Endothelial MICU1 alleviates diabetic cardiomyopathy by attenuating nitrative stress-mediated cardiac microvascular injury.

BACKGROUND: Myocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and trigger of myocardial microvascular disease. Mitochondrial calcium homeostasis plays an important role in maintaining the normal function, survival and death of endothelial cells. Considering that mitochondrial calcium uptake 1 (MICU1) is a key molecule in mitochondrial calcium regulation, this study aimed to investigate the role of MICU1 in CMECs and explore its underlying mechanisms. METHODS: To examine the role of endothelial MICU1 in diabetic cardiomyopathy (DCM), we used endothelial-specific MICU1ecKO mice to establish a diabetic mouse model and evaluate the cardiac function. In addition, MICU1 overexpression was conducted by injecting adeno-associated virus 9 carrying MICU1 (AAV9-MICU1). Transcriptome sequencing technology was used to explore underlying molecular mechanisms. RESULTS: Here, we found that MICU1 expression is decreased in CMECs of diabetic mice. Moreover, we demonstrated that endothelial cell MICU1 knockout exacerbated the levels of cardiac hypertrophy and interstitial myocardial fibrosis and led to a further reduction in left ventricular function in diabetic mice. Notably, we found that AAV9-MICU1 specifically upregulated the expression of MICU1 in CMECs of diabetic mice, which inhibited nitrification stress, inflammatory reaction, and apoptosis of the CMECs, ameliorated myocardial hypertrophy and fibrosis, and promoted cardiac function. Further mechanistic analysis suggested that MICU1 deficiency result in excessive mitochondrial calcium uptake and homeostasis imbalance which caused nitrification stress-induced endothelial damage and inflammation that disrupted myocardial microvascular endothelial barrier function and ultimately promoted DCM progression. CONCLUSIONS: Our findings demonstrate that MICU1 expression was downregulated in the CMECs of diabetic mice. Overexpression of endothelial MICU1 reduced nitrification stress induced apoptosis and inflammation by inhibiting mitochondrial calcium uptake, which improved myocardial microvascular function and inhibited DCM progression. Our findings suggest that endothelial MICU1 is a molecular intervention target for the potential treatment of DCM.

Ag2SO4-Ag2S transformation in SnO2-based nanofibers for high selectivity and response H2S sensors.

Tin-based gas sensors have been developed for many years owing to their advantages of low price, high response and stability. However, selectivity remains a significant issue. Herein, Ag-SnO2nanofibers are synthesized using AgCl as the doping reagent. The 3%Ag-SnO2nanofibers sensors show a high response of 68 toward 1 ppm H2S at 90 °C. Besides, the sensor with 3% AgCl possesses the shortest response time about 136 s at 150 °C which is only 30% value of the sensor without AgCl doping. It is also demonstrated that the nanofibers show a high selectivity towards H2S. According to theex situx-ray photoelectron spectrum and x-ray diffraction results, AgCl was transferred to Ag2S after Ag-SnO2was exposed to H2S, and reversible transformation between Ag2SO4and Ag2S was the main mechanism for H2S detection. Compared with pure SnO2nanofiber sensors, the presence of Ag2S with high conductivity greatly affects the resistance to H2S, resulting in high selectivity and response. This mechanism differs from that of the transformation between Ag2O and Ag2SO4. This study may provide a new strategy for the design and investigation of sensors with high selectivity.

Explainable machine learning model reveals its decision-making process in identifying patients with paroxysmal atrial fibrillation at high risk for recurrence after catheter ablation.

BACKGROUND: A number of models have been reported for predicting atrial fibrillation (AF) recurrence after catheter ablation. Although many machine learning (ML) models were developed among them, black-box effect existed widely. It was always difficult to explain how variables affect model output. We sought to implement an explainable ML model and then reveal its decision-making process in identifying patients with paroxysmal AF at high risk for recurrence after catheter ablation. METHODS: Between January 2018 and December 2020, 471 consecutive patients with paroxysmal AF who had their first catheter ablation procedure were retrospectively enrolled. Patients were randomly assigned into training cohort (70%) and testing cohort (30%). The explainable ML model based on Random Forest (RF) algorithm was developed and modified on training cohort, and tested on testing cohort. In order to gain insight into the association between observed values and model output, Shapley additive explanations (SHAP) analysis was used to visualize the ML model. RESULTS: In this cohort, 135 patients experienced tachycardias recurrences. With hyperparameters adjusted, the ML model predicted AF recurrence with an area under the curve of 66.7% in the testing cohort. Summary plots listed the top 15 features in descending order and preliminary showed the association between features and outcome prediction. Early recurrence of AF showed the most positive impact on model output. Dependence plots combined with force plots showed the impact of single feature on model output, and helped determine high risk cut-off points. The thresholds of CHA2DS2-VASc score, systolic blood pressure, AF duration, HAS-BLED score, left atrial diameter and age were 2, 130 mmHg, 48 months, 2, 40 mm and 70 years, respectively. Decision plot recognized significant outliers. CONCLUSION: An explainable ML model effectively revealed its decision-making process in identifying patients with paroxysmal atrial fibrillation at high risk for recurrence after catheter ablation by listing important features, showing the impact of every feature on model output, determining appropriate thresholds and identifying significant outliers. Physicians can combine model output, visualization of model and clinical experience to make better decision.

