Search

Summary: The composite material-like extracellular matrix (ECM) in the sinoatrial node (SAN) supports the native pacemaking cardiomyocytes (PCMs). To test the roles of SAN ECM in the PCM phenotype and function, we engineered reconstructed-SAN heart tissues (rSANHTs) by recellularizing porcine SAN ECMs with hiPSC-derived PCMs. The hiPSC-PCMs in rSANHTs self-organized into clusters resembling the native SAN and displayed higher expression of pacemaker-specific genes and a faster automaticity compared with PCMs in reconstructed-left ventricular heart tissues (rLVHTs). To test the protective nature of SAN ECMs under strain, rSANHTs and rLVHTs were transplanted onto the murine thoracic diaphragm to undergo constant cyclic strain. All strained-rSANHTs preserved automaticity, whereas 66% of strained-rLVHTs lost their automaticity. In contrast to the strained-rLVHTs, PCMs in strained-rSANHTs maintained high expression of key pacemaker genes (HCN4, TBX3, and TBX18). These findings highlight the promotive and protective roles of the composite SAN ECM and provide valuable insights for pacemaking tissue engineering.

Summary: PRMT1 plays a vital role in breast tumorigenesis; however, the underlying molecular mechanisms remain incompletely understood. Herein, we show that PRMT1 plays a critical role in RNA alternative splicing, with a preference for exon inclusion. PRMT1 methylome profiling identifies that PRMT1 methylates the splicing factor SRSF1, which is critical for SRSF1 phosphorylation, SRSF1 binding with RNA, and exon inclusion. In breast tumors, PRMT1 overexpression is associated with increased SRSF1 arginine methylation and aberrant exon inclusion, which are critical for breast cancer cell growth. In addition, we identify a selective PRMT1 inhibitor, iPRMT1, which potently inhibits PRMT1-mediated SRSF1 methylation, exon inclusion, and breast cancer cell growth. Combination treatment with iPRMT1 and inhibitors targeting SRSF1 phosphorylation exhibits an additive effect of suppressing breast cancer cell growth. In conclusion, our study dissects a mechanism underlying PRMT1-mediated RNA alternative splicing. Thus, PRMT1 has great potential as a therapeutic target in breast cancer treatment.

The pyrolysis parameter S1, which indicates the amount of free hydrocarbons present in shale, is often underestimated due to hydrocarbon loss during sample handling and measurement processes. To remedy this issue, we strongly recommend an immediate three-step hydrocarbon thermal desorption (HTD) approach to be conducted on oil shale at the drilling site. This approach measures Sg, S0, and S1*, which refer to gaseous, light, and free hydrocarbons, respectively. The new shale oil content value, calculated from the total of these three parameters, is far more precise and reliable than traditional pyrolysis S1. Moreover, we thoroughly investigated the components and microscopic occurrence features of hydrocarbons thermally desorbed at three temperature stages using gas chromatography (GC) and X-ray microcomputed tomography (CT). For example, we selected Chang 73 mud shale. Our experimental results irrefutably indicate that the ultimate shale oil content of poor resource rocks is significantly impacted by evaporative loss, with this effect being greater when the total organic carbon (TOC) is lower. Additionally, C1-5 and C1-7 hydrocarbons constitute almost all of Sg and S0, respectively. Sg and S0 are predominantly composed of C1-3 gaseous hydrocarbons, with a maximum proportion of 42.93%. In contrast, S1* contains a substantial amount of C16-31 hydrocarbons. A three-dimensional reconstruction model of an X-ray micro-CT scan shows that while the amount of shale organic matter greatly decreases from the frozen state to 300 °C, the pore volume significantly increases, particularly between 90 and 300 °C. The increased pore volume is mainly due to macropores and fractures. It is imperative to note that the shale oil triple-division boundaries must be adjusted based on more accurate oil content, although this would not affect the resource zones to which the samples already belong (ineffective, low-efficient, and enriched resources). In conclusion, we strongly advise conducting an immediate well-site analysis or utilizing preservation procedures, such as deep freezing or plastic film wrapping followed by core waxing, to minimize volatile loss.

