CCL18 promotes migration and invasion of multiple myeloma cells and is associated with poor prognosis.

CCL18 has recently been implicated in malignancies and is increasingly mentioned as a potential tumoral biomarker and furtherly a molecular target for therapeutic intervention, but its expression and clinical significance in multiple myeloma have not been explored. Serum CCL18 levels were measured by ELISA method in 254 newly diagnosed multiple myeloma (NDMM), 21 monoclonal gammopathy of undetermined significance (MGUS) and 22 healthy adults. The study suggests that the serum CCL18 level in NDMM patients was significantly higher than that in MGUS and healthy adults. High level of CCL18 were associated with advanced ISS and R-ISS stages in MM. Patients with high serum CCL18 displayed a significantly more frequent occurrence of renal impairment and hypercalcemia, while the proportion of achieving complete remission (CR) was lower. More importantly, Cox analysis identified CCL18 and LDH as independent predictors of PFS in MM patients, whereas CCL18, creatinine and LDH were independent predictors of OS. Finally, we show that CCL18 can promote migration and invasion of myeloma cell lines RPMI8226 and MM.1S. CCL18 may play a tumor-promoting role by increasing the migration and invasion abilities of myeloma cells.

Metabolomics reveals the role of Lactobacillus plantarum SHY130 in hepatic metabolic regulation in a mouse model of type 2 diabetes.

BACKGROUND: Among type 2 diabetes (T2D) patients, the incidence rate of liver metabolic disorders is much higher than that in healthy subjects. It was observed in our previous research that diabetic symptoms were improved by Lactobacillus plantarum SHY130 (LPSHY130) isolated from yak yogurt in a murine model of T2D. This study sought to investigate the LPSHY130-mediated hepatic metabolic regulation in a murine model of T2D. RESULTS: Treatment with LPSHY130 improved liver function and pathological damage in diabetic mice. Untargeted metabolome analysis revealed that T2D-induced changes in 11 metabolites were regulated after LPSHY130 treatment, mainly involving purine metabolism, amino acid metabolism, and choline metabolism and pantothenate and coenzyme A biosynthesis pathways. In addition, correlation analysis indicated that hepatic metabolic changes can be adjusted by the intestinal microbiota. CONCLUSION: Overall, this study suggests that treatment with LPSHY130 relieves liver injury and regulates liver metabolism in a murine model of T2D, thus providing a theoretical basis for the use of probiotics as dietary supplements to regulate hepatic metabolic disorders associated with T2D. © 2023 Society of Chemical Industry.

Enhancing predictions of remedial reagent transport via a vertical groundwater circulation well with high-resolution aquifer characterization.

The vertical groundwater circulation well (GCW) is a commonly used technique in contaminated sites to remove secondary contaminants from low permeable zones. Early GCW studies often used simple subsurface hydraulic properties, such as anisotropic homogeneous aquifers or low conductivity lens/blocks, to mimic the complex subsurface heterogeneity. Although studies based on simplified representations of aquifer heterogeneity provide straightforward flow and transport information for engineering design of a GCW, they may over- or under-estimate contaminant fate and transport in the field. The objective of this study is to identify key heterogeneity factors that control the capture zone extension and to examine the extent to which the accuracy of estimated heterogeneity spatial distributions influences the prediction of remedial reagent transport. To achieve these objectives, we utilized Monte Carlo simulation to investigate the extension of the circulation zone in heterogeneous aquifers and to identify the key factors that contribute most to the variability of the circulation zone. Three commonly used geostatistical approaches (equivalent homogeneous, kriging, and highly parameterized methods) were employed to estimate the spatial distributions of key factors. The reliabilities of these estimated fields were evaluated through their remedial reagent transport predictability. The key factor analysis revealed that the mean porosity value, the variance of lnK, and the correlation length of lnK profoundly influence the lateral expansion of the capture zone. Neglecting the aquifer hydraulic conductivity heterogeneity underestimates the extension of the circulation zone and the spread of remedial reagent. Additionally, utilizing a highly parameterized approach to estimate the high-resolution K field can accurately reproduce the key remedial reagent distributions. The concentration arrival time and peak concentration are significantly improved compared to those predictions based on the equivalent homogeneous and kriged K fields.

Research on the diurnal variation characteristics of ozone formation sensitivity and the impact of ozone pollution control measures in "2 + 26" cities of Henan Province in summer.

