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Abstract Background The efficiency of mesenchymal stem cells (MSCs) in treating myocardial infarction (MI) remains inconsistent, which limits their therapeutic applications. Therefore, exploring the mechanism for the inconsistent efficacy of MSCs and identification the criteria for screening MSCs are important for improving the efficiency of MSCs. Methods Mouse model after MI was utilized to test the role of MSCs from different donors and the functional subpopulation in improving cardiac function. Heterogeneity of MSCs was identified using single-cell RNA sequencing (scRNA-seq) of MSC-GY. GSEA and Scissor analyses were used to find the functional subpopulations of MSCs that promote angiogenesis. The role of functional subpopulations in promoting angiogenesis was verified by detecting the secretory proteins, the ratio of N-CADHERIN+/CD168− subpopulations in MSCs, and the tube formation, migration, and proliferation of HUVECs after treatment with conditional medium (CM) derived from different MSCs. Results We found that umbilical cord-derived MSCs (UC-MSCs) from different donors have varied therapeutic efficacy in MI mice and UC-MSCs with higher therapeutic effectiveness exhibited the most potent pro-angiogenic effects by secreting elevated levels of angiogenesis-related proteins, such as MYDGF, VEGFA, and FGF2. ScRNA-seq of 10,463 UC-MSCs revealed that the N-CADHERIN+/CD168− subpopulation was closely associated with pro-angiogenic effects, and the ratio of this cell subpopulation was positively correlated with the angiogenic potential of MSCs. We also found that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in improving cardiac function of MI mice. Conclusions Our study identified that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in treating MI, which was essential for the development and utilization of MSCs in MI treatment.

Humanitarian logistics plays a vital role in disaster management. However, it often faces the challenge of unpredictable road conditions when solving relief prepositioning problems to effectively respond to natural disasters. This study examines the location–allocation problem in humanitarian logistics for disaster relief supplies. The research focuses on determining the optimal number and locations of supply distribution points and developing an efficient allocation scheme for relief items. Herein, we propose a two-stage programming model utilizing the distributionally robust optimization (DRO) approach for the location–allocation problem when considering uncertain road conditions. The DRO approach optimizes the expectation value of worst-case across all distributions within a specified ambiguity set. Relief facility locations, inventory levels, and relief supply distribution plans are all determined simultaneously. By utilizing the Wasserstein metric, an ambiguity set is created to characterize the link-wise uncertainties. This metric can capture uncertainties based on finite sample information, ensuring with high probability that the true distribution is contained within the constructed set. To address the problem, We develop an algorithm based on Benders decomposition. To validate the efficacy of the model and methodology, we conduct a real-life case study on the threats posed by hurricanes occurring in the Gulf of Mexico region. We evaluate the performance of our proposed model by comparing it to the scenario-based stochastic programming model and the traditional robust model. Furthermore, we offer managerial insights based on the application of distributionally robust optimization methodology in humanitarian logistics.

Catalysts play a pivotal role in the efficient conversion of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) through electrochemical oxidation. In this work, a cost-effective and highly efficient cobalt-based electrocatalyst for the synthesis of bio-based carboxylic acids was reported. By the employment of cellulose, which was dissolved in the alkaline-urea with cobalt ion, as the precursor, it derived a carbon-coated Co3O4 (Co3O4@NC) catalyst with a high specific surface area and rich porous structure. When utilized in the electrocatalytic conversion of HMF to FDCA, the catalyst exhibited exceptional yields and Faradaic efficiency which surpassed 95 %. In-situ Raman spectra unveiled that a dual-pathway process occurred on this catalyst, with part of Co3O4 serving as active sites for HMF adsorption, while other Co3O4 transformed into CoOOH during the reaction. This dual-pathway electrocatalysis facilitated the highly efficient conversion of HMF. Additionally, using bio-based alcohols/aldehydes as the feedstocks, eight carboxylic acids were successfully synthesized with yields ranging from 91.5 % to 99 %. This study presents a highly efficient electrocatalyst derived from biomass, enabling diverse bio-based carboxylic acid production with significant potential for sustainable chemical synthesis.

The composition of energy consumption is shifting from fossil fuels to renewable energy sources. Determining if reducing energy use may increase green factor production (GFP) is thus crucial. This study, which examines data from 2013 to 2019, indicates that GFP is impacted by both the Robotics and natural resource markets. It conducts a comprehensive analysis of Robotics's impact on the development of green economies using China as a case study and a suitable mathematical model, namely a static panel model (SPM). By applying robotics analytical powers and predictive modelling, the research sheds light on how economic growth and environmental preservation might be balanced, or “green growth.” The magazine aims to find synergies that support the incorporation of AI-driven solutions into policy frameworks, promoting a shift toward more environmentally sustainable practices globally by carefully analyzing global economic policies. It has been observed that different industries and development phases have other impacts of AI on carbon intensity. Furthermore, this investigation dissects GFP into its component elements, green efficiency improvement effects, and technological advancement to elucidate how AI influences green economic growth.

Abstract Background Endogenous endophthalmitis (EE) is a rare but highly destructive eye emergency secondary to systemic infection. Acute endophthalmitis can lead to irreversible vision impairment or even loss of the whole eye, unless being diagnosed and treated promptly. Case presentation This study reports three typical EE cases of endogenous endophthalmitis secondary to different severe systemic diseases. Patients were recruited from the Department of ophthalmology at Zhongnan hospital of Wuhan University and the Department of ophthalmology at the Second Affiliated Hospital of Fujian Medical University. Patients were followed up for up to 60 days. Among these cases, the eye symptoms is the initial manifestations while secondary to original different special systemic conditions. Patients have been treated under dynamically prompt response undergoing systemic treatment and eye treatment at the same time. Best corrected visual acuity were 20/40, 20/60 and light perception during follow-up evaluation. Conclusions Our observation suggest that prompt identification and treatment could save patients’ vision from EE.

