Lysosome-Associated Membrane Protein Targeting Strategy Improved Immunogenicity of Glycoprotein-Based DNA Vaccine for Marburg Virus.

Marburg hemorrhagic fever (MHF) is a fatal infectious disease caused by Marburg virus (MARV) infection, and MARV has been identified as a priority pathogen for vaccine development by the WHO. The glycoprotein (GP) of MARV mediates viral adhesion and invasion of host cells and therefore can be used as an effective target for vaccine development. Moreover, DNA vaccines have unique advantages, such as simple construction processes, low production costs, and few adverse reactions, but their immunogenicity may decrease due to the poor absorption rate of plasmids. Lysosome-associated membrane protein 1 (LAMP1) can direct antigens to lysosomes and endosomes and has great potential for improving the immunogenicity of nucleic acid vaccines. Therefore, we constructed a DNA vaccine based on a codon-optimized MARV GP (ID MF939097.1) fused with LAMP1 and explored the effect of a LAMP targeting strategy on improving the immunogenicity of the MARV DNA vaccine. ELISA, ELISpot, and flow cytometry revealed that the introduction of LAMP1 into the MARV DNA candidate vaccine improved the humoral and cellular immune response, enhanced the secretion of cytokines, and established long-term immune protection. Transcriptome analysis revealed that the LAMP targeting strategy significantly enriched antigen processing and presentation-related pathways, especially the MHC class II-related pathway, in the candidate vaccine. Our study broadens the strategic vision for enhanced DNA vaccine design and provides a promising candidate vaccine for MHF prevention.

The JNK/P38 signalling pathway activated by testin protects the intestinal epithelial barrier against Crohn's disease-like colitis.

The unknown mechanism that controls intestinal barrier dysfunction in individuals with Crohn's disease (CD) plays a crucial role in the onset of intestinal inflammation. Testin, an intercellular linker protein, has the potential to protect epithelial barrier function. This study aimed to analyse the effects of Testin on CD-like colitis and explore the possible underlying mechanism. Colon samples from CD patients and trinitrobenzene-sulfonic acid (TNBS)-treated mice were collected to examine changes in Testin expression. To assess the therapeutic effects of Testin on CD-like colitis in mice, we examined the symptoms of enteritis, performed histological analysis, and evaluated intestinal barrier permeability. The ability of Testin to stabilize tight junction (TJ) proteins was investigated via immunofluorescence and western blotting. We conducted in vivo and in vitro experiments using colonic organoids and blocking techniques to explore how Testin safeguards the integrity of the intestinal barrier. Testin expression was downregulated in the colons of CD patients and TNBS-treated mice. Increasing Testin expression led to amelioration of colitis symptoms and reduced the production of inflammatory cytokines in the colons of TNBS-induced colitis model mice. Furthermore, increased Testin expression resulted in decreased depletion of TJ proteins (ZO-1 and Claudin-1) and promoted the effectiveness of the intestinal barrier in mice with TNBS-induced colon damage and in lipopolysaccharide (LPS)-stimulated colonic organoids. Elevated Testin levels inactivated the JNK/P38 signalling pathway, potentially contributing to the beneficial impact of Testin on the intestinal barrier. Testin can inhibit the loss of TJ proteins in CD mice by inactivating the JNK/P38 pathway. These findings help to clarify how Testin alleviates CD-like colitis in mice by protecting intestinal barrier function. These findings could lead to the use of a new treatment approach for CD in clinical practice.

Numerical Analysis of Concrete Hydration Heat Impact on Frozen Soil Temperature around Cast-in-Place Piles.

