Dual-Dynamic Chemistries-Based Fast-Reprocessing and High-Performance Covalent Adaptable Networks.

Covalent adaptable networks (CANs) possess multiple functions including reprocessing (or recyclability), self-healing, welding, shape shifting, 3D printing, etc., due to the network rearrangement from dynamic bonds, and favorable performance from their cross-linked feature, and they are supposed to be as sustainable alternatives to thermosets. However, the thermal and mechanical properties, and stability of CANs are often sacrificed for rapid network rearrangement. In this paper, fast-reprocessing CANs with high performance are facilely constructed by in situ polymerization and dynamic cross-linking of styrene (St), maleic anhydride (MA), and acetal diol (BHAD). The rigid and hydrophobic polymer backbone endow the materials with high glass transition temperatures, mechanical performance, and water resistance. Besides, carboxylic group-catalyzed dual dynamic ester and acetal-based networks exhibit faster stress relaxation and realize extrusion reprocessing. This work provides an ingenious and simple strategy of construction of CANs combining rapid network rearrangement and excellent comprehensive performance, which is beneficial for the application of CANs.

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells.

Doxorubicin (Dox) is the standard treatment approach for osteosarcoma (OS), while acquired drug resistance seriously attenuates its treatment efficiency. The present study aimed to investigate the potential roles of metabolic reprogramming and the related regulatory mechanism in Dox-resistant OS cells. The results showed that the ATP levels, lactate generation, glucose consumption and oxygen consumption rate were significantly increased in Dox-resistant OS cells compared with parental cells. Furthermore, the results revealed that the increased expression of estrogen-related receptor alpha (ERRα) was involved in metabolic reprogramming in chemotherapy resistant OS cells, since targeted inhibition of ERRα restored the shifting of metabolic profiles. Mechanistic analysis indicated that the mRNA stability, rather than ERRα transcription was markedly increased in chemoresistant OS cells. Therefore, it was hypothesized that the 3'-untranslated region of ERRα mRNA was methylated by N6-methyladenine, which could further recruit insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress mRNA decay and increase mRNA stability. IGF2BP1 knockdown downregulated ERRα and reversed the metabolic alteration of resistant OS cells. Additionally, the oncogenic effect of the IGF2BP1/ERRα axis on Dox-resistant OS cells was verified by in vitro and in vivo experiments. Clinical analysis also revealed that the expression levels of IGF2BP1 and ERRα were associated with the clinical progression of OS. Collectively, the current study suggested that the IGF2BP1/ERRα axis could regulate metabolic reprogramming to contribute to the chemoresistance of OS cells.

Inhibition of transient receptor potential canonical 6 attenuates fibroblast-like synoviocytes mediated synovial inflammation and joint destruction in rheumatoid arthritis.

OBJECTIVES: We aimed to define the importance of transient receptor potential canonical 6 (TRPC6) expression and function in fibroblast-like synoviocytes (FLSs) and to investigate the contribution of TRPC6 in the model of rheumatoid arthritis (RA). METHODS: We compared TRPC6 expression levels in FLSs from RA patients (RA-FLSs), and in FLSs from osteoarthritis (OA) patients (OA-FLSs). By using vitro functional assays which united with small interfering RNA-induced knockdown and functional modulation of TRPC6 in RA-FLSs. Finally, we confirmed the effectiveness of regulating TRPC6 in a collagen induced arthritis (CIA) mice model. RESULTS: We found that FLSs expressed the TRPC6 as their major Transient receptor potential canonical channel. Both mRNA and protein expression of TRPC6 were found somewhat higher levels in RA-FLSs than in OA-FLSs. Moreover, inhibiting expression of TRPC6 in vitro reduced proliferation of, as well as inflammatory mediator and protease production by, RA-FLSs, whereas opening native TRPC6 enhanced both proliferation and inflammatory mediator of RA-FLSs. Additionally, a TRPC6 deficiency in mice blunted the development of experimental RA, CIA models, reduced joint and bone damage, and inhibited FLS invasiveness and proliferation. CONCLUSIONS: Our results demonstrated a critical role of TRPC6 in regulating FLSs mediated inflammation. Therefore, TRPC6 represents potential therapeutic targets in RA.

