Cantharidin overcomes IL-2Rα signaling-mediated vorinostat resistance in cutaneous T-cell lymphoma through reactive oxygen species.

BACKGROUND: Vorinostat (SAHA) is a histone deacetylase inhibitor that has shown clinical efficacy against advanced cutaneous T-cell lymphoma (CTCL). However, only a subset of patients with CTCL (30-35%) respond to SAHA and the response is not always sustainable. Thus, understanding the mechanisms underlying evasive resistance in this cancer is an unmet medical need to improve the efficacy of current therapies. PURPOSE: This study aims to identify factors contributing to resistance against SAHA in CTCL and ways to mitigate it. METHODS AND RESULTS: In this study, we demonstrated that attenuated reactive oxygen species (ROS) induces the expression of interleukin (IL)-2Rα, one of the IL-2 receptors, which drives resistance to SAHA in CTCL. We also determined that cantharidin could overcome SAHA resistance to CTCL by blocking IL-2Rα-related signaling via ROS-dependent manner. Mechanistically, accelerated translation of IL-2Rα contributes to excessive IL-2Rα protein formation as a result of reduced ROS levels in SAHA-resistant CTCL. At the same time, amplified IL-2R signals are evidenced by strengthened interaction of IL-2Rß with IL-2Rγ and Janus kinase/signal transducer and activator of transcription molecules, and by increased expression of protein kinase B (AKT)/mTOR and mitogen-activated protein kinase signaling. Moreover, cantharidin, an active constituent of Mylabris used in traditional Chinese medicine, markedly increased ROS levels, and thereby restrained IL-2Rα translation, resulting in suppression of downstream pathways in SAHA-resistant cells. Cantharidin is also found to synergize with SAHA and triggers SAHA-resistant cell death via IL-2R signaling both in vitro and in vivo. CONCLUSION: Our study uncovers a novel molecular mechanism of acquired SAHA resistance and also suggests that using cantharidin is a potential approach to overcome CTCL therapy resistance. Our findings underlie the therapeutic potential of cantharidin in treating CTCL.

Enhancing the Photosensitivity of Hypocrellin A by Perylene Diimide Metallacage-Based Host-Guest Complexation for Photodynamic Therapy.

The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy. Here, we report two perylene diimide-based metallacages that can form stable host-guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers (hypocrellin A). Such host-guest complexation not only prevents the aggregation of photosensitizers in aqueous environments, but also offers fluorescence resonance energy transfer (FRET) from the metallacage to the photosensitizers to further improve the singlet oxygen generation (ΦΔ = 0.66). The complexes are further assembled with amphiphilic polymers, forming nanoparticles with improved stability for anticancer study. Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation, showing great potential for cancer photodynamic therapy. This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host-guest complexation-based FRET, which will open a new avenue for host-guest chemistry-based supramolecular theranostics.

Exploring the evolution of CHS gene family in plants.

Chalcone synthase (CHS) is a key enzyme that catalyzes the first committed step of flavonoid biosynthetic pathway. It plays a vital role not only in maintaining plant growth and development, but also in regulating plant response to environmental hazards. However, the systematic phylogenomic analysis of CHS gene family in a wide range of plant species has not been reported yet. To fill this knowledge gap, a large-scale investigation of CHS genes was performed in 178 plant species covering green algae to dicotyledons. A total of 2,011 CHS and 293 CHS-like genes were identified and phylogenetically divided into four groups, respectively. Gene distribution patterns across the plant kingdom revealed the origin of CHS can be traced back to before the rise of algae. The gene length varied largely in different species, while the exon structure was relatively conserved. Selection pressure analysis also indicated the conserved features of CHS genes on evolutionary time scales. Moreover, our synteny analysis pinpointed that, besides genome-wide duplication and tandem duplication, lineage specific transposition events also occurred in the evolutionary trajectory of CHS gene family. This work provides novel insights into the evolution of CHS gene family and may facilitate further research to better understand the regulatory mechanism of traits relating to flavonoid biosynthesis in diverse plants.

Notch-Targeted Therapeutic in Colorectal Cancer by Notch1 Attenuation Via Tumor Microenvironment-Responsive Cascade DNA Delivery.

