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Abstract Recurrence is one of the main causes of treatment failure in early-stage non-small cell lung cancer (NSCLC). However, there are no predictors of the recurrence of early-stage NSCLC, and the molecular mechanism of its recurrence is not clear. In this study, we used clinical sample analysis to demonstrate that low levels of expression of precursor surfactant protein B (pro-SFTPB) in primary NSCLC tissue compared to their adjacent tissues are closely correlated with recurrence and poor prognosis in early-stage NSCLC patients. In vitro and in vivo experiments showed that downregulation of pro-SFTPB expression activates the Akt pathway by upregulating PGK1, which promotes metastasis and tumorigenicity in NSCLC cells. We then demonstrated that pro-SFTPB suppresses the formation of the ADRM1/hRpn2/UCH37 complex by binding to ADRM1, which inhibits PGK1 deubiquitination, thus accelerating ubiquitin-mediated PGK1 degradation. In summary, our findings indicate that low expression of pro-SFTPB in primary NSCLC compared to their adjacent tissue has potential as a predictor of recurrence and poor prognosis in early-stage NSCLC. Mechanistically, downregulation of pro-SFTPB attenuates inhibition of ADRM1-deubiquitinated PGK1, resulting in elevated levels of PGK1 protein; this activates the Akt pathway, ultimately leading to the progression of early-stage NSCLC.

We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated KV1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to KV1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for KV1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with 18F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat model of rheumatoid arthritis. It was also effective in treating disease in a rat model of atopic dermatitis. No signs of toxicity are observed at 10-100 times the in vivo dose. EgK5 shows promise for clinical development as a therapeutic for autoimmune diseases.

Background: Dying tumor cells release intracellular potassium (K+), raising extracellular K+ ([K+]e) in the tumor microenvironment (TME) to 40-50 mM (high-[K+]e). Here, we investigated the effect of high-[K+]e on T cell functions. Materials and Methods: Functional impacts of high-[K+]e on human T cells were determined by cellular, molecular, and imaging assays. Results: Exposure to high-[K+]e suppressed the proliferation of central memory and effector memory T cells, while T memory stem cells were unaffected. High-[K+]e inhibited T cell cytokine production and dampened antitumor cytotoxicity, by modulating the Akt signaling pathway. High-[K+]e caused significant upregulation of the immune checkpoint protein PD-1 in activated T cells. Although the number of KCa3.1 calcium-activated potassium channels expressed in T cells remained unaffected under high-[K+]e, a novel KCa3.1 activator, SKA-346, rescued T cells from high-[K+]e-mediated suppression. Conclusion: High-[K+]e represents a so far overlooked secondary checkpoint in cancer. KCa3.1 activators could overcome such "ionic-checkpoint"-mediated immunosuppression in the TME, and be administered together with known PD-1 inhibitors and other cancer therapeutics to improve outcomes.

ObjectiveTo systematically evaluate the role of blood lipid level in predicting the risk of Alzheimer′s disease (AD). MethodsWe searched Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), Pubmed, Web of Science, Springer, and Cocharne Library for literatures on the correlation between AD incidence and blood lipid level published in Chinese or English till June 2021 and supplementary manual tracing for some of the references was also conducted. Newcastle-Ottawa-Scale literature quality evaluation scale was adopted to evaluate the quality of the included studies. Statistical analyses were performed with RevMan5.3 software. ResultsA total of 15 eligible studies were selected according to the inclusion and exclusion criteria, and the data on blood lipid level were collected from 1 435 healthy elderly people and 2 162 elderly people with AD. Meta-analysis showed that there was no significant difference in total cholesterol (TC) and triglyceride (TG) level between the AD sufferers and the healthy controls；low-density lipoprotein cholesterol (LDL-C) was significantly higher in the AD sufferers than that in the healthy controls (mean difference [MD] = 3.59，95% confidence interval [95% CI]: 0.98 – 6.21); while, high-density lipoprotein cholesterol (HDL-C) was significantly lower in the AD sufferers than that in the healthy controls (MD = – 3.47，95% CI: – 5.94 – – 0.99). ConclusionHigher LDL-C level but lower HDL-C level may indicate a higher risk of AD in older adults.

In order to investigate the interfacial debonding (IC) strain of the reinforced concrete structures strengthened by fiber-reinforced polymer (FRP), this paper proposed some data-driven models to explore it, considering the effect of random factors both in material and environment. The concrete strength, shear span proportion, the proportion of anchorage length to shear width, tensile reinforcement proportion, steel yield strength, stirrup reinforcement ratio, FRP stiffness, the proportion of sheet span to beamwidth, ratios of environmental temperature to the maintenance standard temperature, and ratios of environmental humidity to the relative humidity were regarded as the inputs, the IC debonding strain was regarded as the output. The results indicate that the neural network optimized by the sparrow search algorithm not only has a relatively small error but also has stronger robustness. In addition, a study on the importance of the inputs on the IC debonding strain indicates that the concrete strength, FRP stiffness, and ratios of environmental temperature to the maintenance standard temperature are the most significant factor to influence the IC debonding strain.

