Synthesis, Fluorescence, and Bioactivity of Novel Isatin Derivatives.

The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1PTP with IC50 of 11 ± 3 µM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 µM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.

eDNA Metabarcoding Reveals the Species-Area Relationship of Amphibians on the Zhoushan Archipelago.

The species-area relationship is important for understanding species diversity patterns at spatial scales, but few studies have examined the relationship using environmental DNA (eDNA) techniques. We investigated amphibian diversity on 21 islands of the Zhoushan Archipelago and nearby mainland areas in China using the combination of eDNA metabarcoding and the traditional line transect method (TLTM) and identified the species-area relationship for amphibians on the islands. The mean detection probability of eDNA is 0.54, while the mean detection probability of TLTM is 0.24. The eDNA metabarcoding detected eight amphibian species on the islands and nine species in the mainland areas, compared with seven species on the islands and nine species in the mainland areas that were identified by TLTM. Amphibian richness on the islands increased with island area and habitat diversity. The species-area relationship for amphibians in the archipelago was formulated as the power function (S = 0.47A0.21) or exponential function (S = 2.59 + 2.41 (logA)). Our results suggested that eDNA metabarcoding is more sensitive for the detection of amphibian species. The combined use of eDNA metabarcoding and the traditional line transect method may optimize the survey results for amphibians.

Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NAD+ signaling pathway.

BACKGROUND: Gut microbiota and their metabolites play a regulatory role in skeletal muscle growth and development, which be known as gut-muscle axis. 3-phenylpropionic acid (3-PPA), a metabolite produced by colonic microorganisms from phenylalanine in the gut, presents in large quantities in the blood circulation. But few study revealed its function in skeletal muscle development. RESULTS: Here, we demonstrated the beneficial effects of 3-PPA on muscle mass increase and myotubes hypertrophy both in vivo and vitro. Further, we discovered the 3-PPA effectively inhibited protein degradation and promoted protein acetylation in C2C12 and chick embryo primary skeletal muscle myotubes. Mechanistically, we supported that 3-PPA reduced NAD+ synthesis and subsequently suppressed tricarboxylic acid cycle and the mRNA expression of SIRT1/3, thus promoting the acetylation of total protein and Foxo3. Moreover, 3-PPA may inhibit Foxo3 activity by directly binding. CONCLUSIONS: This study firstly revealed the effect of 3-PPA on skeletal muscle growth and development, and newly discovered the interaction between 3-PPA and Foxo3/NAD+ which mechanically promote myotubes hypertrophy. These results expand new understanding for the regulation of gut microbiota metabolites on skeletal muscle growth and development.

Development and validation of a prognostic model for predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).

BACKGROUND: Accurately predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remains a complex and critical challenge. The primary objective of this study was to develop and validate a robust risk prediction model to assess the 12-month and 24-month mortality risk in STEMI patients after hospital discharge. METHODS: A retrospective study was conducted on 664 STEMI patients who underwent PPCI at Xiangtan Central Hospital Chest Pain Center between 2020 and 2022. The dataset was randomly divided into a training cohort (n = 464) and a validation cohort (n = 200) using a 7:3 ratio. The primary outcome was all-cause mortality following hospital discharge. The least absolute shrinkage and selection operator (LASSO) regression model was employed to identify the optimal predictive variables. Based on these variables, a regression model was constructed to determine the significant predictors of mortality. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: The prognostic model was developed based on the LASSO regression results and further validated using the independent validation cohort. LASSO regression identified five important predictors: age, Killip classification, B-type natriuretic peptide precursor (NTpro-BNP), left ventricular ejection fraction (LVEF), and the usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEI/ARB/ARNI). The Harrell's concordance index (C-index) for the training and validation cohorts were 0.863 (95% CI: 0.792-0.934) and 0.888 (95% CI: 0.821-0.955), respectively. The area under the curve (AUC) for the training cohort at 12 months and 24 months was 0.785 (95% CI: 0.771-0.948) and 0.812 (95% CI: 0.772-0.940), respectively, while the corresponding values for the validation cohort were 0.864 (95% CI: 0.604-0.965) and 0.845 (95% CI: 0.705-0.951). These results confirm the stability and predictive accuracy of our model, demonstrating its reliable discriminative ability for post-discharge all-cause mortality risk. DCA analysis exhibited favorable net benefit of the nomogram. CONCLUSION: The developed nomogram shows potential as a tool for predicting post-discharge mortality in STEMI patients undergoing PPCI. However, its full utility awaits confirmation through broader external and temporal validation.

