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How to realize the game equilibrium between bus and nontransit vehicle is a hot topic in the field of transit signal priority (TSP). To this end, a collaborative transit signal priority (Co-TSP) method is proposed. The core of Co-TSP is a two-objective optimization problem which takes the expected delays of buses and the average delays of nontransit vehicles as the objectives. Different from previous studies, Co-TSP uses game theory to realize collaborative optimization, instead of transforming the problem into a single objective optimization problem by weighting. A finite state machine-based algorithm is developed to estimate the average delays of nontransit vehicles. The stochasticity of bus arrival time is also considered in the estimation of bus delays to improve the robustness. Candidate timing plans obtained by the nondominated sorting genetic algorithm (NSGA) are divided into three priority levels based on the delays of buses. The final timing plans can be picked intuitively from the candidates by rules representing expert knowledge and demands to control the priority level. Co-TSP guarantees theoretically by preliminary screening that the expected delays of bus after optimization must be no higher than that before optimization. Simulation experiments are conducted in Shanghai, China, to verify the performance. Results show that Co-TSP reduces the delays of buses by 27.7%∼41.0% and still performs well under low and high congestion levels, while the conventional TSP (CTSP) fails in some cases. Priority control proves to be effective at last. The research provides a new idea for the benefit allocation among participants at intersections.

In recent years, machine learning technology has achieved fruitful results in many fields. However, in the fields of credit scoring and medical treatment, due to the lack of interpretability of various algorithms, there is a lack of authoritative interpretation when dealing with security-sensitive tasks, resulting in bad decisions made by enterprises. While improving the prediction accuracy of the algorithm model, the interpretability of the algorithm model is enhanced, which is conducive to making optimal decisions. Therefore, it is proposed to use Borderline-SMOTE to balance the data, introduce the influence factor posFac to fine control the random number during the synthesis of new samples, and use Bayesian algorithm to optimize XGBoost. SHAP is used to explain and analyze the prediction results of the optimized XGBoost algorithm model, and the most influential eigenvalue of the output results of the algorithm model and the characteristics of the input eigenvalue of the algorithm model are solved. The experiment improves the prediction accuracy of XGBoost algorithm model and its interpretability, so as to further promote its research and wide application in various fields.

Anti-CRISPR proteins are encoded by phages to inhibit the CRISPR-Cas systems of the hosts. AcrIIC5 inhibits several naturally high-fidelity type II-C Cas9 enzymes, including orthologs fromNeisseria meningitidis(Nme1Cas9) andSimonsiella muelleri(SmuCas9). Here, we solve the structure of AcrIIC5 in complex with Nme1Cas9 and sgRNA. We show that AcrIIC5 adopts a novel fold to mimic the size and charge distribution of double-stranded DNA, and uses its negatively charged grooves to bind and occlude the protospacer adjacent motif (PAM) binding site in the target DNA cleft of Cas9. AcrIIC5 is positioned into the crevice between the WED and PI domains of Cas9, and one end of the anti-CRISPR interacts with the phosphate lock loop and a linker between the RuvC and BH structural domains. We employ biochemical and mutational analyses to build a model for AcrIIC5’s mechanism of action, and identify residues on both the anti-CRISPR and Cas9 that are important for their interaction and inhibition. Together, the structure and mechanism of AcrIIC5 reveal convergent evolution among disparate anti-CRISPR proteins that use a DNA-mimic strategy to inhibit diverse CRISPR-Cas surveillance complexes, and provide new insights into a tool for potent inhibition of type II-C Cas9 orthologs.

