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Riboflavin kinase (RFK) is essential in riboflavin metabolism, converting riboflavin to flavin mononucleotide (FMN), which is further processed to flavin adenine dinucleotide (FAD). While RFK enhances macrophage phagocytosis of Listeria monocytogenes, its role in macrophage polarization is not well understood. Our study reveals that RFK deficiency impairs M(IFN-γ) and promotes M(IL-4) polarization, both in vitro and in vivo. Mechanistically, RFK interacts with inducible nitric oxide (NO) synthase (iNOS), which requires FMN and FAD as cofactors for activation, leading to increased NO production that alters energy metabolism by inhibiting the tricarboxylic acid cycle and mitochondrial electron transport chain. Exogenous FAD reverses the metabolic and polarization changes caused by RFK deficiency. Furthermore, bone marrow adoptive transfer from high-riboflavin-fed mice into wild-type tumor-bearing mice reprograms tumor-associated macrophage polarization and inhibits tumor growth. These results suggest that targeting RFK-iNOS or modulating riboflavin metabolism could be potential therapies for macrophage-related immune diseases.

BackgroundMedical staff often conduct assessments, such as food intake and nutrient sufficiency ratios, to accurately evaluate patients’ food consumption. However, visual estimations to measure food intake are difficult to perform with numerous patients. Hence, the clinical environment requires a simple and accurate method to measure dietary intake. ObjectiveThis study aims to develop a food intake estimation system through an artificial intelligence (AI) model to estimate leftover food. The accuracy of the AI’s estimation was compared with that of visual estimation for liquid foods served to hospitalized patients. MethodsThe estimations were evaluated by a dietitian who looked at the food photo (image visual estimation) and visual measurement evaluation was carried out by a nurse who looked directly at the food (direct visual estimation) based on actual measurements. In total, 300 dishes of liquid food (100 dishes of thin rice gruel, 100 of vegetable soup, 31 of fermented milk, and 18, 12, 13, and 26 of peach, grape, orange, and mixed juices, respectively) were used. The root-mean-square error (RMSE) and coefficient of determination (R2) were used as metrics to determine the accuracy of the evaluation process. Corresponding t tests and Spearman rank correlation coefficients were used to verify the accuracy of the measurements by each estimation method with the weighing method. ResultsThe RMSE obtained by the AI estimation approach was 8.12 for energy. This tended to be smaller and larger than that obtained by the image visual estimation approach (8.49) and direct visual estimation approach (4.34), respectively. In addition, the R2 value for the AI estimation tended to be larger and smaller than the image and direct visual estimations, respectively. There was no difference between the AI estimation (mean 71.7, SD 23.9 kcal, P=.82) and actual values with the weighing method. However, the mean nutrient intake from the image visual estimation (mean 75.5, SD 23.2 kcal, P

Background: Schisandra chinensis (Turcz.) Baill (Schisandraceae) and Acorus tatarinowii Schott (Araceae Juss) (Sc-At) are two traditional Chinese medicinal herbs that are widely used in the treatment of neurological disorders such as insomnia. In our previous study, we found that Sc-At could improve the therapeutic efficacy of Alzheimer’s disease by affecting aromatase activity and estrogen levels, among other pathways. Material and methods: In this study, first, the ameliorative effect of Sc-At on cognitive dysfunction in Alzheimer’s disease model rats was verified by Y-maze test together with Elisa assay. Second, fecal untargeted metabolomics analysis was performed using a UPLC-Q-TOF/MS-based metabolomics approach. 16S rDNA sequencing was utilized to screen the differential flora between groups, and linear discriminantan alysis effect size (LEfSe) was used to find the target flora. Finally, Spearman correlation analysis was combined to find the relationship between differential flora and differential metabolites in feces. Results: (1) The results of Y-maze test and Elisa assay indicated that Sc-At could improve the cognitive dysfunction of AD model rats. (2) Metabolomics results showed that fecal metabolite levels were significantly different from those of rats in the blank group, and 18 potential biomarkers in feces were screened, mainly affecting linoleic acid metabolism, steroid hormone biosynthesis, sphingomyelin metabolism, riboflavin metabolism, etc. The 16S rDNA results showed that the abundance and diversity of intestinal flora in AD rats were destroyed, and the Sc-At treatment was able to reverse these changes. (3) Spearman’s correlation analysis showed a significant correlation between differential metabolites in feces and intestinal flora, further suggesting that Sc-At treats Alzheimer’s disease through the gut-brain axis. Conclusions: In this study, we explored the mechanism of Sc-At in the treatment of Alzheimer’s disease by integrating fecal untargeted metabolomics and 16S rDNA gene sequencing, and the results showed that Sc-At exerts therapeutic effects on Alzheimer’s disease by improving the intestinal flora and related metabolic pathways.

