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Natural biological materials are formed by self-assembly processes and catalyze a myriad of reactions. Here, we report a programmable molecular assembly of designed synthetic polymers with engineered bacterial spores. This self-assembly process is driven by dynamic covalent bond formation on spore surface glycan and yields macroscopic materials that are structurally stable, self-healing, and recyclable. Molecular programming of polymer species shapes the physical properties of these materials while metabolically dormant spores allow for prolonged ambient storage. Incorporation of spores with genetically encoded functionalities enables operationally simple and repeated enzymatic catalysis. Our work lays an important foundation for scalable and programmable synthesis of robust materials for sustainable biocatalysis.

Dissipative behaviors in biology are fuel-driven processes controlled by living cells and shape the structural and functional complexities in biological materials. It has inspired the development of various forms of synthetic dissipative materials controlled by time-dependent consumption of chemical or physical fuels, such as reactive chemical species, light, and electricity. To this date, synthetic living material featuring dissipative behaviors directly controlled by the fuel consumption of their constituent cells is unprecedented. In this paper, we report a chemical fuel-driven dissipative behavior of living materials comprising S. epidermidis and telechelic block copolymers. The macroscopic phase transition is controlled by D-glucose which serves a dual role of a competitive disassembling agent and a biological fuel source for living cells. Our work is a significant step towards constructing a synthetic dissipative living system and provides a new tool and knowledge to design emergent living materials.

Here we report a bio-adhesive porous organic module (Glue COF) composed of hexagonally packed 1D nanopores based on a covalent organic framework. The nanopores are densely decorated with guanidinium ion (Gu+ ) pendants capable of forming salt bridges with oxyanionic species. Glue COF strongly adheres to biopolymers through multivalent salt-bridging interactions with their ubiquitous oxyanionic species. By taking advantage of its strong bio-adhesive nature, we succeeded in creating a gate that possibly opens the nanopores through a selective interaction with a reporter chemical and releases guest molecules. We chose calmodulin (CaM) as a gating component that can stably entrap a loaded guest, sulforhodamine B (SRB), within the nanopores (CaM COF⊃SRB). CaM is known to change its conformation on binding with Ca2+ ions. We confirmed that mixing CaM COF⊃SRB with Ca2+ resulted in the release of SRB from the nanopores, whereas the use of weakly binding Mg2+ ions resulted in a much slower release of SRB.

Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145-5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα.

With advances in the field of synthetic biology increasingly allowing us to engineer living cells to perform intricate tasks, incorporating these engineered cells into the design of synthetic polymeric materials will enable programming materials with a wide range of biological functionalities. However, employable strategies for the design of synthetic polymers that seamlessly integrate cellular functionalities in materials are still largely limited. Herein, we report the first example of programmable living materials constructed with a dynamic covalent interface between designed synthetic polymers and engineered B. subtilis cells. We identified a molecular motif that forms reversible dynamic covalent bonds on B. subtilis cell surface. Combining block copolymers bearing this motif with genetically engineered B. subtilis yields programmable living materials that can be equipped with functionalities such as biosensing and on-demand elution of recombinant proteins. We further demonstrated that encapsulated cells could be reversibly retrieved and subjected to biological analyses. This work advances the current capabilities in engineered living materials, establishes the groundwork for building a myriad of synthetic polymeric materials integrating engineered living cells, and provides a platform for understanding the biology of cells confined within materials.

With advances in the field of synthetic biology increasingly allowing us to engineer living cells to perform intricate tasks, incorporating these engineered cells into the design of synthetic polymeric materials will enable programming materials with a wide range of biological functionalities. However, employable strategies for the design of synthetic polymers that form a well-defined interface with living cells and seamlessly integrate their functionalities in materials are still largely limited. Herein, we report the first example of living materials constructed with a dynamic covalent interface between synthetic polymers and living B. subtilis cells. We showedthat 3-acetamidophenylboronic acid (APBA) and polymers of APBA (pAPBA) form dynamic covalent bonds with available diols on the B. subtilis cell surface. Importantly, pAPBA binding to B. subtilis shows a multivalent effect with complete reversibility upon addition of competitive diol species, such as fructose and sorbitol. On the basis of these findings, we constructed telechelic block copolymers with pAPBA chain ends that crosslink B. subtilis cells and produced self- standing living materials. We further demonstrated that the encapsulated cells could be retrieved upon immersing these materials in solutions containing competitive diols and further subjected to biological analyses. This work establishes the groundwork for building a myriad of synthetic polymeric materials integrating engineered living cells and provides a platform for understanding the biology of cells confined within materials.

