Dissolved trace elements in the upper reaches of Lancang River, southeast Qinghai-Tibet Plateau: Current status and distribution, risk and source.

The environmental impact of dissolved trace element (DTE) pollution is becoming increasingly well understood. The southeastern edge of the Qinghai-Tibet Plateau is a region with high environmental vulnerability, making it highly susceptible to various anthropogenic disturbances. The Lancang River (LCR), as the most representative river in this area, serving as the largest international river in Southeast Asia, the LCR is crucial for the downstream regions, supporting fisheries, agriculture, and even economic development, earning it the title of the "water tower" for these areas. This study mainly focuses on the upstream unbuilt dam area. In this study, we gathered 25 surface water samples from the upstream of the LCR and examined the geographical distribution, primary sources, and associated human health risks of seven dissolved trace elements (Mn, Cr, Fe, Co, Cu, Ni, Zn). Cr, Fe, Co, Ni, and Cu in the main stream are primarily associated with natural sources, including rock weathering, soil erosion, and similar processes. Mn, however, predominantly originates from human activities such as industrial construction and road transportation. Zn mainly originates from the specialized fertilizers used for highland barley in plateau regions. Almost all DTE concentrations exhibited a downward trend from upstream to downstream. However, due to inputs from various sources along the way, there will be some abnormal points. The concentrations of DTE in the study area were within the acceptable limits set by drinking water standards in China, the USA, and the WHO. Overall, the water quality in this region is considered good. The results from a Monte Carlo simulation assessing health risks indicate that the non-carcinogenic health risk caused by DTE in the upper reaches of Lancang River was very weak. The primary pathway through which DTE can harm human health is ingestion, with children being particularly vulnerable. These findings offer a critical scientific basis for understanding the migration of DTE in aquatic environments and for the ecological stewardship of the Lancang River.

High-Detectivity All-Polymer Photodiode Empowers Smart Vitality Surveillance and Computational Imaging Rivaling Silicon Diodes.

Near-infrared (NIR) organic photodetectors (OPDs), particularly all-polymer-based ones, hold substantial commercial promise in the healthcare and imaging sectors. However, the process of optimizing their active layer composition to achieve highly competitive figures of merit lacks a clear direction and methodology. In this work, celebrity polymer acceptor PY-IT into a more NIR absorbing host system PBDB-T:PZF-V, to significantly enhance the photodetection competence, is introduced. The refined all-polymer ternary broadband photodetector demonstrates superior performance metrics, including experimentally measured noise current as low as 6 fA Hz-1/2, specific detectivity reaching 8 × 1012 Jones, linear dynamic range (LDR) of 145 dB, and swift response speed surpassing 200 kHz, striking a fair balance between sensitivity and response speed. Comprehensive morphological and photophysical characterizations elucidate the mechanisms behind the observed performance enhancements in this study, which include reduced trap density, enhanced charge transport, diminished charge recombination, and balanced electron/hole mobilities. Moreover, the practical deployment potential of the proof-of-concept device in self-powered mode is demonstrated through their application in a machine learning-based cuffless blood pressure (BP) estimation system and in high-resolution computational imaging across complex environments, where they are found to quantitatively rival commercial silicon diodes.

Protective Effect of Long Noncoding RNA OXCT1-AS1 on Doxorubicin-Induced Apoptosis of Human Myocardial Cells by the Competitive Endogenous RNA Pattern. / Efeito Protetor do RNA Não Codificante Longo OXCT1-AS1 na Apoptose de Células Miocárdicas Humanas Induzida pela Doxorrubicina pelo Padrão Competitivo de RNA Endógeno.

BACKGROUND: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. OBJECTIVE: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. METHODS: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. RESULTS: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. CONCLUSION: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis.

FUNDAMENTO: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. OBJETIVO: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. MÉTODOS: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. RESULTADOS: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. CONCLUSÃO: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1.

Role of S100ß in Unstable Angina Pectoris: Insights from Quantitative Flow Ratio.

