MOG-antibody-associated transverse myelitis with the H-sign and unusual MRI enhancement: a case report and literature review.

Transverse myelitis is the second most common symptoms in myelin oligodendrocyte antibody-associated diseases (MOGAD), causing obvious clinical manifestation. T2-hyperintense lesions mainly restricted to the gray matter in the spinal cord on axial magnetic resonance imaging, produce the H-sign, which is thought to be the typical finding of MOGAD. Contrast enhancement can be observed in some cases of myelin oligodendrocyte antibody-associated transverse myelitis (MOG-TM). However, reports on the enhancement pattern associated with the H-sign are rarely seen. In this report, we describe a case of pediatric MOG-TM in which the H-sign was observed without enhancement, while the surrounding white matter exhibited enhancement. This pattern contradicts the previously observed gray matter involvement. Then we reviewed the literatures of myelin oligodendrocyte antibody-positive myelitis to focus on the neuroimaging features and discuss the implications of our finding.

Cooperation between SIX1 and DHX9 transcriptionally regulates integrin-focal adhesion signaling mediated metastasis and sunitinib resistance in KIRC.

High invasive capacity and acquired tyrosine kinase inhibitors (TKI) resistance of kidney renal clear cell carcinoma (KIRC) cells remain obstacles to prolonging the survival time of patients with advanced KIRC. In the present study, we reported that sine oculis homeobox 1 (SIX1) was upregulated in sunitinib-resistant KIRC cells and metastatic KIRC tissues. Subsequently, we found that SIX1 mediated metastasis and sunitinib resistance via Focal adhesion (FA) signaling, and knockdown of SIX1 enhanced the antitumor efficiency of sunitinib in KIRC. Mechanistically, Integrin subunit beta 1 (ITGB1), an upstream gene of FA signaling, was a direct transcriptional target of SIX1. In addition, we showed that DExH-box helicase 9 (DHX9) was an important mediator for SIX1-induced ITGB1 transcription, and silencing the subunits of SIX1/DHX9 complex significantly reduced transcription of ITGB1. Downregulation of SIX1 attenuated nuclear translocation of DHX9 and abrogated the binding of DHX9 to ITGB1 promoter. Collectively, our results unveiled a new signal axis SIX1/ITGB1/FAK in KIRC and identified a novel therapeutic strategy for metastatic KIRC patients.

The utilization of quantum dot labeling as a burgeoning technique in the field of biological imaging.

Quantum dots (QDs), with their unique optical and physical properties, have revolutionized the field of biological imaging, providing researchers with tools to explore cellular processes and molecular interactions in unprecedented detail. This review explores the diverse properties of QDs, emphasizing their application in biological imaging and addressing both their advantages and challenges. We discuss the developments in QD technology that have facilitated their integration into bioimaging, highlighting the role of surface modifications in enhancing their biocompatibility and functionality. The varied applications of QDs in both in vitro and in vivo imaging settings are examined, showcasing their capacity to deliver brighter, more stable, and multiplexed imaging solutions compared to traditional fluorescent dyes. Furthermore, we delve into the challenges associated with QD use, particularly concerns regarding their potential toxicity and long-term effects on biological systems, and explore ongoing research aimed at mitigating these issues. Finally, we discuss future directions in QD technology, anticipating advancements that will further solidify their role in biological imaging and open up new avenues for scientific exploration.

Enrichment and detection of polycyclic aromatic hydrocarbon in tea and coffee using phenyl-functionalized NiFe2O4@Ti3C2TX based magnetic solid-phase extraction.

