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Ethyl methanesulfonate (EMS)-induced mutagenesis is a prominent method for generating plant mutants, often resulting in chimera plants; however, their transcriptional and genetic characteristic remain elusive. In this investigation, chimera pea (Pisum sativum L.) specimens, labeled GY1 and GY2, exhibiting a distinctive phenotype with yellow and green leaves were meticulously cultivated via sequential double EMS mutagenesis. The observed color disparity between the yellow and green leaves was attributed to a significant reduction in chlorophyll content coupled with heightened lutein levels in both chimeric variants. Transcriptome profiling revealed the enrichment of differentially expressed genes in both GY1 and GY2, specifically implicating Kyoto Encyclopedia of Genes and Genomes pathways linked to amino acid biosynthesis and ribosome development, alongside Gene Ontology (GO) biological processes linked with stress response mechanisms. Few structural genes associated with chlorophyll and lutein biosynthesis exhibited discernible differential expression. Despite these functional similarities, distinctive nuances were evident between specimens, with GY1 exhibiting enrichment in GO pathways related to chloroplast development and GY2 showing enrichment for ribosome development pathways. Single-nucleotide polymorphism (SNP) analysis uncovered a shared pool of 599 and 598 polymorphisms in the yellow and green leaves of GY1 and GY2, respectively, likely stemming from the initial EMS mutagenesis step. Further investigation revealed an increased number of unique SNPs in the yellow leaves following the second EMS application, whereas the green leaves exhibited sparse and unique SNP occurrences, suggestive of potential evasion from secondary mutagenesis. This inherent genetic variability underpins the mechanism underlying the formation of chimera plants. Predominant base mutations induced by EMS were characterized by G/A and C/T transitions, constituting 74.1% of the total mutations, aligning with established EMS mutation induction paradigms. Notably, genes encoding the eukaryotic translation initiation factor eIIso4G and the ubiquitin ligase RKP, known to modulate leaf color in model plants, harbored two SNPs in the yellow leaves of both GY1 and GY2, implicating their putative role in the yellow leaf phenotype. Collectively, this study provides novel insights into the transcriptional and genetic characteristics of chimera plants via EMS-induced mutagenesis.

Infection and poor osteogenesis are two major causes of implant failure. Surface modification strategy provides solutions to the above problems. However, the functional requirements at different biological stages during infectious bone repair and the oxidative stimulation caused by reactive oxygen species (ROS) in an inflammatory environment pose challenges to the existing approaches. Layer-by-layer (LbL) self-assembly realizes layer by layer superposition and time-dependent acting of different bioactive components, but is demanding to functional groups. Tannic acid (TA) owns abundant phenolic hydroxyl groups, endowing various firm chemical bindings and excellent antioxidant property. To this end, we developed a time-dependent and antioxidant multifunctional coating via TA mediated LbL self-assembly. This layer exhibited higher ROS removal capacity and stronger binding ability. Furthermore, it showed rapid and excellent antibacterial ability of over 85 % against Staphylococcus aureus and Escherichia coli at 24 h, which additionally promoted osteogenic differentiation in vitro in long term. Moreover, the coating exhibited outstanding antibacterial and bone regeneration performance in vivo as well. Thus, this study is expected to provide an antioxidant and time-dependent multifunctional platform for surface modification engineering of dental and orthopedic implantation, as well as other potential biological material designs.

N6-methyladenosine (m6A) methylation is one of the most predominant internal RNA modifications in eukaryotes and has become a hot spot in the field of epigenetics in recent years. Cardiovascular diseases (CVDs) are a leading cause of death globally. Emerging evidence demonstrates that RNA modifications, such as the m6A modification, are associated with the development and progression of many diseases, including CVDs. An increasing body of studies has indicated that programmed cell death (PCD) plays a vital role in CVDs. However, the molecular mechanisms underlying m6A modification and PCD in CVDs remain poorly understood. Herein, elaborating on the highly complex connections between the m6A mechanisms and different PCD signaling pathways and clarifying the exact molecular mechanism of m6A modification mediating PCD have significant meaning in developing new strategies for the prevention and therapy of CVDs. There is great potential for clinical application.

Hepatocellular carcinoma (HCC) is the major cause of cancer-associated mortality worldwide. Despite great advances have been made on the treatment of HCC, the survival rate of patients remains poor. Spindle apparatus coiled-coil protein 1 (SPDL1) is involved in the development of various cancers in humans. However, the role of SPDL1 in HCC remains unclear. In this study, we found high expression of SPDL1 in HCC tissues as compared to normal samples. In vitro, silencing of SPDL1 induced HCC cell apoptosis, and suppressed HCC cell propagation and migration. In vivo, knockdown of SPDL1 inhibited the tumor growth of HCC cells. These findings indicated the tumor-promoting role of SPDL1 in HCC. Mechanistically, we identified farnesyltransferase-beta (FNTB) as the downstream target protein of SPDL1 based on immunoprecipitation and mass spectrometry, which were confirmed by western blotting. Rescue assay determined that FNTB played a tumor promoting role in SPDL1-trigger HCC cell growth. Overexpression of FNTB recovered HCC cell viability and migration in SPDL1 knockdown cells. We also found that silencing of SPDL1 increased the sensitivity of Huh7 cells to sorafenib and lenvatinib, suggesting that SPDL1 is a new therapeutic target in HCC. Collectivity, the present study identified a new axis SPDL1/FNTB involved in the progression of HCC. Hence, SPDL1/FNTB is a potential target for the treatment of HCC.

BackgroundSarcopenia is a condition characterized by the age-related loss of skeletal muscle mass and function. The pathogenesis of the disease is influenced by chronic low-grade inflammation. However, the specific changes in the immune landscape changes of sarcopenic muscle are not yet fully understood.MethodsTo gain insights into the immune cell composition and interactions, we combined single-nucleus RNA sequencing data, bulk RNA sequencing dataset, and comprehensive bioinformatic analyses on the skeletal muscle samples from young, aged, and sarcopenic individuals. Histological staining was then performed on skeletal muscles to validate the distribution of immune cells in clinical samples.ResultsWe analyzed the transcriptomes of 101,862 single nuclei, revealing a total of 10 major cell types and 6 subclusters of immune cell types within the human skeletal muscle tissues. Notable variations were identified in the immune microenvironment between young and aged skeletal muscle. Among the immune cells from skeletal muscle microenvironment, macrophages constituted the largest fraction. A specific marker gene LYVE1 for skeletal muscle resident macrophages was further identified. Cellular subclasses included four distinct groups of resident macrophages, which play different roles in physiological or non-physiological conditions. Utilizing bulk RNA sequencing data, we observed a significant enrichment of macrophage-rich inflammation in sarcopenia.ConclusionsOur findings demonstrate age-related changes in the composition and cross-talk of immune cells in human skeletal muscle microenvironment, which contribute to chronic inflammation in aged or sarcopenia muscle. Furthermore, macrophages emerge as a potential therapeutic target, thus advancing our understanding of the pathogenesis of sarcopenia.

