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Alumina (Al2O3) ceramic has been widely used in various fields, but it has certain difficulties in machining as a hard and brittle material. While laser-assisted grinding (LAG), an alternative and novel method for fabrication of alumina ceramic, can utilize laser beam to locally heat the workpiece before the ceramic is removed, thereby reducing fracture toughness and keeping the surface integrity. In this paper, a thermal model is established to study and understand the processing mechanism of the LAG process. Meanwhile, an orthogonal experiment is designed and implemented to optimize the grinding process. Then, by analyzing the surface topography, the advantages of LAG are strongly proved. It is found that the temperature modelling results matches experimental results well. The processing parameter that has greatest impact on surface roughness is laser power, followed by grinding depth and wheel speed, and feeding speed at last. The optimal surface roughness value can be obtained by certain processing parameters. Also, compared to conventional grinding (CG), the removal method of alumina ceramics alters from brittle fracture to plastic fracture. Overall, this study clearly elucidates that LAG of alumina ceramic is a very promising machining method, and can be potentially utilized for various industrial, aerospace and automobile applications.

In this paper, a mathematical model for simulating the grain evolution process of ceramic materials was constructed to investigate the effects of the sintering parameters on the microstructure in the spark plasma sintering process. Firstly, a new algorithm of removing the right angle of grain was improved and an improved cell state assignment method was proposed based on the cellular automata model. Then the sintering parameters were coupled into the model, and the simulation method of grain growth and pore evolution were proposed. Finally, a ceramic material grain evolution model with stomata structure for spark plasma sintering was constructed. The simulation results showed that the grain size increased exponentially with the increases of holding time and sintering temperature, while the pores gradually decreased with the increase of the two parameters and the density of the material. Besides, the uniformity of grain growth also decreased with the increase of holding time. These results conformed to the topological characteristics of grain growth and the law of grain boundary migration, and can provide support for the sintering parameters optimization of ceramic tool materials.

Advanced glycation end products (AGEs) are associated with the occurrence of human chronic diseases, and exist commonly in thermally processed foods, such as infant formula. Existing research mainly focuses on the discrete simulation system, which is time-consuming and challenging, but accumulates of a large amount of valuable data. This study aimed to propose a specific Molecular Transformer-based model trained on the data curated from literature to predict the chemical reaction of AGEs, and apply it to infant formula to observe which new reactions could generate AGEs. The model achieved top-3 accuracy of 76.0% on the total dataset. Based on the model prediction results, five reactions were selected for experimental verification, and four of them were consistent with the model prediction results. This prospective study might potentially revolutionize the discovery of AGEs reactions and provide theoretical guidelines for designing a safer infant formula.

Background We conducted this study to evaluate whether patients with T1a/b, node-negative (N−), human epidermal growth factor receptor 2-positive (HER2+) breast cancers benefited from adjuvant therapy, and explored better treatment strategies for these patients. Patients and Methods Patients with T1a/b, N−, HER2+ breast cancers during 2000 through 2004 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Gray test was used to evaluate breast cancer-specific death (BCSD) and non-BCSD. To identify patients more suitable for chemotherapy, subgroup analyses were conducted according to tumor size and estrogen receptor (ER) status, and plots of hazard rate of death (HRD) were drawn to present the changes of BCSD. Results A total of 2940 patients with T1a/b, N−, HER2+ breast cancers were included; more patients in the T1b group received chemotherapy compared with the T1a group (65.18% vs. 29.30%; P Conclusion Chemotherapy, which is mainly decided by tumor size, fails to render survival benefits for patients with T1a/b, N−, HER2+ breast cancers. ER status, rather than tumor size, is important for clinicians to make adjuvant treatment decisions. The peak of BCSD occurs 2 to 5 years after diagnosis, and an at least 5-year follow-up is recommended for these patients.

