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Abstract Background Although several cell culture systems have been developed to investigate the function of the mammary gland in dairy livestock, they have potential limitations, such as the loss of alveolar structure or genetic and phenotypic differences from their native counterparts. Overcoming these challenges is crucial for lactation research. Development of protocols to establish lactating organoid of livestock represents a promising goal for the future. In this study, we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process. Results The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resembled the native architecture of mammary tissue. The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors. Upon stimulation with a lactogenic medium containing prolactin, the mammary organoids exhibited efficient lactation, characterized by the accumulation of lipid droplets in the lumen space. The lactation could be sustained for more than 3 weeks. Importantly, the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues. These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids. Conclusion This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants. The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.

Objective: The study objective was to determine if intraoperative peritoneal catheter placement is associated with improved outcomes in neonates undergoing high-risk cardiac surgery with cardiopulmonary bypass. Methods: This propensity score–matched retrospective study used data from 22 academic pediatric cardiac intensive care units. Consecutive neonates undergoing Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery category 3 to 5 cardiac surgery with cardiopulmonary bypass at centers participating in the NEonatal and Pediatric Heart Renal Outcomes Network collaborative were studied to determine the association of the use of an intraoperative placed peritoneal catheter for dialysis or passive drainage with clinical outcomes, including the duration of mechanical ventilation. Results: Among 1490 eligible neonates in the NEonatal and Pediatric Heart Renal Outcomes Network dataset, a propensity-matched analysis was used to compare 395 patients with peritoneal catheter placement with 628 patients without peritoneal catheter placement. Time to extubation and most clinical outcomes were similar. Postoperative length of stay was 5 days longer in the peritoneal catheter placement cohort (17 vs 22 days, P = .001). There was a 50% higher incidence of moderate to severe acute kidney injury in the no-peritoneal catheter cohort (12% vs 18%, P = .02). Subgroup analyses between specific treatments and in highest risk patients yielded similar associations. Conclusions: This study does not demonstrate improved outcomes among neonates with placement of a peritoneal catheter during cardiac surgery. Outcomes were similar apart from longer hospital stay in the peritoneal catheter cohort. The no-peritoneal catheter cohort had a 50% higher incidence of moderate to severe acute kidney injury (12% vs 18%). This analysis does not support indiscriminate peritoneal catheter use, although it may support the utility for postoperative fluid removal among neonates at risk for acute kidney injury. A multicenter controlled trial may better elucidate peritoneal catheter effects.

Abstract In the context of globalization, the integration of cultural elements into scientific research, particularly through the incorporation of traditional Chinese cultural motifs in scientific illustrations, represents a novel frontier in enhancing the universality and appeal of scientific discoveries. This paper explores the innovative practice of embedding traditional Chinese cultural elements into scientific paper illustrations, highlighting its significant role in augmenting the global appeal of research findings, promoting diversity and innovation in scientific inquiry, and facilitating cross-cultural understanding. Through a series of case studies, including symbolic representations of ancient myths and the use of traditional themes to elucidate complex scientific phenomena, we demonstrate how this cultural integration not only makes scientific content more accessible and engaging but also fosters a deeper appreciation of Chinese heritage among international audiences. This approach not only bridges the gap between science and culture but also contributes to a more inclusive and interconnected global scientific community, underscoring the importance of cultural diversity in enriching scientific exploration and communication.

IntroductionAconiti Lateralis Radix Praeparata (lateral roots of Aconitum carmichaelii Debeaux, Fuzi), is commonly used to treat various cardiovascular diseases, particularly heart failure. However, its strong cardiotoxicity limits its clinical applicability. Glycyrrhizae radix et rhizoma, (the root of Glycyrrhiza uralensis Fisch., Gancao), is known to synergistically increase the cardiotonic effects of Fuzi and alleviate the myocardial injury caused by Fuzi to some extent. However, the detailed mechanism via which the combination of Fuzi and Gancao reduces toxicity and increases or preserves the efficacy of Fuzi requires further investigation.MethodsOxidative stress injury models in H9C2 cells and mice with acute heart failure were established to evaluate the optimal synergistic protective concentration of Fuziline and Glycyrrhetinic acid (GA). A GA probe was then synthesized and used for target fishing using chemical and biological methods. Finally, the target and its function were verified using fluorescence co-localization, Western blotting, protein interaction analysis, molecular docking, and calcium ion imaging.ResultsThe best pharmacodynamic potential was achieved with a 1:1 or 2:1 ratio of Fuziline and GA concentrations. At these ratios, they regulated the protein levels of the downstream players of the Ca2+ signaling pathway via MDH2 and CALR, thereby balancing Ca2+ homeostasis in the myocardial tissue and mitigating the effects of heart failure.ConclusionThis study aimed to investigate the compatibility of Fuziline and GA, the active metabolites of a traditional Chinese medicine (TCM) pair, in exerting their cardiac effects, identify the direct biological targets and verify the mechanism of compatibility.

The WRKY transcription factors are integral to plant biology, serving essential functions in growth, development, stress responses, and the control of secondary metabolism. Through the use of bioinformatics techniques, this research has effectively characterized 207 members of the WRKY family (LaWRKY) present in the entire genome of Lavandula angustifolia. Phylogenetic analysis classified LaWRKYs into three distinct categories based on conserved domains. Collinearity analysis revealed tandem repeats, segmental duplications, and whole genome duplications in LaWRKYs, especially for segmental duplication playing a significant role in gene family expansion. LaWRKYs displayed distinct tissue-specific expression profiles across six different tissues of L. angustifolia. Particularly noteworthy were 12 genes exhibiting high expression in flower buds and calyx, the primary sites of volatile terpenoid production, indicating their potential role in terpenoid biosynthesis in L. angustifolia. RT-qPCR analysis revealed a notable increase in the expression levels of most examined LaWRKY genes in flower buds in response to both intense light and low-temperature conditions, whereas the majority of these genes in leaves were primarily induced by drought stress. However, all genes exhibited downregulation following GA treatment in both flower buds and leaves. Overexpression of LaWRKY57 (La13G01665) and LaWRKY75 (La16G00030) in tobacco led to a reduction in the density of glandular trichomes on leaf surfaces, resulting in changes to the volatile terpenoid composition in the leaves. Specifically, the content of Neophytadiene was significantly elevated compared to wild-type tobacco, while compounds such as eucalyptol, cis-3-Hexenyl iso-butyrate, and D-Limonene were produced, which were absent in the wild type. These findings provide a valuable reference for future investigations into the biological functions of the WRKY gene family in L. angustifolia.

Abstract Purpose To investigate the correlation between socioeconomic status (SES) and the incidence of hypertension among adults aged 18 or above in southwest China. Methods A multistage proportional stratified cluster sampling method was employed to recruited 9280 adult residents from 12 counties in southwest China, with all participants in the cohort tracked from 2016 to 2020. The questionnaire survey gathered information on demographics, lifestyle habits, and household income. The physical exam recorded height, weight, and blood pressure. Biochemical tests measured cholesterol levels. The chi-square test was employed to assess the statistical differences among categorical variables, while the Cox proportional hazards regression model was applied to evaluate the association between socioeconomic status (SES) and the incidence of hypertension. Results The finally effective sample size for the cohort study was 3546 participants, after excluding 5734 people who met the exclusion criteria. Adults in the highest household income group had a significantly lower risk of hypertension compared to those in the lowest income group (HR = 0.636, 95% CI: 0.478–0.845). Besides, when compared to individuals in the illiterate population, the risk of hypertension among adults with elementary school, junior high school, senior high school and associate degree educational level decreased respectively by 34.4% (HR = 0.656, 95%CI: 0.533–0.807), 44.9% (HR = 0.551, 95%CI: 0.436–0.697), 44.9% (HR = 0.551, 95%CI: 0.405–0.750), 46.1% (HR = 0.539, 95%CI: 0. 340–0.854). After conducting a thorough analysis of socioeconomic status, compared with individuals with a score of 6 or less, the risk of hypertension in participants with scores of 8, 10, 11, 12, and greater than 12 decreased respectively by 23.9% (HR = 0.761, 95%CI: 0.598–0.969), 29.7% (HR = 0.703, 95%CI: 0.538–0.919), 34.0% (HR = 0.660, 95%CI: 0.492–0.885), 34.3% (HR = 0.657, 95%CI: 0.447–0.967), 43.9% (HR = 0.561, 95%CI: 0.409–0.769). Conclusion The findings indicate a negative correlation between socioeconomic status and hypertension incidence among adults in southwest China, suggesting that individuals with higher socioeconomic status are less likely to develop hypertension.

