AOPPs induces EMT and fibrosis by activating oxidative stress through ERK/p38 MAPK signaling pathway in endometriosis.

Epithelial-mesenchymal transition (EMT) is known to play a crucial role in the development of endometriosis (EMs). However, the exact mechanisms involved in EMT regulation in EMs are not well understood. In this study, we performed comprehensive research using clinical samples, single-cell sequencing, and in vivo/in vitro models to investigate the effects of advanced oxidation protein products (AOPPs) on EMT and the underlying mechanisms in EMs. Combining bioinformatics analysis with experimental validation, our results show that AOPPs accumulate in EMs tissues, and their levels positively correlate with the expression of EMT markers in fibrotic lesions of EMs patients. Stimulation with AOPPs leads to a concentration- and time-dependent alteration of EMT markers expression in both in vitro and in vivo models. These effects are mainly mediated by the generation of reactive oxygen species and nitrite, along with the activation of the ERK and P38 signaling pathways. In chronic administration studies using normal rats, AOPPs induce EMT and enhance collagen deposition. These findings significantly contribute to our understanding of the molecular mechanisms of EMs and provide a foundation for future research and therapeutic development in this field.

Response of soil-microbe-extracellular enzyme stoichiometric characteristics to nitrogen deposition in a Pinus yunnanensis forest in central Yunnan Province, Southwest China.

To understand the effects of nitrogen deposition on element cycling and nutrient limitation status in forest ecosystems, we examined the effects of nitrogen deposition on the stoichiometric characteristics of forest soil-microbial-extracellular enzymes in Pinus yunnanensis forest. We conducted a field experiment with control (CK, 0 g N·m-2·a-1), low nitrogen (LN, 10 g N·m-2·a-1), medium nitrogen (MN, 20 g N·m-2·a-1) and high nitrogen (HN, 25 g N·m-2·a-1) since 2019. We collected soil samples (0-5 cm, 5-10 cm and 10-20 cm) at September 2022, and measured the contents of soil organic, total nitrogen, total phosphorus, microbial biomass carbon, nitrogen and phosphorus (MBC, MBN, MBP) and the activities of C, N, and P acquisition enzymes. The results showed that nitrogen deposition significantly reduced soil organic content, C:N and C:P by 6.9%-29.8%, 7.6%-45.2% and 6.5%-28.6%, and increased soil total N content and N:P by 10.0%-45.0% and 19.0%-46.0%, respectively. Nitrogen addition did not affect soil total P content. Except for soil C:N and C:P, soil nutrient content and stoichiometric ratio were highest in 0-5 cm soil layer. MN and HN treatments significantly decreased MBN by 11.0%-12.7%. MBC, MBP, and their stoichiometry did not change significantly under nitrogen deposition. Soil microbial nutrient content in 0-5 cm soil layer was significantly higher than that in other soil layers. Nitrogen deposition significantly decreased the activities of cellobiose hydrolase and leucine aminopeptidase (decreased by 14.5%-16.2% and 48.7%-66.3%). HN treatment promoted ß-1,4-glucosidase activity (increased by 68.0%), but inhibited soil enzyme stoichiometric carbon to nitrogen ratio and nitrogen to phosphorus ratio (decreased by 95.4% and 88.4%). LN and MN treatment promoted ß-1,4-N-acetylglucosaminidase activity (increased by 68.3%-116.6%), but inhibited enzyme stoichiometric carbon to phosphorus ratio (decreased by 14.9%-29.4%). Alkaline phosphatase activity had no significant change. Soil enzyme activities were significantly decreased with increasing soil depth. Soil total N and total P and microbial nutrients were negatively correlated with vector angle (representing microbial nitrogen or phosphorus limitation), while vector length (representing microbial carbon limitation) was consistently significantly positively correlated with vector angle, suggesting the synergistic promotion between microbial carbon limitation and phosphorus limitation. Nitrogen deposition gradually shifted to phosphorus limitation while alleviating microbial nitrogen limitation in P. yunnanensis forest. In addition, microbial activities in this region was limited by C availability, and the relationship between microbial C and P limitation was proportional.

Cerebrospinal fluid-induced stable and reproducible SERS sensing for various meningitis discrimination assisted with machine learning.

