Real-World Treatment Patterns in Patients With HER2-Amplified Metastatic Colorectal Cancer: A Clinical-Genomic Database Study.

BACKGROUND: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there were no FDA-approved treatments. This study examined real-world treatment patterns in patients with HER2+ mCRC in the United States before and after the emerging awareness of HER2-directed therapies in 2018. METHODS: This was a retrospective observational study of patients with HER2+ mCRC from the GuardantINFORM database, which contains claims data for patients with Guardant360 genomic testing results. Patients were aged ≥18 years, were diagnosed with mCRC between January 2014 and September 2020, and had confirmed ERBB2 amplification via the blood-based Guardant360 test. Treatment patterns and real-world time to next treatment (rwTTNT) were evaluated. RESULTS: This study included 142 patients with a median age of 59 years; 31 (21.8%) patients with ERBB2 amplifications also had ERBB2 mutations. Treatment patterns were heterogeneous and evolved over time; before 2018, the most common regimen prescribed after detection of ERBB2 amplification was anti-VEGF therapy with or without chemotherapy (31.6%; n=25), and after 2018, HER2-directed therapies were the most commonly prescribed (36.5%; n=23). Median rwTTNT among the overall cohort was 8.4 months (95% CI, 6.5-10.0); rwTTNT was numerically longer in patients who received HER2-directed therapy compared with those who received non-HER2-directed therapies (11.0 months [95% CI, 6.3-12.3] vs 7.2 months [95% CI, 5.8-9.6]). CONCLUSIONS: This real-world study of the largest clinically annotated dataset of patients with HER2+ mCRC showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN Guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized. Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.

Automatic measurement of the patellofemoral joint parameters in the Laurin view: a deep learning-based approach.

OBJECTIVES: To explore the performance of a deep learning-based algorithm for automatic patellofemoral joint (PFJ) parameter measurements from the Laurin view. METHODS: A total of 1431 consecutive Laurin views of the PFJ were retrospectively collected and divided into two parts: (1) the model development dataset (dataset 1, n = 1230) and (2) the hold-out test set (dataset 2, n = 201). Dataset 1 was used to develop the U-shaped fully convolutional network (U-Net) model to segment the landmarks of the PFJ. Based on the predicted landmarks, the PFJ parameters were calculated, including the sulcus angle (SA), congruence angle (CA), patellofemoral ratio (PFR), and lateral patellar tilt (LPT). Dataset 2 was used to assess the model performance. The mean of three radiologists who independently measured the PFJ parameters was defined as the reference standard. Model performance was assessed by the intraclass correlation coefficient (ICC), mean absolute difference (MAD), and root mean square (RMS) compared to the reference standard. Ninety-five percent limits of agreement (95% LoA) were calculated pairwise for each radiologist, reference standard, and model. RESULTS: Compared with the reference standard, U-Net showed good performance for predicting SA, CA, PFR, and LPT, with ICC = 0.85-0.97, MAD = 0.06-5.09, and RMS = 0.09-6.90 in the hold-out test set. Except for the PFR, the remaining parameters measured between the reference standard and the model were within the 95% LoA in the hold-out test dataset. CONCLUSIONS: The U-Net-based deep learning approach had a relatively high model performance in automatically measuring SA, CA, PFR, and LPT. KEY POINTS: • The U-Net model could be used to segment the landmarks of the PFJ and calculate the SA, CA, PFR, and LPT, which could be used to evaluate the patellar instability. • In the hold-out test, the automatic measurement model yielded comparable performance with reference standard. • The automatic measurement model could still accurately predict SA, CA, PFR, and LPT in patients with PI and/or PFOA.

Shikonin attenuates kidney tubular epithelial cells apoptosis, oxidative stress, and inflammatory response through nicotinamide adenine dinucleotide phosphate oxidase 4/PTEN pathway in acute kidney injury of sepsis model.