ObjectiveAssess pooled safety results through the end of the phase II/III studies of guselkumab (GUS; ≤ 2 years) in tumor necrosis factor inhibitor (TNFi)-naïve and -experienced patients with psoriatic arthritis (PsA).MethodsData were pooled from the Phase 2 and DISCOVER-1 (both TNFi-naïve and -experienced), DISCOVER-2 (TNFi-naïve), and COSMOS (TNFi-experienced) studies. Patients with active PsA were randomized to GUS 100 mg every 4 or 8 weeks (Q4W + Q8W = Combined GUS) or placebo (PBO) with crossover to GUS Q4W or Q8W at week 24. Time-adjusted adverse event (AE) rates (events/100 patient-years [PY]) and clinical laboratory findings were assessed during the PBO-controlled period and through end of study (≤ 2 years).ResultsOf 1554 randomized patients (n = 373 [GUS Q4W], 664 [GUS Q8W], and 517 [PBO]), 1138 (73.23%) were TNFi-naïve and 416 (26.77%) were TNFi-experienced. Respective AE rates through week 24 were 220.8/100 PY (TNFi-naïve) and 251.6/100 PY (TNFi-experienced) in the Combined GUS group and 196.1/100 PY (TNFi-naïve) and 303.0/100 PY (TNFi-experienced) in the PBO group. Among all GUS-treated patients (including those who crossed over from PBO), low AE rates were maintained during long-term evaluation in both TNFi-naïve (139.7/100 PY) and TNFi-experienced (174.0/100 PY) patients. Rates/100 PY of AEs leading to treatment discontinuation, serious AEs, and other AEs of interest, as well as occurrence of elevated hepatic transaminase levels and decreased neutrophil counts were consistent between PBO and GUS-treated patients through week 24 regardless of prior TNFi use and remained low through the end of the studies.ConclusionThe safety profile of GUS in TNFi-experienced patients was consistent with that in TNFi-naïve patients, which remained favorable for up to 2 years. [ClinicalTrials.gov: Phase 2 (NCT02319759), DISCOVER-1 (NCT03162796), DISCOVER-2 (NCT03158285), and COSMOS (NCT03796858)]

Chang 22-19 belongs to the banshen 51 fault block of changlu oilfield, which is located 3km north of group 10 of changlu salt field. Production fell to 74% by July 2021. Through the analysis of formation potential, a perforating software is used to optimize reasonable perforating and lifting process parameters to make the well produce efficiently and develop efficiently.

The CSCO and ASCO guidelines in 2021 recommend chemotherapy for stage III-IVA (8th edition of AJCC staging) nasopharyngeal carcinoma (NPC). Actually, patients with stage T3-4N0M0 are often excluded from various clinical trials of the locoregionally advanced NPC, and the survival benefit of chemotherapy in such patients has always been controversial. This study aims to explore the benefit of chemotherapy in patients with locoregionally advanced NPC, especially those with negative lymph nodes.A total of 2741 patients were extracted from the SEER database. After a 1:1 PSM analysis, 272 patients were obtained to further explore whether the addition of chemotherapy would achieve survival benefits.After PSM, Kaplan-Meier curves showed that the overall survival (OS) of patients receiving chemoradiotherapy (p = 0.031) was higher than those receiving radiotherapy alone. Similar results were observed for cancer-specific survival (CSS). We further stratified the patients according to lymph node status and found that the addition of chemotherapy in patients with positive lymph nodes could significantly improve 5-year OS rates (58.08% vs. 43.95%; p = 0.025) and 5-year CSS rates (67.42% vs. 51.95%; p = 0.015) compared with radiotherapy alone, but there was no additional benefit of chemotherapy in patients with negative lymph nodes. For all 449 cases of T3-4N0M0 NPC, radiotherapy improved the OS rates (HR 0.293, 95% CI 0.203-0.424) and the CSS rates (HR 0.252, 95% CI 0.171-0.371) compared with no radiotherapy, while chemotherapy did not show significant survival benefit compared with no chemotherapy.Our results reveal that stage T3-4N0M0 NPC may be exempted from chemotherapy, and use radiotherapy alone to reduce toxic and side effects. These results still need to be verified by future prospective trials.

