Dermatoscope for the diagnosis of erythema with purpura induced by lidocaine/prilocaine cream: A case report.

BACKGROUND: Lidocaine/prilocaine (EMLA) cream is a local anesthetic that is applied to the skin or mucosa during painful therapeutic procedures with few reported side effects. CASE SUMMARY: Here, we report the use of dermatoscopy to identify a case of erythema with purpura, a rare side effect, after the application of 5% EMLA cream. CONCLUSION: We conclude that erythema with purpura is caused by irritation and toxicity associated with EMLA, but the specific mechanism by which the toxic substance affects skin blood vessels is unclear. In response to this situation and for cosmetic needs, we recommend tranexamic acid, in addition to routine therapy, to prevent changes in pigmentation in patients with dermatitis.

Tumor cavitation in patients with non-small-cell lung cancer receiving anti-angiogenic therapy with apatinib.

Background: Cavities have been reported in approximately 20% of lung cancer after anti-angiogenesis treatments. However, the effect of which on treatment outcomes remains unclear. This study sought to investigate the incidence and radiographic patterns of tumor cavitation in patients with non-small cell lung cancer (NSCLC) treated with apatinib, and its associations with patients' clinical characteristics and outcomes. Methods: A total of 300 patients with NSCLC treated with apatinib were retrospectively identified. Baseline and follow-up chest computed tomography scans were reviewed to identify tumor cavitation, and the subsequent filling-in of the cavitation. A multivariate logistic regression analysis was conducted to identify the factors associated with tumor cavitation. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 300 patients, 51 (17.0%) developed lung cavitation after initiating apatinib therapy. The results of the multivariate analysis showed that apatinib combination therapy (vs. apatinib monotherapy, odds ratio: 0.593, 95% confidence interval: 0.412-0.854, P=0.005) was significantly associated with tumor cavitation. Patients with tumor cavitation had significantly longer progression-free survival (PFS) than those without cavitation (8.2 vs. 5.2 months, P<0.01). Of the patients, 18 had cavity filling after progression, while 13 had persistent cavities after progression. The corresponding median PFS times were 11.9 and 3.2 months in patients with filled and persistent cavities after disease progression, respectively (P<0.001). Conclusions: Tumor cavitation occurred in 17% of the NSCLC patients treated with apatinib and was associated with better PFS. Patients who had cavities filled after progression had a better prognosis than those with persistent cavities.

A Wild Horse Optimization algorithm with chaotic inertia weights and its application in linear antenna array synthesis.

Antennas play a crucial role in designing an efficient communication system. However, reducing the maximum sidelobe level (SLL) of the beam pattern is a crucial challenge in antenna arrays. Pattern synthesis in smart antennas is a major area of research because of its widespread application across various radar and communication systems. This paper presents an effective technique to minimize the SLL and thus improve the radiation pattern of the linear antenna array (LAA) using the chaotic inertia-weighted Wild Horse optimization (IERWHO) algorithm. The wild horse optimizer (WHO) is a new metaheuristic algorithm based on the social behavior of wild horses. The IERWHO algorithm is an improved Wild Horse optimization (WHO) algorithm that combines the concepts of chaotic sequence factor, nonlinear factor, and inertia weights factor. In this paper, the method is applied for the first time in antenna array synthesis by optimizing parameters such as inter-element spacing and excitation to minimize the SLL while keeping other constraints within the boundary limits, while ensuring that the performance is not affected. For performance evaluation, the simulation tests include 12 benchmark test functions and 12 test functions to verify the effectiveness of the improvement strategies. According to the encouraging research results in this paper, the IERWHO algorithm proposed has a place in the field of optimization.