Abstract CD13 (APN) is an Alanyl-Aminopeptidase with diverse functions. The role of CD13 for gliomas is still unknown. In this study, data of glioma patients obtained by TCGA and CGGA databases were used to evaluate the survival rate and prognostic value of CD13 expression level. Protein expression of CD13 was confirmed by immunofluorescence staining of fresh patient tissues. Eight human glioblastoma cell lines were studied by RT-PCR, Western Blot, immunofluorescence staining and flow cytometry to define CD13 expression. Cell lines with different CD13 expression status were treated with a CD13 inhibitor, bestatin, and examined by MTT, scratch and colony formation assaysas well as by apoptosis assay and Western Blots. Bioinformatics analysis indicated that patients with high expression of CD13 had poor survival and prognosis. Additionally, CD13 protein expression was positively associated with clinical malignant characteristics. Investigated glioblastoma cell lines showed distinct expression levels and subcellular localization of CD13 with intracellular enrichment. Bestatin treatment reduced proliferation, migration and colony formation of glioma cells in a CD13-dependent manner while apoptosis was increased. In summary, CD13 has an impact on glioma patient survival and is important for the main function of specific glioma cells.

Abstract Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Building upon the prior investigations of our team, which established a connection between LA levels in the follicular fluid and PCOS, this study deeply examined the specific impact of LA using a granulosa cell line. Our findings revealed that LA exerts its influence on granulosa cells (GCs) by binding to the estrogen receptor (ER). Activated ER triggers the transcription of the FOXO1 gene. Reactive oxygen species (ROS)-related oxidative stress (OS) and inflammation occur downstream of LA-induced FOXO1 activation. Increased OS and inflammation ultimately culminate in GC apoptosis. In summary, LA modulates the apoptosis and inflammation phenotypes of GCs through the ER-FOXO1-ROS-NF-κB pathway. Our study provides additional experimental evidence to comprehend the pathophysiology of PCOS and provides novel insights into the dietary management of individuals with PCOS.

ABSTRACT Beneficial interactions between plants and rhizosphere fungi can enhance plant adaptability during drought stress. However, harnessing these interactions will require an in-depth understanding of the response of fungal community assembly to drought. Herein, by using different varieties of wheat plants, we analyzed the drought-induced changes in fungal community assembly in rhizosphere and bulk soil. We demonstrated that drought significantly altered the fungal communities, with the contribution of species richness to community beta diversity increased in both rhizosphere and bulk soil compartments during drought stress. The stochastic processes dominated fungal community assembly, but the relative importance of deterministic processes, mainly homogeneous selection, increased in the drought-stressed rhizosphere. Drought induced an increase in the relative abundance of generalists in the rhizosphere, as opposed to specialists, and the top 10 abundant taxa that enriched under drought conditions were predominantly generalists. Notably, the most abundant drought-enriched taxon in rhizosphere was a generalist, and the corresponding Chaetomium strain was found capable of improving root length and activating ABA signaling in wheat plants through culture-based experiment. Together, these findings provide evidence that host plants exert a strong influence on rhizospheric fungal community assembly during stress and suggest the fungal communities that have experienced drought have the potential to confer fitness advantages to the host plants.IMPORTANCEWe have presented a framework to integrate the shifts in community assembly processes with plant-soil feedback during drought stress. We found that environmental filtering and host plant selection exert influence on the rhizospheric fungal community assembly, and the re-assembled community has great potential to alleviate plant drought stress. Our study proposes that future research should incorporate ecology with plant, microbiome, and molecular approaches to effectively harness the rhizospheric microbiome for enhancing the resilience of crop production to drought.

Single pixel imaging is a new method, but imaging quality and speed are the main factors affecting its practicality. Building upon the attributes of the random measurement and deterministic matrices, a Walsh transformation matrix with bicubic interpolation is proposed. This matrix is formulated by integrating the Walsh matrix and a pseudo-random diagonal matrix using a structured construction method alongside bicubic interpolation. The structure of matrix and the effect of single pixel imaging using matrix are simulated and analyzed. The imaging effects of Gaussian, Bernoulli, Topeliz and bicubic interpolation Walsh transform matrix are simulated and analyzed. A single pixel experimental system is set up for experimental verification. The results show that the quality of reconstructed images with bicubic interpolation Walsh transformation matrix is better than that of bicubic interpolation Gold matrix and bicubic interpolation Walsh matrix, and there is no energy concentration in reconstructed images. The results indicate that, under a 25% low sampling rate, obtaining the image of the target object is achievable through a Walsh transformation matrix with bicubic interpolation. Additionally, the imaging performance of the Peudo-random measurement-Walsh Gold (PRM-WG) matrix is better than that of Peudo-random measurement-Hadamard Gold (PRM-HG), and Peudo-random measurement-Like_Walsh Gold (PRM-LG) matrices. These research insights contribute to optimizing single pixel imaging efficiency and lay a theoretical groundwork for advancing the real-world applications of single pixel imaging.

Current single-model methods for fine-grained image classification suffer from insufficient generalisation ability, while multi-model fusion methods suffer from weight curing. The study suggests and experimentally tests a dynamic weight multi-model fusion strategy for transfer learning-based fine-grained picture classification. The results of the experiment showed that the suggested fusion model enhanced recognition accuracy by 1.33%, 1.19%, and 0.83% compared to the single model on the medical dataset and 3.25%, 1.34%, and 7.28% on the agronomy dataset, respectively. Furthermore, when compared to the comparison method, the models under the proposed method of the study improved recognition accuracy by 0.18%, 0.61%, 0.43%, and 0.43% on the medical dataset, and the experimental time consumed was 3.25 minutes less than that of the sum-of-maximum-probabilities method; however, the fusion models of the proposed method of the study had higher recognition accuracy than that of the comparison met Overall, the proposed dynamic weight multi-model fusion method for fine-grained image classification using migration learning has better performance and generalisation ability, which can improve performance while reducing time cost, and has higher application value for the actual fine-grained image classification task.

Dry-hot wind stress causes losses in wheat productivity in major growing regions worldwide, especially winter wheat in the Huang-Huai-Hai Plain of China, and both the occurrence and severity of such events are likely to increase with global climate change. To investigate the recovery of physiological functions and yield formation using a new non-commercial chemical regulator (NCR) following dry-hot wind stress, we conducted a three-year field experiment (2018–2021) with sprayed treatments of tap water (control), monopotassium phosphate (CKP), NCR at both the jointing and flowering stages (CFS), and NCR only at the jointing stage (FSJ) or flowering stage (FSF). The leaf physiology, biomass accumulation and translocation, grain-filling process, and yield components in winter wheat were assessed. Among the single spraying treatments, the FSJ treatment was beneficial for the accumulation of dry matter before anthesis, as well as larger increases in the maximum grain-filling rate and mean grain-filling rate. The FSF treatment performed better in maintaining a high relative chlorophyll content as indicated by the SPAD value, and a low rate of excised leaf water loss in flag leaves, promoting dry matter accumulation and the contribution to grain after anthesis, prolonging the duration of grain filling, and causing the period until the maximum grain-filling rate reached earlier. The CFS treatment was better than any other treatments in relieving the effects of dry-hot wind. The exogenous NCR treatments significantly increased grain yields by 12.45–18.20% in 2018–2019, 8.89–13.82% in 2019–2020, and 8.10–9.00% in 2020–2021. The conventional measure of the CKP treatment only increased grain yield by 6.69% in 2020–2021. The CFS treatment had the greatest mitigating effect on yield loss under dry-hot wind stress, followed by the FSF and FSJ treatments, and the CKP treatment only had a minimal effect. In summary, the CFS treatment could be used as the main chemical control measure for wheat stress resistance and yield stability in areas with a high incidence of dry-hot wind. This treatment can effectively regulate green retention and the water status of leaves, promote dry matter accumulation and efficient translocation, improve the grain-filling process, and ultimately reduce yield losses.