BACKGROUND AND OBJECTIVE: Disturbed autonomic nervous system (ANS) may promote inflammatory, immune, and oxidative stress responses, which may increase the risk of acute coronary events. S100ß has been proposed as a biomarker of neuronal injury that would provide an insightful understanding of the crosstalk between the ANS, immune-inflammatory cells, and plaques that drive atherosclerosis. This study investigates the correlation between S100ß, and functional coronary stenosis as determined by quantitative flow ratio (QFR). METHODS: Patients with unstable angina pectoris (UAP) scheduled for coronary angiography and QFR were retrospectively enrolled. Serum S100ß levels were determined by enzyme-linked immunosorbent assay. The Gensini score was used to estimate the extent of atherosclerotic lesions and the cumulative sum of three-vessel QFR (3V-QFR) was calculated to estimate the total atherosclerotic burden. RESULTS: Two hundred thirty-three patients were included in this study. Receiver operator characteristic (ROC) curve indicated that S100ß>33.28 pg/mL predicted functional ischemia in patients with UAP. Multivariate logistic analyses showed that a higher level of S100ß was independently correlated with a functional ischemia-driven target vessel (QFR ≤0.8). This was also closely correlated with the severity of coronary lesions, as measured by the Gensini score (OR = 5.058, 95% CI: 2.912-8.793, p <0.001). According to 3V-QFR, S100ß is inversely associated with total atherosclerosis burden (B = -0.002, p <0.001). CONCLUSIONS: S100ß was elevated in the functional ischemia stages of UAP. It was independently associated with coronary lesion severity as assessed by Gensini score and total atherosclerosis burden as estimated by 3V-QFR in patients with UAP.

Insights Into Preaggregation Control of Y-Series Nonfullerene Acceptors in Liquid State for Highly Efficient Binary Organic Solar Cells.

Leveraging breakthroughs in Y-series nonfullerene acceptors (NFAs), organic solar cells (OSCs) have achieved impressive power conversion efficiencies (PCEs) exceeding 19%. However, progress in advancing OSCs has decelerated due to constraints in realizing the full potential of the Y-series NFAs. Herein, a simple yet effective solid additive-induced preaggregation control method employing 2-chloro-5-iodopyridine (PDCI) is reported to unlock the full potential of the Y-series NFAs. Specifically, PDCI interacts predominantly with Y-series NFAs enabling enhanced and ordered phase-aggregation in solution. This method leads to a notable improvement and a redshifted absorption of the acceptor phase during film formation, along with improved crystallinity. Moreover, the PDCI-induced preaggregation of NFAs in the solution enables ordered molecule packing during the film-formation process through delicate intermediate states transition. Consequently, the PDCI-induced preaggregated significantly improves the PCE of PM6:Y6 OSCs from 16.12% to 18.12%, among the best values reported for PM6:Y6 OSCs. Importantly, this approach is universally applicable to other Y-series NFA-based OSCs, achieving a champion PCE of 19.02% for the PM6:BTP-eC9 system. Thus, the preaggregation control strategy further unlocks the potential of Y-series NFAs, offering a promising avenue for enhancing the photovoltaic performance of Y-series NFA-based OSCs.

Artesunate alleviates sepsis-induced liver injury by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis.

BACKGROUND: The present study aimed to explore the regulatory effects of artesunate on macrophage polarization in sepsis. METHODS: Cell models and mice models were established using lipopolysaccharide (LPS), followed by treatment with various concentrations of artesunate. The phenotype of the macrophages was determined by flow cytometry. RNA immunoprecipitation was used to confirm the binding between MALAT1 and polypyrimidine tract-binding protein 1 (PTBP1), as well as between PTBP1 and interferon-induced helicase C domain-containing protein 1 (IFIH1). RESULTS: Treatment with artesunate inhibited M1 macrophage polarization in Kupffer cells subjected to LPS stimulation by downregulating MALAT1. Furthermore, MALAT1 abolished the inhibitory effect of artesunate on M1 macrophage polarization by recruiting PTBP1 to promote IFIH. In vivo experiments confirmed that artesunate alleviated septic liver injury by affecting macrophage polarization via MALAT1. CONCLUSION: The present study showed that artesunate alleviates LPS-induced sepsis in Kupffer cells by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis.

Effects of Biochar and Straw Amendment on Soil Fertility and Microbial Communities in Paddy Soils.