Abstract Background The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. Methods In this real‐world study, we enrolled 143 COVID‐19‐vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti‐spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4‐BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. Results Patients with liver cancer receiving booster doses had higher levels of anti‐spike RBD IgG against circulating omicron (BA.4‐BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4‐BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti‐spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti‐spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. Conclusion Our study found that there may be differences in vaccine response and protective effect against COVID‐19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID‐19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Abstract Many different types of stem cells utilize asymmetric cell division (ACD) to produce two daughter cells with distinct fates. Haspin-catalyzed phosphorylation of histone H3 at Thr3 (H3T3ph) plays important roles during mitosis, including ACD in stem cells. However, whether and how Haspin functions in ACD regulation remains unclear. Here, we report that Haspin knockout (Haspin-KO) mouse embryonic stem cells (mESCs) had increased ratio of ACD, which cumulatively regulates cell fate decisions. Furthermore, Wnt5a is significantly downregulated due to decreased Pax2 in Haspin-KO mESCs. Wnt5a knockdown mESCs phenocopied Haspin-KO cells while overexpression of Wnt5a in Haspin-KO cells rescued disproportionated ACD. Collectively, Haspin is indispensable for mESCs to maintain a balanced ratio of ACD, which is essential for normal development and homeostasis.

The diverse applications of various tissues of Polygonum Multiflorum (PM) encompass the use of its leaf and bud as tea and vegetables, as well as the utilization of its expanded root tubers and caulis as medicinal substances. However, previous studies in the field of metabolomics have primarily focused on the medicinal properties of PM. In order to investigate the potential for broader applications of other tissues within PM, a metabolomic analysis was conducted for the first time using UPLC-Q-TOF-MS/MS on 15 fresh PM tissues. A total of 231 compounds, including newly discovered compounds such as torosachrysone and dihydro-trihydroxystilbene acid derivatives, were identified within PM. Through clustering analysis, the PM tissues were categorized into edible and medicinal parts, with edible tissues exhibiting higher levels of phenolic acids, organic acids, and flavonoids, while the accumulation of quinones, dianthrones, stilbenes, and xanthones was observed in medicinal tissues. Comparative analysis demonstrated the potential application of discarded tissues, such as unexpanded root tuber (an industrial alternative to expanded root tuber) and young caulis (with edible potential). Moreover, the quantification of representative metabolites indicated that flowers and buds contained significant amounts of flavonoids or phenolic acids, suggesting their potential as functional food. Additionally, the edible portion of PM exhibited a high content of quercitrin, ranging from 0.59 to 10.37 mg/g. These findings serve as a valuable point of reference for the expanded utilization of PM tissues, thereby mitigating resource waste in this plant.

Abstract Molecular subtyping of cancer can greatly help to understand the development of disease and predict tumor behavior. Exploring detection methods for precise subtyping is appealing to prognosis and personalized therapy. During the past decades, DNA‐based biosensors have exhibited great potential in cancer diagnosis due to their structural programmability and functional diversity. Despite the encouraging progress that has been made, there remains an issue in improving the accuracy and sensitivity of cancer subtyping due to the complex process of disease, especially in preclinical or clinical applications. To accelerate the development of DNA sensors in the identification of cancer subtypes, in this review, we summarized their advances in molecular subtyping by analyzing the heterogeneity in categories and levels of biomarkers between cancer subtypes. The strategies toward genomic and proteomic heterogeneity in cells or on the cell surface, as well as the cancer excretions including extracellular vesicles (EVs) and microRNA (miRNAs) in serum, are summarized. Current challenges and the opportunities of DNA‐based sensors in this field are also discussed.

Nowadays, people give more importance and pay closer attention to the condition of their eyelids and lid margins. This increased recognition of eyelid hygiene is due to the growing awareness that improper eyelid cleaning might lead to various ocular surface diseases such as blepharitis and meibomian gland dysfunction. These ocular surface diseases can greatly affect people's quality of life. This article reviews the latest procedures for proper eyelid cleaning, including indications, methods, tools, detergents, and clinical applications, to maintain a healthy ocular surface and assist in the treatment of dry eye and blepharitis.

CD137 (4‐1BB, TNFRSF9), an inducible T‐cell costimulatory receptor, is expressed on activated T cells, activated NK cells, Treg cells, and several innate immune cells, including DCs, monocytes, neutrophils, mast cells, and eosinophils. In animal models and clinical trials, anti‐CD137 agonistic monoclonal antibodies have shown anti‐tumor potential, but balancing the efficacy and toxicity of anti‐CD137 agonistic monoclonal antibodies is a considerable hindrance for clinical applications. Here, we describe a novel fully human CD137 agonistic antibody (PE0116) generated from immunized harbor H2L2 human transgenic mice. PE0116 is a ligand blocker, which is also the case for Utomilumab (one of the leading CD137 agonistic drugs); PE0116 partially overlaps with Urelumab's recognized epitope. In vitro, PE0116 activates NF‐κB signaling, significantly promotes T‐cell proliferation, and increases cytokine secretion in the presence of cross‐linking. Importantly, PE0116 possesses robust anti‐tumor activity in the MC38 tumor model. In vivo, PE0116 exhibits a good safety profile and has typical pharmacokinetic characteristics of an IgG antibody in preclinical studies of non‐human primates. In summary, PE0116 is a promising anti‐CD137 antibody with a good safety profile in preclinical studies.

