Tiny pH-Resolved DNA Nanospheres for Cellular Pyroptosis or Apoptosis Regulation.

The design and synthesis of nanomedicines capable of regulating programmed cell death patterns to enhance antitumor efficacy remain significant challenges in cancer therapy. In this study, we developed intelligent DNA nanospheres (NS) capable of distinguishing tiny pH changes between different endosomal compartments to regulate pyroptosis or apoptosis. These NS are self-assembled from two multifunctional DNA modules, enabling tumor targeting, acid-responsive disassembly, and photodynamic therapy (PDT) activation. By modifying the embedded i-motif sequence, the NS can be activated in early endosomes (EE) or lysosomes (Ly), producing singlet oxygen (1O2) at specific locations under laser irradiation. Our results demonstrate that EE-activated PDT induces gasdermin-E-mediated pyroptosis in tumor cells, enhancing antitumor efficacy and reducing systemic toxicity compared to Ly-activated apoptosis. This study offers new insights into the design of endosome-activated nanomedicines, advancing the biomedical applications of targeted cancer therapy.

Oxygen extraction fraction mapping based combining quantitative susceptibility mapping and quantitative blood oxygenation level-dependent imaging model using multi-delay PCASL.

BACKGROUND AND PURPOSE: The oxygen extraction fraction is an essential biomarker for the assessment of brain metabolism. A recently proposed method combined with quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude enables noninvasive mapping of the oxygen extraction fraction. Our study investigated the oxygen extraction fraction mapping variations of single-delay and multi-delay arterial spin-labeling. MATERIALS AND METHODS: A total of twenty healthy participants were enrolled. The multi-echo spoiled gradient-echo, multi-delay arterial spin-labeling, and magnetization-prepared rapid gradient echo sequences were acquired at 3.0 T. The mean oxygen extraction fraction was generated under a single delay time of 1780 ms, multi-delay arterial spin-labeling of transit-corrected cerebral blood flow, and multi-delay arterial spin-labeling of arterial cerebral blood volume. The results were compared via paired t tests and the Wilcoxon test. Linear regression analyses were used to investigate the relationships among the oxygen extraction fraction, cerebral blood flow, and venous cerebral blood volume. RESULTS: The oxygen extraction fraction estimate with multi-delay arterial spin-labeling yielded a significantly lower value than that with single-delay arterial spin-labeling. The average values for the whole brain under single-delay arterial spin-labeling, multi-delay arterial spin-labeling of transit-corrected cerebral blood flow, and multi-delay arterial spin-labeling of arterial cerebral blood volume were 41.5 ± 1.7 % (P < 0.05), 41.3 ± 1.9 % (P < 0.001), and 40.9 ± 1.9 % (N = 20), respectively. The oxygen extraction fraction also showed a significant inverse correlation with the venous cerebral blood volume under steady-state conditions when multi-delay arterial spin-labeling was used (r = 0.5834, p = 0.0069). CONCLUSION: These findings suggest that the oxygen extraction fraction is significantly impacted by the arterial spin-labeling methods used in the quantitative susceptibility mapping plus the quantitative blood oxygen level-dependent model, indicating that the differences should be accounted for when employing oxygen extraction fraction mapping based on this model in diseases.

m6A-driven NAT10 translation facilitates fatty acid metabolic rewiring to suppress ferroptosis and promote ovarian tumorigenesis through enhancing ACOT7 mRNA acetylation.

