Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

General Hyperspectral Image Super-Resolution via Meta-Transfer Learning.

Recent advances in deep learning-based methods have led to significant progress in the hyperspectral super-resolution (SR). However, the scarcity and the high dimension of data have hindered further development since deep models require sufficient data to learn stable patterns. Moreover, the huge domain differences between hyperspectral image (HSI) datasets pose a significant challenge in generalizability. To address these problems, we present a general hyperspectral SR framework via meta-transfer learning (MTL). We randomly sample various spectral ranges for SR tasks during MTL, allowing the model to accumulate diverse task experiences. Additionally, we implement a task schedule to gradually expand the number of bands, bridging the significant domain differences between datasets. By leveraging multiple datasets, we are able to achieve better performance and greater generalizability, making it applicable under various circumstances. Meanwhile, as a general framework, our scheme can be applied to existing methods to obtain performance improvements. In addition, we design an advanced network architecture based on the multifusion features to further improve the performance. Experiments demonstrate that our method not only achieves superior performance in both qualitative and quantitative terms but also can adapt robustly to a new and difficult sample, where few epochs can yield quite considerable results.

Intervention Efficacy of Slightly Processed Allergen/Meat in Oral Immunotherapy for Seafood Allergy: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis in Mouse Models and Clinical Patients.

Background: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. Methods: A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case-control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. Results: The meta-analysis included five case-control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = -1.30, p < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = -0.63, p < 0.01, I2 = 0), arginine kinase allergen (MD = -0.83, p < 0.01, I2 = 0), and Maillard reaction processing method (MD = -0.65, p < 0.01, I2 = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, p < 0.01). Subgroup analyses for fish meat (IRR = 2.79, p < 0.01) and a simple cooking treatment (IRR = 2.36, p = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. Conclusions: This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary.

Prognostic marker CD27 and its micro-environmental in multiple myeloma.

BACKGROUND: The Cluster of Differentiation 27 (CD27) is aberrantly expressed in multiple myeloma (MM) -derived. This expression facilitates the interaction between tumor and immune cells within TME via the CD27-CD70 pathway, resulting in immune evasion and subsequent tumor progression. The objective of this study is to investigate the correlation between CD27 expression and the prognosis of MM, and to elucidate its potential relationship with the immune microenvironment. METHODS: In this research, CD27 expression in T cells within the 82 newly diagnosed MM microenvironment was assessed via flow cytometry. We then examined the association between CD27 expression levels and patient survival. Subsequent a series of bioinformatics and in vitro experiments were conducted to reveal the role of CD27 in MM. RESULTS: Clinical evidence suggests that elevated CD27 expression in T cells within the bone marrow serves as a negative prognostic marker for MM survival. Data analysis from the GEO database has demonstrated a strong association between MM-derived CD27 and the immune response, as well as the hematopoietic system. Importantly, patients with elevated levels of CD27 expression were also found to have an increased presence of MDSCs and macrophages in the bone marrow microenvironment. Furthermore, the PERK-ATF4 signaling pathway has been implicated in mediating the effects of CD27 in MM. CONCLUSIONS: We revealed that CD27 expression levels serve as an indicative marker for the prognosis of MM patients. The CD27- PERK-ATF4 is a promising target for the treatment of MM.

Yellow mustard gum: pilot-scale production and characterization.

BACKGROUND: Yellow mustard gum (YMG), which is extracted from the mucilaginous part of yellow mustard bran, has been considered an emerging natural hydrocolloid gum but lacks commercial development and production. To promote commercial utilization of YMG, this study developed a pilot-scale YMG production protocol in an economic and environmentally-friendly way to produce a clean-label YMG product. This pilot-scale produced YMG (YMW) was characterized in terms of chemical composition, rheological properties, and interaction with a commercial gum, κ-carrageenan and was compared with purified YMG through EtOH precipitation (YME). RESULTS: The protocol processed up to 100 L of raw material with zero solvent and minimal steps and showed great quasi-industrial potential. YMW showed a similar chemical composition as YME. However, YMW contained a slightly lower content of carbohydrates and a much larger amount of ash and potassium than YME. The rheological results concluded both YMW and YME solutions exhibited a shear-thinning flow behavior and a weak gel with YME showing higher viscosity and stronger gel structure. Most interestingly, YMW could form unpourable gels when blended with native κ-carrageenan while YME barely achieved this despite the equivalent total gum concentration. CONCLUSION: This study demonstrated the feasibility of YMG production at a large scale with economic and green procedures and discovered its new functionality for commercial utilization. The gelling ability could provide YMG with wider applications as a result of a new potential synergistic combination. All this information should accelerate the process of full commercialization of YMG as a clean-label functional ingredient. This article is protected by copyright. All rights reserved.

