4D label-free proteomics analysis of oxygen-induced retinopathy with or without anti-VEGF treatment.

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.

Non-contact wide-field viewing system-assisted scleral buckling surgery for retinal detachment in silicone oil-filled eyes.

AIM: To evaluate scleral buckling (SB) surgery using a non-contact wide-field viewing system and 23-gauge intraocular illumination for the treatment of rhegmatogenous retinal detachment in silicone oil (SO)-filled eyes. METHODS: Totally 9 patients (9 eyes) with retinal detachment in SO-filled eyes were retrospectively analyzed. All patients underwent non-contact wide-field viewing system-assisted buckling surgery with 23-gauge intraocular illumination. SO was removed at an appropriate time based on recovery. The patients were followed up for at least 3mo after SO removal. Retinal reattachment, complications, visual acuity and intraocular pressure (IOP) before and after surgery were observed. RESULTS: Patients were followed up for a mean of 8.22mo (3-22mo) after SO removal. All patients had retinal reattachment. At the final follow-up, visual acuity showed improvement for 8 patients, and no change for 1 patient. The IOP was high in 3 patients before surgery, but it stabilized after treatment; it was not affected in the other patients. None of the patients had infections, hemorrhage, anterior ischemia, or any other complication. CONCLUSION: This new non-contact wide-field viewing system-assisted SB surgery with 23-gauge intraocular illumination is effective and safe for retinal detachment in SO-filled eyes.

CSSLdb: Discovery of cancer-specific synthetic lethal interactions based on machine learning and statistic inference.

Synthetic lethality (SL) occurs when the inactivation of two genes results in cell death while the inactivation of either gene alone is non-lethal. SL-based therapy has become a promising anti-cancer treatment option with the increasing researches and applications in clinical practice, while the specific therapeutic opportunities for various cancers have not yet been comprehensively investigated. Herein, we described a computational approach based on machine learning and statistical inference to discover the cancer-specific synthetic lethal interactions. First, Random Forest and One-Class SVM were used to perform cancer unbiased prediction of synthetic lethality. Then, two strategies, including mutual exclusivity and differential expression, were used to screen cancer-specific synthetic lethal interactions, resulting in 14,582 SL gene pairs in 33 cancer types. Finally, we developed a freely available database of CSSLdb (Cancer Specific Synthetic Lethality Database, http://www.tmliang.cn/CSSL/) to present cancer-specific synthetic lethal genetic interactions, which would enrich the relevant research and contribute to underlying therapy strategies based on synthetic lethality.

A novel prognostic model of breast cancer based on cuproptosis-related lncRNAs.

OBJECTIVE: Breast cancer (BC) is a deadly form of malignancy responsible for the death of a large number of women every year. Cuproptosis is a newly discovered form of cell death that may have implications for the prognosis of BC. Long non-coding RNAs (lncRNAs) have been shown to be involved in the progression and development of BC. Here within, a novel model capable of predicting the prognosis of patients with BC was established based on cuproptosis-related lncRNAs. METHODS: Data of breast cancer patients was downloaded, including clinical information from The Cancer Genome Atlas (TCGA) database and lncRNAs related to cuproptosis were isolated. In total, nine lncRNAs related to copper death were obtained by Cox regression model based on Least Absolute Shrinkage and Selector Operation (LASSO) algorithm for model construction. The model was verified by overall survival (OS), progression-free survival (PFS) and receiver operating characteristic (ROC) curve. The differences in immune function, tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) between patients with different risk scores were analyzed. RESULTS: Based on cuproptosis-related lncRNAs, a prognostic model for predicting BC was constructed. Each patient was assigned a risk score based on our model formula. We found that patients with higher risk scores had significantly lower OS and PFS, increased TMB, and higher sensitivity to immunotherapy. CONCLUSIONS: The model established in this study based on cuproptosis-related lncRNAs may be capable of improving the OS of patients with BC.

Unlocking a Dual-Channel Pathway in CO2 Hydrogenation to Methanol over Single-Site Zirconium on Amorphous Silica.