RNA epigenetic modifications have been implicated in cancer progression. However, the interplay between distinct RNA modifications and its role in cancer metabolism remain largely unexplored. Our study demonstrates that N-acetyltransferase 10 (NAT10) is notably upregulated in ovarian cancer (OC), correlating with poor patient prognosis. IGF2BP1 enhances the translation of NAT10 mRNA in an m6A-dependent manner in OC cells. NAT10 drives tumorigenesis by mediating N4-acetylcytidine (ac4C) modification of ACOT7 mRNA, thereby augmenting its stability and translation. This NAT10-ACOT7 axis modulates fatty acid metabolism in cancer cells and promotes tumor progression by suppressing ferroptosis. Additionally, our research identifies fludarabine as a small molecule inhibitor targeting NAT10, inhibits the ac4C modification and expression of ACOT7 mRNA. By using cell derived xenograft model and patient derived organoid model, we show that fludarabine effectively suppresses ovarian tumorigenesis. Overall, our study highlights the pivotal role of the NAT10-ACOT7 axis in the malignant cancer progression, underscoring the potential of targeting NAT10-mediated ac4C modification as a viable therapeutic strategy for this disease.

Evaluation of laparo-endoscopic single-site surgery for adnexal mass in pregnant women.

BACKGROUND: Surgery for adnexal mass does occur in pregnant women and therefore the choice of surgery during pregnancy needs to be carefully considered and studied. This study aimed to evaluate the safety and feasibility of Laparo-endoscopic Single-site Surgery (LESS) for adnexal mass during pregnancy and investigate the perioperative condition, pregnancy complications, and obstetric outcomes of operative women during pregnancy. METHODS: This study retrospectively collected medical records and surgery videos of 20 pregnant women who underwent LESS for adnexal mass between November 2019 and January 2022. Baseline characteristics, operative-related variables, and pregnancy outcomes were followed up. RESULTS: LESS for adnexal mass was successfully performed in 20 pregnant women, with very satisfactory surgery outcomes reported in all cases. The average gestational age at operation was 15+2 weeks (range, 5+1- 25+4 weeks). The median operative time was 80.8 min (range, 40 -185 min) and the average operative bleeding was 28.0 ml (range, 10-50 ml). The average VAS of 24 h postoperatively was 1 (range, 0-2), and the average length of hospital stay was 5.15 days (range, 3-7 days). All these women delivered a healthy newborn at full term except 1 woman induced abortion for her own reasons at 16+5 weeks gestational age (GA). The average GA of delivery was 39+1 weeks (range, 37-40+1 weeks), the average birth weight was 3228.95 g (range, 2740-3930 g), and the average Apgar score at 5 min was 9.95 (range, 9-10). CONCLUSIONS: LESS for adnexal mass is safe and feasible for pregnant women.

Ultrafast near-infrared pyroelectric detector based on inhomogeneous plasmonic metasurface.

Pyroelectric (PE) detection technologies have attracted extensive attention due to the cooling-free, bias-free, and broadband properties. However, the PE signals are generated by the continuous energy conversion processes from light, heat, to electricity, normally leading to very slow response speeds. Herein, we design and fabricate a PE detector which shows extremely fast response in near-infrared (NIR) band by combining with the inhomogeneous plasmonic metasurface. The plasmonic effect dramatically accelerates the light-heat conversion process, unprecedentedly improving the NIR response speed by 2-4 orders of magnitude to 22 µs, faster than any reported infrared (IR) PE detector. We also innovatively introduce the concept of time resolution into the field of PE detection, which represents the detector's ability to distinguish multiple fast-moving targets. Furthermore, the spatially inhomogeneous design overcomes the traditional narrowband constraint of plasmonic systems and thus ensures a wideband response from visible to NIR. This study provides a promising approach to develop next-generation IR PE detectors with ultrafast and broadband responses.

Presaccadic preview shapes postsaccadic processing more where perception is poor.

