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Abstract The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. A multiple myeloma patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses reveal lenalidomide as a pivotal disruptor of erythropoiesis. Single-cell transcriptome analysis unveils hyperactive CD8+ T cells and impaired erythropoiesis in the patient’s bone marrow. Unexpectedly, the patient’s erythroid cells display abnormally high expression of genes in the antigen presentation pathway, particularly those for major histocompatibility class I (MHC-I) molecules. Functional assays demonstrate that lenalidomide treatment further augmented MHC-I expression in the patient’s erythroid cells. Blocking MHC-I or depleting T cells alleviates the defective erythropoiesis of PRCA, suggesting that the interaction between erythroid cells with elevated MHC-I and T cells in the bone marrow might contribute to PRCA. Taken together, our study implicates a mechanism underlying lenalidomide-induced PRCA in treating cancer patients.

Summary Due to the convenience of virtualization, the live migration of virtual machines is widely used to fulfill optimization objectives in cloud/edge computing. However, live migration may lead to side effects and performance degradation when migration is overused or an unreasonable migration process is carried out. One pressing challenge is how to capture the best opportunity for virtual machine migration. Leveraging rough sets and AI, this paper provides an innovative strategy based on Q-learning that is designed for migration decisions. The highlight of our strategy is the harmonious mechanism for applying rough sets and Q-learning. For the ABDS (adaptive boundary decision system) strategy in this paper, the exploration space of Q learning is confined by the boundary region of rough sets, while the thresholds of the boundary region can be dynamically adjusted by the reaction results from the computing cluster. The structure and mechanism of the ABDS strategy are described in this paper. The corresponding experiments show a firm advantage for the cooperation of rough sets and reinforcement learning algorithms. Considering both the energy consumption and application performance, the ABDS strategy in this paper outperforms the benchmark strategies in comprehensive performance.

Abstract Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment.

BackgroundDespite the growing availability of smoking cessation apps, low engagement and cessation rates have remained a significant challenge. To address this issue, we used a user-centered design to iteratively develop a mobile app (MO) to provide comprehensive, tailored, and evidence-based content to support smokers in their quitting journey. ObjectiveThis study examined the acceptability, use, and preliminary efficacy of the MO app for smoking cessation. Specifically, we sought to understand smokers’ preferred features, engagement, and satisfaction with MO; identify concerns in using the app and ways to improve the app; and evaluate its smoking cessation outcomes. MethodsThrough 3 cohorts, we recruited 10, 12, and 85 adult smokers who attempted to quit smoking to pilot-test the MO app between December 2019 and July 2022. Participants were instructed to complete a baseline survey, interact with the app for 6 weeks, and fill in a postsurvey at week 6. Participants in cohort 3 completed an additional postsurvey at week 12. Participants’ app use was tracked and analyzed. The primary outcome measures were participants’ 7-day point prevalence abstinence at 6 and 12 weeks. ResultsParticipants reported high levels of satisfaction with the MO app across all 3 cohorts, rating it between 4.40 and 4.76 on a scale of 5 for acceptability. Users engaged with app activities for an average of 89 to 159 times over 35 days. The most liked features of the app included “quit plan,” “tracking,” “reminders and notifications,” “MOtalks,” and “motivational quotes.” The 7-day point prevalence abstinence rate of the modified intention to treat population in cohort 3 was 58% at 6 weeks and 52% at 12 weeks. Those who interacted more frequently with app features and engaged with more diverse activities were more likely to maintain abstinence at weeks 6 and 12. For each additional time logged into the app, the odds of staying abstinent at week 12 increased by 5% (odds ratio [OR] 1.05, 95% CI 1.01-1.08). Participants who earned >5000 points during app use also had higher odds of quitting at both 6 weeks (OR 3.12, 95% CI 1.25-7.75) and 12 weeks (OR 4.65, 95% CI 1.83-11.76), compared with those who earned

Abstract Background Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains a major obstacle in ESCC management. The aim of this study was to investigate the effect of NIMA-related kinase 2 (NEK2) on radioresistance in ESCC cells and to reveal potential molecular mechanisms. Methods Human esophageal epithelial cells (HEEC) and human ESCC cell lines were obtained from the Research Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were applied to assess the proliferation ability, cell cycle, apoptosis rates, and ROS production of ESCC cells. The colony-forming assay was used to estimate the effect of NEK2 on radiosensitivity. Autophagy was investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, and transmission electron microscopy (TEM). Results In the present study, our results showed that NEK2 was associated with radioresistance, cell cycle arrest, apoptosis, ROS production, and survival of ESCC. NEK2 knockdown could significantly inhibit growth while enhancing radiosensitivity and ROS production in ESCC cells. Interestingly, NEK2 knockdown inhibited ESCC cell autophagy and reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, NEK2 bound to and regulated the stability of tripartite motif-containing protein 21 (TRIM21). The accumulation of NEK2-induced light chain 3 beta 2 (LC3B II) can be reversed by the knockdown of TRIM21. Conclusion These results demonstrated that NEK2 activated autophagy through TRIM21, which may provide a promising therapeutic strategy for elucidating NEK2-mediated radioresistance in ESCC.

Abstract Rapeseed (Brassica napus L.), accounts for nearly 16% of vegetable oil, is the world’s second produced oilseed. However, pod shattering has caused significant yield loses in rapeseed production, particularly during mechanical harvesting. The GH28 genes can promote pod shattering by changing the structure of the pod cell wall in Arabidopsis. However, the role of the GH28 gene family in rapeseed was largely unknown. Therefore, a genome-wide comprehensive analysis was conducted to classify the role of GH28 gene family on rapeseed pod shattering. A total of 37 BnaGH28 genes in the rapeseed genome were identified. These BnaGH28s can be divided into five groups (Group A-E), based on phylogenetic and synteny analysis. Protein property, gene structure, conserved motif, cis-acting element, and gene expression profile of BnaGH28 genes in the same group were similar. Specially, the expression level of genes in group A-D was gradually decreased, but increased in group E with the development of silique. Among eleven higher expressed genes in group E, two BnaGH28 genes (BnaA07T0199500ZS and BnaC06T0206500ZS) were significantly regulated by IAA or GA treatment. And the significant effects of BnaA07T0199500ZS variation on pod shattering resistance were also demonstrated in present study. These results could open a new window for insight into the role of BnaGH28 genes on pod shattering resistance in rapeseed.

Abstract Background The rose is one of the most important ornamental flowers in the world for its aesthetic beauty but can be attacked by many pests such as aphids. Aphid infestation causes tremendous damage on plant tissues leading to harmed petals and leaves. Rose cultivars express different levels of resistance to aphid infestation yet the information remains unclear. Not only that, studies about the transcriptional analysis on defending mechanisms against aphids in rose are limited so far. Results In this study, the aphid resistance of 20 rose cultivars was evaluated, and they could be sorted into six levels based on the number ratio of aphids. And then, a transcriptome analysis was conducted after aphid infestation in one high resistance (R, Harmonie) and one highly susceptibility (S, Carefree Wonder) rose cultivar. In open environment the majority of rose cultivars had the highest aphid number at May 6th or May 15th in 2020 and the resistance to infestation could be classified into six levels. Differential expression analysis revealed that there were 1,626 upregulated and 767 downregulated genes in the R cultivar and 481 upregulated and 63 downregulated genes in the S cultivar after aphid infestation. Pathway enrichment analysis of the differentially expressed genes revealed that upregulated genes in R and S cultivars were both enriched in defense response, biosynthesis of secondary metabolites (phenylpropanoid, alkaloid, and flavonoid), carbohydrate metabolism (galactose, starch, and sucrose metabolism) and lipid processing (alpha-linolenic acid and linolenic acid metabolism) pathways. In the jasmonic acid metabolic pathway, linoleate 13S-lipoxygenase was specifically upregulated in the R cultivar, while genes encoding other crucial enzymes, allene oxide synthase, allene oxide cyclase, and 12-oxophytodienoate reductase were upregulated in both cultivars. Transcription factor analysis and transcription factor binding search showed that WRKY transcription factors play a pivotal role during aphid infestation in the R cultivar. Conclusions Our study indicated the potential roles of jasmonic acid metabolism and WRKY transcription factors during aphid resistance in rose, providing clues for future research.

