Structural elucidation and immunomodulatory activities in vitro of type I and II arabinogalactans from different origins of Astragalus membranaceus.

Astragalus membranaceus polysaccharide (APS) possesses excellent immunomodulatory activity. However, there are several studies on the structural characterization of APS. Here, we aimed to elucidate the repeating units of polysaccharides (APS1, 106.5 kDa; APS2, 114.5 kDa) obtained from different Astragalus membranaceus origins and further investigated their immunomodulatory activities. Based on structural analysis, types of the two polysaccharides were identified as arabinogalactan-I (AG-I) and arabinogalactan-II (AG-II), and co-elution of arabinogalactans (AGs) and α-glucan was observed. The backbone of AG-I was 1,4-linked ß-Galp occasionally substituted by α-Araf at O-2 and/or O-3. AG-II was a highly branched polysaccharide with long branches of α-Araf, which were attached to the O-3 of 1,6-linked ß-Galp of the backbone. The presence of AGs in A. membranaceus was confirmed for the first time. The two polysaccharides could promote the expression of IL-6, IL-1ß and TNF-α in RAW264.7 cells via MAPKs and NF-κB signaling pathways. The constants for APS1 and APS2 binding to Toll-like receptor 4 (TLR4) were 1.83 × 10-5 and 2.08 × 10-6, respectively. Notably, APS2 showed better immunomodulatory activity than APS1, possibly because APS2 contained more AGs. Hence, the results suggested that AGs were the vital components of APS in the immunomodulatory effect.

Corrigendum to "SOX8 promotes tumor growth and metastasis through FZD6-dependent Wnt/ß-catenin signaling in colorectal carcinoma" [Heliyon 9(12) (December 2023) e22586].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e22586.].

Twin boundary defect engineering in Au cocatalyst to promote alcohol splitting for coproduction of H2 and fine chemicals.

The microstructure of Au metal cocatalyst has been shown to significantly influence its optical and electronic properties. However, the impact of Au defect engineering on photocatalytic activity remains underexplored. In this study, we synthesize different Au-TiO2 composites by in-situ hybridizing face-centered cubic (F-Au) and twin boundary defect Au (T-Au) nanoparticles (NPs) onto the surface of TiO2. We find that T-Au NPs with twin defects serve as highly efficient cocatalysts for converting alcohols into their corresponding aldehydes while also generating H2. The optimized T-Au/TiO2 composite yields an H2 evolution rate of 6850 µmol h-1 g-1 and a BAD formation rate of 6830 µmol h-1 g-1, about 38 times higher than that of blank TiO2. Compared to F-Au/TiO2, the T-Au/TiO2 composite enhances charge separation, extends the lifetime of electrons, and provides more active sites for H2 reduction. The twin defect also improves alcohol reactant adsorption, boosting overall photocatalytic performance. This research paves the way for more studies on defect engineering in metal cocatalysts for enhanced catalytic activities in organic synthesis and H2 evolution.

Green, recyclable, mechanically robust, wet-adhesive and ionically conductive cellulose-based bioplastics enabled by supramolecular covalent hydrophobic eutectic networks.

The development of novel cellulose-based bioplastics (CBPs) is highly desirable because CBPs are green, rationally use resources, and lead to a reduction in environmental pollution compared to alternative materials. However, incorporating high transparency, water resistance, mechanical robustness, wet-adhesion, ionic conductivity and recyclability into CBP remains a challenge. In this paper, novel CBPs with supramolecular covalent networks are fabricated by introducing polymerizable hydrophobic deep eutectic solvents (HDES) into ethylcellulose (EC) networks through in situ plasticization followed by a rapid photopolymerization process. The excellent molecular interfacial compatibility enables EC to be loaded with a high content of poly(HDES), while allowing high transparency (more than 90 %) of the prepared CBPs. Multiple intermolecular interactions provide CBPs with mechanical robustness, water resistance, and underwater adhesion, and CBPs can be readily recovered by the solvent in a closed loop. Moreover, CBPs possess inherent ionic conductivities, and using them as green substrates, personalized electroluminescent devices can be successfully constructed. The method proposed in this paper provides a new strategy for the preparation of multifunctional CBPs, which will greatly enrich their applications in self-adhesive materials, green flexible electronics and other package materials.