The hydration heat generated during the concreting of cast-in-place piles causes thermal disturbance to the surrounding permafrost, leading to its thawing. This further affects the stability of the pile foundation and degrades the construction progress. To explore the influence mechanisms of the concrete hydration heat on the permafrost temperature field around the pile, as well as that of different construction seasons on the pile-side boundary conditions and permafrost temperature field, monitoring results of on-site tests and numerical simulation were used to analyze the distribution law of the pile soil temperature field in space and time, and the pile-side boundary conditions and permafrost temperature field during construction seasons. The results show that the temperature trend of the pile foundation can be divided into three stages: a rapid rise phase (0∼2 d), a rapid decline phase (2∼10 d), and a slow decline and stabilization phase (10∼90 d). As the radial distance from the pile center decreases, there occur a corresponding acceleration in temperature increase and an elevated maximum temperature rise (MTR). The influence range of the molding temperature and the hydration heat is about 1∼2 times the pile diameter and less than 1.5 m in the depth direction. Compared to the atmospheric temperature, there is a lag in the change in the permafrost temperature caused by accumulation of ground temperature, and the significant difference between the two leads to an increased rate of heat exchange at the boundary condition. Conducting drilling operation and cast-in-place pile construction in the cold seasons is conducive to reducing the thermal disturbance to the permafrost around the pile in permafrost areas.

[Retracted] MicroRNA­519 enhances HL60 human acute myeloid leukemia cell line proliferation by reducing the expression level of RNA­binding protein human antigen R.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric analysis data shown in Fig. 4B on p. 7834 were strikingly similar to data that had already been submitted for publication in different form in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 7830­7836, 2015; DOI: 10.3892/mmr.2015.4455].

Genome-Wide Identification and Characterization of Alternative Oxidase (AOX) Genes in Foxtail Millet (Setaria italica): Insights into Their Abiotic Stress Response.

Alternative oxidase (AOX) serves as a critical terminal oxidase within the plant respiratory pathway, playing a significant role in cellular responses to various stresses. Foxtail millet (Setaria italica), a crop extensively cultivated across Asia, is renowned for its remarkable tolerance to abiotic stresses and minimal requirement for fertilizer. In this study, we conducted a comprehensive genome-wide identification of AOX genes in foxtail millet genome, discovering a total of five SiAOX genes. Phylogenetic analysis categorized these SiAOX members into two subgroups. Prediction of cis-elements within the promoter regions, coupled with co-expression network analysis, intimated that SiAOX proteins are likely involved in the plant's adaptive response to abiotic stresses. Employing RNA sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR), we scrutinized the expression patterns of the SiAOX genes across a variety of tissues and under multiple abiotic stress conditions. Specifically, our analysis uncovered that SiAOX1, SiAOX2, SiAOX4, and SiAOX5 display distinct tissue-specific expression profiles. Furthermore, SiAOX2, SiAOX3, SiAOX4, and SiAOX5 exhibit responsive expression patterns under abiotic stress conditions, with significant differences in expression levels observed between the shoot and root tissues of foxtail millet seedlings. Haplotype analysis of SiAOX4 and SiAOX5 revealed that these genes are in linkage disequilibrium, with Hap_2 being the superior haplotype for both, potentially conferring enhanced cold stress tolerance in the cultivar group. These findings suggest that both SiAOX4 and SiAOX5 may be targeted for selection in future breeding programs aimed at improving foxtail millet's resilience to cold stress.

DNA Vaccines Encoding HTNV GP-Derived Th Epitopes Benefited from a LAMP-Targeting Strategy and Established Cellular Immunoprotection.

Vaccines has long been the focus of antiviral immunotherapy research. Viral epitopes are thought to be useful biomarkers for immunotherapy (both antibody-based and cellular). In this study, we designed a novel vaccine molecule, the Hantaan virus (HTNV) glycoprotein (GP) tandem Th epitope molecule (named the Gnc molecule), in silico. Subsequently, computer analysis was used to conduct a comprehensive and in-depth study of the various properties of the molecule and its effects as a vaccine molecule in the body. The Gnc molecule was designed for DNA vaccines and optimized with a lysosomal-targeting membrane protein (LAMP) strategy. The effects of GP-derived Th epitopes and multiepitope vaccines were initially verified in animals. Our research has resulted in the design of two vaccines based on effective antiviral immune targets. The effectiveness of molecular therapies has also been preliminarily demonstrated in silico and in laboratory animals, which lays a foundation for the application of a vaccines strategy in the field of antivirals.