Converting CO2 into methanol on a large scale is of great significance in the sustainable methanol economy. Zirconia species are considered to be an essential support in Cu-based catalysts due to their excellent properties for CO2 adsorption and activation. However, the evolution of Zr species during the reaction and the effect of their structure on the reaction pathways remain unclear. Herein, single-site Zr species in an amorphous SiO2 matrix are created by enhancing the Zr-Si interaction in Cu/ZrO2 -SiO2 catalysts. In situ X-ray absorption spectroscopy (XAS) reveals that the coordination environment of single-site Zr is sensitive to the atmosphere and reaction conditions. We demonstrate that the CO2 adsorption occurs preferably on the interface of Cu and single-site Zr rather than on ZrO2 nanoparticles. Methanol synthesis in reverse water-gas-shift (RWGS)+CO-hydro pathway is verified only over single-dispersed Zr sites, whereas the ordinary formate pathway occurs on ZrO2 nanoparticles. Thus, it expands a non-competitive parallel pathway as a supplement to the dominant formate pathway, resulting in the enhancement of Cu activity sixfold and twofold based on Cu/SiO2 and Cu/ZrO2 catalysts, respectively. The establishment of this dual-channel pathway by single-site Zr species in this work opens new horizons for understanding the role of atomically dispersed oxides in catalysis science.

OIMHS: An Optical Coherence Tomography Image Dataset Based on Macular Hole Manual Segmentation.

Macular holes, one of the most common macular diseases, require timely treatment. The morphological changes on optical coherence tomography (OCT) images provided an opportunity for direct observation of the disease, and accurate segmentation was needed to identify and quantify the lesions. Developments of such algorithms had been obstructed by a lack of high-quality datasets (the OCT images and the corresponding gold standard macular hole segmentation labels), especially for supervised learning-based segmentation algorithms. In such context, we established a large OCT image macular hole segmentation (OIMHS) dataset with 3859 B-scan images of 119 patients, and each image provided four segmentation labels: retina, macular hole, intraretinal cysts, and choroid. This dataset offered an excellent opportunity for investigating the accuracy and reliability of different segmentation algorithms for macular holes and a new research insight into the further development of clinical research for macular diseases, which included the retina, lesions, and choroid in quantitative analyses.

Visual mapping of global nanoplastics research progresses and hotspots: a scientometric assessment analysis.

Environmental plastic wastes are continuously degraded into microplastics (MPs) and nanoplastics (NPs); the latter are more potentially harmful to organisms and human health as their smaller size and higher surface-to-volume ratio. Previous reviews on NPs mainly concentrate on specific aspects, such as sources, environmental behavior, and toxicological effects, but few focused on NPs-related scientific publications from a global point of view. Therefore, this bibliometric study aims to summarize the research themes and trends on NPs and also propose potential directions for future inquiry. Related papers were downloaded from the Web of Science Core Collection database on NPs published from 2008 to 2021, and then retrieved information was analyzed using CiteSpace 6.1 R2 and VOSviewer (version 1.6.). Research on NPs mainly involved environmental behaviors, toxicological effects, identification and extraction of NPs, whereas aquatic environments, especially marine systems, attracted more attentions from these scientists compare to terrestrial environments. Furthermore, the adsorption behavior of pollutants by NPs and the toxicological effects of organisms exposed to NPs are the present hotspots, while the regulation of humic acid (HA) on NPs behaviors and the environmental behavior of NPs in freshwater, like rivers and lakes, are the frontier areas of research. This study also explored the possible opportunities and challenges that may be faced in NPs research, which provide a valuable summary and outlook for ongoing NPs-related research, which may be of intrigue and noteworthiness for relevant researchers.

Characteristics of the Peripapillary Structure and Vasculature in Patients With Myopic Anisometropia.

Purpose: To evaluate the interocular differences of the peripapillary structural and vascular parameters and that of association with axial length (AL) in participants with myopic anisometropia using swept-source optical coherence tomography. Methods: This prospective cross-sectional study included 90 eyes of 45 participants. Each participant's eyes were divided into the more and less myopic eye respectively according to spherical equivalent. The ß- and γ-parapapillary atrophy (PPA) areas, Bruch's membrane opening distance, border length, and border tissue angle were measured manually. Peripapillary choroidal vascularity index and choroidal thickness (CT) values in superior, nasal, inferior, and temporal were calculated using a custom-built algorithm based on MATLAB. Results: The interocular difference in AL and spherical equivalent was 0.62 ± 0.26 mm and -1.50 (-2.13, -1.25) diopters (D), respectively. The interocular difference in spherical equivalent was highly correlated with that of the AL. The ß- and γ-PPA areas were significantly greater in more myopic eyes. The mean and inferior peripapillary choroidal vascularity index and all regions of peripapillary CT were significantly lower in the more myopic eyes. The interocular difference in AL was significantly positively correlated with the interocular differences in γ-PPA area and border length and negatively correlated with the interocular differences in temporal choroidal vascularity index and mean, inferior, and temporal peripapillary CT. There was an independent correlation between the interocular differences in AL and the interocular differences in γ-PPA area, inferior, and temporal peripapillary CT. Conclusions: Significant differences between both groups were detected in most peripapillary parameters, especially in peripapillary CT. The γ-PPA area, border length, and peripapillary CT were significantly correlated with the elongation of AL. Translational Relevance: The current study characterized and analyzed the peripapillary parameters in myopic anisometropia, which helped to monitor myopic progression.

