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Abstract Background To investigate changes in pulmonary artery pressure (PAP), blood indices, and myocardial microcirculation in rats returning from high altitude (HA) to moderate altitude (MA). Methods Forty 4-week-old male Sprague-Dawley rats were randomly divided into four groups with ten rats in each group. One group was transported to the MA area (MA-group), and the other three groups were transported to HA (HA-group-A, HA-group-B, and HA-group-C). After 28 weeks of age, the rats from the HA area were transported to the MA area for 0 days, 10 days, and 20 days, respectively. PAP, routine blood tests, and computed tomography myocardial perfusion indices were measured. Results Compared with the MA-group, the body weight of HA-groups decreased (p

Abstract Background Plants have evolved various defense mechanisms against insect herbivores, including the formation of physical barriers, the synthesis of toxic metabolites, and the activation of phytohormone responses. Although plant-associated microbiota influence plant growth and health, whether they play a role in plant defense against insect pests in natural ecosystems is unknown. Results Here, we show that leaves of beetle-damaged weeping willow (Salix babylonica) trees are more resistant to the leaf beetle Plagiodera versicolora (Coleoptera) than those of undamaged leaves. Bacterial community transplantation experiments demonstrated that plant-associated microbiota from the beetle-damaged willow contribute to the resistance of the beetle-damaged willow to P. versicolora. Analysis of the composition and abundance of the microbiome revealed that Pseudomonas spp. is significantly enriched in the phyllosphere, roots, and rhizosphere soil of beetle-damaged willows relative to undamaged willows. From a total of 49 Pseudomonas strains isolated from willows and rhizosphere soil, we identified seven novel Pseudomonas strains that are toxic to P. versicolora. Moreover, re-inoculation of a synthetic microbial community (SynCom) with these Pseudomonas strains enhances willow resistance to P. versicolora. Conclusions Collectively, our data reveal that willows can exploit specific entomopathogenic bacteria to enhance defense against P. versicolora, suggesting that there is a complex interplay among plants, insects, and plant-associated microbiota in natural ecosystems. Graphical Abstract Video Abstract

Abstract Morocco is a multilingual country with a diverse culture. When it participated in the Program for International Student Assessment (PISA) for the first time, its reading literacy scores ranked relatively low in the test. Employing hierarchical linear modeling (HLM), the present study examined the effects of both student- and school-level factors on students’ reading literacy in Morocco. Student-level (N = 5800) and school-level (N = 179) data were drawn from the PISA 2018. The results showed that students’ reading literacy differed significantly across schools, accounting for about 40.5% of the overall variation. Further, the results showed that at the student level, when the variables of gender and family indices (i.e., economic, social, and cultural status) were controlled, language spoken at home, understanding and remembering of meta-cognition, self-concept of reading, expected occupational status, adaptation to instruction, teacher support in test language lessons, and duration in early childhood education and care all had significant effects on students’ reading literacy. At the school level, school location, school type, school size, shortage of educational material, and proportion of highly educated teachers had a crucial influence on student reading literacy, either directly or indirectly. To date, the reasons for these effects have not been systematically investigated. Morocco was the only African country to take part in the PISA test and it would be worthwhile to explore the factors affecting reading literacy in this low-performing country. Further, the results may be applicable to some extent to low reading performance in other countries.

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas have been recognized as powerful genome-editing tools in diverse eukaryotic species, including plants, and thus hold great promise for engineering virus resistance in plants. Nevertheless, further attention is required regarding various issues associated with applying new powerful technologies in the field. This mini-review focuses on the recent advances in using CRISPR/Cas9 and CRISPR/Cas13 systems to combat DNA and RNA viruses in plants. We explored the utility of CRISPR/Cas for targeting the viral genome and editing host susceptibility genes in plants. We also provide insights into the limitations and challenges of using CRISPR/Cas for plant virus interference and propose individual combinatorial solutions. In conclusion, CRISPR/Cas technology has the potential to offer innovative and highly efficient approaches for controlling viruses in important crops in the near future.

The combined complexity of wind turbine systems and harsh operating conditions pose significant challenges to the accuracy of operational data in Supervisory Control and Data Acquisition (SCADA) systems. Improving the precision of data cleaning for high proportions of stacked abnormalities remains an urgent problem. This paper deeply analyzes the distribution characteristics of abnormal data and proposes a novel method for abnormal data cleaning based on a classification processing framework. Firstly, the first type of abnormal data is cleaned based on operational criteria; secondly, the quartile method is used to eliminate sparse abnormal data to obtain a clearer boundary line; on this basis, the Random Sample Consensus (RANSAC) algorithm is employed to eliminate stacked abnormal data; finally, the effectiveness of the proposed algorithm in cleaning abnormal data with a high proportion of stacked abnormalities is verified through case studies, and evaluation indicators are introduced through comparative experiments to quantitatively assess the cleaning effect. The research results indicate that the algorithm excels in cleaning effectiveness, efficiency, accuracy, and rationality of data deletion. The cleaning accuracy improvement is particularly significant when dealing with a high proportion of stacked anomaly data, thereby bringing significant value to wind power applications such as wind power prediction, condition assessment, and fault detection.

An induced pluripotent stem cell (iPSC) line (SDUCHi001-A) was established using peripheral blood mononuclear cells (PBMCs) from a healthy 6 years old boy. Reprogramming of the PBMCs was achieved through non-integrating delivery of OCT4, SOX2, KFL4, BCL-XL, and c-MYC. The iPSC line expressed pluripotency markers, had a normal karyotype and trilineage differentiation potential.