The underground environment is complex and superimposed with the uncertainty and nonlinearity of the mine water disaster. The situation of water disaster inundation is changeable and difficult to predict. Regarding the difficulty of obtaining the inundation situation in the roadway at various time points during a flood and quickly determining the escape path based on the inundation situation, in this study, the “bucket principle” is used to construct the submergence path tree, determine the direction of the roadway flow bifurcation, analyze the progressive law of the mine water inrush submersion, simulate the water flow in the underground roadway, and visually display the real-time water flow change, water level height and escape path. The research shows that according to the constructed inundation path tree, the water level and other inundation parameters obtained by recursion are used as the basis for designing the escape path. The differential and integral progressive dynamic design of the escape path solves the problem that the optimal escape path cannot be planned in real time due to the complex underground environment and different water inrush conditions at different times.

IntroductionAs a developing country with the largest older adult population in the world, strengthening the research on falls among the older adults is undoubtedly an urgent item in China. This study aimed to explore the prevalence and risk factors associated with falls and injury from falls among community-dwelling older adults in Guangzhou, China, particularly focusing on their associations with chronic diseases.MethodsA total of 1,629 participants aged 65 years and above were selected from 11 counties in Guangzhou by the multi-stage stratified random sampling method in 2021. Socio-demographic characteristics, health and lifestyle factors, the status of falls, and injury from falls were measured by structured questionnaires through face-to-face interviews. Chi-square tests and logistic regression analysis were used to identify factors associated with falls and injury from falls. Chord diagrams were used to explore their associations with chronic diseases.ResultsA total of 251 participants (15.41%, 95% CI: 13.98%−17.25%) reported falls, and 162 participants (9.46%, 95% CI:7.72%−11.55%) indicated an injury from falls. Logistic regression analysis showed the results as follows: female patients (adjusted OR = 1.721, 95% CI: 1.681–1.761) aged ≥80 years (1.910, 1.847–1.975), unemployed (1.226, 1.171–1.284), uninsured (1.555, 1.448–1.671), average monthly household income of 2,001–4,000 CNY (1.878, 1.827–1.930), number of services provided by the community health center ≥13 times per year (1.428, 1.383–1.475), illness within 2 weeks (1.633, 1.595–1.672), high-intensity physical activity (2.254, 2.191–2.32), sedentary (1.094, 1.070–1.117), and number of chronic disease illnesses ≥3 (1.930, 1.870–1.993). Meanwhile, those risk factors were also associated with injury from falls. The older adults with medium-intensity physical activity were at lower risk (0.721, 0.705–0.737) of falls and higher risk (1.086, 1.057–1.117) of being injured from falls. Chord diagrams showed the correlations between chronic diseases and falls and injury from falls among community-dwelling older adults in Guangzhou, China.ConclusionThe high prevalence of falls is found among community-dwelling older adults in Guangzhou, China, which is related to multiple factors such as demographic variables, lifestyle, and health status, especially for chronic diseases. Therefore, targeted interventions should be developed and implemented urgently.

Directed cardiomyogenesis from human induced pluripotent stem cells (hiPSCs) has been greatly improved in the last decade but directed differentiation to pacemaking cardiomyocytes (CMs) remains incompletely understood. In this study, we demonstrated that inhibition of NODAL signaling by a specific NODAL inhibitor (SB431542) in the cardiac mesoderm differentiation stage downregulated PITX2c, a transcription factor that is known to inhibit the formation of the sinoatrial node in the left atrium during cardiac development. The resulting hiPSC-CMs were smaller in cell size, expressed higher pro-pacemaking transcription factors, TBX3 and TBX18, and exhibited pacemaking-like electrophysiological characteristics compared to control hiPSC-CMs differentiated from established Wnt-based protocol. The pacemaker-like subtype increased up to 2.4-fold in hiPSC-CMs differentiated with the addition of SB431542 relative to the control. Hence, Nodal inhibition in the cardiac mesoderm stage promoted pacemaker-like CM differentiation from hiPSCs. Improving the yield of human pacemaker-like CMs is a critical first step in the development of functional human cell-based biopacemakers.

With the rapid development of mobile services, big data, cloud services, and artificial intelligence, traditional network services cannot no longer meet the requirements of current network development and solve the problems of the resource allocation and scheduling ossification in the current network. Therefore, by using network virtualization technologies, we can provide the flexible network resource configuration information for users to reduce network cost and improve network resource efficiency. The required bandwidth resources of each virtual link are divided into different transmission line rate by employing mixed line rate splitting. We propose an optimized cost approach for Virtual Optical Network (VON) mapping based on mixed line rate. Simulation results show that the proposed optimized cost approach of VON mapping based on mixed line rate can achieve better optimization and balance in terms of the network cost, frequency slot occupation, the configuration of optical transponders, and optical regenerators.