Straw and biochar, two commonly used soil amendments, have been shown to enhance soil fertility and the composition of microbial communities. To compare the effects of straw and biochar on soil fertility, particularly focusing on soil dissolved organic matter (DOM) components, and the physiochemical properties of soil and microbial communities, a combination of high-throughput sequencing and three-dimensional fluorescence mapping technology was employed. In our study, we set up four treatments, i.e., without biochar and straw (B0S0); biochar only (B1S0); straw returning only (B0S1); and biochar and straw (B1S1). Our results demonstrate that soil organic matter (SOM), available nitrogen (AN), and available potassium (AK) were increased by 34.71%, 22.96%, and 61.68%, respectively, under the B1S1 treatment compared to the B0S0 treatment. In addition, microbial carbon (MBC), dissolved organic carbon (DOC), and particulate organic carbon (POC) were significantly increased with the B1S1 treatment, by 55.13%, 15.59%, and 125.46%, respectively. The results also show an enhancement in microbial diversity, the composition of microbial communities, and the degree of soil humification with the application of biochar and straw. Moreover, by comparing the differences in soil fertility, DOM components, and other indicators under different treatments, the combined treatments of biochar and straw had a more significant positive impact on paddy soil fertility compared to biochar. In conclusion, our study revealed the combination of straw incorporation and biochar application has significant impacts and is considered an effective approach to improving soil fertility.

Intracellular and extracellular Cyclophilin a promote cardiac fibrosis through TGF-ß signaling in response to angiotensin â ¡.

Cardiac fibrosis is characterized by abnormal proliferation of cardiac fibroblasts (CFs) and ventricular remodeling, which finally leads to heart failure. Inflammation and oxidative stress play a central role in the development of cardiac fibrosis. CyPA (Cyclophilin A) is a main proinflammatory cytokine secreted under the conditions of oxidative stress. The mechanisms by which intracellular and extracellular CyPA interact with CFs are unclear. Male C57BL/6 J mice received angiotensin Ⅱ (Ang Ⅱ) or vehicle for 4 weeks. Inhibition of CyPA significantly reversed Ang Ⅱ-induced cardiac hypertrophy and fibrosis. Mechanically, TGF-ß (Transforming growth factor-ß) signaling was found to be an indispensable downstream factor of CyPA-mediated myofibroblast differentiation and proliferation. Furthermore, intracellular CyPA and extracellular CyPA activate TGF-ß signaling through NOD-like receptor protein 3 (NLRP3) inflammasome and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, respectively. Pharmacological inhibition of CyPA and its receptor CD147 implemented by Triptolide also attenuated the expression of TGF-ß signaling and cardiac fibrosis in Ang Ⅱ-model. These studies elucidate a novel mechanism by which CyPA promotes TGF-ß and its downstream signaling in CFs and identify CyPA (both intracellular and extracellular) as plausible therapeutic targets for preventing or treating cardiac fibrosis induced by chronic Ang Ⅱ stimulation.

MiR-31-5p alleviates septic cardiomyopathy by targeting BAP1 to inhibit SLC7A11 deubiquitination and ferroptosis.

Septic cardiomyopathy is one of the most severe and common complications in patients with sepsis and poses a great threat to their prognosis. However, the potential mechanisms and effective therapeutic drugs need to be explored. The control of cardiac cell death by miRNAs has emerged as a prominent area of scientific interest in the diagnosis and treatment of heart disorders in recent times. In the present investigation, we discovered that overexpression of miR-31-5p prevented LPS-induced damage to H9C2 cells and that miR-31-5p could inhibit BAP1 production by binding to its 3'-UTR. BRCA1-Associated Protein 1 (BAP1) is a ubiquitin carboxy-terminal hydrolase. BAP1 upregulation blocked effect of miR-31-5p on H9C2 cell injury. Moreover, BAP1 inhibited the expression of solute carrier family 7 member 11 (SLC7A11) by deubiquitinating histone 2 A (H2Aub) on the promoter of SLC7A11. Furthermore, overexpression of miR-31-5p and downregulation of BAP1 inhibited SLC7A11 mediated ferroptosis. In addition, the downregulation of SLC7A11 reversed the inhibitory effect of miR-31-5p on the expression of myocardial injury and inflammatory factors, and cell apoptosis was reversed. In conclusion, these results indicate that miR-31-5p alleviates malignant development of LPS-induced H9C2 cell injury by targeting BAP1 and regulating SLC7A11 deubiquitination-mediated ferroptosis, which confirmed the protective effect of miR-31-5p on H9C2 cell injury and revealed potential mechanisms that may provide new targets for treatment of septic cardiomyopathy.