This study enhances the understanding of the evolution of water transport in karst water flow systems. This paper explores the karst water flow system from a hydrogeochemical perspective. It has been discovered that in the recharge area, the hydrochemical effect of karst water is primarily influenced by dissolution and filtration. In the fault zone and concentrated discharge area, it is primarily influenced by mixing. In the geothermal area, the dominant factors are dissolution, precipitation, and dolomitization. From the southern to the northern area, the hydrochemical type of karst water gradually changes from HCO3-Ca type to SO4·Cl-Ca·Na type. Atmospheric precipitation is the primary recharge source of karst water, with a recharge elevation range of 181–1,495 m. According to geological drilling statistics, the groundwater transport depth transits from the shallow transport in the south to the deep transport in the north, with a depth range of 3,000–3,500 m, and using isotope data to obtain the groundwater retention time range is 6–27,000 years. The groundwater transport mode is divided into three levels: open-shallow transport karst cold water phreatic flow, semi-open-medium-deep transport karst cold water confined flow, and weak open-deep transport geothermal water confined water flow. HIGHLIGHTS This study has revealed the hydrochemical evolution and transport patterns of karst water in the Jinan spring area.; The transport mode of the karst water flow system in the monoclinic structure of the Jinan spring area has been classified.;

Abstract CRISPR-Cas systems endow the bacterial and archaeal species with adaptive immune mechanisms to fend off invading phages and foreign plasmids. The class 2 type VI CRISPR/Cas effector Cas13d has been harnessed to confer the protection against RNA viruses in diverse eukaryotic species. However a vast number of different viruses can potentially infect the same host plant resulting in mixed infection, thus necessitating the generation of crops with broad-spectrum resistance to multiple viruses. Here we report the repurposing of CRISPR/Cas13d coupled with an endogenous tRNA-processing system (polycistronic tRNA-gRNA, PTG) to target the multiple potato RNA viruses. Expression of Cas13d and four different gRNAs were observed in transgenic potato lines expressing the Cas13d/PTG construct. We show that the Cas13d/PTG transgenic plants exhibit resistance to either PVY, PVS, PVX or PLRV alone or two/three viruses simultaneously by reducing viral accumulation in plant cells. In sum, our findings provide an efficient strategy for engineering crops that can simultaneously resist infection by multiple RNA viruses.

High-altitude areas are characterized by low pressure and hypoxia, which have a significant impact on various body systems. This study aimed to investigate the alterations in cardiac index and right ventricular hypertrophy index(RVHI) in rats at different altitudes.Twenty-one male Sprague-Dawley (SD) rats aged 4 weeks were randomly divided into three groups based on altitude. The rats were raised for 28 weeks and then transferred to Qinghai University Plateau Medicine Laboratory. Body weight was measured, heart organs were isolated and weighed, and cardiac index and right ventricular hypertrophy index were determined. Statistical analysis was performed on the data from the three groups. Compared with the plain group, the body weight of the middle-altitude group was significantly decreased (P

Background Recently, with the rapid development of the perinatal medical system and related life-saving techniques, both the short-term and long-term prognoses of extremely preterm infants (EPIs) have improved significantly. In rapidly industrialising countries like China, the survival rates of EPIs have notably increased due to the swift socioeconomic development. However, there is still a reasonably lower positive response towards the treatment of EPIs than we expected, and the current situation of withdrawing care is an urgent task for perinatal medical practitioners.Objective To develop and validate a model that is practicable for EPIs as soon as possible after birth by regression analysis, to assess the risk of mortality and chance of survival.Methods This multicentre prospective cohort study used datasets from the Sino-Northern Neonatal Network, including 46 neonatal intensive care units (NICUs). Risk factors including maternal and neonatal variables were collected within 1 hour post-childbirth. The training set consisted of data from 41 NICUs located within the Shandong Province of China, while the validation set included data from 5 NICUs outside Shandong Province. A total of 1363 neonates were included in the study.Results Gestational age, birth weight, pH and lactic acid in blood gas analysis within the first hour of birth, moderate-to-severe hypothermia on admission and adequate antenatal corticosteroids were influencing factors for EPIs’ mortality with important predictive ability. The area under the curve values for internal validation of our prediction model and Clinical Risk Index for Babies-II scores were 0.81 and 0.76, and for external validation, 0.80 and 0.51, respectively. Moreover, the Hosmer-Lemeshow test showed that our model has a constant degree of calibration.Conclusions There was good predictive accuracy for mortality of EPIs based on influencing factors prenatally and within 1 hour after delivery. Predicting the risk of mortality of EPIs as soon as possible after birth can effectively guide parents to be proactive in treating more EPIs with life-saving value.Trial registration number ChiCTR1900025234.

Due to the influences of geological structures, many confined ascending springs occur in North China's karst area. The electrical conductivity (EC) of karst spring flow is a fundamental variable in characterizing karst systems. However, deeply exploring hidden nonlinear dynamic characteristics is challenging. To avoid overreliance on the fitting polynomial order in the detrending process via classic multifractal detrended fluctuation analysis (MFDFA), the intrinsic time-scale decomposition (ITD) method was applied to identify the external data trend term by decomposing the original data into different frequency modes, and the ITD-MFFA method was proposed to reveal the formation mechanism of spring EC complex characteristics in Jinan's spring area. The results showed that the EC sequences of North China's karst springs are characterized by multifractal behavior and anti-persistence and exhibit multiyear complexity with an overall decreasing trend. Different recharge sources, formation conditions, and seasonal precipitation could be the primary factors driving spring EC complexity. Compared to those of the traditional MFDFA method, the ITD-MFFA method achieved improved anti-interference ability and stability. Timely determination of spring EC data dynamic complexity and monitoring future spring water quality trends can provide guiding significance for protecting karst springs. HIGHLIGHTS Compared with the MFDFA method, the proposed new approach (ITD–MFFA) improves anti-interference ability and stability.; Multifractal fluctuation feature in karst springs’ electrical conductivity data is found.; The complexity of springs' electrical conductivity is not only affected by many factors but also significantly higher in the dry season than in the wet season.;