The Changle goose (CLG), a Chinese indigenous breed, is celebrated for its adaptability, rapid growth, and premium meat quality. Despite its agricultural value, the exploration of its genomic attributes has been scant. Our study entailed whole‐genome resequencing of 303 geese across CLG and five other Chinese breeds, revealing distinct genetic diversity metrics. We discovered significant migration events from Xingguo gray goose to CLG and minor gene flow between them. We identified genomic regions through selective sweep analysis, correlating with CLG's unique traits. An elevated inbreeding coefficient in CLG, alongside reduced heterozygosity and rare single nucleotide polymorphisms (RSNPs), suggests a narrowed genetic diversity. Genomic regions related to reproduction, meat quality, and growth were identified, with the GATA3 gene showing strong selection signals for meat quality. A non‐synonymous mutation in the Sloc2a1 gene, which is associated with reproductive traits in the CLG, exhibited significant differences in allelic frequency. The roles of CD82, CDH8, and PRKAB1 in growth and development, alongside FABP4, FAF1, ESR1, and AKAP12 in reproduction, were highlighted. Additionally, Cdkal1 and Mfsd14a may influence meat quality. This comprehensive genetic analysis underpins the unique genetic makeup of CLG, providing a basis for its conservation and informed breeding strategies. [ABSTRACT FROM AUTHOR]

Magnetic separation is a method for separating particles based on their magnetic properties. Application of magnetic powders (MP) from coal fly ash (CFA) for wastewater treatment has been considered to be a promising approach to improving the separation efficiency. This paper aims to review the perspectives on application of magnetic powders from coal fly ash (MP-CFA) for wastewater treatment based on three major technological functions. MP-CFA can enhance the treatment ability of phosphorate removal through magnetic flocculation-sedimentation process. Among three commonly used phosphorus removal coagulants, i.e., ferric chloride, aluminum sulfate and poly aluminum chloride (PAC), the addition of MP results in the best performance for the floc settling of PAC coagulation. The alkali modified MP can further improve the coagulation precipitation for chemical phosphorus removal. MP-CFA also can enhance the removal of heavy metals by adsorption and chemical precipitation. The MP effectively adsorbs copper ions at low concentration by removing copper ions through chemical precipitation, which can be speed up by adding the magnetic powder, especially using the alkali modified MP. MP-CFA can be delivered to activated sludge process to improve the solid-liquid separation of sludge from treated wastewater. Activated sludge supplemented with MP exhibits excellent settleability and concentration of mixed liquid volatile suspended solids (MLVSS) can be greatly increased to enhance volumetric biotreatment capacity.

We established and validated a sensitive multi-residue analytical method for identifying benzophenone (BP) and nine BP derivatives (2,4-dihydroxybenzophenone [BP-1], 2,2′,4,4′-tetrahydroxydroxybenzophenone, 2-hydroxy-4-methoxy benzophenone, 2,2′-dihydroxy 4-methoxy benzophenone, 2-hydroxybenzophenone [2-OHBP], 4-hydroxybenzophenone, 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl). Solid–liquid extraction pretreatment and ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) were employed in an analysis of 85 packaged cereal-based food samples (25 pastry, 50 rice, and 10 noodle samples). The method had satisfactory linearity (R2 ≥ 0.995), low limits of detection (pastry: 0.02–4.2 ng/g; rice and noodle: 0.02–2 ng/g), and favorable precision, with within-run and between-run coefficient of variation ranges of 1–29% and 1–28%, respectively. BP and 4-MBP were detected in 100% of the pastry samples, and BP-1 and 2-OHBP were found in 76% and 56% of the pastry samples, respectively. BP and 2-OHBP were found in 92% and 38% of the rice samples, respectively. BP was found in 50% of the noodle samples. BP contributed the most to the total level of BPs in pastries, with significantly higher mean ± standard deviation (range) levels for pastries (26.8 ± 32.6 [1.8–115.4] ng/g) than rice (1.2 ± 2.0 [0.4–13.4] ng/g) and noodles (0.7 ± 0.7 [0.4–1.9] ng/g); p < 0.0001). The trace levels of 4-MBP identified in the samples demonstrate the need for the development of analytical methods with high sensitivity and specificity; the proposed method satisfies this need.