The requirement of the mitochondrial protein NDUFS8 for angiogenesis.

Mitochondria are important for the activation of endothelial cells and the process of angiogenesis. NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8) is a protein that plays a critical role in the function of mitochondrial Complex I. We aimed to investigate the potential involvement of NDUFS8 in angiogenesis. In human umbilical vein endothelial cells (HUVECs) and other endothelial cell types, we employed viral shRNA to silence NDUFS8 or employed the CRISPR/Cas9 method to knockout (KO) it, resulting in impaired mitochondrial functions in the endothelial cells, causing reduction in mitochondrial oxygen consumption and Complex I activity, decreased ATP production, mitochondrial depolarization, increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation. Significantly, NDUFS8 silencing or KO hindered cell proliferation, migration, and capillary tube formation in cultured endothelial cells. In addition, there was a moderate increase in apoptosis within NDUFS8-depleted endothelial cells. Conversely, ectopic overexpression of NDUFS8 demonstrated a pro-angiogenic impact, enhancing cell proliferation, migration, and capillary tube formation in HUVECs and other endothelial cells. NDUFS8 is pivotal for Akt-mTOR cascade activation in endothelial cells. Depleting NDUFS8 inhibited Akt-mTOR activation, reversible with exogenous ATP in HUVECs. Conversely, NDUFS8 overexpression boosted Akt-mTOR activation. Furthermore, the inhibitory effects of NDUFS8 knockdown on cell proliferation, migration, and capillary tube formation were rescued by Akt re-activation via a constitutively-active Akt1. In vivo experiments using an endothelial-specific NDUFS8 shRNA adeno-associated virus (AAV), administered via intravitreous injection, revealed that endothelial knockdown of NDUFS8 inhibited retinal angiogenesis. ATP reduction, oxidative stress, and enhanced lipid oxidation were detected in mouse retinal tissues with endothelial knockdown of NDUFS8. Lastly, we observed an increase in NDUFS8 expression in retinal proliferative membrane tissues obtained from human patients with proliferative diabetic retinopathy. Our findings underscore the essential role of the mitochondrial protein NDUFS8 in regulating endothelial cell activation and angiogenesis.

Straw Addition Enhances Crop Yield, Soil Aggregation, and Soil Microorganisms in a 14-Year Wheat-Rice Rotation System in Central China.

Straw return utilizes waste resources to reduce the use of chemical fertilizers worldwide. However, information is still lacking on the relative impact of straw return on soil fertility, the nutrient composition of different soil aggregates, and soil microbial communities. Therefore, this study aimed to understand the effects of different management practices on the crop yield, soil fertility, and soil community composition in a 14-year wheat-rice rotation system. The treatments included a control (without fertilizer and straw addition), chemical fertilization (NPK), straw return without fertilizer (S), and straw addition with chemical fertilizer (NPKS). The results showed that NPKS improved the wheat and rice yield by 185.12% and 88.02%, respectively, compared to the CK treatment. Additionally, compared to the CK treatment, the N, P, and K contents of the wheat stem were increased by 39.02%, 125%, and 20.23% under the NPKS treatment. Compared to the CK treatment, SOM, TN, TP, AN, AP, AK, CEC, AFe, AMn, ACu, and AZn were increased by 49.12%, 32.62%, 35.06%, 22.89%, 129.36%, 48.34%, 13.40%, 133.95%, 58.98%, 18.26% and 33.33% under the NPKS treatment, respectively. Moreover, straw addition promoted the creation and stabilization of macro-aggregates in crop soils. The relative abundance of macro-aggregates (0.25-2 mm) increased from 37.49% to 52.97%. Straw addition was associated with a higher proportion of aromatic and carbonyl carbon groups in the soil, which, in turn, promoted the formation of macro-aggregates. Redundancy analysis showed that straw return significantly increased the microbial community diversity. These findings demonstrate that straw addition together with chemical fertilizer could increase the crop yield by improving soil fertility, soil aggregate stability, and the diversity of fungi.