Anoplophora glabripennis (Coleoptera: Cerambycidae: Lamiinae) is an invasive wood borer pest that has caused considerable damage to forests. Gut bacteria are of great importance in the biology and ecology of herbivores, especially in growth and adaptation; however, change in the gut bacterial community of this pest feeding on different hosts is largely unknown. In this study, we investigated the gut bacterial communities of A. glabripennis larvae fed on different preferred hosts, Salix matsudana and Ulmus pumila, using 16S rDNA high-throughput sequencing technology. A total of 15 phyla, 25 classes, 65 orders, 114 families, 188 genera, and 170 species were annotated in the gut of A. glabripennis larvae fed on S. matsudana or U. pumila using a 97% similarity cutoff level. The dominant phyla were Firmicutes and Proteobacteria and the core dominant genera were Enterococcus, Gibbsiella, Citrobacter, Enterobacter, and Klebsiella. There was significantly higher alpha diversity in the U. pumila group than in the S. matsudana group, and principal co-ordinate analysis showed significant differences in gut bacterial communities between the two groups. The genera with significant abundance differences between the two groups were Gibbsiella, Enterobacter, Leuconostoc, Rhodobacter, TM7a, norank, Rhodobacter, and Aurantisolimonas, indicating that the abundance of larval gut bacteria was affected by feeding on different hosts. Further network diagrams showed that the complexity of the network structure and the modularity were higher in the U. pumila group than in the S. matsudana group, suggesting more diverse gut bacteria in the U. pumila group. The dominant role of most gut microbiota was related to fermentation and chemoheterotrophy, and specific OTUs positively correlated with different functions were reported. Our study provides an essential resource for the gut bacteria functional study of A. glabripennis associated with host diet.

The total viable count (TVC) of bacteria is an important index to evaluate the freshness and safety of dishes. To improve the accuracy and robustness of spectroscopic detection of total viable bacteria count in a complex system, a new method based on a near-infrared (NIR) hyperspectral hybrid model and Support Vector Machine (SVM) algorithms was developed to directly determine the total viable count in intact beef dish samples in this study. Diffuse reflectance data of intact and crushed samples were tested by NIR hyperspectral and processed using Multiplicative Scattering Correction (MSC) and Competitive Adaptive Reweighted Sampling (CARS). Kennard–Stone (KS) and Samples Set Partitioning Based on Joint X-Y Distance (SPXY) algorithms were used to select the optimal number of standard samples transferred by the model combined with root mean square error. The crushed samples were transferred into the complete samples prediction model through the Direct Standardization (DS) algorithm. The spectral hybrid model of crushed samples and full samples was established. The results showed that the Determination Coefficient of Calibration (RP2) value of the total samples prediction set increased from 0.5088 to 0.8068, and the value of the Root Mean Square Error of Prediction (RMSEP) decreased from 0.2454 to 0.1691 log10 CFU/g. After establishing the hybrid model, the RMSEP value decreased by 9.23% more than before, and the values of Relative Percent Deviation (RPD) and Reaction Error Relation (RER) increased by 12.12% and 10.09, respectively. The results of this study showed that TVC instewed beef samples can be non-destructively determined based on the DS model transfer method combined with the hybrid model strategy. This study provided a reference for solving the problem of poor accuracy and reliability of prediction models in heterogeneous samples.

ABSTRACT The rhizosphere of invasive plants presumably develops different soil microbial assemblages compared with native plants, which may hinder or promote their invasion. However, to date, no studies have clearly explored rhizosphere microbial community assemblages during invasion. The invasive species Ambrosia artemisiifolia L. and Bidens pilosa L. are widely distributed in China and are known to reduce local biodiversity and cause agricultural losses. Monoculture of A. artemisiifolia or B. pilosa, a mixture of each invasive and native species, and monoculture of native species were established to simulate different degrees of invasion. Metagenomic sequencing techniques were used to test microbial community structure and function. The aim was to explore the drivers of the assembly of peculiar functional microbes in the rhizosphere soil of invasive species during the long-term invasive-native species interaction. Compared with the native species, the relative abundance of 34 microbial genera was higher in the rhizosphere soil of the invasive species. The NO3-N concentration in the rhizosphere soil from the A. artemisiifolia and B. pilosa monocultures was lower than that from monocultures of the three native plants, whereas pH followed the opposite trend. The NO3-N concentration was significantly and negatively correlated with Sporichthya, Afipia, Actinokineospora, and Pseudolabrys. pH was positively correlated with Bradyrhizobium, Actinoplanes, Micromonospora, Steroidobacter, Burkholderia, and Labilithrix. The differences in soil microbes, NO3-N concentrations, and pH between native and invasive species suggest that the rhizosphere soil microbial assemblages may vary. The reduced NO3-N concentration and increased pH corelated with changes in rhizosphere microbial community during A. artemisiifolia and B. pilosa invasion. IMPORTANCE Soil microbial communities play a vital role in the growth of invasive plants. Invasive species may shape peculiar functional microbes in the rhizosphere soil of an invasive species to benefit its growth. However, the drivers of the assembly of soil microbial communities in the rhizosphere soil of invasive species remain unclear. Our study established the relationship between soil microbial communities and soil chemical properties during invasion by A. artemisiifolia and B. pilosa. Additionally, it showed that the presence of the invasive plants correlated with changes in NO3-N and pH, as well as in rhizosphere microbial community assemblage. Furthermore, the study provided important insights into the difference in the microbial community assembly between native and invasive plant species.

