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Soil salinization, especially in arid environments, is a leading cause of land degradation and desertification. Excessive salt in the soil is detrimental to plants. Plants have developed various sophisticated regulatory mechanisms that allow them to withstand adverse environments. Through cross-adaptation, plants improve their resistance to an adverse condition after experiencing a different kind of adversity. Our analysis of Ammopiptanthus nanus, a desert shrub, showed that mechanical wounding activates the biosynthesis of jasmonic acid (JA) and abscisic acid (ABA), enhancing plasma membrane H+-ATPase activity to establish an electrochemical gradient that promotes Na+ extrusion via Na+/H+ antiporters. Mechanical wounding reduces K+ loss under salt stress, improving the K/Na and maintaining root ion balance. Meanwhile, mechanical damage enhances the activity of antioxidant enzymes and the content of osmotic substances, working together with cellular ions to alleviate water loss and growth inhibition under salt stress. This study provides new insights and approaches for enhancing salt tolerance and stress adaptation in plants by elucidating the signaling mechanisms of cross-adaptation.
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The cloning of resistance-related genes CsROP5/CsROP10 and the analysis of their mechanism of action provide a theoretical basis for the development of molecular breeding of disease-resistant cucumbers. The structure domains of two Rho-related guanosine triphosphatases from plant (ROP) genes were systematically analyzed using the bioinformatics method in cucumber plants, and the genes CsROP5 (Cucsa.322750) and CsROP10 (Cucsa.197080) were cloned. The functions of the two genes were analyzed using reverse-transcription quantitative PCR (RT-qPCR), virus-induced gene silencing (VIGS), transient overexpression, cucumber genetic transformation, and histochemical staining technology. The conserved elements of the CsROP5/CsROP10 proteins include five sequence motifs (G1-G5), a recognition site for serine/threonine kinases, and a hypervariable region (HVR). The knockdown of CsROP10 through VIGS affected the transcript levels of ABA-signaling-pathway-related genes (CsPYL, CsPP2Cs, CsSnRK2s, and CsABI5), ROS-signaling-pathway-related genes (CsRBOHD and CsRBOHF), and defense-related genes (CsPR2 and CsPR3), thereby improving cucumber resistance to Corynespora cassiicola. Meanwhile, inhibiting the expression of CsROP5 regulated the expression levels of ROS-signaling-pathway-related genes (CsRBOHD and CsRBOHF) and defense-related genes (CsPR2 and CsPR3), thereby enhancing the resistance of cucumber to C. cassiicola. Overall, CsROP5 and CsROP10 may participate in cucumber resistance to C. cassiicola through the ROS and ABA signaling pathways.
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Early life stress (ELS) can cause long-term changes by epigenetic factors, especially histone acetylation modification, playing a crucial role, affect normal cognition, mood, and behavior, and increase susceptibility to post-traumatic stress disorder (PTSD) in adulthood. It has been found that paeoniflorin (PF) can cross the blood-brain barrier to exert anti-PTSD effects on adult PTSD rats. However, whether PF can alleviate the harmful effects caused by ELS in adulthood has not yet been reported. Therefore, to explore the relationship between ELS and PTSD susceptibility in adulthood and its mechanism, in this study, SPS was used as a stressor of ELS, and the mathematical tool Z-normalization was employed as an evaluation criterion of behavioral resilience susceptibility. To investigate the regulatory mechanism of PF on histone acetylation in the hippocampus and amygdala of ELS rats in adulthood, using changes in HATs/HDACs as the entry point, meanwhile, the epigenetic marks (H3K9 and H4K12) in the key brain regions of ELS (hippocampus and amygdala) were evaluated, and the effects of PF on behavioral representation and PTSD susceptibility were observed. This study found that ELS lead to a series of PTSD-like behaviors in adulthood and caused imbalance of HATs/HDACs ratio in the hippocampus and amygdala, which confirms that ELS is an important risk factor for the development of PTSD in adulthood. In addition, paeoniflorin may improve ELS-induced PTSD-like behaviors and reduce the susceptibility of ELS rats to develop PTSD in adulthood by modulating the HATs/HDACs ratio in the hippocampus and amygdala.
