Search

C/Cu composites have been widely used in the field of electrical contacts due to their excellent conductivity and anti-ablation properties. However, the poor wettability between C and Cu matrix severely significantly shortens the service life of C/Cu electrical contacts. In this work, we theoretically and experimentally demonstrate that rare earth alloying in Cu matrix enhances the interfacial wettability between C and Cu, leading to the improved electrical contact performance. The wetting angle is reduced from 132° to 46° by the incorporation of La (0.56 wt%) into the Cu matrix, which is attributed to the formation of interfacial LaC2, where the Griffith's separation energy of LaC2/Cu was calculated to be −4.6 J/m2 much lower than those of C/Cu (0.13 J/m2) and C/CuLa (0.06 J/m2). The ablation surface of the electric contact demonstrates that improved wettability can diminish carbon accumulation, thereby reducing the contact resistance from 50 mΩ to 2.2 mΩ after 1000 cycles at 380 V and 60 A, with a reduction of mass loss by 50%.This work reveals the bonding mechanism of C/Cu interface, which paves a way for rational design of C/Cu-based electrical contact materials.

The preferential oxidation of alloying elements has long been recognized as the primary mechanism underlying the oxidation resistance of copper alloys. However, the presence of various alloy phases within the Cu matrix complicates the oxidation behavior. Herein, combined DFT calculations and antioxidation experiment were conducted to evaluate the oxidation behavior and underlying mechanism of Cu–La alloys. The results indicate that the oxidation resistance of Cu is significantly enhanced by La element with a reduced mass gain of 49% at 100 °C for 100 h. The effects of oxidation behavior of Cu6La on the oxidation resistance of Cu is further explored by DFT calculations. It reveals that the Cu6La phase with a low work function exhibits a strong affinity for the O atoms. However, the diffusion activation energy of the absorbed O is calculated to be lower in Cu6La than that of O in Cu, which is conducive to mitigate the further erosion of O on Cu matrix. Moreover, the Cu2O–La layer formed on the Cu6La surface is more stable and the oxygen diffusion coefficient in it is lower, which impedes the entry of oxygen. This work advances the understanding of alloying effect on oxidation of Cu surfaces that can be extended to other metal surfaces.

Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors. Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence. Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows. General patient characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients

FeSiAl alloys with a composition of Fe-9.6Si-5.4Al, also known as Sendust alloys, present the unique potential to exhibit efficient electromagnetic wave absorption (EMA) in the P-band. However, the electromagnetic properties of this type of alloy are highly sensitive to the shape, microstructure, and microchemistry, which then inspire the current research. The evolution of the microstructure/microchemistry of FeSiAl particles was systematically revealed in a single particle scale for the first time, and the resulting influence on the electromagnetic properties was investigated. Recrystallization occurs in the annealing process on FeSiAl particles and the oxide films on the surface evolve evidently when annealed in 5%H2/Ar or air, which can conduce improved electromagnetic properties. The FeSiAl particles annealed in 5%H2/Ar present efficient EMA in the P-L band while those in air contribute to high reflection loss. This work indicates the feasibility of achieving a high and adjustable EMA efficiency in the P-L band through microstructure and microchemistry tailoring.

A finite element method (FEM) combined with subroutines was established and used for tracing the evolution of stresses in M50 steel in quenching. The constitutive relation and thermal physical properties of M50 steel were tested and integrated into the modeling. The finite element analysis, taking into account of thermal stresses and martensitic phase transformation, predicts accurately the high-velocity nitrogen (HNQ) induced residual stresses in the M50 steel bulk. The simulation results suggested that the residual stresses in M50 steel is compressive at the surface while tensive at the center, along with very strong residual stresses at edges. The residual stress reaches to the high level of −810.3 MPa and −1436 MPa in the case of HNQ and water quenching, respectively. The evolution of stress is found to be jointly driven by the thermal stress and phase transformation stress. The thermal stress dominates the evolution at the initial stage while the phase transformation stress becomes dominating once the martensite transformation begins.

A high-strength and anti-intergranular corrosion (IGC) Al-6.8Zn-2.2 Mg-Sc-Zr alloy (AS alloy) was designed, and the effects of Sc addition and Cu removal on the microstructure, mechanical properties and corrosion behavior were systematically investigated. Based on transmission electron microscopy (TEM) and Kelvin probe force microscopy (KPFM) techniques, the underlying causes of IGC and exfoliation corrosion (EXCO) of the AS alloy were investigated, and the corrosion mechanism of AS alloy was finally obtained. The AS alloy exhibits excellent mechanical properties with a tensile strength of 601 MPa in the peak-ageing condition at 120 °C, which comes from the pinning effect of Al3(Sc, Zr) dispersions. Moreover, AS alloys of T6 and T74 conditions show outstanding IGC and EXCO resistance. On the one hand, the fine, near-ellipsoidal grains in AS alloy alleviate the peeling stress caused by IGC products by blocking the formation of wedge-shaped gaps along GBs, which then bring about improved EXCO resistance. On the other hand, the removal of Cu from the traditional Al-Zn-Mg-Cu alloy avoids the segregation of Cu into GBs and thereafter reduces the fluctuations of the potential and the electron work function (EWF) across the GBs; the addition of Sc induces the high fraction of LAGBs and thus weakens the solutes' segregation at GBs, which can be beneficial for smoothing the fluctuation of corrosion potential (Ecorr) to enhance the IGC resistance.

An Al–Zn–Mg-Sc-Zr alloy with high Zn was prepared to obtain ultra-high strength in the present study. The microstructure of the aged samples and the friction stir welding (FSW) joints were investigated by optical microscopy, electron backscatter diffraction and transmission electron microscopy. The mechanical properties were evaluated by microhardness and tensile tests. Results show that the peak microhardness of the aged Al–Zn–Mg-Sc-Zr alloy was ∼212.2 Hv. Strengths up to 697.2 MPa in the yield strength and 721.8 MPa in the ultimate tensile strength were obtained after ageing at 120 °C for 24 h, and the elongation was ∼9%. The ultra-high strength was mainly attributed to the precipitate strengthening from η′ and Al3ScxZr1-x precipitates, solid solution strengthening and fine grain strengthening. Soft regions with hardness of ∼122 Hv were developed near the interfaces between heat-affected zone and thermo-mechanically affected zone due to the coarsening and/or dissolution of strengthening precipitates. The joint coefficient was ∼69.5% for the Al–Zn–Mg-Sc-Zr alloy. Fine recrystallized grains with an average diameter of ∼1.8 μm were formed in the nugget zone (NZ), and these newly formed fine grains experienced further deformation and resulted in high fractions of substructure and deformed grain. The size and shape of Al3ScxZr1-x precipitates remain almost unchanged during ageing at 120 °C and the FSW processing. The existence of η phase in the NZ was associated with the Al3ScxZr1-x particles, indicating the heterogeneous precipitation of η precipitates on the Al3ScxZr1-x precipitates during FSW.

