Quantum Dots-caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome.

Quantum dots (QDs) are widely used, but their health impact on the visual system is little known. This study aims to elucidate the effects and mechanisms of typical metallic QDs on retinas using zebrafish. Comprehensive histology, imaging, and bulk RNA sequencing reveal that InP/ZnS QDs cause retinal degeneration. Furthermore, single-cell RNA-seq reveals a reduction in the number of retinal pigment epithelial cells (RPE) and short-wave cone UV photoreceptor cells (PR(UV)), accompanied by an increase in middle- and long-wave cone red, green, and blue photoreceptor cells [PR(RGB)]. Mechanistically, after endocytosis by RPE, InP/ZnS QDs inhibit the expression of splicing factor prpf8, resulting in gpx4b mRNA unsplicing, which finally decrease glutathione and induce ferroptosis and mitophagy. The decrease of RPE fails to engulf the damaged outer segments of PR, possibly promoting the differentiation of PR(UV) to PR(RGB). Knockout prpf8 or gpx4b with CRISPR/Cas9 system, the retinal damage is also observed. Whereas, overexpression of prpf8 or gpx4b, or supplement of glutathione can rescue the retinal degenerative damage caused by InP/ZnS QDs. In conclusion, this study illustrates the potential health risks of InP/ZnS QDs on eye development and provides valuable insights into the underlying mechanisms of InP/ZnS QDs-caused retinal degeneration.

Accidental ingestion of a fractured piece of orthodontic aligner: a case report.

BACKGROUND: Ingestion and aspiration of orthodontic devices are rare occurrences, typically associated with components such as expansion keys, archwire segments, dislodged fixed appliances (including brackets, buccal tubes, and bands), as well as fractured metal or plastic appliances. This article describes the clinical diagnosis and treatment process of a case of accidental ingestion of a fractured piece of orthodontic aligner. CASE PRESENTATION: A 31-year-old female under orthodontic treatment by aligners accidentally ingested a fractured piece of the aligner. The special difficulty of this case is that the transparent orthodontic aligner has a low radiopacity. At the beginning, no foreign body was found in the commonly used soft tissue window, causing difficulty in its location until greyscale was adjusted to lung window. The 2-centimeter fractured piece was taken out under anesthesia and endoscopic surgery. CONCLUSION: Materials with low radiopacity should be read with a lower grayscale range. Fractured orthodontic appliances with low retention force should not continue to be worn until consultation with attending doctor.

Hb Guigang [α90 (FG2)Lys→Asn; HBA1:c.273G˃T]: a Novel α-Globin Chain Variant.

BACKGROUND: New hemoglobin (Hb) variants are constantly being updated as assays are developed and the testing population expands. Here, we report a novel Hb variant, named Hb Guigang. METHODS: Hemoglobin (Hb) analysis was analyzed by capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). Glycated hemoglobin was performed by CE and HPLC. Routine genetic analysis was done with Gap-PCR and PCR-reverse dot-blot hybridization. The hemoglobin variant was identified by Sanger sequencing. RESULTS: CE of three cases showed the presence of Hb variants in Zone 5 and Zone 12, respectively. HPLC indicated an elevated P3 peak, suggesting the possible presence of the Hb variant. Hb A1c was measured by CE and HPLC, and the results were 6.7% and 4.76%, respectively. Sanger sequencing confirmed an AAG˃AAT mutation at codon 90 of the HBA1 gene. This mutation was reported for the first time, and we named it Hb Guigang based on the proband's place of residence. CONCLUSIONS: Hb Guigang with normal hematological parameters was separated and quantified by CE, whereas HPLC suggested that Hb Guigang co-eluted with the P3 peaks and could not be quantified.

Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity.

The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses.

Diagnostic Value of Ultrasound Endoscopy-Guided Fine-Needle Aspiration for Peritoneal Lesions.