Toxoplasma gondii, an obligate intracellular parasite, is a globally prevalent pathogen capable of infecting a wide range of warm-blooded animals, including humans. Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications. This comprehensive review delves into the current understanding of T. gondii biology, exploring its complex life cycle, diverse transmission routes, and strain diversity. This article provides an in-depth analysis of the clinical manifestations of OT, which can result from both congenital and acquired infections, presenting a spectrum of signs and symptoms. The review examines various diagnostic strategies employed for OT, including clinical examination, multimodal imaging techniques such as fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA), as well as laboratory tests including serology and molecular methods. Despite extensive research, the specific mechanisms underlying ocular involvement in T. gondii infection remain elusive, and current diagnostic options have limitations. Moreover, the treatment of active and recurrent OT remains a challenge. While existing therapies, such as antimicrobial agents and immunosuppressants, can control active infections, they do not offer a definitive cure or completely prevent recurrence. The clinical endpoints for the management of active and recurrent OT are also not yet well-established, and the available treatment methods carry the potential for adverse effects. This article highlights the need for future research to elucidate the pathogenesis of OT, investigate genetic factors influencing susceptibility to infection, and develop more sensitive and specific diagnostic tools. Enhancing global surveillance, implementing robust prevention strategies, and fostering multidisciplinary collaborations will be crucial in reducing the burden of OT and improving patient outcomes. This comprehensive review aims to provide a valuable resource for clinicians, researchers, and policymakers, contributing to a better understanding of T. gondii infection and its impact on ocular health.

Cytomegalovirus (CMV) retinitis is the most common eye disease associated with CMV infection in immunocompromised individuals. The CMVR may initially be asymptomatic; however, relatively mild vitreous inflammation at the onset may be an important differential point from other diseases in HIV patients. Fundus photography, CD4 T-cell count, and telemedicine could be used to screen and monitor the high-risk population, particularly in resource-limited regions. Retinitis generally starts in the peripheral retina and advances toward the posterior pole, which could develop to the characteristic “pizza pie” appearance marked by central retinal necrosis and intraretinal hemorrhage. CMVR causes vision loss if left untreated, and early antiviral therapy significantly reduces the risk of vision loss. Alongside traditional antiviral treatments, immunotherapies including CMV-specific adoptive T-cell therapy and CMV immunoglobulin (CMVIG) are emerging as promising treatment options due to their favorable tolerability and reduced mortality. This review comprehensively examines CMV retinitis, encompassing the clinical features, differential diagnosis, laboratory tests, and updated treatment strategies to inform clinical management.

CD4+CD25+Foxp3+ regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining immune homeostasis and preventing excessive immune responses. This review explores the signaling pathways of the cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, and IL-35, which foster the differentiation and enhance the immunosuppressive capabilities of Tregs. It also examines how, conversely, signals mediated by IL-6 and tumor necrosis factor -alpha (TNF-α) can undermine Treg suppressive functions or even drive their reprogramming into effector T cells. The B7 family comprises indispensable co-stimulators for T cell activation. Among its members, this review focuses on the capacity of CTLA-4 and PD-1 to regulate the differentiation, function, and survival of Tregs. As Tregs play an essential role in maintaining immune homeostasis, their dysfunction contributes to the pathogenesis of autoimmune diseases. This review delves into the potential of employing Treg-based immunotherapy for the treatment of autoimmune diseases, transplant rejection, and cancer. By shedding light on these topics, this article aims to enhance our understanding of the regulation of Tregs by cytokines and their therapeutic potential for various pathological conditions.

Numerous surface modification strategies for ordinary titanium (Ti) implant have been proposed since Ti lacks antibacterial and osteogenic characteristics. However, the majority of surface modifying materials currently do not consider the microenvironmental demands that are constantly changing ——Antibacterial is required at the early stage after implantation and osteogenesis becomes an intense appeal at the later stage. In the present study, strontium ranelate (SrR) and chitosan (CTS) were loaded onto the titanium surface via layer-by-layer (LbL) self-assembly based on tannic acid (TA) with separate antimicrobial and osteogenic layers. The obtained Titanium-Strontium Ranelate-Chitosan (Ti-SrR-CTS) implant achieved an outstanding early-stage antibacterial effect against S. aureus and E. coli and a more prominent late-stage osteogenic effect than ordinary titanium implant in vitro. In vivo results further verified that Ti-SrR-CTS implants had 97.68% antibacterial efficacy and 1.82 times the amount of new bone compared to ordinary titanium at different stages, respectively. This work has successfully designed a novel implant coating with both excellent antimicrobial and osteogenic properties, which provides a promising surface modification strategy for orthopedic applications.

Abstract Angelica sinensis roots (Angelica roots) are rich in many bioactive compounds, including phthalides, coumarins, lignans, and terpenoids. However, the molecular bases for their biosynthesis are still poorly understood. Here, an improved chromosome-scale genome for A. sinensis var. Qinggui1 is reported, with a size of 2.16 Gb, contig N50 of 4.96 Mb and scaffold N50 of 198.27 Mb, covering 99.8% of the estimated genome. Additionally, by integrating genome sequencing, metabolomic profiling, and transcriptome analysis of normally growing and early-flowering Angelica roots that exhibit dramatically different metabolite profiles, the pathways and critical metabolic genes for the biosynthesis of these major bioactive components in Angelica roots have been deciphered. Multiomic analyses have also revealed the evolution and regulation of key metabolic genes for the biosynthesis of pharmaceutically bioactive components; in particular, TPSs for terpenoid volatiles, ACCs for malonyl CoA, PKSs for phthalide, and PTs for coumarin biosynthesis were expanded in the A. sinensis genome. These findings provide new insights into the biosynthesis of pharmaceutically important compounds in Angelica roots for exploration of synthetic biology and genetic improvement of herbal quality.