In-depth understanding of the layer-by-layer process is critical for the quality control of additive manufactured (AM) components. Besides the development of experimental techniques, computational modelling is another important way to study the AM mechanisms in detail. However, currently there is still lack of a modelling platform that integrates all the necessary physics involved in the AM process. In the present study, we develop a modelling framework that integrates a phase field method for microstructure evolution, a lattice Boltzmann method for melt pool dynamics, a modified ray-tracing method for laser-material interaction, and a minimum gravity energy algorithm for powder bed generation to simulate the single-track, powder bed fusion (PBF) process of NiTi shape memory alloy. Our simulation shows that different from keyhole depth, melt pool size does not obey the scaling law with line energy density, the keyhole depth and the overlapping ratio of laser spot vs. keyhole opening together determine the laser absorptivity. Based on the simulation finding, we also develop a self-consistent analytical model to predict the keyhole depth and the absorptivity for given scanning parameters. The present work lays a solid foundation towards quantitative understanding of multi-layer AM process.

The particles stimulated nucleation (PSN) triggered by coarsened T1 phase (Al2CuLi) in Al–Cu–Li alloys is investigated to analyze the formation of recrystallization texture that is unusual from typical PSN. The specimens were uniaxially compressed to a series of compression amount and the recrystallization process is characterized by electron backscattered diffraction (EBSD), scanning electron microscope (SEM) and transmission electron microscope (TEM). Results showed that the recrystallization occurred by progressive rotation of the matrix units that separated by the three-dimensional arranged T1 precipitates. The rotation of the units towards was observed in the initial grains of various orientations all through the recrystallization process. The massively formed fine grains contribute to a strong fiber texture. The fraction of recrystallization is 67% and the grains are averagely 2.5 μm in the specimen received a stain of 1.61. The PSN initiated by coarsened T1 phase fosters the feasibility to obtain textured and refined structure in Al–Cu–Li alloys which will facilitate the performance improvement of the fabricated components.

AlkB homolog 5 (ALKBH5) plays an important role in ischemia/reperfusion (I/R), cardiac hypertrophy and other cardiovascular diseases (CVDs). However, whether ALKBH5 regulates the inflammatory response by mediating M1/M2 macrophage conversion after myocardial infarction (MI) is unclear. In this study, we found that ALKBH5 protein expression was significantly downregulated in MI mice. To investigate the role of ALKBH5 in the inflammatory response after MI, we assessed the expression of interleukin-6 (Il-6), interleukin-1β (Il-1β), tumor necrosis factor-α (Tnf-α) and interferon-Ⅰ (Ifn-Ⅰ) by qRT‒PCR and found that ALKBH5 knockout improved cardiac function, reduced pro-inflammatory cytokine release and decreased cardiomyocyte apoptosis. In addition, the knockdown of ALKBH5 significantly inhibited the release of pro-inflammatory cytokines and the migration of RAW264.7 macrophages treated with lipopolysaccharide (LPS). Mechanistically, our results suggested that ALKBH5 potentially recognized the m 6 A binding site on interferon regulatory factor 3 (IRF3) and regulated the IRF3 expression to influence macrophage M1/M2 phenotypic transition and inflammatory cytokine release. In conclusion, our results indicated that ALKBH5 ablation inhibited inflammation by regulating the transcription of IRF3. This study provides new insights into the clinical management of the inflammatory response after MI., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Misfolded neurotoxic proteins, such as Tau protein, spread within the brain in many neurodegenerative diseases. Receptors play an important role in the recognition of spreading proteins for endocytosis. Blocking the receptors is essential to inhibit neurotoxic proteins spreading in the brain. However, it's a great challenge to identify the membrane receptors of ligand, such as Tau, caused by high dynamic interaction and subsequent endocytosis. Herein, a ligand guided in vivo crosslinking combined with affinity purification mass spectrometry (LGCX-APMS) strategy was developed and enabled the discovery of Tau receptors. With this method, 32 plasma membrane proteins that bind to Tau were identified including the reported neuron receptor LRP1. More importantly, TMPRSS13 was further validated as a potential receptor for Tau fibrils. These results illustrate that LGCX-APMS might capture the interactions of ligand in living cells suitable for the identification of the receptors, and further provide methods for the study of intercellular communication., 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 © 2025 Elsevier B.V. All rights reserved.)

Understanding protein structure is essential for elucidating its function. Cross-linking mass spectrometry (XL-MS) has been widely recognized as a powerful tool for analyzing protein complex structures. However, the effect of cross-linker backbone structure on protein dynamic conformation analysis remains less understood. In this study, we investigated the impact of cross-linker backbone structure on resolving the dynamic conformations of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1), which features a blend of relatively steady intradomain structures and dynamic interdomain regions. Three cross-linkers with varying arm lengths and different oxygen-containing backbones, Disuccinimidyl tartrate (DST), Bis(succinimidyl) di(ethylene glycol) (BS(PEG) 2 ), and Disuccinimidyl dihydroxydodecanedioate (DSDHD), were selected based on the theoretical inter-lysine distances within Pin1. By employing all-atom molecular dynamics (MD) simulations and solution nuclear magnetic resonance (NMR), we characterized the kinetic properties of cross-linkers and their perturbations to the protein structure. Additionally, we systematically evaluated the capability of cross-linkers with different backbones to analyze the structure and interdomain dynamics of Pin1. The results suggest that BS(PEG) 2 , with its optimal arm length and ability to rapidly transition between compact and extended states, provides more interdomain dynamic conformational information of Pin1, while achieving a comparable level of intradomain structural detail to that obtained with the shorter cross-linker DST. Overall, this study highlights the critical role of cross-linker backbone structure in structural analysis of protein dynamics using mass spectrometry., 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. Published by Elsevier B.V.)