Cerebrospinal fluid (CSF)-based pathogen or biochemical testing is the standard approach for clinical diagnosis of various meningitis. However, misdiagnosis and missed diagnosis always occur due to the shortages of unusual clinical manifestations and time-consuming shortcomings, low sensitivity, and poor specificity. Here, for the first time, we propose a simple and reliable CSF-induced SERS platform assisted with machine learning (ML) for the diagnosis and identification of various meningitis. Stable and reproducible SERS spectra are obtained within 30 s by simply mixing the colloidal silver nanoparticles (Ag NPs) with CSF sample, and the relative standard deviation of signal intensity is achieved as low as 2.1%. In contrast to conventional salt agglomeration agent-induced irreversible aggregation for achieving Raman enhancement, a homogeneous and dispersed colloidal solution is observed within 1 h for the mixture of Ag NPs/CSF (containing 110-140 mM chloride), contributing to excellent SERS stability and reproducibility. In addition, the interaction processes and potential enhancement mechanisms of different Ag colloids-based SERS detection induced by CSF sample or conventional NaCl agglomeration agents are studied in detail through in-situ UV-vis absorption spectra, SERS analysis, SEM and optical imaging. Finally, an ML-assisted meningitis classification model is established based on the spectral feature fusion of characteristic peaks and baseline. By using an optimized KNN algorithm, the classification accuracy of autoimmune encephalitis, novel cryptococcal meningitis, viral meningitis, or tuberculous meningitis could be reached 99%, while an accuracy value of 68.74% is achieved for baseline-corrected spectral data. The CSF-induced SERS detection has the potential to provide a new type of liquid biopsy approach in the fields of diagnosis and early detection of various cerebral ailments.

The interplay between persistent pathogen infections with tumor microenvironment and immunotherapy in cancer.

BACKGROUND: Chronic infections by pathogenic microorganisms play a significant role in cancer development, disrupting the body's immune system and microenvironment. This interference impairs the body's ability to eliminate these microorganisms promptly, allowing them to persist by evading immune defenses. AIMS: This study aimed to explore how chronic pathogenic infections influence the immune microenvironment, impacting tumorigenesis, cancer progression, and treatment strategies. Additionally, it seeks to investigate the effects of these infections on specific immune checkpoints and identify potential targets for immunotherapy. METHODS: We conducted searches, readings, and detailed analyses of key terms in databases like PubMed and Web of Science to evaluate the impact of chronic infections by pathogenic microorganisms on the immune microenvironment. RESULTS: Our analysis demonstrates a significant association between persistent chronic infections by pathogenic microorganisms and tumorigenesis. Notable impacts on the immune microenvironment include changes in immune cell function and the regulation of immune checkpoints, offering insights into potential targets for cancer immunotherapy. DISCUSSION: This study highlights the complex relationship between chronic infections and cancer development, presenting new opportunities for cancer immunotherapy by understanding their effects on the immune microenvironment. The influence of these infections on immune checkpoints emphasizes the crucial role of the immune system in cancer treatment. CONCLUSION: Chronic infections by pathogenic microorganisms greatly affect the immune microenvironment, tumorigenesis, and cancer treatment. Unraveling the underlying mechanisms can unveil potential targets for immunotherapy, improving our comprehension of the immune response to cancer and potentially leading to more effective cancer treatments in the future.

Rapid achievement of partial nitrification process by adopting the combined strategy of anoxic starvation and free ammonia inhibition.

Partial nitrification (PN) is a prerequisite step for the short-cut nitrogen removal process, which is crucial to provide stable nitrite accumulation for subsequent units. The present study innovatively proposed a new strategy for the rapid establishment of PN by adopting short-term anoxic starvation combined with high free ammonia inhibition. The sludge obtained from the secondary sedimentation tank of a municipal wastewater treatment plant was starved for 7 days under anoxic conditions, and then wastewater with high ammonia nitrogen (400 mg L-1) was introduced. Within 17 days, stable nitrite accumulation was achieved in the sequencing batch reactor, and the nitrite accumulation rate reached more than 95.0%. The activity of ammonia monooxygenase enzyme increased from 0.0364 ± 0.0074 to 0.1275 ± 0.0021 µg NO2--N·mg-1 protein min-1, while that of hydroxylamine oxidoreductase enzyme increased from 1.5350 ± 0.0208 to 6.3852 ± 0.0400 EU g-1 SS. The relative abundance of Nitrosomonas increased from 0.10% to 25.90%, while that of Nitrospira consistently remained below 0.04%. And the relative abundance of short-cut denitrifying bacteria, including Truepera, OLB8, and OLB13 all increased. The results proved that the short-term anoxic starvation combined with high free ammonia inhibition was an effective strategy for rapid establishment of PN.

