DDIT3 aggravates TMJOA cartilage degradation via Nrf2/HO-1/NLRP3-mediated autophagy.

OBJECTIVE: DNA damage-inducible transcript 3 (DDIT3), as a downstream transcription factor of endoplasmic reticulum (ER) stress, is reported to regulate chondrogenic differentiation under physiological and pathological state. However, the specific involvement of DDIT3 in the degradation of condylar cartilage of TMJOA is unclarified. DESIGN: The expression patterns of DDIT3 in condylar cartilage from monosodium iodoacetate (MIA)-induced TMJOA mice were examined to uncover the potential role of DDIT3 in TMJOA. The Ddit3 knockout (Ddit3-/-) mice and their wildtype littermates (Ddit3+/+) were used to clarify the effect of DDIT3 on cartilage degradation. Primary condylar chondrocytes and ATDC5 cells were applied to explore the mechanisms of DDIT3 on autophagy and extracellular matrix (ECM) degradation in chondrocytes. The autophagy inhibitor chloroquine (CQ) was used to determine the effect of DDIT3-inhibited autophagy in vivo. RESULTS: DDIT3 were highly expressed in condylar cartilage from TMJOA mice. Ddit3 knockout alleviated condylar cartilage degradation and subchondral bone loss, compared with their wildtype littermates. In vitro study demonstrated that DDIT3 exacerbated ECM degradation in chondrocytes induced by TNF-α through inhibiting autophagy. The intraperitoneal injection of CQ further confirmed that Ddit3 knockout alleviated cartilage degradation in TMJOA through activating autophagy in vivo. CONCLUSIONS: Our findings identified the crucial role of DDIT3-inhibited autophagy in condylar cartilage degradation during the development of TMJOA.

Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats.

Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114 days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.

Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.

Antidepressant effect of teriflunomide via oligodendrocyte protection in a mouse model.

Addressing the treatment of depression is crucial; nevertheless, the etiology and pathogenesis remain unelucidated. Therefore, this study investigated the effects of teriflunomide (TF) on corticosterone (CORT)-induced depression-like behaviors in mice. Notably, TF administration resulted in a substantial amelioration of anxiety and depression-like behaviors observed in CORT-treated mice. This was evidenced by behavioral assessments conducted via the sucrose preference test (SPT), open-field test (OFT), novelty-suppressed feeding test (NSFT), forced swimming test (FST), and tail suspension test (TST). The administration of CORT inflicts damage upon oligodendrocytes and neurons within the hippocampus. Our findings indicate that TF offers significant protective effects on oligodendrocytes, mitigating apoptosis both invivo and invitro. Additionally, TF was found to counteract the CORT-induced neuronal loss and synaptic damage, as demonstrated by an increase in Nissl-positive cells across hippocampal regions CA1, CA3, and the dentate gyrus (DG) alongside elevated levels of synapse-related proteins including PSD-95 and synaptophysin. Additionally, TF treatment facilitated a reduction in the levels of apoptosis-related proteins while simultaneously augmenting the levels of Bcl2. Our findings indicate that TF administration effectively mitigates CORT-induced depression-like behaviors and reverses damage to oligodendrocytes and neurons in the hippocampus, suggesting TF as a promising candidate for depression.

Evaluate the groundwater quality and human health risks for sustainable drinking and irrigation purposes in mountainous region of Chongqing, Southwest China.

Groundwater is crucial for agriculture and domestic consumption. This research investigated the hydrogeochemical properties and contaminant sources of groundwater within the mountainous terrain of northern Chongqing, with the objective of evaluating its appropriateness for irrigation and potable use. The hydrochemical type of the groundwater was HCO3 - Ca, dominated by silicate and calcite dissolutions. High NO3- (29.03% exceeds 10 mg/L) were attributed to the overuse of agricultural fertilizers. A comprehensive evaluation was conducted to determine the groundwater suitability for agricultural and potable uses. The results showed that groundwater in the southwestern region, particularly within the Yangtze River mainstem watershed, exhibited less suitability for irrigation owing to its lower mineralization, in contrast to the northeastern region near the Daning River watershed. But this trend is reversed for drinking purposes. Overall, the groundwater was appropriate for both drinking (93.55% were classified as excellent) and irrigation (70.98% were classified as low restriction) purposes in the study area. Deterministic and probabilistic noncarcinogenic health risk analyses centered on nitrate exposure revealed that infants (with 13.79% of samples >1) were at greater risk than children (8.58%), adult males (6.98%), and adult females (5.24%). This underscores the urgency to reduce nitrogen fertilizer usage and improve water management in the region. This research will provide guidance for the sustainable groundwater management in mountainous regions.