AZ91 alloy reinforced by carbon nanotubes coated with MgO（AZ91-MgO@CNTs） was prepared by powder metallurgy, hot extrusion and T4 treatment. The influences of MgO@CNTs content and load on the friction and wear property, surface wear morphology and debris topography of AZ91-MgO@CNTs composites were investigated under the dry sliding friction. The results show that MgO@CNTs can improve the wear properties of AZ91-MgO@CNTs. With increasing the content of MgO@CNTs, the strengthening effect of the wear properties of the composite increases and then decreases. Compared with AZ91-CNTs, AZ91-MgO@CNTs has smaller friction coefficient and lower abrasion loss, indicating that the MgO@CNTs is better than CNTs to improve the wear properties of AZ91 alloy. The main wear mechanism of AZ91-MgO@CNTs is abrasive wear under the load of 10 N. When the load is 50 N, there are three wear mechanisms appeared: abrasive wear, oxidation wear and adhesive wear.

Extractive electrospray ionization (EESI) technology has the advantages of directly ionizing the target molecules in the samples without complex sample pretreatments, and it is widely used for analysis of complex matrix samples, especially for aerosol samples. However, the current EESI device with open structure is easily affected by the surrounding environmental factors, especially susceptible to the airflow disturbance and exogenous aerosols. To solve this problem, an enclosed-structure EESI device was developed in this work. Three standard solutions of histidine, reserpine and MRFA were used to test the performances of the enclosed and open EESI-MS under laboratory conditions, respectively. The results showed that intra-day precision and sensitivity of enclosed EESI device are slightly better than that of open EESI device. Then, the performances of the two EESI-MS devices were tested with reserpine solution under different external air flow rates. As the external air flow rate increased, the intra-day precision of the open EESI device gradually decreased (RSD increased from 3.4% to 5.6%), and the intra-day precision of the enclosed EESI device remained good (RSD increased from 2.4% to 3.6%), indicating that the enclosed EESI device has a strong ability to resist airflow disturbance. The glucose aerosols of different concentrations were used to test the enclosed EESI-MS for 5 consecutive days. The results showed that intra-day precision (RSD

LncRNA NEAT1 can regulate gene expression by the formation of paranuclear plaques, acting as ceRNA, and epigenetic modification, and subsequently participating in the physiological and pathological processes such as inflammatory response, immune response, cell proliferation and differentiation. LncRNA NEAT1 is linked to the pathogenesis of many diseases. LncRNA NEAT1 plays an important pathogenic role in psoriasis and its comorbidities, which exhibit high expression levels of LncRNA NEAT1. Here we review the profile of LncRNA NEAT1 and its research progress in psoriasis and its comorbidities.