A Review of the Carbon-Based Solid Transducing Layer for Ion-Selective Electrodes.

As one of the key components of solid-contact ion-selective electrodes (SC-ISEs), the SC layer plays a crucial role in electrode performance. Carbon materials, known for their efficient ion-electron signal conversion, chemical stability, and low cost, are considered ideal materials for solid-state transducing layers. In this review, the application of different types of carbon materials in SC-ISEs (from 2007 to 2023) has been comprehensively summarized and discussed. Representative carbon-based materials for the fabrication of SC-ISEs have been systematically outlined, and the influence of the structural characteristics of carbon materials on achieving excellent performance has been emphasized. Finally, the persistent challenges and potential opportunities are also highlighted and discussed, aiming to inspire the design and fabrication of next-generation SC-ISEs with multifunctional composite carbon materials in the future.

Acute myocardial infarction with left main coronary artery ostial negative remodelling as the first manifestation of Takayasu arteritis: a case report.

BACKGROUND: Takayasu arteritis is a chronic inflammatory disease involving the aorta and its major branches. Acute myocardial infarction rarely but not so much presents in patients with Takayasu arteritis, and the preferable revascularization strategy is still under debate. CASE PRESENTATION: A 22-year-old female with Takayasu arteritis presented with acute myocardial infarction. Coronary angiography and intravenous ultrasound (IVUS) showed that the right coronary artery (RCA) was occluded and that there was severe negative remodelling at the ostium of the left main coronary artery (LMCA). The patient was treated by primary percutaneous transluminal coronary angioplasty (PTCA) with a scoring balloon in the LMCA, without stent implantation. After 3 months of immunosuppressive medication, the patient received RCA revascularization by stenting. There was progressive external elastic membrane (EEM) enlargement of the LMCA ostium demonstrated by IVUS at 3 and 15 months post-initial PTCA. CONCLUSION: Here, we report a case of Takayasu arteritis with involvement of the coronary artery ostium. Through PTCA and long-term immunosuppressive medication, we found that coronary negative remodelling might be reversible in patients with Takayasu arteritis.

Progress on miRNA in giant panda (Ailuropoda melanoleuca).

MicroRNAs (miRNAs), a family of endogenous non-coding RNAs with a length of about 22 nucleotides, are widely found in eukaryotes. miRNAs can affect gene expression through specific bindings with mRNAs of target genes and participate in the regulation of a variety of biological processes. Giant panda is not only a unique rare animal in China, but also the focus of attention on wildlife preservation worldwide. In recent years, with the popularization of next-generation sequencing (NGS) technology, miRNAs in giant panda have been discovered and identified one after another. In this review, we focus on the research progress on miRNAs in giant panda, involved in immune response, mammary gland development, sperm freezing tolerance and other biological processes, and then discuss future research directions of miRNAs in giant panda, and thus providing the scientific references and new ideas for studying the regulatory mechanisms of miRNAs and promoting the breeding and protection of giant panda.

Catalytic Asymmetric Alkynylation of 3,4-Dihydro-ß-carbolinium Ions Enables Collective Total Syntheses of Indole Alkaloids.

Chiral tetrahydro-ß-carboline (THßC) is not only a prevailing structural feature of many natural alkaloids but also a versatile synthetic precursor for a vast array of monoterpenoid indole alkaloids. Asymmetric synthesis of C1-alkynyl THßCs remains rarely explored and challenging. Herein, we describe the development of two complementary approaches for the catalytic asymmetric alkynylation of 3,4-dihydro-ß-carbolinium ions with up to 96 % yield and 99 % ee. The utility of chiral C1-alkynyl THßCs was demonstrated by the collective total syntheses of seven indole alkaloids: harmicine, eburnamonine, desethyleburnamonine, larutensine, geissoschizol, geissochizine, and akuammicine.

Ultrasensitive xylene gas sensor based on flower-like SnO2/Co3O4 nanorods composites prepared by facile two-step synthesis method.

