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Abstract Background Alterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC). Methods We assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, the Kras LSL−G12D/+ ; Tp53 fl/fl (KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry. Results Our findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs. Conclusion The present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.

Abstract Background Cytoplasmic male sterility (CMS) is the basis of heterosis exploitation. CMS has been used to hybrid production in cotton, but its molecular mechanism remains unclear. CMS is associated with advanced or delayed tapetal programmed cell death (PCD), and reactive oxygen species (ROS) may mediate this process. In this study, we obtained Jin A and Yamian A, two CMS lines with different cytoplasmic sources. Results Compared with maintainer Jin B, Jin A anthers showed advanced tapetal PCD with DNA fragmentation, producing excessive ROS which accumulated around the cell membrane, intercellular space and mitochondrial membrane. The activities of peroxidase (POD) and catalase (CAT) enzymes which can scavenge ROS were significantly decreased. However, Yamian A tapetal PCD was delayed with lower ROS content, and the activities of superoxide dismutase (SOD) and POD were higher than its maintainer. These differences in ROS scavenging enzyme activities may be caused by isoenzyme gene expressions. In addition, we found the excess ROS generated in Jin A mitochondria and ROS overflow from complex III might be the source in parallel with the reduction of ATP content. Conclusion ROS accumulation or abrogation were mainly caused by the joint action of ROS generation and scavenging enzyme activities transformation, which led to the abnormal progression of tapetal PCD, affected the development of microspores, and eventually contributed to male sterility. In Jin A, tapetal PCD in advance might be caused by mitochondrial ROS overproduction, accompanied by energy deficiency. The above studies will provide new insights into the cotton CMS and guide the follow-up research ideas.

Abstract Tissue dynamics play critical roles in many physiological functions and provide important metrics for clinical diagnosis. Capturing real-time high-resolution 3D images of tissue dynamics, however, remains a challenge. This study presents a hybrid physics-informed neural network algorithm that infers 3D flow-induced tissue dynamics and other physical quantities from sparse 2D images. The algorithm combines a recurrent neural network model of soft tissue with a differentiable fluid solver, leveraging prior knowledge in solid mechanics to project the governing equation on a discrete eigen space. The algorithm uses a Long-short-term memory-based recurrent encoder-decoder connected with a fully connected neural network to capture the temporal dependence of flow-structure-interaction. The effectiveness and merit of the proposed algorithm is demonstrated on synthetic data from a canine vocal fold model and experimental data from excised pigeon syringes. The results showed that the algorithm accurately reconstructs 3D vocal dynamics, aerodynamics, and acoustics from sparse 2D vibration profiles.

In this present age, innovation has become inextricably tied to both long-term economic growth and environmentally sound development. In this context, the impact that environmentally focused technological advancements or innovations have on environmental quality is of the utmost importance. Therefore, the main goal of the present study is to determine how Green innovation (GI) affects environmental degradation in the BRICS countries from 1992 to 2021. The ecological footprint (EFT) is an indicator used in the study to measure environmental degradation. The study divides the components that contribute to the explanation into two categories: the GI threshold variable and the independent variables RE, GDP, and population (POP). Additionally, this study investigates the indirect impact of RE, GDP, and POP through the threshold effect of GI. The stochastic impacts of the explanatory factors are explored using sophisticated panel data estimation methods and a panel threshold model. According to the findings of the study, an improvement in environmental quality occurs when the threshold level of GI is achieved, which indicates that innovation in the form of a lower EFT is responsible for the improvement. In light of the findings, recommendations for policymakers and stakeholders in BRICS countries are to promote RE and drive GI.