Efficient solar-driven: Photothermal catalytic reduction of atmospheric CO2 at the gas-solid interface by CuTCPP/MXene/TiO2.

Directly capturing atmospheric CO2 and converting it into valuable fuel through photothermal synergy is an effective way to mitigate the greenhouse effect. This study developed a gas-solid interface photothermal catalytic system for atmospheric CO2 reduction, utilizing the innovative photothermal catalyst (Cu porphyrin) CuTCPP/MXene/TiO2. The catalyst demonstrated a photothermal catalytic performance of 124 µmol·g-1·h-1 for CO and 106 µmol·g-1·h-1 for CH4, significantly outperforming individual components. Density functional theory (DFT) results indicate that the enhanced catalytic performance is attributed to the internal electric field between the components, which significantly enhances carrier utilization. The introduction of CuTCPP reduces free energy of the photothermal catalytic reaction. Additionally, the local surface plasmon resonance (LSPR) effect and high-speed electron transfer properties of MXene further boost the catalytic reaction rate. This well-designed catalyst and catalytic system offer a simple method for capturing atmospheric CO2 and converting it in-situ through photothermal catalysis.

Integrated RNA sequencing and biochemical studies reveal endoplasmic reticulum stress and autophagy dysregulation contribute to Tri (2-Ethylhexyl) phosphate (TEHP)-induced cell injury in Sertoli cells.

Tri (2-Ethylhexyl) phosphate (TEHP), widely used as a fire retardant and plasticizer, has been commonly found in the environment. Its potential health-related risks, especially reproductive toxicity, have aroused concern. However, the potential cellular mechanisms remain unexplored. In this study, we aimed to investigate the molecular mechanisms underlying TEHP-caused cell damage in Sertoli cells, which play a crucial role in supporting spermatogenesis. Our findings indicate that TEHP induces apoptosis in 15P-1 mouse Sertoli cells. Subsequently, we conducted RNA sequencing analyses, which suggested that ER stress, autophagy, and MAPK-related pathways may participate in TEHP-induced cytotoxicity. Furthermore, we demonstrated that TEHP triggers ER stress, activates p38 MAPK, and inhibits autophagy flux. Then, we showed that the inhibition of ER stress or p38 MAPK activation attenuates TEHP-induced apoptosis, while the inhibition of autophagy flux is responsible for TEHP-induced apoptosis. These results collectively reveal that TEHP induces ER stress, activates p38, and inhibits autophagy flux, ultimately leading to apoptosis in Sertoli cells. These shed light on the molecular mechanisms underlying TEHP-associated testicular toxicity.

Discovery and evolution of berberine analogues as anti-Helicobacter pylori agents with multi-target mechanisms.

Thirty protoberberine derivatives, of which twenty five were new, were synthesized and evaluated for their anti-Helicobacter pylori (HP) activities, taking 2,3,10-trimethoxy-9-p-methylbenzylaminoprotopalmatine chloride 1 as the lead. Among them, berberine (BBR) derivative 7c displayed the highest potency against six tested metronidazole (MTZ)-resistant strains and two tested MTZ-susceptible strains with the MIC values of 0.4-1.6 µg/mL with favorable druglike profiles including low toxicity and high stabilities in plasma and artificial gastric fluid. Mechanistic study revealed that 7c might target HP urease with IC50 value of 0.27 µg/mL against Jack bean urease. Furthermore, 7c might change the permeability of the bacterial membrane and direct interact with HP DNA, which also contribute to its bactericidal activity. Therefore, BBR derivatives constituted a new family of anti-HP candidates, with the advantage of good safety profile and multi-target mechanisms, and are worthy for further investigation.

Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.

PD-L1 is overexpressed on the surface of tumor cells and binds to PD-1, resulting in tumor immune escape. Therapeutic strategies to target the PD-1/PD-L1 pathway involve blocking the binding. Immune checkpoint inhibitors have limited efficacy against tumors because PD-L1 is also present in the cytoplasm. PD-L1 of post-translational modifications (PTMs) have uncovered numerous mechanisms contributing to carcinogenesis and have identified potential therapeutic targets. Therefore, small molecule inhibitors can block crucial carcinogenic signaling pathways, making them a potential therapeutic option. To better develop small molecule inhibitors, we have summarized the PTMs of PD-L1. This review discusses the regulatory mechanisms of small molecule inhibitors in carcinogenesis and explore their potential applications, proposing a novel approach for tumor immunotherapy based on PD-L1 PTM.

[Box: see text].

Klotho accelerates the progression of polycystic ovary syndrome through promoting granulosa cell apoptosis and inflammation†.

The morbidity of polycystic ovary syndrome (PCOS) is in highly increasing rate nowadays. PCOS not only affects the fertility in women, but also threatens the health of whole life. Hence, to find the prognostic risk factors is of great value. However, the effective predictors in clinical practice of PCOS are still in blackness. In this study, we found Klotho (KL) was increased in follicular fluid (FF) and primary luteinized granulosa cells (GCs) from PCOS patients with hyperandrogenism. Furthermore, we found follicular KL was negatively correlated with numbers of mature oocytes, and positively correlated with serum testosterone, LH, and LH/FSH levels menstrual cycle and number of total antral follicles in PCOS patients. In primary luteinized GCs, the increased KL was accompanied with upregulation of cell apoptosis and inflammation-related genes. In ovaries of PCOS mice and cultured human KGN cell line, KL was up-regulated and accompanied by apoptosis, inflammation, and mitochondrial dysfunction. Therefore, our findings suggest new mechanisms for granulosa cell injury and revealed to target inhibit KL maybe a new therapeutic strategy for treatment of PCOS.

Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing.

The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern. Microcystin-leucine arginine (MC-LR) is a well-established toxin produced by cyanobacterial blooms, which is widely distributed in eutrophic waters. MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals. However, the underlying mechanisms of MC-LR-induced liver toxicity are unclear. Herein, we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice. We established the first single-cell atlas of mouse livers in response to MC-LR. Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treated with MC-LR are highly heterogeneous. Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3, which potentially contributed to hepatocyte apoptosis in response to MC-LR. Moreover, MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes. Furthermore, the MC-LR increased several subtypes of CD8+ T cells with highly expressed multiple cytokines and chemokines. Overall, apart from directly inducing hepatocytes apoptosis, MC-LR activated proinflammatory Kupffer cell and CD8+ T cells, and their interaction may constitute a hostile microenvironment that contributes to liver injury. Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.

Activation of cGAS/STING Drives Inflammation and Cellular Senescence of Macrophages in Ovarian Endometrioma Induced by Endometriotic Cyst Fluid.

Ovarian endometrioma (OE) is a common gynecological condition characterized by the formation of "chocolate cysts". Recent research indicates that the cyst fluid acts as a "toxic environment" for the ovary and plays a significant role in the development of OE, with macrophages being pivotal. However, the specific molecular and cellular mechanisms of it are not fully understood. In this study, clinical samples are integrated, single-cell sequencing, in vivo and in vitro experimental models to comprehensively investigate the effects of OE fluid on ovarian function and the mechanisms of it. Combined with bioinformatics analysis and experimental validation, the findings demonstrate that OE fluid can cause ovarian function decline, which associated with inflammatory response, and mitochondrial dysfunction and cellular senescence, while activating the cGAS/STING signaling pathway. As a STING inhibitor, H-151 effectively alleviates ovarian dysfunction, inflammatory state and cell apoptosis induced by OE fluid. Furthermore, it is also discovered that H-151 can inhibit OE fluid-induced mitochondrial dysfunction and cellular senescence. These findings provide important theoretical and experimental foundations for further research and development of STING inhibitors as potential drugs for treating ovarian dysfunction.

