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As a novel post-translational modification of proteins, succinylation is widely present in both prokaryotes and eukaryotes. By regulating protein translocation and activity, particularly involved in regulation of gene expression, succinylation actively participates in diverse biological processes such as cell proliferation, differentiation and metabolism. Dysregulation of succinylation is closely related to many diseases. Consequently, it has increasingly attracted attention from basic and clinical researchers. For a thorough understanding of succinylation dysregulation and its implications for disease development, such as inflammation, tumors, cardiovascular and neurological diseases, this paper provides a comprehensive review of the research progress on abnormal succinylation. This understanding of association of dysregulation of succinylation with pathological processes will provide valuable directions for disease prevention/treatment strategies as well as drug development.

The further developments of additive manufacturing (AM) provides a possibility for Ti6Al4V and its functionally graded materials (FGMs), but limits further applications due to its low ductility, low microhardness and poor wear resistance. The key lies in the presence of microstructures such as epitaxial columnar β-grain orientation and heterogeneous phase distribution in AM Ti6Al4V, as well as the interfacial bonding problems (intermetallic phases, delamination, cracking) in AM Ti6Al4V FGMs. In order to address these fundamental intra and inter-layer problems, firstly the microstructure and phase evolution process of AM Ti6Al4V columnar-to-equiaxed transformation (CET) promoted by some alloying strategies was summarized in this paper according to alloying elements and reinforcing particle types. Subsequently, controlled changes in the composition and microstructure of AM Ti6Al4V FGMs were achieved by adding interlayers/introducing gradient interfaces, and the metallurgical reactions and phase transformation mechanisms that inhibit the formation of intermetallic compounds and interfacial defects were explored. Finally, the difficulties and future research directions for alloying strategies to achieve high strength and ductility of AM Ti6Al4V were presented. This review aims to improve the reliability of AM Ti6Al4V and its FGMs for applications in critical load-bearing structures through in-situ alloying and multi-material for the microstructure design of AM Ti6Al4V.

This study focused on analyzing the aroma formation mechanism of retronasal muscat flavor in table grapes. The sensory characteristics and fragrance components of table grape juice with different intensities of Muscat were investigated using GC-Quadrupole-MS, quantitative descriptive analysis and three-alternate forced choice. Free monoterpenoids were the main contributors to the retronasal Muscat flavor. The contribution of Muscat compounds to this flavor was quantified by Stevens coefficient, the most and the least sensitive compounds to concentration changes were citronellol and linalool, respectively. To predict the Muscat flavor intensity by mathematical modeling, established a model between Muscat flavor intensity and monoterpenoids concentration, and an optimal partial least squares regression model with a linear relationship between natural logarithms was obtained. These findings provide reference for understanding the formation mechanism of specific aromas in fruits and provide a basis for the development and quality control of processed products such as Muscat flavor grape juice.

Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson’s r=0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson’s r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.

Triple negative breast cancer (TNBC) presents a formidable challenge due to the lack of effective treatment modalities. Immunotherapy stands as a promising therapeutic approach; however, the emergence of drug resistance mechanisms within tumor cells, particularly those targeting apoptosis and pyroptosis, has hampered its clinical efficacy. SHP2 is intricately involved in diverse physiological processes, including immune cell proliferation, infiltration, and tumor progression. Nevertheless, the precise contribution of SHP2 to tumor cell pyroptosis resistance remains inadequately understood. Herein, we demonstrate that SHP2 inhibition hampers the proliferative, migratory, and invasive capabilities of TNBC, accompanied by noticeable alterations in cellular membrane architecture. Mechanistically, we provide evidence that SHP2 depletion triggers the activation of Caspase-1 and GSDMD, resulting in GSDMD-dependent release of LDH, IL-1β, and IL-18. Furthermore, computational analyses and co-localization investigations substantiate the hypothesis that SHP2 may hinder pyroptosis through direct binding to JNK, thereby impeding JNK phosphorylation. Our cellular experiments further corroborate these findings by demonstrating that JNK inhibition rescues pyroptosis induced by SHP2 knockdown. Strikingly, in vivo experiments validate the suppressive impact of SHP2 knockdown on tumor progression via enhanced JNK phosphorylation. Additionally, SHP2 knockdown augments tumor sensitivity to anti-PD-1 therapy, thus reinforcing the pro-pyroptotic effects and inhibiting tumor growth. In summary, our findings elucidate the mechanism by which SHP2 governs TNBC pyroptosis, underscoring the potential of SHP2 inhibition to suppress cell pyroptosis resistance and its utility as an adjunctive agent for tumor immunotherapy.

