HHCDB: a database of human heterochromatin regions.

Heterochromatin plays essential roles in eukaryotic genomes, such as regulating genes, maintaining genome integrity and silencing repetitive DNA elements. Identifying genome-wide heterochromatin regions is crucial for studying transcriptional regulation. We propose the Human Heterochromatin Chromatin Database (HHCDB) for archiving heterochromatin regions defined by specific or combined histone modifications (H3K27me3, H3K9me2, H3K9me3) according to a unified pipeline. 42 839 743 heterochromatin regions were identified from 578 samples derived from 241 cell-types/cell lines and 92 tissue types. Genomic information is provided in HHCDB, including chromatin location, gene structure, transcripts, distance from transcription start site, neighboring genes, CpG islands, transposable elements, 3D genomic structure and functional annotations. Furthermore, transcriptome data from 73 single cells were analyzed and integrated to explore cell type-specific heterochromatin-related genes. HHCDB affords rich visualization through the UCSC Genome Browser and our self-developed tools. We have also developed a specialized online analysis platform to mine differential heterochromatin regions in cancers. We performed several analyses to explore the function of cancer-specific heterochromatin-related genes, including clinical feature analysis, immune cell infiltration analysis and the construction of drug-target networks. HHCDB is a valuable resource for studying epigenetic regulation, 3D genomics and heterochromatin regulation in development and disease. HHCDB is freely accessible at http://hhcdb.edbc.org/.

Dendrimer nanosystems for adaptive tumor-assisted drug delivery via extracellular vesicle hijacking.

Drug delivery systems (DDSs) that can overcome tumor heterogeneity and achieve deep tumor penetration are challenging to develop yet in high demand for cancer treatment. We report here a DDS based on self-assembling dendrimer nanomicelles for effective and deep tumor penetration via in situ tumor-secreted extracellular vesicles (EVs), an endogenous transport system that evolves with tumor microenvironment. Upon arrival at a tumor, these dendrimer nanomicelles had their payload repackaged by the cells into EVs, which were further transported and internalized by other cells for delivery "in relay." Using pancreatic and colorectal cancer-derived 2D, 3D, and xenograft models, we demonstrated that the in situ-generated EVs mediated intercellular delivery, propagating cargo from cell to cell and deep within the tumor. Our study provides a new perspective on exploiting the intrinsic features of tumors alongside dendrimer supramolecular chemistry to develop smart and effective DDSs to overcome tumor heterogeneity and their evolutive nature thereby improving cancer therapy.

LSD1 in drug discovery: From biological function to clinical application.

Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.

Modulating the Coordination Environment of Carbon-Dot-Supported Fe Single-Atom Nanozymes for Enhanced Tumor Therapy.

Herein, carbon dot (CD)-supported Fe single-atom nanozymes with high content of pyrrolic N and ultrasmall size (ph-CDs-Fe SAzyme) are fabricated by a phenanthroline-mediated ligand-assisted strategy. Compared with phenanthroline-free nanozymes (CDs-Fe SAzyme), ph-CDs-Fe SAzyme exhibit higher peroxidase (POD)-like activity due to their structure similar to that of ferriporphyrin in natural POD. Aberration-corrected high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) analyses show that metal Fe is dispersed in ph-CDs-Fe SAzyme as single atoms. Steady-state kinetic studies show that the maximum velocity (Vmax ) and turnover number (kcat ) of H2 O2  homolytic cleavage catalyzed by ph-CDs-Fe SAzyme are 3.0 and 6.2 more than those of the reaction catalyzed by CDs-Fe SAzyme. Density functional theory (DFT) calculations show that the energy barrier of the reaction catalyzed by ph-CDs-Fe SAzyme is lower than that catalyzed by CDs-Fe SAzyme. Antitumor efficacy experiments show that ph-CDs-Fe SAzyme can efficiently inhibit the growth of tumor cells both in vitro and in vivo by synergistic chemodynamic and photothermal effects. Here a new paradigm is provided for the development of efficient antitumor therapeutic approaches based on SAzyme with POD-like activity.

The antiplasmodial activity of the carboxylic acid metabolite of piperaquine and its pharmacokinetic profiles in healthy volunteers.