The presaccadic preview of a peripheral target enhances the efficiency of its postsaccadic processing, termed the extrafoveal preview effect. Peripheral visual performance-and thus the quality of the preview-varies around the visual field, even at isoeccentric locations: It is better along the horizontal than vertical meridian and along the lower than upper vertical meridian. To investigate whether these polar angle asymmetries influence the preview effect, we asked human participants to preview four tilted gratings at the cardinals, until a central cue indicated which one to saccade to. During the saccade, the target orientation either remained or slightly changed (valid/invalid preview). After saccade landing, participants discriminated the orientation of the (briefly presented) second grating. Stimulus contrast was titrated with adaptive staircases to assess visual performance. Expectedly, valid previews increased participants' postsaccadic contrast sensitivity. This preview benefit, however, was inversely related to polar angle perceptual asymmetries; largest at the upper, and smallest at the horizontal meridian. This finding reveals that the visual system compensates for peripheral asymmetries when integrating information across saccades, by selectively assigning higher weights to the less-well perceived preview information. Our study supports the recent line of evidence showing that perceptual dynamics around saccades vary with eye movement direction.

Eat, Sleep, Console model for neonatal opioid withdrawal syndrome: a meta-analysis.

Background: The rising incidence of drug abuse among pregnant women has rendered neonatal opioid withdrawal syndrome a significant global health concern. Methods: Databases including PubMed, Web of Science, the Cochrane Library, Embase, Elton B. Stephens. Company (EBSCO), China National Knowledge Infrastructure (CNKI), and Wanfang were searched for comparative studies of the Eat, Sleep, Console model vs. traditional assessment tools for neonatal opioid withdrawal syndrome. Two reviewers conducted literature searches, screened according to the inclusion criteria, extracted data, and independently verified accuracy. All meta-analyses were conducted using Review Manager Version 5.4. Results: In total, 18 studies involving 4,639 neonates were included in the meta-analysis. The Eat, Sleep, Console model demonstrated superior outcomes in assessing neonatal opioid withdrawal syndrome, significantly reducing the need for pharmacological treatment [risk ratio = 0.44, 95% confidence interval (CI) = 0.34-0.56, P < 0.001], decreasing the length of hospital stay [standard mean difference (SMD) = -2.10, 95% CI = -3.43 to -0.78, P = 0.002], and shortening the duration of opioid treatment (SMD = -1.33, 95% CI = -2.22 to -0.45, P = 0.003) compared to the Finnegan Neonatal Abstinence Scoring System. Conclusions: The Eat, Sleep, Console model is more effective than the Finnegan Neonatal Abstinence Scoring System in improving the assessment and management of neonatal opioid withdrawal syndrome.

Grifola frondosa polysaccharide's therapeutic potential in oxazolone-induced ulcerative colitis.

Grifola frondosa polysaccharide (GFP) is a consumable fungus recognized for its potential health advantages. The present study aimed to investigate the development and potential etiologies of ulcerative colitis (UC) utilizing oxazolone (OXZ) as an inducer in mice, along with assessing the therapeutic effects of GFP at varying doses in UC mice, with sulfasalazine (SASP) serving as the positive control. The obtained results indicated that OXZ intervention in mice induced numerous physical manifestations of UC, including increased disease activity index (DAI), decreased goblet cell division, enhanced fibrosis, reduced expression of Claudin1 and Zona encludens protein1 (ZO-1), decreased proliferative activity of colonic mucosal epithelial cells, disturbed oxidation balance, and alterations in intestinal flora. Nonetheless, GFP intervention significantly ameliorated or even resolved these abnormal indicators to a considerable extent. Consequently, this study suggests that GFP might serve as a prebiotic to regulate intestinal flora, mitigate enterotoxin production, restore oxidative balance, thereby reducing the generation of inflammatory mediators, restoring the intestinal barrier, and ultimately improving OXZ-induced UC in mice. GFP demonstrates promising potential as a candidate drug for colitis treatment and as a dietary supplement for alleviating intestinal inflammatory issues.

RetroCaptioner: beyond attention in end-to-end retrosynthesis transformer via contrastively captioned learnable graph representation.

