Assessment the Impact of IDH Mutation Status on MRI Assessments of White Matter Integrity in Glioma Patients: Insights From Peak Width of Skeletonized Mean Diffusivity and Free Water Metrics.

BACKGROUND: Gliomas are highly invasive brain tumors that evade accurate geographic assessment by conventional MRI due to microscopic invasion along white matter (WM) tracts. Advanced diffusion MRI techniques are needed to assess occult WM involvement. PURPOSE: To evaluate peak width of skeletonized mean diffusivity (PSMD) and peak width of skeletonized free water (PSFW), and axonal water fraction (AWF) for assessing glioma-induced alterations in normal-appearing WM and their relationship with isocitrate dehydrogenase 1 (IDH1) mutation. STUDY TYPE: Retrospective. POPULATION: One hundred five glioma patients (46 ± 13 years), 53 healthy controls (HCs) (46 ± 9 years). FIELD STRENGTH/SEQUENCE: 3.0 T, T1WI, T1-CE, T2WI, T2FLAIR, and DKI. ASSESSMENT: PSMD and PSFW were compared between lesion and contralateral sides in glioma patients and between patients and HCs. The associations between these metrics and clinical variables, including IDH1 mutation, was assessed. Corpus callosum (CC) injury, quantified by the AWF, was evaluated for its mediated effect of IDH1 mutation on contralesional PSMD and PSFW. STATISTICAL TESTS: Paired-t tests, ANCOVA, univariate and multivariate linear regression, and mediation analysis with significance set at P < 0.05. RESULTS: Contralateral PSMD and PSFW were significantly higher in left-sided gliomas (PSMD: 0.206 ± 0.027 vs. 0.193 ± 0.023; PSFW: 0.119 ± 0.019 vs. 0.106 ± 0.020) than in HCs, with similar increases in right-sided gliomas (PSMD: 0.219 ± 0.036 vs. 0.195 ± 0.023; PSFW: 0.129 ± 0.031 vs. 0.109 ± 0.020). IDH1 wild-type gliomas were associated with higher contralateral PSMD and PSFW (ß = -0.302 and -0.412). AWF of CC mediated the impact of IDH1 mutations on contralesional PSMD and PSFW (mediated proportion: 42.7% and 53.7%). DATA CONCLUSION: PSMD and PSFW are effective biomarkers for assessing WM integrity in gliomas, significantly associated with IDH1 mutation status. AWF of CC mediates the relationship between IDH1 mutation and contralesional PSMD and PSFW. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Low expression of interleukin-1 receptor antagonist correlates with poor prognosis via promoting proliferation and migration and inhibiting apoptosis in oral squamous cell carcinoma.

BACKGROUND: Biomarkers are biochemical indicators that can identify changes in the structure or function of systems, organs, or cells and can be used to monitor a wide range of biological processes, including cancer. Interleukin-1 receptor antagonist (IL1RA) is an important inflammatory suppressor gene and tumor biomarker. The goal of this study was to investigate the expression of IL1RA, its probable carcinogenic activity, and its diagnostic targets in oral squamous cell carcinoma (OSCC). RESULTS: We discovered that IL1RA was expressed at a low level in OSCC tumor tissues compared to normal epithelial tissues and that the expression declined gradually from epithelial hyperplasia through dysplasia to carcinoma in situ and invasive OSCC. Low IL1RA expression was associated not only with poor survival but also with various clinicopathological markers such as increased infiltration, recurrence, and fatalities. Following cellular phenotyping investigations in OSCC cells overexpressing IL1RA, we discovered that recovering IL1RA expression decreased OSCC cell proliferation, migration, and increased apoptosis. CONCLUSIONS: In summary, our investigation highlighted the possible involvement of low-expression IL1RA in OSCC cells in promoting invasive as well as metastatic and inhibiting apoptosis, as well as the efficacy of IL1RA-focused monitoring in the early detection and treatment of OSCC.