Polycyclic aromatic hydrocarbons (PAHs) are commonly found in various environmental matrices and have received significant attention due to their toxic effects on ecosystems and environmental health. In this study, a specific magnetic composite material derived from MXene, known as phenyl-functionalized NiFe2O4@Ti3C2TX, was designed and synthesized using a simple method. This composite material was used to develop an effective magnetic solid-phase extraction (MSPE) method for enriching trace polycyclic aromatic hydrocarbons (PAHs) in tea and coffee samples. The eluted PAHs were analyzed via gas chromatography-tandem mass spectrometry. Under optimal conditions, this method exhibited excellent linear relationships for 16 PAHs within the ranges of 0.001-25 and 0.0005-25 µg/L, with correlation coefficients exceeding 0.9979. The limits of detection for the target PAHs ranged from 0.1 to 0.3 ng/L. The effectiveness of the proposed method was evaluated by analyzing tea and coffee samples, and the satisfactory spiked recoveries of PAHs ranged from 84.5% to 112.6%.

Lefamulin Overcomes Acquired Drug Resistance via Regulating Mitochondrial Homeostasis by Targeting ILF3 in Hepatocellular Carcinoma.

Acquired resistance represents a critical clinical challenge to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) treatment in hepatocellular carcinoma (HCC). Therefore, it is urgent to explore new mechanisms and therapeutics that can overcome or delay resistance. Here, a US Food and Drug Administration (FDA)-approved pleuromutilin antibiotic is identified that overcomes sorafenib resistance in HCC cell lines, cell line-derived xenograft (CDX) and hydrodynamic injection mouse models. It is demonstrated that lefamulin targets interleukin enhancer-binding factor 3 (ILF3) to increase the sorafenib susceptibility of HCC via impairing mitochondrial function. Mechanistically, lefamulin directly binds to the Alanine-99 site of ILF3 protein and interferes with acetyltransferase general control non-depressible 5 (GCN5) and CREB binding protein (CBP) mediated acetylation of Lysine-100 site, which disrupts the ILF3-mediated transcription of mitochondrial ribosomal protein L12 (MRPL12) and subsequent mitochondrial biogenesis. Clinical data further confirm that high ILF3 or MRPL12 expression is associated with poor survival and targeted therapy efficacy in HCC. Conclusively, this findings suggest that ILF3 is a potential therapeutic target for overcoming resistance to TKIs, and lefamulin may be a novel combination therapy strategy for HCC treatment with sorafenib and regorafenib.

GmDFB1, an ARM-repeat superfamily protein, regulates floral organ identity through repressing siRNA- and miRNA-mediated gene silencing in soybean.

The development of flowers in soybean (Glycine max) is essential for determining the yield potential of the plant. Gene silencing pathways are involved in modulating flower development, but their full elucidation is still incomplete. Here, we conducted a forward genetic screen and identified an abnormal flower mutant, deformed floral bud1-1 (Gmdfb1-1), in soybean. We mapped and identified the causal gene, which encodes a member of the armadillo (ARM)-repeat superfamily. Using small RNA sequencing (sRNA-seq), we found an abnormal accumulation of small interfering RNAs (siRNAs) and microRNA (miRNAs) in the Gmdfb1 mutants. We further demonstrated that GmDFB1 interacts with the RNA exosome cofactor SUPER KILLER7 (GmSKI7). Additionally, GmDFB1 interacts with the PIWI domain of ARGONAUTE 1 (GmAGO1) to inhibit the cleavage efficiency on the target genes of sRNAs. The enhanced gene silencing mediated by siRNA and miRNA in the Gmdfb1 mutants leads to the downregulation of their target genes associated with flower development. This study revealed the crucial role of GmDFB1 in regulating floral organ identity in soybean probably by participating in two distinct gene silencing pathways.

miR-4429 inhibits ccRCC proliferation, migration, and invasion by directly targeting CD274.

Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies and a highly immunogenic cancer. Yet, its pathogenesis is still not fully understood. This study analyzed the role of the miR-320 family in ccRCC using bioinformatics algorithms and a series of in vitro experiments. miR-4429 was found to be significantly down-regulated in ccRCC tissues and cell lines, while overexpression of miR-4429 significantly inhibited renal cancer cell proliferation, migration, and invasion in vitro. In addition, the UALCAN database, immunohistochemistry, and protein blotting results showed that CD274 expression was up-regulated in ccRCC tissues and correlated with higher histologic grading. Dual luciferase assay indicated that CD274 was a direct target of miR-4429. Overexpression of miR-4429 in 786-O, Caki-2 cells significantly inhibited CD274 expression. KEGG results indicated that the potential target function of miR-4429 was associated with the PI3K/AKT signaling pathway, and protein blotting verified the results. In summary, this data shows that miR-4429 targets CD274 and inhibits ccRCC proliferation, migration, and invasion by regulating PI3K/AKT signaling, thus potentially providing a promising therapeutic target and prognostic biomarker for renal cell carcinoma patients.

