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Abstract Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer with poor prognosis. Killing cancer cells by inducing DNA damage or blockage of DNA repair is a promising strategy for chemotherapy. It is reported that aldehyde-reactive alkoxyamines can capture the AP sites, one of the most common DNA lesions, and inhibit apurinic/apyrimidinic endonuclease 1(APE1)-mediated base excision repair (BER), leading to cell death. Whether this strategy can be employed for ATC treatment is rarely investigated. The aim of this study is to exploit GSH-responsive AP site capture reagent (AP probe-net), which responses to the elevated glutathione (GSH) levels in the tumor micro-environment (TME), releasing reactive alkoxyamine to trap AP sites and block the APE1-mediated BER for targeted anti-tumor activity against ATC. In vitro experiments, including MTT andγ-H2AX assays, demonstrate their selective cytotoxicity towards ATC cells over normal thyroid cells. Flow cytometry analysis suggests that AP probe-net arrests the cell cycle in the G2/M phase and induces apoptosis. Western blotting (WB) results show that the expression of apoptotic protein increased with the increased concentration of AP probe-net. Further in vivo experiments reveal that the AP probe-net has a good therapeutic effect on subcutaneous tumors of the ATC cells. In conclusion, taking advantage of the elevated GSH in TME, our study affords a new strategy for targeted chemotherapy of ATC with high selectivity and reduced adverse effects.

PurposeTo investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves’ disease (GD) and to further assess predictive value of changes in early stage retrospectively.MethodsWe studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered.ResultsThe levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05).ConclusionBTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Abstract New adjuvants that trigger cellular immune responses are urgently needed for the effective development of cancer and virus vaccines. Motivated by recent discoveries that show activation of type I interferon (IFN‐I) signaling boosts T cell immunity, this study proposes that targeting this pathway can be a strategic approach to identify novel vaccine adjuvants. Consequently, a comprehensive chemical screening of 6,800 small molecules is performed, which results in the discovery of the natural compound picrasidine S (PS) as an IFN‐I inducer. Further analysis reveals that PS acts as a powerful adjuvant, significantly enhancing both humoral and cellular immune responses. At the molecular level, PS initiates the activation of the cGAS‐IFN‐I pathway, leading to an enhanced T cell response. PS vaccination notably increases the population of CD8+ central memory (TCM)‐like cells and boosts the CD8+ T cell‐mediated anti‐tumor immune response. Thus, this study identifies PS as a promising candidate for developing vaccine adjuvants in cancer prevention.

Introduction: and objectives: Extracellular vesicles (EVs) have emerged as key players in intercellular communication within the context of non-alcoholic fatty liver disease (NAFLD). This study aims to explore the intricate crosstalk between hepatocytes and hepatic stellate cells (HSCs) mediated by EVs in NAFLD. Materials and methods: EVs ferritin was detected in hepatocytes stimulated with free fatty acids (FFA) as well as in NAFLD mice. Deferoxamine (DFO) was employed to reduce ferritin levels, while GW4869 was utilized to inhibit EVs. The impact of EVs ferritin on the HSCs activation was evaluated both in vitro and in vivo. Additionally, serum EVs ferritin levels were compared between NAFLD patients and controls. Results: FFA treatment induces the formation and secretion of EVs and facilitates the release of ferritin from hepatocytes via EVs. Subsequently, EVs ferritin is hijacked by HSCs, prompting accelerated HSCs activation. Silencing ferritin with DFO and inhibiting EVs formation and secretion with GW4869 can reverse the effects of FFA treatment and disrupt the communication between hepatocytes and HSCs. Accumulation of ferritin leads to excessive reactive oxygen species (ROS) production, promoting HSCs fibrogenesis. Conversely, depleting EVs ferritin cargo restores liver function, concurrently mitigating NAFLD-associated fibrosis. Notably, NAFLD patients exhibit significantly elevated levels of serum EVs ferritin. Conclusions: This study unveils a previously underestimated role of ferritin in HSCs upon its release from hepatocytes, emphasizing DFO as a promising compound to impede NAFLD advancement.

