Two Mixed-Ligand Co(II) Complexes as Luminescent Materials and Loaded with Temozolomide-gel Particles in Nursing Against Glioma.

By employing a mixed-ligand strategy, we synthesized two new coordination polymers (CPs) featuring Co(II): {Co(H2L)(bib)]·2H2O}n (1) and {Co(L)(bib)2]·2H2O}n (2), where H4L represents 5-(3,5-dicarboxybenzyloxy) isophthalic acid, and bib denotes 1,4-bis(1-imidazolyl)benzene. These CPs were obtained through the reaction of H4L, a flexible carboxylic acid ligand, with Co(NO3)2·6H2O in various solvent mixtures, along with the N-donor co-ligand bib. Complexes 1 and 2 are formed through distinct coordination modes, resulting in their distinct structural features and excellent fluorescent properties. Based on ligand-centered fluorescence emission and the blue shift (CP 1) along with red shift (CP 2) characteristics, both complexes show promise for applications in fields such as blue fluorescence sensing materials and luminescent materials. After successfully synthesizing two CPs, CP 1 was chosen as the carrier for loading temozolomide (TMZ). Subsequently, leveraging the unique advantages of hydrogels, we developed a novel metal gel formulation loaded with TMZ. The inhibitory effect of this formulation on the growth of glioblastoma was evaluated. Our results demonstrate a significant suppression of glioblastoma cell proliferation by this system, providing an effective avenue for glioblastoma treatment.

LncRNA PSMB8-AS1 increases glioma malignancy via the miR-382-3p/BCAT1 axis.

BACKGROUND: This study aimed to investigate the specific roles of the long non-coding RNA (lncRNA) proteasome 20S subunit beta 8 (PSMB8)-antisense RNA 1 (AS1)/microRNA (miR)-382-3p/branched-chain amino acid transaminase 1 (BCAT1) interaction network in gliomas. METHODS: Western blotting and quantitative reverse transcription-polymerase chain reaction were performed to assess the expression levels of lncRNA PSMB8-AS1, BCAT1, and miR-382-3p. Moreover, the cell proliferation, migration, and apoptosis were assessed using the cell counting kit-8, Transwell, and caspase-3 activity assays, respectively. The biological role of lncRNA PSMB8-AS1 in glioma was investigated in vivo using a xenograft mouse model. Additionally, the associations among lncRNA PSMB8-AS1, miR-382-3p, and BCAT1 were analyzed using dual-luciferase and RNA immunoprecipitation assays and bioinformatics analyses. RESULTS: Glioma cell lines and tissues exhibited overexpression of lncRNA PSMB8-AS1 and BCAT1 and low expression of miR-382-3p. Knockdown of PSMB8-AS1 remarkably repressed the tumor growth in vivo and the migration and proliferation of glioma cells in vitro. In contrast, knockdown of lncRNA PSMB8-AS1 increased the cell apoptosis. Mechanistically, PSMB8-AS1 directly targeted miR-382-3p. By sponging miR-382-3p, lncRNA PSMB8-AS1 stimulated the migration and proliferation of glioma cells and suppressed their apoptosis. Additionally, miR-382-3p directly targeted BCAT1. Inhibition of miR-382-3p reversed the antitumor effects of BCAT1 silencing on glioma progression. CONCLUSION: Our study revealed that lncRNA PSMB8-AS1 aggravated glioma malignancy by enhancing BCAT1 expression after competitively binding to miR-382-3p. Therefore, lncRNA PSMB8-AS1 may be a potential biomarker and therapeutic target for glioma treatment.

Role of digitalization, digital competence, and parental support on performance of sports education in low-income college students.

Educational institutions have failed to achieve desired goals due to the lack of technology adoption, and this situation needs researchers' emphasis. Hence, the current study examines the impact of digitalization and digital competencies among students on the educational performance of low-income college students in China. The article also investigates the moderating impact of parental support at the nexus of digitalization, digital competencies among students, and educational performance in low-income college students in China. The questionnaires were used by the researchers to gather the data from the selected respondents. The article has applied the smart-PLS to check the linkage among understudy constructs and test the hypotheses. The results revealed that digitalization and digital competencies among students positively link educational performance. The results also exposed that parental support significantly moderates digitalization, digital competencies, and educational performance in low-income college students in China. This article helps policymakers develop policies to improve educational performance using technology adoption.