Abstract Background Familial hemophagocytic lymphohistiocytosis (FHL) is an immunological disorder characterized by overactivation of macrophages and T lymphocytes. This autosomal recessive condition has been characterized into multiple types depending on the genetic etiology. FHL type 3 is associated with bi-allelic pathogenic variants in the UNC13D gene. Case presentation We present a 12-year diagnostic odyssey for a family with FHL that signifies the advances of FHL genetic testing in a clinical genetic diagnostic laboratory setting. We describe the first case of a large UNC13D gross deletion in trans to a nonsense variant in a family with FHL3, which may have been mediated by Alu elements within introns 12 and 25 of the UNC13D gene. Conclusions This case highlights the importance of re-evaluating past genetic testing for a patient and family as test technology evolves in order to end a diagnostic odyssey.

Land-use and land-cover changes (LUCCs) significantly impact carbon sequestration by modifying the structure and function of terrestrial ecosystems. This study utilized GIS and remote sensing techniques to forecast future LUCC patterns and their influence on regional carbon budgets, which is essential for sustainable development. We devised a coupled system dynamics (SD) model integrated with a patch-generating land-use simulation (PLUS) model to simulate LUCCs under diverse future scenarios using multisource environmental data. Additionally, the InVEST model was employed to quantify carbon storage in terrestrial ecosystems. By establishing three scenarios—ecological priority (EP), highly urbanized (HU), and coordinated development (CD)—this study’s aim was to predict the LUCC patterns and carbon storage distribution of the Tuojiang River Basin (TRB), China, up to 2035. The results showed that (1) from 2000 to 2020, significant LUCCs occurred in the TRB, primarily involving the conversion of cultivated land into construction areas and forestland; (2) LUCCs had a substantial impact on carbon storage in the TRB, with the EP scenario demonstrating the highest carbon storage by 2035 due to extensive forest expansion, while the HU scenario indicated a decline in carbon storage associated with rapid urbanization; and (3) the mountainous regions of the TRB, dominated by forestland, consistently exhibited higher carbon storage, whereas the Chengdu Plain region in the upper basin displayed the lowest. In conclusion, we recommend prioritizing the CD scenario in future development strategies to balance economic growth with ecological protection while simultaneously enhancing carbon storage. Our findings offer valuable insights to shape future LUCC policies in the Tuojiang River Basin, underscoring the adaptability of the coupled model approach to a wide range of geographic scales and contexts.

Rheumatoid arthritis (RA) is characterized by high level of reactive oxygen species (ROS) and proinflammatory cytokines, which facilitate the activation of the inflammatory signaling such as NF-κB pathway and exacerbate the development of inflammation. Herein, we designed a nanodrug by encapsulating the NO donor S-nitrosoglutathione (GSNO) into an emulsion and coating the surface with a polydopamine (PDA) layer to yield GSNO@PDA, which simultaneously scavenged the extra ROS and suppressed NF-κB signaling for potent RA treatment. To enhance the cellular uptake and NO generation efficiency, dextran sulfate (DS) and Cu2+ were anchored on the surface of GSNO@PDA to obtain the final formulation GSNO@PDA@DS. Our results demonstrated that GSNO@PDA@DS were successfully prepared and the modification of DS effectively boosted the cellular uptake of GSNO@PDA@DS. Moreover, GSNO@PDA@DS lowered cellular ROS and elevated intracellular NO, resulting in a decrease of M1 phenotype, inhibition of NF-κB pathway and down-regulation of proinflammatory cytokine tumor necrosis factor-α (TNF-α). Further in vivo studies confirmed that GSNO@PDA@DS significantly relieved symptoms and bone erosion by regulating the microenvironment of RA, highlighting the potential of GSNO@PDA@DS for RA therapy through ROS scavenging and NO-mediated suppression of inflammatory signaling.

Manure application is considered a good way to modify soil structure and hydraulic properties and has the potential to promote water productivity. Therefore, the potential for improving water savings and water productivity through the use of manure as a substitute for mineral fertilizer is worth further exploration in deficit irrigation regions. A field experiment with four irrigation regimes and four types of fertilizer inputs was conducted in the North China Plain. The irrigation regimes included W0 (no irrigation), W1 (irrigation at the presowing stage only), W2 (irrigation at the presowing and jointing stages), and W3 (irrigation at the presowing, jointing, and anthesis stages). The fertilizer inputs included CK (no fertilizer), M0 (mineral fertilizer only), M50 (half mineral plus half manure), and M100 (manure only). Sixteen treatments were laid out in 2012, and samples were collected in 2018–2019 and 2019–2020 during the winter wheat growing season. The results showed that the greatest potential to improve water productivity and obtain a greater grain yield occurred in W2 than in W3 while interacting with precipitation; both of these grain yields were significantly greater than those in the other irrigation treatments. The leaf area index (LAI) plays an important role in regulating soil water consumption and is negatively correlated with evaporation accumulation and the ratio of evaporation to evapotranspiration. However, compared with those under pure mineral fertilizer application, the LAI under manure application alone could not ensure an equal LAI, and the grain yields under M100 were significantly lower than those under M0 by 7.66% and 13.62%, respectively, during the two years. In addition, no advantage in water productivity was observed in M100. However, half-manure substitution for mineral fertilizer maintains a reasonable LAI and grain yield, and its combination with W2 benefits the improvement of water productivity. The study showed that total manure substitution for mineral fertilizer has limitations in improving water productivity, but partial manure substitution combined with irrigation at the presowing and jointing stages has great potential in maintaining high grain yield and improving water productivity. The results of this study could lead to further research exploring the potential for improving water productivity by applying organic fertilizer in the North China Plain.

Pinus taeda is an important forest tree species for plantations because of its rapid growth and high yield of oleoresins. Although P. taeda plantations distribute in warm and wet southern China, drought, sometime serious and long time, often occurs in the region. To explore drought tolerance of P. taeda and usage of beneficial microorganisms, P. taeda seedlings were planted in pots and were inoculated with root endophytic fungus Serendipita indica and finally were treated with drought stress for 53 d. Metabolome and proteome of their needles were analyzed. The results showed that S. indica inoculation of P. taeda seedlings under drought stress caused great changes in levels of some metabolites in their needles, especially some flavonoids and organic acids. Among them, the levels of eriocitrin, trans-aconitic acid, vitamin C, uric acid, alpha-ketoglutaric acid, vitamin A, stachydrine, coumalic acid, itaconic acid, calceolarioside B, 2-oxoglutaric acid, and citric acid were upregulated more than three times in inoculated seedlings under drought stress, compared to those of non-inoculated seedlings under drought stress. KEGG analysis showed that some pathways were enriched in inoculated seedlings under drought stress, such as flavonoid biosynthesis, ascorbate and aldarate metabolism, C5-branched dibasic acid metabolism. Proteome analysis revealed some specific differential proteins. Two proteins, namely, H9X056 and H9VDW5, only appeared in the needles of inoculated seedlings under drought stress. The protein H9VNE7 was upregulated more than 11.0 times as that of non-inoculated seedlings under drought stress. In addition, S. indica inoculation increased enrichment of water deficient-inducible proteins (such as LP3-1, LP3-2, LP3-3, and dehydrins) and those involved in ribosomal structures (such as A0A385JF23). Meanwhile, under drought stress, the inoculation caused great changes in biosynthesis and metabolism pathways, mainly including phenylpropanoid biosynthesis, cutin, suberine and wax biosynthesis, and 2-oxocarboxylic acid metabolism. In addition, there were positive relationships between accumulation of some metabolites and enrichment of proteins in P. taeda under drought stress. Altogether, our results showed great changes in metabolome and proteome in inoculated seedlings under drought stress and provided a guideline to further study functions of metabolites and proteins, especially those related to drought stress.

ABSTRACT Viruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The “host shutoff,” a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis.

We present a rare case of erythrocytosis due to a homozygous SLC30A10 mutation, causative of Hypermanganesemia with Dystonia, Polycythemia, and Cirrhosis (HMDPC). The patient presented at 7 years of age with the incidental finding of hemoglobin up to 22.3 g/dL. Despite extensive phenotypic evaluation and genetic testing for common causes of erythrocytosis, etiology remained unknown for 1.5 years until whole exome sequencing revealed the genetic diagnosis. Upon neurological evaluation, the patient was found to have very mild dystonia due to manganese deposition in the basal ganglia, midbrain, and cerebellum, as seen in brain MRI. Chelation with trientine orally was initiated, which led to resolution of his erythrocytosis along with decrease of Mn deposition in brain tissues. Recurrence of erythrocytosis occurred after 4 years due to inappropriately stored trientine and iron deficiency. This required the temporary addition of intravenous calcium disodium edetate to his treatment regimen. This case illustrates the development of secondary erythrocytosis due to hypermanganesemia leading to manganese deposition in the hepatocytes, causing a sense of tissue hypoxia and stimulating erythropoietin production. It also shows the competition between manganese and iron for absorption in the body. Moreover, it demonstrates the importance of broad genetic evaluation for the diagnosis of ultra-rare diseases. In this case, timely diagnosis and initiation of appropriate treatment prevented irreversible damage to the brain and liver with a profound improvement on his prognosis.

