Electrochemically Enable N-Sulfenylation/Phosphinylation of Sulfoximines via Oxidative Dehydrocoupling Reaction.

An electrochemical oxidative cross-coupling strategy for the synthesis of N-sulfenylsulfoximines from sulfoximines and thiols was accomplished, giving diverse N-sulfenylsulfoximines in moderate to good yields. Moreover, this strategy can be extended to construct the N-P bond of N-phosphinylated sulfoximines. With electrons as reagents, the oxidative dehydrogenation cross-coupling reaction proceeds smoothly in the absence of traditional redox reagents.

Study on the Mechanical Properties of 3D-Printed Sand Mold Specimens with Complex Hollow Structures.

Casting, as a fundamental process in metal forming, finds widespread applications in the manufacturing industry. The advent of 3D printing hollow sand mold technology presents a novel method for casting technology to revolutionize traditional dense sand molds, offering increased flexibility in achieving quality control and improvement in casting processes. Consequently, this study delves into an examination of the mechanical strengths of 3D-printed sand molds with complex hollow structures and further investigates the influence of hollow sand mold concession on castings. The results indicate that compressive and high-temperature residual tensile and bending strengths vary in hollow structures. Multi-layer shells have greater high-temperature residual tensile, compressive, and bending strengths than truss hollow sand molds with roughly the same hollow volume fraction. Compared to dense sand molds, hollow sand molds, which have a lower mechanical strength, have better retractability, which helps reduce the residual stress and crack tendency of castings. The breaking of hollow structures is limited to local areas, unlike the penetrative cracking of dense sand molds. The I-beam-shaped casting test results indicate that a hollow structure is beneficial for the preservation of the integrity of a sand mold during the casting process. Compared to dense and truss hollow molds, a multi-layer shell hollow sand structure has the comprehensive advantages that it improves retractability while maintaining strength relatively well, reduces the residual stress, and avoids cracks in castings and itself.

Aristolochic acid I aggravates oxidative stress-mediated apoptosis by inhibiting APE1/Nrf2/HO-1 signaling.

Nephrotoxicity induced by aristolochic acid I (AAI) is related to redox stress and apoptosis. Apurinic/apyrimidine endonuclease 1 (APE1) has antioxidant and anti-apoptotic effects. This study investigated the potential role of APE1 in AAI-induced nephrotoxicity. Renal injury was successfully induced in C57BL/6J mice by intraperitoneal injection of AAI every other day for 28 days. Expressions of APE1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) in renal tissues of the model mice was inhibited, accompanied by oxidative damage and apoptosis. Similar results were obtained in vitro in human proximal tubular (HK-2) cells damaged by AAI. In the presence of a low concentration of the APE1 inhibitor E3330, expression of Nrf2 and HO-1 proteins in HK-2 cells was decreased and AAI-induced apoptosis was aggravated. Overexpression of APE1 in HK-2 cells promoted the expression of Nrf2 and HO-1, and alleviated apoptosis and renal injury induced by AAI. The collective findings demonstrate that AAI can inhibit the induction of oxidative stress and apoptosis by the APE1/Nrf2/HO-1 axis, leading to AAI renal injury. Targeting APE1 may be an effective therapeutic strategy to treat AA nephrotoxicity.

Geometric Boundary Guided Feature Fusion and Spatial-Semantic Context Aggregation for Semantic Segmentation of Remote Sensing Images.

Semantic segmentation of remote sensing images aims to achieve pixel-level semantic category assignment for input images. This task has achieved significant advances with the rapid development of deep neural network. Most current methods mainly focus on effectively fusing the low-level spatial details and high-level semantic cues. Other methods also propose to incorporate the boundary guidance to obtain boundary preserving segmentation. However, current methods treat the multi-level feature fusion and the boundary guidance as two separate tasks, resulting in sub-optimal solutions. Moreover, due to the large inter-class difference and small intra-class consistency within remote sensing images, current methods often fail to accurately aggregate the long-range contextual cues. These critical issues make current methods fail to achieve satisfactory segmentation predictions, which severely hinder downstream applications. To this end, we first propose a novel boundary guided multi-level feature fusion module to seamlessly incorporate the boundary guidance into the multi-level feature fusion operations. Meanwhile, in order to further enforce the boundary guidance effectively, we employ a geometric-similarity-based boundary loss function. In this way, under the explicit guidance of boundary constraint, the multi-level features are effectively combined. In addition, a channel-wise correlation guided spatial-semantic context aggregation module is presented to effectively aggregate the contextual cues. In this way, subtle but meaningful contextual cues about pixel-wise spatial context and channel-wise semantic correlation are effectively aggregated, leading to spatial-semantic context aggregation. Extensive qualitative and quantitative experimental results on ISPRS Vaihingen and GaoFen-2 datasets demonstrate the effectiveness of the proposed method.

miR-125b-5p-MAPK1-C/EBPα feedback loop regulates all-trans retinoic acid resistance in acute promyelocytic leukemia.

