Targeting microbiota-immune-synaptic plasticity to explore the effect of tea polyphenols on improving memory in the aged type 2 diabetic rat model.

OBJECTIVES: The study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis. METHODS: The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study. RESULTS: Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-κB signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes. DISCUSSION: TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-κB signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease.

[Tea polyphenols improves depression-like behavior in aged type 2diabetes rats by regulating microglia polarization].

OBJECTIVE: To investigate the effect of tea polyphenols(TP) on improving depression-like behavior in aged type 2 diabetes(T2DM) model rats. METHODS: A total of 40 8-week-old SD male rats were randomly divided into the control group(n=10) and the modeling group(n=30) according to the body weight. The rats in the modeling group were fed with high-glucose and high-fat diet and treated with 50 mg/kg D-galactose by intraperitoneal injection daily until the end of the experiment, while the rats in the control group were fed with the standard diet and treated with an equal volume of saline by intraperitoneal injection. After 4 weeks, the rats in the modeling group were injected with 25 mg/kg STZ, meanwhile the rats in the control group were injected with an equal volume of citric acid buffer. The level of fasting blood glucose(FBG) was measured on the 14~(th) day. When FBG≥16.7 mmol/L, the rats were identified as successful model of the T2DM rats. Then, the model rats were randomly divided into the model group, 150, 300 mg/kg TP groups(n=10, respectively), and the rats were given intragastric intervention for 8 weeks. The levels of the FBG were detected, and the depression-like behavior of rats was assessed by the open field test(OFT) and forced swimming test(FST). The density of microglia in hippocampus CA1 region was assessed by immunofluorescence staining, and protein expressions of P53, Iba1, iNOS, Arg-1 and BDNF were determined by western blot. RESULTS: Compared with the control group, the levels of FBG in the rats of the model group were obviously increased(P<0.01). In the OFT, the frequencies of rearing and grooming in the rats of model group markedly was decreased, while in the FST, the immobility time extensively was increased(P<0.01). The density of microglia in hippocampus CA1 region was increased(P<0.01). The expressions of P53, Iba1 and iNOS were increased, and the expressions of Arg-1 and BDNF were decreased(P<0.01). Additionally, compared with the model group, in the OFT, the frequencies of rearing and grooming were increased in the rats in 150 and 300 mg/kg TP group(P<0.01). The density of microglia in hippocampus CA1 region was decreased(P<0.01). The expressions of P53, Iba1 and iNOS were down-regulated, and the expression of BDNF was up-regulated(P<0.01). Additionally, compared with the model group, the levels of FBG was decreased in the rats in the 300 mg/kg TP group(P<0.01). The immobility time was decreased in the FST(P<0.01). The expression of Arg-1 was down-regulated(P<0.01). CONCLUSION: TP can improve depression-like behavior in aged T2DM model rats, and its mechanism may be related to regulate microglia M1/M2 polarization and up-regulate expression of BDNF in hippocampus.

[Mechanism of tea polyphenols improving the sarcopenia in the aged type 2 diabetes model rats via mitochondrial quality control].

