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Purpose: To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III‐IVa). Methods and Materials: Using an NPC‐specific database, 245 elderly patients with stage III‐IVa NPC, receiving CCRT +/− NAC, and an Adult Co‐morbidity Evaluation 27 (ACE‐27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein–Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease‐free survival (DFS). Results: Two risk groups were generated by the RPA model. In the high‐risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III‐IVa), patients treated with NAC plus CCRT achieved improved 5‐year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low‐risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. Conclusions: The addition of NAC to CCRT was associated with better DFS for the high‐risk group of elderly LANPC patients with ACE‐27 score <2. However, the survival benefit of additional NAC was not observed in low‐risk patients. [ABSTRACT FROM AUTHOR]

Ranula is a mucous cyst that occurs in the sublingual gland (SLG) in the floor of the mouth. It can be classified into two types based on origins: One is the the lesser sublingual gland (LSLG) in the anterior segment and the Rivini duct, which is connected to it, and the other is the greater sublingual gland (GSLG) in the posterior segment. Because of the anatomical characteristics, surgical resection of the cysts carries the risk of damaging adjacent tissues and has a high recurrence rate. Intralesional injection of sclerotherapy may be a better alternative treatment. We summarized 65 cases of ranula treated with intralesional injections of bleomycin(BML). According to the origin of the ranula, 60 cases were from the LSLG and the Rivini duct, and 5 cases were from the GSLG. The results showed that 60 cases of ranula from LSLG and Rivini ducts were 100% cured during the follow-up period. The median number of injections for all patients was 1.16. All 5 cases of ranula from the GSLG did not wholly recover. This study confirmed that BLM intralesional injection is a safe and effective treatment modality for cysts from LSLG or the ducts of Rivini rather than GSLG. Therefore, before treatment, it is necessary to determine the type and origin of the cyst by characterizing its morphology to ensure the effectiveness of the treatment. [ABSTRACT FROM AUTHOR]

Background: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC plus cisplatin CCRT ) for LANPC patients. Methods: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. Results: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3–4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). Conclusion: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients. [ABSTRACT FROM AUTHOR]

Feed efficiency (FE) is essential for pig production, has been reported to be partially explained by gut microbiota. Despite an extensive body of research literature to this topic, studies regarding the regulation of feed efficiency by gut microbiota remain fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Meanwhile, structured databases for microbiota analysis are available, yet they often lack a comprehensive understanding of the associated biological processes. Therefore, we have devised an approach to construct a comprehensive knowledge graph by combining unstructured textual intelligence with structured database information and applied it to investigate the relationship between pig gut microbes and FE. Firstly, we created the pgmReading knowledge base and the domain ontology of pig gut microbiota by annotating, extracting, and integrating semantic information from 157 scientific publications. Secondly, we created the pgmPubtator by utilizing PubTator to expand the semantic information related to microbiota. Thirdly, we created the pgmDatabase by mapping and combining the ADDAGMA, gutMGene, and KEGG databases based on the ontology. These three knowledge bases were integrated to form the Pig Gut Microbial Knowledge Graph (PGMKG). Additionally, we created five biological query cases to validate the performance of PGMKG. These cases not only allow us to identify microbes with the most significant impact on FE but also provide insights into the metabolites produced by these microbes and the associated metabolic pathways. This study introduces PGMKG, mapping key microbes in pig feed efficiency and guiding microbiota-targeted optimization. [ABSTRACT FROM AUTHOR]

Background: The neural cells in the brains of patients with Parkinson’s disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson’s disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson’s disease based on the central-peripheral-central theory. Methods: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson’s disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. Discussion: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. Trial registration: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023. [ABSTRACT FROM AUTHOR]

Recent observational studies have reported associations between serum mineral nutrient levels, gut microbiota composition, and neurological, psychiatric, and metabolic diseases. However, the causal effects of mineral nutrients on gut microbiota and their causal associations with diseases remain unclear and require further investigation. This study aimed to identify the associations between serum mineral nutrients, gut microbiota, and risk of neurological, psychiatric, and metabolic diseases using Mendelian randomization (MR). We conducted an MR study using the large-scale genome-wide association study (GWAS) summary statistics of 5 serum mineral nutrients, 196 gut microbes at the phylum, order, family, and genus levels, and a variety of common neurological, psychiatric, and metabolic diseases. Initially, the independent causal associations of mineral nutrients and gut microbiota with diseases were examined by MR. Subsequently, the causal effect of mineral nutrients on gut microbiota was estimated to investigate whether specific gut microbes mediated the association between mineral nutrients and diseases. Finally, we performed sensitivity analyses to assess the robustness of the study results. After correcting for multiple testing, we identified a total of 33 causal relationships among mineral nutrients, gut microbiota, and diseases. Specifically, we found 4 causal relationships between 3 mineral nutrition traits and 3 disease traits, 15 causal associations between 14 gut microbiota traits and 6 disease traits, and 14 causal associations involving 4 mineral nutrition traits and 15 gut microbiota traits. Meanwhile, 118 suggestive associations were identified. The current study reveals multiple causal associations between serum mineral nutrients, gut microbiota, risk of neurological, psychiatric, and metabolic diseases, and potentially provides valuable insights for subsequent nutritional therapies. [ABSTRACT FROM AUTHOR]