Influences of tobacco straw return with lime on microbial community structure of tobacco-planting soil and tobacco leaf quality.

Soil amendment is an important strategy for improving soil quality and crop yield. From 2014 to 2019, we conducted a study to investigate the effects of tobacco straw return with lime on soil nutrients, soil microbial community structure, tobacco leaf yield, and quality in southern Anhui, China. A field experiment was conducted with four treatments: straw removed (CK), straw return (St), straw return with dolomite (St + D), and straw return with lime (St + L). Results showed that after 5 years of application, the St + L significantly increased the soil pH by 16.9%, and the contents of soil alkaline nitrogen (N) and available potassium (K) by 17.2% and 23.0%, respectively, compared with the CK. Moreover, the St + L significantly increased tobacco leaf yield (24.0%) and the appearance (9.1%) and sensory (5.9%) quality of flue-cured tobacco leaves. The addition of soil conditioners (straw, dolomite, and lime) increased both the total reads and effective sequences of soil microorganisms. Bacterial diversity was more sensitive to changes in the external environment compared to soil fungi. The application of soil amendments (lime and straw) promoted the growth of beneficial microorganisms in the soil. Additionally, bacterial species had greater competition and limited availability of resources for survival compared to fungi. The results showed that soil microorganisms were significantly influenced by the presence of AK, AN, and pH contents. These findings can provide an effective method for improving the quality of flue-cured tobacco leaves and guiding the amelioration of acidic soil in regions where tobacco-rice rotation is practiced.

Extraction of Coastal Levees Using U-Net Model with Visible and Topographic Images Observed by High-Resolution Satellite Sensors.

Coastal levees play a role in protecting coastal areas from storm surges and high waves, and they provide important input information for inundation damage simulations. However, coastal levee data with uniformity and sufficient accuracy for inundation simulations are not always well developed. Against this background, this study proposed a method to extract coastal levees by inputting high spatial resolution optical satellite image products (RGB images, digital surface models (DSMs), and slope images that can be generated from DSM images), which have high data availability at the locations and times required for simulation, into a deep learning model. The model is based on U-Net, and post-processing for noise removal was introduced to further improve its accuracy. We also proposed a method to calculate levee height using a local maximum filter by giving DSM values to the extracted levee pixels. The validation was conducted in the coastal area of Ibaraki Prefecture in Japan as a test area. The levee mask images for training were manually created by combining these data with satellite images and Google Street View, because the levee GIS data created by the Ibaraki Prefectural Government were incomplete in some parts. First, the deep learning models were compared and evaluated, and it was shown that U-Net was more accurate than Pix2Pix and BBS-Net in identifying levees. Next, three cases of input images were evaluated: (Case 1) RGB image only, (Case 2) RGB and DSM images, and (Case 3) RGB, DSM, and slope images. Case 3 was found to be the most accurate, with an average Matthews correlation coefficient of 0.674. The effectiveness of noise removal post-processing was also demonstrated. In addition, an example of the calculation of levee heights was presented and evaluated for validity. In conclusion, this method was shown to be effective in extracting coastal levees. The evaluation of generalizability and use in actual inundation simulations are future tasks.

CD137 Signaling Mediates Pulmonary Artery Endothelial Cell Proliferation Under Hypoxia By Regulating Mitochondrial Dynamics.