Abstract Background Recent studies have indicated that some members of the tripartite motif (TRIM) proteins function as important regulators for non-small cell lung cancer (NSCLC), However, the regulatory mechanism underpinning aberrant expression of TRIM in NSCLC remains unclear. Here we report that TRIM15 plays important roles in NSCLC progression through modulating Keap1-Nrf2 signaling pathway. Methods TRIM15 expression was evaluated by western blot analysis, tissue microarray-based immunohistochemistry analysis. The interactions between TRIM15 and Keap1 were analyzed by co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assay. The correlation between TRIM15 and Keap1 was measured by Co-IP and ubiquitination analysis in vitro. Gain- and lost-of-function experiments were used to detect TRIM15 promotes proliferation and invasion of NSCLC cells both in vitro and vivo. Results Here, we revealed that TRIM15 was frequently upregulated in NSCLC samples and associated with poor prognosis. Functionally, TRIM15 knockdown resulted in decreased cancer cell proliferation and metastasis, whereas ectopic TRIM15 expression facilitated tumor cancer cell proliferation and metastasis in vitro and in vivo. Moreover, TRIM15 promoted cell proliferation and metastasis depends on its E3 ubiquitin ligase. Mechanistically, TRIM15 directly targeted Keap1 by ubiquitination and degradation, the principal regulator of Nrf2 degradation, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression. Conclusions Therefore, our study characterizes the pivotal roles of TRIM15 promotes NSCLC progression via Nrf2 stability mediated by promoting Keap1 ubiquitination and degradation and could be a valuable prognostic biomarker and a potential therapeutic target in NSCLC. Video Abstract

Subglottic stenosis (SGS) is a rare yet potentially life-threatening condition that requires prompt identification and treatment. One of the primary symptoms of SGS is a respiratory sound that is tonal. To better understand the effect of SGS on expiratory sound, we used direct noise calculation to simulate sound production in a simplified axisymmetric configuration that included the trachea, the vocal folds, the supraglottal tract, and an open environmental space. This study focused on flow-sustained tones and explored the impact of various parameters, such as the SGS severity, the SGS distance, the flowrate, and the glottal opening size. It was found that the sound pressure level (SPL) of the expiratory sound increased with flowrate. SGS had little effect on the sound until its severity approached 75% and SPL increased rapidly as the severity approached 100%. The results also revealed that the tonal components of the sound predominantly came from hole tones and tract harmonics and their coupling. The spectra of the sound were greatly influenced by constricting the glottis, which suggests that respiratory tasks that involve maneuvers to change the glottal opening size could be useful in gathering more information on respiratory sound to aid in the diagnosis of subglottic stenosis.

Hemicellulose is the second most abundant carbohydrate in lignocellulosic biomass and has extensive applications. In conventional biomass refinery, hemicellulose is easily converted to unwanted by-products in pretreatment and therefore can't be fully utilized. The present study aims to summarize the most recent development of lignocellulosic polysaccharide degradation and fully convert it to value-added bioproducts through microbial and enzymatic catalysis. Firstly, bioprocess and microbial metabolic engineering for enhanced utilization of lignocellulosic carbohydrates were discussed. The bioprocess for degradation and conversion of natural lignocellulose to monosaccharides and organic acids using anaerobic thermophilic bacteria and thermostable glycoside hydrolases were summarized. Xylose transmembrane transporting systems in natural microorganisms and the latest strategies for promoting the transporting capacity by metabolic engineering were summarized. The carbon catabolite repression effect restricting xylose utilization in microorganisms, and metabolic engineering strategies developed for co-utilization of glucose and xylose were discussed. Secondly, the metabolic pathways of xylose catabolism in microorganisms were comparatively analyzed. Microbial metabolic engineering for converting xylose to value-added bioproducts based on redox pathways, non-redox pathways, pentose phosphate pathway, and improving inhibitors resistance were summarized. Thirdly, strategies for degrading lignocellulosic polysaccharides and fully converting hemicellulose to value-added bioproducts through microbial metabolic engineering were proposed.