The prevention of chronic wound formation has already been a primary subject in wound management, particularly for deep wounds. The electrospun nanofiber membranes hold tremendous potential in the prevention of chronic wounds due to their micro/nano pore structures. Currently, many natural and synthetic materials have been utilized in the fabrication of nanofiber membranes. However, striking a balance between the structural stability and the biocompatibility remains challenging. It is necessary not only to ensure the long-term durability of nanofiber membranes but also to enhance their biocompatibility for alleviating patients' suffering. In this study, we reported a nanofiber membrane dressing with excellent biocompatibility and mechanical properties, which is potential for the treatment of deep wounds. The basal material chosen for the preparation of the nanofiber membrane was a co-polyester (NI-LPGD5) synthesized by non-isocyanate polyurethane (NIPU) and polyglycolic acid with a dihydroxy structure (LPGD—synthesized from glycolic acid and neopentyl glycol). Moreover, curcumin was also added as a bioactive substance to enhance the pro-healing effect of dressings. The physicochemical properties of the prepared nanofiber membranes were characterized through various physicochemical tools. Our results demonstrated that the NI-LPGD5 co-polymer can be electrospun into smooth fibers. Meanwhile, curcumin-loaded nanofiber membranes (Cur/NI-LPGD5) also exhibited a favorable microscopic morphology. The fabricated membranes exhibited suitable mechanical properties, outstanding hygroscopic-swelling rate and water vapor transmittance. Besides, in vitro cell culturing, the cells on the NI-LPGD5 membrane maintained their maximum viability. The potential of in vivo wound healing was further demonstrated through animal experiments. The experimental results showed that the nanofiber membranes effectively prevented chronic wounds from forming and promoted granulation tissue growth without replacing the dressing throughout the healing process. We also found that these nanofiber membranes could effectively promote the expression of related biomarkers to accelerate wound healing, particularly the Cur/NI-LPGD5 membrane. In conclusion, the fabricated membranes possess suitable physicochemical properties and promising bioactivity. As a result, it effectively prevented the formation of chronic wounds and demonstrated significant potential in reducing the frequency of dressing changes.

Abstract Background Patients with stroke frequently experience walking dysfunction. Core training can help improve balance and walking function in patients with stroke. However, core training movements in clinical practice are numerous and differently targeted. Therefore, this study will investigate the improvement of walking function in patients with combined diaphragmatic breathing maneuver (DBM) and draw-in breathing technique (ADIM) training. Methods This single-blind, randomized controlled preliminary will analyze the viability of DBM combined ADIM training versus routine rehabilitation therapy in patients with stroke with early to mid-stroke. Patients will be randomly assigned to either the DBM and ADIM training or the routine rehabilitation training. We will recruit 42 stroke inpatients from the Second Rehabilitation Hospital of Shanghai who meet the trial criteria and measure the balance and walking functions and improvement of that after 4 weeks of intervention. The primary outcome is the 10 m maximum walking test (10MWT). The secondary outcomes indices include the limits of stability test (LOS), Berg balance scale test (BBS), Functional Ambulation Categories test (FAC), Timed Up and Go test (TUG), trunk impairment scale test (TIS), ultrasound indicators of the diaphragm and transversus abdominis (UI), rhythmic weight shift test (RWS), walk across test (WA), Fugl-Meyer assessment of lower extremity (FMA-LE), and Barthel index of ADL test. Discussion The primary objective of this project was to investigate the effects of DBM combined with ADIM on balance capacity and walking function for patients with early to mid-stroke. The outcomes of this study will hold significant implications for future clinical applications in rehabilitation. Trial registration Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR2100054897. Registered on 28 December 2021.

The stembase of Flammulina velutipes was pretreated by steam explosion, to explore the effects on antioxidant and anti-inflammatory activities of its water extract. The differences of active components in water extract of F.velutipes stembase before and after steam explosion were analyzed by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). The contents of crude polysaccharides, total phenols and total flavonoids were determined by phenol-sulfuric acid method, Folin-Ciocalteu method and aluminum chloride method. The in vitro antioxidant capacity of water extract of F.velutipes stembase before and after steam explosion was determined by DPPH, ABTS and FRAP methods. The potential anti-inflammatory activity and mechanism of F.velutipes stembase water extract on LPS-activated cells were investigated. The results showed that the relative content of active compounds of F.velutipes stembase increased significantly after steam explosion, such as betaine, trans-3-indoleacrylic acid, adenosine and nicotinamide, which were 1.14 times, 1.32 times, 3.39 times and 3.21 times of that in the non-steam explosion group, respectively, and the content of crude polysaccharide increased by 56.03%. SFVE had better antioxidant activity, the DPPH free radical scavenging ability, ABTS+ free radical scavenging ability and Fe3+ reducing ability were 1.12 times, 1.07 times and 1.12 times of those in the non-steam explosion group (FVE), respectively. The anti-inflammatory result showed that the water extract of F.velutipes stembase after steam explosion had significant inhibitory activity on LPS-induced NO production in RAW264.7 cells (P