Subject(s)
Amygdala , Glucosides , Hippocampus , Histones , Monoterpenes , Stress Disorders, Post-Traumatic , Stress, Psychological , Animals , Glucosides/pharmacology , Glucosides/therapeutic use , Monoterpenes/pharmacology , Monoterpenes/therapeutic use , Hippocampus/metabolism , Hippocampus/drug effects , Acetylation/drug effects , Amygdala/metabolism , Amygdala/drug effects , Histones/metabolism , Rats , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/metabolism , Male , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Rats, Sprague-Dawley , Histone Acetyltransferases/metabolism , Histone Deacetylases/metabolismABSTRACT
Cannabidiol (CBD), one of the most important active ingredients in cannabis, has been reported to have some pharmacological effects such as antibacterial and analgesic effects, and to have therapeutic potential in the treatment of oral diseases such as oral cancer, gingivitis and periodontal diseases. However, there is a lack of relevant systematic research and reviews. Therefore, based on the etiology and clinical symptoms of several common oral diseases, this paper focuses on the therapeutic potential of CBD in periodontal diseases, pulp diseases, oral mucosal diseases, oral cancer and temporomandibular joint diseases. The pharmacological effects of CBD and the distribution and function of its receptors in the oral cavity are also summarized. In order to provide reference for future research and further clinical application of CBD, we also summarize several possible routes of administration and corresponding characteristics. Finally, the challenges faced while applying CBD clinically and possible solutions are discussed, and we also look to the future.
Subject(s)
Cannabidiol , Mouth Diseases , Cannabidiol/therapeutic use , Cannabidiol/administration & dosage , Humans , Mouth Diseases/drug therapy , Animals , Drug Administration RoutesABSTRACT
Fear overgeneralization is widely accepted as a pathogenic marker of post-traumatic stress disorder (PTSD). Recently, GABAergic interneurons have been regarded as key players in the regulation of fear memory. The role of hippocampal GABAergic interneurons in contextual fear generalization of PTSD remains incompletely understood. In the present study, we established a rat model of PTSD with inescapable foot shocks (IFS) and observed the loss of GABAergic interneuron phenotype in the hippocampal cornu ammonis-1 (CA1) subfield. To determine whether the loss of GABAergic interneuron phenotype was associated with fear generalization in PTSD rats, we used adeno-associated virus (AAV) to reduce the expression of GAD67 in CA1 and observed its effect on fear generalization. The results showed that the reduction of GAD67 in CA1 enhanced contextual fear generalization in rats. We investigated whether the PERK pathway was involved in the GABAergic interneuron injury. Increased expression of p-PERK, CHOP, and Caspase12 in GABAergic interneurons of PTSD rats was observed. Then, we used salubrinal, an endoplasmic reticulum stress inhibitor, to modulate the PERK pathway. The salubrinal treatment significantly protected the GABAergic interneurons and relieved fear generalization in PTSD rats. In addition, the results showed that salubrinal down-regulated the expression of CHOP and Caspase12 in GABAergic interneurons of PTSD rats. In conclusion, this study provided evidence that the loss of GABAergic interneuron phenotype in CA1 may contribute to contextual fear generalization in PTSD. The PERK pathway is involved in the GABAergic interneuron injury of PTSD rats and modulating it can protect GABAergic interneurons and constrain contextual fear generalization.