The influence of visual marketing on consumers' purchase intention of fast fashion brands in China-An exploration based on fsQCA method.

Under the rapid development of e-commerce, offline brick-and-mortar stores have been severely impacted. However, the importance of the visual, sensory and even psychological experience in the apparel industry makes offline stores still irreplaceable. The impact on consumers' visual experience cannot be ignored and is a significant influencing factor in determining consumers' psychological change and purchase intention. Especially for fast fashion brands which pursue low costs, visual marketing strategies is a cost-effective marketing tool to enhance the visual experience. In this paper, by adapting SOR theory and using fuzzy set qualitative comparative analysis (fsQCA) research method, 15 fast fashion apparel brands and 374 valid questionnaires are adapted in China to explore not only the influence of individual dimensions in visual marketing on consumers' purchase intention, but also the action of multi-dimensional combinations. The research finds that: (1) there are two driving paths for high consumers' purchase intention. The first path is a combination of high clarity of arrangement and low display density; the second path is a combination of low light intensity, high clarity of arrangement, high tonal harmony and high window appeal. (2) There are also two paths that drive non-high consumers' purchase intentions, and they are asymmetrically related to the paths that drive high consumers' purchase intentions. The findings of this study help to provide direction and suggestions for offline visual marketing strategies of fast fashion apparel brands to increase consumers' psychological perception and purchase intention through a range of visual presentation techniques.

Recent advances and progress on the design, fabrication and biomedical applications of Gallium liquid metals-based functional materials.

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.

GHITM regulates malignant phenotype and sensitivity to PD-1 blockade of renal cancer cells via Notch signalling.

Growth hormone inducible transmembrane protein (GHITM), one member of Bax inhibitory protein-like family, has been rarely studied, and the clinical importance and biological functions of GHITM in kidney renal clear cell carcinoma (KIRC) still remain unknown. In the present study, we found that GHITM was downregulated in KIRC. Aberrant GHITM downregulation related to clinicopathological feature and unfavourable prognosis of KIRC patients. GHITM overexpression inhibited KIRC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, GHITM overexpression could induce the downregulation of Notch1, which acts as an oncogene in KIRC. Overexpression of Notch1 effectively rescued the inhibitory effect induced by GHITM upregulation. More importantly, GHITM could regulate PD-L1 protein abundance and ectopic overexpression of GHITM enhanced the antitumour efficiency of PD-1 blockade in KIRC, which provided new insights into antitumour therapy. Furthermore, we also showed that YY1 could decrease GHITM level via binding to its promoter. Taken together, our study revealed that GHITM was a promising therapeutic target for KIRC, which could modulate malignant phenotype and sensitivity to PD-1 blockade of renal cancer cells via Notch signalling pathway.

Performance Prediction for Surgical Outcomes in Laparoscopic Partial Nephrectomy Using Nephrometry Scores: A Comparison of Zhongshan and Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location Systems.