Suppression of wavelength-dependent polarization fading using hybrid-polarization scheme in OFDR.

What we believe to be a new hybrid-polarization diversity scheme which can eliminate the polarization state variation caused by wavelength tuning of laser in optical frequency domain reflectometry is proposed in the paper. In the scheme, a 45° polarizer is used to maintain the polarization of signals. It decreases the polarization angle fluctuation to 2.81° and realizes a -145 dB test sensitivity with a 32 dB Rayleigh scattering signal-to-noise ratio in a 10 m fiber single test. The polarization fading suppression is achieved for tests with a large wavelength tuning range from 1480 nm to 1640 nm. Meanwhile, a 6 µm spatial resolution is also achieved. The proposed scheme can be applied to the structure measurement of high-precision optical fiber devices with high spatial resolution and sensitivity.

Mitochondrial quality control alterations and placenta-related disorders.

Mitochondria are ubiquitous in eukaryotic cells. Normal maintenance of function is the premise and basis for various physiological activities. Mitochondrial dysfunction is commonly observed in a wide range of pathological conditions, such as neurodegenerative, metabolic, cardiovascular, and various diseases related to foetal growth and development. The placenta is a highly energy-dependent organ that acts as an intermediary between the mother and foetus and functions to maintain foetal growth and development. Recent studies have demonstrated that mitochondrial dysfunction is associated with placental disorders. Defects in mitochondrial quality control mechanisms may lead to preeclampsia and foetal growth restriction. In this review, we address the quality control mechanisms of mitochondria and the relevant pathologies of mitochondrial dysfunction in placenta-related diseases, such as preeclampsia and foetal growth restriction. This review also investigates the relation between mitochondrial dysfunction and placental disorders.

Nucleophile-Controlled Trapping of Gold Carbene by Nitriles and Water: Synthesis of 5H-Pyrimido[5,4-b]indoles and 2-Benzylidene-3-indolinones.

A gold-catalyzed, nucleophile-controlled cascade reaction of N-(2-azidophenyl-ynyl)methanesulfonamides with nitriles and water is described that provides structurally diverse 5H-pyrimido[5,4-b]indoles and 2-benzylidene-3-indolinones in good to excellent yields. Mechanistic studies indicate that the ß-sulfonamido-α-imino gold carbene is the key intermediate which is generated through the gold-catalyzed cyclization of N-(2-azidophenyl-ynyl)methanesulfonamides and undergoes formal [4 + 2] cascade annulation with nitriles and intramolecular SN2' type reaction with water, respectively.

Sex-specific impact of mild obesity on the prognosis of ST-segment elevation myocardial infarction.

This study aimed to clarify the existence of the mild obesity paradox in patients with ST-segment elevation myocardial infarction (STEMI) and assess the impact of mild obesity on the prognosis of STEMI. A retrospective cohort study was conducted on STEMI patients who underwent percutaneous coronary intervention at Xiangtan Central Hospital from January 1, 2020 to July 31, 2022. After excluding individuals with a body mass index (BMI) of no less than 35 kg/m2, subjects were divided into the mildly obese group (BMI, 30-35 kg/m2) and non-obese group (BMI < 30 kg/m2). The cardiovascular events and death were deemed the composite endpoints and were employed as the outcome event. The study recruited 664 patients with STEMI, including 515 males and 149 females. The mildly obese group of male patients exhibited a lower incidence of composite endpoints than the non-obese group (22.4% vs. 41.3%, P < 0.001). For female patients, no significant difference was observed in the incidence of composite endpoints between the two groups (43.6% vs. 43.8%, P = 0.987). After adjusting for confounding factors, the multivariable Cox regression analysis revealed mild obesity as an independent protective factor for male patients [hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.32-0.69; P < 0.001]. Nevertheless, mild obesity was not associated with the prognosis of female patients (HR 0.96; 95% CI 0.47-1.94; P = 0.9). In male STEMI patients, mild obesity presented a paradoxical effect in improving the prognosis and functioned as an independent protective factor for the prognosis of STEMI. However, no association between mild obesity and prognosis was found in female patients, possibly due to distinct physiological and metabolic characteristics between male and female patients, which deserved further investigation and validation.