[Bi10{RuPPh3}3]-: Paramagnetic 13-Vertex Polybismuthide Heteroanion.

Ru(PPh3)3Cl2 reacts with Binn- from an ethylenediamine (en) solution of K5Bi4 to yield a new architype of 13-vertex [Bi10{RuPPh3}3]- (1) composed of unprecedented incomplete cuboidal Bi73- and triangular Bi33- held together by {RuPPh3}2+.

A non-invasive osteopontin-targeted phase changeable fluorescent nanoprobe for molecular imaging of myocardial fibrosis.

Due to the elevated fatality rate of cardiovascular diseases, myocardial fibrosis emerges as a prominent pathological alteration in the majority of heart ailments and their associated pathologies, thereby augmenting the likelihood of sudden cardiac death. Consequently, the prompt and obligatory identification of myocardial fibrosis assumes paramount importance in averting malignant incidents among patients afflicted with cardiac disorders. Herein, with higher expression osteopontin (OPN) found in cardiac fibrosis tissue, we have developed a dual-modality imaging probe, namely OPN targeted nanoparticles (OPN@PFP-DiR NPs), which loaded perfluoropentane (PFP) for ultrasound (US) and 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) for near-infrared fluorescence (NIR) of molecular imaging, to investigate the molecular features of cardiac fibrosis using US and NIR imaging. Subsequently, the OPN@PFP-DiR NPs were administered intravenously to a mouse model of myocardial infarction (MI). The US and NIR molecular imaging techniques were employed to visualize the accumulation of the nanoparticles in the fibrotic myocardium. Hence, this research presents a valuable noninvasive, cost-effective, and real-time imaging method for evaluating cardiac fibrosis, with promising clinical applications.

Effects of natural products on angiogenesis in melanoma.

Melanoma is the most aggressive form of skin cancer and originates from genetic mutations in melanocytes. The disease is multifactorial, but its main cause is overexposure to UV radiation. Currently, available chemotherapy expresses little to no results, which may justify the extensive use of natural products to treat this cancer. In this study, we reviewed the inhibition of melanoma angiogenesis by natural products and its potential mechanisms using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect and China National Knowledge Infrastructure databases. According to summarizes 27 natural products including alkaloids, polyphenols, terpenoids, flavonoids, and steroids that effectively inhibit angiogenesis in melanoma. In addition to these there are 15 crude extracts that can be used as promising agents to inhibit angiogenesis, but their core components still deserve further investigation. There are current studies on melanoma angiogenesis involving oxidative stress, immune-inflammatory response, cell proliferation and migration and capillary formation. The above natural products can be involved in melanoma angiogenesis through core targets such as VE-cadherin, COX-2, iNOS, VEGF, bFGF, FGF2,MMP2,MMP9,IL-1ß,IL-6 play a role in inhibiting melanoma angiogenesis. Effective excavation of natural products can not only clarify the mechanism of drug action and key targets, but also help to promote the preclinical research of natural products for melanoma treatment and further promote the development of new clinical drugs, which will bring the gospel to the vast number of patients who are deeply afflicted by melanoma.

Ginkgetin improved experimental colitis by inhibiting intestinal epithelial cell apoptosis through EGFR/PI3K/AKT signaling.

