CYR61 confers chemoresistance by upregulating survivin expression in triple-negative breast cancer.

Cysteine-rich angiogenic inducer 61 (CYR61) is a protein from the CCN family of matricellular proteins that play diverse regulatory roles in the extracellular matrix. CYR61 is involved in cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence. Here, we show that CYR61 induces chemoresistance in triple-negative breast cancer (TNBC). We observed that CYR61 is overexpressed in TNBC patients, and CYR61 expression correlates negatively with the survival of patients who receive chemotherapy. CYR61 knockdown reduced cell migration, sphere formation and the cancer stem cell (CSC) population and increased the chemosensitivity of TNBC cells. Mechanistically, CYR61 activated Wnt/ß-catenin signaling and increased survivin expression, which are associated with chemoresistance, the epithelial-mesenchymal transition, and CSC-like phenotypes. Altogether, our study demonstrates a novel function of CYR61 in chemotherapy resistance in breast cancer.

Predictors of Postoperative Morphine Milligram Equivalents in Cardiac Surgery.

OBJECTIVES: Given both the short- and long-term deleterious effects of opioids, there has been an increased focused on reducing the use of postoperative opioid analgesia. As patients undergoing cardiac surgery often require high levels opioids postoperatively, understanding risk factors for increased postoperative opioid use may be helpful for the development of patient-specific opioid-sparing pain regimens for this patient population. DESIGN: A retrospective analysis of data from our electronic medical records and the Society of Thoracic Surgeon's database. SETTING: A single-institution study at an academic medical center. PARTICIPANTS: All patients undergoing open adult cardiac surgery were included. Exclusion criteria were patients with continuous intravenous narcotic drips and operative mortality. INTERVENTIONS: As this was a retrospective study, no interventions were conducted on the participants. MEASUREMENTS AND MAIN RESULTS: Data for patient postoperative opioid requirements were extracted from the electronic medical record. Total opioid use on postoperative days 0 to 3 was converted to morphine milligram equivalent (MME) via standard conversion factors. The study cohort comprised 1604 patients, including 456 females and 1066 coronary artery bypass grafting (CABG) recipients. MME was 31.0% greater in patients undergoing CABG (p < 0.001), 76.3% greater in patients with liver disease (p = 0.005), and 48.8% greater in patients with patient-controlled analgesia (p <0.001) during postoperative days 0 to 3. Younger age (p < 0.001) and higher body mass index (BMI) (p < 0.001) also were associated with increased MME prescription. CONCLUSIONS: CABG, liver disease, patient-controlled analgesia, younger age, and higher BMI are associated with increased narcotic use after cardiac surgery. Implementation of more aggressive perioperative multimodal opioid-sparing regimens should be considered for these patient groups.

Factor Eight Inhibitor Bypassing Activity as First-line Therapy for Coagulopathy in Cardiac Surgery.

OBJECTIVES: To compare the outcomes of factor eight inhibitor bypassing activity (FEIBA) versus fresh frozen plasma (FFP) as the primary treatment for postoperative coagulopathy in patients undergoing cardiac surgery. DESIGN: A retrospective, propensity-matched study. SETTING: A single, tertiary hospital. PARTICIPANTS: Patients who underwent noncoronary cardiac surgery with cardiopulmonary bypass between 2015 and 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients into 2 groups based on whether they received intraoperative FFP or FEIBA; cases using both were excluded. We analyzed 434 cases, with 197 receiving FFP and 237 receiving FEIBA. After propensity matching, there was no significant difference in the proportion of the patients who required packed red blood cell transfusions (p = 0.08). However, of those who required packed red blood cell transfusions, patients in the FEIBA group required significantly fewer units of packed red blood cells (p < 0.001). Significantly fewer patients in the FEIBA group required platelet (p < 0.001) and cryoprecipitate (p < 0.001) transfusions. The FEIBA group showed decreased prolonged postoperative intubation (p = 0.05), decreased intensive care unit length of stay (p = 0.04), and lower 30-day readmission rates (p = 0.03). There were no differences in the rates of thrombotic complications between the 2 cohorts. CONCLUSIONS: In the initial treatment of postcardiopulmonary bypass coagulopathy, FEIBA may be more effective than FFP in decreasing blood product transfusions and readmission rates. Further studies are needed to explore the potential routine use of FEIBA as first-line agent in this patient population.

Use of Bioimpedance Spectroscopy for Postoperative Fluid Management in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass.