Natural compounds were used in the treatment of acute kidney injury (AKI) caused by sepsis. This study investigated the function of shikonin from the roots of Arnebia purpurea in sepsis-induced AKI model. The target genes of shikonin were predicted by traditional Chinese medicine integrative database (TCMID). The markers of kidney injury, oxidative stress, and inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The pathological changes of kidney tubules were assessed by Hematoxylin and Eosin staining. Apoptosis of kidney tubular epithelial cells (KTECs) was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Protein expression was measured by western blot. Shikonin significantly improved kidney injury induced by cecal ligation and perforation (CLP). Besides, shikonin reduced KTECs apoptosis, malondialdehyde (MDA), reactive oxygen species (ROS), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels, while augmented SOD and IL-10 levels. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase4 (NOX4) was predicted a target gene of shikonin. The expression of NOX4 was significantly inhibited in shikonin-treated group and the levels of phosphatidylinositol 3,4,5-trisphosphate 3-phosphate and dual specificity protein phosphate (PTEN) and p-p65 were decreased, while level of p-Akt was elevated. In vitro experiments, shikonin inhibited cell apoptosis, inflammatory, and ROS in human HK-2 cells and rat TECs. Shikonin downregulated expression of NOX4, PTEN and p-p65, and upregulated p-AKT and Bcl-2 expression in HK2 cells treated with lipopolysaccharide (LPS). Moreover, overexpression of NOX4 enhanced the effect of LPS on the expression level of PTEN, p-p65, p-AKT, and Bcl-2, which was reversed by the addition of shikonin. Taken together, shikonin could improve sepsis-induced AKI in rats, and attenuate the LPS induced KTECs apoptosis, oxidative stress, and inflammatory reaction via modulating NOX4/PTEN/AKT pathway.

Oncogenic microRNA-765 promotes the growth and metastasis of breast carcinoma by directly targeting ING4.

Previous investigations have proved that microRNA (miR)-765 is significantly overexpressed in multiple tumor types. Nevertheless, the underlying molecular mechanism of miR-765 in mediating breast carcinoma cell growth and metastasis remains unclear. Quantitative real-time polymerase chain reaction was used to determine the levels of miR-765 and inhibitor of growth 4 (ING4) in breast carcinoma tissues and breast carcinoma cells. Cell proliferation, colony formation, wound healing, and Transwell invasion assays were used to analysis the role of miR-765 on breast carcinoma cell growth and aggressiveness. The expressions of ING4 were determined using Western blot analysis and immunohistochemical staining. The direct target of ING4 and miR-765 was confirmed using the luciferase reporter assay. Nude mice were subcutaneously implanted with miR-765 inhibitor transfected MDA-MB-231 cells to determine the potential role of miR-765 in tumor growth in vivo. We observed that miR-765 is overexpressed in breast carcinoma tissue and breast cancer cells. By using luciferase reporter gene bioassay, we find that ING4 is the direct target of miR-765 in breast carcinoma. The level of ING4 is inversely associated with the level of miR-765. The gain-of-function and loss-of-function experiments in vitro indicate that the downregulation of miR-765 suppresses the growth, mobility, and invasion abilities of breast cancer cells by inhibiting ING4. In addition, overexpression of ING4 suppresses the aggressiveness of the MDA-BA-231 cell that is induced by miR-761 in vitro. In this study, we prove that miR-765 regulates the growth and metastasis of breast cancer via modulating miR-765-ING4-negative feedback loop.

Understanding Interactions between Cellular Matrices and Metal Complexes: Methods To Improve Silver Nanodot-Specific Staining.

Metal complexes are frequently used for biological applications due to their special photophysical and chemical characteristics. Due to strong interactions between metals and biomacromolecules, a random staining of cytoplasm or nucleoplasm by the complexes results in a low signal-to-background ratio. In this study, we used luminescent silver nanodots as a model to investigate the major driving force for non-specific staining in cellular matrices. Even though some silver nanodot emitters exhibited excellent specific staining of nucleoli, labeling with nanodots was problematic owing to severe non-specific staining. Binding between silver and sulfhydryl group of proteins appeared to be the major factor that enforced the silver staining. The oxidation of thiol groups in cells with hexacyanoferrate(III) dramatically weakened the silver-cell interaction and consequently significantly improved the efficiency of targeted staining.

Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case-control studies.

