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The distributed permutation flowshop scheduling is a critical issue in various industries, involving jobs allocation and scheduling among multiple flowshops. This paper extends the research to explore the Distributed Mixed No-Wait Permutation Flowshop Scheduling Problems (DMNWPFSP) with minimizing makespan. The innovation lies in an optimized mathematical model, hybrid heuristic algorithms, an improved iterated greedy algorithm (IIG), and high-quality solutions. Extensive experimental results demonstrate the effectiveness and superiority of the proposed IIG in terms of scheduling quality, computational efficiency, and robustness compared to existing approaches. The outcomes of this work contribute to the field of distributed flowshop scheduling, providing valuable insights for practitioners seeking to enhance production efficiency and competitiveness.

Abstract Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+–CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

Abstract Objective Hypertension refers to the persistent elevation of blood pressure above the established normal range, resulting in increased pressure exerted by blood on the walls of blood vessels during its circulation. Recent studies have identified significant associations between obesity and lipid-related indices, as well as hypertension. Nevertheless, these studies have yet to comprehensively examine the correlation between the two variables. Our objective is to identify the fat and lipid-related indices that have the strongest correlation with hypertension. Method There was a total of 9488 elderly and middle-aged Chinese citizens who participated in this investigation. The participants in this research were separated into distinct gender cohorts. The participants were classified into normal and hypertensive categories according to their gender, with hypertension defined as a blood pressure level of 140/90 mmHg or higher, or a history of hypertension. Through the utilization of binary logistic regression analyses and the receiver operator curve (ROC), the optimal among fourteen indicators associated with obesity and lipids were identified. Results After adjusting for variables, statistical analysis showed that all 14 measures of obesity and lipid were risk factors for hypertension. The receiver operating characteristic (ROC) curve analysis reveals that the Chinese visceral adiposity index (CVAI) has the highest degree of relationship to hypertension. Simultaneously, a statistically significant association between hypertension and these 14 variables was observed in both males and females. Conclusion There was a significant independent association between various parameters related to obesity and lipid-related index and the presence of hypertension, indicating that these factors can be considered risk factors for hypertension. CVAI and WHtR (waist height ratio) can be used to screen the high-risk groups of hypertensions in middle-aged and elderly people in China, and then take individualized health care measures to reduce the harm of hypertension.

Sorafenib resistance greatly restricts its clinical application in patients with hepatocellular carcinoma (HCC). Numerous studies have reported that ID1 exerts a crucial effect in cancer initiation and development. Our previous research revealed an inhibitory role of ID1 in sorafenib resistance. However, the upstream regulatory mechanism of ID1 expression is unclear. Here, we discovered that ID1 expression is negatively correlated with promoter methylation, which is regulated by DNMT3B. Knockdown of DNMT3B significantly inhibited ID1 methylation status and resulted in an increase of ID1 expression. The demethylating agent 5‐aza‐2′‐deoxycytidine (5‐aza) remarkably upregulated ID1 expression. The combination of 5‐aza with sorafenib showed a synergistic effect on the inhibition of cell viability.

Introduction: Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates. Objectives: Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species. Methods: Single-cell RNA sequencing (scRNA-seq). Results: We uncovered both conserved and species-specific profiling of gene expression in innate and adaptive immunity. Macrophages exhibited highly-diversified genes and developed sophisticated molecular signaling networks along with evolution, indicating effective and versatile functions in higher species. In contrast, B cells conservatively evolved with less differentially-expressed genes in analyzed species. Interestingly, T cells represented a dominant immune cell populations in all species and unique T cell populations were identified in zebrafish and pig. We also revealed compensatory TCR cascade components utilized by different species. Inter-species comparison of core gene programs demonstrated mouse species has the highest similarity in immune transcriptomes to human. Conclusions: Therefore, our comparative study reveals gene transcription characteristics across multiple vertebrate species during the evolution of immune system, providing insights for species-specific immunity as well as the translation of animal studies to human physiology and disease.

Objective To explore the possibility of using human skin and oral microorganisms to estimate the geographic origin of an individual through the sequencing analysis of bacterial 16S rRNA gene. Methods Microbial DNA was extracted from the palm and oral microorganisms of the Han population in Shanghai and Chifeng, Inner Mongolia, and the composition and diversity of the microbiota were analyzed by full-length 16S rRNA gene sequencing. Then, differential species were screened and a geographic location prediction model was constructed. Results The compositions of palm and oral microorganisms between Shanghai and Chifeng samples were both different. The abundance and uniformity of palm side skin microorganisms were higher in Chifeng samples than in Shanghai samples, while there was no significant difference in oral microorganisms. Permutational multivariate analysis of variance （PERMANOVA） confirmed that the β-diversity between the samples from the two places were statistically significant, and the coefficients of determination （R2） for skin and oral samples were 0.129 and 0.102, respectively. Through principal co-ordinates analysis （PCoA）, the samples from the two places could be preliminarily distinguished. The predictive model had the accuracies of 0.90 and 0.83 for the geographic origin using the skin and oral samples, respectively. Conclusion There are differences in the compositions of palm and oral microbiota between Han populations in Shanghai and Chifeng. The prediction model constructed by the random forest algorithm can trace the unknown individuals from the above two places.