The world produces a huge amount of urban construction waste each year. Scientific planning of the construction waste recycling path is urgently needed to improve the recycling of construction waste. Existing construction waste recycling models do not pay sufficient attention to the uncertainty of the recycling quantity, which limits their ability to provide support for solving practical problems. The purpose of this paper is to solve the problem of uncertain recycling quantities in optimizing the urban construction waste recycling path. Thus, this paper first builds a recycling model for a deterministic environment with the economic objective as the decision criterion and the transportation flow, construction waste treatment capacity and capability, and environmental and social impact as the constraints. Then, a robust optimization method is adopted to optimize the deterministic model for the uncertainty of the recycling quantity. The data of this paper are from Nanjing, China. The validity of the model and the evolution of the recycling path are tested based on the data of Nanjing. The findings of this paper are as follows: Firstly, the robust model is cost-effective in the face of uncertainty in supply. Secondly, the robust model has greater total treatment capacity. Even in the worst-case scenario, it can guarantee a higher treatment capacity. Thirdly, both models follow the proximity principle which reduces the transportation costs and only slowly increases the total cost of the robust model. This paper provides a scientific and convenient tool to plan the recycling path of construction waste in large cities.

Introduction: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists’ interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. Methods: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. Results: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250–500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels > 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. Conclusions: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (

Eucommiae Cortex (EC), the dried stem bark of Eucommia ulmoides Oliv, has been traditionally used to strengthen the muscle and bone tissues and improve liver and kidney functions in East Asian countries, including China, Japan, and Korea. Salty-fried EC (SFEC) is made by using mixing EC and saline together based on the protocol of Chinese Materia Medica Processing (CMMP) for clinical use. However, the clinical effectiveness of SFEC is directly impacted by the frying temperature and time. But precise techniques for evaluating the caliber of SFEC have yet to be developed. Thus, this study aimed to establish a fast and accurate quality-check method for SFEC decoction pieces. According to the frying temperature and time, four different categories of SFEC had been got according to the Chinese Pharmacopoeia method as Raw (R), Under (U), Moderately (M), and Overly (O). The red (R), green (G), blue (B), and light (L) color values of the decoction pieces were quantitated using the Photoshop software to determine the standard value range of the L color (raw [104.44 ​± ​15.06], under [67.28 ​± ​8.20], moderately [39.94 ​± ​6.40], and over [15.02 ​± ​5.03]). Additionally, the tensile strengths and pinoresinol diglucoside (PDG) levels of EC gum-silks were measured using the mechanical tensile test and HPLC, respectively. We also conducted Pearson correlation analysis on the L color value, EC gum-silk tension (FbcN), and PDG level, and established the following multiple-linear regression equation: the decline in PDG level (w) ​= ​0.829–0.001 ​× ​FbcN – 0.009 ​× ​L. In conclusion, the L color value and FbcN could be used for cluster analysis of four categories of SFEC. Additionally, based on the correlation among the L color value, gum-silk tensile test, and PDG level, a rapid and accurate quality-control method for SFEC decoction pieces with different frying temperatures and durations was established. This method facilitates the manufacturing of efficacious SFEC.

Ferroptosis is a novel process of regulated cell death discovered in recent years, mainly caused by intracellular lipid peroxidation. It is morphologically manifested as shrinking of mitochondria, swelling of cytoplasm and organelles, rupture of plasma membrane, and formation of double-membrane vesicles. Work done in the past 5 years indicates that induction of ferroptosis is a promising strategy in the treatment of hepatocellular carcinoma (HCC). System xc-/GSH/GPX4, iron metabolism, p53 and lipid peroxidation pathways are the main focus areas in ferroptosis research. In this paper, we analyze the ferroptosis-inducing drugs and experimental agents that have been used in the last 5 years in the treatment of HCC. We summarize four different key molecular mechanisms that induce ferroptosis, i.e., system xc-/GSH/GPX4, iron metabolism, p53 and lipid peroxidation. Finally, we outline the prognostic analysis associated with ferroptosis in HCC. The findings summarized suggest that ferroptosis induction can serve as a promising new therapeutic approach for HCC and can provide a basis for clinical diagnosis and prevention of this disease.

