Radiotherapy (RT) is a highly effective multimodal nonsurgical treatment that is essential for patients with advanced colorectal cancer (CRC). Nevertheless, cell subpopulations displaying intrinsic ...radioresistance survive after RT. The reactivation of their proliferation and successful colonization at local or distant sites may increase the risk of poor clinical outcomes. Recently, radioresistant cancer cells surviving RT were reported to exhibit a more aggressive phenotype than parental cells, although the underlying mechanisms remain unclear.
By investigating public databases containing CRC patient data, we explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts.
Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling was activated in radioresistant CRC tissues in correlation with local and distant metastases. JAK2 was preferentially overexpressed in the CRC stem cell subpopulation, which was accompanied by the phosphorylation of STAT proteins, especially STAT3. JAK2/STAT3 signaling played an essential role in promoting tumor initiation and radioresistance by limiting apoptosis and enhancing clonogenic potential. Mechanistically, the direct binding of STAT3 to the cyclin D2 (CCND2) promoter increased CCND2 transcription. CCND2 expression was required for persistent cancer stem cell (CSC) growth via the maintenance of an intact cell cycle and proliferation with low levels of DNA damage accumulation.
Herein, we first identified JAK2/STAT3/CCND2 signaling as a resistance mechanism for the persistent growth of CSCs after RT, suggesting potential biomarkers and regimens for improving outcomes among CRC patients.
Edges of 2D transition metal dichalcogenides (TMDs) are well known as highly reactive sites, thus researchers have attempted to maximize the edge site density of 2D TMDs. In this work, metal‐organic ...framework (MOF) templates are introduced to synthesize few‐layered WS2 nanoplates (a lateral dimension of ≈10 nm) confined in Co, N‐doped hollow carbon nanocages (WS2_Co‐N‐HCNCs), for highly sensitive NO2 gas sensors. WS2 precursors are assembled in the surface cavity of Co‐based zeolite imidazole framework (ZIF‐67) and subsequent pyrolysis produced WS2_Co‐N‐HCNCs. During the pyrolysis, the carbonized ZIF‐67 are doped by Co and N elements, and the growth of WS2 is effectively suppressed, creating few‐layered WS2 nanoplates functionalized Co‐N‐HCNCs. The WS2_Co‐N‐HCNCs exhibit outstanding NO2 sensing characteristics at room temperature, in terms of response (48.2% to 5 ppm), selectivity, response and recovery speed, and detection limit (100 ppb). These results are attributed to the enhanced adsorption and desorption kinetics of NO2 on abundant WS2 edges, confined in the gas permeable HCNCs. This work opens up an efficient way for the facile synthesis of edge abundant few‐layered TMDs combined with porous carbon matrix via MOF templating route, for applications relying on highly active sites.
Few‐layered WS2 nanoplates confined in Co, N‐doped hollow carbon nanocages (WS2_Co‐N‐HCNCs) are synthesized using metal‐organic framework (MOF) templating. The porous MOF suppresses the growth of WS2, creating few‐layered WS2 nanoplates in Co‐N‐HCNCs. The WS2_Co‐N‐HCNCs exhibit highly sensitive NO2 sensing characteristics at room temperature, in terms of response, selectivity, response/recovery speed, and detection limits.
With the increasing interest and demand for epidermal electronics, a strong interface between a sensor and a biological surface is essential, yet achieving such interface is still a challenge. Here, ...a calcium (Ca)‐modified biocompatible silk fibroin as a strong adhesive for epidermal electronics is proposed and the physical principles behind its interfacial and adhesive properties are reported. A strong adhesive characteristic (>800 N m−1) is observed because of the increase in both viscoelastic property and mechanical interlocking through the incorporation of Ca ions. Furthermore, additional key characteristics of the Ca‐modified silk: reusability, stretchability, biocompatibility, and conductivity, are reported. These characteristics enable a wide range of applications as demonstrated in four epidermal electronic systems: capacitive touch sensor, resistive strain sensor, hydrogel‐based drug delivery, and electrocardiogram monitoring sensor. As a reusable, biocompatible, conductive, and strong adhesive with water‐degradability, the Ca‐modified silk adhesive is a promising candidate for the next‐generation adhesive for epidermal biomedical sensors.