Blocking of FGFR4 signaling by F30 inhibits hepatocellular carcinoma cell proliferation through HMOX1-dependent ferroptosis pathway.

Excessive activation of FGF19/fibroblast growth factor receptor 4 (FGFR4) signaling is associated with poor survival of patients with hepatocellular carcinoma (HCC). FGFR4 inhibitors show promise for HCC treatment. F30, an indazole derivative designed through computer-aided drug design targeting FGFR4, demonstrated anti-HCC activity as described in our previous studies. However, the precise molecular mechanisms underlying F30's anticancer effects remain largely unexplored. We report here that F30 could effectively induce ferroptosis in HCC cells. The concentrations of cellular ferrous iron, the peroxidation of cell membranes and the homeostasis of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) were dysregulated by F30, thereby affecting cellular redox status. Induction of ferroptosis in HCC by F30 was inhibited by specific ferroptosis inhibitor ferrostatin-1. F30 upregulates various ferroptosis-related genes, including the heme oxygenase enzymes 1 (HMOX1), a key mediator of redox regulation. Surprisingly, F30-induced ferroptosis in HCC is dependent on HMOX1. The dysregulation of cellular ferrous iron concentrations and cell membrane peroxidation was rescued when knocking down HMOX1 with specific small interfering RNA. These findings shed light on the molecular mechanisms underlying FGFR4-targeting F30's anti-HCC effects and suggest that FGFR4 inactivation could be beneficial for HCC treatment involving ferroptosis.

The impact of paramagnetic rim lesions on cortical thickness and gray to white matter contrast in relapsing-remitting multiple sclerosis.

Background: Paramagnetic rim lesions (PRLs) on susceptibility magnetic resonance sequences have been suggested as an imaging marker of disease progression in multiple sclerosis. This retrospective cross-sectional study aimed to investigate the impact of PRLs on cortical thickness and gray matter (GM) to white matter (WM) contrast in relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 82 RRMS patients (40 patients with at least 1 PRL and 42 patients without PRL) and 43 healthy controls (HC) were included in this study. The T1-weighted images (T1WI) were processed with the FreeSurfer pipeline. GM to WM signal intensity ratio (GWR) was obtained from T1WI by dividing the GM signal intensity by the WM signal intensity for each vertex. Group differences in cortical thickness and GWR were tested on reconstructed cortical surface. Results: Compared to HC, patients with PRL had thinner mean cortical thickness (P<0.001), higher mean GWR (P=0.001), and lower brain structure volumes (cortex volume, P=0.001; WM volume, P<0.001; deep GM volume, P<0.001). Vertex-based analysis found significant cortical thinning in several regions and increased GWR in a wider range of regions in patients with PRL. The two types of clusters had both overlapping regions and independent regions. However, in patients without PRL, only a few regions showed significant cortical thickness changes. Correlation analysis found that in patients with PRL, only PRL volume showed a significant negative correlation with mean cortical thickness (P=0.048), and PRL volume and count, non-PRL count, and total lesion volume were significantly and positively correlated with mean GWR (P<0.05). Conclusions: There were significant changes in cortical thickness, GWR, and brain structure volume in RRMS patients with PRL that may contribute to further understanding of the pathological mechanisms underlying neurological tissue damage.

MiRNA-766-3p inhibits gastric cancer via targeting COL1A1 and regulating PI3K/AKT signaling pathway.