Identifying dynamic risk spillovers between crude oil and downstream industries: China's futures market perspective.

Interactions between crude oil and its downstream products are crucial but complex. The main purpose of this study is to examine the risk spillover relationships between the crude oil futures market and the petrochemical downstream futures market in the context of the COVID-19 epidemic in China. By combining the dynamic conditional correlation-generalized autoregressive conditional heteroskedasticity (DCC-GARCH) model and the Diebold-Yilmaz spillover index based on time-varying parameter-vector autoregression (TVP-VAR-DY), we investigate the dynamic correlations between Shanghai crude oil futures (INE) and the downstream futures in China's petrochemical industry chain. At the same time, we also incorporate the representative global crude oil futures (BRENT and WTI) in our study as a comparative analysis. Our results show a significant positive correlation between three crude oil futures and China's downstream future products, with a more pronounced link observed between INE and the downstream futures market. Moreover, the correlation between crude oil futures and various downstream products exhibits heterogeneity; that is, direct derivatives of crude oil show higher sensitivity to price fluctuations compared to products with longer production chains. Furthermore, the spillover results indicate that the international crude oil futures, particularly BRENT, primarily function as spillover transmitters, while INE mainly serves as the recipient. In the post-pandemic period, the international crude oil market still exhibits a high spillover effect, and the spillover effect of INE to polyvinyl chloride, pure terephthalic acid, and bitumen futures increased, reflecting market recovery in China to some extent. These results provide potential insights for policymakers, financial institutions, industry participants, and investors, emphasizing the importance of enhanced risk management, diversified investment strategies, and attention to market dynamics.

Detection of incipient rotor unbalance fault based on the RIME-VMD and modified-WKN.

Due to the high incidence and inconspicuous initial characteristics of rotor unbalance faults, the detection of incipient unbalance faults is becoming a very challenging problem. In this paper, a new method of small rotor unbalance fault diagnosis based on RIME-VMD and modified wavelet kernel network (modified-WKN) is proposed. Firstly, in order to extract the small unbalance fault information from the vibration signals with low signal-to-noise ratio (SNR) more efficiently, the RIME algorithm is used to search for the optimal location of the penalty factor and decomposition layer in the variable mode decomposition (VMD). Secondly, the most relevant decomposition components to the small unbalance fault information are selected by using Pearson Correlation Coefficients and utilized to reconstruct the signal. Finally, the modified-WKN diagnostic model that is used for multi-sensor data fusion is constructed. The model can acquire features of vibration signals from multiple position sensors, which enhances the ability of the modified WKN diagnostic model to deal with incipient fault modes. Based on the experimental analysis of rotor unbalance fault datasets with different SNRs, it is verified that the detection performance of the proposed method is better than the traditional WKN and VMD-WKN methods. Specifically, the proposed method is more sensitive to the initial unbalance faults.

Piceatannol protects against myocardial ischemia/reperfusion injury by inhibiting ferroptosis via Nrf-2 signaling-mediated iron metabolism.

Myocardial tissue ischemia damages myocardial cells. Although reperfusion is an effective technique to rescue myocardial cell damage, it may also exacerbate myocardial cell damage. Ferroptosis, an iron-dependent cell death, occurs following myocardial ischemia-reperfusion (I/R). Piceatannol (PCT) is a natural stilbene compound with excellent antioxidant properties that protect against I/R injury and exerts protective effects against ferroptosis-induced cardiomyocytes following I/R injury; however, the exact mechanism remains to be elucidated. PURPOSE: This study aims to investigate the protective effect and mechanism of PCT on myocardial ischemia-reperfusion injury. METHODS: An ischemia-reperfusion model was established via ligation of the left anterior descending branch of mice's hearts and hypoxia-reoxygenation (H/R) of cardiomyocytes. RESULTS: During ischemia-reperfusion, Nuclear factor E2-related factor 2 (Nrf-2) expression was downregulated, the left ventricular function was impaired, intracellular iron and lipid peroxidation product levels were elevated, and cardiomyocytes underwent ferroptosis. Furthermore, ferroptosis was enhanced following treatment with an Nrf-2 inhibitor. After PCT treatment, Nrf-2 expression significantly increased, intracellular ferrous ions and lipid peroxidation products significantly reduced, Ferroportin1 (FPN1) expression increased, and transferrin receptor-1 (TfR-1) expression was inhibited. CONCLUSIONS: PCT regulates iron metabolism through Nrf-2 to protect against myocardial cell ferroptosis induced by myocardial I/R injury.