Abstract A MBE-prepared Gallium (Ga)-droplet surface on GaAs (001) substrate is in situ irradiated by a single shot of UV pulsed laser. It demonstrates that laser shooting can facilely re-adjust the size of Ga-droplet and a special Ga-droplet of extremely broad size-distribution with width from 16 to 230 nm and height from 1 to 42 nm are successfully obtained. Due to the energetic inhomogeneity across the laser spot, the modification of droplet as a function of irradiation intensity (IRIT) can be straightly investigated on one sample and the correlated mechanisms are clarified. Systematically, the laser resizing can be perceived as: for low irradiation level, laser heating only expands droplets to make mergences among them, so in this stage, the droplet size distribution is solely shifted to the large side; for high irradiation level, laser irradiation not only causes thermal expansion but also thermal evaporation of Ga atom which makes the size-shift move to both sides. All of these size-shifts on Ga-droplets can be strongly controlled by applying different laser IRIT that enables a more designable droplet epitaxy in the future.

For the initiation characteristics of solid rocket motors (SRMs) filled with high-energy solid propellant under fragment impact, the related theoretical critical criterion for shock initiation was established based on the critical energy criterion and equivalent analysis method. Afterward, numerical simulation of fragment impacting SRM was carried out by using the ANSYS/LS-DYNA software and the nonlinear finite element method. Based on the calculated pressure and reactivity in the high-energy solid propellant grain, the shock critical initiation velocity of SRM and its variation with different forms of fragments and impact conditions were determined. It is found that the numerical simulation results under typical conditions are in good agreement with the data calculated with the developed theoretical critical criterion for shock initiation of SRM. However, the shock initiation mechanism becomes more complex when the case thickness of SRM increases to more than 5 mm; thus, the applicability of the developed theoretical critical criterion reduces. Moreover, it is found that all the case thickness, fragment shape, material properties of the fragment, and impact attitude can significantly affect the shock critical initiation velocity of SRM, even the initiation position and time. First, the critical velocity increases linearly with the increase in case thickness, and the increment rate is faster beyond the thickness of 6 mm. Second, the shock critical initiation velocity induced by fragments with different shapes is as follows: spherical fragment > cubic fragment > cylindrical fragment, while the initiation capacity of different fragment materials is ranked as follows: tungsten alloy > 45 steel > 2024 aluminum. Third, the effects of impact attitude on the shock critical initiation velocity, position and time are complex, and these effects are also influenced by fragment shape. When the impact angle is less than 60°, there is a higher shock critical initiation velocity of SRM under inclined impact than that under positive impact. In addition, the critical velocity induced by cubic fragment is the highest under the combination of vertex impact and positive impact. The variation of the critical velocity under this condition is approximately consistent with that by impacting with cylindrical fragment. Furthermore, when the impact angle is greater than 60°, the shock critical initiation velocity of SRM is less obviously influenced by impact attitude and fragment shape. Meanwhile, the critical velocity decreases sharply under this condition, which indicates that it is easier for SRM to detonate.

Abstract Background Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood. Methods Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo. Results We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1β. Conclusions Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1β secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.

Despite the fact that companies increasingly value online star endorsements as Internet celebrity economy booms, scientific knowledge on the effect of online star endorsements on consumers’ purchase intention is limited. Based on the theories of self and construal level theory, this study investigates the impact of online star vs. celebrity endorsements on purchase intention and explores the underlying mechanism as well as boundary conditions. The results of four studies reveal the following: (1) Compared with no endorsement, both celebrity endorsements and online star endorsements lead to increases in consumers’ purchase intention, with no significant difference between the two. (2) Self-concept mediates these relationships; specifically, celebrity and online star endorsements activate the ideal and actual self respectively, and enhance consumers’ willingness to purchase. (3) The effect of endorsements on consumers’ purchase intention is moderated by advertising appeals. That is, celebrity endorsements enhance purchase intention when consumers are exposed to symbolic appeals in advertisements, and online star endorsements enhance purchase intention when it is matched with functional advertising appeals.