BACKGROUND: Various studies have highlighted the significance of miR-125b-5p in tumour chemotherapy resistance; However, whether miR-125b-5p is associated with all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) has not been reported. METHODS: Drug-resistance-related factors in APL were predicted using the DRESIS database. The expression levels of miR-125b-5p in ATRA-sensitive and ATRA-resistant APL cells were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A nitrotetrazolium blue (NBT) reduction assay and flow cytometry (FCM) were used to detect the effect of miR-125b-5p on ATRA resistance in APL cells. An APL xenograft tumour mouse model was established to determine the effect of miR-125b-5p on ATRA resistance. A dual-luciferase gene reporter assay, qRT-PCR, and western blotting verified the regulation by miR-125b-5p of its target gene, MAPK1, and the MAPK1 downstream factor, C/EBPα. An NBT reduction assay and FCM were used to detect the effect of C/EBPα on ATRA resistance in APL cells. Western blotting and qRT-PCR were used to assess the regulation of miR-125b-5p and MAPK1 by C/EBPα. RESULTS: miR-125b-5p expression levels were dramatically increased in ATRA-resistant APL cells. Both in vitro and in vivo experiments revealed that miR-125b-5p overexpression enhanced ATRA resistance in APL. miR-125b-5p promoted ATRA resistance by sponging MAPK1. C/EBPα was negatively regulated by miR-125b-5p, which in addition, regulated ATRA resistance in APL cells. C/EBPα also regulated the miR-125b-5p-MAPK1 axis. CONCLUSION: The findings of this study indicate that the miR-125b-5p-MAPK1-C/EBPα feedback loop regulated ATRA resistance in APL. Thus, miR-125b-5p may be a promising target for treating ATRA resistance in APL.

Aristolocholic acid I promotes renal tubular epithelial fibrosis by upregulating matrix metalloproteinase-9 expression via activating the C3a/C3aR axis of macrophages.

Aristolochic acid I (AAI) can cause nephrotoxicity and is characterized by interstitial fibrosis. The C3a/C3aR axis of macrophages and matrix metalloproteinase-9 (MMP-9) play important roles in fibrosis, but whether they are involved in AAI-induced renal interstitial fibrosis and are related remains to be elucidated. In this study, we investigated whether C3a/C3aR axis of macrophages promotes renal interstitial fibrosis by regulating MMP-9 in aristolochic acid nephropathy (AAN). Intraperitoneal injection of AAI for 28 days successfully induced AAN in C57bl/6 mice. The content of C3a in the kidney of AAN mice was increased, and there was a significant distribution of macrophages in the renal tubules. The same results were observed in the in vitro experiment. We also explored the role and mechanism of macrophages after AAI administration in the epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells (RTECs) and found that AAI could activate the C3a/C3aR axis of macrophages to upregulate p65 expression in macrophages. p65 upregulated MMP-9 expression in macrophages not only directly but also by promoting the secretion if interleukin-6 by macrophages and then activating STAT3 in RTECs. The upregulation of MMP-9 expression could promote the EMT of RTECs. Taken together, our study demonstrated that the AAI-activated the C3a/C3aR axis of macrophages, which induced MMP-9 production, was one of the causes of renal interstitial fibrosis. Therefore, targeting the C3a/C3aR axis of macrophages is an effective therapeutic strategy for the prevention and treatment of renal interstitial fibrosis in AAN.

MEDIATOR SUBUNIT 16 negatively regulates rice immunity by modulating PATHOGENESIS RELATED 3 activity.

Lesion mimic mutants (LMMs) are valuable genetic resources for unraveling plant defense responses including programmed cell death. Here, we identified a rice (Oryza sativa) LMM, spotted leaf 38 (spl38), and demonstrated that spl38 is essential for the formation of hypersensitive response-like lesions and innate immunity. Map-based cloning revealed that SPL38 encodes MEDIATOR SUBUNIT 16 (OsMED16). The spl38 mutant showed enhanced resistance to rice pathogens Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae (Xoo) and exhibited delayed flowering, while OsMED16-overexpressing plants showed increased rice susceptibility to M. oryzae. The OsMED16-edited rice lines were phenotypically similar to the spl38 mutant but were extremely weak, exhibited growth retardation, and eventually died. The C-terminus of OsMED16 showed interaction with the positive immune regulator PATHOGENESIS RELATED 3 (OsPR3), resulting in the competitive repression of its chitinase and chitin-binding activities. Furthermore, the ospr3 osmed16 double mutants did not exhibit the lesion mimic phenotype of the spl38 mutant. Strikingly, OsMED16 exhibited an opposite function in plant defense relative to that of Arabidopsis (Arabidopsis thaliana) AtMED16, most likely because of 2 amino acid substitutions between the monocot and dicot MED16s tested. Collectively, our findings suggest that OsMED16 negatively regulates cell death and immunity in rice, probably via the OsPR3-mediated chitin signaling pathway.