Deoxynivalenol (DON), a type B trichothecene mycotoxin, commonly occurs in cereal grains, and poses significant health risks to humans and animals. Numerous studies reveal its obvious toxic effects on male reproductive performance as well as its ability to transfer from the lactating mother to the suckling offspring through colostrum and milk. The objective of this study was to evaluate the toxic effect of lactational DON exposure on testicular morphology, hormonal levels, inflammation, apoptosis and proliferation of germ cells, tight junction, and sperm quality in male offspring. Sixty-six male offspring mice from lactating dams exposed to DON were euthanized at PND 21 and PND 70 to investigate the reproductive toxicity. Our results indicated that maternal DON exposure had a significant impact on the weight and volume of the testes, caused testicular histopathology, and reduced testosterone levels by downregulating expressions of StAR, CYP11A1, and CYP17A1 in male offspring. We also found that maternal DON exposure led to testicular inflammation in male offspring, which was attributed to increased levels of inflammatory markers, including IL-1β, IL-6, TNF-α, and IFN-γ. Maternal DON exposure resulted in impaired tight junctions of Sertoli cells in male offspring, as evidenced by decreased expressions of ZO-1, Occludin, and Claudin-3. In addition, maternal DON exposure caused a reduction in the number of Sertoli cells and germ cells, ultimately leading to decreased sperm count and quality in adult male offspring. Collectively, these findings provide compelling evidence that maternal exposure to DON during lactation causes testicular toxicity in both pubertal and adult male offspring.

Abstract Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a highly immunosuppressive tumor microenvironment and a typical pattern of disturbances in hepatic lipid metabolism. Long non‐coding RNAs are shown to play an important role in the regulation of gene expression, but much remains unknown between tumor microenvironment and lipid metabolism as a bridging molecule. Here, long intergenic nonprotein coding RNA 01116 (LINC01116) acts as this molecular which is frequently upregulated in HCC patients and associated with HCC progression in vitro and in vivo is identified. Mechanistically, LINC01116 stabilizes EWS RNA‐binding protein 1 (EWSR1) by preventing RAD18 E3 Ubiquitin Protein Ligase (RAD18) ‐mediated ubiquitination. The enhanced EWSR1 protein upregulates peroxisome proliferator activated receptor alpha (PPARA) and fatty acid binding protein1 (FABP1) expression, a long‐chain fatty acid (LCFA) transporter, and thus cancer cells outcompete T cells for LCFAs, especially linoleic acid, for seeding their own growth, leading to T cell malfunction and HCC malignant progression. In a preclinical animal model, the blockade of LINC01116 leads to enhanced efficacy of anti‐PD1 treatment accompanied by increased cytotoxic T cell and decreased exhausted T cell infiltration. Collectively, LINC01116 is an immunometabolic lncRNA and the LINC01116‐EWSR1‐PPARA‐FABP1 axis may be targetable for cancer immunotherapy.

Abstract Background Global health activities (GHAs) reduce health disparities by promoting medical education, professional development, and resource sharing between high- and low- to middle-income countries (HICs and LMICs). Virtual global health activities facilitated continuity and bidirectionality in global health during the COVID-19 pandemic. While virtual engagement holds potential for promoting equity within partnerships, research on equitable access to and interest in virtual global health activities is limited. Methods We conducted a cross-sectional, online, mixed-methods survey from January to February 2022 examining access to virtual activities before and during the pandemic across resource settings. Eligible participants were participants or facilitators of global health activities. Closed- and open-ended questions elicited participants’ access to and interest in virtual global health engagement. Results We analyzed 265 surveys from respondents in 45 countries (43.0% LMIC vs. HIC 57.0%). HIC respondents tended to report greater loss of in-person access due to the pandemic at their own institutions (16 of 17 queried GHAs), while LMIC respondents tended to report greater loss of in-person activities at another institution (9 of 17 queried GHAs). Respondents from LMICs were more likely to gain virtual access through another organization for all 17 queried VGHAs. HIC respondents had significantly more access to global health funding through their own organization (p

[Introduction] Accurate and efficient short-term electricity load forecasting is a prerequisite for ensuring the safe and reliable operation of power system, and it is also the basis for the rational arrangement of power generation plans in the power grid. Therefore, studying the relationship between meteorology and electricity load is of great significance for load forecasting. [Method] Based on the electricity load data at 15 min intervals during the period between January 1 of 2013 and December 31 of 2021 provided by the State Grid Hebei Electric Power Co., Ltd. as well as the corresponding meteorological observation data of Shijiazhuang station, this paper analyzed the temporal variation characteristics of daily peak electricity load in Shijiazhuang, and in particular, the meteorological conditions corresponding to the samples with a daily peak electricity load that was 10% higher than that of the previous day were analyzed. The Spearman's rank correlation method was used to analyze the correlation between daily peak electricity load in Shijiazhuang and the meteorological factors of the previous day, and significantly correlated meteorological factors were identified. The response curves of the significantly correlated meteorological factors to the next day's peak electricity load were drawn using the smooth curve fitting method, and the analysis revealed the changing trend of daily peak electricity load with the variations of meteorological factors, as well as the response thresholds. For different threshold ranges, the relative risk of meteorological factors to the changes of the daily peak electricity load was calculated based on the Poisson distribution. On this basis, the variation magnitudes of daily peak electricity load caused by per unit change in each meteorological factor within different threshold ranges in Shijiazhuang were calculated, that is, the quantitative impacts of the changes in different meteorological factors on the variation of daily peak electricity load were revealed. [Result] Taking temperature as an example, when the daily average, maximum and minimum temperatures are higher (lower) than the thresholds, the relative risk to the next day′s peak electricity load increases (decreases) by 2.25% (0.62%), 1.92% (0.57%) and 2.07% (0.60%) respectively for every 1 °C increase in temperature. [Conclusion] Based on the relative risk of different meteorological factors to daily peak electricity load in Shijiazhuang, a method for predicting the next day′s peak electricity load is proposed. The test performed using the daily electricity load and meteorological data of Shijiazhuang in 2022 reveals that the prediction effect can meet the needs of daily electricity meteorological service.