SOX8 promotes tumor growth and metastasis through FZD6-dependent Wnt/ß-catenin signaling in colorectal carcinoma.

SOX8 plays an important role in several physiological processes. Its expression is negatively associated with overall survival in patients with colorectal carcinoma (CRC), suggesting SOX8 is a potential prognostic factor for this disease. However, the role of SOX8 in CRC remains largely unknown. In this study, our data showed that SOX8 expression was upregulated in CRC cell lines and tumor tissues. Stable knockdown of SOX8 in CRC cell lines dramatically reduced cell proliferation, migration, and invasion. Furthermore, the knockdown of SOX8 decreased the phospho-GSK3ß level and suppressed Frizzled-6 (FZD6) transcription; restoration of FZD6 expression partially abolished the effect of SOX8 on Wnt/ß-catenin signaling and promote CRC cell proliferation. In conclusion, our findings suggested that SOX8 served as an oncogene in CRC through the activation of FZD6-dependent Wnt/ß-catenin signaling.

Immunotherapy: Constructive Approach for Breast Cancer Treatment.

A novel and rapid therapeutic approach is the treatment of human breast cancer by enhancing the host's immune system. In initial findings, program death one (PD-1) and program cell death ligand one (PD-L1) showed positive results towards solid tumors, but tumor relapse and drug resistance are the major concerns. Breast cancer therapy has been transformed by the advent of immune checkpoint blockades (ICBs). Triple-negative breast cancers (TNBCs) have exhibited enduring responses to clinical usage of immune checkpoint inhibitors (ICBs) like atezolizumab and pembrolizumab. Nonetheless, a notable proportion of individuals with TNBC do not experience advantages from these treatments, and there is limited comprehension of the resistance mechanisms. Another approach to overcome resistance is cancer stem cells (CSCs), as these cells are crucial for the initiation and growth of tumors in the body. Various cancer vaccines are created using stem cells (dendritic, whole cell, bacterial) and focus primarily on targeting tumor-related antigens. The ultimate objective of cancer vaccines is to immunize the patients by active artificial immunity against cancer, though. In this review, we primarily focused on existing immunotherapeutic options, immune checkpoint blockers, the latest progress in understanding the molecular mechanisms underlying resistance to immune checkpoint inhibitors (ICBs), advanced strategies to overcome resistance to ICBs, cancer stem cell antigens and molecular markers, ongoing clinical trials for BCs and cancer vaccines for breast cancer.

Facile synthesis of hierarchical CdS nanoflowers for efficient piezocatalytic hydrogen evolution.

Piezocatalytic hydrogen evolution has emerged as a promising field for the collection and utilization of mechanical energy, as well as for generating sustainable energy throughout the day. Hexagonal CdS, an established semiconductor photocatalyst, has been widely investigated for its ability to split water into H2. However, its piezocatalytic performance has received less attention, and the relationship between its structure and piezocatalytic activity remains unclear. In this study, we prepared 3D ultrathin CdS nanoflowers with high voltage electrical response and low impedance. In pure water, without the use of any cocatalyst, CdS exhibited a piezoelectric catalytic hydrogen production rate of 1.46 mmol h-1 g-1, which was three times higher than that of CdS nanospheres (0.46 mmol h-1 g-1). Furthermore, the value-added oxidation product H2O2 was produced during the process of piezoelectric catalysis. These findings provide new insights for the design of high-efficiency piezoelectric catalytic hydrogen production.

Construction of Poly(hydrophobic deep eutectic solvent)/Ethylcellulose Composite Films for Green Recyclable Tapes.

Constructing green recyclable cellulose-based tapes with high transparency, mechanical robustness, and strong wet adhesion using natural components is highly desirable but challenging. Herein, novel cellulose-based self-adhesive tapes were reported by coating a polymerizable hydrophobic deep eutectic solvent (DES) on ethylcellulose followed by photopolymerization. The prepared ethylcellulose-based self-adhesive tape (ECSAT) exhibited an optical transmittance of up to ∼88% and could provide strong adhesion by interfacial intermolecular interactions without obstructing information. Due to the hydrophobic nature of the overall structure, ECSAT does not exhibit significant adhesive strength and mechanical degradation under water, acid, and alkali environments. Notably, ECSAT can be completely dissolved in the resultant DES and furthermore reused as a self-adhesive coating. The recycled ECSAT still maintained good optical transparency, mechanical strength, and wet adhesion. We believe that ECSATs with all-around performances have a wide range of applications in packaging and other engineering fields.