OBJECTIVE: To explore whether tea polyphenols(TP) improve sarcopenia in the aged type 2 diabetes(T2DM)model rats via mitochondrial quality control(MQC). METHODS: A total of 55 2-month-old male SD rats were randomly divided into the control group(n=10), the aged model group(aged, n=10) and the aging T2DM model group(n=35). The aging T2DM model group rats were fed with high-sugar and high-fat diet and intraperitoneally injected with 50 mg/kg D-galactose daily. After 4 weeks, the aging T2DM model group rats were given a single intraperitoneal injection of 30 mg/kg streptozotocin(STZ). After STZ injection for 2 weeks, fasting blood glucose(FBG) ≥ 16.7 mmol/L was defined as successful T2DM model. When the model was successfully induced, the 30 model rats were randomly divided into aged T2DM group(Mod), 300 mg/kg TP teatment group(TP) and 3 mg/kg rosiglitazone treatment group(RSG) according to FBG, with 10 rats in each group. Each group was treated with 50 mg/kg D-galactose to induce senescence and fed with high glucose and fat for 8 weeks. Western blot was used to detect the expression of P53 protein in gastnemius muscle tissue of the model group at the end of the experiment, which was higher than that of the control group, indicating that the aging T2DM model was successfully established. FBG was detected by the blood glucose meter, gastnemius muscle relative weights was calculated, the microstructure of mitochondria of gastnemius muscle was observed by transmission electron microscope(TEM), the expression of mitochondrial biosynthesis-related proteins PGC-1α, mitochondrial dynamics-related proteins(OPA1, DRP1) and mitochondrial autophagy-related proteins(P62, LC3) in gastnemius muscle were detected by western blot. RESULTS: Compared with the control group, the level of FBG and the expression of P53 in the Mod group were increased(P<0.01). The gastnemius muscle relative weights, the expression level of PGC-1α, OPA1 and the ratio of LC3II/LC3I were decreased(P<0.01). The expression level of P62 and DRP1 were significantly increased(P<0.01). The number of mitochondria decreased, the volume decreased and a large number of vacuolization, and there were no obvious autophagolysosomes and fission and fusion. After 8 weeks, compared with the Mod group, the number of mitochondria in the gastrocnemius of TP and RSG groups, vacuolization, fission and fusion were improved, and the autophagolysosomes was significantly increased. The expression levels of P53, DRP1 and P62, the level of FBG in the TP group were significantly decreased(P<0.01, P<0.05). The expression levels of OPA1 and PGC-1α, the ratios of LC3II/LC3I and gastnemius muscle relative weights were significantly increased(P<0.05, P<0.01). CONCLUSION: TP can improve the sarcopenia in the aged T2DM model rats, and its mechanism is related to the regulation of mitochondrial quality control.

1D-CNN-based audio tampering detection using ENF signals.

The extensive adoption of digital audio recording has revolutionized its application in digital forensics, particularly in civil litigation and criminal prosecution. Electric network frequency (ENF) has emerged as a reliable technique in the field of audio forensics. However, the absence of comprehensive ENF reference datasets limits current ENF-based methods. To address this, this study introduces ATD, a blind audio forensics framework based on a one-dimensional convolutional neural network (1D-CNN) model. ATD can identify phase mutations and waveform discontinuities within the tampered ENF signal, without relying on an ENF reference database. To enhance feature extraction, the framework incorporates characteristics of the fundamental harmonics of ENF signals. In addition, a denoising method termed ENF noise reduction (ENR) based on the variational mode decomposition (VMD) and robust filtering algorithm (RFA) is proposed to reduce the impact of external noise on embedded electric network frequency signals. This study investigates three distinct types of audio tampering-deletion, insertion, and replacement-culminating in the design of binary-class tampering detection scenarios and four-class tampering detection scenarios tailored to these tampering types. ATD achieves a tampering detection accuracy of over 93% in the four-class scenario and exceeds 96% in the binary-class scenario. The effectiveness, efficiency, adaptability, and robustness of ATD in the two and four classification scenarios have been confirmed by extensive experiments.

Improving the emulsifying capacity of brewers' spent grain arabinoxylan by carboxymethylation.

Arabinoxylan derived from brewers' spent grain was carboxymethylated, and the emulsifying capacity of carboxymethylated arabinoxylans (CMAX) with different degrees of substitution (DS) was investigated. Results showed that carboxymethylation greatly enhanced the emulsifying capacity and emulsion stability of CMAX compared to the initial arabinoxylan. CMAX developed decreased ζ-potential, higher hydrophilicity, and improved interfacial adsorption capacity. Consequently, the denser and stronger interface on the oil droplet was formed, and the stabilizing mechanism was altered. Moreover, CMAX with lower DS could effectively stabilize emulsions during storage at a concentration of 0.5 % and pH between 6 and 7. Higher DS, however, led to poorer emulsion stability and greater flocculation as a result of the fragile interface formed by excess intermolecular ionic force. The research found CMAX potential in emulsion stabilizing and further applications in food processing.

Exploring trust determinants influencing the intention to use fintech via SEM approach: Evidence from Pakistan.