BACKGROUND: The long-acting antimalarial drug piperaquine can be metabolized into the carboxylic acid metabolite (PQM). However, the clinical relevance of PQM remains unclear. OBJECTIVES: The pharmacodynamics/pharmacokinetics of PQM were studied. METHODS: The antimalarial activity of PQM was studied in vitro (Plasmodium strains Pf3D7 and PfDd2) and in vivo (murine Plasmodium yoelii). The toxicity of PQM was evaluated in mice, in terms of the general measures of animal well-being, serum biochemical examination and ECG monitoring. The pharmacokinetic profiles of piperaquine and its metabolite PQM were investigated in healthy subjects after recommended oral doses of piperaquine. RESULTS: PQM showed no relevant in vitro antimalarial activity (IC50 > 1.0 µM) with no significant toxicity. After recommended oral administration of piperaquine to healthy subjects, the maximum concentration of PQM was less than 30.0 nM, and it did not accumulate after repeated dosing. CONCLUSIONS: With a low antimalarial potency, PQM should not contribute to the efficacy of piperaquine with clinically acceptable doses.

Overcoming Pharmaceutical Bottlenecks for Nucleic Acid Drug Development.

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic and swift approval of two mRNA vaccines have put nucleic acid therapeutics in the spotlight of both the scientific community and the general public. Actually, in addition to mRNAs, multiple nucleic acid therapeutics have been successively commercialized over the past few years. The rapid development of nucleic acid drugs not only demonstrates their superior potency but also marks a new era of the field. Compared with conventional treatments targeting proteins rather than the root causes of diseases at the genetic level, nucleic acids are capable of achieving long-standing or even curative effects against undruggable disorders by modulating gene expression via inhibition, editing, addition, or replacement. This offers a terrific arsenal for expanding therapeutic access to diseases lacking current treatment options and developing vaccines to provide swift responses to emerging global health threats.Despite the stunning success and recent resurgence of interest in the field, the unfavorable physicochemical characteristics (i.e., the negative charge, large molecular weight, and hydrophilicity), susceptibility to nuclease degradation, off-target toxicity, and immunogenicity are a brake for moving nucleic acid therapeutics from bench to bedside. Currently, developing technologies to improve the circulation stability, targeting affinity, cellular entry, endolysosomal escape, efficacy, and safety of nucleic acid drugs still remains a major pharmaceutical bottleneck.In this Account, we outline the research efforts from our group on the development of technology platforms to overcome the pharmaceutical bottlenecks for nucleic acid therapeutics. We have engineered a variety of intelligent delivery platforms such as synthetic nanomaterials (i.e., lipid nanoparticles, polymers, and inorganic nanoparticles), physical delivery methods (i.e., electroporation), and naturally derived vehicles (i.e., extracellular vesicles), aiming at endowing nucleic acids with improved circulation stability, targeting affinity, and cellular internalization (Get in) and stimuli responsive endolysosomal escape capability (Get out). Moreover, we will discuss our progress in developing a series of modification strategies for sequence engineering of nucleic acids to endow them with enhanced nuclease resistance, translation efficiency, and potency while alleviating their off-target toxicity and immunogenicity (Sequence engineering). Integrating these technologies may promote the development of nucleic acid therapeutics with potent efficacy and improved safety (Efficacy & safety). With this Account, we hope to offer insights into rational design of cutting-edge nucleic acid therapeutic platforms. We believe that the continuing advances in nucleic acid technologies together with academic-industry collaborations in the clinic, will promise to usher in more clinically translatable nucleic acid therapeutics in the foreseeable future.

m6A-modified RIPK4 facilitates proliferation and cisplatin resistance in epithelial ovarian cancer.

BACKGROUND: Cisplatin (DDP)-based chemotherapy is a common chemotherapeutic regimen for the treatment of advanced epithelial ovarian cancer (EOC). However, most patients rapidly develop chemoresistance. N6-methyladenosine (m6A) is a pervasive RNA modification, and its specific role and potential mechanism in the regulation of chemosensitivity in EOC remain unclear. METHODS: The expression of RIPK4 and its clinicopathological impact were evaluated in EOC cohorts. The biological effects of RIPK4 were investigated using in vitro and in vivo models. RNA m6A quantification was used to measure total m6A levels in epithelial ovarian cancer cells. Luciferase reporter, MeRIP-qPCR, RIP-qPCR and actinomycin-D assays were used to investigate RNA/RNA interactions and m6A modification of RIPK4 mRNA. RESULTS: We demonstrated that RIPK4, an upregulated mRNA in EOC, acts as an oncogene in EOC cells by promoting tumor cell proliferation and DDP resistance at the clinical, database, cellular, and animal model levels. Mechanistically, METTL3 facilitates m6A modification, and YTHDF1 recognizes the specific m6A-modified site to prevent RIPK4 RNA degradation and upregulate RIPK4 expression. This induces NF-κB activation, resulting in tumor growth and DDP resistance in vitro and in vivo. CONCLUSIONS: Collectively, the present findings reveal a novel mechanism underlying the induction of DDP resistance by m6A-modified RIPK4, that may contribute to overcoming chemoresistance in EOC.