Abstract Background Accurately distinguishing between invasive thymic epithelial tumors (TETs) and anterior mediastinal lymphoma before surgery is crucial for subsequent treatment choices. But currently, the diagnosis of invasive TET is sometimes difficult to distinguish from anterior mediastinal lymphoma. Objective To assess the application of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) in the differential diagnosis of TETs and anterior mediastinal lymphomas. Methods 18F-FDG PET/CT images of 133 invasive TETs and anterior mediastinal lymphomas patients were retrospectively analyzed. In particular, the tumor’s longest diameter and maximum standardized uptake value (SUVmax) were evaluated. The SUVmax and longest diameter values of the two groups were analyzed by using the receiver operating characteristic (ROC) curve to determine the optimal threshold and diagnostic efficiency. Results Age, myasthenia gravis, SUVmax and tumor longest diameter differed significantly between invasive TETs and anterior mediastinal lymphomas patients. The tumor location, calcification, relationship with adjacent vessels and distant metastasis differed significantly between the groups. The ROC analysis showed an AUC for SUVmax and tumor longest diameter of 0.841 and 0.737. Respectively, the cutoff values with the best diagnostic performance were 9.65 (sensitivity: 77.78%, specificity: 81.97%) and 6.65 (sensitivity: 80.56%, specificity: 62.30%) for SUVmax and tumor longest diameter. The diagnostic model of SUVmax, calcification, relationship with surrounding blood vessels, lymph node metastasis and lung metastasis in the highest AUC of 0.935 (sensitivity: 90.16%, specificity: 88.89%). In addition, we incorporated splenic involvement and metastatic sub-diaphragmatic lymph node into Model 2 as a new predictive model 3 for differential diagnosis and found a significant improvement in the diagnostic performance of Model 3. Conclusion The diagnostic model composed of 18F-FDG PET parameters is improving the differential diagnosis of invasive TETs and anterior mediastinal lymphomas.

Panax ginseng C. A. Meyer is a dual-purpose plant for medicine and food, its polysaccharide is considered as an immune enhancer. Four polysaccharides, WGP-20-F, WGP-40-F, WGP-60-F and WGP-80-F were obtained from ginseng via water extraction and gradient ethanol precipitation with different molecular weights (Mw) of 1.720 × 106, 1.434 × 106, 4.225 × 104 and 1.520 × 104 Da, respectively. WGP-20-F and WGP-40-F which with higher Mw and a triple-helix structure are glucans composed of 4-ɑ-Glcp, do not show remarkable immunoregulatory effects. WGP-60-F and WGP-80-F are heteropolysaccharides mainly composed of 4-ɑ-Glcp and also contain t-ɑ-Araf, 5-ɑ-Araf and 3,5-ɑ-Araf. They are spherical branched conformations without a triple-helix structure and can effectively increase the index of immune organs, lymphocyte proliferation, activate macrophages to regulate the immune system in mice and further enhance immune functions by improving delayed-type hypersensitivity reaction and antibody response. These results indicated that WGP-60-F and WGP-80-F could be used as potential immune enhancers, and gradient ethanol precipitation can be applied for the preparation of ginseng bioactive polysaccharide.

Background: Hepatocellular carcinoma (HCC) is a multistep process involving sophisticated genetic, epigenetic, and transcriptional changes. However, studies on microRNA (miRNA)'s regulatory effects of N6-methyladenosine (m6A) modifications on HCC progression are limited. Methods: Cell Counting Kit-8 (CCK-8), clone formation, and Transwell assays were used to investigate changes in cancer cell proliferation, invasion, and migration. RNA m6A levels were verified using methylated RNA immunoprecipitation. Luciferase reporter assay was used to study the potential binding between miRNAs and mRNA. A mouse tumor transplant model was established to study the changes in tumor progression. Results: Follistatin-like 5 (FSTL5) was significantly downregulated in HCC and inhibited its further progression. Additionally, methyltransferase-like 3 (METTL3) reduced FSTL5 mRNA stability in an m6A-YTH domain family 2(YTHDF2)-dependent manner. Functional experiments revealed that METTL3 downregulation inhibited HCC progression by upregulating FSTL5 in vitro and in vivo. Luciferase reporter assay verified that miR-186-5p directly targets METTL3. Additionally, miR-186-5p inhibits the proliferation, migration, and invasion of HCC cells by downregulating METTL3 expression. Conclusions: The miR-186-5p/METTL3/YTHDF2/FSTL5 axis may offer new directions for targeted HCC therapy.

Abstract Despite its involvement in various cancers, the function of the deubiquitinase USP1 (ubiquitin-specific protease 1) is unexplored in cholangiocarcinoma (CCA). In this study, we provide evidence that USP1 promotes CCA progression through the stabilization of Poly (ADP-ribose) polymerase 1 (PARP1), consistent with the observation that both USP1 and PARP1 are upregulated in human CCA. Proteomics and ubiquitylome analysis of USP1-overexpressing CCA cells nominated PARP1 as a top USP1 substrate. Indeed, their direct interaction was validated by a series of immunofluorescence, co-immunoprecipitation (CO-IP), and GST pull-down assays, and their interaction regions were identified using deletion mutants. Mechanistically, USP1 removes the ubiquitin chain at K197 of PARP1 to prevent its proteasomal degradation, with the consequent PARP1 stabilization being necessary and sufficient to promote the growth and metastasis of CCA in vitro and in vivo. Additionally, we identified the acetyltransferase GCN5 as acetylating USP1 at K130, enhancing the affinity between USP1 and PARP1 and further increasing PARP1 protein stabilization. Finally, both USP1 and PARP1 are significantly associated with poor survival in CCA patients. These findings describe PARP1 as a novel deubiquitination target of USP1 and a potential therapeutic target for CCA.

Abstract Background Human hydroxysteroid dehydrogenase-like 2 (HSDL2), which regulates cancer progression, is involved in lipid metabolism. However, the role of HSDL2 in cholangiocarcinoma (CCA) and the mechanism by which it regulates CCA progression by modulating ferroptosis are unclear. Methods HSDL2 expression levels in CCA cells and tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The overall survival and disease-free survival of patients with high vs. low HSDL2 expression were evaluated using Kaplan-Meier curves. The proliferation, migration, and invasion of CCA cells were assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2′-deoxyuridine DNA synthesis, and transwell assays. The effect of p53 on tumor growth was explored using a xenograft mouse model. The expression of SLC7A11 in patients with CCA was analyzed using immunofluorescence. Ferroptosis levels were measured by flow cytometry, malondialdehyde assay, and glutathione assay. HSDL2-regulated signaling pathways were analyzed by transcriptome sequencing. The correlation between p53 and SLC7A11 was assessed using bioinformatics and luciferase reporter assays. Results HSDL2 expression was lower in primary human CCA tissues than in matched adjacent non-tumorous bile duct tissues. HSDL2 downregulation was a significant risk factor for shorter overall survival and disease-free survival in patients with CCA. In addition, HSDL2 knockdown enhanced the proliferation, migration, and invasion of CCA cells. The transcriptome analysis of HSDL2 knockdown cells showed that differentially expressed genes were significantly enriched in the p53 signaling pathway, and HSDL2 downregulation increased SLC7A11 levels. These findings were consistent with the qRT-PCR and western blotting results. Other experiments showed that p53 expression modulated the effect of HSDL2 on CCA proliferation in vivo and in vitro and that p53 bound to the SLC7A11 promoter to inhibit ferroptosis. Conclusions HSDL2 knockdown promotes CCA progression by inhibiting ferroptosis through the p53/SLC7A11 axis. Thus, HSDL2 is a potential prognostic marker and therapeutic target for CCA.