Excessive apoptosis of intestinal epithelial cells leads to intestinal barrier dysfunction, which is not only one of the pathological features of inflammatory bowel disease (IBD) but also a therapeutic target. A natural plant extract, Ginkgetin (GK), has been reported to have anti-apoptotic activity, but its role in IBD is unknown. This study aimed to explore whether GK has anti-colitis effects and related mechanisms. An experimental colitis model induced by dextran sulfate sodium (DSS) was established, and GK was found to relieve colitis in DSS-induced mice as evidenced by improvements in weight loss, colon shortening, Disease Activity Index (DAI), macroscopic and tissue scores, and proinflammatory mediators. In addition, in DSS mice and TNF-α-induced colonic organoids, GK protected the intestinal barrier and inhibited intestinal epithelial cell apoptosis, by improving permeability and inhibiting the number of apoptotic cells and the expression of key apoptotic regulators (cleaved caspase 3, Bax and Bcl-2). The underlying mechanism of GK's protective effect was explored by bioinformatics, rescue experiments and molecular docking, and it was found that GK might directly target and activate EGFR, thereby interfering with PI3K/AKT signaling to inhibit apoptosis of intestinal epithelial cells in vivo and in vitro. In conclusion, GK inhibited intestinal epithelial apoptosis in mice with experimental colitis, at least in part, by activating EGFR and interfering with PI3K/AKT activation, explaining the underlying mechanism for ameliorating colitis, which may provide new options for the treatment of IBD.

Building Vulnerability to Landslides: Broad-Scale Assessment in Xinxing County, China.

This study develops a model to assess building vulnerability across Xinxing County by integrating quantitative derivation with machine learning techniques. Building vulnerability is characterized as a function of landslide hazard risk and building resistance, wherein landslide hazard risk is derived using CNN (1D) for nine hazard-causing factors (elevation, slope, slope shape, geotechnical body type, geological structure, vegetation cover, watershed, and land-use type) and landslide sites; building resistance is determined through quantitative derivation. After evaluating the building susceptibility of all the structures, the susceptibility of each village is then calculated through subvillage statistics, which are aimed at identifying the specific needs of each area. Simultaneously, different landslide hazard classes are categorized, and an analysis of the correlation between building resistance and susceptibility reveals that building susceptibility exhibits a positive correlation with landslide hazard and a negative correlation with building resistance. Following a comprehensive assessment of building susceptibility in Xinxing County, a sample encompassing different landslide intensity areas and susceptibility classes of buildings was chosen for on-site validation, thus yielding an accuracy rate of the results as high as 94.5%.

Preparation of Al-doped mesoporous silica spheres (Al-MSSs) for the improvement of mechanical properties and aging resistance of dental resin composites.

OBJECTIVE: The purpose of this study was to synthesize Al-doped mesoporous silica spheres (Al-MSSs) and evaluate the effect of them as functional fillers on the mechanical properties and aging resistance of dental resin composites. METHODS: Al-MSSs were prepared by a two-step method. The effect of Al-MSSs on the performance of the composites was evaluated using neat resin matrix, commercial composites 3M Z350XT and samples containing mesoporous silica spheres (MSSs) and nonporous silica spheres (NSSs) as control. The neat resin matrix consisted of resin monomer (Bisphenol A glycerolate dimethacrylate/triethylene glycol dimethacrylate, 49.5/49.5, wt%) and photoinitiator (camphor quinone/Ethyl-4-dimethylaminobenzoate, 0.2/0.8, wt%). The mechanical properties (flexural strength, flexural modulus, compressive strength and microhardness) of them were evaluated by a universal testing machine and microhardness tester. The mechanical stabilities of the prepared composites in wet environment were evaluated by immersing them in deionized water at 37 °C. In addition, we evaluated the effect of Al-MSSs on other properties of the dental resin composites such as polymerization shrinkage, degree of conversion, curing depth, contact angle, water sorption and solubility according to ISO 4049: 2019. RESULTS: The synthesized Al-MSSs possessed good dispersibility with an average particle size of about 505 ± 16 nm. The mechanical properties of resin composites gradually increased with the increase of the loading amounts of inorganic fillers. The reinforcing effect of Al-MSSs was similar to that of MSSs and better than that of the NSSs groups at the same filler loading. After aging in deionized water at 37 °C for 30 days, the mechanical properties of all resin composites decreased. However, the decrease percentage of the composites filled with Al-MSSs was significantly lower than the other groups, indicating that the stability of the dental composites in wet environments was significantly improved by the Al-MSSs fillers. Furthermore, Al-MSSs had no obvious influence on the biocompatibility and other properties of dental resins. SIGNIFICANCE: The prepared Al-MSSs could effectively improve the mechanical properties and aging resistance without sacrificing other physic-chemical properties of dental resin composites.