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Background: Alzheimer's disease (AD) is the leading cause of dementia, with its prevalence increasing as the global population ages. AD is a multifactorial and intricate neurodegenerative disease with pathological changes varying from person to person. Because the mechanism of AD is highly controversial, effective treatments remain a distant prospect. Currently, one of the most promising hypotheses posits mitochondrial dysfunction as an early event in AD diagnosis and a potential therapeutic target. Objective: Here, we adopted a systems medicine strategy to explore the mitochondria-related mechanisms of AD. Then, its implications for discovering nutrients combatting the disease were demonstrated. Methods: We employed conditional mutual information (CMI) to construct AD gene dependency networks. Furthermore, the GeneRank algorithm was applied to prioritize the gene importance of AD patients and identify potential anti-AD nutrients targeting crucial genes. Results: The results suggested that two highly interconnected networks of mitochondrial ribosomal proteins (MRPs) play an important role in the regulation of AD pathology. The close association between mitochondrial ribosome dysfunction and AD was identified. Additionally, we proposed seven nutrients with potential preventive and ameliorative effects on AD, five of which have been supported by experimental reports. Conclusions: Our study explored the important regulatory role of MRP genes in AD, which has significant implications for AD prevention and treatment. [ABSTRACT FROM AUTHOR]

Herein, metal-free phosphonation of N-heterocycles with diphenylphosphine oxides, promoted by easily available 1,5-diazabicyclo[5,4,0]undec-5-ene (DBU) in dimethyl carbonate (DMC) as a green solvent under an air atmosphere, is presented. This simple method can accommodate 1,2,4-triazine-3,5(2H,4H)-diones, quinoxalin-2(1H)-ones, quinoxalines and pyrazinones with diverse substituted diphenylphosphine oxides, delivering distinctive monophosphonated N-heterocycles with a broad functional group tolerance, and the transformations are also viable for post-modification of bioactive and pharmaceutical molecules. In addition to the sustainable feature of being metal- and photocatalyst-free and utilization of ambient air as an oxidant, this method efficiently achieves the gram-scale transformation, and the product was isolated through extraction and filtration, rather than column chromatography. [ABSTRACT FROM AUTHOR]

We have identified that NUDT21 plays a vital role in MDS transformations, while the transcription factor RUNX1 is essential for normal hematopoiesis, which is a high expression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and we aim to explore the linkage between the two genes and new pathways for MDS transformation to AML. Prediction of RUNX1 expression levels and its relationship with NUDT21 in AML and MDS patients was performed using bioinformatics techniques and validated in patients. Using lentiviral packaging technology, NUDT21 knockdown and overexpression models were developed in AML and MDS cell lines. These models were validated using quantitative polymerase chain reaction (qPCR) and western blotting. The cell cycle, apoptosis, differentiation, and cytokines were examined by flow cytometry, CCK-8 analyzed proliferation, and the intracellular localization of NUDT21 and RUNX1 was examined by immunofluorescence. mRNA transcriptome sequencing was performed on THP-1, MUTZ-1, and Dapars analyzed SKM-1 cell lines and the sequencing data to observe the knockdown effect of NUDT21 on RUNX1. qPCR and western blot revealed a positive correlation between NUDT21 and RUNX1; both were located in the nucleus. Overexpression of NUDT21 reduced apoptosis, promoted cell proliferation, and possibly increased the invasive ability of cells. It also altered the APA site in the RUNX1 3'-UTRs region. NUDT21 regulates RUNX1 gene expression and promotes AML transformation in MDS through an APA mechanism. [ABSTRACT FROM AUTHOR]

Aiming at the imbalance problem of excavating and anchoring efficiency ratio in the underground coal mine, a new type of parallel operation unit of excavation-supporting-anchoring is proposed to improve the excavating efficiency. Considering the uneven factors of the roof and floor of the coal mine roadway, the influence of different drilling angles and leg support angles on the leg support force is studied under the condition of simultaneous drilling of multiple drilling rigs. The results show that the maximum support force is 4.002 KN when the leg angle is different and the drilling angle is different. By constructing the coupling vibration model of the multi-drill drilling process and using the Lagrange method to solve the vibration law of key components of the anchorage system, the vibration law of drill pipe under different influencing factors such as cantilever extension, multi-drill simultaneous drilling, and drilling incident angle is studied. The results showed: (1) The vibration of the drill pipe in the cantilever extension state is more severe than that in the retracted state, and the maximum vibration peak reaches 7.61 mm. (2) The vibration response of the drill pipe is the most intense under the condition of four top anchor drilling rigs drilling at the same time. Under the working condition of only two drilling rigs, the vibration response of the drill pipe is the smallest. (3) As the drilling angle of the drilling rig increases, the vibration response of the drill pipe is more severe and the vibration amplitude is larger. A test prototype is built to simulate the actual anchoring drilling process, and the vibration law of the support platform and the drilling rig is obtained through the vibration detection system. The test results show that the vibration law of the key components is approximately the same as the theoretical simulation results. The relevant theoretical results can provide a technical basis for the drilling stability of the anchoring system. [ABSTRACT FROM AUTHOR]

Fruit flies are destructive quarantine pests that harm horticultural crops. Their wide distribution and high fecundity cause large economic losses to the fruit and vegetable industry. Moreover, adult females lay their eggs within host plant tissue where the larvae feed making them difficult to control. Semiochemicals, including those derived from insects, plants, and other sources, due to their high activity and strong specificity, have become the preferred tools for the environmentally- friendly prevention and control of fruit flies. Therefore this review focuses on semiochemicals related to foraging, mating, and oviposition behavior and the application of these in pest control, and then provides guidance and a theoretical basis for the integrated management of Tephritidae fruit flies. [ABSTRACT FROM AUTHOR]

