Supermolecular Confined Silicon Phosphorescence Nanoprobes for Time-Resolved Hypoxic Imaging Analysis.

Room temperature phosphorescence (RTP) nanoprobes play crucial roles in hypoxia imaging due to their high signal-to-background ratio (SBR) in the time domain. However, synthesizing RTP probes in aqueous media with a small size and high quantum yield remains challenging for intracellular hypoxic imaging up to present. Herein, aqueous RTP nanoprobes consisting of naphthalene anhydride derivatives, cucurbit[7]uril (CB[7]), and organosilicon are reported via supermolecular confined methods. Benefiting from the noncovalent confinement of CB[7] and hydrolysis reactions of organosilicon, such small-sized RTP nanoprobes (5-10 nm) exhibit inherent tunable phosphorescence (from 400 to 680 nm) with microsecond second lifetimes (up to ∼158.7 µs) and high quantum yield (up to ∼30%). The as-prepared RTP nanoprobes illustrate excellent intracellular hypoxia responsibility in a broad range from ∼0.1 to 21% oxygen concentrations. Compared to traditional fluorescence mode, the SBR value (∼108.69) of microsecond-range time-resolved in vitro imaging is up to 2.26 times greater in severe hypoxia (<0.1% O2), offering opportunities for precision imaging analysis in a hypoxic environment.

Multi-colour room-temperature phosphorescence from fused-ring compounds for dynamic anti-counterfeiting applications.

We present a facile strategy to achieve purely organic multi-colour room-temperature phosphorescence (RTP) films by doping typical fused-ring compounds into a poly(vinyl alcohol) matrix. Such RTP films demonstrate inherent RTP emission ranging from green to red with a long lifetime and high quantum yield (QY) (lifetime: ∼0.56 ms, QY: ∼35.4%). We further exploit such high-performance RTP films for dynamic information encryption.

Curative Effect Analysis of Endoscopic Submucosal Dissection in Giant Laterally Spreading Rectal Tumors.

GOAL: The objective of this study was to investigate the clinical efficacy of endoscopic submucosal dissection (ESD) in the treatment of giant lateral developing rectal-type tumors (laterally spreading tumors, LSTs). BACKGROUND: There are no specialized studies on the efficacy of ESD in the treatment of LSTs measuring >5 cm in diameter, surgery was often used in the past, but it has the disadvantages of large trauma, many complications, and high cost. METHODS: The data of 185 patients with rectal LSTs who had undergone ESD in the digestive endoscopy center of our hospital from January 2012 to June 2020 were retrospectively analyzed. Based on the size of the lesions, the patients were divided into 2 groups: diameter ≤5 cm (110 cases) and diameter >5 cm (75 cases), and we summarized and analyzed the en bloc resection rate, curative resection rate, procedure time, muscle injury, bleeding, perforation, postoperative stricture, and recurrence. RESULTS: There was no difference in the en bloc resection rate and R0 resection rate between the 2 groups ( P =0.531). Moreover, there was no difference in the incidence of delayed perforation, postoperative stenosis, and recurrence, but the incidence of delayed bleeding was significantly higher in the giant LST group than the small LST group ( P =0.001). Moreover, for giant rectal LSTs, the growth pattern of the lesion, JNET classification, and the extent of postoperative mucosal defect do not significantly affect the efficacy of ESD. It is worth mentioning that the operation time was longer in the group with a diameter >5 cm, in which perforation was more frequent and the muscle layer was more likely to be injured during ESD ( P <0.001). The muscle injury during ESD was mainly related to the diameter of the lesion, the crossing the rectal pouch, and the operation time. CONCLUSIONS: The use of ESD to treat giant rectal LSTs (>5 cm) is relatively difficult and can easily lead to intraoperative muscle injury, perforation, and late postoperative bleeding. However, if active intervention is performed, patients can still achieve good efficacy and prognosis, which can be applied in hospitals with certain conditions.

[Application of Bionano-DNA Full-Length Optical Mapping Technology in Genetic Diagnosis of Hemophilia A Carriers].