Background: Periorbital aging typically manifests with dermatochalasis and depression of the upper eyelid. While blepharoplasty is a popular choice for addressing upper eyelid skin laxity, it is not effective for treating sunken eyelids. This study introduces an innovative approach for periorbital rejuvenation by simultaneously addressing dermatochalasis and sunken upper eyelids in aging Asian women., Method: This study involved 45 patients with upper eyelid dermatochalasis accompanied by moderate to severe depression. Sub-brow blepharoplasty was performed in conjunction with upper eyelid granular fat grafting in the orbital septum for these patients. Preoperative measurements of the depth and volume of the upper eyelid depressions were taken, and surgical outcomes were assessed at 3 and 6 months postoperatively using the Global Aesthetic Improvement Scale (GAIS) score and the Antera 3D camera., Result: The average depth of the upper eyelid depression before surgery was 6.501 ± 1.473 mm, and the average volume was 0.579 ± 0.144 cm 3 . Significant improvements in both the depth and volume of the depressions were observed at 3 and 6 months after surgery compared to preoperative measurements. The GAIS scores were also improved and postoperative outcomes were deemed satisfactory., Conclusion: For patients with dermatochalasis accompanied by moderate to severe upper eyelid depression, standard blepharoplasty alone is insufficient to correct the sunken eyelid. This novel technique, which combines autologous granular fat injection into the orbital septum with blepharoplasty, effectively addresses periorbital aging, enhancing facial rejuvenation., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Vibrio alfacsensis is traditionally seen as an environmental symbiont within its genus, with no detailedly documented pathogenicity in marine aquaculture to date. This study delves into the largely unexplored pathogenic potential and emerging antibiotic resistance of V. alfacsensis. The VA-1 strain, isolated from recirculating aquaculture system (RAS) effluent of cultured turbot (Scophthalmus maximus), underwent comprehensive analysis including biochemical identification, antibiotic susceptibility testing and reinfection trials. The results confirmed VA-1's pathogenicity and significant multiple antibiotic resistance. VA-1 could induce systemic infection in turbot, with symptoms like kidney enlargement, exhibiting virulence comparable to known Vibrio pathogens, with an LD 50 around 2.36 × 10 6 CFU/fish. VA-1's remarkable resistance phenotype (14/22) suggested potential for genetic exchange and resistance factor acquisition in aquaculture environments. Phylogenetic analysis based on 16S rDNA sequences and whole-genome sequencing has firmly placed VA-1 within the V. alfacsensis clade, while genome-wide analysis highlights its similarity and diversity in relation to strains from across the globe. VA-1 contained numerous replicons, indicating the possibility for the spread of resistance and virulence genes. This study suggests V. alfacsensis may acquire and transfer pathogenic and resistant traits through horizontal gene transfer, a likelihood intensified by changing environmental and aquaculture conditions, highlighting the need for vigilant pathogen monitoring and new non-antibiotic treatments., 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.)

Background: Upper eyelid tissue swelling is a common characteristic among Asian monolid individuals and is associated with a high incidence of complications following eyelid surgery. Currently, there is no precise definition for upper eyelid tissue swelling; thus, further research is required to elucidate the specific causes contributing to upper eyelid puffiness., Method: Between June 2023 and February 2024, we recruited 84 Asian monolid women categorized into groups based on the severity of upper eyelid tissue swelling: the puffy eyelid group and normal eyelid group. High-frequency ultrasound was employed to capture images of the upper eyelids and measure the thickness of various tissue layers. This study aimed to conduct a comparative analysis to identify the factors contributing to upper eyelid fullness, focusing on elucidating the underlying causes of this condition., Result: All volunteers underwent bilateral upper eyelid ultrasound imaging. Significant differences were observed in the thickness of subcutaneous fat, pre-tarsal fat, retro-orbicularis oculi fat (ROOF), and composite fat (ROOF and preaponeurotic fat) layer between the puffy and normal eyelid groups. However, no significant differences were found in skin thickness or orbicularis oculi muscle thickness. Additionally, no significant differences were observed in the thickness of various layers of the upper eyelid tissue between the left and right eyes in all participants., Conclusion: Thickening of the upper eyelid fat layer is a primary cause of upper eyelid puffiness. In upper blepharoplasty, targeted removal of preaponeurotic fat, ROOF, and pre-tarsal fat can achieve precise reduction to correct upper eyelid puffiness effectively., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Emotion recognition is crucial for human-computer interaction, and electroencephalography (EEG) stands out as a valuable tool for capturing and reflecting human emotions. In this study, we propose a hierarchical hybrid model called Mixed Attention-based Convolution and Transformer Network (MACTN). This model is designed to collectively capture both local and global temporal information and is inspired by insights from neuroscientific research on the temporal dynamics of emotions. First, we introduce depth-wise temporal convolution and separable convolution to extract local temporal features. Then, a self-attention-based transformer is used to integrate the sparse global emotional features. Besides, channel attention mechanism is designed to identify the most task-relevant channels, facilitating the capture of relationships between different channels and emotional states. Extensive experiments are conducted on three public datasets under both offline and online evaluation modes. In the multi-class cross-subject online evaluation using the THU-EP dataset, MACTN demonstrates an approximate 8% enhancement in 9-class emotion recognition accuracy in comparison to state-of-the-art methods. In the multi-class cross-subject offline evaluation using the DEAP and SEED datasets, a comparable performance is achieved solely based on the raw EEG signals, without the need for prior knowledge or transfer learning during the feature extraction and learning process. Furthermore, ablation studies have shown that integrating self-attention and channel-attention mechanisms improves classification performance. This method won the Emotional BCI Competition's final championship in the World Robot Contest. The source code is available at https://github.com/ThreePoundUniverse/MACTN., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mechanical stress stands as a fundamental factor in the intricate processes governing the growth, development, morphological shaping, and maintenance of skeletal mass. The profound influence of stress in shaping the skeletal framework prompts the assertion that stress essentially births the skeleton. Despite this acknowledgment, the mechanisms by which the skeleton perceives and responds to mechanical stress remain enigmatic. In this comprehensive review, our scrutiny focuses on the structural composition and characteristics of sclerotin, leading us to posit that it serves as the primary structure within the skeleton responsible for bearing and perceiving mechanical stress. Furthermore, we propose that osteocytes within the sclerotin emerge as the principal mechanical-sensitive cells, finely attuned to perceive mechanical stress. And a detailed analysis was conducted on the possible transmission pathways of mechanical stress from the extracellular matrix to the nucleus., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bo Wei reports financial support was provided by Zhanjiang Science and Technology Bureau. Chengshuo Huang reports financial support was provided by Zhanjiang Science and Technology Bureau. Bo Wei reports financial support was provided by Affiliated Hospital of Guangdong Medical University. If there are other authors, they 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO 2 ) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO 2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO 2 dosage on the production of methane (CH 4 ) and nitrous oxide (N 2 O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO 2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N 2 O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO 2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus_Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH 4 production at increased CaO 2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO 2 /m 2 achieved 41.21 % and 84.40 % reductions in CH 4 and N 2 O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH 4 and N 2 O, from urban landscape water but also suggests a methodology for optimizing CaO 2 dosage, providing valuable insights for its practical application., 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. Published by Elsevier B.V.)

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery., 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 Inc. All rights reserved.)

The central nervous system relies heavily on neurotransmitters (NTMs), and NTM imbalances have been linked to a wide range of neurological conditions. Thus, the development of reliable detection techniques is essential for advancing brain studies. This review offers a comprehensive analysis of metal-organic frameworks (MOFs), transition metal oxides (TMOs), and MOFs-derived TMOs (MOFs/TMOs) as materials for electrochemical (EC) sensors targeting the detection of key NTMs, specifically dopamine (DA), epinephrine (EP), and serotonin (SR). The unique properties and diverse families of MOFs and TMOs, along with their nanostructured hybrids, are discussed in the context of EC sensing. The review also addresses the challenges in detecting NTMs and proposes a systematic approach to tackle these obstacles. Despite the vast amount of research on MOFs and TMOs-based EC sensors for DA detection, the review highlights the gaps in the literature for MOFs/TMOs-based EC sensors specifically for EP and SR detection, as well as the limited research on microneedles (MNs)-based EC sensors modified with MOFs, TMOs, and MOFs/TMOs for NTMs detection. This review serves as a foundation to encourage researchers to further explore the potential applications of MOFs, TMOs, and MOFs/TMOs-based EC sensors in the context of neurological disorders and other health conditions related to NTMs imbalances., 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 Elsevier B.V. All rights reserved.)

