Asymmetric Synthesis of Chiral 1,2-Bis(Boronic) Esters Featuring Acyclic, Non-Adjacent 1,3-Stereocenters.

The construction of acyclic, non-adjacent 1,3-stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long-standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2-bis(boronic) esters featuring acyclic and nonadjacent 1,3-stereocenters. Notably, this reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct allylation byproducts. This approach introduces a new activation mode for selective transformations of gem-diborylmethane in asymmetric catalysis. Additionally, we found that other gem-diborylalkanes, previously challenging due to steric hindrance, also successfully participated in this reaction. The incorporation of 1,2-bis(boryl)alkenes facilitated the diversification of the alkenyl and two boron moieties in our target compounds, thereby enabling access to a broad array of versatile molecules. DFT calculations were performed to elucidate the reaction mechanism and shed light on the factors responsible for the observed excellent enantioselectivity and diastereoselectivity. These were determined to arise from ligand-substrate steric repulsions in the syn-addition transition state.

Ir-Catalyzed Enantioselective Synthesis of gem-Diborylalkenes Enabled by 1,2-Boron Shift.

Asymmetric cross-couplings based on 1,2-carbon migration from B-ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by 1,2-boron shift have remained to be unaddressed synthetic challenge. Here, Ir-catalyzed asymmetric allylic alkylation enabled by 1,2-boron shift was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of allylic carbonates at the elevated temperature. Notably, the highly valuable (bis-boryl)alkenes have enabled an array of diversifications to access versatile molecules. Extensive experimental and computational studies were conducted to elucidate the reaction mechanism of DKR process and clarify the origin of excellent enantioselectivities.

Hepatic Microwave Ablation-Induced Tumor Destruction and Animal End Point Survival Can Be Improved by Suppression of Heat Shock Protein 90.

OBJECTIVES: To investigate the effect of heat shock protein 90 (HSP90) modulation on tumor necrosis, apoptosis, tumor growth delay, and end point survival by combining microwave ablation (MWA) with an HSP90 inhibitor in a nude mouse model. METHODS: This study was approved by the Ethics Committee. Forty mice with HepG2 subcutaneous xenograft tumors (10 ± 1 mm) were randomized into 4 groups: (1) no treatment, (2) MWA only, (3) the HSP90 inhibitor ganetespib only, and (4) ganetespib combined with MWA. Tumors were harvested 24 hours after treatment, and gross coagulation diameters were measured. The effect of ganetespib on HSP90 and caspase 3 expression in the periablational rim was assessed. Another 40 mice with the same tumors and groupings were observed after treatment. Tumor growth curve and Kaplan-Meier survival analyses were performed with a tumor diameter of 2.2 cm and 40 days of survival as the defined survival end points. RESULTS: Combination treatment significantly increased the coagulation size compared to tumors treated with MWA or ganetespib alone (P < 0.05). The combination of MWA and ganetespib decreased HSP90 expression and increased cleaved caspase 3 expression 24 hours after treatment. Compared with MWA or ganetespib only, combination treatment could lengthen the end point survival and reduce the tumor growth rate. CONCLUSIONS: Modulation of HSP production can improve MWA-induced tumor apoptosis and destruction, reduce residual tumor growth rates, and prolong end point survival.

Comparison of Sonazoid and SonoVue in the Diagnosis of Focal Liver Lesions: A Preliminary Study.

OBJECTIVE: This study aimed to compare the efficacy of Sonazoid and SonoVue in subjects with focal liver lesions. METHODS: The patients who had untreated focal solid liver lesions confirmed by B-mode ultrasonography were eligible for the study. The target lesion and whole liver were scanned by gray scale ultrasonography; then, contrast-enhanced ultrasonography was performed, and the results were evaluated blindly. The main end point was accuracy improvement with postcontrast versus precontrast ultrasound examination for diagnosis of the target lesion of interest as malignant or benign against the reference standard. RESULTS: There were 65 patients with 65 hepatic tumors enrolled in the study. The improvement of diagnostic accuracy was 0.30 in the Sonazoid group and 0.16 in the SonoVue group (95% confidence interval, -0.828-0.168; P = .24). Using 20% as the noninferiority margin, the upper limit of the 95% confidence interval (0.168) was less than 0.20. The number of lesions detected during the whole-liver scanning in the Sonazoid group was significantly more than that detected in the SonoVue group (P = .024). CONCLUSION: The diagnosis value of Sonazoid is noninferior to SonoVue, and this new contrast agent can improves the whole-liver image quality.

Corneal nerve changes by anti-glaucoma medications examined by in vivo confocal microscopy.

AIM: To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy (IVCM). METHODS: This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals. Among the glaucoma patients, 54 were treated with medication, while 25 remained untreated. Central corneal images were evaluated by IVCM, and then ACCMetrics was used to calculate the following parameters: corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman's rank correlation coefficient. RESULTS: The CNFD was reduced in glaucoma groups compared to healthy subjects (P<0.01). Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients. As the number of medications and usage count increased, CNFD, CNBD, CNFL, CTBD, CNFA, and CNFrD experienced a decline, while CNFW increased (all P<0.01). For the brinzolamide-therapy group, there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups (P<0.001). In the absence of medication, CNFD in males was lower than that in females (P<0.05). Among patients under medication therapy, CNFD remained consistent between males and females. CONCLUSION: Antiglaucoma eye drops affect the microstructure of corneal nerves. IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.

Unicentric Castleman disease was misdiagnosed as pancreatic mass: A case report.