MOTIVATION: Retrosynthesis identifies available precursor molecules for various and novel compounds. With the advancements and practicality of language models, Transformer-based models have increasingly been used to automate this process. However, many existing methods struggle to efficiently capture reaction transformation information, limiting the accuracy and applicability of their predictions. RESULTS: We introduce RetroCaptioner, an advanced end-to-end, Transformer-based framework featuring a Contrastive Reaction Center Captioner. This captioner guides the training of dual-view attention models using a contrastive learning approach. It leverages learned molecular graph representations to capture chemically plausible constraints within a single-step learning process. We integrate the single-encoder, dual-encoder, and encoder-decoder paradigms to effectively fuse information from the sequence and graph representations of molecules. This involves modifying the Transformer encoder into a uni-view sequence encoder and a dual-view module. Furthermore, we enhance the captioning of atomic correspondence between SMILES and graphs. Our proposed method, RetroCaptioner, achieved outstanding performance with 67.2% in top-1 and 93.4% in top-10 exact matched accuracy on the USPTO-50k dataset, alongside an exceptional SMILES validity score of 99.4%. In addition, RetroCaptioner has demonstrated its reliability in generating synthetic routes for the drug protokylol. AVAILABILITY AND IMPLEMENTATION: The code and data are available at https://github.com/guofei-tju/RetroCaptioner.

NCS-Mediated Direct C(sp3)-H Oxygenation of 2-Methylindoles Using Water as the Oxygen Source.

In continuation of our research interest in the green oxidation of indoles, we further explore the direct oxidation of 2-methylindoles to 2-formyl indoles promoted by NCS and associated with H2O as the oxygen source. This methodology was demonstrated to be a robust protocol consisting of chlorination, SN2', and oxidation processes, and presents a reasonably broad substrate scope and excellent functional group tolerance, thus enabling the preparation of high added-value versatile building blocks susceptible to further functionalization.

Analysis of Clinical Isolation Characteristics of Nontuberculous Mycobacteria and Drug Sensitivity of Rapidly Growing Mycobacteria in the General Hospital of Guangzhou, China.

Purpose: The clinical distribution characteristics of nontuberculous mycobacteria (NTM) in general hospital were explored to guide the clinical diagnosis and treatment of NTM infection. Methods: Samples with positive mycobacterium culture in the First Affiliated Hospital of Guangzhou Medical University were collected and identified through PCR. Phenotypic drug sensitivity experiments were conducted on 44 Mycobacteroides abscessus isolated from clinical departments with broth microdilution method, and rrl, rrs and erm (41) genes associated with drug resistance were detected. Results: From September 2020 to July 2023, 314 mycobacterium-positive isolates were separated from patients in the First Affiliated Hospital of Guangzhou Medical University, with 147 (46.8%) NTM isolates were included in our study. The samples were respiratory tract specimens mainly, with 64% bronchoalveolar lavage fluid. Of 144 cases identified, samples were from 133 patients (60 males and 73 females; gender ratio of 0.82:1). NTM was mainly isolated from the people aged 40 and above, especially females (χ2 = 10.688, P = 0.014). M. abscessus (61, 42.36%), M. intracellulare (35, 24.31%) were the two most NTMs in this hospital. Clinical strains of M. abscessus exhibited high resistance to antibiotics, except for cefoxitin (31.8%), linezolid (25.0%), amikacin (0%), and clarithromycin (18.2%). Among 8 strains of M. abscessus with clarithromycin acquired resistance, just 4 strains (50.0%) showed mutations (A2270G, A2271G) in rrl gene, but a new mutation (C2750T) was detected in 1 strain. Among 14 strains of M. abscessus with clarithromycin-induced resistance, 13 (93.0%) strains had T28 erm (41) gene and 1 (7.0%) strain had C28 erm (41) gene. Conclusion: M. avium-intracellulare complex was gradually becoming predominant strain in Guangzhou area. The resistant situation of M. abscessus in general hospital had shown severe. Potential mutation in rrl gene associated with clarithromycin acquired resistance of M. abscessus were found, but drug-resistant mechanism remained unclear.

Fabrication of multifunctional hybrid pigment for color cosmetics based on chitosan-modified palygorskite and sappanwood extract.

