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.

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.

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.

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.

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.

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.

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.

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.

Correlation of photoreceptor damage with anti-retina antibodies level in aqueous humor in macular edema patients.

This study aimed to investigate the correlation between the severity of photoreceptor damage and the level of anti-retina antibodies (ARAs) in aqueous humor, including recoverin, CA II and enolase-α IgG antibody of macular edema patients. Aqueous humor samples were collected from macular edema patients and from cataract patients. Patients were divided into three groups according to the severity of discontinuity of ellipsoid zone (EZ) shown on optical coherence tomography (OCT) imaging: cataract patients with intact EZ, macular edema patients with mild EZ damage, and macular edema patients with severe EZ damage. The level of ARAs was determined with enzyme-linked immunosorbent assay (ELISA). The correlation between the level of ARAs and the degree of photoreceptor damage was analyzed. The level of ARAs of the intact EZ group was significantly lower than that in the severely damaged group (P < 0.05). The level of recoverin IgG of the intact EZ group was significantly lower than mildly damaged group (P = 0.030). In a subgroup analysis, the level of recoverin IgG of DME patients was correlated with their central retinal thickness (CRT) (r = 0.462, P = 0.035). The level of ARAs in aqueous humor of patients with DME and RVO-ME was correlated with the degree of photoreceptor damage.

Wolfram syndrome 1b mutation suppresses Mauthner-cell axon regeneration via ER stress signal pathway.

Wolfram Syndrome (WS) is a fatal human inherited disease with symptoms of diabetes, vision decreasing, and neurodegeneration caused by mutations in the endoplasmic reticulum (ER)-resident protein WFS1. WFS1 has been reported to play an important role in glucose metabolism. However, the role of WFS1 in axonal regeneration in the central nervous system has so far remained elusive. Herein, we established a model of the wfs1b globally deficient zebrafish line. wfs1b deficiency severely impeded the Mauthner-cell (M-cell) axon regeneration, which was partly dependent on the ER stress response. The administration of ER stress inhibitor 4-Phenylbutyric acid (4-PBA) promoted M-cell axon regeneration in wfs1b-/- zebrafish larvae, while the ER stress activator Tunicamycin (TM) inhibited M-cell axon regeneration in wfs1b+/+ zebrafish larvae. Moreover, complementation of wfs1b at the single-cell level stimulated M-cell axon regeneration in the wfs1b-/- zebrafish larvae. Altogether, our results revealed that wfs1b promotes M-cell axon regeneration through the ER stress signal pathway and provide new evidence for a therapeutic target for WS and axon degeneration.

Comparison of efficacy and safety of intravitreal ranibizumab and conbercept before vitrectomy in Chinese proliferative diabetic retinopathy patients: a prospective randomized controlled trial.

BACKGROUND: To compare the efficacy and safety of preoperative intravitreal injections of ranibizumab and conbercept in Chinese proliferative diabetic retinopathy (PDR) patients. METHODS: This prospective randomized controlled trial enrolled 90 eyes of 80 patients with PDR. Forty-four eyes of 40 patients that received intravitreal ranibizumab (IVR) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVR group. Forty-six eyes of 40 patients that received intravitreal conbercept (IVC) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVC group. Intraoperative and postoperative indices were assessed for further comparison between the two groups. RESULTS: There were no statistically significant differences in all surgery indices, including intraoperative indices (surgery time, P = 0.225; intraoperative bleeding, P = 0.808; endodiathermy use, P = 0.693; incidence of iatrogenic retinal breaks, P = 0.740; relaxing retinotomy, P = 0.682; retinal reattachment, P = 0.682 and silicone oil tamponade, P = 0.814) and postoperative indices (postoperative vitreous hemorrhage (VH), P = 0.808; neovascular glaucoma (NVG), P = 0.964; recurrent retinal detachment, P = 0.531; postoperative fibrovascular proliferation progression, P = 0.682 and reoperation, P = 0.955) between the two groups. There were no statistically significant differences in best-corrected visual acuity (BCVA) at each follow-up visit (P = 0.939, 0.669, 0.741 and 0.717, respectively) or in central retinal thickness (CRT) (P = 0.976, 0.699, 0.551 and 0.686, respectively). As for safety profile, both groups had no ocular or system adverse events during the observation period. CONCLUSIONS: IVR and IVC as a pretreatment of vitrectomy had similar efficacy and safety profile for Chinese PDR patients. TRIAL REGISTRATION: Registered at ClinicalTrials.gov ( NCT05414149 ).

Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in Chinese with type 2 diabetes.