Unleashing the Power of Synthetic Lethality: Augmenting Treatment Efficacy through Synergistic Integration with Chemotherapy Drugs.

Cancer is the second leading cause of death in the world, and chemotherapy is one of the main methods of cancer treatment. However, the resistance of cancer cells to chemotherapeutic drugs has always been the main reason affecting the therapeutic effect. Synthetic lethality has emerged as a promising approach to augment the sensitivity of cancer cells to chemotherapy agents. Synthetic lethality (SL) refers to the specific cell death resulting from the simultaneous mutation of two non-lethal genes, which individually allow cell survival. This comprehensive review explores the classification of SL, screening methods, and research advancements in SL inhibitors, including Poly (ADP-ribose) polymerase (PARP) inhibitors, Ataxia telangiectasia and Rad3-related (ATR) inhibitors, WEE1 G2 checkpoint kinase (WEE1) inhibitors, and protein arginine methyltransferase 5 (PRMT5) inhibitors. Emphasizing their combined use with chemotherapy drugs, we aim to unveil more effective treatment strategies for cancer patients.

Biomethane is produced by acetate cleavage, not direct interspecies electron transfer: genome-centric view and carbon isotope.

Understanding the source of methane (CH4) is of great significance for improving the anaerobic fermentation efficiency in bioengineering, and for mitigating the emission potential of natural ecosystems. Microbes involved in the process named direct interspecies electron transfer coupling with CO2 reduction, i.e., electrons released from electroactive bacteria to reduce CO2 into CH4, have attracted considerable attention for wastewater treatment in the past decade. However, how the synergistic effect of microbiota contributes to this anaerobic carbon metabolism accompanied by CH4 production still remains poorly understood, especial for wastewater with antibiotic exposure. Results show that enhancing lower-abundant acetoclastic methanogens and acetogenic bacteria, rather than electroactive bacteria, contributed to CH4 production, based on a metagenome-assembled genomes network analysis. Natural and artificial isotope tracing of CH4 further confirmed that CH4 mainly originated from acetoclastic methanogenesis. These findings reveal the contribution of direct acetate cleavage (acetoclastic methanogenesis) and provide insightsfor further regulation of methanogenic strategies.

Homologous genes shared between probiotics and pathogens affect the adhesion of probiotics and exclusion of pathogens in the gut mucus of shrimp.

Clarifying mechanisms underlying the selective adhesion of probiotics and competitive exclusion of pathogens in the intestine is a central theme for shrimp health. Under experimental manipulation of probiotic strain (i.e., Lactiplantibacillus plantarum HC-2) adhesion to the shrimp mucus, this study tested the core hypothesis that homologous genes shared between probiotic and pathogen would affect the adhesion of probiotics and exclusion of pathogens by regulating the membrane proteins of probiotics. Results indicated that the reduction of FtsH protease activity, which significantly correlated with the increase of membrane proteins, could increase the adhesion ability of L. plantarum HC-2 to the mucus. These membrane proteins mainly involved in transport (glycine betaine/carnitine/choline ABC transporter choS, ABC transporter, ATP synthase subunit a atpB, amino acid permease) and regulation of cellular processes (histidine kinase). The genes encoding the membrane proteins were significantly (p < 0.05) up-regulated except those encoding ABC transporters and histidine kinases in L. plantarum HC-2 when co-cultured with Vibrio parahaemolyticus E1, indicating that these genes could help L. plantarum HC-2 to competitively exclude pathogens. Moreover, an arsenal of genes predicted to be involved in carbohydrate metabolism and bacteria-host interactions were identified in L. plantarum HC-2, indicating a clear strain adaption to host's gastrointestinal tract. This study advances our mechanistic understanding of the selective adhesion of probiotics and competitive exclusion of pathogens in the intestine, and has important implications for screening and applying new probiotics for maintaining gut stability and host health.

Neurometabolic and structural alterations of medial septum and hippocampal CA1 in a model of post-operative sleep fragmentation in aged mice: a study combining 1H-MRS and DTI.