Newcastle disease virus LaSota strain induces apoptosis and activates the TNFα/NF-κB pathway in canine mammary carcinoma cells.

Spontaneous canine mammary carcinomas (CMCs) have been widely considered a good research model for human breast cancers, which brings much attention to CMCs. In recent years, the oncolytic effect of Newcastle disease virus (NDV) on cancer cells has been widely studied, but its effect on CMCs is still unclear. This study aims to investigate the oncolytic effect of NDV LaSota strain on canine mammary carcinoma cell line (CMT-U27) in vivo and in vitro. The in vitro cytotoxicity and immunocytochemistry experiments showed that NDV selectively replicated in CMT-U27 cells, and inhibited cell proliferation and migration but not in MDCK cells. KEGG analysis of transcriptome sequencing indicated the importance of the TNFα and NF-κB signalling pathways in the anti-tumour effect of NDV. Subsequently, the significantly increased expression of TNFα, p65, phospho-p65, caspase-8, caspase-3 and cleaved-PARP proteins in the NDV group suggested that NDV induced CMT-U27 cells apoptosis by activating the caspase-8/caspase-3 pathway and the TNFα/NF-κB signalling pathway. Nude mice tumour-bearing experiments showed that NDV could significantly decrease the growth rate of CMC in vivo. In conclusion, our study demonstrates the effective oncolytic effects of NDV on CMT-U27 cells in vivo and in vitro, and suggests NDV as a promising candidate for oncolytic therapy.

Characterization of quinoa starch nanoparticles as a stabilizer for oil in water Pickering emulsion.

Quinoa starch nanoparticles (QSNPs) prepared by nanoprecipitation had a uniform particle size of 191.20 nm. QSNPs with amorphous crystalline structure had greater contact angle than QS with orthorhombic crystalline structure, which can therefore be utilized to stabilize Pickering emulsions. QSNPs-based Pickering emulsions prepared by suitable formulations (QSNPs concentration of 2.0-2.5 %, oil volume fraction of 0.33-0.67) exhibited good stability against pH of 3-9 and ionic strength of 0-200 mM. The oxidative stability of the emulsions increased with increasing starch concentration and ionic strength. Microstructural and rheological results indicated that the structure of the starch interfacial film and the thickening effect of the water phase affected the emulsion stability. The emulsion had excellent freeze-thaw stability and can be produced as a re-dispersible dry emulsion using the freeze-drying technique. These results implied that the QSNPs had great potential for application in the preparation of Pickering emulsions.

Design and Experiment of Combined Infrared and Hot-Air Dryer Based on Temperature and Humidity Control with Sea Buckthorn (Hippophae rhamnoides L.).

A drying device based on infrared radiation heating technology combined with temperature and humidity process control technology was created to increase the drying effectiveness and quality of sea buckthorn. Based on the conventional k-turbulence model, the velocity field in the air distribution chamber was simulated using COMSOL 6.0 software. The airflow of the drying medium in the air distribution chamber was investigated, and the accuracy of the model was verified. Given that the inlet of each drying layer in the original model had a different velocity, the velocity flow field was improved by including a semi-cylindrical spoiler. The results showed that installation of the spoiler improved the homogeneity of the flow field for various air intakes, as the highest velocity deviation ratio dropped from 26.68% to 0.88%. We found that sea buckthorn dried more rapidly after being humidified, reducing the drying time by 7.18% and increasing the effective diffusion coefficient from 1.12 × 10-8 to 1.23 × 10-8 m2/s. The L*, rehydration ratio, and vitamin C retention rate were greater after drying with humidification. By presenting this hot-air drying model as a potential high-efficiency and high-quality preservation technology for sea buckthorn, we hope to advance the development of research in the sea buckthorn drying sector.

CNTN1 Aggravates Neuroinflammation and Triggers Cognitive Deficits in Male Mice by Boosting Crosstalk between Microglia and Astrocytes.