biBackground:/i/bThe microbial community in human milk is associated with many maternal and neonatal factors. This study aimed to investigate the effect of antibiotic exposure on the microbial community structure of colostrum.biMethods:/i/bTwenty women with antibiotic treatment immediately after delivery and 10 age-matched control women were enrolled at the Guangdong Women and Children Hospital. Colostrum samples were collected within postpartum 30 hours. The V4 variable region of the bacterial 16S rRNA gene was sequenced to characterize the microbial profile using Illumina MiSeq platform.biResults:/i/bPhylaiProteobacteria/iandiFirmicutes/iwere the predominant bacteria in colostrum samples. The core and abundant genera in colostrum includediStreptococcus/i,iStaphylococcus/i, andiPseudomonas/i. Compared with the control group, principal coordinate analysis based on the Bray-Curtis distance showed a significant difference in milk microbial community in women with antibiotic exposure, accompanied by a significantly lower alpha diversity and a different microbial ecological network. Furthermore, the relative abundances of generaiActinomyces/i,iAnaerobacter/i, andiClostridium_/isensui_stricto/isignificantly decreased after antibiotic treatment.biConclusions:/i/bThis study provided evidence of alterations in the colostrum microbial community with antibiotic exposure, improving our understanding of the effects of antibiotic treatment on the milk microbiome.

Locoweeds are leguminous forbs known for their toxicity to livestock caused by the endophytic fungi Alternaria sect. Undifilum. Unlike the defensive mutualisms reported in many toxin-producing endophytes and their plant hosts, the benefits that A. sect. Undifilum can confer to it host plants remains unclear. Here, we conducted physiological and genetic analyses to show that A. (sect. Undifilum) oxytropis influences growth, especially root development, in its locoweed host Oxytropis ochrocephala and Arabidopsis. The presence of A. oxytropis significantly decreased primary root length while increasing the numbers of lateral roots and root hairs, and increasing plant leaf area and fresh weight. The fungus also increased the concentrations of plant endogenous auxin, and the expression of key genes for auxin biosynthesis, signaling, and transport. These effects on root development were abolished in mutants deficient in auxin signaling and polar transport. Alternaria oxytropis down-regulated expression of PIN1 but increased expression of PIN2, PIN7, and AUX1, which might reflect alterations in the spatial accumulation of auxin responsible for the changes in root architecture. Plant growth was insensitive to A. oxytropis when naphthylphthalamic acid was applied. Our findings indicate a function of A. oxytropis in promoting the growth and development of Arabidopsis via the regulation of auxin, which in turn suggests a possible role in benefiting its locoweed hosts via a process independent of its toxin production.

In this paper, in order to improve the corrosion resistance of 316 stainless steel (316 SS) in molten chloride salt, an in situ grown Al2O3 diffusion barrier is prepared through, first, electrodepositing an inner Ni-Al/NiO composite transition layer and an outer Ni layer through double-pulse composite electroplating technique, followed by annealing at 800°C for 12 h under Ar. The obtained Al2O3/Ni composite coating is dense and shows good adherence to the substrate. Then the corrosion resistance of Al2O3/Ni composite coating in molten 52MgCl2-48NaCl (wt%) is measured through electrochemical technique and immersion tests and the corrosion mechanism is also discussed. The results show that the 316 SS is effectively protected by the Al2O3/Ni composite coating from the corrosion of molten chloride salt.

Objective. To analyze the differentially expressed genes (DEGs) in rats with endogenous acute respiratory distress syndrome (ARDS) lung injury and explore the pathogenesis and early diagnostic molecular markers using whole transcriptomic data. Methods. Twelve 8-week-old male Sprague Dawley rats were selected and randomly and equally divided into ARDS lung injury group and normal control group. RNA was extracted from the left lung tissues of both the groups and sequenced using the paired-end sequencing mode of the Illumina Hiseq sequencing platform. The DEGs of miRNA, cirRNA, lncRNA, and mRNA were screened using DESeq2 software, and the ceRNA regulatory network was constructed using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the mRNA DEGs. STRING and Cytoscape software were used to construct the protein interaction network and identify the 15 key genes, which were verified using quantitative real-time polymerase chain reaction (qRT-PCR). Results. Based on different screening conditions, and compared with the control group, the ARDS lung injury group showed 836 mRNA DEGs (386 upregulated and 450 downregulated), 110 lncRNA DEGs (53 upregulated and 57 downregulated), 19 circRNA DEGs (3 upregulated and 16 downregulated), and 6 miRNA DEGs (5 upregulated and 1 downregulated gene). GO showed that the DEGs of mRNA were mainly involved in biological processes, such as defense response to lipopolysaccharide and other organisms, leukocyte chemotaxis, neutrophil chemotaxis, and cytokine-mediated signaling. KEGG enrichment analysis showed that the DEGs played their biological roles mainly by participating in IL-17, TNF, and chemokine signaling pathways. The PPI analysis showed a total of 281 node proteins and 634 interaction edges. The top 15 key genes, which were screened, included Cxcl10, Mx1, Irf7, Isg15, Ifit3, Ifit2, Rsad2, Ifi47, Oasl, Dhx58, Usp18, Cmpk2, Herc6, Ifit1, and Gbp4. The ceRNA network analysis showed 69 nodes and 73 correlation pairs, where the key gene nodes were miR-21-3p, Camk2g, and Stx2. Conclusions. The chemotaxis, migration, and degranulation of inflammatory cells, cytokine immune response, autophagy, and apoptosis have significant biological functions in the occurrence and development of endogenous acute lung injury during ARDS. Thus, the camk2g/miR-21-3p/lncRNA/circRNA network, CXCL10/CXCR3, and IL-17 signaling pathways might provide novel insights and targets for further studying the lung injury mechanism and clinical treatment.