Introduction: There are few studies on the relationship between the occurrence of clopidogrel-related high residual platelet reactivity (HRPR) and estimated glomerular filtration rate (eGFR) at admission in patients with ischemic stroke. The aim of this study was to investigate the possible relationship between the two. Methods: Patients who were hospitalized and diagnosed with acute ischemic stroke were recruited from July 1, 2017, to June 30, 2018, at Shanghai TCM-Integrated Hospital. Renal function was measured within 24 h of enrollment and eGFR was calculated. Patients were tested for platelet reactivity using the VerifyNow system after 7 days of antiplatelet therapy with clopidogrel 75 mg/d alone, and patients with P2Y12 reaction unit values ≥230 were diagnosed with HRPR. The association between HRPR and eGFR was analyzed. Results: A total of 274 patients were enrolled in the study, of whom 91 (33.21%) had HRPR. Multivariate logistic regression analysis suggested that an increased risk of HRPR was independently associated with female sex and reduced eGFR (female sex: OR = 2.24, 95% CI: 1.26–3.99, p = 0.006; mild chronic kidney disease [CKD]: OR = 2.95, 95% CI: 1.47–5.93, p = 0.002; moderate CKD: OR = 3.07, 95% CI: 1.08–8.75, p = 0.04). Conclusion: Decreased eGFR is an independent risk factor for the occurrence of HRPR in patients with ischemic stroke.

Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy.

Abstract Prime editing is limited by low efficiency in plants. Here, we develop an upgraded engineered plant prime editor in hexaploid wheat, ePPEplus, by introducing a V223A substitution into reverse transcriptase in the ePPEmax* architecture. ePPEplus enhances the efficiency by an average 33.0-fold and 6.4-fold compared to the original PPE and ePPE, respectively. Importantly, a robust multiplex prime editing platform is established for simultaneous editing of four to ten genes in protoplasts and up to eight genes in regenerated wheat plants at frequencies up to 74.5%, thus expanding the applicability of prime editors for stacking of multiple agronomic traits.

Abstract Background To compare the outcomes of sutured transscleral fixation and sutureless intrascleral fixation for the treatment of a dislocated intraocular lens (IOL). Methods Thirty-five eyes of 35 patients who required IOL repositioning surgery due to IOL dislocation were included in this retrospective study. Sixteen eyes underwent two-point sutured transscleral fixation, eight eyes underwent one-point sutured transscleral fixation, and 11 eyes underwent sutureless intrascleral IOL fixation. The patients were followed for ≥ 12 months after repositioning surgery, and their postoperative outcomes were recorded and analyzed. Results The major cause of IOL dislocation was ocular blunt trauma (19/35, 54.3%). The mean corrected distance visual acuity (CDVA) improved significantly after IOL repositioning (P = 0.022). The mean postoperative change in endothelial cell density (ECD) was − 4.5%. There were no significant differences in the changes in CDVA or ECD among the three groups with different repositioning techniques (both P > 0.1). The mean vertical tilt of the IOLs in all enrolled patients was significantly greater than the horizontal value (P = 0.001). The vertical tilt was greater in the two-point scleral fixation group than that in the sutureless intrascleral fixation group (P = 0.048). The mean decentration values in the one-point scleral fixation group in the horizontal and vertical directions were greater than those in the other two groups (all P

Abstract Immunogenic cell death (ICD) is a form of cell death that stimulates the immune system to produce an immune response by releasing tumour-associated antigens and tumour-specific antigens and is considered to play an important role in tumour immunotherapy. In the present study, we identified two ICD-related subtypes in osteosarcoma (OS) by consensus clustering. The ICD-low subtype was associated with favourable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signalling. We also established and validated an ICD-related prognostic model, which could not only be used to predict the overall survival of OS patients but was also found to be closely related to the tumour immune microenvironment of OS patients. Overall, we established a new classification system for OS based on ICD-related genes, which can be used to predict the prognosis of OS patients and to select appropriate immunotherapy drugs.

Background: Recognizing human emotions by micro-expression recognition is one of the most critical issues in human-computer interaction applications. Cross-database micro-expression recognition (CDMER) is an increasingly significant problem in micro-expression recognition and analysis in recent years. Since the training data and testing data in CDMER come from different micro-expression databases, CDMER is more challenging than the conventional micro-expression recognition. Methods: In this paper, an Adaptive Spatio-Temporal Attention Neural Network (ASTANN) using attention mechanism is presented to deal with this challenging and critical problem. To this end, the micro-expression database SMIC and CASME II are firstly preprocessed by optical flow approach, which extract motion information among video frames that represents discriminative features of micro-expression. After preprocessing, a novel adaptive framework with spatio-temporal attention module is designed to assign spatial and temporal weights to enhance the most discriminative features. Then the deep neural network extracts cross-domain feature, in which the second-order statistics of the sample features in source domain is aligned with the ones in the target domain by minimizing the correlation alignment (CORAL) loss such that source and target database share similar distributions. Results: To evaluate the performance of ASTANN, experiments are conducted based on SMIC and CASME II databases under a standard experimental evaluation protocol of CDMER. The experimental results demonstrate that ASTANN outperforms other methods in relevant cross-database tasks. Conclusions: Extensive experiments are conducted on the benchmark tasks and results show that ASTANN achieves the best performance over all other approaches. This remarkable performance demonstrates the superiority of our method for solving CDMER problem.

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.

Four undescribed sesquiterpenoids, lemneolemnanes A–D (1–4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1–4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer’s disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5–10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.

BackgroundPrimary Sjögren’s syndrome (pSS) is a progressive inflammatory autoimmune disease. Immune cell infiltration into glandular lobules and ducts and glandular destruction are the pathophysiological hallmarks of pSS. Macrophages are one of the most important cells involved in the induction and regulation of an inflammatory microenvironment. Although studies have reported that an abnormal tissue microenvironment alters the metabolic reprogramming and polarisation status of macrophages, the mechanisms driving macrophage infiltration and polarisation in pSS remain unclear.MethodsImmune cell subsets were characterised using the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from patients with pSS (n = 5) and healthy individuals (n = 5) in a public dataset. To evaluate macrophage infiltration and polarisation in target tissues, labial salivary gland biopsy tissues were subjected to histological staining and bulk RNA-seq (pSS samples, n = 24; non-pSS samples, n = 12). RNA-seq data were analysed for the construction of macrophage co-expression modules, enrichment of biological processes and deconvolution-based screening of immune cell types.ResultsDetailed mapping of PBMCs using scRNA-seq revealed five major immune cell subsets in pSS, namely, T cells, B cells, natural killer (NK) cells, dendritic cells (DCs) and monocyte-macrophages. The monocyte-macrophage subset was large and had strong inflammatory gene signatures. This subset was found to play an important role in the generation of reactive oxygen species and communicate with other innate and adaptive immune cells. Histological staining revealed that the number of tissue-resident macrophages was high in damaged glandular tissues, with the cells persistently surrounding the tissues. Analysis of RNA-seq data using multiple algorithms demonstrated that the high abundance of pro-inflammatory M1 macrophages was accompanied by the high abundance of other infiltrating immune cells, senescence-associated secretory phenotype and evident metabolic reprogramming.ConclusionMacrophages are among the most abundant innate immune cells in PBMCs and glandular tissues in patients with pSS. A bidirectional relationship exists between macrophage polarisation and the inflammatory microenvironment, which may serve as a therapeutic target for pSS.