Near-surface ozone pollution is becoming an increasingly serious air quality issue in China, especially in "2 + 26" cities (Beijing-Tianjin-Hebei and nearby cities). HN2 + 26 cities ("2 + 26" cities of Henan Province) are located in the south of "2 + 26" cities, with frequent and severe ozone pollution events in recent years. This study investigated the diurnal evolution characteristics of ozone formation sensitivity (OFS) of HN2 + 26 cities from May to September in 2021 by the innovative combination of Global Ozone Monitoring Experiment (GOME-2B) and Ozone Monitoring Instrument (OMI) satellite data, and assessed the impact of ozone pollution control measures (OPCMs) implemented from June 26 to July 1, 2021. The localized FNR (ratio of formaldehyde to nitrogen dioxide of satellite measurement) threshold (1.4-2.55) was established, and it was found that OFS in May-September 2021 was mainly in VOCs-limited regime in the morning (∼10:00), while transitional/NOx-limited regime in the afternoon (∼14:00). Three periods (before, during and after the OPCMs) were divided to evaluate the impact of OPCMs on OFS. It was indicated that OPCMs had no impact on the morning OFS, but had a significant impact on the afternoon OFS. Specifically, the OFS in two industrial cities Xinxiang (XX) and Zhengzhou (ZZ) shifted from transitional regime to NOx-limited regime after the OPCMs. We further investigated OFS differences between urban and suburban areas and found that OFS shift of XX only existed in urban areas, while that of ZZ existed in both urban and suburban areas. We compared their measures and found that it is effective to take hierarchical control measures on different levels of ozone pollution days to alleviate ozone pollution. This study provides an improved understanding of diurnal evolution characteristics of OFS and the impacts of OPCMs on it, which will provide a theoretical basis for formulating more scientific ozone pollution control policies.

Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma?

Multiple myeloma (MM) is the second most common hematologic malignancy, resulting from the clonal proliferation of malignant plasma cells within the bone marrow. Despite significant advances that have been made with novel drugs over the past two decades, MM patients often develop therapy resistance, especially to bortezomib, the first-in-class proteasome inhibitor that was approved for treatment of MM. As highly secretory monoclonal protein-producing cells, MM cells are characterized by uploaded endoplasmic reticulum stress (ERS), and rely heavily on the ERS response for survival. Great efforts have been made to illustrate how MM cells adapt to therapeutic stresses through modulating the ERS response. In this review, we summarize current knowledge on the mechanisms by which ERS response pathways influence MM cell fate and response to treatment. Moreover, based on promising results obtained in preclinical studies, we discuss the prospect of applying ERS modulators to overcome drug resistance in MM.

LORM: a novel reinforcement learning framework for biped gait control.

Legged robots are better able to adapt to different terrains compared with wheeled robots. However, traditional motion controllers suffer from extremely complex dynamics properties. Reinforcement learning (RL) helps to overcome the complications of dynamics design and calculation. In addition, the high autonomy of the RL controller results in a more robust response to complex environments and terrains compared with traditional controllers. However, RL algorithms are limited by the problems of convergence and training efficiency due to the complexity of the task. Learn and outperform the reference motion (LORM), an RL based framework for gait controlling of biped robot is proposed leveraging the prior knowledge of reference motion. The proposed trained agent outperformed the reference motion and existing motion-based methods. The RL environment was finely crafted for optimal performance, including the pruning of state space and action space, reward shaping, and design of episode criterion. Several improvements were implemented to further improve the training efficiency and performance including: random state initialization (RSI), the noise of joint angles, and a novel improvement based on symmetrization of gait. To validate the proposed method, the Darwin-op robot was set as the target platform and two different tasks were designed: (I) Walking as fast as possible and (II) Tracking specific velocity. In task (I), the proposed method resulted in the walking velocity of 0.488 m/s, with a 5.8 times improvement compared with the original traditional reference controller. The directional accuracy improved by 87.3%. The velocity performance achieved 2× compared with the rated max velocity and more than 8× compared with other recent works. To our knowledge, our work achieved the best velocity performance on the platform Darwin-op. In task (II), the proposed method achieved a tracking accuracy of over 95%. Different environments are introduced including plains, slopes, uneven terrains, and walking with external force, where the robot was expected to maintain walking stability with ideal speed and little direction deviation, to validate the performance and robustness of the proposed method.

Lactobacillus plantarum SHY130 isolated from yak yogurt attenuates hyperglycemia in C57BL/6J mice by regulating the enteroinsular axis.

Diabetes, one of the most serious and common chronic metabolic diseases affecting people worldwide in the 21st century, has become a major problem that needs to be addressed urgently. This study was designed to elucidate the anti-diabetic effect of yak yogurt-derived Lactobacillus (L.) plantarum SHY130 on C57BL/6J mice fed high-fat diet and streptozotocin (HFD/STZ), and the potential regulatory mechanisms involved. Mice were divided into 3 groups: normal control, diabetes, and diabetes treated with L. plantarum SHY130 (SHY130). Treatment with L. plantarum SHY130 had a regulatory effect on blood glucose and clearly ameliorated insulin resistance in T2DM mice. L. plantarum SHY130 inhibited the reduction in ß-cell mass and α-cell proliferation in the pancreas and increased the expression of the short-chain fatty acid (SCFA) receptors GPR43 and GPR41 in the colon of T2DM mice. Furthermore, L. plantarum SHY130 treatment readjusted intestinal flora structure, enhanced the abundance of SCFA-producing bacteria, such as Faecalibaculum, Odoribacter, Alistipes, and increased the levels of SCFAs in diabetic mice. In summary, L. plantarum SHY130 ameliorated hyperglycemia in HFD/STZ-induced diabetic mice by regulating the enteroinsular axis.

