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Abstract Background Oilseed rape (B. napus L.) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Soil properties and the presence of other soluble compounds or ions, cause a heterogeneous distribution of Cd. Results The aim of our study was to reveal the differential responses of B. napus to different Cd abundances. Herein, we found that high Cd (50 μM) severely inhibited the growth of B. napus, which was not repressed by low Cd (0.50 μM) under hydroponic culture system. ICP-MS assays showed that the Cd2+ concentrations in both shoots and roots under 50 μM Cd were over 10 times higher than those under 0.50 μM Cd. Under low Cd, the concentrations of only shoot Ca2+/Mn2+ and root Mn2+ were obviously changed (both reduced); under high Cd, the concentrations of most cations assayed were significantly altered in both shoots and roots except root Ca2+ and Mg2+. High-throughput transcriptomic profiling revealed a total of 18,021 and 1408 differentially expressed genes under high Cd and low Cd conditions, respectively. The biological categories related to the biosynthesis of plant cell wall components and response to external stimulus were over-accumulated under low Cd, whereas the terms involving photosynthesis, nitrogen transport and response, and cellular metal ion homeostasis were highly enriched under high Cd. Differential expression of the transporters responsible for Cd uptake (NRAMPs), transport (IRTs and ZIPs), sequestration (HMAs, ABCs, and CAXs), and detoxification (MTPs, PCR, MTs, and PCSs), and some other essential nutrient transporters were investigated, and gene co-expression network analysis revealed the core members of these Cd transporters. Some Cd transporter genes, especially NRAMPs and IRTs, showed opposite responsive patterns between high Cd and low Cd conditions. Conclusions Our findings would enrich our understanding of the interaction between essential nutrients and Cd, and might also provide suitable gene resources and important implications for the genetic improvement of plant Cd accumulation and resistance through molecular engineering of these core genes under varying Cd abundances in soils.

Globin loci harbor genes that are expressed embryonically and silenced postnatally. Here the authors show that zeta-globin silencing depends upon selective hypoacetylation of its TAD subdomain, which blocks its interaction with the alpha-globin super-enhancer, and zeta-globin can be reactivated by acetylation.

Abstract Background B-box (BBX) genes play important roles in plant growth regulation and responses to abiotic stresses. The plant growth and yield production of allotetraploid rapeseed is usually hindered by diverse nutrient stresses. However, no systematic analysis of Brassicaceae BBXs and the roles of BBXs in the regulation of nutrient stress responses have not been identified and characterized previously. Results In this study, a total of 536 BBXs were identified from nine brassicaceae species, including 32 AtBBXs, 66 BnaBBXs, 41 BoBBXs, 43 BrBBXs, 26 CrBBXs, 81 CsBBXs, 52 BnBBXs, 93 BjBBXs, and 102 BcBBXs. Syntenic analysis showed that great differences in the gene number of Brassicaceae BBXs might be caused by genome duplication. The BBXs were respectively divided into five subclasses according to their phylogenetic relationships and conserved domains, indicating their diversified functions. Promoter cis-element analysis showed that BBXs probably participated in diverse stress responses. Protein-protein interactions between BnaBBXs indicated their functions in flower induction. The expression profiles of BnaBBXs were investigated in rapeseed plants under boron deficiency, boron toxicity, nitrate limitation, phosphate shortage, potassium starvation, ammonium excess, cadmium toxicity, and salt stress conditions using RNA-seq data. The results showed that different BnaBBXs showed differential transcriptional responses to nutrient stresses, and some of them were simultaneously responsive to diverse nutrient stresses. Conclusions Taken together, the findings investigated in this study provided rich resources for studying Brassicaceae BBX gene family and enriched potential clues in the genetic improvement of crop stress resistance.

Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF12.5%, TKPF25% and TKPF50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Such gene vectors exhibited the following features: (1) fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions; (2) The fluorophilic effect mediated efficient cellular uptake and endosomal escape; (3) ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. Notably, TKPFs also exhibited great serum resistance in gene delivery and TKPF50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrates that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.

