Automatic Segmentation of Hemorrhages in the Ultra-wide Field Retina: Multi-scale Attention Subtraction Networks and An Ultra-wide Field Retinal Hemorrhage Dataset.

Ultra-wide field (UWF) retinal imaging can improve the detection rate of retinal hemorrhage as compared with conventional fundus images. However, hemorrhages in UWF retinal images can also become smaller and more widely distributed, which can be time consuming and labor intensive. With the development of computer technology, automatic segmentation techniques can assist physicians in diagnosis. However, the lack of publicly available UWF retinal hemorrhage segmentation datasets has limited the development of automatic hemorrhage segmentation techniques in UWF retinal images. We present a large-scale high-quality UWF retinal hemorrhage segmentation dataset, named UWF-RHS Dataset, for public use. To the best of our knowledge, we are the first team to make the UWF retinal hemorrhage segmentation dataset publicly available. In addition, we propose a multi-scale attention subtraction network (MASNet) for UWF retinal hemorrhage segmentation. Specifically, highly focused lesion features are extracted by using the proposed multi-scale attention subtraction (MAS) module at the progress of the skip-connection. Several comparative experiments and ablation experiments were performed at the UWF-RHS Dataset, and all experiments state that our proposed method is effective in diagnosing retinal hemorrhages with state-of-the-art results. The proposed UWF-RHS dataset and MASNet will greatly facilitate the development of automated segmentation techniques for UWF retinal hemorrhages. Links to the UWF-RHS dataset and the MASNet model code are available from https://github.com/wurenkai/UWF-RHS-Dataset-and-MASNet.

Multi-omics characterization of the monkeypox virus infection.

Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay. In addition to expected perturbations of immune-related pathways, we uncover regulation of the HIPPO and TGF-ß pathways. We identify dynamic phosphorylation of both host and viral proteins, which suggests that MAPKs are key regulators of differential phosphorylation in MPXV-infected cells. Among the viral proteins, we find dynamic phosphorylation of H5 that influenced the binding of H5 to dsDNA. Our extensive dataset highlights signaling events and hotspots perturbed by MPXV, extending the current knowledge on poxviruses. We use integrated pathway analysis and drug-target prediction approaches to identify potential drug targets that affect virus growth. Functionally, we exemplify the utility of this approach by identifying inhibitors of MTOR, CHUK/IKBKB, and splicing factor kinases with potent antiviral efficacy against MPXV and VACV.

Mucosal IFNλ1 mRNA-based immunomodulation effectively reduces SARS-CoV-2 induced mortality in mice.

RNA vaccines elicit protective immunity against SARS-CoV-2, but the use of mRNA as an antiviral immunotherapeutic is unexplored. Here, we investigate the activity of lipidoid nanoparticle (LNP)-formulated mRNA encoding human IFNλ1 (ETH47), which is a critical driver of innate immunity at mucosal surfaces protecting from viral infections. IFNλ1 mRNA administration promotes dose-dependent protein translation, induction of interferon-stimulated genes without relevant signs of unspecific immune stimulation, and dose-dependent inhibition of SARS-CoV-2 replication in vitro. Pulmonary administration of IFNλ1 mRNA in mice results in a potent reduction of virus load, virus-induced body weight loss and significantly increased survival. These data support the development of inhaled administration of IFNλ1 mRNA as a potential prophylactic option for individuals exposed to SARS-CoV-2 or at risk suffering from COVID-19. Based on the broad antiviral activity of IFNλ1 regardless of virus or variant, this approach might also be utilized for other respiratory viral infections or pandemic preparedness.

MCF-SMSIS: Multi-tasking with complementary functions for stereo matching and surgical instrument segmentation.

Stereo matching and instrument segmentation of laparoscopic surgical scenarios are key tasks in robotic surgical automation. Many researchers have been studying the two tasks separately for stereo matching and instrument segmentation. However, the relationship between these two tasks is often neglected. In this paper, we propose a model framework for multi-tasking with complementary functions for stereo matching and surgical instrument segmentation (MCF-SMSIS). We aim to complement the features of instrument prediction segmentation to the parallax matching block of stereo matching. We also propose two new evaluation metrics (MINPD and MAXPD) for assessing how well the parallax range matches the migrated domain when the model used for the stereo matching task undergoes domain migration. We performed stereo matching experiments on the SCARED , SERV-CT dataset as well as instrumentation segmentation experiments on the AutoLaparo dataset. The results demonstrate the effectiveness of the proposed method. In particular, stereo matching supplemented with instrument features reduced EPE, >3px and RMSE Depth in the surgical instrument section by 9.5%, 12.7% and 6.51%, respectively. The instrumentation segmentation performance also achieves a DSC value of 0.9233. Moreover, MCF-SMSIS takes only 0.14 s to infer a set of images. The model code and model weights for each stage are available from https://github.com/wurenkai/MCF-SMSIS.

Neuronal-enriched small extracellular vesicles trigger a PD-L1-mediated broad suppression of T cells in Parkinson's disease.