Adenosine triphosphate (ATP) is a multifunctional small molecule, necessary for all modern Earth life, which must be a component of the last universal common ancestor (LUCA). However, the relatively complex structure of ATP causes doubts about its accessibility on prebiotic Earth. In this paper, based on previous studies on the synthesis of ATP components, a plausible prebiotic pathway yielding this key molecule is constructed, which relies on terrestrial volcanism to provide the required materials and suitable conditions. [ABSTRACT FROM AUTHOR]

Fluorescent chemosensors are powerful imaging tools used in a broad range of biomedical fields. However, the application of fluorescent dyes in bioimaging still remains challenging, with small Stokes shifts, interfering signals, background noise, and self-quenching on current microscope configurations. In this work, we reported a supramolecular cage (CA) by coordination-driven self-assembly of benzothiadiazole derivatives and Eu(OTf)3. The CA exhibited high fluorescence with a quantum yield (QY) of 38.57%, good photoluminescence (PL) stability, and a large Stokes shift (153 nm). Furthermore, the CCK-8 assay against U87 glioblastoma cells verified the low cytotoxicity of CA. We revealed that the designed probes could be used as U87 cells targeting bioimaging. [ABSTRACT FROM AUTHOR]

An improved hybrid firefly algorithm with probability attraction model (IHFAPA) is proposed to solve the problems of low computational efficiency and low computational accuracy in solving complex optimization problems. First, the method of square-root sequence was used to generate the initial population, so that the initial population had better population diversity. Second, an adaptive probabilistic attraction model is proposed to attract fireflies according to the brightness level of fireflies, which can minimize the brightness comparison times of the algorithm and moderate the attraction times of the algorithm. Thirdly, a new location update method is proposed, which not only overcomes the deficiency in that the relative attraction of two fireflies is close to 0 when the distance is long but also overcomes the deficiency that the relative attraction of two fireflies is close to infinity when the distance is small. In addition, a combinatorial variational operator based on selection probability is proposed to improve the exploration and exploitation ability of the firefly algorithm (FA). Later, a similarity removal operation is added to maintain the diversity of the population. Finally, experiments using CEC 2017 constrained optimization problems and four practical problems in engineering show that IHFAPA can effectively improve the quality of solutions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is exploring the effects of segment dynamic and temporal dynamic triggered by the COVID-19 pandemic on classifying service quality attributes, thereby formulating improvement strategies to satisfy customers and respond to threats. Design/methodology/approach: Given the dynamics of the attractive quality theory, this paper designs a framework with four phases by embedding techniques of text mining and deep learning based on evidence from online reviews. Findings: This paper figures out dynamics of service quality attributes for distinct segments and their dynamic proportion along with different stages of the pandemic. Another finding demonstrates segment dynamic and temporal dynamic effects of sentiments toward service quality attributes on customer satisfaction under the impacts of pandemic. Classification results and improvement strategies are derived for varying segments at different pandemic situations. Practical implications: This paper reveals dynamic effects on classifying service quality attributes, which contributes to assisting hospitality practitioners from different segments in improving service quality when facing with the challenges of crisis and potential risks. Originality/value: Given hospitality industry is time- and segment-sensitive, the authors achieve the quantification of dynamics of attractive quality theory and extend it into hospitality marketing and crisis management from the perspective of dynamics with evidence from online reviews. [ABSTRACT FROM AUTHOR]

Focusing on the issues of slow convergence speed and the ease of falling into a local optimum when optimizing the weights and thresholds of a back-propagation artificial neural network (BPANN) by the gradient method, a prediction method for pork supply based on an improved mayfly optimization algorithm (MOA) and BPANN is proposed. Firstly, in order to improve the performance of MOA, an improved mayfly optimization algorithm with an adaptive visibility coefficient (AVC-IMOA) is introduced. Secondly, AVC-IMOA is used to optimize the weights and thresholds of a BPANN (AVC-IMOA_BP). Thirdly, the trained BPANN and the statistical data are adopted to predict the pork supply in Heilongjiang Province from 2000 to 2020. Finally, to demonstrate the effectiveness of the proposed method for predicting pork supply, the pork supply in Heilongjiang Province was predicted by using AVC-IMOA_BP, a BPANN based on the gradient descent method and a BPANN based on a mixed-strategy whale optimization algorithm (MSWOA_BP), a BPANN based on an artificial bee colony algorithm (ABC_BP) and a BPANN based on a firefly algorithm and sparrow search algorithm (FASSA_BP) in the literature. The results show that the prediction accuracy of the proposed method based on AVC-IMOA and a BPANN is obviously better than those of MSWOA_BP, ABC_BP and FASSA_BP, thus verifying the superior performance of AVC-IMOA_BP. [ABSTRACT FROM AUTHOR]

In recent years, incredible endeavors have been devoted to the design and self-assembly of discrete metal–organic cages (MOCs) with expanding intricacy and functionality. The controlled synthesis of metal–organic supramolecular cages with large branched chains remains an interesting and challenging work in supramolecular chemistry. Herein, a tetrahedral metal–organic supramolecular cage (ZnII4L4) containing 12 dendritic carbazole arms is unprecedentedly constructed through coordination-driven subcomponent self-assembly and characterized in different ways. Interestingly, tetrahedral supramolecular Cage-1 exhibited the potential for aggregation-induced emission (AIE) performance and stimulus-responsive luminescence features, and it achieved color-tunable photoluminescence due to the introduction of dendritic carbazole arms. Crucially, owing to the great photophysical properties of Cage-1 in solution, Cage-1 was enabled to act as a fluorescent ink for the vapor-responsive recording and wiping of information. [ABSTRACT FROM AUTHOR]