Consumer perception and market demand have driven the replacement of synthetic colorants with naturally derived alternatives in the cosmetic industry. This study describes a facile way to prepare durable inorganic-organic hybrid pigment with advanced biocompatibility, antibacterial and hydrophobic properties tailored for color cosmetics by initial modification of palygorskite with chitosan to anchor sappanwood dye extract and subsequently coating with amino-modified silicone oil (ASO). The hybrid pigments were characterized by transmittance electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and the Brunauer-Emmett-Teller method. The results indicated that the sappanwood dye was loaded on chitosan-modified palygorskite via hydrogen bonding and electrostatic interaction. Furthermore, the chitosan-palygorskite/sappanwood hybrid pigment exhibited enhanced biocompatibility and color stability on exposure to different heating temperatures and UVA radiation after subsequent hydrophobic modification with amino-modified silicone oil. Moreover, facial foundation cosmetics based on the chitosan-palygorskite/sappanwood@ASO composites exhibited excellent brightening and skin color corrective effect on human volunteers without any adverse response. And no significant difference was observed in 12 out of 14 sensory evaluation indexes in the comparison of this hybrid pigment-based makeup with two commercially available products. This study provides a new route to stabilize natural botanical colorant for cosmetic use by chitosan-modified clay minerals.

The AI revolution in glaucoma: Bridging challenges with opportunities.

Recent advancements in artificial intelligence (AI) herald transformative potentials for reshaping glaucoma clinical management, improving screening efficacy, sharpening diagnosis precision, and refining the detection of disease progression. However, incorporating AI into healthcare usages faces significant hurdles in terms of developing algorithms and putting them into practice. When creating algorithms, issues arise due to the intensive effort required to label data, inconsistent diagnostic standards, and a lack of thorough testing, which often limits the algorithms' widespread applicability. Additionally, the "black box" nature of AI algorithms may cause doctors to be wary or skeptical. When it comes to using these tools, challenges include dealing with lower-quality images in real situations and the systems' limited ability to work well with diverse ethnic groups and different diagnostic equipment. Looking ahead, new developments aim to protect data privacy through federated learning paradigms, improving algorithm generalizability by diversifying input data modalities, and augmenting datasets with synthetic imagery. The integration of smartphones appears promising for using AI algorithms in both clinical and non-clinical settings. Furthermore, bringing in large language models (LLMs) to act as interactive tool in medicine may signify a significant change in how healthcare will be delivered in the future. By navigating through these challenges and leveraging on these as opportunities, the field of glaucoma AI will not only have improved algorithmic accuracy and optimized data integration but also a paradigmatic shift towards enhanced clinical acceptance and a transformative improvement in glaucoma care.

A gene regulatory network-aware graph learning method for cell identity annotation in single-cell RNA-seq data.

Cell identity annotation for single-cell transcriptome data is a crucial process for constructing cell atlases, unraveling pathogenesis, and inspiring therapeutic approaches. Currently, the efficacy of existing methodologies is contingent upon specific data sets. Nevertheless, such data are often sourced from various batches, sequencing technologies, tissues, and even species. Notably, the gene regulatory relationship remains unaffected by the aforementioned factors, highlighting the extensive gene interactions within organisms. Therefore, we propose scHGR, an automated annotation tool designed to leverage gene regulatory relationships in constructing gene-mediated cell communication graphs for single-cell transcriptome data. This strategy helps reduce noise from diverse data sources while establishing distant cellular connections, yielding valuable biological insights. Experiments involving 22 scenarios demonstrate that scHGR precisely and consistently annotates cell identities, benchmarked against state-of-the-art methods. Crucially, scHGR uncovers novel subtypes within peripheral blood mononuclear cells, specifically from CD4+ T cells and cytotoxic T cells. Furthermore, by characterizing a cell atlas comprising 56 cell types for COVID-19 patients, scHGR identifies vital factors like IL1 and calcium ions, offering insights for targeted therapeutic interventions.

Progression Patterns and Risk Factors of Axial Elongation in Young Adults With Nonpathologic High Myopia: Three-Year Large Longitudinal Cohort Follow-Up.

