Graph convolutional network with attention mechanism improve major depressive depression diagnosis based on plasma biomarkers and neuroimaging data.

BACKGROUND: The absence of clinically-validated biomarkers or objective protocols hinders effective major depressive disorder (MDD) diagnosis. Compared to healthy control (HC), MDD exhibits anomalies in plasma protein levels and neuroimaging presentations. Despite extensive machine learning studies in psychiatric diagnosis, a reliable tool integrating multi-modality data is still lacking. METHODS: In this study, blood samples from 100 MDD and 100 HC were analyzed, along with MRI images from 46 MDD and 49 HC. Here, we devised a novel algorithm, integrating graph neural networks and attention modules, for MDD diagnosis based on inflammatory cytokines, neurotrophic factors, and Orexin A levels in the blood samples. Model performance was assessed via accuracy and F1 value in 3-fold cross-validation, comparing with 9 traditional algorithms. We then applied our algorithm to a dataset containing both the aforementioned protein quantifications and neuroimages, evaluating if integrating neuroimages into the model improves performance. RESULTS: Compared to HC, MDD showed significant alterations in plasma protein levels and gray matter volume revealed by MRI. Our new algorithm exhibited superior performance, achieving an F1 value and accuracy of 0.9436 and 94.08 %, respectively. Integration of neuroimaging data enhanced our novel algorithm's performance, resulting in an improved F1 value and accuracy, reaching 0.9543 and 95.06 %. LIMITATIONS: This single-center study with a small sample size requires future evaluations on a larger test set for improved reliability. CONCLUSIONS: In comparison to traditional machine learning models, our newly developed MDD diagnostic model exhibited superior performance and showed promising potential for inclusion in routine clinical diagnosis for MDD.

From polyphenol to o-quinone: Occurrence, significance, and intervention strategies in foods and health implications.

Polyphenol oxidation is a chemical process impairing food freshness and other desirable qualities, which has become a serious problem in fruit and vegetable processing industry. It is crucial to understand the mechanisms involved in these detrimental alterations. o-Quinones are primarily generated by polyphenols with di/tri-phenolic groups through enzymatic oxidation and/or auto-oxidation. They are highly reactive species, which not only readily suffer the attack by nucleophiles but also powerfully oxidize other molecules presenting lower redox potentials via electron transfer reactions. These reactions and subsequent complicated reactions are capable of initiating quality losses in foods, such as browning, aroma loss, and nutritional decline. To attenuate these adverse influences, a variety of technologies have emerged to restrain polyphenol oxidation via governing different factors, especially polyphenol oxidases and oxygen. Despite tremendous efforts devoted, to date, the loss of food quality caused by quinones has remained a great challenge in the food processing industry. Furthermore, o-quinones are responsible for the chemopreventive effects and/or toxicity of the parent catechols on human health, the mechanisms by which are quite complex. Herein, this review focuses on the generation and reactivity of o-quinones, attempting to clarify mechanisms involved in the quality deterioration of foods and health implications for humans. Potential innovative inhibitors and technologies are also presented to intervene in o-quinone formation and subsequent reactions. In future, the feasibility of these inhibitory strategies should be evaluated, and further exploration on biological targets of o-quinones is of great necessity.

Investigation of the Quinone-quinone and Quinone-catechol products using 13C labeling, UPLC-Q-TOF/MS and UPLC-Q-Exactive Orbitrap/MS.

Quinones are highly reactive oxidants and play an essential role in inducing quality deterioration of fruit and vegetable products. Here, a novel stable isotope-labeling approach in combination with high-resolution tandem mass spectrometry UPLC-Q-TOF/MS and UPLC-Q-Exactive Orbitrap/MS, was successfully applied in tracking quinone reaction pathways in both real wines and model reaction systems. Unexpectedly, the binding products of quinone-quinone and quinone-catechol that are not derived from either nucleophilic reaction or redox reaction were discovered and showed the significant high peak area.Self-coupling reactions of semiquinone radicals might provide a possible interpretation for the formation of quinone-quinone products, and a charge transfer reaction coupled with a complementary donor-acceptor interaction is feasibly responsible for the products with a quinone-catechol structure. These findings endow a new perspective for quinone metabolic pathway in foods.