Many fintech consumers are hesitant to perform online transactions given the lack of trust in online companies. In response to this reality, we construct and evaluate a trust-theoretic user acceptability model for financial technologies. The research seeks to look at the influence of trust on the intention to use fintech. A sampling of potential users in Pakistan is used to validate the model experimentally. Smart PLS 3 has been used to robust the theorized configuration of constructs (structural equation modeling) based on 275 survey responses. Contrary to other scenarios, the findings indicate that "customer trust in fintech" is more important than other aspects in determining technology adoption. Pakistani consumers' intention is positively affected by trust. Trust facilitators influence consumers' trust; among them, trust propensity is the factor having high values, followed by perceived size, interaction with online customers, perceived benefit, third-party seal, perceived ease of use, and perceived reputation.

Preliminary research on the flavor substance and antioxidant capacity of beers produced with baking Qingke.

The addition of baked Qingke improves the flavor profile of beer. In this study, beer was brewed using Qingke baked at various temperatures. The beer produced with Qingke baked at 180 °C achieved the highest sensory score (40/50), an alcohol content of 6.92% (v/v), a total phenolic content of 446.42 mg/L, melanoidin concentration of 98.22 g/L, a color value of 10.88 EBC, and exhibited satisfactory antioxidant activity. Analysis of volatile compounds using HS-SPME-GC-MS revealed 48 compounds, of which esters accounted for 63% and alcohols accounted for 27% of the total content. The flavor profile of the beer varied across different baking temperatures. Pyrazines and aldehydes were predominantly present in samples baked at higher temperatures (T3, T4, and T5). Correlation analysis showed that the baking flavor in the beer was primarily correlated with 2, 5-dimethyl-pyrazine, trimethyl-pyrazine, phenylacetaldehyde, and ethyl 9-decenoate (R > 0.9).

Surfactant-mediated bio-manufacture: A unique strategy for promoting microbial biochemicals production.

Biochemicals are widely used in the medicine and food industries and are more efficient and safer than synthetic chemicals. The amphipathic surfactants can interact with the microorganisms and embed the extracellular metabolites, which induce microbial metabolites secretion and biosynthesis, performing an attractive prospect of promoting the biochemical production. However, the commonness and differences of surfactant-mediated bio-manufacture in various fields are largely unexplored. Accordingly, this review comprehensively summarized the properties of surfactants, different application scenarios of surfactant-meditated bio-manufacture, and the mechanism of surfactants increasing metabolites production. Various biochemical productions such as pigments, amino acids, and alcohols could be enhanced using the cloud point and the micelles of surfactants. Besides, the amphiphilicity of surfactants also promoted the utilization of fermentation substrates, especially lignocellulose and waste sludge, by microorganisms, indirectly increasing the metabolites production. The increase in target metabolites production was attributed to the surfactants changing the permeability and composition of the cell membrane, hence improving the secretion ability of microorganisms. Moreover, surfactants could regulate the energy metabolism, the redox state and metabolic flow in microorganisms, which induced target metabolites synthesis. This review aimed to broaden the application fields of surfactants and provide novel insights into the production of microbial biochemicals.

The association between the triglyceride-glucose index and prognosis in postoperative renal cell carcinoma patients: a retrospective cohort study.

Background: Insulin resistance has been proven to be associated with renal cell carcinoma (RCC). However, the prognostic value of the triglyceride-glucose (TyG) index, as a marker for insulin resistance (IR), is still unclear. Therefore, we conducted research to explore the prognostic value and the predictive performance of the TyG index in postoperative RCC patients. Methods: A total of 651 postoperative RCC patients from January 2016 to June 2018 were enrolled in the final study. Their clinical and laboratory parameters were collected from medical records and through follow-up by phone. The triglyceride-glucose (TyG) index was calculated as follows: TyG = Ln[TG (mg/dl) × FBG (mg/dL)/2]. The overall survival (OS) and disease-free survival (DFS) were identified as the main outcomes. Results: The TyG index is an independent prognostic factor for OS (HR = 2.340, 95% CI = 1.506 to 3.64, P < 0.001) and DFS (HR = 2.027, 95% CI = 1.347 to 3.051, P < 0.001) in postoperative RCC patients. Kaplan-Meier survival curves of the different TyG index levels showed statistically significant differences in terms of OS and DFS (log-rank test, P < 0.0001). Furthermore, the TyG index was significantly associated with RCC risk factors. Conclusion: The TyG index is significantly associated with RCC survival. The mechanisms responsible for these results may contribute toward the improvement of RCC prognosis and immunotherapy efficacy and the development of new immunotherapeutic targets.

