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Chatter is a kind of self-excited unstable vibration during machining process, which always leads to multiple negative effects such as poor surface quality, dimension accuracy error, excessive noise, and tool wear. For purposes of monitoring the processing state of milling process and detecting chatter timely, a novel online chatter detection method was proposed. In the proposed method, the acceleration signals acquired by sensor were decomposed into a series of intrinsic mode functions (IMFs) by the adaptive analysis method named ensemble empirical mode decomposition (EEMD), and the IMFs which contain the feature information of milling process were selected as the analyzed signals. The two indicators power spectral entropy and fractal dimension which is obtained by morphological covering method are introduced to detect the chatter features. Then, both the frequency characteristic and morphological feature of the extracted signals can be reflected by the two indicators. To verify the approach, milling experiments were performed; the experiment results show that the proposed method can detect chatter timely and effectively, which is important in the aspect of improving the milling quality. And finally, in order to detect milling chatter timely, an online milling chatter monitoring system was developed. [ABSTRACT FROM AUTHOR]

[Display omitted] • According to the degree of deformation of the surface metamorphic layer, it is divided into SDL (region A) and MDL (region B). The main feature of SDL is grain refinement (AGD is 0.944 μm) reduced by dynamic recrystallization. MDL is the transition part, the grain size (AGD from 1 μm to 20 μm) is gradient distributed with depth, and the proportion of SGBF and LGBF increases significantly. • There is a good corresponding relationship between metamorphic layer and microhardness. The results of the micropillar compression test showed that the young's modulus and yield stress of region A, region B, and bulk material decreased in turn, but fluctuated greatly due to the influence of grain orientation. • The model of h SDL based on dynamic recrystallization and shear energy in the cutting process is established. There is a good linear relationship between Δ U s and h SDL , which can be used to control and predict h SDL. • The mechanism that the microhardness and yield stress of region A and region B is higher than that of the bulk material are the Hall-Petch effect caused by grain boundary strengthening and Taylor strengthening caused by dislocation tangles, respectively. Turning process results in microstructure alteration and forms a metamorphic layer beneath the machined surface, which influence micromechanical properties. The metamorphic layer induced by turning was divided into severe deformation layer (SDL) and moderate deformation layer (MDL) through grain size distribution, and the microstructure was observed and characterized by electron backscattered diffraction (EBSD) and transmission electron microscope (TEM). The model to predict the depth of SDL (h SDL) based on dynamic recrystallization and specific shear energy (US) in the cutting process was established, and the results showed that Δ U S had a linear relationship with h SDL (R 2 = 0.8799). The micromechanical properties of SDL, MDL, and bulk material were characterized by micro-hardness and micropillar compression tests. The increment of micro-hardness in SDL (increased by 66.4 % on the bulk material) is mainly due to the Hall-Petch effect caused by nanocrystals formed through dynamic recrystallization, and the micro-hardness in MDL (increased by 24.1 % on the bulk material) is affected by the superposition of the Hall-Petch effect and Taylor strengthening caused by the gradient distribution of grain size and dislocation density. The yield stress (σ y) obtained from the micropillar compression test decreased successively in SDL, MDL, and bulk material (from 1072 MPa to 604 MPa). The influence mechanism of the critical resolved shear stress (τ CRSS) and Schmidt factor (SF) on SDL, MDL, and bulk material were illustrated. [ABSTRACT FROM AUTHOR]

• Under the same strain rate, the phase difference between stress and strain was approximately considered unchanged. The loss of elastic modulus is caused by inelastic and plastic strain, which increased with the increasing of loading strain amplitude. • Due to cyclic hardening/softening and loss of elastic modulus, the plastic strain energy evolves linearly approximately with the cyclic numbers, which should be considered in the fatigue life prediction model. • A modified fatigue life prediction model according to the evolution law of plastic strain energy is proposed. The prediction error of proposed model decreased significantly from 13.73% to 7.68% after parameters correction compared with the prediction error of the strain-based life model. Accurately predicting the fatigue life of materials and components is of great significance for ensuring the safety of mechanical equipment. In most strain-controlled fatigue experiments, before fatigue fracture occurs, plastic strain accumulation and microstructure changes have a great impact on the cyclic stress–strain response of the material, which manifests as a hysteretic loop evolution. In this paper, the cyclic hardening/softening tendency under different strain amplitudes, the loss mechanism of the loading modulus and unloading modulus, as well as the evolution law of plastic strain energy of 45CrNiMoVA steel were investigated. A life prediction model based on the modified plastic strain energy was proposed according to the evolution law of plastic strain energy. The results showed that the prediction error of the modified plastic strain energy model was within the 2 times error band, which decreased significantly from 13.73% to 7.68% after parameters correction compared with the prediction error of the strain-based prediction model. [ABSTRACT FROM AUTHOR]