Metabolomics facilitates differential diagnosis in common inherited retinal degenerations by exploring their profiles of serum metabolites.

The diagnosis of inherited retinal degeneration (IRD) is challenging owing to its phenotypic and genotypic complexity. Clinical information is important before a genetic diagnosis is made. Metabolomics studies the entire picture of bioproducts, which are determined using genetic codes and biological reactions. We demonstrated that the common diagnoses of IRD, including retinitis pigmentosa (RP), cone-rod dystrophy (CRD), Stargardt disease (STGD), and Bietti's crystalline dystrophy (BCD), could be differentiated based on their metabolite heatmaps. Hundreds of metabolites were identified in the volcano plot compared with that of the control group in every IRD except BCD, considered as potential diagnosing markers. The phenotypes of CRD and STGD overlapped but could be differentiated by their metabolomic features with the assistance of a machine learning model with 100% accuracy. Moreover, EYS-, USH2A-associated, and other RP, sharing considerable similar characteristics in clinical findings, could also be diagnosed using the machine learning model with 85.7% accuracy. Further study would be needed to validate the results in an external dataset. By incorporating mass spectrometry and machine learning, a metabolomics-based diagnostic workflow for the clinical and molecular diagnoses of IRD was proposed in our study.

Mussel shell-derived pro-regenerative scaffold with conductive porous multi-scale-patterned microenvironment for spinal cord injury repair.

It is well-established that multi-scale porous scaffolds can guide axonal growth and facilitate functional restoration after spinal cord injury (SCI). In this study, we developed a novel mussel shell-inspired conductive scaffold for SCI repair with ease of production, multi-scale porous structure, high flexibility, and excellent biocompatibility. By utilizing the reducing properties of polydopamine, non-conductive graphene oxide (GO) was converted into conductive reduced graphene oxide (rGO) and crosslinkedin situwithin the mussel shells.In vitroexperiments confirmed that this multi-scale porous Shell@PDA-GO could serve as structural cues for enhancing cell adhesion, differentiation, and maturation, as well as promoting the electrophysiological development of hippocampal neurons. After transplantation at the injury sites, the Shell@PDA-GO provided a pro-regenerative microenvironment, promoting endogenous neurogenesis, triggering neovascularization, and relieving glial fibrosis formation. Interestingly, the Shell@PDA-GO could induce the release of endogenous growth factors (NGF and NT-3), resulting in the complete regeneration of nerve fibers at 12 weeks. This work provides a feasible strategy for the exploration of conductive multi-scale patterned scaffold to repair SCI.

Reference intervals for thyroid function from the fifth to seventh day of life in twin-pregnancy preterm neonates: an 8-year retrospective study.

PURPOSE: The immature and developing hypothalamic-pituitary-thyroid axis leads to different levels of thyroid function in twin neonates, including free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) levels. No reference intervals for twins have been established until now. To compensate for this lack, we collected data and established this standard across different gestational ages (GAs) and sexes. METHODS: A total of 273 pairs of neonates admitted to the NICU in Southeast China from 2015 to 2022 were included. Each pair was divided into Neonate A (relatively heavy birth weight (BW)) and Neonate B (relatively light BW). Their thyroid functions were analyzed to establish reference intervals and comparisons were made stratified by GA and sex. RESULTS: The FT3, FT4, and TSH reference intervals in twin neonates with a GA of 26-36 weeks were as follows: Neonate A and B: 3.59 ± 0.99 and 3.57 ± 1.00 pmol/L; Neonate A and B: 17.03 ± 5.16 and 16.77 ± 5.29 pmol/L; and Neonate A and B: 4.097 ± 3.688 and 4.674 ± 4.850 mlU/L, respectively. There were significant differences between serum FT3 and FT4 reference intervals and GA (p < 0.05). The serum FT3 and FT4 reference intervals for male neonates were lower than those for female neonates in the 29-32-week group (p < 0.05). CONCLUSION: This was the first study, to our knowledge, to establish reference intervals for thyroid function in twin neonates from the fifth to seventh day of life, which will be beneficial for the diagnosis and management of congenital hypothyroidism.

Function and mechanism exploring of icariin in schizophrenia through network pharmacology.