Selective nerve block for the treatment of neuralgia in Kummell's disease: A case report.

BACKGROUND: Neuralgia is frequently noted in patients with Kummell's disease, and its mechanism is complex, rendering it challenging to treat. Percutaneous kyphoplasty (PKP) has been widely used to treat osteoporotic vertebral compression fractures with satisfactory outcomes. However, it is not optimal for managing severely collapsed vertebrae, as cement injection may not be feasible. This report describes the use of a selective nerve block for the treatment of neuralgia caused by severely collapsed vertebrae in a patient with Kummell's disease. CASE SUMMARY: In our patient, three vertebrae were involved. The collapse of T11 was particularly severe. After managing T8 and T9 using PKP, these two segments were effectively strengthened; consequently, back pain was significantly relieved. However, the structure and strength of T11 could not be effectively restored using a minimally invasive surgical method because there was little room for cement injection. This caused obvious neuralgia according to the postoperative status of the PKP. Thus, we performed selective nerve blocks for the treatment of neuralgia, which resulted in satisfactory outcomes. CONCLUSION: Selective nerve block may be a possible therapeutic strategy for neuralgia due to severely collapsed vertebrae in Kummell's disease.

The anti-inflammatory effect of Pien Tze Huang in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease that may progress to nonalcoholic steatohepatitis (NASH), hepatic tissue fibrosis, liver cirrhosis, and hepatocellular carcinoma. In this study, we investigated the effects of Pien Tze Huang (PTH), a well-known traditional Chinese herbal formula with liver protective effect, in methionine-choline deficient diet (MCD)- and high-fat diet (HFD)-induced NASH mouse models. Our results showed that PTH could exert hepatoprotective effects by improving liver weight and steatosis and reducing the fibrosis and serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) in both animal models. The effects of PTH was accompanied with the reduction of infiltrated macrophages, the inhibition of the expression of cytokines, and the induction of adiponectin expression. Mechanistically, we found that PTH could inhibit the activation of proinflammatory transcription factor nuclear factor-κB (NF-κB) by preventing the degradation of inhibitor of κBα (IκBα). These results demonstrate that PTH can improve NAFLD largely due to its suppression of the NF-κB inflammatory pathway.

Epidemiological characteristics of 561 cases of intracerebral hemorrhage in Chengdu, China.

ABSTRACT: To explore the epidemiology of patients with spontaneous intracerebral hemorrhage (sICH) in Chengdu, China, we retrieved the data of patients with spontaneous cerebral hemorrhage admitted to the First Affiliated Hospital of Chengdu Medical College from January 2017 to December 2019. We performed a comprehensive analysis of the location of hemorrhage, demographics, factors of hemorrhage, condition of body, severity of disturbance of consciousness, treatment, length of stay (days), inpatient costs, prognosis, and mortality rate in patients with sICH. In total, data of 561 in patients with sICH were included. The hemorrhage site was primarily located in the basal ganglia and thalamus (64.71%). The mean patient age was 63.2 ±â€Š12.4 years (64.17% men, 35.83% women). Male patients (mean age 62.3 ±â€Š12.5 year) were younger than female patients (mean age 64.9 ±â€Š12.1 year). The age of sICH onset in our sample was between 40 and 79 years; this occurred in 87.70% of the included cases. There were more males than females, which may be related to more daily smoking, longer drinking years, and overweight in males than in females. Cases occurred most frequently during the winter and spring months, and the relationship between sICH visits and hospitalizations appeared as a U-shape. The median time from illness onset to hospital admission was 3.0 hours. According to the Glasgow Coma Scale (GCS) score at admission, 20.50% of sICH cases were of mild intensity, 39.93% were moderate, and 39.57% were severe. Moderate disorder is the most common sICH severity. Factors influencing the disturbance of consciousness were blood glucose level at the time of admission as well as the number of years with hypertension. The lower the degree of disturbance of consciousness and the more they smoked per day indicated they had a higher likelihood of receiving surgical treatment while in hospital. The median hospital stay was 13.0 days, while the median inpatient cost was USD 3609. The 30-day mortality rate was 18.36%. sICH is an important public health problem in Chengdu, China. A governmental initiative is urgently needed to establish a sICH monitoring system that covers the Chengdu region to develop more effective and targeted measures for sICH prevention, treatment, and rehabilitation.

