The vascular endothelial growth factor pathway plays a key role in the pathogenesis of gastric cancer. In the multicenter, double-blind phase 3 FRUTIGA trial, 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma who progressed on fluorouracil- and platinum-containing chemotherapy were randomized (1:1) to receive fruquintinib (an inhibitor of vascular endothelial growth factor receptor-1/2/3; 4 mg orally, once daily) or placebo for 3 weeks, followed by 1 week off, plus paclitaxel (80 mg/m2 intravenously on days 1/8/15 per cycle). The study results were positive as one of the dual primary endpoints, progression-free survival (PFS), was met (median PFS, 5.6 months in the fruquintinib arm versus 2.7 months in the placebo arm; hazard ratio 0.57; 95% confidence interval 0.48-0.68; P < 0.0001). The other dual primary endpoint, overall survival (OS), was not met (median OS, 9.6 months versus 8.4 months; hazard ratio 0.96, 95% confidence interval 0.81-1.13; P = 0.6064). The most common grade ≥3 adverse events were neutropenia, leukopenia and anemia. Fruquintinib plus paclitaxel as a second-line treatment significantly improved PFS, but not OS, in Chinese patients with advanced gastric or gastroesophageal junction adenocarcinoma and could potentially be another treatment option for these patients. ClinicalTrials.gov registration: NCT03223376 .
The synthesis of InVO4-CdS heterojunction photocatalysts has been achieved by a novel two-step approach, including a microwave-assisted technique, followed by a moderate hydrothermal method, marking the first successful instance of such a synthesis. X-ray diffraction, field-emission scanning electron microscopy, elemental color mapping, high-resolution transmission electron microscopy, UV-vis diffuse reflectance spectroscopy, Raman analysis, photoluminescence, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller were employed to investigate the crystal structures, surface morphologies and particle sizes, chemical compositions, and optical characteristics of the as-synthesized materials. The research results indicated that the heterojunction InVO4-CdS, as synthesized, consisted of InVO4 microrods with an average size of around 15 nm and cadmium sulfide (CdS) microflowers with a diameter of 1.5 µm. Furthermore, all of the heterojunctions had favorable photoabsorption properties throughout the visible-light spectrum. The photocatalytic efficiency of the samples obtained was thoroughly assessed by the degradation of acid violet 7 (AV 7) under visible light irradiation with a wavelength greater than 420 nm. The photocatalytic efficiency for the decomposition of AV 7 was greatly enhanced in the InVO4-CdS (IVCS) heterojunctions when compared to prepared bare InVO4 and CdS. Additionally, it was observed that the composite material consisting of IVCS 3 wt % InVO4 combined with CdS exhibited the most significant enhancement in catalytic effectiveness for the photodegradation of AV 7 dye. Specifically, the catalytic performance of this composite material was found to be around 69.4 and 76.2 times greater than that of pure InVO4 and CdS, respectively. Furthermore, the experimental procedure including active species trapping provided evidence that h+ and â¢O2- radicals were the primary active species involved in the photocatalytic reaction process. Additionally, a potential explanation for the improved photocatalytic activity of the InVO4-CdS heterojunction was presented, taking into account the determination of band positions.
The interactions of environmental compartments with epithelial cells are essential for mammary gland development and homeostasis. Currently, the direct crosstalk between the endothelial niche and mammary epithelial cells remains poorly understood. Here, we show that faciogenital dysplasia 5 (FGD5) is enriched in mammary basal cells (BCs) and mediates critical interactions between basal and endothelial cells (ECs) in the mammary gland. Conditional deletion of Fgd5 reduced, whereas conditional knockin of Fgd5 increased, the engraftment and expansion of BCs, regulating ductal morphogenesis in the mammary gland. Mechanistically, murine mammary BC-expressed FGD5 inhibited the transcriptional activity of activating transcription factor 3 (ATF3), leading to subsequent transcriptional activation and secretion of CXCL14. Furthermore, activation of CXCL14/CXCR4/ERK signaling in primary murine mammary stromal ECs enhanced the expression of HIF-1α-regulated hedgehog ligands, which initiated a positive feedback loop to promote the function of BCs. Collectively, these findings identify functionally important interactions between BCs and the endothelial niche that occur through the FGD5/CXCL14/hedgehog axis.