Objective MiRNA-766-3p has been shown to be associated with a variety of cancers. However, few studies have been done in gastric cancer (GC). This study explores the mechanism of miR-766-3p in GC. Methods The potential targets of microRNA (miRNA) were predicted using Tarbase and Targetscan databases. The results are intersected with differential genes (DEGs) (fold change > 1.5, P < 0.05) in gastric cancer to obtain potential core targets. The hub targets screened by constructing PPI networks (degree > 5, expression > 0.5). Validating the differential expression and expression in immunohistochemistry of these targets through the database. And the binding sites between miRNAs and mRNAs were verified using dual-luciferase Assay. Finally, qRT-PCR and Western Blot experiments were conducted to validate the hub targets and signal pathways. Results The potential hub targets from the PPI network were THBS2, COL1A1, FGG, FGB, and PLAU. Combining database, luciferase Assay and experimental validation, miR-766-3p can sponge COL1A1 and it plays the most important role in gastric cancer progression. In GC, COL1A1 was upregulated and the enrichment analysis revealed that COL1A1 regulates PI3K/AKT signal pathway, and AKT is also highly expressed in gastric cancer. Conclusion The miR-766-3p can inhibit the progression of gastric cancer by targeting COL1A1 and regulating the PI3K/AKT signal pathway. It could be a potential therapy option for the GC.

Automatic Recognition of Concealed Fish Bones under Laryngoscopy: A Practical AI Model Based on YOLO-V5.

BACKGROUND: Fish bone impaction is one of the most common problems encountered in otolaryngology emergencies. Due to their small and transparent nature, as well as the complexity of pharyngeal anatomy, identifying fish bones efficiently under laryngoscopy requires substantial clinical experience. This study aims to create an AI model to assist clinicians in detecting pharyngeal fish bones more efficiently under laryngoscopy. METHODS: Totally 3133 laryngoscopic images related to fish bones were collected for model training and validation. The images in the training dataset were trained using the YOLO-V5 algorithm model. After training, the model was validated and its performance was evaluated using a test dataset. The model's predictions were compared to those of human experts. Seven laryngoscopic videos related to fish bone were used to validate real-time target detection by the model. RESULTS: The model trained in YOLO-V5 demonstrated good generalization and performance, with an average precision of 0.857 when the intersection over union (IOU) threshold was set to 0.5. The precision, recall rate, and F1 scores of the model are 0.909, 0.818, and 0.87, respectively. The overall accuracy of the model in the validation set was 0.821, comparable to that of ENT specialists. The model processed each image in 0.012 s, significantly faster than human processing (p < 0.001). Furthermore, the model exhibited outstanding performance in video recognition. CONCLUSION: Our AI model based on YOLO-V5 effectively identifies and localizes fish bone foreign bodies in static laryngoscopic images and dynamic videos. It shows great potential for clinical application. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2162-2169, 2024.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

An off-on fluorescent nanoprobe for L-cysteine sensing based on the FRET effect.

A self-assembled fluorescent nanosensor for the determination of L-cysteine (Cys) was constructed based on the mechanism of fluorescence resonance energy transfer (FRET). In this system, CdTe/ZnS QDs serve as the energy donor while AuNPs serve as the receptor, resulting in the occurrence of FRET with dramatic fluorescence quenching of the QDs (turn off). Once Cys is added, AuNPs can adsorb Cys, leading to the release of the QDs. The process would inhibit the FRET, which contributed to the recovery of fluorescence (turn on) and an off-on fluorescence aptasensor for Cys detection was constructed accordingly. The linear response range of the fluorescence sensor is from 0.8 to 50 µM, and the detection limit is 0.24 µM. The sensor demonstrates great sensitivity and selectivity to Cys. More importantly, the QD-based sensing platform was successfully used for the detection of Cys in milk samples with high precision and accuracy, indicating the potential of the probe in practical applications.

Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways.

Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 treatment increased 2-hydroxyglutarate levels in cultured H3K27M-DMG cells and patient CSF samples. This corresponded with increases in repressive H3K27me3 in vitro and in human tumors accompanied by epigenetic downregulation of cell cycle regulation and neuroglial differentiation genes. Overall, ONC201 demonstrates efficacy in H3K27M-DMG by disrupting integrated metabolic and epigenetic pathways and reversing pathognomonic H3K27me3 reduction. SIGNIFICANCE: The clinical, radiographic, and molecular analyses included in this study demonstrate the efficacy of ONC201 in H3K27M-mutant DMG and support ONC201 as the first monotherapy to improve outcomes in H3K27M-mutant DMG beyond radiation. Mechanistically, ONC201 disrupts integrated metabolic and epigenetic pathways and reverses pathognomonic H3K27me3 reduction. This article is featured in Selected Articles from This Issue, p. 2293.

