ARHGAP17 Inhibits Hepatocellular Carcinoma Progression by Inactivation of Wnt/ß-Catenin Signaling Pathway.

As a member of Rho GAPs family, Rho GTPase-Activating Protein 17 (ARHGAP17) regulates cytoskeletal recombination, cell polarity, cell proliferation and cell migration. ARHGAP17 is identified as a tumor suppressor in numerous cancer types. Current study intends to examine ARHGAP17 expression and its possible influence on the progression of hepatocellular carcinoma (HCC). ARHGAP17 expression in HCC cells was verified by RT-PCR and western blot. The proliferation and invasion of HCC cells were evaluated by CCK8 assay and transwell assay, respectively. The mRNA expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, GSK-3ß, Axin1, and APC were detected by RT-PCR. The protein expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, p-ß-catenin, GSK-3ß, p-GSK-3ß, Axin1, and APC were detected by western blot. ARHGAP17 staining was evaluated by immunohistochemistry and immunofluorescence. ARHGAP17 expression decreased significantly in HCC tumors and HCC cells after EMT. In response to overexpression of ARHGAP17, the capacities of HCC cell proliferation and invasion were reduced significantly, which were also confirmed by tumorigenesis experiments in vivo. With overexpression of ARHGAP17 in HCC cells, the p-GSK3ß/GSK3ß decreased, while the p-ß-catenin/ß-catenin, Axin1 and APC increased. In conclusion, ARHGAP17 inhibits HCC progression by inactivating the Wnt/ß-catenin signaling pathway.

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

Femtosecond Laser Fabrication of High-Linearity Liquid Metal-Based Flexible Strain Sensor.

Liquid metal (LM) is widely used in flexible electronic devices due to its excellent metallic conductivity and ductility. However, the fabrication of LM flexible strain sensors with high sensitivity and linearity is still a huge challenge, since the resistance of LM does not change much with strain. Here, a highly sensitive and linear fully flexible strain sensor with a resistive sensing function is proposed. The sensor comprises an Fe-doped liquid metal (Fe-LM) electrode for enhanced performance. The design and manufacturing of flexible strain sensors are based on the technology of controlling surface wettability by femtosecond laser micro/nano-processing. A supermetalphobic microstructure is constructed on a polydimethylsiloxane (PDMS) substrate to achieve the selection adhesion of Fe-LM on the PDMS substrate. The Fe-LM-based flexible strain sensor has high sensitivity and linearity, a gauge factor (GF) up to 1.18 in the strain range of 0-100%, excellent linearity with an R2 of 0.9978, a fast response time of 358 ms, and an excellent durability of more than 2400 load cycles. Additionally, the successful monitoring of human body signals demonstrates the potential of our developed flexible strain sensor in wearable monitoring applications.

Carbon monoxide poisoning with hippocampi lesions on MRI: cases report and literature review.

BACKGROUND: Carbon monoxide (CO) poisoning is now one of the leading causes of poisoning-related mortality worldwide. The central nervous system is the most vulnerable structure in acute CO poisoning. MRI is of great significance in the diagnosis and prognosis of CO toxic encephalopathy. The imaging features of CO poisoning are diverse. We report atypical hippocampal lesions observed on MRI in four patients after acute CO exposure. CASE PRESENTATIONS: We report four patients who presented to the emergency department with loss of consciousness. The diagnosis of CO poisoning was confirmed on the basis of their detailed history, physical examination and laboratory tests. Brain MRI in all of these patients revealed abnormal signal intensity in hippocampi bilaterally. They all received hyperbaric oxygen therapy. The prognosis of all four patients was poor. CONCLUSION: Hippocampi, as a relatively rare lesion on MRI of CO poisoning, is of important significance both in the early and delayed stages of acute CO poisoning. In this article, we summarize the case reports of hippocampal lesions on MRI in patients with CO poisoning in recent years, in order to provide reference for the diagnosis and prognosis of CO poisoning.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

The Intersection of cerebral cholesterol metabolism and Alzheimer's disease: Mechanisms and therapeutic prospects.

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly, the exact pathogenesis of which remains incompletely understood, and effective preventive and therapeutic drugs are currently lacking. Cholesterol plays a vital role in cell membrane formation and neurotransmitter synthesis, and its abnormal metabolism is associated with the onset of AD. With the continuous advancement of imaging techniques and molecular biology methods, researchers can more accurately explore the relationship between cholesterol metabolism and AD. Elevated cholesterol levels may lead to vascular dysfunction, thereby affecting neuronal function. Additionally, abnormal cholesterol metabolism may affect the metabolism of ß-amyloid protein, thereby promoting the onset of AD. Brain cholesterol levels are regulated by multiple factors. This review aims to deepen the understanding of the subtle relationship between cholesterol homeostasis and AD, and to introduce the latest advances in cholesterol-regulating AD treatment strategies, thereby inspiring readers to contemplate deeply on this complex relationship. Although there are still many unresolved important issues regarding the risk of brain cholesterol and AD, and some studies may have opposite conclusions, further research is needed to enrich our understanding. However, these findings are expected to deepen our understanding of the pathogenesis of AD and provide important insights for the future development of AD treatment strategies targeting brain cholesterol homeostasis.