The Notch signaling is a key molecular pathway that regulates cell fate and development. Aberrant Notch signaling can lead to carcinogenesis and progression of malignant tumors. However, current therapies targeting Notch pathway lack specificity and induce high toxicity. In this report, a tumor microenvironment-responsive and injectable hydrogel is designed to load plasmid DNA complexes as a cascade gene delivery system to achieve precise Notch-targeted gene therapy of colorectal cancer (CRC). The hydrogels are prepared through cross-linking between phenylboric acid groups containing poly(oligo(ethylene glycol)methacrylate) (POEGMA) and epigallocatechin gallate (EGCG), used to load the complexes between plasmid DNA encoding short hairpin RNAs of Notch1 (shNotch1) and fluorinated polyamidoamine (PAMAM-F) (PAMAM-F/shNotch1). In response to low pH and H2O2 in tumor microenvironment, the hydrogel can be dissociated and release the complexes for precise delivery of shNotch1 into tumor cells and inhibit Notch1 activity to suppress malignant biological behaviors of CRC. In the subcutaneous tumor model of CRC, PAMAM-F/shNotch1-loaded hydrogels can accurately attenuate Notch1 activity and significantly inhibit tumor growth without affecting Notch signal in adjacent normal tissues. Therefore, this therapeutic system can precisely inhibit Notch1 signal in CRC with high responsiveness and low toxicity, providing a promising Notch-targeted gene therapeutic for human malignancy.

pH-responsive bioadhesive with robust and stable wet adhesion for gastric ulcer healing.

Development of bioadhesives that can be facilely delivered by endoscope and exhibit instant and robust adhesion with gastric tissues to promote gastric ulcer healing remains challenging. In this study, an advanced bioadhesive is prepared through free radical polymerization of ionized N-acryloyl phenylalanine (iAPA) and N-[tris (hydroxymethyl) methyl] acrylamide (THMA). The precursory polymer solution exhibits low viscosity with the capability for endoscope delivery, and the hydrophilic-hydrophobic transition of iAPA upon exposure to gastric acid can trigger gelation through phenyl groups assisted multiple hydrogen bonds formation and repel water molecules on tissue surface to establish favorable environment for interfacial interactions between THMA and functional groups on tissues. The in-situ formed hydrogel features excellent stability in acid environment (14 days) and exhibits firm wet adhesion to gastric tissue (33.4 kPa), which can efficiently protect the wound from the stimulation of gastric acid and pepsin. In vivo studies reveal that the bioadhesive can accelerate the healing of ulcers by inhibiting inflammation and promoting capillary formation in the acetic acid-induced gastric ulcer model in rats. Our work may provide an effective solution for the treatment of gastric ulcers clinically.

"Gear-driven"-type chirality transfer of tetraphenylethene-based supramolecular organic frameworks for peptides in water.

Chirality transfer for natural chiral biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we report the synthesis and characterization of a series of achiral supramolecular organic frameworks (SOF-1, SOF-2, and SOF-3), constructed from cucurbit[8]uril (CB[8]) and tetraphenylethene (TPE) derivatives (1, 2, and 3), respectively, as chirality-sensing platforms to explore their chirality transfer mechanism for peptides in water. Given the right-handed (P) and left-handed (M) rotational conformation of TPE units and the selective binding of CB[8] to aromatic amino acids, these achiral SOFs can be selectively triggered in water by peptides containing N-terminal tryptophan (W) and phenylalanine (F) residues into their P- or M-rotational conformation, exhibiting significantly different circular dichroism (CD) spectra. Although various peptides have the same l-type chiral configuration, they can induce positive CD signals of SOF-1 and negative CD signals of SOF-2 and SOF-3, respectively. Based on the structural analysis of the linkage units between CB[8] and TPE units in these SOFs, a "gear-driven"-type chirality transfer mechanism has been proposed to visually illustrate the multiple-step chirality transfer process from the recognition site in the CB[8]'s cavity to TPE units. Furthermore, by utilizing the characteristic CD signals generated through the "gear-driven"-type chirality transfer, these SOFs can serve as chiroptical sensor arrays to effectively recognize and distinguish various peptides based on their distinctive CD spectra.

Pro-Inflammatory Diet as a Risk Factor for Stomach Cancer: Findings from a Multicenter Study in Central and Western China.

