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Abstract Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease. Graphical Abstract

ObjectiveTo explore the relationship between plasma lactoferrin (Lf) and glaucoma, assessing the clinical utility of Lf in glaucoma.MethodsA cross-sectional study involved 161 glaucoma patients and 115 healthy controls, with a follow-up of 14 subjects after approximately 2 years. Plasma Lf markers were quantified using ELISA, comparing levels between glaucoma patients and healthy controls, and analyzing plasma Lf across different glaucoma severity grades.ResultsGlaucoma patients had significantly elevated plasma Lf levels compared to healthy controls (p

Abstract At present, the separation technology of fluorite and calcite is still immature, and the research in this paper can promote the improvement of the separation technology of fluorite and calcite. The selective inhibition mechanism of tannin and humate sodium on calcite was studied by means of actual ore flotation test, single mineral flotation test, Zeta potential measurement and FT-IR spectroscopy. The results show that the mixture of tannin and sodium humate inhibitor has a good inhibitory effect on carbonate under weak alkaline condition. The reaction products of sodium humate, tannin and calcium ions in solution interact with organic compounds adsorbed on the surface of calcite, forming multilayer adsorption on the surface of calcite, making calcite more hydrophilic. Based on density functional theory, Materials Studio (MS) was used to calculate the relevant adsorption energy, and the result was as follows: (a) compared with fluorite, tannin and humate sodium molecules are more easily adsorbed on the surface of calcite. (b) Compared with calcite alone adsorption of tannin molecules or sodium humate molecules, the adsorption state will be more stable, and the effect of tannin and sodium humate synergistic inhibition of calcite is better than the effect of inhibition alone. Therefore, using tannin and sodium humate as a combination inhibitor can effectively separate fluorite and calcite, which will promote the development and utilization of fluorite ore in industry.

Building a “Maritime Community with a Shared Future” (MCSF) is a maritime development concept with Chinese characteristics proposed by Chinese President Xi Jinping in 2019. It is based on the rich cultural tradition and unique historical value of China’s maritime civilization. It aims to solve real ocean problems and has outlined the future direction of human ocean development from the perspective of China. The essence of the MCSF is an issue of both ocean cultural and development concepts. It is a conceptual issue that transcends specific national boundaries and regions and is based on how all of humankind, with common interests and common values, can develop in harmony with the oceans. It is not a covert discourse strategy adopted by China in order to realize its “maritime power” ambition, as occasionally described by some Western countries. Starting with an analysis of the essential nature and implications of maritime culture by Chinese researchers, this article clarifies and summarizes the interaction, exchange, and integration of Chinese maritime culture in East Asia from a historical perspective, and extracts the unique characteristics and values of Chinese maritime culture. From the perspective of human–sea interactions, the three historical stages, as well as the existing problems of transforming and upgrading human–ocean culture, are analyzed. The article also contrasts Chinese and Western maritime cultures and proposes to absorb the outstanding achievements of both Chinese and Western maritime civilizations into a common framework in order to fundamentally reverse the antagonistic human–sea relationship that has existed historically. Finally, we propose giving full play to the fundamental role of marine cultural exchange and integration and, through international cooperation on specific issues in the field of global ocean international relations, propose specific and feasible practical pathways to promoting the realization of the MCSF.

Abstract Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments. Here, we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy. We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy, especially those with acute necrotizing encephalopathy (AE). This was characterized a marked reduction of various lymphocytes (e.g., CD8+ T and CD4+ T cells) and significant increases in other inflammatory cells (e.g., monocytes). Further analysis revealed activation of multiple cell apoptosis pathways (e.g., granzyme/perforin-, FAS- and TNF-induced apoptosis) may be responsible for lymphopenia. A systemic S100A12 upregulation, primarily from classical monocytes, may have contributed to cytokine storms in patients with AE. A dysregulated type I interferon (IFN) response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE. In COVID-19 patients with AE, myeloid cells (e.g., monocytic myeloid-derived suppressor cells) were the likely contributors to immune paralysis. Finally, the immune landscape in COVID-19 patients with encephalopathy, especially for AE, were also characterized by NK and T cells with widespread exhaustion, higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response. Taken together, this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments, especially for those with AE.

We investigated the influence of DNA fragmentation index (DFI) on in vitro fertilization (IVF), embryo transfer (ET), and intracytoplasmic sperm injection (ICSI). We analyzed the semen parameters of 61 cycles in infertile couples undergoing IVF-ET and ICSI and determined DFI by sperm chromatin dispersion testing. Based on DFI, the patients were differentiated into a control group (DFI < 25%, n = 35) and a test group (DFI ≥ 25%, n = 26). Flow cytometry and immunofluorescence were used to investigate the extent of sperm reactive oxygen species (ROS) and apoptosis. We also investigated the effect of DFI on pregnancy outcomes of IVF-ET/ICSI. DFI was negatively related to sperm motility and positively correlated with ROS and apoptosis (P < 0.05). Abnormally elevated DFI reduced the rate of transplantable, high-quality embryos, implantation, clinical pregnancy, delivery, and live birth after IVF-ET, and increased the chance of early abortion per transfer cycle (P < 0.05). However, there was no significant correlation between DFI and fertilization rate, cleavage rate, transplantable rate, high-quality embryo rate, implantation rate, clinical pregnancy rate, early abortion rate, delivery rate and live birth rate when assisted by ICSI (P > 0.05). Sperm DNA integrity is crucial for fertilization and the development of healthy offspring. ROS may increase the level of DFI by inducing apoptosis in sperm.