Changes in the retina and choroid in patients with internal carotid artery stenosis: a systematic review and meta-analysis.

Background: Internal carotid artery stenosis (ICAS) is a prevalent vascular condition associated with ischemic cerebrovascular disease. The ophthalmic artery is the first branch of the internal carotid artery stenosis (ICA). Given the crucial role of the ICA in ocular perfusion, we aimed to assess the thickness and vessel density of the retina and choroid in individuals with ICAS. Methods: The PubMed and Embase databases were searched from inception to 10 January 2023 for studies evaluating retinal and choroidal changes between ICAS patients and healthy controls using optical coherence tomography (OCT) or optical coherence tomography angiography (OCTA). Data of interest were extracted and analyzed using Stata software version 16. Results: Thirteen studies involving 419 ICAS eyes and 398 healthy eyes were included. The pooled results demonstrated that the average thickness of peripapillary retinal nerve fiber layer (pRNFL) (WMD = -0.26, 95% CI: -0.45 to -0.08, P = 0.005), ganglion cell complex (GCC) (WMD = -0.36, 95% CI: -0.65 to -0.06, P = 0.017), and choroid (WMD = -1.06, 95% CI: -1.59 to -0.52, P = 0.000), were significantly thinner in patients with ICAS than in healthy controls. The overall vessel density of the radial peripapillary capillaries (RPC) in whole-image scans was lower in ICAS patients than in healthy control subjects (WMD = -0.94, 95% CI: -1.49 to -0.39, P = 0.001). No differences were detected in the vessel density of the superficial capillary plexus (SCP) (WMD = -0.84, 95% CI: -1.15 to -0.53, P = 0.092), the deep capillary plexus (DCP) (WMD = -0.27, 95% CI: -0.56 to 0.03, P = 0.074), or the choriocapillaris (CC) (WMD = -0.39, 95% CI: -1.12 to 0.35, P = 0.300). Conclusion: This systematic review and meta-analysis demonstrated that ICAS can reduce the vessel density of the RPC and the thickness of the retina and choroid. The retinal and choroidal microvasculature is a potential biomarker of the initial signal of ICAS. Systematic review registration: https://inplasy.com/, identifier NPLASY202410038.

Global research trends and future directions in diabetic macular edema research: A bibliometric and visualized analysis.

BACKGROUND: Diabetic Macular Edema (DME) significantly impairs vision in diabetics, with varied patient responses to current treatments like anti-vascular endothelial growth factor (VEGF) therapy underscoring the necessity for continued research into more effective strategies. This study aims to evaluate global research trends and identify emerging frontiers in DME to guide future research and clinical management. METHODS: A qualitative and quantitative analysis of publications related to diabetic macular edema retrieved from the Web of Science Core Collection (WoSCC) between its inception and September 4, 2023, was conducted. Microsoft Excel, CiteSpace, VOSviewer, Bibliometrix Package, and Tableau were used for the bibliometric analysis and visualization. This encompasses an examination of the overall distribution of annual output, major countries, regions, institutions, authors, core journals, co-cited references, and keyword analyses. RESULTS: Overall, 5624 publications were analyzed, indicating an increasing trend in DME research. The United States was identified as the leading country in DME research, with the highest h-index of 135 and 91,841 citations. Francesco Bandello emerged as the most prolific author with 97 publications. Neil M. Bressler has the highest h-index and highest total citation count of 46 and 9692, respectively. The journals "Retina - the Journal of Retinal and Vitreous Diseases" and "Ophthalmology" were highlighted as the most prominent in this field. "Retina" leads with 354 publications, a citation count of 11,872, and an h-index of 59. Meanwhile, "Ophthalmology" stands out with the highest overall citation count of 31,558 and the highest h-index of 90. The primary research focal points in diabetic macular edema included "prevalence and risk factors," "pathological mechanisms," "imaging modalities," "treatment strategies," and "clinical trials." Emerging research areas encompassed "deep learning and artificial intelligence," "novel treatment modalities," and "biomarkers." CONCLUSION: Our bibliometric analysis delineates the leading role of the United States in DME research. We identified current research hotspots, including epidemiological studies, pathophysiological mechanisms, imaging advancements, and treatment innovations. Emerging trends, such as the integration of artificial intelligence and novel therapeutic approaches, highlight future directions. These insights underscore the importance of collaborative and interdisciplinary approaches in advancing DME research and clinical management.