Pulmonary nodules evaluation is clinically crucial because they may be the early predictors of lung cancer. Except for CT screening and serum tumor biomarkers testing, genetic alteration analysis by next-generation sequencing (NGS) technology can also help to find cancer earlier. In this study, we report a case of multiple pulmonary nodules patient with EGFR R776H and FANCE R381H germline mutations. Her father, paternal aunt, and elder uncle harbored either one or both two mutations and were found with multiple pulmonary ground-glass or sub-solid nodules. Her 7-year-old daughter also inherited the same two mutations.

PurposeThe purpose of this study is to analyze the topics of COVID-19 news articles for better obtaining the relationship among and the evolution of news topics, helping to manage the infodemic from a quantified perspective.Design/methodology/approachTo analyze COVID-19 news articles explicitly, this paper proposes a prism architecture. Based on epidemic-related news on China Daily and CNN, this paper identifies the topics of the two news agencies, elucidates the relationship between and amongst these topics, tracks topic changes as the epidemic progresses and presents the results visually and compellingly.FindingsThe analysis results show that CNN has a more concentrated distribution of topics than China Daily, with the former focusing on government-related information, and the latter on medical. Besides, the pandemic has had a big impact on CNN and China Daily's reporting preference. The evolution analysis of news topics indicates that the dynamic changes of topics have a strong relationship with the pandemic process.Originality/valueThis paper offers novel perspectives to review the topics of COVID-19 news articles and provide new understandings of news articles during the initial outbreak. The analysis results expand the scope of infodemic-related studies.

In order to improve the effect of engineering safety management, this paper combines intelligent monitoring technology to construct a monitoring robot system. Moreover, this paper analyzes the characteristics of the digital impulse signal and analyzes the least square filtering and infinite impulse response filtering. At the same time, this paper detects the sample material on the detection test platform, obtains the digital pulse signal, and selects different filtering algorithms and filtering parameters. In addition, this paper uses a signal analysis and processing platform to establish a gamma energy spectrum and analyze the resolution of hydrogen peaks in the gamma energy spectrum. Finally, this paper compares and verifies the filtering algorithms and constructs an engineering safety management system based on robot intelligent monitoring. From the simulation monitoring test results, it can be seen that the engineering safety management system based on robot intelligent detection proposed in this paper has a good effect.

Aidi injection (ADI), a traditional Chinese medicine antitumor injection, is usually combined with doxorubicin (DOX) for the treatment of malignant tumours. The cardiotoxicity of DOX is ameliorated by ADI in the clinic. However, the relevant mechanism is unknown.To investigate the effects of ADI on DOX-induced cardiotoxicity and its mechanism.ICR mice were randomly divided into six groups: control, ADI-L, ADI-H, DOX, DOX + ADI-L and DOX + ADI-H. DOX (High-dose ADI significantly reduced DOX-induced pathological changes and the levels of AST, LDH, CK, CK-MB and BNP to normal. Combined treatment with ADI (1, 4, 10%) improved the cell viability, and IC50 increased from 68.51 μM (DOX alone) to 83.47, 176.9, and 310.8 μM, reduced caspase-3 activity by 39.17, 43.96, and 61.82%, respectively. High-dose ADI inhibited the expression of CBR1 protein by 32.3%, reduced DOXol levels in heart, serum and H9c2 cells by 59.8, 72.5 and 48.99%, respectively.ADI reduces DOX-induced cardiotoxicity by inhibiting CBR1 expression, which provides a scientific basis for the rational use of ADI.