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Idiopathic multicentric Castleman disease is a rare and complex disease characterized by systemic inflammation, lymphadenopathy, and multiorgan involvement. This case report presents a 66-year-old Chinese man with idiopathic multicenter Castleman disease without significant lymphadenopathy and challenging diagnosis. Patients present with fever, fatigue, loss of appetite, weight loss, and acute kidney injury. Initially, a urinary tract infection was suspected, but despite anti-infective treatment, the patient's symptoms persisted. Lymph node biopsy, although there is no significant lymphadenopathy, confirms idiopathic multicenter Castleman disease. Treatment includes thalidomide, cyclophosphamide, and dexamethasone, as well as supportive measures and infection control. After 8 months of follow-up, the patient's clinical symptoms, inflammatory markers and renal function were significantly improved, and there was no symptomatic recurrence. This case underscores the importance of considering idiopathic multicenter Castleman's disease in patients with persistent fever and systemic inflammation, even in the absence of significant lymphadenopathy. Early identification and accurate diagnosis of idiopathic multicenter Castleman's disease can lead to the initiation of targeted therapy strategies that ultimately yield favorable outcomes.
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BACKGROUND: Since coronavirus 2019 (COVID-19) swept the world, a variety of novel therapeutic and prevention strategies have been developed, among which nirmatrelvir-ritonavir is highly recommended. We intended to assess the effectiveness and safety of nirmatrelvir-ritonavir in the elderly mild-to-moderate COVID-19 population caused by the omicron BA.2.2 variant in real-world settings. METHODS: An observational study was conducted retrospectively to review the outcomes of mild-to-moderate COVID-19 patients admitted between April 26 and June 30, 2022. Patients' baseline characteristics were collected and assessed. Participants in the intervention group were administered nirmatrelvir-ritonavir in addition to standard care, whereas those in the control group only received standard care. The primary outcome was the duration between the initial positive reverse-transcription polymerase chain reaction (RT-PCR) test and the subsequent conversion to a negative result. RESULTS: The analysis included 324 patients who were administered nirmatrelvir-ritonavir and an equal number of control patients. The patient characteristics in both groups were evenly matched. The average duration from the initial positive RT-PCR to negative conversion was similar in both groups (16.2 ± 5.0 vs. 16.1 ± 6.3 days, p = .83). Control patients exhibited slower conversion in comparison to patients who received nirmatrelvir-ritonavir treatment within 10 days of symptom onset. CONCLUSIONS: These findings suggest that administering nirmatrelvir-ritonavir within 10 days of symptom onset could potentially reduce the time it takes for SARS-CoV-2-infected patients to negative RT-PCR results, thereby expanding the current usage guidelines for nirmatrelvir-ritonavir.
Subject(s)
COVID-19 , Ritonavir , Aged , Humans , Retrospective Studies , Ritonavir/therapeutic use , COVID-19 Drug Treatment , SARS-CoV-2ABSTRACT
Trehalose, a biological macromolecule with osmotic adjustment properties, plays a crucial role during osmotic stress. As a psammophyte, Ammopiptanthus nanus relies on the accumulation of organic solutes to respond to osmotic stress. We utilized virus-induced gene silencing technology for the first time in the desert shrub A. nanus to confirm the central regulatory role of AnWRKY29 in osmotic stress, as it controls the transcription of AnTPS11 (trehalose-6-phosphate synthase 11). Further investigation has shown that AnHSP90 may interact with AnWRKY29. The AnHSP90 gene is sensitive to osmotic stress, underscoring its pivotal role in orchestrating the response to such adverse conditions. By directly targeting the W-box element within the AnTPS11 promoter, AnWRKY29 effectively enhances the transcriptional activity of AnTPS11, which is facilitated by AnHSP90. This discovery highlights the critical role of AnWRKY29 and AnHSP90 in enabling organisms to adapt to and cope effectively with osmotic stress, which can be a crucial factor in A. nanus survival and overall ecological resilience. Collectively, uncovering the molecular mechanisms underlying the osmotic responses of A. nanus is paramount for comprehending and augmenting the osmotic tolerance mechanisms of psammophyte shrub plants.
Subject(s)
Fabaceae , Trehalose , Osmotic Pressure , Plant Leaves/genetics , OsmosisABSTRACT
Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.