Impact of exercise dosages based on American College of Sports Medicine recommendations on lipid metabolism in patients after PCI: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The impact of exercise dosages based on American College of Sports Medicine(ACSM) recommendations on lipid metabolism in patients after PCI remains unclear. This study conducted a meta-analysis of reported exercise dosages from the literature to address this knowledge gap. METHODS: A comprehensive search of databases was conducted to identify eligible randomized controlled studies of exercise interventions in patients after PCI, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the recommended exercise dosages from ACSM for patients with coronary heart disease, exercise doses in the literature that met the inclusion criteria were categorized into groups that were highly compliant with ACSM recommendations and those with low or uncertain ACSM recommendations. The topic was the effect of exercise dose on lipid metabolism in post-PCI patients. This was assessed using standardized mean difference (SMD) and 95% confidence intervals (95% CI) for changes in triglycerides, total cholesterol, LDL, and HDL. RESULTS: This systematic review included 10 randomized controlled studies. The subgroup analysis revealed statistically significant differences in the high compliance with ACSM recommendations group for triglycerides [SMD=-0.33 (95% CI -0.62, -0.05)], total cholesterol [SMD=-0.55 (95% CI -0.97, -0.13)], low-density lipoprotein [SMD=-0.31 (95% CI -0.49, -0.13)], high-density lipoprotein [SMD = 0.23 (95% CI 0.01, 0.46)], and body mass index [SMD=-0.52 (95% CI -0.87, -0.17)]. Compared to the low or uncertain compliance with ACSM recommendations group, the high compliance group exhibited significant differences in improving TC levels (-0.55(H) vs. -0.46(L)), HDL levels (0.23(H) vs. 0.22(L)), and BMI (-0.52(H) vs. -0.34(L)). CONCLUSIONS: This study supports that high compliance with ACSM-recommended exercise dosages has significant impacts on improving TC levels, HDL levels, and BMI. However, no advantage was observed for TG or LDL levels.

Enhancing electrochemical water-splitting efficiency with superaerophobic nickel-coated catalysts on Chinese rice paper.

The quest for efficient hydrogen production highlights the need for cost-effective and high-performance catalysts to enhance the electrochemical water-splitting process. A significant challenge in developing self-supporting catalysts lies in the high cost and complex modification of traditional substrates. In this study, we developed catalysts featuring superaerophobic microstructures engineered on microspherical nickel-coated Chinese rice paper (Ni-RP), chosen for its affordability and exceptional ductility. These catalysts, due to their microspherical morphology and textured surface, exhibited significant superaerophobic properties, substantially reducing bubble adhesion. The nickel oxy-hydroxide (NiOxHy) and phosphorus-doped nickel (PNi) catalysts on Ni-RP demonstrated effective roles in oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), achieving overpotentials of 250 mV at 20 mA cm-2 and 87 mV at -10 mA cm-2 in 1 M KOH, respectively. Moreover, a custom water-splitting cell using PNi/Ni-RP and NiOxHy/Ni-RP electrodes reached an impressive average voltage of 1.55 V at 10 mA cm-2, with stable performance over 100 h in 1 M KOH. Our findings present a cost-effective, sustainable, and easily modifiable substrate that utilizes superaerophobic structures to create efficient and durable catalysts for water splitting. This work serves as a compelling example of designing high-performance self-supporting catalysts for electrocatalytic applications.

Nanosheets of a Layered Metal-Organic Framework for Separation of CO2/CH4 using Mixed Matrix Membranes.

Mixed matrix membranes represent an important technology for gas separations. Nanosheets of metal-organic framework (MOF) materials of high aspect ratio and size-selective gas transport properties have the potential to promote the efficient mixing of components to form membranes for gas separation. Herein, we report a bottom-up synthesis of extended sheets of kagomé (kgm) topology, kgmt-Bu, via the linkage of [Cu2(O2CR)4] paddlewheels with 5-tert-butylisophthalic acid. The growth of the layered structure can be controlled by the choice of solvent and modulator. Nanosheets of kgmt-Bu of average thickness of 20 nm and aspect ratio of 40 to 50 can be obtained, and the sieving effect of the channels in kgmt-Bu boost the efficient separation of CO2 over CH4. A mixed matrix membrane comprising kgmt-Bu nanosheets with Matrimid shows a 32% enhancement in CO2/CH4 selectivity compared with the membrane incorporating the MOF in the particulate form.

Functional characterization of the InR/PI3K/AKT signaling pathway in female reproduction of the predatory bug Cyrtorhinus lividipennis (Hemiptera: Miridae).

