OBJECTIVE QUANTIFICATION OF DEPTH-OF-FIELD ADVANTAGE IN 3D SURGICAL VIDEO SYSTEM FOR VITREORETINAL SURGERY: Safety and Efficacy in Macular Diseases.

PURPOSE: The objective of this study was to demonstrate, based on objective clinical indicators, the advantages of depth of field provided by the 3D surgical video system compared with the traditional microscope during vitrectomy for treating epiretinal membranes or macular holes. METHODS: A total of 38 patients were included in this study and randomly assigned to either the 3D surgical video group or the conventional microscope group. Surgical parameters, such as the focal plane adjustment frequency, membrane peeling time, and number of attempts to peel the membrane, were recorded for each patient. In addition, patients were followed up for 3 months postoperatively. RESULTS: No significant differences were observed in age, sex, operated eyes, or follow-up rates between the groups. The 3D group had significantly lower focal plane adjustment frequency in macular hole surgery and epiretinal membrane surgery. No significant differences were observed in peeling maneuvers, time, or total surgical time. Postoperative follow-up data showed no significant differences. CONCLUSION: In conclusion, the 3D surgical video system exhibits potential advantages in depth of field. The 3D surgical video system is a safe and effective technology in vitrectomy for macular diseases.

Enhancing surgical precision and efficiency: a study and comparison of a three-dimensional surgical video system in proliferative diabetic retinopathy surgery.

Purpose: This study aimed to investigate the safety and efficacy of three-dimensional (3D) surgical video systems for proliferative diabetic retinopathy (PDR). Methods: This retrospective clinical case study included 30 patients (30 eyes) with PDR. Patients were divided into two groups: one underwent surgery using a 3D surgical video system (14 cases, 14 eyes), while the other underwent traditional microscope surgery (16 cases, 16 eyes). Safety and efficacy were assessed through predetermined surgical parameters, including surgical duration, intraoperative membrane removal rate, and occurrences during intraoperative and postoperative phases. Results: Our study revealed noteworthy differences in various aspects between the 3D surgical video system group and the traditional microscope surgery group. Specifically, the mean surgical time was 30.25 ± 14.43 mins in the 3D surgical video system group, while it was 38.56 ± 18.71 mins in the traditional microscope surgery group (p = 0.051). Furthermore, the mean membrane removal time was significantly shorter in the 3D group at 2.53 ± 1.52 mins, as compared to 3.23 ± 1.76 mins in the traditional group (p = 0.042). Importantly, the membrane removal rate also displayed a significant difference, with the 3D group at 0.55 ± 0.07 and the traditional group at 0.41 ± 0.11 (p = 0.018). However, no notable differences were observed between the two groups in terms of intraoperative and postoperative incidences. Conclusion: The safety and efficacy obtained using the 3D surgical video system in PDR surgery were comparable to those obtained in traditional microscopic surgery.

Establishment and validation of a prognostic nomogram for long-term low vision after diabetic vitrectomy.

Purpose: We aimed to evaluate the risk factors and develop a prognostic nomogram of long-term low vision after diabetic vitrectomy. Methods: This retrospective study included 186 patients (250 eyes) that underwent primary vitrectomy for proliferative diabetic retinopathy with a minimum follow-up period of one year. Patients were assigned to the training cohort (200 eyes) or validation cohort (50 eyes) at a 4:1 ratio randomly. Based on a cutoff value of 0.3 in best-corrected visual acuity (BCVA) measurement, the training cohort was separated into groups with or without low vision. Univariate and multivariate logistic regression analyses were performed on preoperative systemic and ocular characteristics to develop a risk prediction model and nomogram. The calibration curve and the area under the receiver operating characteristic curves (AUC) were used to evaluate the calibration and discrimination of the model. The nomogram was internally validated using the bootstrapping method, and it was further verified in an external cohort. Results: Four independent risk factors were selected by stepwise forward regression, including tractional retinal detachment (ß=1.443, OR=4.235, P<0.001), symptom duration ≥6 months (ß=0.954, OR=2.595, P=0.004), preoperative BCVA measurement (ß=0.540, OR=1.716, P=0.033), and hypertension (ß=0.645, OR=1.905, P=0.044). AUC values of 0.764 (95% CI: 0.699-0.829) in the training cohort and 0.755 (95% CI: 0.619-0.891) in the validation cohort indicated the good predictive ability of the model. Conclusion: The prognostic nomogram established in this study is useful for predicting long-term low vision after diabetic vitrectomy.