Bacillus can help plants to acquire nutrients either directly or indirectly. However, the role of Bacillus community on the competitive growth of invasive Ambrosia artemisiifolia is poorly understood. Native Setaria viridis is often found in areas that have been invaded by A. artemisiifolia. We sought to determine whether the quantitative and/or qualitative differences in the Bacillus community present on the invasive A. artemisiifolia and native S.viridis provide a competitive advantage to the invasive over native species. A field experiment was established to imitate the invasion of A. artemisiifolia. The 16S rRNA gene was commercially sequenced to identify the bacilli isolated from the rhizosphere soil of field-grown A. artemisiifolia and S. viridis. The Bacillus communities in their rhizosphere were compared, and their effects on the competitive growth of A. artemisiifolia and S. viridis were tested in the pot experiments. Bacillus in the rhizosphere soil of A. artemisiifolia significantly enhanced its intra-specific competitive ability. The relative abundance of B. megaterium in the rhizosphere soil of A. artemisiifolia was significantly higher than that of S. viridis. Inoculation with B. megaterium that was isolated from the rhizosphere soil of both A. artemisiifolia and S. viridis significantly enhanced the relative competitiveness of A. artemisiifolia and inhibited that of S. viridis. The higher abundance of B. megaterium in the rhizosphere of A. artemisiifolia creates higher levels of available nutrients than that in the native S. viridis, which enhance the competitive growth of A. artemisiifolia. The result helps to discover the mechanism of Bacillus community in the invasion of A. artemisiifolia.

To determine the allelopathic effects of root exudates from Flaveria bidentis on function of Bacillus, pot experiment was used to collect root exudates from living plants and test its allelopathic effects on function of Bacillus frigoritolerans and Bacillus megaterium, which were two dominant bacteria in the rhizosphere soil of F. bidentis. To obtain the allelopathic substances, the root exudates were successively extracted by N-hexane, dichloromethane, ethyl acetate, and N-butanol, and their allelopathic effects were tested. The results showed that B. frigoritolerans and B. megaterium considerably increased the concentration of available phosphorus and nitrogen, respectively, when the soil was treated with different concentrations of root exudates. Among the four organic solvent extracts, dichloromethane extracts significantly increased the abundances of B. frigoritolerans and B. megaterium and promoted their nitrogen-fixing and phosphate-solubilizing abilities. Phenol was detected in dichloromethane extracts by gas chromatograph-mass spectrometer (GC-MS). Meanwhile, phenol promoted the ability to fix nitrogen of B. megaterium and its growth by increasing the soil available nitrogen concentration, but phenol promoted the ability to solubilize phosphate of B. frigoritolerans only in 0.1mg/mL concentration. Therefore, phenol was an allelochemicals in the root exudates of F. bidentis that affects the growth and activities of B. megaterium.

The invasive weed Ageratina adenophora can form a positive symbiotic relationship with native arbuscular mycorrhizal fungi (AMF) to promote its invasion ability. However, the function of AMF during the feeding of Aphis gossypii in A. adenophora was poorly understand. This study aimed to investigate the effects of two dominant AMF (Claroideoglomus etunicatum and Septoglomus constrictum) on A. adenophora in response to the feeding of the generalist herbivore A. gossypii. The results showed that A. gossypii infestation could significantly reduce the biomass, nutrient and proline contents of A. adenophora, and increase the antioxidant enzyme activities, defense hormone and secondary metabolite contents of the weed. Compared with the A. gossypii infested A. adenophora, inoculation C. etunicatum and S. constrictum could significantly promote the growth ability and enhanced the resistance of A. adenophora to A. gossypii infestation, and the aboveground biomass of A. adenophora increased by 317.21% and 114.73%, the root biomass increased by 347.33% and 120.58%, the polyphenol oxidase activity heightened by 57.85% and 12.62%, the jasmonic acid content raised by 13.49% and 4.92%, the flavonoid content increased by 27.29% and 11.92%, respectively. The survival rate of A. gossypii and density of nymphs were significantly inhibited by AMF inoculation, and the effect of C. etunicatum was significantly greater than that of S. constrictum. This study provides clarified evidence that AMF in the rhizosphere of A. adenophora are effective in the development of tolerance and chemical defense under the feeding pressure of insect herbivory, and offer references for the management of the A. adenophora from the perspective of soil microorganisms.

This study traced changes in Chinese college English teachers’ professional identities as a result of participating in international professional development programs and examined how the teachers negotiated their professional identities upon return to China. Five college English teachers with at least 10 months of overseas professional development experience took part in the study. Data were collected through semi-structured interviews and relevant documents. It was found that international experiences had a great impact on the teachers’ professional identity construction by empowering them to develop multiple identities as language teaching professionals, university academics, and change agents. The teachers’ reconstruction of professional identities upon return to China was not a linear and smooth process. It was a dynamic process of negotiating with the constraints of the personal and professional contexts to which the teachers returned. The study sheds light on the identity development of internationally trained language teachers and contributes to a deeper understanding of the impact of international experiences on the professional development of second language teachers in similar contexts. It has implications for study abroad programs and for home institutions about how to support the long-term professional development of returnee teachers.

ABSTRACT Objective: To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers. Materials and methods: This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m2 and T2DM. Beinaglutide was administered for three months. Changes in body weight, fasting plasma glucose (FPG) level, 2 h postprandial plasma glucose (2h-PG) level, glycosylated hemoglobin (HbA1c) level, BMI and visceral and subcutaneous fat areas were measured at baseline and after three months of treatment. In addition, relevant inflammation/obesity cytokines and biomarkers were measured. Results: After three months, beinaglutide treatment led to significant changes, including in body weight, BMI, FPG level, HbA1c level, visceral and subcutaneous fat areas. In addition, serpin E1, leptin, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) also decreased significantly. The plasma protein concentrations of CRP (Log2 transformed) were found to be positively correlated with the percentage of weight loss (R = 0.514 and p-value = 0.021). Conclusion: Beinaglutide treatment resulted in weight loss, plasma glucose control and anti-inflammatory effects in patients with T2DM and overweight/obesity.