OBJECTIVE: To assess whether bioimpedance spectroscopy analysis (BIA) can be used as a tool to guide postoperative fluid management in patients undergoing cardiac surgery. DESIGN: An observational study. SETTING: A single tertiary hospital. PARTICIPANTS: Patients who underwent cardiac surgery with cardiopulmonary bypass between June and November 2023 who were able to undergo BIA measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between BIA measurements of extracellular fluid (ECF) and total body water (TBW) volumes and daily changes in weight and 24-hour net intake and output (I/O) of fluids were assessed. Correlations between predischarge ECF volume as a percentage of TBW volume (ECF%TBW) and predischarge pro-B-type natriuretic peptide (Pro-BNP) levels and readmissions were analyzed. Changes in daily ECF volume significantly correlated with daily weight changes (p < 0.01) and 24-hour I/O (p < 0 .01). TBW volume significantly correlated with daily weight changes (p < 0.01) and with 24-hour I/O (p = 0.04). Daily weight changes did not correlate with 24-hour I/O (p = 0.06). The patients with predischarge ECF%TBW(%) greater than or equal to 51 had significantly higher predischarge Pro-BNP than those with ECF%TBW(%) less than 51 (p < 0.01). Patients who had heart failure revisits or admissions after discharge had a higher predischarge ECF%TBW(%) on index admission compared with patients who did not have heart failure readmissions (p = 0.01). CONCLUSIONS: BIA measurements in postoperative cardiac surgery patients may be a valuable tool to quantitatively determine fluid status to help guide fluid management in this patient population. Further studies validating the use of BIA for postoperative care in this population are warranted.

YAP, CTGF and Cyr61 are overexpressed in tamoxifen-resistant breast cancer and induce transcriptional repression of ERα.

About 70% of breast cancers overexpress estrogen receptor α (ERα, encoded by ESR1). Tamoxifen, a competitive inhibitor of estrogen that binds to ER, has been widely used as a treatment for ER-positive breast cancer. However, 20-30% of breast cancer is resistant to tamoxifen treatment. The mechanisms underlying tamoxifen resistance remain elusive. We found that Yes-associated protein (YAP; also known as YAP1), connective tissue growth factor (CTGF; also known as CCN2) and cysteine-rich angiogenic inducer 61 (Cyr61; also known as CCN1) are overexpressed, while ERα is downregulated in tamoxifen-resistant breast cancer. Inhibition of YAP, CTGF and Cyr61 restored ERα expression and increased sensitivity to tamoxifen. Overexpression of YAP, CTGF, and Cyr61 led to downregulation of ERα and conferred resistance to tamoxifen in ER-positive breast cancer cells. Mechanistically, CTGF and Cyr61 downregulated ERα expression at the transcriptional level by directly binding to the regulatory regions of the ERα-encoding gene, leading to increased tamoxifen resistance. Also, CTGF induced Glut3 (also known as SLC2A3) expression, leading to increased glycolysis, which enhanced cell proliferation and migration in tamoxifen-resistant cells. Together, these results demonstrate a novel role of YAP, CTGF and Cyr61 in tamoxifen resistance and provide a molecular basis for their function in tamoxifen-resistant breast cancer.

Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages.

Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC involving EGFR and/or HER2 expression and interactions between tumor and tumor-associated macrophages (TAMs) were explored. The prognosis of breast cancer patients who underwent surgery at Samsung Medical Center was analyzed. It was found that the co-expression of EGFR and HER2 was associated with a worse prognosis. Therefore, we generated EGFR-positive BLBC cells with stable HER2 overexpression and analyzed the profile of secretory cytokines. Chemokine (C-C motif) ligand 2 (CCL2) expression was increased in HER2-overexpressed BLBC cells. Recombinant human CCL2 treatment augmented the motility of TAMs. In addition, the conditioned culture media of HER2-overexpressed BLBC cells increased the motility of TAMs. Furthermore, activation of TAMs by CCL2 or the conditioned culture media of HER2-overexpressed cells resulted in the production of pro-inflammatory cytokines, such as IL-8 and IL-1ß. These observations reveal that CCL2 derived from EGFR and HER2 co-expressed BLBC cells can lead to increased TAM recruitment and the induction of IL-8 and IL-1ß from recruited TAMs, triggering the tumorigenesis of breast cancer with the expression of both EGFR and HER2. Our findings demonstrate that EGFR+ and HER2+ BLBC aggressiveness is partially mediated through the interaction between BLBC and TAMs recruited by CCL2.