Background: Peritoneal lesions present diagnostic challenges, necessitating precise imaging techniques. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) offers a promising approach for accurate diagnosis, aiding in optimal patient management and treatment planning. Objective: This study aims to assess the diagnostic efficacy of EUS-FNA in peritoneal lesions to offer insight in guiding optimal patient management. Methods: A prospective observational study was conducted, and a total of 58 patients who underwent EUS-FNA of the peritoneum at our hospital between October 2021 and November 2021 were included. The ultrasound diagnostic instrument facilitated puncture guidance, with 2-5 punctures performed in various parts of the selected peritoneal lesion areas. The analysis encompassed evaluating the sensitivity, specificity, positive predictive value, and negative predictive value of biopsy for diagnosing peritoneal-associated lesions, alongside assessing the number of punctures, puncture satisfaction, and incidence of postoperative complications. Results: The included patients undergoing EUS-FNA revealed that 41 (70.69%) had malignant lesions, while 17 (29.31%) presented with benign lesions. The diagnostic accuracy of EUS-FNA for peritoneal lesions was determined to be 94.83%, with a diagnostic sensitivity of 97.30% for malignant tumors, specificity of 90.48%, positive predictive value of 94.74%, and negative predictive value of 95%. Lesions exhibited a size range of 2.5cm × 2.9cm to 15.2cm × 9.8cm. Each patient underwent 2-5 punctures (3.3 ± 1.4), with a puncture satisfaction rate of 96.55%. The incidence of postoperative complications following EUS-FNA was found to be 3.45%. Conclusion: EUS-FNA exhibits substantial diagnostic utility for peritoneal-related lesions, marked by exceptional accuracy, sensitivity, specificity, and favorable safety. Its clinical adoption is warranted, promising improved patient care and management.

Two-stage convolutional neural network for segmentation and detection of carotid web on CT angiography.

BACKGROUND: Carotid web (CaW) is a risk factor for ischemic stroke, mainly in young patients with stroke of undetermined etiology. Its detection is challenging, especially among non-experienced physicians. METHODS: We included patients with CaW from six international trials and registries of patients with acute ischemic stroke. Identification and manual segmentations of CaW were performed by three trained radiologists. We designed a two-stage segmentation strategy based on a convolutional neural network (CNN). At the first stage, the two carotid arteries were segmented using a U-shaped CNN. At the second stage, the segmentation of the CaW was first confined to the vicinity of the carotid arteries. Then, the carotid bifurcation region was localized by the proposed carotid bifurcation localization algorithm followed by another U-shaped CNN. A volume threshold based on the derived CaW manual segmentation statistics was then used to determine whether or not CaW was present. RESULTS: We included 58 patients (median (IQR) age 59 (50-75) years, 60% women). The Dice similarity coefficient and 95th percentile Hausdorff distance between manually segmented CaW and the algorithm segmented CaW were 63.20±19.03% and 1.19±0.9 mm, respectively. Using a volume threshold of 5 mm3, binary classification detection metrics for CaW on a single artery were as follows: accuracy: 92.2% (95% CI 87.93% to 96.55%), precision: 94.83% (95% CI 88.68% to 100.00%), sensitivity: 90.16% (95% CI 82.16% to 96.97%), specificity: 94.55% (95% CI 88.0% to 100.0%), F1 measure: 0.9244 (95% CI 0.8679 to 0.9692), area under the curve: 0.9235 (95%CI 0.8726 to 0.9688). CONCLUSIONS: The proposed two-stage method enables reliable segmentation and detection of CaW from head and neck CT angiography.

An Unexpected Finding of Klinefelter Syndrome during Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) Genetic Analysis.

BACKGROUND: Klinefelter syndrome is a common sex chromosome abnormality in males, characterized by an extra X chromosome compared to normal males. Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked incomplete dominant defect disorder. In this study, we reported the unexpected detection of Klinefelter syndrome in a patient with G6PD. METHODS: G6PD enzyme activity was measured by immunoenzyme assay, and genetic analysis was performed using a fluorescent PCR melting curve method (PCR-melting curve). Sex chromosome number abnormalities were detected by multiplex ligation-dependent probe amplification (MLPA). The patient also underwent peripheral blood chromosome karyotype analysis. RESULTS: The patient's G6PD and 6PGD enzyme activities were 21.34 U/L and 22.85 U/L, respectively, and their ratio was below the reference range (0.93). The PCR-melting curve displayed a c.1388 heterozygous mutation in this boy, and the Sanger sequencing provided the same results. MLPA results suggested the presence of approxi-mately two copies of the X-chromosome in the boy. Finally, chromosome karyotype analysis confirmed that the boy had Klinefelter syndrome with a karyotype of 47, XXY. CONCLUSIONS: Klinefelter syndrome was accidentally detected during G6PD genetic analysis in a male. X-chromosomes can interfere with the results of G6PD genetic analysis and should be noted.