The origin of seeds is a crucial environmental factor that significantly impacts crop production. Accurate identification of seed origin holds immense importance for ensuring traceability in the seed industry. Currently, traditional methods used for identifying the origin of maize seeds involve mineral element analysis and isotope fingerprinting, which are laborious, destructive, time-consuming, and suffer from various limitations. In this experiment, near-infrared spectroscopy was employed to collect 1360 maize seeds belonging to 12 different varieties from 8 distinct origins. Spectral information within the range of 11,550–3950 cm−1 was analyzed while eliminating multiple interferences through first-order derivative combined with standard normal transform (SNV). The processed one-dimensional spectral data were then transformed into three-dimensional spectral maps using Gram’s Angle Field (GAF) to be used as input values along with the VGG-19 network model. Additionally, a convolution layer with a step size of 1 × 1 and the padding value set at 1 was added, while pooling layers had a step size of 2 × 2. A batch size of 48 and learning rate set at 10−8 were utilized while incorporating the Dropout mechanism to prevent model overfitting. This resulted in the construction of the GAF-VGG network model which successfully decoded the output into accurate place-of-origin labels for maize seed detection. The findings suggest that the GAF-VGG network model exhibits significantly superior performance compared to both the original data and the PCA-based origin identification model in terms of accuracy, recall, specificity, and precision (96.81%, 97.23%, 95.35%, and 95.12%, respectively). The GAF-VGGNet model effectively captures the NIR features of different origins of maize seeds without requiring feature wavelength extraction, thereby reducing training time and enhancing accuracy in identifying maize seed origin. Moreover, it simplifies near-infrared (NIR) spectral modeling complexity and presents a novel approach to maize seed origin identification and traceability analysis.

Abstract Background Hormones play an indispensable role during fruit ripening, nine clades in 2-oxoglutarate-dependent dioxygenase (2OGD) superfamily are responsible for the hormone biosynthesis and metabolism, but less information is known about them. Results A total of 163 Vv2OGD superfamily members were identified from grape genome, which were mainly expanded by local (tandem and proximal) duplication. Phylogenetic analysis of 2OGD members in grape and Arabidopsis indicates 37 members in Vv2OGD superfamily are related to hormone biosynthesis and metabolism process (Vv2OGD-H), which could be divided into 9 clades, gibberellin (GA) 3-oxidase (GA3ox), GA 20-oxidase (GA20ox), carbon-19 GA 2-oxidase (C19-GA2ox), carbon-20 GA 2-oxidase (C20-GA2ox), 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), dioxygenase for auxin oxidation (DAO), lateral branching oxidoreductas (LBO), downy mildew resistant 6 and DMR6-like oxygenase (DMR6/DLO) and jasmonate-induced oxygenase (JOX). Sixteen of these 37 Vv2OGD-Hs are expressed in grape berry, in which the expression patterns of VvGA2oxs, VvDAOs and VvJOXs shows a correlation with the change patterns of GAs, indole-3-acetic acid (IAA) and jasmonates (JAs), indicating the involvement of these genes in grape berry development by regulating corresponding hormones. Twelve Vv2OGD-Hs respond to methyl JA (MeJA) treatment, of which eight may lead to the inhibition of the ripening process by the crosstalk of JAs-salicylic acids (SAs), JAs-GAs and JAs-JAs, while seven Vv2OGD-Hs respond to ABA treatment may be responsible for the promotion of ripening process by the interplay of abscisic acid (ABA)-strigolactones (SLs), ABA-SAs, ABA-GAs, ABA-JAs. Especially, VvLBO1 reach an expression peak near véraison and up-regulate about four times after ABA treatment, which implies SLs and ABA-SLs crosstalk may be related to the onset of berry ripening in grape. Conclusions This study provides valuable clues and new insights for the mechanism research of Vv2OGD-Hs in hormones regulation during the grape berry development.

The cover of corn stover has a significant effect on the emergence and growth of soybean seedlings. Detecting corn stover covers is crucial for assessing the extent of no-till farming and determining subsidies for stover return; however, challenges such as complex backgrounds, lighting conditions, and camera angles hinder the detection of corn stover coverage. To address these issues, this study focuses on corn stover and proposes an innovative method with which to extract corn stalks in the field, operating an unmanned aerial vehicle (UAV) platform and a U-Net model. This method combines semantic segmentation principles with image detection techniques to form an encoder–decoder network structure. The model utilizes transfer learning by replacing the encoder with the first five layers of the VGG19 network to extract essential features from stalk images. Additionally, it incorporates a concurrent bilinear attention module (CBAM) convolutional attention mechanism to improve segmentation performance for intricate edges of broken stalks. A U-Net-based semantic segmentation model was constructed specifically for extracting field corn stalks. The study also explores how different data sizes affect stalk segmentation results. Experimental results prove that our algorithm achieves 93.87% accuracy in segmenting and extracting corn stalks from images with complex backgrounds, outperforming U-Net, SegNet, and ResNet models. These findings indicate that our new algorithm effectively segments corn stalks in fields with intricate backgrounds, providing a technical reference for detecting stalk cover in not only corn but also other crops.

Mucosal vaccines have great potential and advantages in preventing infection caused by multiple pathogens. In developing mucosal vaccines, the biggest challenge comes from finding safe and effective adjuvants and drug delivery systems. Great progress has been made in the generation of mucosal adjuvants using detoxified bacterial toxin derivatives, pathogen-related molecules, cytokines, and various vaccine delivery systems. However, many problems, relating to the safety and efficacy of mucosal vaccine adjuvants, remain. Certain natural substances can boost the immune response and thus could be used as adjuvants in vaccination. These natural-product-based immune adjuvants have certain advantages over conventional adjuvants, such as low toxicity, high stability, and low cost of production. In this review, we summarize the latest natural-product-based immune adjuvants, and discuss their properties and clinical applications.