A Development of the Self Shape Adjustment Cushion Mechanism for Improving Sitting Comfort.

The seat comfort of automobiles is one of the significant factors for determining the driver's fatigue, emotional experience, and individual space (which captures their individuality, rather than just a means of transportation in modern society). Conventional automobile seats could not provide seating comfort suitable for all drivers, in the form of seats that fit each driver's body type and the difficulty of meeting individual needs. This study proposes self-shape adjustable (the SSA seats) seats that improve the sitting comfort, safety, and secure the stability, by adjusting shape fit to the driver's body type. The SSA seats transforms the seat itself, in a way that improves the distribution of contact pressure and reduces sitting fatigue, with the pneumatic system. The transformed seats provide better sitting comfort and safety than the conventional automobile seat, by providing a seat shape suitable for the body shape of all users. It was verified that the SSA seats, proposed in this paper, have a uniform and improved pressure distribution, compared to the conventional seat, in various sitting postures; the contact area between the seat and user is enlarged, and the pressure concentrated on the ischial bone is lowered. In addition, it was proven (through user evaluation) that quantitative evaluation verification was the same as qualitative evaluation results.

Development of Wrist Interface Based on Fully Actuated Coaxial Spherical Parallel Mechanism for Force Interaction.

To develop a wrist robotic exoskeleton-type interface (REI) for force interaction, it should have a suitable range of motion similar to human wrist activities of daily living, large torque output performance, and low moving parts inertia for dynamic motion response to cover the human behavior frequency. In this paper, a wrist REI based on a fully actuated coaxial spherical parallel mechanism (CSPM) is proposed to satisfy the aforementioned features. The fully actuated CSPM-based wrist REI (FC-WREI) has the characteristics of pure rotation similar to the human wrist, high torque output by parallel torque synthesis, and low moving parts inertia due to the base arrangement of the actuators. Due to the mechanical advantages and design optimization, the FC-WREI maximally provides torque as much as 56.49-130.43% of the maximum isometric torque of the human wrist, while providing a consistent range of motion to the human wrist without interference problem. Moreover, it is confirmed that the inertia of the FC-WREI is up to 5.35 times lower than similar devices. These advantages of the FC-WREI mean that the device is applicable to various fields of REIs for force interaction.

One-pot conversion of alginic acid into furfural using Amberlyst-15 as a solid acid catalyst in γ-butyrolactone/water co-solvent system.

One-pot conversion of alginic acid, which was derived from brown algae, to furfural was investigated using various solid acid catalysts. Among the solid acid catalysts tested, Amberlyst-15 showed the highest activity in furfural production in aqueous media. When the effect of reaction media was examined by applying various organic solvent mixtures, it was found that γ-butyrolactone/water co-solvent system was selected as the most appropriate system for the reaction. Maximum furfural yield of 32.2% was obtained using Amberlyst-15 in the γ-butyrolactone/H2O at 210 °C for 20 min. Catalyst showed gradual deactivation behavior as the reaction proceeded, although the catalyst recovered its activity upon the simple treatment with sulfuric acid. N2 adsorption-desorption experiments, Fourier-transform infrared spectroscopy (FT-IR), back titration, and CHNS analysis were applied to investigate the physicochemical property of post-reaction samples, confirming that the leaching of the active sulfonic acid group and decrease in acid density was the major cause of deactivation.

Toxicological assessment of phthalates and their alternatives using human keratinocytes.

Phthalates are mainly used as binders and plasticizers in various industrial products including detergents, surfactants, waxes, paints, pharmaceuticals, food products, and cosmetics. However, they have been reported to be endocrine disruptors, which are chemicals that can mimic or disturb endocrines, causing interference to the endocrine system. Recently, there have been numerous reports showing that phthalates have negative health impacts such as asthma, breast cancer, obesity, type II diabetes, and male infertility. Due to these effects, there is an urgent need for phthalate alternatives. In this study, the potential cytotoxicity of phthalates and their substitutes were screened in HaCaT cells, a human keratinocyte cell line, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) thiazolyl blue assay, immunocytochemistry, flow cytometric analysis, and western blotting. We confirmed that common phthalates such as butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP) have genotoxic effects, leading to cell death. Among the known phthalate substitutes, tributyl O-acetylcitrate (ATBC), triethyl 2-acetylcitrate (ATEC), and trihexyl O-acetylcitrate (ATHC) were tested for cytotoxicity. As a result, ATEC showed similar levels of cytotoxicity with the phthalates whereas ATBC and ATHC did not show significant cytotoxicity even in high doses (5 mg/ml).

