Stilbenoid derivatives as potent inhibitors of HIF-1α-centric cancer metabolism under hypoxia.

Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor associated with cancer metabolism and is regarded as a potent anticancer therapeutic strategy within the hypoxic microenvironment of cancer. In this study, stilbenoid derivatives were designed, synthesized, and assessed for their capacity to inhibit HIF-1α-associated cancer metabolism and evaluated for inhibition of cancer cell viability and HIF activation. Through the structure-activity relationship studies, compound 28e was identified as the most potent derivative. Specifically, under the hypoxic condition, 28e reduced the accumulation of HIF-1α protein and the expression of its target genes related to glucose metabolism without affecting the expression of HIF-1α mRNA. Furthermore, 28e inhibited glucose uptake, glycolytic metabolism, and mitochondrial respiration, decreasing cellular ATP production under hypoxic conditions. In addition, 28e displayed significant anti-tumor effects and effectively suppressed the accumulation of HIF-1α protein in tumor tissue in vivo xenograft model. These findings suggest that our stilbenoid derivatives exert their anticancer effects by targeting HIF-1α-centered cancer metabolism under hypoxic conditions.

Float-stacked graphene-PMMA laminate.

Semi-infinite single-atom-thick graphene is an ideal reinforcing material that can simultaneously improve the mechanical, electrical, and thermal properties of matrix. Here, we present a float-stacking strategy to accurately align the monolayer graphene reinforcement in polymer matrix. We float graphene-poly(methylmethacrylate) (PMMA) membrane (GPM) at the water-air interface, and wind-up layer-by-layer by roller. During the stacking process, the inherent water meniscus continuously induces web tension of the GPM, suppressing wrinkle and folding generation. Moreover, rolling-up and hot-rolling mill process above the glass transition temperature of PMMA induces conformal contact between each layer. This allows for pre-tension of the composite, maximizing its reinforcing efficiency. The number and spacing of the embedded graphene fillers are precisely controlled. Notably, we accurately align 100 layers of monolayer graphene in a PMMA matrix with the same intervals to achieve a specific strength of about 118.5 MPa g-1 cm3, which is higher than that of lightweight Al alloy, and a thermal conductivity of about 4.00 W m-1 K-1, which is increased by about 2,000 %, compared to the PMMA film.

Therapeutic potential of mesenchymal stem cells from human iPSC-derived teratomas for osteochondral defect regeneration.

Human induced pluripotent stem cells (iPSCs) hold great promise for personalized medicine, as they can be differentiated into specific cell types, especially mesenchymal stem cells (MSCs). Therefore, our study sought to assess the feasibility of deriving MSCs from teratomas generated from human iPSCs. Teratomas serve as a model to mimic multilineage human development, thus enriching specific somatic progenitors and stem cells. Here, we discovered a small, condensed mass of MSCs within iPSC-generated teratomas. Afterward, we successfully isolated MSCs from this condensed mass, which was a byproduct of teratoma development. To evaluate the characteristics and cell behaviors of iPSC-derived MSCs (iPSC-MSCs), we conducted comprehensive assessments using qPCR, immunophenotype analysis, and cell proliferation-related assays. Remarkably, iPSC-MSCs exhibited an immunophenotype resembling that of conventional MSCs, and they displayed robust proliferative capabilities, similar to those of higher pluripotent stem cell-derived MSCs. Furthermore, iPSC-MSCs demonstrated the ability to differentiate into multiple lineages in vitro. Finally, we evaluated the therapeutic potential of iPSC-MSCs using an osteochondral defect model. Our findings demonstrated that teratomas are a promising source for the isolation of condensed MSCs. More importantly, our results suggest that iPSC-MSCs derived from teratomas possess the capacity for tissue regeneration, highlighting their promise for future therapeutic applications.

Proposal of a Token-Based Node Selection Mechanism for Node Distribution of Mobility IoT Blockchain Nodes.