A wealth of knowledge regarding glial cell-mediated neuroinflammation, which contributes to cognitive deficits in Alzheimer's disease (AD) has emerged in recent years. Contactin 1(CNTN1), a member of the cell adhesion molecule and immunoglobulin supergene family, is centrally involved in axonal growth regulation and is also a key player in inflammation-associated disorders. However, whether CNTN1 plays a role in inflammation-related cognitive deficits and how this process is triggered and orchestrated remain to be fully elucidated. In this study, we examined postmortem brains with AD. CNTN1 immunoreactivity was markedly increased, particularly in the CA3 subregion, as compared with non-AD brains. Furthermore, by applying an adeno-associated virus-based approach to overexpress CNTN1 directly via stereotactic injection in mice, we demonstrated that hippocampal CNTN1 overexpression triggered cognitive deficits detected by novel object-recognition, novel place-recognition and social cognition tests. The mechanisms underlying these cognitive deficits could be attributed to hippocampal microglia and astrocyte activation, which led to aberrant expression of excitatory amino acid transporters (EAAT)1/EAAT2. This resulted in long-term potentiation (LTP) impairment that could be reversed by minocyline, an antibiotic and the best-known inhibitor of microglial activation. Taken together, our results identified Cntn1 as a susceptibility factor involved in regulating cognitive deficits via functional actions in the hippocampus. This factor correlated with microglial activation and triggered astrocyte activation with abnormal EAAT1/EAAT2 expression and LTP impairment. Overall, these findings may significantly advance our understanding of the pathophysiological mechanisms underlying the risk of neuroinflammation related cognitive deficits.

Rapid and quantitative detection of neutrophil gelatinase-associated lipocalin in synovial fluid using fluorescence immunochromatographic test strips for diagnosing prosthetic joint infections.

OBJECTIVES: We developed a rapid and highly sensitive method for quantitatively analyzing neutrophil gelatinase-associated lipocalin (NGAL) levels in synovial fluid and assessed its diagnostic performance for prosthetic joint infection (PJI). DESIGNS OR METHODS: We conducted a preliminary analysis of the performance of the developed test strips utilizing clinical specimens to verify their sensitivity, precision, specificity and accuracy. RESULTS: The standard curve of the test strip NGAL values was linear. The detection limit and the limit of quantification (LOQ) were 12.37 and 29.49 ng/mL, respectively, and the approximate detection range was 12.37 to 1250 ng/mL. The interbatch and intrabatch precision of the test strips were each less than 10%, and the cross-reaction rate with competitors' systems was less than 1%. CONCLUSIONS: The test strips can be used for the determination of synovial fluid NGAL levels; the test strips are highly sensitive, precise, specific, and stable. Furthermore, they demonstrated good performance in clinical verification.

FTO Promotes the Stemness of Gastric Cancer Cells.

The full name of the FTO gene is fat mass and obesity-associated gene. In recent years, it has also been found that FTO is involved in m6A demethylation and regulates the progression of multiple cancers, including gastric cancer. The cancer stem cell theory argues that cancer stem cells are key factors in cancer metastasis, and inhibiting the expression of stemness genes is a good method to inhibit metastasis of gastric cancer. Currently, the role of the FTO gene in regulating stemness of gastric cancer cells is still unclear. By analyzing public databases, it was discovered that FTO gene expression was increased in gastric cancer, and high expression of FTO was associated with poor prognosis of patients with gastric cancer. After gastric cancer stem cells were isolated, it was found that FTO protein expression was increased in gastric cancer stem cells; stemness of gastric cancer cells was reduced after the FTO gene knockdown; subcutaneous tumors of nude mice were smaller than those of the control group after FTO knockdown; and stemness of gastric cancer cells was enhanced after FTO was overexpressed by plasmid. By reviewing additional literature and experimental validation, we found that SOX2 may be the factor by which FTO promotes the stemness of gastric cancer cells. Therefore, it was concluded that FTO could promote the stemness of gastric cancer cells, and targeting FTO may be a potential therapeutic approach for patients with metastatic gastric cancer. CTR number: TOP-IACUC-2021-0123.