Abstract Background Aroma, berry firmness and berry shape are three main quality traits in table grape production, and also the important target traits in grapevine breeding. However, the information about their genetic mechanisms is limited, which results in low accuracy and efficiency of quality breeding in grapevine. Mapping and isolation of quantitative trait locus (QTLs) based on the construction of genetic linkage map is a powerful approach to decipher the genetic determinants of complex quantitative traits. Results In the present work, a final integrated map consisting of 3411 SLAF markers on 19 linkage groups (LGs) with an average distance of 0.98 cM between adjacent markers was generated using the specific length amplified fragment sequencing (SLAF-seq) technique. A total of 9 significant stable QTLs for Muscat flavor, berry firmness and berry shape were identified on two linkage groups among the hybrids analyzed over three consecutive years from 2016 to 2018. Notably, new stable QTLs for berry firmness and berry shape were found on LG 8 respectively for the first time. Based on biological function and expression profiles of candidate genes in the major QTL regions, 3 genes (VIT_08s0007g00440, VIT_08s0040g02740 and VIT_08s0040g02350) related to berry firmness and 3 genes (VIT_08s0032g01110, VIT_08s0032g01150 and VIT_08s0105g00200) linked to berry shape were highlighted. Overexpression of VIT_08s0032g01110 in transgenic Arabidopsis plants caused the change of pod shape. Conclusions A new high-density genetic map with total 3411 markers was constructed with SLAF-seq technique, and thus enabled the detection of narrow interval QTLs for relevant traits in grapevine. VIT_08s0007g00440, VIT_08s0040g02740 and VIT_08s0040g02350 were found to be related to berry firmness, while VIT_08s0032g01110, VIT_08s0032g01150 and VIT_08s0105g00200 were linked to berry shape.

Nanostructure Y2O3–ZrO2 (YSZ), 4 mol% Gd2O3-YSZ (4Gd-YSZ), 6 mol% Gd2O3-YSZ (6Gd-YSZ), 8 mol% Gd2O3-YSZ (8Gd-YSZ) coatings were prepared by atmospheric plasma spraying (APS) technology under the same spraying parameters. The phase composition, microstructure, hardness, adhesion strength, water quenching behavior and failure mechanism of nano-YSZ and GdYSZ were investigated systemically. Results showed that the value of hardness, adhesion strength and water quenching lifetime of the coatings decreased in a sequence of nano-YSZ, 4Gd-YSZ, 6Gd-YSZ, 8Gd-YSZ coatings. This indicated that doping Gd2O3 into YSZ could decrease the hardness, adhesion strength, and water quenching lifetime of the coatings. The higher doping content, the more obvious effects. The related mechanisms were discussed in detail. Keywords: Atmospheric plasma spraying, Nano-YSZ coatings, Gd2O3 doping, Properties

After publication of this supplement [1, 2], it was brought to our attention that due to an error authors were missing in the following abstracts. This has now been included in this correction.

Abstract Background We recently reported a 56% objective response rate in patients with advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a biomarker predicting clinical response was not identified. Methods Pretreatment FFPE tumor specimens (n = 26) were stained for CD8, PD-L1, and PD-1 by immunohistochemistry/immunofluorescence (IHC/IF), and the density and distribution of positive cells was quantified to determine the associations with anti-PD-1 response. Multiplex IF was used to test a separate cohort of MCC archival specimens (n = 16), to identify cell types expressing PD-1. Results Tumors from patients who responded to anti-PD-1 showed higher densities of PD-1+ and PD-L1+ cells when compared to non-responders (median cells/mm2, 70.7 vs. 6.7, p = 0.03; and 855.4 vs. 245.0, p = 0.02, respectively). There was no significant association of CD8+ cell density with clinical response. Quantification of PD-1+ cells located within 20 μm of a PD-L1+ cell showed that PD-1/PD-L1 proximity was associated with clinical response (p = 0.03), but CD8/PD-L1 proximity was not. CD4+ and CD8+ cells in the TME expressed similar amounts of PD-1. Conclusions While the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, we show that quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response. Cell types expressing PD-1 in the TME include CD8+ T-cells, CD4+ T-cells, Tregs, and CD20+ B-cells, supporting the notion that multiple cell types may potentiate tumor regression following PD-1 blockade.