Transcriptomics and systems network-based molecular mechanism of herbal formula Huosu-Yangwei inhibited gastric cancer in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Huosu-Yangwei (HSYW) in the treatment of advanced gastric cancer and chronic atrophic gastritis with precancerous lesions has been reported in clinical trials. However, the molecular mechanisms underlying its inhibition of gastric tumor are not well-understood. AIM OF THE STUDY: Combined with transcriptomics and systems network-based molecular mechanism to explore the potential circRNA-miRNA-mRNA network of HSYW in the treatment of gastric cancer. MATERIALS AND METHODS: Animal experiments were conducted to investigate the effect of HSYW on tumor growth in vivo. RNA sequencing (RNA-seq) was implemented to identify the differentially expressed (DE) genes. Predictive miRNA targets and mRNA were used to construct circRNA-miRNA-mRNA networks and protein-protein interaction (PPI) networks. Quantitative real-time PCR (qRT-PCR) was utilized to verify the accuracy of the proposed circRNA-miRNA-mRNA networks. Additionally, the differentially expressed target proteins between gastric cancer (GC) and normal patients were assessed using data from the TCGA (The Cancer Genome Atlas) and HPA (The Human Protein Atlas) databases. RESULTS: We demonstrate HSYW significantly inhibits tumor growth of N87 cell-bearing Balb/c mice. Transcriptomic analysis revealed the existence of 119 differentially expressed (DE) circRNAs and 200 DE mRNAs between HSYW-treated and model mice. By associating predicted circRNA-miRNA pairs and miRNA-mRNA pairs, we constructed a circRNA-miRNA-mRNA (CMM) network. Furthermore, a protein-protein interaction (PPI) network was developed using the differential expressed mRNAs. Consequently, the reconstructed core CMM network and qRT-PCR validation indicated that 4 circRNAs, 5 miRNAs and 6 mRNAs could potentially serve as biomarkers to assess the therapeutic effects of HSYW-treated N87-bearing Balb/c mice. The TCGA and HPA databases also demonstrated that mRNA KLF15 and PREX1 had substantial differences between gastric cancer (GC) and healthy controls. CONCLUSIONS: By combining the experimental and bioinformatics analysis, this study confirms that the circRNA_00240/hsa-miR-642a-5p/KLF15 and circRNA_07980/hsa-miR-766-3p/PREX1 pathways play critical roles in HSYW-treated gastric cancer.

Interleukin-1 receptor antagonist: a promising cytokine against human squamous cell carcinomas.

Inflammation, especially chronic inflammation, is closely linked to tumor development. As essential chronic inflammatory cytokines, the interleukin family plays a key role in inflammatory infections and malignancies. The interleukin-1 (IL-1) receptor antagonist (IL1RA), as a naturally occurring receptor antagonist, is the first discovered and can compete with IL-1 in binding to the receptor. Recent studies have revealed the association of the polymorphisms in IL1RA with an increased risk of squamous cell carcinomas (SCCs), including squamous cell carcinoma of the head and neck (SCCHN), cervical squamous cell carcinoma, cutaneous squamous cell carcinoma (cSCC), esophageal squamous cell carcinoma (ESCC), and bronchus squamous cell carcinoma. Here, we reviewed the antitumor potential of IL1RA as an IL-1-targeted inhibitor.

Targeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas.