Differential privacy, a cornerstone of privacy-preserving techniques, plays an indispensable role in ensuring the secure handling and sharing of sensitive data analysis across domains such as in census, healthcare, and social networks. Histograms, serving as a visually compelling tool for presenting analytical outcomes, are widely employed in these sectors. Currently, numerous algorithms for publishing histograms under differential privacy have been developed, striving to balance privacy protection with the provision of useful data. Nonetheless, the pivotal challenge concerning the effective enhancement of precision for small bins (those intervals that are narrowly defined or contain a relatively small number of data points) within histograms has yet to receive adequate attention and in-depth investigation from experts. In standard DP histogram publishing, adding noise without regard for bin size can result in small data bins being disproportionately influenced by noise, potentially severely impairing the overall accuracy of the histogram. In response to this challenge, this paper introduces the SReB_GCA sanitization algorithm designed to enhance the accuracy of small bins in DP histograms. The SReB_GCA approach involves sorting the bins from smallest to largest and applying a greedy grouping strategy, with a predefined lower bound on the mean relative error required for a bin to be included in a group. Our theoretical analysis reveals that sorting bins in ascending order prior to grouping effectively prioritizes the accuracy of smaller bins. SReB_GCA ensures strict ϵ-DP compliance and strikes a careful balance between reconstruction error and noise error, thereby not only initially improving the accuracy of small bins but also approximately optimizing the mean relative error of the entire histogram. To validate the efficiency of our proposed SReB_GCA method, we conducted extensive experiments using four diverse datasets, including two real-life datasets and two synthetic ones. The experimental results, quantified by the Kullback–Leibler Divergence (KLD), show that the SReB_GCA algorithm achieves substantial performance enhancement compared to the baseline method (DP_BASE) and several other established approaches for differential privacy histogram publication.

Digital quantum simulation has broad applications in approximating unitary evolution of Hamiltonians. In practice, many simulation tasks for quantum systems focus on quantum states in the low-energy subspace instead of the entire Hilbert space. In this paper, we systematically investigate the complexity of digital quantum simulation based on product formulas in the low-energy subspace. We show that the simulation error depends on the effective low-energy norm of the Hamiltonian for a variety of digital quantum simulation algorithms and quantum systems, allowing improvements over the previous complexities for full unitary simulations even for imperfect state preparations due to thermalization. In particular, for simulating spin models in the low-energy subspace, we prove that randomized product formulas such as qDRIFT and random permutation require smaller Trotter numbers. Such improvement also persists in symmetry-protected digital quantum simulations. We prove a similar improvement in simulating the dynamics of power-law quantum interactions. We also provide a query lower bound for general digital quantum simulations in the low-energy subspace.

Abstract Background Vernalization, as a vital process in the life cycle of winter cereal, has important effects on floral organ formation and flowering time. Many morphological changes together with molecular changes occur during the vernalization period. Here, we used transcriptome sequencing to analyze the transcriptomic changes in wheat leaves before, during and after vernalization using the winter wheat cultivar ‘Shiluan02-1’. Results A total of 16,370 differentially expressed genes were obtained across different vernalization periods. Gene Ontology enrichment analysis revealed that photoperiodism, photoprotection, photosynthesis, lipid transport and biosynthetic process, and chlorophyll metabolic process were closely related to vernalization. In addition, AP2/ERF, C2H2, bHLH, WRKY, MYB, MYB-related, and NAC transcription factors were significantly enriched during vernalization, and the transcription factor expression patterns suggested the intricate regulation of transcription factor modules in plant vernalization pathways. Analysis of gene expression patterns of the MADS-box transcription factor genes showed different expression patterns during vernalization phases, among which VERNALIZATION1 (VRN1) genes were found to gradually increase during vernalization periods from V0 to V35, while decline in the V42 phase, then increase after vernalization. The Tavrt-2 gene cooperated with Tavrn1 to regulate flowering induced by vernalization, and its expression level was rapidly increased by vernalization but declined in the V42 phase and then increased after vernalization. Some genes from the ICE-CBF-COR pathway were also identified, and additional analysis indicated that some key genes related to phytohormone biosynthesis and signal transduction were enriched during the vernalization period, such as gibberellic acid, ethylene, abscisic acid and jasmonic acid biosynthesis and signaling pathway genes. Conclusions Our study provides valuable molecular information for future studies on wheat vernalization regulation and also serves as an excellent reference for future wheat breeding.

The identification of stable quantitative trait locus (QTL) for yield-related traits and tightly linked molecular markers is important for improving wheat grain yield. In the present study, six yield-related traits in a recombinant inbred line (RIL) population derived from the Zhongmai 578/Jimai 22 cross were phenotyped in five environments. The parents and 262 RILs were genotyped using the wheat 50K single nucleotide polymorphism (SNP) array. A high-density genetic map was constructed with 1 501 non-redundant bin markers, spanning 2 384.95 cM. Fifty-three QTLs for six yield-related traits were mapped on chromosomes 1D (2), 2A (9), 2B (6), 2D, 3A (2), 3B (2), 4A (5), 4D, 5B (8), 5D (2), 7A (7), 7B (3) and 7D (5), which explained 2.7–25.5% of the phenotypic variances. Among the 53 QTLs, 23 were detected in at least three environments, including seven for thousand-kernel weight (TKW), four for kernel length (KL), four for kernel width (KW), three for average grain filling rate (GFR), one for kernel number per spike (KNS) and four for plant height (PH). The stable QTLs QKl.caas-2A.1, QKl.caas-7D, QKw.caas-7D, QGfr.caas-2B.1, QGfr.caas-4A, QGfr.caas-7A and QPh.caas-2A.1 are likely to be new loci. Six QTL-rich regions on 2A, 2B, 4A, 5B, 7A and 7D, showed pleiotropic effects on various yield traits. TaSus2-2B and WAPO-A1 are potential candidate genes for the pleiotropic regions on 2B and 7A, respectively. The pleiotropic QTL on 7D for TKW, KL, KW and PH was verified in a natural population. The results of this study enrich our knowledge of the genetic basis underlying yield-related traits and provide molecular markers for high-yield wheat breeding.

Abstract Background The main surgical procedure for Bismuth‒Corlette III–IV hilar cholangiocarcinoma (HCCA) is hemihepatectomy/extended hemihepatectomy. However, many patients have no opportunity for surgery due to having an insufficient remnant liver volume. Preservation of more liver volume on the premise of ensuring R0 resection is the goal. Mesohepatectomy with caudate lobectomy may be a new method to meet these requirements. Methods The clinical data of 41 patients with Bismuth‒Corlette III–IV HCCA, including 18 patients who underwent mesohepatectomy with caudate lobectomy (the mesohepatectomy group) and 23 patients who underwent hemihepatectomy or extended hemihepatectomy (the hemihepatectomy group), were analyzed retrospectively. The perioperative indicators and prognostic survival time between the two groups were analyzed. Results The mesohepatectomy group was compared with the hemihepatectomy group, and the operation time was 7.95 ± 1.2 vs. 7.15 ± 1.5 h (P > 0.05); the intraoperative blood loss was 600.0 ± 153.4 vs. 846.1 ± 366.8 mL (P 0.05). The postoperative complications of the two groups included bile leakage (22.2% vs. 21.7%), pleural effusion (11.1% vs. 8.7%), and fever (16.7% vs. 8.7%), with no significant differences in the incidences (P > 0.05). The 1-, 3-, and 5-year survival rates of the two groups were 87.5%, 55.7%, 27.8% and 83.5%, 56.1%, 24.5%, respectively, with no significant differences (P > 0.05). Conclusions Mesohepatectomy with caudate lobectomy can preserve more functional liver volume while ensuring the bile duct margin. It can be applied as the surgical treatment of Bismuth‒Corlette III–IV HCCA.