Background: Deficits in response inhibition are associated with numerous psychiatric disorders. Previous studies have revealed the crucial role of the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and beta activity in these brain regions in response inhibition. Multi-channel transcranial alternating current stimulation (tACS) has garnered significant attention for its ability to modulate neural oscillations in brain networks. In this study, we employed multi-channel tACS targeting rIFG-preSMA network to investigate its impact on response inhibition in healthy adults., Methods: In Experiment 1, 70 healthy participants were randomly assigned to receive 20 Hz in-phase, anti-phase, or sham stimulation over rIFG-preSMA network. Response inhibition was assessed using the stop-signal task during and after stimulation, and impulsiveness was measured via the Barratt Impulsiveness Scale. Additionally, 25 participants received stimulation at the left supraorbital area to account for potential effects of the "return" electrode. Experiment 2, consisting of 25 participants, was conducted to validate the primary findings of Experiment 1, including both in-phase and sham stimulation conditions, based on prior estimations derived from the results of Experiment 1., Results: In Experiment 1, we found that in-phase stimulation significantly improved response inhibition compared with sham stimulation, whereas anti-phase stimulation did not. These findings were consistently replicated in Experiment 2. We also conducted an exploratory analysis of the multi-channel tACS impact, revealing that its effects primarily emerged during the post-stimulation phase. Furthermore, individuals with higher baseline attentional impulsiveness showed greater improvements in the in-phase stimulation group., Conclusions: These results demonstrate that in-phase beta-tACS over rIFG-preSMA network can effectively improve response inhibition in healthy adults and provides a new potential treatment for patients with deficits in response inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The effects of isoflavones on postmenopausal female's blood lipid profile have yielded conflicting results in previous studies. Further investigation is necessary to determine the potential benefits of isoflavone therapy in managing cardiovascular health in this population. This meta-analysis aimed to assess the effects of isoflavones on blood lipid concentrations in postmenopausal females. A comprehensive search was conducted in major databases for randomized controlled trials published between 2000 and 2023. Eighteen studies were included in the analysis, which examined the impact of isoflavone intake on blood lipids in postmenopausal females. Isoflavone consumption resulted in a significant reduction in triacylglycerol (TG) concentrations (-12.50 mg/dL; 95% CI: -23.09, -1.91) and a modest increase in high-density lipoprotein cholesterol (HDL cholesterol) concentrations (1.83 mg/dL; 95% CI: 0.03, 3.64). Subgroup analysis showed that isoflavones significantly decreased TG (-15.79 mg/dL; 95% CI: -28.36, -3.22) and increased HDL cholesterol (2.49 mg/dL; 95% CI: 1.80, 3.19) in postmenopausal females under 65 y old. No significant effects were observed in females over 65 y old. Both low (≤80 mg/d) and high (>80 mg/d) doses of isoflavones exhibited TG-lowering effects, whereas only the high dose increased HDL cholesterol. Longer treatment duration (≥24 wk) was associated with a significant reduction in TG, whereas HDL cholesterol improvement occurred during the early period (<24 wk) of supplementation. The consumption of isoflavones resulted in a significant reduction in TG concentrations and an increase in HDL cholesterol concentrations among postmenopausal females under 65 y of age., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the manual dynamic surface-enhanced Raman spectroscopy (D-SERS) detection process, it is difficult to focus on sample drop due to the constantly changing hotspot and easy judgment method. In this paper, we proposed an automatic focusing method based on long time stable hotspot with aid of optimization of hill-climbing algorithm and achieved on a designed device. First, set up a high temperature accelerating evaporation process to obtain hotspot and then cool to a low temperature rapidly to maintain it. Then, the spectral intensity was used as a focus of feedback signal in optimized hill-climbing algorithm to drive the sample stage to move up and down to adjust the depth of the laser on the samples to realize automatic focusing. As a result, the hotspot can be maintained for 5 min, and the autofocusing result can be achieved within 9 s, while the sensitivity was improved with two orders of magnitude in D-SERS detection of crystal violet (CV) compared with manual focusing., 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. Published by Elsevier B.V.)

- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration., 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 Elsevier Ltd. All rights reserved.)

Comprehensive interactome analysis of targeted proteins is important to understand how proteins work together in regulating functions. Commonly, affinity purification followed by mass spectrometry (AP-MS) has been recognized as the most often used technique for studying protein-protein interactions (PPIs). However, some proteins with weak interactions, which are responsible for key roles in regulation, are easily broken during cell lysis and purification through an AP approach. Herein, we have developed an approach termed in vivo cross-linking-based affinity purification and mass spectrometry (ICAP-MS). By this method, in vivo cross-linking was introduced to covalently fix intracellular PPIs in their functional states to assure all PPIs could be integrally maintained during cell disruption. In addition, the chemically cleavable crosslinkers which were employed enabled unbinding of PPIs for in-depth identification of components within the interactome and biological analysis, while allowing binding of PPIs for cross-linking-mass spectrometry (CXMS)-based direct interaction determination. Multi-level information on targeted PPIs network can be obtained by ICAP-MS, including composition of interacting proteins, as well as direct interacting partners and binding sites. As a proof of concept, the interactome of MAPK3 from 293A cells was profiled with 6.15-fold improvement in identification than by conventional AP-MS. Meanwhile, 184 cross-link site pairs of these PPIs were experimentally identified by CXMS. Furthermore, ICAP-MS was applied in the temporal profiling of MAPK3 interactions under activation by cAMP-mediated pathway. The regulatory manner of MAPK pathways was presented through the quantitative changes of MAPK3 and its interacting proteins at different time points after activation. Therefore, all reported results demonstrated that the ICAP-MS approach may provide comprehensive information on interactome of targeted protein for functional exploration., 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. Published by Elsevier B.V.)

