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In an attempt to improve the utilization efficiency of multi-energy coupling in park-level integrated energy system (PIES), promote wind power consumption and reduce carbon emissions, a low-carbon economic operation optimization model of PIES integrating flexible load and carbon trading mechanism is constructed. Firstly, according to the characteristics of load response, the demand response is divided into four types: which can be shifted, transferred, reduced and replaced. Secondly, the PIES basic architecture is given by considering the combined heat and power generation coupling equipment, new energy and flexible load in the park. Finally, introducing the ladder-type carbon trading mechanism into the system and minimize the total operating cost, the low-carbon economic operation optimization model of PIES is established. The YALMIP toolbox and CPLEX solver are used to solve the example, the simulation results show that the participation of electrical and thermal coupled scheduling and flexible electric or thermal loads can significantly reduce the system operating cost, reduce the load peak-to-valley difference and relieve peak power consumption pressure., Comment: accepted by Energy Reports

Objective: To elucidate the role and mechanism of cysteine protease inhibitor SN (CST1) in promoting the metastasis of gastric cancer. Methods: (1) Firstly, 6 pairs of cancer and paracancer tissue samples from gastric cancer patients without distant metastasis and 5 pairs of cancer and paracancer tissue samples from gastric cancer patients with peritoneal metastasis were collected for transcriptome sequencing. Statistical analysis was performed on the sequencing results to identify significantly upregulated differential genes. (2) Another 75 pairs of cancer and paracancer tissue samples were collected from gastric cancer patients, and the protein and total RNA of gastric cancer tissue samples were extracted. Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression of CST1 protein and messenger RNA (mRNA) in gastric cancer and adjacent tissues. (3) The total protein and total RNA of AGS, BGC823, HGC-27, MGC803, MKN45, SGC7901, and SNU-1 gastric cancer cells and normal gastric mucosal epithelial cells GES-1 were extracted. Western blot and qRT-PCR were used to detect CST1 protein and mRNA expression. Results: (1) The significantly upregulated differential gene CST1 was screened, and the expression of CST1 in gastric cancer tissues was significantly higher than that in adjacent tissues. (2) Compared with normal gastric mucosal epithelial cells GES-1, the expression of CST1 in gastric cancer cell lines was upregulated, and the expression of CST1 in HGC-27 and SNU-1 was relatively low, while the expression of CST1 in AGS and MKN45 was relatively high. At the same time, a stable cell line of HGC-27 overexpressing CST1 and MKN45 knocking down CST1 was successfully constructed. (3) Overexpression or knockdown of CST1 did not significantly change the proliferation ability of gastric cancer cells, but can promote the migration and invasion of gastric cancer cells. (4) CST1 may promote the metastasis of gastric cancer cells by activating the epithelial–mesenchymal transition (EMT) signaling pathway. Conclusion: CST1 gene promotes the migration of gastric cancer cells, and we found through animal experiments that CST1 can affect the metastasis and invasion function of gastric cancer and is negatively correlated with the level of E-cadherin.

Elevated IgG expression in cancer cells has been implicated in exacerbated malignancy and poor clinical prognosis. Accumulating evidence indicates that a nonconventional sialylation modification is critical for the function of cancer-derived IgG, indicating the need for a better understanding of the regulatory mechanisms that control the expression and function of sialylated cancer IgG (SIA-cIgG). Here, we conducted genome-wide CRISPR activation screening and identified OCT4 and SOX2 as the key factors that promote SIA-cIgG expression. Functional investigation revealed that SIA-cIgG reciprocally stimulated SOX2 by activating the c-Met/Akt/Erk signaling axis, constituting a self-propagating loop of SIA-cIgG/c-Met/SOX2/SIA-cIgG signaling. This signaling loop was highly active in stem-like cells from many epithelial cancers and was crucial for cancer stemness in vitro and in vivo. Notably, the mAb RP215, which specifically recognizes the Asn162 sialylation–related epitope on SIA-cIgG, effectively blocked the SIA-cIgG–driven signaling loop. Furthermore, RP215 significantly inhibited lung cancer cell stemness and tumor growth in a patient-derived xenograft model. In conclusion, these findings revealed a self-propagating c-Met/SOX2/SIA-cIgG signaling loop that promotes cancer stemness, identifying novel therapeutic strategies for cancer treatment. Significance: Sialylated cancer IgG activates c-Met-SOX2 signaling to promote stemness properties in cancer cells and can be targeted to suppress tumor growth.