Objective: Previous studies are insufficient to confirm a causal association between physical activity (PA) and low back pain (LBP), intervertebral disc degeneration (IDD), and sciatica. The present study used a two-sample Mendelian randomization (MR) analysis method to demonstrate whether or not there was a causal connection.Methods: First, four PA phenotypes were selected [accelerometer-based PA (average acceleration), accelerometer-based PA (acceleration fraction >425 mg), self-reported moderate-to-vigorous PA, and self-reported vigorous PA], setting thresholds for single nucleotide polymorphisms (SNPs) significantly concerned with PA p < 5 × 10−8, linkage disequilibrium (LD) r2 < 0.01, genetic distance >5,000 kb, and F-value >10. SNPs associated with the outcome and confounding factors were then excluded using the PhenoScanncer database. Finally, after coordinating the genetic instruments from genome-wide association studies (GWAS) effect alleles for exposure and outcomes, multiplicative random effects inverse variance weighting (IVW), MR-Egger, weighted median method (WMM), and weighted mode method were used to assess exposure-outcome causality and perform sensitivity analysis on the estimated results.Results: The current study’s IVW findings revealed proof of a causal connection between PA and LBP. While there was a positive causal tie between accelerometer-based PA (acceleration fraction >425 mg) and LBP [OR: 1.818, 95% CI:1.129–2.926, p = 0.012], there was a negative causal link between accelerometer-based PA (average acceleration) and LBP [OR: 0.945, 95% CI: 0.909–0.984, p = 0.005]. However causal relationship between PA and IDD or sciatica was not found.Conclusion: Increasing average PA but needing to avoid high-intensity PA may be an effective means of preventing low back pain. Although PA is not directly causally related to disc degeneration and sciatica, it can act through indirect pathways.

Background and purpose: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. This study aimed to investigate the potential of R-(+)-WIN55212-2 (WIN), a cannabinoid receptor 1 agonist (CB1), as a treatment for retinal ischemia/reperfusion (I/R) injury. Experimental approach: Male Wistar rats were subjected to retinal I/R injury by increasing intraocular pressure in the anterior chamber. The rats were randomly divided into four groups: normal control, I/R, vehicle (pre-treated with dimethyl sulfoxide [DMSO] via intraperitoneal injection), and experimental (pre-treated with WIN at a dose of 1 ml/kg via intraperitoneal injection). The rats were sacrificed at different time points of reperfusion (1 hour, 3 hours, 6 hours, and 1 day) after inducing retinal I/R injury, and their retinas were collected for analysis. Oxygen-glucose deprived/reperfusion (OGD/R) was performed by initially perfusing the retinas with oxygenated artificial cerebrospinal fluid (ACSF), then switching to an OGD solution to simulate ischemia, followed by another perfusion with ACSF. Pericyte contraction and the ''no-reflow'' phenomenon were observed using infrared differential interference contrast (IR-DIC) microscopy and immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), and nitric oxide (NO) detection were used to explore the potential mechanism. Key results: In both the OGD/R and I/R models, retinal pericytes exhibited persistent contraction even after reperfusion. The ability of WIN to regulate the tone of retinal pericytes and capillaries was specifically blocked by the BKCa inhibitor iberiotoxin (100 nM). WIN demonstrated a protective effect against retinal I/R injury by preserving blood flow in vessels containing pericytes. Pretreatment with WIN alleviated the persistent contraction and apoptosis of retinal pericytes in I/R-induced rats, accompanied by a reduction in intracellular calcium ion (Ca2+) concentration. The expression of CB1 decreased in a time-dependent manner in the I/R group. After I/R injury, endothelium-derived nitric oxide (eNOS) levels were reduced at all time points, which was successfully reversed by WIN therapy except for the 1 day group. Additionally, the downregulation of cyclic guanosine monophosphate (cGMP) and BKCa expression at 3 hours, 6 hours, and 1 day after I/R injury was restored by pretreatment of WIN. Conclusions & implications: WIN exerted its protective effects on retinal I/R injury by inhibiting the contraction and apoptosis of pericytes through the CB1-eNOS-cGMP-BKCa signaling pathway, thus ameliorated the occlusion of retinal capillaries.

The target recognition performance of steady-state visual evoked potential (SSVEP)-based brain-computer interfaces can be significantly improved with a training-based approach. However, the training procedure is time consuming and often causes fatigue. Consequently, the number of training data should be limited, which may reduce the classification performance. Thus, how to improve classification accuracy without increasing the training time is crucial to SSVEP-based BCI system. This study proposes a transfer-related component analysis (TransRCA) method for addressing the above issue. In this method, the SSVEP-related components are extracted from a small number of training data of the current individual and combined with those extracted from a large number of existing training data of other individuals. The TransRCA method maximizes not only the inter-trial covariances between the source and target subjects, but also the correlation between the reference signals and SSVEP signals from the source and target subjects. The proposed method was validated on the SSVEP public Benchmark and BETA datasets, and the classification accuracy and information transmission rate of the ensemble version of the proposed TransRCA method were compared with those of the state-of-the-art eCCA, eTRCA, ttCCA, LSTeTRCA, and eIISMC methods on both datasets. The comparison results indicate that the proposed method provides a superior performance compared with these state-of-the-art methods, and thus has high potential for the development of a SSVEP-based brain-computer interface system with high classification performance that only uses a small number of training data.

AbstractLycium ruthenicum is a characteristic plant resource in Northwest China. The fruit with high anthocyanin content is the main reason for its high nutritional value and economic value, while the regulation of key genes regulating anthocyanin biosynthesis in black fruit is not clear. In this study, high-throughput sequencing technology was used to compare the expression differences of all genes in black and purple fruits. The purple samples obtained 45.13 and 51.49 M Raw reads, while the black fruit samples measured 53.85 and 47.38 M Raw Reads. After splicing and assembly, 162,842 transcripts were obtained after removing redundant and duplicated results. Homology comparison of all predicted proteins found that 36,978 (22.43%) genes in Lycium ruthenicum were homologous to Solanum tuberosum, followed by 24,459 (14.84%) genes were homologous to Capsicum annuum. Overall, 3685 genes were up-regulated in purple fruit, 2837 genes were down-regulated in purple fruit, and the remaining 156320 genes were not differentially expressed in black and purple fruit. Through homology comparison of anthocyanin biosynthesis and metabolism structure genes in Lycium ruthenicum, 63 homologous genes, 4 MYB transcription factors and 5 bHLH transcription factors were screened. LrAN2p (909 bp) in purple fruit was 136 bp more upstream of ‘ATG’ than LrAN2 (774 bp) in black fruit. Three highly expressed copies of bHLH transcription factors AN1b with different lengths were screened in black fruit, but they were almost not expressed in purple fruit. This study possibly identified the major LrAN1b genes regulating the black fruit trait.