Post-operative sleep disturbance is a common feature of elderly surgical patients, and sleep fragmentation (SF) is closely related to post-operative cognitive dysfunction (POCD). SF is characterized by sleep interruption, increased number of awakenings and sleep structure destruction, similar to obstructive sleep apnea (OSA). Research shows that sleep interruption can change neurotransmitter metabolism and structural connectivity in sleep and cognitive brain regions, of which the medial septum and hippocampal CA1 are key brain regions connecting sleep and cognitive processes. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method for the evaluation of neurometabolic abnormalities. Diffusion tensor imaging (DTI) realizes the observation of structural integrity and connectivity of brain regions of interest in vivo. However, it is unclear whether post-operative SF induces harmful changes in neurotransmitters and structures of the key brain regions and their contribution to POCD. In this study, we evaluated the effects of post-operative SF on neurotransmitter metabolism and structural integrity of medial septum and hippocampal CA1 in aged C57BL/6J male mice. The animals received a 24-h SF procedure after isoflurane anesthesia and right carotid artery exposure surgery. 1H-MRS results showed after post-operative SF, the glutamate (Glu)/creatine (Cr) and glutamate + glutamine (Glx)/Cr ratios increased in the medial septum and hippocampal CA1, while the NAA/Cr ratio decreased in the hippocampal CA1. DTI results showed post-operative SF decreased the fractional anisotropy (FA) of white matter fibers in the hippocampal CA1, while the medial septum was not affected. Moreover, post-operative SF aggravated subsequent Y-maze and novel object recognition performances accompanied by abnormal enhancement of glutamatergic metabolism signal. This study suggests that 24-h SF induces hyperglutamate metabolism level and microstructural connectivity damage in sleep and cognitive brain regions in aged mice, which may be involved in the pathophysiological process of POCD.

Realizing room temperature catalytic hydrogenation of sodium phenoxide by Ru/TiO2 for hydrogen storage.

Sodium phenoxide is a potentially promising hydrogen storage material due to its high hydrogen capacity and enhanced thermodynamic properties. Nevertheless, efficient catalysts are still lacking due to the high kinetic barrier for the reversible hydrogen uptake and release of sodium phenoxide. In the current work, a comparative study on the catalytic hydrogenation of sodium phenoxide was conducted. To our delight, a simple yet effective ruthenium-based catalyst was identified to respond aggressively to hydrogen in the solid-state hydrogenation of sodium phenoxide even at room temperature. The activity was enhanced by 6 fold with the as-synthesized 5.0% Ru/TiO2 catalyst as compared to that with commercial 5.0% Ru/Al2O3, respectively, under the same conditions.

The effect comparison of ILM flap and traditional ILM peeling in iMH.

Purpose: To compare the changes in anatomical structure and visual function after idiopathic macular hole (iMH) treatment with internal limiting membrane (ILM) peeling and inverted ILM flap and determine the value of the inverted ILM flap for the treatment of iMH. Methods: Forty-nine patients with iMH (49 eyes) were included in this study and followed up for 1 year (12 months) after treatment with inverted ILM flap and ILM peeling respectively. The main foveal parameters assessed included the preoperative minimum diameter (MD), intraoperative residual fragments, and postoperative ELM reconstruction. Visual function was assessed using best-corrected visual acuity. Results: The hole closure rate was 100% for 49 patients; 15 patients were treated with the inverted ILM flap, and 34 patients underwent ILM peeling. There were no differences between the postoperative best-corrected visual acuities and the rates of ELM reconstruction for the flap and peeling groups with different MDs. In the flap group, ELM reconstruction was associated with the preoperative MD, presence of an ILM flap, and hyperreflective changes in the inner retina 1 month after surgery. In the peeling group, ELM reconstruction was associated with the preoperative MD, intraoperative residual fragments at the hole edge, and hyperreflective changes in the inner retina. Conclusion: The inverted ILM flap and the ILM Peeling were both able to obtain high closure rate. However, the inverted ILM flap showed no obvious advantages related to anatomical morphology and visual function over ILM peeling.

A comprehensive pan-cancer analysis reveals cancer-associated robust isomiR expression landscapes in miRNA arm switching.