Abstract The present-day globalized economy and diverse market demands have compelled an increasing number of manufacturing enterprises to move toward the distributed manufacturing pattern and the model of multi-variety and small-lot. Taking these two factors into account, this study investigates an extension of the distributed hybrid flowshop scheduling problem (DHFSP), called the distributed hybrid flowshop scheduling problem with consistent sublots (DHFSP_CS). To tackle this problem, a mixed integer linear programming (MILP) model is developed as a preliminary step. The NP-hard nature of the problem necessitates the use of the iterated F-Race (I/F-Race) as the automated algorithm design (AAD) to compose a metaheuristic that requires minimal user intervention. The I/F-Race enables identifying the ideal values of numerical and categorical parameters within a promising algorithm framework. An extension of the collaborative variable neighborhood descent algorithm (ECVND) is utilized as the algorithm framework, which is modified by intensifying efforts on the critical factories. In consideration of the problem-specific characteristics and the solution encoding, the configurable solution initializations, configurable solution decoding strategies, and configurable collaborative operators are designed. Additionally, several neighborhood structures are specially designed. Extensive computational results on simulation instances and a real-world instance demonstrate that the automated algorithm conceived by the AAD outperforms the CPLEX and other state-of-the-art metaheuristics in addressing the DHFSP_CS.

This bibliometric study examined the development of research on the learning and teaching of second language (L2) listening from 1948 to 2020 (73 years). Specifically, the study involved: (1) a search and analysis of all the noun phrases to identify important research topics in the abstracts of the published journal articles on L2 listening over the 73 years (divided into three periods) using self-made Python scripts and (2) three co-citation analyses of the references in these articles regarding highly cited authors, publications, and journals, respectively, via the VOSviewer program. The keyword/phrase analysis produced results that helped uncover and delineate the research trends in L2 listening across the three time periods. The co-citation analyses identified the most highly cited authors, publications, and journals as well as the interrelations among the most highly cited items in each of the three categories illustrated with network maps. The results of the analyses and their implications are discussed.

Abstract Malignant pleural effusion (MPE), which is a complex microenvironment that contains numerous immune and tumour signals, is common in lung cancer. Gene alterations, such as driver gene mutations, are believed to affect the components of tumour immunity in the microenvironment (TIME) of non-small-cell lung cancer. In this study, we have shown that pleural CD39 + CD8 + T cells are selectively elevated in lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFRwt) compared to those with newly diagnosed mutant EGFR (EGFRmu). Furthermore, these CD39 + CD8 + T cells are more prevalent in MPE with acquired resistance to EGFR-tyrosine kinase inhibitors (AR-EGFR-TKIs). Our analysis reveals that pleural CD39 + CD8 + T cells exhibit an exhausted phenotype while still retaining cytolytic function. Additionally, they have a higher T cell receptor (TCR) repertoire clonality compared to CD39-CD8 + T cells, which is a unique characteristic of LUAD-related MPE. Further investigation has shown that TCR-Vβ clonality tends to be more enhanced in pleural CD39 + CD8 + T cells from MPE with AR-EGFR-TKIs. In summary, we have identified a subset of CD8 + T cells expressing CD39 in MPE, which may potentially be tumour-reactive CD8 + T cells. This study provides new insights into the dynamic immune composition of the EGFRmu tumour microenvironment.

Abstract Background Delirium occurs frequently in critically ill children and has been reported in many countries, but delirium is not well-characterized in China. The aim of this study was to represent the incidence of delirium in critically ill children in China, its associated factors, and the influence of delirium on in-hospital outcomes. Methods This observational prospective cohort study was set up in a large academic medical center with a 57-bed PICU in southwestern China. Critically ill children who required PICU stays over 24 h and were admitted between November 2019 and February 2022 were included in this study. The Cornell Assessment of Pediatric Delirium was used twice daily for delirium evaluation by bedside nurses, and twenty-four clinical features were collected from medical and nursing records during hospitalization. Results The incidence of delirium was 26.0% (n = 410/1576). Multivariate analysis revealed that seven independent risk factors including days of mechanical ventilation and physical restraints, admission diagnosis (neurologic disorder), sleep deprivation, use of benzodiazepines and dexmedetomidine, liver failure/liver dysfunction associated with delirium in critically ill children. One potentially protective factor was the watching television /listening to music/playing with toys. Children with delirium had longer lengths of stay in the PICU (median 11 vs. 10 days, p

Abstract Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.