Various elements, such as evolutions in IoT services resulting from sensoring by vehicle parts and advances in small communication technology devices, have significantly impacted the mass spread of mobility services that are provided to users in need of limited resources. In particular, business models are progressing away from one-off costs towards longer-term costs, as represented by shared services utilizing kick-boards or bicycles and subscription services for vehicle software. Advances in shared mobility services, as described, are calling for solutions that can enhance the reliability of data aggregated by users leveraging mobility services in the next-generation mobility areas. However, the mining process to renew status ensures continued network communication, and block creation demands high performance in the public block chain. Therefore, easing the mining process for state updates in public blockchains is a way to alleviate the high-performance process requirements of public blockchains. The proposed mechanism assigns token-based block creation authority instead of the mining method, which provides block creation authority to nodes that provide many resources. Blocks are created only by a group of participants with tokens, and after creation, tokens are updated and delivered to new nodes to form a new token group. Additionally, tokens are updated in each block after their initial creation, making it difficult to disguise the tokens and preventing resource-centered centralization.

Rescue technique for self-expandable metallic stent placement using ultrathin endoscope after failure of the conventional method in patients with malignant colon obstruction: a multicenter retrospective study.

BACKGROUND AND AIMS: Self-expandable metallic stents (SEMS) can be used to treat malignant colorectal obstruction (MCO). Guidewire insertion to the proximal site of MCO is the most important step for SEMS placement. However, some patients cannot undergo guidewire insertion because of total obstruction or location at anatomically challenging areas. We report a guidewire insertion technique using an ultrathin endoscope (UTE) in patients with MCO in whom conventional SEMS insertion failed. METHODS: This study was a retrospective cohort study conducted at three academic centers in Korea. The medical records of 956 consecutive patients who underwent SEMS placement during 2012-2021 were analyzed. After failing guidewire insertion using a colonoscope, a UTE was inserted. Guidewire insertion was done through the working channel of the UTE. Following guidewire insertion, the endoscope was removed from the patient. While removing the endoscope, the guidewire was advanced to be located at the originally inserted site. Then, the colonoscope was inserted over the guidewire, and SEMS was replaced. RESULTS: Conventional SEMS insertion failed in 75 patients. Of these, guidewire insertion using a UTE was tried in 59 patients. The rate of technical success was 91.5% (54/59). Considering all patients, the overall technical success rate of SEMS placement was 97.8% (935/956). This technique increased the technical success rate by 5.6% among the total cohort. CONCLUSIONS: The UTE facilitated guidewire insertion and enhanced the overall success rate for SEMS placement. In addition, this technique can be used as a rescue method when guidewire insertion fails using a colonoscope.

Axion Dark Matter Search around 4.55 µeV with Dine-Fischler-Srednicki-Zhitnitskii Sensitivity.

We report an axion dark matter search at Dine-Fischler-Srednicki-Zhitnitskii sensitivity with the CAPP-12TB haloscope, assuming axions contribute 100% of the local dark matter density. The search excluded the axion-photon coupling g_{aγγ} down to about 6.2×10^{-16} GeV^{-1} over the axion mass range between 4.51 and 4.59 µeV at a 90% confidence level. The achieved experimental sensitivity can also exclude Kim-Shifman-Vainshtein-Zakharov axion dark matter that makes up just 13% of the local dark matter density. The CAPP-12TB haloscope will continue the search over a wide range of axion masses.

Near-Quantum-Noise Axion Dark Matter Search at CAPP around 9.5 µeV.

We report the results of an axion dark matter search over an axion mass range of 9.39-9.51 µeV. A flux-driven Josephson parametric amplifier (JPA) was added to the cryogenic receiver chain. A system noise temperature of as low as 200 mK was achieved, which is the lowest recorded noise among published axion cavity experiments with phase-insensitive JPA operation. In addition, we developed a two-stage scanning method which boosted the scan speed by 26%. As a result, a range of two-photon coupling in a plausible model for the QCD axion was excluded with an order of magnitude higher in sensitivity than existing limits.

Mixing times for two classes of stochastically modeled reaction networks.