Effect of Sheet Properties of Cellulosic Polyglycidyl Methacrylate-Grafted Fibers in a Cationic Polyacrylamide/SiO2/Anionic Polyacrylamide Retention Aid System.

As increasing fiber hydrophobicity can significantly improve the paper dewatering process, we found that replacing SBKP and HBKP with 0.5% superhydrophobic CPGMA can significantly improve the dewatering of paper sheets. Therefore, it can be concluded that if CPGMA has little effect on paper properties, it will have potential industrial value in the papermaking industry. Consequently, it is necessary to further study the effect of the CPGMAs@CPAM/SiO2/APAM system on paper properties. To evaluate the application potential of the system in the papermaking industry, we investigated the effects of CPGMAs, which replaced the fibers in the stocks, on the paper properties in the CPAM/SiO2/APAM system. The findings demonstrate that as the CPGMA replacement increased, the paper's tensile strength, bursting strength, tear resistance, and folding endurance all declined. The trend can be segmented into two phases: a rapid decrease for substitution amounts below 0.5% and a gradual decline for substitution amounts exceeding 0.5%. When replaced with a small amount of CPGMAs, there was a negligible effect on these properties. Second, the paper air permeability increased with the CPGMA substitution amount in the stock. Furthermore, the trend of paper air permeability can be divided into two stages-a rapid stage with a substitution amount of <0.5% and a slow stage with a substitution amount of >0.5%. A small amount of CPGMAs could distinctly improve the paper's air permeability. Third, CPGMAs, which replaced fibers in the stock, minutely affected the paper formation. A small amount of CPGMAs substantially boosted the efficacy of the process of paper manufacture and certain characteristics of the paper, and it had a negligible impact on the strength of paper. The CPGMAs@CPAM/SiO2/APAM technology has the potential to improve the retention and filtration performance of CPAM/SiO2/APAM.

Peiminine ameliorates Crohn's disease-like colitis by enhancing the function of the intestinal epithelial barrier through Nrf2/HO1 signal.

BACKGROUND AND AIMS: Impaired intestinal barrier function is key in maintaining intestinal inflammation in Crohn's disease (CD). However, no targeted treatment in clinical practice has been developed. Peiminine (Pm) strongly protects the epithelial barrier, the purpose of this study is to investigate whether Pm affects CD-like colitis and potential mechanisms for its action. METHODS: Trinitro-benzene-sulfonic acid (TNBS)-induced mice and Il-10-/- mice were used as CD animal models. Colitis symptoms, histological analysis, and intestinal barrier permeability were used to assess the Pm's therapeutic effect on CD-like colitis. The colon organoids were induced by TNF-α to evaluate the direct role of Pm in inhibiting apoptosis of the intestinal epithelial cells. Western blotting and small molecule inhibitors were used to investigate further the potential mechanism of Pm in inhibiting apoptosis of intestinal epithelial cells. RESULTS: Pm treatment reduced body weight loss, disease activity index (DAI) score, and inflammatory score, demonstrating that colonic inflammation in mice were alleviated. Pm decreased the intestinal epithelial apoptosis, improved the intestinal barrier function, and prevented the loss of tight junction proteins (ZO1 and claudin-1) in the colon of CD mice and TNF-α-induced colonic organoids. Pm activated Nrf2/HO1 signaling, which may protect intestinal barrier function. CONCLUSIONS: Pm inhibits intestinal epithelial apoptosis in CD mice by activating Nrf2/HO1 pathway. This partially explains the potential mechanism of Pm in ameliorating intestinal barrier function in mice and provides a new approach to treating CD.

Magnolin inhibits intestinal epithelial cell apoptosis alleviating Crohn's disease-like colitis by suppressing the PI3K/AKT signalling pathway.

