Cell-free supernatant of Lactococcus lactis IDCC 2301 exerts anti-inflammatory effects in LPS-induced macrophages via NF-κB and MAPK signaling pathways.

This study investigated the anti-inflammatory effects of cell-free supernatant of Lactococcus lactis IDCC 2301 on lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Expression of inflammatory mediators and cytokines, and the production of nitric oxide (NO) and prostaglandin E2 (PGE2) were qualitatively analysed. The expression of signal transductors in inflammatory cascades was quantified by western blot. Treatment with cell-free supernatant of L. lactis IDCC 2301 significantly decreased the mRNA expression levels of tumour necrosis factor (TNF-α) and interleukins including IL-1ß and IL-6. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) were also remarkably reduced in LPS-induced macrophages after the treatment. Furthermore, L. lactis IDCC 2301 reduced the levels of both dephosphorylated and phosphorylated forms of nuclear factor-kappa B (NF-κB), IκB-α, extracellular signal-regulated kinases (ERK), c-Jun amino-terminal kinases (JNK), and p38 in LPS-induced RAW 264.7 cells. Therefore, L. lactis IDCC 2301 shows anti-inflammatory activity by suppressing the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways.

Concise synthesis of 2,3-disubstituted quinoline derivatives via ruthenium-catalyzed three-component deaminative coupling reaction of anilines, aldehydes and amines.

The Ru-H complex (PCy3)2(CO)RuHCl (1) was found to be a highly effective catalyst for the three-component deaminative coupling reaction of anilines with aldehydes and allylamines to form 2,3-disubstituted quinoline products. The analogous coupling reaction of anilines with aldehydes and cyclic enamines led to the selective formation of the tricyclic quinoline derivatives. The reaction profile study showed that the imine is initially formed from the dehydrative coupling of aniline and aldehyde, and it undergoes the deaminative coupling and annulation reaction with amine substrate to form the quinoline product. The catalytic coupling method provides a step-efficient synthesis of 2,3-disubstituted quinoline derivatives without employing any reactive reagents or forming wasteful byproducts.

Correction: Concise synthesis of 2,3-disubstituted quinoline derivatives via ruthenium-catalyzed three-component deaminative coupling reaction of anilines, aldehydes and amines.

Correction for 'Concise synthesis of 2,3-disubstituted quinoline derivatives via ruthenium-catalyzed three-component deaminative coupling reaction of anilines, aldehydes and amines' by Aldiyar Shakenov et al., Org. Biomol. Chem., 2023, https://doi.org/10.1039/d3ob00348e.

At odds? How European governments decided on public health restrictions during COVID-19.

OBJECTIVES: This study aimed to understand how politics, economics, and public health restrictions affected each other during the COVID-19 pandemic. METHODS: We use seemingly unrelated regressions on a monthly data set of government approval ratings, the stringency index, the time-dependent reproduction number (R), and unemployment, allowing the residuals in each regression to be correlated with each other. We also conduct sensitivity tests using weekly data and the growth in polls. RESULTS: The study covers 27 European countries from April 2020 to April 2021. A unit increase in the R and COVID-19 cases per million increases the stringency index by 23.742 and 4.207, respectively; a unit increase in stringency boosts the incumbent's popularity by 0.384; the poll positively affects the stringency index; stringency has negative effects on the R; and the poll and stringency index have opposite effects on unemployment. CONCLUSION: Political and economic pressures did not hinder the government from introducing stronger measures.

Synthesis of Flavanone and Quinazolinone Derivatives from the Ruthenium-Catalyzed Deaminative Coupling Reaction of 2'-Hydroxyaryl Ketones and 2-Aminobenzamides with Simple Amines.

The cationic Ru-H complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1) with 3,4,5,6-tetrachloro-1,2-benzoquinone (L1) was found to be a highly effective catalyst for the deaminative coupling reaction of 2'-hydroxyaryl ketones with simple amines to form 3-substituted flavanone products. The analogous deaminative coupling reaction of 2-aminobenzamides with branched amines directly formed 3,3-disubstituted quinazolinone products. The catalytic method efficiently installs synthetically useful flavanone and quinazolinone core structures without employing any reactive reagents.

Experimental and Computational Studies on the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with Aldehydes for the Synthesis of 2-Alkylphenol, Benzofuran, and Xanthene Derivatives.