The past few decades have seen robust research on questions regarding the existence, form, and properties of stationary distributions of stochastically modeled reaction networks. When a stochastic model admits a stationary distribution an important practical question is: what is the rate of convergence of the distribution of the process to the stationary distribution? With the exception of [1] pertaining to models whose state space is restricted to the non-negative integers, there has been a notable lack of results related to this rate of convergence in the reaction network literature. This paper begins the process of filling that hole in our understanding. In this paper, we characterize this rate of convergence, via the mixing times of the processes, for two classes of stochastically modeled reaction networks. Specifically, by applying a Foster-Lyapunov criteria we establish exponential ergodicity for two classes of reaction networks introduced in [2]. Moreover, we show that for one of the classes the convergence is uniform over the initial state.

Long-term outcomes after endoscopic versus surgical resection of T1 colorectal carcinoma.

BACKGROUND: The long-term outcomes of patients with T1 colorectal cancer (CRC) who undergo endoscopic and/or surgical treatment are not well understood. Invasive CRC confined to the colonic submucosa (T1 CRC) is challenging in terms of clinical decision-making. We compared the long-term outcomes of T1 CRC by treatment method. METHODS: We examined 370 patients with pathological T1 CRC treated between 2000 and 2015 at Seoul St. Mary's Hospital. In total, 93 patients underwent endoscopic resection (ER) only, 82 underwent additional surgery after ER, and 175 underwent surgical resection only. Patients who did not meet the curative criteria were defined as "high-risk." High-risk patients were classified into three groups according to the treatment modalities: ER only (Group A: 35 patients), additional surgery after ER (Group B: 72 patients), and surgical resection only (Group C: 133 patients). The recurrence-free and overall survival (OS) rates, and factors associated with recurrence and mortality, were analyzed. Factors associated with lymph node metastasis (LNM) were subjected to multivariate analysis. RESULTS: Of the 370 patients, 7 experienced recurrence and 7 died. All recurrences occurred in the high-risk group and two deaths were in the low-risk group. In high-risk groups, there was no significant group difference in recurrence-free survival (P = 0.511) or OS (P =0.657). Poor histology (P =0.042) was associated with recurrence, and vascular invasion (P =0.044) with mortality. LNMs were observed in 30 of 277 patients who underwent surgery either initially or secondarily. Lymphatic invasion was significantly associated with the incidence of LNM (P < 0.001). CONCLUSIONS: ER prior to surgery did not affect the prognosis of high-risk T1 CRC patients, and did not worsen the clinical outcomes of patients who required additional surgery. Lymphatic invasion was the most important predictor of LNM.

Effects of submicron magnetite particles on granulation of flocculent sludge and process stability in upflow anaerobic sludge blanket reactor.

Promoting direct interspecies electron transfer (DIET) with conductive additives is considered a promising approach to enhance methanogenesis. This study investigated the effects of adding submicron magnetite particles on sludge granulation and methanogenic performance in upflow anaerobic sludge blanket reactors inoculated with flocculent sludge. The reactor supplemented with magnetite was more stable and resilient than the no-magnetite control, with higher degree of granulation (up to 26.6-fold) and biomass retention. Magnetite addition to unstable reactors improved the methane yield in both reactors (1.2-1.3-fold). Electroactive Deltaproteobacteria bacteria, including Geobacter and Syntrophobacter, were enriched in the presence of magnetite. Methanogenic functional genes involved in DIET-based syntrophy were more abundant under magnetite-supplemented conditions. However, the improvement of methanogenic performance and granulation was limited, and inducing the self-embedment of magnetite into mature sludge granules rather than granulating flocculent sludge with magnetite appears to be a better strategy for engineering DIET in anaerobic granular sludge systems.

Stochastic models of nucleosome dynamics reveal regulatory rules of stimulus-induced epigenome remodeling.