Pine wilt disease caused by Bursaphelenchus xylophilus poses a serious threat to the economic and ecological value of forestry. Nematode trapping fungi trap and kill nematodes using specialized trapping devices, which are highly efficient and non-toxic to the environment, and are very promising for use as biological control agents. In this study, we isolated several nematode-trapping fungi from various regions and screened three for their high nematocidal efficiency. However, the effectiveness of these fungi as nematicides is notably influenced by temperature and exhibits different morphologies in response to temperature fluctuations, which are categorized as "NA," "thin," "dense," and "sparse." The trend of trap formation with temperature was consistent with the trend of nematocidal efficiency with temperature. Both of which initially increased and then decreased with increasing temperature. Among them, Arthrobotrys cladodes exhibited the highest level of nematocidal activity and trap formation among the tested species. Transcriptome data were collected from A. cladodes with various trap morphologies. Hydrolase activity was significantly enriched according to GO and KEGG enrichment analyses. Eight genes related to hydrolases were found to be consistent with the trend of trap morphology with temperature. Weighted gene co-expression analysis and the Cytoscape network revealed that these 8 genes are associated with either mitosis or autophagy. This suggests that they contribute to the formation of "dense" structures in nematode-trapping fungi. One of these genes is the serine protein hydrolase gene involved in autophagy. This study reveals a potentially critical role for hydrolases in trap formation and nematocidal efficiency. And presents a model where temperature affects trap formation and nematocidal efficiency by influencing the serine protease prb1 involved in the autophagy process.
We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.
Magnetic Resonance Imaging , Saimiri , Spinal Cord , White Matter , Animals , White Matter/diagnostic imaging , White Matter/physiology , Spinal Cord/physiology , Spinal Cord/diagnostic imaging , Magnetic Resonance Imaging/methods , Rest/physiology , Oxygen/blood , Oxygen/metabolism , Male , Gray Matter/diagnostic imaging , Gray Matter/physiology , Female
Anaerobic fermentation is a crucial route to realize effective waste activated sludge (WAS) resource recovery and utilization, while the overall efficiency is commonly restrained by undesirable disruptors (i.e., chemical dewatering agents). This work unveiled the unexpectedly positive effects of biodewatering tannic acid (TA) on the volatile fatty acids (VFAs) biosynthesis during WAS anaerobic fermentation. The total VFAs yield was remarkably increased by 15.6 folds with enriched acetate and butyrate in TA-occurred systems. TA was capable to disintegrate extracellular polymeric substances to promote the overall organics release. However, TA further modulated the soluble proteins structure by hydrogen bonding and hydrophobic interactions, resulting in the decrease of proteins bioavailability and consequential alteration of metabolic substrate feature. These changes reshaped the microbial community and stimulated adaptive regulatory systems in hydrolytic-acidogenic bacteria. The keystone species for carbohydrate metabolism (i.e., Solobacterium and Erysipelotrichaceae) were preferentially enriched. Also, the typical quorum sensing (i.e., enhancing substrate transport) and two-component systems (i.e., sustaining high metabolic activity) were activated to promote the microbial networks connectivity and ecological cooperative behaviors in response to TA stress. Additionally, the metabolic functions responsible for carbohydrate hydrolysis, transmembrane transport, and intracellular metabolism as well as VFA biosynthesis showed increased relative abundance, which maintained high microbial activities for VFAs biosynthesis. This study underscored the advantages of biodewatering TA for WAS treatment in the context of resource recovery and deciphered the interactive mechanisms.
Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), a significant member of the conserved RNA-binding protein family, plays various roles in numerous physiological and pathological processes. However, the specific function of IGF2BP2 in regulating endometrial function in sheep remains largely unknown. In this study, we observed a significant upregulation in IGF2BP2 mRNA abundance in the endometrium during the luteal phase (LP) compared to the follicular phase (FP) in Hu sheep. The knockdown of IGF2BP2 resulted in accelerated cell proliferation and migration of Hu sheep endometrial stromal cells (ESCs). Moreover, RNA sequencing analysis revealed that genes with significantly altered expression in IGF2BP2 knockdown cells were predominantly enriched in endometrial receptivity-related signaling pathways, such as cytokine-cytokine receptor interaction, NOD-like receptor, PI3K-AKT, and JAK-STAT signaling pathway. Additionally, the knockdown of IGF2BP2 significantly increased the expression of matrix metalloprotein 9 (MMP9), vascular endothelial growth factor (VEGF), and prolactin (PRL) in ESCs. The knockdown of IGF2BP2 was also observed to stimulate the PI3K/AKT/mTOR pathway by upregulating integrin ß4 (ITGB4) expression. Notably, the downregulation of ITGB4 attenuates IGF2BP2 knockdown-induced facilitation of proliferation and migration of Hu sheep ESCs by inhibiting the PI3K/AKT/mTOR pathway. Collectively, these findings highlight the important role of IGF2BP2 in regulating endometrial function, particularly through the modulation of ESC proliferation and migration via the PI3K/AKT/mTOR pathway.