Key role of exosomes derived from M2 macrophages in maintaining cancer cell stemness (Review).

Cancer stem cells (CSCs) constitute a specific subset of cells found within tumors that are responsible for initiating, advancing and resisting traditional cancer treatments. M2 macrophages, also known as alternatively activated macrophages, contribute to the development and progression of cancer through their involvement in promoting angiogenesis, suppressing the immune system, supporting tumor growth and facilitating metastasis. Exosomes, tiny vesicles released by cells, play a crucial role in intercellular communications and have been shown to be associated with cancer development and progression by influencing the immune response; thus, they may serve as markers for diagnosis and prognosis. Currently, investigating the impact of exosomes derived from M2 macrophages on the maintenance of CSCs is a crucial area of research with the aim of developing novel therapeutic strategies to target this process and improve outcomes for individuals with cancer. Understanding the biological functions of exosomes derived from M2 macrophages and their involvement in cancer may lead to the formulation of novel diagnostic tools and treatments for this disease. By targeting M2 macrophages and the exosomes they secrete, promising prospects emerge for cancer treatment, given their substantial contribution to cancer development and progression. Further research is required to fully grasp the intricate interactions between CSCs, M2 macrophages and exosomes in cancer, and to identify fresh targets for cancer therapy. The present review explores the pivotal roles played by exosomes derived from M2 cells in maintaining the stem­like properties of cancer cells.

Retina and microvascular alterations in migraine: a systemic review and meta-analysis.

Objective: This study aimed to evaluate the retina and microvascular alterations with optical coherence tomography (OCT) or optical coherence tomography angiography (OCTA) in patients with migraine with aura (MA) and migraine without aura (MO). Methods: PubMed, Embase, and Cochrane Library databases were searched to find relevant literature on patients with MA or MO using OCT/OCTA devices. The eligible data were analyzed by Stata Software (version 15.0). Results: There were 16 studies identified, involving 379 eyes with MA, 583 eyes with MO, and 658 eyes of healthy controls. The thickness of the peripapillary retinal nerve fiber layer (pRNFL) of patients with MA decreased significantly in most regions. The foveal avascular zone (FAZ) area and perimeter in MA patients significantly enlarged, while the perfusion density (PD) in the macular deep capillary plexus (mDCP) significantly decreased in the whole image and its subregions except for the fovea, with the PD in radial peripapillary capillary (RPC) decreasing inside the disk. Patients with MO demonstrated a significantly decreased thickness of pRNFL in most regions, and the FAZ parameters were significantly enlarged. No statistical significance was observed in the retina and microvascular features of patients with MA and MO. Conclusion: The eyes affected by MA and MO demonstrated significantly reduced thickness of pRNFL and enlarged FAZ. Patients with MA showed retinal microvascular impairments, including a decreased PD in mDCP. The OCT and OCTA could detect membrane morphology and circulation status in migraine and might provide the basis for the diagnosis and follow-up of patients with migraine. Systematic review registration: https://www.crd.york.ac.uk/prospero/, CRD42023397653.

A genetically engineered Pseudomonas fluorescens strain possesses the dual activity against phytopathogenic fungi and insects.

A Pseudomonas fluorescens strain was isolated and showed antagonistic activity against phytopathogenic fungi and found to possess a gene responsible for production of antibiotic 2, 4-diacetylphloroglucinol. For the extension of biocontrol range, a gene for an Androctonus australis Hector insect toxin 1 (AaHIT1), one of the most toxic known insect-selective peptides, was designed and synthesized according to the preferred codon usage of Pseudomonas fluorescens, cloned and transformed into the strain by pSUP106 vector, a broad-host-range plasmid. Bioassays indicated that the engineered strain was able to produce AaHIT1 with insecticidal activity, in the same time retained the activity against plant pathogen. The experiments for nonplanted soil and rhizosphere colonization showed that, similar to the population of the wild-type strain, that of the engineered strain remained relatively constant in the first 10 d, and the subsequent 50 d, suggesting that AaHIT expression in the bacterial cell does not substantially impair its long-term colonization. It is first reported that a Pseudomonas fluorescens strain expressing an active scorpion neurotoxin has dual activity against phytopathogenic fungi and insects, attractive for agronomic applications.