Altered mitochondrial dynamics affect pulmonary artery endothelial cells (PAECs) proliferation, contributing to the development of pulmonary hypertension. CD137 signaling promotes mitochondrial fission. We hypothesize CD137 signaling is involved in the excessive proliferation of PAECs. The levels of CD137 protein were increased in the lung tissue of hypoxic mice and hypoxic-stimulated PAECs. Activation of CD137 signal in hypoxic-PAECs upregulated the levels of hypoxia-inducible factor-2α (HIF-2α), glucose transporters type 4, the lactate transporter monocarboxylate transporter 4, key glycolysis rate-limiting enzymes and promoted mitochondrial division; moreover, increased glucose uptake, lactic acid and ATP production and proliferative cells were observed in these PAECs. Whereas, knockdown HIF-2α reversed CD137 signal-mediated effects in PAECs mentioned above. Compared with wild-type mice, the proliferation of PAECs and the percentage of vascular lateral wall thickness decreased in CD137 knockout mice. Together, CD137 signal participated in pulmonary vascular remodeling through the regulation of mitochondrial dynamics dependent on HIF-2α in PAECs.

Gene and stem cell therapy for inherited cardiac arrhythmias.

Inherited cardiac arrhythmias are a group of genetic diseases predisposing to sudden cardiac arrest, mainly resulting from variants in genes encoding cardiac ion channels or proteins involved in their regulation. Currently available therapeutic options (pharmacotherapy, ablative therapy and device-based therapy) can not preclude the occurrence of arrhythmia events and/or provide complete protection. With growing understanding of the genetic background and molecular mechanisms of inherited cardiac arrhythmias, advancing insight of stem cell technology, and development of vectors and delivery strategies, gene therapy and stem cell therapy may be promising approaches for treatment of inherited cardiac arrhythmias. Recent years have witnessed impressive progress in the basic science aspects and there is a clear and urgent need to be translated into the clinical management of arrhythmic events. In this review, we present a succinct overview of gene and cell therapy strategies, and summarize the current status of gene and cell therapy. Finally, we discuss future directions for implementation of gene and cell therapy in the therapy of inherited cardiac arrhythmias.

High performance solar-blind UV detector with Mg0.472Zn0.528O/Mg0.447Zn0.553O double layer structure on MgO substrate.

Mg0.472Zn0.528O/Mg0.447Zn0.553O double layer structure UV detectors are made on single structure MgO substrate by PLD method, and the effect of different thickness top MgZnO layer on the UV response characteristics of the detector are studied. Compared with the single layer MgZnO detector that made by Mg0.3Zn0.7O target, the Mg0.472Zn0.528O/Mg0.447Zn0.553O double layer detector with 30 nm top layer, shows much higher deep UV response (21.3 A W-1at 265 nm), much smaller dark current(66.9 pA) and much higher signal-to-noise ratio (2.8 × 105) at 25 V bias voltage. And the device also shows relative high response (23.1 A W-1) at 235 nm deep UV light at 25 V bias voltage, which is mainly attributed by the bottom MgZnO layer with higher Mg composition. When the top layer is 66.7 nm thick, the response of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector reached 228.8 A W-1at 255 nm under 25 V bias voltage, the signal-to-noise ratio of which is 10573 under 20 V bias voltage, and the near UV response of the device is also big because of more h-MgZnO in top MgZnO layer. When the top layer reached 90.2 nm, there are much more h-MgZnO in the top MgZnO layer, the peak response of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector is just 6.65 A W-1at 320 nm under 25 V bias voltage, the signal-to-noise ratio of which is 1248. The high Mg composition bottom MgZnO decrease the dark current of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector, both the 2DEG effect of the double layer structure and the amplify effect of the mix-phase MgZnO top layer, increased theIuvand deep UV response of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector. Therefore, the double layer Mg0.472Zn0.528O/Mg0.447Zn0.553O detector is more sensitive at faint deep UV light compared with previous reported MgZnO detectors, and the MgxZn1-xO/MgyZn1-yO detector shows similarIuvand signal-noise-ratio at faint deep UV light as high-temperature fabricated AlxGa1-xN/AlyGa1-yN detectors.

Alterations in the composition and metabolite profiles of the saline-alkali soil microbial community through biochar application.

