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Herein, a divergent stepped magnetic fluid seal with a single magnetic source is designed to improve the pressure capability of ordinary magnetic fluid seal under small clearance. To explore the effects of injection volume, axial clearance, radial clearance, axial tooth number and radial tooth number on divergent stepped magnetic fluid seal, the pressure capability of magnetic fluid seal with an ordinary structure was comparatively analyzed through experimentation. According to the experimental results, there is no leakage or ejection of magnetic fluid from the sealing device when the critical pressure of divergent stepped magnetic fluid sealing is reached. The divergent stepped magnetic fluid seal structure performs better in pressure resistance the magnetic fluid seal with an ordinary structure. Also, the existence of axial teeth in the stepped magnetic fluid sealing structure leads to an increase in polar teeth, which not only extends the leakage path of the sealing medium but also exacerbates energy loss for the magnetic fluid carried by the sealed medium. This is effective in improving the pressure resistance of the magnetic fluid seal. When the axial tooth number reaches or exceeds the radial tooth number and the axial clearance falls below the radial clearance, the divergent stepped magnetic fluid seal with small clearance has a pressure capability that is 4.1–6 times higher than the critical pressure of ordinary magnetic fluid seal. When the axial clearance exceeds the radial clearance and the axial tooth number falls below the radial tooth number, the divergent stepped magnetic fluid seal has a critical pressure that is 1.9–3.6 times higher than that of conventional magnetic fluid seal.

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DNA repair mechanisms are crucial for cell survival. It increases the cancer cell's ability to resist DNA damage. FEN1 is involved in DNA replication and repair, specifically long-patch base excision repair. Although the gene function and post-translational modification of FEN1 are well studied, the regulatory mechanism of FEN1 by upstream signal pathways remains unclear. In this article, we have identified AKT as a regulator of FEN1 activity in lung cancer cells. Sustained activation of AKT can phosphorylate nuclear transcription factor NF-κB/p65. NF-κB/p65 directly binds to FEN1 promoter to promote a high transcription level of FEN1, revealing the contribution of the AKT signaling pathway to drug resistance of cancer cells. The combination of an AKT inhibitor and cisplatin efficiently suppressed lung cancer cell growth both in vitro and in vivo. Our study illustrated an upstream regulatory mechanism of FEN1, which will contribute to the development of effective lung cancer therapies.These findings identified AKT as a regulator of FEN1 activity and revealed the AKT signaling pathway's contribution to drug resistance, which will contribute to the development of effective lung cancer therapy.

The spread of antibiotic resistance genes (ARGs), especially those on plasmids, poses a major risk to global health. However, the extent and frequency of ARG transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a new fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. The tool integrates a fluorescent tag immediately downstream ARGs, allowing for gene transfer tracking without affecting host cell antibiotic susceptibility, fitness, conjugation, or transposition. Our experiments show that sfGFP-tagged plasmid-borne mcr-1 can transfer across different bacteria species in feces, including Escherichia, Shigella, Lactobacillus, Staphylococcus, Enterococcus, and Bacillus. CRISPR-AMRtracker offers a powerful tool for monitoring ARG transfer in microbiota communities and can inform strategies to combat the threat of antibiotic resistance.

DNA methylation is considered as a potential cancer biomarker. The evaluation of DNA methylation level will contribute to the prognosis and diagnosis of cancer. Herein, we propose a novel assay based on endonuclease-assisted protospacer adjacent motif (PAM)-free recombinase polymerase amplification coupling with CRISPR/Cas12a (E-PfRPA/Cas) for sensitive detection of DNA methylation. The methylation-sensitive restriction enzyme (MSRE) is first used to selectively digest unmethylated DNA, while the methylated target remains structurally intact. Therefore, the methylated target can initiate the RPA reaction to generate a large amount of double-stranded DNA (dsDNA). To avoid the dependence of PAM site of CRISPR/Cas12a, one of the RPA primers is designed with 5'-phosphate terminuses. After treating with Lambda, the sequence with 5'-phosphate modification will be degraded, leaving the single-stranded DNA (ssDNA). The CRISPR/Cas12a can accurately locate ssDNA without PAM, then initiating its trans-cleavage activity for further signal amplification. Meanwhile, non-specific amplification can be also avoided under Lambda, effectively filtering the detection background. Benefiting from the specificity of MSRE, the high amplification efficiency of Lambda-assisted RPA, and the self-amplification effect of CRISPR/Cas, the E-PfRPA/Cas assay shows outstanding sensitivity and selectivity, and as low as 0.05% of methylated DNA can be distinguished. Moreover, the lateral flow assay is also introduced to exploit the point-of-care diagnostic platform. Most importantly, the proposed method shows high sensitivity for determination of genomic DNA methylation from cancer cells, indicating its great potential for tumor-specific gene analysis.