Objective: The aim of this study is to compare the precision and applicability of the Zhongshan (ZS) score against the radius, exophytic/endophytic, nearness, anterior/posterior, and location (RENAL) score in forecasting perioperative outcomes during laparoscopic partial nephrectomy (LPN). Materials and Methods: We retrospectively analyzed data from 99 renal cancer patients who underwent LPN between January 2017 and August 2023. Patients were scored and categorized based on both the ZS and RENAL scores. The study then compared perioperative outcomes across these groups and further investigated the correlation between ZS and RENAL scores and overall complication rates. Results: LPN was successfully accomplished in 94 patients, whereas 5 patients necessitated conversion to open or radical surgery. The high-risk group, according to the ZS score, manifested more warm ischemic time (WIT) than the low-risk group (P = .007). Furthermore, the incidence of overall complications escalated with increase in the ZS score grade (P = .045). A higher RENAL score corresponded to a greater risk of conversion to open or radical treatment (P = .012). Correlation analyses revealed associations between both ZS and RENAL scores and overall complications. The RENAL score also correlated with changes in blood creatinine values, while the ZS score was associated with WIT (all P < .05). In the univariate analysis, both ZS and RENAL scores were substantial factors for the occurrence of total complications (P = .029 and P = .027, respectively), but they were not statistically significant in the multivariate analysis. The receiver operating characteristic curves suggested that both individual and combined ZS and RENAL scores held predictive potential for the onset of overall complications (area under the curve = 0.652, 0.660, and 0.676, respectively). Conclusions: Compared with the RENAL score, the ZS score provides a more comprehensive assessment of tumor complexity in patients undergoing LPN. Integrating these two scores could potentially improve the accuracy of predicting surgical risks.

UV-B irradiation-activated E3 ligase GmILPA1 modulates gibberellin catabolism to increase plant height in soybean.

Plant height is a key agronomic trait that affects yield and is controlled by both phytohormone gibberellin (GA) and ultraviolet-B (UV-B) irradiation. However, whether and how plant height is modulated by UV-B-mediated changes in GA metabolism are not well understood. It has not been reported that the E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) is involved in the regulation of plant growth in response to environmental factors. We perform a forward genetic screen in soybean and find that a mutation in Glycine max Increased Leaf Petiole Angle1 (GmILPA1), encoding a subunit of the APC/C, lead to dwarfism under UV-B irradiation. UV-B promotes the accumulation of GmILPA1, which ubiquitinate the GA catabolic enzyme GA2 OXIDASE-like (GmGA2ox-like), resulting in its degradation in a UV-B-dependent manner. Another E3 ligase, GmUBL1, also ubiquitinate GmGA2ox-like and enhance the GmILPA1-mediated degradation of GmGA2ox-like, which suggest that GmILPA1-GmGA2ox-like module counteract the UV-B-mediated reduction of bioactive GAs. We also determine that GmILPA1 is a target of selection during soybean domestication and breeding. The deletion (Indel-665) in the promoter might facilitate the adaptation of soybean to high UV-B irradiation. This study indicates that an evolutionary GmILPA1 variant has the capability to develop ideal plant architecture with soybean cultivars.

Effects of Dietary Valine Chelated Zinc Supplementation on Growth Performance, Antioxidant Capacity, Immunity, and Intestine Health in Weaned Piglets.