Cyclic air braking is a key factor affecting the safe operation of trains on long downhill sections. However, a train’s cycle braking strategy is constrained by multiple factors such as driving environment, speed, and air-refilling time. A Q-learning algorithm-based cyclic braking strategy for a heavy haul train on long downhill sections is proposed to address this challenge. First, the operating environment of a heavy haul train on long downhill sections is designed, considering various constraint parameters, such as the characteristics of special operating routes, allowable operating speeds, and train tube air-refilling time. Second, the operating status and braking operation of a heavy haul train on long downhill sections are discretized in order to establish a Q-table based on state–action pairs. The training of algorithm performance is achieved by continuously updating Q-tables. Finally, taking the heavy haul train formation as the study object, actual line data from the Shuozhou–Huanghua Railway are used for experimental simulation, and different hyperparameters and entry speed conditions are considered. The results show that the safe and stable cyclic braking of a heavy haul train on long downhill sections is achieved. The effectiveness of the Q-learning control strategy is verified.

Cyclic air braking is a key element for ensuring safe train operation when running on a long and steep downhill railway section. In reality, the cyclic braking performance of a train is affected by its operating environment, speed and air-refilling time. Existing optimization algorithms have the problem of low learning efficiency. To solve this problem, an intelligent control method based on the deep Q-network (DQN) algorithm for heavy-haul trains running on long and steep downhill railway sections is proposed. Firstly, the environment of heavy-haul train operation is designed by considering the line characteristics, speed limits and constraints of the train pipe’s air-refilling time. Secondly, the control process of heavy-haul trains running on long and steep downhill sections is described as the reinforcement learning (RL) of a Markov decision process. By designing the critical elements of RL, a cyclic braking strategy for heavy-haul trains is established based on the reinforcement learning algorithm. Thirdly, the deep neural network and Q-learning are combined to design a neural network for approximating the action value function so that the algorithm can achieve the optimal action value function faster. Finally, simulation experiments are conducted on the actual track data pertaining to the Shuozhou–Huanghua line in China to compare the performance of the Q-learning algorithm against the DQN algorithm. Our findings revealed that the DQN-based intelligent control strategy decreased the air braking distance by 2.1% and enhanced the overall average speed by more than 7%. These experiments unequivocally demonstrate the efficacy and superiority of the DQN-based intelligent control strategy.

Urbanization has accelerated in China, resulting in a noticeable conflict between urban expansion and land use/land cover (LULC). This issue can exacerbate ecological and developmental problems in urban neighborhoods, so it is crucial to explore the relationship between long-term urban expansion and LULC spatial and temporal transitions. We first defined urban built-up areas in terms of human economic activity and then used spatial measures to examine urban expansion and spatio-temporal changes in 25 LULC classes by analyzing 369 cities across China. Our findings indicate that China’s urban built-up areas expanded 9.1 times between 1995 and 2020, with the fastest growth rate occurring between 1995 and 2005 at about 16%. We observed a negative association between China’s urban built-up area and dry farming land, forests, and grassland in that order, with grassland exhibiting the weakest correlation. The negative correlation between urban built-up areas and paddy fields became positive after 2010, while the positive correlation with reservoirs and canals became negative after 2015. This study utilized spatial measures to demonstrate the spatial heterogeneity of urban expansion in China and explored the extent to which different LULC area changes explained urban expansion. We provide a reference for decision-making efforts on land management and sustainable use in urban areas.

Abstract It is difficult to directly obtain pathological diagnosis of perihilar cholangiocarcinoma (pCCA). Analysis of bile in the pCCA microenvironment, based on metabolomics and statistical methods, can help in clinical diagnosis. Clinical information, bile samples, blood liver function, blood CA199, CEA, and other indicators were collected from 33 patients with pCCA and 16 patients with gallstones. Bile samples were analyzed using untargeted metabolomics methods. A combination of multivariate and univariate analyses were used to screen for potential differential metabolites Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and differential metabolite remodeling, we explored changes in the pCCA pathway and potential therapeutic targets. There were significant differences in patient blood TBIL, ALT, AST, TBA, CA19-9, and CEA indices (p

Background and Aim: World Health Organization (WHO) grade 4 glioma is a malignancy of the central nervous system characterized by refractoriness to treatment and a high mortality rate. Isocitrate dehydrogenase (IDH) mutation is a crucial molecular event for the classification of glioma and associated with prognosis and exploring genetic and molecular differences between IDH mutant and wildtype glioma is crucial. The aim of this study was to investigate the prognostic gene between IDH mutant and wildtype WHO grade 4 glioma and its functional significance. Materials and Methods: The mRNA expression profile data of WHO grade 4 glioma were downloaded from the Gene Expression Omnibus and Chinese Glioma Genome Atlas databases. Bioinformatic analysis was performed to identify the differentially expressed genes between IDH1-mutant and wildtype WHO grade 4 glioma. Survival analysis, functional enrichment analysis, immune cell infiltration evaluation, and in vitro experimental validation were conducted to evaluate the prognostic and functional significance of Fras1-related extracellular matrix 3 (FREM3). This study was approved by the Institutional Ethics Committee of Xinqiao Hospital, Third Military Medical University (approval No. 2021-Y068-01). Results: Elevated expression of FREM3 in IDH1-mutant WHO grade 4 astrocytoma predicted favorable prognosis in glioma. FREM3 was negatively associated with epithelial–mesenchymal transition (EMT), angiogenesis, and hypoxia; notably, low expression of FREM3 was associated with a higher degree of immune cell infiltration. In vitro experiments demonstrated that high FREM3 expression might attenuate the process of EMT and cellular proliferation in glioma. Conclusions: The gene FREM3 plays a major role in IDH1-mutant WHO grade 4 glioma and elevated FREM3 predicts a favorable prognosis of glioma. Further investigation on FREM3 is warranted to elucidate the mechanisms underlying the malignant evolution of glioma.

Abstract Background Biliary fistula is a common but serious complication after radical resection of hilar cholangiocarcinoma. We aimed to evaluate the influencing factors of biliary fistula after radical resection, to provide insights to the clinical treatment of hilar cholangiocarcinoma. Methods Patients undergoing radical resection of hilar cholangiocarcinoma from January 1, 2015 to March 31, 2022 were selected. Patients’ personnel characteristics and laboratory test results of patients with and without biliary fistula were collected and compared. Logistic regression analyses were conducted to evaluate the associated risk factors of biliary fistula. Results 160 patients undergoing radical resection of hilar cholangiocarcinoma were included, the incidence of postoperative biliary fistulas was 20.63%. There were significant differences in the age, preoperative cholangitis and number of biliary anastomosis between biliary fistula and no biliary fistula patients (all p

Inflammatory bowel disease (IBD) is a chronic, recurrent, and refractory inflammatory disease of the gastrointestinal tract, accompanied by inflammatory cell infiltration and damage to the intestinal mucosa, with a certain risk of cancer. A large number of studies have shown that dietary fiber, as a prebiotic, has significant effects in improving intestinal flora structure, strengthening intestinal barrier function, alleviating intestinal inflammation and other aspects, with multiple nutritional and health functions, showing great potential in the intervention of IBD, but the mechanism of action remains unclear. In addition, DFs can be classified into soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) according to their water solubility, which have different characteristics and effects on IBD. Therefore, this paper reviews the basic principles, existing evidence and mechanism of SDF and IDF in the prevention and treatment of IBD, and comprehensively analyzes DFs intervention strategies for IBD, so as to provide reference for further research, development and application of DFs.