Novel imidazo[1,2,4] triazole derivatives: Synthesis, fluorescence, bioactivity for SHP1.

The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. The development of efficient methods for rapidly tracing and modulating the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. Thus, we designed and synthesized a series of imidazo[1,2,4] triazole derivatives containing salicylic acid to explore novel scaffolds with inhibitory activities and good fluorescence properties for SHP1. The photophysical properties and inhibitory activities of these imidazo[1,2,4] triazole derivatives (5a-5y) against SHP1PTP were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound 5p exhibited remarkable fluorescence response (P: 0.002) with fluorescence quantum yield (QY) of 0.37 and inhibitory rate of 85.21 ± 5.17% against SHP1PTP at the concentration of 100 µM. Furthermore, compound 5p showed obvious aggregation caused quenching (ACQ) effect and had high selectivity for Fe3+ ions, good anti-interference and relatively low detection limit (5.55 µM). Finally, the cellular imaging test of compound 5p also exhibited good biocompatibility and certain potential biological imaging application. This study provides a potential way to develop molecules with fluorescent properties and bioactivities for SHP1.

Prognostic impact of lung ultrasound detected B-lines on hospitalised ischaemic heart failure with mildly reduced ejection fraction patients.

OBJECTIVES: Prognostic impact of lung ultrasound-derived B-lines (LUS-BL) in heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) patients remains elusive. We evaluated the correlation between LUS-BL and prognosis in HFmrEF patients. METHODS: This is a subgroup analysis based on our previously published retrospective study with 1691 HFmrEF patients. This subgroup analysis involved 574 patients with LUS-BL results at admission. After discharge, patients underwent clinical follow-up for a minimum of 1 year through telephone, clinical visits or community visits. The primary endpoint was defined as cardiovascular (CV) event, including CV-related mortality or HF hospitalisation at 90 days and 1 year after discharge. RESULTS: CV event at 90 days was significantly increased with higher LUS-BL number (0, 1-2, 3-9 and ≥10: 20%, 14%, 18% and 33%, p=0.008), while CV event rate at 1 year was similar among groups (45% vs 45% vs 42% vs 50%, p=0.573). Older age, hypertension (HR=2.06, 95% CI 1.31 to 3.25), higher right ventricular diameter (>23 mm, HR=2.008, 95% CI 1.37 to 2.94), increased ratio of early transmitral flow velocity to early mitral annular velocity (>24, HR=1.79, 95% CI 1.11 to 2.26) and higher LUS-BL number (>11, HR=1.510, 95% CI 1.01 to 2.26) were identified as independent determinants associated with increased risk of CV event at 90 days after discharge. The Harrell's C-Statistic analysis, based on the Cox regression models, demonstrated a significant improvement in the predictive ability of the model that incorporated both clinical and echocardiographic risk factors along with LUS-BL (areas under the curve (AUC)=0.72) compared with the model comprising only clinical risk factors and LUS-BL (AUC=0.69, p=0.036), or to the model with echocardiographic risk factors and LUS-BL (AUC=0.68, p=0.025). CONCLUSION: In HFmrEF patients with ischaemic heart disease, admission LUS-BL>11 is independently associated with an increased risk of CV event at 90 days following discharge.

Impact of signs and symptoms on the prognosis of patients with HFmrEF.