This study was conducted to investigate the effects of dietary valine chelated zinc (ZnVal) supplementation on growth performance, antioxidant capacity, immunity, and intestine health in weaned piglets. A total of 240 healthy 35-day-old weaned piglets (Duroc × Landrace × Yorkshire, average weight 10.70 ± 0.14 kg) were randomly divided into five groups with six replicate pens and eight piglets per pen. Dietary treatments were a corn-soybean meal basal diet supplemented with 0, 25, 50, 75, and 100 mg/kg ZnVal, respectively. The experiment lasted for 28 days. Results showed that average daily gain (ADG) was increased (P < 0.05) by ZnVal with 75-100 mg/kg supplementation on days 15-28 and with 50-100 mg/kg supplementation on days 1-28. Supplementation of 25-100 mg/kg ZnVal reduced (P < 0.01) the diarrhea rate of weaned piglets on days 1 to 14 and 1 to 28. Dietary supplementation with 25-100 mg/kg ZnVal increased (P < 0.05) copper/zinc-superoxide dismutase (Cu/Zn-SOD) and decreased malonaldehyde (MDA) activities in the serum on day 14 and 28. Supplementation of 25-100 mg/kg ZnVal increased (P < 0.05) glutathione peroxidase (GSH-Px) activity in serum on day 14. Additionally, the supplementation of 75 mg/kg ZnVal significantly increased the activity of superoxide dismutase (SOD) and Cu/Zn-SOD in the liver (P < 0.05). Furthermore, the supplementation of 25-100 mg/kg ZnVal significantly increased the total antioxidant capacity (T-AOC) in the liver (P < 0.05). Higher (P < 0.05) concentrations of IgG in the serum were measured from piglets supplemented with 75-100 mg/kg ZnVal on day 14 and dietary supplementation with 25-100 mg/kg ZnVal increased the level of immunoglobulin G (IgG) in serum on day 28 (P < 0.05). In addition, higher (P < 0.05) concentrations of immunoglobulin A (IgA) in the duodenum and ileum were measured from piglets supplemented with 75 mg/kg ZnVal and the supplementation of 25-100 mg/kg ZnVal also showed a higher (P < 0.05) concentration of immunoglobulin G (IgG) in duodenum. Supplementation of 50-100 mg/kg ZnVal increased the villus height and villus height/crypt depth of jejunum (P < 0.05). Moreover, dietary supplementation with 75-100 mg/kg ZnVal showed a higher (P < 0.05) concentration of zinc in the liver and supplementation of 50-100 mg/kg ZnVal increased (P < 0.05) the concentration of zinc in the heart, spleen, and kidney. In conclusion, the present research showed that supplementation of ZnVal improves growth performance by increasing antioxidant capacity and immunity and regulating intestinal morphology and the optimal inclusion level of ZnVal was 65~80 mg/kg.

Identification and functional analysis of myeloid differentiation factor 88 (MyD88) in early development of Haliotis diversicolor.

Myeloid differentiation factor 88 (MyD88) is a universal adaptor protein and plays an important role in the signal transduction of Toll like receptors (TLR) family. In this study, the MyD88 gene from the Haliotis diversicolor (hdMyD88) was identified. The full-length cDNA of hdMyD88 has a 1927 base pairs (bp), with an open reading frame of 1314 bp encoding 437 amino acids including a death domain (DD) at the N-terminus and TIR domain at the C-terminus which are typical features of MyD88 family proteins. Three conserved boxes are also found in the hdMyD88, which are similar to MyD88 in vertebrates. The expression levels of hdMyD88 mRNA at different early embryonic developmental stages of abalone were measured by qPCR revealed that their constitutive expression at all developmental stages analyzed with the considerably highest values at 8 cell stage and the lowest level at the trochosphere stage. Additionally, the mRNA expression of hdMyD88 decreased significantly (P < 0.05) after MyD88-dsRNA soak in the stage of trochosphere and veliger than EGFP-dsRNA group and blank control group. Whole embryo in situ hybridization showed that the positive signals of hdMyD88 were in visceral mass of trochophore larvae and veliger larvae. These results indicate hdMyD88 may could respond to pathogenic infection and may play an important role in early innate immunity in the process of abalone larval development.

Nephroprotective Effects of Cardamonin on Renal Ischemia Reperfusion Injury/UUO-Induced Renal Fibrosis.