The tubulin colchicine binding site has been recognized as an attractive drug target to combat cancer, but none of the candidate drugs have been approved for medical treatment. We recently identified a structurally distinct small molecule S-40 as an oral potent tubulin destabilizing agent. Crystal structure analysis of S-40 in a complex with tubulin at a resolution of 2.4 A indicated that S-40 occupies all 3 zones in the colchicine pocket with interactions different from known microtubule inhibitors, presenting unique effects on assembly and curvature of tubulin dimers. S-40 overcomes paclitaxel resistance and lacks neurotoxicity, which are the main obstacles limiting clinical applications of paclitaxel. Moreover, S-40 harbors the ability to inhibit growth of cancer cell lines as well as patient-derived organoids, induce mitotic arrest and cell apoptosis. Xenograft mouse models of human prostate cancer DU145, non-small cell lung cancer NCI–H1299 and paclitaxel-resistant A549 were strongly restrained without apparent side effects by S-40 oral administration once daily. These findings provide evidence for the development of S-40 as the next generation of orally effective microtubule inhibitors for cancer therapy.

In this work, we conduct a systematic experimental investigation of surface integrity for steel and aluminum alloys processed via nanosecond laser-based high-throughput surface nanostructuring (nHSN) process. nHSN surface morphology and surface chemistry are first experimentally characterized, and the results show that surface nanostructure with proper surface chemistry is generated due to the combined effect of chemical etching and attachment of functional groups of low surface energy. Desired surface wetting behavior is achieved using a proper silane reagent during the nHSN chemical immersion treatment phase, while surface nanostructure can be finely modulated by adjusting the laser processing parameters. nHSN nanostructures with fluorosilane chemistry exhibit strong capability to repel water, leading to superhydrophobicity achieved on two important engineering metal alloys, namely steel and aluminium alloys. It is further experimentally demonstrated that the microhardness and anti-corrosion performance of the nHSN surface can be significantly enhanced compared with the untreated surface, indicating that the nHSN process is very effective for enhancing the mechanical strength and corrosion resistance of these important metal alloys. These results show that nHSN simultaneously creates random nanostructures, attains desirable surface chemistry and enhances surface integrity over large-area metal alloy surfaces.

Antibiotic-metal complexes (AMCs) formed by antibiotics and metal ions have attracted considerable attentions in recent years. Although different removal methods for AMCs have been reported in the literature, very few investigations have focused on the mechanisms and toxic effects of antibiotic-metal coordination. This review briefly describes the structural characteristics of various commonly used antibiotics and the coordination mechanisms with metal ions. Considering the complexity of the real environment, various environmental factors affecting AMC formation are highlighted. The effects of AMCs on microbial community structure and the role of metal ions in influencing resistant genes from the molecular perspective are of interest within this work. The toxicities and mechanisms of AMCs on different species of biota are also discussed. These findings underline the need for more targeted detection and analysis methods and more suitable toxicity markers to verify the combination of antibiotics with metal ions and reveal environmental toxicities in future. This review presents an innovative idea that antibiotics combined with metal ions will change the toxicity and environmental behavior of antibiotics.

This paper proposes a calibrated phase-shifting digital holography by using a single camera. In the proposed system, two types of information are recorded simultaneously in a single image based on the space-division-multiplexing technique. One type of information is used to reconstruct the object image, while the other is used to calculate the phase-shifting amount. As the proposed method can detect the phase-shifting amount accurately without using any additional electronic devices, a simple low-cost high-quality image reconstruction phase-shifting digital holography system can be developed. The effectiveness of the proposed system is demonstrated through experiments.

In this paper, we investigate the stochastic Novikov equation with an additive noise. Using regularization, the local well-posedness of this equation is established by trilinear estimates of the approximate solution.

The machining performance of a high-energy nanosecond pulse laser with a near-infrared wavelength is investigated for carbon fiber-reinforced polymer (CFRP) with two different fiber arrangements. This research work demonstrates for the first time that a keyhole mode cutting can be achieved for CFRP materials using a high-energy nanosecond pulse laser of a Long Pulse mode (120 ns). Specifically, it is shown that the short-duration Q-Switch mode (8 ns) results in ineffective material removal for CFRP, despite much higher peak laser power intensity than the Long Pulse mode. In Long Pulse mode, multi-pass straight line and contour cutting experiments are further performed to investigate the effect of laser processing parameters and resultant machined surface integrity. Plasma absorption effects using both pulse modes are discussed. The results show that a 2.2 mm thick cross-ply CFRP panel can be cut through using as few as 6 laser passes, and a high-quality machined surface can be produced with a limited heat-affected zone and minimal fiber pull-out using Argon assist gas. The successful outcomes from this work provide the key to enable efficient CFRP laser machining using high-energy nanosecond pulse lasers, and offer insight into the unique energy absorption mechanisms for CFRP laser machining.