Xylene is a volatile organic compound which is harmful to the human health and requires precise detection. The detection of xylene by an oxide semiconductor gas sensor is an important research direction. In this work, Co3O4 decorated flower-like SnO2 nanorods (SnO2/Co3O4 NRs) were synthesized by a simple and effective two-step method. The SnO2/Co3O4 NRs show high xylene response (R g/R a = 47.8 for 100 ppm) and selectivity at the operating temperature of 280 °C, and exhibit high stability in continuous testing. The resulting SnO2/Co3O4 NRs nanocomposites show superior sensing performance towards xylene in comparison with pure SnO2 nanorods. The remarkable enhancement in the gas-sensing properties of SnO2/Co3O4 NRs are attributed to larger specific surface area and the formation of p-n heterojunction between Co3O4 and SnO2. These results demonstrate that particular nanostructures and synergistic effect of SnO2 and Co3O4 enable gas sensors to selectively detect xylene.

Serum miR-133 as a Potential Biomarker in Acute Cerebral Infarction Patients.

BACKGROUND: The study explores the expression and significance of miR-133 expression in peripheral blood of patients with acute cerebral infarction (ACI), so as to provide new evidence for the diagnosis and treatment of ACI. METHODS: Serum levels of miR-133, interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were examined using RT-PCR and ELISA, respectively. Pearson's correlation assay was used to analyze the relationship between the level of serum miR-133 and inflammatory factors. Kaplan-Meier method was used to analyze the 10-year survival rate of ACI patients with different levels of miR-133 expression. RESULTS: The level of serum miR-133 in the ACI group was significantly higher than that in healthy group. Mean-while, the level of serum miR-133 in the large infarction group, middle infarction group, small infarction group, and lacunar infarction group was higher than in the healthy group. Moreover, the serum levels of miR-133 in patients with atherosclerotic thrombotic cerebral infarction (AT) and cardioembolic stroke (CE) were significantly higher than those in healthy subjects and small artery occlusive cerebral infarction (SAD) subjects. Serum levels of IL-6, IL-8, CRP and TNF-α in ACI group were significantly higher than those in healthy group. The correlation analysis showed that serum miR-133 was positively correlated with IL-6, IL-8, CRP, and TNF-α in ACI patients. The 10-year survival rate of the low-expression group was significantly higher than that of the high-expression group. CONCLUSIONS: Serum level of miR-133 may indicate the onset and progression of cerebral infarction and may be a potential biomarker for the diagnosis of ACI.

A General, Concise Strategy that Enables Collective Total Syntheses of over 50 Protoberberine and Five Aporhoeadane Alkaloids within Four to Eight Steps.

A concise, catalytic, and general strategy that allowed efficient total syntheses of 22 natural 13-methylprotoberberines within four steps for each molecule is reported. This synthesis represents the most efficient and shortest route to date, featuring three catalytic processes: CuI-catalyzed redox-A(3) reaction, Pd-catalyzed reductive carbocyclization, and PtO2 -catalyzed hydrogenation. Importantly, this new strategy to the tetracyclic framework has also been applied to the collective concise syntheses of >30 natural protoberberines (without 13-methyl group) and five aporhoeadane alkaloids.

Formal Synthesis of (+)-Kopsihainanine A and Synthetic Study toward (+)-Limaspermidine.

The formal synthesis of (+)-kopsihainanine A has been achieved via stereoselective reduction of tetracyclic iminium ion intermediates (24). However, attempts to synthesize (+)-limaspermidine by reduction of the same tetracyclic iminium ion intermediates have failed. The synthesis features a Suzuki cross-coupling reaction, a cyclization reaction mediated by trifluoromethanesulfonic anhydride, and stereoselective reduction of an iminium ion.

An ultra-soft conductive elastomer for multifunctional tactile sensors with high range and sensitivity.

Flexible tactile sensors have become important as essential tools for facilitating human and object interactions. However, the materials utilized for the electrodes of capacitive tactile sensors often cannot simultaneously exhibit high conductivity, low modulus, and strong adhesiveness. This limitation restricts their application on flexible interfaces and results in device failure due to mechanical mismatch. Herein, we report an ultra-low modulus, highly conductive, and adhesive elastomer and utilize it to fabricate a microstructure-coupled multifunctional flexible tactile sensor. We prepare a supramolecular conductive composite film (SCCF) as the electrode of the tactile sensor using a supramolecular deep eutectic solvent, polyvinyl alcohol (PVA) solution, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), and MXene suspension. We employ a polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) film containing 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM:TFSI) as the dielectric layer to fabricate capacitive sensors with an electrical double layer structure. Furthermore, we enhance the performance of the device by incorporating coupled pyramid and dome microstructures, which endow the sensor with multi-directional force detection. Our SCCF exhibits extremely high conductivity (reaching 710 S cm-1), ultra-low modulus (0.8 MPa), and excellent interface adhesion strength (>120 J m-2). Additionally, due to the outstanding conductivity and unique structure of the SCCF, it possesses remarkable electromagnetic shielding ability (>50 dB). Moreover, our device demonstrates a high sensitivity of up to 1756 kPa-1 and a wide working range reaching 400 kPa, combining these attributes with the requirements of an ultra-soft human-machine interface to ensure optimal contact between the sensor and interface materials. This innovative and flexible tactile sensor holds great promise and potential for addressing various and complex demands of human-machine interaction.