BackgroundHepatocellular carcinoma (HCC) represents a complex ailment characterized by an unfavorable prognosis in advanced stages. The involvement of immune cells in HCC progression is of significant importance. Moreover, metastasis poses a substantial impediment to enhanced prognostication for HCC patients, with anoikis playing an indispensable role in facilitating the distant metastasis of tumor cells. Nevertheless, limited investigations have been conducted regarding the utilization of anoikis factors for predicting HCC prognosis and assessing immune infiltration. This present study aims to identify hepatocellular carcinoma-associated anoikis-related genes (ANRGs), establish a robust prognostic model for HCC, and delineate distinct immune characteristics based on the anoikis signature. Cell migration and cytotoxicity experiments were performed to validate the accuracy of the ANRGs model.MethodsConsensus clustering based on ANRGs was employed in this investigation to categorize HCC samples obtained from both TCGA and Gene Expression Omnibus (GEO) cohorts. To assess the differentially expressed genes, Cox regression analysis was conducted, and subsequently, prognostic gene signatures were constructed using LASSO-Cox methodology. External validation was performed at the International Cancer Genome Conference. The tumor microenvironment (TME) was characterized utilizing ESTIMATE and CIBERSORT algorithms, while machine learning techniques facilitated the identification of potential target drugs. The wound healing assay and CCK-8 assay were employed to evaluate the migratory capacity and drug sensitivity of HCC cell lines, respectively.ResultsUtilizing the TCGA-LIHC dataset, we devised a nomogram integrating a ten-gene signature with diverse clinicopathological features. Furthermore, the discriminative potential and clinical utility of the ten-gene signature and nomogram were substantiated through ROC analysis and DCA. Subsequently, we devised a prognostic framework leveraging gene expression data from distinct risk cohorts to predict the drug responsiveness of HCC subtypes.ConclusionIn this study, we have established a promising HCC prognostic ANRGs model, which can serve as a valuable tool for clinicians in selecting targeted therapeutic drugs, thereby improving overall patient survival rates. Additionally, this model has also revealed a strong connection between anoikis and immune cells, providing a potential avenue for elucidating the mechanisms underlying immune cell infiltration regulated by anoikis.

Owing to the excellent mechanical performance, the metal foam sandwich structures have potential applications in the design of protective equipment, which can improve the impact resistance of engineering structures. In this paper, the nonlinear finite element model is employed to investigate the dynamic behaviors of metal foam sandwich beam (MFSB), and the accuracy of the finite element method is verified by repeated impact tests. In addition, the effects of impact location and face thickness on the dynamic behavior of the MFSB are examined. Results show that, as the distance from the impact position to the middle span of the beam increases, the deflections of face sheets decrease gradually, and the loading and unloading stiffness increases. The thickness of front face sheet affects the depth of indentation, while the total thickness of the front and back face sheets decides the overall deformation, loading and unloading stiffness. Overall, as the impact number increases, the influences of impact location and face thickness on the dynamic behavior of MFSB enhances gradually.

Ice-strengthened ships inevitably suffer from ice floe impacts during navigation in icy regions. Under some extreme-ice-impact loadings, the ship structure will experience plastic deformations. The magnitude of plastic deformation is highly correlated with the ice floe-impact energy level. During most ice impacts, only the ship’s plate undergoes minor plastic deformation. Considering that the structure still has a high structural strength with a minor permanent deformation, developing a structural plastic design method for polar ships has become a hot research issue in current studies. Therefore, in this paper, based on the rigid-plastic theory and the ice-crushing-energy approach, an experimentally verified theoretical model for predicting plastic deformations of the vertical-side plate of polar ship subjected to ice floe impacts was established. According to the analytical solutions of the plastic deformation, the plastic design formula to determine the plating thickness of ice-strengthened ships subjected to ice floe impacts was further derived based on the plastic design criteria. In addition, the parameter analysis of ice strength described by the ice pressure–area relationship, allowable-permanent-set parameter, impact energy and ice shape were conducted, and plating-thickness design curves with different design parameters were given. The design of plating thickness is very sensitive to the determinations of the allowable-permanent set and ice pressure–area curves. The designed plating thickness decreased with the increase of the allowable-permanent set. Moreover, a comparative analysis of the designed plating thickness for ice floe impact and rigid-mass impact was also carried out. Under the same impact conditions, due to energy absorption caused by ice damage, the designed thickness of the plate for rigid-mass impact was much larger than that for the ice impact. It is necessary to consider the impact-induced ice damage and energy dissipation in a structural design, instead of using rigid impact loads for conservative design. The research in this paper can provide some useful references for the structural design of ice-strengthened ships subject to ice floe impacts.

Abstract The incidence of hepatocellular carcinoma (HCC) is increasing in the world. However, its role and underlying molecular mechanism in HCC progression remain unclear. We found that CYB5A plays a key role in HCC metastasis by inhibiting the JAK1/STAT3 pathway through binding to STOML2. CYB5A combined with STOML2 can predict the outcome of patients. To demonstrate the effect of CYB5A on JAK1 inhibitor function, we applied Ruxolitinib in metastatic tumors with high CYB5A expression and found that it slowed disease progression and prolonged survival in mice. To the best of our knowledge, this study is the first to report the Ruxolitinib effect on the metastatic ability of HCC cells in vivo and in vitro.

Lactation is a unique physiological process to produce and secrete milk. Deoxynivalenol (DON) exposure during lactation has been demonstrated to affect adversely the growth development of offspring. However, the effects and potential mechanism of DON on maternal mammary glands remain largely unknown. In this study, we found the length and area of mammary glands were significantly reduced after DON exposure on lactation day (LD) 7 and LD 21. RNA-seq analysis results showed that the differentially expressed genes (DEGs) were significantly enriched in acute inflammatory response and HIF-1 signaling pathway, which led to an increase of myeloperoxidase activity and inflammatory cytokines. Furthermore, lactational DON exposure increased blood-milk barrier permeability by reducing the expression of ZO-1 and Occludin, promoted cell apoptosis by upregulating the expression of Bax and cleaved Caspase-3 and downregulating the expression of Bcl-2 and PCNA. Additionally, lactational DON exposure significantly decreased serum concentration of prolactin, estrogen, and progesterone. All these alterations eventually resulted in a decrease of β-casein expression on LD 7 and LD 21. In summary, our findings indicated that lactational exposure to DON caused lactation-related hormone disorder and mammary gland injury induced by inflammatory response and blood-milk barrier integrity impairment, ultimately resulting in lower production of β-casein.

Objective Our goal is to establish the feasibility of using an artificially intelligent chatbot in diverse healthcare settings to promote COVID-19 vaccination. Methods We designed an artificially intelligent chatbot deployed via short message services and web-based platforms. Guided by communication theories, we developed persuasive messages to respond to users’ COVID-19-related questions and encourage vaccination. We implemented the system in healthcare settings in the U.S. between April 2021 and March 2022 and logged the number of users, topics discussed, and information on system accuracy in matching responses to user intents. We regularly reviewed queries and reclassified responses to better match responses to query intents as COVID-19 events evolved. Results A total of 2479 users engaged with the system, exchanging 3994 COVID-19 relevant messages. The most popular queries to the system were about boosters and where to get a vaccine. The system's accuracy rate in matching responses to user queries ranged from 54% to 91.1%. Accuracy lagged when new information related to COVID emerged, such as that related to the Delta variant. Accuracy increased when we added new content to the system. Conclusions It is feasible and potentially valuable to create chatbot systems using AI to facilitate access to current, accurate, complete, and persuasive information on infectious diseases. Such a system can be adapted to use with patients and populations needing detailed information and motivation to act in support of their health.