Acute kidney injury and chronic renal fibrosis are intractable pathological processes to resolve, yet limited strategies are able to effectively address them. Cardamonin (CAD) is a flavonoid with talented antioxidant, anti-inflammatory capacity, and satisfactory biosafety. In our study, animal and cellular models of renal ischemia/reperfusion (I/R) and unilateral ureteral obstruction (UUO) were successfully constructed to confirm whether CAD confers protective effects and underlying mechanisms. Animal experiments demonstrated that CAD application (100 mg/kg) distinctly ameliorated tissue damage and improved renal function. Meanwhile, the continuous oral administration of CAD after UUO surgery efficiently inhibited renal fibrosis as confirmed by hematoxylin-eosin (H&E), Sirius red, and Masson staining as well as the downregulated mRNA and protein expression of collagen I, α-smooth muscle actin (α-SMA), collagen III, and fibronectin. Interestingly, in transforming growth factor ß1 (TGF-ß1)-stimulated and hypoxia/reoxygenation (H/R)-exposed human kidney-2 (HK-2) cells, protective effects of CAD were again authenticated. Meanwhile, we performed bioinformatics analysis and constructed the "ingredient-target-pathway-disease" network to conclude that the potential mechanisms of CAD protection may be through the regulation of oxidative stress, inflammation, apoptosis, and mitogen-activated protein kinase (MAPK) pathway. Furthermore, experimental data validated that CAD evidently decreased the reactive oxygen species (ROS) production and malondialdehyde (MDA) content while depressing the mRNA and protein expression of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Il-1ß) and inhibiting apoptosis as evidenced by decreased levels of P53, BAX, cleaved caspase-3, and apoptotic rate in renal I/R and UUO models. In addition, the impact of CAD on restraining oxidative stress and inflammation was attributed to its ability to elevate antioxidant enzyme activities including catalase, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) and to inhibit the inflammation-associated MARK/nuclear factor-κB (MAPK/NF-κB) signaling pathway. In conclusion, cardamonin restored the antioxidative capacity to block oxidative stress and suppressed the MAPK/NF-κB signaling pathway to alleviate inflammatory response, thus mitigating I/R-generated acute kidney injury/UUO-induced renal fibrosis in vivo and in vitro, which indicated the potential therapeutic advantage of cardamonin in attenuating acute and chronic kidney injuries.

Magnetic resonance-enhanced high-resolution three-dimensional water-selective cartilage sequence visualization of hip vessels in children.

PURPOSE: Hip vessel examination provides key information on many hip-related pediatric diseases, and it has an important role in the evaluation of femoral head (FH) blood supply and diagnosis of avascular necrosis (AVN). The aim of this study was to investigate the feasibility of MR-enhanced high-resolution three-dimensional water-selective cartilage (3D-WATSc) sequence in visualizing the vessels of the hip joint in children. PATIENTS AND METHODS: Children with hip disease were randomly enrolled prospectively at our hospital from January 2021 to August 2022. We performed our institution's hip MRI protocol and enhanced high-resolution 3D-WATSc sequence. The 3D-WATSc images were reconstructed and analyzed, and images of the normal hip were categorized into grades 0-3. The abnormal hip images were compared with those of the normal side using the χ2 test. RESULTS: Twenty-four patients with unilateral hip abnormalities were included in this study. The cartilaginous vascular canal and ossification centre vessels of normal FHs were observed in 18 patients (75%) and met the grade 3 standard. An abnormal cartilaginous canal was observed in 16 patients (67%); meanwhile, 18 patients (75%) had abnormal extrachondral vessels. Comparison of high-resolution 3D-WATSc images with those of the normal side provided effective abnormal vascular information in 95.8% of patients. CONCLUSIONS: Enhanced high-resolution 3D-WATSc can visualize the blood vessels of the hip in children. This may provide a new method for the vascular study of various pediatric hip diseases.

DOT1L Epigenetically Regulates Autophagy and Mitochondria Fusion in Cell Lines of Renal Cancer.

OBJECTIVES: DOT1L, a histone methylase, is overexpression in renal cell cancer. However, the role and detailed molecular mechanism of DOT1L involved in renal cancer development remain unknown. METHODS: The inhibition of DOT1L was used by SGC0946 and short hairpin RNA silencing. Monodansylcadaverine staining and transmission electron microscope were performed to detect autophagy changes as a result of the inhibition of DOT1L. MitoTracker Red assay was used to analyze mitochondrial morphology. The autophagy markers and mitochondria-related proteins were analyzed by Western blot, qPCR, or immunofluorescence. ChIP assay was performed to demonstrate H3K79me2 is involved in the direct regulation of Farnesoid X receptor transcription. RESULTS: DOT1L inhibition increased autophagy activity and promoted mito chondria fusion in cell lines of renal cancer. Inhibition of DOT1L upregulated levels of LC3α/ß, P62, MFN1, and MFN2, which contributed to autophagy activity or mitochondria fusion. DOT1L knockdown showed a similar the above process. DOT1L inhibition or silencing resulted in AMP-activated protein kinase activation and mammalian target of rapamycin inhibition. Mechanistically, the DOT1L inhibitor and its short hairpin RNAs decreased the expression of Farnesoid X receptor in a histone methylase-dependent manner. CONCLUSION: We revealed the essential role of Farnesoid X receptor in regulating DOT1L-induced autophagy and mitochondrial fission through the AMP-activated protein kinase/mammalian target of rapamycin pathway in cell lines of renal cancer, which may provide new insights into the pathogenesis of renal cell cancer.