With the rapid development of mobile services, big data, cloud services, and artificial intelligence, traditional network services cannot no longer meet the requirements of current network development and solve the problems of the resource allocation and scheduling ossification in the current network. Therefore, by using network virtualization technologies, we can provide the flexible network resource configuration information for users to reduce network cost and improve network resource efficiency. The required bandwidth resources of each virtual link are divided into different transmission line rate by employing mixed line rate splitting. We propose an optimized cost approach for Virtual Optical Network (VON) mapping based on mixed line rate. Simulation results show that the proposed optimized cost approach of VON mapping based on mixed line rate can achieve better optimization and balance in terms of the network cost, frequency slot occupation, the configuration of optical transponders, and optical regenerators.

Abstract The decay width of the $$D_s^{*}$$ D s ∗ meson is dominated by the electromagnetic mode $$D_s^*\rightarrow D_s \gamma $$ D s ∗ → D s γ , and it is thus the longest-lived charged vector meson. In light of this point, we perform the first QCD LCSRs calculation of $$D_s^{*}\rightarrow \phi $$ D s ∗ → ϕ helicity form factors and discuss the experiment potential of discovering exclusive $$D_s^{*}$$ D s ∗ weak decays. The main result is the partial decay widths, which read as $$\varGamma _{D_s^*\rightarrow l \nu } = 2.44 \times 10^{-12} \, \textrm{GeV}$$ Γ D s ∗ → l ν = 2.44 × 10 - 12 GeV , $$\varGamma _{D_s^*\rightarrow \phi l \nu } = (3.28^{+0.82}_{-0.71}) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ l ν = ( 3 . 28 - 0.71 + 0.82 ) × 10 - 14 GeV , $$\varGamma _{D_s^{*} \rightarrow \phi \pi } = ( 3.81^{+1.52}_{-1.33} ) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ π = ( 3 . 81 - 1.33 + 1.52 ) × 10 - 14 GeV and $$\varGamma _{D_s^{*}\rightarrow \phi \rho } = ( 1.16^{+0.42}_{-0.39} ) \times 10^{-13} \, \textrm{GeV}$$ Γ D s ∗ → ϕ ρ = ( 1 . 16 - 0.39 + 0.42 ) × 10 - 13 GeV . We show that these channels are promising in the near future, serving as the first experimental observation of weak decays of a vector meson, and would open up a new playground for precision test of the standard model.

Three kinds of 6061 aluminum alloy cast-rolled plates with Mg/Si mass ratios of 1.23, 1.45, and 1.7 are prepared using NF6–300 vertical twin-roll casting and rolling mill. Metallurgical microscope (OM), x-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive spectrometer (EDS), room temperature tensile test, and other analysis methods studied the influence law and mechanism of Mg/Si ratio on the microstructure and texture of 6061 cast-rolled sheet. The best Mg/Si ratio cast-rolled sheet is then analyzed for formability. Research indicates that with increasing Mg/Si ratio, the grain size shows first decreasing and then increasing trend. Morphology of precipitated phases at the edge and the central of the sheet are different, however, the texture type has no obvious change, and a strong {112} 〈110〉 texture and weaker rotating cube {001} 〈110〉 texture is always observed. When the Mg/Si ratio is 1.45, the average grain size is the smallest, the edge size is 39.78 μ m, the central size is 31.31 μ m, and the precipitated phase is evenly distributed at the edge and central of the cast-rolled sheet. In addition, the elongation reaches 8.9%, the n-value is 0.072, and the r-value is 1.161 when the cast-rolled sheet reaches 90° along the cast-rolled direction under T6 state heat treatment.

IntroductionMultimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies.MethodsIn this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment. ResultsThere was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8+ effector T (CD8+ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway. ConclusionThis study confirmed that MTT could more effectively activate peripheral CD8+ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.