TREM-2 negatively regulates LPS-mediated inflammatory response in rat bone marrow-derived MSCs.

To the best of our knowledge, our previous study demonstrated the expression of triggering receptor expressed on myeloid cells 2 (TREM­2) in human bone marrow mesenchymal stem cells (MSCs) for the first time. However, the inflammation regulatory role of TREM­2 in MSCs remain elusive. The aim of the present study was to investigate the immune regulation and the underlying mechanism of TREM­2 in rat bone marrow MSCs. MSCs were divided into three groups: NullMSCs, TREM­2MSCs, and NormMSCs. TREM­2 was expressed in MSCs at the mRNA and protein level. Following stimulation by lipopolysaccharide (LPS), the gene transcription levels of TREM­2 and inflammatory cytokines were increased. The expression levels of inflammatory cytokines, including tumor necrosis factor­α (TNF­α) and interleukin­1ß (IL­1ß), in the TREM­2MSCs lentiviral vector group were significantly downregulated, and the expression of IL­10 was significantly upregulated compared with the controls. Western blot analysis revealed that TREM­2 downregulated the LPS­induced inflammatory response in MSCs, which was probably associated with regulating AKT serine/threonine kinase and p38 mitogen­activated protein kinase downstream signaling proteins. The results of the current study demonstrated that TREM­2 negatively regulates the LPS­mediated inflammatory response in MSCs suggesting that TREM­2 is a potential target of immune regulation in rat MSCs.

Regulation of human mesenchymal stem cell differentiation by TREM-2.

Activation of the triggering receptor expressed on myeloid cells 2 (TREM-2) regulates myeloid cell function in vitro. However, the failure to detect TREM-2 protein expression in vivo has hampered studies on immunological and other physiological TREM-2 functions. This study demonstrates that TREM-2 is expressed by human mesenchymal stem cells (h-MSCs) and responds to the toll-like receptor (TLR) ligand lipopolysaccharide (LPS). Knockdown of TREM-2 in h-MSCs using a small interfering RNA (siRNA) reduced the expression levels of TLR2, TLR4, and TLR6, inhibited osteogenic, chondrogenic, and adipogenic differentiation under specific induction conditions, and enhanced LPS-evoked inflammatory cytokine production. Thus, activation of TREM-2 may restrain h-MSC immune activation and promote differentiation for tissue repair.

Structural differences between Fusarium strains investigated by FT-IR spectroscopy.

The structural characteristics of Fusarium have received attention from both pure and applied scientists. Because many genes and physiological mechanisms are involved in the development of a particular structure type, this research is complicated. For revealing the structure of macromolecule in these fungal cells, FT-IR spectroscopy combined with multivariate statistical analysis was performed to characterize the structure of protein and polysaccharide of spores and mycelia obtained from different culture medium. The second derivative FT-IR spectra exhibited strain-specific infrared characteristics in the protein secondary structure sensitive amide I region. The region between 750 and 950 cm(-1) assigned to alpha- and beta-glucans was investigated for studied samples. Principal components analysis (PCA) allowed us to separate mycelia into two clusters according to different growth medium, indicating that spectra of strains may have been greatly affected by cultivation conditions.

Mutational analysis of the GDD sequence motif of classical swine fever virus RNA-dependent RNA polymerases.

To define the function of the GDD motif of the RNA-dependent RNA polymerase (RdRp) of classical swine fever virus (CSFV), single amino acid substitutions were introduced into the CSFV NS5B. All substitutions within the GDD motif were detrimental to the polymerase activity, the binding activity and the terminal nucleotidyl transferase activity of the NS5B protein. It was also found that the wild-type NS5B had higher RdRp activity with Mg(+2) than with Mn(+2) whereas some mutants worked better with Mn(+2) than with Mg(+2), suggesting that substitutions within the GDD motif modified the enzyme cation preferences and the GDD sequence of CSFV NS5B might be involved in polymerase-metal interaction. Therefore, the GDD amino acid sequence is important for the function of CSFV RdRp.