Cardiac resynchronization therapy (CRT) for heart failure requires transvenous insertion of a left ventricular pacing lead through the coronary sinus. However, repeated intraoperative dislocations often occur. Therefore, we describe a novel technique that uses the loop technique to treat patients with repeated intraoperative dislocations during transvenous left ventricular lead implantation to stabilize the lead in its final position. In five patients with repeated intraoperative dislocation during transvenous left ventricular lead implantation, the loop technique was successfully used to stabilize the lead in its final position. The pacing and sensing parameters were satisfactory in all patients at implantation and 12 months post-operatively. Compared with the pre-operative values, the 12-month post-operative values for the left ventricular ejection fraction were significantly increased and the left ventricular end systolic dimension and left ventricular end diastolic dimension were significantly decreased (P < 0.05). The left ventricular ejection fraction of these 5 patients increased by more than 15%. CRT significantly improved the left ventricular structure and function of these 5 patients. During the 1-, 3-, 6-, and 12-month follow-ups, no left ventricular lead dislocations were observed. This loop technique is safe and effective and can be considered for repeated intraoperative dislocation during transvenous left ventricular lead implantation through the coronary sinus of a CRT device.

Abstract Transcription factor SP1 could manipulate pathways involved in ovarian cancer progression. LncRNAs are involved in SP1‐mediated tumorigenesis. LncRNA DANCR could promote metastasis of ovarian cancer. However, the regulatory function and involvement of SP1‐induced lncRNA DANCR in ovarian cancer remain elusive. Data from this study showed that SP1 was up‐regulated in ovarian cancer tissues and cells (CAOV3, SKOV3, A2780), and SP1 could bind to the promoter region of DANCR through chromatin immunoprecipitation and leuciferase activity assays. Therefore, DANCR was transcriptionally induced by SP1 in ovarian cancer tissues and cells (CAOV3, SKOV3, A2780). Functionally, reduced expression of DANCR suppressed cell viability, migration and invasion of CAOV3, while enhanced DANCR expression contributed to SKOV3 growth. Over‐expression of SP1 reversed the suppressive effects of DANCR interference on ovarian cancer progression. In conclusion, SP1‐induced DANCR contributed to oncogenic potential of ovarian cancer, suggesting a promising therapeutic target for ovarian cancer.

Abstract Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses. Herein we investigate their functions in human epithelial cells, the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A deficiency in MDA5, RIG-I or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication. The expression of the type I/III interferon (IFN) during infection was impaired in MDA5 −/− and MAVS −/−, but not in RIG-I −/−, when compared to wild type (WT) cells. The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2), the cellular entry receptor for SARS-CoV-2, was ~ 2.5-fold higher in RIG-I −/− than WT cells. These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor, IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-I in epithelial cells.

This paper focuses on the application of pile foundation underpinning technology in a deep foundation pit of a subway Viaduct Project in Beijing. The study aims to address the engineering characteristics of the project, including a large number of new piles, a wide span of underpinning abutment, a long length of deep foundation pit, and a wide range of influences. This research utilizes field monitoring and numerical simulation methods to investigate the pile foundation underpinnings. The impact and management of road-deep foundation pit construction are considered, as well as their combined effect on subway viaducts and track structures. The primary accomplishments are as follows: (1) By analyzing the data from on-site deformation monitoring, it is evident that the pier exhibits maximum vertical deformation and maximum transverse deformation at the same location. The measuring locations are specifically situated on Pier 7# at the pile foundation underpinning. The maximum vertical and transverse deformations of the track are directly proportional to the maximum deformation of the pier. (2) By comparing the numerical simulation results with the field monitoring data, it is observed that although there is some discrepancy between the two, the deformation trend is largely consistent. This suggests that the numerical simulation analysis method is effective in reflecting the deformation of the bridge and track. (3) Through the numerical model and changing the values of the retaining structure parameters, the sensitivity of the pier deformation near the road foundation pit to the retaining structure parameters is systematically analyzed. The sensitivity of the pier deformation to the foundation pit parameters is as follows: the embedded depth insertion ratio of the retaining pile > the diameter of the retaining pile > the pile spacing. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether there is a correlation between the inflammatory state and the pathogenesis and clinical features of sudden hearing loss (SHL) by studying the expression of inflammation‐related cytokines in the peripheral blood of patients with SHL. Methods: In this work, we analyzed the cytokine profiles of 48 analytes in 38 patients with SHL compared to 38 healthy donors using a multiplex immunoassay. This study used appropriate statistical methods to screen for inflammatory cytokines associated with the pathogenesis of SHL, to analyze their network correlation, and to analyze the relationship between clinical features of SHL and inflammatory cytokines. Results: Several cytokines, including CTACK, Eotaxin, HGF, INF‐α2, IFN‐β, IL‐1β, IL‐1ra, IL‐2Rα, IL‐4, IL‐7, IL‐8, IL‐9, IL‐10, IL‐12(p40), IL‐13, MIG, β‐NGF, SCF, and TNF‐α, exhibited significantly higher levels in the peripheral blood of the SHL group compared to the control group. An inflammatory network composed of multiple cytokines, including IL‐1β, is a risk factor for the development of SHL. Conclusion: This study identified several inflammatory cytokines with elevated expression, which may be linked with the onset of SHL. The results of this study also provide a basis for the theoretical hypothesis of inflammation in SHL. Level of Evidence: 3 Laryngoscope, 134:3293–3301, 2024 [ABSTRACT FROM AUTHOR]