Centrosomal Localization of RXRα Promotes PLK1 Activation and Mitotic Progression and Constitutes a Tumor Vulnerability.

Retinoid X receptor alpha (RXRα), a nuclear receptor of transcription factor, controls various physiological and pathological pathways including cellular growth, proliferation, differentiation, and apoptosis. Here, we report that RXRα is phosphorylated at its N-terminal A/B domain by cyclin-dependent kinase 1 (Cdk1) at the onset of mitosis, triggering its translocation to the centrosome, where phosphorylated-RXRα (p-RXRα) interacts with polo-like kinase 1 (PLK1) through its N-terminal A/B domain by a unique mechanism. The interaction promotes PLK1 activation, centrosome maturation, and mitotic progression. Levels of p-RXRα are abnormally elevated in cancer cell lines, during carcinogenesis in animals, and in clinical tumor tissues. An RXRα ligand XS060, which specifically inhibits p-RXRα/PLK1 interaction but not RXRα heterodimerization, promotes mitotic arrest and catastrophe in a tumor-specific manner. These findings unravel a transcription-independent action of RXRα at the centrosome during mitosis and identify p-RXRα as a tumor-specific vulnerability for developing mitotic drugs with improved therapeutic index.

BI1071, a Novel Nur77 Modulator, Induces Apoptosis of Cancer Cells by Activating the Nur77-Bcl-2 Apoptotic Pathway.

Nur77 (also called TR3 or NGFI-B), an orphan member of the nuclear receptor superfamily, induces apoptosis by translocating to mitochondria where it interacts with Bcl-2 to convert Bcl-2 from an antiapoptotic to a pro-apoptotic molecule. Nur77 posttranslational modification such as phosphorylation has been shown to induce Nur77 translocation from the nucleus to mitochondria. However, small molecules that can bind directly to Nur77 to trigger its mitochondrial localization and Bcl-2 interaction remain to be explored. Here, we report our identification and characterization of DIM-C-pPhCF3 +MeSO3 - (BI1071), an oxidized product derived from indole-3-carbinol metabolite, as a modulator of the Nur77-Bcl-2 apoptotic pathway. BI1071 binds Nur77 with high affinity, promotes Nur77 mitochondrial targeting and interaction with Bcl-2, and effectively induces apoptosis of cancer cells in a Nur77- and Bcl-2-dependent manner. Studies with animal model showed that BI1071 potently inhibited the growth of tumor cells in animals through its induction of apoptosis. Our results identify BI1071 as a novel Nur77-binding modulator of the Nur77-Bcl-2 apoptotic pathway, which may serve as a promising lead for treating cancers with overexpression of Bcl-2.

Sensing, monitoring, and release of therapeutics: the translational journey of next generation bandages (Erratum).

This erratum corrects an error in "Sensing, monitoring, and release of therapeutics: the translational journey of next generation bandages," by Z. Li et al.

Sensing, monitoring, and release of therapeutics: the translational journey of next generation bandages.

This article aims to be a progress report on the Sensing, Monitoring And Release of Therapeutics (SMART) bandage-one of the three technologies that received the inaugural SPIE Photonics West Translational Research Symposium Award in 2015. Invented and developed by Dr. Conor L. Evans and his research team at the Wellman Center for Photomedicine, Massachusetts General Hospital, the SMART bandage is a tool aiming to provide measurements of physiological parameters in the skin alongside the administration of therapeutics on-demand. Since the project began in 2012, the chemists, physicists, and biomedical engineers in the team have worked closely with partners from academia and industry to develop oxygen-sensing SMART bandage prototypes that are now in first-in-human clinical studies. This report gives perspectives on the genesis and translational journey of the technology with an emphasis on the challenges encountered, and the solutions innovated at each stage of development.