An experimental study was conducted to characterize the laser-textured surfaces fabricated by using a novel nanosecond Laser-based High-throughput Surface Nanostructuring (nHSN) method. While the two-step nHSN approach (i.e., water-confined nanosecond laser texturing and chemical immersion treatment) in producing superhydrophobicity over metal surfaces is described in great details, a throughput analysis of different laser-based surface texturing methods is also performed in the term of Specific Laser Scanning Time (SLST). It is found that the nHSN process significantly increases the processing rate from hundreds of minutes per square inch to seconds in comparison to the existing ultrashort laser-based surface texturing techniques. In order to examine the performance of the novel nHSN-treated surfaces in the term of “water-/ice-repellency”, a series of experiments were performed in the present study to not only characterize the surface structures and wettability of the nHSN-treated aluminum surfaces, but also evaluate the effects of the nHSN treatment on the dynamics of water droplet during the impacting process (i.e., spreading, receding, and rebounding), as well as their capability in reducing ice adhesion strength. It is found that, while the untreated bare aluminum surface and the only laser-textured aluminum surface are hydrophilic with the static contact angle being smaller than 90° and the contact angle hysteresis being larger than 90°, the nHSN-treated surfaces appear to be superhydrophobic with a significantly larger static contact angle (i.e., ~170°) and a much smaller contact angle hysteresis (i.e., ~20°). The superhydrophobicity of the nHSN surfaces is further promoted to “ice-repellency” by the complete droplet rebounding phenomenon in the dynamic water droplet impacting process and the reduced ice adhesion strength.

In this work, an innovative high-throughput laser surface nanostructuring process was developed to enhance the hydrophobicity and reduce the reflectivity of the Ti-6Al-4V surface using a nanosecond pulse laser. The laser textured Ti-6Al-4V surfaces exhibit combined anti-reflective, highly hydrophobic and mechanically enhanced effects. In the meantime, the anti-reflective Ti-6Al-4V surfaces show different colors when treated by different laser processing parameters. Compared with the existing ultra-short laser-based surface-texturing methods which often rely on the generation of micro-scale patterns using a focused laser spot and very fine spatial resolution, this innovative laser surface treatment method significantly increases the processing speed and reduces the production cost. This novel process will bring a new avenue for controlling the surface color, wettability and mechanical property of the important engineering surfaces.

Towards clarifying underlying behavior of dwell fatigue in Ti alloys, we here present the first example of 1 second- and 1 μm-resolved full-field dynamic strain mapping. It has been realized by developing a video sampling moire method combined with a video acquisition way in a scanning electron microscope (SEM). Monotonic strain increments during displacement holding for 10 min in dwell fatigue are visually characterized in both smooth and cracked Ti-6Al-4V specimens. The strain rates from 10−6 to 10−5 s−1 of average and maximum strains, as well as the remaining plastic strain were experimentally measured in both specimens. The strain distributions are coupled with grain boundaries to discuss the strain evolution characteristics. Experimental results indicate that both crack initiation and growth in the Ti-6Al-4V alloy are sensitive to even several tens of second-scale load/displacement holding.

Herein, a schematic model was established to assess the combined effect of deposited CaCO3 and thermophilic sulfate-reducing bacteria (SRB), at high CO2 and low O2 dissolution levels on the corrosion behavior and growth of corrosion scale on X65 pipeline carbon steel. Field emission scanning electron microscopy, energy-dispersive spectrometry, X-ray diffraction, confocal laser scanning microscopy, open circuit potential, and electrochemical impedance spectroscopy were used to characterize the corrosion pattern of water injection pipe. The results showed that a synergistic effect exists between CaCO3 and thermophilic SRB, both uniform and localized corrosion of CaCO3-coated X65 steel were promoted when inoculated with SRB. The corrosion process was comprised of three stages depending on the metabolism of SRB.