Purpose: To identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical application. Methods: This case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups. Result: Mean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA. Conclusion: This is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.

Prospective Comparison of Surgery Outcome Between Preoperative and Intraoperative Intravitreal Injection of Ranibizumab for Vitrectomy in Proliferative Diabetic Retinopathy Patients.

INTRODUCTION: To compare the efficacy and safety of intravitreal injections of ranibizumab (IVR) before and at the end of vitrectomy in proliferative diabetic retinopathy (PDR) patients. METHODS: A prospective comparative study was performed on 60 eyes of 52 PDR patients who received ranibizumab injection (0.5 mg/0.05 ml) 3-5 days before vitrectomy (preoperative group) and 55 eyes of 50 PDR patients who received ranibizumab injection (0.5 mg/0.05 ml) at the end of vitrectomy (intraoperative group). Intra- and postoperative indices were collected for further comparison. RESULTS: Postoperative best-corrected visual acuity (BCVA) in preoperative group was better than in intraoperative group at 1 week after surgery (P < 0.05) but comparable at 1- and 3-month follow-up (P = 0.20 and P = 0.37, respectively). Central retinal thickness (CRT) in preoperative group was lower than in intraoperative group at 1 week postoperatively (P < 0.05), but comparable at 1- and 3-month follow-up (P = 0.39 and P = 0.77, respectively). The average surgery time was significantly shorter in preoperative group than in intraoperative group (61.50 ± 11.44 min vs. 74.49 ± 12.01 min, P < 0.01). The incidence of intraoperative bleeding was significant lower in preoperative group than in intraoperative group (21.7% vs. 40.0%, P < 0.05). Moreover, the incidence of intraocular electrocoagulation use, iatrogenic retinal breaks, relaxing retinotomy and silicone oil tamponade were all significantly lower in preoperative group than that in intraoperative group (P < 0.05, respectively). The incidences of postoperative vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, postoperative fibrovascular proliferation progression and reoperation showed no statistical differences between the two groups (P > 0.05, respectively). Both groups had no ocular or system adverse events during observation period. CONCLUSION: In vitrectomy for PDR, preoperative IVR can significantly reduce surgery time and lower the incidence of intraoperative bleeding, intraocular electrocoagulation use, iatrogenic retinal breaks, relaxing retinotomy and silicone oil tamponade during surgery and gain short-term better postoperative BCVA and thinner CRT. TRIAL REGISTRATION: ClinicalTrials.gov (identifier, NCT05408416).

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.

Treatment for Retinopathy of Prematurity in Twins: The Small Twin without High Birth Weight Discordant Is Not at Increased Risk.

Purpose: As common retinopathy is observed in low-birth infants, the characteristics of ROP in twins are worth exploring. The present study tried to demonstrate the risk factors of treatment for retinopathy of prematurity (ROP) in twins both diagnosed with ROP. Methods: A retrospective, institution-based cohort study of 62 premature ROP twin pairs with a mean gestational age (GA) younger than 35 weeks and a birth weight (BW) lower than 2500 g. Only infants with a follow-up period longer than 6 months and complete treatment records were included. The demographic data, treatment requirements and further rescue treatments were all collected and analyzed for all infants according to whether they accepted treatments. Moreover, all twin infants were divided into small and large twin groups according to birth weight, and they were also categorized as three groups according to the treatment requirement including both twins receiving treatment (BT group), one of the twins receiving treatment (ST group) and none of the twins receiving treatment (NT group). Comparisons of demographic data, treatment requirements and further rescue treatments were all conducted according to the different grouping methods. Results: The mean GA of the enrolled infants was (29.29 ± 2.45) weeks with a mean BW of (1335.77 ± 390.36) grams. Among them, 110 infants were mechanically ventilated. Fifty-one of the infants did not receive any treatment and 73 infants received laser or intravitreal injection of anti-VEGF agents. In total, 64 infants only underwent intravitreal injection of anti-VEGF agents or laser treatment, while the other nine infants received scleral buckling or vitrectomy as a necessary treatment when the retinal detachment was observed. No significantly different mechanical ventilation or treatment requirements could be observed between the small twin group and the large twin group (p = 0.73, 0.94). The twins in the BT groups showed the lowest BW, while the NT group infants had the highest BW. The GA for the BT, ST and NT groups were (27.86 ± 1.87) weeks, (29.60 ± 1.52) weeks and (31.33 ± 2.39) weeks, respectively, and showed significant differences as well (p < 0.001). Conclusion: Being a small twin in twin-paired ROP without a high BW discordant will not increase the risk for treatment requirement or additional surgery necessity with a much more severe stage of ROP.