Abstract To deter herbivore attacks, plants employ a diverse array of volatile compounds, particularly during the early developmental stages. The highly expressed genes LaTPS7, LaTPS8, and LaCYP71D582 were identified during the budding phases of Lavandula angustifolia. In vitro studies revealed that LaTPS7 generated nine distinct compounds, including camphene, myrcene, and limonene. LaTPS8 enzymatically converted eight volatiles by utilizing geranyl diphosphate and nerolidyl diphosphate as substrates. Overexpression of plastid-localized LaTPS7 in Nicotiana benthamiana resulted in the production of limonene. Furthermore, the endoplasmic reticulum-associated enzyme LaCYP71D582 potentially converted limonene into carveol. In N. benthamiana, LaTPS8 is responsible for the synthesis of α-pinene and sylvestrene. Furthermore, leaves transfected with LaTPS7 and leaves cotransfected with LaTPS7 and LaCYP71D582 exhibited a repellent effect on aphids, with an approximate rate of 70%. In comparison, leaves with an empty vector displayed a repellent rate of approximately 20%. Conversely, tobacco leaves expressing LaTPS7 attracted ladybugs at a rate of 48.33%, while leaves coexpressing LaTPS7 and LaCYP71D582 attracted ladybugs at a slightly higher rate of 58.33%. Subsequent authentic standard tests confirmed that limonene and carveol repel Myzus persicae while attracting Harmonia axyridis. The promoter activity of LaTPS7 and LaCYP71D582 was evaluated in Arabidopsis thaliana using GUS staining, and it was observed that wounding stimulated the expression of LaTPS7. The volatile compounds produced by LaTPS7, LaTPS8, and LaCYP71D582 play a crucial role in plant defence mechanisms. In practical applications, employing biological control measures based on plant-based approaches can promote human and environmental health.

The Ningbo International Conference Center Project incorporates elements of Chinese traditional culture into its architectural style, resulting in the world’s first cantilever bridge international conference center. During the construction process, it faced challenges such as complex engineering geological environments and diverse architectural styles. By harnessing building information modeling (BIM) technology, many challenges encompassing intricate environmental conditions, architectural structures, and construction complexities are effectively visualized in three dimensions, thereby offering viable solutions for engineering implementation. In the scheme design stage, BIM technology plays a pivotal role in bridging the gap between design and construction, optimizing engineering pile and wall material designs. During the deepening design stage, BIM aids in refining designs through intricate node optimization for the ultralong comb type inclined water panel curtain wall and glued wood column decoration, thereby enhancing construction efficiency. Additionally, BIM technology has also played an important role in the simulation and scheme analysis of the entire construction process of complex steel structures. Through the implementation of BIM technology, numerous challenges encountered during the construction phase of the Ningbo International Conference Center project have been effectively resolved, which serves as a valuable reference for employing BIM technology in large-scale international conference center projects.

Abstract Wild barley, from “Evolution Canyon (EC)” in Mount Carmel, Israel, are ideal models for cereal chromosome evolution studies. Here, the wild barley EC_S1 is from the south slope with higher daily temperatures and drought, while EC_N1 is from the north slope with a cooler climate and higher relative humidity, which results in a differentiated selection due to contrasting environments. We assembled a 5.03 Gb genome with contig N50 of 3.53 Mb for wild barley EC_S1 and a 5.05 Gb genome with contig N50 of 3.45 Mb for EC_N1 using 145 Gb and 160.0 Gb Illumina sequencing data, 295.6 Gb and 285.35 Gb Nanopore sequencing data and 555.1 Gb and 514.5 Gb Hi-C sequencing data, respectively. BUSCOs and CEGMA evaluation suggested highly complete assemblies. Using full-length transcriptome data, we predicted 39,179 and 38,373 high-confidence genes in EC_S1 and EC_N1, in which 93.6% and 95.2% were functionally annotated, respectively. We annotated repetitive elements and non-coding RNAs. These two wild barley genome assemblies will provide a rich gene pool for domesticated barley.

Abstract Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated potent clinical efficacy in the treatment of hematopoietic malignancies. However, the application of CAR-T in solid tumors has been limited due in part to the expression of inhibitory molecules in the tumor microenvironment, leading to T-cell exhaustion. To overcome this limitation, we have developed a synthetic T-cell receptor (TCR) that targets programmed death-ligand 1 (PD-L1), a molecule that is widely expressed in various solid tumors and plays a pivotal role in T-cell exhaustion. Our novel TCR platform is based on antibody-based binding domain, which is typically a single-chain variable fragment (scFv), fused to the γδ TCRs (TCRγδ). We have utilized the T-cell receptor alpha constant (TRAC) locus editing approach to express cell surface scFv of anti-PD-L1, which is fused to the constant region of the TCRγ or TCRδ chain in activated T cells derived from peripheral blood mononuclear cells (PBMCs). Our results indicate that these reconfigured receptors, both γ-TCRγδ and δ-TCRγδ, have the capability to transduce signals, produce inflammatory cytokines, degranulate and exert tumor killing activity upon engagement with PD-L1 antigen in vitro. Additionally, we have also shown that γ-TCRγδ exerted superior efficacy than δ-TCRγδ in in vivo xenograft model.

Objectives: The up-regulation of proinflammatory cytokines in the hypothalamic paraventricular nucleus (PVN) is well demonstrated to be involved in the development of neurogenic hypertension, including stress-induced hypertension (SIH). IL-17A has been found to be increased in the PVN of several hypertensive animal models and has been shown to play a key role in the development of hypertension. Although IL-36γ was found to be expressed in spinal neurons, its role in hypertension remains elusive. Here, we investigated the co-expression of IL-17 receptor A (IL-17RA) and IL-36γ in the PVN cells of SIH rats. Methods: The electric foot shock combined with buzzer noise stressors were used to make hypertensive rat model. The immunochemical staining or immunofluorescence staining was used to reveal cells as requested. The Western blot was used to detect the related protein levels. Results and Conclusion: In the PVN of the SIH rats, the number of CD3 + CD4 + T cells was significantly increased by the immunochemical staining. Additionally, the protein levels of RORγt and IL-17A were significantly upregulated by Western blot, confirming the infiltration of CD4 + T cells and differentiation into Th17 cells in the PVN of SIH rats. Immunofluorescence staining revealed abundant expression of IL-17RA in PVN neurons, with relatively less expression in astrocytes or microglia. Furthermore, IL-36γ positive cells and protein expression of IL-36R were significantly increased. Notably, this study demonstrates for the first time that most IL-36γ cells were strongly colocalized with IL-17RA positive cells in the PVN of SIH rats, and the colocalized cells were significantly higher in SIH rats. This suggests that IL-17A secreted by infiltrated Th17 cells may stimulate PVN neurons to produce IL-36γ via IL-17RA, indicating that the combination of IL-17 and IL-36γ might produce strong pro-inflammatory effects in the PVN of SIH rats.

To bolster the dual-circulation development model and green economy, this study delves into the spatiotemporal dynamics of implied carbon transfer in China's inter-provincial and inter-industrial trade, emphasizing its significance for the "dual carbon" objectives. Utilizing multi-regional input-output data from 2012, 2015, and 2017, we employed the multi-region input-output model to gauge embodied carbon transfers across 31 provinces and 28 industries. The Structural Decomposition Analysis (SDA) model further decomposed the growth of trade-related carbon emissions. Key findings include: (1) The electricity and thermal power sectors dominate carbon transfers, with secondary industries seeing rapid growth; (2) Northern provinces significantly outweigh southern ones in carbon transfers and the main direction of it is towards affluent southern coastal regions; (3) Scale effect plays a pivotal role in these transfers. Conclusively, it is crucial for regulatory authorities to rationally formulate region-specific emission policies for inter-regional coordination, and future studies can focus on industrial and spatial clustering effects.