Tissue injury and leukocyte changes in post-acute sequelae of SARS-CoV-2: review of 2833 post-acute patient outcomes per immune dysregulation and microbial translocation in long COVID.

A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This phenomenon, termed post-acute sequelae of SARS-CoV-2 (PASC) or long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of autoantibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder, including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include the degree of host responses (inflammation, NETinjury), residual viral antigen (persistent antigen), and exogenous factors (microbial translocation). Determinants of PASC may be amplified by comorbidities, age, and sex.

GPRC6A is a key mediator of palmitic acid regulation of lipid synthesis in bovine mammary epithelial cells.

Fatty acids (FAs) can promote lipid synthesis in the mammary gland via stimulating lipogenic gene expression, but the underlying molecular mechanism is still not fully understood. Here, we showed the dose-dependent effects of palmitic acid (PA) on lipid synthesis in primary bovine mammary epithelial cells (BMECs) and explored the corresponding molecular mechanism. BMECs were treated with PA (0, 50, 100, 150, and 200 µM), and the 100 µM treatment had the best stimulatory effect on lipid synthesis and expression and maturation of sterol regulatory element-binding protein 1c (SREBP-1c) in cells. Inhibition of phosphatidylinositol 3-kinase (PI3K) almost totally blocked the stimulation of PA on SREBP-1c expression, whereas protein kinase Cα (PKCα) knockdown only partially decreased the stimulation of PA on SREBP-1c expression but abolished the stimulation of PA on its maturation. Knockdown of GPR120 did not change the stimulation of PA on the SREBP-1c signaling. G protein-coupled receptor family C group 6 member A  (GPRC6A) knockdown almost totally blocked the stimulation of FA on PI3K and PKCα phosphorylation as well as SREBP-1c expression and maturation. Furthermore, PA dose-dependently promoted GPRC6A expression and plasma membrane localization. Together, these above results reveal that GPRC6A is a key mediator of PA signaling to lipid synthesis in BMECs via the PI3K/PKCα-SREBP-1c pathways.

Targeting Sphingosine Kinase by ABC294640 against Diffuse Intrinsic Pontine Glioma (DIPG).

As a highly aggressive pediatric brainstem tumor, diffuse intrinsic pontine glioma (DIPG) accounts for 10% to 20% of childhood brain tumors. The survival rate for DIPG remains very low, with a median survival time as less than one year even under radiotherapy, the current standard treatment. Moreover, over than 250 clinical trials have failed when trying to improve the survival compared to radiotherapy. The sphingolipid metabolism and related signaling pathways have been found closely related to cancer cell survival; however, the sphingolipid metabolism targeted therapies have never been investigated in DIPG. In the current study, the anti-DIPG activity of ABC294640, the only first-in-class orally available Sphingosine kinase (SphK) inhibitor was explored. Treatment with ABC294640 significantly repressed DIPG cell growth by inducing intracellular pro-apoptotic ceramides production and cell apoptosis. We also profiled ABC294640-induced changes in gene expression within DIPG cells and identified many new genes tightly controlled by sphingolipid metabolism, such as IFITM1 and KAL1. These genes are required for DIPG cell survival and display clinical relevance in DIPG patients' samples. Together, our findings in this study indicate that targeting sphingolipid metabolism may represent a promising strategy to improve DIPG treatment.

Two-generation reproduction and limited teratology studies of ethanamizuril fed to rats.

Ethanamizuril, a new anticoccidial agent that belongs to triazine derivatives, has a broad and good anticoccidial activity. To evaluate the reproductive toxicity and teratogenic potential of ethanamizuril, different concentrations of ethanamizuril were administered to Sprague-Dawley rats by feeding diets containing 0, 2, 8, and 30 ppm, respectively. Each group consisting of 30 males and 30 females (F0) was treated with different concentrations of ethanamizuril through a 13-week period before mating and during mating, gestation, parturition and lactation. In the 30 ppm dose group, pup body weight on days 7 and 21 in F1 offspring and day 21 in the F2a offspring were significantly decreased. A limited teratogenicity study was performed in combination with the F1 generation of a two-generation reproduction study. F1 offspring of the reproduction study were mated after weaning of the F2a offspring. Pregnant female rats were subjected to cesarean section on gestational day 20 for teratogenic examination. No obvious body weights, fetal body lengths, tail lengths, litter weights, number of viable fetuses, external, skeletal, or visceral malformations in fetuses were noted in any groups in the teratogenic test, but ethanamizuril could be passed on to offspring through lactation.