The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10−4) as might its ER+ subtype (FDR = 1.51 × 10−4). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10−6). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10−3) as could total testosterone (TT) (FDR = 5.81 × 10−3). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10−6) as could TT (FDR = 5.55 × 10−4). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density. [ABSTRACT FROM AUTHOR]

This research provided a detailed characterization of fatigue crack propagation paths under different stress ratios and analyzed the contributions of average stress and stress amplitude on the fatigue crack propagation life. Ultimately, it further elucidated the fundamental influencing factors of fatigue crack propagation under different stress ratios, drawing insights from the twist angle, Schmid factor and crack tip shielding. [Display omitted] • The fatigue crack propagation paths under different stress ratios have been characterized detailly by crystallographic model. • At larger stress ratios, fatigue cracks tend to propagate to grains with smaller twist angles and higher Schmid factors. • Stress ratio has little effect on the effective stress intensity factor versus fatigue crack propagation rate curves. • Increase in stress ratio weakens the shielding of the crack propagation rate by the plastic deformation zone at the crack tip. The fatigue load that a material experiences and its microstructure are important factors influencing fatigue crack propagation behavior. This study employed laser scanning microscopy and electron backscatter diffraction (EBSD) technology, along with fatigue crack propagation experiments, to investigate the fatigue crack propagation behavior of 2024 aluminum alloy under varying stress ratios (R). The results showed that the stress amplitude (σ p) was the main factor controlling the fatigue crack propagation life (N). Additionally, detailed characterization of the fatigue crack propagation path was conducted using crystal models and EBSD. A fatigue crack propagation model for 2024 aluminum alloy under different R -values was established based on the grain twist angle and Schmid factor. Finally, the impact of R on the crack tip shielding (K s) was systematically analyzed, elucidating the intrinsic mapping relationship between R , microstructure, and crack propagation characteristics. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the structural and hydrogenation characteristics of TiF3-doped Zintl phase alloy SrAl2 were studied by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and hydrogenation measurements. The results show that the hydrogenation kinetics of the Zintl phase alloy SrAl2 is improved greatly after doping with TiF3. By adjusting the doping amount and ball milling time, the optimal doping conditions were obtained. The catalytic mechanism of TiF3 for the hydrogenation of SrAl2 was also investigated. SrAl2 does not react with TiF3 during the ball milling process. However, it reacts with TiF3 to form SrAl2H2, SrF2, SrAl4 and Ti during the hydrogenation process, among which Ti plays an important role in the hydrogenation kinetics of SrAl2. [Copyright &y& Elsevier]

• IGWO algorithm with higher optimization accuracy was obtained. • The fitness function of the evaluation of axis straightness error was reconstructed. • IGWO was successfully applied to the evaluation of axis straightness error with good accuracy. • The uncertainty analysis model of the measurement and evaluation of error was constructed. Currently, it has been considered a nonlinear optimization problem to accurately evaluate axis straightness error of shaft and hole parts. Using intelligent optimization algorithm to solve this problem can avoid complex mathematical modeling process, while showing the advantages of high solution accuracy, fast search speed and easy convergence. By using the grey wolf optimization (GWO) algorithm with strong convergence performance, the global search performance was improved by regulating the linear convergence factor to nonlinear, and the wolf in the optimal position was endowed with the capability of receiving information and moving autonomously. Thus, an improved grey wolf optimization (IGWO) algorithm with better optimization accuracy was yielded. Moreover, the fitness function of optimization was rebuilt, thereby avoiding the unscientific setting of the parameter optimization range based on the subjective experience. Lastly, IGWO was successfully applied to the evaluation of axis straightness error of shaft and hole parts with good accuracy. [ABSTRACT FROM AUTHOR]

The original version of this article contained mistakes. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium channels (VGSC) are essential for triggering and relaying action potentials (AP), which perform critical functions in a variety of physiological processes, such as controlling muscle contractions and facilitating the release of neurotransmitters. In this study, we used a mouse C2C12 cell differentiation model to study the molecular expression and channel dynamics of VGSC and to investigate the exact role of VGSC in the development of muscle regeneration. Immunofluorescence, Real-time quantitative polymerase chain reaction, Western blot, and whole-cell patch clamp were employed for this purpose in mouse myoblasts. The findings revealed an increase in intracellular sodium concentration, Na V 1.4 gene expression, and protein expression with the progress of differentiation (days 0, 1, 3, 5 and 7). Furthermore, VGSC dynamics exhibit the following characteristics: ① The increase of sodium current (I Na); ② The decrease in the activation threshold and the voltage trigger maximum of I Na ; ③ A positive shift in the steady-state inactivation curve; ④ The recovery of I Na during repolarization is delayed, the activity-dependent decay rate of I Na was accelerated, and the proportionate amount of the fraction of activated channels was reduced. Based on these results, it is postulated that the activation threshold of AP could be decreased, and the refractory period could be extended with the extension of differentiation duration, which may contribute to muscle contraction. Taken together, VGSC provides a theoretical and empirical basis for exploring potential targets for neuromuscular diseases and other therapeutic muscle regeneration dysfunctions. The present research employed a differentiation model (D0、D1、D3、D5、D7)utilizing mouse myoblast C2C12 cells to investigate the expression of Na V 1.4 and channel kinetics. [Display omitted] • It is the first time to confirm the electrophysiological changes of VGSC in myoblast at different stages of differentiation. • It is the first elucidation of functional changes in Na V 1.4 with differentiation time in myoblast. • The increase of sodium ions in myoblasts makes the cells more sensitive to electrical excitation. [ABSTRACT FROM AUTHOR]