The traveling salesman problem (TSP) widely exists in real-life practical applications; it is a topic that is under investigation and presents unsolved challenges. The existing solutions still have some challenges in convergence speed, iteration time, and avoiding local optimization. In this work, a new method is introduced, called the discrete carnivorous plant algorithm (DCPA) with similarity elimination to tackle the TSP. In this approach, we use a combination of six steps: first, the algorithm redefines subtraction, multiplication, and addition operations, which aims to ensure that it can switch from continuous space to discrete space without losing information; second, a simple sorting grouping method is proposed to reduce the chance of being trapped in a local optimum; third, the similarity-eliminating operation is added, which helps to maintain population diversity; fourth, an adaptive attraction probability is proposed to balance exploration and the exploitation ability; fifth, an iterative local search (ILS) strategy is employed, which is beneficial to increase the searching precision; finally, to evaluate its performance, DCPA is compared with nine algorithms. The results demonstrate that DCPA is significantly better in terms of accuracy, average optimal solution error, and iteration time. [ABSTRACT FROM AUTHOR]

A nitrogen-doped carbon supported Co/Ni bimetallic catalyst 2wt%Co/Ni@NC-700-10 was prepared and found to be efficient in the reductive N-formylation of 2,4-diamino-5-nitroso-6-hydroxypyrimidine (DANHP) to 2,4-diamino-5-formyl-6-hydroxypyrimidine (DAFHP) for the synthesis of guanine. Under optimal conditions, the conversion of DANHP reached up to 95.6% with a DAFHP selectivity of 97.6%. The characterization results revealed that the cobalt/nickel nanoparticles of the catalyst uniformly dispersed and encapsulated in the nitrogen-dopped carbon, and the catalyst has the characters of large surface area, as well as uniform dispersion and small diameters of metal nanoparticles in the form of Co/Ni alloy, which endowed its good catalytic performance in the reaction. [ABSTRACT FROM AUTHOR]

A Fe embedded MgAl layered double hydroxide (MgAlFe0.4-LDH) showed excellent performances in the epoxidation of various olefins with O2/benzaldehyde as oxidant at mild conditions. Under optimal conditions, the olefins including terminal aliphatic olefins, cyclohexene and styrene were all converted to the corresponding epoxides in conversions close to 100% and selectivity higher than 95%. The epoxidation is accomplished in two elementary steps, which are catalytic oxidation of benzaldehyde to peroxybenzoic acid, and epoxidation of olefin to epoxide by peroxybenzoic acid generated in situ. The catalyst also exhibited good stability and recyclability. The characterization results revealed that the Fe species are present in the state of Fe3+ fully incorporated into the Mg/Al-LDH layers, and act as active sites in the catalyst. The embedment of Fe into MgAl-LDH largely increased the surface area and pore volume of Mg/Al-LDH, which is another factor enhancing the activity of the catalyst. [ABSTRACT FROM AUTHOR]

Space exploration has brought many challenges to human physiology. In order to evaluate and reduce possible pathological reactions triggered by space environments, we conducted bioinformatics analyses on the methylation data of the Mars 520 mission and human transcriptome data in the experiment simulating gravity changes. The results suggest that gene expression levels and DNA methylation levels were changed under the conditions of isolation and gravity changes, and multiple viral infection-related pathways were found in the enrichment analysis results of changed genes including Epstein Barr virus (EBV) infection, Hepatitis B virus (HBV) infection, Herpes simplex virus (HSV) infection and Kaposi's sarcoma-associated herpesvirus (KHSV) infection. In this study, we found that Epigallocatechin-3-gallate (EGCG) and vitamin D are helpful in reducing viral infection risk. In addition, the causal associations between nutrients and viral infections were calculated using Two sample Mendelian Randomization (2SMR) method, the results indicated that vitamin D can reduce EBV infection and HBV infection risk. In summary, our study suggests that space environments increase the risk of human viral infection, which may be reduced by supplementing EGCG and vitamin D. These results can be used to formulate medical plans for astronauts, which have practical application value for future space exploration. [ABSTRACT FROM AUTHOR]

Cumulative evidence has revealed the association between mitochondrial dysfunction and Alzheimer's disease (AD). Because the number of mitochondrial genes is very limited, the mitochondrial pathogenesis of AD must involve certain nuclear genes. In this study, we employed systems genetic methods to identify mitochondrion-associated nuclear genes that may participate in the pathogenesis of AD. First, we performed a mitochondrial genome-wide association study (MiWAS, n = 809) to identify mitochondrial single-nucleotide polymorphisms (MT-SNPs) associated with AD. Then, epistasis analysis was performed to examine interacting SNPs between the mitochondrial and nuclear genomes. Weighted co-expression network analysis (WGCNA) was applied to transcriptomic data from the same sample (n = 743) to identify AD-related gene modules, which were further enriched by mitochondrion-associated genes. Using hub genes derived from these modules, random forest models were constructed to predict AD risk in four independent datasets (n = 743, n = 542, n = 161, and n = 540). In total, 9 potentially significant MT-SNPs and 14,340 nominally significant MT-nuclear interactive SNPs were identified for AD, which were validated by functional analysis. A total of 6 mitochondrion-related modules involved in AD pathogenesis were found by WGCNA, from which 91 hub genes were screened and used to build AD risk prediction models. For the four independent datasets, these models perform better than those derived from AD genes identified by genome-wide association studies (GWASs) or differential expression analysis (DeLong's test, p  <  0.05). Overall, through systems genetics analyses, mitochondrion-associated SNPs/genes with potential roles in AD pathogenesis were identified and preliminarily validated, illustrating the power of mitochondrial genetics in AD pathogenesis elucidation and risk prediction. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC‐derived small extracellular vesicles (MSC‐sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC‐sEV on DCs in allergic diseases remain unclear. MSC‐sEV were prepared from the induced pluripotent stem cells (iPSC)‐MSCs by anion‐exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte‐derived DCs were generated and cultured in the presence of MSC‐sEV to differentiate the so‐called sEV‐immature DCs (sEV‐iDCs) and sEV‐mature DCs (sEV‐mDCs), respectively. The phenotypes and the phagocytic ability of sEV‐iDCs were analyzed by flow cytometry. sEV‐mDCs were co‐cultured with isolated CD4+T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC‐sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA‐DR, but had no effects on mDCs with these markers. However, MSC‐sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti‐IL‐10 monoclonal antibody or IL‐10Rα blocking antibody, we identified that sEV‐mDCs suppressed the Th2 immune response by reducing the production of IL‐4, IL‐9, and IL‐13 via IL‐10. Furthermore, sEV‐mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC‐sEV inhibited the Th2 responses, providing novel evidence of the potential cell‐free therapy acting on DCs in allergic airway diseases. [ABSTRACT FROM AUTHOR]