The small scale gap test is a very important method to study the sensitivity characteristics of a composite solid propellant under shock waves. In this paper, the small scale gap test is taken as the research object. The theoretical model of shock wave conduction in the small scale gap test is established. The detonation parameters of mixed explosives and the shock wave incident parameters of propellants corresponding to different sizes of inert barriers are calculated. The reliability of the method is verified by classical examples. A numerical model is established for the small scale gap test, and the critical thickness of the partition plate is obtained with a 50% probability of initiation. The results can predict the development and safe use of a high-energy composite solid propellant and provide theoretical support for the establishment of safety standards of high-energy composite solid propellants.

The demand prediction of emergency resources is helpful for rational allocation and optimization of emergency resources for railway rescue when emergency incident occurs. In this paper, a case base containing China railway traffic accident that has occurred since 1978 is established, and the case-based reasoning (CBR) method is applied in railway emergency resource demand predicting research. The core case attributes of railway emergencies are described. In view of the attribute types of railway emergency cases, five types of attributes, including enumeration, numerical, interval, character and fuzzy type, are considered, and the local similarity calculation models of different attributes are given. In order to avoid the problem of missing attribute in the traditional nearest neighbor algorithm, a global case similarity calculation method based on structural similarity and attribute similarity is designed. The empirical results show that case 3 is the most similar to the target case, and the calculating quantities of the proposed model are closer to the actual usage quantity and more accurate in the demand prediction of railway emergency resources, compared with the traditional empirical method. The relative errors of demand forecasts for the 9 resources have been, respectively, reduced by 15.9884%, 15.1471%, 6.4286%, 17.1429%, 66.6667%, 38.8889%, 27.5%, 0%, and 17.7778%. Therefore, the proposed model is both reasonable and applicable. The research results are of great significance to effectively deal with railway emergencies.

Based on the dynamic loading (1-100 s−1) experiments under different temperatures (223–298 K) and stress states, uniaxial and biaxial strength criterion of a Hydroxyl-terminated polybutadiene (HTPB) based composite solid propellant were further investigated. These experiments were conducted through the use of a new uniaxial INSTRON testing machine, different new designed gripping apparatus and samples with different configurations. According to the test results, dynamic uniaxial tensile strength criterion of the propellant was directly constructed with the master curve of the uniaxial maximum tensile stress. Whereas, a new method was proposed to determine the dynamic uniaxial compressive strength of the propellant in this study. Then uniaxial compressive strength criterion of the propellant was constructed based on the related master curve. Moreover, it found that the uniaxial tensile-compressive strength ratio of the propellant is more sensitive to loading temperature under the test conditions. The value of this parameter is about 0.4 at room temperature, and it reduces to 0.2–0.3 at low temperatures. Finally, the theoretical biaxial strength criterion of HTPB propellant under dynamic loading was constructed with the unified strength theory, the uniaxial strength and the typical biaxial tensile strength. In addition, the theoretical limit lines of the principal stress plane for the propellant under dynamic loading at different temperatures were further plotted, and the scope of the limit line increases with decreasing temperature. Keywords: Strength criterion, Unified strength theory, Composite solid propellant, Dynamic loading, Biaxial tension