Saline-alkali soil poses significant chanllenges to sustainable development of agriculture. Although biochar is commonly used as a soil organic amendment, its microbial remediation mechanism on saline-alkali soil requires further confirmation. To address this, we conducted a pot experiment using cotton seedlings to explore the potential remediation mechanism of rice straw biochar (BC) at three different levels on saline-alkaline soil. The results showed that adding of 2% biochar greatly improved the quality of saline-alkaline soil by reducing pH levels, electrical conductivity (EC), and water-soluble ions. Moreover, biochar increased the soil organic matter (SOM), nutrient availability and extracellular enzyme activity. Interestingly, it also reduced soil salinity and salt content in various cotton plant tissues. Additionally, biochar had a notable impact on the composition of the microbial community, causing changes in soil metabolic pathways. Notably, the addition of biochar promoted the growth and metabolism of dominant salt-tolerant bacteria, such as Proteobacteria, Bacteroidota, Acidobacteriota, and Actinobacteriota. By enhancing the positive correlation between microorganisms and metabolites, biochar alleviated the inhibitory effect of salt ions on microorganisms. In conclusion, the incorporation of biochar significantly improves the soil microenvironment, reduces soil salinity, and shows promise in ameliorating saline-alkaline soil conditions.

A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation.

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.

Inhibition of Sema4D attenuates pressure overload-induced pathological myocardial hypertrophy via the MAPK/NF-κB/NLRP3 pathways.

Sema4D (CD100) is closely related to pathological and physiological processes, including tumor growth, angiogenesis and cardiac development. Nevertheless, the role and mechanism of Sema4D in cardiac hypertrophy are still unclear to date. To assess the impact of Sema4D on pathological cardiac hypertrophy, TAC surgery was performed on C57BL/6 mice which were transfected with AAV9-mSema4D-shRNA or AAV9-mSema4D adeno-associated virus by tail vein injection. Our results indicated that Sema4D knockdown mitigated cardiac hypertrophy, fibrosis and dysfunction when exposed to pressure overload, and Sema4D downregulation markedly inhibited cardiomyocyte hypertrophy induced by angiotensin II. Meanwhile, Sema4D overexpression had the opposite effect in vitro and in vivo. Furthermore, analysis of signaling pathways showed that Sema4D activated the MAPK pathway during cardiac hypertrophy induced by pressure overload, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed Sema4D overexpression-induced deteriorated phenotype, resulting in improved cardiac function. Further research indicated that myocardial hypertrophy induced by Sema4D was closely related to the expression of the pyroptosis-related proteins PP65, NLRP3, caspase-1, ASC, GSDMD, IL-18 and IL-1ß. In conclusion, our study demonstrated that Sema4D regulated the process of pathological myocardial hypertrophy through modulating MAPK/NF-κB/NLRP3 pathway, and Sema4D may be the promising interventional target of cardiac hypertrophy and heart failure.

Downregulation of B4GALT5 attenuates cardiac fibrosis through Lumican and Akt/GSK-3ß/ß-catenin pathway.

Virtually all forms of cardiac disease exhibit cardiac fibrosis as a common trait, which ultimately leads to adverse ventricular remodeling and heart failure. To improve the prognosis of heart disease, it is crucial to halt the progression of cardiac fibrosis. Protein function is intricately linked with protein glycosylation, a vital post-translational modification. As a fundamental member of the ß1,4-galactosyltransferase gene family (B4GALT), ß1,4-galactosyltransferase V (B4GALT5) is associated with various disorders. In this study, significant levels of B4GALT5 expression were observed in cardiac fibrosis induced by transverse aortic constriction (TAC) or TGFß1 and the activation of cardiac fibroblasts (CFs). Subsequently, by administering AAV9-shB4GALT5 injections to TAC animals, we were able to demonstrate that in vivo B4GALT5 knockdown decreased the transformation of CFs into myofibroblasts (myoFBs) and reduced the deposition of cardiac collagen fibers. In vitro tests revealed the same results. Conversely, both in vivo and in vitro experiments indicated that overexpression of B4GALT5 stimulates CFs activation and exacerbates cardiac fibrosis. Initially, we elucidated the primary mechanism by which B4GALT5 regulates the Akt/GSK-3ß/ß-catenin pathway and directly interacts with laminin, thereby affecting cardiac fibrosis. Our findings demonstrate that B4GALT5 promotes cardiac fibrosis through the Akt/GSK-3ß/ß-catenin pathway and reveal laminin as the target protein of B4GALT5.