Single-Step Control of Liquid-Liquid Crystalline Phase Separation by Depletion Gradients.

Fine-tuning nucleation and growth of colloidal liquid crystalline (LC) droplets, also known as tactoids, is highly desirable in both fundamental science and technological applications. However, the tactoid structure results from the trade-off between thermodynamics and nonequilibrium kinetics effects, and controlling liquid-liquid crystalline phase separation (LLCPS) in these systems is still a work in progress. Here, a single-step strategy is introduced to obtain a rich palette of morphologies for tactoids formed via nucleation and growth within an initially isotropic phase exposed to a gradient of depletants. The simultaneous appearance is shown of rich LC structures along the depleting potential gradient, where the position of each LC structure is correlated with the magnitude of the depleting potential. Changing the size (nanoparticles) or the nature (polymers) of the depleting agent provides additional, precise control over the resulting LC structures through a size-selective mechanism, where the depletant may be found both within and outside the LC droplets. The use of depletion gradients from depletants of varying sizes and nature offers a powerful toolbox for manipulation, templating, imaging, and understanding heterogeneous colloidal LC structures.

Topological wetting states of microdroplets on closed-loop structured surfaces: Breakdown of the Gibbs equation at the microscale.

Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation.

OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death.

Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.

Differential inhibition of sildenafil and macitentan on saxagliptin metabolism.

The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the treatment of DM, sildenafil for the treatment of ED and PAH, and macitentan for the treatment of PAH are all substrates of CYP3A4, which indicates their potential involvement in drug-drug interactions. Therefore, we investigated potential pharmacokinetic interactions between saxagliptin and sildenafil/macitentan. We investigated this speculation both in vitro and in vivo, and explored the underlying mechanism using in vitro hepatic metabolic models and molecular docking assays. The results showed that sildenafil substantially inhibited the metabolism of saxagliptin by occupying the catalytic site of CYP3A4 in a competitive manner, leading to the alterations in the pharmacokinetic properties of saxagliptin in terms of increased maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to 24 h (AUC(0-t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0-∞)), decreased clearance rate (CLz/F), and prolonged terminal half-life (t1/2). In contrast, a slight inhibition was observed in saxagliptin metabolism when concomitantly used with macitentan, as no pharmacokinetic parameters were altered, except for CLz/F. Thus, dosage adjustment of saxagliptin may be required in combination with sildenafil to achieve safe therapeutic plasma concentrations and reduce the risk of potential toxicity, but it is not necessary for co-administration with macitentan.

Three-Dimensional Optothermal Manipulation of Light-Absorbing Particles in Phase-Change Gel Media.

Rational manipulation and assembly of discrete colloidal particles into architected superstructures have enabled several applications in materials science and nanotechnology. Optical manipulation techniques, typically operated in fluid media, facilitate the precise arrangement of colloidal particles into superstructures by using focused laser beams. However, as the optical energy is turned off, the inherent Brownian motion of the particles in fluid media impedes the retention and reconfiguration of such superstructures. Overcoming this fundamental limitation, we present on-demand, three-dimensional (3D) optical manipulation of colloidal particles in a phase-change solid medium made of surfactant bilayers. Unlike liquid crystal media, the lack of fluid flow within the bilayer media enables the assembly and retention of colloids for diverse spatial configurations. By utilizing the optically controlled temperature-dependent interactions between the particles and their surrounding media, we experimentally exhibit the holonomic microscale control of diverse particles for repeatable, reconfigurable, and controlled colloidal arrangements in 3D. Finally, we demonstrate tunable light-matter interactions between the particles and 2D materials by successfully manipulating and retaining these particles at fixed distances from the 2D material layers. Our experimental results demonstrate that the particles can be retained for over 120 days without any change in their relative positions or degradation in the bilayers. With the capability of arranging particles in 3D configurations with long-term stability, our platform pushes the frontiers of optical manipulation for distinct applications such as metamaterial fabrication, information storage, and security.

NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis.