The genomic positions of nucleosomes are a defining feature of the cell's epigenomic state, but signal-dependent transcription factors (SDTFs), upon activation, bind to specific genomic locations and modify nucleosome positioning. Here we leverage SDTFs as perturbation probes to learn about nucleosome dynamics in living cells. We develop Markov models of nucleosome dynamics and fit them to time course sequencing data of DNA accessibility. We find that (1) the dynamics of DNA unwrapping are significantly slower in cells than reported from cell-free experiments, (2) only models with cooperativity in wrapping and unwrapping fit the available data, (3) SDTF activity produces the highest eviction probability when its binding site is adjacent to but not on the nucleosome dyad, and (4) oscillatory SDTF activity results in high location variability. Our work uncovers the regulatory rules governing SDTF-induced nucleosome dynamics in live cells, which can predict chromatin accessibility alterations during inflammation at single-nucleosome resolution.

De-Identification Mechanism of User Data in Video Systems According to Risk Level for Preventing Leakage of Personal Healthcare Information.

A problem with biometric information is that it is more sensitive to external leakage, because it is information that cannot be changed immediately compared to general authentication methods. Regarding facial information, a case in which authentication was permitted by facial information output by a 3D printer was found. Therefore, a method for minimizing the leakage of biometric information to the outside is required. In this paper, different levels of identification information according to the authority of the user are provided by the de-identification of metadata and face information in stages. For face information and metadata, the level of de-identification is determined and achieved according to the risk level of the de-identified subject. Then, we propose a mechanism to minimize the leakage path by preventing reckless data access by classifying access rights to unidentified data according to four roles. The proposed mechanism provides only differentially de-identified data according to the authority of the accessor, and the required time to perform the de-identification of one image was, on average, 3.6 ms for 300 datapoints, 3.5 ms for 500 datapoints, and 3.47 ms for 1000 datapoints. This confirmed that the required execution time was shortened in proportion to the increase in the size of the dataset. The results for the metadata were similar, and it was confirmed that it took 4.3 ms for 300 cases, 3.78 ms for 500 cases, and 3.5 ms for 1000 cases.

Comparison of 2 L Polyethylene Glycol Plus Ascorbic Acid and 4 L Polyethylene Glycol in Elderly Patients Aged 60-79: A Prospective Randomized Study.

BACKGROUND: The bowel-cleansing efficacy and safety of 2 L polyethylene glycol (PEG) with ascorbic acid (2L PEG + Asc) has rarely been studied in the elderly population. In this randomized trial, we compared the bowel cleanliness, safety, and tolerability of 2L PEG + Asc with those of 4 L PEG in an elderly population aged 60-79. METHODS: Study participants were randomized either to 2L PEG + Asc or 4L PEG. The primary endpoint was the success rate of bowel preparation, using the Boston Bowel Preparation Scale. Before colonoscopy, all participants were questioned about adverse events and tolerability regarding purgative ingestion. RESULTS: A total of 347 individuals were enrolled (2L PEG + Asc, 174; 4L PEG, 173). Mean age in the 2L PEG + Asc and the 4L PEG was 69.3 ± 5.6 and 69.3 ± 5.0, respectively (P = 0.917). The rate for successful bowel cleansing was comparable between the 2L PEG + Asc (92%) and the 4L PEG (96%, P = 0.118). Total ingested liquid including purgative and water was lower in the 2L PEG + Asc group (2.9 L) than in the 4L PEG group (4.2 L, P < 0.001). The tolerability of purgative was superior in the 2L PEG + Asc (overall satisfaction, P < 0.001; willingness to reuse, P < 0.001). There were no serious adverse events during the trial. CONCLUSIONS: The bowel-cleansing efficacy of 2L PEG + Asc was comparable to that of 4L PEG. Tolerability was superior in the 2L PEG + Asc group. For older people, 2L PEG + Asc is an efficacious and safe bowel cleanser. (Clinical trial registration number: KCT0004123).

Second Victim Experience and Perception Discordance of the Colonoscopic Perforation.