The insulin signaling (IIS) pathway plays a key role in the regulation of various physiological functions in animals. However, the involvement of IIS pathway in the reproduction of natural enemy insects remains enigmatic. Here, 3 key genes (named ClInR, ClPI3K, and ClAKT) related to IIS pathway were cloned from Cyrtorhinus lividipennis (Reuter) (Hemiptera: Miridae), an important natural enemy in the rice ecosystem. These 3 proteins had the typical features of corresponding protein families and shared high similarity with their respective homologs from the Hemipteran species. The ClInR, ClPI3K, and ClAKT were highly expressed in the adult stage. Tissue distribution analysis revealed that ClInR, ClPI3K, and ClAKT were highly expressed in the midgut and ovary of adults. Silencing of ClInR, ClPI3K, and ClAKT caused 92.1%, 72.1%, and 57.8% reduction in the expression of ClVg, respectively. Depletion of these 3 genes impaired vitellogenin synthesis and ovary development. Moreover, the fecundity in the dsInR, dsPI3K, and dsAKT injected females were 53.9%, 50.8%, and 48.5% lower than the control treatment, respectively. These results indicated that ClInR, ClPI3K, and ClAKT are of great importance for the reproduction of C. lividipennis. Our results advance the knowledge about the molecular mechanism of reproduction regulation in natural enemy insects.

Current state of research on copper complexes in the treatment of breast cancer.

Breast cancer, a malignancy originating from the epithelium or ductal epithelium of the breast, is not only highly prevalent in women but is also the leading cause of cancer-related deaths in women worldwide. Research has indicated that breast cancer incidence is increasing in younger women, prompting significant interest from scientists actively researching breast cancer treatment. Copper is highly accumulated in breast cancer cells, leading to the development of copper complexes that cause immunogenic cell death, apoptosis, oxidative stress, redox-mediated cell death, and autophagy by regulating the expression of key cell death proteins or assisting in the onset of cell death. However, they have not yet been applied to clinical therapy due to their solubility in physiological buffers and their different and unpredictable mechanisms of action. Herein, we review existing relevant studies, summarize the detailed mechanisms by which they exert anti-breast cancer effects, and propose a potential mechanism by which copper complexes may exert antitumor effects by causing copper death in breast cancer cells. Since copper death in breast cancer is closely related to prognosis and immune infiltration, further copper complex research may provide an opportunity to mitigate the high incidence and mortality rates associated with breast cancer.

Mating behavior and responses to sublethal concentrations of imidacloprid in the predator Cyrtorhinus lividipennis.

BACKGROUND: Mating is an essential factor that governs the size of insect populations that reproduce sexually. The extensive application of insecticides has both lethal and sublethal effects on the physiology and mating behavior of insect natural enemies. The predatory bug Cyrtorhinus lividipennis is a natural enemy of planthopper and leafhopper populations in the rice ecosystem. Unfortunately, the effects of insecticides on the mating behavior of C. lividipennis are not well-understood. RESULTS: The mating behavior of C. livdipennis consisted of mounting, antennal touch and mating attempts, genital insertion, adjustment of posture, and separation of the mating pair. Approximately 82.5% of the C. lividipennis mating pairs displayed their first mating at 12-36 h postemergence. Mating activity occurred throughout a 24-h period, with peak activity at 12:00-14:00 h, and the mean duration of mating was 48.75 min. Sublethal exposure to imidacloprid increased mating latency. Compared with the controls, the duration of courtship, pre-mating and adjusting posture for males treated with imidacloprid were prolonged. The duration of mating for females treated with imidacloprid was prolonged relative to untreated controls. The fecundity and daily spawning capacity of females treated with imidacloprid were higher than the untreated controls. CONCLUSION: Our results provide insight into the mating process of C. lividipennis. Imidacloprid prolonged the duration of mating, which may explain the enhanced reproductive output in C. lividipennis females treated with imidacloprid. These findings will be useful in both rearing C. lividipennis and deploying this natural enemy in rice fields. © 2024 Society of Chemical Industry.

Wearable Sensors for Breath Monitoring Based on Water-Based Hexagonal Boron Nitride Inks Made with Supramolecular Functionalization.