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BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a phenomenon that pathological injury of ischemic brain tissue is further aggravated after the restoration of blood supply. The complex pathological mechanism of CIRI has led to the failure of multiple neuroprotective agents in clinical studies. Salvianolic acid A (SAA) is a neuroprotective extract from Salvia miltiorrhiza Bge., with significant pharmacological activities in the treatment of brain injury. However, the neuroprotective mechanisms of SAA remain unclear. PURPOSE: To explore the potential protective effect of SAA on CIRI and its mechanism, and to provide experimental basis for the research of new drugs for CIRI. STUDY DESIGN: A model of transient middle cerebral artery occlusion (tMCAO) in rats was used to simulate clinical CIRI, and the neuroprotective effect of SAA on tMCAO rats was investigated within 14 days after reperfusion. The improvement effects of SAA on cognitive impairment of tMCAO rats were investigated by behavioral tests from days 7-14. Finally, the neuroprotective mechanism of SAA was investigated on day 14. METHODS: The neuroprotective effects and mechanism of SAA were investigated by behavioral tests, HE and TUNEL staining, RNA sequence (RNA-seq) analysis and Western blot in tMCAO rats. RESULTS: The brain protective effects of SAA were achieved by alleviating cerebral infarction, cerebral edema, cerebral atrophy and nerve injury in tMCAO rats. Meanwhile, SAA could effectively improve the cognitive impairment and pathological damage of hippocampal tissue, and inhibit cell apoptosis in tMCAO rats. Besides, SAA could provide neuroprotective effects by up-regulating the expression of Bcl-2, inhibiting the activation of Caspase 3, and regulating PKA/CREB/c-Fos signaling pathway. CONCLUSION: SAA can significantly improve brain injury and cognitive impairment in CIRI rats, and this neuroprotective effect may be achieved through the anti-apoptotic effect and the regulation of PKA/CREB/c-Fos signaling pathway.
Subject(s)
Brain Injuries , Brain Ischemia , Caffeic Acids , Lactates , Neuroprotective Agents , Reperfusion Injury , Rats , Animals , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Rats, Sprague-Dawley , Signal Transduction , Brain Ischemia/pathology , Reperfusion Injury/metabolism , Apoptosis , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Brain Injuries/drug therapyABSTRACT
Diabetic retinopathy (DR) is one of the leading causes of blindness. However, because the data distribution of classes is not always balanced, it is challenging for automated early DR detection using deep learning techniques. In this paper, we propose an adaptive weighted ensemble learning method for DR detection based on optical coherence tomography (OCT) images. Specifically, we develop an ensemble learning model based on three advanced deep learning models for higher performance. To better utilize the cues implied in these base models, a novel decision fusion scheme is proposed based on the Bayesian theory in terms of the key evaluation indicators, to dynamically adjust the weighting distribution of base models to alleviate the negative effects potentially caused by the problem of unbalanced data size. Extensive experiments are performed on two public datasets to verify the effectiveness of the proposed method. A quadratic weighted kappa of 0.8487 and an accuracy of 0.9343 on the DRAC2022 dataset, and a quadratic weighted kappa of 0.9007 and an accuracy of 0.8956 on the APTOS2019 dataset are obtained, respectively. The results demonstrate that our method has the ability to enhance the ovearall performance of DR detection on OCT images.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnostic imaging , Bayes Theorem , Tomography, Optical Coherence/methods , Machine LearningABSTRACT
BACKGROUND: Interleukin-35 (IL-35), secreted by regulatory T cells (Treg) and B cells, is immunosuppressive under both physiological and pathological conditions. However, the role of IL-35 in all responses has yet to be investigated. Here, we demonstrate that IL-35 protects allografts by stabilizing the Treg phenotype and suppressing CD8 + T-cell activation in a mouse heart transplantation model. METHODS: The effect of IL-35 on immune cell infiltration in grafts and secondary lymphoid organs was examined using mass cytometry, flow cytometry, and immunofluorescence. Moreover, using quantitative real-time polymerase chain reaction, flow cytometry, and phospho-flow assays, we demonstrated that IL-35 maintains Treg phenotypes to restrain CD8 + T cells via the gp130/signal transducer and activator of transcription 1 pathway. RESULTS: Mass cytometry analysis of intragraft immune cells showed that IL-35 decreased CD8 + T-cell infiltration and increased Foxp3 and IL-35 expressions in Treg. In vitro, we demonstrated that IL-35 directly promoted Treg phenotypic and functional stability and its IL-35 secretion, generating a positive feedback loop. However, Treg are required for IL-35 to exert its suppressive effect on CD8 + T cells in vitro. After depleting Treg in the recipient, IL-35 did not prolong graft survival or decrease CD8 + T-cell infiltration. Mechanistically, we found that IL-35 sustained Treg stability via the gp130/signal transducer and activator of transcription 1 signaling pathway. CONCLUSIONS: Our findings highlight that IL-35 stabilizes the Treg phenotype to ameliorate CD8 + T-cell infiltration in the allograft, which has never been described in the transplanted immunological milieu.