Relatively low catalytic activity and poor targeting limit the applications of nanoceria (CeO 2 ) nanozymes in the treatment of tumors. Here, we designed a unique pushpin-like Au/CeO 2 hybrid nanozyme with high catalytic activity by combining site-selective growth and steric restriction strategies. The enhanced enzyme activity was attributed to plasmon-induced hot electrons. Furthermore, the pushpin-like structure facilitated targeting molecule modification. The nanozyme exhibited superior antitumor effects both in vitro and in vivo due to its high catalytic activity and targeting effects. Importantly, its potential mechanism of anti-tumor therapy was studied by quantitative proteomics. The reactive oxygen species (ROS) generated by folic acid-PEG thiol-Au/CeO 2 (FA-Au/CeO 2 ) caused mitochondrial and proteasomal damage in tumor cells and further evoked a response to oxidative stress and innate immunity in vivo. This study provided a spatiotemporal approach to enhance the antitumor activity of nanozymes by structural design. The designed pushpin-like Au/CeO 2 could be utilized as a multifunctional nanoplatform for in vitro and in vivo plasmon-enhanced cancer therapy with active targeting effects. Moreover, this study systematically explored the anti-tumor mechanism of the nanozyme in both cell and mouse models, promoting its translation to the clinic. STATEMENT OF SIGNIFICANCE: A strategy combining the principles of site-selective growth and steric restriction was developed to prepare a unique pushpin-like Au/CeO 2 hybrid nanozyme with high catalytic activity and low steric hindrance. The hybrid nanozyme showed superior antitumor activity at both the cellular and tissue levels. Furthermore, the antitumor mechanism was investigated in terms of the differential proteins and their pathways using quantitative proteomics, thus promoting the translation of nanozymes to the clinic., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In-depth proteome quantitation is of great significance for understanding protein functions, advancing biological, medical, environmental and metabolic engineering research. Herein, benefiting from the high formation efficiencies and intensities of dimethyl-labeled a1 ions for accurate quantitation, we developed an in-depth a1 ion-based proteome quantitation method, named deep-APQ, by a sequential MS/MS acquisition of the high mass range for identification and the low mass range for a1 ion intensity extraction to increase quantitative protein number and sequence coverage. By the analysis of HeLa protein digests, our developed method showed deeper quantitative coverage than our previously reported a1 ion-based quantitation method without mass range segmentation and lower missing values than widely-used label-free quantitation method. It also exhibited excellent accuracy and precision within a 20-fold dynamic range. We further integrated a workflow combining the deep-APQ method with highly efficient sample preparation, high-pH and low-pH reversed-phase separation and high-field asymmetric waveform ion mobility spectrometry (FAIMS) to study E. coli proteome responses under the nutritional conditions of glucose and acetate. A total of 3447 proteins were quantified, representing 82% of protein-coding genes, with the average sequence coverage up to 40%, demonstrating the high coverage of quantitation results. We found that most of the quantified proteins related to chemotaxis were differentially expressed, including the low-abundance proteins such as tap, trg, aer, cheA and cheB, indicating that chemotaxis would play an important role for E. coli cell to survive from acetate toxicity. The above results demonstrated that the deep-APQ method is of great promising to achieve the deep-coverage proteome quantitation with high confidence., 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 Elsevier B.V. All rights reserved.)

Protein de novo sequencing based on tandem mass spectrometry is a crucial technology that enables the identification of peptides without searching databases and assembling unknown sequence proteins, especially for monoclonal antibodies (mAbs). However, the discrimination of leucine (Leu) and isoleucine (Ile) residues in the target protein sequence is still challenging. Herein, we developed an accurate method by continuous digestion with MS 3 -based fragmentation and multiple spectra integration (evaluated by combined verification score, CVS) to distinguish Leu and Ile residues. Continuous digestion promotes the diversity of peptides in order to expose more Leu and Ile at the N-terminal. CVS integrates multiple MS 3 spectra to reduce the interference from noise and co-fragmented ions and improve accuracy. This method successfully resolved all 75 Leu/Ile in bovine serum albumin, especially 3 consecutive Leu/Ile. We further applied the method to analyze trastuzumab and 67 out of the 68 Leu/Ile from the light chain and heavy chain were accurately discriminated, demonstrating the great potential in mAbs sequencing., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Protein N-phosphorylation is increasingly recognized as a critical post-translational modification in central metabolism and cell signaling. However, other functions of N-phosphorylation in organism are largely unexplored which is attributed to lack high efficient enrichment methods. To address this, Bis(zinc(II)-dipicolylamine) functionalized graphene oxide nanocomposites (Zn(II)-DPA-GO) was designed via loading bis(zinc(II)-dipicolylamine) (Zn(II)-DPA) on graphene oxide surface by π-π stacking, with the advantages of large immobilization amount of Zn(II)-DPA, layered structure, excellent solubility and low non-special adsorption. The material was firstly verified excellent enrichment ability for standard proteins and E.coli lysates. By integrating the enrichment method into proteomics workflow, 36 N-phosphoproteins functioned in metabolic process, biological regulation, localization, cellular processes were identified from Bacillus subtilis. Furthermore, motif analysis showed that leucine and isoleucine were enriched near the sites, providing potential clues for the discovery of new sites. The method provides an alternative for the discovery of N-phosphoproteins with significant biological functions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cell surface-exposed proteins (CSPs), termed the surfaceome, play a key role in many cellular processes. In-depth CSP analysis is significant for screening candidate biomarkers and drug targets. Highly selective enrichment of CSPs in physiological cellular environments is attractive but remains technically challenging. Here, we present a photocrosslinking-assisted cell surface protein enrichment (PCSPE) strategy. In this strategy, CSP labeling would be achieved within 2 min of UV irradiation by developing a new photocrosslinking probe (SDB) followed by one-step enrichment. The enrichment selectivity of CSPs reached 70.5%, and we identified up to 1017 CSPs from living HEK-293T cells, attributed to the high photocrosslinking reactivity and inherent impermeability of SDB, as well as the high cell viability maintained after rapid cell surface labeling to decrease the interference of intracellular proteins. Finally, this strategy was successfully applied to sorafenib-resistance cells for quantitative surfaceome analysis. All results demonstrated that our developed PCSPE method might provide a valuable toolkit for in-depth surfaceome profiling and comprehensive functional analysis., 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 Elsevier B.V. All rights reserved.)