Surgery remains the preferred treatment option for early-stage gallbladder cancer (GBC). According to the anatomical position of the primary tumor, accurate preoperative stage and strict control of surgical indications, appropriate surgical strategies are selected to achieve the optimal surgical effect. However, most patients have already been at the locally advanced stage or the tumor has metastasized at the initial diagnosis. The postoperative recurrence rate and 5-year survival rate remain unsatisfactory even after radical resection for gallbladder cancer. Hence, there is an urgent need for more treatment options, such as neoadjuvant therapy, postoperative adjuvant therapy and first-line and second-line treatments of local progression and metastasis, in the whole-course treatment management of gallbladder cancer patients. In recent years, the application of molecular targeted drugs and immunotherapy has brought greater hope and broader prospects for the treatment of gallbladder cancer, but their effects in improving the prognosis of patients still lack sufficient evidence-based medicine evidence, so many problems should be addressed by further research. Based on the latest progress in gallbladder cancer research, this review systematically analyzes the treatment trends of gallbladder cancer.

Summary: The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is involved in the regulation of tumor oncogenesis and immune cell functions, but whether it can contribute to macrophage polarization remains elusive. Here, we show that MTHFD2 suppresses polarization of interferon-γ-activated macrophages (M(IFN-γ)) but enhances that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo. Mechanistically, MTHFD2 interacts with phosphatase and tensin homolog (PTEN) to suppress PTEN’s phosphatidylinositol 3,4,5-trisphosphate (PIP3) phosphatase activity and enhance downstream Akt activation, independent of the N-terminal mitochondria-targeting signal of MTHFD2. MTHFD2-PTEN interaction is promoted by IL-4 but not IFN-γ. Furthermore, amino acid residues (aa 215–225) of MTHFD2 directly target PTEN catalytic center (aa 118–141). Residue D168 of MTHFD2 is also critical for regulating PTEN’s PIP3 phosphatase activity by affecting MTHFD2-PTEN interaction. Our study suggests a non-metabolic function of MTHFD2 by which MTHFD2 inhibits PTEN activity, orchestrates macrophage polarization, and alters macrophage-mediated immune responses.

Traditional Chinese medicine targeted at gut microbiota has good effects in relieving the clinical manifestation of Alzheimer's disease, and intestinal metabolites are considered as a bridge of communication between the brain-gut axis. In order to explore the molecular mechanism of Ganmaidazao decoction treatment, first, the model rats induced by Aβ25-35 and d-gal were used to test the therapy of Ganmaidazao extract using the Morris Water Maze, Western Blot and Elisa. Then the 16S rDNA gene sequencing of the gut microbiota as well as UPLC-QTOF/MS-based metabolomic analysis of feces were carried out. Last, the relationship between Alzheimer's disease, gut microbiota and metabolites was analyzed. Results showed that the abundance and diversity of gut microbiota were rescued and the changes of fecal metabolites in rats with Alzheimer's disease were reversed after Ganmaidazao decoction administration, which were mainly related to lipid metabolism, steroid hormone metabolism, energy metabolism, amino acid metabolism and bile acid metabolism. After associating with Spearman’s correlation analysis, we concluded that gut microbiota and metabolites were closely related and Ganmaidazao decoction could interfere with the balance of gut microbiota and their corresponding metabolites to exert anti- Alzheimer’s disease effect. Combined with PICRUSt2 functional prediction of gut microbiota and metabolomics results, phenylalanine metabolism has been focused as a key metabolic pathway, and Ganmaidazao decoction can reduce the abnormal accumulation of phenylalanine and phenylpyruvate and promote their metabolism by restoring the activity of phenylalanine hydroxylase. This integrated omics approach has potential roles in understanding the complex mechanisms of Ganmaidazao decoction in treating Alzheimer’s disease.