Subject(s)
Allografts , Interleukins , T-Lymphocytes, Regulatory , Animals , Mice , Allografts/immunology , Allografts/metabolism , Cytokine Receptor gp130/metabolism , Mice, Inbred BALB C , Mice, Inbred C57BL , Phenotype , STAT1 Transcription Factor/metabolism , T-Lymphocytes, Regulatory/metabolismABSTRACT
Urinary catheters and other medical devices associated with the urinary tract such as stents are major contributors to nosocomial urinary tract infections (UTIs) as they provide an access path for pathogens to enter the bladder. Considering that catheter-associated urinary tract infections (CAUTIs) account for approximately 75% of UTIs and that UTIs represent the most common type of healthcare-associated infections, novel anti-infective device technologies are urgently required. The rapid rise of antimicrobial resistance in the context of CAUTIs further highlights the importance of such preventative strategies. In this review, the risk factors for pathogen colonization in the urinary tract are dissected, taking into account the nature and mechanistics of this unique environment. Moreover, the most promising next-generation preventative strategies are critically assessed, focusing in particular on anti-infective surface coatings. Finally, emerging approaches in this field and their likely clinical impact are examined.
Subject(s)
Anti-Infective Agents , Catheter-Related Infections , Urinary Tract Infections , Humans , Urinary Catheterization/adverse effects , Catheters, Indwelling/adverse effects , Catheter-Related Infections/drug therapy , Catheter-Related Infections/prevention & control , Catheter-Related Infections/etiology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Urinary Tract Infections/drug therapy , Urinary Tract Infections/etiology , Urinary Tract Infections/prevention & control , Urinary Catheters/adverse effectsABSTRACT
The present study was designed to investigate potential biomarkers of depression and targets of antidepressants from the perspective of hippocampal endoplasmic reticulum stress (ERS) based on cerebrospinal fluid (CSF) proteomics. Firstly, a six-week depression model was established and treated with fluoxetine (FLX). We found antidepressant-FLX could ameliorate depression-like behaviors and cognition in depressed rats caused by chronic unpredictable mild stress (CUMS). FLX significantly increased neuronal numbers in dentate gyrus (DG) and CA3 regions of hippocampus. CSF proteome data revealed thirty-seven differentially expressed proteins (DEPs) co-regulated by CUMS and FLX, including GRP94 and EIF2α. Results of Gene Oncology (GO) annotation and KEGG pathway enrichment for DEPs mainly included PERK-mediated unfolded protein response, endoplasmic reticulum, and translational initiation. The expression levels of GRP94, p-PERK, p-EIF2α, CHOP and Caspase-12 were increased in hippocampus of CUMS rats, and FLX worked the opposite way. FLX had strong affinity and binding activity with GRP94 protein, and four key proteins on the PERK pathway (PERK, EIF2α, p-EIF2α, CHOP). We proposed that FLX may exert antidepressant effects and neuroprotective action by alleviating excessive activation of the hippocampal PERK pathway and reducing neuronal deficits in depressed rats. PERK, EIF2α, p-EIF2α, and CHOP may be potential targets for antidepressant-FLX. GRP94 in CSF may be a potential biomarker of depression and the therapeutic effects of antidepressants.