BACKGROUND: NUDT21 (Nudix Hydrolase 21) has been shown to play an essential role in multiple biological processes. Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world. However, the biological function of NUDT21 in PAAD remains rarely understood. The aim of this research was to identify the prediction value of NUDT21 in diagnosis, prognosis, immune infiltration, and signal pathway in PAAD. METHODS: Combined with the data in online databases, we analyzed the expression, immune infiltration, function enrichment, signal pathway, diagnosis, and prognosis of NUDT21 in PAAD. Then, the biological function of NUDT21 and its interacted protein in PAAD was identified through plasmid transduction system and protein mass spectrometry. Expression of NUDT21 was further verified in clinical specimens by immunofluorescence. RESULTS: We found that NUDT21 was upregulated in PAAD tissues and was significantly associated with the diagnosis and prognosis of pancreatic cancer through bioinformatic data analysis. We also found that overexpression of NUDT21 enhanced PAAD cells proliferation and migration, whereas knockdown NUDT21 restored the effects through in vitro experiment. Moreover, NDUFS2 was recognized as a potential target of NUDT21.We further verified that the expression of NDUFS2 was positively correlated with NUDT21 in PAAD clinical specimens. Mechanically, we found that NUDT21 stabilizes NDUFS2 and activates the PI3K-AKT signaling pathway. CONCLUSION: Our investigation reveals that NUDT21 is a previously unrecognized oncogenic factor in the diagnosis, prognosis, and treatment target of PAAD, and we suggest that NUDT21 might be a novel therapeutic target in PAAD.

Developments and current status of cell-free DNA in the early detection and management of hepatocellular carcinoma.

Nowadays, hepatocellular carcinoma (HCC) is still a major threat to human health globally, with a disappointing prognosis. Regular monitoring of patients at high risk, utilizing abdominal ultrasonography combined with alpha-fetoprotein (AFP) serum analysis, enables the early detection of potentially treatable tumors. However, the approach has limitations due to its lack of sensitivity. Meanwhile, the current standard procedure for obtaining a tumor biopsy in cases of HCC is invasive and lacks the ability to assess the dynamic progression of cancer or account for tumor heterogeneity. Hence, there is a pressing need to develop non-invasive, highly sensitive biomarkers for HCC which can improve the accuracy of early diagnosis, assess treatment response and accurately predict the prognosis. In contrast to the conventional method of tissue biopsy, liquid biopsy offers a non-invasive approach that can be readily repeated. As a liquid biopsy approach, the analysis of cell-free DNA (cfDNA) offers real-time insights that can accurately portray the tumor burden and provide a comprehensive depiction of the genetic profile associated with HCC. In this review, we present a comprehensive summary of the recent research findings pertaining to the significance and potential practicality of cfDNA analysis in the early detection and effective management of HCC.

Tunable bandpass microwave photonic filter with largely reconfigurable bandwidth and steep shape factor based on cascaded silicon nitride micro-ring resonators.

Bandpass microwave photonic filter (MPF) can be achieved based on the well-known phase to intensity conversion method by using phase modulation and single micro-ring resonator (MRR) notch filter. Since MRR could introduce residual phase in handling one optical sideband, the out-of-band radio frequency (RF) rejection ratio and the shape factor of the bandpass MPF are very limited. Here, by introducing another MRR to handle the other optical sideband, the residual phase can be greatly suppressed, thus the filter's performance can be greatly improved. The proposed bandpass MPF was both verified theoretically and experimentally. Compared with the single MRR, the out-of-band RF rejection ratio and the shape factor were improved by 20 dB and 1.67, respectively. Furthermore, the bandpass MPF's bandwidth is reconfigurable by adjusting the optical carrier's frequency or the two MRRs' amplitude coupling coefficients. The bandpass MPF's center frequency is also tunable by changing the resonant wavelengths of two MRRs in the opposite direction simultaneously. Experimentally, bandwidth reconfiguration from 0.38 GHz to 15.74 GHz, the shape factor optimization from 2 to 1.23, and frequency tuning from 4 GHz to 21.5 GHz were achieved. We believe that the proposed bandpass MPF has great potential for microwave photonic signal processing.