Two different electrochemical sensors (Hemin-G4/Au/GCE and Hemin-G4/Au/ITO) were developed and applied to explore the electrocatalytic capacity of H2O2 reduction. Due to the excellent catalytic activity of Hemin-G4 and high conductivity of gold nanoparticles, both electrodes show excellent electrochemical performances towards H2O2 with a low LOD (0.67 μM for Hemin-G4/Au/GCE and 0.65 μM for Hemin-G4/Au/ITO), rapid response (

Integrating metal–organic frameworks (MOFs) of different components or structures together and exploiting them as electrochemical sensors for electrochemical sensing has aroused great interest. Furthermore, the incorporation of noble metals with MOFs is conducive to the improvement of catalytic performance. In this work, Pd@UiO-66-on-ZIF-L nanomaterials were successfully synthesised onto a self-supported flexible carbon cloth (Pd@UiO-66-on-ZIF-L/CC) through a novel strategy called MOF-on-MOF. Then, Au nanoparticles were electrodeposited onto Pd@UiO-66-on-ZIF-L/CC to obtain Au–Pd@UiO-66-on-ZIF-L/CC, which can serve as an excellent electrocatalyst for the reduction of hydrogen peroxide (H2O2). The obtained flower-like Pd@UiO-66-on-ZIF-L/CC hybrid MOF changes the structure of the monomeric MOF alone and adds more attachment sites. The synergy of the bimetals greatly improved the catalytic performance of the as-developed sensor. Electrochemical experiment results show that the proposed sensor based on Au–Pd@UiO-66-on-ZIF-L/CC has an extended linear range from 1 μM to 19.6 mM with a sensitivity of 390 μA mM−1 cm−2, and a low limit of detection (LOD) of 21.2 nM (S/N = 3). Moreover, it has good anti-interference, reproducibility, repeatability and excellent stability. Furthermore, the real-time in situ detection of H2O2 secreted from human adenocarcinomic alveolar basal epithelial cells (A549 cells) was achieved by culturing cells on Au–Pd@UiO-66-on-ZIF-L/CC, which indicates the potential of the sensor for applications in cancer pathology. Both the synthesis strategy and the sensor design provide new methods and ideas for the production of ultrasensitive H2O2 electrochemical sensors.

The development of metal nanoparticles (MNP) combined with a metal-organic framework (MOF) has received more and more attention due to its excellent synergistic catalytic ability, which can effectively broaden the scope of catalytic reactions and enhance the catalytic ability. In this work, we developed a novel ternary nanocomposite named Cu2O-mediated Au nanoparticle (Au NP) grown on MIL-53(Fe) for real-time monitoring of hydrogen peroxide (H2O2) released from living cells. First, Cu2O-MIL-53(Fe) was prepared by redox assembly technology, which provided the growth template, and active sites for AuCl4−. Au@Cu2O-MIL-53(Fe)/GCE biosensor was prepared by further loading nano-Au uniformly on the surface of Cu2O by electrochemical deposition. Compared to individual components, the hybrid nanocomposite showed superior electrochemical properties as electrode materials due to the synergistic effect between AuNPs, Cu2O, and MIL-53(Fe). Electrochemical measurement showed that the Au@Cu2O-MIL-53(Fe)/GCE biosensor presented a satisfactory catalytic activity towards H2O2 with a low detection limit of 1.01 μM and sensitivity of 351.57 μA mM−1 cm−2 in the linear range of 10–1520 μM. Furthermore, this biosensor was successfully used for the real-time monitoring of dynamic H2O2 activated by PMA released from living cells. And the great results of confocal fluorescence microscopy of the co-culture cells with PMA and Au@Cu2O-MIL-53(Fe) verified the reliability of the biosensor, suggesting its potential application to the monitoring of critical pathological processes at the cellular level.