BACKGROUND: Castleman's disease (CD) is a lymphatic proliferative disorder of unknown cause and is rarely seen clinically. It has been divided into unicentric and multicentric types. Unicentric CD (UCD) occurs as a solitary enlarged mass and mediastinal lymph nodes are the most common site. Surgical excision has proven to be curative for UCD. Multicentric CD (MCD) appears as a systemic disease with peripheral lymphadenopathy. MCD had a poor response to surgery and monoclonal antibodies with rituximab have become a research hotspot. CASE SUMMARY: A 44-year-old woman presented with a pancreatic mass during routine physical examination. She had no obvious symptoms, such as fever, abdominal pain, abdominal distension, or jaundice. Ultrasound examination indicated a hypoechoic mass between the body of the pancreas, left lobe of the liver and stomach. It had a clear boundary, irregular shape, uneven echo, and no obvious blood flow signals. To clarify the diagnosis, contrast-enhanced ultrasound examination was performed, which showed a benign pancreatic lesion. Neuroendocrine or solid pseudopapillary tumor was a possible diagnosis. The patient underwent further contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging, which were suggestive of solid pseudopapillary tumor or neuroendocrine tumor. All the examinations failed to give a definitive diagnosis, and the patient underwent surgery. The final pathological and immunohistochemical results showed that the mass was CD. CONCLUSION: This case highlights when lymphadenopathy is encountered clinically, CD should be considered and a biopsy should be performed.

Effective components of Panax quinquefolius and Corydalis tuber protect the myocardium by inhibiting platelet activation and improving the hypercoagulable state.

The aim of the present study was to investigate the effects of extract of Panax quinquefolius and Corydalis tuber (EPC) on platelet activation and the hypercoagulable state in rats with acute myocardial infarction (AMI). The MI model in Wistar rats was induced by coronary artery ligation. Sham surgery was performed as a control. The surviving rats that underwent MI surgery were divided into control (administered normal saline), metoprolol (9 mg/kg) and low-, moderate- and high-dose EPC groups (0.54, 1.08 g/kg and 2.16 g/kg, respectively). Saline, metoprolol and EPC were administered by gastrogavage for two consecutive weeks. The morphological changes of the myocardium were assessed by hematoxylin and eosin and nitroblue tetrazolium staining. Serum von Willebrand factor (vWF), D-dimer (DD), platelet membrane glycoproteins IIb-IIIa (GPIIb-IIIa) and CD62P levels were assessed using enzyme-linked immunosorbent assay. EPC attenuated the pathological changes of the myocardium. High-dose EPC decreased the serum concentration of vWF when compared with control group. Moderate and high doses of EPC decreased the DD and GPIIb-IIIa levels, and the CD62P level was gradually decreased with EPC dose escalation. The results therefore demonstrated that EPC protects the myocardium by inhibiting platelet activation and improving the hypercoagulable state in a rat model of AMI.

Xuezhikang, extract of red yeast rice, improved abnormal hemorheology, suppressed caveolin-1 and increased eNOS expression in atherosclerotic rats.

BACKGROUND: Xuezhikang is the extract of red yeast rice, which has been widely used for the management of atherosclerotic disease, but the molecular basis of its antiatherosclerotic effects has not yet been fully identified. Here we investigated the changes of eNOS in vascular endothelia and RBCs, eNOS regulatory factor Caveolin-1 in endothelia, and hemorheological parameters in atherosclerotic rats to explore the protective effects of Xuezhikang. METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats were divided into 4 groups (n = 12/group) group C, controls; group M, high-cholesterol diet (HCD) induced atherosclerotic models; group X, HCD+Xuezhikang; and group L, HCD +Lovastatin. In group X, Xuezhikang inhibited oxidative stress, down-regulated caveolin-1 in aorta wall (P<0.05), up-regulated eNOS expression in vascular endothelia and erythrocytes (P<0.05), increased NOx (nitrite and nitrate) in plasma and cGMP in erythrocyte plasma and aorta wall (P<0.05), increased erythrocyte deformation index (EDI), and decreased whole blood viscosity and plasma viscosity (P<0.05), with the improvement of arterial pathology. CONCLUSIONS/SIGNIFICANCE: Xuezhikang up-regulated eNOS expression in vascular endothelia and RBCs, increased plasma NOx and improved abnormal hemorheology in high cholesterol diet induced atherosclerotic rats. The elevated eNOS/NO and improved hemorheology may be beneficial to atherosclerotic disease.

Shenyuan, an extract of American Ginseng and Corydalis Tuber formula, attenuates cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and oxidative stress in a porcine model of acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of American Ginseng and Corydalis Tuber has been widely used for treatment of cardiovascular diseases due to their anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate the anti-apoptotic effect of Shenyuan, which is composed of the bioactive components extracted from the mixture of American Ginseng and Corydalis Tuber, and to explore potential mechanisms involved in the regulation of apoptosis. MATERIALS AND METHODS: A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Thirty-eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kg·d, n=6); Group M, AMI+moderate-dose Shenyuan (320 mg/kg·d, n=6); Group H, AMI+high-dose Shenyuan (400 mg/kg·d, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kg·d, n=6). The treatment of Shenyuan or Metoprolol started one week before AMI and continued for another two weeks after AMI. RESULTS: Treatment with all doses of Shenyuan as well as Metoprolol produced a significant decrease of apoptotic index (P < 0.05), which was confirmed by TUNEL staining method. This anti-apoptotic effect was accompanied by less release of cardiac enzymes and limit of infarct size. In Group H, levels of MDA, 8-iso-prostaglandin F2α, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly increased (P < 0.05). In groups M and L, some results did not show statistical difference. There was no statistical difference in cardiac function between treatment groups and Group C. CONCLUSION: Shenyuan treatment significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs with a large anterior wall AMI. This was accompanied by less release of cardiac enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may have a therapeutic role in improving the natural process of AMI.