Arsenic pollution prevails in rivers and reservoirs in nonferrous metal mining areas, especially in lead–zinc mining areas, which affects the health of the people residing in such areas. Arsenic usually exists as As(III) and As(V) in water, and the adsorption of As(III) and As(V) changes with the type of adsorbent used. In this work, we report a novel adsorbent Fe/Mn–CO3-layered double hydroxide (Fe/Mn–CO3-LDH) composite that can efficiently remove both As(III) and As(V) from water. When the initial concentrations of As(III) and As(V) were 5, 10 and 50 mg/L, the adsorption capacities were 10.12–53.90 and 10.82–48.24 mg/g in the temperature range of 25–45 °C, respectively. The adsorption kinetics conformed well to the pseudo-second-order kinetic model, with all of the fitted correlation coefficients being above 0.998 for all the three initial concentrations (5, 10 and 50 mg/L) tested, suggesting a chemisorption-dominated process. The adsorption isotherms of As(III) and As(V) by Fe/Mn–CO3-LDHs conformed better to the Freundlich model than to the Langmuir one, indicating a heterogeneous reversible adsorption process. The theoretical maximum adsorption capacity increased with the increase in temperature. During adsorption, As(III) was partially converted to As(V), which was further interacted with intralayer anions. While the electrostatic attraction played an important role in the adsorption of As(V). HIGHLIGHTl Successful preparation of Fe/Mn–CO3-LDH material with a high-specific surface area and a large pore volume.; Pseudo-second-order kinetic model and Freundlich model can all well described the adsorption of As(III) and As(V) on Fe/Mn–CO3-LDH; Fe/Mn–CO3-LDH has good adsorption effect on As(III) and As(V) in a vast range of pH = 2-12.; pH only have a slight effect on the As(III) adsorbed by Fe/Mn -CO3-LDH, but obvious for As(V) adsorption.;

Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between decreased expression levels of Forkhead Box J1 (FOXJ1) and the activation of the NF-κB pathway in autoimmune pulmonary inflammation of MRL/Lpr mice. Methods: The female BALB/c mice (n=6) and MRL/Lpr mice (n=30) were divided into 5 groups including a control group (BALB/c), and five MRL/Lpr mice groups (8W, 12W, 16W, 24W, and 32W). The infiltration of the inflammatory cells was determined in lung tissue by performing the histological analysis. The western blotting was used to examine the expression levels of the age-related FOXJ1, and p50 and p65 proteins in the lungs of MRL/Lpr mice. The expression levels of MMP2 and MMP9 were determined via immunohistochemistry and immunofluorescence. Results: There were severe infiltrates of lung cells with high levels of tracheal damage, perivascular injury and interstitial inflammatory cell infiltration when the MRL/Lpr mice from 16w to 32w comparing to the 8w old healthy MRL/Lpr mice in the control group (p

Dry eye is one of the most common chronic diseases in ophthalmology. It affects quality of life and has become a public health problem that cannot be ignored. The current treatment methods mainly include artificial tear replacement therapy, anti-inflammatory therapy, and local immunosuppressive therapy. These treatments are mainly limited to improvement of ocular surface discomfort and other symptoms. In recent years, regenerative medicine has developed rapidly, and ophthalmologists are working on new methods to treat dry eye. Mesenchymal stromal cells (MSCs) have anti-inflammatory, tissue repair, and immune regulatory effects, and have become a promising tool for the treatment of dry eye. These effects can also be produced by MSC-derived exosomes (MSC-Exos). As a cell-free therapy, MSC-Exos are hypoimmunogenic, serve more stable entities, and compared with MSCs, reduce the safety risks associated with the injection of live cells. This article reviews current knowledge about MSCs and MSC-Exos, and highlights the latest progress and future prospects of MSC-based therapy in dry eye treatment.

The brown planthopper (BPH) is a major pest in rice cultivation, significantly affecting both yield and quality; accordingly, exploring and utilizing anti-herbivory genes to enhance rice’s inherent resistance to BPH can be an effective strategy for mitigating infestation. The effects of transposon insertion polymorphisms (TIPs) on rice’s resistance to insect pests have not been reported. In this study, through the identification of transposon insertion sites in susceptible and resistant rice varieties, a total of six possible candidate insect resistance genes were potentially located. Among them, a segment of the LTR/Copia transposon insertion was verified in the promoter of LOC_Os04g02720, which carries a cis-acting element binding site in rice involved in the abscisic acid reaction. Quantitative analysis showed a significant difference of the gene expression between insect-resistant and insect-susceptible varieties (p < 0.05). This study provides insights into the functional analysis of transposons and population transposon polymorphisms, whereas the identification of candidate insect resistance genes offers a theoretical foundation for the development of insect-resistant rice varieties.

Graves’ disease (GD), an organ-specific autoimmune disease, is t he most common cause of hyperthyroidism. Tumour necrosis factor-alpha (TNF-α) exhibits immunological and metabolic activities involved in the induction and maintenance of immune responses. We attempted to evaluate the relationship between GD and serum TNF-α and its soluble receptors (sTNFRs), soluble TNF receptor 1 and 2 (sTNF-R1 and s TNF-R2). A total of 72 GD patients and 72 matched healthy individuals were recruited for this study. Serum TNF-α and sTNFRs were measured by sandwich ELISA. In our study, no s ignificant difference was observed in TNF-α, but sTNFRs were found to be significantly elevated in GD patients compared to healthy individuals. Serum sTNFR levels we re positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and TNF-α was negatively correlated with thyroid-stimulating hormone (TSH) in the GD gro up. It was also shown that thyrotropin receptor antibody (TRAb) was positively correlated with TNF-α and sTNFRs. Spearman’s correlation analysis showed that only sTNF-R1 was po sitively correlated with complement C3. Multiple linear regression analysis suggests tha t serum levels of sTNF-R1 and FT4 may play an important role in the serum level of FT3. A ccording to the median value of FT3 level, GD patients were further divided into a hig h FT3 group and a low FT3 group. The serum levels of sTNF-R1 in the high FT3 GD group wer e significantly higher than those in the low FT3 GD group. In conclusion, sTNFRs may play a n important role in anti-inflammatory and immune response in GD.