Luliconazole (LCZ) is a novel antifungal imidazole with broad-spectrum and high susceptibility of Aspergillus and Fusarium are the dominant species of fungal keratitis, may potentially be a new medical treatment option for ocular fungal infection. To evaluate LCZ distribution in ocular tissues after topical application for the development of ophthalmic delivery system, it is important to have a bioanalytical method for measuring the drug concentrations in different ocular tissues and aqueous humor (AH). A selective and sensitive ultrahigh performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantification of LCZ in rabbit ocular tissues, including conjunctiva, cornea, AH, iris, lens, vitreous humor (VH), retinal choroid and sclera, using lanoconazole as internal standard (IS). Chromatographic separation was achieved on a Xterra MS, C18 column (2.1 × 50 mm, 3.5 μm) using mobile phase with formic acid solution (0.2%, v/v): acetonitrile (50:50, v/v) at a flow rate of 0.2 ml/min, and the run time was 2.5 min. Detection was performed using the transitions 354.1 → 150.3 m/z for LCZ and 320.1 → 150.3 m/z for IS by positive ion electrospray ionization in multiple reaction monitoring (MRM) mode. Method validation was conducted in accordance with U.S. Food and Drug Administration's regulatory guidelines for bioanalytical method validation. The calibration curves were linear over the concentration range from 2.80 ng/ml to 2038 ng/ml for conjunctiva, cornea and sclera, 2.09 ng/ml to 1019 ng/ml for AH, 2.09 ng/ml to 509.5 ng/ml for iris, 2.09 ng/ml to 203.8 ng/ml for retinal choroid and VH, 2.04 ng/ml to 101.9 ng/ml for lens, with all the squared correlation coefficients (r 2 ) more than 0.99. The accuracy of the method was within the acceptable limit of 89.34%∼112.78% at the lower limit of quantification and other concentrations, Inter-day and intra-day precision values, expressed in terms of RSD (%), in all tissues were within 15% at all concentrations. The mean recoveries of LCZ in rabbit ocular tissues was 84.85%∼100.52%. No interference was found due to matrix components. Luliconazole was stable during the stability studies, including autosampler stability, benchtop stability, freeze/thaw stability and long-term stability. The method was successfully applied to the ocular pharmacokinetic and tissues distribution studies of LCZ in rabbit after topical administration of LCZ ophthalmic drug delivery system., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Atmospheric fine particle pollution is known to cause many adverse health effects. However, the potential mechanisms of PM 2.5 -induced cytotoxicity still needs further understanding. Herein, we integrated cytotoxicity, component profiling, metabolomics and proteomics data to deeply explain the biological responses of human bronchial epithelial cells exposed to PM 2.5 . We observed that PM 2.5 caused cell cycle arrest, calcium influx, cell damage and further induced cell apoptosis. The contents of heavy metals and 4-6 rings PAHs in PM 2.5 were positively correlated with intracellular ROS, indicating that they might be the important components to induce the above cytotoxicity. Integrated metabolomics and proteomics analysis revealed the significant alterations of many metabolic processes, such as glycolysis, the citric acid cycle, amino acid metabolism and lipid metabolism. Notably, we found that PM 2.5 inhibited the integrin signaling pathway, including down-regulating the protein expression of integrins and the phosphorylation of downstream signaling kinases, which might ultimately affect cell cycle progression, cell metabolism and apoptosis. This study provided a comprehensive data resource for the deep understanding of biological toxicity mechanisms caused by atmospheric fine particles in human lung-bronchial epithelium cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

To enhance therapeutic efficacy and reduce adverse effects, ancient practitioners of traditional Chinese medicine (TCM) prescribe combinations of plant species/animal species and minerals designated "TCM formulae" developed based on TCM theory and clinical experience. TCM formulae have been shown to exert curative effects on complex diseases via immune regulation but the underlying mechanisms remain unknown at present. Considerable progress in the field of immunometabolism, referring to alterations in the intracellular metabolism of immune cells that regulate their function, has been made over the past decade. The core context of immunometabolism is regulation of the allocation of metabolic resources supporting host defense and survival, which provides a critical additional dimension and emerging insights into how the immune system and metabolism influence each other during disease progression. This review summarizes research findings on the significant association between the immune function and metabolic remodeling in health and disease as well as the therapeutic modulatory effects of TCM formulae on immunometabolism. Progressive elucidation of the immunometabolic mechanisms involved during the course of TCM treatment continues to aid in the identification of novel potential targets against pathogenicity. In this report, we have provided a comprehensive overview of the benefits of TCM based on regulation of immunometabolism that are potentially applicable for the treatment of modern diseases., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

There are increasing concerns with regard to spontaneous abortion (SAB), the loss of pregnancy without external intervention before 20 weeks of gestation, among reproductive-aged women. To date, limited evidence is available concerning the association between SAB and air pollutants, especially in developing countries. Daily baseline outpatient data for SAB from January 1, 2014, to December 31, 2018 (1826 days) were obtained in Chongqing, a metropolis of southwest China. The over-dispersed Poisson generalized additive model with control of meteorological conditions and day of week was used to estimate the short-term effects of ambient air pollution on the daily number of SAB outpatients. A total of 42,334 SAB outpatient visits for SAB were recorded. No statistically significant association was observed between SAB and CO, PM 2.5 , PM 10 , O 3 , and SO 2 . The positive association only appeared for NO 2 : positive associations between SAB and NO 2 were observed in both single-day models (lag 0, lag 1, lag 3, and lag 4) and cumulative exposure models (lag 01, lag 03, and lag 05) and the most significant effects were observed at lag 05 (3.289%; 95% CI: 1.568%, 5.011%). Moreover, the women with higher ages (30-39 and > 39) were more sensitive than those with lower ages (18-29), and the effect estimates were more evident in cool seasons. Collectively, our results suggested that short-term NO 2 exposure was associated with higher risk of SAB, especially in elder women and cool seasons, which may contribute to further understand the role of air pollution on SAB and other adverse obstetric outcomes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, we developed a fully integrated protein absolute quantification platform for simultaneous analysis of multiple tumor markers in human plasma, by which multiple target proteins (alpha-fetoprotein, prostate-specific antigen, carcino-embryonic antigen and mucin-1) were firstly enriched by aptamers immobilized capillary column using graphene oxide modified polymer microsphere as the separation matrix, and then the eluted target proteins were online denatured, reduced, desalted and digested by our developed fully automated sample treatment device (FAST), finally the resulting peptides were analyzed by parallel reaction monitoring (PRM) on LTQ-orbitrap velos mass spectrometry. Compared to traditional ELISA assay, the platform exhibited significant advantages such as short analysis time, low limit of detection, and ease of automation. Furthermore, our developed platform was also applied in the absolute quantification of tumor markers from clinical human plasma samples, and the results were comparable to those obtained by clinical immunoassay. All the results demonstrated that such a platform could provide a promising tool for achieving high sensitivity, high accuracy, and high throughput detection of disease related protein markers in the routine physical examination and clinical disease diagnosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

SUMOylation is a reversible post-translational modification that plays crucial roles in numerous cellular processes. Although anti-SUMO antibodies have been applied to analyze exogenous and endogenous SUMOylation, such immunoprecipitation enrichment strategy is applicable only for the enrichment of one specific SUMO type in mammalian cells, unable to map the global landscape of all endogenous SUMOylation simultaneously. To address this issue, we proposed an antibody-free strategy to enrich and profile endogenous SUMO1/2/3-modified peptides simultaneously. Upon trypsin digestion, the SUMO1- and SUMO2/3-modified peptides contained SUMO remnants with 7 and 9 acidic amino acids respectively, which carried more negative charges at high pH and could interact with strong anion exchange (SAX) materials more strongly than non-SUMOylated peptides, thus enabling the specific enrichment of endogenous SUMOylated peptides. Followed by the secondary digestion with Asp-N/Glu-C to generate smaller SUMOylated peptides with proper length for MS identification, off-line high-pH C18 pre-fractionation and low pH nanoRPLC-ESI-MS/MS analysis, 177 SUMO1-modified sites and 74 SUMO2/3-modified sites were unbiasedly identified in HeLa cell lysate. To the best of our knowledge, this was the first antibody-free strategy to comprehensively profile various endogenous SUMOylation sites, demonstrating the great potential in the comprehensive analysis of endogenous SUMOylation across various species and organs, which might further facilitate the understanding of SUMO's function in physiology and pathology., 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 © 2021 Elsevier B.V. All rights reserved.)

