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Abstract To determine the characteristics of posterior precortical vitreous pockets (PPVPs) and to observe vitreous changes in myopic eyes by swept-source optical coherence tomography (SS-OCT) and en face imaging in a cohort of the Chinese Han population. This was a cross-sectional study. Volunteers (235 participants, 374 eyes) received an SS-OCT examination. The heights and widths of the PPVPs were measured by SS-OCT. The area of the PPVPs was measured on en face images. The relationships between PPVP size and sex, age, axial length (AL) and spherical equivalent (SE) were evaluated. The mean width and height were 6711.64 ± 1241.87 μm and 662.47 ± 326.39 μm, respectively. The area of the PPVPs was 30.296 ± 9.114 mm2. Boat-shaped, oval, and hook-shaped PPVPs were observed in 73.26%, 21.12%, and 5.62% of all eyes, respectively; 73.53% of all PPVPs had channels communicating with Cloquet’s tubes. There was a significant difference in the PPVP width among the participates over and under 50 years old (t = -2.508, P = 0.031). Age had a positive correlation with the PPVP width (r = 0.53, P = 0.001). The PPVP height showed significant differences among the different myopia groups (F = 3.618, P = 0.013). SE had a negative correlation with the PPVP height (r = -0.176, P = 0.001). However, there were no correlations between the AL and the width, height or area of the PPVPs (P = 0.117; P = 0.334; P = 0.057, respectively). Age and myopia affect the size of PPVPs. SS-OCT greatly facilitates visualization of the complex structure of the vitreous.

Abstract To define the characteristics of fundus manifestations in patients after SARS-CoV-2 infection with multimodal imaging techniques. This is a retrospective multicenter and multimodal imaging study including 90 patients. All patients with a visual complaint occurring immediately after SARS-CoV-2 infection were referred to six clinics between December 2022 and February 2023. Demographic information and the temporal relationship between SARS-CoV-2 infection and visual symptoms were documented. The characteristics of the fundus lesions were evaluated using multimodal imaging. Ninety patients from six hospitals were included in this study, including 24 males (26.67%) and 66 (73.33%) females. Seventy-eight patients (86.66%) (146 eyes) were diagnosed with Acute Macular Neuroretinopathy (AMN). The AMN patients were primarily young women (67.95%). Sixty-eight patients (87.18%) had AMN in both eyes. Thirty-eight eyes (24.36%) included Purtscher or Purtscher-like lesions. optical coherence tomography and infrared retinal photographs can show AMN lesions well. Eleven cases were diagnosed with simple Purtscher or Purtscher-like retinopathy (2 cases, 2.22%), Vogt‒Koyanagi‒Harada (VKH) syndrome or VKH-like uveitis (3 cases, 3.33%), multiple evanescent white-dot syndrome (MEWDS) (2 cases, 2.22%), and rhino-orbital-cerebral mucormycosis (ROCM) (5 cases, 5.56%). After SARS-CoV-2 infection, diversified fundus lesions were evident in patients with visual complaints. In this report, AMN was the dominant manifestation, followed by Purtscher or Purtscher-like retinopathy, MEWDS, VKH-like uveitis, and ROCM.

Abstract Background Several autoimmune disorders have been linked to polymorphisms in IL10 and IL6R genes. This research aimed to study whether single nucleotide polymorphisms (SNPs) in the genes of IL10 and IL6R were associated with acute anterior uveitis (AAU) in Han Chinese. Methods Genotyping was carried out by the iPLEX Gold Genotyping Assay. Our study comprised 420 patients with AAU and 918 healthy subjects from Han Chinese. Using the chi-square (χ2) test, alleles and genotypes were analyzed between AAU subjects and healthy controls. Results All ten SNPs were successfully genotyped and four SNPs (IL10/rs1800871, IL10/rs3021094, IL10/rs2222202, IL6R/rs4845618) exhibited weak associations with AAU, as indicated by their Puncorr values. However, upon applying the Bonferroni correction, there was no significant association between AAU and the control subjects. Additionally, the haplotype analysis of the ten SNPs revealed no association with AAU. Conclusion Our findings suggested that polymorphisms of the tested ten SNPs on the IL10 and IL6R genes did not show any association with the risk of developing AAU among the Han Chinese population.

ABSTRACTThe gut microbiota has coevolved with the host for hundreds of millions of years, playing a beneficial role in host health. Human parasitic helminths are widespread and pose a pervasive global public health issue. Although Type 2 immunity provides partial resistance to helminth infections, the composition of the gut microbiota can change correspondingly. Therefore, it raises the question of what role the gut microbiota plays during helminth infection. Akkermansia muciniphila has emerged as a notable representative of beneficial microorganisms in the gut microbiota. Recent studies indicate that A. muciniphila is not merely associated with helminth infection but is also causally linked to infection. Here, we provide an overview of the crosstalk between A. muciniphila and enteric helminth infection. Our goal is to enhance our understanding of the interplay among A. muciniphila, helminths, and their hosts while also exploring the potential underlying mechanisms.