Asymptotic analysis on a new stochastic epidemic model involving isolation mechanism.

In this paper, a new stochastic epidemic model is established and the dynamical behavior of its solutions is studied for this model. A deterministic epidemic model (ordinary differential equation) is first proposed by considering the isolation mechanism, and the transmission probability function is determined by a Wells-Riley model method to analyze the transmission in the quarantine. For this deterministic model, the basic reproduction number R0 is computed and it is used to determine the existence of disease-free and positive equilibria. The linearized stability of the equilibria is also discussed by analyzing the distribution of eigenvalues of the linear system. Following that, a corresponding stochastic epidemic model is further established by introducing stochastic disturbance. Then, the extinction result of the model is derived also with the help of the basic reproduction number R0s. Furthermore, by applying the theory of Markov semigroups, it is proved that the densities of the distributions of the solutions can converge to an invariant density or sweeping under certain conditions. At last, some numerical simulations are provided and discussed to illustrate the practicability of the model and the obtained theoretical results.

Enhancer selectivity across cell types delineates three functionally distinct enhancer-promoter regulation patterns.

BACKGROUND: Multiple enhancers co-regulating the same gene is prevalent and plays a crucial role during development and disease. However, how multiple enhancers coordinate the same gene expression across various cell types remains largely unexplored at genome scale. RESULTS: We develop a computational approach that enables the quantitative assessment of enhancer specificity and selectivity across diverse cell types, leveraging enhancer-promoter (E-P) interactions data. We observe two well-known gene regulation patterns controlled by enhancer clusters, which regulate the same gene either in a limited number of cell types (Specific pattern, Spe) or in the majority of cell types (Conserved pattern, Con), both of which are enriched for super-enhancers (SEs). We identify a previously overlooked pattern (Variable pattern, Var) that multiple enhancers link to the same gene, but rarely coexist in the same cell type. These three patterns control the genes associating with distinct biological function and exhibit unique epigenetic features. Specifically, we discover a subset of Var patterns contains Shared enhancers with stable enhancer-promoter interactions in the majority of cell types, which might contribute to maintaining gene expression by recruiting abundant CTCF. CONCLUSIONS: Together, our findings reveal three distinct E-P regulation patterns across different cell types, providing insights into deciphering the complexity of gene transcriptional regulation.

PhosMap: An ensemble bioinformatic platform to empower interactive analysis of quantitative phosphoproteomics.

BACKGROUND: Liquid chromatography-mass spectrometry (LC-MS)-based quantitative phosphoproteomics has been widely used to detect thousands of protein phosphorylation modifications simultaneously from the biological specimens. However, the complicated procedures for analyzing phosphoproteomics data has become a bottleneck to widening its application. METHODS: Here, we develop PhosMap, a versatile and scalable tool to accomplish phosphoproteomics data analysis. A standardized phosphorylation data format was created for data analyses, from data preprocessing to downstream bioinformatic analyses such as dimension reduction, differential phosphorylation analysis, kinase activity, survival analysis, and so on. For better usability, we distribute PhosMap as a Docker image for easy local deployment upon any of Windows, Linux, and Mac system. RESULTS: The source code is deposited at https://github.com/BADD-XMU/PhosMap. A free PhosMap webserver (https://huggingface.co/spaces/Bio-Add/PhosMap), with easy-to-follow fashion of dashboards, is curated for interactive data analysis. CONCLUSIONS: PhosMap fills the technical gap of large-scale phosphorylation research by empowering researchers to process their own phosphoproteomics data expediently and efficiently, and facilitates better data interpretation.

Epigenome-augmented eQTL-hotspots reveal genome-wide transcriptional programs in 36 human tissues.

Expression quantitative trait loci (eQTLs) are used to inform the mechanisms of transcriptional regulation in eukaryotic cells. However, the specificity of genome-wide eQTL identification is limited by stringent control for false discoveries. Here, we described a method based on the non-homogeneous Poisson process to identify 125 489 regions with highly frequent, multiple eQTL associations, or 'eQTL-hotspots', from the public database of 59 human tissues or cell types. We stratified the eQTL-hotspots into two classes with their distinct sequence and epigenomic characteristics. Based on these classifications, we developed a machine-learning model, E-SpotFinder, for augmented discovery of tissue- or cell-type-specific eQTL-hotspots. We applied this model to 36 tissues or cell types. Using augmented eQTL-hotspots, we recovered 655 402 eSNPs and reconstructed a comprehensive regulatory network of 2 725 380 cis-interactions among eQTL-hotspots. We further identified 52 012 modules representing transcriptional programs with unique functional backgrounds. In summary, our study provided a framework of epigenome-augmented eQTL analysis and thereby constructed comprehensive genome-wide networks of cis-regulations across diverse human tissues or cell types.