Targeted inhibition of autophagy in hepatic stellate cells by hydroxychloroquine: An effective therapeutic approach for the treatment of liver fibrosis.

BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis. METHODS: The delivery system of HCQ@retinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-ß-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo. RESULTS: HCQ@ROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs. CONCLUSION: Construction of HCQ@ROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases.

Exosomal YB-1 facilitates ovarian restoration by MALAT1/miR-211-5p/FOXO3 axis.

Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) are attractive candidates for ovarian function restoration and folliculogenesis for POF due to their safety and efficacy, however, the key mediator in MSCs-sEVs that modulates this response and underlying mechanisms remains elusive. Herein, we reported that YB-1 protein was markedly downregulated in vitro and in vivo models of POF induced with H2O2 and CTX respectively, accompanied by granulosa cells (GCs) senescence phenotype. Notably, BMSCs-sEVs transplantation upregulated YB-1, attenuated oxidative damage-induced cellular senescence in GCs, and significantly improved the ovarian function of POF rats, but that was reversed by YB-1 depletion. Moreover, YB-1 showed an obvious decline in serum and GCs in POF patients. Mechanistically, YB-1 as an RNA-binding protein (RBP) physically interacted with a long non-coding RNA, MALAT1, and increased its stability, further, MALAT1 acted as a competing endogenous RNA (ceRNA) to elevate FOXO3 levels by sequestering miR-211-5p to prevent its degradation, leading to repair of ovarian function. In summary, we demonstrated that BMSCs-sEVs improve ovarian function by releasing YB-1, which mediates MALAT1/miR-211-5p/FOXO3 axis regulation, providing a possible therapeutic target for patients with POF.

New meroterpenoids and polyketides from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1 and their anti-inflammatory and SARS-CoV-2 Mpro inhibitory activities.

Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of 1H, 13C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC50 values of 1.78 µM and 1.54 µM, respectively. Moreover, they inhibited the secretion of IL-1ß and CASP-1, resulting in a reduction in the activity levels of NLRP3 inflammasomes. Fluorescence microscopy results indicated that compound 7 concentration-dependently attenuated cell pyroptosis. Additionally, compounds 4 and 7 showed potential inhibitory effects on the severe acute respiratory syndrome coronavirus-2 main protease (SARS-CoV-2 Mpro), with IC50 values of 10.8 ± 0.9 µM and 12.9 ± 0.7 µM, respectively.

M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis.

BACKGROUND: Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated ß-gal (SA-ß-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed. RESULTS: Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition. CONCLUSION: H-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.

DiseaseMeth version 3.0: a major expansion and update of the human disease methylation database.

DNA methylation has a growing potential for use as a biomarker because of its involvement in disease. DNA methylation data have also substantially grown in volume during the past 5 years. To facilitate access to these fragmented data, we proposed DiseaseMeth version 3.0 based on DiseaseMeth version 2.0, in which the number of diseases including increased from 88 to 162 and High-throughput profiles samples increased from 32 701 to 49 949. Experimentally confirmed associations added 448 pairs obtained by manual literature mining from 1472 papers in PubMed. The search, analyze and tools sections were updated to increase performance. In particular, the FunctionSearch now provides for the functional enrichment of genes from localized GO and KEGG annotation. We have also developed a unified analysis pipeline for identifying differentially DNA methylated genes (DMGs) from the original data stored in the database. 22 718 DMGs were found in 99 diseases. These DMGs offer application in disease evaluation using two self-developed online tools, Methylation Disease Correlation and Cancer Prognosis & Co-Methylation. All query results can be downloaded and can also be displayed through a box plot, heatmap or network module according to whichever search section is used. DiseaseMeth version 3.0 is freely available at http://diseasemeth.edbc.org/.

LC-HRMS methods for the quantification of two artemisinin drugs and their metabolites in rat blood and plasma.