The alleviation of salt stress on rice through increasing photosynthetic capacity, maintaining redox homeostasis and regulating soil enzyme activities by Enterobacter sp. JIV1 assisted with putrescine.

The detrimental impact of soil salinization on crop productivity and agricultural economy has garnered significant attention. A rhizosphere bacterium with favorable salt tolerance and plant growth-promoting (PGP) functions was isolated in this work. The bacterium was identified as Enterobacter through 16 S rDNA sequencing analysis and designated as Enterobacter sp. JIV1. Interestingly, the presence of putrescine (Put), which had been shown to contribute in reducing abiotic stress damage to plants, significantly promoted strain JIV1 to generate 1-aminocyclopropane-1-carboxylic (ACC) deaminase, dissolve phosphorus and secrete indole-3-acetic acid (IAA). However, the synergy of plant growth promoting rhizobacteria (PGPR) and Put in improving plant salt resistance has not been extensively studied. In this study, strain JIV1 and exogenous Put effectively mitigated the inhibitory impact of salt stress simulated by 200 mM NaCl on rice (Oryza sativa L.) growth. The chlorophyll accumulation, photosynthetic efficiency and antioxidant capacity of rice were also significantly strengthened. Notably, the combined application of strain JIV1 and Put outperformed individual treatments. Moreover, the co-addition of strain JIV1 and Put increased soil protease and urease activities by 451.97% and 51.70% compared to that of salt treatment group. In general, Put-assisted PGPR JIV1 provides a new perspective on alleviating the salt-induced negative impacts on plants.

S100A8, S100A9 and S100A8/A9 heterodimer as novel cachexigenic factors for pancreatic cancer-induced cachexia.

BACKGROUND: Cancer cachexia, occurring in ~ 80% pancreatic cancer (PC) patients overall, is a paraneoplastic syndrome mediated by cancer-induced systemic inflammation and characterized by weight loss and skeletal muscle wasting. Identifying clinically relevant PC-derived pro-inflammatory factors with cachexigenic potential may provide novel insights and therapeutic strategies. METHODS: Pro-inflammatory factors with cachexigenic potential in PC were identified by bioinformatic analysis. The abilities of selected candidate factors in inducing skeletal muscle atrophy were investigated. Expression levels of candidate factors in tumors and sera was compared between PC patients with and without cachexia. Associations between serum levels of the candidates and weight loss were assessed in PC patients. RESULTS: S100A8, S100A9, and S100A8/A9 were identified and shown to induce C2C12 myotube atrophy. Tumors of PC patients with cachexia had markedly elevated expression of S100A8 (P = 0.003) and S100A9 (P < 0.001). PC patients with cachexia had significantly higher serum levels of S100A8, S100A9 and S100A8/A9. Serum levels of these factors positively correlated with percentage of weight loss [correlation coefficient: S100A8: 0.33 (P < 0.001); S100A9: 0.30 (P < 0.001); S100A8/A9: 0.24 (P = 0.004)] and independently predicted the occurrence of cachexia [adjusted odds ratio (95% confidence interval) per 1ng/ml increase: S100A8 1.11 (1.02-1.21), P = 0.014; S100A9 1.10 (1.04-1.16), P = 0.001; per 1 µg/ml increase: S100A8/A9 1.04 (1.01-1.06), P = 0.009]. CONCLUSIONS: Atrophic effects of S100A8, S100A9, and S100A8/A9 indicated them as potential pathogenic factors of PC-induced cachexia. In addition, the correlation with the degree of weight loss and prediction of cachexia in PC patients implicated their potential utility in the diagnosis of PC-induced cachexia.

Piceatannol protects against age-related hearing loss by inhibiting cellular pyroptosis and inflammation through regulated Caspase11-GSDMD pathway.