MicroRNAs (miRNAs), important regulators of gene expression, play critical roles in various biological processes and tumorigenesis. To reveal the potential relationships between multiple isomiRs and arm switching, we performed a comprehensive pan-cancer analysis to discuss their roles in tumorigenesis and cancer prognosis. Our results showed that many miR-#-5p and miR-#-3p pairs from the two arms of pre-miRNA may have abundant expression levels, and they are often involved in distinct functional regulatory networks by targeting different mRNAs, although they may also interact with common targets. The two arms may show diverse isomiR expression landscapes, and their expression ratio might vary, mainly depending on tissue type. Dominantly expressed isomiRs can be used to determine distinct cancer subtypes that are associated with clinical outcome, indicating that they may be potential prognostic biomarkers. Our findings indicate robust and flexible isomiR expression landscapes that will enrich the study of miRNAs/isomiRs and aid in revealing the potential roles of multiple isomiRs yielded by arm switching in tumorigenesis.

GBCdb: RNA expression landscapes and ncRNA-mRNA interactions in gallbladder carcinoma.

Gallbladder carcinoma (GBC), an aggressive malignant tumor of the biliary system, is characterized by high cellular heterogeneity and poor prognosis. Fewer data have been reported in GBC than other common cancer types. Multi-omics data will contribute to the understanding of the molecular mechanisms of cancer, cancer diagnosis and prognosis. Herein, to provide better understanding of the molecular events in GBC pathogenesis, we developed GBCdb ( http://tmliang.cn/gbc/ ), a user-friendly interface for the query and browsing of GBC-associated genes and RNA interaction networks using published multi-omics data, which also included experimentally supported data from different molecular levels. GBCdb will help to elucidate the potential biological roles of different RNAs and allow for the exploration of RNA interactions in GBC. These resources will provide an opportunity for unraveling the potential molecular features of Gallbladder carcinoma.

Prediction of protein-coding small ORFs in multi-species using integrated sequence-derived features and the random forest model.

Proteins encoded by small open reading frames (sORFs) can serve as functional elements playing important roles in vivo. Such sORFs also constitute the potential pool for facilitating the de novo gene birth, driving evolutionary innovation and species diversity. Therefore, their theoretical and experimental identification has become a critical issue. Herein, we proposed a protein-coding sORFs prediction method merely based on integrative sequence-derived features. Our prediction performance is better or comparable compared with other nine prevalent methods, which shows that our method can provide a relatively reliable research tool for the prediction of protein-coding sORFs. Our method allows users to estimate the potential expression of a queried sORF, which has been demonstrated by the correlation analysis between our possibility estimation and codon adaption index (CAI). Based on the features that we used, we demonstrated that the sequence features of the protein-coding sORFs in the two domains have significant differences implying that it might be a relatively hard task in terms of cross-domain prediction, hence domain-specific models were developed, which allowed users to predict protein-coding sORFs both in eukaryotes and prokaryotes. Finally, a web-server was developed and provided to boost and facilitate the study of the related field, which is freely available at http://guolab.whu.edu.cn/codingCapacity/index.html.

Uptake, distribution, and elimination of selenite in earthworm Eisenia fetida at sublethal concentrations based on toxicokinetic model.

Natural and anthropogenic causes have promoted the rapid increase in environmental selenium (Se) levels, and the complex Se metabolism and dynamic in organisms make it challenging to evaluate the toxicity and ecological risks. In this study, the kinetics of selenite in earthworm Eisenia fetida were investigated based on toxicokinetic (TK) model (uptake-elimination phases: 14-14 days). The results showed the highest sub-tissue Se concentrations in pre-clitellum (PC), post-clitellum (PoC) parts, and total earthworms were 95.71, 70.40, and 79.94 mg/kg, respectively, which indicates the distinctive Se uptake capacities of E. fetida. Se kinetic rates in PCs were faster than that of the total E. fetida for both uptake (Kus = 0.30-0.80 mg/kg/day) and elimination phases (Kee = 0.024-0.056 mg/kg/day). Longer half-life times (LT1/2) were observed in the total earthworms (17.85-47.15 d) than PCs (12.28-29.22 d), while non-significant difference was found for the kinetic Se bioaccumulation factor (BAFk) in PC and total earthworms (12-19), which demonstrates that Se can be efficiently bioaccumulated and eliminated in earthworm PC part. Besides, the significant increase Se concentration in PoC with rapid elimination in PC also illustrates that earthworms can alleviate the Se stress by the transformation strategy of Se from the head to tail tissues. In conclusion, the investigation of Se kinetic accumulation and elimination characteristics in this study is helpful for understanding the metabolism and detoxification processes of Se in earthworms, and also providing a theoretical basis for further Se risk assessment using TK model.