We report that the pincer nickel complexes display prostate cancer antitumor properties through inhibition of cell proliferation. Notably, they display better antitumor properties than cisplatin. Mechanistic studies reveal that these pincer nickel complexes trigger cell apoptosis, most likely due to cell cycle arrest. Interestingly, these complexes also inhibit androgen receptor (AR) and prostate-specific antigen (PSA) signaling, which are critical for prostate cancer survival and progression. Our study reveals a novel function of pincer nickel complexes as potential therapeutic drugs in prostate cancer. [ABSTRACT FROM AUTHOR]

Adenosine triphosphate (ATP) may be the most important biological small molecule. Since it was discovered in 1929, ATP has been regarded as life's energy reservoir. However, this compound means more to life. Its legend starts at the dawn of life and lasts to this day. ATP must be the basic component of ancient ribozymes and may facilitate the origin of structured proteins. In the existing organisms, ATP continues to construct ribonucleic acid (RNA) and work as a protein cofactor. ATP also functions as a biological hydrotrope, which may keep macromolecules soluble in the primitive environment and can regulate phase separation in modern cells. These functions are involved in the pathogenesis of aging-related diseases and breast cancer, providing clues to discovering anti-aging agents and precision medicine tactics for breast cancer. [ABSTRACT FROM AUTHOR]

UDP glucose dehydrogenase (UDP-GlcDH) can catalyze UDP glucose to UDP glucuronic acid, which is an essential precursor for the formation of polysaccharide. The UDP-GlcDH gene sequence of Aspergillus flavus was used as the template, and the cDNA sequence of UDP-GlcDH gene from Ganoderma lucidum was obtained by searching the EST library of Ganoderma lucidum through the electronic cloning method, and then verified by using the RT-PCR testing. The bioinformatics method was used to analyze the UDP-GlcDH gene, showing that the cDNA sequence was 1591 bp in length, which contained 471 amino acid sequences with the molecular weight of 51.8 kD and PI of 6.29. The UDP-GlcDH gene was found in the endoplasmic reticulum, which was highly homologous to the amino acid sequence encoded by UDP-GlcDH gene in the fungi such as Dichomitus squalens and Coriolus versicolor. [ABSTRACT FROM AUTHOR]

The research provides a multi-criteria group decision support model for hotel selection according to traveller preference characteristics. Specifically, the study attempts to identify characteristic preferences among travellers through online reviews and then generate recommendation lists under these characteristics. Utilizing a sample of 48,756 online reviews on TripAdvisor.com, the research exploits natural language processing to acquire high-frequency feature words and employs these features to group online reviews for filtering unrelated ones. Subsequently, online reviews and fuzzy theory are combined to develop a decision support model, by utilising the information of user ratings and text comments. In addition, the related extension of the theoretic knowledge is presented. The findings demonstrate that, hotel quality varies under different characteristics and a comprehensive evaluation of hotels would encounter difficulty meeting travellers' demands, and the proposed model exhibits great performance in addressing this condition. The study can enable travellers to make a satisfactory hotel selection that matches their expectation to a high degree and also provides implications for hoteliers to understand tourist preferences and for tourism websites to optimize management strategies. [ABSTRACT FROM AUTHOR]

Suitability of different substrates for enriched mixed microbial cultures (MMCs) is of importance to the polyhydroxyalkanoate (PHA) fermentation using renewable carbon. In this study, three enriched MMCs were evaluated for their fermentation features and kinetics with different carbon sources (sodium acetate, glucose, or starch). The results showed that the highly specific bacterial community composition was developed depending on the applied carbon source. Correspondence analysis suggested that the genus affiliated in Gammaproteobacteria_unclassified was related to 3-hydroxybutyrate (HB) synthesis in acetate-fed MMC (relative abundance of 38%) and glucose-fed MMC (relative abundance of 76.7%), whereas Vibrio genus was related to 3-hydroxyvalerate (HV) production in glucose-fed MMC (relative abundance of 0.4%) and starch-fed MMC (relative abundance of 94.6%). The acetate-fed MMC could not use glucose and starch as fermentation carbon sources, showing the limitation of microbial species developed with the specific metabolic substrate. Glucose-fed MMC produced the highest PHA cell content of 64.2% cell dry weight when using sodium acetate as the fermentation carbon. Glucose-fed MMC showed wide resilience and adaptation to various carbon sources. When actual landfill leachate was used for fermentation by glucose-fed MMC, maximum PHA cell content of 45.5% cell dry weight and the PHA volumetric productivity of 0.265 g PHA/(L·h) were obtained. This study suggested carbon sources applied in the MMC enrichment stage had a significant influence on utilization of carbon in the fermentation stage. [ABSTRACT FROM AUTHOR]