Age-related hearing loss (ARHL) is a common issue associated with aging. One of the typical causes of hearing loss is the damage to inner ear hair cells. In addition, oxidative stress and inflammation contribute to ARHL. To avoid excessive inflammatory responses, non-classical scorch death pathway by cell membrane lipopolysaccharide (LPS) activates of caspase-11. Piceatannol (PCT) is also known for anti-tumor, antioxidant and anti-inflammatory effects; however, the protective effect of piceatannol (PCT) on ARHL is unclear. The aim of this study was to elucidate the mechanism underlying protective effect of PCT on ARHL-induced inner ear hair cell damage. In vivo experiments showed that PCT could protect mice from inflammatory aging-induced hearing loss as well as from inner hair cells (IHC) and spiral ganglion (SG) deficits. In addition, inflammatory vesicle inhibitor BAY11-7082 ameliorated ARHL, inhibited NLRP3 and reduced GSDMD expression. In in vitro experiments we used LPS and D-gal to simulate the aging inflammatory environment. The results showed that intracellular reactive oxygen species levels, expression of Caspase-11, NLRP3, and GSDMD were significantly increased, yet treatment with PCT or BAY11-7082 significantly improved HEI-OC-1 cell injury while reducing inflammation-associated protein expression as well as the occurrence of pyroptosis. In conclusion, these results suggest a protective role for PCT against ARHL, possibly through Caspase-11-GSDMD pathway. Our findings may provide a new target and theoretical basis for hearing loss treatment using PCT.

RNA binding protein SAMD4: current knowledge and future perspectives.

SAMD4 protein family is a class of novel RNA-binding proteins that can mediate post-transcriptional regulation and translation repression in eukaryotes, which are highly conserved from yeast to humans during evolution. In mammalian cells, SAMD4 protein family consists of two members including SAMD4A/Smaug1 and SAMD4B/Smaug2, both of which contain common SAM domain that can specifically bind to different target mRNAs through stem-loop structures, also known as Smaug recognition elements (SREs), and regulate the mRNA stability, degradation and translation. In addition, SAMD4 can form the cytoplasmic mRNA silencing foci and regulate the translation of SRE-containing mRNAs in neurons. SAMD4 also can form the cytosolic membrane-less organelles (MLOs), termed as Smaug1 bodies, and regulate mitochondrial function. Importantly, many studies have identified that SAMD4 family members are involved in various pathological processes including myopathy, bone development, neural development, and cancer occurrence and progression. In this review, we mainly summarize the structural characteristics, biological functions and molecular regulatory mechanisms of SAMD4 protein family members, which will provide a basis for further research and clinical application of SAMD4 protein family.

Combined application of allantoin and strain JIT1 synergistically or additively promotes the growth of rice under 2, 4-DCP stress by enhancing the phosphate solubility, improving soil enzyme activities and photosynthesis.

Environmental pollution by 2, 4 dichlorophenol (2, 4-DCP) has become a widespread concern due to its detrimental influence on human and natural ecosystem. With the increasing accumulation of 2, 4-DCP in soil, it is of great significance to explore some appropriate approaches for enhancing plant tolerance to 2, 4-DCP stress. In the current study, a strain resistant to 2, 4-DCP was obtained from the tall fescue rhizosphere soil and named as Pseudomonas sp. JIT1. The strain JIT1 exhibited several remarkable plant growth-promoting traits, including the production of IAA, fixation of biological nitrogen and solubilization of phosphate. The inoculation of strain JIT1 significantly increased biomass, photosynthesis, antioxidant levels, chlorophyll contents and the osmotic substance contents in rice seedlings exposed to 2, 4-DCP. Meanwhile, inoculation of strain JIT1 also enhanced activities of soil alkaline phosphatase, urease, sucrase and cellulase. Moreover, under 2, 4-DCP stress, the content of allantoin in seedlings significantly increased and the pretreatment of exogenous allantoin noticeably ameliorated the negative effects caused by 2, 4-DCP stress in rice seedlings. Interesting, allantoin treatment also enhanced phosphate solubilization properties of strain JIT1. The chlorophyll contents, photosynthesis and osmotic substance further increased by combination use of strain JIT1 and allantoin, which improved the growth of seedlings, most likely to be attributed to the synergistic or additive effect between allantoin and strain JIT1. The results of this study highlight the important roles of combined use of strain JIT1 and allantoin for improving the tolerance of rice to 2, 4-DCP to stress.

The combined use of a plant growth promoting Bacillus sp. strain and GABA promotes the growth of rice under salt stress by regulating antioxidant enzyme system, enhancing photosynthesis and improving soil enzyme activities.