OBJECTIVE: To apply Bionano Saphyr visual full-length DNA optical mapping technology to the precise genetic diagnosis of hemophilia A carriers. METHODS: For 2 suspected F8 gene deficiency female carriers who could not be diagnosed by conventional next-generation sequencing technology, the full-length DNA optical mapping technology was used to detect and scan the sample X chromosome full-length visual haplotype characteristic map, which was compared with the normal haplotype. The gene structure variation information of the samples was obtained by compare with DNA atlas library. RESULTS: The average fluorescent marker length of the X chromosome DNA molecular where the F8 gene was located in the two samples was greater than 2.5 Mbp, and the average copy number was greater than 20×. After comparative analysis, one of the samples was a proximal inversion of intron 22 of the F8 gene, and another was an inversion of intron 22 accompanied by multiple deletions of large fragments. CONCLUSIONS: Bionano technology has a good detection rate for gene defects with large length and complex variation. In the absence of a proband or accurate genetic diagnosis results of the proband, the application of this technology to detect the heterozygous complex variant of the F8 gene is of great significance for the prenatal diagnosis and pre-pregnancy diagnosis of hemophilia carriers.

Magnifying image-enhanced endoscopy-only mode boosted early cancer diagnostic efficiency: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown. METHODS: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively. RESULTS: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively). CONCLUSIONS: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.).

Supramolecularly Engineered Reporters with Superoxide Anion-Triggered Chemiluminescence for Early Diagnosis and Efficient Amelioration of Acute Kidney Injury.

We report the "water-in-oil-in-water" preparation of kidney injury molecule-1-targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L-serine-modified poly(lactic-co-glycolic) acid (PLGA)-encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2 ⋅- , a biomarker of AKI, triggers the oxidation of CPPO to 1,2-dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L-serine-modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long-lived CL (half-lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non-invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI.

Fist Detection of Hb Suqian[ß42(CD1) Phe→Leu, HBB:c.129T > A] in Han Chinese.

We have identified a variant on the ß-globin gene in a Chinese female. Sequencing of the HBB gene revealed a Phe→Leu substitution at codon 42[ß42(CD1) Phe→Leu, HBB:c.129T > A] which has been named Hb Suqian for where the proband was born.

RUNX1 together with DAT mutations predicted poor outcome in acute myeloid leukemia.

We retrospectively explored the prognostic impact of DAT mutations at diagnosis in 122 RUNX1mut AML patients. RUNX1 missense mutation was dominant in the RUNT domain, and frameshift mutation was dominant in the TAD domain. DAT mutations occurred in 38.5% of RUNX1mut AML. After propensity score matching, DATpos patients had worse two-year relapse-free survival (RFS) than DATneg patients (p = .041). Moreover, RUNX1high (VAF ≥ 37.6%) patients showed poorer two-year overall survival (OS) and RFS than RUNX1low (VAF < 37.6%) patients (OS, p = .033; RFS, p = .027), especially in the RUNX1highDATpos group. Additionally, multivariate analysis confirmed that DAT mutations at diagnosis were an independent adverse factor for RFS. There were no significant differences in two-year OS and RFS between DATpos and DATneg patients or between RUNX1high and RUNX1low patients who undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Collectively, DAT mutations at diagnosis were adverse factors for RFS, and allo-HSCT could likely improve the poor outcomes of these patients.

Identification of variants in 94 Chinese patients with hereditary spherocytosis by next-generation sequencing.

Hereditary spherocytosis (HS) is the most common type of hereditary erythrocyte membrane disease and has varied phenotypic features and genetic patterns. We herein performed a retrospective study of 94 patients with HS and aimed to investigate the genetic variations and genotype-phenotype correlations using targeted next-generation sequencing. In 79/94 (84%) patients, 83 HS variants including 67 novel variants were identified. Pathogenic variants of SPTB, ANK1, SLC4A1, SPTA1, and EPB42 were found in 32/79(41%), 22/79(28%), 15/79 (19%), 8/79 (9%), and 3/79 (4%) of the patients respectively, revealing that SPTB is the most frequently mutated HS gene in Eastern China. Most SPTB and ANK1 gene variations were nonsense and frameshift variations. Missense variants were the main variant type of SLC4A1, SPTA1, and EPB42 genes. Interestingly, one SPTA1 variant (p. Arg1757Cys) showed an autosomal dominant inheritance pattern and one EPB42 variant (p. Gln377His) was apparent as a hotspot variation. Furthermore, genotype-phenotype analysis was performed among the five mutated gene groups. Besides the finding that patients with the SLC4A1 variant had the highest mean corpuscular hemoglobin levels, no clear correlations between genotype and phenotype were observed.