Purpose: We conducted a multicenter cross-sectional study in central and western China to explore the association between inflammatory diet and stomach cancer odds. Patients and Methods: Participants from five hospitals in the central and western regions were collected. All participants completed the questionnaire we provided before the gastroscopy examination, which includes inquiries about risk factors for stomach cancer and food frequency. All participants underwent gastroscopy, and a mucosal biopsy was confirmed pathologically. Pathological findings were classified as chronic gastritis group, precancerous lesions group and stomach cancer group. Dietary Inflammatory Index (DII) scores were calculated based on the frequency of food occurrences in the questionnaire, and finally SPSS was used to calculate the correlation between variables. Results: A total of 1162 patients were included in this study, including 668 cases of chronic gastritis, 411 cases of precancerous lesions, and 83 cases of cancer. A single factor analysis was conducted to examine the risk factors of stomach cancer, revealing a significant association between a pro-inflammatory diet and the stomach cancer odds (p value < 0.05). The results of binary classification analysis further confirmed that a pro-inflammatory diet is a risk factor for stomach cancer 【odds ratio (OR) =7.400)】. Moreover, correlation analysis demonstrated a positive correlation between the severity of gastric mucosal diseases and an inflammatory diet (including anti-inflammatory and pro-inflammatory diets) (rs=0.274, p-value < 0.001). Conclusion: Pro-Inflammatory diet is a risk factor for stomach cancer, and may accelerate the progression of stomach mucosal disease.

Multifunctional On-Demand Removability Hydrogel Dressing Based on in Situ Formed AgNPs, Silk Microfibers and Hydrazide Hyaluronic Acid for Burn Wound Healing.

Elevated temperatures can deactivate tissues in the burn wound area, allowing pathogenic bacteria to multiply on the wound surface, ultimately leading to local or systemic infection. An ideal burn dressing should provide antibacterial properties and facilitate painless dressing changes. Silk microfibers coated with poly (2, 3, 4-trihydroxybenzaldehyde) (referred to as mSF@PTHB) to in situ reduce AgNO3 to silver nanoparticles (AgNPs) in a hydrazide hyaluronic acid-based hydrogel are utilized. The findings indicate a more homogeneous distribution of the silver elements compared to directly doped AgNPs, which also conferred antioxidant and antibacterial properties to the hydrogel. Moreover, hydrogels containing pH-responsive dynamic acylhydrazone bonds can undergo a gel-sol transition in a weak acid environment, leading to the painless removal of adhesive hydrogel dressings. Notably, the on-demand replaceable self-healing antioxidant hydrogel dressing exhibits antibacterial effects and cytocompatibility in vitro, and the wound-healing performance of the hydrogel is validated by treating a burn mouse model with full-thickness skin defects. It is demonstrated that hydrogel dressings offer a viable therapeutic approach to prevent infection and facilitate the healing of burn wounds.

The association between Helicobacter pylori and gastrointestinal disorders during pregnancy: A Multicenter retrospective study.

BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.

Injectable Antiswelling and High-Strength Bioactive Hydrogels with a Wet Adhesion and Rapid Gelling Process to Promote Sutureless Wound Closure and Scar-free Repair of Infectious Wounds.

Developing injectable antiswelling and high-strength bioactive hydrogels with wet tissue adhesiveness and a rapid gelling process to meet the requirements for rapid hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds continues to have ongoing challenges. Herein, injectable, antibacterial, and antioxidant hydrogel adhesives based on poly(citric acid-co-polyethylene glycol)-g-dopamine and amino-terminated Pluronic F127 (APF) micelles loaded with astragaloside IV (AS) are prepared. The H2O2/horseradish peroxidase (HRP) system is used to cause cross-linking of the hydrogel network through oxidative coupling between catechol groups and chemical cross-linking between the catechol group and the amino group. The hydrogels exhibit a rapid gelling process, high mechanical strength, an antiswelling effect, good antioxidant property, H2O2 release behavior, and degradability. In addition, the hydrogels present good wet tissue adhesiveness, high bursting pressure, excellent antibacterial activity, long-term sustained release of AS, and good biocompatibility. The hydrogels perform good hemostasis on mouse liver, rat liver, and rabbit femoral vein bleeding models and achieve much better closure and healing of skin incisions than biomedical glue and surgical sutures. Furthermore, the hydrogel dressing significantly improved the scar-free repair of MRSA-infected full thickness skin defect wounds by modulating inflammation, regulating the ratio of collagen I/III, and improving the vascularization and granulation tissue formation. Thus, AS-loaded hydrogels show huge potential as multifunctional dressings for in vivo hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds.

Identification of Chemical Constituents in Blumea balsamifera Using UPLC-Q-Orbitrap HRMS and Evaluation of Their Antioxidant Activities.