AbstractJerusalem artichoke (Helianthus tuberosus L.) is a fructan-accumulating plant and an industrial raw material for fructan production. However, the genetic mechanism of fructan biosynthesis remains unclear. Therefore, this study performed transcriptome analysis to determine the genetic differences between two Jerusalem artichoke genotypes and different fructan contents. Approximately 19.73 Gb of clean data were obtained after filtering, and a total of 164,006 unigenes were annotated based on GO, KOG and KEGG functional classification. Then, seven homologous genes involved in fructan biosynthesis were obtained by homology comparison. CL11458.Contig2 and CL7122.Contig14 were candidate genes for sucrose:sucrose 1-fructosyl-transferase (1-SST) and fructan:fructan 1-fructosyl-transferase (1-FFT), respectively. The genetic relationship between SST and SST from artichoke in the phylogenetic tree are relatively close, and FFT is located in the same branch as FFT from ‘Qingyu No.1’ Jerusalem artichoke and Viguiera. SST and FFT were the main regulatory genes of fructan accumulation in Jerusalem artichoke. Therefore, this study successfully identified major genes involved in fructan biosynthesis. Future studies should aim to prove the role of each candidate gene in fructan biosynthesis in Jerusalem artichoke.

BackgroundPrimary Sjogren Syndrome (pSS) is an autoimmune disease characterized by immune cell infiltration. While the presence of follicular T helper (Tfh) cells in the glandular microenvironment has been observed, their biological functions and clinical significance remain poorly understood.MethodsWe enrolled a total of 106 patients with pSS and 46 patients without pSS for this study. Clinical data and labial salivary gland (LSG) biopsies were collected from all participants. Histological staining was performed to assess the distribution of Tfh cells and B cells. Transcriptome analysis using RNA-sequencing (RNA-seq) was conducted on 56 patients with pSS and 26 patients without pSS to uncover the underlying molecular mechanisms of Tfh cells. To categorize patients, we employed the single-sample gene set enrichment analysis (ssGSEA) algorithm, dividing them into low- and high-Tfh groups. We then utilized gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and deconvolution tools to explore functional and immune infiltration differences between the low- and high-Tfh groups.ResultsPatients with pSS had a higher positive rate of the antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB and hypergammaglobulinaemia and higher levels of serum IgG compared to the non-pSS. Histopathologic analyses revealed the presence of Tfh cells (CD4+CXCR5+ICOS+) in germinal centers (GC) within the labial glands of pSS patients. GSEA, WGCNA, and correlation analysis indicated that the high-Tfh group was associated with an immune response related to virus-mediated IFN response and metabolic processes, primarily characterized by hypoxia, elevated glycolysis, and oxidative phosphorylation levels. In pSS, most immune cell types exhibited significantly higher infiltration levels in the high-Tfh group compared to the low-Tfh group. Additionally, patients in the Tfh-high group demonstrated a higher positive rate of the ANA, rheumatoid factor (RF), and hypergammaglobulinaemia, as well as higher serum IgG levels.ConclusionOur study suggests that Tfh cells may play a crucial role in the pathogenesis of pSS and could serve as potential therapeutic targets in pSS patients.

The interior problem, a persistent ill-posed challenge in CT imaging, gives rise to truncation artifacts capable of distorting CT values, thereby significantly impacting clinical diagnoses. Traditional methods have long struggled to effectively solve this issue until the advent of supervised models built on deep neural networks. However, supervised models are constrained by the need for paired data, limiting their practical application. Therefore, we propose a simple and efficient unsupervised method based on the Cycle-GAN framework. Introducing an implicit disentanglement strategy, we aim to separate truncation artifacts from content information. The separated artifact features serve as complementary constraints and the source of generating simulated paired data to enhance the training of the sub-network dedicated to removing truncation artifacts. Additionally, we incorporate polar transformation and an innovative constraint tailored specifically for truncation artifact features, further contributing to the effectiveness of our approach. Experiments conducted on multiple datasets demonstrate that our unsupervised network outperforms the traditional Cycle-GAN model significantly. When compared to state-of-the-art supervised models trained on paired datasets, our model achieves comparable visual results and closely aligns with quantitative evaluation metrics.

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32–73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

Abstract Background Myocardial dysfunction is common in septic shock and has long been recognized. Takotsubo syndrome is an acute and usually reversible myocardial injury without evidence of an obstructive coronary artery disease, yet little is known about this syndrome in septic shock patients. Case presentation Among 84 septic shock patients admitted to the ICU over a period of 8 months, 7 patients (8.3%) were diagnosed with Takotsubo syndrome. The percentage of men was 71%, and the mean age was 58 (19–87) years. Sudden hemodynamic deterioration and/or dyspnea were the presenting symptoms in 6 patients. T-wave inversion was the major ECG anomaly in 5 patients. The mean left ventricular ejection fraction was 31.8% (20.0–53.0). Mild elevation of cardiac troponin disproportionate to the extent of regional wall motion abnormalities was present in all patients. Cardiac complications occurred in 6 patients. The mean time to recover the cardiac function was 6.5 (3–11) days. In-hospital death was observed in 2 patients. Conclusions Takotsubo syndrome is not uncommon in septic shock patients and may be the cause of some patients with sepsis-induced myocardial dysfunction. New-onset hemodynamic and respiratory worsening could arouse the suspicion of Takotsubo syndrome and prompt the screening for this syndrome using echocardiography in this clinical context.

Abstract Background Acute respiratory distress syndrome (ARDS) has high mortality and is mainly related to the circulatory failure.Therefore, real-time monitoring of cardiac function and structural changes has important clinical significance.Transthoracic echocardiography (TTE) is a simple and noninvasive real-time cardiac examination which is widely used in intensive care unit (ICU) patients.The purpose of this study was to analyze the effect of TTE on the prognosis of ICU patients with ARDS. Methods The data of ARDS patients were retrieved from the MIMIC-III v1.4 database and patients were divided into the TTE group and non-TTE group. The baseline data were compared between the two groups. The effect of TTE on the prognosis of ARDS patients was analyzed through multivariate logistic analysis and the propensity score (PS). The primary outcome was the 28-d mortality rate. The secondary outcomes included pulmonary artery catheter (PAC) and Pulse index continuous cardiac output (PiCCO) administration, the ventilator-free and vasopressor-free days and total intravenous infusion volume on days 1, 2 and 3 of the mechanical ventilation. To illuminate the effect of echocardiography on the outcomes of ARDS patients,a sensitivity analysis was conducted by excluding those patients receiving either PiCCO or PAC. We also performed a subgroup analysis to assess the impact of TTE timing on the prognosis of patients with ARDS. Results A total of 1,346 ARDS patients were enrolled, including 519 (38.6%) cases in the TTE group and 827 (61.4%) cases in the non-TTE group. In the multivariate logistic regression, the 28-day mortality of patients in the TTE group was greatly improved (OR 0.71, 95%CI 0.55–0.92, P = 0.008). More patients in the TTE group received PAC (2% vs. 10%, P