Many molecular epidemiological studies have been performed to explore the association between MTHFR C677T polymorphism and cancer risk in diverse populations. However, the results were inconsistent. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR C677T (150,086 cases and 200,699 controls from 446 studies) polymorphism. Overall, significantly increased cancer risk was found when all eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significantly increased breast cancer risk was found in Asians and Indians, significantly decreased colon cancer risk was found, significantly decreased colorectal cancer risk was found in male population, significantly increased gastric cancer risk was found in Caucasians and Asians, significantly increased hepatocellular cancer risk was found in Asians, significantly decreased adult acute lymphoblastic leukemia (AALL) risk was found in Caucasians, significantly decreased childhood acute lymphoblastic leukemia (CALL) risk was found in Asians, and significantly increased multiple myeloma and NHL risk was found in Caucasians. In summary, this meta-analysis suggests that MTHFR C677T polymorphism is associated with increased breast cancer, gastric cancer, and hepatocellular cancer risk in Asians, is associated with increased gastric cancer, multiple myeloma, and NHL risk in Caucasians, is associated with decreased AALL risk in Caucasians, is associated with decreased CALL risk in Asians, is associated with increased breast cancer risk in Asians, is associated with decreased colon cancer risk, and is associated with decreased colorectal cancer risk in male population. Moreover, this meta-analysis also points out the importance of new studies, such as Asians of HNC, Asians of lung cancer, and Indians of breast cancer, because they had high heterogeneity in this meta-analysis (I(2) > 75%).

Effects of a student pharmacist consultation on patient knowledge and attitudes about vaccines.

OBJECTIVE To measure the impact of student pharmacists' consultation on participant knowledge and attitudes about influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines. DESIGN Pre- and post-consultation surveys. SETTING Free health care service and immunization clinics in Vallejo and Martinez, CA. PARTICIPANTS Children and adults 13 years of age or older. INTERVENTION A convenience sample of participants completed a preintervention survey (PrIs) on basic vaccine knowledge and attitudes. Student pharmacists then delivered the intervention, which consisted of a 5-minute consultation on vaccines. A postintervention (PoIs) survey was administered immediately after the intervention. MAIN OUTCOME MEASURES Cumulative scores for eight knowledge-based questions and four attitude-based questions. RESULTS 198 participants completed both PrIs and PoIs. Compared with the PrI scores, the PoI scores showed significant improvement in basic vaccine knowledge and attitudes toward receiving vaccinations. Participants also were more likely to view pharmacists as a source of information about vaccines after the intervention. Student pharmacists administered 109 total vaccinations during the study, including 68 influenza vaccinations and 41 Tdap vaccinations. CONCLUSION A short, 5-minute consultation by a student pharmacist may increase vaccination rates and help serve as a vehicle to change the public's view of vaccines as well as pharmacists and their role in primary and preventive care.

Quantitative measurement of the ureter on three-dimensional magnetic resonance urography images using deep learning.

BACKGROUND: Accurate measurement of ureteral diameters plays a pivotal role in diagnosing and monitoring urinary tract obstruction (UTO). While three-dimensional magnetic resonance urography (3D MRU) represents a significant advancement in imaging, the traditional manual methods for assessing ureteral diameters are characterized by labor-intensive procedures and inherent variability. In the realm of medical image analysis, deep learning has led to a paradigm shift, yet the development of a comprehensive automated tool for the precise segmentation and measurement of ureters in MR images is an unaddressed challenge. PURPOSE: The ureter was quantitatively measured on 3D MRU images using a deep learning model. METHODS: A retrospective cohort of 445 3D MRU scans (443 patients, 52 ± 18 years; 217 female patients) was collected and split into training, validation, and internal testing cohorts. A 3D V-Net model was trained for urinary tract segmentation, and a post-processing algorithm was developed for ureteral measurements. The accuracy of the segmentation was evaluated using the Dice similarity coefficient (DSC) and volume intraclass correlation coefficient (ICC), with ground truth segmentations provided by experienced radiologists. The external cohort comprised 50 scans (50 patients, 55 ± 21 years; 30 female patients), and the model-predicted ureteral diameter measurements were compared with manual measurements to assess system performance. The various diameter parameters of ureter among the different measurement methods (ground truth, auto-segmentation with automatic diameter extraction, and manual segmentation with automatic diameter extraction) were assessed with Friedman tests and post hoc Dunn test. The effectiveness of the UTO diagnosis was assessed by receiver operating characteristic (ROC) curves and their respective areas under the curve (AUC) between different methods. RESULTS: In both the internal test and external cohorts, the mean DSC values for bilateral ureters exceeded 0.70. The ICCs for the bilateral ureter volume obtained by comparing the model and manual segmentation were all greater than 0.96 (p  < â€¯0.05), except for the right ureter in the internal test cohort, for which the ICC was 0.773 (p  < â€¯0.05). The mean DSCs for interobserver and intraobserver reliability were all above 0.97. The maximum diameter of the ureter exhibited no statistically significant differences either in the dilated (p = 0.08) or in the non-dilated (p = 0.32) ureters across the three measurement methods. The AUCs of ground truth, auto-segmentation with automatic diameter extraction, and manual segmentation with automatic diameter extraction in diagnosing UTO were 0.988 (95% CI: 0.934, 1.000), 0.961 (95% CI: 0.893, 0.991), and 0.979 (95% CI: 0.919, 0.998), respectively. There was no statistical difference between AUCs of the different methods (p > 0.05). CONCLUSION: The proposed deep learning model and post-processing algorithm provide an effective means for the quantitative evaluation of urinary diseases using 3D MRU images.

