Search

This study analyzed the interconnectivity of climate change adaptation measures in the water management, health, and disaster sectors. A survey encompassing inputs from 94 experts was conducted for the analysis. Then a social network analysis was performed, based on the results of the survey, using Netminer 4.0. The findings confirmed that climate change adaptation measures in the water management, health and disaster sectors are interconnected. In addition, the results demonstrated that adaptation measures across these sectors are effective at addressing interconnected risks of climate change. Findings from this study have value as they can be used to prepare climate change adaptation measures that reflect climate risk. It is also significant that clusters of climate change adaptation measures have been derived from the results of this study.

Significance This study provides proof-of-principle evidence for intravesical delivery of messenger RNA (mRNA) via a mucoadhesive nanoparticle (NP) strategy and reveals the therapeutic potential of KDM6A in treating bladder cancer metastasis, which remains difficult due to the physiological bladder barriers. The mucoadhesive NPs could protect loaded mRNA, prolong exposure of mRNA in disease sites, and benefit the penetration and effective expression, which all represent challenging hurdles for intravesical delivery of mRNA therapeutics. mRNA local delivery can also avoid potential toxicity issues via systemic delivery and unwanted protein expression throughout the body. We expect this mucoadhesive mRNA nanotechnology can be useful for the effective up-regulation of targeted proteins in bladder tissues in situ for both mechanistic understanding and translational study of bladder-related diseases.

Summary Phosphorus plays an indispensable role in energy metabolism, acid-base balance, and genetic substances transfer. As nanotechnology advances, plenty of phosphorus-based nanomaterials have been developed and widely used in the fields of biology and medicine. The size and structure of phosphorus-based nanomaterials give them unique physicochemical, optical, and biological properties, greatly increasing the variety of nanomedicine. The excellent properties further promote the applications of phosphorus-based nanomaterials in drug nanocarriers, tumor theranostics, biosensors, and bone formation. In this review, we first introduce the phosphorus science to unify current phosphorus-based nanomaterials and discuss their synthesis methods. Furthermore, the representative nanoplatforms utilizing the corresponding properties are highlighted. Finally, research development, potential challenges, and perspectives for further improvement of phosphorus-based nanomaterials in biomedicines are presented.

Intravesical instillation is an efficient drug delivery route for the local treatment of various urological conditions. Nevertheless, intravesical instillation is associated with several challenges, including pain, urological infection, and frequent clinic visits for catheterization; these difficulties support the need for a simple and easy intravesical drug delivery platform. Here, we propose a novel biodegradable intravesical device capable of long-term, local drug delivery without a retrieval procedure. The intravesical device is composed of drug encapsulating biodegradable polycaprolactone (PCL) microcapsules and connected by a bioabsorbable Polydioxanone (PDS) suture with NdFeB magnets in the end. The device is easily inserted into the bladder and forms a 'ring' shape optimized for maximal mechanical stability as informed by finite element analysis. In this study, inserted devices were retained in a swine model for 4 weeks. Using this device, we evaluated the system's capacity for delivery of lidocaine and resiquimod and demonstrated prolonged drug release. Moreover, a cost-effectiveness analysis supports device implementation compared to the standard of care. Our data support that this device can be a versatile drug delivery platform for urologic medications.

The rapid development of nanotechnology results in the emergence of nanomedicines, but the effective delivery of drugs to tumor sites remains a great challenge. Prodrug-based cancer nanomedicines thus emerged due to their unique advantages, including high drug load efficiency, reduced side effects, efficient targeting, and real-time controllability. A distinctive characteristic of prodrug-based nanomedicines is that they need to be activated by a stimulus or multi-stimulus to produce an anti-tumor effect. A better understanding of various responsive approaches could allow researchers to perceive the mechanism of prodrug-based nanomedicines effectively and further optimize their design strategy. In this review, we highlight the stimuli-responsive pathway of prodrug-based nanomedicines and their anticancer applications. Furthermore, various types of prodrug-based nanomedicines, recent progress and prospects of stimuli-responsive prodrug-based nanomedicines and patient data in the clinical application are also summarized. Additionally, the current development and future challenges of prodrug-based nanomedicines are discussed. We expect that this review will be valuable for readers to gain a deeper understanding of the structure and development of prodrug-based cancer nanomedicines to design rational and effective drugs for clinical use.

Introduction The purpose of this study was to investigate if machined springs in nickel-titanium (NiTi) rotary instruments can improve their mechanical properties. The bending and torsion properties were assessed using finite element (FE) model analysis. Methods A basic 3-dimensional file model without a spring was created with apical size #25, 25-mm full length, and 16-mm cutting flutes. Three other models were created with a spring machined into their shaft portion with different numbers of spring coils: standard (STspr), 10% more (INspr), and 10% less (DEspr). To compare the mechanical responses among the 4 FE models, file bending and torsion were simulated using FE analysis. Results Spring machined NiTi rotary instruments showed higher torsional resistance and less bending stiffness than the same instrument without. The spring machined models required more torque to bend or rotate the DEspr model than was required for the STspr and INspr models; however, the STSpr and INSpr models were similar. Conclusions Within the limitations of this study, the FE analysis indicated that machining a spring into the shaft of NiTi rotary instruments improved torsional resistance and bending flexibility. Therefore, spring machining has the potential to increase the durability of the NiTi rotary instruments.