Wearable humidity sensors are attracting strong attention as they allow for real-time and continuous monitoring of important physiological information by enabling activity tracking as well as air quality assessment. Amongst 2Dimensional (2D) materials, graphene oxide (GO) is very attractive for humidity sensing due to its tuneable surface chemistry, high surface area, processability in water, and easy integration onto flexible substrates. However, strong hysteresis, low sensitivity, and cross-sensitivity issues limit the use of GO in practical applications, where continuous monitoring is preferred. Herein, a wearable and wireless impedance-based humidity sensor made with pyrene-functionalized hexagonal boron nitride (h-BN) nanosheets is demonstrated. The device shows enhanced sensitivity towards relative humidity (RH) (>1010 Ohms/%RH in the range from 5% to 100% RH), fast response (0.1 ms), no appreciable hysteresis, and no cross-sensitivity with temperature in the range of 25-60 °C. The h-BN-based sensor is able to monitor the whole breathing cycle process of exhaling and inhaling, hence enabling to record in real-time the subtlest changes of respiratory signals associated with different daily activities as well as various symptoms of flu, without requiring any direct contact with the individual.

Contrasting roles of fungal and oomycete pathogens in mediating nitrogen addition and winter grazing effects on biomass.

Both bottom-up and top-down processes modulate plant communities. Fungal and oomycete pathogens are most common in global grasslands, and due to differences in their physiology, function, host range, and life cycles, they may differentially affect plants (in both intensity and direction). However, how fungal and oomycete pathogens regulate bottom-up and top-down effects on plant community biomass remains unclear. To this end, we conducted a 3-year field experiment in an alpine meadow incorporating mammalian herbivore exclosure, fungicide/oomyceticide application, and nitrogen addition treatments. We arranged 12 blocks with half randomly assigned to be mammalian herbivore exclosures (fenced to exclude grazing sheep), and the other half were fenced most of the year but not in winter (winter grazing control). Six 2.5 × 2.5 m square plots were established in each block, with each of the six plots assigned as control, nitrogen addition, fungicide application, oomyceticide application, nitrogen addition + fungicide application, and nitrogen addition + oomyceticide application. We found that fungicide application significantly increased plant community biomass (mainly Poaceae species) under nitrogen addition and promoted the bottom-up effect of nitrogen addition on plant community biomass by altering the community-weighted mean of plant height (via species turnover). Meanwhile, oomyceticide application significantly increased plant community biomass (mainly Poaceae species) when mammalian herbivores were excluded and weakened the top-down effect of winter grazing on plant community biomass by driving intraspecific variation in plant height. Our results highlight that fungal and oomycete pathogens play important (but differing) roles in mediating the effects of nutrient availability and higher trophic levels on plant community biomass. Mechanistically, we demonstrated that plant pathogen-related modulation of plant community biomass is achieved by alterations to plant height. Overall, this study combines both community and disease ecology to reveal complex interactions among higher trophic levels and their potential impacts on terrestrial ecosystem functioning under human disturbance.

Preparation and modification mechanism study of microwave-treated crumb rubber and waste engine oil-modified asphalt.

The objective of this study was to characterize the performance of waste engine oil (WEO) and microwave-treated crumb rubber (CR)-modified asphalt (WEO-MCRA) and analyze the modification mechanism. The viscosity and dynamic shear rheological (DSR) tests were carried out to evaluate the viscoelasticity property of WEO-MCRA. The storage stability and fluorescence microscope (FM) tests were used to characterize the compatibility of the components. The Fourier transform infrared spectroscopy (FTIR) and molecular dynamic simulation were introduced to analyze the change of function groups and modification mechanism. The results demonstrated that introducing Wt.20% CR treated with microwave and Wt.6% WEO obtained a lower viscosity, excellent storage stability, and satisfactory elasticity properties of asphalt. The morphology of modifiers presented a thread-like structure microscopic with the range of WEO content Wt.3%-Wt.6%. Molecular dynamic simulations revealed that the aromatic may be intensively absorbed by CR and increase the likelihood of phase separation. WEO reduced the binding energy of CR to aromatic from 178.0 to 151.5 kcal/mol, which will contribute to the disaggregation of CR clusters. The diffusion coefficient shows a more obvious decrease with the addition of WEO and microwave treatment, which will benefit the stability of the asphalt. This study can provide a reference for the recycling of CR and WEO.

miR-129-2-3p mediates LPS-induced macrophage polarization and ferroptosis by targeting the SMAD3-GPX4 axis.