Interleukin-18 binding protein (IL-18BP), a natural regulator molecule of the pro-inflammatory cytokine interleukin-18 (IL-18), plays an important role in regulating the expression of the cellular immunity factor interferon-γ (IFN-γ). In a previous RNA-seq analysis of porcine alveolar macrophages (PAM) infected with the TIM and TJ strains of porcine reproductive and respiratory syndrome virus (PRRSV), we unexpectedly found that the mRNA expression of porcine interleukin 18-binding protein (pIL-18BP) in PAM cells infected with the TJM strain was significantly higher than that infected with the TJ strain. Studies have shown that human interleukin-18 binding protein (hIL-18bp) plays an important role in regulating cellular immunity in the course of the disease. However, there is a research gap on pIL-18BP. At the same time, PRRSV infection in pigs triggers weak cellular immune response problems. To explore the expression and the role of pIL-18BP in the cellular immune response induced by PRRSV, we strived to acquire the pIL-18BP gene from PAM or peripheral blood mononuclear cell (PBMC) with RT-PCR and sequencing. Furthermore, pIL-18BP and pIL-18 were both expressed prokaryotically and eukaryotically. The colocalization and interaction based on recombinant pIL-18BP and pIL-18 on cells were confirmed in vitro. Finally, the expression of pIL-18BP, pIL-18, and pIFN-γ was explored in pigs with different PRRSV infection states to interpret the biological function of pIL-18BP in vivo. The results showed there were five shear mutants of pIL-18BP. The mutant with the longest coding region was selected for subsequent functional validation. First, it was demonstrated that TJM-induced pIL-18BP mRNA expression was higher than that of TJ. A direct interaction between pIL-18BP and pIL-18 was confirmed through fluorescence colocalization, bimolecular fluorescent complimentary (BIFC), and co-immunoprecipitation (CO-IP). pIL-18BP also can regulate pIFN-γ mRNA expression. Finally, the expression of pIL-18BP, pIL-18, and pIFN-γ was explored in different PRRSV infection states. Surprisingly, both mRNA and protein expression of pIL-18 were suppressed. These findings fill the gap in understanding the roles played by pIL-18BP in PRRSV infection and provide a foundation for further research.IMPORTANCEPRRSV-infected pigs elicit a weak cellular immune response and the mechanisms of cellular immune regulation induced by PRRSV have not yet been fully elucidated. In this study, we investigated the role of pIL-18BP in PRRSV-induced immune response referring to the regulation of human IL-18BP to human interferon-gamma (hIFN-γ). This is expected to be used as a method to enhance the cellular immune response induced by the PRRSV vaccine. Here, we mined five transcripts of the pIL-18BP gene and demonstrated that it interacts with pIL-18 and regulates pIFN-γ mRNA expression. Surprisingly, we also found that both mRNA and protein expression of pIL-18 were suppressed under different PRRSV strains of infection status. These results have led to a renewed understanding of the roles of pIL-18BP and pIL-18 in cellular immunity induced by PRRSV infection, which has important implications for the prevention and control of PRRS.
Background: The dysregulated immune response to sepsis still remains unclear. Stratification of sepsis patients into endotypes based on immune indicators is important for the future development of personalized therapies. We aimed to evaluate the immune landscape of sepsis and the use of immune clusters for identifying sepsis endotypes. Methods: The indicators involved in innate, cellular, and humoral immune cells, inhibitory immune cells, and cytokines were simultaneously assessed in 90 sepsis patients and 40 healthy controls. Unsupervised k-means cluster analysis of immune indicator data were used to identify patient clusters, and a random forest approach was used to build a prediction model for classifying sepsis endotypes. Results: We depicted that the impairment of innate and adaptive immunity accompanying increased inflammation was the most prominent feature in patients with sepsis. However, using immune indicators for distinguishing sepsis from bacteremia was difficult, most likely due to the considerable heterogeneity in sepsis patients. Cluster analysis of sepsis patients identified three immune clusters with different survival rates. Cluster 1 (36.7%) could be distinguished from the other clusters as being an "effector-type" cluster, whereas cluster 2 (34.4%) was a "potential-type" cluster, and cluster 3 (28.9%) was a "dysregulation-type" cluster, which showed the lowest survival rate. In addition, we established a prediction model based on immune indicator data, which accurately classified sepsis patients into three immune endotypes. Conclusion: We depicted the immune landscape of patients with sepsis and identified three distinct immune endotypes with different survival rates. Cluster membership could be predicted with a model based on immune data.