Due to the asymmetry of quantum errors, phase-shift errors are more likely to occur than qubit-flip errors. Consequently, there is a need to develop asymmetric quantum error-correcting (QEC) codes that can safeguard quantum information transmitted through asymmetric channels. Currently, a significant body of literature has investigated the construction of asymmetric QEC codes. However, the asymmetry of most QEC codes identified in the literature is limited by the dual-containing condition within the Calderbank-Shor-Steane (CSS) framework. This limitation restricts the exploration of their full potential in terms of asymmetry. In order to enhance the asymmetry of asymmetric QEC codes, we utilize entanglement-assisted technology and exploit the algebraic structure of cyclotomic cosets of constacyclic codes to achieve this goal. In this paper, we generalize the decomposition method of the defining set for constacyclic codes and apply it to count the number of pre-shared entangled states in order to construct four new classes of asymmetric entanglement-assisted quantum maximal-distance separable (EAQMDS) codes that satisfy the asymmetric entanglement-assisted quantum Singleton bound. Compared with the codes existing in the literature, the lengths of the constructed EAQMDS codes and the number of pre-shared entangled states are more general, and the codes constructed in this paper have greater asymmetry.

ABSTRACT: With the large-scale and intensive development of pigeon breeding industry and the improvement of production level, stress factors have an important impact on the immune, antioxidant capacity, and productivity of pigeons. In this study, the extenuating effect of Astragalus, Epimedium, and Ligustrum lucidum (AEF) on the antioxidant, production performance, and immune mechanism was investigated in breeding pigeons. Eighty pairs of 11-month-old healthy breeding pigeons with the same egg production batch were randomly divided into 4 groups: control group (C group), treated with AEF (AEF group), in restraint stress (S group) and treated with AEF and in restraint stress (S+AEF group). Results showed that AEF reduces weight loss during lactation and increases spleen weight, increased IgA, IgG, T4, GSH-Px, and SOD in serum and decreased T3 and MDA (P < 0.05). Furthermore, treatment with AEF declined HSP60, HSP70, HSP90, GR levels in liver and cFOS, GR mRNA levels in the Hypothalamus, GR mRNA levels in the pituitary (P < 0.05). Meanwhile, the results of the intestine studies showed that AEF promoted relative abundances of Firmicutes and relieve intestinal injury in the colon of pigeons. These results indicated AEF enhanced stress resistance, immunity, production performance and antioxidant capacity of pigeons.

Calmodulin (CaM) and calmodulin-like (CML) genes are widely involved in plant growth and development and mediating plant stress tolerance. However, the whole genome scale studies about CaM and CML gene families have not been done in wheat, and the possible functions of most wheat CaM/CML gene members are still unknown. In this study, a total of 18 TaCaM and 230 TaCML gene members were identified in wheat genome. Among these genes, 28 TaCaM/CML gene members have 74 duplicated copies, while 21 genes have 48 transcript variants, resulting in 321 putative TaCaM/CML transcripts totally. Phylogenetic tree analysis showed that they can be classified into 7 subfamilies. Similar gene structures and protein domains can be found in members of the same gene cluster. The TaCaM/CML genes were spread among all 21 chromosomes with unbalanced distributions, while most of the gene clusters contained 3 homoeologous genes located in the same homoeologous chromosome group. Synteny analysis showed that most of TaCaM/CMLs gene members can be found with 1–4 paralogous genes in T. turgidum and Ae. Tauschii. High numbers of cis-acting elements related to plant hormones and stress responses can be observed in the promoters of TaCaM/CMLs. The spatiotemporal expression patterns showed that most of the TaCaM/TaCML genes can be detected in at least one tissue. The expression levels of TaCML17, 21, 30, 50, 59 and 75 in the root or shoot can be up-regulated by abiotic stresses, suggesting that TaCML17, 21, 30, 50, 59 and 75 may be related with responses to abiotic stresses in wheat. The spatiotemporal expression patterns of TaCaM/CML genes indicated they may be involved widely in wheat growth and development. Our results provide important clues for exploring functions of TaCaMs/CMLs in growth and development as well as responses to abiotic stresses in wheat in the future.

Simultaneous targeting of BCL-xL and BCL-2 is an attractive approach for cancer treatment. Based on information gained by computational structure modelling, the authors develop a PROTAC that induces degradation of both BCL-xL and BCL-2 and effectively targets BCL-xL/2-dependent leukaemia cells.

Marine structures are frequently subjected to repeated-impact loadings during navigation and operation. The structural damage accumulates, resulting in structural failures and even serious accidents. Experiments were performed using an INSTRON drop tower to investigate the dynamic behaviors of aluminum foam sandwich beams (AFSBs) subjected to repeated impacts; moreover, the mechanism of plastic deformation and damage and the energy absorption characteristics were analyzed. The results showed that as the number of impacts increased, the AFSB experienced progressive failure. The peak impact force, the deflection of the face sheets, and the rebound velocity gradually increased with increasing numbers of impacts, while their increments declined. However, when cracks occurred on the aluminum foam core and face sheets, as the number of impacts increased, the peak force and the rebound velocity decreased, while the amount of deflection in the front and back faces progressively increased. Before the foam core cracked, as the number of impacts increased, the elastic energy increased, while the plastic energy decreased. Once the foam core cracked, the plastic energy increased suddenly. During repeated impacts, the energy absorbed via local indentation in each impact initially increased with the number of impacts, and then decreased before finally becoming constant.

ABSTRACT: Oxidative stress is an essential inducement in follicle atresia and ovarian aging, resulting in decline in female fecundity. As a natural and effective antioxidant, naringin was investigated to relieve chicken follicle atresia and ovarian aging. First, the cultured small white follicles (SWFs) from D280 hens were pretreated with 0.5 mM naringin for 24 h and then treated with H2O2 for 72 h to establish the oxidative stress model to evaluate the putative attenuating effects of naringin on follicle atresia. Meanwhile, SWFs of D580 hens were treated with naringin for 72 h to examine the attenuating effect on the physiological aging of SWFs. Finally, each hen was fed with naringin at a dose of 50 mg/kg every day to explore the effect of naringin on follicular development and laying performance in D580 hens. Results showed that naringin could rescue the antioxidant capacity decline by increasing the antioxidant-related indexes and expression of antioxidation-associated genes. It could also maintain the homeostasis of SWFs in both the H2O2-induced group and natural physiological aging group. In addition, naringin increased estrogen levels, capacity of antioxidants, and the laying performance in aged laying chickens. The thickness and strength of the eggshell were increased in the naringin-treated group as well. In conclusion, this study showed that naringin is capable of relieving SWFs atresia that was induced by oxidative stress and maintaining the laying performance of aging low-yielding hens by reducing oxidative stress.

Abstract We propose a new metric called s-LID based on the concept of Local Intrinsic Dimensionality to identify and quantify hierarchies of kinematic patterns in heterogeneous media. s-LID measures how outlying a grain’s motion is relative to its s nearest neighbors in displacement state space. To demonstrate the merits of s-LID over the conventional measure of strain, we apply it to data on individual grain motions in a set of deforming granular materials. Several new insights into the evolution of failure are uncovered. First, s-LID reveals a hierarchy of concurrent deformation bands that prevails throughout loading history. These structures vary not only in relative dominance but also spatial and kinematic scales. Second, in the nascent stages of the pre-failure regime, s-LID uncovers a set of system-spanning, criss-crossing bands: microbands for small s and embryonic-shearbands at large s, with the former being dominant. At the opposite extreme, in the failure regime, fully formed shearbands at large s dominate over the microbands. The novel patterns uncovered from s-LID contradict the common belief of a causal sequence where a subset of microbands coalesce and/or grow to form shearbands. Instead, s-LID suggests that the deformation of the sample in the lead-up to failure is governed by a complex symbiosis among these different coexisting structures, which amplifies and promotes the progressive dominance of the embryonic-shearbands over microbands. Third, we probed this transition from the microband-dominated regime to the shearband-dominated regime by systematically suppressing grain rotations. We found particle rotation to be an essential enabler of the transition to the shearband-dominated regime. When grain rotations are completely suppressed, this transition is prevented: microbands and shearbands coexist in relative parity.