Macrophages has become a promising target of sepsis treatment because macrophages dysfunction contributes to the progress of sepsis. The targeted therapy of sepsis based on macrophages ferroptosis is drawing more and more attention, but the molecular mechanism involved is poorly understood. In this study, Mus musculus-derived macrophages were used for in-vitro experiments. We found that LPS could induce ferroptosis in macrophages via the detection of apoptosis, GSH, lipid peroxide and GPX4 levels. Meanwhile, miR-129-2-3p was up-regulated in macrophages exposure to LPS. Next, we confirmed that miR-129-2-3p promoted the LPS-induced polarization of M1 phenotype in macrophages via the detection of Arg-1 and iNOS levels; miR-129-2-3p promoted the LPS-induced ferroptosis in macrophages. Further, luciferase assay showed that SMAD3 was identified as a target gene of miR-129-2-3p and its expression was negatively regulated by miR-129-2-3p and LPS. SMAD3 could inhibit the LPS-induced polarization of M1 phenotype and ferroptosis in macrophages by targeting GPX4. Collectively, we demonstrated the target gene and molecular mechanism of miR-129-2-3p mediating LPS-induced polarization and ferroptosis in macrophages by targeting the SMAD3-GPX4 axis, which would provide a novel strategy for sepsis targeted therapy based on macrophages polarization and ferroptosis.

Research trends and hotspots in exercise rehabilitation for coronary heart disease: A bibliometric analysis.

Exercise rehabilitation can improve the prognosis of patients with coronary heart disease. However, a bibliometric analysis of the global exercise rehabilitation for coronary heart disease (CHD) research topic is lacking. This study investigated the development trends and research hotspots in the field of coronary heart disease and exercise rehabilitation. CiteSpace software was used to analyze the literature on exercise therapy for CHD in the Web of Science Core Collection database. We analyzed the data of countries/institutions, journals, authors, keywords, and cited references. A total of 3485 peer-reviewed papers were found, and the number of publications on the topic has steadily increased. The most productive country is the USA (1125), followed by China (477) and England (399). The top 3 active academic institutions are Research Libraries UK (RLUK) (236), Harvard University (152), and the University of California System (118). The most commonly cited journals are Circulation (2596), The most commonly cited references are "Exercise-based cardiac rehabilitation for coronary heart disease" (75), Lavie CJ had published the most papers (48). World Health Organization was the most influential author (334 citations). The research frontier trends in this field are body composition, participation, and function. Research on the effects of physical activity or exercise on patients with CHD is a focus of continuous exploration in this field. This study provides a new scientific perspective for exercise rehabilitation and CHD research and gives researchers valuable information for detecting the current research status, hotspots, and emerging trends for further research.

Oxidative stress drives vascular smooth muscle cell damage in acute Stanford type A aortic dissection through HIF-1α/HO-1 mediated ferroptosis.

Background: Acute Stanford type A aortic dissection (ATAAD) is characterized by intimal tearing and false lumen formation containing large amounts of erythrocytes with heme. Heme oxygenase 1 (HO-1) is the key enzyme to degrade heme for iron accumulation and further ferroptosis. The current study aimed at investigating the role of HO-1 in the dissection progression of ATAAD. Methods: Bioinformatic analyses and experimental validation were performed to reveal ferroptosis and HO-1 expression in ATAAD. Human aortic vascular smooth muscle cell (HA-VSMC) was used to explore underlying molecular mechanisms and the role of HO-1 overexpression in ATAAD. Results: Ferroptosis was identified as a critical manner of regulated cell death in ATAAD. HO-1 was screened as a key signature of ferroptosis in ATAAD, which was closely associated with oxidative stress. Single cell/nucleus transcriptomic analysis and histological staining revealed that HO-1 and HIF-1α were upregulated in vascular smooth muscle cell (VSMC) of ATAAD. Further in vitro experiments showed that H2O2-induced oxidative stress increased VSMC ferroptosis with the overexpression of HO-1, which could be suppressed by HIF-1α inhibitor PX-478. HIF-1α could transcriptionally regulate the expression of HO-1 through binding to its promoter region. Pharmacological inhibition of HO-1 by zinc protoporphyrin (ZnPP) did not reduce H2O2-induced HA-VSMC damage without heme co-incubation. However, H2O2-induced HA-VSMC damage was worsened when heme was added into the medium, and ZnPP could reduce HA-VSMC damage in this condition. Conclusion: HO-1 is a key signature of VSMC ferroptosis in ATAAD. HIF-1α/HO-1 mediated ferroptosis might participate in oxidative stress induced VSMC damage.