Diffuse midline gliomas (DMGs) including diffuse intrinsic pontine gliomas (DIPGs) bearing lysine-to-methionine mutations in histone H3 at lysine 27 (H3K27M) are lethal childhood brain cancers. These tumors harbor a global reduction in the transcriptional repressive mark H3K27me3 accompanied by an increase in the transcriptional activation mark H3K27ac. We postulated that H3K27M mutations, in addition to altering H3K27 modifications, reprogram the master chromatin remodeling switch/sucrose nonfermentable (SWI/SNF) complex. The SWI/SNF complex can exist in two main forms termed BAF and PBAF that play central roles in neurodevelopment and cancer. Moreover, BAF antagonizes PRC2, the main enzyme catalyzing H3K27me3. We demonstrate that H3K27M gliomas show increased protein levels of the SWI/SNF complex ATPase subunits SMARCA4 and SMARCA2, and the PBAF component PBRM1. Additionally, knockdown of mutant H3K27M lowered SMARCA4 protein levels. The proteolysis targeting chimera (PROTAC) AU-15330 that simultaneously targets SMARCA4, SMARCA2, and PBRM1 for degradation exhibits cytotoxicity in H3.3K27M but not H3 wild-type cells. AU-15330 lowered chromatin accessibility measured by ATAC-Seq at nonpromoter regions and reduced global H3K27ac levels. Integrated analysis of gene expression, proteomics, and chromatin accessibility in AU-15330-treated cells demonstrated reduction in the levels of FOXO1, a key member of the forkhead family of transcription factors. Moreover, genetic or pharmacologic targeting of FOXO1 resulted in cell death in H3K27M cells. Overall, our results suggest that H3K27M up-regulates SMARCA4 levels and combined targeting of SWI/SNF ATPases in H3.3K27M can serve as a potent therapeutic strategy for these deadly childhood brain tumors.

Prediction of postoperative effective lens position using iris root depth in primary angle-closure diseases.

PURPOSE: To evaluate the role of a new parameter, iris root depth (IRD), in intraocular lens power calculation using ultrasound biomicroscopy (UBM) in primary angle-closure diseases (PACDs), and to compare the accuracy of 6 formulas in PACDs: Barrett Universal II (BUII), Haigis, Hill-Radial Basis Function (RBF) v. 3.0, Hoffer Q, Kane and Sanders Retzlaff Kraff/Theoretical (SRK)/T. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Retrospective consecutive case series. METHODS: Patients diagnosed with PACDs who had undergone cataract surgery were reviewed to first evaluate the performance of 6 formulas. Then preoperative UBM examinations of 58 eyes were used to measure IRD and predict effective lens position (ELP) to generate the Haigis IRD formula. The accuracy of Haigis IRD was compared with BUII, Haigis and Kane formulas. The SD of predicted error was the main indicator evaluating formula performance, according to heteroscedastic analysis. RESULTS: 103 eyes (103 patients) were included. The SDs of Kane (0.59, P = .01), RBF 3.0 (0.61, P = .02) and SRK/T formula (0.62, P = .04) were significantly lower than Hoffer Q. Modified with IRD, Haigis IRD generated the lowest SD (0.41), which was significantly lower than Haigis formula (0.54, P = .03) and was equal to Kane formula (0.45, P = .37). CONCLUSIONS: Kane, RBF 3.0 and SRK/T were more accurate in PACD eyes. Optimized with IRD, Haigis IRD formula achieved the lowest SD and had comparable accuracy with Kane formula. IRD could be a promising parameter to improve accuracy of IOL power calculation for PACDs.

Self-assembled nanoplatforms with ZIF-8 as a framework for FRET-based glutathione sensing in biological samples.