The cationic Ru-H complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1) was found to be an effective catalyst for the dehydrative C-H coupling reaction of phenols and aldehydes to form 2-alkylphenol products. The coupling reaction of phenols with branched aldehydes selectively formed 1,1-disubstituted benzofurans, while the coupling reaction with salicylaldehydes yielded xanthene derivatives. A normal deuterium isotope effect was observed from the coupling reaction of 3-methoxyphenol with benzaldehyde and 2-propanol/2-propanol-d8 (kH/kD = 2.3 ± 0.3). The carbon isotope effect was observed on the benzylic carbon of the alkylation product from the coupling reaction of 3-methoxyphenol with 4-methoxybenzaldehyde (C(3) 1.021(3)) and on both benzylic and ortho-arene carbons from the coupling reaction with 4-trifluorobenzaldehdye (C(2) 1.017(3), C(3) 1.011(2)). The Hammett plot from the coupling reaction of 3-methoxyphenol with para-substituted benzaldehydes p-X-C6H4CHO (X = OMe, Me, H, F, Cl, CF3) displayed a V-shaped linear slope. Catalytically relevant Ru-H complexes were observed by NMR from a stoichiometric reaction mixture of 1, 3-methoxyphenol, benzaldehyde, and 2-propanol in CD2Cl2. The DFT calculations provided a detailed catalysis mechanism featuring an electrophilic aromatic substitution of the aldehyde followed by the hydrogenolysis of the hydroxy group. The calculations also revealed a mechanistic rationale for the strong electronic effect of the benzaldehdye substrates p-X-C6H4CHO (X = OMe, CF3) in controlling the turnover-limiting step. The catalytic C-H coupling method provides an efficient synthetic protocol for 2-alkylphenols, 1,1-disubstituted benzofurans, and xanthene derivatives without employing any reactive reagents or forming wasteful byproducts.

Sympathetic predominance before tourniquet deflation is associated with a reduction in arterial blood pressure after tourniquet deflation during total knee arthroplasty.

High dependency of arterial blood pressure (ABP) on enhanced sympathetic activity, which maintains vascular tone, leads to hypotension after hemodynamic insults that blunt the sympathetic activity. Therefore, we hypothesized that sympathovagal balance before tourniquet deflation (TD) determines the extent of a reduction in ABP after TD during total knee arthroplasty (TKA). Fifty-four hypertensive female patients undergoing TKA under spinal anesthesia were analyzed. The sympathovagal balance [low-to-high frequency ratio of heart rate variability (LF/HF)] before TD was defined as (LF/HF during 5 min before TD-preanesthetic LF/HF)/preanesthetic LF/HF (%). An increase in its value represents a shift in sympathovagal balance toward sympathetic predominance. The percent change in the mean ABP (MAP) after TD was defined as (minimum MAP during 10 min after TD-averaged MAP during 5 min before TD)/averaged MAP during 5 min before TD (%). Simple linear regression was performed to assess the correlation between the sympathovagal balance before TD and change in MAP after TD. The correlation was also assessed by multiple linear regression controlling for age, duration of tourniquet inflation, and spinal anesthesia-induced hypotension. Thirty-two minutes (on average) after tourniquet inflation, the MAP was decreased by 12.1 (-3.0 to 47.9) % [mean (range)] upon TD (P<0.001). The sympathovagal balance before TD was negatively proportional to the change in MAP after TD in both simple and multiple linear regression models (R2=0.323 and 0.340, P<0.001). A shift in sympathovagal balance toward sympathetic predominance before TD is associated with a decrease in ABP after TD.

Programmable hyperbolic polaritons in van der Waals semiconductors.

Collective electronic modes or lattice vibrations usually prohibit propagation of electromagnetic radiation through the bulk of common materials over a frequency range associated with these oscillations. However, this textbook tenet does not necessarily apply to layered crystals. Highly anisotropic materials often display nonintuitive optical properties and can permit propagation of subdiffractional waveguide modes, with hyperbolic dispersion, throughout their bulk. Here, we report on the observation of optically induced electronic hyperbolicity in the layered transition metal dichalcogenide tungsten diselenide (WSe2). We used photoexcitation to inject electron-hole pairs in WSe2 and then visualized, by transient nanoimaging, the hyperbolic rays that traveled along conical trajectories inside of the crystal. We establish here the signatures of programmable hyperbolic electrodynamics and assess the role of quantum transitions of excitons within the Rydberg series in the observed polaritonic response.

