Tyrosine phosphorylation of the lectin receptor-like kinase LORE regulates plant immunity.

Plant pattern recognition receptors (PRRs) perceive pathogen-associated molecular patterns (PAMPs) to activate immune responses. Medium-chain 3-hydroxy fatty acids (mc-3-OH-FAs), which are widely present in Gram-negative bacteria, were recently shown to be novel PAMPs in Arabidopsis thaliana. The Arabidopsis PRR LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) is a G-type lectin receptor-like kinase that recognizes mc-3-OH-FAs and subsequently mounts an immune response; however, the mechanisms underlying LORE activation and downstream signaling are unexplored. Here, we report that one of the mc-3-OH-FAs, 3-OH-C10:0, induces phosphorylation of LORE at tyrosine residue 600 (Y600). Phosphorylated LORE subsequently trans-phosphorylates the receptor-like cytoplasmic kinase PBL34 and its close paralogs, PBL35 and PBL36, and therefore activates plant immunity. Phosphorylation of LORE Y600 is required for downstream phosphorylation of PBL34, PBL35, and PBL36. However, the Pseudomonas syringae effector HopAO1 targets LORE, dephosphorylating the tyrosine-phosphorylated Y600 and therefore suppressing the immune response. These observations uncover the mechanism by which LORE mediates signaling in response to 3-OH-C10:0 in Arabidopsis.

Optical coherence tomography angiography-guided vs indocyanine green angiography-guided half-dose photodynamic therapy for acute central serous chorioretinopathy: 6-month randomized trial results.

PURPOSE: This study aimed to compare the anatomic and functional results of optical coherence tomography angiography (OCTA)-guided half-dose photodynamic therapy (PDT) versus indocyanine green angiography (ICGA)-guided PDT in eyes with acute central serous chorioretinopathy (CSC). METHODS: One hundred and thirty-one eyes of 131 patients with acute central serous chorioretinopathy (CSC) were recruited, and randomly assigned to the OCTA-guided group and ICGA-guided group. The primary outcome measures were the rates of complete subretinal fluid (SRF) resolution at 1 month, 3 months, and 6 months. The secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal capillary flow deficit density at each scheduled visit, and recurrence rate of SRF at 3 months and 6 months. RESULTS: There were 110 eyes that finished the follow-up, with 56 eyes in the OCTA-guided group and 54 eyes in the ICGA guided group. OCTA-guided PDT was demonstrated to be noninferior to ICGA-guided PDT for SRF resolution rate at 1 months and 6 months (P = 0.021 and P = 0.037), but not at 3 months for acute CSC (P = 0.247). The average CRT of the ICGA-guided group was significantly lower than that of the OCTA-guided group at 3-month visit (P = 0.046), but no significant difference was found between them at the 1-month and 6-month visits (P = 0.891 and 0.527). There was no significant difference between the two groups for BCVA (P = 0.359, 0.700, and 0.143, respectively) and the deficit area on CC (P = 0.537, 0.744,and 0.604, respectively) at 1, 3, and 6 months. CONCLUSION: OCTA may replace ICGA to guide PDT for the treatment of acute CSC and their follow-up.

Deletion of the chd7 Hinders Oligodendrocyte Progenitor Cell Development and Myelination in Zebrafish.

CHD7, an encoding ATP-dependent chromodomain helicase DNA-binding protein 7, has been identified as the causative gene involved in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia choanae, Retardation of growth and/or development, Genital abnormalities and Ear abnormalities). Although studies in rodent models have expanded our understanding of CHD7, its role in oligodendrocyte (OL) differentiation and myelination in zebrafish is still unclear. In this study, we generated a chd7-knockout strain with CRISPR/Cas9 in zebrafish. We observed that knockout (KO) of chd7 intensely impeded the oligodendrocyte progenitor cells' (OPCs) migration and myelin formation due to massive expression of chd7 in oilg2+ cells, which might provoke upregulation of the MAPK signal pathway. Thus, our study demonstrates that chd7 is critical to oligodendrocyte migration and myelination during early development in zebrafish and describes a mechanism potentially associated with CHARGE syndrome.