Abstract The decline of oocyte quality has profound impacts on fertilization, implantation, embryonic development, and the genetic quality of future generations. One factor that is often ignored but is involved in the decline of oocyte quality is mitochondrial DNA (mtDNA) abnormalities. Abnormalities in mtDNA affect the energy production of mitochondria, the dynamic balance of the mitochondrial network, and the pathogenesis of mtDNA diseases in offspring. In this review, we have detailed the characteristics of mtDNA in oocytes and the maternal inheritance of mtDNA. Next, we summarized the mtDNA abnormalities in oocytes derived from aging, diabetes, obesity, and assisted reproductive technology (ART) in an attempt to further elucidate the possible mechanisms underlying the decline in oocyte health. Because multiple infertility factors are often involved when an individual is infertile, a comprehensive understanding of the individual effects of each infertility-related factor on mtDNA is necessary. Herein, we consider the influence of infertility-related factors on the mtDNA of the oocyte as a collective perspective for the first time, providing a supplementary angle and reference for multi-directional improvement strategies of oocyte quality in the future. In addition, we highlight the importance of studying ART-derived mitochondrial abnormalities during every ART procedure.

IMPORTANCE:. Extubation failure (EF) after pediatric cardiac surgery is associated with increased morbidity and mortality. OBJECTIVES:. We sought to describe the risk factors associated with early (< 48 hr) and late (48 hr ≤ 168 hr) EF after pediatric cardiac surgery and the clinical implications of these two types of EF. DESIGN, SETTING, AND PARTICIPANTS:. Retrospective cohort study using prospectively collected clinical data for the Pediatric Cardiac Critical Care Consortium (PC4) Registry. Pediatric patients undergoing Society of Thoracic Surgeons benchmark operation or heart transplant between 2013 and 2018 available in the PC4 Registry were included. MAIN OUTCOMES AND MEASURES:. We analyzed demographics and risk factors associated with EFs (primary outcome) including by type of surgery. We identified potentially modifiable risk factors. Clinical outcomes of mortality and length of stay (LOS) were reported. RESULTS:. Overall 18,278 extubations were analyzed. Unplanned extubations were excluded from the analysis. The rate of early EF was 5.2% (948) and late EF was 2.5% (461). Cardiopulmonary bypass time, ventilator duration, airway anomaly, genetic abnormalities, pleural effusion, and diaphragm paralysis contributed to both early and late EF. Extubation during day remote from shift change and nasotracheal route of initial intubation was associated with decreased risk of early EF. Extubation in the operating room was associated with an increased risk of early EF but with decreased risk of late EF. Across all operations except arterial switch, EF portrayed an increased burden of LOS and mortality. CONCLUSION AND RELEVANCE:. Both early and late EF are associated with significant increase in LOS and mortality. Study provides potential benchmarking data by type of surgery. Modifiable risk factors such as route of intubation, time of extubation as well as treatment of potential contributors such as diaphragm paralysis or pleural effusion can serve as focus areas for reducing EFs.

Meteorological factors have significant impacts on crop yield. To account for the impact of meteorological factors on foxtail millet (Setaria italica Beauv.) production in different water conditions, a total of 38 collected varieties were grown in nine seasons from 2011 to 2020 (except 2016) under well-watered (WW) and water-stressed (WS) conditions. The results showed that there was a large seasonal variation in GY; the variation ranged from 4.92 t ha−1 to 6.95 t ha−1 under the WW treatment and from 3.50 t ha−1 to 5.77 t ha−1 under the WS treatment. The impacts of meteorological factors on foxtail millet under the WW and WS treatments were different; sunshine duration during the whole stage, vegetative stage and reproductive stage had the greatest impact under the WW treatment, while under the WS treatment, sunshine duration and the diurnal temperature range during the whole stage and reproductive stage were the greatest impact factors on grain yield. This work could help us in high-yield foxtail millet cultivation and breeding.

Abstract Background In rodents, research has revealed a role of liver X receptors (LXR) in controlling lipid homeostasis and regulating the synthesis of polyunsaturated fatty acids (PUFA). Recent data suggest that LXRB is the predominant LXR subtype in ruminant mammary cells, but its role in lipid metabolism is unknown. It was hypothesized that LXRB plays a role in lipid homeostasis via altering the synthesis of PUFA in the ruminant mammary gland. We used overexpression and knockdown of LXRB in goat primary mammary epithelial cells (GMEC) to evaluate abundance of lipogenic enzymes, fatty acid profiles, content of lipid stores and activity of the stearoyl-CoA desaturase (SCD1) promoter. Results Overexpression of LXRB markedly upregulated the protein abundance of LXRB while incubation with siRNA targeting LXRB markedly decreased abundance of LXRB protein. Overexpression of LXRB plus T0901317 (T09, a ligand for LXR) dramatically upregulated SCD1 and elongation of very long chain fatty acid-like fatty acid elongases 5–7 (ELOVL 5–7), which are related to PUFA synthesis. Compared with the control, cells overexpressing LXRB and stimulated with T09 had greater concentrations of C16:0, 16:1, 18:1n7,18:1n9 and C18:2 as well as desaturation and elongation indices of C16:0. Furthermore, LXRB-overexpressing cells incubated with T09 had greater levels of triacylglycerol and cholesterol. Knockdown of LXRB in cells incubated with T09 led to downregulation of genes encoding elongases and desaturases. Knockdown of LXRB attenuated the increase in triacylglycerol and cholesterol that was induced by T09. In cells treated with dimethylsulfoxide, knockdown of LXRB increased the concentration of C16:0 at the expense of C18:0, while a significant decrease in C18:2 was observed in cells incubated with both siLXRB and T09. The abundance of sterol regulatory element binding transcription factor 1 precursor (pSREBP1) and its mature fragment (nSREBP1) was upregulated by T09, but not LXRB overexpression. In the cells cultured with T09, knockdown of LXRB downregulated the abundance for pSREBP1 and nSREBP1. Luciferase reporter assays revealed that the activities of wild type SCD1 promoter or fragment with SREBP1 response element (SRE) mutation were decreased markedly when LXRB was knocked down. Activity of the SCD1 promoter that was induced by T09 was blocked when the SRE mutation was introduced. Conclusion The current study provides evidence of a physiological link between the LXRB and SREBP1 in the ruminant mammary cell. An important role was revealed for the LXRB-SREBP1 network in the synthesis of PUFA via the regulation of genes encoding elongases and desaturases. Thus, targeting this network might elicit broad effects on lipid homeostasis in ruminant mammary gland.

To investigate the role of glucose in regulating milk fatty acid synthesis, 6 lactating Guanzhong dairy goats were infused with 0, 60, or 100 g/d glucose via the external pubic artery in a 3 × 3 repeated Latin square experiment. A concomitant in vitro experiment was conducted to investigate possible mechanisms whereby glucose regulates milk fatty acid synthesis. RNA sequencing was used for cellular transcriptome analysis. Drugs, MK-2206, rapamycin, and dorsomorphin were used to block cellular mammalian AMP-activated protein kinase (AMPK), AKT serine/threonine kinase 1, and mechanistic target of rapamycin kinase signaling pathways, respectively. Carbohydrate response element binding protein (ChREBP) was knockdown and overexpressed to investigate its role in regulating milk fatty acid synthesis in mammary epithelial cells. Glucose infusion linearly elevated the concentration of C8:0 (P = 0.039) and C10:0 (P = 0.041) in milk fat while it linearly decreased (P = 0.049) that of C16:0. This result was in agreement with the upregulation of genes related to de novo synthesis of fatty acids and lipid droplet formation, including adipose differentiation-related protein, butyrophilin subfamily 1 member A1, fatty acid synthase (FASN) and ChREBP. Their expression increased (P