A fast, robust, and sensitive analytical method was developed and validated for the simultaneous identification of benzophenone (BP) and nine BP analogs (BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone, 4-hydroxybenzophenone, 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl) in 25 samples of rice cereal. Fast pesticide extraction (FaPEx) coupled with ultrahigh-performance liquid chromatography–tandem mass spectrometry was applied. The developed method exhibited satisfactory linearity (r > 0.997), favorable recoveries between 71% and 119%, and a limit of detection ranging from 0.001 to 0.5 ng/g. The detection frequencies of BP, 4-MBP, and BP-3 were 100%, 88%, and 52%, respectively. BP had higher geometric levels, with a mean of 39.8 (19.1–108.9) ng/g, and 4-MBP had low levels, with a mean of 1.9 (1.3–3.3) ng/g. The method can be applied to routine rice cereal analysis at the nanogram-per-gram level. For infants aged 0–3 years, the hazard quotients of BP and 4-MBP were lower than one, and the margin of exposure for BP was higher than 10,000, suggesting that rice cereal consumption poses no health concern for Taiwanese infants.

Mechanisms underlying plant non-host resistance to Xanthomonas oryzae pv. oryzicola (Xoc), the pathogen causing rice leaf streak disease, are largely unknown. Cyclic nucleotide-gated ion channels (CNGCs) are calcium-permeable channels that are involved in various biological processes including plant resistance. In this study, functions of two tomato CNGC genes SlCNGC1 and SlCNGC14 in non-host resistance to Xoc were analyzed. Silencing of SlCNGC1 and SlCNGC14 in tomato significantly enhanced Xoc-induced hypersensitive response (HR) and non-host resistance, demonstrating that both SlCNGC1 and SlCNGC14 negatively regulate non-host resistance related HR and non-host resistance to Xoc in tomato. Silencing of SlCNGC1 and SlCNGC14 strikingly increased Xoc-induced callose deposition and strongly promoted both Xoc-induced and flg22-elicited H2O2, indicating that these two SlCNGCs repress callose deposition and ROS accumulation to attenuate non-host resistance and PAMP-triggered immunity (PTI). Importantly, silencing of SlCNGC1 and SlCNGC14 apparently compromised cytosolic Ca2+ accumulation, implying that SlCNGC1 and SlCNGC14 function as Ca2+ channels and negatively regulate non-host resistance and PTI-related responses through modulating cytosolic Ca2+ accumulation. SlCNGC14 seemed to play a stronger regulatory role in the non-host resistance and PTI compared to SlCNGC1. Our results reveal the contribution of CNGCs and probably also Ca2+ signaling pathway to non-host resistance and PTI.

Calmodulin-binding transcription activators (CAMTAs) play important roles in various plant biological processes including disease resistance and abiotic stress tolerance. Oilseed rape (Brassica napus L.) is one of the most important oil-producing crops worldwide. To date, compositon of CAMTAs in genomes of Brassica species and role of CAMTAs in resistance to the devastating necrotrophic fungal pathogen Sclerotinia sclerotiorum are still unknown. In this study, 18 CAMTA genes were identified in oilseed rape genome through bioinformatics analyses, which were inherited from the nine copies each in its progenitors B. rapa and B. oleracea and represented the highest number of CAMTAs in a given plant species identified so far. Gene structure, protein domain organization and phylogentic analyses showed that the oilseed rape CAMTAs were structurally similar and clustered into three major groups as other plant CAMTAs, but had expanded subgroups CAMTA3 and CAMTA4 genes uniquely in rosids species occurring before formation of oilseed rape. A large number of stress response-related cis-elements existed in the 1.5 kb promoter regions of the BnCAMTA genes. BnCAMTA genes were expressed differentially in various organs and in response to treatments with plant hormones and the toxin oxalic acid (OA) secreted by S. sclerotiorum as well as the pathogen inoculation. Remarkably, the expression of BnCAMTA3A1 and BnCAMTA3C1 was drastically induced in early phase of S. sclerotiorum infection, indicating their potential role in the interactions between oilseed rape and S. sclerotiorum. Furthermore, inoculation analyses using Arabidopsis camta mutants demonstrated that Atcamta3 mutant plants exhibited significantly smaller disease lesions than wild-type and other Atcamta mutant plants. In addition, compared with wild-type plants, Atcamta3 plants accumulated obviously more hydrogen peroxide in response to the PAMP chitin and exhibited much higher expression of the CGCG-box-containing genes BAK1 and JIN1, which are essential to the PAMP triggered immunity (PTI) and/or plant resistance to pathogens including S. sclerotiorum. Our results revealed that CAMTA3 negatively regulated PTI probably by directly targeting BAK1 and it also negatively regulated plant defense through suppressing JA signaling pathway probably via directly targeting JIN1.