In construction safety management practices, identifying key stakeholders and specifying their safety behavior patterns are critical to avoid unsafe practices, which are the major cause of construction accidents. This paper argues that the main contractor and construction workers are key safety stakeholders in the construction safety management in China. The purpose of this paper is to develop an evolutionary game model to explore the safety behavior strategies of the main contractor and construction workers. In this framework, we explored the effects of model parameter changes on the evolution of safety behavior strategies and verify the evolution paths under different initial values by numerical simulations. The findings of this paper are as follows: Firstly, the safety and stability of construction projects are related to the possible losses caused by accidents, the amount of work required by construction workers to comply with safety regulations, the gain of bravado, the probability of accidents, and cost savings from the main contractor’s lax supervision. Secondly, the role of restraining the unsafe behavior of construction workers through the form of fines is limited, and increasing the fines to the main contractor cannot effectively reduce the unsafe behaviors. Thirdly, strengthening safety education, creating a safe atmosphere, and optimizing operating procedures are effective measures to improve the effectiveness of safety behavior. This study further extends the application of evolutionary game theory to construction safety management, and the findings can provide clear guidance for the development of effective incentives and constraints on safety behavior.

The evaluations of resource and environment carrying capacity and territorial development suitability, also referred to as “double evaluations”, have been taken by China as an important direction in territorial space planning. Based on the evaluation of resource and environment carrying capacity, the double evaluations can contribute to protecting ecological safety and territorial safety and promoting regional sustainable development. The focus of this study was to integratedly evaluate the resource and environment carrying capacity of the Huaihe River Ecological and Economic Belt. First, the overall weights of the factors at the dimension level and the index level in the established integration evaluation system were calculated with the fuzzy analytical hierarchy process (FAHP) method; and then, using the linear weighted function, the overall resource and environment carrying capacities of 25 cities in the belt were calculated. On that basis, the resource and environment carrying capacity evaluation model was established. Through model analysis, this study comprehensively investigated the resource and environment carrying capacity of the Huaihe River Eco-economic Belt and provided a foundation for the future territorial space planning and layout of the Huaihe River Eco-economic Belt.

This paper studies outward foreign direct investment (OFDI) enterprises in the Yangtze River Economic Belt. Using geographical information system (GIS) spatial analysis and SPSS correlation analysis methods, it analyzes the change in the spatial distribution of OFDI enterprises in 2010, 2014, and 2018. It explores the influencing factors that have an impact on this change. The results show the following: (1) The geographical distribution of OFDI enterprises in the Yangtze River Economic Belt is uneven. In the downstream region, OFDI enterprises have significant advantages in both quantity and quality over those in the mid- and up-stream regions. In recent years, a multi-core spatial pattern has gradually emerged. (2) The factors influencing the spatial distribution of OFDI enterprises have been gradually changing from one dominant factor, i.e., technological innovation capability, to four core factors, namely, urbanization level, economic development level, technological innovation capability, and degree of economic openness. The research results serve as an important reference for future policy adjustment in the Yangtze River Economic Belt. First, the Yangtze River Economic Belt should adjust industrial policies; comprehensively increase the level of OFDI; accelerate the upgrading and transformation of regional industries; and, at the same time, inject vitality into the development of the world economy. Moreover, the downstream region should fully play a leading role in the Yangtze River Economic Belt, especially in encouraging OFDI enterprises to establish global production networks. Meanwhile, enterprises in the upstream region are encouraged to establish regional production networks to accelerate the development of inland open highlands.