Blumea balsamifera (L.) DC., a perennial herb in the Asteraceae family native to China and Southeast Asia, has a notable history of medicinal use due to its pharmacological properties. Using UPLC-Q-Orbitrap HRMS techniques, we systematically investigated the chemical constituents of this plant. A total of 31 constituents were identified, of which 14 were flavonoid compounds. Significantly, 18 of these compounds were identified in B. balsamifera for the first time. Furthermore, the mass spectrometry fragmentation patterns of significant chemical constituents identified in B. balsamifera were analyzed, providing important insights into their structural characteristics. The in vitro antioxidative potential of the methanol extract of B. balsamifera was assessed using DPPH and ABTS free-radical-scavenging assays, total antioxidative capacity, and reducing power. The antioxidative activity exhibited a direct correlation with the mass concentration of the extract, with IC50 values of 105.1 ± 0.503 µg/mL and 12.49 ± 0.341 µg/mL for DPPH and ABTS, respectively. For total antioxidant capacity, the absorbance was 0.454 ± 0.009 at 400 µg/mL. In addition, the reducing power was 1.099 ± 0.03 at 2000 µg/mL. This study affirms that UPLC-Q-Orbitrap HRMS can effectively discern the chemical constituents in B. balsamifera, primarily its flavonoid compounds, and substantiates its antioxidative properties. This underscores its potential utility as a natural antioxidant in the food, pharmaceutical, and cosmetics sectors. This research provides a valuable theoretical basis and reference value for the comprehensive development and utilization of B. balsamifera and expands our understanding of this medicinally valuable plant.

The prognostic impact of BMI on colorectal cancer is stratified by tumor location.

Purpose: Recent studies have revealed the contrasting prognostic roles of body mass index (BMI) and tumor location in colorectal cancer (CRC). Given that right- and left-sided CRC may exhibit inverse effects on outcome and body weight, the present study aimed to examine whether the prognostic value of BMI and tumor location could be reciprocally stratified. Methods: This prospective, observational study recruited 4,086 patients diagnosed with stage III CRC from five independent clinical centers in China. The association of patients' outcomes with BMI and tumor location was evaluated hierarchically by Kaplan-Meier and Cox proportional-hazards models. Results: Although BMI was not associated with overall outcome, the association was significantly modified by tumor location. Among left-sided tumors, obesity and overweight were significantly associated with adverse overall survival (OS) and disease-specific survival (DSS). In contrast, among right-sided tumors, overweight was significantly associated with more favorable OS and DSS compared with the normal-weight group. The association of survival with tumor location did not reach statistical significance. However, hierarchical analysis by BMI revealed that left-sided tumors were associated with more favorable outcomes in the normal-weight group, while there was no statistically significant difference in the overweight or obese group. Conclusions: BMI and tumor location may have opposing effects on CRC prognosis, when stratified by each other, after adjusting for other known prognostic factors. These findings are the first to show the interactive prognostic impact of BMI and tumor location, which could be relevant to the stratification of patient management.

Efficient Photoinduced Electron Transfer from Pyrene-o-Carborane Heterojunction to Selenoviologen for Enhanced Photocatalytic Hydrogen Evolution and Reduction of Alkynes.

A series of pyrene or pyrene-o-carborane-appendant selenoviologens (Py-SeV2+ , Py-Cb-SeV2+ ) for enhanced photocatalytic hydrogen evolution reaction (HER) and reduction of alkynes is reported. The efficient photoinduced electron transfer (PET) from electron-rich pyrene-o-carborane heterojunction (Py-Cb) with intramolecular charge transfer (ICT) characteristic to electron-deficient selenoviologen (SeV2+ ) (kET = 1.2 × 1010 s-1 ) endows the accelerating the generation of selenoviologen radical cation (SeV+• ) compared with Py-SeV2+ and other derivatives. The electrochromic/electrofluorochromic devices' (ECD and EFCD) measurements and supramolecular assembly/disassembly processes of SeV2+ and cucurbit[8]uril (CB[8]) results show that the PET process can be finely tuned by electrochemical and host-guest chemistry methods. By combination with Pt-NPs catalyst, the Py-Cb-SeV2+ -based system shows high-efficiency visible-light-driven HER and highly selective phenylacetylene reduction due to the efficient PET process.