Rapid label-free impedimetric detection of progesterone enhanced by immunomagnetic bead-based competitive immunoreaction.

Detecting progesterone (P4) concentration in cow serum is essential for monitoring the pregnancy progress after fertilization and is significant for the dairy farming industry and veterinary medicine. This study reports enzyme-free immunomagnetic beads (IMBs)-based competitive immunoassay for detecting P4 by P4-bovine serum albumin (BSA)-modified biosensors. The anti-P4 antibody-conjugated IMBs serve as collectors to capture P4 in undiluted serum samples to prevent the biosensor surface from biosample contamination and as insulated labels to report the electron-transfer resistance signal of electrochemical impedance spectroscopy (EIS) measurement. The IMBs and P4-containing samples were mixed for 15-30 min, capable of obtaining stable P4@IMB complexes. The 0.2-kGauss pulsed magnetic field (PMF) of the 20-s pulse width and 20-s relaxation time applied for 5 min can shorten the immunoreaction time between the P4@IMBs and the P4-BSA-modified biosensor and reduce the IMB's nonspecific adsorption on the biosensor surface. This competitive immunoassay's cut-off value and detection limit were 7.71 ng/mL and 7.33 ng/mL, respectively, which is lower than the serum's P4 plateau concentration (over 8 ng/mL) of dairy cows on days 6-16 of estrus cycles and that in pregnancy. The IMB-based immunoassay combining the PMF attraction and the label-free EIS measurement exhibits promising potential for rapidly detecting P4 in undiluted serum.

Efficient complete denture metal base design via a dental feature-driven segmentation network.

BACKGROUND AND OBJECTIVE: Complete denture is a common restorative treatment in dental patients and the design of the core components (major connector and retentive mesh) of complete denture metal base (CDMB) is the basis of successful restoration. However, the automated design process of CDMB has become a challenging task primarily due to the complexity of manual interaction, low personalization, and low design accuracy. METHODS: To solve the existing problems, we develop a computer-aided Segmentation Network-driven CDMB design framework, called CDMB-SegNet, to automatically generate personalized digital design boundaries for complete dentures of edentulous patients. Specifically, CDMB-SegNet consists of a novel upright-orientation adjustment module (UO-AM), a dental feature-driven segmentation network, and a specific boundary-optimization design module (BO-DM). UO-AM automatically identifies key points for locating spatial attitude of the three-dimensional dental model with arbitrary posture, while BO-DM can result in smoother and more personalized designs for complete denture. In addition, to achieve efficient and accurate feature extraction and segmentation of 3D edentulous models with irregular gingival tissues, the light-weight backbone network is also incorporated into CDMB-SegNet. RESULTS: Experimental results on a large clinical dataset showed that CDMB-SegNet can achieve superior performance over the state-of-the-art methods. Quantitative evaluation (major connector/retentive mesh) showed improved Accuracy (98.54 ± 0.58 %/97.73 ± 0.92 %) and IoU (87.42 ± 5.48 %/70.42 ± 7.95 %), and reduced Maximum Symmetric Surface Distance (4.54 ± 2.06 mm/4.62 ± 1.68 mm), Average Symmetric Surface Distance (1.45 ± 0.63mm/1.28 ± 0.54 mm), Roughness Rate (6.17 ± 1.40 %/6.80 ± 1.23 %) and Vertices Number (23.22 ± 1.85/43.15 ± 2.72). Moreover, CDMB-SegNet shortened the overall design time to around 4 min, which is one tenth of the comparison methods. CONCLUSIONS: CDMB-SegNet is the first intelligent neural network for automatic CDMB design driven by oral big data and dental features. The designed CDMB is able to couple with patient's personalized dental anatomical morphology, providing higher clinical applicability compared with the state-of-the-art methods.

In Operando X-ray Spectroscopic and DFT Studies Revealing Improved H2 Evolution by the Synergistic Ni-Co Electron Effect in the Alkaline Condition.