Polarization detection in deep-ultraviolet light with monoclinic gallium oxide nanobelts.

Detection of polarization in deep-ultraviolet (DUV) wavelength is of great importance, especially in secure UV communication. In this paper, we report DUV polarization detectors based on ultra-wide bandgap ß-Ga2O3 nanobelts, which belong to a monoclinic system with a strong anisotropic lattice structure. Single-crystalline ß-Ga2O3 nanobelts are synthesized at high-temperature via chemical vapor deposition (CVD). Crystallographic investigation is performed to determine the crystal orientation of the nanobelts, by the combination of selected area electron diffraction (SAED), high-resolution transmission electron microscopy (HRTEM), crystal modeling and diffraction simulation. The photoresponse to unpolarized DUV light shows a high responsivity of 335 A W-1 and high sensitivity even to a low illumination power of pW. Strong anisotropy in responsivity and response speed, depending on incident light polarization, is observed. The underlying mechanism is attributed to the combination of internal dichroism and 1D morphology, as indicated by the DFT calculation and FDTD simulation. This work shows a way of DUV polarization detection using CVD grown Ga2O3 nanobelts, which could broaden the investigation of the Ga2O3 material and DUV photodetection.

Identification and formation mechanism of a novel noncoding RNA produced by avian infectious bronchitis virus.

Viral noncoding (nc) RNAs have been shown to play important roles in viral life cycle. Many viruses employ different mechanism to produce ncRNAs. Here, we report that coronavirus infectious bronchitis virus (IBV) produces a novel ncRNA in virus-infected cells. This ncRNA consists of 563 nucleotides excluding a poly(A) tail, is mainly derived from the 3'-untranslated region of IBV genome, and contains a 63-nt-long of terminal leader sequence derived from the 5' end of the viral genome. Using mutagenesis and reverse genetics, we reveal that this ncRNA is a subgenomic RNA generated by discontinuous transcription mechanism.

Immune Responses of Chickens Infected with Wild Bird-Origin H5N6 Avian Influenza Virus.

Since April 2014, new infections of H5N6 avian influenza virus (AIV) in humans and domestic poultry have caused considerable economic losses in the poultry industry and posed an enormous threat to human health worldwide. In previous research using gene sequence and phylogenetic analysis, we reported that H5N6 AIV isolated in February 2015 (ZH283) in Pallas's sandgrouse was highly similar to that isolated in a human in December 2015 (A/Guangdong/ZQ874/2015), whereas a virus (i.e., SW8) isolated in oriental magpie-robin in 2014 was highly similar to that of A/chicken/Dongguan/2690/2013 (H5N6). However, the pathogenicity, transmissibility, and host immune-related response of chickens infected by those wild bird-origin H5N6 AIVs remain unknown. In response, we examined the viral distribution and mRNA expression profiles of immune-related genes in chickens infected with both viruses. Results showed that the H5N6 AIVs were highly pathogenic to chickens and caused not only systemic infection in multiple tissues, but also 100% mortality within 3-5 days post-infection. Additionally, ZH283 efficiently replicated in all tested tissues and transmitted among chickens more rapidly than SW8. Moreover, quantitative real-time polymerase chain reaction analysis showed that following infection with H5N6, AIVs immune-related genes remained active in a tissue-dependent manner, as well as that ZH283 induced mRNA expression profiles such as TLR3, TLR7, IL-6, TNF-α, IL-1ß, IL-10, IL-8, and MHC-II to a greater extent than SW8 in the tested tissues of infected chickens. Altogether, our findings help to illuminate the pathogenesis and immunologic mechanisms of H5N6 AIVs in chickens.

Generation and evaluation of a genetically attenuated Newcastle disease virus rGM-VIIm as a genotype-matched vaccine.