Wheat-rye T1BL·1RS translocation lines are widely used, especially in China, but their processing quality is generally poor. An interfering expression vector targeting the ω-secalin genes was constructed with the 1Bx7 seed-specific promoter. Biolistic-mediated genetic transformation of the wheat cultivar KN199 carrying the T1BL·1RS translocation generated 10 transgenic lines. Two representative transgenic lines, 8-2 and 13-7, were selected for analysis. Compared with the control, the two transformants showed an up to 4.5-fold decrease in total ω-secalins and various levels of decrease in ω-gliadins, γ-gliadins, and low-molecular-weight glutenins. A decrease in high molecular weight (HMW) glutenin 1Bx7 was detected only in 8-2, owing possibly to promoter methylation. Increased levels of α-gliadins were observed in both transformants, but increased levels of HMW glutenins were observed only in 13-7. Line 13-7 showed increases in gluten index, Zeleny sedimentation value, stabilization time, and maximum resistance. Its bread volume was 849.6 mL, an 11.9% increase over that of the control. Line 8-2 showed decreases in these parameters, but its total cake-making quality score was 88, an 17.3% increase over that of the control. The study demonstrates that the same RNAi construct may produce different effects on wheat processing quality and highlights the influence of the vector promoter in RNA interference.

Abstract Background Maize (Zea mays L.) is one of the most important food sources in the world and has been one of the main targets of plant genetics and phenotypic research for centuries. Observation and analysis of various morphological phenotypic traits during maize growth are essential for genetic and breeding study. The generally huge number of samples produce an enormous amount of high-resolution image data. While high throughput plant phenotyping platforms are increasingly used in maize breeding trials, there is a reasonable need for software tools that can automatically identify visual phenotypic features of maize plants and implement batch processing on image datasets. Results On the boundary between computer vision and plant science, we utilize advanced deep learning methods based on convolutional neural networks to empower the workflow of maize phenotyping analysis. This paper presents Maize-IAS (Maize Image Analysis Software), an integrated application supporting one-click analysis of maize phenotype, embedding multiple functions: (I) Projection, (II) Color Analysis, (III) Internode length, (IV) Height, (V) Stem Diameter and (VI) Leaves Counting. Taking the RGB image of maize as input, the software provides a user-friendly graphical interaction interface and rapid calculation of multiple important phenotypic characteristics, including leaf sheath points detection and leaves segmentation. In function Leaves Counting, the mean and standard deviation of difference between prediction and ground truth are 1.60 and 1.625. Conclusion The Maize-IAS is easy-to-use and demands neither professional knowledge of computer vision nor deep learning. All functions for batch processing are incorporated, enabling automated and labor-reduced tasks of recording, measurement and quantitative analysis of maize growth traits on a large dataset. We prove the efficiency and potential capability of our techniques and software to image-based plant research, which also demonstrates the feasibility and capability of AI technology implemented in agriculture and plant science.

Abstract Microsomal prostaglandin E2 synthase 1 (mPGES-1) is recognized as a promising target for a next generation of anti-inflammatory drugs that are not expected to have the side effects of currently available anti-inflammatory drugs. Lapatinib, an FDA-approved drug for cancer treatment, has recently been identified as an mPGES-1 inhibitor. But the efficacy of lapatinib as an analgesic remains to be evaluated. In the present clinical data mining (CDM) study, we have collected and analyzed all lapatinib-related clinical data retrieved from clinicaltrials.gov. Our CDM utilized a meta-analysis protocol, but the clinical data analyzed were not limited to the primary and secondary outcomes of clinical trials, unlike conventional meta-analyses. All the pain-related data were used to determine the numbers and odd ratios (ORs) of various forms of pain in cancer patients with lapatinib treatment. The ORs, 95% confidence intervals, and P values for the differences in pain were calculated and the heterogeneous data across the trials were evaluated. For all forms of pain analyzed, the patients received lapatinib treatment have a reduced occurrence (OR 0.79; CI 0.70–0.89; P = 0.0002 for the overall effect). According to our CDM results, available clinical data for 12,765 patients enrolled in 20 randomized clinical trials indicate that lapatinib therapy is associated with a significant reduction in various forms of pain, including musculoskeletal pain, bone pain, headache, arthralgia, and pain in extremity, in cancer patients. Our CDM results have demonstrated the significant analgesic effects of lapatinib, suggesting that lapatinib may be repurposed as a novel type of analgesic.

Abstract Background Plant calmodulin-binding transcription activator (CAMTA) proteins play important roles in hormone signal transduction, developmental regulation, and environmental stress tolerance. However, in wheat, the CAMTA gene family has not been systematically characterized. Results In this work, 15 wheat CAMTA genes were identified using a genome-wide search method. Their chromosome location, physicochemical properties, subcellular localization, gene structure, protein domain, and promoter cis-elements were systematically analyzed. Phylogenetic analysis classified the TaCAMTA genes into three groups (groups A, B, and C), numbered 7, 6, and 2, respectively. The results showed that most TaCAMTA genes contained stress-related cis-elements. Finally, to obtain tissue-specific and stress-responsive candidates, the expression profiles of the TaCAMTAs in various tissues and under biotic and abiotic stresses were investigated. Tissue-specific expression analysis showed that all of the 15 TaCAMTA genes were expressed in multiple tissues with different expression levels, as well as under abiotic stress, the expressions of each TaCAMTA gene could respond to at least one abiotic stress. It also found that 584 genes in wheat genome were predicted to be potential target genes by CAMTA, demonstrating that CAMTA can be widely involved in plant development and growth, as well as coping with stresses. Conclusions This work systematically identified the CAMTA gene family in wheat at the whole-genome-wide level, providing important candidates for further functional analysis in developmental regulation and the stress response in wheat.

Abstract Background Leaf senescence comprises numerous cooperative events, integrates environmental signals with age-dependent developmental cues, and coordinates the multifaceted deterioration and source-to-sink allocation of nutrients. In crops, leaf senescence has long been regarded as an essential developmental stage for productivity and quality, whereas functional characterization of candidate genes involved in the regulation of leaf senescence has, thus far, been limited in wheat. Results In this study, we analyzed the expression profiles of 97 WRKY transcription factors (TFs) throughout the progression of leaf senescence in wheat and subsequently isolated a potential regulator of leaf senescence, TaWRKY42-B, for further functional investigation. By phenotypic and physiological analyses in TaWRKY42-B-overexpressing Arabidopsis plants and TaWRKY42-B-silenced wheat plants, we confirmed the positive role of TaWRKY42-B in the initiation of developmental and dark-induced leaf senescence. Furthermore, our results revealed that TaWRKY42-B promotes leaf senescence mainly by interacting with a JA biosynthesis gene, AtLOX3, and its ortholog, TaLOX3, which consequently contributes to the accumulation of JA content. In the present study, we also demonstrated that TaWRKY42-B was functionally conserved with AtWRKY53 in the initiation of age-dependent leaf senescence. Conclusion Our results revealed a novel positive regulator of leaf senescence, TaWRKY42-B, which mediates JA-related leaf senescence via activation of JA biosynthesis and has the potential to be a target gene for molecular breeding in wheat.