BACKGROUND: Perforation is the most serious adverse event of colonoscopy, but rarely considered from the view of colonoscopists' second victim experience and perception discordance between colonoscopists and patients. AIMS: We aimed to evaluate colonoscopists' second victim experience and the perception discordance between colonoscopists and patients for the colonoscopic perforation. METHODS: A survey for colonoscopic perforation was performed for the colonoscopists and outpatients who visited the university hospital between February 1, 2020, and April 30, 2020. The questionnaire included questions regarding colonoscopists' satisfaction for the intervention strategies offered to patients and patient-colonoscopist perception on colonoscopic perforation. A modified Korean version of the "Second Victim Experience and Support Tool (K-SVEST)" was used to assess the second victim experiences and supportive resources for the colonoscopists. RESULTS: Survey results from 160 colonoscopists and 165 patients were analyzed. The colonoscopists' satisfaction scores were higher for strategies related to sufficient explanation, empathy, courteous listening, and monetary compensation. The scores of the K-SVEST for the second victim experience were highest in psychological distress, followed by loss of professional self-efficacy, colleague support, physical distress, non-work-related support, institutional support, and turnover intentions/absenteeism. Significant patient-colonoscopist discordance was noted for the same colonoscopic perforation scenario on the judgment of medical error, health professionals' apology, monetary compensation, and criminal penalties for the colonoscopists. CONCLUSIONS: Colonoscopists can suffer emotionally and physically from the second victim experience after colonoscopic perforation. In addition, the significant patient-colonoscopist discordance should be considered to make a better communication for the colonoscopic perforation.

Formation and characterization of conductive magnetite-embedded granules in upflow anaerobic sludge blanket reactor treating dairy wastewater.

Promoting direct interspecies electron transfer (DIET) with conductive additives has proved effective in improving anaerobic digestion performance and stability. However, its application is limited by the need to replenish the washout loss of conductive materials. This study reports the formation of conductive magnetite-embedded granular sludge and its long-term influence on the performance of upflow anaerobic sludge blanket reactors treating dairy wastewater. The magnetite-supplemented reactor maintained better performance than the no-magnetite control, with greater sludge settling and electron transport activity, throughout the 192-d experiment at increasing organic loading rates (1.2-8.5 g chemical oxygen demand/L·d). The abundance of electroactive microbes also remained higher in the magnetite-supplemented reactor. The results suggest that DIET-based electric syntrophy was promoted in the magnetite-embedded granules. This study is the first to demonstrate the self-embedment of submicron conductive material into granular sludge and its benefits. These findings offer a new approach to enhancing anaerobic granular sludge systems.

Highly Soluble Fluorinated Polyimides Synthesized with Hydrothermal Process towards Sustainable Green Technology.

Polyimides, a widely used engineering plastic, require use of large amounts of toxic and hazardous organic solvents which threaten our daily lives, calling for new and easy synthetic methods for sustainable environmentally friendly development. In this paper, highly soluble fluorinated polyimides based on 4,4'-(hexafluoroisopropylidene) diphthalic anhydride were synthesized via hydrothermal process without using any toxic organic solvents and the advantages of the newly demonstrated synthetic methods are shown by comparative analysis performed with the two conventional synthetic methods using organic solvent: thermal and chemical imidization. Lower temperature is required (~200 °C) compared to thermal imidization and functional groups for high fusibility formed more easily compared to chemical imidization. According to the comparative analysis, hydrothermally synthesized PIs showed excellent solubility and maintained high thermal stability (>500 °C) and glass transition temperature (>300 °C) compared to conventional PI. The hydrothermally synthesized polyimide is much more convenient to store and manage than other form of polyimide which is much more stable when it is exposed to humidity as it is a powder form. The hydrothermal synthetic method is verified to be a "Green" and facile method for sustainable PI synthesis.

Factors Affecting Route Selection of Balloon-Assisted Enteroscopy in Patients with Obscure Gastrointestinal Bleeding: A KASID Multicenter Study.

