ABSTRACT
A literature review showed that Atg7 biological role was associated with the development and pathogenesis of nervous system, but very few reports focused on Atg7 role on neurogenesis at the region of spinal cord, so that we are committed to explore the subject. Atg7 expression in neural tube is incrementally increased during neurogenesis. Atg7 neural-specific knockout mice demonstrated the impaired motor function and imbalance of neuronal and glial cell differentiation during neurogenesis, which was similarly confirmed in primary neurosphere culture and reversely verified by Atg7 overexpression in unilateral neural tubes of gastrula chicken embryos. Furthermore, activating autophagy in neural stem cells (NSCs) of neurospheres did not rescue Atg7 deficiency-suppressed neuronal differentiation, but Atg7 overexpression on the basis of autophagy inhibition could reverse Atg7 deficiency-suppressed neuronal differentiation, which provides evidence for the existence of Atg7 role of autophagy-independent function. The underlying mechanism is that Atg7 deficiency directly caused the alteration of cell cycle length of NSCs, which is controlled by Atg7 through specifically binding Mdm2, thereby affecting neuronal differentiation during neurogenesis. Eventually, the effect of overexpressing Atg7-promoting neuronal differentiation was proved in spinal cord injury model as well. Taken together, this study revealed that Atg7 was involved in regulating neurogenesis by a non-autophagic signaling process, and this finding also shed light on the potential application in regenerative medicine.
ABSTRACT
Glaucoma is one of the leading cause of blindness worldwide. Individuals affected by glaucoma, including patients and their family members, frequently encounter a deficit in dependable support beyond the confines of clinical environments. Seeking advice via the internet can be a difficult task due to the vast amount of disorganized and unstructured material available on these sites, nevertheless. This research explores how Large Language Models (LLMs) can be leveraged to better serve medical research and benefit glaucoma patients. We introduce Xiaoqing, a Natural Language Processing (NLP) model specifically tailored for the glaucoma field, detailing its development and deployment. To evaluate its effectiveness, we conducted two forms of experiments: comparative and experiential. In the comparative analysis, we presented 22 glaucoma-related questions in simplified Chinese to three medical NLP models (Xiaoqing LLMs, HuaTuo, Ivy GPT) and two general models (ChatGPT-3.5 and ChatGPT-4), covering a range of topics from basic glaucoma knowledge to treatment, surgery, research, management standards, and patient lifestyle. Responses were assessed for informativeness and readability. The experiential experiment involved glaucoma patients and non-patients interacting with Xiaoqing, collecting and analyzing their questions and feedback on the same criteria. The findings demonstrated that Xiaoqing notably outperformed the other models in terms of informativeness and readability, suggesting that Xiaoqing is a significant advancement in the management and treatment of glaucoma in China. We also provide a Web-based version of Xiaoqing, allowing readers to directly experience its functionality. The Web-based Xiaoqing is available at https://qa.glaucoma-assistant.com//qa.
Subject(s)
Glaucoma , Humans , Glaucoma/drug therapy , Glaucoma/physiopathology , Natural Language Processing , Male , FemaleABSTRACT
Hyperglycemia in pregnancy can increase the risk of congenital disorders, but little is known about craniofacial skeleton malformation and its corresponding medication. Our study first used meta-analysis to review the previous findings. Second, baicalin, an antioxidant, was chosen to counteract high glucose-induced craniofacial skeleton malformation. Its effectiveness was then tested by exposing chicken embryos to a combination of high glucose (HG, 50 mM) and 6 µM baicalin. Third, whole-mount immunofluorescence staining and in situ hybridization revealed that baicalin administration could reverse HG-inhibited neural crest cells (NCC) delamination and migration through upregulating the expression of Pax7 and Foxd3, and mitigate the disordered epithelial-mesenchymal transition (EMT) process by regulating corresponding adhesion molecules and transcription factors (i.e., E-cadherin, N-cadherin, Cadherin 6B, Slug and Msx1). Finally, through bioinformatic analysis and cellular thermal shift assay, we identified the AKR1B1 gene as a potential target. In summary, these findings suggest that baicalin could be used as a therapeutic agent for high glucose-induced craniofacial skeleton malformation.