[Display omitted] • SiNPs exposure induced pulmonary fibrosis in the mouse model in an exposure time and concentration dependent manner. • C5a/C5aR1 axis was a key driver in SiNPs-induced pulmonary fibrosis. • Acetylated HMGB1-mediated EMT was involved in C5a/C5aR1 axis-promoted pulmonary fibrosis. Previous studies have shown that silica nanoparticles (SiNPs) exposure can affect the respiratory, cardiovascular, reproductive and other systems, with the lung being the primary target organ for the direct effect, causing damage with a central feature of pulmonary inflammation and fibrosis. However, the underlying mechanisms of pulmonary fibrosis due to SiNPs are not fully understood. The aim of the study was to investigate the role of complement anaphylatoxin C5a in SiNPs-induced pulmonary fibrosis. A mouse model of SiNPs-induced pulmonary fibrosis was established, and pulmonary fibrosis-related indicators, epithelial-to-mesenchymal transition (EMT), C5a/C5aR1 and high mobility group protein B1 (HMGB1) proteins were measured. An in vitro study using the human lung epithelial cell line BEAS-2B investigated whether C5a leads to epithelial-to-mesenchymal trans -differentiation. In vivo studies revealed that SiNPs-induced pulmonary fibrosis mainly manifested as EMT trans -differentiation in airway epithelial cells, which subsequently led to excessive deposition of extracellular matrix (ECM). Furthermore, we found that C5a and C5aR1 proteins were also increased in SiNPs-induced pulmonary fibrosis tissue. In vitro studies also showed that C5a directly activated HMGB1/RAGE signaling and induced EMT in BEAS-2B cells. Finally, treatment of SiNPs-exposed mice with the C5aR1 inhibitor PMX205 effectively reduced C5aR1 levels and inhibited the activation of HMGB1/RAGE signaling and the expression of EMT-related proteins, culminating in a significant alleviation of pulmonary fibrosis. Taken together, our results suggest that C5a/C5aR1 is the main signaling pathway for SiNPs-induced pulmonary fibrosis, which induces EMT in airway epithelial cells via the HMGB1/RAGE axis. [ABSTRACT FROM AUTHOR]

• The process damping and multiple mode shapes at tool-workpiece contact zone were considered simultaneously with a multi-mode model in four spatial dimensions. • The proposed model considering material removal could assemble the change in mass and stiffness quickly by using geometric judgment conditions, and then the IPW dynamics would be extracted. • Different kinds of frequencies under different dominant modes of milling tool or workpiece were identified and expounded. • The three-dimensional stability lobe diagram (SLD) with the proposed model could predict the stability accurately. Especially when the workpiece dominated the machining process, the comprehensive SLD considering material removal was closer to the experimental results. Reasonable machining parameters would be selected to avoid chatter vibration in the practical processing. As an unfavorable factor of machining process, chatter threatens the machined quality of workpiece, which determines the assembly and fatigue performance of the workpiece. During the interaction between machine tool and thin-walled workpiece, the process damping effect, multiple modes response and dynamic changes caused by the material removal of the in-process workpiece (IPW) will make the machining process more complicated and introduce great difficulties to dynamic modeling and performance prediction. In this paper, we considered the process damping determined by the indentation volume between flank face of milling tool and machined surface, and used multi-mode model to describe this behavior. In order to establish the assembled material removal model of the IPW dynamics with multiple modes, the structure dynamic modification (SDM) and finite element method (FEM) were combined together. The updated third-order full discretization method was applied to solve the dynamic equation in modal space. Then, the three-dimensional stability lobe diagrams (SLDs) with and without material removal along the tool path were obtained respectively by enveloping multiple modes of the IPW and milling tool together. Finally, the cutting tests were carried out. The experiments showed that the assembled model could predict the dynamics of IPW accurately, and the proposed stability analysis model was relatively close to experimental results. Besides, the modes of thin-walled workpiece with weak rigidity do not always play a dominant role in the process of machining. Although the material removal rate is limited by considering the multiple modes of the system, the processing quality can be ensured. [ABSTRACT FROM AUTHOR]