Gender difference in the impact of coexisting diabetes mellitus on long-term clinical outcome in people with heart failure: a report from the Korean Heart Failure Registry.

AIM: Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure. METHODS: A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission. RESULTS: People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P < 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P > 0.05). CONCLUSIONS: In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.

Synthesis of Quinazoline and Quinazolinone Derivatives via Ligand-Promoted Ruthenium-Catalyzed Dehydrogenative and Deaminative Coupling Reaction of 2-Aminophenyl Ketones and 2-Aminobenzamides with Amines.

The in situ formed ruthenium catalytic system ([Ru]/L) was found to be highly selective for the dehydrogenative coupling reaction of 2-aminophenyl ketones with amines to form quinazoline products. The deaminative coupling reaction of 2-aminobenzamides with amines led to the efficient formation of quinazolinone products. The catalytic coupling method provides an efficient synthesis of quinazoline and quinazolinone derivatives without using any reactive reagents or forming any toxic byproducts.

Predictive value of a fragmented QRS complex in diagnosing patients with myocardial ischemia.

BACKGROUND: A fragmented QRS complex (fQRS) is caused by conduction abnormalities of the ventricle secondary to myocardial ischemia and/or scar in patients with myocardial infarction. However, the implications of the fQRS in the development of coronary artery disease with myocardial ischemia in those without a scar remain unknown. METHODS: We studied electrocardiograms (ECGs) obtained from 150 patients (60.5 ± 8.5 years, 102 men) with myocardial ischemia, which was confirmed by performing both, a nuclear exercise stress test and coronary angiography. We also studied ECGs obtained from 601 patients (58.5 ± 10.0 years, 315 men) who showed a negative nuclear exercise stress test (control group). Patients in whom the nuclear exercise stress test showed a myocardial scar were excluded. RESULTS: An fQRS was more commonly observed in patients with myocardial ischemia (n = 48, 32.0%) than in the control group (n = 133, 22.1%) (P = 0.011). The sensitivity, specificity, positive, and negative predictive values of fQRS in diagnosing myocardial ischemia were 32.0, 77.9, 26.5, and 82.1%, respectively. The fQRS (odds ratio 1.580, 95% confidence interval 1.020-2.446, P = 0.040) was an independent predictor of myocardial ischemia after adjusting for age, sex, current smoking habits, ST-T changes on ECG, as well as histories of hypertension, diabetes, and dyslipidemia. Moreover, the fQRS showed an incremental prognostic value over conventional risk factors (χ2 = 5, P = 0.032) and over a combination of conventional factors and ST-T changes (χ2 = 9, P = 0.014). CONCLUSIONS: The fQRS is a moderately sensitive and independent predictor of myocardial ischemia.

Experimental and Computational Study of the ( Z)-Selective Formation of Trisubstituted Olefins and Benzo-Fused Oxacycles from the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with Ketones.

The cationic Ru-H complex was found to be an effective catalyst for the dehydrative C-H coupling of phenols with ketones to form the trisubstituted olefin products. The coupling of phenol with linear ketones led to highly stereoselective formation of the ( Z)-olefin products. The dehydrative coupling of phenol with enones and diones efficiently formed the benzopyrene and related oxacyclic derivatives. The reaction of 3,5-dimethoxyphenol with cyclohexanone-2,2,6,6- d4 showed a significant H/D exchange to both vinyl and α-CH2 positions on the olefin product (72-75% D). A significant carbon isotope effect was observed on the ortho-arene carbon of the olefin product. The free energies of intermediate species for the entire catalytic cycle were successfully computed by using the DFT method. The DFT study revealed that the E/ Z stereoselectivity is a result of the energy difference in the insertion step of ortho-metalated phenol to an enol form of the ketone substrate (ΔΔ E = 9.6 kcal/mol). The coupling method provides a direct catalytic C-H olefination method for ketones to form trisubstituted olefins without employing any reactive reagents or forming any wasteful byproducts.

Neutrophil-lymphocyte ratio predicts response to chemotherapy in triple-negative breast cancer.