Titanium dioxide nanoparticles induce apoptosis by interfering with EGFR signaling in human breast cancer cells.

Titanium dioxide nanoparticles, due to their smaller size and increased surface area comparted to the bulk form, are known to be bioreactive and have unexpected toxicological outcomes. Previous studies have shown that nanoscale titanium dioxide induces reactive oxygen species (ROS)-mediated cytotoxicity and genotoxicity. Although many reports have discussed the ROS-mediated cytotoxic effects of titanium dioxide nanoparticles (TiO2-NPs), their effects on the receptor-ligand association are unknown. In this study, the possibility that TiO2-NPs can interfere with the receptor-ligand binding was assessed by monitoring alterations in the phosphorylation status of proteins downstream of the epidermal growth factor receptor (EGFR) signaling cascade. TiO2-NPs blocked ligand-induced EGFR autophosphorylation, leading to the deactivation of EGFR downstream effectors such as Akt and extracellular signal-regulated kinase signaling, inducing cell death.

Cytotoxicity measurement of Bisphenol A (BPA) and its substitutes using human keratinocytes.

Bisphenol-A (BPA) was first synthesized in the 1890s and has been used in many plastic products. However, BPA is known to act as an endocrine disruptor and has been found to be toxic to human health. Many alternative substances have been developed to replace BPA, but it is still widely used worldwide. In this study, we identified the potential cytotoxicity of BPA by evaluating toxicity using human keratinocytes. Also, we evaluated cytotoxicity of BPA substitutes to determine their suitability as an alternative to BPA. The proliferation assay using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and western blot analysis showed that BPA significantly affect cell viability, induction of apoptotic fraction and increased activation of DNA-damage marker protein. In addition, through the same experiments, the substitutes of BPA were shown to be significantly less toxic than BPA, and the least toxicity was observed with 1,4-cyclohexanedimethanol (CHDM) and terephthalic acid (TPA). In conclusion, this study suggests that cytotoxicity of BPA induces apoptosis of human keratinocytes, and that CHDM and TPA are the most suitable substitutes for BPA.

Comparative toxicological evaluation of nonylphenol and nonylphenol polyethoxylates using human keratinocytes.

Nonylphenol polyethoxylates (NPEOs) are a major group of nonionic surfactants widely used in various detergents, cleaners, plastics, papers, and agro-chemical products. Nonylphenol (NP), which is a final degraded metabolite derived from NPEOs, has been reported as an endocrine disrupter, known to mimic or disturb reproductive hormone functions. Concern about the hazards of NP and NPEOs has generated legal restrictions and action plans worldwide. Considering the fact that NP and NPEOs are majorly used in the production of products such as detergents, shampoos, and cosmetics which frequently come into contact with the skin, we investigated the effects of NP and NPEOs on a human keratinocyte cell line (HaCaT). In this study, the toxicity of NP and NPEOs was screened in HaCaT cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide thiazolyl blue assay and Western blotting. The potential cytotoxicity of substitutes was assessed by dose-response assays, relative cell viability, and genotoxicity caused by specific alterations in DNA damage response proteins (including ataxia-telangiectasia mutated, p53, Chk1, Chk2, and Histone H2A.X). We demonstrated that NP and NPEOs are toxic to HaCaT cells, as revealed by the decreased cell viability after 24 h treatment. NPs and NPEOs also induced apoptosis and DNA damage as shown by the activation of Poly(ADP-ribose) polymerase, Caspase-3, and Histone H2A.X.

Silencing of Glut1 induces chemoresistance via modulation of Akt/GSK-3ß/ß-catenin/survivin signaling pathway in breast cancer cells.

Cancer cells require increased aerobic glycolysis to support rapid cell proliferation. For their increased energy demands, cancer cells express glucose transporter (Glut) proteins at a high level. Glut1 is associated with basal-like breast cancer and is considered a potential therapeutic target. To investigate the possibility of Glut1 as a therapeutic target in breast cancer cells, we downregulated Glut1 in triple-negative breast cancer (TNBC) cell lines using a short hairpin system. We determined whether Glut1 silencing might enhance anti-proliferative effect of chemotherapeutic agents. Contrary to our hypothesis, ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3ß (Ser9)/ß-catenin/survivin. These results indicated that the potential of Glut1 as a therapeutic target should be carefully reevaluated.