As first-line antimalarials used in the artemisinin combination therapy, artemisinin drugs exert their action inside red blood cells. However, the blood pharmacokinetic characteristics of artemisinin drugs have not been fully revealed owing to their built-in chemical instability initiated by Fe2+ released from hemoglobin, with limited information on their metabolites. In this study, liquid chromatography tandem high-resolution mass spectrometric (LC-HRMS) methods were developed for the quantification of two representative artemisinin drugs (artemisinin, ART; dihydroartemisinin, DHA) and their respective metabolite (deoxyartemisinin, D-ART; dihydroartemisinin glucuronide, DHA-Glu) in rat blood/plasma. The blood samples were pretreated with the stabilizer (0.4 m potassium dichromate and 3% EDTA-2Na). The methods displayed excellent specificity, linearity, accuracy and precision for ART (17.7-709.2 nm) and its metabolite D-ART (18.8-751.9 nm), and the linear range was 40.0-4,000.0 nm for both DHA and DHA-Glu. The methods were successfully applied to the pharmacokinetic studies of ART and DHA in rats. The blood-to-plasma ratio was 0.8-1.5 for ART, 1.0-1.5 for D-ART, 1.2-2.2 for DHA and 0.9-1.3 for DHA-Glu, which was time dependent. The results indicated that artemisinin drugs and their metabolites showed a high but different blood-to-plasma ratio, which should be considered when optimizating their dosing regimens or evaluating their clinical outcomes.

Three Undescribed Protoilludane-type Sesquiterpene Aryl Esters from Armillaria gallica.

Three previously undescribed protoilludane-type sesquiterpene aryl esters, armillanals A-C (1-3), along with seven known ones (4-10) were obtained from Armillaria gallica Marxm. & Romagn. Compounds 1 and 2 were a rare class of sesquiterpenes featuring the Δ2(3) and Δ12(13)-protoilludane skeleton. Their structures were established by extensive spectroscopic methods. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of three new compounds (1-3) were determined. The anti-inflammatory activity of compounds 1-10 was screened and compound 3 could dose-dependently decrease the level of lactate dehydrogenase, showing IC50 value of 4.525 µM.

Two new oleanane triterpenes from Maytenus hookeri.

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.

HPV-related cervical diseases: Alteration of vaginal microbiotas and promising potential for diagnosis.

Vaginal microbiota is closely associated with women's health, however, the correlation between HPV-related cervical disease (HRCD) and vaginal microbiota is still obscure. In this study, patients with HRCD (n = 98) and healthy controls (n = 58) in Hangzhou were recruited, and their vaginal microbiota were collected and analyzed. The composition of the vaginal microbial community was explored, and a disease classification model was developed by random forest algorithm. The results suggested that the diversity of vaginal microbiota was significantly higher in HRCDs than that in healthy controls (p < 0.05). Firmicutes is the dominant phylum in vaginal microbiota, and Lactobacillus was identified as the most altered genus between two groups (p < 0.01). Kyoto Encyclopedia of Genes and Genomes analysis suggested the difference in vaginal microbial community functions between two groups. Furthermore, we identified 10 biomarkers as the optimal marker sets for the random forest model and found a higher probability of disease values in HRCD group in discovery cohort (p < 0.0001), with an area under the receiver operating characteristic curve reaching 89.7% (95% confidence interval: 78.3%-100%). We further validated the model in both validation and independent diagnosis cohorts, confirming its accuracy in the prediction of HRCD. In conclusion, this study revealed the community composition of vaginal microbiota in HRCDs and successfully constructed a diagnostic model for HRCD.

New High-Performance Piezoelectric: Ferroelectric Carbon-Boron Clathrate.

High-performance piezoelectrics have been extensively reported with a typical perovskite structure, in which a huge breakthrough in piezoelectric constants is found to be more and more difficult. Hence, the development of materials beyond perovskite is a potential means of achieving lead-free and high piezoelectricity in next-generation piezoelectrics. Here, we demonstrate the possibility of developing high piezoelectricity in the nonperovskite carbon-boron clathrate with the composition of ScB_{3}C_{3} using first-principles calculations. The robust and highly symmetric B-C cage with mobilizable Sc atom constructs a flat potential valley to connect the ferroelectric orthorhombic and rhombohedral structures, which allows an easy, continuous, and strong polarization rotation. By manipulating the cell parameter b, the potential energy surface can be further flattened to produce an extra-high shear piezoelectric constant d_{15} of 9424 pC/N. Our calculations also confirm the effectiveness of the partial chemical replacement of Sc by Y to form a morphotropic phase boundary in the clathrate. The significance of large polarization and high symmetric polyhedron structure is demonstrated for realizing strong polarization rotation, offering the universal physical principles to aid the search for new high-performance piezoelectrics. This work takes ScB_{3}C_{3} as an example to exhibit the great potential for realizing high piezoelectricity in clathrate structure, which opens the door to developing next-generation lead-free piezoelectric applications.