BACKGROUND: Worsening of heart failure (HF) symptoms is the leading cause of medical contact and hospitalization of patients with mildly reduced ejection fraction (HFmrEF). The prognostic value of signs and symptoms for patients with HFmrEF is currently unclear. This study investigated the prognostic impact of signs and symptoms in HFmrEF patients. METHODS: A Cox proportional risk regression model analyzed the relationship between the number of signs/symptoms and outcomes in 1691 hospitalized HFmrEF patients. Ten significant signs and symptoms were included. Patients were divided into three groups (A: ≤2, B: 3-5, C: ≥6 signs/symptoms). Stratified analysis on male and female patients was performed. The primary endpoint was all-cause mortality, and the secondary outcome was a composite of cardiovascular death and heart failure readmission (CV events) post-discharge. RESULTS: After a median follow-up of 33 months, all-cause mortality occurred in 457 patients and CV events occurred in 977 patients. Incidence of all-cause mortality was 20.7%, 32.3%* and 49.4%*† in group A, B and C of male patients, (*P < 0.05 vs. A, †P < 0.05 vs. B) and 18.8%, 33.6% and 55.8%* in group A, B and C of female patients. Incidence of CV events was 64.8%, 70.1%* and 87.5%* in group A, B and C of male patients, 61.9%, 75.3%, and 86.1%* in group A, B and C of female patients. Multivariate Cox regression showed older age, renal insufficiency, higher number of signs and symptoms (≥ 3, hazard ratio [HR] 1.317, 95% confidence interval [CI] 1.070-1.621, P = 0.009; ≥6, HR 1.982, 95% CI 1.402-2.801, P < 0.001), myocardial infarction, stroke, faster heart rate on admission, and diabetes were independently associated with all-cause mortality(all P < 0.05). Similarly, higher number of signs and symptoms (≥ 3, HR 1.271, 95% CI 1.119-1.443, P < 0.001; ≥6, HR 1.955, 95% CI 1.524-2.508, P < 0.001), older age, renal insufficiency, atrial fibrillation, and diabetes were independently associated with cardiovascular events (all P < 0.05). CONCLUSIONS: Higher number of symptoms and signs is associated with increased risk of all-cause mortality and CV events in HFmrEF patients. Our results highlight the prognostic importance of careful inquiry on HF symptoms and related physical examination in HFmrEF patients.

Red blood cell count and risk of adverse outcomes in patients with mildly reduced left ventricular ejection fraction.

BACKGROUND: Anemia is associated with increased rates of heart failure (HF)-related mortality and hospitalization. No studies have focused on the association between the red blood cell (RBC) count and the prognosis of patients with HF with mildly reduced left ventricular ejection fraction (HFmrEF). We retrospectively analyzed the effect of the RBC count on outcome events in patients with HFmrEF. METHODS: We investigated the association of the RBC count with outcome events in 1691 patients with HFmrEF (mean age: 68 years; 35% female) in Xiangtan Central Hospital. Using Cox proportional hazards models, the RBC count was assessed as both a continuous and categorical variable. RESULTS: During follow-up (median: 33 months), cardiovascular death occurred in 168 patients (114 men and 54 women). After adjusting for established risk factors, each 1.0 × 1012 cell/L increase in the RBC count was associated with a 28% lower risk of cardiovascular death in men and a 43% lower risk in women. Patients with low RBC counts had a 0.5-fold higher risk of cardiovascular death than those with normal RBC counts. The hazard ratio for men was 1.42 (95% confidence interval [CI]: 1.07-1.89), and the hazard ratio for women was 1.79 (95% CI: 1.20-2.67). The RBC count was not significantly associated with the composite endpoint of cardiovascular death and HF readmission (cardiovascular events) (p > .05). CONCLUSIONS: A decreased RBC count is associated with increased cardiovascular mortality in patients with HFmrEF. Correcting a low RBC count might potentially reduce the risk of cardiovascular death in patients with HFmrEF.

Exploring the mechanism of the PTP1B inhibitors by molecular dynamics and experimental study.

Protein tyrosine phosphatase 1B (PTP1B) has proven to be an attractive target for the treatment of cancer, diabetes and other diseases. Although many PTP1B inhibitors with various scaffolds have been developed, there is still a lack of PTP1B inhibitor with high specificity and acceptable pharmacological properties. Therefore, it is urgent to develop more methods to explore complex action mode of PTP1B and ligands for designing ideal PTP1B modulators. In this work, we developed a potential molecular dynamics (MD) analytic mode to analyze the mechanism of active compounds 6a and 6e against PTP1B from different perspectives, including the stable ability, interactions and binding site of ligand and protein, the binding energy, relative movement between residues and changes in protein internal interactions. The simulated results demonstrated that compound 6a bound more stably to the active pocket of PTP1B than 6e due to its smaller molecular volume (326 Å3), matched electronegativity, and enhanced the positive correlation motion of residues, especially for WPD loop and P loop. Lastly, compound 6a as a competitive inhibitor for PTP1B was verified by enzyme kinetic assay. This work successfully studied the mechanism of compound 6a against PTP1B from various aspects, enriched the analysis of interaction mode between PTP1B and inhibitors. In summary, we hope that this work could provide more theoretical information for designing and developing more novel and ideal PTP1B inhibitors in the future.