Combining the advantages of porosity and crystallinity of MOF and COF photocatalysts to build a covalently connected MOF–COF hybrid heterostructure has been proved to be an effective way to assemble efficient photocatalysts. However, until now, only MOFs with –NH2 groups in the ligand have been used to build covalently connected MOF–COF hybrid materials by a Schiff base reaction between the components. In this work, we develop a new strategy for constructing covalently connected MOF–COF hybrid materials by post-synthetic modification of metal nodes with MOFs without –NH2 in the ligand. A typical Zr-MOF without –NH2 ligands, MOF-808, was modified by coordination with p-aminobenzoic acid on Zr6 clusters to graft it with –NH2 groups. Then, the core–shell MOF-808@TpPa-1-COF with a covalent linkage between the two components was synthesized by an in situ reaction. The core–shell morphology of the hybrid material and the covalent linkage between the components were confirmed by various characterizations. The results of photocatalytic hydrogen evolution under visible light irradiation confirm that MOF-808@TpPa-1-COF (6/4) shows a hydrogen evolution rate of 11.88 mmol g−1 h−1, which is 5.6 times higher than that of the parent TpPa-1-COF. Further investigations confirm the significant role of the covalent linkage between the components in the efficient separation and transfer of photogenerated electrons in the photocatalytic hydrogen evolution reaction. The strategy of assembling MOF@COF in this work could be applied for constructing more covalently linked MOF–COF hybrid materials with the desired morphology and function. [ABSTRACT FROM AUTHOR]

Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin−) cells. PBMCs and Lin− cells were cocultured with induced pluripotent stem cell‐derived MSCs (iPSC‐MSCs) under the stimulation of epithelial cytokines IL‐25 and IL‐33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS‐ICOSL pathway. iPSC‐MSCs successfully decreased the high levels of IL‐13, IL‐9, and IL‐5 in PBMCs in response to IL‐25, IL‐33, and the high percentages of IL‐13+ILC2s and IL‐9+ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC‐MSCs. However, iPSC‐MSCs were found directly to enhance ILC2 levels and functions via ICOS‐ICOSL interaction in Lin− cells and pure ILC2s. iPSC‐MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS‐ICOSL interaction. The MSC‐induced Treg cells then suppressed ILC2s by secreting IL‐10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS‐ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders. [ABSTRACT FROM AUTHOR]

Owing to the demand for strategic metals, the dissolution of scrap superalloys is imperative for their recycling. This study investigates the electrochemical dissolution process of superalloys in different electrolytes. The results indicate that the dissolution rate of the samples is significantly emulative in organic electrolyte at current densities greater than 0.7 A cm−2. The dissolution behavior of the sample in aqua regia electrolyte can be classified as dissolution of the oxidation layer, formation of the anode product layer, and formation of the Cr-rich hindered-dissolution layer. While in organic electrolyte, the dissolution behavior can be partitioned as dissolution of the oxidation layer, formation of the porous Cr-rich hindered-dissolution layer, formation of dissolved pores, and detachment of the porous Cr-rich hindered-dissolution layer. Therefore, the formation of dissolved pores and detachment of the porous Cr-rich hindered-dissolution layer can effectively reduce the electrolytic resistance and the diffusion resistance in the electrolyte. [ABSTRACT FROM AUTHOR]

With the excessive consumption and pollution of water resources, the sustainable development of water resources poses a serious threat currently. How to perceive and prevent the degradation of water resource in advance is an urgent problem. The water resource carrying capacity (WRCC) is a significant indicator to reflect the condition of water resources in a region. Resounding to these circumstances, our research establishes a decision support framework to solve WRCC risk evaluation issues. First, hesitant probabilistic fuzzy sets (HPFSs) are selected as a representation for the evaluation information in the expert group. Aimed at existing studies of HPFSs, some limitations are overcome involving the distance and comparison rule. Secondly, a TODIM‐PROMETHEE II based multi‐criteria group decision making (MCGDM) method is developed to overcome the inherent restrictions of PROMETHEE II method and make it suitable for a practical decision‐making condition with bounded rationality. Subsequently, a case study is utilized to demonstrate the feasibility of our newly proposed decision support framework, followed by a sensitivity analysis and a comparison analysis. The outcome indicates that the framework has an excellent performance to solve this kind of MCGDM issues. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed asymmetric intramolecular Heck reaction of aryl iodides with alkynyl carboxylic acids has been developed, delivering various indoline frameworks in moderate to excellent yields (up to 95 %) with excellent enantioselectivities (up to 96 % ee) and diastereoselectivities (>20 : 1) using BINOL‐based phosphoramidite as chiral ligand. This cascade annulation protocol, which tolerates a broad variety of functional groups and is conducted under an argon atmosphere, provides efficient and atom‐economical access to structurally diverse 2,3‐disubstituted indolines bearing vicinal tertiary and quaternary stereocenters. Additionally, the synthetic products could be converted to useful unique indoline derivatives without loss of enantiomeric excess. [ABSTRACT FROM AUTHOR]