Drying treatments are an effective method of preserving the beneficial properties of postharvest mushrooms. The effects of natural-air drying (ND), hot-air drying (HD), vacuum-freeze drying (FD), heat pump drying (HPD) and microwave-vacuum drying (MVD) on the microstructure, flavor- and health-related compounds of F. velutipes root were investigated. The results showed that FD had the least impact on the microstructure of F. velutipes root and its original porous fiber structure appeared complete. It also possessed the highest content of volatile compounds. MVD gave the highest contents of umami amino acids, total phenolics and total flavonoids, and its extract exhibited high antioxidant activity. In addition, different drying treatments had significant effect on the chemical components of F. velutipes root, with FD and MVD may be the potent drying strategies for preservation of flavor and nutraceuticals respectively. Therefore, our results provided essential data support for F. velutipes root processing and functional product development.

The irregularities in the collection and transmission of user power data in the low-voltage power distribution station area have led to errors in the subsequent application analysis of the station area. In order to ensure the integrity of power data in low-voltage stations, a multi-user power missing data complement method based on improved deep convolutional self-encoding is proposed. First, according to the characteristics of the lack of multi-user power data in the low-voltage station area, the power data is formed into a spatio-temporal tensor data format that can be used for one-dimensional convolution operations. Then use the encoding and decoding capabilities of the improved deep convolutional self-encoding network to realize the reconstruction of missing data, and optimize the network structure by introducing residual learning and batch normalization (BN). Finally, based on the proposed method, two cases of random and continuous loss of user power data in a certain area are complemented. The results show that the method can accurately complete 40% of randomly missing data and 2 consecutive days of missing data. The proposed method has improved completion accuracy compared with traditional methods to varying degrees.

Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. The effects of sex on intestinal microbiota after IOP absorption was determined. In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases.

Objective and aims: Osteopontin (OPN), an oxidant stress sensitive cytokine, plays a central role in liver fibrosis. While OPN expression can be reduced by small interfering RNA (siRNA), the challenge to deliver siRNA safely and effectively into liver remains unresolved. Exosomes are promising natural nanocarriers for drug delivery that are able to enter cells with different biological barriers efficiently. In this study, we used exosomes as a delivery vehicle to target OPN in liver fibrosis.Methods: Exosomes selectively home to fibrotic liver according to small animal imaging system. Electroporation technique was used to engineer exosomes to carry siRNA targeting OPN (ExosiRNA−OPN). Primary hepatic stellate cells (HSCs) were isolated and treated with ExosiRNA−OPN to assess the effect on activated HSCs (aHSCs). Immunofluorescence for α−SMA, an aHSCs marker, and sirius red staining were performed to assess ECM deposition. Finally, plasma OPN from patients with liver fibrosis was identified by ELISA assay.Results: Exosome-mediated siRNA delivery systems show high uptake and low toxicity. Besides, ExosiRNA−OPN suppressed HSCs activation and ECM deposition and more efficiently improved liver function when compared to naked siRNA-OPN. Moreover, ExosiRNA−OPN was assumed inhibiting TGF-β1 signaling activation, along with other fibrotic-related genes based on a GEO datasheet of liver fibrosis samples for correlation analyzes. ExosiRNA−OPN inhibited TGF-β1 signaling by decreasing high-mobility group box-1 (HMGB1). Plasma proteins from chronic HBV-induced fibrosis patients were identified that patients with high OPN expression correlates with more advanced fibrosis progression.Discussion: This study shows that exosome-mediated siRNA-OPN delivery may be an effective option for the treatment of liver fibrosis.