Abstract: Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1. In addition, because the Epstein-Barr virus (EBV) residing in some CHL tumors is strongly immunogenic, we hypothesized that characteristics of the tumor immune microenvironment in EBV+ CHL would be distinct from EBV− CHL, with specific implications for designing combination treatment regimens. Employing immunohistochemistry for immune cell subsets and checkpoint molecules, as well as gene expression profiling, we characterized 32 CHLs from the Johns Hopkins archives, including 12 EBV+ and 20 EBV− tumors. Our results revealed a dichotomous cellular and cytokine immune milieu in EBV+ vs EBV− CHL. EBV+ tumors displayed a T helper 1 (Th1) profile typical of effective antitumor immunity, with increased infiltration of CD8+ T cells and coordinate expression of the canonical Th1 transcription factor Tbet (TBX21), interferon-γ (IFNG), and the IFN-γ–inducible immunosuppressive enzyme indoleamine 2,3-dioxygenase. In contrast, EBV− tumors manifested a pathogenic Th17 profile and ongoing engagement of the interleukin-23 (IL-23)/IL-17 axis, with heightened phosphorylated signal transducer and activator of transcription 3 expression in infiltrating lymphocytes. These findings suggest that drugs blocking the IL-23/IL-17 axis, which are already in the clinic for treating certain autoimmune disorders, may enhance the therapeutic impact of anti-PD-1 therapy in EBV− CHL.

The recent literature concerning globalizing regional development has placed significant emphasis on the Global Production Network (GPN 2.0). GPN 2.0 in economic geography emphasizes that regional growth is caused by a shift in the strategic coupling mode from a low to high level. In addition, GPN 2.0 regards firm-level value capture trajectories as key analytical object, rather than the interactive relationships among scalar and divergent actors in GPN 1.0. To provide a better understanding of causal linkages between the GPNs and uneven regional development in the background of globalization and to test the applicability of GPN 2.0 analysis framework, the paper analyzed 62 Korean-invested automotive firms in Jiangsu Province, China. In order to explore the value capture trajectories of lead firms in the GPNs, the authors applied K-means clustering method to quantitatively analyze the local supply networks of lead firms from organizational and spatial dimensions. Then, comparisons were made between strategic coupling modes of GPNs and regional development in North and South Jiangsu. This study found obvious similarities within these two regions but obvious differences between them in terms of value capture trajectories. We observed that North Jiangsu is currently in the stage of “structural coupling”, whereas South Jiangsu is in the stage of “functional coupling.” Thus, this article argues that spatial settings such as regional assets and autonomy are key factors influencing uneven economic development. This research may provide a crucial reference for the regional development of Jiangsu, China.

In the process of electron-beam freeform fabrication deposition, the surface of the deposit layer becomes rough because of the instability of the feeding wire and the changing of the thermal diffusion condition. This will make the droplet transfer distance change in the deposition process, and the droplet transfer cannot always be stable in the liquid bridge transfer state. It is easy to form a large droplet or make wire and substrate stick together, which makes the deposition quality worsen or even interrupts the deposition process. The current electron-beam freeform fabrication deposition is mostly open-loop control, so it is urgent to realize the real-time and closed-loop control of the droplet transfer and to make it stable in the liquid bridge transfer state. In this paper, a real-time monitoring method based on machine vision is proposed for the droplet transfer of electron-beam freeform fabrication. The detection accuracy is up to ± 0.08 mm. Based on this method, the measured droplet transfer distance is fed back to the platform control system in real time. This closed-loop control system can stabilize the droplet transfer distance within ± 0.14 mm. In order to improve the detection stability of the whole system, a droplet transfer detection algorithm suitable for this scenario has been written, which improves the adaptability of the droplet transfer distance detection method by means of dilatation/erosion, local minimum value suppression, and image segmentation. This algorithm can resist multiple disturbances, such as spatter, large droplet occlusion and so on.