The interaction of immune checkpoint molecules in the tumor microenvironment reduces the anti-tumor immune response by suppressing the recognition of T cells to tumor cells. Immune checkpoint inhibitor (ICI) therapy is emerging as a promising therapeutic option for cancer treatment. However, modulating the immune system with ICIs still faces obstacles with severe immunogenic side effects and a lack of response against many cancer types. Plant-derived natural compounds offer regulation on various signaling cascades and have been applied for the treatment of multiple diseases, including cancer. Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules. Recently, several phytochemicals have been reported to show the modulatory effects of immune checkpoints in various cancers in in vivo or in vitro models. This review summarizes druggable immune checkpoints and their regulatory factors. In addition, phytochemicals that are capable of suppressing PD-1/PD-L1 binding, the best-studied target of ICI therapy, were comprehensively summarized and classified according to chemical structure subgroups. It may help extend further research on phytochemicals as candidates of combinational adjuvants. Future clinical trials may validate the synergetic effects of preclinically investigated phytochemicals with ICI therapy.

Resveratrol (3,4′,5-trans-trihydroxystilbene) and piceatannol (3,3′,4′,5-trans-tetraphydroxystilbene) are major stilbene compounds that are predominantly present in various natural foods, such as berries and fruits. Both phytochemical compounds are consumed as dietary supplements to prevent various metabolic diseases and for their anti-aging properties. Adipose-derived stem cells from human visceral adipose tissue (vASCs) are a useful in vitro model for evaluating their adipogenic effect. Treatment with resveratrol and piceatannol significantly inhibited lipid accumulation in vASCs. Their effective concentrations were 5, 10, and 20 μM for inhibiting adipogenesis of vASCs. Interestingly, despite the similar chemical structures of the two compounds, piceatannol showed a higher anti-adipogenic effect at 20 μM than resveratrol in vASCs. Moreover, the inhibitory capacity of lipid droplet generation was higher for piceatannol at 20 μM than that of resveratrol. Piceatannol significantly attenuated the expression level of adipogenic markers (e.g., CCAAT/enhanced binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte fatty acid binding protein (aP2)) compared to resveratrol at the mRNA and protein levels. These results suggest that piceatannol is a superior anti-adipogenic compound compared to resveratrol in the vASC model of visceral obesity.

Background: : Studies examining the relationship between obesity and female-specific cancers have been mainly conducted in Western populations. We aimed to investigate the risk of female-specific cancers according to obesity and menopausal status using a nationwide cohort in Korea. Methods: : We identified 2,708,938 women from the National Health Insurance Service cohort, and obtained baseline body mass index (BMI), waist circumference (WC), and other healthcare data, measured and collected during a health examinations and cancer-screening survey. By setting a normal weight/WC group (BMI, 18•5–22•9 kg/m2 or WC, 80•0–84•9 cm) as the reference, we conducted multivariate analyses using the Cox proportional hazard model to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for each cancer. Findings: : The total follow-up duration was 22389854•63 person-years. In post-menopausal women, the risk of breast, endometrial, and ovarian cancers significantly increased as the BMI classification level increased from normal to class II obesity (aHRs [95% CIs], 1•49 [1•38–1.61], 2•11 [1•81–2•46], and 1•38 [1•20–1•58], respectively). The risk of breast and endometrial cancers also increased as the WC classification increased from < 75•0 to ≥ 95•0 cm. With a WC of 80•0–84•9 cm as the reference, the lowest risk of breast and endometrial cancers was observed in WC < 75•0 cm (aHRs [95% CIs], 0•85 [0•81–0•89] and 0•75 [0•67–0•84], respectively) while the highest risk was observed in WC ≥ 95•0 cm (aHRs [95% CIs], 1•19 [1•10–1•29] and 1•56 [1•33–1•82], respectively). In pre-menopausal women, the risk of breast cancer significantly decreased in those with class I and II obesity compared to those with normal BMI (aHRs [95% CIs], 0•96 [0•92–0•999] and 0•89 [0•81–0•97], respectively), whereas the trends of endometrial and ovarian cancer incidence in pre-menopausal women were similar to those observed in post-menopausal women. For cervical cancer, only class II obesity was significantly associated with increased risks in both post-menopausal and pre-menopausal women (aHRs [95% CIs], 1•18 [1•01–1•39] and 1•27 [1•02–1•57], respectively). Interpretation: : In this large population-based cohort study in Korean women, we observed that the impact of obesity on the development of female-specific cancers differs according to the malignancy type and menopausal status. Similar trends were observed between Korean and Western women. Funding: : The Korea Health Industry Development Institute (no. HI16C2037).