The high performance parameterization for deep learning in pulse shaping.

In high energy physics, front-end data acquisition systems based on analog-to-digital converters (ADC) can provide multiple aspects (time, energy, position) of information when an incident particle is detected. To process the shaped semi-Gaussian pulses from ADCs, multi-layer neural networks (aka. deep learning recently) show excellent accuracy and promising real-time capability. However, several factors, such as sampling rate and precision, neural network quantization bits, and intrinsic noise, complicate the problem and make it hard to find a cost-effective solution with high performance. In this article, we analyze above factors in a systematic way to study the effect of each one on the performance of the network individually when other factors are controlled. Moreover, the proposed network architecture can provide both the time and energy information from a single pulse. When the sampling rate is 2.5 MHz, sampling precision is 5-bit, the network tested in this work with an 8-bit encoder and a 16-bit decoder (designated as N2) achieved the best comprehensive performance in all conditions.

Highly sensitive, wide-pressure and low-frequency characterized pressure sensor based on piezoresistive-piezoelectric coupling effects in porous wood.

Lightweight and highly compressible materials have received considerable attention in flexible pressure sensing devices. In this study, a series of porous woods (PWs) are produced by chemical removal of lignin and hemicellulose from natural wood by tuning treatment time from 0 to 15 h and extra oxidation through H2O2. The prepared PWs with apparent densities varying from 95.9 to 46.16 mg/cm3 tend to form a wave-shaped interwoven structure with improved compressibility (up to 91.89 % strain under 100 kPa). The sensor assembled from PW with treatment time of 12 h (PW-12) exhibits the optimal piezoresistive-piezoelectric coupling sensing properties. For the piezoresistive properties, it has high stress sensitivity of 15.14 kPa-1, covering a wide linear working pressure range of 0.06-100 kPa. For its piezoelectric potential, PW-12 shows a sensitivity of 0.443 V·kPa-1 with ultralow frequency detection as low as 0.0028 Hz, and good cyclability over 60,000 cycles under 0.41 Hz. The nature-derived all-wood pressure sensor shows obvious superiority in the flexibility for power supply requirement. More importantly, it presents fully decoupled signals without cross-talks in the dual-sensing functionality. Sensor like this is capable of monitoring various dynamic human motions, making it an extremely promising candidate for the next generation artificial intelligence products.

Formaldehyde gas sensor with extremely high response employing cobalt-doped SnO2 ultrafine nanoparticles.

Formaldehyde is a common carcinogen in daily life and harmful to health. The detection of formaldehyde by a metal oxide semiconductor gas sensor is an important research direction. In this work, cobalt-doped SnO2 nanoparticles (Co-SnO2 NPs) with typical zero-dimensional structure were synthesized by a simple hydrothermal method. At the optimal temperature, the selectivity and response of 0.5% Co-doped SnO2 to formaldehyde are excellent (for 30 ppm formaldehyde, R a/R g = 163 437). Furthermore, the actual minimum detectable concentration of 0.5%Co-SnO2 NPs is as low as 40 ppb, which exceeds the requirements for formaldehyde detection in the World Health Organization (WHO) guidelines. The significant improvement of 0.5%Co-SnO2 NPs gas performance can be attributed to the following aspects: firstly, cobalt doping effectively improves the resistance of SnO2 NPs in the air; moreover, doping creates more defects and oxygen vacancies, which is conducive to the adsorption and desorption of gases. In addition, the crystal size of SnO2 NPs is vastly small and has unique physical and chemical properties of zero-dimensional materials. At the same time, compared with other gases tested, formaldehyde has a strong reducibility, so that it can be selectively detected at a lower temperature.

Hybrid cobalt-manganese oxides prepared by ordered steps with a ternary nanosheet structure and its high performance as a binder-free electrode for energy storage.