Sepsis , Humans , Sepsis/immunology , Sepsis/diagnosis , Sepsis/mortality , Male , Female , Middle Aged , Aged , Cluster Analysis , Adult , Cytokines/immunology , Cytokines/metabolism , Biomarkers , Immunity, Innate , Adaptive Immunity
PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.
The C-terminal to LisH (CTLH) complex is a ubiquitin ligase complex that recognizes substrates with Pro/N-degrons via its substrate receptor Glucose-Induced Degradation 4 (GID4), but its function and substrates in humans remain unclear. Here, we report PFI-7, a potent, selective and cell-active chemical probe that antagonizes Pro/N-degron binding to human GID4. Use of PFI-7 in proximity-dependent biotinylation and quantitative proteomics enabled the identification of GID4 interactors and GID4-regulated proteins. GID4 interactors are enriched for nucleolar proteins, including the Pro/N-degron-containing RNA helicases DDX21 and DDX50. We also identified a distinct subset of proteins whose cellular levels are regulated by GID4 including HMGCS1, a Pro/N-degron-containing metabolic enzyme. These data reveal human GID4 Pro/N-degron targets regulated through a combination of degradative and nondegradative functions. Going forward, PFI-7 will be a valuable research tool for investigating CTLH complex biology and facilitating development of targeted protein degradation strategies that highjack CTLH E3 ligase activity.
It is still challenging to stabilize α-FAPbI3 perovskite for high performance optoelectrical devices. Herein, a novel strategy is proposed utilizing the synergetic electrostatic and steric effect to stabilize the α-FAPbI3 phase and suppress the ion migration. Dimethylamine (DMA+) cations are chosen as the dopant to fabricate FA0.96DMA0.04PbI3 single crystals (SCs). DFT calculations reveal that DMA+ cations can improve the stability of α-FAPbI3 phase in both thermodynamics (lower Gibbs free energy) and kinetics (higher defect formation and migration energy). The resulting SCs exhibit an environmental stability over 100 days and an extraordinary low dark current drift of 3.7 × 10-7 nA cm-1 s-1 V-1, comparable to 2D perovskite SCs. The X-ray detectors have also achieved the-state-of-the-art performance in X-ray detection and imaging. This work demonstrates the significance of electrostatic and steric effects in improving the phase and operational stability of perovskites.
Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.
Objective: This study examined the effects of a multicomponent intervention program on cognitive function in community-dwelling older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Methods: This was a 2-arm, randomized controlled trial in which a multicomponent intervention was applied. Participants were recruited from June 2020 to August 2020, randomization and intervention began in August 2020, and the entire program ended in January 2021. It included cognitive training (mnemonic strategy training) and lifestyle guidance (diet, sleep, and exercise guidance) for 7 weeks. A total of 123 Chinese community-dwelling older adults experiencing MCI or SCD were randomly divided into a multicomponent intervention group (n = 62) and a health education group (n = 61). The global cognitive function was measured using the Mini-Mental State Examination (MMSE). The cognitive domains outcomes included memory functions measured using the immediate and delayed tests of the Auditory Verbal Learning Test (AVLT) and Logical Memory Test (LMT), and executive function and attention measured using the Digital Symbol Substitution Test (DSST) and Digit Span Test (DST). Data were collected at baseline and postintervention.Results: For cognitive outcome, the results of linear mixed-effect model showed significant time × group effects in the MMSE (Cohen d =0.63 [95% CI, 0.27 to 1.00], F = 10.25, P = .002). This study found significant time × group effects in AVLT-immediate (Cohen d = 0.47 [95% CI, 0.11 to 0.83], F = 8.18, P = .005), AVLT delayed (Cohen d = 0.45 [95% CI, 0.10 to 0.81], F = 4.59, P = .034), LMT-delayed (Cohen d = 0.71 [95% CI, 0.34 to 1.07], F = 4.59, P = .034), DSST (Cohen d = 0.27 [95% CI, -0.08 to 0.63], F = 4.83, P = .030), and DST (Cohen d =0.69 [95% CI, 0.33 to 1.05], F = 8.58, P = .004).Conclusions and Implications: The results support the feasibility and effectiveness of the multicomponent intervention program in improving cognitive function in community dwelling older adults at risk of dementia. The high adherence of this program shows its potential for promotion in the community and supports a larger and longer trial.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200061420).