Since the end of 2022, when China adjusted its COVID-19 response measures, the SARS-CoV-2 epidemic has rapidly grown in the country. It is very necessary to monitor the evolutionary dynamic of epidemic variants. However, detailed reports presenting viral genome characteristics in China during this period are limited. In this study, we examined the epidemiological, genomic, and evolutionary characteristics of the SARS-CoV-2 genomes from China. We analyzed nearly 20,000 genomes belonging to 17 lineages, predominantly including BF.7.14 (22.3%), DY.2 (17.3%), DY.4 (15.5%), and BA.5.2.48 (11.9%). The Rt value increased rapidly after mid-November 2022, reaching its peak at the end of the month. We identified forty-three core mutations in the S gene and forty-seven core mutations in the ORF1ab gene. The positive selection of all circulating lineages was primarily due to non-synonymous substitutions in the S1 region. These findings provide insights into the genomic characteristics of SARS-CoV-2 genomes in China following the relaxation of the ‘dynamic zero-COVID’ policy and emphasize the importance of ongoing genomic monitoring.

Objectives The operative microscope (OM) has revolutionized the field of modern spine surgery, however, it remains limited by several drawbacks. Recently, the exoscope (EX) system has been designed to assistant spine surgery. It provides a three‐dimensional (3D) high‐definition (HD) operative experience and becomes an alternative to the OM. The aim of the study was to evaluate the clinical outcomes, advantages and limitations of EX‐assisted minimally invasive transforaminal lumbar interbody fusion (EMIS‐TLIF) and OM‐assisted MIS‐TLIF (OMIS‐TLIF). Methods The clinical outcomes were assessed in 47 patients with lumbar degenerative diseases (LDD) who underwent MIS‐TLIF assisted with the OM or EX between January 2019 and September 2020. A total of 22 were treated with EMIS‐TLIF, and 25 received OMIS‐TLIF. Perioperative parameters (including sex, age, number of fusion levels and body mass index), perioperative parameters (operation time, intraoperative blood loss, postoperative drainage, postoperative hospitalization stay, and duration of follow‐up), visual analogue scale (VAS) of back pain, VAS of leg pain, Oswestry disability index (ODI) scores and clinical outcomes were assessed and compared. Image quality, handling of equipment, ergonomics, 3D glasses and educational usefulness were scored according to a questionnaire. Results Operation time in the OMIS‐TLIF group (121.92 ± 16.92 min) was significantly increased compared with that in the EMIS‐TLIF group (111.00 ± 19.87 min) (P

Although previous studies have reported the use of metabolomics for infectious diseases, little is known about the potential function of plasma metabolites in children infected with Mycoplasma pneumoniae (MP). Here, a combination of liquid chromatography-quadrupole time-of-flight mass spectrometry and random forest-based classification model was used to provide a broader range of applications in MP diagnosis. In the training cohort, plasma from 63 MP pneumonia children (MPPs), 37 healthy controls (HC) and 29 infectious disease controls (IDC) was collected. After multivariate analyses, 357 metabolites were identified to be differentially expressed among MPP, HC and IDC groups, and 3 metabolites (568.5661, 459.3493 and 411.3208) had high diagnostic values. In an independent cohort with 57 blinded subjects, samples were successfully classified into different groups, demonstrating the reliability of these biomarkers for distinguishing MPPs from controls. A metabolomic signature analysis identified major classes of glycerophospholipids, sphingolipids and fatty acyls were increased in MPPs. These markedly altered metabolites are mainly involved in glycerophospholipid and sphingolipid metabolism. As the ubiquitous building blocks of eukaryotic cell membranes, dysregulated lipid metabolism indicates damage of the cellular membrane and the activation of immunity in MPPs. Moreover, lipid metabolites, differentially expressed between severe and mild MPPs, were correlated with the markers of extrapulmonary complications, suggesting that they may be involved in MPP disease severity. These findings may offer new insights into biomarker selection and the pathogenesis of MPP in children.

The SARS-CoV-2 is still undergoing rapid evolution, resulting in the emergence of several variants of concern, especially the Omicron variants (B.1.1.529), which are surging worldwide. In this study, we tracked Omicron subvariant BA.5.1.3 as the causative agent in the Hainan Province wave in China, which started on 1 August 2022. This was China’s first case of Omicron subvariant BA.5.1.3 and led to an indefinite total lockdown in Hainan with more than 8,500 confirmed cases. We obtained 391 whole genomes from positive nasopharyngeal swab samples in the city of Sanya in Hainan Province, which was the center of this outbreak. More than half of the infected cases were female (58%, 227/391) with a median age of 37.0 years (IQR 23.0–53.0). Median Ct values were 24.9 (IQR 22.6–27.3) and 25.2 (IQR 22.9–27.6) for ORF1ab and N genes, respectively. The total single-nucleotide polymorphism (SNP) numbers of Omicron BA.5.1.3 sampled in Sanya (median 69.0, IQR = 69.0–70.0) compared to those worldwide (median 63.0, IQR = 61.0–64.0) showed a significant difference (p