The application of plasma technology for the preparation of supercapacitor electrode materials.

With the rapidly growing demand for clean energy and energy interconnection, there is an urgent need for rapid and high-capacity energy storage technologies to realize large-scale energy storage, transfer energy, and establish the energy internet. Supercapacitors, which have advantages such as high specific capacitance, fast charging and discharging rates, and long cycle lifetimes, are being widely used in electric vehicles, information technology, aerospace, and other fields. The performance of supercapacitors is crucially dependent on electrode materials. These can be categorized into electric double-layer capacitors and pseudocapacitors, primarily made from carbon and transition metal oxides, respectively. However, effectively monitoring the physicochemical properties of electrode materials during preparation and processing is challenging, which limits the improvement of supercapacitors' performance. Plasma materials preparation technology can effectively affect the materials preparation processing by energetic electrons, ions, free radicals, and multiple effects in plasma, which are easily manipulated by operation parameters. Therefore, plasma material preparation technology is considered a promising method to precisely monitor the physicochemical and electrochemical properties of energy storage materials and has been widely studied. This paper provides an overview of plasma materials preparation mechanisms, and details of the plasma technology application in the preparation of transition metal hybrids, carbon, and composite electrode materials, as well as a comparison with traditional methods. In conclusion, the advantages, challenges, and research directions of plasma materials preparation technology in the field of electrode materials preparation are summarized.

SIMarker: Cellular similarity detection and its application to diagnosis and prognosis of liver cancer.

BACKGROUND: The emergence of single-cell technology offers a unique opportunity to explore cellular similarity and heterogeneity between precancerous diseases and solid tumors. However, there is lacking a systematic study for identifying and characterizing similarities at single-cell resolution. METHODS: We developed SIMarker, a computational framework to detect cellular similarities between precancerous diseases and solid tumors based on gene expression at single-cell resolution. Taking hepatocellular carcinoma (HCC) as a case study, we quantified the cellular and molecular connections between HCC and cirrhosis. Core analysis modules of SIMarker is publicly available at https://github.com/xmuhuanglab/SIMarker ("SIM" means "similarity" and "Marker" means "biomarkers). RESULTS: We found PGA5+ hepatocytes in HCC showed cirrhosis-like characteristics, including similar transcriptional programs and gene regulatory networks. Consequently, the genes constituting the gene expression program of these cirrhosis-like subpopulations were designated as cirrhosis-like signatures (CLS). Strikingly, our utilization of CLS enabled the development of diagnosis and prognosis biomarkers based on within-sample relative expression orderings of gene pairs. These biomarkers achieved high precision and concordance compared with previous studies. CONCLUSIONS: Our work provides a systematic method to investigate the clinical translational significance of cellular similarities between HCC and cirrhosis, which opens avenues for identifying similar paradigms in other categories of cancers and diseases.

Unveiling the Role of Ge in CZTSSe Solar Cells by Advanced Micro-To-Atom Scale Characterizations.

Kesterite is an earth-abundant energy material with high predicted power conversion efficiency, making it a sustainable and promising option for photovoltaics. However, a large open circuit voltage Voc deficit due to non-radiative recombination at intrinsic defects remains a major hurdle, limiting device performance. Incorporating Ge into the kesterite structure emerges as an effective approach for enhancing performance by manipulating defects and morphology. Herein, how different amounts of Ge affect the kesterite growth pathways through the combination of advanced microscopy characterization techniques are systematically investigated. The results demonstrate the significance of incorporating Ge during the selenization process of the CZTSSe thin film. At high temperature, the Ge incorporation effectively delays the selenization process due to the formation of a ZnSe layer on top of the metal alloys through decomposition of the Cu-Zn alloy and formation of Cu-Sn alloy, subsequently forming of Cu-Sn-Se phase. Such an effect is compounded by more Ge incorporation that further postpones kesterite formation. Furthermore, introducing Ge mitigates detrimental "horizontal" grain boundaries by increasing the grain size on upper layer. The Ge incorporation strategy discussed in this study holds great promise for improving device performance and grain quality in CZTSSe and other polycrystalline chalcogenide solar cells.