Salt stress poses a global challenge for agriculture, crop growth, and food production. In this study, a strain of rhizobacteria with both plant growth-promoting (PGP) traits and salt tolerance was isolated. The strain was identified as Bacillus pumilus via 16 S rDNA sequencing and was named B. pumilus JIZ13. This strain had the potential to solubilize phosphates and produce 1-aminocyclopropane-1-carboxylic acid deaminase, siderophores, and indole-3-acetic acid. After 35 days of salt stress exposure, the root length, plant height, dry weight, fresh weight, and relative water content of rice plants inoculated with strain JIZ13 were significantly higher than those without inoculation. Interestingly, the PGP properties of strain JIZ13 were significantly improved by the exogenous addition of gamma-aminobutyric acid (GABA). Moreover, GABA also enhanced the growth and development of rice plants under salt stress by providing substrates for the tricarboxylic acid cycle. Furthermore, the synergistic roles of GABA and strain JIZ13 in mitigating the damage caused by salt stress in rice plants was investigated. The results showed that the co-application of GABA and JIZ13 significantly increased photosynthetic efficiency, chlorophyll accumulation, antioxidant levels, levels of osmotic adjustment substances, and biomass of rice under salinity stress. In addition, the activities of urease, protease, invertase, and catalase enzymes in soil significantly improved under the combination of strain JIZ13 and GABA and increased by 39.65%, 36.88%, 70.21%, and 65.23%, respectively, compared to those without rhizobacterial and GABA additions. The enhancement of these four soil enzyme activities might thus improve soil quality and increase root elongation and biomass in rice plants. The results of this study provide the first evidence that PGP-rhizobacterial strain JIZ13 along with GABA can attenuate the negative effects of salt stress in rice plants.

Investigating the effects of biodegradable microplastics and copper ions on probiotic (Bacillus amyloliquefaciens): Toxicity and application.

Currently, microplastic pollution is more serious and complicates the toxic effects of other co-existing pollutants in the environment. However, the effect and mechanism of biodegradable plastics on the growth and metabolism of probiotic remain unclear. This work selected Bacillus amyloliquefaciens as model bacterium for a three-day exposure experiment to probe the issues. The results showed that 100 mg/L polylactic acid microplastics (PLA MPs) (3-4 mm, flake shape) caused oxidative damage to cell membranes, disrupted cell wall composition and inhibited cell growth by 21.2-27.5 %. The toxicity was not simply additive or synergistic effects when PLA MPs (100 mg/L) and copper ions (10 mg/L) coexisted. PLA MPs did not significantly increase the toxicity of copper to bacteria, instead triggered some mechanisms to resist the toxicity of copper. The bacteria formed spores to resist PLA MPs, while the copper ions toxicity was weaken by chelation and efflux. It is worth noting that copper ions instead increased the expression of genes related fengycin and iturin then improving the bacteriostatic activity of the probiotic. This paper deeply analyzes the toxicity mechanism of combined pollution on Bacillus amyloliquefacien, and also provides new perspective for helping to inhibit pathogenic bacteria under biodegradable microplastics and metal stress.

Recent Progress in Biosensors for Detection of Tumor Biomarkers.

Cancer is a leading cause of death worldwide, with an increasing mortality rate over the past years. The early detection of cancer contributes to early diagnosis and subsequent treatment. How to detect early cancer has become one of the hot research directions of cancer. Tumor biomarkers, biochemical parameters for reflecting cancer occurrence and progression have caused much attention in cancer early detection. Due to high sensitivity, convenience and low cost, biosensors have been largely developed to detect tumor biomarkers. This review describes the application of various biosensors in detecting tumor markers. Firstly, several typical tumor makers, such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), squamous cell carcinoma antigen (SCCA), carbohydrate, antigen19-9 (CA19-9) and tumor suppressor p53 (TP53), which may be helpful for early cancer detection in the clinic, are briefly described. Then, various biosensors, mainly focusing on electrochemical biosensors, optical biosensors, photoelectrochemical biosensors, piezoelectric biosensors and aptamer sensors, are discussed. Specifically, the operation principles of biosensors, nanomaterials used in biosensors and the application of biosensors in tumor marker detection have been comprehensively reviewed and provided. Lastly, the challenges and prospects for developing effective biosensors for early cancer diagnosis are discussed.