ABSTRACT Hyperactivation of pro-inflammatory type 1 cytokines (e.g., tumor necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ]) mirrors the inflammation of coronavirus disease 2019. Helminths could alleviate excessive immune responses. Here, helminth Trichinella spiralis (Ts) infection was shown to protect against TNF-α- and IFN-γ-induced shock. Mechanistically, Ts-induced protection was interleukin-9 (IL-9) dependent but not IL-4Rα. Recombinant IL-9 treatment not only improved the survival of wild-type mice with TNF-α- and IFN-γ-induced shock but also that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected K18-human angiotensin-converting enzyme 2 (hACE2) mice, emphasizing the significance of IL-9 in alleviating cytokine storm syndromes during SARS-CoV-2 infection. Interestingly, Ts excretory/secretory (TsES)-induced protection was also observed in SARS-CoV-2 infection, indicating that identifying anti-inflammatory molecules from TsES could be a novel way to mitigate adverse pathological inflammation during pathogen infection.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is linked to cytokine storm triggered by type 1 pro-inflammatory immune responses. TNF-α and IFN-γ shock mirrors cytokine storm syndromes, including COVID-19. Helminths (e.g., Trichinella spiralis, Ts) can potently activate anti-inflammatory type 2 immune response. Here, we found that helminth Ts-induced protection against TNF-α and IFN-γ shock was IL-9 dependent. Treatment with recombinant IL-9 could protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in K18-hACE2 mice. Helminth Ts excretory/secretory (TsES) products also ameliorated SARS-CoV-2 infection-related cytokine storm. In conclusion, our study emphasizes the significance of IL-9 in protecting from cytokine storm syndromes associated with SARS-CoV-2 infection. Anti-inflammatory molecules from TsES could be a new source to mitigate adverse pathological inflammation associated with infections, including COVID-19.

Abstract Background Open-globe injuries (OGIs) remain the important cause of visual impairment and loss in all ages. Computed Tomography (CT) is a useful and common tool in the evaluation of the injuries of the eyeball. Prognostic value of CT scan in OGIs has been evaluated in many studies. However, there is no published consistent systematic scoring method for CT scan in OGIs. The purpose of this study was to evaluate the CT characteristics of OGIs and build a scoring method according to the CT scans which may aid the clinicians in management of OGIs. Methods Retrospective chart review of inpatients with clinical diagnosis of OGIs between 2017 and 2021 at Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan provincial People’s Hospital (Zhengzhou, China). Results There were 1120 eyes from 1117 patients included in our study. The mean age was 35.7 ± 21.9 years with the range from 1 to 91 years. Significant male predominance was noted (889, 79.6%). CT scans of the OGIs were evaluated. Abnormality of anterior segment, posterior segment, and globe contour and volume were graded respectively. The most serious abnormality of anterior segment, posterior segment, and globe contour and volume were grade 3, 4 and 3 respectively and score 3, 4 and 3 respectively. Score of the CT scans of an open-injured globe ranged from 0 to 10. The correlation coefficient between the score and wound length was 0.798. The correlation coefficient between the score and final visual acuity was 0.799. In 78 eyes with 0 score, 70 eyes (89.7%) gained final visual acuity of 0.3 or better. In 31 eyes with 10 score, 20 eyes (64.5%) underwent evisceration of the eye globe and 10 eyes got visual acuity of no light perception and 1 eye lost to follow-up. Conclusions CT scans is a useful tool in evaluating the severity of an open-injured globe. Scoring of the CT scans of an open-injured globe is a meaningful attempt and it may provide useful prognostic information regarding the outcome of an open-injured globe.

Abstract Introduction With advancements in imaging technology, researchers have been able to identify more distinctive imaging features of central serous chorioretinopathy (CSC). However, existing research primarily concentrates on young patients aged 50 years and below, leaving a dearth of studies on elderly CSC patients. Previous studies indicate that elderly CSC patients may exhibit unique imaging characteristics and have a clinical prognosis that significantly differs from younger patients. This study aimed to evaluate the characteristics of retina, choroid structure, and blood flow in elderly patients with chronic CSC (cCSC) examined multimode imaging and try to find new pathogenesis information of it. Methods Using a cut-off age of 50 years, patients with chronic central serous chorioretinopathy were divided into two groups: older and younger. The control group consisted of 40 healthy individuals, with their right eyes assigned. Various clinical features were recorded, including the incidence of ellipsoid zone rupture (EZ-), fibrin in the subretinal fluid (SRF), pachydrusen, subretinal drusenoid deposits (SDD), pigment epithelial detachment (PED), double-layer sign (DLS), and choroidal lipid globule cavern. Measurements were taken for the thickness of the outer nuclear layer (ONL), the length of the extended outer photoreceptor segment (POS), the height and width of SRF, the vascular density of each layer of the retinal capillary plexus, the central macular thickness (CMT), and the subfoveal choroidal thickness (SFCT). Results The proportion of females in the elderly group (43.75%) was significantly higher than that in the youth group (22.41%) (p = 0.034). The degree of hyperopia in the elderly group (1.03 ± 0.73) was higher than that in the youth group (0.26 ± 1.06), with a significant difference in BCVA (p = 0.05). The thickness of SFCT, CMT, ONL in the elderly group, and the length of photoreceptor outer segment in the elderly group were thinner than those in the youth group (p