Prognostic model and treatment choices for patients with primary intracranial central nervous system lymphoma: A population-based study.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that occurs in the CNS. With the advancement of medical care, its prognosis and treatment have also undergone tremendous changes. This study aimed to construct a prognostic model and compare the effects of different treatments for intracranial PCNSL. METHODS: Cases diagnosed as PCNSL between 2004 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Data were analyzed using Kaplan-Meier method and Cox regression analysis. Nomogram was built and validated using the R program. RESULTS: A total of 2861 PCNSL patients were included in the analysis. Age, year of diagnosis, surgery and chemotherapy were independent predictors for both overall survival (OS) and cancer-specific survival (CSS). A nomogram was established to predict 3-, 5- and 10-year OS and CSS for patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) showed the nomogram had good predictive performance and clinical application value. We also revealed that gross total resection had significantly better OS and CSS than biopsy alone (P < 0.001). Patients who received only chemotherapy had the best prognosis and did not benefit from additional radiotherapy. CONCLUSION: We developed a nomogram to predict patient survival rates based on independent predictors. It is an effective tool to help clinicians make survival predictions. Our results showed that patients can benefit from gross total resection of tumor, if it is feasible, and chemotherapy. The role of radiotherapy remained to be further assessed.

Pan-precancer and cancer DNA methylation profiles revealed significant tissue specificity of interrupted biological processes in tumorigenesis.

DNA methylation (DNAme) alterations are known to initiate from the precancerous stage of tumorigenesis. Herein, we investigated the global and local patterns of DNAme perturbations in tumorigenesis by analysing the genome-wide DNAme profiles of the cervix, colorectum, stomach, prostate, and liver at precancerous and cancer stages. We observed global hypomethylation in tissues of both two stages, except for the cervix, whose global DNAme level in normal tissue was lower than that of the other four tumour types. For alterations shared by both stages, there were common hyper-methylation (sHyperMethyl) and hypo-methylation (sHypoMethyl) changes, of which the latter type was more frequently identified in all tissues. Biological pathways interrupted by sHyperMethyl and sHypoMethyl alterations demonstrated significant tissue specificity. DNAme bidirectional chaos indicated by the enrichment of both sHyperMethyl and sHypoMethyl changes in the same pathway was observed in most tissues and was a common phenomenon, particularly in liver lesions. Moreover, for the same enriched pathways, different tissues may be affected by distinct DNAme types. For the PI3K-Akt signalling pathway, sHyperMethyl enrichment was observed in the prostate dataset, but sHypoMethyl enrichment was observed in the colorectum and liver datasets. Nevertheless, they did not show an increased possibility in survival prediction of patients in comparison with other DNAme types. Additionally, our study demonstrated that gene-body DNAme changes of tumour suppressor genes and oncogenes may persist from precancerous lesions to the tumour. Overall, we demonstrate the tissue specificity and commonality of cross-stage alterations in DNA methylation profiles in multi-tissue tumorigenesis.

Comprehensive Analysis of the Sorafenib-Associated Druggable Targets on Differential Gene Expression and ceRNA Network in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the predominant pathological type of liver cancer. Several therapeutic treatments, including sorafenib and regorafenib, have only modestly improved survival in patients with HCC. The aim of this study was to investigate the expression profiles and the regulation of competitive endogenous RNAs (ceRNAs) of the sorafenib-related target genes in HCC. Based on clinical information and expression profiles of HCC clinical samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, shared differentially expressed genes (DEGs) were analyzed and identified. Sorafenib-associated DEGs (SADs) were obtained by intersecting the DEGs with the sorafenib target genes from SuperTarget database. The expression patterns of SADs were verified in the Oncomine database. The biological functions of the SADs were annotated by gene set enrichment analysis (GSEA). In addition, a ceRNA network associated with SADs was constructed. Long non-coding RNAs (lncRNAs) in network that were significantly associated with overall survival were identified as prognosis of patients by Cox regression analysis. Finally, the expression levels of prognostic genes in HCC tissues and cell lines were verified using qRT-PCR. Gene expression differential analysis yielded a total of 146 common DEGs were obtained, including 21 upregulated and 125 downregulated DEGs. Among them, ten SADs were detected to be differentially expressed between tumor and normal tissues, including AXL, CYP2C19, CYP2C8, CYP2C9, CYP3A4, FGFR2, GMNN, PDGFRA, and TTK. GSEA analysis grouped them into three categories by function. The first category (CYP2C19, CYP2C8, CYP2C9 and CYP3A4) and second category (GMNN, TTK and EGER2) had the opposite roles in the enriched terms and pathways, while the third class (AXL and PDGFRA) has enrichment terms and pathways that intersect with those of the first and second categories. A ceRNA network associated with SADs was also constructed including 49 lncRNAs, 14 miRNAs, and 8 mRNAs. Three of these lncRNAs, SNHG7, GAS5 and HCP5, were found upregulated in HCC tissues and to be independent predictors in HCC patients. Significant correlations were found in expression between the prognostic lncRNAs and SADs. Ten SADs were systematically identified using expression data from HCC and normal tissues from TCGA and GEO datasets. GSEA analysis provided us with insight into the function of SADs. In the future, we will continue to explore the mechanisms of coordinated regulation of SADs-related prognostic lncRNAs and SADs at the ceRNA axis level and their potential functions in the development of HCC.