Abstract Background We aimed to explore the changes in the axial length and related factors after vitrectomy for rhegmatogenous retinal detachment (RRD). Methods This study retrospectively evaluated patients who underwent vitrectomy with silicone oil (SO) tamponade for RRD and subsequent silicone oil removal at our clinic. Using a Zeiss IOLMaster 700, axial length was measured before vitrectomy for RRD and SO removal. The change in axial length (ΔAL) was calculated, and multivariate binary logistic regression analysis was performed to investigate the potential correlation between ΔAL and clinical factors, such as preoperative hypotony, extreme myopia, age, macular involvement, choroidal detachment, operation duration, and operation history. Results In total, 213 eyes from 213 patients were included. The mean axial length changed significantly pre- and post-vitrectomy (25.98 ± 2.87 mm and 26.25 ± 3.07 mm, respectively, P

Current implant systems still lack the ability to combat implant-associated infections (IAI) and insufficient osseointegration to reduce the risk of implant failure. There’s an urgent need to develop an effective implant modification method to match the needs of different biological stages post-implantation, which requires anti-infection at the initial stage and osseointegration at the latter long-term stage. Here, we constructed a mussel-inspired layer-by-layer (LbL) self-assembly implant modification platform via tannic acid (TA), sequentially anchoring osteoanabolic drug (Abaloparatide, ABL) and antibacterial (Dimethylaminohexadecyl methacrylate, DMAHDM) to the Titanium (Ti) surface (Ti/ABL/DMAHDM). The Ti/ABL/DMAHDM exhibited outstanding antibacterial properties at the initial stage with an antibacterial rate of 100 % both in vitro (24 h) and in vivo (48 h). Moreover, it showed significant osteogenic induction ability at the latter long-term stage both in vitro (7 days and 14 days) and in vivo (4 weeks), accompanied by good biocompatibility. This TA-mediated self-assembly modification implants platform with staged regulation of anti-infection and osteoinduction offers potential clinical prospects for improving osseointegration after implantation.

Abstract Background Nitraria sibirica Pall. is an economic plant with two kinds of fruit color, widely spreads in the Qinghai Tibet Plateau. The chemical analysis and pharmacological evaluation had been carried out for several tens of years, the mechanism behind the fruit color differentiation is still unclear. Results In this manuscript, the chemical analysis of the extractions showed that the chemical composition of fruit color was anthocyanin, and two kind of Nitraria sibirica Pall. were caused by the content differentiation with the same anthocyanin kinds. Cyanidin-3-[2”-(6′”-coumaroyl)-glucosyl]-glucoside (C3G) was the major anthocyanin. Transcriptome analysis and the qRT-PCR revealed that the structural genes relative to anthocyanin biosynthesis except CHS, F3’5’H and ANS were up-regulated in the peels of BF (Black fruit) compared with the peels of RF (Red fruit), which indicated that transcript factor should be the reason for the expression difference of the structure genes. In the unigenes of the transcript factor MYB and bHLH, relative to anthocyanin, only NsMYB1 (Cluster 8422.10600), was high-expression and up-expression in the peels of BF. NsMYB1 encoded the same length protein with four amino acid differences in the RF and BF, and both contained the intact DNA, HTH-MYB and SANT domains. NsMYB1 was close to the AtMYB114, AtMYB113 and AtPAP1, regulating anthocyanin biosynthesis, in phylogenetic relationship. Both NsMYB1r and NsMYB1b could promote the transcript of the structural genes, and induced the anthocyanin accumulation in all tissues of transgenic tobacco. The insertion of ‘TATA’ in the promoter of NsMYB1r gave one more promoter region, and was the reason for higher transcripts in black fruit possibly. Conclusions Cyanidin-3-[2′’-(6′”-coumaroyl)-glucosyl]-glucoside was the major anthocyanin in black fruit of Nitraria sibirica Pall.. NsMYB1 was a functional R2R3-MYB transcription factor, regulated the anthocyanin biosynthesis, and led to the fruit color differentiation in Nitraria sibirica Pall.

Flammulina velutipes is a renowned edible and medicinal fungus. Commercially cultivated F. velutipes occurs in two distinct phenotypes: white and yellow. However, the underlying mechanism contributing to the yellow phenotype and high nutritional value remain uncertain. We reconfirmed that the browning process in F. velutipes is attributable to melanin accumulation, although the initial yellow cap seemed unrelated to melanin. A transcriptomic and metabolomic joint analysis revealed that 477 chemical compounds categorized into 11 classes, among which 191 exhibited significantly different levels of accumulation between different phenotypes. Specifically, 12 compounds were unique to the yellow F. velutipes, including ferulic acid, and 3-Aminosalicylic acid. Free fatty acids and xanthine were identified as the primary compounds correlating with the yellow and oily cap. A total of 44,087 genes were identified, which were more homologous to Pleurotus ostreatus PC15. Structural genes such as PAL (phenylalanine ammonialyase), C4H (cinnamate 4-hydroxylase), C3H (Coumarin-3-hydroxylase), AoMT (caffeoyl coenzyme A-O-methyltransferase), and 4CL (4-coumarate: CoA ligase) were up-regulated, thereby activating the lignin biosynthesis and metabolism pathway. Additionally, FvbHLH1 can lead to the consumption of a huge amount of phenylalanine while generating flavonoids and organic acid compounds. Meanwhile, ferulic acid biosynthesis was activated. Therefore, this study clarifies the chemical and molecular bases for the yellow phenotype and nutritional value of F. velutipes.

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt–Koyanagi–Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles–mumps–rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.