Abstract Background Several studies have reported the roles of Trichinella spiralis extracellular vesicles in immune regulation and pathogen diagnosis. Currently, the T. spiralis muscle larvae excretory/secretory product (Ts-ML-ES) is the antigen recommended by the International Commission on Trichinellosis (ICT) for serological diagnosis of trichinellosis. However, it can only be used to detect middle and late stages of infections, and cross-reactions with other parasite detections occur. Therefore, there is a need to identify antigens for specific detection of early stage trichinellosis. Methods Extracellular vesicles of T. spiralis muscle larvae (Ts-ML-EVs) were isolated by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, flow cytometry and western blot. Ts-ML-EVs protein profiles were analyzed by LC-MS/MS proteomics for identification of potential antigens (Ts-TTPA). Ts-TTPA were cloned into pMAL-c5X vector and expressed as recombinant proteins for evaluation of potential as detected antigens by western blot and ELISA. Results Isolated Ts-ML-EVs were round or elliptic (with diameters between 110.1 and 307.6 nm), showing a bilayer membrane structure. The specific surface markers on the Ts-ML-EVs were CD81, CD63, enolase and the 14-3-3 protein. A total of 53 proteins were identified by LC-MS/MS, including a variety of molecules that have been reported as potential detection and vaccine candidates. The cDNA of Ts-TTPA selected in this study has a total length of 1152 bp, encoding 384 amino acids with a molecular weight of 44.19 kDa. It contains a trypsin domain and can be recognized by anti-His antibody. It reacted with swine sera infected with 10,000 T. spiralis at 15, 25, 35 and 60 days post-infection (dpi). At 10 μg/ml, this antigen could detect T. spiralis antibodies from the swine sera at 13 dpi. There were no cross-reactions with the swine sera infected with other parasites including Clonorchis sinensis, Toxoplasma gondii, Taenia suis, Ascaris suis and Trichuris suis. Conclusions This study identifies potential early stage detection antigens and more thoroughly characterizes a serine protease domain-containing protein. Extracellular vesicle proteins may be explored as effective antigens for the early stage detection of trichinellosis. Graphical Abstract

Abstract Upon encountering exogenous pathogens, polymorphonucleocytes (PMNs) engage in various processes to destroy them, including releasing neutrophil extracellular traps (NETs) that trap pathogens and induce phagocytosis and cytokine production. Parasites have unique strategies with which to evade the host's immune response. However, the strategy employed by Trichinella spiralis in response to the reaction of PMNs has yet to be elucidated. This study explored the effect of excretory/secretory products (ESP) on three major functions: NETs, phagocytosis, and cytokine production. Specifically, PMNs were pre-treated with the ESP of 3-day-old adults and then stimulated with phorbol 12-myristate 13-acetate (PMA). We found that in PMNs pretreated with ESP, PMA-induced NET generation was suppressed by ESP. ROS production is a hallmark of PMA-induced NETosis. The LDH assay results showed that ESP inhibits NETs by suppressing ROS rather than promoting PMN death. Furthermore, ESP enhanced Escherichia coli engulfment by PMNs, improving overall phagocytic function. Finally, cytokine analysis revealed an increase in pro-inflammatory cytokine IL-1β, and other cytokines (IL-10, TNF-α), while IL-4 displayed a significant reduction. In conclusion, this study has unraveled T. spiralis' evasion and regulation mechanisms against innate immune cells, providing insights into parasite strategies to manipulate host immunity, potentially informing new treatments for NET-related autoimmune diseases. Graphical Abstract

Abstract Different human and animal pathogens trigger distinct immune responses in their hosts. The infection of bacteria or viruses can trigger type I pro-inflammatory immune responses (e.g., IFN-γ, TNF-α, TH1 cells), whereas infection by helminths typically elicits a type II host resistance and tolerizing immune response (e.g., IL-4, IL-5, IL-13, TH2 cells). In some respects, the type I and II immune responses induced by these different classes of pathogens are antagonistic. Indeed, recent studies indicate that infection by helminths differentially shapes the response and outcome of subsequent infection by viruses and bacteria. In this review, we summarize the current knowledge on how helminth infections influence concurrent or subsequent microbial infections and also discuss the implications for helminth-mediated immunity on the outcome of SARS-CoV-2 disease.

IntroductionDisulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn’s disease (CD) has not been thoroughly explored.MethodsFirstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of S100A12 with AS, UC and CD.ResultsIn this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes (S100A12 and LILRA5) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis.DiscussionIn this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.

Helminth Trichinella spiralis (Ts) is one of the major pathogens of human infective myocarditis that can lead to cardiac fibrosis (CF). The gut microbiota involved in this pathology are of interest. Here, we use mice infected with Ts as a model to examine the interactions between gut microbes and host protection to CF. Infected mice show enhanced CF severity. We find that antibiotics treatment to deplete the microbiota aggravates the disease phenotype. Attempts to restore microbiota using fecal microbiota transplantation ameliorates helminth-induced CF. 16S rRNA gene sequencing and metagenomics sequencing reveal a higher abundance of Akkermansia muciniphila in gut microbiomes of Ts-infected mice. Oral supplementation with alive or pasteurized A. muciniphila improves CF via TLR2. This work represents a substantial advance toward our understanding of causative rather than correlative relationships between the gut microbiota and CF.