Balloon-assisted enteroscopy (BAE) is an important diagnostic modality for ongoing obscure gastrointestinal bleeding (OGIB). However, it is difficult to determine the optimal insertion route. We retrospectively analyzed the records of patients with OGIB contained in a multicenter enteroscopy database of 1108 balloon-assisted enteroscopy (BAE) procedures (875 patients) to find out factors affecting BAE route selection in patients with OGIB. A total of 603 BAE procedures in 512 patients were investigated: there were 392 (65.0%) bidirectional and 211 (35.0%) unidirectional procedures. Overt OGIB was more frequent in the latter group (p = 0.024). Computed tomography (CT) was more frequently performed in the unidirectional group (p < 0.001). Capsule endoscopy and a small bowel barium study were performed more frequently in the bidirectional group (p < 0.001 and p = 0.039, respectively). Multivariate analysis showed that occult OGIB, capsule endoscopy and a small bowel barium study were independently associated with use of the bidirectional approach (p = 0.011, p = 0.013 and p = 0.046, respectively). Conversely, CT was associated with use of the unidirectional approach (p < 0.001). Conclusion: CT can aid the selection of an optimal insertion route in OGIB patients. However, capsule endoscopy and small bowel barium study are unhelpful.

Two-Color Duplex Platform for Point-of-Care Differential Detection of Malaria and Typhoid Fever.

Malaria and typhoid fever are two febrile illnesses prevalent in the tropics that often present overlapping symptoms. In this work, we demonstrate an optical reader-based diagnostics platform for rapid codetection and quantification of two antigen targets: lipopolysaccharide (LPS) for typhoid fever and plasmodium lactate dehydrogenase (pLDH) for malaria infections. We report a limit of detection (LoD) of 5 ng/mL for LPS and 10 ng/mL for pLDH in a spiked serum test. We also validated the duplex test's performance of differentiating malaria infection, typhoid fever infection, and coinfection by testing clinical samples in human serum. Our platform provides the potential for further multiplexing by encoding different color codes to various detection targets. The rapid result (∼15 min), low cost (∼$2), and minimal volume requirement for human serum clinical samples (4 µL) of our diagnostic platform offer great potential for deployment in resource-limited settings to help distinguish common causes for acute febrile illnesses at the point-of-need.

Orbit topology analyzed from π phase shift of magnetic quantum oscillations in three-dimensional Dirac semimetal.

With the emergence of Dirac fermion physics in the field of condensed matter, magnetic quantum oscillations (MQOs) have been used to discern the topology of orbits in Dirac materials. However, many previous researchers have relied on the single-orbit Lifshitz-Kosevich (LK) formula, which overlooks the significant effect of degenerate orbits on MQOs. Since the single-orbit LK formula is valid for massless Dirac semimetals with small cyclotron masses, it is imperative to generalize the method applicable to a wide range of Dirac semimetals, whether massless or massive. This report demonstrates how spin-degenerate orbits affect the phases in MQOs of three-dimensional massive Dirac semimetal, NbSb2 With varying the direction of the magnetic field, an abrupt π phase shift is observed due to the interference between the spin-degenerate orbits. We investigate the effect of cyclotron mass on the π phase shift and verify its close relation to the phase from the Zeeman coupling. We find that the π phase shift occurs when the cyclotron mass is half of the electron mass, indicating the effective spin gyromagnetic ratio as g s = 2. Our approach is not only useful for analyzing MQOs of massless Dirac semimetals with a small cyclotron mass but also can be used for MQOs in massive Dirac materials with degenerate orbits, especially in topological materials with a sufficiently large cyclotron mass. Furthermore, this method provides a useful way to estimate the precise g s value of the material.

Incomplete Removal of an Intrauterine Device Perforating the Sigmoid Colon.

Intrauterine devices (IUDs) are widely used for contraception in South Korea. However, several complications of IUDs have been reported, including inflammation, obstruction, perforation, and fistula. IUD perforation is the rarest of these complications but is also severe. Migrated IUDs can be retrieved through endoscopy, laparoscopy, or laparotomy. Presented below is an atypical case of an IUD perforating the sigmoid colon, which could not be removed endoscopically, and was subsequently incompletely removed through laparoscopic surgery. The present case underlines the importance of appropriate diagnosis and treatment approach in the management of IUD perforation.