Two-dimensional (2D) nanosheets are characterized by their ultra-thin structure which sets them apart from their bulk materials. Due to this unique 2D structure, they have a high surface-to-volume ratio that can be beneficial for the delivery of various drugs including therapeutic DNAs and RNAs. In addition, various 2D materials exhibit excellent photothermal conversion efficiency when exposed to the near infrared (NIR) light. Therefore, this 2D nanosheet-based photonic nanomedicine has been gaining tremendous attention as both gene delivering vehicles and photothermal agents, which create synergistic effects in the treatment of different diseases. In this review, we briefly provide an overview of the following two parts regarding this type of photonic nanomedicine: (1) mechanism and advantages of nanosheets in gene delivery and photothermal therapy, respectively. (2) mechanism of synergistic effects in nanosheet-mediated combined gene and photothermal therapies and their examples in a few representative nanosheets (e.g., graphene oxide, black phosphorus, and translational metal dichalcogenide). We also expect to provide some deep insights into the possible opportunities associated with the emerging 2D nanosheets for synergistic nanomedicine research.

Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers, for example, in ~36% of hepatocellular carcinomas (HCCs) and ~68% of non-small cell lung cancers (NSCLCs). Current methods for restoration of p53 expression, including small molecules and DNA therapies, have yielded progressive success, but each has formidable drawbacks. Here, a redox-responsive nanoparticle (NP) platform is engineered for effective delivery of p53-encoding synthetic messenger RNA (mRNA). We demonstrate that the synthetic p53-mRNA NPs markedly delay the growth of p53-null HCC and NSCLC cells by inducing cell cycle arrest and apoptosis. We also reveal that p53 restoration markedly improves the sensitivity of these tumor cells to everolimus, a mammalian target of rapamycin (mTOR) inhibitor that failed to show clinical benefits in advanced HCC and NSCLC. Moreover, cotargeting of tumor-suppressing p53 and tumorigenic mTOR signaling pathways results in marked antitumor effects in vitro and in multiple animal models of HCC and NSCLC. Our findings indicate that restoration of tumor suppressors by the synthetic mRNA NP delivery strategy could be combined together with other therapies for potent combinatorial cancer treatment.

In article number 1901211, Wei Tao, Omid C. Farokhzad, Xiaobin Zeng, and co‐workers provide a novel exfoliation approach combining calcination, n‐butyllithium exchange and intercalation, and liquid exfoliating processes for the high‐quality synthesis of ultrathin biotite nanosheets. The developed nanosheets can be engineered as an intelligent theranostic platform for cancer combination therapy with unique features. Cover image designed by Xiaoyuan Ji.

Biotite, also called black mica (BM), is a group of sheet silicate minerals with great potential in various fields. However, synthesis of high‐quality BM nanosheets (NSs) remains a huge challenge. Here, an exfoliation approach is provided that combines calcination, n‐butyllithium exchange and intercalation, and liquid exfoliating processes for the high‐yield synthesis of ultrathin BM NSs. Due to the presence of MgO, Fe2O3, and FeO in these NSs, PEGylated BM can be engineered as an intelligent theranostic platform with the following unique features: i) Fe3+ can damage the tumor microenvironment (TME) through glutathione consumption and O2 production; ii) Generated O2 can be further catalyzed by MgO with oxygen vacancy to generate ·O2 −; iii) The Fe2+‐catalyzed Fenton reaction can produce ·OH by disproportionation reactions of H2O2 in the TME; iv) Reactions in (i) and (iii) circularly regenerate Fe2+ and Fe3+ for continuous consumption of glutathione and H2O2 and constant production of ·OH and O2; v) The NSs can be triggered by a 650 nm laser to generate ·O2 − from O2 as well as by an 808 nm laser to generate local hyperthermia; and vi) The fluorescent, photoacoustic, and photothermal imaging capabilities of the engineered NSs allow for multimodal imaging‐guided breast cancer treatment.

Benzo[a]pyrene (BaP) is a well-known carcinogen formed during the cooking process. Although BaP exposure has been implicated as one of the risk factors for lung cancer in animals and humans, there are only limited data on BaP-induced gastrointestinal cancer. Therefore, this study investigated the protective effects of curcumin on BaP-induced DNA damage in rat stomach tissues. BaP (20 mg/kg/day) and curcumin (50, 100, or 200 mg/kg) were administered daily to Sprague-Dawley rats by oral gavage over 30 days. Curcumin was pre-administered before BaP exposure. All rats were euthanized, and liver, kidney, and stomach tissues were removed at 24 h after the last treatment. We observed that aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose levels were significantly reduced in rats treated with high dose co-administration of curcumin (200 mg/kg) compared to BaP alone. The expression levels of cytochrome P450 (CYP) 1A1 and CYP1B1 were significantly increased in the liver of rats treated with BaP. However, co-administration of curcumin (200 mg/kg) with BaP markedly reduced CYP1A1 expression in a dose-dependent manner. Furthermore, plasma levels of BaP-diolepoxide (BPDE) and BaP metabolites were significantly reduced by co-administration of curcumin (200 mg/kg). Additionally, co-administration of curcumin (200 mg/kg) with BaP significantly reduced the formation of BPDE-I-DNA and 8-hydroxydeoxy guanosine (8-OHdG) adducts in the liver, kidney, and stomach tissues. The inhibition of these adduct formations were more prominent in the stomach tissues than in the liver. Overall, our observations suggest that curcumin might inhibit BaP-induced gastrointestinal tumorigenesis and shows promise as a chemopreventive agent.

