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Background: Radix Sophorae flavescentis (Kushen), a Chinese herb, is widely used in the treatment of ulcerative colitis (UC) with damp-heat accumulation syndrome (DHAS) according to traditional Chinese medicine (TCM) theory. Objective: The aim of this study was to illuminate the clinical efficacy and potential mechanisms of Kushen-based TCM formulations in the treatment of UC with DHAS. Materials and Methods: A systematic literature search was performed in the PubMed, EMBASE, Chinese Biomedical Literature database, China National Knowledge Infrastructure database, Chongqing VIP Information database, and Wanfang database for articles published between January 2000 and July 2020 on randomized controlled trials (RCTs) that used Kushen-based TCM formulations in the treatment of UC with DHAS. A network pharmacology approach was conducted to detect the potential pathways of Kushen against UC with DHAS. Results: Eight RCTs with a total of 983 subjects were included in the meta-analysis. Compared with the control subjects (5-aminosalicylic acid therapy), those who received Kushen-based TCM formulations for the treatment of UC showed a significantly higher clinical remission rate (RR = 1.20, 95% CI: [1.04, 1.38], p = 0.02) and lower incidence of adverse events (RR = 0.63, 95% CI [0.39, 1.01], p = 0.06). A component-target-pathway network was constructed, indicating five main components ( quercetin , luteolin , matrine , formononetin , and phaseolin ), three major targets (Interleukin-6, Myc proto-oncogene protein, and G1/S-specific cyclin-D1) and one key potential therapeutic pathway (PI3K-Akt signaling) of Kushen against UC with DHAS. Conclusion: Kushen-based TCM formulations provide good efficacy and possess great potential in the treatment of UC. Large-scale and high-quality clinical trials and experimental verification should be considered for further confirmation of the efficacy of Kushen-based formulations.

Ferroptosis is triggered by intracellular iron leading to accumulation of lipid peroxidation consequent promotion of cell death. Cancer cell exhibits ability to evade ferroptosis by activation of antioxidant signaling pathways such as SLC7A11/GPX4 axis. In addition to transcriptional regulation on ferroptosis by NRF2, SREBP1, YAP, and p53, ferroptosis is modulated by ubiquitination or autophagic degradation. Moreover, zinc or Ca 2+ could modulate ferroptosis by inducing lipid peroxidation and ferroptosis. Induction of ferroptosis enhances immune cell activity such as T cells or macrophages, which is associated with the release of DAMPs (damage-associated molecular patterns) and IFNγ. Therefore, combined immune checkpoint inhibitors with ferroptosis inducers effectively enhance antitumor immunotherapy, whereas induction of ferroptosis could impair T cell activity or survival, suggesting that rational combined therapy for cancer is essential. In this review, we discussed the regulatory role of ferroptosis on tumor progression and immunotherapy.

Three-dimensional flexible piezoresistive porous sensors are of interest in health diagnosis and wearable devices. In this study, conductive porous sensors with complex triply periodic minimal surface (TPMS) structures were fabricated using the 3D printed sacrificial mold and enhancement of MWCNTs. A new curing routine by the self-resistance electric heating was implemented. The porous sensors were designed with different pore sizes and unit cell types of the TPMS (Diamond (D), Gyroid (G), and I-WP (I)). The impact of pore characteristics and the hybrid fabrication technique on the compressive properties and piezoresistive response of the developed porous sensors was studied. The results indicate that the porous sensors cured by the self-resistance electric heating could render a uniform temperature distribution in the composites and reduce the voids in the walls, exhibiting a higher elastic modulus and a better piezoresistive response. Among these specimens, the specimen with the D-based structure cured by self-resistance electric heating showed the highest responsive strain (61%), with a corresponding resistance response value of 0.97, which increased by 10.26% compared to the specimen heated by the external heat sources. This study provides a new perspective on design and fabrication of porous materials with piezoresistive functionalities, particularly in the realm of flexible and portable piezoresistive sensors.