Identifying risk factors for in-stent restenosis in symptomatic intracranial atherosclerotic stenosis: a systematic review and meta-analysis.

Background: In-stent restenosis (ISR) is an adverse and notable event in the treatment of intracranial atherosclerotic stenosis (ICAS) with percutaneous transluminal angioplasty and stenting (PTAS). The incidence and contributing factors have not been fully defined. This study was performed to evaluate factors associated with ISR after PTAS. Data source: We identified studies on ISR after PTAS from an electronic search of articles in PubMed, Ovid MEDLINE, and the Cochrane Central Database (dated up to July 2022). Results: A total of 19 studies, including 452 cases of ISR after 2,047 PTAS, were included in the meta-analysis. The pooled incidence rate of in-stent restenosis was 22.08%. ISR was more likely to occur in patients with coronary artery disease (OR = 1.686; 95% CI: 1.242-2.288; p = 0.0008), dissection (OR = 6.293; 95% CI: 3.883-10.197; p < 0.0001), and higher residual stenosis (WMD = 3.227; 95% CI: 0.142-6.311; p = 0.0404). Patients treated with Wingspan stents had a significantly higher ISR rate than those treated with Enterprise stents (29.78% vs. 14.83%; p < 0.0001). Conclusions: The present study provides the current estimates of the robust effects of some risk factors for in-stent restenosis in intracranial atherosclerotic stenosis. The Enterprise stent had advantages compared with the Wingspan stent for ISR. The significant risk factors for ISR were coronary artery disease, dissection, and high residual stenosis. Local anesthesia was a suspected factor associated with ISR.

Comprehensive analysis of anoikis-related lncRNAs for predicting prognosis and response of immunotherapy in hepatocellular carcinoma.

Nowadays, primary liver cancer is still a major threat to human health. Anoikis is a particular form of programed cell death that has an inhibitory effect on neoplasm metastasis. Although several prognostic models based on anoikis-related genes for Hepatocellular carcinoma (HCC) have been established, signatures associated with anoikis-related lncRNAs have not been identified. To fill this blank space, the authors built up a prognostic signature and appraised its value in guiding immunotherapy. Eleven prognostic anoikis-related lncRNAs were identified through Least Absolute Shrinkage and Selection Operator Cox analysis. The accuracy of the risk signature in predicting prognosis was verified by K-M survival analysis and Receiver operating characteristic analysis. We further discovered that the high-risk group was often enriched in signal pathways related to cell growth and death and immune response; in addition, in the low-risk group, cells often undergo metabolic changes through gene set enrichment analysis. Finally, we realised that HCC patients in the high-risk group were upregulated in immune-checkpoint molecules and tend to have a higher tumour mutation burden level which indicated a higher sensitivity to immunotherapy. All in all, the anoikis-related lncRNAs risk signature showed excellent ability in predicting prognosis and may guide the application of immunotherapy in future clinical practice.

Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Assess the effectiveness and safety of treatment options atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib in clinical practice for patients with advanced hepatocellular carcinoma (HCC) patients. METHODS: To compare the effectiveness of Atez/Bev and lenvatinib in treating advanced HCC, we systematically searched the PubMed, EMBASE, and Web of Science databases. We utilized Review Manager 5.3 to extract and analyze the data. RESULTS: The present systematic review included 8 nonrandomized studies comprising a total of 6628 cases. There was no significant difference in 0.5-, 1-, 1.5-year OS rates and 0.5-, 1-year PFS rates between the 2 groups. However, patients with HCC caused by viral hepatitis would benefit more from the Atez/Bev therapy (hazard ratio = 0.75, 95% confidence interval: 0.63-0.89) but patients with a Child-Pugh class B liver function would benefit more from lenvatinib (hazard ratio = 1.70, 95% confidence interval: 1.07-2.70). At the same time, there are no major differences in safety between the 2 treatment options. CONCLUSION: Our study did not find any significant difference in effectiveness and safety between Atez/Bev and lenvatinib. However, Additional verification is required to determine whether these 2 therapeutic approaches have varying effects on distinct populations.

A bibliometric and visualized analysis of preoperative future liver remnant augmentation techniques from 1997 to 2022.

Background: The size and function of the future liver remnant (FLR) is an essential consideration for both eligibility for treatment and postoperative prognosis when planning surgical hepatectomy. Over time, a variety of preoperative FLR augmentation techniques have been investigated, from the earliest portal vein embolization (PVE) to the more recent Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) procedures. Despite numerous publications on this topic, no bibliometric analysis has yet been conducted. Methods: Web of Science Core Collection (WoSCC) database was searched to identify studies related to preoperative FLR augmentation techniques published from 1997 to 2022. The analysis was performed using the CiteSpace [version 6.1.R6 (64-bit)] and VOSviewer [version 1.6.19]. Results: A total of 973 academic studies were published by 4431 authors from 920 institutions in 51 countries/regions. The University of Zurich was the most published institution while Japan was the most productive country. Eduardo de Santibanes had the most published articles, and Masato Nagino was the most frequently co-cited author. The most frequently published journal was HPB, and the most cited journal was Ann Surg, with 8088 citations. The main aspects of preoperative FLR augmentation technique is to enhance surgical technology, expand clinical indications, prevent and treat postoperative complications, ensure long-term survival, and evaluate the growth rate of FLR. Recently, hot keywords in this field include ALPPS, LVD, and Hepatobiliary Scintigraphy. Conclusion: This bibliometric analysis provides a comprehensive overview of preoperative FLR augmentation techniques, offering valuable insights and ideas for scholars in this field.

Probing the Protein Folding Energy Landscape: Dissociation of Amyloid-ß Fibrils by Laser-Induced Plasmonic Heating.

Insoluble amyloid fibrils made from proteins and peptides are difficult to be degraded in both living and artificial systems. The importance of studying their physical stability lies primarily with their association with human neurodegenerative diseases, but also owing to their potential role in multiple bio-nanomaterial applications. Here, gold nanorods (AuNRs) were utilized to investigate the plasmonic heating properties and dissociation of amyloid-ß fibrils formed by different peptide fragments (Aß16-22/Aß25-35/Aß1-42) related to the Alzheimer's disease. It is demonstrated that AuNRs were able to break mature amyloid-ß fibrils from both the full length (Aß1-42) and peptide fragments (Aß16-22/Aß25-35) within minutes by triggering ultrahigh localized surface plasmon resonance (LSPR) heating. The LSPR energy absorbed by the amyloids to unfold and move to higher levels in the protein folding energy landscape can be measured directly and in situ by luminescence thermometry using lanthanide-based upconverting nanoparticles. We also show that Aß16-22 fibrils, with the largest persistence length, displayed the highest resistance to breakage, resulting in a transition from rigid fibrils to short flexible fibrils. These findings are consistent with molecular dynamics simulations indicating that Aß16-22 fibrils possess the highest thermostability due to their highly ordered hydrogen bond networks and antiparallel ß-sheet orientation, hence affected by an LSPR-induced remodeling rather than melting. The present results introduce original strategies for disassembling amyloid fibrils noninvasively in liquid environment; they also introduce a methodology to probe the positioning of amyloids on the protein folding and aggregation energy landscape via nanoparticle-enabled plasmonic and upconversion nanothermometry.