In this study, we developed an integrated plasma proteome sample preparation system, by which high-abundance proteins from human plasma were first depleted by immunoaffinity column, followed by on-line middle and low-abundance proteins denaturation, reduction, desalting and tryptic digestion. To evaluate the performance of such a system, 20 μL plasma was processed automatically, followed by 1-h gradient liquid chromatography-mass spectrometry analysis (LC-MS). Compared to conventional in-solution protocols, not only the sample preparation time could be shortened from 20 h to 20 min, but also the number of identified proteins were greatly increased by 1.4-2.0 times. Such an integrated system allows us to process 36 human plasma samples per day, with more than 300 proteins and 52 FDA approved disease markers per sample being identified. With combination of such an integrated sample preparation system with label-free single-shot LC-MS/MS, the human plasma proteins could be quantified across more than 6 orders of magnitude of abundance range with high reproducibility (Pearson R = 0.99, n = 9). In addition, the relative quantification of human plasma samples from diabetic retinopathy patients and diabetic patients demonstrated the feasibility of our developed workflow for clinic plasma proteome profiling. All these results demonstrated that our developed integrated plasma proteome sample preparation system would provide a new tool for high throughput biomarker discovery., 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 © 2021 Elsevier B.V. All rights reserved.)

Mammalian sperm is highly susceptible to reactive oxygen species (ROS) during the cryopreservation process. Astaxanthin (AST), a red pigment of the carotenoid family, is recognized as having a variety of beneficial biological activities and effects, including antioxidant, anticancer, anti-diabetic, and anti-inflammatory. The present study aimed to investigate whether the presence of AST protected boar sperm from ROS stress during cryopreservation. Boar sperm was diluted with a freezing medium supplemented with different concentrations of AST (0, 0.5, 1, 2, or 5 μM). The addition of AST, especially at a concentration of 2 μM, exerted positive effects on post-thaw sperm motility parameters. Meanwhile, sperm plasma membrane integrity and acrosome integrity of post-thaw sperm were significantly increased, while lipid peroxidation was inhibited in response to 2 μM AST treatment. Interestingly, compared to the control, supplementation with 2 μM AST increased unsaturated fatty acids (UFAs) levels and decreased saturated fatty acids (SFAs) content in post-thaw sperm, leading to a decreased ratio of SFAs/UFAs in the AST group. In conclusion, the addition of AST to freezing extenders inhibited lipid peroxidation and regulated fatty acid composition of the sperm membrane, improved post-thaw sperm quality, and had no adverse effect on boar sperm in vitro fertilization (IVF) capacity and potential for embryonic development. Our data provide a novel insight into understanding the mechanisms of AST concerning protecting boar sperm quality against ROS damage during cryopreservation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The case spectrum in hand surgery is one of extremes-purely elective day surgery cases under local anesthesia to mangling limb injuries that require immediate, and frequently, lengthy, surgery. Despite the cancellation of most elective orthopedic and plastic surgical procedures, hand surgeons around the world continue to see a steady stream of limb-threatening cases such as severe trauma and infections that require emergent surgical care. With the increase in community-spread, an increasing number of COVID-19-infected patients may be asymptomatic or have mild, nonspecific or atypical symptoms. Some of them may already have an ongoing, severe infection. The time-sensitive nature of some of these cases means that hand surgeons may need to operate urgently on patients who may be suspected of COVID-19 infections, often before confirmatory test results are available. General guidelines for perioperative care of the COVID-19-positive patient have been published. However, our practices differ from those of general orthopedic and plastic surgery, primarily because of the focus on trauma. This article discusses the perioperative and technical considerations that are essential to manage the COVID-19 patient requiring emergency care, without compromising clinical outcomes and while ensuring the safety of the attending staff., (Copyright © 2020 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Urinary proteome, as an important component of body fluid proteome, could reflect kidney, urogenital tract function and pathological changes of human organs. This study reports a convenient strategy for urine proteome analysis through ampholine immobilized polymer microsphere (ampholine@PM) fractionation strategy. After ampholine@PM treatment, 16,543 unique peptides corresponding to 2173 non-redundant urinary proteins were identified, while only 856 proteins, corresponding to 3524 peptides were identified in the crude urine sample. The number of proteins and peptides was increased by 1.54 and 3.69 times, respectively. 31 urinary candidate biomarkers have also been identified (17 candidate biomarkers of glomerular injury and 14 candidate biomarkers of tubular injury), showing the potential of our strategy in urinary biomarker discovery study. In additional to the urine proteome, N-glycoproteome analysis was also performed after ampholine@PM fractionation followed by the N-glycopeptides enrichment. The number was increased from 144 to 281 for N-glycoproteins, 261 to 709 for N-glycopeptides, and 226 to 493 for N-glycosylation sites, after ampholine@PM treatment. Based on the significant increase on the identified N-glycoprotein number, ampholine@PM fractionation strategy also offered a beneficial tool for the post translational modification analysis of urine proteome., 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 © 2020 Elsevier B.V. All rights reserved.)

Carbon monoxide (CO) is a well-known "toxic gas". It represents a toxic inhalation hazard at high concentration and is commonly found in polluted air. However, a series of recent studies have suggested that low concentration of CO can also produce protective functions. This study was performed to investigate the association between ambient CO exposure and vaginitis outpatient visits. Daily baseline outpatient data of vaginitis from January 1, 2013 to December 31, 2015 were obtained from Xi'an, a heavily-polluted metropolis in China. The over-dispersed Poisson generalized additive model was applied to discover the relations between short-term ambient CO exposure and the number of vaginitis outpatient visits by adjusting day of the week and weather conditions. A total of 16,825 outpatient hospital visits for vaginitis were recorded. The mean daily concentration of carbon monoxide (CO) was well below Chinese and WHO guidelines. During the study period, increased levels of ambient CO was associated with reduced outpatient-visits through concurrent to lag 5 days, and the most significant association was evidenced at lag 05. A 0.1 mg/m 3 increase in daily average CO at lag 05 corresponded to -1.25% (95%CI: -1.85%, -0.65%) change in outpatient-visits for vaginitis. Moreover, the association was more significant in those women aged 20-29 years. After adjustment for PM 10 , PM 2.5 , SO 2 , and NO 2 , and O 3 , the negative associations of CO with vaginitis kept significant, suggesting relative stability of effect estimates. In summary, this is the first evidence that increased ambient CO exposure can be related to reduced daily outpatient visits for vaginitis. The results of our study may not only help to establish more comprehensive understanding of the health effects of ambient air on vaginitis and other gynecological diseases, but also provide a clue to new potential interventions., 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 © 2020 Elsevier B.V. All rights reserved.)