PURPOSE: To investigate the progression patterns and risk factors of axial elongation in young adults with nonpathologic high myopia. DESIGN: Prospective, clinical observational cohort study with 2- to 4-year follow-up. METHODS: A total of 1043 eyes of 563 participants (3515 medical records) aged 18 to 50 years with nonpathologic high myopia (axial length [AL] ≥ 26 mm; myopic maculopathy < diffuse chorioretinal atrophy; without posterior staphyloma) were included from 1546 participants (6318 medical records). Annual axial elongation was calculated via linear mixed-effect models. The associated risk factors of axial elongation were determined by ordinal logistic regression analysis, with generalized estimate equations for eliminating an interocular correlation bias. RESULTS: Based on 5359 times of AL measurements, the annual axial elongation of participants (mean [SD] age 31.39 [9.22] years) was 0.03 mm/year (95% confidence interval [CI], 0.03-0.04; P < .001) during a 30.23 (6.06) months' follow-up. Severe (>0.1 mm/year), moderate (0.05-0.09 mm/year), mild (0-0.049 mm/year), and nil (≤0 mm/year) elongation was observed in 122 (11.7%), 211 (20.2%), 417 (40.0%), and 293 (28.1%) eyes. The following risk factors were significantly associated with axial elongation: baseline AL ≥ 28 mm (odds ratio [OR], 4.23; 95% CI, 2.95-6.06; P < .001); age < 40 years (OR, 1.64; 95% CI, 1.18-2.28; P = .003); axial asymmetry (OR, 2.04; 95% CI, 1.26-3.29; P = .003), and women (OR, 1.52; 95% CI, 1.13-2.2.05; P = .006). Using antiglaucoma medications was a protective factor (OR, 0.46; 95% CI, 0.27-0.79; P = .005), which slowed 75% of axial elongation from 0.04 (0.06) to 0.01 (0.06) mm/y (P < .001). CONCLUSIONS: Axial elongation continued in young adults with nonpathologic myopia. Risk factors included longer baseline AL and axial asymmetry, younger age, and woman. Topical use of antiglaucoma medications may be useful to reduce ongoing axial elongation.

Safety and efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial.

Background: Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods: A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings: No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation: hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding: National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

Identification of CGNL1 as a diagnostic marker in fibroblasts of diabetic foot ulcers: Insights from single cell RNA sequencing and bulk sequencing data.

OBJECTIVES: This study aimed to explore the unique transcriptional feature of fibroblasts subtypes and the role of ferroptosis in diabetic foot ulcers (DFUs). METHODS: The GEO (Gene Expression Omnibus) was searched to obtain the DFUs single-cell and transcriptional datasets. After identifying cell types by classic marker genes, the integrated single-cell dataset was used to run trajectory inference, RNA velocity, and ligand-receptor interaction analysis. Next, bulk RNA-seq datasets of DFUs were analyzed to the key ferroptosis genes. RESULTS: Here, we profile 83529 single transcriptomes from the foot samples utilizing single-cell sequencing (scRNA-seq) data of DFU from GEO database and identified 12 cell types, with fibroblasts exhibiting elevated levels of ferroptosis activity and substantial cellular heterogeneity. Our results defined six main fibroblast subsets that showed mesenchymal, secretory-reticular, secretory-papillary, pro-inflammatory, myogenesis, and healing-enriched functional annotations. Trajectory inference and cell-cell communication analysis revealed two major cell fates with subpopulations of fibroblasts and altered ligand-receptor interactions. Bulk RNA sequencing data identified CGNL1 as a distinctive diagnostic signature in fibroblasts. Notably, CGNL1 positively correlated with pro-inflammatory fibroblasts. CONCLUSIONS: Overall, our analysis delineated the heterogeneity present in cell populations of DFUs, showing distinct fibroblast subtypes characterized by their own unique transcriptional features and enrichment functions. Our study will help us better understand DFUs pathogenesis and identifies CGNL1 as a potential target for DFUs therapies.