Despite intensive vaccination campaigns, outbreaks of Newcastle disease (ND) have been frequently reported in China, especially of genotype VII that first emerged in the late 1990s. Given the dire need for vaccines against the circulating genotype VII virus, we developed an alternative method to recover a highly virulent recombinant GM (rGM) virus that involves a T7 system with a hammerhead ribozyme sequence introduced downstream of the T7 promoter. By changing the F0 polybasic cleavage site RRQKR↓F to the monobasic GRQGR↓L, we generated a mutant virus (rGM-VIIm) that was found to be highly attenuated in chickens. The rGM-VIIm virus not only produced fourfold higher hemagglutination assay (HA) titers than the parental virus, but also exhibited genetic stability after 15 continuous passages in specific-pathogen-free (SPF) embryonated eggs. Whether live or inactivated, rGM-VIIm and LaSota vaccines can protect vaccinated birds from GM challenge infection. However, live and inactivated rGM-VIIm vaccines reduced virus shedding of the homologous challenge virus significantly better than the LaSota virus vaccine did. Altogether, our results suggest that rGM-VIIm vaccines could aid in the control of ND in China.

Interferon regulatory factor 7- (IRF7-) mediated immune response affects Newcastle disease virus replication in chicken embryo fibroblasts.

Interferon regulatory factor 7 (IRF7) is essential for the induction of an antiviral response. Previous studies have shown that virus replication causes the activation or expression of Type I interferon (IFN) in cells, which further activates IFN-stimulated genes (ISGs) to retard virus growth. In this study, after infection of chicken embryo fibroblasts (CEFs) with the lentogenic Newcastle disease virus (NDV) strain LaSota or the velogenic NDV strain GM, the mRNA and protein levels of IRF7 showed a significant increase, and part of the IRF7 protein was translocated from the cytoplasm to the nucleus. In order to further explore the effect of IRF7-mediated innate immune response on the replication of NDV in CEFs, the mRNA levels of IFN-α, IFN-ß and STAT1 were measured and the replication kinetics of NDV determined. The results showed that specific siRNA could inhibit the expression of IRF7 and limit the mRNA level of IFN-α, IFN-ß and STAT1 and, accordingly, the replication kinetics of both NDVs were enhanced after the inhibition of IRF7. In conclusion, IRF7 is an important nuclear transcription factor for the induction of Type I IFNs during the antiviral response, which can affect the replication of NDV and spread to CEFs in the early phase of viral infection.

Phylogenetic relationships and pathogenicity variation of two Newcastle disease viruses isolated from domestic ducks in Southern China.

BACKGROUND: Newcastle disease (ND) is an OIE listed disease caused by virulent avian paramyxovirus type 1 (APMV-1) strains, which is enzootic and causes large economic losses in the poultry sector. Genotype VII and genotype IX NDV viruses were the predominant circulating genotype in China, which may possibly be responsible for disease outbreaks in chicken flocks in recent years. While ducks and geese usually have exhibited inapparent infections. METHODS: In the present study, we investigate the complete genome sequence, the clinicopathological characterization and transmission of two virulent Newcastle disease viruses, SS-10 and NH-10, isolated from domestic ducks in Southern China in 2010. RESULTS: F, and the complete gene sequences based on phylogenetic analysis demonstrated that SS-10 (genotype VII) and NH-10 (genotype IX) belongs to class II. The deduced amino acid sequence was (112)R-R-Q-K/R-R-F(117) at the fusion protein cleavage site. Animal experiment results showed that the SS-10 virus isolated from ducks was highly pathogenic for chickens and geese, but low pathogenic for ducks. It could be detected from spleen, lung, kidney, trachea, small intestine, bursa of fabricius, thymus, pancreas and cecal tonsils, oropharyngeal and cloacal swabs, and could transmit to the naive contact birds. Moreover, it could transmit to chickens, ducks and geese by naive contact. However, the NH-10 virus isolated from ducks could infect some chickens, ducks and geese, but only caused chickens to die. Additionally, it could transmit to the naive contact chickens, ducks, and geese. CONCLUSION: The two NDV isolates exhibited different biological properties with respect to pathogenicity and transmission in chickens, ducks and geese. Therefore, no species-preference exists for chicken, duck or goose viruses and more attention should be paid to the trans-species transmission of VII NDVs between ducks, geese and chickens for the control and eradication of ND.

Complete genome sequence of a newly emerging newcastle disease virus isolated in china.

Goose/GD/2010 is a newly emerging Newcastle disease virus (NDV) isolated from a sick goose flock in southern China. Here, we report the complete genome sequence of this isolate, which belongs to NDV subgenotype VIIb. This is the first report about the complete genome information of an isolate of subgenotype VIIb in China.