Generation of α-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes.

Recent progress in genetic manipulation of pigs designated for xenotransplantation ha6s shown considerable promise on xenograft survival in primates. However, genetic modification of multiple genes in donor pigs by knock-out and knock-in technologies, aiming to enhance immunological tolerance against transplanted organs in the recipients, has not been evaluated for health issues of donor pigs. We produced transgenic Massachusetts General Hospital piglets by knocking-out the α-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in an expression cassette containing five different human genes including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20) [GT-(DAF/CD39/TFPI/C1-INH/TNFAIP3)/+] that are connected by 2A peptide cleavage sequences to release individual proteins from a single translational product. All five individual protein products were successfully produced as determined by western blotting of umbilical cords from the newborn transgenic pigs. Although gross observation and histological examination revealed no significant pathological abnormality in transgenic piglets, hematological examination found that the transgenic piglets had abnormally low numbers of platelets and WBCs, including neutrophils, eosinophils, basophils, and lymphocytes. However, transgenic piglets had similar numbers of RBC and values of parameters related to RBC compared to the control littermate piglets. These data suggest that transgenic expression of those human genes in pigs impaired hematopoiesis except for erythropoiesis. In conclusion, our data suggest that transgenic expression of up to five different genes can be efficiently achieved and provide the basis for determining optimal dosages of transgene expression and combinations of the transgenes to warrant production of transgenic donor pigs without health issues.

Preoperative prediction of anterior cruciate ligament tibial footprint size by anthropometric variables.

PURPOSE: The purpose of this study was to evaluate whether the ACL tibial footprint size can be predicted by anthropometric variables including height, weight, leg length, femur length, tibia length, and anteroposterior and mediolateral diameters of proximal tibia. METHODS: This study included 209 out of the 378 eligible patients. The inclusion criterion was ACL with normal gross appearance. Patients with conditions that could have affected the measurement were excluded: torn ACL, osteophyte formation around the ACL tibial attachment, presence of inflammatory arthritis, or history of knee joint infection. According to the above criteria, 169 patients were excluded from this study; 138 had torn ACL, 24 had osteophyte around the ACL footprint, 5 had history of rheumatoid arthritis, and 2 had history of previous knee joint infection. The ACL tibial footprint was carefully dissected and measured during total knee arthroplasty. Anthropometric variables regarding bone lengths were measured on radiography. The association of the ACL tibial footprint size (length and width) with anthropometric variables was analysed using simple and multiple linear regression analyses. RESULTS: The height, weight, leg length, femur length, tibia length, and the size of proximal tibia were associated with the ACL tibial footprint length and width. The ACL tibial footprint length could be predicted by the equation using tibia length: ACL tibial footprint length = -9.361 + 0.759 * (tibia length in cm) (R 2 = 0.44, P < 0.001) and width by the equation using weight and tibia length: ACL tibial footprint width = -0.5615 + 0.279 * (tibia length in cm) + 0.0333 * (weight in kgs) (R 2 = 0.17, P < 0.001). The concordance correlation coefficient for the measured and predicted values of ACL tibial footprint length and width showed moderate and low agreement, respectively (0.61, 95 % CI 0.53-0.68; 0.30, 95 % CI 0.21-0.38). CONCLUSION: The ACL tibial footprint length and width are associated with anthropometric variables, especially with tibial length. The predictive equation developed from this study can serve as supplementary guides to determine the surgical techniques and graft options in preoperative planning of an individual ACL reconstruction. LEVEL OF EVIDENCE: IV.

Cyr61 expression is associated with prognosis in patients with colorectal cancer.