Zinc phthalocyanine-soybean phospholipid complex based drug carrier for switchable photoacoustic/fluorescence image, multiphase photothermal/photodynamic treatment and synergetic therapy.

For the purpose of precision theranostic of tumor, multifunctional drug delivery systems are always receiving great attentions. Here, we developed a zinc phthalocyanine-soybean phospholipid (ZnPc-SPC) complex based drug delivery system with doxorubicin (Dox) as loading cargo to achieve additional chemotherapy while the carrier itself could serve as multifunctional and switchable theranostic agent. In the early phase, the ZnPc-SPC complex assembled to nanostructure displaying photothermal therapy (PTT) and photoacoustic (PA) properties while in the late phase, the prepared NPs dis-assembled into ZnPc-SPC complex again performing photodynamic therapy (PDT) and low-background fluorescence (FL) image. With the decoration of folate receptors α (FRα) targeted MTX, Dox-loaded, MTX-decorated self-assembled ZnPc-SPC complex NPs (DZSM) was formed. In vitro and in vivo evaluations both indicated that DZSM presented high selectivity for FRα over-expressed tumor cells, excellent switchable PA/FL image, significant multiphase PTT/PDT effect, as well as great synergetic therapy potential, leading to notable inhibition of tumor growth.

Non-invasive monitoring of skin inflammation using an oxygen-sensing paint-on bandage.

Inflammation involves a cascade of cellular and molecular mediators that ultimately lead to the infiltration of immune cells into the affected area. This inflammatory process in skin is common to many diseases including acne, infection, and psoriasis, with the presence or absence of immune cells a potential diagnostic marker. Here we show that skin inflammation can be non-invasively measured and mapped using a paint-on oxygen sensing bandage in an in vivo porcine inflammation model. After injection of a known inflammatory agent, the bandage could track the increase, plateau, and decrease in oxygen consumption at the injury site over 7 weeks, as well as discern inflammation resultant from injection at various depths beneath the surface of the skin. Both the initial rate of pO2 change and the change in bandage pO2 at equilibration (CBP20) were found to be directly related to the metabolic oxygen consumption rate of the tissue in contact. Healthy skin demonstrated an initial pO2 decrease rate of 6.5 [Formula: see text], and CBP20 of 84 [Formula: see text]. Inflamed skin had a significantly higher initial consumption rate of 55 [Formula: see text], and a larger CBP20 of 140 [Formula: see text]. The change in the bandage pO2 before and after equilibration with tissue was found to correlate well with histological evidence of skin inflammation in the animals.

Oxygen-Sensing Paint-On Bandage: Calibration of a Novel Approach in Tissue Perfusion Assessment.

BACKGROUND: Knowledge of tissue oxygenation status is fundamental in the prevention of postoperative flap failure. Recently, the authors introduced a novel oxygen-sensing paint-on bandage that incorporated an oxygen-sensing porphyrin with a commercially available liquid bandage matrix. In this study, the authors extend validation of their oxygen-sensing bandage by comparing it to the use of near-infrared tissue oximetry in addition to Clark electrode measurements. METHODS: The oxygen-sensing paint-on bandage was applied to the left hind limb in a rodent model. Simultaneously, a near-infrared imaging device and Clark electrode were attached to the right and left hind limbs, respectively. Tissue oxygenation was measured under normal, ischemic (aortic ligation), and reperfused conditions. RESULTS: On average, the oxygen-sensing paint-on bandage measured a decrease in transdermal oxygenation from 85.2 mmHg to 64.1 mmHg upon aortic ligation. The oxygen-sensing dye restored at 81.2 mmHg after unclamping. Responses in both control groups demonstrated a similar trend. Physiologic changes from normal to ischemic and reperfused conditions were statistically significantly different in all three techniques (p < 0.001). CONCLUSIONS: The authors' newly developed oxygen-sensing paint-on bandage exhibits a comparable trend in oxygenation recordings in a rat model similar to conventional oxygenation assessment techniques. This technique could potentially prove to be a valuable tool in the routine clinical management of flaps following free tissue transfer. Incorporating oxygen-sensing capabilities into a simple wound dressing material has the added benefit of providing both wound protection and constant wound oxygenation assessment.