Abstract Backgound Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these remains unclear. Methods For this purpose, renal cancer-derived exosomes (RDEs) were first labeled with PKH67 and been observed the internalization by MDSCs. Flow cytometry analysis showed the proportion and activity change of MDSCs in spleen and bone marrow induced by RDEs. Further, western blot experiments were used to verify triggered mechanism of MDSCs by RDEs. Finally, proliferation and cytotoxicity of cytotoxic T lymphocytes (CTLs) co-cultured with MDSCs in vitro and a series of experiments in vivo were performed to demonstrate the specific inhibitory effect of RDEs-induced MDSCs. Results This study suggested that RDEs crucially contributed to presenting antigenic information, activating and driving specific immunosuppressive effect to MDSCs. HSP70, which is highly expressed in RDEs, initiate this process in a toll like receptor 2 (TLR2)-dependent manner. Importantly, RDEs-induced MDSCs could exert an antigen-specific immunosuppression effect on CTL and specific promote renal tumors-growth and immune escape in consequence. Conclusion The immunosuppression mediated by MDSCs which is induced by RDEs is antigen-specific. HSP70, which is highly expressed in RDEs, plays a pivotal role in this process. Targeted abrogating the function of MDSCs, or eliminating the expression of HSP70 in exosomes, or blocking the crosstalk between them provides a new direction and theoretical support for future immunotherapy. Video abstract Graphical abstract

ObjectivesHuman leucocyte antigen B27 (HLA-B27) is an important biomarker for ankylosing spondylitis (AS). However, delay in the diagnosis of AS is still common in clinical practice. Several single nucleotide polymorphisms (SNPs) in the coding gene of tumor necrosis factor alpha (TNFα) have been reported to be AS susceptibility loci. Our aim was to explore whether SNPs in TNFα could be used to improve the performance of HLA-B27 for predicting AS.MethodsFive SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) spanning TNFα were genotyped by qPCR-Invader assay in 93 AS patients and 107 healthy controls for association analysis and linkage disequilibrium (LD) analysis. Random forest algorithm was utilized to construct the predictive classifiers for AS. HLA-B was genotyped by PCR-sequence-based typing in a subset of the HLA-B27-positive subjects (38 AS patients and 5 healthy controls).ResultsThe T allele of rs1799724 was verified to significantly increase the risk of AS (OR = 4.583, p < 0.0001), while the A allele of rs361525 showed an association with the reduced AS risk (OR = 0.168, p = 0.009). In addition, the rs1799964T-rs1800630C-rs1799724T-rs1800629G-rs361525G haplotype was significantly associated with a higher risk of AS (p < 0.0001). The optimal set of variables for classifiers to predict AS only consisted of HLA-B27. Strong associations with HLA-B27 status were found in both rs1799724 (p < 0.0001) and rs361525 (p = 0.001), and all the analyzed HLA-B27-positive subjects carried HLA-B*27:04 or HLA-B*27:05.ConclusionIn the Chinese Han population, the minor allele T of rs1799724 could increase the risk of AS, while the minor allele A of rs361525 protects individuals from AS. However, the contributions of rs1799724 and rs361525 to AS risk were dependent on HLA-B27 status, suggesting the importance of taking the independence and specificity into consideration in AS susceptibility loci studies.

The 2b proteins encoded by cucumber mosaic virus (CMV) subgroup I strains suppress RNA silencing primarily by competitively binding small RNAs (sRNAs) in the host cell cytoplasm. Interestingly, 2b proteins encoded by CMV subgroup II strains accumulate predominantly in nuclei. Here we determined that whereas the 2b protein (Fny2b) of subgroup IA strain Fny-CMV is highly effective in suppressing both sense RNA-induced and inverted repeat-induced posttranscriptional gene silencing, the 2b protein (LS2b) of the subgroup II strain LS-CMV was not as effective. Reducing nuclear accumulation of LS2b by mutating a residue in its nuclear localization sequence had no effect on RNA silencing suppressor activity, while attenuated viral symptoms. Electrophoretic mobility shift assays showed that the sRNA binding of LS2b was weaker and more selective than that of Fny2b. The domain determining the differential sRNA-binding ability was delimited to the putative helix α1 region. Moreover, LS2b mutants that completely lost suppressor activity still retained their weak sRNA-binding ability, suggesting that sRNA binding is not sufficient for LS2b to suppress RNA silencing. Considering the subgroup I strain-encoded 2b proteins that require sRNA-binding ability for the suppression of RNA silencing, we suggest that in addition to binding sRNA, the 2b proteins of subgroup II CMV strains would require extra biological activities to achieve RNA silencing inhibition.

Abstract Background The basic helix–loop–helix (bHLH) is the second largest gene family in the plant, some members play important roles in pistil development and response to drought, waterlogging, cold stress and salt stress. The bHLH gene family has been identified in many species, except for Brassica oleracea and B. napus thus far. This study aims to identify the bHLH family members in B. oleracea, B. rapa and B. napus, and elucidate the expression, duplication, phylogeny and evolution characters of them. Result A total of 268 bHLH genes in B. oleracea, 440 genes in B. napus, and 251 genes in B. rapa, including 21 new bHLH members, have been identified. Subsequently, the analyses of the phylogenetic trees, conserved motifs and gene structures showed that the members in the same subfamily were highly conserved. Most Ka/Ks values of homologous gene were