CDK4/6 Inhibitor Efficacy in ESR1-Mutant Metastatic Breast Cancer.

BACKGROUND: In estrogen receptor-positive metastatic breast cancer, ESR1 mutations (ESR1m) are a common mechanism of acquired resistance to aromatase inhibitors (ArIh). However, the impact ESR1 alterations have on CDK4/6 inhibitor (CDK4/6i) sensitivity has not been established. Analyses of CDK4/6i trials suggest that the endocrine therapy partner and specific ESR1 allele may affect susceptibility. We analyzed a real-world data set to investigate CDK4/6i efficacy in ESR1m metastatic breast cancer and associated clinical factors. METHODS: ESR1m were identified by analysis of circulating-tumor deoxyribonucleic acid. The GuardantINFORM database contains genomic information from tumors linked with claims data. Patients who started a CDK4/6i within 30 days of sequencing were categorized as having ESR1m or non-ESR1-mutant (non-ESR1m) breast cancer. Data were analyzed to determine the real-world time-to-next-treatment, defined as the start of a breast cancer treatment to initiation of the subsequent treatment. RESULTS: One hundred forty-five patients with ESR1m and 612 with non-ESR1m metastatic breast cancer were analyzed. ESR1m and non-ESR1m tumors had similar real-world time-to-next-treatment on CDK4/6i regimens (hazard ratio, 1.02; 95% confidence interval, 0.82 to 1.23). Duration on therapy in the first-line and second-line plus treatment settings were comparable regardless of ESR1 status. We stratified treatment duration by concurrent endocrine therapy, and patients with ESR1m had worse outcomes on ArIh but comparable real-world time-to-next-treatment on fulvestrant. CONCLUSIONS: These data suggest ESR1 variants are not associated with pan-CDK4/6i resistance and are consistent with the hypothesis that CDK4/6 blockade combined with a selective estrogen receptor degrader is potentially an effective option for ESR1m metastatic breast cancer.

Colorimetric and fluorescent dual detection of paraquat and diquat based on an anionic polythiophene derivative.

We have developed a colorimetric and fluorescent dual-response probe for the detection of paraquat and diquat in aqueous solutions based on an anionic polythiophene derivative. The detection limit of this approach can be as low as 10(-9) M by fluorescence measurements.

Developing luminescent silver nanodots for biological applications.

Though creation and characterization of water soluble luminescent silver nanodots were achieved only in the past decade, a large variety of emitters in diverse scaffolds have been reported. Photophysical properties approach those of semiconductor quantum dots, but relatively small sizes are retained. Because of these properties, silver nanodots are finding ever-expanding roles as probes and biolabels. In this critical review we revisit the studies on silver nanodots in inert environments and in aqueous solutions. The recent advances detailing their chemical and physical properties of silver nanodots are highlighted with an effort to decipher the relations between their chemical/photophysical properties and their structures. The primary results about their biological applications are discussed here as well, especially relating to their chemical and photophysical behaviours in biological environments (216 references).

Open Linear Polymer Host-Guest Interactions Sensed by Luminescent Silver Nanodots.