Discovery and biological evaluation of biaryl acetamide derivatives as selective and in vivo active sphingosine kinase-2 inhibitors.

Sphingosine kinase 2 (SphK2) has emerged as a promising target for cancer therapy due to its critical role in tumor growth. However, the lack of potent and selective inhibitors has hindered its clinical application. Herein, we report the design and synthesis of a series of novel SphK2 inhibitors, culminating in the identification of compound 12q as a highly selective and potent inhibitor of SphK2. Molecular dynamics simulations suggest that the incorporation of larger substitution groups facilitates a more effective occupation of the binding site, thereby stabilizing the complex. Compared to the widely used inhibitor ABC294640, compound 12q exhibits superior anti-proliferative activity against various cancer cells, inducing G2 phase arrest and apoptosis in liver cancer cells HepG2. Notably, 12q inhibited migration and colony formation in HepG2 and altered intracellular sphingolipid content. Moreover, intraperitoneal administration of 12q in mice resulted in decreased levels of S1P. 12q provides a valuable tool compound for exploring the therapeutic potential of targeting SphK2 in cancer.

The chromosome-level genomes of the herbal magnoliids Warburgia ugandensis and Saururus chinensis.

Warburgia ugandensis and Saururus chinensis are two of the most important medicinal plants in magnoliids and are widely utilized in traditional Kenya and Chinese medicine, respectively. The absence of higher-quality reference genomes has hindered research on the medicinal compound biosynthesis mechanisms of these plants. We report the chromosome-level genome assemblies of W. ugandensis and S. chinensis, and generated 1.13 Gb and 0.53 Gb genomes from 74 and 27 scaffolds, respectively, using BGI-DIPSEQ, Nanopore, and Hi-C sequencing. The scaffold N50 lengths were 82.97 Mb and 48.53 Mb, and the assemblies were anchored to 14 and 11 chromosomes of W. ugandensis and S. chinensis, respectively. In total, 24,739 and 20,561 genes were annotated, and 98.5% and 98% of the BUSCO genes were fully represented, respectively. The chromosome-level genomes of W. ugandensis and S. chinensis will be valuable resources for understanding the genetics of these medicinal plants, studying the evolution of magnoliids and angiosperms and conserving plant genetic resources.

Tris(2-ethylhexyl) phosphate induces cytotoxicity in TM3 Leydig cells by modulating autophagy and endoplasmic reticulum stress.

Tris (2-ethylhexyl) phosphate (TEHP) is a frequently used organophosphorus flame retardant with significant ecotoxicity and widespread human exposure. Recent research indicates that TEHP has reproductive toxicity. However, the precise cell mechanism is not enough understood. Here, by using testicular mesenchymal stromal TM3 cells as a model, we reveal that TEHP induces apoptosis. Then RNA sequencing analysis, immunofluorescence, and western blotting results show that THEP inhibits autophagy flux and enhances endoplasmic reticulum (ER) stress. Moreover, the activation of the ER stress is critical for TEHP-induced cell injury. Interestingly, TEHP-induced ER stress is contributed to autophagic flux inhibition. Furthermore, pharmacological inhibition of autophagy aggravates, and activation of autophagy attenuates TEHP-induced apoptosis. In summary, these findings indicate that TEHP triggers apoptosis in mouse TM3 cells through ER stress activation and autophagy flux inhibition, offering a new perspective on the mechanisms underlying TEHP-induced interstitial cytotoxicity in the mouse testis.

Gemfibrozil-Platinum(IV) Precursors for New Enhanced-Starvation and Chemotherapy In Vitro and In Vivo.