Blockade of the programmed death 1 (PD‐1)/ programmed death ligand 1 (PD‐L1) immune checkpoint could increase antitumor immunotherapy for multiple types of cancer, but the response rate of patients is about 10%–40%. Peroxisome proliferator activated receptor γ (PPARγ) plays an important role in regulating cell metabolism, inflammation, immunity, and cancer progression, while the mechanism of PPARγ on cancer cell immune escape is still unclear. Here we found that PPARγ expression exhibits a positive correlation with activation of T cells in non‐small‐cell lung cancer (NSCLC) by clinical analysis. Deficiency of PPARγ promoted immune escape of NSCLC by inhibiting T‐cell activity, which was associated with increased PD‐L1 protein level. Further analysis showed that PPARγ reduced PD‐L1 expression independent of its transcriptional activity. PPARγ contains the microtubule‐associated protein 1A/1B‐light chain 3 (LC3) interacting region motif, which acts as an autophagy receptor for PPARγ binding to LC3, leading to degradation of PD‐L1 in lysosomes, which in turn suppresses NSCLC tumor growth by increasing T‐cell activity. These findings suggest that PPARγ inhibits the tumor immune escape of NSCLC by inducing PD‐L1 autophagic degradation. (1) PPARγ acts as an autophagic receptor for PD‐L1 autophagic degradation. (2) Agonist enhanced PD‐1 antibody against NSCLC tumor immune escape. (3) PPARγ agonist could be a therapic strategy for antitumor immunotherapy of NSCLC. (1) PPARγ induced PD‐L1 autophagic degradation. (2) Loss of PPARγ led to NSCLC tumor immune escape. (3) PPARγ acts as autophagic receptor for PD‐L1 autophagic degradation

SiCp/Al composite materials are widely used in various industries such as the aerospace and the electronics industries, primarily due to their excellent material properties. However, their machinability is significantly weakened due to their unique characteristics. Consequently, efficient and precise machining technology for SiCp/Al composite materials has become a crucial research area. By conducting a comprehensive analysis of the relevant research literature from both domestic and international sources, this study examines the processing mechanism, as well as the turning, milling, drilling, grinding, special machining, and hybrid machining characteristics, of SiCp/Al composite materials. Moreover, it summarizes the latest research progress in composite material processing while identifying the existing problems and shortcomings in this area. The aim of this review is to enhance the machinability of SiCp/Al composite materials and promote high-quality and efficient processing methods.

In this study, the deposition, powder spreading, and laser fusion processes during the laser powder bed fusion (L-PBF) process were studied using molecular dynamics (MD) simulation. The effect of Ni content on the characteristic phase transformation temperatures was also investigated. Shape memory effect and superelasticity of NiTi alloys with Ni content ranged from 48.0% to 51.0% were analyzed. By employing MEAM potentials, the effects of the laser power, spot diameter, and scanning speed on the molten pool size and element evaporation were studied. Simulation results showed that a larger spot diameter renders a higher Ni content in the molten pool, also a larger molten pool. A faster scanning speed leads to a higher Ni content in the molten pool, and a smaller molten pool. The element is difficult to evaporate using small laser power and a large spot diameter. The element in the molten pool expresses a great evaporation effect when the Es is larger than 0.4 eV/ų. According to Ni content within the molten pool during laser fusion, characteristic phase transition temperatures in single crystalline NiTi alloys with variant Ni content were investigated by employing a 2NN-MEAM potential. Characteristic phase transition temperature changes as the Ni content increases from 48.0% to 51.0%. Austenite boundaries and Ni content in the boundary were found to be the keys for controlling the characteristic phase transformation temperature.

Permanent-magnet small ball-end magnetorheological polishing method can be used to polish the small part with complex structure. However, the material removal rate of this method is low, which is difficult to improve the output and reduce the cost. In this research, the effect of magnetorheological fluid temperature on the material removal rate is theoretically analyzed by measuring the effect of temperature on the flow properties of magnetorheological fluid, establishing the hydrodynamic model of polishing zone and solving the material removal parameters. It is found that with the increase of the magnetorheological fluid temperature, the polishing relative velocity increases accordingly, which can promote the improvement of material removal rate. But the shear stress decreases accordingly, which inhibits the improvement of material removal rate. The verification experiment results show that the promoting effect can exceeds the inhibitory effect, so that the material removal rate increases with the increase of magnetorheological fluid temperature. When the magnetorheological fluid temperature increases to 60 °C, the material removal rate is improved by 108.4% and the polished surface roughness Sa can reach 14.9 nm. Therefore, increasing the magnetorheological fluid temperature can significantly improve the efficiency of permanent-magnet small ball-end magnetorheological polishing and obtain high quality polished surface.