Subject(s)
Depression , Membrane Proteins , Proteomics , Animals , Rats , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depression/drug therapy , Depression/etiology , Depression/metabolism , Endoplasmic Reticulum Stress/genetics , Fluoxetine/pharmacology , HSP70 Heat-Shock Proteins/antagonists & inhibitors , HSP70 Heat-Shock Proteins/metabolismABSTRACT
The excitatory-inhibitory imbalance has been considered an important mechanism underlying stress-related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS-exposed rats exhibited increased anxiety-like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67-immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα-immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV-immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN-coated PV-positive interneurons in CA1. The number of PSD95-positive excitatory synaptic puncta on the soma of PNN-free PV-positive interneurons was significantly higher than that of PNN-coated PV-positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell-type-specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV-PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety-like behavior.
Subject(s)
Neurons , Parvalbumins , Humans , Rats , Animals , Parvalbumins/metabolism , Extracellular Matrix/metabolism , Interneurons/metabolism , Hippocampus/metabolism , AnxietyABSTRACT
Background: Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by Candida in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of Candida in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC. Methods: Vaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with Candida-specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate Candida growth in the human vagina. The presence of Candida biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated Candida biofilms to fluconazole at the peak serum concentration was evaluated. Results: Candida species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. Candida biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based Candida biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole. Conclusions: In summary, our study provides direct evidence to support the presence of Candida biofilms in RVVC and an important role of biofilm formation in disease persistence.
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Biofilm formation is an important microbial strategy for fungal pathogens, such as Fusarium, Aspergillus, and Candida, to establish keratitis in patients wearing soft contact lenses. Despite the well-documented 2006 outbreak of Fusarium keratitis that eventually led to the withdrawal of the Bausch & Lomb multipurpose lens care solution ReNu with MoistureLoc ("MoistureLoc") from the global market, contact lens care systems and solutions currently available on the market do not specifically target fungal biofilms. This is partially due to the lack of recognition and understanding of important roles that fungal biofilms play in contact lens associated fungal keratitis (CLAFK). This review aims to reemphasize the link between fungal biofilms and CLAFK, and deepen our comprehension of its importance in pathogenesis and persistence of this medical device-related infection.
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BACKGROUND: Whether the positive associations of blood lipids with psychiatric disorders are causal is uncertain. We conducted this two-sample Mendelian randomization (MR) analysis to comprehensively investigate associations of blood lipids with psychiatric disorders. METHODS: Univariable and multivariable models were established for MR analyses. Inverse variance-weighted (IVW) MR was employed as the main approach; weighted median and MR-Egger were used as sensitivity analysis methods. The possibility of violating MR assumptions was evaluated utilizing several sensitivity analyses, including heterogeneity statistics, horizontal pleiotropy statistics, single SNP analysis, leave-one-out analysis and MR-PRESSO analysis. As instrumental variables, we screened 362 independent single-nucleotide polymorphisms (SNP) related to blood lipids from a recent genome-wide association study involving 76,627 individuals of European ancestry, with a genome-wide significance level of p < 5 × 10- 8. Summary-level information for the six psychiatric disorders was extracted from Psychiatric Genomics Consortium and Alzheimer Disease Genetics Consortium. RESULTS: We observed eight significant associations in univariable MR analysis, four of which were corroborated by multivariable MR (MVMR) analysis modified for the other three lipid traits: high-density lipoprotein cholesterol (HDL-C) level with the risk of PTSD (OR = 0.91, 95% CI = 0.85-0.97, p = 0.002) and AD (OR = 0.79, 95% CI = 0.71-0.88, p < 0.001) and triglycerides (TG) level with the risk of MDD (OR = 1.02, 95% CI = 1.003-1.03, p = 0.01) and panic disorder (OR = 0.83, 95% CI = 0.74-0.92, p < 0.001). In addition, four associations were not significant in MVMR analysis after adjustment for three lipid traits: total cholesterol (TC) level with the risk of PTSD, low-density lipoprotein cholesterol (LDL-C) level with the risk of MDD and AD and TG level with the risk of AD. CONCLUSIONS: Our results show that blood lipids and psychiatric disorders may be related in a causal manner. This shows that abnormal blood lipid levels may act as reliable biomarker of psychiatric disorders and as suitable targets for their prevention and treatment.