Cognitive Dysfunction , Humans , Male , Female , Aged , Cognitive Dysfunction/prevention & control , Cognitive Dysfunction/therapy , Dementia/prevention & control , Life Style , Independent Living , Middle Aged , Cognitive Behavioral Therapy/methods , Executive Function , China , Cognitive Training
Myoblast differentiation depends on fatty acid oxidation (FAO)ï¼and its rate-limiting enzyme acetyl-CoA carboxylase 2 (ACC2) participate in the regulation skeletal muscle development. However, the precise regulatory mechanism is still unknown. Using previous RNA-sequencing data from our laboratory, we explored the effect of ACC2 on myoblast differentiation, as a candidate gene, since its expression is higher in myoblasts of lamb (first day of age) than that of the fetus (75th day of pregnancy). Our findings show that siACC2 inhibited myoblast proliferation, promoted differentiation, and boosted mitochondrial and fatty acid oxidation activities. The effect of ACC2 on goat muscle cell differentiation was modulated by Etomoxir, a CPT1A inhibitor. Notably, the AMPK/ACC2 pathway was found to regulate fatty acid oxidation and goat muscle cell differentiation. Inhibiting the AMPK/ACC2 pathway significantly reduced CPT1A expression. These findings indicate that AMPK/ACC2 regulate goat myoblast differentiation via fatty acid oxidation, contributing to understanding the mechanism of goat skeletal muscle development.
Near-infrared phosphorescent materials have received significant attention due to their potential applications in bioimaging and diagnostics. Although, many types of organic phosphors with near-infrared emission have been developed, the low phosphorescence efficiency in aqueous solution hampers their practical applications in biological systems. Hence, there is an urgent need to develop near-infrared phosphorescent materials with high emission efficiency in aqueous media. Metallotweezers, based on d8 transition metal complexes, emerge as the potential candidates for realizing this objective. Specifically, metallotweezers, featuring two positively charged platinum(II) terpyridine and neutral gold(III) diphenylpyridine pincers on diphenylpyridine spacer, have been designed and synthesized, respectively. The pre-organization effect, rendered by the rigid spacer, enables the resulting metallotweezers to complex with each other, resulting in the formation of clipping complex. The synergistic rigidifying and shielding effects of clipping structure results in enhanced phosphorescent emission intensity. Concurrently, due to phase segregation between the clipping units and the polyethylene glycol tail, the clipping complex undergoes self-assembly in aqueous solution, resulting in phosphorescent emission in the near-infrared region. Overall, non-covalent clipping of metallotweezers illustrated in this study presents a new and effective approach toward near-infrared phosphorescent materials.
Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RTâPCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/ß-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.
Dynamic vision perception and processing (DVPP) is in high demand by booming edge artificial intelligence. However, existing imaging systems suffer from low efficiency or low compatibility with advanced machine vision techniques. Here, we propose a reconfigurable bipolar image sensor (RBIS) for in-sensor DVPP based on a two-dimensional WSe2/GeSe heterostructure device. Owing to the gate-tunable and reversible built-in electric field, its photoresponse shows bipolarity as being positive or negative. High-efficiency DVPP incorporating front-end RBIS and back-end CNN is then demonstrated. It shows a high recognition accuracy of over 94.9% on the derived DVS128 data set and requires much fewer neural network parameters than that without RBIS. Moreover, we demonstrate an optimized device with a vertically stacked structure and a stable nonvolatile bipolarity, which enables more efficient DVPP hardware. Our work demonstrates the potential of fabricating DVPP devices with a simple structure, high efficiency, and outputs compatible with advanced algorithms.
Diabetic encephalopathy (DE), characterized by cognitive impairment, currently lacks targeted treatment. Previous studies have shown that Sarcandra glabra extracted residue polysaccharide (SERP) exhibited hypoglycemic effects either in vitro or in streptozotocin-induced diabetes mice. However, the therapeutic effect of SERP on DE was not elucidated. This study investigated the therapeutic effect of SERP on DE and its underlying mechanism. Our results revealed that SERP regulates glucose and lipid metabolism, improves cognitive function, and exhibits diminished activity post-antibiotic intervention. Importantly, we discovered a novel mechanism by which SERP modulates the gut microbiota, specifically enriching Bacteroidales S24-7, resulting in elevated levels of butyric acid in the intestine. This regulation modulates the intestinal endocrine cell lipid metabolism level, restores damaged intestinal barriers and neural epithelial circuits, thus exhibiting cure effects. Our findings suggest that SERP could become a candidate for treating DE, potentially involving the regulation mechanism of the "microbiota-gut-brain axis". This study underscores the unique therapeutic efficacy of SERP in managing DE, offering fresh drug candidates and innovative treatment strategies for this challenging condition.