Lung Cancer Risk Attributable to Active Smoking in China: A Systematic Review and Meta-Analysis.

Objective: No consensus exists on the relative risk ( RR) of lung cancer (LC) attributable to active smoking in China. This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population. Methods: A systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China. Primary articles on LC providing risk estimates with their 95% confidence intervals ( CIs) for "ever" "former" or "current" smokers from China were selected. Meta-analysis was used to estimate the pooled RR of active smoking. Results: Forty-four unique studies were included. Compared with that of nonsmokers, the pooled RR (95% CI) for "ever" "former" and "current" smokers were 3.26 (2.79-3.82), 2.95 (1.71-5.08), and 5.16 (2.58-10.34) among men, 3.18 (2.78-3.63), 2.70 (2.08-3.51), and 4.27 (3.61-5.06) among women, and 2.71 (2.12-3.46), 2.66 (2.45-2.88), and 4.21 (3.25-5.45) in both sexes combined, respectively. Conclusion: The RR of LC has remained relatively stable (range, 2-6) over the past four decades in China. Early quitting of smoking could reduce the RR to some extent; however, completely refraining from smoking is the best way to avoid its adverse effects.

Photocatalytic Intramolecular Alkene Hydroamination of N-Alkoxy Ureas: An Approach to Imidazolinones.

Imidazolinones were obtained in good yields by intramolecular hydroamination of N-alkoxy ureas in the presence of an organic photocatalyst and an inorganic base. In this reaction, the N-alkoxy urea anion generated by deprotonation undergoes photocatalyzed single-electron-transfer oxidation to generate the corresponding radical, which cyclizes to afford the imidazolinone ring. This new protocol grants access to an array of complex molecules containing a privileged imidazolinone core.

The Modification Mechanism, Evaluation Method, and Construction Technology of Direct-to-Plant SBS Modifiers in Asphalt Mixture: A Review.

To further promote the development of research on direct-to-plant SBS-modified asphalt, this article analyzes the development of direct-to-plant SBS modifiers. Starting from the material composition and mechanism of action, common direct-to-plant SBS modifiers were analyzed and classified into four categories based on their mechanism of action, including the instant dissolution principle, intramolecular lubrication principle, non-granulation principle, and vulcanization principle. From the evaluation of the modification effect, the method of studying the performance of direct-to-plant SBS-modified asphalt is summarized, including fluorescence microscopy, AFM technology, and molecular dynamics simulation technology. From the perspective of practical application, the construction process of direct-to-plant SBS-modified asphalt was discussed, including the design stage, raw material preparation stage, mix design stage, and on-site construction stage. The results show that common direct-to-plant SBS modifiers are primarily SBS with a small particle size (less than 200 mesh) or specific model, supplemented by additives (EVA, naphthenic oil, sulfur, petroleum resin, etc.), which improve melting efficiency and lubricity or make it undergo vulcanization reaction, change the proportion of asphalt components, and improve stability. In the evaluation of the modification effect of direct-to-plant SBS-modified asphalt, the disparity of the direct-to-plant SBS modifier is determined by observing the particle residue after dry mixing. Macroscopic indexes of modified asphalt and modified asphalt mixture are used to determine the cross-linking effect of direct-to-plant SBS modifier and asphalt, and the modification mechanism and modification effect of wet SBS modifier are evaluated at the microscopic level. The development of direct-to-plant SBS-modified asphalt should combine the characteristics of direct-to-plant SBS modifiers and the attributes of field application, targeted research, and the development of high-performance direct-to-plant SBS modifiers and complete production technologies applicable to different regions, strengthen the improvement of modification effect evaluation, and form a complete theoretical system.

Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway.

AIMS: BACH1 is up-regulated in hypertrophic hearts, but its function in cardiac hypertrophy remains largely unknown. This research investigates the function and mechanisms of BACH1 in the regulation of cardiac hypertrophy. METHODS AND RESULTS: Male cardiac-specific BACH1 knockout mice or cardiac-specific BACH1 transgenic (BACH1-Tg) mice and their respective wild-type littermates developed cardiac hypertrophy induced by angiotensin II (Ang II) or transverse aortic constriction (TAC). Cardiac-specific BACH1 knockout in mice protected the hearts against Ang II- and TAC-induced cardiac hypertrophy and fibrosis, and preserved cardiac function. Conversely, cardiac-specific BACH1 overexpression markedly exaggerated cardiac hypertrophy and fibrosis and reduced cardiac function in mice with Ang II- and TAC-induced hypertrophy. Mechanistically, BACH1 silencing attenuated Ang II- and norepinephrine-stimulated calcium/calmodulin-dependent protein kinase II (CaMKII) signalling, the expression of hypertrophic genes, and hypertrophic growth of cardiomyocytes. Ang II stimulation promoted the nuclear localization of BACH1, facilitated the recruitment of BACH1 to the Ang II type 1 receptor (AT1R) gene promoter, and then increased the expression of AT1R. Inhibition of BACH1 attenuated Ang II-stimulated AT1R expression, cytosolic Ca2+ levels, and CaMKII activation in cardiomyocytes, whereas overexpression of BACH1 led to the opposite effects. The increased expression of hypertrophic genes induced by BACH1 overexpression upon Ang II stimulation was suppressed by CaMKII inhibitor KN93. The AT1R antagonist, losartan, significantly attenuated BACH1-mediated CaMKII activation and cardiomyocyte hypertrophy under Ang II stimulation in vitro. Similarly, Ang II-induced myocardial pathological hypertrophy, cardiac fibrosis, and dysfunction in BACH1-Tg mice were blunted by treatment with losartan. CONCLUSION: This study elucidates a novel important role of BACH1 in pathological cardiac hypertrophy by regulating the AT1R expression and the Ca2+/CaMKII pathway, and highlights potential therapeutic target in pathological cardiac hypertrophy.

Spontaneous Internal Electric Field in Heterojunction Boosts Bifunctional Oxygen Electrocatalysts for Zinc-Air Batteries: Theory, Experiment, and Application.

Heterojunctions are a promising class of materials for high-efficiency bifunctional oxygen electrocatalysts in both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, the conventional theories fail to explain why many catalysts behave differently in ORR and OER, despite a reversible path (* O2 ⇋* OOH⇋* O⇋* OH). This study proposes the electron-/hole-rich catalytic center theory (e/h-CCT) to supplement the existing theories, it suggests that the Fermi level of catalysts determines the direction of electron transfer, which affects the direction of the oxidation/reduction reaction, and the density of states (DOS) near the Fermi level determines the accessibility for injecting electrons and holes. Additionally, heterojunctions with different Fermi levels form electron-/hole-rich catalytic centers near the Fermi levels to promote ORR/OER, respectively. To verify the universality of the e/h-CCT theory, this study reveals the randomly synthesized heterostructural Fe3 N-FeN0.0324 (Fex N@PC with DFT calculations and electrochemical tests. The results show that the heterostructural F3 N-FeN0.0324 facilitates the catalytic activities for ORR and OER simultaneously by forming an internal electron-/hole-rich interface. The rechargeable ZABs with Fex N@PC cathode display a high open circuit potential of 1.504 V, high power density of 223.67 mW cm-2 , high specific capacity of 766.20 mAh g-1 at 5 mA cm-2 , and excellent stability for over 300 h.