Multimodal emotion recognition (MER) refers to the identification and understanding of human emotional states by combining different signals, including—but not limited to—text, speech, and face cues. MER plays a crucial role in the human–computer interaction (HCI) domain. With the recent progression of deep learning technologies and the increasing availability of multimodal datasets, the MER domain has witnessed considerable development, resulting in numerous significant research breakthroughs. However, a conspicuous absence of thorough and focused reviews on these deep learning-based MER achievements is observed. This survey aims to bridge this gap by providing a comprehensive overview of the recent advancements in MER based on deep learning. For an orderly exposition, this paper first outlines a meticulous analysis of the current multimodal datasets, emphasizing their advantages and constraints. Subsequently, we thoroughly scrutinize diverse methods for multimodal emotional feature extraction, highlighting the merits and demerits of each method. Moreover, we perform an exhaustive analysis of various MER algorithms, with particular focus on the model-agnostic fusion methods (including early fusion, late fusion, and hybrid fusion) and fusion based on intermediate layers of deep models (encompassing simple concatenation fusion, utterance-level interaction fusion, and fine-grained interaction fusion). We assess the strengths and weaknesses of these fusion strategies, providing guidance to researchers to help them select the most suitable techniques for their studies. In summary, this survey aims to provide a thorough and insightful review of the field of deep learning-based MER. It is intended as a valuable guide to aid researchers in furthering the evolution of this dynamic and impactful field.

Abstract Background Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Cross-database micro-expression recognition (CDMER) is a difficult task, where the target (testing) and source (training) samples come from different micro-expression (ME) databases, resulting in the inconsistency of the feature distributions between each other, and hence affecting the performance of many existing MER methods. To address this problem, we propose a dual-stream convolutional neural network (DSCNN) for dealing with CDMER tasks. In the DSCNN, two stream branches are designed to study temporal and facial region cues in ME samples with the goal of recognizing MEs. In addition, in the training process, the domain discrepancy loss is used to enforce the target and source samples to have similar feature distributions in some layers of the DSCNN. Extensive CDMER experiments are conducted to evaluate the DSCNN. The results show that our proposed DSCNN model achieves a higher recognition accuracy when compared with some representative CDMER methods.

Purpose. To compare ultrasound biomicroscopy (UBM), Coulter counter, and B-scan ultrasonography in the evaluation of silicone oil (SO) emulsification. Methods. Patients who underwent primary pars plana vitrectomy with SO tamponade for rhegmatogenous retinal detachment and SO removal were included. UBM images were acquired before the SO removal, and B-scan images were taken after removal. The number of droplets in the first and last 2 mL of washout fluid was analyzed using a Coulter counter. The correlations between these measurements were analyzed. Results. Thirty-four eyes received both UBM and Coulter counter analysis for the first 2 mL of washout fluid, and 34 underwent B-scan and Coulter counter analysis of the last 2 mL washout fluid. The mean UBM grading was 26.41 ± 9.71 (range: 1–36); the mean SO index obtained with B-scan was 5.25 ± 5.00% (range: 0.10–16.49%), and the mean number of SO droplets was 1.26 ± 2.45 × 107/mL and 3.34 ± 4.22 × 106/mL in the first and last 2 mL of washout fluid, respectively. There were significant correlations between UBM grading and SO droplets in the first 2 mL and between B-scan grading and SO droplets in the last 2 mL (all P

IntroductionHTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1–associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti–vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF165, the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF165 is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection in vitro.MethodsWe used MT2 and TL-Om1 cells as HTLV-1–infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1–infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments.ResultsAnti-VEGF antibody treatment had no effect on activated NF-κB production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-κB, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1–infected T cells.ConclusionThis preliminary in vitro assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1–related inflammation and thus may be safe for use.

Background and Objective: This study aims to find the key immune genes and mechanisms of low bone mineral density (LBMD) in ankylosing spondylitis (AS) patients.Methods: AS and LBMD datasets were downloaded from the GEO database, and differential expression gene analysis was performed to obtain DEGs. Immune-related genes (IRGs) were obtained from ImmPort. Overlapping DEGs and IRGs got I-DEGs. Pearson coefficients were used to calculate DEGs and IRGs correlations in the AS and LBMD datasets. Louvain community discovery was used to cluster the co-expression network to get gene modules. The module most related to the immune module was defined as the key module. Metascape was used for enrichment analysis of key modules. Further, I-DEGs with the same trend in AS and LBMD were considered key I-DEGs. Multiple machine learning methods were used to construct diagnostic models based on key I-DEGs. IID database was used to find the context of I-DEGs, especially in the skeletal system. Gene–biological process and gene-pathway networks were constructed based on key I-DEGs. In addition, immune infiltration was analyzed on the AS dataset using the CIBERSORT algorithm.Results: A total of 19 genes were identified I-DEGs, of which IFNAR1, PIK3CG, PTGER2, TNF, and CCL3 were considered the key I-DEGs. These key I-DEGs had a good relationship with the hub genes of key modules. Multiple machine learning showed that key I-DEGs, as a signature, had an excellent diagnostic performance in both AS and LBMD, and the SVM model had the highest AUC value. Key I-DEGs were closely linked through bridge genes, especially in the skeletal system. Pathway analysis showed that PIK3CG, IFNAR1, CCL3, and TNF participated in NETs formation through pathways such as the MAPK signaling pathway. Immune infiltration analysis showed neutrophils had the most significant differences between case and control groups and a good correlation with key I-DEG.Conclusion: The key I-DEGs, TNF, CCL3, PIK3CG, PTGER2, and IFNAR1, can be utilized as biomarkers to determine the risk of LBMD in AS patients. They may affect neutrophil infiltration and NETs formation to influence the bone remodeling process in AS.

ObjectivesTo analyze obstructive sleep apnea (OSA)-related quality of life (QoL), the statuses of depression and anxiety, and to reveal the correlation between OSA-related QoL and two mental statuses in Chinese adolescent patients with cleft palate (CP).MethodsThe Obstructive Sleep Apnea Questionaire-18 (OSA-18), the Generalized Anxiety Disorder Scale (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) were applied to assess OSA-related QoL and the statuses of anxiety and depression in Chinese adolescent patients with CP, respectively. Non-CP adolescents were also included in the control group. OSA-related QoL and the two mental statuses were compared between the study and control groups. The correlation between the OSA-related QoL and two mental statuses was estimated in Chinese adolescent patients with CP.ResultsA total of 8.7% patients showed a moderate or high impact of OSA on QoL, while all the adolescents from the control group showed little impact. The mean total OSA-18 score of the study group (36.261 ± 13.500) was significantly higher than the control (28.435 ± 8.934). The mean PHQ-9 scores of the study group and the control group were statistically different (3.957 vs. 2.113). The GAD-7 score in the study group was slightly higher than the control group (3.043 vs. 2.194), while the proportion of moderate-severe anxiety in the study group was relatively larger than that in the control group (6.5% vs. 1.6%). Moreover, there was a positive correlation between the OSA-related QoL and the statuses of anxiety and depression respectively, and the differences in GAD-7 and PHQ-9 scores between the moderate or high impact group and the little impact group were statistically significant.ConclusionChinese adolescents with CP reported a rate of moderate or high impact of OSA on QoL of 8.7%, which was significantly higher than adolescents without CP. The OSA-related QoL was worse and depression was severer in Chinese CP adolescents than in the control, while anxiety and depression in Chinese CP adolescents were associated with OSA-related QoL.