Single-cell transcriptomics provides insights into the origin and microenvironment of human oesophageal high-grade intraepithelial neoplasia.

BACKGROUND: High-grade intraepithelial neoplasia (HIN) is the precursor of oesophageal squamous cell carcinoma. The molecular and functional properties of HIN are determined by intrinsic origin cells and the extrinsic microenvironment. Yet, these factors are poorly understood. METHODS: We performed single-cell RNA sequencing of cells from HINs and adjacent tissues from the human oesophagus. We analysed the heterogeneity of basal layer cells and confirmed it using immunostaining. Aneuploid cells in HIN were studied using primary cell culture combined with karyotype analysis. We reconstructed the lineage relationship between tumour and normal populations based on transcriptome similarity. Integration analysis was applied to our epithelial data and published invasive cancer data, and results were confirmed by immunostaining and 3D organoid functional experiments. We also analysed the tumour microenvironment of HIN. RESULTS: The basal layer contained two cell populations: KRT15high STMN1low and KRT15high STMN1high cells, which were located mainly in the interpapillary and papillary zones, respectively. The KRT15high STMN1low population more closely resembled stem cells and transcriptome similarity revealed that HIN probably originated from these slow-cycling KRT15high STMN1low cells. 3D Organoid experiments and RNA-sequencing showed that basal-cell features and the differentiation ability of the normal epithelium were largely retained in HIN, but may change dramatically in tumour invasion stage. Moreover, the tumour microenvironment of HIN was characterised by both inflammation and immunosuppression. CONCLUSIONS: Our study provides a comprehensive single-cell transcriptome landscape of human oesophageal HIN. Our findings on the origin cells and unique microenvironment of HIN will allow for the development of strategies to block tumour progression and even prevent cancer initiation.

Endoscopic features of esophageal high-grade intraepithelial neoplasia dominated by cytological atypia.

Little is known about esophageal high-grade intraepithelial neoplasia dominated by cytological atypia (HGINc). We aimed to elucidate the endoscopic features of HGINc compared with esophageal high-grade intraepithelial neoplasia dominated by architectural atypia (HGINa). All patients pathologically diagnosed as esophageal high-grade intraepithelial neoplasia after endoscopic submucosal dissection at our center between January 2018 and December 2019 were included in this study. According to the pathological diagnosis, the patients were divided into two groups: HGINa group and HGINc group. Basic characteristics and endoscopic information were collected in detail. Data were analyzed statistically. Binary logistic regression was performed and a predictive model for HGINc was established. Then we evaluated its predictive value and built a nomogram for clinical application. A total of 175 patients were included in this study (126 with HGINa and 49 with HGINc). Among 228 lesions found in all patients, there were 148 HGINa and 80 HGINc. The independent relevant factors for HGINc were tobacco and alcohol usage, color, and gross type. To predict risk of HGINc, a three-factor model (TFM) was established with a highest area under curve (AUC) as 0.869 (95% CI, 0.852, 0.939). When the cut-off value was set as 0.3569184, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for HGINc was 81.14%, 88.75%, 77.03%, 67.62%, and 92.68%, respectively. HGINc differs greatly in endoscopic features from HGINa in our study. It's important to reduce misdiagnosis that our model was established with good predictive value for clinical application.

Effectiveness of Vitamin C Solution in Reducing Adverse Reactions Caused by Painless Lugol Chromoendoscopy: A Multicenter Randomized Controlled Trial.

GOAL: The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy. BACKGROUND: Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation. STUDY: In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa. RESULTS: VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW ( P <0.05). Regarding 0.5% LIS staining, VCS reduced the incidence of acute adverse reactions and heartburn within 1 week ( P <0.05). Both VCS and STS had similar effects. In addition, compared with spraying NS, VCS caused rapid decolorization of iodine-stained esophageal mucosa. After 120 seconds of deiodination, the color of the esophageal mucosa faded by 90%, which is similar to the results seen in the STS group. This contrasts with the results seen in the DW group, which showed fading by only 50.97% ( P <0.05). CONCLUSION: VCS can effectively reduce adverse reactions caused by different concentrations of LIS, indicating its important clinical application in the screening of superficial esophageal squamous cell carcinoma.