Background: The neutrophil-lymphocyte ratio (nlr) has been reported to correlate with patient outcome in several cancers, including breast cancer. We evaluated whether the nlr can be a predictive factor for pathologic complete response (pcr) after neoadjuvant chemotherapy (nac) in patients with triple-negative breast cancer (tnbc). Methods: We analyzed the correlation between response to nac and various factors, including the nlr, in 87 patients with tnbc who underwent nac. In addition, we analyzed the association between the nlr and recurrence-free survival (rfs) in patients with tnbc. Results: Of the 87 patients, 25 (28.7%) achieved a pcr. A high Ki-67 index and a low nlr were significantly associated with pcr. The pcr rate was higher in patients having a high Ki-67 index (≥15%) than in those having a low Ki-67 index (35.7% vs. 0%, p = 0.002) and higher in patients having a low nlr (≤1.7) than in those having a high nlr (42.1% vs. 18.4%, p = 0.018). In multiple logistic analysis, a low nlr remained the only predictive factor for pcr (odds ratio: 4.274; p = 0.008). In the survival analysis, the rfs was significantly higher in the low nlr group than in the high nlr group (5-year rfs rate: 83.7% vs. 66.9%; log-rank p = 0.016). Conclusions: Our findings that the nlr is a predictor of pcr to nac and also a prognosticator of recurrence suggest an association between response to chemotherapy and inflammation in patients with tnbc. The pretreatment nlr can be a useful predictive and prognostic marker in patients with tnbc scheduled for nac.

Synthesis of Symmetric and Unsymmetric Secondary Amines from the Ligand-Promoted Ruthenium-Catalyzed Deaminative Coupling Reaction of Primary Amines.

The catalytic system generated in situ from the tetranuclear Ru-H complex with a catechol ligand (1/L1) was found to be effective for the direct deaminative coupling of two primary amines to form secondary amines. The catalyst 1/L1 was highly chemoselective for promoting the coupling of two different primary amines to afford unsymmetric secondary amines. The analogous coupling of aniline with primary amines formed aryl-substituted secondary amines. The treatment of aniline- d7 with 4-methoxybenzylamine led to the coupling product with significant deuterium incorporation on CH2 (18% D). The most pronounced carbon isotope effect was observed on the α-carbon of the product isolated from the coupling reaction of 4-methoxybenzylamine (C(1) = 1.015(2)). A Hammett plot was constructed from measuring the rates of the coupling reaction of 4-methoxyaniline with a series of para-substituted benzylamines 4-X-C6H4CH2NH2 (X = OMe, Me, H, F, CF3) (ρ = -0.79 ± 0.1). A plausible mechanistic scheme has been proposed for the coupling reaction on the basis of these results. The catalytic coupling method provides an operationally simple and chemoselective synthesis of secondary amine products without using any reactive reagents or forming wasteful byproducts.

Association between basal-like phenotype and BRCA1/2 germline mutations in Korean breast cancer patients.

INTRODUCTION: BRCA mutation testing allows index patients and their families to be provided with appropriate cancer risk-reduction strategies. Because of the low prevalence of BRCA mutations in unselected breast cancer patients and the high cost of genetic testing, it is important to identify the subset of women who are likely to carry BRCA mutations. In the present study, we examined the association between BRCA1/2 germline mutations and the immunohistochemical features of breast cancer. METHODS: In a retrospective review of 498 breast cancer patients who had undergone BRCA testing at Seoul National University Bundang Hospital between July 2003 and September 2012, we gathered immunohistochemical information on estrogen receptor (er), progesterone receptor (pr), her2 (human epidermal growth factor receptor 2), cytokeratin 5/6, egfr (epidermal growth factor receptor), and p53 status. RESULTS: Among the 411 patients eligible for the study, 50 (12.2%) had germline mutations in BRCA1 or BRCA2. Of the 93 patients with triple-negative breast cancer (tnbc), 25 with BRCA1/2 mutations were identified (BRCA1, 20.4%; BRCA2, 6.5%). On univariate analysis, er, pr, cytokeratin 5/6, egfr, and tnbc were found to be related to BRCA1 mutations, but on multivariate analysis, only tnbc was significantly associated with BRCA1 mutations. Among patients with early-onset breast cancer or with a family history of breast or ovarian cancer, BRCA1 mutations were significantly more prevalent in the tnbc group than in the non-tnbc group. CONCLUSIONS: In the present study, tnbc was the only independent predictor of BRCA1 mutation in patients at high risk of hereditary breast and ovarian cancers. Other histologic features of basal-like breast cancer did not improve the estimate of BRCA1 mutation risk.