We aimed to develop a diagnostic model identifying ovarian cancer (OC) from benign ovarian tumors using metagenomic data from serum microbe-derived extracellular vesicles (EVs). We obtained serum samples from 166 patients with pathologically confirmed OC and 76 patients with benign ovarian tumors. For model construction and validation, samples were randomly divided into training and test sets in the ratio 2:1. Isolation of microbial EVs from serum samples of the patients and 16S rDNA amplicon sequencing were carried out. Metagenomic and clinicopathologic data-based OC diagnostic models were constructed in the training set and then validated in the test set. There were significant differences in the metagenomic profiles between the OC and benign ovarian tumor groups, specifically, genus Acinetobacter was significantly more abundant in the OC group. More importantly, Acinetobacter was the only common genus identified by seven different statistical analysis methods. Among the various metagenomic and clinicopathologic data-based OC diagnostic models, the model consisting of age, serum CA-125 levels, and relative abundance of Acinetobacter showed the best diagnostic performance with the area under the receiver operating characteristic curve of 0.898 and 0.846 in the training and test sets, respectively. Thus, our findings establish a metagenomic analysis of serum microbe-derived EVs as a potential tool for the diagnosis of OC.

A three-dimensional Mn(II) framework, [Mn2(H2L)(L)0.5(MeOH)(DEF)]·0.1MeOH·0.1DEF·1.4H2O (1; H4L = 2,3-dioxido-1,4-benzenedicarboxylic acid), was synthesized under solvothermal conditions in diethylformamide/methanol (DEF/MeOH), where the Mn centers adopt octahedral and unusual pentagonal bipyramidal geometries. The ligand H4L was subject to deprotonation to create μ4-H2L2– and μ6-L4– anionic bridges, leading to the construction of a coordination network. The MeOH exchange process of crystalline 1 allowed for another crystalline phase (1a), which reversibly returned to the original crystalline state upon resolvation in DEF/MeOH. After evacuation of 1a, the amorphous phase 1b was irreversibly formed, followed by the restoration of the original phase 1 upon resolvation in DEF/MeOH. Consequently, this framework underwent cyclic structural transformations from the crystalline (1) to crystalline (1a) to amorphous (1b) and back to crystalline (1) phase, which are unique transformations for soft coordination netw...

Background and purpose: Ovarian cancer is the most lethal gynecologic cancer in females worldwide. The high mortality rate is due primarily to the lack of early diagnosis strategies and the high rate of recurrence. Ascites is detected in over one-third of ovarian cancer patients at initial diagnosis and present in almost all the patients with recurrence. Extracellular vesicles (EVs) are double-membrane particles secreted by cells into extracellular space. EV-mediated intercellular communication in the tumor microenvironment is crucial in cancer progression. Additionally, EVs are present in various body fluids, serving as fine analytes for liquid biopsy. Our research is aimed to explore the role of malignant ascites-derived EVs in ovarian cancer metastasis and the underlying mechanisms focusing on the miRNA cargos. Methods: Patient-derived samples were collected from Seoul National University Hospital with the approval of the Institutional Review Board. EVs were isolated from ascites using the commercial kit and identified through transmission electron microscopy, nanoparticle tracking analysis and western blotting. Transwell assay was performed to investigate the effects of ascites-derived EVs on ovarian cancer cells. MiRNA sequencing was carried out in EVs derived from malignant ascites(n=10) and benign peritoneal fluids(n=9). Results: Malignant ascites-derived EVs were characterized as double-membrane particles sizing ranging from 30nm to 150nm with the expression of CD63 and CD81. Those EVs significantly promoted the invasion and migration ability of ovarian cancer cells. MiRNA sequencing data showed that 118 miRNAs were upregulated and 44 miRNAs were downregulated in the ascites-derived EVs compared with benign peritoneal fluid-derived EVs. Among those, miR-1246 and miR-1290 were the top two upregulated miRNAs, which were negatively associated with the overall survival of ovarian cancer patients. Moreover, miR-1246 and miR-1290 could enhance the invasion and migration ability through activating Wnt/β-catenin signaling pathway via binding to RAR-related orphan receptor alpha (RORα). Conclusion: Malignant ascites-derived EVs could facilitate the metastatic potential of ovarian cancer cells through transferring miR-1246 and miR-1290. Targeting miR-1246 and miR-1290 might be a promising therapeutic strategy in ovarian cancer treatment. Citation Format: Wenyu Wang, HyunA Jo, Yong Sang Song. Malignant ascites-derived extracellular vesicles promote metastasis of ovarian cancer by transferring miR-1246 and miR-1290 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2366.