The gut microbiota plays an important role in parasite-host interactions and the induction of immune defense responses. Trichinella spiralis is an important zoonotic parasite that can directly or indirectly interact with the host in the gut. Changes in the gut microbiota following infection with T. spiralis and the role of the gut microbiota in host immune defense against T. spiralis infection were investigated in our study. 16S rRNA sequencing analysis revealed that infection with T. spiralis can reduce the diversity of the gut microbiota and alter the structure of the gut microbiota during early infection, which was restored when the worm left the gut. Antibiotic treatment (ABX) and fecal bacterial transplantation (FMT) were used to investigate the role of the gut microbiota in the host expulsion response during infection with T. spiralis. We found that ABX mice had a higher burden of parasites, and the burden of parasites decreased after fecal bacterial transplantation. The results of flow cytometry and qPCR revealed that the disturbance of the gut microbiota affects the proportion of CD4+ T cells and the production of IL-4, which weakens Th2 responses and makes expulsion difficult. In addition, as the inflammatory response decreased with the changes of the microbiota, the Th1 response also decreased. The metabolomic results were in good agreement with these findings, as the levels of inflammatory metabolites such as ceramides were reduced in the ABX group. In general, T. spiralis infection can cause changes in the gut microbiota, and the presence or absence of microbes may also weaken intestinal inflammation and the expulsion of T. spiralis by affecting the immune response of the host. Author summary Due to the complexity of intestinal environment and function, we are interested in the relationship between Trichinella spiralis and the gut microbiota. In our study, we reported the effects of T. spiralis infection on the gut microbiota of the host and gut microbiota intervention in T. spiralis expulsion by influencing the immune status of the host. On the one hand, we demonstrated that the infection of T. spiralis in the intestinal stage could lead to a decrease in the diversity of the gut microbiota and changes in community structure, and these results are conducive to T. spiralis invasion. On the other hand, the gut microbiota plays an important role in T. spiralis infection. The balance of gut microbiota is largely involved in the invasion and colonization of T. spiralis and the state of host immunity. Our findings further elucidated the relationship among host, parasite and gut microbiota, and provided new insights into the prevention and control of T. spiralis. In addition, the study also provides a new basis for the important role of the gut microbiota in pathogen infection and host homeostasis.

Trichinella spiralis (T. spiralis) adult-specific deoxyribonuclease II-7 (TsDNase II-7), a member of the DNase II-like nuclease family with no DNase II activity, was identified in the excretory-secretory (ES) products of adult worms (AWs). However, its biological functions are still unclear. Our previous study revealed that TsDNase II-7 is located around the infection site in the intestinal tissue, speculating that it was involved in the T. spiralis invasion of host intestinal epithelial cells (IECs). This study aimed to use RNA interference to verify our speculation that TsDNase II-7 in 3-day old adult T. spiralis (Ad3) plays a role in intestinal invasion. TsDNase II-7-specific small interfering RNAs (siRNAs) were delivered into muscle larvae (MLs) to knockdown TsDNase II-7 expression by electroporation. Twenty-four hours later, the MLs transfected with 2 μM siRNA-841 exhibited decreased in TsDNase II-7 transcription and expression as compared to the control MLs. The knockdown of TsDNase II-7 expression did not affect ML viability, and the low expression of TsDNase II-7 still maintained in Ad3 recovered from TsDNase II-7-RNAi-ML infected mice, resulting in a weakened ability of Ad3 to invade intestinal epithelial cells (IECs). These results indicated that knockdown of TsDNase II-7 gene expression via RNA interference (RNAi) suppressed adult worm invasion and confirmed that TsDNase II-7 plays a crucial role during the intestinal phase of T. spiralis infections, which provided new candidate for vaccine development of T. spiralis.

Abstract Background To report the multimodal imaging and treatment of fifteen retinal capillary hemangioblastomas (RCHs) associated with Von Hippel-Lindau syndrome in a monocular patient during a long-term following-up, which supply high-resolution exquisite SS-OCTA images (VG200; SVision Imaging, Ltd., Luoyang, China) and management experience about multiple RCHs. Case presentation A 34-year-old monocular male patient complained decreased visual acuity (20/100) without pain and redness in the left eye five years ago. Von Hippel-Lindau syndrome were diagnosed with genetic testing. He, his son and daughter all carried a heterozygosity missense variant c.499C > T (p. Arg167Trp) in the Hg19 gene, a VHL gene located in Chr3:10,191,506. Fifteen RCHs were identified by the application of multimodal imaging, which including fundus photo, fundus autofluorescence (FAF), B-scan ultrasonography (US), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) and swept-source optical coherence tomography angiography (SS-OCTA). Transscleral cryotherapy and laser photocoagulation were performed to destroy the largest RCH with the size of 4 PD in diameter. Laser photocoagulation was conducted to seal the middle or tiny RCHs (

The COVID-19 pandemic, caused by the SARS-CoV-2, is the most serious global health calamity since the 2 nd World War. The COVID-19 pandemic threatens public health systems worldwide, both in developed and developing countries. In the present report we discuss various effects of the pandemic on the status of neglected tropical diseases (NTDs). COVID-19 will be a public health issue for an extended period. COVID-19 presented several challenges and opportunities for NTD prevention and control. Significant alterations include impact of the pandemic on preventive/control measures and poverty-related plans, service failures and injury to health workers, delayed treatment of NTDs, health service funding, and worsening poverty in marginalized societies. Additionally, the COVID-19 pandemic necessitated school and university closures on public education and research institutes. Furthermore, the COVID-19 pandemic has also provided opportunities, such as improving health literacy, changing approaches to NTD treatments, restructuring the health system and emergency responses, and enhancing science communication.