Clinical Outcome of Simultaneous Native Nephrectomy and Kidney Transplantation in Patients With Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: End-stage renal disease patients with autosomal dominant polycystic kidney disease may require native nephrectomy for various indications. However, the appropriate timing for nephrectomy in kidney transplantation and its effect on allograft survival have not been fully investigated. METHODS: We retrospectively analyzed 41 kidney transplant recipients with autosomal dominant polycystic kidney disease in whom transplantation was done simultaneously, after, or without native nephrectomy at Seoul St. Mary's hospital between January 1987 and February 2014. We divided patients into 2 groups based on when native nephrectomy was performed: simultaneously (group A, n = 13) and after or without nephrectomy (group B, n = 28), and compared perioperative outcomes, posttransplantation complications, and allograft survival rates. RESULTS: The mean operative time was significantly longer in group A than in group B (6.48 ± 1.84 vs 5.27 ± 0.84 hours; P = .048). The mean numbers of units required for intraoperative blood transfusions were also significantly higher in group A than in group B (3.66 ± 3.43 vs 0.75 ± 0.26 units; P = .018). However, there were no differences between groups in the incidence of acute rejection and other complications such as postoperative bleeding and infectious complications (P > .05, for all). The allograft survival rate also did not differ between groups (P > .05). CONCLUSIONS: Our study showed that patients undergoing simultaneous nephrectomy and kidney transplantations had clinical outcomes, in terms of complications and allograft survival, that were comparable to those in patients undergoing kidney transplantations with or without previous nephrectomy.

Catalytic Synthesis of Substituted Indoles and Quinolines from the Dehydrative C-H Coupling of Arylamines with 1,2- and 1,3-Diols.

The cationic ruthenium-hydride complex catalyzes dehydrative C-H coupling reaction of arylamines with 1,2-diols to form the indole products. The analogous coupling of arylamines with 1,3-diols afforded the substituted quinolines. The catalytic method directly forms these coupling products in a highly regioselective manner without generating any toxic byproducts.

Intermolecular Markovnikov-Selective Hydroacylation of Olefins Catalyzed by a Cationic Ruthenium-Hydride Complex.

The cationic Ru-H complex was found to be an effective catalyst for the intermolecular hydroacylation of aryl-substituted olefins with aldehydes to form branched ketone products. The preliminary kinetic and spectroscopic studies elucidated a ruthenium-acyl complex as the key intermediate species. The catalytic method directly afforded branched ketone products in a highly regioselective manner while tolerating a number of heteroatom functional groups.

Scope and Mechanistic Analysis for Chemoselective Hydrogenolysis of Carbonyl Compounds Catalyzed by a Cationic Ruthenium Hydride Complex with a Tunable Phenol Ligand.

A cationic ruthenium hydride complex, [(C6H6)(PCy3)(CO)RuH](+)BF4(-) (1), with a phenol ligand was found to exhibit high catalytic activity for the hydrogenolysis of carbonyl compounds to yield the corresponding aliphatic products. The catalytic method showed exceptionally high chemoselectivity toward the carbonyl reduction over alkene hydrogenation. Kinetic and spectroscopic studies revealed a strong electronic influence of the phenol ligand on the catalyst activity. The Hammett plot of the hydrogenolysis of 4-methoxyacetophenone displayed two opposite linear slopes for the catalytic system 1/p-X-C6H4OH (ρ = -3.3 for X = OMe, t-Bu, Et, and Me; ρ = +1.5 for X = F, Cl, and CF3). A normal deuterium isotope effect was observed for the hydrogenolysis reaction catalyzed by 1/p-X-C6H4OH with an electron-releasing group (kH/kD = 1.7-2.5; X = OMe, Et), whereas an inverse isotope effect was measured for 1/p-X-C6H4OH with an electron-withdrawing group (kH/kD = 0.6-0.7; X = Cl, CF3). The empirical rate law was determined from the hydrogenolysis of 4-methoxyacetophenone: rate = kobsd[Ru][ketone][H2](-1) for the reaction catalyzed by 1/p-OMe-C6H4OH, and rate = kobsd[Ru][ketone][H2](0) for the reaction catalyzed by 1/p-CF3-C6H4OH. Catalytically relevant dinuclear ruthenium hydride and hydroxo complexes were synthesized, and their structures were established by X-ray crystallography. Two distinct mechanistic pathways are presented for the hydrogenolysis reaction on the basis of these kinetic and spectroscopic data.