Genetically encoded fluorescent voltage indicators, such as ArcLight, have been used to report action potentials (APs) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). However, the ArcLight expression, in all cases, relied on a high number of lentiviral vector-mediated random genome integrations (8-12 copy/cell), raising concerns such as gene disruption and alteration of global and local gene expression, as well as loss or silencing of reporter genes after differentiation. Here, we report the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease technique to develop a hiPSC line stably expressing ArcLight from the AAVS1 safe harbor locus. The hiPSC line retained proliferative ability with a growth rate similar to its parental strain. Optical recording with conventional epifluorescence microscopy allowed the detection of APs as early as 21 days postdifferentiation, and could be repeatedly monitored for at least 5 months. Moreover, quantification and analysis of the APs of ArcLight-CMs identified two distinctive subtypes: a group with high frequency of spontaneous APs of small amplitudes that were pacemaker-like CMs and a group with low frequency of automaticity and large amplitudes that resembled the working CMs. Compared with FluoVolt voltage-sensitive dye, although dimmer, the ArcLight reporter exhibited better optical performance in terms of phototoxicity and photostability with comparable sensitivities and signal-to-noise ratios. The hiPSC line with targeted ArcLight engineering design represents a useful tool for studying cardiac development or hiPSC-derived cardiac disease models and drug testing.

In view of the high operating current of ±800 kV UHVDC， the influence of earth current at the grounding electrode on the magnetic bias of transformers and the treatment has become a research topic. Given the construction of the ±800kV Baihetan-Zhebei DC transmission project， historical magnetotelluric detection data was used to establish a three-dimensional grounding resistivity model near the grounding electrode of Chen’an Village in northern Zhejiang province. The calculation of station ground potential of power grid near the grounding electrode was completed according to the working condition of 5， 000 A grounding current， and the ground potential calculation results of 124 power plants and substations in the north Zhejiang power grid were obtained. Moreover， a power grid bias current model was established， the bias current was calculated， and a bias treatment plan was proposed. The research results show that compared with the influence of the Jinsi earth pole of the ±800 kV Xiluodu-West Zhejiang DC project， the influence of the current of the grounding electrode in Chen’an Village is less because the transmission lines of North Zhejiang power grid are relatively denser and the lines are short.

Abstract Many cell types migrate in response to naturally generated electric fields. Furthermore, it has been suggested that the external application of an electric field may be used to intervene in and optimize natural processes such as wound healing. Precise cell guidance suitable for such optimization may rely on predictive models of cell migration, which do not generalize. Here, we present a machine learning model that can forecast directedness of cell migration given a timeseries of previous directedness and electric field values. This model is trained using time series galvanotaxis data of mammalian cranial neural crest cells obtained through time-lapse microscopy of cells cultured at 37 °C in a galvanotaxis chamber at ambient pressure. Next, we show that our modeling approach can be used for a variety of cell types and experimental conditions with very limited training data using transfer learning methods. We adapt the model to predict cell behavior for keratocytes (room temperature, ~ 18–20 °C) and keratinocytes (37 °C) under similar experimental conditions with a small dataset (~ 2–5 cells). Finally, this model can be used to perform in silico studies by simulating cell migration lines under time-varying and unseen electric fields. We demonstrate this by simulating feedback control on cell migration using a proportional–integral–derivative (PID) controller. This data-driven approach provides predictive models of cell migration that may be suitable for designing electric field based cellular control mechanisms for applications in precision medicine such as wound healing.

Abstract Wastewater containing cobalt and copper comprised of plating wash water, plant wash water, and equipment cooling and wash water is generated in the electroplating industry. These metals can be detrimental to humans, animals, plants, and the environment. Thus, it is necessary to treat electroplating wastewater to remove these toxic metals. Carbonate and hydroxide precipitation were utilized for the removal of Co (II) and Cu (II) from synthetic electroplating wastewater by jar tests in this work. The effects of solution pH, precipitant-to-metal ratio, and type of precipitant on the precipitation efficiency of cobalt and copper from the single- and co-contaminated systems were investigated. Carbonate precipitation achieved higher removal efficiency for both target metals in the single- and co-contaminated wastewater streams. Furthermore, it can operate at relatively low pH range of about 7–8. Cobalt in both pollutant systems was almost completely removed at pH 10 using both precipitant systems. Copper was found to be easily removed which was possibly brought about by precipitation-adsorption mechanism. The extent of the co-removal of cobalt with copper is significantly pH dependent. The effect of precipitant-to-metal ratio for cobalt and copper treatment varied in single- and co-contaminated streams. Carbonate precipitation led to higher sludge volume than that of hydroxide precipitation.