Cross-shaped chisel edge thinning is an effective method to improve the drilling performance of non-coaxial helical flank micro-drill. In order to study the effect of the cross-shaped chisel edge on drilling performance, the mathematical model of cross-shaped chisel edge is proposed. The rake angle, lip inclination angle, uncut chip thickness, and uncut chip width are calculated by MATLAB software. Finite element models of four kinds of micro-drills with a different thinned chisel edge are established using DEFORM-3D software, and micro-drilling simulations on 304 austenitic stainless steel are carried out. The simulation results show that with a decrease in chisel edge length, the drilling force, tool temperature, tool wear, and curl degree of the chip are clearly reduced. However, for micro-drill without chisel edge, the torque and tool temperature are larger than other micro-drills, and string chips are generated during the drilling process. Furthermore, the non-coaxial helical flank micro-drill with an optimal cross-shaped chisel edge is manufactured by a six-axis CNC grinding machine, and the measurement results indicate that the geometrical parameters meet the designed values. At last, the micro-drill with an optimal cross-shaped chisel edge has a satisfactory drilling performance by the micro-drilling experiment. [ABSTRACT FROM AUTHOR]

• Gumbel distribution can better fit the surface defect size, and the larger the surface defect size is, the greater the fatigue stress concentration factor is, and the shorter the fatigue life is. • The method combining extreme value statistics and Murakami model has a good predictability for 2024 aluminum alloy fatigue limit. • The extended Kitagawa-Takahashi diagram created allows for a good evaluation of the defect tolerance. • The proposed fatigue life prediction model based on surface defects-induced surface roughness and considering short crack extension and crack closure is highly accurate and has good applicability. Surface defects and microstructure have a significant impact on the fatigue properties of materials. In this paper, surface roughness was considered as surface micro-defects, and the correlation between surface defects and fatigue properties of 2024 aluminum alloy was investigated by applying laser scanning microscopy and electron backscatter diffraction (EBSD) techniques, combined with monotonic tensile tests and fatigue tests. It was found that the Gumbel distribution could better describe the size distribution of surface defects. Meanwhile, the fatigue limit was predicted based on the extreme value statistics of surface defects and the modified Murakami model, and compared with the experimental fatigue limit. Then an extended Kitagawa-Takahashi diagram was developed to evaluate the defect tolerance. In addition, a fatigue life prediction model considering surface roughness as a surface defect and taking into account short crack extension was proposed and validated against experimental data. [ABSTRACT FROM AUTHOR]

• SIRT1-mediated inflammation is involved in trichloroethylene induced renal injury. • SIRT1 down-regulation promotes HSP70 release from renal tubular epithelial cells. • SIRT1 weakens HSP70 and TLR4 interaction in trichloroethylene induced renal injury. Trichloroethylene (TCE) is a volatile chlorinated solvent widely used for cleaning and degreasing industrial metal parts. Due to the widespread use and improper disposal of TCE, exposure to TCE causes a variety of adverse effects on human and animal health. However, the underlying mechanism of the damage remains unclear. The purpose of this study is to investigate the role of Sirtuin-1 (SIRT 1) in TCE-induced immune renal tubular injury. 6–8-week-old female BALB/c mice were used to construct a TCE sensitized mouse model. SIRT 1 activator, SRT 1720 (0.1 ml, 5 mg/kg) and toll like receptor 4 (TLR 4) inhibitor, TAK-242 (0.1 ml, 3 mg/kg) were used for treatment. Results show that SIRT 1 and heat shock protein 70 (HSP 70) levels are significantly down-regulated in renal tubules, serum and urine HSP 70 levels are significantly increased, and inflammatory cytokines levels are significantly increased in renal tubules in TCE-sensitized positive mice. After SRT 1720 treatment, intracellular HSP 70 level is significantly increased and extracellular HSP 70 level is decreased, and inflammatory cytokines levels get alleviated. In addition, HSP 70 and Toll-like Receptor 4 (TLR 4) proteins exist an interaction that can be significantly attenuated by SIRT 1. Subsequently, inflammation of the renal tubules mediated by SIRT 1 downregulation is attenuated after TAK-242 treatment. In conclusion, SIRT 1 alleviates renal tubular epithelial cells immune injury by inhibiting the release of HSP 70 and thereby weakening interaction with HSP 70 and TLR 4. [ABSTRACT FROM AUTHOR]

The height of conventional compound parabolic concentrator (CPC) increase greatly with increasing geometric concentration ratio, resulting in large reflector consumption and deteriorative optical performance. A new truncated CPC with highest truncation position called HEMR was proposed in the previous study (Xie et al., 2016), which can improve the tradeoff between cost reduction and optical performance. In order to further improve the tradeoff to make the CPC more competitive in the commercial field, the truncated CPC with lowest truncation position called LEMR is designed by eliminating multiple reflections in the present study, and the performance is researched by the material consumption assessment and Monte-Carlo simulation theoretically under the conditions of 156 mm wide best concentration plane and 4 times geometric concentration ratio. The results show that the material consumption of LEMR is about 80% of HEMR while the optical performance including uniformity and optical efficiency is almost the same as HEMR, indicating that LEMR has a better tradeoff between cost reduction and optical performance and thus has more extensive application potential. [ABSTRACT FROM AUTHOR]