PTPMT1 regulates mitochondrial death through the SLC25A6-NDUFS2 axis in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma is a highly malignant cancer with poor prognosis, for which effective therapeutic strategies are urgently needed. The dual-specificity phosphatase PTPMT1 is localized in mitochondria and highly expressed in various cancers. Here, we investigated the function of PTPMT1 in pancreatic ductal adenocarcinoma. We inhibited its expression in pancreatic cancer cell lines using siRNAs or the specific PTPMT1 inhibitor alexidine dihydrochloride and observed that PTPMT1 silencing in pancreatic cancer cell lines drastically reduced cell viability, caused mitochondrial damage, and impaired mitochondrial function. Co-immunoprecipitation analysis demonstrated that PTPMT1 could interact with SLC25A6 and NDUFS2, indicating that it may modulate mitochondrial function via the SLC25A6-NDUFS2 axis. Collecively, our data highlight PTPMT1 as an important factor in pancreatic ductal adenocarcinoma and a potential therapeutic target.

mRNA sequencing and CyTOF analysis revealed ASPP2 altered the response patterns of hepatocellular carcinoma HepG2 cells to usnic acid.

In a previous study, our team found that ASPP2 overexpression increases the sensitivity of liver cancer cells to sorafenib. ASPP2 is an important target in the study of drug therapy for hepatocellular carcinoma. In this study, we demonstrated that ASPP2 altered the response of HepG2 cells to usnic acid (UA) by using mRNA sequencing and CyTOF. CCK8 assay was used to detect cytotoxicity of UA on HepG2 cells. Annexin V-RPE assay, TUNEL assay, and cleaved caspase 3 assay were performed to examine the apoptotic cell death induced by UA. Transcriptomic sequencing and a single-cell mass cytometry were used to analyze the dynamic response of HepG2shcon and HepG2shASPP2 cells to UA treatment. We have demonstrated that UA could inhibit proliferation in HepG2 cells in a concentration-dependent manner. Apoptotic cell death was significantly induced by UA in HepG2 cells, while knocking down ASPP2 could increase the resistance of HepG2 cells to UA. Data from mRNA-Seq indicated that knockout of ASPP2 in HepG2 cells affected cell proliferation, cycle, and metabolism. ASPP2 knockdown resulted in increased stemness and decreased apoptosis of HepG2 cells under the action of UA. CyTOF analysis confirmed the above results, ASPP2 knockdown increased oncoproteins in HepG2 cells and altered response patterns of HepG2 cells to UA. Our data suggested that the natural compound UA could inhibit liver cancer HepG2 cells; meanwhile, ASPP2 knockdown could affect response patterns of HepG2 cells to UA. The above results indicate that ASPP2 could be a research target in the chemoresistance of liver cancer.

Functional evaluation of intracranial atherosclerotic stenosis by pressure ratio measurements.

Background: Fractional flow reserve is widely used for the functional evaluation of coronary artery stenosis. Some studies have similarly used the translesional pressure ratio measurements for the functional evaluation of intracranial atherosclerotic stenosis. In this paper, we aimed to investigate the relationship between pressure ratio and cerebral tissue perfusion by MR perfusion imaging and provided a non-invasive method for evaluating the functional significance of intracranial atherosclerotic stenosis. Methods: A total of 18 consecutive patients with intracranial atherosclerotic stenosis patients including 19 stenotic vessels were recruited. The pressure was measured using a pressure guidewire, the pressure ratio before and after the endovascular intervention was calculated and compared with the severity of diameter stenosis and perfusion-derived MR (the time to maximum tissure residue function (Tmax)). Moreover, the DSA-derived pressure ratio was computed using a novel computational fluid dynamics-based model, termed CFD-PR, and was compared with the actual pressure ratio to assess its diagnostic accuracy. Results: The pressure ratio increased after percutaneous transluminal angioplasty or stenting, while the correlation between pressure ratio and diameter stenosis was not significant. The pressure ratio was negatively correlated with Tmax (r = -0.73, P < 0.01), and a 95% confidence interval for the cutoff value of pressure ratio = 0.67 (95% confidence interval: 0.58-0.76) was suggested. There was a good correlation (mean = 0.02, Spearman's correlation coefficient r = 0.908, P < 0.001) and agreement (limits of agreement: -0.157 to 0.196, P = 0.954) between CFD-PR and the actual pressure ratio. Conclusions: This exploratory study indicates the pressure ratio may correlate with the perfusion status. The pressure ratio can be calculated through a non-invasive method using a computational fluid dynamics-based method.