MXene-incorporated C60NPs and Au@Pt with dual-electric signal outputs for accurate detection of Mycobacterium tuberculosis ESAT-6 antigen.

Rapid and effective detection of Mycobacterium tuberculosis (MTB) is the crux of minimizing tuberculosis (TB) spread. Consequently, a new electrochemical aptasensor based on dual-signal output for ultrasensitive detection of MTB early secreted antigenic target 6 (ESAT-6) antigen was developed. Especially, a new nanocomposite MXene/C60NPs/Au@Pt was synthesized for signal generation and amplification. In this biosensing architecture, dual independent signal outputs were achieved by coupling the electrochemical redox activity of fullerene nanoparticles (C60NPs) with the effective electrocatalytic activity of Au@Pt nanoparticles. MXene possesses a large specific surface area, allowing densely loaded of these two electroactive materials, further improved sensing capability. In addition, specific ESAT-6 antigen binding aptamers were attached to Au@Pt to create the tracer label. With a typical sandwich format along with the introduction of the gold nanoparticle-loaded molybdenum disulfide (MoS2-Au) as the sensing interface, the limit of detection (LOD) of the proposed aptasensor was 2.88 fg mL-1 (DPV measurement) and 13.50 fg mL-1 (IT measurement), respectively, with a broad linear range of 100 fg mL-1 to 50 ng mL-1. Significantly, it exhibited better specificity and accuracy with a sensitivity of 97.5% and a specificity of 96.7% to distinguish healthy donors, other lung diseases and TB patients compared to commercial ELISA assay, holding a promising prospect in clinical diagnosis.

Effects of Process Parameters on Bond Properties of Ag-2.35Au-0.7Pd-0.2Pt-0.1Cu Alloy Wire.

Bond properties were performed on Ag-2.35Au-0.7Pd-0.2Pt-0.1Cu alloy wire with a diameter of 25 µm under different process parameters. The effects of electrical flaming off (EFO) current and EFO time on the deformability of the free air ball (FAB) were investigated using scanning electron microscopy (SEM), as well as the effects of ultrasonic power and bonding force on the bond characteristic. The experimental results show that FAB grows from a preheated tip to a small ball, a regular ball, and finally to a golf ball with increasing either the EFO current or the EFO time, and the FAB presents an optimal shape at 25 mA and 650 µs. Moreover, a nonlinear relationship between FAB diameter and EFO time is obtained at an EFO current of 25 mA, which could be expressed by a cubic equation. Further, at a constant bonding force, as the ultrasonic power increased, the mashed ball diameter grew larger and larger, the capillary hole imprint became more and more obvious, and the tail width also increased, and vice versa. The optimal ultrasonic power and bonding force are 70 mW and 45 gf for ball bonding and 90 mW and 75 gf for wedge bonding, respectively. Finally, for all the bonded wire samples prepared under optimal process parameters, no ball and wedge bond lifts happened after the destructive pull test, and full intermetallic compound coverage with perfect morphology occurred on the bond pad after the ball shear test, which meant that the bonded wire samples had high bond strength and hence improved the reliability of microelectronic products. It provided technical support for the reliability research of Pt-containing Ag-based bonding alloy wires.

Copper Wire Bonding: A Review.

This paper provides a comprehensive review on copper (Cu) wire bonding. Firstly, it introduces the common types of Cu wire available in the market, including bare Cu wire, coated Cu wire, insulated Cu wire, and alloyed Cu wire. For each type, their characteristics and application areas are discussed. Additionally, we provide detailed insights into the impact of Free Air Ball (FAB) morphology on bonding reliability, including its effect on bond strength and formation mechanisms. Next, the reliability of Cu wire bonding is analyzed, with a focus on the impact of intermetallic compounds and corrosion on bonding reliability. Specifically, the formation, growth, and stability of intermetallic compounds at bonding interfaces are discussed, and their effects on bonding strength and reliability are evaluated. The detrimental mechanisms of corrosion on Cu wire bonding and corrosion inhibition methods are also analyzed. Subsequently, the applications of simulation in Cu wire bonding are presented, including finite element analysis and molecular dynamics simulations, which provide important tools for a deeper understanding of the bonding process and failure mechanisms. Finally, the current development status of Cu wire bonding is summarized, and future research directions are discussed.

Study on the Effect of Cold Deformation and Heat Treatment on the Properties of Cu-Ag Alloy Wire.