Emission characteristics of coal gasification fine slag direct combustion and co-firing with coal.

Coal gasification is an effective way to use coal cleanly and efficiently, and coal gasification fine slag is a by-product of coal gasification with high carbon content, large specific surface area, developed pore structure and large output during production. At present, combustion has become an effective way to dispose of coal gasification fine slag on a large scale, and the coal gasification fine slag after combustion treatment can be further used for construction raw materials. In this paper, the emission characteristics of gas-phase pollutants and particulate matter under different combustion temperatures (900 °C, 1100 °C, 1300 °C) and combustion atmosphere (5%, 10%, 21% O2 concentration) are studied with the drop tube furnace experimental system. By co-firing different proportions of coal gasification fine slag (10%, 20%, 30%) and raw coal, the pollutants formation law under co-firing conditions is studied. Scanning electron microscopy-energy spectroscopy (SEM-EDS) is used to characterize the apparent morphology and elemental composition of particulate samples. The measurement results of gas-phase pollutants show that the increase of furnace temperature and O2 concentration can effectively promote combustion and improve burnout characteristics, but the emission of gas-phase pollutants increases. A certain proportion (10%-30%) of coal gasification fine slag is added to the raw coal, which reduces the total emission of gas-phase pollutants (NOx and SOx). Studies on the characteristics of particulate matter formation show that co-firing with coal gasification fine slag in raw coal can effectively reduce submicron particle emission, and the lower fine particle emission is also detected at lower furnace temperature and oxygen concentration. The element analysis of particulate matter formation shows that the Fe, Si and S elements content of submicron particle generated by YL (the coal gasification fine slag generated by water slurry furnace in of Shaanxi Extended China Coal Yulin Energy Chemical Co., Ltd) sample increases significantly with the increase of furnace temperature and O2 concentration, which is the main influencing factor for the increase of submicron particle. With the increase of the mixing ratio of YL sample, the content of major elements such as Fe, K and Mg of submicron particle decreases significantly, which is an important reason why the amount of the submicron particle decreases.

Case series: pachychoroid pigment epitheliopathy transformed to polypoidal choroidal vasculopathy after long-term follow-up.

BACKGROUND: Pachychoroid pigment epitheliopathy (PPE), a retinal disorder that falls into the pachychoroid spectrum, is characterized by retinal pigment epithelium changes in pachychoroid eyes without existing or previous subretinal fluid or soft drusen. Previous reports have indicated that PPE may share some pathophysiologic component with other pachychoroid spectrum diseases and could transform into central serous chorioretinopathy (CSC) during follow-up. CSC transformation to PNV and PCV has also been reported, but PPE transformation to PCV has not been reported.  CASE PRESENTATION: Seven eyes of seven patients (four male three female, aged 62.7 ± 8.4 years) who presented with PPE at baseline transformed to PCV during follow-up. All study eyes had baseline contralateral eye diagnoses of PCV. All PPE eyes reported no symptoms at baseline and were followed up regularly for the treatment of their contralateral eyes. All PPE presented as pigment epithelium detachment (PED) at baseline. The mean central macular thickness (CMT) was 217.6 ± 14.6 µm, the mean subfoveal choroidal thickness (SFCT) was 354.9 ± 94.9 µm, and the mean sub-PPE choroidal thickness was 332.3 ± 84.6 µm. The mean PPE width and height were 1326.4 ± 791.4 µm and 58.7 ± 23.6 µm, respectively, at baseline. Disruption of the ellipsoid zone (EZ) was noted in 3 eyes, while choroidal vascular hyperpermeability (CVH) was noted in 5 eyes at baseline. The follow-up period was 75.0 ± 41.1 months, and the mean transformation time was 49.6 ± 24.8 months. All study eyes received no intervention before transformation. CONCLUSIONS: PPE could transform to PCV after a long follow-up period. Regular follow-ups for a long time should be recommended for patients with PPE.