ABSTRACT Cardiac fibrosis is an integral aspect of every form of cardiovascular diseases, which is one of the leading causes of death worldwide. It is urgent to explore new effective drugs and treatments. In this paper, transverse aortic constriction (TAC)-induced cardiac fibrosis was significantly alleviated by a cocktail of antibiotics to clear the intestinal flora, indicating that the gut microbiota was associated with the disease process of cardiac fibrosis. We transplanted feces from sham-operated and TAC-treated mice to mice treated with a cocktail of antibiotics. We found that TAC-treated gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis, indicating that targeted probiotics and related metabolite intervention may restore a normal microenvironment for the treatment or prevention of cardiac fibrosis. We used 16S rRNA sequencing of fecal samples and discovered that butyric acid-producing bacteria and Bifidobacterium pseudolongum were the dominant bacteria in the group with the lowest degree of cardiac fibrosis. Moreover, we demonstrated that sodium butyrate prevented the development of cardiac fibrosis. The effect of Clostridium butyricum (butyric acid-producing bacteria) was better than that of B. pseudolongum on cardiac fibrosis. Surprisingly, the cocktail of two probiotics had a stronger ability than a single probiotic. In conclusion, therapies targeting the gut microbiota and metabolites such as probiotics present new strategies for treating cardiovascular disease. IMPORTANCE Cardiac fibrosis is a basic process in cardiac remodeling. It is related to almost all types of cardiovascular diseases (CVD) and has become an important global health problem. Basic research and a number of clinical studies have shown that myocardial fibrosis can be prevented and reversed to a certain extent. It is urgent to explore new effective drugs and treatments. We indicated a causal relationship between cardiac fibrosis and gut microbiota. Gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis. According to our findings, the combined use of butyric acid-producing bacteria and B. pseudolongum can help prevent cardiac fibrosis. Therapies targeting the gut microbiota and metabolites, such as probiotics, represent new strategies for treating cardiovascular disease.

Trichinellosis caused by Trichinella spiralis is a serious zoonosis with a worldwide distribution. Lentinan (LNT) is known to modulate the intestinal environment with noted health benefits, yet the effect of LNT against intestinal helminth is unknown. In our study, we first observed that LNT could trigger worm expulsion by promoting mucus layer functions through alteration of gut microbiota. LNT restored the abundance of Bacteroidetes and Proteobacteria altered by T. spiralis infection to the control group level. Interestingly, LNT triggered the production of butyrate. Then, we determined the deworming capacity of probiotics (butyrate-producing bacteria) in mice. Collectively, these findings indicated that LNT could modulate intestinal dysbiosis by T. spiralis, drive the expulsion of intestinal helminth and provided an easily implementable strategy to improve the host defence against T. spiralis infection.

Abstract Trichinella spiralis maintains chronic infections within its host. Muscle larvae excretory-secretory products (MLES) typically induce parasite-specific immune responses such as the Th2 response and regulatory T cells (Tregs) by modulating dendritic cell (DC) phenotype via the recognition of pattern recognition receptors (PRRs), such as Nod-like receptors (NLRs). We aimed to investigate the role of NLRP3 in T. spiralis-triggered immune response. We found that larvae burden was increased in NLRP3−/− mice compared to wild type (WT) mice. Administration of MLES induced higher levels of IL-4, IL-10, TGF-β and population of Tregs in WT mice than in NLRP3−/− mice. In vitro, we showed that increased expression of CD40 on the surface of MLES-treated DCs was inhibited after NLRP3 knockout. Increased production of IL-1β, IL-18, IL-10 and TGF-β, but not IL-12p70, was significantly diminished in the absence of NLRP3. Furthermore, our results demonstrated that MLES-treated DCs induced higher levels of IL-4, IL-10 and TGF-β and populations of Tregs in vitro. These inductions were abolished by NLRP3 deficiency in DCs, suggesting that NLRP3 in MLES-treated DCs plays a role in promoting the Th2 and Treg response. Taken together, we identified for the first time the involvement of NLRP3 in host defences against T. spiralis.

We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article:Wencui Wan, Weiwei Wan, Yang Long, Qiuming Li, Xuemin Jin, Guangming Wan, Fengyan Zhang & Yong Lv. (2020). Physcion 8-O-β-glucopyranoside exerts protective roles in high glucose-induced diabetic retinopathy via regulating lncRNA NORAD/miR-125/STAT3 signalling. Artificial Cells, Nanomedicine, and Biotechnology, 48(1), 463–472, DOI: 10.1080/21691401.2019.1709861Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors checked their data and confirmed there are fundamental errors associated with the figures presented. In addition, the corresponding author of the article, Qiuming, has informed us they were not aware of the submission made under their name. The authors have agreed to the retraction of this article, and we have also informed the institution about the authorship issues related to this article.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

PurposeTo describe the characteristics, managements, and outcomes of pediatric open globe injury (OGI) in central China.MethodsRetrospective chart review of pediatric diagnosis in patients with OGI between 2017 and 2020 at Henan Eye Hospital. Four hundred and one eyes of the patients younger than 17 years were included in this study. Open globe injury was classified according to the Birmingham Eye Trauma Terminology system (BETT). Age, sex, history, cause, month of trauma, treatment received, and outcomes were recorded. Visual acuity was documented according to standard visual acuity chart (decimals).ResultsFour hundred and one eyes of patients were included in the study. The mean age was 6.6 ± 3.4 years with the range from 8 months to 16 years. Open globe injuries (OGIs) occurred most frequently in the 2–8 year age and significant male predominance was noted (70.8%). The incidence of pediatric OGIs was lowest in summer months while it increased in the winter months. The most common type of pediatric OGI was penetration (89%). Scissors/knife accounted for 22%, followed by pen/pencil (15.2%), and wood/bamboo sticks (14.5%) of all the pediatric OGIs. Among the injuries, the most frequently involved is the zone I (76.1%). Initially, 70.8% of the eyes received primary debridement and wound closure without any additional intervention, while only one eye has no possibility of anatomical reconstruction when it received an evisceration. After the initial management, 198 eyes received subsequent operation, including 44 eyes that underwent cataract removal + intraocular lens (IOL) implantation, and 24 eyes underwent IOL implantation. Finally, over 6 months of follow-up, 129 eyes (32.2%) got visual acuity (VA) of 0.3–1.5 and, 63 eyes (15.7%) got VA of 0.01–0.25, while 11 eyes (2.7%) were eviscerated.ConclusionThis study showed that pediatric OGIs in central China are most seen in 2–8-year age group with significant male predominance. Scissors/knife, pen/pencil, and wood/bamboo sticks accounted for over half of all cases. Pediatric OGIs often result in significant vision loss. In some severe cases (2.7%), evisceration was ultimately performed. We should call on the public to pay more attention to their children and build a safer environment for them.