Flavonoids played critical roles in stabilizing microbial homoeostasis when animals suffered exoteric stresses. However, whether flavonoids attenuated heat stress of dairy cows is still not clear. Therefore, in the present article, flavonoids extracted from honeycomb were supplemented to investigate the production, digestibility, and rumen microbial metabolism responses of cows under heat stress conditions. A total of 600 multiparous dairy herds were randomly allotted into the control treatment (CON), the heat stress (HS) treatment, and the honeycomb flavonoids supplement under heat stress conditions (HF) treatment for a 30-day-long trial. Each treatment contains 4 replicates, with 50 cows in each replicate. Production performances including dry matter intake (DMI), milk production, and milk quality were measured on the basis of replicate. Furthermore, two cows of each replicate were selected for the measurement of the nutrient digestibility, the ruminal fermentable parameters including ruminal pH, volatile fatty acids, and ammonia-N, and the rumen microbial communities and metabolism. Results showed that HF effectively increased DMI, milk yield, milk fat, and ruminal acetate content (p < 0.05) compared with HS. Likewise, digestibility of NDF was promoted after HF supplement compared with HS. Furthermore, relative abundances of rumen microbial diversities especially Succiniclasticum, Pseudobutyrivibrio, Acetitomaculum, Streptococcus, and Succinivibrio, which mainly participated in energy metabolism, significantly improved after HF supplement. Metabolomic investigation showed that HF supplement significantly upregulated relative content of lipometabolic-related metabolites such as phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine, while it downregulated biogenic amines. In summary, HF supplement helps proliferate microbial abundances, which further promoted fiber digestibility and energy provision, and ultimately enhances the production performances of dairy cows under heat stress conditions.

Biomolecules participate in various physiological and pathological processes through intermolecular interactions generally driven by non-covalent forces. In the present review, the force-induced remnant magnetization spectroscopy (FIRMS) is described and illustrated as a novel method to measure non-covalent forces. During the FIRMS measurement, the molecular magnetic probes are magnetized to produce an overall magnetization signal. The dissociation under the interference of external force yields a decrease in the magnetic signal, which is recorded and collected by atomic magnetometer in a spectrum to study the biological interactions. Furthermore, the recent FIRMS development with various external mechanical forces and magnetic probes is summarized.

Introduction: Pancreatic cancer is one of the most common malignant digestive system tumors. Current treatment options for pancreatic cancer cannot achieve the expected curative effect. MicroRNAs (miRNAs and miRs) participate in many biological and pathological processes. miR-486 has been reported to be involved in diverse types of malignant tumors; however, its role in pancreatic cancer remains unclear.Material and Methods: miR-486 mimics and inhibitors were transfected into Capan-2 cells to increase or decrease the expression of miR-486. Western blot was used to detect protein expression levels. EdU proliferation assay and flow cytometry were applied to identify changes in proliferation. In combination with a PTEN overexpression plasmid, miR-486 mimics were used to determine whether PTEN upregulation abolished the proliferative effect of miR-486.Results: Overexpression of miR-486 promoted proliferation and cell cycle progression of Capan-2 cells. Conversely, the proliferation and cell cycle of Capan-2 cells were attenuated after inhibition of miR-486. Using a combination of bioinformatics and Western blot analysis, PTEN was identified as a downstream target gene of miR-486. The effect of miR-486 on Capan-2 cell proliferation could be abolished by PTEN overexpression.Conclusions: miR-486 promotes the proliferation of Capan-2 cells by targeting PTEN. Inhibition of miR-486 might be a novel therapy for pancreatic cancer.

Vaccinium dunalianum Wight, usually processed as a traditional folk tea beverage, is widely distributed in the southwest of China. The present study aimed to investigate the antioxidant, α-glucosidase and pancreatic lipase inhibitory activities of V.dunalianum extract and isolate the bioactive components. In this study, the crude extract (CE) from the buds of V. dunalianum was prepared by the ultrasound-assisted extraction method in 70% methanol and then purified with macroporous resin D101 to obtain the purified extract (PM). Five fractions (Fr. A–E) were further obtained by MPLC column (RP-C18). Bioactivity assays revealed that Fr. B with 40% methanol and Fr. D with 80% methanol had better antioxidant with 0.48 ± 0.03 and 0.62 ± 0.01 nM Trolox equivalent (TE)/mg extract for DPPH, 0.87 ± 0.02 and 1.58 ± 0.02 nM TE/mg extract for FRAP, 14.42 ± 0.41 and 19.25 ± 0.23 nM TE/mg extract for ABTS, and enzyme inhibitory effects with IC50 values of 95.21 ± 2.21 and 74.55 ± 3.85 for α-glucosidase, and 142.53 ± 11.45 and 128.76 ± 13.85 µg/mL for pancreatic lipase. Multivariate analysis indicated that the TPC and TFC were positively related to the antioxidant activities. Further phytochemical purification led to the isolation of ten compounds (1–10). 6-O-Caffeoylarbutin (7) showed significant inhibitory effects on α-glucosidase and pancreatic lipase enzymes with values of 38.38 ± 1.84 and 97.56 ± 7.53 µg/mL, and had the highest antioxidant capacity compared to the other compounds.