Cinobufagin induces acute promyelocytic leukaemia cell apoptosis and PML-RARA degradation in a caspase-dependent manner by inhibiting the ß-catenin signalling pathway.

CONTEXT: Acute promyelocytic leukaemia (APL) is a malignant hematological tumour characterized by the presence of promyelocytic leukaemia-retinoic acid receptor A (PML-RARA) fusion protein. Cinobufagin (CBG) is one of the main effective components of toad venom with antitumor properties. However, only a few reports regarding the CBG treatment of APL are available. OBJECTIVE: We explored the effect and mechanism of action of CBG on NB4 and NB4-R1 cells. MATERIALS AND METHODS: We evaluated the viability of NB4 and NB4-R1 cells treated with 0, 20, 40, and 60 nM CBG for 12, 24, and 48 h. After treatment with CBG for 24 h, Bcl-2 associated X (Bax), B-cell lymphoma 2 (Bcl-2), ß-catenin, cyclin D1, and c-myc expression was detected using western blotting and real-time polymerase chain reaction. Caspase-3 and PML-RARA expression levels were detected using western blotting. RESULTS: CBG inhibited the viability of NB4 and NB4-R1 cells. The IC50 values of NB4 and NB4-R1 cells treated with CBG for 24 h were 45.2 nM and 37.9 nM, respectively. CBG induced NB4 and NB4-R1 cell apoptosis and PML-RARA degradation in a caspase-dependent manner and inhibited the ß-catenin signalling pathway. DISCUSSION AND CONCLUSION: CBG induced NB4 and NB4-R1 cell apoptosis and PML-RARA degradation in a caspase-dependent manner by inhibiting the ß-catenin signalling pathway. This study proposes a novel treatment strategy for patients with APL, particularly those with ATRA-resistant APL.

Genome-Wide Analysis of Soybean Lateral Organ Boundaries Domain Gene Family Reveals the Role in Phytophthora Root and Stem Rot.

The plant-specific lateral organ boundaries (LOB) domain (LBD) proteins, a family of transcription factors, play important roles in plant growth and development, as well as in responses to various stresses. However, little is known about the functions of LBD genes in soybean (Glycine max). In this study, we investigated the evolution and classification of the LBD family in soybean by a phylogenetic tree of the LBD gene family from 16 species. Phylogenetic analysis categorized these proteins into two classes (Class I and Class II) with seven subgroups. Moreover, we found that all the 18 LBD ancestors in angiosperm were kept in soybean, common bean genomes, and genome-wide duplication, suggesting the main force for the expansion of LBD from common bean to soybean. Analysis of gene expression profiling data indicated that 16 GmLBD genes were significantly induced at different time points after inoculation of soybean plants (cv. Huachun 6) with Phytophthora sojae (P. sojae). We further assessed the role of four highly upregulated genes, GmLBD9, GmLBD16, GmLBD23, and GmLBD88, in plant defense in soybean hairy roots using the transient overexpression and knockdown assays. The results showed that GmLBD9 and GmLBD23 negatively regulate plant immunity against P. sojae, whereas GmLBD16 and GmLBD88 positively manipulate plant immunity against P. sojae. Collectively, our findings expand our knowledge of the origin and evolution of the GmLBD gene family in soybean and promote the potential application of these genes in soybean genetic improvement.

Facile Preparation of Ni2P with a Sulfur-Containing Surface Layer by Low-Temperature Reduction of Ni2P2S6.

Preparation of Ni2P by temperature-programmed reduction (TPR) of a phosphate precursor is challenging because the P-O bond is strong. An alternative approach to synthesizing Ni2P, by reduction of nickel hexathiodiphosphate (Ni2P2S6), is presented. Conversion of Ni2P2S6 into Ni2P occurs at 200-220 °C, a temperature much lower than that required by the conventional TPR method (typically 500 °C). A sulfur-containing layer with a thickness of about 4.7 nm, composed of tiny crystallites, was observed at the surface of the obtained Ni2 P catalyst (Ni2P-S). This is a direct observation of the sulfur-containing layer of Ni2P, or the so-called nickel phosphosulfide phase. Both the hydrodesulfurization activity and the selective hydrogenation performance of Ni2P-S were superior to that of the catalyst prepared by the TPR method, suggesting a positive role of sulfur on the surface of Ni2P-S. These features render Ni2P-S a legitimate alternative non-precious metal catalyst for hydrogenation reactions.