Background: Hypoxia significantly impacts cancer progressions, in various types of solid tumors including ovarian cancer. Exosomes (30-150nm) secreted from cells in the hypoxic tumor microenvironment play a critical role in cancer progression through transferring functional proteins, mRNAs, and miRNAs as mediators of intercellular communication. However, the underlying mechanisms how cancer exosomes induced by hypoxia regulate cancer progressions remain elusive. This study aims to assess the effect of exosomes secreted from hypoxic cancer cells on the metastatic ability of ovarian cancer cells. Methods: Two ovarian cancer cell lines, Kuramochi and SKOV-3, were used. Exosomes from cancer cells cultured under normoxic or hypoxic conditions (normoxic or hypoxic exosomes) were isolated using Exoquick-TC kit and identified by nanoparticle tracking analysis, transmission electron microscopy, and western blotting. BCA assay was done to evaluate the concentration of exosomes. Normoxic or hypoxic exosomes were treated on ovarian cancer cells. Cell migration and invasion abilities were examined by wound healing assay and MatriGel invasion assay respectively. Furthermore, miRNA sequencing was performed to explore the miRNA profiling of hypoxic and normoxic exosomes. Results: The size of exosomes was ranging from 52nm to 121nm (mean diameter = 85nm). The quantity of hypoxic exosomes was significantly more than that of normoxic exosomes. Hypoxic exosomes increased the migration and invasion ability of kuramochi and SKOV-3 cells. In addition, hypoxic exosomes treatment on ovarian cancer cells up-regulated the expression of MMP-2 and Snail-1 at the protein level. MiRNA sequencing showed that miR-376c-3p was significantly upregulated in hypoxic exosomes in both ovarian cancer cell lines. Moreover, miR376c-3p enhanced migration and invasion ability of ovarian cancer cells, validated by miR376c-3p inhibitor and mimics. Conclusions: Taken together, our study suggests that miR376c-3p transferred by hypoxic exosomes could promote the metastatic potential of ovarian cancer cells by inducing MMP-2 and Snail-1. Citation Format: HyunA Jo, Wenyu Wang. Hypoxia-induced exosomal miR-376c-3p promotes metastatic potential of ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2384.

With regard to fluorescence quenching commonly observed during metal-ion detection, "turn-on" chemical sensing has been rarely reported, but could be extremely important because it facilitates the selective recognition of target objects of interest against a dark background. A metal-organic framework (MOF) chemosensor has been prepared that serves as an efficient platform for the selective detection of Cu2+ and Cd2+ ions over other metal ions. In particular, this framework shows the highest fluorescence enhancement (≈60-fold relative to Cd-free MOF) for the hazardous metal ion Cd2+ among luminescent MOFs and displays excellent reusability in repeated cycles. The direct diffusion of Cd2+ into the crystal pores has also been visualized for the first time.

Tumor-suppressive effects of resveratrol have been shown in various types of cancer. However, regulation of tumor microenvironment by resveratrol is still unclear. Recent findings suggest resveratrol can potentiate its tumor-suppressive effect through modulation of the signaling pathways of cellular components (fibroblasts, macrophages and T cells). Also, studies have shown that resveratrol can suppress malignant phenotypes of cancer cells acquired in response to stresses of the tumor microenvironment, such as hypoxia, oxidative stress and inflammation. We discuss the effects of resveratrol on cancer cells in stress environment of tumors as well as interactions between cancer cells and non-cancer cells in this review.

Various well-known cloud providers [1] and open source communities [2] have launched a kind of edge solution to gather and process data in a localized area, not in a centralized cloud. Especially, an industrial IoT domain, i.e. I-IoT, such as smart factory, requires edge device to gather lots of data generated from factory robots and machines. In this paper, we propose Pharos solution which is our light-weight service lifecycle management solution for containerized services exploiting Docker framework, which is fit to I-IoT domain.