Abstract Background Metabolic rewiring is a common feature of many cancer types, including prostate cancer (PCa). Alterations in master genes lead to mitochondrial metabolic rewiring and provide an appealing target to inhibit cancer progression and improve survival. Phospholipase C (PLC)ε is a regulator of tumor generation and progression. However, its role in mitochondrial metabolism remains unclear. Methods The GEO, The Cancer Genome Atlas, and the GTEx databases were used to determine Twist1 mRNA levels in tumors and their non-tumor counterparts. Fifty-five PCa and 48 benign prostatic hypertrophy tissue samples were tested for the presence of PLCε and Twist1 immunohistochemically. An association between PLCε and Twist1 was determined by Pearson’s correlation analysis. PLCε was knocked down with a lentiviral short hairpin RNA. Mitochondrial activity was assessed by measuring the oxygen consumption rate. Western blotting analyses were used to measure levels of PPARβ, Twist1, phosphorylated (p)-Twist1, p-MEK, p-ERK, p-P38, and p-c-Jun N-terminal kinase (JNK). Cells were treated with inhibitors of MEK, JNK, and P38 MAPK, and an agonist and inhibitor of peroxisome proliferator activated receptor (PPAR) β, to evaluate which signaling pathways were involved in PLCε-mediated Twist1 expression. The stability of Twist1 was determined after blocking protein synthesis with cycloheximide. Reporter assays utilized E-cadherin or N-cadherin luciferase reporters under depletion of PLCε or Twist1. Transwell assays assessed cell migration. Finally, a nude mouse tumor xenograft assay was conducted to verify the role of PLCε in tumor formation. Results Our findings revealed that the expression of PLCε was positively associated with Twist1 in clinical PCa samples. PLCε knockdown promoted mitochondrial oxidative metabolism in PCa cells. Mechanistically, PLCε increased phosphorylation of Twist1 and stabilized the Twist1 protein through MAPK signaling. The transcriptional activity of Twist1, and the Twist1-mediated epithelial-to-mesenchymal transition, cell migration, and transcription regulation, were suppressed by PLCε knockdown and by blocking PPARβ nuclear translocation. The tumor xenograft assay demonstrated that PLCε depletion diminished PCa cell tumorigenesis. Conclusions These findings reveal an undiscovered physiological role for PLCε in the suppression of mitochondrial oxidative metabolism that has significant implications for understanding PCa occurrence and migration.

The unique high/cold environment of the Qinghai–Tibet Plateau (QTP) limits the natural distribution of the population living there and threatens local residents’ health. Thus, exploring the quality of human settlements in this area is of great significance. In this study, 5 first-level indicators and 25 second-level indicators were initially selected, and the entropy TOPSIS method was used to determine the weight of each indicator and evaluate the quality of the human settlements in each county of the QTP. Then, the coefficient of variation and spatial autocorrelation were used to analyze the spatial differences in human settlement quality. Finally, the obstacle degree model was used to identify those obstacles that affect the quality of the human settlements in the QTP. This study has gathered important findings. (1) The human settlement quality in these counties can be divided into 18 high-level areas, 45 mid- and high-level areas, 44 mid-level areas, 79 mid- and low-level areas, and 28 low-level areas. (2) In terms of spatial patterns, the north is higher than the south, the east is slightly higher than the west, and the surrounding area is higher than the interior. (3) In the clustering model, the high–high clustering trend is mainly concentrated in the north of the QTP, whereas the south-central part of the QTP and the zone where Tibet, Qinghai, and Sichuan meet exhibit obvious low–low clustering. (4) The variability of human settlement quality occurs in the order of Sichuan < Yunnan < Gansu < Xinjiang Autonomous Region < Tibet Autonomous Region < Qinghai. (5) The main first-level obstacles affecting human settlement quality in the counties of the QTP are living conditions, construction level of public service facilities, and infrastructure. The main second-level obstacles are the number of living service facilities, the number of residential districts, and the density of the road networks.

Background: The relationship between fasting hyperglycemia (FHG) and new-onset atrial fibrillation (AF) in patients with acute myocardial infarction (AMI) is unclear, and whether their co-occurrence is associated with a worse in-hospital and long-term prognosis than FHG or AF alone is unknown.Objective: To explore the correlation between FHG and new-onset AF in patients with AMI, and their impact on in-hospital and long-term all-cause mortality.Methods: We performed a retrospective cohort study comprising 563 AMI patients. The patients were divided into the FHG group and the NFHG group. The incidence of new-onset AF during hospitalization was compared between the two groups and sub-groups under different Killip grades. Logistic regression was used to assess the association between FHG and new-onset AF. In-hospital mortality and long-term all-cause mortality were compared among patients with FHG, AF, and with both FHG and AF according to 10 years of follow-up information.Results: New-onset AF occurred more frequently in the FHG group than in the NFHG group (21.6 vs. 9.2%, p < 0.001). This trend was observed for Killip grade I (16.6 vs. 6.5%, p = 0.002) and Grade II (17.1 vs. 6.9%, p = 0.005), but not for Killip grade III–IV (40 vs. 33.3%, p = 0.761). Logistic regression showed FHG independently correlated with new-onset AF (OR, 2.56; 95% CI, 1.53–4.30; P < 0.001), and 1 mmol/L increased in fasting glucose was associated with a 5% higher rate of new-onset AF, after adjustment for traditional AF risk factors. AMI patients complicated with both fasting hyperglycemia and AF showed the highest in-hospital mortality and long-term all-cause mortality during an average of 11.2 years of follow-up. Multivariate Cox regression showed FHG combined with AF independently correlated with long-term all-cause mortality after adjustment for other traditional risk factors (OR = 3.13, 95% CI 1.64–5.96, p = 0.001), compared with the group with neither FHG nor new-onset AF.Conclusion: FHG was an independent risk factor for new-onset AF in patients with AMI. AMI patients complicated with both FHG and new-onset AF showed worse in-hospital and long-term all-cause mortality than with FHG or AF alone.