Proton-conducting materials are a key component of proton exchange membrane fuel cells (PEMFCs) and the advantage of clear structural information in crystal materials offers a pathway for the investigation of the proton-conducting mechanism and pathway. In this work, a new Cd2+ coordination polymer material (compound 1) with the formula {[Cd3(bipy)3(H2O)4][Fe(CN)6]2·2H2O·2(bipy)} n was successfully synthesized by a solution diffusion method and its proton conduction ability was further determined. Crystal structure analysis confirms the coordination of [Fe(CN)6]3–, 4,4′-bipyridine, and H2O molecules to Cd2+ in the three dimensional structure of compound 1. Also, we confirmed that compound 1 of 500–800 nm particle size could be synthesized on a large scale by a facile stirring method. Proton-conductivity analyses revealed that compound 1 shows a water-mediated proton conduction behaviour because the conductivity increased apparently with the increase of relative humidity. Further investigation shows that the highest proton-conductivity of 8.36 × 10−4 S cm−1 was observed at 60°C and 95 % relative humidity, and the mechanism analysis suggests a Vehicle mechanism exists in the proton conduction process of compound 1. A Cd2+ based coordination polymer material featuring 3D network was synthesized by a facile stirring method for water-mediated proton conduction. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis. Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram. Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892–0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570–0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953–1.000), the validation cohort (AUC = 0.822, 95% CI 0.635–1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608–0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model. Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients. [ABSTRACT FROM AUTHOR]

To monitor and manage water environments, China developed a centralized multi-level administrative system where governments and agencies at each level are responsible for water quality within their regions. In this case, regional water quality assessment has become a critical issue. However, as a complex multi-criteria decision making (MCDM) problem, it faces many challenges such as diverse implement indicator framework, complicated indicator interrelations, and lack of reliable assessment methods. Therefore, this paper constructs a novel multistage decision support framework for regional water quality assessment. In phase I, we determine indicator framework strictly according to the national standards, involving PH, dissolved oxygen (DO), chemical oxygen demand (COD), etc., totally 21 water quality indicators where the temperature indicator is excluded due to its lack of assessment standard. In addition, considering the matching between the characteristic of water quality data and the probabilistic linguistic term set (PLTS) technique, we employ PLTS theory to process massive monitoring data. In phase II, relative weight considering indicators' interrelationship is produced by the proposed regression-based decision-making trial and evaluation laboratory (DEMATEL) method, and further forms combined weight by balancing single-factor weight. In phase III, we present a new PLTS measure and extend the fuzzy technique for order performance by similarity to ideal solution (FTOPSIS) method to generate assessment results. Then, we investigate water quality status of 16 administrative districts in Shanghai, China, with the proposed method. The collected data are derived from 26 water quality monitoring sites and covers the period during September 2018 to February 2019. The results confirm a hypothesis that the statistically significant interrelationship does exist among indicators, and point out that Huang Pu District remains the best water quality with highest values of C C i in the range of (0.79–0.85) over the 6 months. Moreover, the parameter analysis and comparative analysis are further given that verifies the robustness and reliability of the model in details. [ABSTRACT FROM AUTHOR]

Metazoans harbor a wealth of symbionts that are ever‐changing the environment by taking up resources and/or excreting metabolites. One such common environmental modification is a change in pH. Conventional wisdom holds that symbionts facilitate the survival and production of their hosts in the wild, but this notion lacks empirical evidence. Here, we report that symbiotic bacteria in the genus Enterococcus attenuate the oviposition avoidance of alkaline environments in Drosophila. We studied the effects of alkalinity on oviposition preference for the first time, and found that flies are robustly disinclined to oviposit on alkali‐containing substrates. This innate repulsion to alkaline environments is explained, in part, by the fact that alkalinity compromises the health and lifespan of both offspring and parent Drosophila. Enterococcus dramatically diminished or even completely reversed the ovipositional avoidance of alkalinity in Drosophila. Mechanistically, Enterococcus generate abundant lactate during fermentation, which neutralizes the residual alkali in an egg‐laying substrate. In conclusion, Enterococcus protects Drosophila from alkali stress by acidifying the ovipositional substrate, and ultimately improves the fitness of the Drosophila population. Our results demonstrate that symbionts are profound factors in the Drosophila ovipositional decision, and extend our understanding of the intimate interactions between Drosophila and their symbionts. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common primary liver tumor, and the main reason is the unclear pathogenesis of HCC, which leads to a high fatality rate of HCC. Therefore, it is of great clinical significance to explore the molecular mechanism of HCC and find a targeted therapeutic approach from the molecular level. Materials and Methods: MicroRNA-15a-5p (miR-15a-5p) expression level was measured by bioinformatics and qRT-PCR. Luciferase assay and RIP assays were used to verify the relationship between programmed cell death protein 1 (PD1) PD 1 with miR-15a-5p. Exosomes were identified using TEM, Zetasizer Nano ZS, and western blot. Edu, Transwell, and scratch assay were performed to explore the role of miR-15a-5p or exo-miR-15a-5p on HepG2 cells progression. Results: MicroRNA-15a-5p (miR-15a-5p) was decreased in HCC tissues and cell lines, which indicated a poor prognosis. Overexpression of miR-15a-5p inhibited viability, proliferation, migration and invasion of HepG2 cells. Then, we isolated exosomes from cancer cells, and found that miR-15a-5p was packaged into exosomes from cancer cells. Furthermore, exo-miR-15a-5p was secreted into CD8+ T cells, then directly inhibited PD1 expression via targeted binding. Then, we co-cultured CD8+ T cells transfected with PD1 with HepG2 transfected with miR-15a-5p, PD1 remitted the inhibitory role of miR-15a-5p on HCC progression. Conclusion: Together, present study revealed exo-miR-15a-5p from cancer cells inhibited PD1 expression in CD8+ T cells, which suppressed the development of HCC. [ABSTRACT FROM AUTHOR]