Bactrian camels have specific mucosa-associated lymphoid tissue (MALT) throughout the large intestine, with species-unique cystic Peyer’s patches (PPS) as the main type of tissue. However, detailed information about the molecular characteristics of PPS remains unclear. This study applied a transcriptomic analysis, untargeted metabolomics, and 16S rDNA sequencing to compare the significant differences between PPS and the adjacent normal intestine tissues (NPPS) during the healthy stage of three young Bactrian camels. The results showed that samples from PPS could be easily differentiated from the NPPS samples based on gene expression profile, metabolites, and microbial composition, separately indicated using dimension reduction methods. A total of 7,568 up-regulated and 1,266 down-regulated differentially expressed genes (DEGs) were detected, and an enrichment analysis found 994 DEGs that participated in immune-related functions, and a co-occurance network analysis identified nine hub genes (BTK, P2RX7, Pax5, DSG1, PTPN2, DOCK11, TBX21, IL10, and HLA-DOB) during multiple immunologic processes. Further, PPS and NPPS both had a similar pattern of most compounds among all profiles of metabolites, and only 113 differentially expressed metabolites (DEMs) were identified, with 101 of these being down-regulated. Deoxycholic acid (DCA; VIP = 37.96, log2FC = −2.97, P = 0), cholic acid (CA; VIP = 13.10, log2FC = −2.10, P = 0.01), and lithocholic acid (LCA; VIP = 12.94, log2FC = −1.63, P = 0.01) were the highest contributors to the significant dissimilarities between groups. PPS had significantly lower species richness (Chao1), while Firmicutes (35.92% ± 19.39%), Bacteroidetes (31.73% ± 6.24%), and Proteobacteria (13.96% ± 16.21%) were the main phyla across all samples. The LEfSe analysis showed that Lysinibacillus, Rikenellaceae_RC9_gut_group, Candidatus_Stoquefichus, Mailhella, Alistipes, and Ruminococcaceae_UCG_005 were biomarkers of the NPPS group, while Escherichia_Shigella, Synergistes, Pyramidobacter, Odoribacter, Methanobrevibacter, Cloacibacillus, Fusobacterium, and Parabacteroides were significantly higher in the PPS group. In the Procrustes analysis, the transcriptome changes between groups showed no significant correlations with metabolites or microbial communities, whereas the alteration of metabolites significantly correlated with the alteration of the microbial community. In the co-occurrence network, seven DEMs (M403T65-neg, M329T119-neg, M309T38-neg, M277T42-2-neg, M473T27-neg, M747T38-1-pos, and M482t187-pos) and 14 genera (e.g., Akkermansia, Candidatus-Stoquefichus, Caproiciproducens, and Erysipelatoclostridium) clustered much more tightly, suggesting dense interactions. The results of this study provide new insights into the understanding of the immune microenvironment of the cystic PPS in the cecum of Bactrian camels.

BackgroundAn accurate evaluation of the nutritional status of malnourished hospitalized patients at a higher risk of complications, such as frailty or disability, is crucial. Visual methods of estimating food intake are popular for evaluating the nutritional status in clinical environments. However, from the perspective of accurate measurement, such methods are unreliable. ObjectiveThe accuracy of estimating leftover liquid food in hospitals using an artificial intelligence (AI)–based model was compared to that of visual estimation. MethodsThe accuracy of the AI-based model (AI estimation) was compared to that of the visual estimation method for thin rice gruel as staple food and fermented milk and peach juice as side dishes. A total of 576 images of liquid food (432 images of thin rice gruel, 72 of fermented milk, and 72 of peach juice) were used. The mean absolute error, root mean squared error, and coefficient of determination (R2) were used as metrics for determining the accuracy of the evaluation process. Welch t test and the confusion matrix were used to examine the difference of mean absolute error between AI and visual estimation. ResultsThe mean absolute errors obtained through the AI estimation approach were 0.63 for fermented milk, 0.25 for peach juice, and 0.85 for the total. These were significantly smaller than those obtained using the visual estimation approach, which were 1.40 (P

