S-O coupling under Cu catalysis, based on both experimental and theoretical results. The reaction manifests its synthetic potential by the ready preparation of challenging chiral alcohols featuring congested stereocentres, the expedient valorization of the biomass-derived feedstock glycerol, and the remarkable catalytic 4,6-desymmetrization of inositol. These results demonstrate the potential of enantioselective radical heteroatomic cross-coupling as a general chiral heteroatom-heteroatom formation strategy.

Single-Step Synthesis of Atropisomers with Vicinal C-C and C-N Diaxes by Cobalt-Catalyzed Atroposelective C-H Annulation.

The atroposelective synthesis of atropisomers with vicinal diaxes remains rare and challenging, due to the steric influence between the two axes and their unique topology. Herein, we disclose a single-step construction of atropisomers with vicinal C-C and C-N chiral diaxes by cyclopentadiene (Cp)-free cobalt-catalyzed intramolecular atroposelective C-H annulation, providing the desired diaxial atropisomers of unique structures with decent stereocontrols of both axes (up to >99 % ee and 70 : 1 dr). The optically pure products bearing fluorophores show circular polarized luminescence (CPL) properties, being candidate materials for potential CPL applications. Atropisomerization experiments and density function theory (DFT) calculations are conducted to study the rotational barriers and rotation pathways of the diaxes.

Mechanism-based ligand design for copper-catalysed enantioconvergent C(sp3)-C(sp) cross-coupling of tertiary electrophiles with alkynes.

In contrast with the well-established enantioconvergent radical C(sp3)-C cross-coupling of racemic secondary alkyl electrophiles, the corresponding coupling of tertiary electrophiles to forge all-carbon quaternary stereocentres remains underexplored. The major challenge arises from the steric hindrance and the difficult enantio-differentiation of three distinct carbon substituents of prochiral tertiary radicals. Here we demonstrate a general copper-catalysed enantioconvergent C(sp3)-C(sp) cross-coupling of diverse racemic tertiary alkyl halides with terminal alkynes (87 examples). Key to the success is the rational design of chiral anionic N,N,N-ligands tailor-made for the computationally predicted outer-sphere radical group transfer pathway. This protocol provides a practical platform for the construction of chiral C(sp3)-C(sp/sp2/sp3) bonds, allowing for expedient access to an array of synthetically challenging quaternary carbon building blocks of interest in organic synthesis and related areas.

Human cytomegalovirus glycoprotein B inhibits migration of breast cancer MDA-MB-231 cells and impairs TGF-ß/Smad2/3 expression.

Breast cancer is a leading cause of cancer-associated mortality in females worldwide and evidence suggests that human cytomegalovirus (HCMV) infection may be implicated in the progress of breast cancer. HCMV glycoprotein B (gB) is the most abundant envelope protein and serves an important role in host cell entry. The present study aimed to clarify the role of HCMV gB in breast cancer cells. A HCMV gB construct (UL55) was generated and stable vUL55 gene lentivirus-transfected MDA-MB-231 cells were established. Subsequently, the effect of HCMV gB on the apoptosis and proliferation of MDA-MB-231 cells was measured by flow cytometry and Cell Counting Kit-8 assay. Furthermore, whether HCMV gB may modulate MDA-MB-231 cell migration was examined using Transwell and cell scratch assays. In addition, alterations in HCMV gB-modulated protein levels of transforming growth factor-ß (TGF-ß) and Mothers against decapentaplegic homologs 2/3 (Smad2/3) were detected using western blot analysis. The results indicated that UL55 cDNA was stably transfected into MDA-MB-231 cells, and that HCMV gB protein was stably expressed. No significant differences in cell apoptosis and proliferation between transfected (231-GB-OE) and negative control (231-NC) cells were observed, while the rate of cell migration was significantly decreased in the 231-GB-OE cells compared with the 231-NC cells. Additionally, the expression level of TGF-ß and phosphorylation level of Smad2/3 were also decreased in 231-GB-OE cells compared with the 231-NC cells. Although certain previous studies indicated that HCMV infection was associated with breast carcinogenesis, the results of the present study indicate that the envelope protein HCMV gB exhibits no effect on cell apoptosis and proliferation, but inhibits breast cancer cell migration. This may be due to downregulated TGF-ß/Smad signaling. Taken together, these studies may assist in developing anti-TGF-ß agents that contribute to tumor suppression.

[Expression of cyclooxygenase-2 and inducible nitric oxide synthase in tongue hyperplasia and tongue squamous cell carcinoma].

BACKGROUND & OBJECTIVE: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogenous factors of human tumor progression. However, the biological significance of the adnormal expression of COX-2 and iNOS in tongue squamous cell carcinoma remains unclear. This study was to investigate the expression of COX-2 and iNOS in tongue squamous cell carcinoma and precancerous lesions, and analyze their interrelation. METHODS: The expression of COX-2 and iNOS in 59 specimens of tongue squamous cell carcinoma (SCC), 45 specimens of hyperplasia (22 cases of mild hyperplasia, 20 cases of moderate hyperplasia, and 3 cases of severe hyperplasia), and 36 specimens of pericancerous normal epithelium was detected by SP immunohistochemistry. RESULTS: The positive rates of COX-2 were 8.3% in normal epithelium, 4.5% in mild hyperplasia, 5.0% in moderate hyperplasia, 0 in severe hyperplasia, and 45.8% in SCC, respectively; those of iNOS were 44.4% in normal epithelium, 72.7% in mild hyperplasia, 80.0% in moderate hyperplasia, 100% in severe hyperplasia, and 98.3% in SCC, respectively. The positive rates of COX-2 and iNOS were significantly higher in SCC than in normal epithelium (P < 0.001); the positive rate of iNOS was also significantly higher in hyperplasia than in normal epithelium (P < 0.001). The overexpression of COX-2 and iNOS was positively correlated with pathologic grade of the lesions (r = 0.418, P < 0.001; r = 0.607, P < 0.001). COX-2 expression was positively correlated with iNOS expression (r = 0.245, P < 0.001). CONCLUSOIN: The overexpression of COX-2 and iNOS is closely related to the carcinogenesis of the tongue.