Abstract Background Enzymatically inactive chitinase-like protein CHI3L1 drives inflammatory response and promotes tumor progression. However, its role in gastric cancer (GC) tumorigenesis and metastasis has not yet been fully elucidated. We determined the significance of CHI3L1 expression in patients with GC. We also explored an as-yet unknown receptor of CHI3L1 and investigated the involved signaling in GC metastasis. Methods CHI3L1 expression was evaluated by immunoblotting, tissue microarray-based immunohistochemistry analysis (n = 100), and enzyme linked immunosorbent assay (ELISA) (n = 150). The interactions between CD44 and CHI3L1 or Interleukin-13 receptor alpha 2 (IL-13Rα2) were analyzed by co-immunoprecipitation, immunofluorescence co-localization assay, ELISA, and bio-layer interferometry. The roles of CHI3L1/CD44 axis in GC metastasis were investigated in GC cell lines and experimental animal model by gain and loss of function. Results CHI3L1 upregulation occurred during GC development, and positively correlated with GC invasion depth, lymph node status, and tumor staging. Mechanically, CHI3L1 binding to CD44 activated Erk and Akt, along with β-catenin signaling by phosphorylating β-catenin at Ser552 and Ser675. CD44 also interacted with IL-13Rα2 to form a complex. Notably, CD44v3 peptide and protein, but not CD44v6 peptide or CD44s protein, bound to both CHI3L1 and IL-13Rα2. Our in vivo and in vitro data further demonstrated that CHI3L1 promoted GC cell proliferation, migration, and metastasis. Conclusions CHI3L1 binding to CD44v3 activates Erk, Akt, and β-catenin signaling, therefore enhances GC metastasis. CHI3L1 expression is a novel biomarker for the prognosis of GC, and these findings have thus identified CHI3L1/CD44 axis as a vital pathway and potential therapeutic target in GC.

Aiming at the problems of selection parameter step-size and premature convergence that occurred when searching the local area in the optimal design of adaptive gradient projection algorithm in this paper, adaptive variable step-size mechanism strategy and adaptive variable step-size mechanism were established. They were introduced into the gradient projection algorithm, and were used to control iteration step length. Through the examples of non-probabilistic reliability index, it can be showed that the method could quickly and accurately calculate the reliability index when the model had multiple variables and complex limit state function. To compare and contrast this algorithm with the simple gradient projection algorithm, this algorithm is not sensitive to the initial point position. And it not only takes into account both local performance and global search ability, but also has fast convergence speed and high precision. So it is an efficient and practical optimization algorithm.

Both nitric oxide (NO) and hydrogen sulfide (H2S) have been shown to have positive effects on the maintenance of fruit quality during storage; however, the mechanisms by which NO regulates the endogenous H2S metabolism remain unknown. In this experiment, peaches were immersed in solutions of NO, potassium 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO, as an NO scavenger), N-nitro-l-arginine methyl ester (l-NAME, as an inhibitor of nitric oxide synthase (NOS)-like activity), and sodium tungstate (as an inhibitor of nitrate reductase), and the resulting changes in the H2S metabolism of peaches were studied. The results showed that exogenous NO reduced the contents of endogenous H2S, Cys, and sulfite; decreased the activities of l-/d-cysteine desulfhydrase (l-/d-CD), O-acetylserine (thiol)lyase (OAS-TL), and sulfite reductase (SiR); and increased the activity of β-cyanoalanine synthase (β-CAS). Both c-PTIO and sodium tungstate had similar roles in increasing the H2S content by sustaining the activities of l-/d-CDs, OAS-TL, and SiR. l-NAME increased the H2S content, mainly by maintaining the d-CD activity. The results suggest that NO, c-PTIO, l-NAME, and sodium tungstate differently regulate the H2S metabolism of peaches during storage.

We numerically solved the acoustic and flow field around cicada wing models with parametrically varied flexibility using the hydrodynamic/acoustic splitting method. We observed a gradual change of sound directivity with flexibility. We found that flexible wings generally produce lower sound due to reduced aerodynamic forces, which were further found to scale with the dynamic pressure force defined as the integration of dynamic pressure over the wing area. Unlike conventional scaling where the incoming flow velocity is used as the reference to calculate the force coefficients, here only the normal component of the relative velocity of the wing to the flow was used to calculate the dynamic pressure, putting kinematic factors into the dynamic pressure force and leaving the more fundamental physics to the force coefficients. A high correlation was found between the aerodynamic forces and the dynamic pressure. The scaling is also supported by previously reported data of revolving wing experiments.