Subject(s)
Mendelian Randomization Analysis , Mental Disorders , Humans , Genome-Wide Association Study , Mental Disorders/genetics , Cholesterol, LDL , Lipids , Polymorphism, Single NucleotideABSTRACT
AIM: To access the agreement of intraocular pressure (IOP) values obtained from biomechanically corrected tonometer [Corvis ST (CST)], non-contact tonometer (NCT), and Goldmann applanation tonometer (GAT) in children with NCT measured-IOP (NCT-IOP) values of 22 mm Hg or more, and related factors. METHODS: A total of 51 eyes with NCT-IOP≥22 mm Hg in children aged 7 to 14y were examined and IOP was measured by CST, NCT, and GAT. Based on GAT measured IOP (GAT-IOP), ocular hypertension (OHT) group (≥22 mm Hg, 24 eyes) and the non-OHT group (<22 mm Hg, 27 eyes) were defined. We compared the agreement of the three measurements, i.e., CST measured IOP (CST-IOP), GAT-IOP, and NCT-IOP, and further analyzed the correlation between the differences in tonometry readings, central corneal thickness (CCT), axial length (AL), optic disc rim volume, and age. RESULTS: Compared with the OHT group, thicker CCT, larger rim volume, and higher differences between NCT-IOP and GAT-IOP, were found in the non-OHT group. The differences between CST-IOP and GAT-IOP were lower than the differences between NCT-IOP and GAT-IOP in both groups. The mean differences in CST-IOP and GAT-IOP were 1.26 mm Hg (95% limit of agreement ranged from 0.1 to 2.41 mm Hg, OHT group) and 1.20 mm Hg (95% limit of agreement ranged from -0.5 to 3.00 mm Hg, non-OHT group), and the mean differences in NCT and GAT were 3.90 mm Hg (95% limit of agreement ranged from -0.19 to 9.70 mm Hg, OHT group) and 6.00 mm Hg (95% limit of agreement ranged from 1.50 to 10.50 mm Hg, non-OHT group). The differences between CST-IOP and GAT-IOP were not related to CCT, age, and AL in both groups; while the differences between NCT-IOP and GAT-IOP were related to CCT in the OHT group (r=0.93, P<0.001) and to CCT and AL in the non-OHT group (r=0.66, P<0.001, r=-0.81, P<0.001). CONCLUSION: The accuracy of NCT in the diagnosis of pediatric OHT is low. The agreement of CST-IOP and GAT-IOP was significantly higher in children with and without OHT than in those with NCT-IOP and GAT-IOP. Therefore, CST can be used as a good alternative for IOP measurement in children. The impacts of CCT and AL on NCT measurement need to be fully considered when managing childhood IOP.
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Currently, clinical strategies for the treatment of wounds are limited, especially in terms of achieving rapid wound healing. In recent years, based on the technique of electrospinning (ES), cell electrospinning (C-ES) has been developed to better repair related tissues or organs (such as skin, fat and muscle) by encapsulating living cells in a microfiber or nanofiber environment and constructing 3D living fiber scaffolds. Therefore, C-ES has promising prospects for promoting wound healing. In this article, C-ES technology and its advantages, the differences between C-ES and traditional ES, the parameters suitable for maintaining cytoactivity, and material selection and design issues are summarized. In addition, we review the application of C-ES in the fields of biomaterials and cells. Finally, the limitations and improved methods of C-ES are discussed. In conclusion, the potential advantages, limitations and prospects of C-ES application in wound healing are presented.