The different electrolyte conditions, e.g., pH value, for driving efficient HER and OER are one of the major issues hindering the aim for electrocatalytic water splitting in a high efficiency. In this regard, seeking durable and active HER electrocatalysts to align the alkaline conditions of the OER is a promising solution. However, the success in this strategy will depend on a fundamental understanding about the HER mechanism at the atomic scale. In this work, we have provided thorough understanding for the electrochemical HER mechanisms in KOH over Ni- and Co-based hollow pyrite microspheres by in operando X-ray spectroscopies and DFT calculations, including NiS2, CoS2, and Ni0.5Co0.5S2. We discovered that the Ni sites in hollow NiS2 microspheres were very stable and inert, while the Co sites in hollow CoS2 microspheres underwent reduction and generated Co metallic crystal domains under HER. The generation of Co metallic sites would further deactivate H2 evolution due to the large hydrogen desorption free energy (-1.73 eV). In contrast, the neighboring Ni and Co sites in hollow Ni0.5Co0.5S2 microspheres exhibited the electronic interaction to elevate the reactivity of Ni and facilitate the stability of Co without structure or surface degradation. The energy barrier in H2O adsorption/dissociation was only 0.73 eV, followed by 0.06 eV for hydrogen desorption over the Ni0.5Co0.5S2 surface, revealing Ni0.5Co0.5S2 as a HER electrocatalyst with higher durability and activity than NiS2 and CoS2 in the alkaline medium due to the synergy of neighboring Ni and Co sites. We believe that the findings in our work offer a guidance toward future catalyst design.

Seeing the Unseen: The Structural Influence of the Lone Pair Electrons in PbWO4.

Pair distribution function (PDF) analysis of the scheelite-type material PbWO4 reveals previously unidentified short-range structural distortions in the PbO8 polyhedra and WO4 tetrahedra not observed in the similarly structured CaWO4. These local distortions are a result of the structural influence of the Pb2+ 6s2 lone pair electrons. These are not evident from the Rietveld analysis of synchrotron X-ray or neutron powder diffraction data, nor do they strongly influence the X-ray PDF (XPDF). This illustrates the importance of neutron PDF (NPDF) in the study of such materials. First-principles density function theory (DFT) calculations show that the Pb2+ 6s2 electrons are hybridized with the O2- 2p electrons near the Fermi level. The presence of local-scale distortions has previously been neglected in studies of structure-functionality relationships in PbWO4 and other scheelite-structured photocatalytic materials, including BiVO4, and this observation opens new avenues for their optimization.

Superhalide-Anion-Motivator Reforming-Enabled Bipolar Manipulation toward Longevous Energy-Type Zn||Chalcogen Batteries.

Neutrophilic superhalide-anion-triggered chalcogen conversion-based Zn batteries, despite latent high-energy merit, usually suffer from a short lifespan caused by dendrite growth and shuttle effect. Here, a superhalide-anion-motivator reforming strategy is initiated to simultaneously manipulate the anode interface and Se conversion intermediates, realizing a bipolar regulation toward longevous energy-type Zn batteries. With ZnF2 chaotropic additives, the original large-radii superhalide zincate anion species in ionic liquid (IL) electrolytes are split into small F-containing species, boosting the formation of robust solid electrolyte interphases (SEI) for Zn dendrite inhibition. Simultaneously, ion radius reduced multiple F-containing Se conversion intermediates form, enhancing the interion interaction of charged products to suppress the shuttle effect. Consequently, Zn||Se batteries deliver a ca. 20-fold prolonged lifespan (2000 cycles) at 1 A g-1 and high energy/power density of 416.7 Wh kgSe-1/1.89 kW kgSe-1, outperforming those in F-free counterparts. Pouch cells with distinct plateaus and durable cyclability further substantiate the practicality of this design.

CrossZoom: Simultaneous Motion Deblurring and Event Super-Resolving.

Even though the collaboration between traditional and neuromorphic event cameras brings prosperity to frame-event based vision applications, the performance is still confined by the resolution gap crossing two modalities in both spatial and temporal domains. This paper is devoted to bridging the gap by increasing the temporal resolution for images, i.e., motion deblurring, and the spatial resolution for events, i.e., event super-resolving, respectively. To this end, we introduce CrossZoom, a novel unified neural Network (CZ-Net) to jointly recover sharp latent sequences within the exposure period of a blurry input and the corresponding High-Resolution (HR) events. Specifically, we present a multi-scale blur-event fusion architecture that leverages the scale-variant properties and effectively fuses cross-modal information to achieve cross-enhancement. Attention-based adaptive enhancement and cross-interaction prediction modules are devised to alleviate the distortions inherent in Low-Resolution (LR) events and enhance the final results through the prior blur-event complementary information. Furthermore, we propose a new dataset containing HR sharp-blurry images and the corresponding HR-LR event streams to facilitate future research. Extensive qualitative and quantitative experiments on synthetic and real-world datasets demonstrate the effectiveness and robustness of the proposed method. Codes and datasets are released at https://bestrivenzc.github.io/CZ-Net/.