We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic effects in type 2 diabetes db/db mice and spontaneous diabetic monkeys. In this study, we investigated the pharmacokinetics and pharmacodynamics of supaglutide by single subcutaneous and intravenous injection(s) in rats and rhesus monkeys, as well as fourconsecutive subcutaneous injections in monkeys.We found the half-life (t1/2) of supaglutide was 39.7 h and 35.8 h at dosing 0.1 mg/kg upon subcutaneous or intravenous administration respectively, in rhesus monkeys. The plasma supaglutide peaked at 8-10 h, while the plasma drug exposure levels increased with the increase of dose, showing approximately a linear pharmacokinetic characteristic. The elimination kinetics (Ke) were found to be similar between subcutaneous (∼0.025 in rats and ∼0.018 in monkeys) and intravenous administration (0.021 in rats and 0.020 in monkeys), whereas the bioavailability was found to be 31.1% in rats and 63.9% in monkeys. In monkeys, a single dose injection of supaglutide markedly decreased the random blood glucose levels that reaching the maxima effects in 14-16 h, gradually recovered and returned to the baseline level approximately after 72 h.

Intracerebral hemorrhage (ICH) has a high mortality and disability rate. Fewer studies focus on white matter injury (WMI) after ICH, especially the corticospinal tract (CST) injury located in the spinal cord, which correlates with motor impairments. Recent studies have shown that gut microbiota dysbiosis occurs after ICH. Furthermore, NLRP3 inflammasome can be activated after ICH, resulting in inflammatory cascade reactions and aggravating brain injury. However, no direct and causal correlation among NLRP3 inflammasome inhibition, altered gut microbiota, and CST injury following ICH has been reported. This study aimed to investigate the effect of MCC950, a selective NLRP3 inflammasome inhibitor, on the gut microbiota and CST injury after ICH. We observed that compared with the sham group, the members of Firmicutes, such as Faecalibaculum and Dubosiella, were depleted in the ICH + Vehicle group, whereas the members of Proteobacteria and Campilobacterota were enriched, such as Enterobacter and Helicobacter. After treatment with MCC950, the Bacteroides, Bifidobacterium and Paenibacillus were relatively abundant in the gut flora of mice. Moreover, we observed CST injury located in cervical enlargement of the spinal cord, and MCC950 alleviated it. Furthermore, treatment with MCC950 decreased the mNSS score and brain water content in ICH. Taken together, the present study showed that MCC950 modulated gut microbiota, effectively attenuated CST injury located in cervical enlargement of the spinal cord, and ameliorated neurological deficits after ICH. This study provided a novel report that links NLRP3 inflammasome inhibition, gut microbiota alteration and CST injury following ICH and profound implications for ICH treatment.

Heat shock protein 70 family (HSP70s) is one of the most conserved and important group of HSPs as molecular chaperones, which plays an important role in cytoprotection, anti-apoptosis and so on. However, the molecular mechanism of HSP70s in animal regeneration remains to be delineated. In this study, we investigate the roles of HSP70s in regeneration of planarian. The four genes, Djhsp70a, Djhsp70b, Djhsp70c, and Djhsp70d of the HSP70s, are selected from the transcriptome database, because of their high expression levels in planarians. We then study the biological roles of each gene by conducting various experimental techniques, including RNAi, RT-PCR, WISH, Whole-mount immunostaining and TUNEL. The results show: (1) External stressors, such as temperature, tissue damage and ionic liquid upregulate the expression of Djhsp70s significantly. (2) The gene expression of Djhsp70s in planarians exhibits dynamic patterns. According to the result of WISH, the Djhsp70s are mainly expressed in parenchymal tissues on both sides of the body as well as blastema. It is consistent with the data of qRT-PCR. (3) After RNA interference of Djhsp70s, the worms experience cephalic regression and lysis, body curling, stagnant regeneration and death. (4) Knockdown of Djhsp70s affect the cell proliferation and apoptosis. These results suggest that Djhsp70s are not only conserved in cytoprotection, but involved in homeostasis maintenance and regeneration process by regulating coordination of cell proliferation and apoptosis in planarians.