Cell wall lignification is a key step in forming functional endodermis and protoxylem (PX) in plant roots. Lignified casparian strips (CS) in endodermis and tracheary elements of PX are essential for selective absorption and transport of water and nutrients. Although multiple key regulators of CS and PX have been identified, the spatial information that drives the developmental shift to root lignification remains unknown. Here, we found that brassinosteroid (BR) signaling plays a key role in inhibiting root lignification in the root elongation zone. The inhibitory activity of BR signaling occurs partially through the direct binding of BRASSINAZOLE-RESISTANT 1 (BZR1) to SHORT-ROOT (SHR), repressing the SHR-mediated activation of downstream genes that are involved in root lignification. Upon entering the mature root zone, BR signaling declines rapidly, which releases SHR activity and initiates root lignification. Our results provide a mechanistic view of the developmental transition to cell wall lignification in Arabidopsis thaliana roots.

Lung adenocarcinoma (LUAD) is the major cause of cancer mortality. Traditional prognostic factors have limited importance after including other parameters. Thus, developing a more credible prognostic model combined with genes and clinical parameters is necessary.The messenger RNA (mRNA) expression and clinical information from The Cancer Genome Atlas (TCGA)-LUAD datasets and microarray data from three Gene Expression Omnibus (GEO) databases were obtained. We identified differentially-expressed genes (DEGs) between lung tumor and normal tissues through integrated analysis of the three GEO datasets. Univariate and multivariate Cox regression analyses were conducted to select survival-associated DEGs and to establish a prognostic gene signature which was associated with overall survival (OS). The expression of gene proteins was assessed in 180 LUAD tissue microarrays (TMAs) by immunohistochemistry (IHC). We verified its predictive performance with a Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and Harrell's concordance index (C-index) and validated it in external GEO databases. Multivariate Cox regression analysis was performed to identify the significant prognostic indicators in LUAD. Furthermore, we established a prognostic nomogram based on TCGA-LUAD dataset.A three-gene signature was constructed to predict the OS of LUAD patients. The KM analysis, ROC curve, and C-index present a good predictive ability of the gene signature in TCGA dataset [P0.0001; C-index 0.6375; 95% confidence interval (CI): 0.5632-0.7118; area under the ROC curve (AUC) 0.674] and the external GEO datasets (P=0.05, 0.004, and 0.04, respectively). Univariate and multivariate Cox regression analyses also verified that LUAD patients with low-risk scores had a decreased risk of death compared to those with a high-risk score in TCGA database [hazard ratio (HR) =0.3898; 95% CI: 0.1938-0.7842; P0.05]. Finally, we constructed a nomogram integrating the gene signature and clinicopathological parameters (P0.0001; C-index 0.762; 95% CI: 0.714-0.845; AUC 0.8136). Compared with conventional staging, a nomogram can effectively improve prognosis prediction.The nomogram is closely associated to the OS of LUAD patients. This consequence may be beneficial to individualized treatment and clinical decision-making.

With the rapid development of molten salt reactors, the problem of post-treatment of spent fuel salt discharged from the core becomes increasingly prominent. Like molten fluoride salts, solid fluoride salts are also highly corrosive, which poses a serious challenge to container materials. This paper describes the corrosion behavior of 316 stainless steel (316 SS) with and without Ni coating in low-temperature solid fluoride salt. Results show that 316 SS without Ni coating experiences pitting corrosion with the prolongation of corrosion time. 316 SS with Ni coating experiences intergranular corrosion. In addition, a loose hollow interlayer is formed between Ni coating and matrix. Corrosion of both samples increases with the extension of exposure time with solid fluoride salts.