Cisplatin has been widely studied and found to be a highly effective anti-tumor drug. It has several side effects, including acute kidney injury (AKI). Cisplatin-induced AKI can be primarily attributed to oxidative stress, inflammation, and apoptosis. The CTRP3 adipokine is a new adipokine that exhibits antioxidant, anti-inflammatory, and antiapoptotic properties. Despite this, the role of CTRP3 in AKI remain unclear. In cisplatin-induced AKI models, our findings demonstrated that CTRP3 expression was decreased in human proximal tubule epithelial cells (HK-2). In the in vitro experiments, HK-2 cells were first transfected with an overexpression plasmid of CTRP3 (pcDNA-CTRP3) or a small interfering RNA for CTRP3 (si-CTRP3) and induced by cisplatin; and cell oxidative stress, inflammation, proliferation, and apoptosis were found to be present. Overexpressing CTRP3 inhibited oxidative stress through decreasing malondialdehyde (MDA) levels and increasing the activity of SOD and CAT. The mRNA levels of SOD1 and SOD2 were increased in response to CTRP3 overexpression. Additionally, CTRP3 decreased TNF-α and MCP-1 levels. Moreover, CTRP3 overexpression increased cisplatin-induced cell activity and decreased cell apoptosis, as indicated by the elevated numbers of EdU positive cells and decreased numbers of apoptotic cells. Consistent with these results, the overexpression of CTRP3 effectively elevated the mRNA levels of Bcl-2 and reduced the mRNA levels of Bax. In contrast, inhibition of CTRP3 expression by si-CTRP3 reversed the cisplatin-induced indices. Mechanistically, we found that the overexpression of CTRP3 can increase expression of Nrf2 and inhibit the activation of MAPK phosphorylation (ERK, JNK, and p38). Furthermore, inhibition of ERK, JNK and p38 activity eliminated aggravation of cisplatin-induced inflammation and apoptosis caused by CTRP3 knockdown. Additionally, the cisplatin-induced oxidative stress and activation of MAPK phosphorylation (ERK, JNK, and p38) in HK-2 cells were reversed by Nrf2 suppression by siRNA. Collectively, these results indicated that CTRP3 may identify as a novel target for AKI treatment and protect against cisplatin-induced AKI through the Nrf2/MAPK pathway.

Yellow seed breeding is an effective method to improve oil yield and quality in rapeseed (Brassica napus L.). However, naturally occurring yellow-seeded genotypes have not been identified in B. napus. Mustard (Brassica juncea L.) has some natural, yellow-seeded germplasms, yet the molecular mechanism underlying this trait remains unclear. In this study, a BC9 population derived from the cross of yellow seed mustard “Wuqi” and brown seed mustard “Wugong” was used to analyze the candidate genes controlling the yellow seed color of B. juncea. Subsequently, yellow-seeded (BY) and brown-seeded (BB) bulks were constructed in the BC9 population and subjected to bulked segregant RNA sequencing (BSR-Seq). A total of 511 differentially expressed genes (DEGs) were identified between the brown and yellow seed bulks. Enrichment analysis revealed that these DEGs were involved in the phenylpropanoid biosynthetic process and flavonoid biosynthetic process, including key genes such as 4CL, C4H, LDOX/TT18, PAL1, PAL2, PAL4, TT10, TT12, TT4, TT8, BAN, DFR/TT3, F3H/TT6, TT19, and CHI/TT5. In addition, 111,540 credible single-nucleotide polymorphisms (SNPs) and 86,319 INDELs were obtained and used for quantitative trait locus (QTL) identification. Subsequently, two significant QTLs on chromosome A09, namely, qSCA09-3 and qSCA09-7, were identified by G’ analysis, and five DEGs (BjuA09PAL2, BjuA09TT5, BjuA09TT6, BjuA09TT4, BjuA09TT3) involved in the flavonoid pathway were identified as hub genes based on the protein-to-protein network. Among these five genes, only BjuA09PAL2 and BjuA09F3H had SNPs between BY and BB bulks. Interestingly, the majority of SNPs in BjuA09PAL2 were consistent with the SNPs identified between the high-quality assembled B. juncea reference genome “T84-66” (brown-seed) and “AU213” (yellow-seed). Therefore, BjuA09PAL2, which encodes phenylalanine lyase, was considered as the candidate gene associated with yellow seed color of B. juncea. The identification of a novel gene associated with the yellow seed coloration of B. juncea through this study may play a significant role in enhancing yellow seed breeding in rapeseed.

Confining stress response is considered an accompanying behavior of hydraulic fracturing. Along these lines, an evaluation model of confining stress response was presented in this work. It was established on a rock representative volume element (RVE) and based on the hydraulic volumetric opening model, which stems from the theories of poroelasticity, breakdown damage, and hydraulic fracture mechanics. From the extracted outcomes, it was demonstrated that the confinement of the stress response depends on the matching among the characteristic parameters (εb,εs,m) of the rock breakdown, the volumetric opening, and channel flow regimes of the fracturing fluid. Examples in four limiting fracturing regimes show that (1) the confinement of the stress response is strongly determined by the existence of various fracturing regimes and takes place in a different manner during fracture initiation and opening. More specifically, during fracturing initiation, the ratio of the confining stress response to the far-field stress (Pcmax/σh) is 2.0500 in the M regime, 1.9600 in the M˜ regime, 2.7126 in the K regime, and 1.7448 in the K˜ regime, while when the fracture is opened, these values (PC/σh) are 1.8994, 1.8314, 1.6378, and 1.2846, respectively. (2) The impact of the confined stress response to the fluid pressure is also affected by the fracturing regimes; e.g., in both M and M˜ regimes, the peak confinement stress responses lag behind peak pore pressures, but in the K and K˜ regimes, lag off disappears. (3) The pore volumetric opening (Vpe) leads to an increase in the confining stress response, while the fracture opening (Vpd) leads to a reduction in the confining stress response.

Abstract Background The basic helix-loop-helix (bHLH) transcription factors (TFs), as one of the largest families of TFs, are essential regulators of plant terpenoid biosynthesis and response to stresses. Lavender has more than 75 volatile terpenoids, yet few TFs have been identified to be involved in the terpenoid biosynthesis. Results Based on RNA-Seq, reverse transcription-quantitative polymerase chain reaction, and transgenic technology, this study characterized the stress-responsive transcription factor LaMYC4 regulates terpenoid biosynthesis. Methyl jasmonate (MeJA) treatment increased volatile terpenoid emission, and the differentially expressed gene LaMYC4 was isolated. LaMYC4 expression level was higher in leaf than in other tissues. The expression of LaMYC4 decreased during flower development. The promoter of LaMYC4 contained hormone and stress-responsive regulatory elements and was responsive to various treatments, including UV, MeJA treatment, drought, low temperature, Pseudomonas syringae infection, and NaCl treatment. LaMYC4 overexpression increased the levels of sesquiterpenoids, including caryophyllenes, in Arabidopsis and tobacco plants. Furthermore, the expression of crucial node genes involved in terpenoid biosynthesis and glandular trichome number and size increased in transgenic tobacco. Conclusions We have shown that the stress-responsive MYC TF LaMYC4 from ‘Jingxun 2’ lavender regulates volatile terpenoid synthesis. This study is the first to describe the cloning of LaMYC4, and the results help understand the role of LaMYC4 in terpenoid biosynthesis.

ABSTRACT: (–)-Epicatechin-3-gallate (ECG), a bioactive polyphenolic compound, has contributed a lot to the health benefits of green tea. Great attention has been focused on (–)-epigallocatechin-3-gallate (EGCG), but limited research has been performed towards ECG. Like EGCG, ECG also possesses various pharmacological and physiological properties, such as mediation of antioxidant activities, anti-inflammation response, regulation of cell proliferation and apoptosis, as well as anticancer properties during angiogenesis, invasion and metastasis stages. Nontoxic ECG has various molecular targets within the cells, including CYP enzymes, phase II detoxification and antioxidant enzymes, as well as pro-inflammatory mediators. The antineoplastic mechanism contains inhibition of phase 1 CYP enzymes, induction of phase II detoxification and antioxidant enzymes, high anti-inflammatory efficacy, arrest of cell cycle progression, regulation of apoptosis, as well as mediation of metastasis processes. In particular, the gallate moiety of ECG is critical for mediating inhibitory effects towards cancer cells. Besides regulation of intracellular signaling pathways, ECG also inhibits RNase A and matrix metalloproteinase enzymatic activity via chelating metals (copper and zinc) in cancer cells. This review has summarized recent studies on pharmacological properties of ECG, and discussed corresponding mechanism on modulation of cellular signaling events by ECG, hoping to broaden its multiple usage.