Impact of atrial fibrillation on cerebro-cardiovascular outcome of heart failure with mildly-reduced ejection fraction.

AIMS: Atrial fibrillation (AF) and heart failure (HF) often co-exist and are closely intertwined. The impact of AF on the outcome of patients with heart failure with mildly-reduced ejection fraction (HFmrEF) is not fully clear. This study aimed to investigate the impact of AF on the outcomes of hospitalized HFmrEF patients. METHODS AND RESULTS: The study included 1691 consecutive patients with HFmrEF (mean 68.2 years, 64.8% male) including 296 AF patients. Patients completed 1 year and mean of 33 month clinical follow-up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was cerebro-cardiovascular events (CCE, composite of HF rehospitalization, stroke, or cardiovascular death). After propensity score matching, 296 patients were included into the AF group (mean 71.5 years) and 592 patients into the non-AF group (mean 70.6 years). After propensity score matching, CCE at 1 year (59.1% vs. 48.5%, P = 0.003) and at a mean of 33 month (77.0% vs. 70.6%, P = 0.043). AF was independently associated with increased CCE within 1 year (HR = 1.31, 95% CI 1.07 to 1.61, P = 0.010) and at 33 months (HR = 1.20, 95% CI 1.00 to 1.43, P = 0.050) post-discharge after adjusted for other clinical confounders including discharge heart rate, NT-proBNP, haemoglobin, and uric acid. CONCLUSIONS: AF is independently associated with an increased risk of CCE in HFmrEF patients within 1 year and at a mean of 33 months after discharge.

Design, Synthesis and Evaluation of Fluorescent Properties of Benzothiazole Derivatives.

Fluorescence imaging is conducive to establish a bridge between molecular biology and clinical medicine, and provides new tools for disease process research, early diagnosis, and efficacy evaluation, because of the advantages of rapid imaging and nondestructive detection. Herein, a series of fluorescent molecules with thiadiazole, or thiazole, or benzothiazole cores were designed and synthesized to develop more excellent fluorescent molecules in bio-imaging. According to theoretical and experimental methods, we found that benzothiazole derivative 14 B with conjugate expansion by (4-aminophenyl) ethynyl group was the most excellent fluorescent molecule among all the investigated compounds and exhibited low cytotoxicity and strong blue and green fluorescence by confocal cell imaging.

Experimental study on carbon capture characteristics of marine engine exhaust gas by activated potassium carbonate absorbent.

Post-combustion carbon capture is a direct and effective way for onboard carbon capture. Therefore, it is important to develop onboard carbon capture absorbent that can both ensure a high absorption rate and reduce the energy consumption of the desorption process. In this paper, a K2CO3 solution was first established using Aspen Plus to simulate CO2 capture from the exhaust gases of a marine dual-fuel engine in diesel mode. The lean and rich CO2 loading results from the simulation were used to guide the selection and optimization of the activators used in the experiment. During the experiment, five amino acid salt activators including SarK, GlyK, ProK, LysK, and AlaK and four organic amine activators including MEA, PZ, AEEA, and TEPA were used. Experiments only considered the activation effect of CO2 loading between lean and rich conditions. The results showed that after adding a small amount of activator, the absorption rate of CO2 by the absorbent was greatly improved, and the activation effect of organic amine activators was stronger than that of amino acid salts. Among the amino acid salts, the SarK-K2CO3 composite solution showed the best performance in both absorption and desorption. Among the amino acid salts and the organic amino activators, SarK-K2CO3 showed the best performance in strengthening the CO2 desorption while PZ-K2CO3 enhanced the CO2 absorption process the most. In the study of the concentration ratio, it was found that when the mass concentration ratio was 1:1 for SarK:K2CO3 and PZ:K2CO3, the CO2 absorption and desorption processes improved well.