PurposeTo investigate the clinical therapy for giant intraocular foreign bodies (IOFBs) and evaluate the best treatment method with minimum secondary injury.MethodsWe retrospectively analyzed the data of 73 eyes of 73 patients with ocular trauma caused by giant IOFBs between January 2016 and December 2018. The IOFB size, localization, shape, and magnetic properties were recorded. The best corrected visual acuity (BCVA), ocular tissue injuries, entrance wound, interval time from injury to second phase surgery, silicone oil removal, and globe recovery were also observed. The cases were divided into three groups based on the following IOFB extraction paths: limbus path, the pars plana path, and the entrance wound path. The BCVA, IOFB size and shape, the wound, endophthalmitis, and silicone oil removal were compared among the three groups.ResultsThe IOFBs were 46 cases of magnetic and 27 cases of nonmagnetic, with a shape of thin flat in 19 cases, thick flat in 12 cases, long in seven cases, and irregular in 35 cases. Multiple damages were caused by the giant IOFBs, mainly involving the severe cornea, lens, and retina injuries. The postoperative BCVA increased compared with the preoperative BCVA (z = −6.06, P < 0.01). The rate of recovery from blindness was 40.85% (29/71). The thin flat IOFB and long IOFB resulted in a better postoperative BCVA than the other two IOFB shapes (all P < 0.05). The irregular IOFB had a poorer silicone oil removal rate than the other three IOFB shapes (all P < 0.05). The IOFB extraction followed the limbus path in 18 cases, pars plana path in 27 cases, and entrance wound path in 28 cases. The IOFB length and width in the pars plana path group were significantly lower than that in the limbus path group (all P < 0.05), the preoperative BCVA of the pars plana path group was superior to that of the limbus path group (P < 0.05), and the IOFB length, width, and entrance wound length in the pars plana path group were significantly lower than in the entrance wound path group (all P < 0.05). But the postoperative BCVA in the pars plana path group was not better than that in the other two groups (all P > 0.05). The postoperative BCVA of the entrance wound path group was significantly superior to that of the limbus path group (z = −2.01, P = 0.04), while there was no difference between the two groups in IOFB length, width, entrance wound length, or preoperative BCVA (all P > 0.05).ConclusionThe entrance wound path would benefit to minimize secondary injury in giant IOFB extraction procedure, compared with the limbus and pars plana path.

Purpose: Vascular endothelial growth factor-A (VEGF-A) is an important pathogenic factor in proliferative diabetic retinopathy (PDR), and aflibercept (Eylea) is one of the widely used anti-VEGF agents. This study investigated the microRNA (miRNA) profiles in the vitreous of 5 idiopathic macular hole patients (non-diabetic controls), 5 untreated PDR patients (no-treatment group), and 5 PDR patients treated with intravitreal aflibercept injection (treatment group).Methods: Next-generation sequencing was performed to determine the miRNA profiles. Deregulated miRNAs were validated with quantitative real-time PCR (qRT-PCR) in another cohort. The mRNA profile data (GSE160310) of PDR patients were retrieved from the Gene Expression Omnibus (GEO) database. The function of differentially expressed miRNAs and mRNAs was annotated by bioinformatic analysis and literature study.Results: Twenty-nine miRNAs were significantly dysregulated in the three groups, of which 19,984 target mRNAs were predicted. Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group versus controls, and significantly downregulated in treatment group versus no-treatment group. In the GSE160310 profile, 204 deregulated protein-coding mRNAs were identified, and finally 179 overlapped mRNAs between the 19,984 target mRNAs and 204 deregulated mRNAs were included for further analysis. Function analysis provided several roles of aflibercept-induced miRNAs, promoting the alternation of drug sensitivity or resistance-related mRNAs, and regulating critical mRNAs involved in angiogenesis and retinal fibrosis.Conclusion: Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were highly expressed in PDR patients, and intravitreal aflibercept injection could reverse this alteration. Intravitreal aflibercept injection may involve in regulating cell sensitivity or resistance to drug, angiogenesis, and retinal fibrosis.