• An updated robotic milling chatter stability prediction method was proposed. • The proposed stability prediction method converges faster than other methods. • A robotic milling dynamic model including multifactor coupling effects was proposed. • The stability of robotic milling under different cutter orientations was investigated. • The influence factors of robotic milling chatter stability were revealed. • The results provide theoretical basis for robotic milling chatter stability analysis. Chatter can easily occur during robotic milling owing to the low rigidity of serial robots. Chatter affects the quality of the workpiece surface and damages the robot equipment, which is a bottleneck that hinders the application of robotic milling. An effective way to ensure milling stability is to rationally select the cutting parameters using high-precision stability lobe diagrams (SLDs). In this study, an updated full-discretization chatter stability prediction method based on the fourth-order Hermite and third-order Newton interpolation polynomial was proposed. A dynamical model of robotic milling was established by considering the regenerative effect, cutter structure modal coupling effect, and the influence of cutter orientations. Based on the established robotic milling dynamic model and the proposed full-discretization method, SLDs related to the axial depth of cut, spindle speed, lead angle, and tilt angle were generated. The dominant influencing factors of the robotic milling chatter stability under different robot postures and cutter orientations were analysed. The robotic milling experiment results show that the dynamic characteristics of the robot are different in each direction. When the milling cutter feeding direction is parallel to the x -axis direction of the global coordinate system, the regenerative effect is dominant. When the feed direction of the milling cutter is parallel to the y -axis of the global coordinate system, the cutter structure modal coupling effect is more obvious. This is possibly because the dynamic characteristics of the tool tip change during the milling process under different robot postures. However, the milling process becomes more stable with an increase in the lead or tilt angle. This is mainly because when the cutting depth is constant, the cutter–workpiece engagement area gradually decreases with an increase in the tool angle. [ABSTRACT FROM AUTHOR]

• New measurement system for roundness and axis straightness errors of deep-hole parts. • Gross error removal method based on the distribution of measurement points. • Evaluation and uncertainty analysis models of roundness and axis straightness errors. • The accuracy and repeatability of the developed system are verified by experiments. Precision deep-hole parts are widely used in various fields of industrial production. Their machining quality has a significant impact on fatigue limit, geometric accuracy, and stability of products. Since roundness and axis straightness errors are essential technical indexes to evaluate the machining quality of deep-hole parts, their accurate measurement is essential to ensure the performance of related products. In this study, a multi-sensor integrated system that can measure two kinds of shape errors simultaneously was developed based on laser displacement sensor, circular grating, two-dimensional position-sensitive detector (PSD) and laser interferometer. It is suitable for deep-hole parts with a diameter of 150–165 mm and a length of 600–20000 mm. Furthermore, the uncertainty analysis models of roundness and axis straightness errors for this system were constructed. Eventually, the effectiveness of the measurement system was successfully verified through experiments. [ABSTRACT FROM AUTHOR]

This paper presented the influence of machined surface texture on fretting cracks behaviors of Titanium alloy Ti–6Al–4V under radial loading in conformal contact. The contacted holes of specimen were machined with combined helical and flank milling before fretting fatigue tests, and a special fretting fatigue test apparatus was proposed to focus on conformal contact fretting fatigue (CCFF) test under radial loading. The test results showed that all the specimens failed at the contact area where characterizes an inner obtuse angle between the material flow direction (or cutting direction) and the direction of the tangential component of the contact force. The area with higher surface skewness and kurtosis values was also prone to nucleate fretting fatigue crack. These results suggested that the corresponding machining conditions in hole-making and surface strengthen processes should be adjusted to guide the production of surface texture properties, in terms of obtaining desirable lower skewness and kurtosis features to relieve nucleation of fretting cracks. Additionally, the debris in conformal contact tended to aggregate towards the partial slip zone (PSZ) due to the conformal geometry and form a compacted layer in the gross slip zone (GSZ) subjected to radial loading. These characteristics exacerbated and alleviated fretting damage in the PSZ and GSZ, respectively. In this research, a set of suitable milling parameters for the hole flank milling process in terms of prolonging fretting fatigue life were also defined. Image 1 • A test apparatus for conformal contact fretting fatigue under radial load was proposed. • Obtuse angle between material flow direction and the direction of the tangential component of the contact force was apt to nucleate crack. • Higher surface skewness and kurtosis value was prone to nucleate fretting crack. • The compacted debris layer in the gross slip zone alleviated fretting damage. [ABSTRACT FROM AUTHOR]

Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the livers of TCE-drinking mice and found that the expression of KDM4A, M1-type polarization indicators, and related inflammatory factors in the livers of TCE-drinking mice. In the study, BALB/c mice were randomly divided into four groups: 2.5 mg/mL TCE dose group and 5.0 mg/mL TCE dose group, the vehicle control group, and the blank control group. We found that TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines. Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 and increased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to β-catenin activation, a signal critical for the pro-inflammatory activation of macrophages. Furthermore, KDM4A inhibitor JIB-04 treatment resulted in a decrease in β-catenin expression and prevented TCE-induced M1 polarization and the expression of the pro-inflammatory cytokines TNF-α and IL-1β. These results suggest that the association of KDM4A and Wnt/β-catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3/me2/me1. Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE., (© 2024 International Federation for Cell Biology.)

Trichloroethylene (TCE), a widely distributed environmental chemical contaminant, is extensively dispersed throughout the environment. Individuals who are exposed to TCE may manifest occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Renal impairment typically manifests in the initial phase of OMDT and is intricately linked to the disease progression and patient outcomes. Although recombinant human tumor necrosis factor-α receptor II fusion protein (rh TNFR:Fc) has been employed in the clinical management of OMDT, there was no substantial improvement in renal function observed in patients following one week of treatment. This study primarily examined the mechanism of TNFα- and IFNγ-induced endothelial cells (ECs) PANoptosis in TCE-induced kidney injury and hypothesized that the synergistic effect of TNFα and IFNγ could be the key factor affecting the efficacy of rh TNFR:Fc therapy in OMDT patients. A TCE-sensitized mouse model was utilized in this study to investigate the effects of TNFα and IFNγ neutralizing antibodies on renal vascular endothelial cell PANoptosis. The gene of interferon regulatory factor 1 (IRF1) in human umbilical vein endothelial cells (HUVEC) was silenced by using small interfering RNA (siRNA), and the cells were then treated with TNFα and IFNγ recombinant protein to investigate the mechanism of TNFα combined with IFNγ-induced PANoptosis in HUVEC. The findings indicated that mice sensitized to TCE exhibited increased levels of PANoptosis-related markers in renal endothelial cells, and treatment with TNFα and IFNγ neutralizing antibodies resulted in a significant reduction in PANoptosis and improvement in renal function. In vitro experiments demonstrated that silencing IRF1 could reverse TNFα and IFNγ-induced PANoptosis in endothelial cells. These results suggest that the efficacy of rh TNFR:Fc may be influenced by TNFα and IFNγ-mediated PANoptosis in kidney vascular endothelial cells. The joint application of TNFα and IFNγ neutralizing antibody represented a solid alternative to existing therapeutics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Trichloroethylene (TCE) is a common environmental contaminant that can cause a severe allergic reaction called TCE hypersensitivity syndrome, which often implicates the patient's kidneys. Our previous study revealed that C5b-9-induced tubular ferroptosis is involved in TCE-caused kidney damage. However, the study did not explain how tubule-specific C5b-9 causes free iron overload, a key event in ferroptosis. Here, we aimed to explore the role of NCOA4-mediated ferritinophagy in C5b-9-induced iron overload and ferroptosis in TCE-sensitized mice. Our results showed that TCE sensitization does not affect iron import or export, but does affect iron storage, causing ferritin degradation and free iron overload. In addition, mitochondrial ROS was upregulated, and these changes were blocked by C5b-9 inhibition. Interestingly, TCE-induced ferritin degradation and ferroptosis were significantly antagonized by the application of the mitochondrial ROS inhibitor, Mito-TEMPO. Moreover, all of these modes of action were further verified in C5b-9-attack signalling HK-2 cells. Further investigation demonstrated that C5b-9-upregulated mitochondrial ROS induced a marked increase in nuclear receptor coactivator 4 (NCOA4), a master regulator of ferritinophagy. In addition, the application of NCOA4 small interfering RNA not only significantly reversed ferritinophagy caused by C5b-9 but also reduced C5b-9-induced ferroptosis in HK-2 cells. Taken together, these results suggest that tubule-specific C5b-9 deposition activates NCOA4 through the upregulation of mitochondrial ROS, causing ferritin degradation and elevated free iron, which ultimately leads to tubular epithelial cell ferroptosis and kidney injury in TCE-sensitized mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glutamate is a neurotransmitter that can cause excitatory neurotoxicity when its extracellular concentration is too high, leading to disrupted calcium balance and increased production of reactive oxygen species (ROS). Cordycepin, a nucleoside adenosine derivative, has been shown to protect against excitatory neurotoxicity induced by glutamate. To investigate its potential neuroprotective effects, the present study employed fluorescence detection and spectrophotometry techniques to analyze primary hippocampal-cultured neurons. The results showed that glutamate toxicity reduced hippocampal neuron viability, increased ROS production, and increased intracellular calcium levels. Additionally, glutamate-induced cytotoxicity activated acetylcholinesterase and decreased glutathione levels. However, cordycepin inhibited glutamate-induced cell death, improved cell viability, reduced ROS production, and lowered Ca 2+ levels. It also inhibited acetylcholinesterase activation and increased glutathione levels. This study suggests that cordycepin can protect against glutamate-induced neuronal injury in cell models, and this effect was inhibited by adenosine A 1 receptor blockers, indicating that its neuroprotective effect is achieved through activation of the adenosine A 1 receptor., Competing Interests: Declarations of interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Karst lands provide a poor substrate to support plant growth, as they are low in nutrients and water content. Common buckwheat ( Fagopyrum esculentum ) is becoming a popular crop for its gluten-free grains and their high levels of phenolic compounds, but buckwheat yields are affected by high water requirements during grain filling. Here, we describe a wild population of drought-tolerant Fagopyrum leptopodum and its potential for enhancing drought tolerance in cultivated buckwheat. We determined that the expression of a gene encoding a Basic leucine zipper (bZIP) transcription factor, FlbZIP12 , from F. leptopodum is induced by abiotic stresses, including treatment with the phytohormone abscisic acid, salt, and polyethylene glycol. In addition, we show that overexpressing FlbZIP12 in Tartary buckwheat ( Fagopyrum tataricum ) root hairs promoted drought tolerance by increasing the activities of the enzymes superoxide dismutase and catalase, decreasing malondialdehyde content, and upregulating the expression of stress-related genes. Notably, FlbZIP12 overexpression induced the expression of key genes involved in flavonoid biosynthesis. We also determined that FlbZIP12 interacts with protein kinases from the FlSnRK2 family in vitro and in vivo . Taken together, our results provide a theoretical basis for improving drought tolerance in buckwheat via modulating the expression of FlbZIP12 and flavonoid contents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Liu, Li, Li, Zhang, Kong, Liu, Yang and Wang.)