The effects of various drawing parameters and annealing processes on the structure and properties of Cu-Ag wires, containing 1 wt% silver, were investigated using specialized equipment including fine wire-drawing machines, very fine wire-drawing machines, heat treatment equipment, tensile testing machines, microcomputer-controlled electronic universal testers, resistance testers, and scanning electron microscopes. The results revealed that continuous drawing of Cu-1%Ag alloy wires led to elongation of the grains, resulting in a uniform and tightly fibrous microstructure. Moreover, the tensile strength of the alloy wire increased from 670 MPa to 783.9 MPa after a single pass with a deformation of 14%. Subsequently, when the wire was drawn at a speed of 500 m/min, the tensile strength further increased to 820.1 MPa. After annealing the Փ0.08 mm Cu-1% Ag alloy wire, an increase in annealing temperature up to 500 °C resulted in the wire's tensile strength decreasing from 820.1 MPa to 377.5 MPa. Simultaneously, the elongation increased from 1.94% to 15.21%, and the resistivity decreased from 1.931 × 10-8 Ω·m to 1.723 × 10-8 Ω·m. Additionally, when annealing was conducted at a rate of 80 m/min, the wire resistivity dropped to 1.635 × 10-8 Ω·m.

Study on Remote Field Eddy Current Testing Technology for Crack-like Defects in Long Truss Structure of Aircraft.

Detection of hidden defects of aircraft long truss structures (aluminum alloy) is a challenging problem. The shape of the aircraft truss structure is complex, and the crack defects are buried in a large depth. Without the restriction of skin effect, remote field eddy current (RFEC) has great advantages in detecting buried depth defects. In this paper, in order to detect the hidden defects of the aluminum alloy aircraft long truss structure, the remote field eddy current probe is improved from two aspects of magnetic field enhancement and near-field signal suppression using the finite element method. The results show that indirect coupling energy is greatly enhanced when the connected magnetic circuit is added to the excitation coil. By adding a composite shielding structure outside the excitation coil and the detection coil, respectively, the direct coupling energy is effectively restrained. As a result, the size of the probe is reduced. By optimizing the coil spacing and probe placement position, the detection sensitivity of the probe is improved. The simulation is verified by experiments, and the experimental results are consistent with the simulation conclusions.

Perturbation of Specific Signaling Pathways Is Involved in Initiation of Mouse Liver Fibrosis.

BACKGROUND AND AIMS: To identify the regulatory role of protein phosphatase 2A (PP2A) in the development of liver disease, we generated a mouse model with hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit). APPROACH AND RESULTS: Homozygote (HO) mice and matched wild-type littermates were investigated at 3, 6, 9, 12, 15, and 18 months of age. Pathological examination showed that PP2A Aα deficiency in hepatocytes resulted in progressive liver fibrosis phenotype from 9 months of age. No hepatocyte death was observed in HO mice. However, perturbation of pathways including epidermal growth factor receptor 1 (EGFR1), amino acid metabolism, and translation factors as well as leptin and adiponectin led to pronounced hepatic fibrosis. In vitro studies demonstrated the involvement of specific B subunit complexes in the regulation of EGFR1 signaling pathway and cross talk between defected hepatocytes and stimulation of interstitial hyperplasia. It is noteworthy that HO mice failed to develop hepatocellular carcinoma for as long as 22 months of age. We further demonstrate that PP2A Aß-containing holoenzymes played a critical role in preventing hepatocyte apoptosis and antagonizing tumorigenesis through specific pathways on Aα loss. Furthermore, PP2A Aα and Aß were functionally distinct, and the Aß isoform failed to substitute for Aα in the development of inflammation and liver fibrosis. CONCLUSIONS: These observations identify pathways that contribute to the pathogenesis of liver fibrosis and provide putative therapeutic targets for its treatment.

Benzene-induced mouse hematotoxicity is regulated by a protein phosphatase 2A complex that stimulates transcription of cytochrome P4502E1.

Chronic benzene exposure is associated with hematotoxicity and the development of aplastic anemia and leukemia. However, the signaling pathways underlying benzene-induced hematotoxicity remain to be defined. Here, we investigated the role of protein phosphatase 2A (PP2A) in the regulation of benzene-induced hematotoxicity in a murine model. Male mice with a hepatocyte-specific homozygous deletion of the Ppp2r1a gene (encoding PP2A Aα subunit) (HO) and matched wildtype (WT) mice were exposed to benzene via inhalation at doses of 1, 10, and 100 ppm for 28 days. Peripheral white blood cell counts and activation of bone marrow progenitors were attenuated in the HO mice, indicating that Ppp2r1a deletion protects against benzene-induced hematotoxicity. Moreover, elevation of urinary S-phenyl mercapturic acid, a benzene metabolite, was much greater in WT mice than in HO mice. Real-time exhalation analysis revealed more exhaled benzene but fewer benzene metabolites in HO mice than in WT mice, possibly because of the down-regulation of Cyp2e1, encoding cytochrome P4502E1, in hepatocytes of the HO mice. Loss-of-function screening disclosed that PP2A complexes containing the B56α subunit participate in regulating Cyp2e1 expression. Notably, PP2A-B56α suppression in HepG2 cells resulted in persistent ß-catenin phosphorylation at Ser33-Ser37-Thr41 in response to CYP2E1 agonists. In parallel, nuclear translocation of ß-catenin was inhibited, concomitant with a remarkable decrease of Cyp2e1 expression. These findings support the notion that a regulatory cascade comprising PP2A-B56α, ß-catenin, and Cyp2e1 is involved in benzene-induced hematotoxicity, providing critical insight into the role of PP2A in responses to the environmental chemicals.