Many clinical studies indicate a significant decrease of peripheral T cells in Parkinson's disease (PD). There is currently no mechanistic explanation for this important observation. Here, we found that small extracellular vesicles (sEVs) derived from in vitro and in vivo PD models suppressed IL-4 and INF-γ production from both purified CD4+ and CD8+ T cells and inhibited their activation and proliferation. Furthermore, neuronal-enriched sEVs (NEEVs) isolated from plasma of A53T-syn mice and culture media of human dopaminergic neurons carrying A53T-syn mutation also suppressed Th1 and Th2 differentiation of naive CD4+ T cells. Mechanistically, the suppressed phenotype induced by NEEVs was associated with altered programmed death ligand 1 (PD-L1) level in T cells. Blocking PD-L1 with an anti-PD-L1 antibody or a small molecule inhibitor BMS-1166 reversed T cell suppression. Our study provides the basis for exploring peripheral T cells in PD pathogenesis and as biomarkers or therapeutic targets for the disease.

Function of hemocyanin-mediated succinate dehydrogenase in glucose metabolism and immunity of Penaeus vannamei.

Succinate dehydrogenase (SDH) is a crucial enzyme in the tricarboxylic acid cycle (TCA) and has established roles in immune function. However, the understanding of SDH in Penaeus vannamei, particularly its involvement in immune responses, is currently limited. Through affinity proteomics, a potential interaction between hemocyanin (HMC) and SDH in shrimp has been identified. The successful cloning of PvSDH in this study has revealed a high degree of evolutionary conservation. Additionally, it has been found that hemocyanin regulates SDH not only at the transcriptional and enzymatic levels but also through confirmed protein-protein interactions observed via Co-immunoprecipitation (CoIP) assay. Moreover, by combining PvHMC knockdown and Vibrio parahaemolyticus challenge, it was demonstrated that fumaric acid, a product of SDH, enhances the host's immune resistance to pathogen infection by modulating the expression of antimicrobial peptides. This research provides new insights into HMC as a crucial regulator of SDH, potentially impacting glycometabolism and the dynamics of immune responses.

Brucellosis-induced peritonitis and abdominal aortitis in a non-endemic area patient on peritoneal dialysis: a case report and literature review.

Background: Brucella infection is uncommon among peritoneal dialysis (PD) patients in non-endemic areas, and the occurrence of both peritonitis and abdominal aortitis is rare. Case presentation: In December 2023, a 63-year-old male patient undergoing PD was admitted to Shaoxing Second Hospital due to fever, abdominal pain, and cloudy dialysate. Upon physical examination, diffuse mild abdominal pain and tenderness were observed. Subsequent investigation into the patient's medical history revealed consumption of freshly slaughtered lamb from local farmers 3 days prior to the onset of symptoms. Various diagnostic tests, including routine blood tests, procalcitonin levels, and PD fluid analysis, indicated the presence of infection. Abdominal computed tomography (CT) imaging revealed localized lumen widening of the abdominal aorta with surrounding exudative changes. On the sixth day in the hospital, blood and PD fluid cultures confirmed Brucella melitensis infection. The patient was diagnosed with brucella-associated peritonitis and aortitis. Treatment was adjusted to include rifampin and doxycycline for 6 weeks, and the decision was made to keep the PD catheter. Remarkably, the patient exhibited resolution of peritonitis and abdominal aortitis within the initial week of the adjusted treatment. Currently, the patient continues to receive ongoing clinical monitoring. Conclusion: Brucella is rare but can cause PD-associated peritonitis and arteritis. Prompt diagnosis and treatment can lead to a good outcome in PD patients. Dual therapy is effective, but the need for catheter removal is unclear. Consider international guidelines and patient factors when deciding on catheter removal.

Sex-specific associations of urinary mixed-metal concentrations with femoral bone mineral density among older people: an NHANES (2017-2020) analysis.

Background: Heavy metal exposure is an important cause of reduced bone mineral density (BMD). Epidemiological studies focusing on the effects of mixed heavy metal exposure on BMD in middle-aged and older people are scarce. In single-metal studies, men and women have shown distinct responses of BMD to environmental metal exposure. This study therefore aimed to elucidate the association between mixed heavy metal exposure and BMD and to investigate whether it is sex-specific. Methods: Data from the 2017-2020 National Health and Nutrition Examination Survey were selected for this cross-sectional study. The study used three statistical methods, i.e., linear regression, Bayesian kernel machine regression (BKMR) modeling, and weighted quartiles (WQS) regression, to explore the association between the urinary concentrations of 11 metals (barium, cadmium, cobalt, cesium, manganese, molybdenum, lead, antimony, tin, thallium, and Tungsten), either individually or as a mixture, and total femoral BMD. Results: A total of 1,031 participants were included in this study. Femoral BMD was found to be higher in men than women. A significant negative correlation between the urinary concentrations of the 10 metals and femoral BMD was found in the overall cohort. Further gender sub-stratified analyses showed that in men, urinary metal concentrations were negatively correlated with femoral BMD, with cobalt and barium playing a significant and non-linear role in this effect. In women, although urinary metal concentrations negatively modulated femoral BMD, none of the correlations was statistically significant. Antimony showed sex-specific differences in its effect. Conclusion: The urinary concentrations of 10 mixed heavy metals were negatively correlated with femoral BMD in middle-aged and older participants, and this effect showed gender differences. These findings emphasize the differing role of mixed metal exposure in the process of BMD reduction between the sexes but require further validation by prospective studies.