Abstract Background Baculoviruses act as effective biological control agents against the invasive pest Hyphantria cunea Drury. In this study, two Chinese Hyphantria cunea nucleopolyhedrovirus (HycuNPV) isolates, HycuNPV-BJ and HycuNPV-HB, were deep sequenced and compared with the Japanese isolate, HycuNPV-N9, to determine whole-genome level diversity and evolutionary history. Results The divergence of the phylogenetic tree and the K2P distances based on 38 core-gene concatenated alignment revealed that two Chinese HycuNPV isolates were a novel species of Alphabaculovirus that infected Hyphantria cunea in China. The gene contents indicated significant differences in the HycuNPV genomes between the Chinese and Japanese isolates. The differences included gene deletions, acquisitions and structural transversions, but the main difference was the high number of single nucleotide polymorphisms (SNPs). In total, 10,393 SNPs, corresponding to approximately 8% of the entire HycuNPV-N9 genome sequence, were detected in the aligned reads. By analyzing non-synonymous variants, we found that hotspot mutation-containing genes had mainly unknown functions and most were early expressing genes. We found that the hycu78 gene which had early and late promoter was under positive selection. Biological activity assays revealed that the infectivity of HycuNPV-HB was greater than that of HycuNPV-BJ, and the killing speed of HycuNPV-HB was faster than that of HycuNPV-BJ. A comparison of molecular genetic characteristics indicated that the virulence differences between the two isolates were affected by SNP and structural variants, especially the homologous repeat regions. Conclusions The genomes of the two Chinese HycuNPV isolates were characterized, they belonged to a novel species of Alphabaculovirus that infected Hyphantria cunea in China. We inferred that the loss or gain of genetic material in the HycuNPV-HB and HycuNPV-BJ genomes resulted in new important adaptive capabilities to the H. cunea host. These results extend the current understanding of the genetic diversity of HycuNPV and will be useful for improving the applicability of this virus as a biological control agent.

Low-cost UAV RGB imagery combined with deep learning models has demonstrated the potential for the development of a feasible tool for field-scale yield prediction. However, collecting sufficient labeled training samples at the field scale remains a considerable challenge, significantly limiting the practical use. In this study, a split-merge framework was proposed to address the issue of limited training samples at the field scale. Based on the split-merge framework, a yield prediction method for winter wheat using the state-of-the-art Efficientnetv2_s (Efficientnetv2_s_spw) and UAV RGB imagery was presented. In order to demonstrate the effectiveness of the split-merge framework, in this study, Efficientnetv2_s_pw was built by directly feeding the plot images to Efficientnetv2_s. The results indicated that the proposed split-merge framework effectively enlarged the training samples, thus enabling improved yield prediction performance. Efficientnetv2_s_spw performed best at the grain-filling stage, with a coefficient of determination of 0.6341 and a mean absolute percentage error of 7.43%. The proposed split-merge framework improved the model ability to extract indicative image features, partially mitigating the saturation issues. Efficientnetv2_s_spw demonstrated excellent adaptability across the water treatments and was recommended at the grain-filling stage. Increasing the ground resolution of input images may further improve the estimation performance. Alternatively, improved performance may be achieved by incorporating additional data sources, such as the canopy height model (CHM). This study indicates that Efficientnetv2_s_spw is a promising tool for field-scale yield prediction of winter wheat, providing a practical solution to field-specific crop management.

The application of BIM technology in building construction provides the possibility to realize design accuracy, to visualize the construction details, to optimize construction schemes, and to enhance cooperation among various professionals. The Yancheng Nanyang Airport terminal 2 project, with its large span of steel roof structure, complex installation in mechanical and electrical pipeline (MEP) engineering, and difficulty in construction organization, is taken as the engineering background. The whole process application of BIM technology in the construction process is introduced. In structural engineering construction, the application of BIM technology can provide guidance for plane layout of the construction site, and can also assist in deepening the designs of irregular steel components. In steel construction, the application of BIM technology gives a commendable visual demonstration of the construction process of the metal roof system and the single-layer reticulated shell. In MEP engineering, the application of BIM technology provides a great approach to establish a synthesis of pipeline drawings to further form pipeline section diagrams and operation drawings. By integrating the dimension of time, precision control, and deviation rectification, a recursive construction drawing can be built. With respect to synergistic management, the quality and safety management in the construction site can be implemented on the basis of BIM terminal equipment as well. This paper will give a great reference on the application of BIM technology in the airport terminal construction.

Winter wheat is a major food source for the inhabitants of North China. However, its yield is affected by drought stress during the growing period. Hence, it is necessary to develop drought-resistant winter wheat varieties. For breeding researchers, yield measurement, a crucial breeding indication, is costly, labor-intensive, and time-consuming. Therefore, in order to breed a drought-resistant variety of winter wheat in a short time, field plot scale crop yield estimation is essential. Unmanned aerial vehicles (UAVs) have developed into a reliable method for gathering crop canopy information in a non-destructive and time-efficient manner in recent years. This study aimed to evaluate strategies for estimating crop yield using multispectral (MS) and hyperspectral (HS) imagery derived from a UAV in single and multiple growth stages of winter wheat. To accomplish our objective, we constructed a simple linear regression model based on the single growth stages of booting, heading, flowering, filling, and maturation and a multiple regression model that combined these five growth stages to estimate winter wheat yield using 36 vegetation indices (VIs) calculated from UAV-based MS and HS imagery, respectively. After comparing these regression models, we came to the following conclusions: (1) the flowering stage of winter wheat showed the highest correlation with crop yield for both MS and HS imagery; (2) the VIs derived from the HS imagery performed better in terms of estimation accuracy than the VIs from the MS imagery; (3) the regression model that combined the information of five growth stages presented better accuracy than the one that considered the growth stages individually. The best estimation regression model for winter wheat yield in this study was the multiple linear regression model constructed by the VI of ‘b1−b2/b3−b4’ derived from HS imagery, incorporating the five growth stages of booting, heading, flowering, filling, and maturation with r of 0.84 and RMSE of 0.69 t/ha. The corresponding central wavelengths were 782 nm, 874 nm, 762 nm, and 890 nm, respectively. Our study indicates that the multiple temporal VIs derived from UAV-based HS imagery are effective tools for breeding researchers to estimate winter wheat yield on a field plot scale.

As a bridge between genome and phenotype, metabolome is closely related to plant growth and development. However, the research on the combination of genome, metabolome and multiple agronomic traits in foxtail millet (Setaria italica) is insufficient. Here, based on the linkage analysis of 3,452 metabolites via with high-quality genetic linkage maps, we detected a total of 1,049 metabolic quantitative trait loci (mQTLs) distributed in 11 hotspots, and 28 metabolite-related candidate genes were mined from 14 mQTLs. In addition, 136 single-environment phenotypic QTL (pQTLs) related to 63 phenotypes were identified by linkage analysis, and there were 12 hotspots on these pQTLs. We futher dissected 39 candidate genes related to agronomic traits through metabolite-phenotype correlation and gene function analysis, including Sd1 semidwarf gene, which can affect plant height by regulating GA synthesis. Combined correlation network and QTL analysis, we found that flavonoid-lignin pathway maybe closely related to plant architecture and yield in foxtail millet. For example, the correlation coefficient between apigenin 7-rutinoside and stem diameter reached 0.98, and they were co-located at 41.33-44.15 Mb of chromosome 5, further gene function analysis revealed that 5 flavonoid pathway genes, as well as Sd1, were located in this interval . Therefore, the correlation and co-localization between flavonoid-lignins and plant architecture may be due to the close linkage of their regulatory genes in millet. Besides, we also found that a combination of genomic and metabolomic for BLUP analysis can better predict plant agronomic traits than genomic or metabolomic data, independently. In conclusion, the combined analysis of mQTL and pQTL in millet have linked genetic, metabolic and agronomic traits, and is of great significance for metabolite-related molecular assisted breeding.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Here, the authors identify a series of rare variants in DSP and PPL in multiplex families with EoE and uncover a pathogenic role for desmosomal dysfunction in EoE.

Waterlogging severely affects wheat growth and development. Limited availability of oxygen in the root zone negatively affects the metabolism of plants. The formation of adventitious roots (ARs) and root cortical aerenchyma (RCA) are the most important adaptive trait contributing to plants’ ability to survive in waterlogged soil conditions. This study used a genome-wide association study (GWAS) approach with 90K single nucleotide polymorphisms (SNPs) in a panel of 329 wheat genotypes, to reveal quantitative trait loci (QTL) conferring ARs and RCA. The wheat genotypes exposed to waterlogging were evaluated for ARs and RCA in both field and glasshouse over two consecutive years. Six and five significant marker-trait associations (MTAs) were identified for ARs and RCA formation under waterlogging, respectively. The most significant MTA for AR and RCA was found on chromosome 4B. Two wheat cultivars with contrasting waterlogging tolerance (tolerant: H-242, sensitive: H-195) were chosen to compare the development and regulation of aerenchyma in waterlogged conditions using staining methods. Results showed that under waterlogging conditions, H2O2 signal generated before aerenchyma formation in both sensitive and tolerant varieties with the tolerant variety accumulating more H2O2 and in a quicker manner compared to the sensitive one. Several genotypes which performed consistently well under different conditions can be used in breeding programs to develop waterlogging-tolerant wheat varieties.