Background: Recent studies have clearly demonstrated the promotion role of Nod-like receptor protein 3 (NLRP3) inflammasome in melanoma progression. Immune checkpoint inhibitors (ICI) therapy dramatically extended the survival interval of advanced melanoma patients. However, immunologic and immunotherapy implications of mutations of NLRP3 in melanoma were unknown. Methods: We utilized public genomic data of 750 melanoma patients to explore the association of NLRP3 mutations with immunologic and genomic features. In addition, we curated 336 advanced/metastatic melanoma patients treated with ICI from 6 published studies to analyze response rate and survival outcome in relation to NLRP3 mutations. Findings: Patients with NLRP3 mutations had significantly higher TML ( P < 0.001) and neoantigen load ( P < 0.001). Significantly lower tumor heterogeneity ( P = 0.048) and purity ( P = 0.022) were observed in patients with NLRP3 mutations. NLRP3 mutant patients harbored elevated infiltration of immune-response cells and decreased enrichment of immune-suppressive cells. Immune response signals were also enriched in patients with NLRP3 mutations. Higher response rate ( P = 0.031) and prolonged overall survival ( P = 0.006) were observed in NLRP3 mutated patients in the pooled ICI-treated cohort. Interpretation: NLRP3 mutations were correlated with better immunological characteristics. Patients with NLRP3 mutations had favorable ICI response rate and survival outcome. These results suggest the predictive value of NLRP3 mutations for ICI treatment efficacy in melanoma. Funding: This study was supported by the Shandong Provincial Youth Innovation Team Development Plan of Colleges and Universities [No. 2019-6-156, Lu-Jiao]. Declaration of Interests: The authors declare that there is no conflict of interest regarding the publication of this article.

Background: Immunotherapies have dramatically improved survival of melanoma patients. MUC16 encodes cancer antigen 125 (CA125), which is frequently mutated in melanoma. However, association of MUC16 mutation with tumor mutation load (TML), microenvironment, outcome and immunotherapeutic efficacy in melanoma remains elusive. Methods: We obtained 467 melanoma samples from the Cancer Genome Atlas (TCGA). We correlated MUC16 mutation status with TML, multiple immune-related signals in microenvironment, dysregulated pathways and outcome. An independent dataset containing 183 samples was used for validation. The association of MUC16 mutation with immune checkpoint inhibitor (ICI) efficacy was estimated with 144 ICI treated patients from a published study. Findings: MUC16 mutation exhibited the most significant correlation with TML in TCGA cohort. In both cohorts, patients with MUC16 mutations had significantly higher TML than those without MUC16 mutations. Enriched pro-inflammatory CD8 T cells and M1 macrophages, abundant total immune cells infiltration, enhanced interferon gamma (IFNγ) and T cell-inflamed signatures, and increased cytolytic activity were associated with MUC16 mutation. Immune-suppressive M2 macrophages was enriched in MUC16 wild-type patients. Immune checkpoints expression were also elevated in patients with MUC16 mutation. Patients with MUC16 mutations exhibited significantly better prognosis in both cohorts. For patients received ICI treatment, MUC16 mutation was associated with better response rate and survival outcome in male group but not in female and overall group. Interpretation: MUC16 mutation was associated with high TML, immune-activated microenvironment and favorable prognosis in melanoma. Male patients with MUC16 mutations had better ICI therapy efficacy. These findings provide new implications for tailoring immunotherapeutic strategies of melanoma patients. Funding Statement: This study was supported by the Program for Changjiang Scholars and Innovative Research Team in University in China [IRT_14R40 to K. C.], and the National Natural Science Foundation of China [no. 31801117 to X. L.]. Declaration of Interests: The authors stated: "None." Ethics Approval Statement: This study has been approved by the Tianjin Medical University Cancer Institute and Hospital.

Patulin (PAT) contamination in fruit and fruit products is a significant public health concern. Here, we developed a ratiometric fluorescent aptasensor for PAT detection based on aptamer-recognition and Exonuclease III amplification. Two structure selective dyes, SYBR Green I (SGI) and N-methyl mesoporphyrin IX (NMM), were used as fluorescent probes. In the developed biosensing system, the binding of patulin to aptamer triggered the liberation of cDNA. Subsequently, amplification was mediated by Exonuclease III. S1 was released from the S1-S2 duplex by enzymatic hydrolyzation and incorporated into a stable G-quadruplex. As a result, the fluorescence of SYBR Green I decreased, whereas that of NMM increased. There was a strong linear correlation between the relative fluorescence intensity and PAT concentrations (20 to 500 ng·L-1 range) (R2=0.99). The biosensing system was highly sensitive, and could detect PAT concentration as low as 4.7 ng·L-1. The sensor was also highly specific, and could differentiate PAT from several other related mycotoxins. In summary, we developed a new bioassay for the accurate detection of PAT contamination in fruits and fruit products. This research provides a new approach for developing ratiometric bioassays based on structure-selective dyes and enzymatic conversion processes.