FMS-like receptor tyrosine kinase-3 (FLT3) is expressed on acute leukemia cells and is implicated in the survival, proliferation and differentiation of hematopoietic cells in most acute myeloid leukemia (AML) patients. Despite recent achievements in the development of FLT3-targeted small-molecule drugs, there are still unmet medical needs related to kinase selectivity and the progression of some mutant forms of FLT3. Herein, we describe the discovery of novel orally available type 1 FLT3 inhibitors from structure-activity relationship (SAR) studies for the optimization of indirubin derivatives with biological and pharmacokinetic profiles as potential therapeutic agents for AML. The SAR exploration provided important structural insights into the key substituents for potent inhibitory activities of FLT3 and in MV4-11 cells. The profile of the most optimized inhibitor (36) showed IC50 values of 0.87 and 0.32 nM against FLT3 and FLT3/D835Y, respectively, along with potent inhibition against MV4-11 and FLT3/D835Y expressed MOLM14 cells with a GI50 value of 1.0 and 1.87 nM, respectively. With the high oral bioavailability of 42.6%, compound 36 displayed significant in vivo antitumor activity by oral administration of 20 mg/kg once daily dosing schedule for 21 days in a mouse xenograft model. The molecular docking study of 36 in the homology model of the DFG-in conformation of FLT3 resulted in a reasonable binding mode in type 1 kinases similar to the reported type 1 FLT3 inhibitors Crenolanib and Gilteritinib.

Two-dimensional (2D) nanomaterials have drawn tremendous attention due to their unique physicochemical properties and promising applications in the fields of electronics, energy storage, and catalysis. Recently, the biomedicine community has gradually started to recognize the great potential of these nanostructured materials for biomedical applications - in particular those related to cancer therapy. In this review, we provide a brief overview of a few representative 2D nanomaterials, discuss their preparation strategies and physicochemical properties, and highlight their applications in cancer nanomedicine. We expect that this review will shed some light on the new opportunities associated with 2D nanomaterials for biomedical research.

The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro. In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency.

Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers, for example, in ~36% of hepatocellular carcinomas (HCCs) and ~68% of non–small cell lung cancers (NSCLCs). Current methods for restoration of p53 expression, including small molecules and DNA therapies, have yielded progressive success, but each has formidable drawbacks. Here, a redox-responsive nanoparticle (NP) platform is engineered for effective delivery of p53-encoding synthetic messenger RNA (mRNA). We demonstrate that the synthetic p53-mRNA NPs markedly delay the growth of p53-null HCC and NSCLC cells by inducing cell cycle arrest and apoptosis. We also reveal that p53 restoration markedly improves the sensitivity of these tumor cells to everolimus, a mammalian target of rapamycin (mTOR) inhibitor that failed to show clinical benefits in advanced HCC and NSCLC. Moreover, cotargeting of tumor-suppressing p53 and tumorigenic mTOR signaling pathways results in marked antitumor effects in vitro and in multiple animal models of HCC and NSCLC. Our findings indicate that restoration of tumor suppressors by the synthetic mRNA NP delivery strategy could be combined together with other therapies for potent combinatorial cancer treatment.

The current research investigated whether the content of organizational identity determines affective commitment to the work dyad, particularly when opinion difference exists within such dyads. The...

This study proposes that creative self-efficacy protects individuals from emotional exhaustion through the mediating effects of cognitive reappraisal and positive affect. The results of a pilot stu...

This paper examines how individuation, a view that organizational members are all unique individuals, induces a perception of psychological safety and how perception of psychological safety, in turn, increases one's organizational identification. Results from 66 respondents in Study 1 provided first support for the proposed mechanism. In Study 2, data collected from 176 employees in work organizations also provided evidence for this mediation model. It was found in both studies that individuation has a significantly positive association with the perception of psychological safety such that the more employees view individual members of the organization as unique individuals, the more likely they perceive that their organization is a safe environment for self-expression. Furthermore, perception of psychological safety was found to serve as a mediator linking individuation and organizational identification.

The current research examines the interplay of individualism- collectivism and team composition in team cohesion. I predict that individualism generates greater cohesion in diverse teams than does ...

With the acceleration of globalization and diversification of the workforce in contemporary organizations, managing diversity to realize much potential benefits in diverse work groups has become mo...

We explore the relationship between individual's social network position and emotional labor. Specifically, by presenting friendship network centrality within an organization as a relational antece...