Serum Untargeted Metabolomics Reveal Potential Biomarkers of Progression of Diabetic Retinopathy in Asians.

Purpose: To reveal molecular mechanisms of diabetic retinopathy (DR) in Asians and facilitate the identification of new therapeutic targets through untargeted metabolomics. To determine the differences in serum metabolites and metabolic pathways between different stages of diabetic retinopathy in patients with type 2 diabetic mellitus (T2DM) and proliferative DR (PDR) and non-proliferative DR (NPDR) and identify differential metabolites between T2DM and DR (NPDR and PDR) patients. Methods: This prospective observational registration study described the differential metabolites between 45 T2DM patients and 15 control cases with no significant differences in clinical characteristics. Their biospecimens and clinical information were collected and recorded in their medical reports. DR phenotypes of the subjects were verified by retina specialists. Serum metabolites were analyzed using high-resolution mass spectrometry with liquid chromatography. Untargeted metabolomics was performed on serum samples from 15 T2DM patients, 15 non-proliferative diabetic retinopathy patients, 15 proliferative diabetic retinopathy patients, and 15 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis (PLS-DA), hierarchical clustering analysis (HCA), and generalized linear regression models. Result: Through untargeted metabolomics, 931 features (523 in positive and 408 in negative modes) with 102 common metabolites highly relevant to the presence of DR were detected. In the adjusted analysis, 67 metabolic features differed significantly between T2DM and NPDR patients. Pathway analysis revealed alterations in metabolisms of amino acids and fatty acids. Glutamate, phosphatidylcholine, and 13-hydroperoxyoctadeca-9,11-dienoic acid (13-PHODE) were key contributors to these pathway differences. A total of 171 features distinguished PDR patients from T2DM patients, and pathway analysis revealed alterations in amino acid metabolism, fatty acid metabolism, nitrogen metabolism, and tricarboxylic acid cycle. Aspartate, glutamate, glutamine, ornithine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, citrate, succinate, N-(L-arginino)succinate, 2-oxoglutarate, 13-hydroperoxyoctadeca-9,11-dienoic acid, methionine, lysine, threonine, phenylalanine, N(pi)-methyl-l-histidine, phosphatidylcholine, and linoleate were major contributors to the pathway differences. Between NPDR patients and PDR patients, there were 79 significant differential metabolites. Enrichment pathway analysis showed changes in amino acid metabolism, fatty acid metabolism, pantothenate, and CoA biosynthesis. Aspartate, glutamine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, pantothenate, dihomo-gamma-linolenate, docosahexaenoic acid, and icosapentaenoic acid were key factors for the differences of these pathways. Conclusion: This study demonstrated that the pathways of arginine biosynthesis metabolism, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, as well as d-glutamine and d-glutamate metabolism, were dysregulated in DR patients of the Asian population. Increased levels of glutamate, aspartate, glutamine, N-acetyl-l-glutamate, and N-acetyl-l-aspartate and decreased levels of dihomo-gamma-linolenate, docosahexaenoic, and icosapentaenoic were considered as the metabolic profile that could distinguish PDR from NPDR in Asians. Phosphatidylcholine and 13-PHODE were identified as two major novel metabolite markers in advanced stages of DR in our study.

Correlation between Patient-Derived Xenograft Modeling and Prognosis in Osteosarcoma.

OBJECTIVE: To retrospectively analyze and compare the relationship between the success rate of patient-derived xenograft (PDX) modeling of osteosarcoma and prognosis (3-year overall survival rate and disease-free survival rate) and incidence of lung metastasis. METHODS: The sample group consisted of 57 osteosarcoma patients with definite pathological diagnoses from Shanghai General Hospital from 2015-2017. PDX models in 57 patients were analyzed by retrospective analyses. Among the patients currently inoculated, 20 were tumorigenic in the PDX model, and 37 were nontumorigenic. According to the tumorigenicity of PDXs, the corresponding osteosarcoma patients were divided into two groups. The effects of clinically related indicators on the model were retrospectively compared. The patients were followed, and the 3-year survival, 3-year disease-free survival (DFS), and lung metastasis rates were collected. The relationship between the modeling success and patient prognosis was investigated. RESULTS: In the chemotherapy-treated group, the PDX modeling success rate was 17.4%, and in the nonchemotherapy group, the success rate was 47.1%. The success of PDX modeling was related to whether patients received chemotherapy. The success rate of PDX modeling is significantly reduced after receiving chemotherapy. The 3-year overall survival rate of the PDX-grafted group was 49.23%, and that of the PDX-nongrafted group was 65.71%. There was a significant difference between the two groups, showing a strong negative correlation between the 3-year survival rate and the success rate of the PDX model. The 3-year disease-free survival rate of the PDX-grafted group was 29.54%. The 3-year DFS of the PDX-nongrafted group was 50.34%. There was a significant difference between the two groups. Lower grafted rates indicate a higher DFS rate. The incidence of lung metastasis in the PDX-grafted group was 32.4%, and that in the nongrafted group was 13.1%. There was a significant difference between the two groups. The successful establishment of the PDX model indicates that patients are more likely to have lung metastases. CONCLUSIONS: The success of PDX modeling often indicates poor prognosis (low 3-year overall survival rate and disease-free survival rate) and a greater possibility of lung metastasis. Therefore, PDX modeling in osteosarcoma patients can accurately predict the prognosis of patients and the risk of lung metastasis in advance to help us develop better therapeutic strategies.