More and more clinical evidence shows that occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) patients often present immune kidney damage. However, the exact mechanisms of cell-to-cell transmission in TCE-induced immune kidney damage remain poorly understood. The present study aimed to explore the role of high mobility group box-1 (HMGB 1) in glomerular endothelial cell-podocyte transmission. 17 OMDT patients and 34 controls were enrolled in this study. We observed that OMDT patients had renal function injury, endothelial cell activation and podocyte injury, and these indicators were associated with serum HMGB 1. To gain mechanistic insight, a TCE-sensitized BALB/c mouse model was established under the interventions of sirtuin 1 (SIRT 1) activator SRT 1720 (0.1 ml, 5 mg/kg) and receptor for advanced glycation end products (RAGE) inhibitor FPS-ZM 1 (0.1 ml, 1.5 mg/kg). We identified HMGB 1 acetylation and its endothelial cytoplasmic translocation following TCE sensitization, but SRT 1720 abolished the process. RAGE was located on podocytes and co-precipitated with extracellular acetylated HMGB 1, promoting podocyte injury, while SRT 1720 and FPS-ZM 1 both alleviated podocyte injury. The results demonstrate that interventions to upstream and downstream pathways of HMGB 1 may weaken glomerular endothelial cell-podocyte transmission, thereby alleviating TCE-induced immune renal injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with occupational medicamentose-like dermatitis due to trichloroethylene often suffer from immune kidney injury. Our previous study reveals that C5b-9-dependent cytosolic Ca 2+ overload-induced ferroptosis is involved in trichloroethylene sensitized kidney injury. However, how C5b-9 causes cytosolic Ca 2+ rise and the specific mechanism whereby overloaded Ca 2+ induces ferroptosis remain unknown. The purpose of our study was to explore the role of IP3R-dependent mitochondrial dysfunction in C5b-9 mediated ferroptosis in trichloroethylene sensitized kidney. Our results showed that IP3R was activated, and mitochondrial membrane potential was decreased in the renal epithelial cells of trichloroethylene-sensitized mice, and these changes were antagonized by CD59, a C5b-9 inhibitory protein. Moreover, this phenomenon was reproduced in a C5b-9-attacked HK-2 cell model. Further investigation showed that RNA interference with IP3R not only alleviated C5b-9-induced cytosolic Ca 2+ overload and mitochondrial membrane potential loss but also attenuated C5b-9-induced ferroptosis in HK-2 cells. Mechanistically, IP3R-dependent cytosolic Ca 2+ overload activated the mitochondrial permeability transition pore, resulting in the loss of mitochondrial membrane potential and ferroptosis of HK-2 cells. Finally, cyclosporin A, a mitochondrial permeability transition pore inhibitor, not only ameliorated IP3R-dependent mitochondrial dysfunction but also blocked C5b-9-induced ferroptosis. Taken together, these results suggest that IP3R-dependent mitochondrial dysfunction plays an important role in trichloroethylene sensitized renal tubular ferroptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Ma, Zuo, Zhang, Xie, Wang, Wu, Zhang and Zhu.)