Abstract The molecules of programmed cell death protein‐1 (PD‐1) and ligand‐1 (PD‐L1) become new therapeutic targets for cancer therapy. Although tumor‐expressed PD‐L1 molecule is frequently dispensable for checkpoint blockade in some cancer patients, recent studies suggest that T cell‐expressed PD‐L1 molecule might play a crucial role in antitumor immunity. Here, to investigate CD22 chimeric antigen receptor (CAR)‐T cell therapy, we have generated the different CD22 CAR‐T constructs. We noticed that tumor cells induced PD‐L1 expression on the surface of CD22 CAR‐T cells. The induced PD‐L1 might limit immunogenic responses of CAR‐T cells. T cell‐expressed PD‐L1 leads to a suppressive signal by PD‐1/PD‐L1 engagement of CD22 CAR‐T cells. Meanwhile, PD‐L1 suppresses CD22 CAR‐T cell differentiation into memory T cells and negatively affected secretions of several essential cytokines, such as interleukin‐2 (IL‐2) and tumor necrosis factor (TNF)‐α. We further observed that anti‐PD‐L1 monoclonal antibodies rescued cytokine secretion of CD22 CAR‐T cells rather than anti‐PD‐1 monoclonal antibodies. Our current studies provide a potential mechanism to understand the functions and roles of T cell‐expressed PD‐L1 in tumor microenvironment. These results will encourage the physicians to re‐recognize the important roles of PD‐L1 in cancer immunotherapy studies and provide the helpful guidance for clinical operation of PD‐L1 inhibition drugs.

Abstract Background B7-H3, an immune-checkpoint molecule and a transmembrane protein, is overexpressed in non-small cell lung cancer (NSCLC), making it an attractive therapeutic target. Here, we aimed to systematically evaluate the value of B7-H3 as a target in NSCLC via T cells expressing B7-H3-specific chimeric antigen receptors (CARs) and bispecific killer cell engager (BiKE)-redirected natural killer (NK) cells. Methods We generated B7-H3 CAR and B7-H3/CD16 BiKE derived from an anti-B7-H3 antibody omburtamab that has been shown to preferentially bind tumor tissues and has been safely used in humans in early-phase clinical trials. Antitumor efficacy and induced-immune response of CAR and BiKE were evaluated in vitro and in vivo. The effects of B7-H3 on aerobic glycolysis in NSCLC cells were further investigated. Results B7-H3 CAR-T cells effectively inhibited NSCLC tumorigenesis in vitro and in vivo. B7-H3 redirection promoted highly specific T-cell infiltration into tumors. Additionally, NK cell activity could be specially triggered by B7-H3/CD16 BiKE through direct CD16 signaling, resulting in significant increase in NK cell activation and target cell death. BiKE improved antitumor efficacy mediated by NK cells in vitro and in vivo, regardless of the cell surface target antigen density on tumor tissues. Furthermore, we found that anti-B7-H3 blockade might alter tumor glucose metabolism via the reactive oxygen species-mediated pathway. Conclusions Together, our results suggest that B7-H3 may serve as a target for NSCLC therapy and support the further development of two therapeutic agents in the preclinical and clinical studies.

Perovskite quantum-dots are promising candidates for light-emitting diodes but the defects limit the device performance. Here Xu et al. show a passivation strategy to reduce the defect density at both interfaces, which increases the external quantum efficiency (EQE) and lifetime by more than 2-fold and 20-fold, respectively.

Abstract Perovskite based light‐emitting diodes (PeLEDs) have become a powerful candidate for next‐generation solid‐state lightings and high‐definition displays due to their high photoluminescence quantum yield (PLQY), tunable emission wavelength over the visible spectrum, and narrow emission linewidths. Over the past few years, the development of red‐ and green‐emissive PeLEDs has rapidly increased, and the corresponding external quantum efficiencies (EQE) have exceeded 20%. However, the research progress of blue‐emitting PeLEDs is limited by its poor material quality and inappropriate device structure. Currently, the maximum EQE of blue PeLED is only 6.2%, which is far from the industrialization requirements. In order to promote the development of blue PeLEDs, we summarize the recent research progress of blue perovskite materials and LEDs and discuss several fatal challenges, mainly embodied in low efficiency and poor stability. In order to overcome these challenges, detailed analysis and strategies are put forward in terms of the materials and devices. For the former, we summarize the feasible strategy for the preparation of efficient and stable blue‐emissive perovskites using component engineering. For the latter, we analyze the advantages and limitations of the different strategies for blue‐emissive perovskite in LEDs. At the end of the review, a comprehensive outlook is detailed, including future development directions and several technical problems to be solved. Thus, we aim to highlight the significance and promote the industrialization of PeLEDs.