Dual-emission fluorescent silicon nanoparticle-based nanothermometer for ratiometric detection of intracellular temperature in living cells.

In this article, we present a kind of dual-emission fluorescent nanothermometer, which is made of europium (Eu3+)-doped silicon nanoparticles (Eu@SiNPs), allowing the detection of intracellular temperature in living cells with high accuracy. In particular, the presented SiNP-based thermometer features dual-emission fluorescence (blue (455 nm) and red (620 nm) emission), negligible toxicity (cell viability of treated cells remains above 90% during 24 h of treatment) and robust photostability in living cells (i.e., preserving >90% of fluorescence intensity after 45 min of continuous UV irradiation). More significantly, the fluorescence intensity of the Eu@SiNPs exhibits a linear ratiometric temperature response in a broad range from 25 to 70 °C. Taking advantage of these attractive merits, the Eu@SiNP-based nanothermometer is able to accurately (∼4.5% change per °C) determine dynamic changes in intracellular temperature in a quantitative and long-term (i.e., 30 min) manner.

Multifunctional Silicon-Carbon Nanohybrids Simultaneously Featuring Bright Fluorescence, High Antibacterial and Wound Healing Activity.

In this work, a class of multifunctional silicon-carbon nanohybrids (designated as SiCNs), which simultaneously possess aqueous dispersibility, bright fluorescence (photoluminescence quantum yield [PLQY]: ≈28%), as well as high antibacterial and wound healing activity, is presented. Taking advantage of these unique merits, cell distribution and pharmacological behavior of the SiCNs is first investigated through tracking their strong and stable fluorescence. The high bacteria inhibition ability (≈82.9% killing rate toward S. aureus) and hemostatic effects (shorten the bleeding time from ≈60 to ≈15 s) of the resultant SiCNs are then demonstrated. Moreover, the wound closure promotion activity (10% lead in wound contraction) is systematically demonstrated in vivo, which is especially suitable for wound healing applications. The results suggest the SiCNs as a new kind of high-performance multifunctional nanoagents suitable for various biological and biomedical utilizations.

Photostable and Biocompatible Fluorescent Silicon Nanoparticles-Based Theranostic Probes for Simultaneous Imaging and Treatment of Ocular Neovascularization.

Ocular neovascularization can result in devastating diseases that lead to marked vision impairment and eventual visual loss. In clinical implementation, neovascular eye diseases are first diagnosed by fluorescein angiography and then treated by multiple intravitreal injections, which nevertheless involves vision-threatening complications, as well as lack of real-time monitoring disease progression and timely assessment of therapeutic outcomes. To address this critical issue, we herein present a kind of theranostic agents made of peptide-functionalized silicon nanoparticles (SiNPs), suitable for simultaneous ocular neovascularization imaging and therapy. Typically, in addition to negligible toxicity and high specific binding ability to human retinal microvascular endothelial cells tube formation, the cyclo-(Arg-Gly-Asp-d-Tyr-Cys) ( c-(RGDyC))-conjugated SiNPs (SiNPs-RGD) features efficacious antiangiogenic ability in wound healing migration, transwell migration, transwell invasion, and tube formation assays. Taking advantage of these unique merits, we further employ the SiNPs-RGD for labeling angiogenic blood vessels and neovascularization suppression, demonstrating obvious inhibition of new blood vessels formation in mouse corneas. These results suggest the SiNPs-RGD as a novel class of high-quality theranostic probes is suitable for simultaneous diagnosis and treatment in ocular neovascular diseases.

Excitation-wavelength-dependent photoluminescence of silicon nanoparticles enabled by adjustment of surface ligands.

We herein present pioneering studies to reveal that excitation-wavelength-dependent photoluminescence properties of fluorescent silicon nanoparticles (SiNPs) can be realized by rationally designing surface ligands, i.e., several kinds of oxidized indole derivatives. The resultant ligand-decorated SiNPs exhibit strong fluorescence, with significant excitation-wavelength-dependent emissive shifting from ∼420 nm to ∼550 nm. Taking advantage of their unique optical merits, we further exploit the resultant ligand-decorated SiNPs as novel fluorescent labels for anti-counterfeiting and cell imaging.