As a hard and brittle material, KDP crystal is easily damaged by the irradiation of laser in a laser-driven inertial confinement fusion device due to various factors, which will also affect the quality of subsequent incident laser. Thus, the mechanism of laser-induced damage is essentially helpful for increasing the laser-induced damage threshold and the value of optical crystal elements. The intrinsic damage mechanism of crystal materials under laser irradiation of different pulse duration is reviewed in detail. The process from the initiation to finalization of laser-induced damage has been divided into three stages (i.e., energy deposition, damage initiation, and damage forming) to ensure the understanding of laser-induced damage mechanism. It is clear that defects have a great impact on damage under short-pulse laser irradiation. The burst damage accounts for the majority of whole damage morphology, while the melting pit are more likely to appear under high-fluence laser. The three stages of damage are complementary and the multi-physics coupling technology needs to be fully applied to ensure the intuitive prediction of damage thresholds for various initial forms of KDP crystals. The improved laser-induced damage threshold prediction can provide support for improving the resistance of materials to various types of laser-induced damage.

Immune cells can protect against tumor progression by killing cancer cells, while aberrant expression of the immune checkpoint protein PD‐L1 (programmed death ligand 1) in cancer cells facilitates tumor immune escape and inhibits anti‐tumor immunotherapy. As a serine/threonine kinase, CK2 (casein kinase 2) regulates tumor progression by multiple pathways, while it is still unclear the effect of CK2 on tumor immune escape. Here it is found that ING4 induced PD‐L1 autophagic degradation and inhibites non‐small cell lung cancer (NSCLC) immune escape by increasing T cell activity. However, clinical analysis suggests that high expression of CK2 correlates with low ING4 protein level in NSCLC. Further analysis shows that CK2 induce ING4‐S150 phosphorylation leading to ING4 ubiquitination and degradation by JFK ubiquitin ligase. In contrast, CK2 gene knockout increases ING4 protein stability and T cell activity, subsequently, inhibites NSCLC immune escape. Furthermore, the combined CK2 inhibitor with PD‐1 antibody effectively enhances antitumor immunotherapy. These findings provide a novel strategy for cancer immunotherapy. ING4 acts as an autophagy receptor to induce PD‐L1 autophagic degradation leading to inhibition of tumor immune escape, whereas CK2 can induce ING4‐S150 phosphorylation and degradation by JFK ubiquitin ligase resulting in tumor immune escape. Importantly, CK2 inhibitor can effectively enhance PD‐1 antibody anti‐tumor immunotherapy by inhibiting CK2‐ING4 pathway. This study reveals a novel mechanism of the coordination of CK2 with ING4 to regulate PD‐L1 expression.

Xylem development plays a crucial role in wood formation in woody plants. In recent years, there has been growing attention towards the impact of brassinosteroids (BRs) on this xylem development. In the present study, we evaluated the dynamic variation of xylem development in Fraxinus mandshurica (female parent, M8) and a novel interspecific hybrid × (1601) from May to August 2020. We obtained RNA-Seq transcriptomes of three tissue types (xylem, phloem, and leaf) to identify the differences in xylem-differentially expressed genes (X-DEGs) and xylem-specifically expressed genes (X-SEGs) in M8 and 1601 variants. We then further evaluated these genes via weighted gene co-expression network analysis (WGCNA) alongside overexpressing FmCPD, a BR biosynthesis enzyme gene, in transient transgenic . Our results indicated that the xylem development cycle of 1601 was extended by 2 weeks compared to that of M8. In addition, during the later wood development stages (secondary wall thickening) of 1601, an increased cellulose content (14%) and a reduced lignin content (11%) was observed. Furthermore, vessel length and width increased by 67% and 37%, respectively, in 1601 compared with those of M8. A total of 4589 X-DEGs were identified, including enzymes related to phenylpropane metabolism, galactose metabolism, BR synthesis, and signal transduction pathways. WGCNA identified hub X-SEGs involved in cellulose synthesis and BR signaling in the 1601 wood formation-related module and ; in contrast, genes involved in phenylpropane metabolism were significantly enriched in the M8 wood formation-related module ( and ). Moreover, overexpression of in transient transgenic affected the expression of genes associated with lignin and cellulose biosynthesis signal transduction. Finally, BR content was determined to be approximately 20% lower in the M8 xylem than in the 1601 xylem, and the exogenous application of BRs (24-epi brassinolide) significantly increased the number of xylem cell layers and altered the composition of the secondary cell walls in . Our findings suggest that BR biosynthesis and signaling play a critical role in the differing wood development and properties observed between M8 and 1601 .