Rhizophagus intraradices, one of the common arbuscular mycorrhizal fungi (AMF) grown in the roots of Flaveria bidentis, facilitates the invasion of this exotic plant species into China. However, it is still unknown whether nutrient transfer through the common mycorrhizal networks (CMN) between this exotic species and the native species enhances the competitive growth of F. bidentis over the native species. To elucidate this question and the related mechanism, an isotopic labeling technique was used to test the transfer of carbon (C) and nitrogen (N) by CMN. Native species like Setaria viridis and Eclipta prostrata were selected to compete with F. bidentis in a polyvinyl chloride (PVC) box. Two competitive groups (F. bidentis-S. viridis and F. bidentis- E. prostrata), three treatments (monoculture of F. bidentis, the mixture of F. bidentis and the native plant, and the monoculture of the native plant), and two levels of AMF (presence or absence) were assigned. Results showed that the corrected index of relative competition intensity (CRCI) of F. bidentis in the presence of AMF < 0 suggests that the competition facilitated the growth of F. bidentis with either S. viridis or E. prostrata. The reason was that the inoculation of R. intra radices significantly increased the C and N contents of F. bidentis in the mixtures. However, the effects of R. intra radices on the two native species were different: negative effect on the growth of S. viridis and positive effect on the growth of E. prostrata. The change of N content in S. viridis or E. prostrata was consistent with the variation of the biomass, suggesting that the N uptake explains the effects of R. intraradices on the competitive interactions between F. bidentis and the two native species. Moreover, the transfer of C and N via AMF hyphal links did occur between F. bidentis and the native species. However, the transfer of C and N by the CMN was not positively related to the competitive growth of F. bidentis.

Plant-parasitic nematodes cause huge agricultural economic losses. Two major families of Bacillus thuringiensis crystal proteins, Cry5 and Cry6, show nematicidal activity. Previous work showed that binding to midgut receptors is a limiting step in Cry toxin mode of action. In the case of Cry5Ba, certain Caenorhabditis elegans glycolipids were identified as receptors of this toxin. However, the receptors for Cry6 toxin remain unknown. In this study, the C. elegans CUB-like-domain containing protein RBT-1, released by phosphatidylinositol-specific phospholipase C (PI-PLC), was identified as a Cry6Aa binding protein by affinity chromatography. RBT-1 contained a predicted glycosylphosphatidylinositol (GPI) anchor site and was shown to locate in lipid rafts in the surface of the midgut cells. Western ligand blot assays and ELISA binding analysis confirmed the binding interaction between Cry6Aa and RBT-1 showing high affinity and specificity. In addition, the mutation of rbt-1 gene decreased the susceptibility of C. elegans to Cry6Aa but not that of Cry5Ba. Furthermore, RBT-1 mediated the uptake of Cry6Aa into C. elegans gut cells, and was shown to be involved in triggering pore-formation activity, indicating that RBT-1 is required for the interaction of Cry6Aa with the nematode midgut cells. These results support that RBT-1 is a functional receptor for Cry6Aa.

Objective: The objective of this study was to determine whether copious irrigation of peritoneal cavity during laparoscopic appendectomy for complicated appendicitis effectively reduces the incidence of postoperative complications and improves the postoperative recovery in adults compared with suction alone. Methods: In this prospective randomized trial, adult patients with complicated appendicitis were randomized to “irrigation and suction”(IS) group or “suction only”(SO) group. All surgery was performed with a standardized 3-port laparoscopic approach. The IS group received peritoneal irrigation with a minimum of 2000 mL sterile normal saline. The study primary outcomes included wound infection and postoperative intra-abdominal abscess. The study secondary outcomes included duration of operation, first anal exsufflation time, duration of hospital stay and hospital charges. Chi-squared and t-tests were used to analyze the study data. Results: Between January 2015 and June 2016, a total of 260 patients with complicated appendicitis were enrolled in the study. The peritoneal irrigation resulted in a longer operation time (51.6 ± 16.1 vs. 41.5 ± 15.2 min, p

Long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) has been reported to promote tumorigenesis via regulating microRNA (miR)-99a in gastric cancer cells. However, the role of each component involved in it is still not well understood. This study aimed to verify the role of ANRIL in gastric cancer as well as the underlying mechanisms. ANRIL levels in clinical gastric cancer tissues and cell lines were tested by qPCR. Effects of ANRIL silence on cell viability, migration and invasion, apoptosis, and miR-99a expression in MKN-45 and SGC-7901 cells were measured using CCK-8, Transwell assay, flow cytometry, and qPCR assays, respectively. Then, effects of miR-99a inhibition on ANRIL-silenced cells were evaluated. B-lymphoma Mo-MLV insertion region 1 (BMI1) expression, after abnormal expression of ANRIL and miR-99a, was determined. Finally, expression of key proteins in the apoptotic, Notch, and mTOR pathways was assessed. ANRIL level was elevated in gastric cancer tissues and cell lines. Knockdown of ANRIL suppressed cell viability, migration, and invasion, and increased apoptosis through up-regulating miR-99a. Furthermore, ANRIL silence down-regulated BMI1 via up-regulating miR-99a. BMI1 silence down-regulated Bcl-2 and key kinases in the Notch and mTOR pathways and up-regulated p16 and cleaved caspases. We verified the tumor suppressive effects of ANRIL knockdown in gastric cancer cells via crosstalk with miR-99a. Together, we provided a novel regulatory mechanism for ANRIL in gastric cancer, in which ANRIL silence down-regulated BMI1 via miR-99a, along with activation of the apoptotic pathway and inhibition of the Notch and mTOR pathways.

Cell death plays an important role in host-pathogen interactions. Crystal proteins (toxins) are essential components of Bacillus thuringiensis (Bt) biological pesticides because of their specific toxicity against insects and nematodes. However, the mode of action by which crystal toxins to induce cell death is not completely understood. Here we show that crystal toxin triggers cell death by necrosis signaling pathway using crystal toxin Cry6Aa-Caenorhabditis elegans toxin-host interaction system, which involves an increase in concentrations of cytoplasmic calcium, lysosomal lyses, uptake of propidium iodide, and burst of death fluorescence. We find that a deficiency in the necrosis pathway confers tolerance to Cry6Aa toxin. Intriguingly, the necrosis pathway is specifically triggered by Cry6Aa, not by Cry5Ba, whose amino acid sequence is different from that of Cry6Aa. Furthermore, Cry6Aa-induced necrosis pathway requires aspartic protease (ASP-1). In addition, ASP-1 protects Cry6Aa from over-degradation in C. elegans. This is the first demonstration that deficiency in necrosis pathway confers tolerance to Bt crystal protein, and that Cry6A triggers necrosis represents a newly added necrosis paradigm in the C. elegans. Understanding this model could lead to new strategies for nematode control.