This study aims to explore the therapeutic effect and possible mechanisms of icariin in schizophrenia. SD rats were divided into five groups, a control group, a MK801-induced schizophrenia model group, and three icariin treatment groups, with twelve rats in each group. Morris water maze and open field were used to observe the spatial learning and memory ability of rats. Compared with the control group, rats in the MK801-induced model group showed an increase in stereotypic behavior score, distance of spontaneous activities, escape latency, malondialdehyde (MDA) content, and IL-6, IL-1ß, TNF-α expression, but a decrease in platform crossing times and superoxide dismutase (SOD) activity (P < 0.05). Furthermore, all the above changes of the model group were reversed after icariin treatment in a dose-dependent manner (P < 0.05). Network pharmacology found that icariin can exert anti-schizophrenic effects through some signaling pathways, such as relaxin, estrogen, and TNF signaling pathways. MAPK1, MAPK3, FOS, RELA, TNF, and JUN were the key targets of icariin on schizophrenia, and their expression was detected in animal models, which was consistent with the predicted results of network pharmacology. Icariin treatment may improve the spatial learning and memory ability of schizophrenic rats through TNF signaling pathway.

Antrodia cinnamomea prevents ovariectomized-promoted bone loss by inhibiting osteoclast formation.

Osteoporosis is a common bone disease in aging populations, particularly in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are linked with a variety of adverse effects. Antrodia cinnamomea extracts (ACE) are highly renowned for their anticancer, antioxidative, and anti-inflammatory properties. However, whether ACE-enriched anti-osteoporosis functions are largely unknown. In a preclinical animal model, we found that ovariectomy significantly decreased bone volume in the ovariectomized (OVX) rats. Administration of ACE antagonized OVX-induced bone loss. In addition, ACE reversed OVX-reduced biomechanical properties. The serum osteoclast marker also showed improvement in the ACE-treated group. In the cellular model, it was indicated that ACE inhibits RANKL-induced osteoclast formation. Taken together, ACE seems to be a hopeful candidate for the development of novel anti-osteoporosis treatment.

Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 µg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.

Beneficial Effects of Fibroblast Growth Factor-1 on Retinal Pigment Epithelial Cells Exposed to High Glucose-Induced Damage: Alleviation of Oxidative Stress, Endoplasmic Reticulum Stress, and Enhancement of Autophagy.

Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance (p < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR.

Outcomes of FETD versus UBE in the treatment of L5S1 foraminal stenosis: A comparative study.

Background: The L5S1 level exhibits unique anatomical features compared with other levels. This makes minimally invasive surgery for L5S1 foraminal stenosis (FS) challenging. This study compared the surgical outcomes of full endoscopic transforaminal decompression (FETD) and unilateral biportal endoscopy with the far-lateral approach (UBEFLA) in patients with L5S1FS. Methods: In this retrospective study, 49 patients with L5S1FS were divided into two groups. Of these, 24 patients underwent FETD, 25 patients underwent UBEFLA. The study assessed demographic data, leg pain visual analog scale (VAS) score, back pain VAS score, Oswestry Disability Index (ODI), modified MacNab outcome scale, and radiographic parameters including postoperative lateral facet preservation (POLFP). Results: The Mann-Whitney U test revealed that the UBEFLA group exhibited a higher VAS score for back pain at one week after the operation, whereas the FETD group exhibited a higher leg pain VAS score 6 weeks after the operation. All four undesired MacNab outcomes in the FETD group were attributed to residual leg pain, whereas all five undesired MacNab outcomes in the UBEFLA group were due to recurrent symptoms. Radiographically, the FETD group exhibited greater POLFP. Conclusions: When L5S1FS is performed, there may be challenges in adequately clearing the foraminal space in FETD. On the other hand, UBEFLA allowed for a more comprehensive clearance. However, this advantage of UBEFLA was associated with spinal instability as a future outcome.

Identification, expression analysis, and functional verification of three opsin genes related to the phototactic behaviour of Ostrinia furnacalis.

Ostrinia furnacalis is a disreputable herbivorous pest that poses a serious threat to corn crops. Phototaxis in nocturnal moths plays a crucial role in pest prediction and control. Insect opsins are the main component of insect visual system. However, the inherent molecular relationship between phototactic behaviour and vision of insects remains a mystery. Herein, three opsin genes were identified and cloned from O. furnacalis (OfLW, OfBL, and OfUV). Bioinformatics analysis revealed that all opsin genes had visual pigment (opsin) retinal binding sites and seven transmembrane domains. Opsin genes were distributed across different developmental stages and tissues, with the highest expression in adults and compound eyes. The photoperiod-induced assay elucidated that the expression of three opsin genes in females were higher during daytime, while their expression in males tended to increase at night. Under the sustained darkness, the expression of opsin genes increased circularly, although the increasing amplitude in males was lower when compared with females. Furthermore, the expression of OfLW, OfBL, and OfUV was upregulated under green, blue, and ultraviolet light, respectively. The results of RNA interference showed that the knockout of opsin genes decreased the phototaxis efficiency of female and male moths to green, blue, and ultraviolet light. Our results reveal that opsin genes are involved in the phototactic behaviour of moths, providing a potential target gene for pest control and a basis for further investigation on the phototactic behaviour of Lepidoptera insects.

Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma.

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

DDIT3/CHOP promotes LPS/ATP-induced pyroptosis in osteoblasts via mitophagy inhibition.

Inflammatory environments can trigger endoplasmic reticulum (ER) stress and lead to pyroptosis in various tissues and cells, including liver, brain, and immune cells. As a key factor of ER stress, DNA damage-inducible transcript 3 (DDIT3)/CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is upregulated in osteoblasts during inflammatory stimulation. DDIT3/CHOP may therefore regulate osteoblast pyroptosis in inflammatory conditions. During this investigation, we found that lipopolysaccharides (LPS)/adenosine 5'-triphosphate (ATP) stimulation in vitro induced osteoblasts to undergo pyroptosis, and the expression of DDIT3/CHOP was increased during this process. The overexpression of DDIT3/CHOP further promoted osteoblast pyroptosis as evidenced by the increased expression of the inflammasome NLR family pyrin domain containing 3 (NLRP3) and ratios of caspase-1 p20/caspase-1 and cleaved gasdermin D (GSDMD)/GSDMD. To explore the specific mechanism of this effect, we found through fluorescence imaging and Western blot analysis that LPS/ATP stimulation promoted PTEN-induced kinase 1 (PINK1)/E3 ubiquitin-protein ligase parkin (Parkin)-mediated mitophagy in osteoblasts, and this alteration was suppressed by the DDIT3/CHOP overexpression, resulting in increased ratio of pyroptosis compared with the control groups. The impact of DDIT3/CHOP on pyroptosis in osteoblasts was reversed by the application of carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a specific mitophagy agonist. Therefore, our data demonstrated that DDIT3/CHOP promotes osteoblast pyroptosis by inhibiting PINK1/Parkin-mediated mitophagy in an inflammatory environment.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Choroidal Changes in Patients with Diabetic Retinopathy: A Retrospective Study.

This study aimed to investigate the characteristic choroidal changes in patients with diabetic retinopathy and identify factors affecting choroidal thickness (CTh), choroidal vascular index (CVI), and choriocapillaris flow. We retrospectively analyzed 79 eyes of 48 patients with diabetes between August 2021 and February 2022. We collected laboratory data, including HbA1c, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) levels. Optical coherence tomography images of the foveal avascular zone, retinal vascular density, choroidal flow, retinal thickness, CTh, and CVI were analyzed. Possible determining factors affecting CTh, CVI, and choriocapillaris flow were analyzed using nonparametric multivariate analysis. LDL (p < 0.001) positively correlated with CTh, whereas CVI (p = 0.007) was negatively correlated with CTh in diabetic patients with diabetes. We also identified a negative correlation between choriocapillaris flow and deep parafoveal retinal vessel density in patients with low-grade diabetic retinopathy (DR), which diminished in those with more advanced DR. Our study provides further information on the changes in choroidal structure and blood flow in patients with diabetes.

Integrated transcriptomic and proteomic analyses reveal the molecular mechanism underlying the thermotolerant response of Spodoptera frugiperda.

Spodoptera frugiperda (Lepidoptera: Noctuidae) is a highly destructive invasive pest with remarkable adaptability to extreme climatic conditions, posing a substantial global threat. Although the effects of temperature stress on the biological and ecological properties of S. frugiperda have been elucidated, the molecular mechanisms underlying its responses remain unclear. Herein, we combined transcriptomic and proteomic analyses to explore the key genes and proteins involved in thermotolerance regulation in S. frugiperda larvae at 42 °C. Overall, 1528 differentially expressed genes (DEGs) and 154 differentially expressed proteins (DEPs) were identified in S. frugiperda larvae under heat stress, including antioxidant enzymes, heat shock proteins (Hsps), cytochrome P450s, starch and sucrose metabolism genes, and insulin signaling pathway genes, indicating their involvement in heat tolerance regulation. Correlation analysis of DEGs and DEPs revealed that seven and eight had the same and opposite expression profiles, respectively. After nanocarrier-mediated RNA interference knockdown of SfHsp29, SfHsp20.4, SfCAT, and SfGST, the body weight and mortality of S. frugiperda larvae significantly decreased and increased under heat stress, respectively. This indicates that SfHsp29, SfHsp20.4, SfCAT, and SfGST play a crucial role in the thermotolerance of S. frugiperda larvae. These results provide insight into the mechanism of heat tolerance in S. frugiperda.

Correction: MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer.

Correction for 'MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer' by Jie Liu et al., Biomater. Sci., 2022, 10, 4596-4611, https://doi.org/10.1039/D2BM00543C.