Fucoidan enhances the anti-tumor effect of anti-PD-1 immunotherapy by regulating gut microbiota.

Currently, the clinical efficacy of anti-PD-1/PD-L1 monotherapy strategies against breast cancer is limited, and low response rates need to be improved. Gut microbiota plays a crucial role in the sensitization process of immunotherapy. As a natural dietary supplement, fucoidan has been reported to have immunomodulatory effects, while some studies have found that oral fucoidan may act as a potential prebiotic to modulate the gut microbiota. Therefore, this study investigated whether fucoidan could enhance the effects of anti-PD-1 monoclonal antibody antitumor immunotherapy by modulating gut microbiota and its metabolites. We found that the anti-tumor effect of the combination treatment was significantly enhanced, while fucoidan significantly improved the composition of the gut microbiota by increasing the number of potentially beneficial bacteria, such as Bifidobacterium, Faecalibaculum and Lactobacillus. Interference with the gut microbiota by antibiotics revealed impaired antitumor efficacy, confirming the necessity of gut microbiota in the antitumor effects of fucoidan in vivo. Metabolomics further revealed that fucoidan may have reversed the metabolic disturbances induced by the breast cancer model through tryptophan metabolism and glycerophospholipid metabolism pathways, with the most significant increase in the content of short-chain fatty acids, especially acetic and butyric acids. These modulations improved the function of effector T cells and suppressed Treg cell production. Thus, our findings suggest that fucoidan combined with the anti-PD-1 monoclonal antibody may be a novel strategy to sensitize breast cancer patients to anti-PD-1 monoclonal antibody immunotherapy. Meanwhile, the gut microbiota might serve as a new biomarker to predict the anti-PD-1 monoclonal antibody response to breast cancer immunotherapy.

Nondestructive Direct Optical Patterning of Perovskite Nanocrystals with Carbene-Based Ligand Cross-Linkers.

Microscale patterning of colloidal perovskite nanocrystals (NCs) is essential for their integration in advanced device platforms, such as high-definition displays. However, perovskite NCs usually show degraded optical and/or electrical properties after patterning with existing approaches, posing a critical challenge for their optoelectronic applications. Here we achieve nondestructive, direct optical patterning of perovskite NCs with rationally designed carbene-based cross-linkers and demonstrate their applications in high-performance light-emitting diodes. We reveal that both the photochemical properties and the electronic structures of cross-linkers need to be carefully tailored to the material properties of perovskite NCs. This method produces high-resolution (∼4000 ppi) NC patterns with preserved photoluminescent quantum efficiencies and charge transport properties. Prototype light-emitting diodes with patterned/cross-linked NC layers show a maximum luminance of over 60000 cd m-2 and a peak external quantum efficiency of 16%, among the highest for patterned perovskite electroluminescent devices. Such a material-adapted patterning method enabled by designs from a photochemistry perspective could foster the applications of perovskite NCs in system-level electronic and optoelectronic devices.

Deapioplatycodin D promotes cell senescence induced by P21 through the mediation of incomplete mitophagy via BNIP3L.