Purpose: To describe the characteristics, management, and outcomes of adult severe open-globe injured (OGI) eyes.Methods: Retrospective chart review of inpatients with initial visual acuity (VA) of light perception (LP) or no light perception (NLP) associated with OGI between 2017 and 2020 at Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan provincial People's Hospital.Results: Six hundred twenty-five eyes of 622 adult patients with initial VA of LP or NLP associated with open-globe injuries (OGIs) were included. The mean age was 47.8 ± 14.1 years with the range from 18 to 91 years. Significant male predominance was noted (81.5%). The most common type of these severe OGIs was rupture (65.8%). Traffic accidents accounted for 13.5% followed by fall/tumble (10.9%) and nail/wire (10.9%) of all the severe OGIs. Almost half of the injuries happened at workplace (47.2%). Initially, 78.7% eyes just received primary debridement and wound closure, while 8.5% eyes with no possible of anatomical reconstruction received evisceration. After initial management, 350 eyes received subsequent operation, including 239 eyes underwent vitrectomy + silicone oil/(+cataract remove). Finally, over 6 months follow-up, 137 eyes (21.9%) were eviscerated, 150 eyes (24.0%) got atrophied, while 132 eyes (21.1%) retain some VA. Fifty-three eyes (8.5%) got VA of 0.3–1.5.Conclusion: Severe OGIs are most seen in the young, middle-aged, and male working population and remain a serious public health problem, resulting in significant vision loss or Evisceration of eyes. Effective preventive measures should be taken for the individuals in these groups.

In the past 30 years, few researches focus on the efficacy of adjuvant against Trichinella spiralis infection. Identifying new, improved vaccine adjuvants for T. spiralis infection are required. β-glucan are effective and safe as adjuvant for infectious diseases. In this paper, we first observed the adjuvanticity of β-glucan as adjuvant for defensing helminth T. spiralis in vivo. We showed that IgG and IgE were elevated in the mice immunized with β-glucan combined with recombinant T. spiralis serine protease inhibitor (rTs-Serpin), which is one of the vaccine candidates. Furthermore, in vitro, the combination of β-glucan and rTs-Serpin enhanced the maturation of bone marrow dendritic cells (BMDCs) compared to rTs-Serpin alone. We showed that β-glucan + rTs-Serpin –treated BMDCs secreted higher production of IL-12 and IL-10. Moreover, β-glucan + rTs-Serpin –treated BMDCs not only promoted the population of CD4+ IFN-γ+ T cells, but also enhanced the population of CD4+ IL-4+ T cells. These findings suggested that β-glucan, as an adjuvant, have the capacity to protect against T. spiralis infection via activating both Th1 and Th2 immune response.

Trichinella spiralis induced alternative activated macrophages (M2), leading to protect against Crohn’s disease, known as Th1 –related inflammation, which enhances oxidative stress in the host. However, the relationship of oxidative stress and T. spiralis –mediated immune response is still unknown. In our study, we showed that nuclear factor erythroid 2-related factor-2 (Nrf2), a key transcription factor in antioxidant, participated in M2 polarization induced by T. spiralis muscle larval excretory/secretory (ES) products in vitro. ES –treated M2 were injected intravenously after TNBS challenge and we demonstrated that ES-M could alleviate the severity of the colitis in mice. Adoptive transfer of ES –treated M2 decreased the level of IFN-γ and increased the levels of IL-4 and IL-10 in vivo. However, the capacity of ES –treated Nrf2 KO macrophages to treat colitis was dramatically impaired. ES –treated Nrf2 KO macrophages was insufficient to result in the elevated levels of IL-4 and IL-10. These findings indicate that Nrf2 was required for M2 polarization induced by T. spiralis ES to alleviate colitis in mice.

Trichinella spiralis (T. spiralis) is a widely distributed pathogenic microorganism that causes trichinellosis, a disease that has the potential of causing severe harm to their host. Numerous studies have demonstrated that autophagy can be triggered by microbial infection, such as bacteria, viruses, protozoa, and parasitic helminths. However, it's still unknown whether autophagy can facilitate host resistance to T. spiralis infection. The present study examined the role of autophagy in striated muscle cell transformation following infection with T. spiralis in BALB/c mice. Transmission electron microscopy (TEM) was used to detect the production of the host diaphragm autophagosome after T. spiralis infection, and changes in the protein and transcriptional levels of autophagic marker proteins were also detected. The significance of autophagy in T. spiralis infection, namely inhibition of T. spiralis growth, was preliminarily evaluated by conducting in vivo experiments using autophagy inhibitors. Besides, we studied the effect of excretory-secretory products (ES) of T. spiralis on autophagy of C2C12 myoblasts. The changes in protein and gene expression levels in autophagy-related pathways in vitro and in vivo were measured as further evidence. The results showed that T. spiralis infection induced autophagy in the host muscle cells. Meanwhile, ES inhibited autophagy of myoblasts in vitro, but this did not affect the cell viability. The upregulation and downregulation of autophagy-related factors in skeletal muscle cells may indicate an adaptive mechanism providing a comfortable niche for the parasite.

There is an urgent need for the development of new, improved vaccine adjuvants against T. spiralis infection. Polysaccharides are effective, safe, and biodegradable as adjuvant. In our study, we first observed the protective efficacy of lentinan as adjuvant against helminth T. spiralis infection. Recombinant T. spiralis Serpin (rTs-Serpin) immunoscreened from a cDNA library of T. spiralis, as a vaccine, protect host against Trichinella infection. The reduction rate of helminth burden of rTs-Serpin+lentinan-immunized mice was significantly increased compared with rTs-Serpin+FCA -immunized mice. rTs-Serpin+lentinan induced IgG1-dominant immune response and higher levels of IFN-γ and IL-4. rTs-Serpin+lentinan displayed a lower reduction rate of parasite burden in NLRP3-/- mice than that in WT mice and lower level of IgG1 than that in WT mice. The level of IL-4, but not IFN-γ, from NLRP3-/- mice immunized by rTs-Serpin+lentinan was significantly lower than that from WT mice, suggesting that NLRP3 is associated with rTs-Serpin+lentinan -triggering Th2 protective immunity against T. spiralis infection. In summary, we revealed that lentinan was a novel adjuvant against T. spiralis infection via NLRP3. NLRP3 therefore represents an important target for adjuvant discovery and the control of T. spiralis infection.