The effects of Nrf2 knockout on regulation of benzene-induced mouse hematotoxicity.

Previous studies have demonstrated that oxidative stress is implicated in benzene-induced hematotoxicity. However, the low dose-response effects and the mechanism underlying perturbation of hematopoiesis remain to be defined. This study aims to address the role of Nrf2 pathway in mediating benzene-induced hematotoxicity. Nrf2+/+ (wildtype, Nrf2-WT) and Nrf2-/- (knockout, Nrf2-KO) mice were administrated with benzene at doses of 0.1, 1.0, 10.0, 100.0 mg/kg by oral gavage for a consecutive 4 weeks (6 times/week). As a result, benzene exposure caused a decline of WBC and lymphocyte counts in a dose-dependent manner at a dose range from 1.0 to 100.0 mg/kg, while low dose benzene induced hormesis effects. Interestingly, Nrf2 deficiency seemed to relieve the decline of peripheral blood cell counts upon benzene exposure, indicating the involvement of Nrf2 in regulation of benzene-induced hematotoxicity. The suppression of phase II enzyme expression in Nrf2-KO mice resulted in considerable reduction in detoxification indicated by the decrease of urinary S-phenylmercapturic acid (SPMA), a metabolite of benzene. Ex vivo assay revealed enhanced cytotoxicity and oxidative stress were induced by benzene in Nrf2-KO mice. Notably, the depletion of Nrf2 triggered the proliferation and differentiation of hematopoietic cells, but induced aberrant morphological changes in periphery erythrocytes and bone marrow cells, implicating the compensatory effects carried on at the expense of induction of dysfunctional blood cells. Our findings provide a new insight into a low dose-response towards benzene-induced hematotoxicity and uncover the critical role of Nrf2 pathway in mediating abnormal hematopoiesis in response to oxidative stress.

Enhanced H3K4me3 modifications are involved in the transactivation of DNA damage responsive genes in workers exposed to low-level benzene.

In this study, we explore whether altered global histone modifications respond to low-level benzene exposure as well as their association with the hematotoxicity. We recruited 147 low-level benzene-exposed workers and 122 control workers from a petrochemical factory in Maoming City, Guangdong Province, China. The internal exposure marker level, urinary S-phenylmercapturic acid (SPMA), in benzene-exposed workers was 1.81-fold higher than that of the controls (P < 0.001). ELISA method was established to examine the specific histone modifications in human peripheral blood lymphocytes (PBLCs) of workers. A decrease in the counts of white blood cells (WBC), neutrophils, lymphocytes, and monocytes appeared in the benzene-exposed group (all P < 0.05) compared to the control group. Global trimethylated histone 3 lysine 4 (H3K4me3) modification was enhanced in the benzene-exposed group (P < 0.05) and was positively associated with the concentration of urinary SPMA (ß = 0.103, P = 0.045) and the extent of DNA damage (% Tail DNA: ß = 0.181, P = 0.022), but was negatively associated with the leukocyte count (WBC: ß = -0.038, P = 0.023). The in vitro study revealed that H3K4me3 mark was enriched in the promoters of several DNA damage responsive (DDR) genes including CRY1, ERCC2, and TP53 in primary human lymphocytes treated with hydroquinone. Particularly, H3K4me3 modification was positively correlated with the expression of CRY1 in the PBLCs of benzene-exposed workers. These observations indicate that H3K4me3 modification might mediate the transcriptional regulation of DDR genes in response to low-dose benzene exposure.

Disarrangement of actin filaments and Ca²âº gradient by CdCl2 alters cell wall construction in Arabidopsis thaliana root hairs by inhibiting vesicular trafficking.

Cadmium (Cd), one of the most toxic heavy metals, inhibits many cellular and physiological processes in plants. Here, the involvement of cytoplasmic Ca²âº gradient and actin filaments (AFs) in vesicular trafficking, cell wall deposition and tip growth was investigated during root (hair) development of Arabidopsis thaliana in response to CdCl2 treatment. Seed germination and root elongation were prevented in a dose- and time-dependent manner by CdCl2 treatment. Fluorescence labelling and non-invasive detection showed that CdCl2 inhibited extracellular Ca²âº influx, promoted intracellular Ca²âº efflux, and disturbed the cytoplasmic tip-focused Ca²âº gradient. In vivo labelling revealed that CdCl2 modified actin organization, which subsequently contributed to vesicle trafficking. Transmission electron microscopy revealed that CdCl2 induced cytoplasmic vacuolization and was detrimental to organelles such as mitochondria and endoplasmic reticulum (ER). Finally, immunofluorescent labelling and Fourier transform infrared (FTIR) analysis indicated that configuration/distribution of cell wall components such as pectins and cellulose was significantly altered in response to CdCl2. Our results indicate that CdCl2 induces disruption of Ca²âº gradient and AFs affects the distribution of cell wall components in root hairs by disturbing vesicular trafficking in A. thaliana.