Mesoporous silica stabilized Cu-Fe bimetallic nanozymes for total antioxidant capacity assay of fruit foods.

Total antioxidant capacity (TAC) is currently considered as a vital indicator of food quality in antioxidant ability and attracts much attention for human healthcare. It is thus of great significance to realize the accurate and rapid detection of TAC in foods. Herein, we have constructed a preferable hybrid nanozyme based on the mesoporous silica-stabilized CuO composited Fe3O4 nanoparticles (Fe3O4@MSNs@CuO, FMC NPs), which possess the enhanced peroxidase (POD)-like activity via cascade response for specific and sensitive determination of TAC in fruit foods. The results showed the hybrid nanozyme displayed a remarkable POD-like activity, excellent selectivity and sensitivity, and the limit of detection (LOD) of the colorimetric sensor was 6.13 mM with the concentration range from 10 to 45 mM. Therefore, the fabricated hybrid nanozyme can be regarded as an effective biosensor for the evaluation of antioxidant quality in fruit foods in future. KEY POINTS: • The stabilized bimetallic nanozyme was constructed for TAC analysis in fruits. • The hybrid nanozyme possessed the enhanced POD-like activity by cascading effects. • The nanozyme was an effective biosensor for antioxidant quality evaluation in fruits.

Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants.

The decrease of antibody efficacy to mutated SARS-CoV-2 spike RBD explains the breakthrough infections and reinfections by Omicron variants. Here, we analyzed broadly neutralizing antibodies isolated from long-term hospitalized convalescent patients of early SARS-CoV-2 strains. One of the antibodies named NCV2SG48 is highly potent to broad SARS-CoV-2 variants including Omicron BA.1, BA.2, and BA.4/5. To reveal the mode of action, we determined the sequence and crystal structure of the Fab fragment of NCV2SG48 in a complex with spike RBD from the original, Delta, and Omicron BA.1. NCV2SG48 is from a minor VH but the multiple somatic hypermutations contribute to a markedly extended binding interface and hydrogen bonds to interact with conserved residues at the core receptor-binding motif of RBD, which efficiently neutralizes a broad spectrum of variants. Thus, eliciting the RBD-specific B cells to the longitudinal germinal center reaction confers potent immunity to broad SARS-CoV-2 variants emerging one after another.

Selective fluorescent probe for sensitive determination of bisphenol A based on molecularly imprinted polymers decorated carbon dots derived from citric acid and ethylenediamine.

Bisphenol A (BPA) is an endocrine disrupting chemical and poses a grave threat to the human health. Herein, a fluorescent probe constructed with molecularly imprinted polymers decorated carbon dots (CDs@MIPs) was proposed for determination of BPA with high selectivity. The CDs@MIPs were constructed using BPA, 4-vinylpyridine and ethylene glycol dimethacrylate as template, functional monomer and cross linker, respectively. The obtained fluorescent probe not only owned a highly selective recognition function derived from MIPs but also displayed an excellent sensitivity for sensing BPA stemmed from CDs. The fluorescence intensity of CDs@MIPs was varied before and after the removal of BPA templates. The fluorescent decrease fraction of the fluorescent probe demonstrates a nice linearity in BPA concentration range of 10-2000 nM (r2 = 0.9998) and the detection limit is as low as 1.5 nM. The fluorescent probe was triumphantly utilized to sense the level of BPA in real aqueous and plastic samples with good results. Moreover, the fluorescent probe offered a wonderful means for fast identification and sensitive detection of BPA from environmental aqueous samples.