Anti-recoverin antibodies indicate fundus abnormalities in systemic lupus erythematosus.

OBJECTIVES: Lupus fundus abnormalities are a sight-threatening complication of systemic lupus erythematosus (SLE) and its pathogenesis remains to be studied. The aim of this study was to assess the clinical characteristics associated with the presence of anti-recoverin antibodies in patients with SLE, especially those with fundus abnormalities. METHODS: Seventy-six participants were enrolled, including 21 patients with fundus abnormalities (fundus group), 30 patients without fundus abnormalities (non-fundus group) and 25 healthy individuals. Serum anti-recoverin antibody levels were measured using enzyme-linked immunosorbent assay, and clinical and laboratory data were obtained from medical records. RESULTS: Compared with the non-fundus group, the fundus group had a higher incidence of hematuria (p < 0.05). The Systemic Erythematosus Disease Activity Index (SLEDAI) score in the fundus group was significantly higher than the non-fundus group (21.48 ± 8.06 versus 10.80 ± 5.74, p < 0.001). The levels of serum anti-recoverin antibodies in the fundus group were significantly higher than the non-fundus group (p = 0.029) or the healthy control group (p = 0.011). Anti-recoverin-negative and -positive patients differed on a number of clinical parameters, including incidence of fever, rash, antinuclear antibody, anti-dsDNA antibody, erythrocyte sedimentation rate, immunoglobulin G, complement C3 and complement C4. The average SLEDAI score of anti-recoverin-positive patients was significantly higher than anti-recoverin-negative patients (17.73 ± 8.11 versus 12.56 ± 8.37, p < 0.05). CONCLUSIONS: Anti-recoverin antibodies were related to higher disease activities in SLE, especially those with fundus abnormalities, suggesting that anti-recoverin antibodies may play an important role in the pathogenesis of fundus abnormalities in SLE.

Reduction-responsive polypeptide nanomedicines significantly inhibit progression of orthotopic osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor with high metastasis and mortality. Neoadjuvant chemotherapy is an effective therapeutic regimen, but the clinical application is limited by the unsatisfactory efficacies and considerable side effects. In this study, the reduction-responsive polypeptide micelles based on methoxy poly(ethylene glycol)-block-poly(S-tert-butylmercapto-L-cysteine) copolymers (mPEG113-b-PBMLC4, P4M, and mPEG113-b-PBMLC9, P9M) were developed to control the delivery of doxorubicin (DOX) in OS therapy. Compared to free DOX, P4M/DOX and P9M/DOX exhibited 2.6 and 3.5 times increase in the area under the curve of pharmacokinetics, 1.6 and 2.0 times increase in tumor accumulation, and 1.6 and 1.7 times decrease of the distribution in the heart. Moreover, the selective accumulation of micelles, especially P9M/DOX, in tumors induced stronger antitumor effects on both primary and lung metastatic OSs with less systematic toxicity. These micelles with smart responsiveness to intracellular microenvironments are highly promising for the targeted delivery of clinical chemotherapeutic drugs in cancer therapy.

Meptyldinocap and azoxystrobin residue behaviors in different ecosystems under open field conditions and distribution on processed cucumber.

BACKGROUND: Several diseases and insects may cause damage to the normal growth of cucumber. Azoxystrobin and meptyldinocap, because of their novel mode of action, are effective against pathogens that have developed reduced sensitivity to other fungicides. Azoxystrobin is persistent in various crops and environments. However, there is a lack of research on the dissipation of these two pesticides, especially meptyldinocap. RESULTS: Analytes could be quantified with decent recoveries of 90-101%, with relative standard deviations (RSDs) of 3.0-10.1%. The terminal residues of meptyldinocap and azoxystrobin in cucumber were all < limit of quantification (LOQ) (0.02 and 0.05 mg kg-1 ). The half-lives of meptyldinocap and azoxystrobin were 0.8-1.1 and 1.2-2.8 days, respectively. The processing factors (PFs) for washing were all < 1, but the removal rate for washing was < 29.0%. Peeling had a significant effect on the removal of pesticide. The largest residue reductions were noticed through the pickling process, but special care should be taken regarding residues in the pickling solution as pesticides could transfer to them from cucumber. A more interesting finding was that the degradation of two pesticides was accelerated by the addition of calcium oxide. CONCLUSION: Pesticide residues on cucumber decreased after these processes. These results enable the health-risks from dietary exposures to pesticide residues to be characterized. They enable maximum residue limits (MRLs) to be established for pesticide residues in food products. They also assist the optimization of food processing with regard to pesticide residue dissipation. © 2019 Society of Chemical Industry.