Delta-like ligand 4 level in colorectal cancer is associated with tumor aggressiveness and clinical outcome.

BACKGROUND: The Notch signaling regulates numerous cell growth, differentiation, and death. However, the expression pattern of its ligand Delta-like 4 (DLL4) in tumors is still uncertain. OBJECTIVE: In the present study, we examined DLL4 expression in colorectal cancer as well as assessed its role as a prognostic indicator in the present study. METHODS: DLL4 expression was examined by immunohistochemistry in 289 surgically resected specimens of colorectal cancer and adjacent normal tissues. The relationship between DLL4 expression and clinicopathological characteristics was analyzed. The association of DLL4 expression with the patients' overall survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression. RESULTS: Increased DLL4 level was detected in colorectal cancer compared with that of normal tissues. Elevated DLL4 level in colorectal cancer was associated with increased body mass index of patients. Moreover, increased DLL4 level was also found to be correlated with tumor invasion, metastases and unfavorable clinical outcom of patients. CONCLUSIONS: DLL4 level is increased in colorectal cancer, especially in patients with increased body mass index, indicating potential involvement of obesity-related tumorigenesis and development. It might also serve as a novel molecular marker to predicate outcome of patients.

On-demand manipulation of tumorigenic microenvironments by nano-modulator for synergistic tumor therapy.

Proper manipulation of tumorigenic microenvironments has been considered as one of the most effective approaches for tumor therapy, which is still a challenge to be well performed. Herein, a nano-modulator was fabricated to manipulate the hypoxia, glucose, radicals and local temperature in tumor tissue as needed, which consists of hemoglobin (Hb) and ferric ion (Fe3+) co-conjugated polydopamine (PDA) as core, glucose oxidase (GOD) as shell, and folic acid (FA) modified polyethylene glycol (PEG) as corona. The PEG-FA corona not only protected Hb and GOD against protease in blood circulation, but serve as tumor targeting agent for tumor specific accumulation of the nano-modulator. The Hb is in charge of oxygen supply to reverse the hypoxic environment of tumor tissue, which promotes the function of GOD to achieve rapid glucose consumption and hydrogen peroxide generation. The polydopamine was employed to raise local temperature under NIR irradiation, meanwhile to continuously reduce Fe3+ to produce ferrous ions (Fe2+), which further catalyze hydrogen peroxide to cytotoxic hydroxyl radicals via Fenton reaction. Both in vitro and in vivo results showed excellent tumor inhibition and high survival rate of tumor-bearing mice after treatment by our nano-modulator, indicating this synergistic therapy via on-demand manipulation of various tumorigenic microenvironments could be a green approach for tumor treatment with high efficiency and minimum side effects.

Injectable Self-Healing Adhesive pH-Responsive Hydrogels Accelerate Gastric Hemostasis and Wound Healing.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established therapeutics for gastrointestinal neoplasias, but complications after EMR/ESD, including bleeding and perforation, result in additional treatment morbidity and even threaten the lives of patients. Thus, designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge. Herein, a series of injectable pH-responsive self-healing adhesive hydrogels based on acryloyl-6-aminocaproic acid (AA) and AA-g-N-hydroxysuccinimide (AA-NHS) were developed, and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model. The hydrogels showed a suitable gelation time, an autonomous and efficient self-healing capacity, hemostatic properties, and good biocompatibility. With the introduction of AA-NHS as a micro-cross-linker, the hydrogels exhibited enhanced adhesive strength. A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding. A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition, α-SMA expression, and blood vessel formation. These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.

Highly Stretchable, Tough, Resilient, and Antifatigue Hydrogels Based on Multiple Hydrogen Bonding Interactions Formed by Phenylalanine Derivatives.

Noncovalent cross-linked hydrogels with promising mechanical properties are on demand for applications in tissue engineering, flexible electronics, and actuators. However, integrating excellent mechanical properties with facile preparation for the design of hydrogen bond cross-linked hydrogels is still challenging. In this work, an advanced hydrogel was prepared from acrylamide and N-acryloyl phenylalanine by one-pot free-radical copolymerization. Owing to hydrophobicity-assisted multiple hydrogen bonding interactions among phenylalanine derivatives, the hydrogels exhibited fascinating mechanical behaviors: tensile strength of 0.35 MPa, elongation at break of 2100%, tearing energy of 1134 J/m2, and compression strength of 3.56 MPa. The hydrogels also showed robust elasticity and fatigue resistance, and the compression strength did not show any decline, even after 100 successive cycles, as well as promising self-recovery property. In addition, the cytotoxicity test in vitro proved that the hydrogel showed good biocompatibility with normal human liver cells (LO2 cells). The excellent stretchability, robust elasticity, high toughness, fatigue resistance, and biocompatibility of the hydrogel demonstrated its vast potential in the biomedical field and flexible electronic devices.