Developing Key Safety Management Factors for Construction Projects in China: A Resilience Perspective.

It is acknowledged that construction safety is pivotal to the project management objectives. Meanwhile, the concept of resilience provides an effective and pragmatic countermeasure to improve the safety management level of construction projects. However, the "resilience" has not gained considerable attention in the construction safety management system. In this context, the paper aims to develop the key safety management factors for construction projects from the resilience perspective. Firstly, the theoretical framework and key safety management factors of construction safety management system based on the resilience theory are proposed. The importance of each factor is then obtained by using the method of structural equation modeling (SEM). The results indicate that information management, material and technology management, organization management and personnel management would improve the safety and resilience of the project. Specifically, improving the resilience of information flow to strengthen the interaction among elements of the system can enhance the safety management level. These findings can be used as references for construction safety managers to improve the abilities of preventing safety accidents and recovering after safety accidents.

Microbial Insight into a Pilot-Scale Enhanced Two-Stage High-Solid Anaerobic Digestion System Treating Waste Activated Sludge.

High solid anaerobic digestion (HSAD) is a rapidly developed anaerobic digestion technique for treating municipal sludge, and has been widely used in Europe and Asia. Recently, the enhanced HSAD process with thermal treatment showed its advantages in both methane production and VS reduction. However, the understanding of the microbial community is still poor. This study investigated microbial communities in a pilot enhanced two-stage HSAD system that degraded waste activated sludge at 9% solid content. The system employed process "thermal pre-treatment (TPT) at 70 °C, thermophilic anaerobic digestion (TAD), and mesophilic anaerobic digestion (MAD)". Hydrogenotrophic methanogens Methanothermobacter spp. dominated the system with relative abundance up to about 100% in both TAD and MAD. Syntrophic acetate oxidation (SAO) bacteria were discovered in TAD, and they converted acetate into H2 and CO2 to support hydrogenotrophic methanogenesis. The microbial composition and conversion route of this system are derived from the high solid content and protein content in raw sludge, as well as the operational conditions. This study could facilitate the understanding of the enhanced HSAD process, and is of academic and industrial importance.

[Microbial Structure of an Enhanced Two-phase High-solid Anaerobic Digestion System Treating Sludge].

High-solid anaerobic digestion (HSAD) of sludge has several advantages like smaller reactor, lower energy consumption and less digestate. However, the understanding about the mechanism especially the microbial mechanism is still limited. In this study, microbial communities of a pilot-scale sludge HSAD system at steady state were investigated with 16S rRNA clone library technology. The system employed an enhanced two-phase anaerobic digestion process, i. e. 'hyperthermophilic acidogenesis (70℃, 3 d)-thermophilic methanogenesis (55℃, 12.5 d)' to treat waste activated sludge with a solid content of about 9%. The volatile solid (VS) removal rate was 35.7% and methane yield (CH4/VSremoved) was 0.648 m3·kg-1. The bacterial compositions of the two phases were significantly different:there were plenty of proteolytic bacteria in hyperthermophilic acidogenesis phase; and the bacteria degrading polysaccharides like cellulose and the bacteria utilizing long-chain fatty acids were found in thermophilic methanogenesis phase; some bacteria degrading simple saccharides existed in both phases. In both phases, the dominant archaea were Methanothermobacter. Especially, 100% of the retrieved archaea in the thermophilic methanogenesis phase belonged to genus Methanothermobacter. This indicated that hydrogenotrophic methanogenesis was the predominant methanogenesis pathway in this system since methane was only detected in the methanogenesis phase.

[Pilot study of thermal treatment/thermophilic anaerobic digestion process treating waste activated sludge of high solid content].

A pilot-scale experiment about the process of "thermal pretreatment at 70°C/thermophilic anaerobic digestion" of waste activated sludge of high solid content (8% -9% ) was conducted. The process employed thermal treatment of 3 days to accelerate the hydrolysis and thermophilic digestion to enhance anaerobic reaction. Thus it was good at organic removal and stabilization. When the solid retention time (SRT) was longer than 20 days, the VSS removal rate was greater than 42. 22% and it was linearly correlated to the SRT of the aerobic digestion with the R2 of 0. 915 3. It was suggested that SRT of anaerobic digestion was 25 days in practice. VSS removal rate and biogas production rate of the pilot experiment were similar to those of the run-well traditional full-scale sludge anaerobic digestion plants (solid content 3% -5% ) and the plant of high solid content using German technique.