Plant-parasitic nematodes (PPNs) are piercing/sucking pests, which cause severe damage to crops worldwide, and are difficult to control. The cyst and root-knot nematodes (RKN) are sedentary endoparasites that develop specialized multinucleate feeding structures from the plant cells called syncytia or giant cells respectively. Within these structures the nematodes produce feeding tubes, which act as molecular sieves with exclusion limits. For example, Heterodera schachtii is reportedly unable to ingest proteins larger than 28 kDa. However, it is unknown yet what is the molecular exclusion limit of the Meloidogyne hapla. Several types of Bacillus thuringiensis crystal proteins showed toxicity to M. hapla. To monitor the entry pathway of crystal proteins into M. hapla, second-stage juveniles (J2) were treated with NHS-rhodamine labeled nematicidal crystal proteins (Cry55Aa, Cry6Aa, and Cry5Ba). Confocal microscopic observation showed that these crystal proteins were initially detected in the stylet and esophageal lumen, and subsequently in the gut. Western blot analysis revealed that these crystal proteins were modified to different molecular sizes after being ingested. The uptake efficiency of the crystal proteins by the M. hapla J2 decreased with increasing of protein molecular mass, based on enzyme-linked immunosorbent assay analysis. Our discovery revealed 140 kDa nematicidal crystal proteins entered M. hapla J2 via the stylet, and it has important implications in designing a transgenic resistance approach to control RKN.

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Small noncoding RNAs (sncRNAs) regulate many genes in eukaryotic cells. Hua enhancer 1 (Hen1) is a 2′-O-methyltransferase that adds a methyl group to the 2′-OH of the 3′-terminal nucleotide of sncRNAs. The types and properties of sncRNAs may vary among different species, and the domain composition, structure, and function of Hen1 proteins differ accordingly. In mammals, Hen1 specifically methylates sncRNAs called P-element–induced wimpy testis-interacting RNAs (piRNAs). However, other types of sncRNAs that are methylated by Hen1 have not yet been reported, and the structures and the substrates of mammalian Hen1 remain unknown. Here, we report that mouse Hen1 (mHen1) performs 3′-end methylation of classical piRNAs, as well as those of most noncanonical piRNAs derived from rRNAs, small nuclear RNAs and tRNAs in murine spermatogonial stem cells. Moreover, we found that a distinct class of tRNA-derived sncRNAs are mHen1 substrates. We further determined the crystal structure of the putative methyltransferase domain of human Hen1 (HsHen1) in complex with its cofactor AdoMet at 2.0 Å resolution. We observed that HsHen1 has an active site similar to that of plant Hen1. We further found that the putative catalytic domain of HsHen1 alone exhibits no activity. However, an FXPP motif at its N terminus conferred full activity to this domain, and additional binding assays suggested that the FXPP motif is important for substrate binding. Our findings shed light on its methylation substrates in mouse spermatogonial stem cells and the substrate-recognition mechanism of mammalian Hen1. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the expression of microRNA (miRNA or miR)-186 in tumor tissues and peripheral blood of patients with pancreatic cancer (PC), as well as its mechanism of regulation. A total of 65 patients with PC who underwent surgery between June 2013 and October 2015 were included. In addition, 59 healthy subjects were recruited as controls. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of mRNA and miRNA. Western blotting and enzyme-linked immunosorbent assay were used to determine protein expression. Bioinformatics was employed for the prediction of the target gene of miR-186, whereas dual luciferase reporter assay was performed to identify whether miR-186 directly bound to YAP1 mRNA. Human pulmonary aortic endothelial cells (HPACs) were transfected with ago-miR-186. YAP1 expression in HPACs was silenced by siRNA. MTT assay was used to evaluate the viability of HPACs. YAP1 mRNA and protein expression levels were elevated in PC. In addition, expression levels of miR-186 in PC were downregulated. miR-186 regulated the expression of YAP1 by binding with the 3'-untranslated region of YAP1. Elevated expression of miR-186 inhibited the proliferation of HPACs by downregulating the expression of YAP1. Decreased expression of YAP1 by siRNA reduced the viability of HPACs. The present study demonstrates that YAP1 is upregulated in the tumor tissues and blood of PC patients, and this may be associated with the downregulation of miR-186. In addition, miR-186 may affect the occurrence and development of PC by controlling the proliferation of PC cells via YAP1. [ABSTRACT FROM AUTHOR]

Objective: To investigate the reactivation of the hepatitis B virus (HBV) following transarterial chemoembolization (TACE) in Chinese hepatocellular carcinoma (HCC) patients with low serum HBV DNA level, and to analyze the factors related to HBV reactivation in HCC patients with low serum HBV DNA level.Methods: From November 2011 to January 2014, 109 patients newly diagnosed with HCC with an HBV DNA level less than 2,000 IU/mL were enrolled in the study. These patients underwent at least two TACE procedures and were followed-up for at least 3 months to assess the reactivation of HBV DNA. Ten variables were compared in patients with and without HBV reactivation to evaluate the factors related to HBV reactivation in HCC patients with low serum HBV DNA level.Results: Of 109 HCC patients with low level HBV DNA, nine patients were HBeAg-positive, the other 100 patients were HBeAg-negative. Twenty-three of 109 (21.1%) patients developed HBV reactivation after TACE. Of nine HBeAg-positive patients, 55.6% (5/9) developed HBV reactivation, while in 100 HBeAg-negative patients, the rate of HBV reactivation was 18% (18/100) (P=0.019). Of ten variables of patients with low level HBV DNA, the levels of AFP and HBeAg status were found to be significantly correlated with HBV reactivation. Nevertheless, on binary logistic regression analysis, only HBeAg-positive status was the independent predictor of HBV reactivation in HCC patients with low serum HBV DNA level (odds ratio, 7.41; P=0.013).Conclusion: HCC patients with low serum HBV DNA level still remain associated with risk of viral reactivation after TACE, and HBeAg-positive HCC patients have a higher risk than patients with HBeAg-negative status. [ABSTRACT FROM AUTHOR]