Bright, "Clickable" Porphyrins for the Visualization of Oxygenation under Ambient Light.

A new group of "clickable" and brightly emissive metalloporphyrins has been developed for the visualization of oxygenation under ambient light with the naked eye. These alkynyl-terminated compounds permit the rapid and facile synthesis of oxygen-sensing dendrimers through azide-alkyne click chemistry. With absorption maxima overlapping with the wavelengths of common commercial laser sources, they are readily applicable to biomedical imaging of tissue oxygenation. An efficient synthetic methodology, featuring the stable trimethylacetyl (pivaloyl) protecting group, is described for their preparation. A paint-on liquid bandage containing a new, click-synthesized porphyrin dendrimer has been used to map oxygenation across an ex vivo porcine skin burn model.

Oxygen-Sensing Methods in Biomedicine from the Macroscale to the Microscale.

Oxygen monitoring has been a topic of exhaustive study given its central role in the biochemistry of life. The ability to quantify the physiological distribution and real-time dynamics of oxygen from sub-cellular to macroscopic levels is required to fully understand the mechanisms associated with both normal physiology and disease states. This Review will present the most significant recent advances in the development of oxygen-sensing materials and techniques, including polarographic, nuclear medicine, magnetic resonance, and optical approaches, that can be applied specifically for the real-time monitoring of oxygen dynamics in cellular and tissue environments. As some of the most exciting recent advances in synthetic methods and biomedical applications have been in the field of optical oxygen sensors, a major focus will be on the development of these toolkits.

Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage.

Oxygen plays an important role in wound healing, as it is essential to biological functions such as cell proliferation, immune responses and collagen synthesis. Poor oxygenation is directly associated with the development of chronic ischemic wounds, which affect more than 6 million people each year in the United States alone at an estimated cost of $25 billion. Knowledge of oxygenation status is also important in the management of burns and skin grafts, as well as in a wide range of skin conditions. Despite the importance of the clinical determination of tissue oxygenation, there is a lack of rapid, user-friendly and quantitative diagnostic tools that allow for non-disruptive, continuous monitoring of oxygen content across large areas of skin and wounds to guide care and therapeutic decisions. In this work, we describe a sensitive, colorimetric, oxygen-sensing paint-on bandage for two-dimensional mapping of tissue oxygenation in skin, burns, and skin grafts. By embedding both an oxygen-sensing porphyrin-dendrimer phosphor and a reference dye in a liquid bandage matrix, we have created a liquid bandage that can be painted onto the skin surface and dries into a thin film that adheres tightly to the skin or wound topology. When captured by a camera-based imaging device, the oxygen-dependent phosphorescence emission of the bandage can be used to quantify and map both the pO2 and oxygen consumption of the underlying tissue. In this proof-of-principle study, we first demonstrate our system on a rat ischemic limb model to show its capabilities in sensing tissue ischemia. It is then tested on both ex vivo and in vivo porcine burn models to monitor the progression of burn injuries. Lastly, the bandage is applied to an in vivo porcine graft model for monitoring the integration of full- and partial-thickness skin grafts.

Surface charge and cellular processing of covalently functionalized multiwall carbon nanotubes determine pulmonary toxicity.