BACKGROUND AND AIMS: Previous reports have shown that preventing excessive intestinal epithelial cell (IEC) apoptosis is a crucial approach for protecting the intestinal barrier in patients with Crohn's disease (CD). Magnolin (MGL) has various biological activities, including antiapoptotic activities, but its role in CD has largely not been determined. This study investigated how MGL impacts CD-like colitis and the underlying mechanism involved. METHODS: Mice were treated with TNBS to establish a disease model, and these mice were used to assess the therapeutic effects of MGL on CD-like colitis. TNF-α-treated colon organoids were used to evaluate the impact of MGL on intestinal barrier function and IEC apoptosis. Enrichment analysis was performed to examine the potential pathways through which MGL inhibits IEC apoptosis. Finally, rescue experiments showed the mechanism by which MGL suppresses IEC apoptosis. RESULTS: The animal experiments demonstrated that MGL treatment alleviated the weight loss, colon shortening, elevated disease activity index (DAI) scores, increased colitis histological scores and upregulated inflammatory factor expression that were observed in model mice. MGL ameliorated intestinal barrier dysfunction and the loss of tight junction (TJ) proteins (ZO-1 and Claudin-1) by inhibiting IEC apoptosis in both TNBS-treated mice and TNF-α-treated colon organoids. MGL inhibited the PI3K/AKT signalling pathway, thus safeguarding the intestinal barrier and alleviating CD-like colitis in vivo and in vitro. CONCLUSIONS: MGL improves the intestinal barrier integrity and prevents CD-like colitis by inhibiting IEC apoptosis. The potential mechanism of its anti-apoptotic impact on IECs could be associated with the PI3K/AKT pathway, presenting novel approaches and avenues for the clinical management of CD.

Complanatuside A ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by regulating the Th17/Treg balance via the JAK2/STAT3 signaling pathway.

Immunity imbalance of T helper 17 (Th17)/regulatory T (Treg) cells is involved in the pathogenesis of Crohn's disease (CD). Complanatuside A (CA), a flavonol glycoside, exerts anti-inflammatory activities and our study aimed to identify its effect on TNBS-induced colitis and the possible mechanisms. We found that CA alleviated the symptoms of colitis in TNBS mice, as demonstrated by prevented weight loss and colon length shortening, as well as decreased disease activity index scores, inflammatory scores, and levels of proinflammatory factors. Flow cytometry analysis showed that CA markedly reduced the percentage of Th17 cells while increasing the percentage of Treg cells in TNBS mice. Under Th17 cell polarizing conditions, CA inhibited the differentiation of Th17 cells while the Treg cell differentiation was elevated under Treg cell polarizing conditions. Furthermore, it was observed that JAK2 interacted with CA through six hydrogen bonds via molecular docking. The phosphorylation of JAK2/STAT3 was reduced by CA, which might be correlated with the protective effect of CA on colitis. In conclusion, CA reduced the imbalance of Th17/Treg cells by inhibiting the JAK2/STAT3 signaling pathway in TNBS-induced colitis, which may provide novel strategies for CD treatment.

HA2-FimA DNA Vaccine Treats Experimental Periodontitis.