Sorafenib has been demonstrated to improve survival rate in patients with advanced hepatocellular carcinoma (HCC); however, the survival benefit remains modest and the response rates remain poor. Transarterial chemoembolization (TACE) may be used for the treatment of advanced HCC with well-preserved liver function and has a high local tumor control rate. We hypothesized that patients with advanced HCC may benefit from the combination of sorafenib with TACE. A retrospective study was conducted involving patients with advanced HCC, who had received at least one TACE session. Patients subsequently received 400 mg sorafenib twice per day and were monitored monthly. A dose reduction from 400 to 200 mg of sorafenib twice per day was permitted. The overall survival and side effects were subsequently followed up. In total, 38 patients were included from April 1st, 2009 to March 31st, 2012. All patients were treated with sorafenib after TACE was performed. As of March 31st, 2013, seven patients remained on sorafenib, and were censored at that time point. The median overall survival time was 12 months (95% confidence interval, 6.3-17.7 months). The sorafenib dose was reduced temporarily in 32 patients (84.2%). The most common toxicities were dermatological adverse effects (94.7%), diarrhea (63.2%) and alopecia (26.3%). The survival benefit of sorafenib combined with TACE for advanced HCC is promising, with no intolerable adverse events, provided that dose adjustment is permitted. [ABSTRACT FROM AUTHOR]

The article presents a study regarding the relevant change of sensitivity index d' in the human brain sensory processing during the wake-sleep transition. The study has recorded response times of wakefulness over wake-sleep transition in 14 healthy undergraduate volunteers. The study has found that the sensation capacity for transfer information from the external world through the internal system decreased during the transition to sleep.

Objectives: Homoharringtonine (HHT) was efficient in therapying patients with acute myeloid leukemia (AML) in China, but little is known about the mechanism of its action. As the abnormal activation of JAK2 associated pathway is important to AML, we try to explore the effect of HHT on JAK2-STAT pathway in AML cells, thus supplying theoretical basis for wider use of HHT. Methods: The cell viability was tested by MTT. Apoptosis was tested by flow cytometry. RT-PCR was used to measure the expression of JAK2, STAT5 and the effect gene Bcl-xL. The signal proteins such as p-JAK2, p-STAT5, p-AKT, p-ERK activated by abnormal activated JAK2 were tested by Western blotting. Results: HHT obviously inhibited the viability of primary AML cells and AML cell lines HEL, K562 and HL-60 cells, AnnexinV-PI double staining confirmed early apoptosis in a dose-dependent manner. In immunoblotting analysis, when AML cells were affected by HHT for 6 h (much ahead of the time when apoptosis could be induced). The expressions of p-JAK2, p-STAT5, and p-AKT were down-regulated, while the total JAK2, STAT5 and AKT protein levels were stable. There were no changes in p-ERK and BcL-xL proteins. When it prolonged to 24 h, Bcl-xL decreased obviously. Similar results were obtained by using JAK2 specific inhibitor AG490. Conclusions: HHT possibly acts as a broad-spectrum PTK inhibitor and inhibits the phosphorylation of the signal proteins caused by oncogenic proteins such as JAK2V617F, BCR/ABL, thus blocking the survival and proliferative signal pathway of malignant cells. [ABSTRACT FROM AUTHOR]

In this study, the effects of volatile substances from Trichoderma erinaceum M6-5 on the cell membrane and wall of Alternaria alternata were investigated. To evaluate the antifungal effect, the culture medium inoculated with T. erinaceum and cultured for 5 days was covered with the culture medium containing A. alternata and cultured at 30 ℃ for 3, 5 and 7 days. The mycelia of A. alternata in the treatment and control groups were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and were collected to observe the integrity of the cell membrane by propidiumiodide (PI) staining, and cell membrane-related indexes such as electrical conductivity were measured. The morphological changes of apical growth cells were detected by calcofluor white (CFW) staining, and alkaline phosphatase (AKP) activity and N-acetylglucosamine concentration were determined. The results showed that during the culture period, the volatile substances produced by T. erinaceum had good antifungal effects on A. alternata. SEM and TEM images showed that the mycelia of A. alternata appeared shriveled, swollen and broken partially after the treatment. A greater reduction in cytoplasmic matrix was noted when compared with the control group, which was accompanied by local plasmolysis. For the control group, the mycelium growth was normal, the spore structure was complete, the cross-section structure was clear, the cytoplasm was uniform, and the cell wall and membrane structures were normal. After the treatment, the electrical conductivity, malondialdehyde (MDA) level, protein and nucleic acid leakage significantly increased relative to the control group. PI staining showed that the mycelia of the treated group emitted red fluorescence, indicating that the volatile substances of T. erinaceum damaged the integrity of the cell membrane, thus resulting in the leakage of cellular contents and marked disruption of the normal function of the cell membrane. CFW staining showed no significant differences between the treated and control groups with respect to the fluorescence intensity of mycelia, AKP activity or n-acetylglucosamine concentration indicating that the volatile substances of T. erinaceum did not damage the cell wall of A.alternata, and their major targets were not the cell wall. In conclusion, the antifungal target of volatile substances from T. erinaceum M6-5 is the cell membrane of A. alternata.