ABSTRACT
The cause of Posner-Schlossman syndrome (PSS) remains unknown and its frequent recurrence may eventually lead to irreversible damage of the optic nerve. The influence of immune factors in the pathophysiology of PSS is gaining more and more interest. Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of neurodegenerative and immune-related diseases. However, alterations of the gut microbiota in PSS patients have not been well defined yet. In this study, 16S rRNA sequencing was used to explore the difference of gut microbiota between PSS patients and healthy controls, and the correlation between the microbiota profile and clinical features was also analyzed. Our data demonstrated a significant increase of Prevotella and Prevotellaceae, and a significant reduction of Bacteroides and Bacteroidaceae in PSS patients, and KEGG analysis showed dysfunction of gut microbiota between PSS patients and healthy controls. Interestingly, further analysis showed that the alteration of gut microbiota was correlated with the PSS attack frequency of PSS. This study demonstrated the gut microbiota compositional profile of PSS patients and speculated the risk microbiota of PSS, which is expected to provide new insights for the diagnosis and treatment of PSS.
Subject(s)
Gastrointestinal Microbiome , Microbiota , Humans , RNA, Ribosomal, 16S/geneticsABSTRACT
BACKGROUND: 2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyrimidine (PhIP) is a known carcinogen generated mainly from cooking meat and environmental pollutants. It is worth exploring the potential of natural small-molecule drugs to protect against adverse effects on embryonic development. PURPOSE: In this study, we investigated the potential toxicological effects of PhIP on embryonic heart tube formation and the effect of Sulforaphane (SFN) administration on the anti-toxicological effects of PhIP on embryonic cardiogenesis. STUDY DESIGN AND METHODS: First, the chicken embryo model was used to investigate the different phenotypes of embryonic heart tubes induced by various concentrations of PhIP exposure. We also proved that SFN rescues PhIP-induced embryonic heart tube malformation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR) and flow cytometry experiments were employed to explore the mechanisms by which SFN protects cardiac cells from oxidative damage in the presence of PhIP. We used RNA-seq analysis, molecular docking, in situ hybridization, cellular thermal shift assay and solution nuclear magnetic resonance spectroscopy to explore whether SFN protects cardiogenesis through the EGFR/MAPK signaling pathway. RESULTS: The study showed that PhIP might dose-dependently interfere with the C-looping heart tube (mild) or the fusion of a pair of bilateral endocardial tubes (severe) in chick embryos, while SFN administration prevented cardiac cells from oxidative damage in the presence of high-level PhIP. Furthermore, we found that excessive reactive oxygen species (ROS) production and subsequent apoptosis were not the principal mechanisms by which low-level PhIP induced malformation of heart tubes. This is due to PhIP-disturbed Mitogen-activated protein kinase (MAPK) signaling pathway could be corrected by SFN administration. CONCLUSIONS: This study provided novel insight that PhIP exposure could increase the risk of abnormalities in early cardiogenesis and that SFN could partially rescue various concentrations of PhIP-induced abnormal heart tube formation by targeting EGFR and mediating EGFR/MAPK signaling pathways.
Subject(s)
Heart Defects, Congenital , Imidazoles , Isothiocyanates , Sulfoxides , Animals , Chick Embryo , Molecular Docking Simulation , Isothiocyanates/pharmacology , MAP Kinase Signaling System , Reactive Oxygen Species/metabolism , ErbB Receptors/metabolism , ApoptosisABSTRACT
INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of combined trabeculotomy-non-penetrating deep sclerectomy (CTNS) in the treatment of Sturge-Weber syndrome (SWS) secondary glaucoma. METHODS: This retrospective study reviewed cases that underwent CTNS as initial surgery for SWS secondary glaucoma at our Ophthalmology Department center from April 2019 to August 2020. Surgical success was defined as an intraocular pressure (IOP) ≤ 21 mm Hg with (qualified success) or without (complete success) the use of anti-glaucoma medications. IOP >21 mm Hg or <5 mm Hg despite 3 or more applications of anti-glaucoma medications on 2 consecutive follow-up visits or at the last follow-up, performance of additional glaucoma (IOP-lowering) surgery, or with vision-threatening complications were classified as failure. RESULTS: A total of 22 eyes of 21 patients were included. Twenty-one eyes were of early-onset type and 1 eye was of adulthood onset. For Kaplan-Meier survival analysis, the overall success rates at 1st and 2nd years were 95.2% and 84.9%, while the complete success rates at 1st and 2nd years were 42.9% and 36.7%. At the last follow-up (22.3 ± 4.0 months, range: 11.2â¼31.2), overall success was achieved in 19 (85.7%) eyes and complete success in 12 (52.4%) eyes. Postoperative complications included transient hyphema (11/22, 50.0%) and transient â degree shallow anterior chamber (1/22, 4.5%), and retinal detachment (1/22, 4.5%). No other severe com plications were detected during the follow-up. CONCLUSION: CTNS significantly reduces IOP in SWS secondary glaucoma patients who have serious episcleral vascular malformation. CTNS in SWS secondary glaucoma patients is safe and effective for short and medium periods. A randomized controlled study comparing the long-term prognosis of SWS early-onset and late-onset glaucoma underwent CTNS is worth conducting.