Aberrant expression of microRNAs plays an important role in the pathogenesis and progression of retinoblastoma. MiR-25, a member of the miR-106b˜25 cluster, has been reported to be abnormally expressed in retinoblastoma, but the exact role of it remains unclear. In our study, we found that miR-25-3p was upregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-25-3p in retinoblastoma cell line WERI-RB-1 increased cell growth, colony formation, anchorage-independent growth, cell migration and invasion in vitro and tumor xenograft growth in vivo. In contrast, inhibited miR-25-3p expression in retinoblastoma cell line Y79 suppressed cell growth, colony formation, anchorage-independent growth, cell migration and invasion. Through luciferase reporter assay, we found that phosphatase and tensin homolog (PTEN) was a direct target of miR-25-3p. This was verified by western blot that miR-25-3p overexpression suppressed PTEN and activated Akt signaling. In addition, miR-25-3p was found to promote epithelial-mesenchymal transition (EMT) of WERI-RB-1 cells through PTEN/Akt pathway. Western blot analysis revealed that miR-25-3p overexpression increased Vimentin and Snail expression, and suppressed E-cadherin expression, but this could be reversed by restoring PTEN. Moreover, LY294002 treatment or restoring PTEN expression abolished the effects of miR-25-3p on cell invasion, colony formation and anchorage-independent growth in vitro and tumor xenograft growth in vivo. Taken together, our results suggested that miR-25-3p promotes malignant transformation of retinoblastoma cells by suppressing PTEN.

Doxycycline (Dox), a semisynthetic antibiotic, has been reported to exert multiple immunomodulatory effects. Treatment with Dox has a satisfactory curative effect against leptospirosis. In addition to its antibacterial action, we supposed that Dox also modulated immune response in controlling leptospira infection. Using J774A.1 mouse macrophages, the effects of Dox on protein and mRNA levels of IL-1β and TNF-α were investigated after infection with live or sonicated Leptospira interrogans serovar Lai strain Lai (56601). Specifically, the level of IL-1β but not TNF-α was sharply decreased when treated with Dox in leptospira-infected macrophages. Western blot analysis showed that Dox suppressed the activation of leptospira-induced MAPK and NF-κB signaling pathways. Using NLRP3-deficient and NLRC4-deficient mice, the data showed that the expression of leptospira-induced IL-1β was mainly dependent on the presence of NLRP3 inflammasome in macrophages. Meanwhile, Dox suppressed leptospira-induced NLRP3 inflammasome priming with the upregulation of the Na/K-ATPase Pump β1 subunit. The inhibition effect of Dox on IL-1β was also conspicuous in cells with lipopolysaccharide and ATP stimulation. These results were confirmed in vivo, as peritoneal fluids of mice and organs of hamsters expressed less IL-1β after treatment of leptospiral infection with Dox. Our results indicated that Dox also modulated immune response to attenuate leptospira-induced IL-1β by suppressing p38, JNK, p65, and NLRP3 inflammasome priming.

Leptospirosis, caused by Leptospira, is one of the most important of neglected emerging zoonotic diseases that has important impacts on public health worldwide. Polyclonal antibody (pcAb) therapy is a potential method to process a series of pathogens for which there are limited determination of treatment, such as leptospirosis. First, we evaluated the efficacy of pcAb, derived from the sera of rabbits inoculated with Leptospira, against homotype (Leptospira interrogans serovar Lai) or heterotype (Leptospira interrogans serovar Autumnalis) Leptospira infection in a lethal hamster model. The pcAb treatment improved survival compared to the controls. The histopathology's of the infected kidney, liver and lung were also examined by hematoxylin and eosin staining. Using real-time quantitative PCR, we determined that most of the leptospires in the primary organs were almost completely removed by pcAb. In the second experiment, treatments, including antibiotic, pcAb, and combination, were started immediately after occurrence of the first serious sickness mouse in any group. No significant difference in survival rate between pcAb group and antibiotic group was found, but the combination therapy group significantly improved survival rate compared to the others (P

Abstract In the production of oil and natural gas, excessive clearance volume is an important factor affecting the normal operation of oil-gas multiphase pump. Currently, little research has been conducted on the effect of clearance volume on the output characteristics of multiphase pump at home and abroad, leading to extremely low efficiency in the field application of multiphase pump. Therefore, this study conducted numerical calculations on the internal flow characteristics and output performance of multiphase pump under different clearance volumes using FLUENT software. Results show that pressure and fluid velocity gradually decrease as the clearance volume increases. Simultaneously, the number and intensity of vortex flow gradually increase, media pressurization speed becomes slower, and the lag angle of the discharge valve opening becomes larger. Moreover, under conditions with a higher gas volume fraction, multiphase pump with larger clearance volumes experiences gas locking. Furthermore, this study provides a theoretical basis for the reasonable design of clearance volume for multiphase pump by drawing a relationship curve between gas volume fraction and clearance volume. These research findings can provide theoretical support for the performance optimization and design improvement of multiphase pumps.