CA-125 elimination rate constant K (KELIM) as a promising predictor of complete cytoreduction after neoadjuvant chemotherapy in advanced ovarian cancer patients: a retrospective study from two Chinese hospitals.

BACKGROUND: The modeled CA-125 elimination constant K (KELIM) is a potential marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy (NACT) before interval surgery. The objective of this study was to externally validate the KELIM (rate of elimination of CA-125) score in patients with high-grade serous ovarian cancer (HGSC) undergoing NACT and explore its relation to the completeness of IDS and survival. METHODS: The study was based on a retrospective cohort of 133 patients treated for advanced HGSC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV, with neoadjuvant chemotherapy, folllowed by interval surgery, in two centres in China. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. We used standardized (std) KELIM for subsequent analysis. Clinicopathologic parameters were collected, and Kaplan‒Meier survival analyses were performed for PFS and OS. RESULTS: KELIM was an independent predictor of the probability of complete surgery and survival in our cohort. The median std KELIM score of patients with complete surgery was significantly higher than that of patients with incomplete IDS (1.20 vs. 0.71, P < 0.001). Multivariate analysis showed that a std KELIM score ≥0.925 was an independent predictive factor for achieving complete resection (OR = 5.480; 95% CI, 2.409-12.466, P < 0.001) and better PFS (HR = 0.544; 95% CI: 0.349-0.849, P = 0.007) and OS (HR = 0.484; 95% CI: 0.251-0.930, P = 0.030). CONCLUSIONS: The tumor-primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during NACT, is a major parameter to consider for decision-making regarding IDS attempts and predicting patient survival.

Deciphering metabolic heterogeneity in retinoblastoma unravels the role of monocarboxylate transporter 1 in tumor progression.

BACKGROUND: Tumors exhibit metabolic heterogeneity, influencing cancer progression. However, understanding metabolic diversity in retinoblastoma (RB), the primary intraocular malignancy in children, remains limited. METHODS: The metabolic landscape of RB was constructed based on single-cell transcriptomic sequencing from 11 RB and 5 retina samples. Various analyses were conducted, including assessing overall metabolic activity, metabolic heterogeneity, and the correlation between hypoxia and metabolic pathways. Additionally, the expression pattern of the monocarboxylate transporter (MCT) family in different cell clusters was examined. Validation assays of MCT1 expression and function in RB cell lines were performed. The therapeutic potential of targeting MCT1 was evaluated using an orthotopic xenograft model. A cohort of 47 RB patients was analyzed to evaluate the relationship between MCT1 expression and tumor invasion. RESULTS: Distinct metabolic patterns in RB cells, notably increased glycolysis, were identified. This metabolic heterogeneity correlated closely with hypoxia. MCT1 emerged as the primary monocarboxylate transporter in RB cells. Disrupting MCT1 altered cell viability and energy metabolism. In vivo studies using the MCT1 inhibitor AZD3965 effectively suppressed RB tumor growth. Additionally, a correlation between MCT1 expression and optic nerve invasion in RB samples suggested prognostic implications. CONCLUSIONS: This study enhances our understanding of RB metabolic characteristics at the single-cell level, highlighting the significance of MCT1 in RB pathogenesis. Targeting MCT1 holds promise as a therapeutic strategy for combating RB, with potential prognostic implications.

Visual Tracking in Amblyopia: A Continuous Psychophysical Approach.

Purpose: This study aimed to explore the underlying mechanisms of the observed visuomotor deficit in amblyopia. Methods: Twenty-four amblyopic (25.8 ± 3.8 years; 15 males) and 22 normal participants (25.8 ± 2.1 years; 8 males) took part in the study. The participants were instructed to continuously track a randomly moving Gaussian target on a computer screen using a mouse. In experiment 1, the participants performed the tracking task at six different target sizes. In experiments 2 and 3, they were asked to track a target with the contrast adjusted to individual's threshold. The tracking performance was represented by the kernel function calculated as the cross-correlation between the target and mouse displacements. The peak, latency, and width of the kernel were extracted and compared between the two groups. Results: In experiment 1, target size had a significant effect on the kernel peak (F(1.649, 46.170) = 200.958, P = 4.420 × 10-22). At the smallest target size, the peak in the amblyopic group was significantly lower than that in the normal group (0.089 ± 0.023 vs. 0.107 ± 0.020, t(28) = -2.390, P = 0.024) and correlated with the contrast sensitivity function (r = 0.739, P = 0.002) in the amblyopic eyes. In experiments 2 and 3, with equally visible stimuli, there were still differences in the kernel between the two groups (all Ps < 0.05). Conclusions: When stimulus visibility was compensated, amblyopic participants still showed significantly poorer tracking performance.