The design of cathode material with unique structure and excellent electrochemical property is critical for the development of energy storage device. We report herein the synthesis of a nanocomposite with heterostructure of metallic nickel (Ni) and nickel sulfide (Ni3S2) through a facile solid-gas state reaction method, using Ni-ZIF MOFs and sulfur as precursors. The electrochemical energy storage capabilities of the synthesized composite as cathodes for both supercapacitor and zinc ion batteries have been investigated. Owing to the good conductivity of metallic Ni and superior pseudocapacitive behavior of the Ni3S2, the Ni/Ni3S2 nanocomposite exhibit excellent energy storage capability in both supercapacitor and zinc ion batteries. It was revealed that the Ni/Ni3S2 nanocomposite exhibit an excellent specific capacity of 2228 F g−1 at a current density of 4 A g−1. A high capacity of 1496 F g−1 is remained even at a high current density of 12 A g−1, demonstrating good rate capability of the electrode material. When the Ni/Ni3S2 was used as the cathode material for zinc ion battery, the assembled Ni/Ni3S2//Zn aqueous zinc ion battery can provide a high energy density of 379 Wh kg−1 at power density of 0.34 kW kg−1. The battery also exhibits long-term cyclic stability with capacity retention ratio of 84.1% after 1000 cycles and good rate performance. Our work proposed a facile route to produce transition metal sulfide nanocomposite with excellent capacitive properties as cathode material for the supercapacitor and aqueous zinc ion batteries in green energy storage application.

An ultrasonic-vibration-assisted laser annealing method was developed to enhance the performance of fluorine-doped tin oxide (FTO) thin films. The influences of ultrasonic vibration, laser scan line overlapping rate (LOR) and laser spot overlapping rate (SOR) on surface morphology, FTO layer thickness, RMS roughness, crystal structure and photoelectric properties of the FTO films were investigated. The results indicated that the presence of ultrasonic vibration during laser annealing could significantly enhance the film compactness, and using moderate LOR and SOR values resulted in significantly decreased FTO layer thicknesses and RMS roughnesses as well as slightly increased crystallite sizes, thus yielding significantly improved optical transmittance values and slightly enhanced electrical conductivity values. It was found that the optimal LOR and SOR values for ultrasonic-vibration-assisted laser annealing of the FTO films were 80% and 90%, respectively. The as-obtained film possessed the best overall photoelectric property with an average transmittance (400–800 nm) of 85.9%, a sheet resistance of 8.7 Ω/sq and a figure of merit of 2.51 × 10–2 Ω–1. This work may be of great significance in terms of performance optimization of transparent conducting oxide (TCO) thin films.

For strain measurement in the case of complex situations such as when defects (including cracks, notches and stains) exist, the traditional phase unwrapping algorithm will bring great error in strain distributions around defects. In this study, a simple local phase unwrapping algorithm was proposed to minimize the influence of defects on full-field strain measurement. From the specimen grid images before and after deformation, the Moire phases are first acquired by the sampling Moire technique. The wrapped Moire phase difference is then calculated to determine the strain distributions by only unwrapping the phase difference at the boundaries of the wrapped phase. In other words, the partial differentials of the Moire phase difference are corrected by local phase compensation for strain calculation. The accuracy of the developed strain measurement method was verified from numerical simulations. As applications, this method was successfully used in microscale strain distribution measurements of an aluminum specimen with a prefabricated crack and several grid defects under tensile loading, and a titanium alloy specimen with a prefabricated notch and an emerged irregular crack under tensile-fatigue loading. The local phase unwrapping algorithm can also be integrated with geometric phase analysis for strain measurement.