Magnetic anchoring and guidance-assisted endoscopic irreversible electroporation for gastric mucosal ablation: a preclinical study in canine model.

BACKGROUND: The aim of this study was to evaluate the feasibility, safety, and efficacy of magnetic anchoring and guidance-assisted endoscopic irreversible electroporation (MAG-IRE) for gastric mucosal ablation. METHODS: A catheter-based, donut-like, and MAG-assisted electrode was developed. MAG-IRE for gastric mucosal ablation was performed in eight beagle canines. The parameters of one set of IRE was 500 V voltage, 100 µs pulse duration, and 99 pulses. The MAG time, operation time, success rate, and adverse events were measured. Endoscopic examination was performed from 30 min to 28 days post-IRE. Full-thickness gastric tissue was harvested by wedge biopsy for histopathological analysis. RESULTS: 30 (93.75%) of the 32 lesions were successfully ablated by MAG-IRE. The median MAG time was 300 s (IQR 120-422.5 s), and the median operation time was 491.5 s (IQR 358.3-632.5 s). No adverse events occurred. Ulceration was observed, starting from 3 days post-IRE. The mucosa healed 14 to 28 days post-IRE. Hematoxylin-Eosin (H&E) staining showed inflammatory infiltration, edema, and congestion in the ablated mucosa. Masson's Trichrome staining showed that the gastric wall and blood vessels in the ablation area were intact. TUNEL assay showed diffuse positive cells in ablated mucosa as early as 30 min post-IRE. CONCLUSIONS: MAG-IRE for gastric mucosal ablation is feasible, safe, and effective. It can be a potential therapeutic option for minimally invasive treatment of gastric neoplasm.

Adaptive Chirality of an Achiral Cucurbit[8]uril-Based Supramolecular Organic Framework for Chirality Induction in Water.

Chiral framework materials have been developed for many applications including chiral recognition, chiral separation, asymmetric catalysis, and chiroptical materials. Herein, we report that an achiral cucurbit[8]uril-based supramolecular organic framework (SOF-1) with the dynamic rotational conformation of tetraphenylethene units can exhibit adaptive chirality to produce M-SOF-1 or P-SOF-1 with mirror-image circular dichroism (CD) with gabs ≈±10-4 and circularly polarized luminescence (CPL) with glum ≈±10-4 induced by L-/D-phenylalanine in water, respectively. The chirality induction in CD (gabs ≈-10-4 ) and CPL (glum ≈-10-4 ) of P-SOF-1 from achiral SOF-1 can be presented by using a small amount of adenosine-5'-triphosphate disodium (ATP) or adenosine-5'-diphosphate disodium (ADP) (only 0.4 equiv) in water. Furthermore, the adaptive chirality of SOF-1 can be used to determine dipeptide sequences (e.g., Phe-Ala and Ala-Phe) and distinguish polypeptides/proteins (e.g., somatostatin and human insulin) with characteristic CD spectra. Therefore, achiral SOF-1 as an ideal chiroptical platform with adaptive chirality may be applied to determine the enantiopurity of amino acids (e.g., L-/D-phenylalanine), develop aqueous CPL materials, and distinguish biological chiral macromolecules (e.g., peptides/proteins) via chirality induction in water.

[Research Progress of Catheter-based Irreversible Electroporation for Tissue Ablation].

Irreversible electroporation (IRE) is an emerging tissue ablation technique. Compared with thermal ablation technique such as radiofrequency, IRE can achieve focal ablation in a shorter time without heat sink effect while sparing the tissue scaffold. IRE has been demonstrated to be a feasible therapeutic modality for the liver, pancreatic, and prostatic cancer. In recent years, several studies regarding of catheter-directed IRE for digestive tract, bronchus, urinary tract, and myocardium have been performed, which preliminarily demonstrated the safety and efficacy of IRE for tissue ablation under endoscopic or interventional technique. This study summarized the research progress of catheter-directed IRE for tissue ablation. The critical technique and future direction of catheter-based IRE are prosp.