PurposeThe purpose of this paper is to recover the waste heat of flue gas heat exchanger (FGHE) as efficiently as possible and avoid the acid dew corrosion of that.Design/methodology/approachA novel flue gas waste heat recovery system was proposed in the paper. The dynamic mathematical models of key equipment in that were established based on theory and experiment method. The proportion integration differentiation-differentiation (PID-P) cascade control method based on particle swarm optimization algorithm was used to control the outlet temperature of FGHE. The dynamic characteristics of the flue gas heat exchange system were simulated by the particle swarm optimization algorithm with different fitness functions.FindingsThe PID-P temperature controller parameters can be quickly and effectively obtained by the particle swarm optimization algorithm based on the fitness function of integral time absolute error (ITAE). The overshoot, rise time and adjusting time of the novel system are 2, 83 and 105s, respectively. Compared with the traditional two-step tuning (T-ST) method, the novel system is better in dynamic and steady-state performance. The overshoot and the adjustment time of the system are reduced by 44% and 328s, respectively. ITAE is a performance evaluation index for control system with good engineering practicability and selectivity.Originality/valueThe dynamic mathematical model of key equipment in the new flue gas waste heat recovery system is established and the system's control strategies and methods are explored.

Despite remarkable initial responses of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC) patients, cancers eventually develop resistance within one to two years. This study aimed to compare the properties of iruplinalkib (WX‑0593) with other ALK inhibitors and report the comprehensive characterization of iruplinalkib against the crizotinib resistance. The inhibitory effect of iruplinalkib on kinase activity was detected. A kinase screen was performed to evaluate the selectivity of iruplinalkib. The effect of iruplinalkib on related signal transduction pathways of ALK and c-ros oncogene 1 (ROS1) kinases was examined. The cellular and in vivo activities of ALK inhibitors were compared in engineered cancer-derived cell lines and in mice xenograft models, respectively. Human hepatocytes derived from three donors were used for evaluating hepatic enzyme inducing activity. HEK293 cell lines expressing transportors were used to invesigated the drug interaction potential mediated by several transporters. The results showed iruplinalkib potently inhibited the tyrosine autophosphorylation of wild-type ALK, ALKL1196M, ALKC1156Y and epidermal growth factor receptor (EGFR)L858R/T790M. The inhibitory effects of iruplinalkib in patient-derived xenograft and cell line-derived xenograft models were observed. Moreover, iruplinalkib showed robust antitumor effects in BALB/c nude mice xenograft models with ALK-/ROS1-positive tumors implanted subcutaneously, and the tumor suppressive effects in crizotinib-resistant model was significantly better than that of brigatinib. Iruplinalkib did not induce CYP1A2, CYP2B6 and CYP3A4 at therapeutic concentration, and was also a strong inhibitor of MATE1 and MATE2K transporters, as well as P-gp and BCRP. In conclusion, iruplinalkib, a highly active and selective ALK/ROS1 inhibitor, exhibited strong antitumor effects in vitro and in crizotinib-resistant models.

PURPOSE The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.

Ambient air pollution of fine particulate matter with diameters less than 2.5 μm (PM

Domain generalization aims at generalizing the network trained on multiple domains to unknown but related domains. Under the assumption that different domains share the same classes, previous works can build relationships across domains. However, in realistic scenarios, the change of domains is always followed by the change of categories, which raises a difficulty for collecting sufficient aligned categories across domains. Bearing this in mind, this article introduces union domain generalization (UDG) as a new domain generalization scenario, in which the label space varies across domains, and the categories in unknown domains belong to the union of all given domain categories. The absence of categories in given domains is the main obstacle to aligning different domain distributions and obtaining domain-invariant information. To address this problem, we propose category-stitch learning (CSL), which aims at jointly learning the domain-invariant information and completing missing categories in all domains through an improved variational autoencoder and generators. The domain-invariant information extraction and sample generation cross-promote each other to better generalizability. Additionally, we decouple category and domain information and propose explicitly regularizing the semantic information by the classification loss with transferred samples. Thus our method can breakthrough the category limit and generate samples of missing categories in each domain. Extensive experiments and visualizations are conducted on MNIST, VLCS, PACS, Office-Home, and DomainNet datasets to demonstrate the effectiveness of our proposed method.

A simple and metal-free catalytic system composed of NaOtBu/DMF efficiently converted 5-HMF to FDCA with an 80.85% yield. 5-HMF analogues and various types of alcohols were also transformed to corresponding acids in satisfactory to excellent yield.

Oral administration of BL-99 can enrich the beneficial SCFA-producing bacteria, restrain the pathogenic microbes and preclude the infiltration of pulmonary inflammatory monocyte/macrophage, therefore alleviating colitis-related lung injury.