PI3K/Akt signaling pathway mediates the effect of low-dose boron on barrier function, proliferation and apoptosis in rat intestinal epithelial cells.

Boron is an essential trace element with roles in growth, development, and physiological functions; however, its mechanism of action is still unclear. In this study, the regulatory roles of the PI3K/Akt signaling pathway on boron-induced changes in barrier function, proliferation, and apoptosis in rat intestinal epithelial cells were evaluated. Occludin levels, the proportion of cells in the G2/M phase, cell proliferation rate, and mRNA and protein expression levels of PCNA were higher, while the proportions of cells in the G0/G1 and S phases, apoptosis rate, and caspase-3 mRNA and protein expression levels were lower in cells treated with 0.8 mmol/L boron than in control IEC-6 cells (P < 0.01 or P < 0.05). However, 40 mmol/L boron decreased ZO-1 and Occludin levels, the proportion of cells in the G2/M phase, cell proliferation rate, and mRNA and protein levels of PCNA and increased the apoptosis rate and caspase-3 mRNA expression (P < 0.01 or P < 0.05). After specifically blocking PI3K and Akt signals (using LY294002 and MK-2206 2HCL), 0.8 mmol/L boron had no effects on Occludin, PCNA level, apoptosis rates, and caspase-3 levels (P < 0.05); however, the proliferation rate and PCNA levels decreased significantly (P < 0.01 or P < 0.05). The addition of 40 mmol/L boron did not affect ZO-1 and Occludin levels and did not affect the apoptosis rate or PCNA and caspase-3 levels. These results suggested that the PI3K/Akt signaling pathway mediates the effects of low-dose boron on IEC-6 cells.

Cd-Free Pure Sulfide Kesterite Cu2 ZnSnS4 Solar Cell with Over 800 mV Open-Circuit Voltage Enabled by Phase Evolution Intervention.

The Cd-free Cu2 ZnSnS4 (CZTS) solar cell is an ideal candidate for producing low-cost clean energy through green materials owing to its inherent environmental friendliness and earth abundance. Nevertheless, sulfide CZTS has long suffered from severe open-circuit voltage (VOC ) deficits, limiting the full exploitation of performance potential and further progress. Here, an effective strategy is proposed to alleviate the nonradiative VOC loss by manipulating the phase evolution during the critical kesterite phase formation stage. With a Ge cap layer on the precursor, premature CZTS grain formation is suppressed at low temperatures, leading to fewer nucleation centers at the initial crystallization stage. Consequently, the CZTS grain formation and crystallization are deferred to high temperatures, resulting in enhanced grain interior quality and less unfavorable grain boundaries in the final film. As a result, a champion efficiency of 10.7% for Cd-free CZTS solar cells with remarkably high VOC beyond 800 mV (63.2% Schockley-Queisser limit) is realized, indicating that nonradiative recombination is effectively inhibited. This strategy may advance other compound semiconductors seeking high-quality crystallization.

CovidShiny: An Integrated Web Tool for SARS-CoV-2 Mutation Profiling and Molecular Diagnosis Assay Evaluation In Silico.

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuing to evolve and accumulate mutations. While various bioinformatics tools have been developed for SARS-CoV-2, a well-curated mutation-tracking database integrated with in silico evaluation for molecular diagnostic assays is currently unavailable. To address this, we introduce CovidShiny, a web tool that integrates mutation profiling, in silico evaluation, and data download capabilities for genomic sequence-based SARS-CoV-2 assays and data download. It offers a feasible framework for surveilling the mutation of SARS-CoV-2 and evaluating the coverage of the molecular diagnostic assay for SARS-CoV-2. With CovidShiny, we examined the dynamic mutation pattern of SARS-CoV-2 and evaluated the coverage of commonly used assays on a large scale. Based on our in silico analysis, we stress the importance of using multiple target molecular diagnostic assays for SARS-CoV-2 to avoid potential false-negative results caused by viral mutations. Overall, CovidShiny is a valuable tool for SARS-CoV-2 mutation surveillance and in silico assay design and evaluation.