Magnolol, an essential bioactive natural lignans isolated from Magnolia Officinalis, has various pharmacological activities, such as antibacterial, anti-inflammatory, antioxidation and anti-tumor. In this study, a practical strategy based on ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was established to reveal the metabolic fate of magnolol in rat plasma and urine. First of all, in the data-dependent scanning (DDS) acquisition mode, the ESI-MSn data sets of biological samples and reference standard were obtained by using a high-quality online data analysis method. Subsequently, off-line data-mining techniques including multiple mass defect filters (MMDFs) and high-resolution extracted ion chromatograms (HREICs) were applied to screen major-to-trace metabolites of magnolol at the full-scan ESI-MS1 level. Finally, a total of 177 metabolites (prototype compound included) were preliminarily observed and characterized according to accurate mass measurement, the characteristic fragmentation patterns, chromato-graphic behaviors, and corresponding Clog P values. The results showed that magnolol experienced a variety of biotransformation reactions in rats, including hydroxylation, methoxylation, dehydrogenation, carboxylation, sulfonation, glucuronide conjugation, glucose conjugation, N-acetylcysteine (NAC) conjugation, glutathione conjugation and their composite reactions. In conclusion, this study not only greatly expanded the understanding of the therapeutic material basis and pharmacological mechanism of magnolol, but also provided new ideas for its toxicity evaluation, safety monitoring and drug delivery forms design.

Pydiflumetofen is a novel and efficient broad-spectrum chiral fungicide consisting of a pair of enantiomers. A simple and sensitive chiral analytical method was established to determine the enantiomers of this chiral fungicide in food and environmental samples by ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) using QuEChERS method coupled with octadecylsilane-dispersive solid-phase extraction (C18-dSPE) as extraction procedure. The specific optical rotation and the absolute configuration of the enantiomers were identified by polarimetry and electronic circular dichroism (ECD). The elution order of the pydiflumetofen enantiomers on Lux Cellulose-2 was S-(−)-pydiflumetofen and R-(+)-pydiflumetofen. The average recoveries of eleven matrices ranged from 71.3% to 107.4%. The intraday relative standard deviations (RSDs) were less than 11.8%, and the interday RSDs were less than 12.6% for the two enantiomers. Stereoselective dissipation in pakchoi and soil were observed: S-(−)-pydiflumetofen was degraded faster than R-(+)-pydiflumetofen in pakchoi, causing the enantiomer fraction (EF) of the enantiomers to change from 0.50 to 0.42 in 7 days. However, R-(+)-pydiflumetofen was degraded faster than S-(−)-pydiflumetofen in soil, causing the EF of the enantiomers to change from 0.49 to 0.52 in 21 days. This study provides a method for monitoring pydiflumetofen enantiomer residues, which is crucial for improving risk assessments and the development of chiral pesticides.

A novel material named Fe/Mn-C layered double hydroxide composite (Fe/Mn-C-LDH) was synthesized to remove arsenic from an aqueous solution. The removal performance of the composite toward arsenic ions was studied through the batch experiments. The experiment results showed that Fe/Mn-C-LDH exhibited a high adsorption capacity of 46.47 mg/g for As(III) and 37.84 mg/g for As(V) at 318 K, respectively. In addition, the investigation of the release of Fe3+ and Mn2+ in the process of arsenic adsorption revealed that the Fe/Mn-C-LDH exhibited better stability than Fe/Mn-layer double hydroxide (Fe/Mn-LDH) with fewer Mn2+ and Fe3+ releasing under the same condition. The BET results showed that the specific surface area of Fe/Mn-C-LDH decreased after adsorption of As (III) and As (V). Furthermore, the Density Functional Theory (DFT) calculation results proved that the adsorbent combining arsenic by T-site to produce a better adsorption effect for arsenic. Possessing better stability and adsorption capacity, Fe/Mn-C-LDH could potentially serve as a perfect adsorbent for arsenic removal from an aqueous environment. It would provide a promising approach for removing heavy metal from the aquatic environment in the future.

Abstract Background Cytokinin is a classical phytohormone that plays important roles in numerous plant growth and development processes. In plants, cytokinin signals are transduced by a two-component system, which involves many genes, including cytokinin response factors (CRFs). Although CRFs take vital part in the growth of Arabidopsis thaliana and Solanum lycopersicum, little information of the CRFs in the Brassica U-triangle species has been known yet. Results We identified and compared 141 CRFs in the diploids and amphidiploids of Brassica species, including B. rapa, B. oleracea, B. nigra, B. napus, and B. juncea. For all the 141 CRFs, the sequence and structure analysis, physiological and biochemical characteristics analysis were performed. Meanwhile, the Ka/Ks ratios of orthologous and paralogous gene pairs were calculated, which indicated the natural selective pressure upon the overall length or a certain part of the CRFs. The expression profiles of CRFs in different tissues and under various stresses were analyzed in B. oleracea, B. nigra, and B. napus. The similarities and differences in gene sequences and expression profiles among the homologous genes of these species were discussed. In addition, AtCRF11 and its ortholog BrCRF11a were identified to be related to primary root growth in Arabidopsis. Conclusion This study performed a genome-wide comparative analysis of the CRFs in the diploids and amphidiploids of the Brassica U-triangle species. Many similarities and differences in gene sequences and expression profiles existed among the CRF homologous genes of these species. In the bioinformatics analysis, we found the close relativity of the CRF homologous genes in the Brassica A and C genomes and the distinctiveness of those in the B genome, and the CRF homologous genes in B subgenome were considerably influenced by the A subgenome of B. juncea. In addition, we identified a new function of the Clade V CRFs related to root growth, which also clarified the functional conservation between Arabidopsis and B. rapa. These results not only offer useful information on the functional analysis of CRFs but also provide new insights into the evolution of Brassica species.