[Progress in preparation of plant biomass-derived biochar and application in pesticide residues field].

Pesticides such as insecticides, fungicides, and herbicides play an important role in the global agricultural industry as they reduce the occurrence of crop diseases, kill pests, and remove weeds. On the other hand, these pesticides are a double-edged sword because they have both acute effects and chronic adverse effects on human health. The widespread use of pesticides has led to their persistence in soil, water, and agricultural products, thus posing a serious threat to public health. Therefore, the removal and analysis of pesticides are critical to protecting human safety and health. When removing pesticides from the environment, it is imperative to ensure high removal efficiency while preventing secondary pollution to the environment. Because of the low concentrations of pesticide residue in the environment, complex matrix, and large throughput of pesticide residue analysis, a low-cost fast pre-treatment technique that has strong selectivity and an enrichment effect on the target pesticide residue, with little environmental impact, is required. Plant biomass-derived biochar is obtained from wheat straw, corn cob, rice husk, etc. This material has a large specific surface area, high pore capacity, tunable surface functional groups, and good environmental compatibility, which make it an inexpensive and efficient adsorbent. Hence, there is a need to systematically review the knowledge regarding the application of plant-based biochar on pesticide removal and pesticide residue analysis. This paper reviews the application progress of plant biomass-derived biochar in the above mentioned two areas over the last decade. The pesticide removal applications include reducing the mobility of pesticides in soil, eliminating the pollution caused by chiral pesticides, loading pesticide-degrading bacteria, and releasing fertilizers sustainably when removing pesticide. As mentioned above, plant biomass-derived biochar has a large specific surface area, a high number of functional groups on the surface, and good environmental compatibility. Therefore, it can effectively remove pesticides or their metabolites from the environment without causing any secondary pollution. During pre-treatment, plan biomass-derived biochar is used as an adsorbent for dispersive solid-phase extraction, solid-phase microextraction, and magnetic solid-phase extraction to selectively adsorb organophosphorus and triazole pesticides in fruits and vegetables, as well as organochlorine pesticides in the aquatic environment. This paper also introduces the adsorption mechanism of plant biomass-derived biochar, where studies based on computational simulations such as the density functional theory, molecular dynamics simulation, and giant canonical Monte Carlo simulation are carefully discussed. The benefits of adopting computational simulations are also mentioned. Finally, this paper summarizes the advantages and disadvantages of using plant biomass-derived biochar in pesticide removal and pre-treatment, as well as the future research trends in this area.

A 3D-Bioprinted Multiple Myeloma Model.

Multiple myeloma (MM) is a malignancy of plasma cells accounting for ≈12% of hematological malignancies. In this study, the fabrication of a high-content in vitro MM model using a coaxial extrusion bioprinting method is reported, allowing formation of a human bone marrow-like microenvironment featuring an outer mineral-containing sheath and the inner soft hydrogel-based core. MM cells are mono-cultured or co-cultured with HS5 stromal cells that can release interleukin-6 (IL-6), where the cells show superior behaviors and responses to bortezomib in 3D models than in the planar cultures. Tocilizumab, a recombinant humanized anti-IL-6 receptor (IL-6R), is investigated for its efficacy to enhance the chemosensitivity of bortezomib on MM cells cultured in the 3D model by inhibiting IL-6R. More excitingly, in a proof-of-concept demonstration, it is revealed that patient-derived MM cells can be maintained in 3D-bioprinted microenvironment with decent viability for up to 7 days evaluated, whereas they completely die off in planar culture as soon as 5 days. In conclusion, a 3D-bioprinted MM model is fabricated to emulate some characteristics of the human bone marrow to promote growth and proliferation of the encapsulated MM cells, providing new insights for MM modeling, drug development, and personalized therapy in the future.