A bHLH transcription activator regulates defense signaling by nucleo-cytosolic trafficking in rice.

Crosstalk between plant hormone signaling pathways is vital for controlling the immune response during pathogen invasion. Salicylic acid (SA) and jasmonic acid (JA) often play important but antagonistic roles in the immune responses of higher plants. Here, we identify a basic helix-loop-helix transcription activator, OsbHLH6, which confers disease resistance in rice by regulating SA and JA signaling via nucleo-cytosolic trafficking in rice (Oryza sativa). OsbHLH6 expression was upregulated during Magnaporthe oryzae infection. Transgenic rice plants overexpressing OsbHLH6 display increased JA responsive gene expression and enhanced disease susceptibility to the pathogen. Nucleus-localized OsbHLH6 activates JA signaling and suppresses SA signaling; however, the SA regulator OsNPR1 (Nonexpressor of PR genes 1) sequesters OsbHLH6 in the cytosol to alleviate its effect. Our data suggest that OsbHLH6 controls disease resistance by dynamically regulating SA and JA signaling.

Anlotinib, a novel small molecular tyrosine kinase inhibitor, suppresses growth and metastasis via dual blockade of VEGFR2 and MET in osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with highly aggressive behavior and early systemic metastasis. The survival rates for osteosarcoma remain unchanged over the past two decades. Studies aiming to find new or alternative therapies for patients with refractory osteosarcoma are urgently needed. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging clinical activity in NSLCC and soft tissue sarcoma, whereas its effect on osteosarcoma has not been studied. In our study, we investigated the anti-tumor activity and underlying mechanism of anlotinib in osteosarcoma. Various in vitro and in vivo models of human osteosarcoma were used to determine the anti-proliferative, anti-angiogenesis and anti-metastasis efficacy of anlotinib. Our results showed that anlotinib suppressed tumor growth and increased the chemo-sensitivity of osteosarcoma. In addition, anlotinib inhibited migration and invasion in osteosarcoma cells. Furthermore, in order to explore the anti-tumor mechanism of anlotinib, phospho-RTK antibody arrays were performed. These analyses confirmed that anlotinib suppressed the phosphorylation of MET, VEGFR2 and the downstream signaling pathway activation. Moreover, we demonstrated that anlotinib blocked hepatocyte growth factor (HGF)-induced cell migration, invasion and VEGF-induced angiogenesis. Notably, a 143B-Luc orthotopic osteosarcoma model further showed that anlotinib significantly inhibited growth and lung metastasis of implanted tumor cells. Our preclinical work indicates that anlotinib acts as a novel inhibitor of VEGFR2 and MET that blocks tumorigenesis in osteosarcoma, which could be translated into future clinical trials.

Circadian genes period1b and period2 differentially regulate inflammatory responses in zebrafish.

The circadian clock has been shown to regulate various immune processes in different animals. Our previous report demonstrated that the innate immune responses in zebrafish show significant rhythmicity that could be regulated by melatonin. Here, we used diurnal zebrafish to determine the role of circadian genes in the inflammatory responses. Our results indicate that circadian genes exhibit rhythmic oscillations in zebrafish leukocytes, and mutations of the clock genes period1b (per1b) and period2 (per2) considerably affect these oscillations. Using a wounded zebrafish inflammation model, we found that under constant dark conditions (DD), the expression of pro-inflammatory cytokines is significantly downregulated in per1b gene mutant zebrafish and significantly upregulated in the per2 gene mutant zebrafish. Furthermore, using real-time imaging technology, we found that the per1b gene markedly disturbs the rhythmic recruitment of neutrophils toward the injury, whereas the per2 gene does not show a significant effect. Taken together, our results reveal differential functions of the circadian genes per1b and per2 in the inflammatory responses, serving as evidence that circadian rhythms play a vital role in immune processes.