Turnip, one of the oldest groups of cultivated Brassica rapa species, is a traditional crop as well as a form of animal fodder, a vegetable, and a herbal medicine that is widely cultivated in farming and farming-pastoral regions in Tibet. Different regions of the Qinghai–Tibet Plateau (QTP) are home to a rich diversity of turnip owing to their high altitudes and variable climate types. However, information on the morphology and genetic diversity of Tibetan turnip remains limited. Therefore, the genetic diversity of 171 turnip varieties from China and elsewhere (Japan, Korea, and Europe) was analyzed using 58 morphological characteristics and 31 simple sequence repeat (SSR) markers in this study. The varieties showed that the genetic distance ranged from 0.12 to 1.00, and the genetic similarity coefficient ranged between 0.73 and 0.95. Cluster tree showed two distinct clusters. Both morphotype and geography contributed to the group classification. A combination of morphological traits and molecular markers could refine the precision of accurate identification compared to the separate morphological and molecular data analyses. The sampling ratio of 15% to utmost precisely represent the initial population was compared to ratios of 10% and 20%, and the sampling ratio of 15% is recommended for future works when a primary core collection of turnip resources is constructed. These results could furnish a foundation for germplasm conservation and effective turnip breeding in future studies.

Background/Aims: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide because the survival rate remains low. Cell division cycle 5-like (CDC5L) is highly expressed in some cancer cells, but the mechanism requires clarification. Human telomerase reverse transcriptase (hTERT) plays important roles in CRC. Methods: This study aimed to identify a link between CDC5L and hTERT and to determine their effects on the signaling pathways, migration and prognosis of CRC cells. We first treated LoVo cells with biotin-labeled hTERT and identified CDC5L. Then, pulldown and ChIP assays were used to verify whether CDC5L was a promoter of hTERT. The roles of CDC5L and hTERT in cell growth and migration were studied using siRNA in vivo and in vitro. 130 human CRC specimens were analyzed using immunohistochemistry. Western blot and wound scratch analyses were used to determine the signaling pathway for CDC5L-mediated activation of CRC growth and migration. Results: We identified CDC5L as a new hTERT promoter-binding protein. Clinically, CDC5L and hTERT expression levels were key factors in the prognosis of CRC patients. CDC5L knockdown inhibited tumor growth by down-regulating hTERT expression, and CDC5L was shown to be a transcriptional activator of hTERT in a luciferase reporter assay. Conclusion: Altogether, the above results demonstrated that CDC5L was positively correlated with hTERT as a key promoter of CRC cells. To some extent, our findings suggest that CDC5L may serve as a novel therapeutic target for human colorectal cancer.

Castration-resistant prostate cancer (CRPC) is a progressed stage of prostate cancer, which requires better understanding of the mechanisms and remains an unmet clinical need. As a common oncogene, K-Ras is associated with malignant behavior in different types of tumors but its role in CRPC is unknown. The present study aims to find the mechanism of K-Ras in CRPC and whether it can be used as a crucial molecule for the treatment of CRPC. For this purpose, tissue samples from primary prostate cancer (PPC) and CRPC patients were analyzed by immunohistochemistry and the data showed that K-Ras was elevated in CRPC. More importantly, higher K-Ras expression was related to a shorter recurrence-free survival time in patients with CRPC. In addition, K-Ras promoted the invasion, migration, and drug resistance of CRPC cells by activation of PLCε/PKCε signaling pathway. Meanwhile, the inhibitor of K-RasG12C mutants was able to inhibit malignant behavior of CRPC cells in vitro and in vivo. Inhibitors of K-RasG12C mutants have entered clinical trials. Taken together, the study shows that K-Ras may activate PKCε through PLCε, resulting in the alterations of malignant behavior of CRPC. Inhibitor 9, an inhibitor of the K-RasG12C mutant, has a strong anti-tumor effect in CRPC, which potentially suggests that inhibitors of this nature may serve as a promising treatment for CRPC.

Background/Aims: Bufalin can induce apoptosis in certain human cancer cell lines, but bufalin has not yet been thoroughly evaluated in colorectal cancer cells. Cleavage and polyadenylation specific factor 4 (CPSF4) and human telomerase reverse transcriptase (hTERT) play important roles in colorectal cancer growth. The aim of this study was to investigate the roles and interactions of bufalin, CPSF4 and hTERT and the effects of bufalin in human colorectal cancer. Methods: We treated LoVo and SW620 cells with bufalin to investigate the effect of bufalin on proliferation, apoptosis and migration. We verified the relationship between CPSF4 and hTERT using pulldown assays, luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. Results: Bufalin inhibited the proliferation and migration of and induced apoptosis in LoVo and SW620 cells. We identified CPSF4 as an hTERT promoter-binding protein in colorectal cancer cells. Conclusion: Our study identified bufalin as a potential small molecule inhibitor for cancer therapy.

Potentiometric plasticizer-free solid-contact Pb2+-selective electrodes based on copolymer methyl methacrylate-n-butyl acrylate (MMA-BA) as membrane matrix and multi-walled carbon nanotubes (MWCNTs) as intermediate ion-to-electron transducing layer have been developed. The disposable electrodes were prepared by drop-casting the copolymer membrane onto a layer of MWCNTs, which deposited on golden disk electrodes. The obtained electrodes exhibited a sub-ppb level detection limit of 10−10 mol·L−1. The proposed electrodes demonstrated a Nernstian slope of 29.1 ± 0.5 mV/decade in the linear range from 2.0 × 10−10 to 1.5 × 10−3 mol·L−1. No interference from gases (O2 and CO2) or water films was observed. The electrochemical impedance spectroscopy of the fabricated electrodes was compared to that of plasticizer-free Pb2+-selective electrodes without MWCNTs as intermediated layers. The plasticizer-free MWCNTs-based Pb2+-selective electrodes can provide a promising platform for Pb(II) detection in environmental and clinical application.