A novel fluorescent biosensor was proposed for detecting the CaMV 35S promoter in genetically modified organisms (GMOs). It was based on a proximity extension mediated multiple cascade strand displacement amplification connected with CRISPR/Cpf 1 (termed PE-MC/SDA-CRISPR/Cpf1). In this protocol, the CaMV 35S was recognized by proximity reaction in the presence of two adjacent primer probes. The proximity extension further triggered the multiple cascade strand displacement amplification (MC/SDA), generating a mass of ssDNA. The products compelled the trans-cleavage activity of CRISPR/Cpf 1, so as to cleave nearby ssDNA-FQ reporters and generate a strong fluorescent signal. The ingenious three-link combination design allowed the CaMV 35S a low background interference. And the MC/SDA combined with CRISPR/Cpf 1 dramatically improved the detection sensitivity. Under optimized conditions, the detection linear range of ultrasensitive fluorescent biosensor for CaMV 35S was from 50 fM to10 pM and 10 pM-500 pM, along with the limit of detection (LOD) down to 14.4 fM. The sensing platform also had excellent performance in the assay of selectivity and real samples. Therefore, the method earned great application potential for transgenic crops.

Noninvasive Prenatal Testing (NIPT) has advanced the detection of fetal chromosomal aneuploidy by analyzing cell-free DNA in peripheral maternal blood. The statistic Z-test that it utilizes, which measures the deviation of each chromosome dosage from its negative control, is now widely accepted in clinical practice. However, when a chromosome has loss and gain regions which offset each other in the z-score calculation, merely using the Z-test for the result tends to be erroneous. To improve the performance of NIPT in this aspect, a novel graphic-aided algorithm (gNIPT) that requires no extra experiment procedures is reported in this study. In addition to the Z-test, this method provides a detailed analysis of each chromosome by dividing each chromosome into multiple 2 Mb size windows, calculating the z-score and copy number variation of each window, and visualizing the z-scores for each chromosome in a line chart. Data from 13537 singleton pregnancy women were analyzed and compared using both the normal NIPT (nNIPT) analysis and the gNIPT method. The gNIPT method had significantly improved the overall positive predictive value (PPV) of nNIPT (88.14% vs. 68.00%, p=0.0041) and the PPV for trisomy 21 (T21) detection (93.02% vs. 71.43%, p=0.0037). There were no significant differences between gNIPT and nNIPT in PPV for trisomy 18 (T18) detection (88.89% vs. 63.64%, p=0.1974) and in PPV for trisomy 13 (T13) detection (57.14% vs. 50.00%, p=0.8004). One false-negative T18 case in nNIPT was detected by gNIPT, which demonstrates the potency of gNIPT in discerning chromosomes that have variation in multiple regions with an offsetting effect in z-score calculation. The gNIPT was also able to detect copy number variation (CNV) in chromosomes, and one case with pathogenic CNV was detected during the study. With no additional test requirement, gNIPT presents a reasonable solution in improving the accuracy of normal NIPT.

Aiming at the requirement of the intelligent vehicle for the fast and stable tracking control of the wheel slip, a novel robust adaptive anti-windup wheel slip tracking control method with fast terminal sliding mode observer is proposed. First, a fast terminal sliding mode observer based on equivalent control on the sliding surface is proposed to estimate the states of the wheel slip dynamic system to lay the foundation for the full state feedback control law design. Second, a robust adaptive anti-windup wheel slip tracking control law with lumped uncertainty observer and additional anti-windup dynamics is derived based on Lyapunov-based method. The lumped uncertainty observer utilizes the nonlinear mapping ability of the radius basis function neural network to estimate and compensate the lumped uncertainty of the system, and the unknown optimal weight vector of the radius basis function neural network is updated by adaptive law. The additional anti-windup dynamics is used to suppress the effect of the input saturation on the stability of the system. Finally, the performance of the proposed method is verified through simulations of various maneuvers on vehicle dynamics simulation software.