Low immunity at birth increases risk of disease of young livestock, such as goat kids. Microbiomes change as animals mature, and a healthy microbiome is related to decreased risk of disease. The relationship between microbiota profiles and immunity at different developmental stages remains unclear. Young (female, n = 12, 30 d) and adult (female, n = 12, 2 yrs. old) Saanen dairy goats were used to investigate changes in rumen microbiomes, fecal microbiomes, and their correlations to circulating immune factors. Serum IgG (P = 0.02) and IgM (P < 0.01) were higher at 2 years than 30 d of age, but there were no differences in IgA (P = 0.34), IL-2 (P = 0.05), IL-4 (P = 0.37) and IL-6 (P = 0.73) between ages. Amplicon sequencing analysis revealed young goats had a higher diversity of bacterial communities in rumen and lower diversity in feces compared with adult goats. Ten genera in rumen and 14 genera in feces were positively correlated with serum IgM concentration across both ages. Olsenella, Methanosphaera, Quinella, Candidatus_Saccharimonas, and Methanobrevibacter in rumen and Ruminobacter, Treponema, Rikenelaceae_ RC9_ gut_ Group in feces were positively correlated with the concentration of IgG. The correlation analysis using weighted gene co-expression network analysis showed the MEblue module was positively associated with the IgG and IgM. These data provide novel insight into the association between rumen-feces microbiota and immune response. Further experiments are needed to investigate whether inoculating young livestock with immune-related bacteria identified can improve the immune status. Our data suggest a possible strategy to improve the immunity of the kids by alterative microbiota profiles.

Recently, atypical infectious bursal disease (IBD) caused by a novel variant infectious bursal disease virus (varIBDV) suddenly appeared in immunized chicken flocks in East Asia and led to serious economic losses. The epizootic varIBDV can partly circumvent the immune protection of the existing vaccines against the persistently circulating very virulent IBDV (vvIBDV), but its mechanism is still unknown. This study proved that the neutralizing titer of vvIBDV antiserum to the epizootic varIBDV reduced by 7.0 log2, and the neutralizing titer of the epizootic varIBDV antiserum to vvIBDV reduced by 3.2 log2. In addition, one monoclonal antibody (MAb) 2-5C-6F had good neutralizing activity against vvIBDV but could not well recognize the epizootic varIBDV. The epitope of the MAb 2-5C-6F was identified, and two mutations of G318D and D323Q of capsid protein VP2 occurred in the epizootic varIBDV compared to vvIBDV. Subsequently, the indirect immunofluorescence assay based on serial mutants of VP2 protein verified that residue mutations 318 and 323 influenced the recognition of the epizootic varIBDV and vvIBDV by the MAb 2-5C-6F, which was further confirmed by the serial rescued mutated virus. The following cross-neutralizing assay directed by MAb showed residue mutations 318 and 323 also affected the neutralization of the virus. Further data also showed that the mutations of residues 318 and 323 of VP2 significantly affected the neutralization of the IBDV by antiserum, which might be deeply involved in the immune circumvention of the epizootic varIBDV in the vaccinated flock. This study is significant for the comprehensive prevention and control of the emerging varIBDV.

Flowering time is an indicator of adaptation in maize and a key trait for selection in breeding. The genetic basis of flowering time in maize, especially in response to plant density, remains unclear. The objective of this study was to identify maize quantitative trait loci (QTL) associated with flowering time-related traits that are stably expressed under several plant densities and show additive effects that vary with plant density. Three hundred recombinant inbred lines (RIL) derived from a cross between Ye 478 and Qi 319, together with their parents, were planted at three plant densities (90,000, 120,000, and 150,000 plants ha−1) in four environments. The five traits investigated were days to tasseling (DTT), days to silking (DTS), days to pollen shed (DTP), interval between anthesis and silking (ASI), and interval between tasseling and anthesis (TAI). A high-resolution bin map was used for QTL mapping. In the RIL population, the DTT, DTS, and DTP values increased with plant density, whereas the ASI and TAI values showed negligible response to plant density. A total of 72 QTL were identified for flowering time-related traits, including 15 stably expressed across environments. Maize flowering time under different densities seems to be regulated by complex pathways rather than by several major genes or an independent pathway. The effects of some stable QTL, especially qDTT8-1 and qDTT10-4, varied with plant density. Fine mapping and cloning of these QTL will shed light on the mechanism of flowering time and assist in breeding early-maturing maize inbred lines and hybrids.

The superimposed slab shear wall has been found to be more and more applicable in the building construction industry due to its building industrialization superiority. The hysteretic behavior of superimposed slab shear walls accounts for an important part of seismic performance analysis. This paper presents the results of a numerical study to investigate the hysteretic behavior of superimposed slab shear walls. Different calculation methods of the shear capacity of the combined interface and horizontal connection are introduced. The calculated results show that the shear capacity of the combined interface and horizontal connection is much larger than the ultimate shear capacity of a superimposed slab shear wall. Therefore, the bond slip effect of a combined interface and horizontal connection can be ignored in finite element analysis on the premise of it not affecting calculation precision. Three different theoretical analysis models, namely the vertical multi-line element model, bend–shear coupled fiber model and layered shell element model, were established in OpenSEES based on a macro-model and a micro-model. The results show that the calculated results of the vertical multi-line element model and the bend–shear coupled fiber model agree reasonably with the experiment results, whereas the calculated results of the layered shell model gave a relatively larger initial stiffness.

Infectious bursal disease (IBD) is an acute, highly contagious, immunosuppressive, and fatal infectious disease of young chickens caused by infectious bursal disease virus (IBDV). Since 2017, a new trend has been discovered in the IBDV epidemic, with very virulent IBDV (vvIBDV) and novel variant IBDV (nVarIBDV) becoming the two current dominant strains in East Asia including China. In this study, we compared the biological characteristics of the vvIBDV (HLJ0504 strain), nVarIBDV (SHG19 strain), and attenuated IBDV (attIBDV, Gt strain) using specific-pathogen-free (SPF) chicken infection model. The results showed that vvIBDV distributed in multiple tissues, replicated the fastest in lymphoid organs such as bursa of Fabricius, induced significant viremia and virus excretion, and is the most pathogenic virus with a mortality of more than 80%. The nVarIBDV had a weaker replication capability and did not kill the chickens but caused severe damage to the central immune organ bursa of Fabricius and B lymphocytes and induced significant viremia and virus excretion. The attIBDV strain was found not to be pathogenic. Further studies preliminarily suggested that the expression level of inflammatory factors triggered by HLJ0504 was the highest, followed by the SHG19 group. This study is the first to systematically compare the pathogenic characteristics of three IBDVs closely related to poultry industry from the perspectives of clinical signs, micro-pathology, virus replication, and distribution. It is of great importance to obtain an extensive knowledge of epidemiology, pathogenicity, and comprehensive prevention, and control of various IBDV strains.

Acer truncatum Bunge is a versatile, oil-producing, woody tree natively and widely distributed in northern China. In 2011, The People’s Republic of China’s Ministry of Health certified Acer truncatum seed oil (Aoil) as a new food resource. Unsaturated fatty acids account for up to 92% of the entire Aoil. When Aoil is processed or stored, it can easily oxidize. In this study, the effects of rosemary (Rosmarinus officinalis L.) extract on the oxidation stability of Aoil were analysed from multiple angles. The results of radical scavenging ability, malondialdehyde, and free fatty acid reveal that rosemary crude extract (RCE), rosmarinic acid (RA), and carnosic acid (CA) can significantly inhibit the oxidation of Aoil, and CA has the best oxidative stability for Aoil among the tested components of the crude rosemary. The delayed oxidation ability of CA for Aoil was slightly weaker than that of tert-butylhydroquinone (TBHQ), but stronger than that of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and α-tocopherol (α-T), which was confirmed by microstructures, kinematic viscosity, Aoil weight change, and functional group. Additionally, CA-enriched Aoil had the smallest content of volatile lipid oxidation products. Moreover, lecithin-CA particles were added to enhance the oxidative stability of Aoil. These findings show that CA is a potent antioxidant, capable of successfully preventing Aoil oxidation.