CNTN1 in the Nucleus Accumbens is Involved in Methamphetamine-Induced Conditioned Place Preference in Mice.

Methamphetamine (Meth), a commonly used central nervous system stimulant, is highly addictive. Currently, there is no effective treatment for Meth dependence and abuse, although cell adhesion molecules (CAMs) have been shown to play an important role in the formation and remodeling of synapses in the nervous system while also being involved in addictive behavior. Contactin 1 (CNTN1) is a CAM that is widely expressed in the brain; nevertheless, its role in Meth addiction remains unclear. Therefore, in the present study, we established mouse models of single and repeated Meth exposure and subsequently determined that CNTN1 expression in the nucleus accumbens (NAc) was upregulated in mice following single or repeated Meth exposure, whereas CNTN1 expression in the hippocampus was not significantly altered. Intraperitoneal injection of the dopamine receptor 2 antagonist haloperidol reversed Meth-induced hyperlocomotion and upregulation of CNTN1 expression in the NAc. Additionally, repeated Meth exposure also induced conditioned place preference (CPP) in mice and upregulated the expression levels of CNTN1, NR2A, NR2B, and PSD95 in the NAc. Using an AAV-shRNA-based approach to specifically silence CNTN1 expression in the NAc via brain stereotaxis reversed Meth-induced CPP and decreased the expression levels of NR2A, NR2B, and PSD95 in the NAc. These findings suggest that CNTN1 expression in the NAc plays an important role in Meth-induced addiction, and the underlying mechanism may be related to the expression of synapse-associated proteins in the NAc. The results of this study improved our understanding of the role of cell adhesion molecules in Meth addiction.

Rotating Magnetic Field Mitigates Ankylosing Spondylitis Targeting Osteocytes and Chondrocytes via Ameliorating Immune Dysfunctions.

Ankylosing spondylitis (AS) is clinically characterized by bone fusion that is induced by the pathological formation of extra bone. Unfortunately, the fundamental mechanism and related therapies remain unclear. The loss of SHP-2 (encoded by Ptpn11) in CD4-Cre;Ptpn11f/f mice resulted in the induction of AS-like pathological characteristics, including spontaneous cartilage and bone lesions, kyphosis, and arthritis. Hence, this mouse was utilized as an AS model in this study. As one of the basic physical fields, the magnetic field (MF) has been proven to be an effective treatment method for articular cartilage degeneration. In this study, the effects of a rotating magnetic field (RMF; 0.2 T, 4 Hz) on an AS-like mouse model were investigated. The RMF treatment (2 h/d, 0.2 T, 4 Hz) was performed on AS mice from two months after birth until the day before sampling. The murine specimens were subjected to transcriptomics, immunomics, and metabolomics analyses, combined with molecular and pathological experiments. The results demonstrated that the mitigation of inflammatory deterioration resulted in an increase in functional osteogenesis and a decrease in dysfunctional osteolysis due to the maintenance of bone homeostasis via the RANKL/RANK/OPG signaling pathway. Additionally, by regulating the ratio of CD4+ and CD8+ T-cells, RMF treatment rebalanced the immune microenvironment in skeletal tissue. It has been observed that RMF interventions have the potential to alleviate AS, including by decreasing pathogenicity and preventing disease initiation. Consequently, RMF, as a moderately physical therapeutic strategy, could be considered to alleviate the degradation of cartilage and bone tissue in AS and as a potential option to halt the progression of AS.

Effects of Different Drying Methods on Drying Characteristics and Quality of Glycyrrhiza uralensis (Licorice).

Large amounts of waste result from licorice mold rot; moreover, prompt drying directly influences product quality and value. This study compared various glycyrrhiza drying methods (Hot air drying (HAD), infrared combined hot air drying (IR-HAD), vacuum freeze drying (VFD), microwave vacuum drying (MVD), and vacuum pulsation drying (VPD)) that are used in the processing of traditional Chinese medicine. To investigate the effects of various drying methods on the drying characteristics and internal quality of licorice slices, their color, browning, total phenol, total flavonoid, and active components (liquiritin and glycyrrhizic acid) were chosen as qualitative and quantitative evaluation indices. Our results revealed that VFD had the longest drying time, but it could effectively maintain the contents of total phenol, total flavonoid, and liquiritin and glycyrrhizic acid. The results also showed that VFD samples had the best color and the lowest degree of browning, followed by HAD, IR-HAD, and VPD. We think that VFD is the best approach to ensure that licorice is dry.