HNRNPA2B1-mediated m6A modification of TLR4 mRNA promotes progression of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a malignancy of plasma cells that remains incurable. Toll-like receptor 4 (TLR4) acts as a stress-responsive signal, protecting mitochondria during proteasome inhibitor (PI) exposure, maintaining mitochondrial metabolism and increasing drug resistance in MM. However, the mechanism of TLR4 regulation remains elusive. AIMS: The purpose of this study was to investigate the methylation pattern of multiple myeloma and its effect on the expression of HNRNPA2B1 and downstream targets. METHODS: The methylation level in MM and normal bone marrow specimens was detected using a colorimetric assay. HNRNPA2B1 gene knockdown was achieved in RPMI 8226 MM cells via adenovirus transfection. CCK8 and flow cytometric assays were used to detect proliferation and apoptosis, respectively. Transcriptome sequencing and m6A methylation MeRIP sequencing were applied, and differentially expressed genes (DEGs) were detected. Three independent NCBI GEO datasets were applied to examine the effects of HNRNPA2B1 and TLR4 expression on MM patient survival. RESULTS: HNRNPA2B1 promoted MM progression. Clinical data from database revealed that HNRNPA2B1 was adverse prognostic factor for survival among MM patients. Furthermore, transcriptome sequencing and methylation sequencing showed that HNRNPA2B1 recognized and was enriched at the m6A sites of TLR4 and TLR4 was down-regulated of both the m6A level and transcription level in HNRNPA2B1-knockdown MM cells. Moreover, TLR4 was an adverse survival prognostic factor based on database analysis. CONCLUSION: Overall, our study implies that the RNA-binding protein HNRNPA2B1 increases cell proliferation and deregulates cell apoptosis in MM through TLR4 signaling. Our study suggests HNRNPA2B1 as a potential therapeutic target for MM.

Mechanistic understanding of the effect of zein-chlorogenic acid interaction on the properties of electrospun nanofiber films.

The interaction mechanism between zein and chlorogenic acid (CA) and the effect of interaction on the performance of coaxial nanofiber films were investigated. The interactions between zein and CA were characterized by multiple spectroscopic methods. Ultraviolet spectrum analysis revealed the formation of a zein-CA complex. Fluorescence analysis pointed out that the quenching of zein by CA was static. FTIR and thermodynamic analyses showed that hydrogen bonds and electrostatic interactions dominated the interaction between zein and CA. Zein-based nanofiber films were successfully prepared by coaxial electrospinning. The interaction between zein and CA enhanced the mechanical properties but reduced the thermal stability of nanofiber films. The presence of CA endowed nanofiber films with antioxidant and antibacterial properties. This research provides significant insight into the effect of protein-polyphenol interactions on the properties of electrospun nanofiber films, which can be applied in the field of active packaging to improve food safety.

FAM96A and FAM96B function as new tumor suppressor genes in breast cancer through regulation of the Wnt/ß-catenin signaling pathway.

AIMS: Family with sequence similarity 96 member A and B (FAM96A and FAM96B) are two highly conserved homologous proteins belonging to MIP18 family. Some studies have shown that FAM96A and FAM96B are significantly down-regulated in human gastrointestinal stromal tumors, colon cancer, and liver cancer. However, the molecular mechanisms of FAM96A/B in breast cancer are unknown. This work aims to explore the roles of FAM96A/B in breast cancer progression. MAIN METHODS: Specific siRNAs were used to down-regulate FAM96A/B expression, and recombinant plasmids were used to up-regulate FAM96A/B expression in breast cancer cells. Cell proliferation was measured using MTT and colony formation. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion were examined by wound healing and transwell assays. The relationships among FAM96A/B, EMT and Wnt/ß-catenin pathway were determined by analyzing expression changes of classical markers. KEY FINDINGS: We found that FAM96A/B expression was down-regulated in breast cancer. FAM96A/B overexpression suppressed breast cancer cell proliferation, invasion and migration, induced cell apoptosis and caused cell cycle arrest. Conversely, FAM96A/B knockdown exhibited the opposite effects. Moreover, our data demonstrated that FAM96A/B overexpression suppressed EMT and Wnt/ß-catenin pathway, while FAM96A/B knockdown showed the promoting effects on EMT and Wnt/ß-catenin pathway. Furthermore, a Wnt pathway inhibitor, XAV-939 reversed the promoting effects of FAM96A/B knockdown on breast cancer progression. SIGNIFICANCE: Our findings suggest that FAM96A/B may function as new tumor suppressor genes and inhibit breast cancer progression via modulating Wnt/ß-catenin pathway, which can provide the potential markers for breast cancer diagnosis and therapy.