Let $\lambda$ and $\mu$ be beta-Jacobi and beta-Laguerre ensembles with joint density function $f_{\beta, m, a_1, a_2}$ and $f_{\beta, m, a_1}$, respectively. Here $\beta>0$ and $a_1, a_2$ and $m$ satisfying . $a_1, a_2>\frac{\beta}{2}(m-1).$ In this paper, we consider the distance between $2(a_1+a_2)\lambda$ and $\mu$ in terms of total variation distance and Kullback-Leibler distance. Following the idea in \cite{JM2017}, we are able to prove that both the two distances go to zero once $a_1m=o(a_2)$ and not so if $\lim_{a_2\to\infty}a_1m/a_2=\sigma>0.$, Comment: 34 pages

Domain generalization aims to generalize a network trained on multiple domains to unknown yet related domains. Operating under the assumption that invariant information generalizes well to unknown domains, previous work has aimed to minimize the discrepancies amongst distributions across given domains. However, without prior regularization of feature distributions in unknown domains, the network in practice overfits the invariant information in the given domains. Moreover, if there are insufficient samples in given domains, then domain generalizability is limited, as diverse domain variations are not captured. To address these two drawbacks, we propose to explicitly map features in known and unknown domains onto latent space in a fixed Gaussian mixture distribution by variational coding. As a result, features in different classes follow Gaussian distributions with different mean values. The predefined latent space narrows discrepancies between known and unknown domains and effectively separates samples into different classes. Moreover, we propose to perturb sample features with gradients from the distribution regularized loss. This perturbation generates samples beyond but near the latent space of prior distributions, which has a profound impact on domain variations. Experiments and visualizations demonstrate the effectiveness of our proposed method.

For a long time, because of China’s large population and small per capita resource occupancy, the use of natural resources is unreasonable. Soil degradation problem due to the long-term irrational utilization of land resources is becoming more and more serious, which seriously damaging the ecological environment and hindering China’s modernization process. Facing the problem of soil remediation, biochar technology has become a research hotspot because of its advantages of green environmental protection, low cost, high efficiency, and wide application. And black soil in northeast China and southern region of red soil as important soil types of agroforestry in China, over the years have experienced serious soil degradation crisis. In this paper, black soil and red soil are selected as research objects to explore the impact of biochar on the physical and chemical properties of the two soils. This paper intends to use the methods of investigation and analysis, and comparison in many aspects. Through the study, it was found that the application of biochar had the same trend of influence on the organic carbon content and C/N ratio of the two soils, but the index of black soil increased more significantly. The change trend of soil bulk density and pH was also consistent with the application of biochar, and the difference was not significant. The effects of biochar applied to the two soils on greenhouse gas emissions were quite different. The soil health of black soil and red soil is of great significance in China’s agricultural production and life. This paper expects to bring reference value to the improvement of the overall soil function and the promotion of ecological restoration process of China’s biochar modification work for different soil types in the north and south, by comparing the impact of biochar on the physical and chemical properties of the two soils. A better soil improvement program can be obtained after comparative analysis, so as to provide suggestions on sustainable development and comprehensively promote ecological construction.

Introduction: It is crucial to identify predictors of mortality in the early stage of acute ischemic stroke for the oldest old (aged ≥80 years) because of their poor overall survival outcomes. However, limited data are available as the oldest old have often been excluded from previous clinical studies. Hence, we aimed to assess the predictive effect of red blood cell distribution width on in-hospital mortality and the dose-response relationship between the red blood cell distribution width and in-hospital mortality in oldest old with acute ischemic stroke. Methods: A retrospective cohort study was performed in two tertiary hospitals. Patients aged ≥80 years admitted due to acute ischemic stroke from January 1, 2014, to January 31, 2020, were included in the study. We divided the eligible patients into 3 groups with tertiles of red blood cell distribution width. Restrictive cubic spline and robust locally weighted regression analysis were performed to test the dose-response relationship between red blood cell distribution width and the in-hospital mortality risk. All-cause in-hospital mortality was the main study outcome. Results: Overall, 606 patients were included in the final analysis. Red blood cell distribution width was categorized into 3 groups (T1: 15.7%). The rationality of this categorization was then validated with restricted cubic spline and robust locally regression smoothing scatterplot, respectively. After adjusting for demographic and clinical features, a higher red blood cell distribution width was independently associated with in-hospital mortality and the hazard ratio (HR) was 3.31 (95% CI 2.47–4.45, p < 0.001). There was a positive dose-response relationship between red blood cell distribution width and mortality risk. Sensitivity analysis identified no conspicuous change in the HR. Conclusions: Red blood cell distribution width may be a valuable and simple measure for predicting in-hospital mortality in oldest old patients with acute ischemic stroke.