Subject(s)
Glaucoma , Sturge-Weber Syndrome , Trabeculectomy , Humans , Adult , Trabeculectomy/adverse effects , Sturge-Weber Syndrome/complications , Sturge-Weber Syndrome/diagnosis , Sturge-Weber Syndrome/surgery , Retrospective Studies , Antiglaucoma Agents , Treatment Outcome , Glaucoma/surgery , Glaucoma/etiology , Intraocular Pressure , Sclera/surgery , Follow-Up StudiesABSTRACT
PURPOSE: To perform an in vivo evaluation of the changes in Schlemm's canal (SC) among patients with primary angle-closure disease (PACD) using swept-source optical coherence tomography (SS-OCT). METHODS: Patients diagnosed with PACD who had not undergone surgery were recruited. The SS-OCT quadrants scanned herein included the nasal and temporal sections at 3 and 9 o'clock, respectively. The diameter and cross-sectional area of the SC were measured. A linear mixed-effects model was performed to analyze the effects of parameters on the SC changes. The hypothesis of interest was related to the angle status (iridotrabecular contact, ITC/open angle, OPN), which was further explored with pairwise comparisons of the estimated marginal means (EMMs) of the SC diameter and SC area. In the ITC regions, the relationship between the trabecular-iris contact length (TICL) percentage and SC parameters was also studied by a mixed model. RESULTS: A total of 49 eyes of 35 patients were included for measurements and analysis. The percentage of observable SCs in the ITC regions was only 58.5% (24/41), whereas it was 86.0% (49/57) in the OPN regions (χ2 = 9.44, p = 0.002). ITC was significantly associated with a decreasing SC size. The EMMs for the diameter and cross-sectional area of SC at the ITC and OPN regions were 203.34 µm versus 261.41 µm (p = 0.006) and 3174.43 µm2 versus 5347.63 µm2 (p = 0.022), respectively. Sex, age, spherical equivalent refraction, intraocular pressure, axial length, extent of angle closure, history of acute attack and treatment with LPI were not significantly associated with SC parameters. In the ITC regions, a larger TICL percentage was significantly associated with a decrease in SC diameter and area (p = 0.003 and 0.019, respectively). CONCLUSIONS: The morphologies of SC could be affected by the angle status (ITC/OPN) in patients with PACD, and ITC was significantly associated with a decreasing SC size. These changes in SC as described by OCT scans might help to elucidate the progression mechanisms of PACD.
Subject(s)
Glaucoma, Angle-Closure , Trabecular Meshwork , Humans , Tomography, Optical Coherence/methods , Schlemm's Canal , Sclera , Tonometry, Ocular , Intraocular Pressure , Glaucoma, Angle-Closure/diagnosis , Glaucoma, Angle-Closure/surgeryABSTRACT
BACKGROUND: The brain-computer interface (BCI) is a highly cross-discipline technology and its successful application in various domains has received increasing attention. However, the BCI-enabled automobile industry is has been comparatively less investigated. In particular, there are currently no studies focusing on brain-controlled driving mode selection. Specifically, different driving modes indicate different driving styles which can be selected according to the road condition or the preference of individual drivers. METHODS: In this paper, a steady-state visual-evoked potential (SSVEP)-based driving mode selection system is proposed. Upon this system, drivers can select the intended driving modes by only gazing at the corresponding SSVEP stimuli. A novel EEG processing algorithm named inter-trial distance minimization analysis (ITDMA) is proposed to enhance SSVEP detection. Both offline and real-time experiments were carried out to validate the effectiveness of the proposed system. CONCLUSION: The results show that a high selection accuracy of up to 92.3% can be realized, although this depends on the specific choice of flickering duration, the number of EEG channels, and the number of training signals. Additionally, energy consumption is investigated in terms of which the proposed brain-controlled system considerably differs from a traditional driving mode selection system, and the main reason is shown to be the existence of a detection error.