PURPOSE: To study the therapeutic effect of hemagglutinin-2 and fimbrial (HA2-FimA) vaccine on experimental periodontitis in rats. MATERIALS AND METHODS: The first batch of rats was divided into two groups and immunised with pure water or pVAX1-HA2-FimA at the age of 6, 7, and 9 weeks. After sacrificing the animals, total RNA was extracted from the spleens for RNA high-throughput sequencing (RNA-Seq) analysis. The second batch of rats was divided into four groups (A, B, C, D), and an experimental periodontitis rat model was established by suturing silk thread around the maxillary second molars of rats in groups B, C, and D for 4 weeks. The rats were immunised with pure water, pVAX1-HA2-FimA vaccine, empty pVAX1 vector, and pure water at 10, 11, and 13 weeks of age, respectively. Secretory immunoglobulin A (SIgA) antibodies and cathelicidin antimicrobial peptide (CAMP) levels in saliva were measured by enzyme-linked immunosorbent assay (ELISA). All rats were euthanised at 17 weeks of age, and alveolar bone loss was examined using micro-computed tomography (Micro-CT). RESULTS: Through sequencing analysis, six key genes, including Camp, were identified. Compared with the other three groups, the rats in the periodontitis+pVAX1-HA2-FimA vaccine group showed higher levels of SIgA and CAMP (p < 0.05). Micro-CT results showed significantly less alveolar bone loss in the periodontitis+pVAX1-HA2-FimA vaccine group compared to the periodontitis+pVAX1 group and periodontitis+pure water group (p < 0.05). CONCLUSION: HA2-FimA DNA vaccine can increase the levels of SIgA and CAMP in the saliva of experimental periodontitis model rats and reduce alveolar bone loss.

Bumblebee Foraging Dynamics and Pollination Outcomes for Cherry Tomato and Pear Varieties in Northern China.

Bumblebees (Bombus terrestris) have strong environmental adaptability and high pollen transfer efficiency, making them well-suited pollinators of economic crops. However, bumblebee pollination is still not widely applied in northern China due to the lack of data on foraging behavior and pollination effects. We conducted a three-year experiment involving cherry tomatoes (Solanum lycopersicum L.) and pears (Pyrus spp.) treated with bumblebee pollination to evaluate the foraging behavior and pollination effects on these two crops. Results showed that B. terrestris had enhanced foraging activities as daytime temperatures rose from 18 °C to 26 °C, as indicated by the increased number of bees leaving the hive and returning bees carrying pollen in greenhouses in winter. There were two peaks in the foraging activity of bumblebees in pear orchards in early spring, which was closely related to the temperature change in the daytime. Undoubtedly, cherry tomatoes treated with B. terrestris had higher fruit setting rate, weight, seed number, and fruit yields compared to those with hormone 2,4-dichlorophenoxyacetic acid treatments, as well as a lower rate of deformed fruits. B. terrestris pollination can significantly increase the fruit setting rate and fruit yield of pears, compared with open pollination, and can fully achieve the effect of hand pollination. B. terrestris pollination can improve cultivation efficiency, increase yield, and produce more economic benefits. Moreover, it can also contribute to reducing hormone residues and ensure the safety of agricultural products. We recommend its application to cherry tomatoes in greenhouses in winter and potential application to pears in orchards in early spring in northern China. However, the risk to local bumblebee species of introducing commercially available bumblebees into orchards should be considered and evaluated in future research. This study provides both empirical support and a theoretical basis for the selection of bumblebees as pollinators in the production of economically important crops and the improvement of crop cultivation management in northern China.

A novel GSK3ß inhibitor 5n attenuates acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality caused by various factor. The specific strategies for AKI are still lacking. GSK3ß is widely expressed in the kidneys. In acute models of injury, GSK3ß promotes the systemic inflammatory response, increases the proinflammatory release of cytokines, induces apoptosis, and alters cell proliferation. We screened a series of 3-(4-pyridyl)-5-(4-sulfamido-phenyl)-1,2,4-oxadiazole derivatives which are recognized as new GSK3ß inhibitors, and found that 5n had the least toxicity and the best cell protection. We then tested the anti-inflammatory and reno-protective effect of 5n in cisplatin-treated tubular epithelial cells. 5n had anti-inflammation effect indicated by phosphor-NF-κB detection. Finally, we found that 5n ameliorated renal injury and inflammation in cisplatin-induced AKI mouse model. Silencing GSK3ß inhibited cell injury and inflammation induced by cisplatin. We found that GSK3ß interacted with PP2Ac to modulate the activity of NF-κB. In conclusion, 5n, the novel GSK3ß inhibitor, protects against AKI via PP2Ac-dependent mechanisms which may provide a potential strategy for the treatment of AKI in clinic.