The intestinal mucus layer plays an important role in the management of inflammatory bowel disease. The aim of this study was to investigate the effects of oxyresveratrol (OXY), an antioxidant, on the stimulation of mucin production in human LS 174T goblet cells and the underlying mechanism thereof. OXY increased MUC2 expression at both the mRNA and protein levels. By performing two-dimensional gel electrophoresis, we found that the expression of nicotinic acid phosphoribosyltransferase1 (NaPRT1) in OXY-treated LS 174T cells was greatly increased compared with that in negative control cells. In addition, the NAD

Facile postsynthetic oxidation of the thiol-laced UiO-66-type framework UiO-66(SH)2 enabled the generation of UiO-66(SO3 H)2 with sulfonic acid groups covalently linked to the backbone of the system. The oxidized material exhibited a superprotonic conductivity of 8.4×10(-2) S cm(-1) at 80 °C and 90 % relative humidity, and long-term stability of the conductivity was observed. This level of conductivity exceeds that of any proton-conducting MOF reported to date and is equivalent to the conductivity of the most effective known electrolyte, Nafion.

A porous Mg2(dondc) framework (H4dondc = 1,5-dioxido-2,6-naphthalenedicarboxylic acid) with open metal sites was prepared and functionalized with primary or secondary diamines (en = ethylenediamine, mmen = N,N′-dimethylethylenediamine, or ppz = piperazine). The CO2 adsorption was substantial under post-combustion flue gas conditions as compared to other reported metal–organic frameworks. Interestingly, the IR spectroscopic measurements demonstrated that the CO2 adsorption mechanism is based on the combination of physisorption and chemisorption. The CO2 adsorption capacity of 1-mmen was greater than that of 1-en and 1-ppz, which can likely be attributed to the basicity of the free amine groups tethered to the open coordination sites. Ultrahigh selectivity and superior dynamic separation of CO2 over N2 were evident in 1-ppz. Such exceptional CO2 uptake and CO2/N2 selectivity of diamine-functionalized materials hold potential promise for post-combustion CO2 capture applications.

Recently, a micro-service architecture has been adopted to an edge device in smart factory due to its maintainability and scalability. In the architecture, all services are generally implemented as Docker containers and deployed by Docker APIs which might be harsh to a factory operator. In this paper, we propose an easy-to-use web-based service deployment method for containerized service to in-factory edge device for supporting DevOps to factory operator.

A series of metal-organic frameworks (MOFs) M2 (dobpdc) (M=Mn, Co, Ni, Zn; H4 dobpdc=4,4'-dihydroxy-1,1'-biphenyl-3,3'-dicarboxylic acid), with a highly dense arrangement of open metal sites along hexagonal channels were prepared by microwave-assisted or simple solvothermal reactions. The activated materials were structurally expanded when guest molecules including CO2 were introduced into the pores. The Lewis acidity of the open metal sites varied in the order MnCoNiZn, as confirmed by C=O stretching bands in the IR spectra, which are related to the CO2 adsorption enthalpy. DFT calculations revealed that the high CO2 binding affinity of transition-metal-based M2 (dobpdc) is primarily attributable to the favorable charge transfer from CO2 (oxygen lone pair acting as a Lewis base) to the open metal sites (Lewis acid), while electrostatic effects, the underlying factor responsible for the particular order of binding strength observed across different transition metals, also play a role. The framework stability against water coincides with the order of Lewis acidity. In this series of MOFs, the structural stability of Ni2 (dobpdc) is exceptional; it endured in water vapor, liquid water, and in refluxing water for one month, and the solid remained intact on exposure to solutions of pH 2-13. The DFT calculations also support the experimental finding that Ni2 (dobpdc) has higher chemical stability than the other frameworks.

An amine-functionalized metal-organic framework (MOF), dmen-Mg-2(dobpdc) (dmen = N, N-dimethylethylenediamine), which contains a heterodiamine with both primary and tertiary amines, was prepared via a post-synthetic method. This material exhibits a significant selectivity factor for CO2 over N-2 that is commensurate with top-performing MOFs. It is remarkable that the solid is fully regenerated under vacuum or flowing Ar at low desorption temperatures, and following this can take up CO2 at more than 13 wt%. An exceptionally high working capacity is achieved at low regeneration temperatures and after exposure to humid conditions, which are important parameters for a real post-combustion CO2 capture process.