Protein phosphorylation is one of the most important post-translational modifications (PTM) and plays critical roles in maintaining many biological processes of plant species, such as being a significant signal related to resistance to tobacco mosaic virus (TMV) infection in tobacco. Compared to other organisms, in-depth profiling of plant phosphoproteome remains challenging due to the harsh extraction environment of plant proteins and low abundance of plant phosphorylation, generally requiring large amount of plant materials. Herein, we developed an integrated strategy for efficient sample preparation of amounts of plant tissues, by integrating ionic liquid (IL)-assisted protein extraction, in-solution digestion, precipitation-assisted IL removal, as well as immobilized metal ion affinity chromatography (IMAC) enrichment of phosphopeptides together. In this strategy, to improve the efficiency of protein extraction and enzymatic digestion, IL of 1-dodecyl-3-methylimidazolium chloride (C12Im-Cl) was used as the solubilizer due to its excellent solubilizing ability and enzyme compatibility demonstrated in our previous work. Briefly, the extraction capability of C12Im-Cl for protein amount from tobacco leaves was improved 1.9-fold compared to the commonly used urea-assisted method. Notably, to avoid its interference with subsequent LC-MS analysis, the IL was easily removed from the peptide solution by our proposed ion substitution-mediated C12Im + precipitation strategy with high efficiency. By handling 10 mg of starting protein materials of tobacco leaves, 14,441 unique phosphopeptides, assigned to 5153 unique phosphoproteins were confidently identified. To the best of our knowledge, this was the most comprehensive phosphorylation dataset for tobacco so far. All the results demonstrated our strategy was of great potential to promote the large-scale analysis of plant phosphoproteome., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier B.V.)

Menstrual disorders are common diseases among reproductive-aged women with increasing concerns. Until now, there have been limited studies about the association between menstrual disorders and air pollution. This study aimed to investigate the association between short-term (concurrent day and within 1 week prior) ambient air pollution exposure and menstrual disorder outpatient visits in Xi'an, a metropolis in northwestern China. Daily baseline outpatient data of menstrual disorders from January 1, 2010 to February 18, 2016 (2239 days) were obtained. An over-dispersed Poisson generalized additive model was applied to discover the relationship between short-term air pollution exposure and the number of menstrual disorder outpatient visits by adjusting the day of the week and weather conditions. A total of 51,893 outpatient visits for menstrual disorders were recorded. A 10 μg/m 3 increase of PM 10 and NO 2 concentrations corresponded to 0.236% (95% Cl: 0.075%, 0.397%) and 2.173% (95% Cl: 0.990%, 3.357%) elevations in outpatient-visits for menstrual disorders at lag 7 and lag 01 (concurrent day and previous 1 day), respectively. The association was more significant in young females (18-29 years) and there was no obvious association observed between SO 2 and menstrual disorder outpatient visits. This is the first evidence that short-term exposure to ambient air pollution can be associated with an increased risk of menstrual disorder attacks. The results of our study may help to establish more comprehensive understanding of the health effects of ambient air pollution on menstrual disorders and other reproductive diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Diabetic nephropathy (DN), a kind of microvascular complication, is a primary cause of end-stage renal disease worldwide. However, therapeutic drugs for DN treatment are still in lack. The glomerular endothelium is essential to maintain selective permeability of glomerular filtration barrier and glomerular vasculature function. Growing evidences show that endothelial dysfunction or injury is the initial stage of vascular damage in DN, which can be induced by hyperglycemia, lipotoxicity, and inflammation. Therefore, to improve the function of vascular endothelium in kidney is a key point for treatment of DN. As a plant isoflavone, tectorigenin (TEC) has attracted considerable attention due to its anti-proliferative and anti-inflammatory functions. However, whether TEC could inhibit the DN development remains unknown. In this study, we examined the effects of TEC on DN development in db/db mice, a type of genetic defect diabetic mice that can spontaneously develop into severe renal dysfunction. Intriguingly, TEC treatment restored diabetes-induced glucose and lipid metabolic disorder; and improved the deterioration of renal function, particularly the renal endothelium function in db/db mice. Additionally, TEC inhibited the renal inflammation via reducing macrophages infiltration and M1 polarization. Moreover, TEC inhibited lipopolysaccharide (LPS)-induced endothelial injury and M1 polarization in vitro. Mechanistically, TEC partially restored the reduction in expression of adiponectin receptor 1/2 (AdipoR1/2), pi-LKB1, pi-AMPKα, and PPARα in vitro and in vivo. Noteworthy, these beneficial pharmacological activities mediated by TEC were significantly attenuated after AdipoR1/2 knockdown by siRNA, indicating that AdipoR1/2 plays a critical role in protection against DN. Collectively, these results suggested that TEC have a potently effect for retarding type 2 diabetes-associated DN., Competing Interests: Declaration of Competing Interest None declared, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Velvet antlers (VA) have been used as medicines and nutraceuticals for over 2000 years. Meanwhile, deer antlers are the only mammalian organs that can fully regenerate after annual shedding. The antler formation and regeneration rely on the stem cells resident in antlerogenic periosteum (AP), transplantation of which can induce ectopic antler formation. Here, a comprehensive quantitative proteomic analysis of antlerogenic periosteal cells (AP cells), compared with the adjacent facial periosteal cells (FP cells), was carried out, from both extracellular and intracellular perspectives. In this study, the stable isotope labeling by amino acids in cell culture (SILAC) was applied to ensure the precision of quantification. Then, the protein equalization strategy and reverse-phase liquid chromatography (RPLC) separation in high pH were utilized to improve the depth of proteome profiling. Proteomics analysis of the conditioned media (CM) from AP and FP cells showed that significantly over-expressed extracellular proteins in AP cells were involved in cell proliferation, angiogenesis and neurogenesis. Combining the extracellular and intracellular proteomes, we found several potential secreted proteins might regulate antler formation and regeneration, such as SFRP4 and LUM. These results provide new insight into the underlying mechanism of antler formation and regeneration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Heat stroke is a symptom of hyperthermia with a temperature of more than 40 °C, which usually leads to all kinds of physical discomfort and even death. It is necessary to study the mechanism of action of heat stroke on cells or organelles (such as cytotoxicity of heat) and the processes of cells or organelles during heat stroke. Recent studies have shown that there is a certain correlation between heat stroke and lysosome acidity. In order to clarify their relationship, Lyso-NIR-pH, a photostable Si-rhodamine-based near-infrared fluorescent probe, was developed for sensing pH changes in lysosomes during heat stroke in this paper. For Lyso-NIR-pH, a morpholine group is employed as the lysosome-targeting unit and a H + -triggered openable deoxylactam is employed as the response unit to pH. Lyso-NIR-pH can detect pH with a high selectivity and a sensitivity, and its pK a is 4.63. Lyso-NIR-pH also has outstanding imaging performances, such as excellent lysosome-targeting ability, low autofluorescence and photostable fluorescence signal, which are in favor of long-term imaging of pH with accurate fluorescence signals. Moreover, we successfully applied Lyso-NIR-pH to monitor lysosomal pH increases induced by chloroquine and apoptosis in live cells. Finally, we successfully applied Lyso-NIR-pH for monitoring changes of lysosomal pH during heat stroke. These results confirmed that Lyso-NIR-pH is a powerful tool to monitor pH change in lysosomes and study its possible effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)