Temporal Convolutional Network-Based Signal Detection for Magnetotactic Bacteria Communication System.

Molecular communication (MC) aims to use signaling molecules as information carriers to achieve communication between biological entities. However, MC systems severely suffer from inter symbol interference (ISI) and external noise, making it virtually difficult to obtain accurate mathematical models. Specifically, the mathematically intractable channel state information (CSI) of MC motivates the deep learning (DL) based signal detection methods. In this paper, a modified temporal convolutional network (TCN) is proposed for signal detection for a special MC communication system which uses magnetotactic bacteria (MTB) as information carriers. Results show that the TCN-based detector demonstrates the best overall performance. In particular, it achieves better bit error rate (BER) performance than sub-optimal maximum a posteriori (MAP) and deep neural network (DNN) based detectors. However, it behaves similarly to the bidirectional long short term memory (BiLSTM) based detector that has been previously proposed and performs worse than the optimal MAP detector. When both BER performance and computational complexity are taken into account, the proposed TCN-based detector outperforms BiLSTM-based detectors. Furthermore, in terms of robustness evaluation, the proposed TCN-based detector outperforms all other DL-based detectors.

Sex differences in patients with heart failure and mildly reduced left ventricular ejection fraction.

Clinical studies on heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) have gradually increased. However, studies on the prognostic differences between men and women among patients with HFmrEF are few, and no evidence on sex differences in such patients exists. Therefore, we retrospectively assessed the data of patients with HFmrEF using propensity score-matched analysis (PSMA). A total of 1691 patients with HFmrEF were enrolled in the Outcome of Discharged HFmrEF Patients study (OUDI-HF study), which included 1095 men and 596 women. After propensity score matching, we compared the difference in cardiovascular (CV) events (cardiovascular death or heart failure readmission) and all-cause mortality at 90 days and 1 year after discharge between men and women using Kaplan-Meier analysis and Cox regression. After PSMA, men with HFmrEF were 2.2 times more likely to die at 90 days than women with HFmrEF [hazard ratio (HR) 1.88; 95% confidence interval (95% CI) 1.03-3.46; P = 0.041]. However, there was no difference in the 90-day CV events (HR 0.96; 95% CI 0.75-1.22; P = 0.718). Similarly, there was no difference in all-cause mortality (HR 1.16; 95% CI 0.81-1.65; P = 0.417) and CV events (HR 0.98; 95% CI 0.83-1.16; P = 0.817) between men and women after 1 year. Among the patients with HFmrEF, men had a higher 90-day risk of all-cause mortality than women after hospital discharge, and this risk disappeared after 1 year.Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT05240118 (ESC Heart Failure. (2022). doi: https://doi.org/10.1002/ehf2.14044 ).

Gold-Catalyzed Cascade Reaction of 2-Alkynyl Aryl Azides with Enecarbamates for Direct Synthesis of α-(3-Indolyl)ketones.

α-(3-Indolyl)ketones are essential building blocks for the generation of biologically active molecules. We described a new method for the direct assembly of α-(3-indolyl)ketones through the cascade reaction of 2-alkynyl aryl azides with enecarbamates, in which the in situ generated α-imino gold carbene intermediate was trapped by enecarbamate to achieve umpolung reactivity of indole at the 3-position.

Research Update on the Pathophysiological Mechanisms of Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) is a serious clinical syndrome, usually occurs at the advanced stage of various cardiovascular diseases, featured by high mortality and rehospitalization rate. According to left ventricular (LV) ejection fraction (LVEF), HF has been categorized as HF with reduced EF (HFrEF; LVEF<40%), HF with mid-range EF (HFmrEF; LVEF 40-49%), and HF with preserved EF (HFpEF; LVEF ≥50%). HFpEF accounts for about 50% of cases of heart failure and has become the dominant form of heart failure. The mortality of HFpEF is similar to that of HFrEF. There are no welldocumented treatment options that can reduce the morbidity and mortality of HFpEF now. Understanding the underlying pathological mechanisms is essential for the development of novel effective therapy options for HFpEF. In recent years, significant research progress has been achieved on the pathophysiological mechanism of HFpEF. This review aimed to update the research progress on the pathophysiological mechanism of HFpEF.