When LCL -type converter is attached to weak grid, its current control and phase-locked loop (PLL) will interact with each other, via the point of common coupling voltage. Unfortunately, the conventional PLL controller design methods are mainly for PLL independent systems, regardless of the aforesaid interaction. As a consequence, PLL dynamic might deteriorate the grid current control and even leads to instability problem. For this issue, this article proposes an improved design of PLL controller parameters to mitigate the negative effect of PLL on the current control. First, the small-signal model of the current control system considering PLL effect is established, and the system stability with the conventional PLL controller design method is analyzed. Then, an improved design of PLL controller parameters is proposed, and the design guideline is given in detail. With the method, not only the dynamic and static response performance of PLL independent system can be maintained, but also the negative influence of PLL dynamic on the current control can be effectively reduced in weak grid. Moreover, the grid current control has a strong robustness to the grid impedance variation. Finally, the proposed method is validated by the simulation and experiment.

When the three-phase LCL -type converter is attached to a weak grid, its grid current control will interact with a phase-locked loop (PLL), via the point of common coupling voltage. And, the PLL dynamic has a negative influence on the current control, rendering an undesired performance to grid current control, even leading to the instability issue, if no effective measure is employed. To mitigate this problem, this article proposes a simple and visualized small-signal disturbance compensation control method for the LCL -type grid-connected converter. First, the effect mechanism of PLL dynamic on the current control is analyzed, and the root of the small-signal disturbance caused by PLL dynamic is identified subsequently. Based on this, an improved control method is proposed to compensate the aforesaid PLL-introduced small-signal disturbance terms in current loop, and then, the negative effect of PLL dynamic on the grid current control can be effectively reduced in the weak grid, without modifying the PLL parameters and structure. Moreover, the method is not influenced by the circuit parameters change, and it is robust to the variation of grid impedance. Finally, the proposed method is validated by the experiment.

DNA repair mechanisms are crucial for cell survival. It increases the cancer cell's ability to resist DNA damage. FEN1 is involved in DNA replication and repair, specifically long-patch base excision repair. Although the gene function and post-translational modification of FEN1 are well studied, the regulatory mechanism of FEN1 by upstream signal pathways remains unclear. In this article, we have identified AKT as a regulator of FEN1 activity in lung cancer cells. Sustained activation of AKT can phosphorylate nuclear transcription factor NF-κB/p65. NF-κB/p65 directly binds to FEN1 promoter to promote a high transcription level of FEN1, revealing the contribution of the AKT signaling pathway to drug resistance of cancer cells. The combination of an AKT inhibitor and cisplatin efficiently suppressed lung cancer cell growth both in vitro and in vivo. Our study illustrated an upstream regulatory mechanism of FEN1, which will contribute to the development of effective lung cancer therapies. These findings identified AKT as a regulator of FEN1 activity and revealed the AKT signaling pathway's contribution to drug resistance, which will contribute to the development of effective lung cancer therapy.