Effect of oral administration of gabapentin on the minimum alveolar concentration of isoflurane in cats.

Objective: To determine if oral gabapentin decreases the minimum alveolar concentration (MAC) of isoflurane in cats. Study design: Prospective, randomized, blinded, crossover, and experimental study. Animals: A total of six healthy adult cats (three male, three female) aged 18-42 months, weighing 3.31 ± 0.26 kg. Methods: Cats were randomly given oral gabapentin (100 mg cat-1) or placebo 2 h before starting MAC determination, with the crossover treatment given at least 7 days apart. Anesthesia was induced and maintained with isoflurane in oxygen. Isoflurane MAC was determined in duplicate using an iterative bracketing technique and tail clamp method. Hemodynamic and other vital variables were recorded at each stable isoflurane concentration and were compared between gabapentin and placebo treatments at lowest end-tidal isoflurane concentration when cats did not respond to tail clamping. A paired t-test was used to compare normally distributed data, and a Wilcoxon signed-rank test was applied for non-normally distributed data. Significance was set at p < 0.05. Data are mean ± standard deviation. Results: Isoflurane MAC in the gabapentin treatment was 1.02 ± 0.11%, which was significantly lower than that in the placebo treatment (1.49 ± 0.12%; p < 0.001), decreasing by 31.58 ± 6.94%. No significant differences were found in cardiovascular and other vital variables between treatments. Conclusion and clinical relevance: Oral administration of gabapentin 2 h before starting MAC determination had a significant isoflurane MAC-sparing effect in cats with no observed hemodynamic benefit.

The mtDNA-STING pathway plays an important role in both navitoclax- and S63845-induced autophagy and enhances cell death.

Targeting BCL2 family proteins to induce cancer cell death has been successful in the treatment of cancer. BH3 mimetics such as ABT-737 not only induce cell death, but also activate autophagy. The molecular mechanism by which the BH3 mimetics induce autophagy is still controversial. In this study, we show that the BCL2/BCLXL/BCLw inhibitor navitoclax and the MCL1 inhibitor S63845 induce both apoptosis and autophagy in mouse embryonic fibroblasts (MEFs) and leukemia cell lines, while autophagy induced by navticlax and S63845 in leukemia cell lines requires the inhibition of caspase activities. Further experiments demonstrate that the autophagy induced by navitoclax or S63845 does not depend on Beclin 1, but downstream of Bax/Bak. Moreover, both navitoclax and S63845 treatment induce mtDNA release in MEFs, which activates STING and thereby induces autophagy, while STING KO inhibits both navitoclax- and S63845-induced autophagy. Furthermore, STING KO diminishes navitoclax- or S63845-induced apoptosis, suggesting that STING activation enhances rather than inhibits apoptosis. Thus, our findings provide new insights into the regulations of navitoclax- or S63845-induced autophagy and cell death.

Physicochemical, Structural Structural and Functional Properties of Non-Waxy and Waxy Proso Millet Protein.

The physicochemical, structural and functional properties of proso millet protein from waxy and non-waxy proso millet were investigated. The secondary structures of proso millet proteins consisted mainly of a ß-sheet and ɑ-helix. The two diffraction peaks of proso millet protein appeared at around 9° and 20°. The solubility of non-waxy proso millet protein was higher than that of waxy proso millet protein at different pH values. Non-waxy proso millet protein had a relatively better emulsion stability index (ESI), whereas waxy proso millet protein had a better emulsification activity index (EAI). Non-waxy proso millet protein showed a higher maximum denaturation temperature (Td) and enthalpy change (ΔH) than its waxy counterpart, indicating a more ordered conformation. Waxy proso millet exhibited higher surface hydrophobicity and oil absorption capacity (OAC) than non-waxy proso millet, suggesting that the former may have potential applications as a functional ingredient in the food industry. There was no significant difference in the intrinsic fluorescence spectra of different waxy and non-waxy proso millet proteins at pH 7.0.