The Bacterial Effector AvrB-Induced RIN4 Hyperphosphorylation Is Mediated by a Receptor-Like Cytoplasmic Kinase Complex in Arabidopsis.

Bacterial pathogen Pseudomonas syringae delivers diverse type III effectors into host cells to interfere with their immune responses. One of the effectors, AvrB, targets a host guardee protein RIN4 and induces RIN4 phosphorylation in Arabidopsis. Phosphorylated RIN4 activates the immune receptor RPM1 to mount defense. AvrB-induced RIN4 phosphorylation depends on RIPK, a receptor-like cytoplasmic kinase (RLCK). In this study, we found several other RLCKs that were also able to phosphorylate RIN4. We demonstrated that these RLCKs formed a complex with RIPK and were functionally redundant to RIPK. We also found that unphosphorylated RIN4 was epistatic to phosphorylated RIN4 in terms of RPM1 activation. AvrB-induced RLCK gene expression and phosphorylated RIN4-triggered RPM1 activation required RAR1, a central regulator in plant innate immunity. Our results unravel a mechanism in which plants employ multiple kinases to hyperphosphorylate the guardee protein RIN4 to ensure immune activation during pathogen invasion.

Short communication: interaction of bovine milk protein with chlorpyrifos.

Dairy products are considered as nutrient-dense foods and consumed by many people in western countries, as well as an increasing number of Asian people. Excessive and frequent application of pesticides on vegetables and fruits leads to a potential health hazard to consumers. The organophosphate insecticide chlorpyrifos has been reported to bind with human and bovine serum albumin. Thus, it is necessary to explore the interaction between food protein and chlorpyrifos. In this study, equilibrium dialysis and fluorescence spectra were used to demonstrate binding of milk proteins to chlorpyrifos. The amount of milk protein bound was 0.03±0.01mg/g. Moreover, the milk protein-chlorpyrifos complexes were stable at pH 3.5to 9.5 and ion concentrations from 0.1 to 1.0M. The amount of chlorpyrifos bound to milk proteins decreased to 50% after being in vitro digested by pepsin and trypsin. The results showed that the interaction between food proteins and the pesticide might partially remove the insecticide and reduce the concentration of pesticide absorbed into the blood and, thus, alleviate the corresponding toxicity.

Effects of the pesticide carbendazim on broiler chicken health and carbendazim residue levels in broiler tissues.

Pesticide residues may enter the human body through the food chain when livestock and poultry consume pesticide-contaminated feed. Therefore, monitoring and limiting pesticide residues in animal feed and animal-origin foods is necessary. Carbendazim is one of the most frequently detected pesticides in food and feed and has various toxic effects on non-target animals. This study investigated the effects of varying concentrations of carbendazim contamination in feed on broiler chicken growth performance, serum biochemical indicators, histopathology, and carbendazim residues in broiler muscles and livers. The results demonstrated that contamination of 5-100 mg/kg carbendazim in feed did not affect broiler growth performance or health. Carbendazim contamination in feed at 200-800 mg/kg slightly reduced growth performance. Broiler kidneys showed minor histopathological alterations after 400 mg/kg carbendazim exposure. Furthermore, when the carbendazim content in feed was less than 25 mg/kg, the residual carbendazim in the muscles and livers of broilers did not exceed the maximum residue level set by the European Union and China. Based on the above findings, carbendazim residues in the feed of less than 25 mg/kg can be considered safe for chicken products.

Sevoflurane postconditioning ameliorates cerebral hypoxia/reoxygenation injury in zebrafish involving the Akt/GSK-3ß pathway activation and the microtubule-associated protein 2 promotion.

Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3ß pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3ß inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3ß, p-GSK-3ß, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3ß/GSK-3ß. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3ß pathway and promotion of MAP2 expression.

Magnetic-driven hydrogel microrobots for promoting osteosarcoma chemo-therapy with synthetic lethality strategy.

The advancements in the field of micro-robots for drug delivery systems have garnered considerable attention. In contrast to traditional drug delivery systems, which are dependent on blood circulation to reach their target, these engineered micro/nano robots possess the unique ability to navigate autonomously, thereby enabling the delivery of drugs to otherwise inaccessible regions. Precise drug delivery systems can improve the effectiveness and safety of synthetic lethality strategies, which are used for targeted therapy of solid tumors. MYC-overexpressing tumors show sensitivity to CDK1 inhibition. This study delves into the potential of Ro-3306 loaded magnetic-driven hydrogel micro-robots in the treatment of MYC-dependent osteosarcoma. Ro-3306, a specific inhibitor of CDK1, has been demonstrated to suppress tumor growth across various types of cancer. We have designed and fabricated this micro-robot, capable of delivering Ro-3306 precisely to tumor cells under the influence of a magnetic field, and evaluated its chemosensitizing effects, thereby augmenting the therapeutic efficacy and introducing a novel possibility for osteosarcoma treatment. The clinical translation of this method necessitates further investigation and validation. In summary, the Ro-3306-loaded magnetic-driven hydrogel micro-robots present a novel strategy for enhancing the chemosensitivity of MYC-dependent osteosarcoma, paving the way for new possibilities in future clinical applications.

An achieved strategy for magnetic biochar for removal of tetracyclines and fluoroquinolones: Adsorption and mechanism studies.

In this study, poplar wood biochar modified with Fe3O4 (MPBC) was prepared using poplar wood as carbon source applied to remove tetracyclines and fluoroquinolones. The adsorption behavior was investigated by batch experiments, and a series of characterization techniques were used to study the corresponding mechanism. Characterizations indicated that pore filling, electrostatic interactions, π-π interaction, surface complexation, and hydrogen bond contributed to the adsorption of antibiotics on MPBC. Most importantly, the thermodynamic experiment results showed that the adsorption capacity of MPBC for tetracyclines (70.28-89.58 mg⋅g-1) was significantly higher than fluoroquinolones (35.54-60.31 mg⋅g-1), which was further explained by hydrogen bond interactions calculated from Conductor-like screening model for real solvents (COSMO-RS). In addition, the adsorption between MPBC and antibiotics was favorable at lower ionic strengths and neutral conditions. Conclusively, this study could provide a promising approach to controlling the pollution of tetracyclines and fluoroquinolones.

Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema.

To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME.

Acute Macular Neuroretinopathy after SARS-CoV-2 Infection: An Analysis of Clinical and Multimodal Imaging Characteristics.

BACKGROUND: This study aimed to analyze clinical and multimodal imaging characteristics of acute macular neuroretinopathy (AMN) post-recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Retrospective observational study. Medical records and multimodal imaging of 12 AMN eyes of eight patients (six female and two male) with recent SARS-CoV-2 infection were retrospectively analyzed. RESULTS: Four patients (50%) presented with bilateral AMN. Fundus ophthalmoscopy revealed a reddish-brown lesion around the macula, and two eyes had cotton-wool spots at the posterior pole. Three eyes showed mild hypo-autofluorescence. All FFA images (7 eyes) showed no abnormal signs. On OCT scans, all eyes showed outer nuclear layer (ONL) thinning, 8 eyes (66.7%) showed ONL hyperreflectivity, 5 eyes (41.7%) showed outer plexiform layer (OPL) hyperreflectivity, 8 eyes (66.7%) showed interdigitation zone (IZ) disruption, 11 eyes (91.6%) showed ellipsoid zone (EZ) disruption, 2 eyes (16.7%) showed cotton-wool spots and inner plexiform layer (IPL) hyperreflectivity, 1 eye (8.3%) had intraretinal cyst and 1 eye (8.3%) had inner nuclear layer (INL) thinning. Persistent scotoma, ONL hyperreflectivity and IZ/EZ disruption as well as recovery of OPL hyperreflectivity were reported after follow-up in three cases. CONCLUSIONS: AMN post-SARS-CoV-2 mostly affected young females and could present unilaterally or bilaterally. Dark lesions on IR reflectance and outer retinal hyperreflectivity on OCT are useful in diagnosing AMN. OPL/ONL hyperreflectivity on OCT could disappear after follow-up, but ONL thinning and IZ/EZ could persist.

Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global public health problem. Chronic hepatitis B (CHB) patients can be divided into treatment indication and non-treatment indication individuals according to alanine transaminase (ALT), HBV DNA, serum hepatitis B e antigen status, disease status [liver cirrhosis, hepatocellular carcinoma (HCC), or liver failure], liver necroinflammation or fibrosis, patients' age, and family history of HCC or cirrhosis. For example, normal ALT patients in 'immune-tolerant' phase with HBV DNA higher than 107 or 2 × 107 IU/mL, and those in 'inactive-carrier' phase with HBV DNA lower than 2 × 103 IU/mL do not require antiviral therapy. However, is it reasonable to set the defined values of HBV DNA as the fundamental basis to estimate the disease state and to determine whether to start treatment? In fact, we should pay more attention to those who do not match the treatment indications (gray-zone patients both in the indeterminate phase and in the 'inactive-carrier' phase). AIM: To analyze the correlation of HBV DNA level and liver histopathological severity, and to explore the significance of HBV DNA for CHB with normal ALT. METHODS: From January 2017 to December 2021, a retrospective cross-sectional set of 1299 patients with chronic HBV infection (HBV DNA > 30 IU/mL) who underwent liver biopsy from four hospitals, including 634 with ALT less than 40 U/L. None of the patients had received anti-HBV treatment. The degrees of liver necroinflammatory activity and liver fibrosis were evaluated according to the Metavir system. On the basis of the HBV DNA level, patients were divided into two groups: Low/moderate replication group, HBV DNA ≤ 107 IU/mL [7.00 Log IU/mL, the European Association for the Study of the Liver (EASL) guidelines] or ≤ 2 × 107 IU/mL [7.30 Log IU/mL, the Chinese Medical Association (CMA) guidelines]; high replication group, HBV DNA > 107 IU/mL or > 2 × 107 IU/mL. Relevant factors (demographic characteristics, laboratory parameters and noninvasive models) for liver histopathological severity were analyzed by univariate analysis, logistics analysis and propensity score-matched analysis. RESULTS: At entry, there were 21.45%, 24.29%, and 30.28% of the patients had liver histopathological severities with ≥ A2, ≥ F2, and ≥ A2 or/and ≥ F2, respectively. HBV DNA level (negative correlation) and noninvasive model liver fibrosis 5 value (positive correlation) were independent risk factors for liver histopathological severities (liver necroinflammation, liver fibrosis, and treatment indication). The AUROCs of the prediction probabilities (PRE_) of the models mentioned above (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.814 (95%CI: 0.770-0.859), 0.824 (95%CI: 0.785-0.863), and 0.799 (95%CI: 0.760-0.838), respectively. HBV DNA level (negative correlation) was still an independent risk factor when diagnostic models were excluded, the P values (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.011, 0.000, and 0.000, respectively. For the propensity score-matched pairs, whether based on EASL guidelines or CMA guidelines, the group with significant liver histology damage (≥ A2 or/and ≥ F2) showed much lower HBV DNA level than the group with non- significant liver histology damage (< A2 and < F2). Patients in the moderate replication group (with indeterminate phase) had the most serious liver disease pathologically and hematologically, followed by patients in the low replication group (with 'inactive-carrier' phase) and then the high replication group (with 'immune-tolerant' phase). CONCLUSION: HBV DNA level is a negative risk factor for liver disease progression. The phase definition of CHB may be revised by whether the level of HBV DNA exceeds the detection low limit value. Patients who are in the indeterminate phase or 'inactive carriers' should receive antiviral therapy.