A glutathione (GSH) optical sensor with high sensitivity and exceptional selectivity was established for the first time. Zeolitic imidazolate framework-8 (ZIF-8) as a model was used for the first time to entrap Mn2+:ZnS quantum dots (QDs) and a rhodamine B derivative (RBD) by self-assembly. Benefiting from the confinement effect of ZIF-8, the loaded QDs and RBD can be brought into close proximity for energy transfer to occur. In the presence of GSH, the fluorescence resonance energy transfer (FRET) process from the QDs to RBD can be initiated, rendering the fluorescent nanoprobe to exhibit a response to GSH. The fluorescence intensity of Mn2+:ZnS@ZIF-8@RBD decreased with an increase in the GSH concentration in the linear range of 5-120 µM and a detection limit of 1.5 µM. This finding leads to a method for the fluorescence detection of GSH with excellent selectivity over other reactive thiols. Moreover, because of its good accuracy and excellent recovery, the nanoplatform can be applied for GSH sensing in real human serum and urine samples. Hence, the developing probe may be extended to other optical sensing domains or drug carriers and has tremendous potential in the field of biomedicine.

Antimicrobial peptide functionalized gold nanorods combining near-infrared photothermal therapy for effective wound healing.

Photothermal therapy using laser activated gold nanorods (AuNRs) is a strategy for treatment of bacterial infections. Nevertheless, it also exerts cytotoxicity against human cells which leads to adverse effects in healthy human tissues and limits the applicable dose. Functionalization of AuNRs with a selective antimicrobial peptide (AMP) with higher selectivity for bacteria over human cells is a promising strategy for increasing the selectivity of the AuNRs for bacteria, hence increasing their cellular uptake by the bacteria in order to achieve stronger antimicrobial effects with lower doses of AuNRs without damaging the human cells. In this study, the surface of AuNRs was functionalized with a short AMP named C-At5 and the efficiency of the peptide functionalized AuNRs in killing gram-positive and gram-negative bacteria was evaluated in vitro as well as their potential for facilitating wound healing in a mouse model of wound infection with and without application of laser. The peptide-conjugated AuNRs exhibited higher antibacterial activity in vitro compared to the plain AuNRs both in the presence and absence of laser irradiation. Furthermore, AuNR@C-At5 had very low toxicity against human skin fibroblasts and human red blood cells indicating their higher biocompatibility compared to the plain AuNRs. Treatment of wounded mice with AuNR@C-At5 accelerated the wound healing process which was further enhanced by applying laser. The system developed in this study has great potential for customization for specific antimicrobial or antifungal therapy via conjugation of different types of AMPs with higher selectivity and can therefore serve as a guide for any future attempts in this regard.

Anticancer effect of rationally designed α-helical amphiphilic peptides.

Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells. In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.

Retinitis pigmentosa-associated anterior subcapsular cataract: morphological features and visual performance.

PURPOSE: To investigate the morphological features and surgical outcomes of retinitis pigmentosa (RP)-associated anterior subcapsular cataract (ASC). METHODS: Consecutive RP-associated ASC cases were reviewed, and one hundred patients (171 eyes) were included. Anterior segment photographed images by slit-lamp microscope were reviewed. Best-corrected visual acuity (BCVA) was recorded. The cases were classified according to preoperative best BCVA, the area (central, midperipheral and peripheral) and the density (Grade 1, vacuolar/bubble-like; Grade 2, plaque-like/translucent; and Grade 3, fibrotic/opaque) of ASC; subgroup analysis of surgical outcomes was then performed. RESULTS: The mean age was 52.1 ± 13.7 years, and the 41-50-year group had the best BCVA. 13.5% of eyes had BCVA better than 20/63, 30.4% were between 20/400 and 20/63, and 56.1% were worse than 20/400. The percentage of ASCs in the central, midperipheral and peripheral areas was 55.0%, 37.4% and 7.6%, respectively. Postoperative BCVA was improved in the central and midperipheral groups (P < 0.001) but was not in the peripheral group (P = 0.07). The percentage of ASCs in density of Grade 1, 2 and 3 was 11.1%, 38.6% and 50.3%, respectively. Grade 2 and 3 achieved improved postoperative BCVA (P < 0.001), but Grade 1 did not (P = 0.693). CONCLUSIONS: Mostly, ASC is located at the center of the pupillary area and affected the residual vision of RP patients. The patients benefited from cataract removal except for those with ASC extended to peripheral area. Surgery was also recommended for RP with ASC developed to be plaque-like and even fibrotic.