Binder-free electrodes for supercapacitors have attracted much attention as no additive is required in their preparation processes. Herein, a hybrid metal oxide composed of graphene oxide (Co3O4/MnO2/GO) was successfully prepared. Briefly, electrochemical deposition and sintering were applied to grow Co3O4 nanosheets on nickel foam. Subsequently, MnO2 nanosheets were deposited on Co3O4 nanosheets via the thermal decomposition of a KMnO4 aqueous solution. Finally, graphene oxide was added to improve the performance of the composite. Particularly, the as-obtained Co3O4/MnO2/GO sample grown on nickel foam possessed a ternary nanosheet structure, and when applied as a binder-free electrode in a supercapacitor, it exhibited an excellent electrochemical performance. Firstly, the electrode exhibited an ultrahigh capacitance value of 2928 F g-1 at 1 A g-1 in a three-electrode system. Besides, the electrode showed a promising rate performance of 853 F g-1 at a high current density of 20 A g-1. Moreover, the electrode displayed a relatively high energy density of 97.92 W h kg-1 at a power density of 125 W kg-1 and long cycle life of 93% retention after 5000 cycles at 10 A g-1 in a two-electrode system. Thus, all the electrochemical tests suggest that the Co3O4/MnO2/GO binder-free electrode is a potential candidate for energy storage.

Rich oxygen vacancies, mesoporous TiO2 derived from MIL-125 for highly efficient photocatalytic hydrogen evolution.

Here we report a mesoporous TiO2 with a large specific surface area and rich oxygen vacancies using a Ti-based MOF (MIL-125) as a precursor through high-temperature annealing. Such integration of a unique mesoporous structure and oxygen vacancies provides effective carrier transport channels, increases surface active sites, and enhances photocatalytic activity for the hydrogen evolution reaction.

Gas sensing materials roadmap.

Gas sensor technology is widely utilized in various areas ranging from home security, environment and air pollution, to industrial production. It also hold great promise in non-invasive exhaled breath detection and an essential device in future internet of things. The past decade has witnessed giant advance in both fundamental research and industrial development of gas sensors, yet current efforts are being explored to achieve better selectivity, higher sensitivity and lower power consumption. The sensing layer in gas sensors have attracted dominant attention in the past research. In addition to the conventional metal oxide semiconductors, emerging nanocomposites and graphene-like two-dimensional materials also have drawn considerable research interest. This inspires us to organize this comprehensive 2020 gas sensing materials roadmap to discuss the current status, state-of-the-art progress, and present and future challenges in various materials that is potentially useful for gas sensors.

Nanoporous Carbon Derived from Green Material by an Ordered Activation Method and Its High Capacitance for Energy Storage.

Carbon materials have been widely used as electrode materials for supercapacitors, while the current carbon precursors are mainly derived from fossil fuels. Biomass-derived carbon materials have become new and effective materials for electrodes of supercapacitors due to their sustainability, low pollution potential, and abundant reserves. Herein, we present a new biomass carbon material derived from water hyacinth by a novel activation method (combination of KOH and HNO3 activation). According to the electrochemical measurements, the material presents an ultrahigh capacitance of 374 F g-1 (the current density is 1 A g-1). Furthermore, the material demonstrates excellent rate performance (105 F g-1 at a higher density of 20 A g-1) and ideal cycling stability (87.3% capacity retention after 5000 times charge-discharge at 2 A g-1). When used for a symmetrical supercapacitor device, the material also shows a relatively high capacity of 330 F g-1 at 1 A g-1 (a two-electrode system). All measurements suggest the material is an effective and noteworthy material for the electrodes of supercapacitors.

Platinum-Supported Cerium-Doped Indium Oxide for Highly Sensitive Triethylamine Gas Sensing with Good Antihumidity.

Triethylamine is extremely harmful to human health, and chronic inhalation can lead to respiratory and hematological diseases and eye lesions. Hence, it is essential to develop a triethylamine gas-sensing technology with high response, selectivity, and stability for use in healthcare and environmental monitoring. In this work, a simple and low-cost sensor based on the Pt- and Ce-modified In2O3 hollow structure to selectively detect triethylamine is developed. The experimental results reveal that the sensor based on 1% Pt/Ce12In exhibits excellent triethylamine-sensing performance, including its insusceptibility to water, reduced operating temperature, enhanced response, and superior long-term stability. This work suggests that the enhancement of sensing performance toward triethylamine can be attributed to the high relative contents of OV and OC, large specific surface area, catalytic effect, the electronic sensitization of Pt, and the reversible redox cycle properties of Ce. This sensor represents a unique and highly sensitive means to detect triethylamine, which shows great promise for potential applications in food safety inspection and environmental monitoring.