Background: Single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies only explain part of the heritability of Alzheimer's disease (AD). Epistasis has been considered as one of the main causes of "missing heritability" in AD. Methods: We performed genome-wide epistasis screening (N = 10,389) for the clinical diagnosis of AD using three popularly adopted methods. Subsequent analyses were performed to eliminate spurious associations caused by possible confounding factors. Then, candidate genetic interactions were examined for their co-expression in the brains of AD patients and analyzed for their association with intermediate AD phenotypes. Moreover, a new approach was developed to compile the epistasis risk factors into an epistasis risk score (ERS) based on multifactor dimensional reduction. Two independent datasets were used to evaluate the feasibility of ERSs in AD risk prediction. Results: We identified 2 candidate genetic interactions with PFDR < 0.05 (RAMP3-SEMA3A and NSMCE1-DGKE/C17orf67) and another 5 genetic interactions with PFDR < 0.1. Co-expression between the identified interactions supported the existence of possible biological interactions underlying the observed statistical significance. Further association of candidate interactions with intermediate phenotypes helps explain the mechanisms of neuropathological alterations involved in AD. Importantly, we found that ERSs can identify high-risk individuals showing earlier onset of AD. Combined risk scores of SNPs and SNP-SNP interactions showed slightly but steadily increased AUC in predicting the clinical status of AD. Conclusions: In summary, we performed a genome-wide epistasis analysis to identify novel genetic interactions potentially implicated in AD. We found that ERS can serve as an indicator of the genetic risk of AD. [ABSTRACT FROM AUTHOR]

Sintered silver with high thermal conductivity and reliability has been considered as a promising substrate bonding solution in power modules. The traditional double printing process is complex, and the second layer of silver paste is too thin to ensure complete wetting. We greatly simplified the sample preparation process by single printing and optimized the sintering process by means of open-face contact drying technology and staged heating method. In this article, the effect of predrying steps and heating rate on the quality of sintered silver joint on large area silver-plated DBC substrate and its mechanism are discussed. The microstructure shows that the samples sintered by the optimized sintering process have no obvious defects, and the sintered silver layer is dense and uniform. In order to evaluate the bonding quality of the whole joint, the sample was cut into 16 small pieces by metallographic cutter, the average shear strength was 55.65 MPa, and the strength distribution between the center and the edge of the sample was uniform. The samples sintered by an optimized sintering process show cohesive failure mode and typical ductile fracture morphology. The energy dispersive spectrum analysis shows that the composition distribution of the sintered silver layer in the center and edge of the sample was relatively uniform, which is consistent with the distribution of shear strength. The scanning electron microscopy image of cross section demonstrated that the porosity of the adhesive layer is 3.08%, which is far lower than that of the traditional double printing process, with good interface bonding and no delamination. [ABSTRACT FROM AUTHOR]

Group 2 innate lymphoid cells (ILC2s) are recently reported to play a more critical role in allergic diseases. We previously identified that mesenchymal stromal cells (MSCs) elicited therapeutic effects on allergic airway inflammation. Small extracellular vesicles (sEV) derived from MSCs possess striking advantages including low immunogenicity and high biosafety, and is extremely promising cell-free therapeutic agents. However, the effects of MSC-sEV on ILC2s are still unclear. Additionally, scalable isolation protocols are required for the mass production of homogenous MSC-sEV especially in clinical application. We previously reported that induced pluripotent stem cells-derived MSCs were the ideal cellular source for the large preparation of MSC-sEV. Here we developed a standardized scalable protocol of anion-exchange chromatography for isolation of MSC-sEV, and investigated the effects of MSC-sEV on ILC2 function from patients with allergic rhinitis and in a mouse ILC2-dominant asthma model. The characterization of MSC-sEV was successfully demonstrated in terms of size, morphology and specific markers. Using flow cytometry and human Cytokine Antibody Array, MSC-sEV but not fibroblasts-sEV (Fb-sEV) were found to significantly inhibit the function of human ILC2s. Similarly, systemic administration of MSC-sEV but not Fb-sEV exhibited an inhibition of ILC2 levels, inflammatory cell infiltration and mucus production in the lung, a reduction in levels of T helper 2 cytokines, and alleviation of airway hyperresponsiveness in a mouse model of asthma. Using RNA sequencing, miR-146a-5p was selected as the candidate to mediate the above effects of MSC-sEV. We next revealed the uptake of ILC2s to MSC-sEV, and that transfer of miR-146a-5p in MSC-sEV to ILC2s in part contributed to the effects of MSC-sEV on ILC2s in vitro and in a mouse model. In conclusion, we demonstrated that MSC-sEV were able to prevent ILC2-dominant allergic airway inflammation at least partially through miR-146a-5p, suggesting that MSC-sEV could be a novel cell-free strategy for the treatment of allergic diseases. [ABSTRACT FROM AUTHOR]

In the multi‐criteria group decision‐making (MCGDM) problems with great uncertainty, making full use of participants' evaluation information could help improve the accuracy and reliability of decision results. Probabilistic linguistic term set (PLTS) is an effective tool to represent qualitative data and can fully express the hesitation and preference of decision makers. Therefore, this paper aims to propose an MCGDM method based on PLTSs. In the proposed method, the projection of PLTSs is explored to measure the distance and angle differences between two objects, and Bayesian best–worst method (Bayesian BWM) is used to determine the aggregated final weights of criteria. Besides, the elimination and choice translating reality III (ELECTRE III) method combined with distillation algorithm deals with the projection of PLTSs to obtain the alternatives' ranking of each decision maker. Then, the weighted convex median voting rule is developed to integrate the rankings results regarding all decision makers, which can solve the conflict of ranking results among experts and ensure that the comprehensive ranking results are reasonable and practical. Finally, a case study of health‐care waste management is designed and comparative analyses are implemented to show the effectiveness and advantages of the proposed method. [ABSTRACT FROM AUTHOR]