Three new species of Isodon (Lamiaceae) from China are described and illustrated, based on both morphological evidence and our recent phylogenomic studies of the genus. Isodon attenuatus, a herbaceous new species known only from the Fanjing Mountain, is shown to be sister to I. villosus, but they can be easily distinguished by leaf and inflorescence indumentum, calyx teeth shape and corolla tube morphology. Isodon gongshanensis, a herbaceous new species collected from the Hengduan Mountains in southwest China, represents a distinct lineage within the genus. Isodon sukungii, a shrubby new species also endemic to the Hengduan Mountains, was previously misidentified as I. tenuifolius, but they are phylogenetically distantly related and differ in lamina size and margin, inflorescence type and corolla length and shape. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) therapies function by alleviating immunosuppression on tumor-infiltrating lymphocytes (TILs) but are often insufficient to fully reactivate these dysfunctional TILs. Although interleukin 12 (IL-12) has been used in combination with ICB to improve efficacy, this remains limited by severe toxicity associated with systemic administration of this cytokine. Here, we engineer a fusion protein composed of an anti-PD-1 antibody and a mouse low-affinity IL-12 mutant-2 (αPD1-mIL12mut2). Systemic administration of αPD1-mIL12mut2 displays robust antitumor activities with undetectable toxicity. Mechanistically, αPD1-mIL12mut2 preferentially activates tumor-infiltrating PD-1+CD8+T cells via high-affinity αPD-1 mediated cis-binding of low-affinity IL-12. Additionally, αPD1-mIL12mut2 treatment exerts an abscopal effect to suppress distal tumors, as well as metastasis. Collectively, αPD1-mIL12mut2 treatment induces robust systemic antitumor responses with reduced side effects. IL-12 has been shown to enhance the efficacy of anti-PD-1 therapy, but this has been hampered by issues with toxicity and poor delivery to the tumour site. In this study, the authors generate an anti-PD-1 antibody/IL-12 fusion protein for specific targeting of IL-12 to tumour sites, resulting in potent anti-tumour immunity with limited toxicity. [ABSTRACT FROM AUTHOR]

The role of BRD4 and Mediator in regulating enhancer-promoter interactions is poorly understood. Here the authors find that treatment with BET inhibitors or pharmacological degradation of BRD4 disrupts transcription while having very little effect on enhancer-promoter interactions.

Host-plant volatiles play an important role as cues for herbivores in search of resources, mates and oviposition sites in complex environments. Plant volatile-based attractants can be developed for pest monitoring and control. Previously, we indicated that mated female adults of Callosobruchus chinensis showed choice preference behavior toward 2-hexenal and benzaldehyde. Our objective here was to investigate the synergistic effect of host-derived attractive volatiles in attracting C. chinensis under laboratory and field conditions in Shanxi Province, China. We hypothesized that the ratio and concentration of volatiles derived from Vigna radiata play critical roles for C. chinensis in locating this host. Therefore, we collected and identified the volatiles of mungbean by using headspace collection and GC-MS. The effectiveness of different ratios and concentrations of two compounds (2-hexenal and benzaldehyde) that elicit C. chinensis searching behavior were examined in Y-tube olfactometer assays. The combination of 300 μg μL−1 2-hexenal and 180 μg μL−1 benzaldehyde loadings exhibited a synergistic effect on attracting C. chinensis (82.35%). Compared to control traps, the adults were significantly attracted to traps baited with blends, and more attraction to females than males was found for blend traps in the field experiments. Our results suggest that blends of this specific concentration and ratio of benzaldehyde and 2-hexenal can be used in traps as attractants for C. chinensis monitoring and control in the field.