The selectivity of the linear polymer chain toward its binding moieties has been considered negligible; thus, a clear demonstration showing the best-fit binding of a linear polymer to its guest counterpart is still unknown. Luminescent poly(acrylic acid) (PAA)-stabilized silver nanodots (PAA-AgNDs) have been applied as a turn-on sensor to monitor the interaction between the PAA chain and its binding cations. The binding of cations ions to the PAA chain may cross-link the linear PAA chain via coordination with carboxylate, which increases the rigidity of the polymer chain, retards the nonradiative decay of PAA-AgNDs, and consequently enhances the emission of silver nanodots while inducing a blue-shift of its emission spectrum. For the first time, we have demonstrated that a linear polymer chain can act as an open host to selectively bind to its best-matching cations. Specifically, among Group 2 cations (Mg2+, Ca2+, Sr2+, Ba2+), calcium ions show the strongest bonding to the PAA polymer chain. Our research suggests that, with extra rigidity, the polymer improves its chemical stability as calcium ions cross-linked the linear polymer. Meanwhile, it has also been demonstrated that luminescent silver nanodots can be excellent probes for the detection of polymer activities with straightforward and simple visualization methods.

Multiple epithelioid angiosarcoma of stomach and small intestine with multiple lymph node metastases: A case report.

RATIONALE: Angiosarcoma is a mesenchymal soft tissue sarcoma with a tendency for vascular endothelial differentiation. It is highly malignant with a poor prognosis but has a low incidence. Epithelioid angiosarcoma of the gastrointestinal tract is rare, and simultaneous multiple lesions of the stomach and small intestine are even rarer. It is easy to be misdiagnosed clinically. We report on a case of preoperative misdiagnosis of gastric cancer and postoperative diagnosis of epithelioid angiosarcoma with multiple lymph node metastases. PATIENT CONCERNS: A 75-year-old patient who was admitted to the hospital because of fatigue, melena and dysuria for >1 month. DIAGNOSIS, INTERVENTIONS AND OUTCOMES: Gastroscopy revealed gastric fundus ulcer and the biopsy revealed poorly differentiated adenocarcinoma of the fundus. We performed a radical gastrectomy for gastric cancer during which multiple ulcers were found in the jejunum and resected. Postoperative pathology showed multiple epithelioid angiosarcoma in the stomach and small intestine with lymph node metastases. The patient did not receive further treatment and died 2 month after the surgery. LESSONS: Gastrointestinal epithelioid angiosarcoma is one of the differential diagnoses of gastrointestinal adenocarcinoma and surgery is the main treatment. The lymph nodes are one of the main sites of metastasis.

The cost-effectiveness of immediate treatment, percutaneous biopsy and active surveillance for the diagnosis of the small solid renal mass: evidence from a Markov model.

PURPOSE: The most effective diagnostic strategy for the very small, incidentally detected solid renal mass is uncertain. We assessed the cost-effectiveness of adding percutaneous biopsy or active surveillance to the diagnosis of a 2 cm or less solid renal mass. MATERIALS AND METHODS: A Markov state transition model was developed to observe a hypothetical cohort of healthy 60-year-old men with an incidentally detected, 2 or less cm solid renal mass, comparing percutaneous biopsy, immediate treatment and active surveillance. The primary outcomes assessed were the incremental cost-effectiveness ratio measured by cost per life-year gained at a willingness to pay threshold of $50,000. Model results were assessed by sensitivity analysis. RESULTS: Immediate treatment was the highest cost, most effective diagnostic strategy, providing the longest overall survival of 18.53 life-years. Active surveillance was the lowest cost, least effective diagnostic strategy. On cost-effectiveness analysis using a societal willingness to pay threshold of $50,000 active surveillance was the preferred choice at a $75,000 willingness to pay threshold while biopsy and treatment were acceptable ($56,644 and $70,149 per life-year, respectively). When analysis was adjusted for quality of life, biopsy dominated immediate treatment as the most cost-effective diagnostic strategy at $33,840 per quality adjusted life-year gained. CONCLUSIONS: Percutaneous biopsy may have a greater role in optimizing the diagnosis of an incidentally detected, 2 cm or less solid renal mass.

Generation of luminescent noble metal nanodots in cell matrices.

Cell matrices were used as rich libraries to screen proteins for the production of luminescent silver and gold nanodots. The study indicates that the proteins for silver and gold nanodot protection are quite different. The identification of such proteins in future may enrich the family of luminescent nanodots.

High power 2 MHz passively Q-switched nanosecond Nd:YVO4/Cr4+:YAG 914 nm laser.

We report a high-power, high-repetition-rate end-pumped passively Q-switched Nd:YVO4/Cr4+: yttrium aluminum garnet 914 nm laser. The maximum output power of 3.8 W at 914 nm is achieved at 2 MHz with the absorbed pump power of 25.2 W. The highest single pulse energy of a pulsed 914 nm laser reaches 2.3 µJ with a pulse width of 27.1 ns.