BACKGROUND: Cysteine-rich 61 (Cyr61), a member of the CCN protein family, possesses diverse functionality in cellular processes such as adhesion, migration, proliferation, and survival. Cyr61 can also function as an oncogene or a tumour suppressor, depending on the origin of the cancer. Only a few studies have reported Cyr61 expression in colorectal cancer. In this study, we assessed the Cyr61 expression in 251 colorectal cancers with clinical follow up. METHODS: We examined Cyr61 expression in 6 colorectal cancer cell lines (HT29, Colo205, Lovo, HCT116, SW480, SW620) and 20 sets of paired normal and colorectal cancer tissues by western blot. To validate the association of Cyr61 expression with clinicopathological parameters, we assessed Cyr61 expression using tissue microarray analysis of primary colorectal cancer by immunohistochemical analysis. RESULTS: We verified that all of the cancer cell lines expressed Cyr61; 2 cell lines (HT29 and Colo205) demonstrated Cyr61 expression to a slight extent, while 4 cell lines (Lovo, HCT116, SW480, SW620) demonstrated greater Cyr61 expression than HT29 and Colo205 cell lines. Among the 20 cases of paired normal and tumour tissues, greater Cyr61 expression was observed in 16 (80%) tumour tissues than in normal tissues. Furthermore, 157 out of 251 cases (62.5%) of colorectal cancer examined in this study displayed strong Cyr61 expression. Cyr61 expression was found to be associated with pN (p = 0.018). Moreover, Cyr61 expression was associated with statistically significant cancer-specific mortality (p = 0.029). The duration of survival was significantly lesser in patients with Cyr61 high expression than in patients with Cyr61 low expression (p = 0.001). These results suggest that Cyr61 expression plays several important roles in carcinogenesis and may also be a good prognostic marker for colorectal cancer. CONCLUSIONS: Our data confirmed that Cyr61 was expressed in colorectal cancers and the expression was correlated with worse prognosis of colorectal cancers.

Synthesis and chemosensing properties of indole based donor- Π-acceptor dye material.

In this work, we have designed and synthesized a new chemosensor for the detection of various metal ions. The chemosensor named 2-[2-(1 H-indole-2-ylmethylene)-3-oxo-indan-1-yliden]- malononitrile was synthesized using 3-formyl indole and 2-(3-oxo-indan-1-yliden)-malononitrile. This chemosensor has been investigated the properties which are able to detect and recognize the detection function of heavy metal ions. D-π-A system of dye chemosensor between electron withdrawing malononitrile and electron donating indole moieties provides the functions to interact with target metal ions. These recognizing sensing effects were studied using the absorption behaviors. Furthermore, cyclic voltammogram was used to determine HOMO/LUMO energy levels from their redox onset points. Measured energy levels of HOMO/LUMO were compared with computational calculation and discussed in details. Finally, the interaction type of metal ions binding was determined by Job's plot measurements.

A bisindolylmaleimide-naphthalimide building block for the construction of the energy transfer cassette.

Double build-in chromophores with naphthalimide and bisindolylmaleimide incorporating to one molecule were synthesized efficiently and characterized fully. Its spectral properties were investigated. Effective intramolecular energy transfer together with the strong emission in solution and solid state were discussed in terms of its electronic structures. Optimized structure and frontier molecular orbital were calculated based on D3(mol) platform. Obviously electron delocalization before and after excitation was observed according to the molecular orbital calculation, which corresponds to the mechanism of excitation energy transfer through space occurred in the donor-linker-acceptor molecular system. The opto-physical properties of the dye indicated potential application of electro-optical materials.

Recent Advances in Nanomaterials for Modulation of Stem Cell Differentiation and Its Therapeutic Applications.

Challenges in directed differentiation and survival limit the clinical use of stem cells despite their promising therapeutic potential in regenerative medicine. Nanotechnology has emerged as a powerful tool to address these challenges and enable precise control over stem cell fate. In particular, nanomaterials can mimic an extracellular matrix and provide specific cues to guide stem cell differentiation and proliferation in the field of nanotechnology. For instance, recent studies have demonstrated that nanostructured surfaces and scaffolds can enhance stem cell lineage commitment modulated by intracellular regulation and external stimulation, such as reactive oxygen species (ROS) scavenging, autophagy, or electrical stimulation. Furthermore, nanoframework-based and upconversion nanoparticles can be used to deliver bioactive molecules, growth factors, and genetic materials to facilitate stem cell differentiation and tissue regeneration. The increasing use of nanostructures in stem cell research has led to the development of new therapeutic approaches. Therefore, this review provides an overview of recent advances in nanomaterials for modulating stem cell differentiation, including metal-, carbon-, and peptide-based strategies. In addition, we highlight the potential of these nano-enabled technologies for clinical applications of stem cell therapy by focusing on improving the differentiation efficiency and therapeutics. We believe that this review will inspire researchers to intensify their efforts and deepen their understanding, thereby accelerating the development of stem cell differentiation modulation, therapeutic applications in the pharmaceutical industry, and stem cell therapeutics.