The physical mechanism of a biocompatible silk adhesive is demonstrated by metal–chelate bonding and water‐capturing by Ca ions that contribute to forming a suitable viscoelasticity of a Ca‐modified silk adhesive. The silk adhesive adheres to various substrates, facilitating a strong mechanical contact of epidermal electronics on human skin while being reusable.
The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper ...whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.
Solar fuel production, water splitting, and CO2 reduction by sunlight‐assisted catalytic reactions, are attractive and environmentally sustainable approaches used to generate energy. Since many ...different parameters, including energy band structures, electronic conductivity, surface area, porosity, catalytic activity, and stability of photocatalytic materials, determine the photocatalytic reaction, a single photocatalytic material is often insufficient to fulfill all the requirements. Hybridization to complement the limitations of two or more component materials can provide a viable solution. Particularly, hybridization with metal organic frameworks (MOFs), a new class of materials with excellent controllability of topology, surface area, porosity, morphology, band structure, electrical conductivity, and composition, enables the on‐demand design of a myriad of high‐performance photocatalysts. Moreover, hybrids formed by MOF‐derived materials inherit the distinctive merits from the MOF and offer further diversification for hybrid photocatalysts. Here, the rational design of MOF‐based hybrid photocatalysts for solar fuel production is discussed. The synthetic strategies of diverse MOF‐based hybrids, the key physicochemical parameters of hybrids to determine photocatalytic and photoelectrochemical reactions, and the mechanisms underlying the synergistic enhancement of solar fuel production are reviewed. Moreover, remaining challenges and future perspectives are addressed.
Metal organic frameworks (MOFs) and their derived materials are attractive platforms to design hybrid photocatalysts that can complement the limitations of a single photocatalytic material. Here, key physicochemical parameters of MOF‐based hybrid materials to determine synergistic photocatalytic activity and rational strategies to design MOF‐based hybrids for bolstering solar fuel production are discussed.
Background
Inactivation of
TP53
, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the ...correlation between the overexpression of p53 and survival in different Lauren-type GCs.
Methods
From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression.
Results
Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (
P
= 0.026) and Early gastric cancer (
P
= 0.044) in intestinal-type GC, and with advanced TNM stage (
P
< 0.001) and Advanced gastric cancer (
P
< 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio aHR = 1.423,
P
= 0.022; OS in diffuse-type: aHR = 1.401
P
= 0.035; cancer recurrence in diffuse-type: aHR = 1.502,
P
= 0.039).
Conclusion
p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.
The rampant generation of lithium hydroxide and carbonate impurities, commonly known as residual lithium, is a practical obstacle to the mass‐scale synthesis and handling of high‐nickel (>90 %) ...layered oxides and their use as high‐energy‐density cathodes for lithium‐ion batteries. Herein, we suggest a simple in situ method to control the residual lithium chemistry of a high‐nickel lithium layered oxide, Li(Ni0.91Co0.06Mn0.03)O2 (NCM9163), with minimal side effects. Based on thermodynamic considerations of the preferred reactions, we systematically designed a synthesis process that preemptively converts residual Li2O (the origin of LiOH and Li2CO3) into a more stable compound by injecting reactive SO2 gas. The preformed lithium sulfate thin film significantly suppresses the generation of LiOH and Li2CO3 during both synthesis and storage, thereby mitigating slurry gelation and gas evolution and improving the cycle stability.