Identification of a tripartite motif family gene signature for predicting the prognosis of patients with glioma.

Objectiove: The tripartite motif (TRIM) family genes, which encode a protein subfamily of the RING type E3 ubiquitin ligases, function as important regulators of oncogenesis and development. It is thus of great importance to investigate the potential value of the TRIM family genes for prognostic prediction in glioma. METHODS: The gene expression RNA-Seq data and corresponding clinical information of glioma patients were obtained from The Cancer Genome Atlas (TCGA) dataset and the Chinese Glioma Genome Atlas (CGGA) dataset. LASSO regression and multivariate Cox regression analyses were performed to construct a risk signature of the TRIM family genes. The accuracy of the risk signature in predicting the prognosis of glioma patients was evaluated. The effects of TRIM17 on glioma cell proliferation were further explored. RESULTS: We constructed a prognostic signature based on eight TRIMs for the prediction of overall survival of glioma patients. Internal and external cohorts confirmed the satisfactory accuracy and generalizability of the signature in predicting the prognosis of glioma patients. Of the eight TRIMs, TRIM17 was significantly downregulated in glioma, and decreased with an increase in the tumor grade. Moreover, low expression of TRIM17 predicted poor prognosis in glioma. CCK-8 and colony formation assays indicated that TRIM17 overexpression significantly inhibited cell proliferation. Conversely, silencing of TRIM17 had the opposite effects. CONCLUSION: Our eight-gene signature based on the TRIM gene family is a novel and clinically useful biomarker, which may be helpful for clinical decision-making. Additionally, TRIM17 might be a therapeutic target for glioma.

Tuning the fast generation of luminescent silver nanodots on a surface.

Silver nanodots, predominantly a near-IR emitter, can be instantly generated on a surface by silver cluster transfer. Kinetic trapping of ssDNA molecules on the surface limits the reorganization of the resulting silver nanodots for other silver nanodot emitters. Adjusting the freedom of the adsorbed ssDNA can tune the generation of various silver nanodots on the surface.

Taurine-Upregulated Gene 1 Attenuates Cerebral Angiogenesis following Ischemic Stroke in Rats.

Objective: Angiogenesis is one of the therapeutic targets of cerebral infarction. Long noncoding RNAs (lncRNAs) can regulate the pathological process of angiogenesis following ischemic stroke. Taurine-upregulated gene 1 (TUG1), an lncRNA, is correlated to ischemic stroke. We intended to determine the effect of TUG1 on angiogenesis following an ischemic stroke. Materials and Methods: Middle cerebral artery occlusion (MCAO) was adopted to build a focal ischemic model of the rat brain, and pcDNA-TUG1 and miR-26a mimics were injected into rats. Neurological function was estimated through modified neurological severity scores. The volume of focal brain infarction was calculated through 2,3,5-triphenyltetrazolium chloride staining. The level of TUG1 and miR-26a was measured by PCR. The expression of vascular endothelial growth factor (VEGF) and CD31 was checked using immunohistochemistry and western blot. The correlation between miR-26a and TUG1 was verified through a luciferase reporter assay. Results: TUG1 increased noticeably while miR-26a was markedly reduced in MCAO rats. Overexpression of miR-26a improved neurological function recovery and enhanced cerebral angiogenesis in MCAO rats. TUG1 overexpression aggravated neurological deficits and suppressed cerebral angiogenesis in MCAO rats. Bioinformatics analysis revealed that miR-26a was one of the predicted targets of TUG1. Furthermore, TUG1 combined with miR-26a to regulate angiogenesis. TUG1 overexpression antagonized the role of miR-26a in neurological recovery and angiogenesis in MCAO rats. Conclusions: TUG1/miR-26a, which may act as a regulatory axis in angiogenesis following ischemic stroke, can be considered a potential target for cerebral infarction therapy.

Tailoring silver nanodots for intracellular staining.

Through tailored oligonucleotide scaffolds, Ag nanocluster syntheses have yielded thermally and cell-culture medium stable silver cluster-based emitters. Optimizing ssDNA stability has enabled creation of highly concentrated and spectrally pure nanocluster emitters with strong intracellular emission. Both fixed and live-cell staining become possible, and intracellular delivery is demonstrated both through conjugation to cell-penetrating peptides and via microinjection.