The reservoir underneath the salt bed usually has high formation pressure and large production rate. However, downhole complexities such as wellbore shrinkage, stuck pipe, casing deformation and brine crystallization prone to occur in the drilling and completion of the salt bed. The drilling safety is affected and may lead to the failure of drilling to the target reservoir. The drilling fluid density is the key factor to maintain the salt bed’s wellbore stability. The in-situ stress of the composite salt bed (gypsum-salt -gypsum-salt-gypsum) is usually uneven distributed. Creep deformation and wellbore shrinkage affect each other within layers. The wellbore stability is difficult to maintain. Limited theorical reference existed for drilling fluid density selection to mitigate the borehole shrinkage in the composite gypsum-salt layers. This paper established a composite gypsum-salt model based on the rock mechanism and experiments, and a safe-drilling density selection layout is formed to solve the borehole shrinkage problem. This study provides fundamental basis for drilling fluid density selection for gypsum-salt layers. The experiment results show that, with the same drilling fluid density, the borehole shrinkage rate of the minimum horizontal in-situ stress azimuth is higher than that of the maximum horizontal in-situ stress azimuth. However, the borehole shrinkage rate of the gypsum layer is higher than salt layer. The hydration expansion of the gypsum is the dominant reason for the shrinkage of the composite salt-gypsum layer. In order to mitigate the borehole diameter reduction, the drilling fluid density is determined that can lower the creep rate less than 0.001, as a result, the borehole shrinkage of salt-gypsum layer is slowed. At the same time, it is necessary to improve the salinity, filter loss and plugging ability of the drilling fluid to inhibit the creep of the soft shale formation. The research results provide technical support for the safe drilling of composite salt-gypsum layers. This achievement has been applied to 135 wells in the Amu Darya, which completely solved the of wellbore shrinkage problem caused by salt rock creep. Complexities such as stuck string and well abandonment due to high-pressure brine crystallization are eliminated. The drilling cycle is shortened by 21% and the drilling costs is reduced by 15%.

Programmed cell death (PCD), including necroptosis, has emerged as a significant pathway in cardiovascular diseases. The infection of viral myocarditis (VMC) could cause cardiomyocytes degeneration, necrosis, and immune-inflammatory myocardial response. In this review, we summarized and evaluated the available evidence on the pathogenesis, molecule mechanism, diagnosis, and potential treatment strategies of viral myocarditis, with a special focus on the novel mechanism of necroptosis for cardiomyocytes death. Studies have shown that tumor necrosis factor-alpha (TNF-α) is an important cytokine involved in the activation of necroptosis; an elevated level of TNF-α is continually reported in patients suffering from VMC, implicating its involvement in the pathogenesis of VMC. It is of great interest to explore the clinical implication of TNF-α. We subsequently conducted a meta-analysis on the efficacy of serum TNF-α expression level and its diagnostic accuracy on acute viral myocarditis detection. Taken together, the review demonstrates a compelling role of necroptosis involved in the pathogenesis of VMC. Further, applying TNF-α as a serological marker for the diagnosis of VMC may be a useful strategy.

Integrating metal-organic frameworks (MOFs) of different components or structures together and exploiting them as electrochemical sensors for electrochemical sensing has aroused great interest. Furthermore, the incorporation of noble metals with MOFs is conducive to the improvement of catalytic performance. In this work, Pd@UiO-66-on-ZIF-L nanomaterials were successfully synthesised onto a self-supported flexible carbon cloth (Pd@UiO-66-on-ZIF-L/CC) through a novel strategy called MOF-on-MOF. Then, Au nanoparticles were electrodeposited onto Pd@UiO-66-on-ZIF-L/CC to obtain Au-Pd@UiO-66-on-ZIF-L/CC, which can serve as an excellent electrocatalyst for the reduction of hydrogen peroxide (H

Two different electrochemical sensors (Hemin-G4/Au/GCE and Hemin-G4/Au/ITO) were developed and applied to explore the electrocatalytic capacity of H

ZIF-67-derived Co nanoparticles supported on N-doped carbon skeletons have been prepared from melamine foam (Co-NPs/NCs) for non-enzymatic electrochemical H2O2 detection. The synthesis of Co-NPs/NCs was demonstrated via calcination treatment using melamine foam (MF) and ZIF-67 as precursors. The experimental results show that Co-NPs/NCs composites exhibit eminent catalytic activity toward specific determination of H2O2 with high selectivity and sensitivity (252.43 and 203.88 μA mM-1 cm-2), low LOD (0.12 μM), and wide linear ranges (10-2080 and 2080-11,800 μM). The excellent performance might be ascribed to the synergetic effects of MOF and N-doped carbon skeletons. The carbon skeletons serve as a conductive bridge and provide a large specific surface area, which can facilitate electron transfer and well disperse nanoparticles. This non-enzymatic electrochemical sensor based on Co-NPs/NCs can successfully detect H2O2 secreted by living cells, indicating its great potential in the early diagnosis and pathological exploration of disease.