A simple in situ method to control the residual lithium in high‐nickel lithium layered oxide is designed. Residual Li2O (the origin of LiOH and Li2CO3) is preemptively converted into the Li2SO4 thin film by injecting SO2 gas during calcination. This method suppresses the generation of LiOH and Li2CO3 during both synthesis and storage, thereby mitigating slurry gelation and gas evolution and improving cycle stability.
The attachment phenomena of various hierarchical architectures found in nature have extensively drawn attention for developing highly biocompatible adhesive on skin or wet inner organs without any ...chemical glue. Structural adhesive systems have become important to address the issues of human–machine interactions by smart outer/inner organ‐attachable devices for diagnosis and therapy. Here, advances in designs of biologically inspired adhesive architectures are reviewed in terms of distinct structural properties, attachment mechanisms to biosurfaces by physical interactions, and noteworthy fabrication methods. Recent demonstrations of bioinspired adhesive architectures as adhesive layers for medical applications from skin patches to multifunctional bioelectronics are presented. To conclude, current challenges and prospects on potential applications are also briefly discussed.
Nature has inspired various developments of hierarchically structured adhesive architectures for clean, reversible attachment to skin or organs within the human body. Recent progress in biologically inspired adhesive architectures is reviewed, from their geometric, material features, fabrication methods, and various medical applications from skin patches for wound protection to integrated bioelectronics with diagnostic and therapeutic functionalities.
Induced pluripotent stem cells (iPSCs) can be generated by introducing several factors into mature somatic cells. Banking of iPSCs can lead to wider application for treatment and research. In an ...economical view, it is important to store cells that can cover a high percentage of the population. Therefore, the use of homozygous human leukocyte antigen‐iPSCs (HLA‐iPSCs) is thought as a potential candidate for effective iPSC banking system for further clinical use. We screened the database stored in the Catholic Hematopoietic Stem Cell Bank of Korea and sorted the most frequent homozygous HLA types of the South Korean population. Blood cells with the selected homozygous HLA types were obtained and transferred to the GMP facility in the Catholic Institute of Cell Therapy. Cells were reprogrammed to iPSCs inside the facility and went through several quality controls. As a result, a total of 13 homozygous GMP‐grade iPSC lines were obtained in the facility. The generated iPSCs showed high pluripotency and normal karyotype after reprogramming. Five HLA‐homozygous iPSCs had the type that was included in the top five most frequent HLA types. Homozygous HLA‐iPSCs can open a new opportunity for further application of iPSCs in clinical research and therapy.
Chiral mesogens spontaneously form a cholesteric phase and show structural colors through wavelength‐selective reflection. Although chiral mesogens are pragmatic materials to build cholesteric phase ...due to their low toxicity, low cost, and robustness, an elaborate encapsulation technique is not reported yet. In this work, cholesteryl esters are encapsulated with a calcium‐alginate hydrogel shell using oil‐in‐water‐in‐oil double‐emulsion droplets. With capillary microfluidic devices, monodisperse double‐emulsion droplets are prepared to have a mixture of cholesteryl ester and toluene in the innermost droplets and an aqueous solution of sodium alginate and calcium‐carrying complex in the outer droplets. As toluene diffuses out from the core, cholesteryl ester forms the cholesteric phase. At the same time, calcium ions are dissociated from the complex upon chemical cues, which causes ionic crosslinking of alginate. The microcapsules show the thermochromic property as the structural color of the cholesteric core blue‐shifts along with the temperature. Therefore, the microcapsules report local temperatures with colors or reflectance spectra. As the range and sensitivity of the colorimetric temperature measurement are controllable by adjusting the composition of cholesteryl esters, a wide range of temperature can be covered by employing a proper set of compositions while maintaining high sensitivity.
Photonic microcapsules are designed by enclosing a core of cholesteryl esters with alginate shell using double‐emulsion templates. The microcapsules show high suspension stability and thermochromic property. The microcapsules report local temperatures in microenvironments through structural colors. A wide range of temperature measurement can be achieved by employing a proper set of various compositions while securing high sensitivity.
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