Background: Oral mucositis is an acute adverse reaction with high incidence during radiotherapy. Severe oral mucositis can seriously affect patients' quality of life and compliance with radiotherapy. The aim of this study was to identify the risk factors for severe oral mucositis and to develop a nomogram for predicting severe oral mucositis in patients with nasopharyngeal carcinoma., Methods: One hundred and ninety patients with nasopharyngeal carcinoma were retrospectively screened in this study. Least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were performed to identify the best predictors of severe oral mucositis. A nomogram was constructed based on the factors. Finally, the discriminative ability of the nomogram was evaluated., Results: Four independent factors predicting severe oral mucositis were identified: age, N stage, the cycle of induction chemotherapy, and dose-volumetric parameter V40 (%) of oral cavity. The area under the receiver of operating characteristic curve of the nomogram was 0.759 (95% confidence interval: 0.691-0.827)., Conclusions: A predictive nomogram for severe oral mucositis was established and validated in this study. The nomogram provides a reliable and practical model for clinically predicting the probability of severe oral mucositis in patients with nasopharyngeal carcinoma before intensity-modulated radiation therapy.

Occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) is a systemic allergic disease similar to drug eruption-like dermatitis that occurs in workers after exposure to trichloroethylene. In addition to skin and mucosa damage, OMDT patients often accompanied by severe multiorgan damage, including kidney injury. However, the mechanism remains unclear. The aim of our research was to explore the role of increased cytosolic mitochondrial DNA in the activation of cGAS-STING signaling and in the kidney injury of trichloroethylene sensitization mice using a mouse model and an in vitro model. By analyzing the kidneys of TCE-sensitized mice, we found obvious tubular mitochondrial damage, decreased expression of COX-IV and TFAM proteins and increased cytosolic mitochondrial DNA in TCE-sensitized-positive mice. Further study found that cytosolic mitochondrial DNA activated cGAS-STING signaling, resulting in the nuclear translocation of P-IRF3 and NF-κB P65 and the transcription and synthesis of type Ⅰ interferons and cytokines, which ultimately led to immune kidney injury in trichloroethylene-sensitized mice. Interestingly, pretreatment with C-176, a STING inhibitor, not only blocked the nuclear translocation of P-IRF3 and NF-κB P65, but also alleviated the kidney injury induced by TCE sensitization. Consistently, in vitro studies also found that mitochondrial DNA pretreatment can activate the cGAS-STING pathway, causing the nuclear translocation of P-IRF3 and NF-κB P65 and the transcription of type Ⅰ interferons and cytokines in HK-2 cells. Overall, our results suggested that cytosolic mitochondrial DNA plays an important role in the activation of the cGAS-STING pathway and TCE sensitization-induced immune kidney injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Asymmetric recurrent time-varying neural networks (ARTNNs) can enable realistic brain-like models to help scholars explore the mechanisms of the human brain and thus realize the applications of artificial intelligence, whose dynamical behaviors such as synchronization has attracted extensive research interest due to its superior applicability and flexibility. In this paper, we examined the outer-synchronization of ARTNNs, which are described by the differential-algebraic system (DAS). By designing appropriate centralized and decentralized data-sampling approaches which fully account for information gathering at the times t k and t k i . Using the characteristics of integral inequalities and the theory of differential equations, several novel suitable outer-synchronization conditions were established. Those conditions facilitate the analysis and applications of dynamical behaviors of ARTNNs. The superiority of the theoretical results was then demonstrated by using a numerical example., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Liu and Liu.)

Photocatalytic technology based on silver phosphate (Ag 3 PO 4 ) has excellent potential in removing antibiotic pollutants, but the low separation rate of photogenerated hole-electron pairs restricts the application of the photocatalyst. In this study, it was found that the combination of nitrogen-doped carbon (NDC) with carbon defects and Ag 3 PO 4 can significantly enhance the photocatalytic ability of Ag 3 PO 4 . After it was exposed to visible light for 5 min, the photocatalytic degradation efficiency of oxytetracycline (OTC) by the composite photocatalyst Ag 3 PO 4 @NDC could reach 100%. In addition, the structure of NDC, Ag 3 PO 4, and Ag 3 PO 4 @NDC was systematically characterized by SEM, TEM, XRD, Raman, and EPR. The XPS results revealed intense interface interaction between Ag 3 PO 4 and NDC, and electrons would transfer from Ag 3 PO 4 to the NDC surface. A possible mechanism for enhancing the photocatalytic reaction of the Ag 3 PO 4 @NDC composite catalyst was proposed. This study provides a highly efficient visible light catalytic material, which can be a valuable reference for designing and developing a new highly efficient visible light catalyst.