A nomogram and risk classification system predicting esophageal stricture after endoscopic submucosal dissection of a large area for early esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal stricture is a troublesome adverse effect of endoscopic submucosal dissection (ESD) for early esophageal cancer. However, risk factors of post-ESD esophageal stricture formation are incomprehensive. This study aimed to conduct a comprehensive analysis of independent risk factors and provide predictive tools. METHODS: Patients who underwent ESD for early esophageal cancer between 2014 and 2021 at the Beijing Friendship Hospital, Capital Medical University, were recruited. A nomogram and risk classification system was established based on Cox proportional hazards analyses and validated using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) curves. RESULTS: Stricture formed in 36 patients, while stricture was not observed in the remaining 112 patients. Operative time (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00-1.01; p < 0.01); lesions >3/4 circumferential range of esophagus (OR: 3.82; 95% CI: 1.90-7.66; p < 0.01), and tumor infiltration to the mucosal lamina propria (m2) or deeper (OR: 2.40; 95% CI: 1.24-4.66; p = 0.01) were independent predictive factors for post-ESD esophageal stricture. The nomogram and risk classification system was developed and validated with 0.79 C-index, good calibration curves, good DCA results, and good K-M curves. CONCLUSIONS: We developed a nomogram and risk stratification system to predict post-ESD esophageal stricture using three independent risk factors.

Comparison of endoscopic submucosal dissection outcomes between early gastric cardiac and non-cardiac cancers: a retrospective single-center study.

OBJECTIVES: This study aims to compare the efficacy of endoscopic submucosal dissection (ESD) between early gastric cardiac cancer (EGCC) and early gastric non-cardiac cancer (EGNCC), and investigate associated risk factors for non-curative resection. METHODS: Early gastric cancer (EGC) patients who underwent ESD from January 2015 to September 2020 in Beijing Friendship Hospital were consecutively enrolled. The clinical, histopathological and endoscopic data were retrospectively analyzed. The study was registered in Chinese Clinical Trial Registry (ChiCTR1800017117). RESULTS: Among 500 patients with 534 EGC lesions, 117 patients with 118 lesions were allocated to the EGCC group, and 383 patients with 416 lesions to the EGNCC group. The rates of en bloc resection, complete resection and curative resection in the EGCC group were 97.5%, 78.8% and 71.2%, respectively, significantly lower than those in the EGNCC group (99.8%, 94.5% and 90.4%, p = .010, <.001 and <.001). Among non-curative resected lesions, EGCC had more cases in both endoscopic curability (eCura) C-1 and C-2 groups than EGNCC (10.2% and 18.6% vs. 2.4% and 7.2%, p < .001). Multivariate analysis showed that tumor size (OR 2.393, 95% CI 1.388-4.126) and submucosal invasion (OR 11.498, 95% CI 3.759-35.175) were risk factors for non-curative resection in the EGCC group. For EGCC larger than 3 cm, none achieved curative resection, 86.7% were classified as eCura C-2 and 46.7% exhibited deep submucosal infiltration. CONCLUSIONS: The curative resection rate of ESD for EGCC was lower than that for EGNCC. ESD for EGCC larger than 3 cm should be cautiously considered.

Insight into the Ultrahigh Electric Performance of Aurivillius CBTa-CBN Solid Solution.

For bismuth layered structural ferroelectrics (BLSFs), CaBi2Ta2O9 (CBTa) demonstrates valuable application potential for a high Curie temperature (TC) of 923 °C and a good high-temperature resistivity, but low piezoelectric constant d33 values. Compared with CBTa-based ceramics, CaBi2Nb2O9 (CBN) with a high TC of 940 °C is easy to modify and realize excellent enhancement of piezoelectric properties. Here, by introducing a CBN-based component into CBTa, a new type of solid-solution ceramic with the formula Ca0.94(LiCe)0.03Bi2Ta2O9-xCa0.94(LiCe)0.03Bi2Nb2O9 (LC-CBTa-xCBN) is fabricated to obtain the advantages of both of them. Moreover, optimal electrical performances are obtained in the LC-CBTa-0.4CBN ceramic (d33 ∼ 14.1 pC/N, ρ ∼ 1.08 × 106 at 600 °C, TC ∼ 940 °C). The correlated characterizations, including structure and electricity, provide further realization of an enhanced performance mechanism. Therefore, this method of constructing a new type of solid solution provides a new strategy to modify BLSFs.