A brand-new enhanced starvation is put forward to trigger sensitized chemotherapy: blocking tumor-relation blood vessel formation and accelerating nutrient degradation and efflux. Following this concept, two cisplatin-like gemfibrozil-derived Pt(IV) prodrugs, GP and GPG, are synthesized. GP and GPG had nanomolar IC50 against A2780 cells and higher selectivity against normal cells than cisplatin. Bioactivity results confirmed that GP and GPG highly accumulated in cells and induced DNA damage, G2-phase arrest, and p53 expression. Besides, they could increase ROS and MDA levels and reduce mitochondrial membrane potential and Bcl-2 expression to promote cell apoptosis. In vivo, GP showed superior antitumor activity in A2780 tumor-bearing mice with no observable tissue damage. Mechanistic studies suggested that highly selective chemotherapy could be due to the new enhanced starvation effect: blocking vasculature formation via inhibiting the CYP2C8/EETs pathway and VEGFR2, NF-κB, and COX-2 expression and cholesterol efflux and degradation acceleration via increasing ABCA1 and PPARα.

Modulators for palmitoylation of proteins and small molecules.

As an essential form of lipid modification for maintaining vital cellular functions, palmitoylation plays an important role in in the regulation of various physiological processes, serving as a promising therapeutic target for diseases like cancer and neurological disorders. Ongoing research has revealed that palmitoylation can be categorized into three distinct types: N-palmitoylation, O-palmitoylation and S-palmitoylation. Herein this paper provides an overview of the regulatory enzymes involved in palmitoylation, including palmitoyltransferases and depalmitoylases, and discusses the currently available broad-spectrum and selective inhibitors for these enzymes.

S-scheme heterojunction Cu-porphyrin/TiO2 nanosheets with highly efficient photocatalytic reduction of CO2 in ambient air.

Directly capturing CO2 in ambient air and converting it into value-added fuels using photocatalysis is a potentially valuable technology. In this study, Cu-porphyrin (tetrakis-carboxyphenyl porphyrin copper, CuTCPP) was innovatively anchored on the surface of TiO2 (titanium dioxide) nanosheets to form an S-scheme heterojunction. Based on this, a photocatalytic reaction system for stably converting CO2 in ambient air into value-added fuels at the gas-solid interface was constructed without addition of sacrificial agents and alkaline liquids. Under the illumination of visible light and sunlight, the evolution rate of CO is 56 µmol·g-1·h-1 and 73 µmol·g-1·h-1, respectively, with a potential CO2 conversion rate of 35.8 % and 50.4 %. The enhanced of photocatalytic performance is attributed to the introduction of CuTCPP, which provides additional active sites, significantly improves capture capacity of CO2 and the utilization of electrons. Additionally, the formation of S-scheme heterojunction expands the redox range and improves the separation efficiency of photo-generated charges.

Blautia Coccoides is a Newly Identified Bacterium Increased by Leucine Deprivation and has a Novel Function in Improving Metabolic Disorders.

Gut microbiota is linked to human metabolic diseases. The previous work showed that leucine deprivation improved metabolic dysfunction, but whether leucine deprivation alters certain specific species of bacterium that brings these benefits remains unclear. Here, this work finds that leucine deprivation alters gut microbiota composition, which is sufficient and necessary for the metabolic improvements induced by leucine deprivation. Among all the affected bacteria, B. coccoides is markedly increased in the feces of leucine-deprived mice. Moreover, gavage with B. coccoides improves insulin sensitivity and reduces body fat in high-fat diet (HFD) mice, and singly colonization of B. coccoides increases insulin sensitivity in gnotobiotic mice. The effects of B. coccoides are mediated by metabolizing tryptophan into indole-3-acetic acid (I3AA) that activates the aryl hydrocarbon receptor (AhR) in the liver. Finally, this work reveals that reduced fecal B. coccoides and I3AA levels are associated with the clinical metabolic syndrome. These findings suggest that B. coccoides is a newly identified bacterium increased by leucine deprivation, which improves metabolic disorders via metabolizing tryptophan into I3AA.

Global trends in diabetic eye disease research from 2012 to 2021.

JOURNAL/nrgr/04.03/01300535-202410000-00032/figure1/v/2024-02-06T055622Z/r/image-tiff Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries--the United States, China, Japan, the United Kingdom, Spain, Germany, and France--by searching for all global diabetic eye disease journal articles in the Web of Science and PubMed databases, all global registered clinical trials in the ClinicalTrials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority (89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema (9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development (58.19%). Approximately half of the trials (49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic (40 out of 1830; 2.19%) and diabetic eye disease (3 out of 1830; 0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.