Single-cell RNA sequencing and cell-cell communication analysis reveal tumor microenvironment associated with chemotherapy responsiveness in ovarian cancer.

BACKGROUND: To investigate the impact of the tumor microenvironment (TME) on the responsiveness to chemotherapy in ovarian cancer (OV). METHODS: We integrated single cell RNA-seq datasets of OV containing chemo-response information, and characterize their clusters based on different TME sections. We focus on analyzing cell-cell communication to elaborate on the mechanisms by which different components of the TME directly influence the chemo-response of tumor cells. RESULTS: scRNA-seq datasets were annotated according to specific markers for different cell types. Differential analysis of malignant epithelial cells revealed that chemoresistance was associated with the TME. Notably, distinct TME components exhibited varying effects on chemoresistance. Enriched SPP1+ tumor-associated macrophages in chemo-resistant patients could promote chemoresistance through SPP1 binding to CD44 on tumor cells. Additionally, the overexpression of THBS2 in stromal cells could promote chemoresistance through binding with CD47 on tumor cells. In contrast, GZMA in the lymphocytes could downregulate the expression of PARD3 through direct interaction with PARD3, thereby attenuating chemoresistance in tumor cells. CONCLUSION: Our study indicates that the non-tumor cell components of the TME (e.g. SPP1+ TAMs, stromal cells and lymphocytes) can directly impact the chemo-response of OV and targeting the TME was potentially crucial in chemotherapy of OV.

Understanding natural language: Potential application of large language models to ophthalmology.

Large language models (LLMs), a natural language processing technology based on deep learning, are currently in the spotlight. These models closely mimic natural language comprehension and generation. Their evolution has undergone several waves of innovation similar to convolutional neural networks. The transformer architecture advancement in generative artificial intelligence marks a monumental leap beyond early-stage pattern recognition via supervised learning. With the expansion of parameters and training data (terabytes), LLMs unveil remarkable human interactivity, encompassing capabilities such as memory retention and comprehension. These advances make LLMs particularly well-suited for roles in healthcare communication between medical practitioners and patients. In this comprehensive review, we discuss the trajectory of LLMs and their potential implications for clinicians and patients. For clinicians, LLMs can be used for automated medical documentation, and given better inputs and extensive validation, LLMs may be able to autonomously diagnose and treat in the future. For patient care, LLMs can be used for triage suggestions, summarization of medical documents, explanation of a patient's condition, and customizing patient education materials tailored to their comprehension level. The limitations of LLMs and possible solutions for real-world use are also presented. Given the rapid advancements in this area, this review attempts to briefly cover many roles that LLMs may play in the ophthalmic space, with a focus on improving the quality of healthcare delivery.

An early effect of the parafoveal preview on post-saccadic processing of English words.

A key aspect of efficient visual processing is to use current and previous information to make predictions about what we will see next. In natural viewing, and when looking at words, there is typically an indication of forthcoming visual information from extrafoveal areas of the visual field before we make an eye movement to an object or word of interest. This "preview effect" has been studied for many years in the word reading literature and, more recently, in object perception. Here, we integrated methods from word recognition and object perception to investigate the timing of the preview on neural measures of word recognition. Through a combined use of EEG and eye-tracking, a group of multilingual participants took part in a gaze-contingent, single-shot saccade experiment in which words appeared in their parafoveal visual field. In valid preview trials, the same word was presented during the preview and after the saccade, while in the invalid condition, the saccade target was a number string that turned into a word during the saccade. As hypothesized, the valid preview greatly reduced the fixation-related evoked response. Interestingly, multivariate decoding analyses revealed much earlier preview effects than previously reported for words, and individual decoding performance correlated with participant reading scores. These results demonstrate that a parafoveal preview can influence relatively early aspects of post-saccadic word processing and help to resolve some discrepancies between the word and object literatures.