Deapioplatycodin D (DPD) is a triterpenoid saponin extracted from the root of Platycodon grandiflorum, which is a common source of medicine and food. Platycodon grandiflorum saponins have anti-inflammatory, antioxidative, antitumor, and immunity-promoting effects. However, the effect of DPD on hepatocellular carcinoma (HCC) cells has not been reported. The purpose of this study was to explore the cytotoxic effects and molecular mechanisms of DPD on HCC cells. Our study revealed that DPD significantly inhibits the proliferation of HCC, as demonstrated by the CCK-8 assay, and then we analyzed the inhibitory effects and pathways of DPD on HCC cells by Western blot and immunofluorescence assay, and found that DPD could increase the changes of autophagy-related protein levels, but had no significant effect on the expression of apoptosis-related proteins, and induced cell senescence. Then, transcriptomics analysis revealed that differential genes were significantly enriched in cell senescence and autophagy pathways and significant expression of mitochondrial autophagy-related gene BNIP3L and senescence-related gene P21. Subsequently, autophagy and cell senescence were analyzed using gene silencing, and it was found that DPD caused mitochondrial damage and promoted reactive oxygen species production, leading to the inhibition of autophagic fluxes and mitophagy via BNIP3L, and that DPD also mediated cell senescence via P21. Here, we found that autophagy promoted cell senescence, resulting in the inhibition of HCC cell proliferation. Similar results were obtained in the tumor-bearing model in vivo. In conclusion, DPD induces incomplete mitophagy and cell senescence in HCC cells, thereby inhibiting HCC cell proliferation. DPD is a potential new strategy for treating HCC.

Targeting ERS-mitophagy in hippocampal neurons to explore the improvement of memory by tea polyphenols in aged type 2 diabetic rats.

Increasing evidence demonstrated that mitophagy and endoplasmic reticulum stress (ERS) was closely associated with memory decline in elderly type 2 diabetes mellitus (T2DM). Tea polyphenols (TP), an excellent natural antioxidant, has been reported to have neuroprotective properties in aging and diabetes, but the underlying mechanisms are still not fully understood. This study targets ERS-mitophagy in hippocampal neurons to investigate the improvement effect of memory in aged T2DM rats by TP. Rats were randomly divided into the control group, the aged group, the aged T2DM model group, the TP 75, 150, 300 mg/kg groups. TP 300 mg/kg ameliorated mitophagy by decreasing the levels of p-mTOR (S2448), P62 and HSP60 and increasing the levels of PINK1 and Parkin, the ratio of LC3Ⅱ/LC3Ⅰ, co-localization of LC3 and HSP60 and the number of autophagosomes and autolysosomes. TP 300 mg/kg attenuated ERS by downregulating the levels of p-PERK, p-eIF2α, ATF4, GRP78 and restoring the ER structure. To further verify epigallocatechin gallate (EGCG), which is the main active component of TP, enhanced mitophagy by inhibiting ERS, PC12 cells were pretreated with ERS activator tunicamycin (TM) or ERS inhibitor 4-phenylbutyric acid (4-PBA). The results showed that the improvement of mitophagy by EGCG was inhibited by TM and promoted by 4-PBA. Collectively, ERS-mitophagy in hippocampal neurons plays a key role in the improvement of memory by TP in aged T2DM rats. This study will provide a new perspective and strategy for the prevention of memory decline in elderly with T2DM.

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

Wheat gluten hydrolysates promotes fermentation performance of brewer's yeast in very high gravity worts.

The effects of wheat gluten hydrolysates (WGH) and their ethanol elution fractions obtained on XAD-16 resin on physiological activity and fermentation performance of brewer's yeast during very-high-gravity (VHG) worts fermentation were investigated. The results showed that the addition of WGH and their elution fractions in VHG worts significantly enhanced yeast biomass and viability, and further increased the fermentability, ethanol yield and productivity of yeast. Supplementation with 40% ethanol fraction exhibited the highest biomass (6.9 g/L dry cell), cell viability, fermentability (82.05%), ethanol titer (12.19%, v/v) and ethanol productivity during VHG worts fermentation. In addition, 40% ethanol fraction supplementation also caused the most consumption of amino acid and the highest accumulation of intracellular glycerol and trehalose, 15.39% of increase in cell-membrane integrity, 39.61% of enhancement in mitochondrial membrane potential (MMP), and 18.94% of reduction in intracellular reactive oxygen species (ROS) level in yeast under VHG conditions. Therefore, WGH supplementation was an efficient method to improve fermentation performance of brewer's yeast during VHG worts.