Free-running InGaAs/InP single-photon avalanche photodiodes (SPADs) typically operate in the active-quenching mode, facing the problems of long dead time and large timing jitter. In this paper, we demonstrate a 1-GHz gated InGaAs/InP SPAD with the sinusoidal gating signals asynchronous to the incident pulsed laser, enabling free-running single-photon detection. The photon-induced avalanche signals are quenched within 1 ns, efficiently reducing the SPAD’s dead time and achieving a count rate of up to 500 Mcount/s. However, the timing jitter is measured to be ~168 ps, much larger than that of the SPAD with synchronous gates. We adjust the delay between the gating signals and the incident pulsed laser to simulate the random arrival of the photons, and record the timing jitter, respectively, to figure out the cause of the jitter deterioration. In addition, the effects of the incident laser power and working temperature of the APD on the time resolution have been investigated, broadening the applications of the GHz gated free-running SPAD in laser ranging and imaging, fluorescence spectroscopy detection and optical time-domain reflectometry.

Summary: Innate immunity is the first line of host defense against viral infection. As one of the innate immune cell types, antigen-presenting cells play an important role in the process of antiviral immunity. This protocol describes the analysis of innate immunity induced by vesicular stomatitis virus infection of peritoneal macrophages in vitro and in vivo detection of IFN-β production and lung injury.For complete details on the use and execution of this protocol, please refer to Shen et al. (2021).

Introduction: The novel Coronavirus disease 2019 pandemic is sweeping through China, posing the greatest ever threat to its public health and economy. As a tertiary cancer center in Southwest China, we formulated and implemented an anti-infection protocol to prevent the spread of Coronavirus disease 2019 in our department. Methods: The anti-infection protocol divided patients into 3 categories, namely outpatients, inpatients, and patients receiving radiation therapy at our cancer center, and each category had a distinct anti-infection protocol to minimize the risk of Coronavirus disease 2019 transmission. In each category, the patients were classified into high-, intermediate-, and low-risk groups. Each risk group was managed differently. A survey of patient volume changes prior to and during the Coronavirus disease 2019 outbreak was performed. Results: We carried out the anti-infection protocol at our cancer center during the Coronavirus disease 2019 outbreak. We found that the total volume of both outpatient visits and inpatient treatment declined significantly depending on the conditions of each group. Radiation therapy and palliative service had the lowest and highest volume reductions at 58.3% and 100%, respectively. The decline in outpatient volumes was higher than the decline in inpatient treatment services (78.8% vs 71.8%). There was no Coronavirus disease 2019 cross-infection at our center, or Coronavirus disease 2019–related injury or death. The anti-infection protocol measures continue to be taken at the hospital even today but they have been modified depending on the prevalent local conditions. Conclusions: Challenges from the Coronavirus disease 2019 pandemic remain in our community. The anti-infection protocol implemented at our cancer center has been effective in preventing cross-infection. Whether our anti-infection protocol experience can be applied to curb the spread of the infection in other parts of the world remains to be tested.

Mastitis is associated with release of free radicals, increased total oxidant capacity and decreased total antioxidants capacity in milk. Antioxidant vitamins and minerals protect the body from free radicals either by directly scavenging free radicals or by inhibiting the activity of oxidizing enzymes. The supplementation of mastitic dairy cows with antioxidant vitamins as vitamin A (VA) and β-carotene (BC), vitamin C (VC), vitamin E (VE), and antioxidant minerals as selenium (Se), Zinc (Zn) and copper (Cu) is very important to help the animal recover early. The aim of this review was to discuss the oxidative stress in dairy cows’ mastitis, and the roles of VA and BC, VC, VE, Se, Zn, and Cu in mastitis of dairy cows. Before deciding to supplement dairy cow rations with the levels of vitamins and minerals, dairy farmers should have their animal feeds tested and their rations evaluated by a competent dairy cow nutritionist and a trustworthy laboratory to be sure what levels of supplementation may be warranted. While inadequate intake and absorption of certain nutrients may result in a weakened immune system and perhaps more mastitis during the lactation period, unjustified supplementation can be expensive and lead to other animal health problems.