Subject(s)
Brain-Computer Interfaces , Algorithms , Brain/physiology , Electroencephalography/methods , Evoked Potentials, Visual , Photic StimulationABSTRACT
The upgrading of plastic waste is one of the grand challenges for the 21st century owing to its disruptive impact on the environment. Here, we show the first example of the upgrading of various aromatic plastic wastes with C-O and/or C-C linkages to arenes (75-85 % yield) via catalytic hydrogenolysis over a Ru/Nb2 O5 catalyst. This catalyst not only allows the selective conversion of single-component aromatic plastic, and more importantly, enables the simultaneous conversion of a mixture of aromatic plastic to arenes. The excellent performance is attributed to unique features including: (1)â the small sized Ru clusters on Nb2 O5 , which prevent the adsorption of aromatic ring and its hydrogenation; (2)â the strong oxygen affinity of NbOx species for C-O bond activation and Brønsted acid sites for C-C bond activation. This study offers a catalytic path to integrate aromatic plastic waste back into the supply chain of plastic production under the context of circular economy.
ABSTRACT
Neutrophils play critical roles during the initial phase of hepatic ischemia/reperfusion injury (HIRI). However, the regulation of neutrophil activation, infiltration, and proinflammatory cytokine secretion has not been fully elucidated. In this study, we revealed that OX40 was expressed by neutrophils, its expression in neutrophils was time-dependently upregulated following HIRI, and Ox40 knockout markedly alleviated liver injury. Compared with wild-type neutrophils, the adoptive transfer of Ox40-/- neutrophils decreased HIRI in neutrophil-depleted Rag2/Il2rg-/- or Ox40-/- mice. Moreover, consistently, the in vitro experiments showed that Ox40 not only prolonged neutrophil survival but also promoted proinflammatory cytokines, ROS production, and even neutrophil chemotaxis. Further investigation demonstrated that the knockout of Ox40 in neutrophils inhibited NF-κB signaling via the TRAF1/2/4 and IKKα/IKKß/IκBα pathways. OX40L and OX86 stimulation could enhance neutrophil activation and survival in vitro and in vivo. In conclusion, our study provides a new understanding of OX40, which is expressed not only in adaptive immune cells but also in innate immune cells, i.e., neutrophils, contributing to the activation and survival of neutrophils. These findings provide a novel potential therapeutic target for the prevention of HIRI during liver transplantation or hepatic surgery.
Subject(s)
Liver/blood supply , Neutrophils/metabolism , Receptors, OX40/metabolism , Reperfusion Injury/metabolism , Animals , Chemotaxis, Leukocyte , Cytokines/biosynthesis , Inflammation Mediators/metabolism , Liver/surgery , Liver Transplantation , Mice , Mice, Knockout , Reactive Oxygen Species/metabolism , Receptors, OX40/geneticsABSTRACT
OBJECTIVE: To understand the trend of gastric cancer mortality based on the exploration of the death data from 1970 to 2004 in Zhaoyuan County. METHODS: The death data of 1970-1974 were collected from the first malignant tumor death survey of China, and the data of 1985-2004 were derived from the cancer registration network of Zhaoyuan. The appreciation indexes were crude mortality rate and standardized mortality rates by the percentages of Chinese population in 1982 and the percentages of world population in 1966. RESULTS: The crude mortality rates in the five periods of 1970-1974, 1985-1989, 1990-994, 1995-1999, and 2000-2004 were 34.94, 44.34, 40.05, 48.73, and 40.18 per 100,000, respectively; the standardized mortality rates by Chinese population were 30.82, 30.35, 27.78, 31.63, and 20.10 per 100,000, respectively. The gastric cancer mortality remained stability from 1970 to 1999, however, the standardized mortality rate of gastric cancer in 2000-2004 declined by 34.8% compared with that in 1970-1974. The study also observed that the highest age-specific gastric cancer mortality, in the past 35 years, has been postponed by 10 years. And, the gastric cancer mortality ranked from top first to top three. CONCLUSION: There is a decreasing trend for the incidence of stomach cancer and this might be associated with the changes of dietary consumption and pattern.