Functionalized carbon nanotubes (f-CNTs) are being produced in increased volume because of the ease of dispersion and maintenance of the pristine material physicochemical properties when used in composite materials as well as for other commercial applications. However, the potential adverse effects of f-CNTs have not been quantitatively or systematically explored. In this study, we used a library of covalently functionalized multiwall carbon nanotubes (f-MWCNTs), established from the same starting material, to assess the impact of surface charge in a predictive toxicological model that relates the tubes' pro-inflammatory and pro-fibrogenic effects at cellular level to the development of pulmonary fibrosis. Carboxylate (COOH), polyethylene glycol (PEG), amine (NH2), sidewall amine (sw-NH2), and polyetherimide (PEI)-modified MWCNTs were successfully established from raw or as-prepared (AP-) MWCNTs and comprehensively characterized by TEM, XPS, FTIR, and DLS to obtain information about morphology, length, degree of functionalization, hydrodynamic size, and surface charge. Cellular screening in BEAS-2B and THP-1 cells showed that, compared to AP-MWCNTs, anionic functionalization (COOH and PEG) decreased the production of pro-fibrogenic cytokines and growth factors (including IL-1ß, TGF-ß1, and PDGF-AA), while neutral and weak cationic functionalization (NH2 and sw-NH2) showed intermediary effects. In contrast, the strongly cationic PEI-functionalized tubes induced robust biological effects. These differences could be attributed to differences in cellular uptake and NLRP3 inflammasome activation, which depends on the propensity toward lysosomal damage and cathepsin B release in macrophages. Moreover, the in vitro hazard ranking was validated by the pro-fibrogenic potential of the tubes in vivo. Compared to pristine MWCNTs, strong cationic PEI-MWCNTs induced significant lung fibrosis, while carboxylation significantly decreased the extent of pulmonary fibrosis. These results demonstrate that surface charge plays an important role in the structure-activity relationships that determine the pro-fibrogenic potential of f-CNTs in the lung.

Chitin microparticles for the control of intestinal inflammation.

BACKGROUND: Chitin is a polymer of N-acetylglucosamine with the ability to regulate innate and adaptive immune responses. However, the detailed mechanisms of chitin-mediated regulation of intestinal inflammation are only partially known. METHODS: In this study chitin microparticles (CMPs) or phosphate-buffered saline (PBS) were orally administered to acute and chronic colitis models every 3 days for 6 consecutive weeks beginning at weaning age. The effects of this treatment were evaluated by histology, cytokine production, coculture study, and enteric bacterial analysis in dextran sodium sulfate (DSS)-induced colitis or T-cell receptor alpha (TCRα) knockout chronic colitis models. RESULTS: Histologically, chitin-treated mice showed significantly suppressed colitis as compared with PBS-treated mice in both animal models. The production of interferon-gamma (IFN-γ) was upregulated in the mucosa of chitin-treated mice compared with control mice. The major source of IFN-γ-producing cells was CD4+ T cells. In mouse dendritic cells (DCs) we found that CMPs were efficiently internalized and processed within 48 hours. Mesenteric lymph nodes (MLNs) CD4+ T cells isolated from chitin-treated mice produced a 7-fold higher amount of IFN-γ in the culture supernatant after being cocultured with DCs and chitin as compared with the control. Proliferation of carboxyfluorescein succinimidyl ester (CFSE)(low) CD4+ T cells in MLNs and enteric bacterial translocation rates were significantly reduced in chitin-treated mice when compared with the control. In addition, CMPs improved the imbalance of enteric bacterial compositions and significantly increased interleukin (IL)-10-producing cells in noninflamed colon, indicating the immunoregulatory effects of CMPs in intestinal mucosa. CONCLUSIONS: CMPs significantly suppress the development of inflammation by modulating cytokine balance and microbial environment in colon.

Mesoporous silica nanoparticles in biomedical applications.

This tutorial review provides an outlook on nanomaterials that are currently being used for theranostic purposes, with a special focus on mesoporous silica nanoparticle (MSNP) based materials. MSNPs with large surface area and pore volume can serve as efficient carriers for various therapeutic agents. The functionalization of MSNPs with molecular, supramolecular or polymer moieties, provides the material with great versatility while performing drug delivery tasks, which makes the delivery process highly controllable. This emerging area at the interface of chemistry and the life sciences offers a broad palette of opportunities for researchers with interests ranging from sol-gel science, the fabrication of nanomaterials, supramolecular chemistry, controllable drug delivery and targeted theranostics in biology and medicine.