In this paper, we investigate a challenging but interesting task in the research of speech emotion recognition (SER), i.e., cross-corpus SER. Unlike the conventional SER, the training (source) and testing (target) samples in cross-corpus SER come from different speech corpora, which results in a feature distribution mismatch between them. Hence, the performance of most existing SER methods may sharply decrease. To cope with this problem, we propose a simple yet effective deep transfer learning method called progressive distribution adapted neural networks (PDAN). PDAN employs convolutional neural networks (CNN) as the backbone and the speech spectrum as the inputs to achieve an end-to-end learning framework. More importantly, its basic idea for solving cross-corpus SER is very straightforward, i.e., enhancing the backbone's corpus invariant feature learning ability by incorporating a progressive distribution adapted regularization term into the original loss function to guide the network training. To evaluate the proposed PDAN, extensive cross-corpus SER experiments on speech emotion corpora including EmoDB, eNTERFACE, and CASIA are conducted. Experimental results showed that the proposed PDAN outperforms most well-performing deep and subspace transfer learning methods in dealing with the cross-corpus SER tasks.

Hyperspectral image (HSI) super-resolution is a practical and challenging task as it requires the reconstruction of a large number of spectral bands. Achieving excellent reconstruction results can greatly benefit subsequent downstream tasks. The current mainstream hyperspectral super-resolution methods mainly utilize 3D convolutional neural networks (3D CNN) for design. However, the commonly used small kernel size in 3D CNN limits the model’s receptive field, preventing it from considering a wider range of contextual information. Though the receptive field could be expanded by enlarging the kernel size, it results in a dramatic increase in model parameters. Furthermore, the popular vision transformers designed for natural images are not suitable for processing HSI. This is because HSI exhibits sparsity in the spatial domain, which can lead to significant computational resource waste when using self-attention. In this paper, we design a hybrid architecture called HyFormer, which combines the strengths of CNN and transformer for hyperspectral super-resolution. The transformer branch enables intra-spectra interaction to capture fine-grained contextual details at each specific wavelength. Meanwhile, the CNN branch facilitates efficient inter-spectra feature extraction among different wavelengths while maintaining a large receptive field. Specifically, in the transformer branch, we propose a novel Grouping-Aggregation transformer (GAT), comprising grouping self-attention (GSA) and aggregation self-attention (ASA). The GSA is employed to extract diverse fine-grained features of targets, while the ASA facilitates interaction among heterogeneous textures allocated to different channels. In the CNN branch, we propose a Wide-Spanning Separable 3D Attention (WSSA) to enlarge the receptive field while keeping a low parameter number. Building upon WSSA, we construct a wide-spanning CNN module to efficiently extract inter-spectra features. Extensive experiments demonstrate the superior performance of our HyFormer.

Abstract Multi‐view facial action unit (AU) analysis has been a challenging research topic due to multiple disturbing variables, including subject identity biases, variational facial action unit intensities, facial occlusions and non‐frontal head‐poses. A deep feature enhancement (DFE) framework is presented to tackle some of these coupled complex disturbing variables for multi‐view facial action unit detection. The authors' DFE framework is a novel end‐to‐end three‐stage feature learning model with taking subject identity biases, dynamic facial changes and head‐pose into consideration. It contains three feature enhancement modules, including coarse‐grained local and holistic spatial feature learning (LHSF), spatio‐temporal feature learning (STF) and head‐pose feature disentanglement (FD). Experimental results show that the proposed method achieved state‐of‐the‐art recognition performance on the FERA2017 dataset. The code is released at http://aip.seu.edu.cn/cgtang/.

PurposeThe aim of this study was to investigate the role and mechanism of berberine (BBR) in the protection of injured retinal ganglion cells (RGCs) in diabetic retinopathy (DR).MethodsExperimental diabetic retinopathy rat model was successfully induced by a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in male SD rats with sufficient food and water for 8 weeks. Animals were randomly divided into four groups: (1) non-diabetic, (2) diabetic, (3) diabetic + BBR + PBS, and (4) diabetic + BBR + SR95531. BBR (100 mg/kg) was given daily by gavage to rats in the group (3) and group (4) for 8 weeks, and weekly intravitreal injections were conducted to rats in the group (3) with 5 μL of 1×PBS and rats in the group (4) with 5 μL of GABA-alpha receptor antagonist SR95531 to investigate the underlying mechanisms. The survival and apoptosis of RGCs were observed by fluorescence gold labeling technology and TUNEL staining. Visual function was evaluated by visual electrophysiological examination. Western blotting and immunofluorescence staining were used to analyze the expression of GABA-alpha receptors in RGCs.ResultsIn an animal model, BBR can increase the survival of RGCs, reduce RGCs apoptosis, and significantly improve the visual function. The reduction of GABA, PKC-α, and Bcl-2 protein expression caused by DR can be considerably increased by BBR. SR95531 inhibits BBR's protective effect on RGC and visual function, as well as its upregulation of PKC-α and Bcl-2.ConclusionBBR is a promising preventive or adjuvant treatment for DR complications, and its key protective effect may involve the regulation of RGC apoptosis through the GABA-alpha receptor/protein kinase C-alpha (GABAAR/PKC-α) pathway.

Human T-cell lymphotropic virus type 1 (HTLV-1) was the first retrovirus identified as the causative agent of human diseases, such as adult T-cell leukemia, HTLV-1-associated myelopathy, and HTLV-1 uveitis (HU). HU is one of the most frequent ocular inflammatory diseases in endemic areas, which has raised considerable public health concerns. Approximately 30% of HU patients develop secondary glaucoma, which is higher than the general uveitis incidence. We therefore investigated the mechanism underlying the high incidence of glaucoma secondary to HU in vitro. After contact with HTLV-1-producing T cells (MT-2), human trabecular meshwork cells (HTMCs) were infected. The infected cells increased in number, and nuclear factor (NF)-κB expression was activated. Contact between MT-2 cells and HTMCs resulted in significantly upregulated production of inflammatory cytokines, such as IL-6, and chemokines, such as CXCL10, CCL2, and CXCL-8. These findings indicate that the mechanism underlying secondary glaucoma in HU may involve proliferation of trabecular meshwork tissue after contact with HTLV-1-infected cells, resulting in decreased aqueous humor outflow. Upregulated production of inflammatory cytokines and chemokines simultaneously disrupts the normal trabecular meshwork function. This mechanism presumably leads to increased intraocular pressure, eventually resulting in secondary glaucoma.