Comparison of three chemometric methods for processing HPLC-DAD data with time shifts: Simultaneous determination of ten molecular targeted anti-tumor drugs in different biological samples.

Three intelligent chemometric multi-way calibration methods including alternating trilinear decomposition (ATLD), alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) and multivariate curve resolution-alternating least squares (MCR-ALS) combined with high performance liquid chromatography-diode array detection (HPLC-DAD) were used to quantify ten molecular targeted anti-tumor drugs in three complex biological matrices (plasma, urine and cell culture media matrices). All analytes can be successfully eluted in 6.5 min. In this experiment, various degrees of time shifts occurred in different samples. While slight time shifts exist in the chromatographic analysis, satisfactory results can be obtained by the three proposed methods. When the time shift was large (5.6 s), the average spiked recoveries obtained by ATLD analysis were in the range of 58.9%-116.5%, which was less than satisfactory. However, the average recoveries obtained by MCR-ALS and ATLD-MCR analysis were 89.8%-114.8% and 84.5%-106.1% respectively, and more satisfactory results were obtained. For further research, ATLD-MCR and MCR-ALS methods were compared, and the results were evaluated by statistical tests. Accuracies of concentrations obtained by them were considered to be no significant difference. In addition, compared with other methods currently published, the proposed chemometric methods combined with the HPLC-DAD can rapidly, simultaneously and accurately determine varieties of molecular targeted anti-tumor drugs in different complex biological matrices even in the presence of severe peak overlaps, severe time shifts, slight baseline drifts and different unknown background interferences.

Improved Processing and Properties for Polyphenylene Oxide Modified by Diallyl Orthophthalate Prepolymer.

Diallyl orthophthalate (DAOP) prepolymer was investigated as a reactive plasticizer to improve the processability of thermoplastics. The rheology of blends of DAOP prepolymer initiated by 2,3-dimethyl-2,3-diphenylbutane (DMDPB) and polyphenylene oxide (PPO) was monitored during the curing process, and their thermal properties and morphology in separated phases were also studied. Differential scanning calorimetry (DSC) results showed that the cure degree of the reactively plasticized DAOP prepolymer was reduced with increasing PPO due to the dilution effect. The increasing amount of the DAOP prepolymer led to a gradual decrease in the viscosity of the blends and the rheology behavior was consistent with the chemical gelation of DAOP prepolymer in blends. This indicated that the addition of the DAOP prepolymer effectively improved processability. The phase separation occurring during curing of the blend and the transition from the static to dynamic mode significantly influences the development of the morphology of the blend corresponding to limited evolution of the conversion around the gel point.

Derivation and applications of human hepatocyte-like cells.

Human hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) promise a valuable source of cells with human genetic background, physiologically relevant liver functions, and unlimited supply. With over 10 years' efforts in this field, great achievements have been made. HLCs have been successfully derived and applied in disease modeling, toxicity testing and drug discovery. Large cohorts of induced pluripotent stem cells-derived HLCs have been recently applied in studying population genetics and functional outputs of common genetic variants in vitro. This has offered a new paradigm for genome-wide association studies and possibly in vitro pharmacogenomics in the nearly future. However, HLCs have not yet been successfully applied in bioartificial liver devices and have only displayed limited success in cell transplantation. HLCs still have an immature hepatocyte phenotype and exist as a population with great heterogeneity, and HLCs derived from different hPSC lines display variable differentiation efficiency. Therefore, continuous improvement to the quality of HLCs, deeper investigation of relevant biological processes, and proper adaptation of recent advances in cell culture platforms, genome editing technology, and bioengineering systems are required before HLCs can fulfill the needs in basic and translational research. In this review, we summarize the discoveries, achievements, and challenges in the derivation and applications of HLCs.