In the process of electron beam freeform fabrication (EBF3), due to the continuous change of thermal conditions and variability in wire feeding in the deposition process, geometric deviations are generated in the deposition of each layer. In order to prevent the layer-by-layer accumulation of the deviation, it is necessary to perform online geometry measurement for each deposition layer, based on which the error compensation can be done for the previous deposition layer in the next deposition layer. However, the traditional three-dimensional reconstruction method that employs structured laser cannot meet the requirements of long-term stable operation in the manufacturing process of EBF3. Therefore, this paper proposes a method to measure the deposit surfaces based on the position information of electron beam speckle, in which an electron beam is used to bombard the surface of the deposit to generate the speckle. Based on the structured information of the electron beam in the vacuum chamber, the three-dimensional reconstruction of the surface of the deposited parts is realized without need of additional structured laser sensor. In order to improve the detection accuracy, the detection error is theoretically analyzed and compensated. The absolute error after compensation is smaller than 0.1 mm, and the precision can reach 0.1%, which satisfies the requirements of 3D reconstruction of the deposited parts. An online measurement system is built for the surface of deposited parts in the process of electron beam freeform fabrication, which realizes the online 3D reconstruction of the surface of the deposited layer. In addition, in order to improve the detection stability of the whole system, the image processing algorithm suitable for this scene is designed. The reliability and speed of the algorithm are improved by ROI extraction, threshold segmentation, and expansion corrosion. In addition, the speckle size information can also reflect the thermal conditions of the surface of the deposited parts. Hence, it can be used for online detection of defects such as infusion and voids.

B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3's role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO) and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE), experimental asthma, and collagen-induced arthritis (CIA); these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively. Here, we demonstrate that B7-H3 KO mice have significantly less inflammation, decreased pathogenesis, and limited disease progression in both EAE and CIA mouse models when compared with littermates; these results were accompanied by a decrease in IFN-γ and IL-17 production. In sharp contrast, B7-H3 KO mice developed severe ovalbumin (OVA)-induced asthma with characteristic infiltrations of eosinophils in the lung, increased IL-5 and IL-13 in lavage fluid, and elevated IgE anti-OVA antibodies in the blood. Our results suggest B7-H3 has a costimulatory function on Th1/Th17 but a coinhibitory function on Th2 responses. Our studies reveal that B7-H3 could affect different T cell subsets which have important implications for regulating pathogenesis and disease progression in human autoimmune disease.

A pathogenic hallmark of rheumatoid arthritis (RA) is persistent inflammatory responses in target tissues and organs. Immune responses mediated by T cells and autoantibodies are known to play pivotal roles. A possible interpretation for this observation is a loss of negative regulation of autoimmune responses. Here we sought to investigate whether B7-H4, a cell surface inhibitory molecule of the B7-CD28 signaling pathway, may play a role in the pathogenesis of RA.In a cross-sectional study of a clinical convenience sample using monoclonal antibodies against human B7-H4 molecules, we detected high levels of the soluble form of B7-H4 (sH4) in the sera of 65% of patients with RA (n = 68) versus only 13% of healthy donors (n = 24). Elevated sH4 was associated with an increased disease severity score (DAS28) in a cross-sectional analysis. In a mouse model of RA, transgenic expression of sH4 or genetic deletion of B7-H4 accelerated the progression of collagen-induced arthritis, accompanied by enhanced T and B cell-mediated autoimmune responses as well as increased activity of neutrophils. Expression in vivo of an agonist, a B7-H4-immunoglobulin Fc fusion protein, profoundly suppressed disease progression in the mouse model.Our findings in mice indicate that sH4 acts as a decoy molecule to block the inhibitory functions of cell-surface B7-H4, leading to exacerbation of collagen-induced arthritis. If the preliminary correlation between sH4 levels and disease activity in patients with RA can be confirmed to reflect a similar mechanism, these findings suggest a novel target for treatment approaches. Please see later in the article for the Editors' Summary.

A green smart city is important in the urbanization of countries, and an evaluation system for the functionality and management of the green smart city is inevitable in its construction and maintenance. In this study, we used the fuzzy Delphi method to establish an evaluation index system of the green smart city in line with 5G technology and IoT based on a literature review. The fuzzy hierarchical analysis method was adopted to create questionnaires for experts and extract the weights of the index in the green smart city evaluation system. The method was applied to Shanghai and Taipei in China to assess the level of the application of the green smart city. On the basis of the results, suggestions for the improvement of the evaluation system and development strategies for the green smart city were made, which is an important reference for promoting the construction of green smart cities. [ABSTRACT FROM AUTHOR]