LFA-1/ ICAM-1 promotes NK cell cytotoxicity associated with the pathogenesis of ocular toxoplasmosis in murine model.

Ocular toxoplasmosis (OT) is one of the most common causes of posterior uveitis. However, the pathogenic mechanisms of OT have not been well elucidated. Here, we used C57BL/6 (B6) mice to establish OT by peroral infection with 20 cysts of the TgCtWh6 strain, and severe ocular damage was observed by histopathological analysis in the eyes of infected mice. RNA-sequencing results showed that infection with T. gondii increased the expression of the NK-mediated cytotoxicity gene pathway at Day 30 after ocular T. gondii infection. Both NK-cell and CD49a+ NK-cell subsets are increased in ocular tissues, and the expression levels of LFA-1 in NK cells and ICAM-1 in the OT murine model were upregulated upon infection. Furthermore, inhibition of the interaction between LFA-1 and ICAM-1 with lifitegrast, a novel small molecule integrin antagonist, inhibited the protein expression of LFA-1 and ICAM-1 in murine OT and NK cells, improved the pathology of murine OT and influenced the secretion of cytokines in the OT murine model. In conclusion, the interaction between LFA-1 and ICAM-1 plays a role in the early regulation of the CD49a+ NK-cell proportion in an OT murine model. LFA-1/ ICAM-1 may be a key molecule in the pathogenesis of OT, and may provide new insights for potential immunotherapy.

Protective effects of ZIP8 on Toxoplasma gondii-induced acute hepatocyte injury in mice.

Toxoplasma gondii (T. gondii), as an intracellular protozoan parasite, has the potential to disturb the homeostasis of trace metal elements in host cells. Zinc (Zn) is one of those essential metals that is required for combating infection. Zinc cellular homeostasis is controlled by zinc membrane transporters, including efflux and influx transporters. One of the Zrt-Irt-like protein (ZIP) transporters, ZIP8, facilitates zinc influx into the cytosol. It was recently reported to play significant roles in facilitating Zn uptakes during infection. Here, we investigated the function of ZIP8 in host defense against T. gondii infection in cultured alpha mouse liver 12 (AML12) hepatocytes and mice, with loss of ZIP8 function. Herein, C57BL/6 J female wild-type (WT) and ZIP8-KD mice (Slc39a8 knockdown mice), that were infected with tachyzoites of ToxoDB#9(TgCtwh3), were used as a model of acute toxoplasmosis. AML12 hepatocytes were transfected with lentivirus (LV), with silenced ZIP8 expression. Finally, we observed the function of hepatocytes pretreated with ZnCl2 before TgCtwh3 infection in vivo and in vitro. In vivo, the levels of zinc ions and ZIP8 protein were upregulated after TgCtwh3 infection. ZIP8 knockdown exacerbated liver damage, further decreased antioxidant enzyme activity, promoted inflammatory mediator expression, and upregulated the rate of apoptosis. ZnCl2 pretreatment before TgCtwh3 infection improved liver injury, increased antioxidant enzyme activity, restrained the expression of inflammatory mediators, and decreased the rate of apoptosis. The results in vitro were almost the same as those in vivo. This study defines the function of ZIP8-dependent zinc in hepatocyte damage during intracellular pathogen infection. Reagents that regulate ZIP8 activity might be developed as therapeutics to protect the liver function of toxoplasmosis.

Early and Short-Term Interventions in the Gut Microbiota Affects Lupus Severity, Progression, and Treatment in MRL/lpr Mice.

There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr mice, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr mice were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus mice with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr mice. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment.

Molecular characteristics of kappa-selenocarrageenan and application in green synthesis of silver nanoparticles.

Selenium is an essential trace element in human body, and kappa-selenocarrageenan (Se-car) is an organic source of selenium supplement. To further utilize Se-car in food packaging, biotherapy or biosensor, the molecular information of Se-car was characterized here and multi-functional Ag NPs synthesized by Se-car were fabricated. Results of GPC-MALLS, FTIR, potentiometric titration, and intrinsic viscosity showed that Se-car was polymerized by nearly 22 basic units of disaccharide. Sixty-four percentage of sulfated groups (SO42-) in carrageenan was replaced by selenium acid (SeO32-), which belonged to weak acid resulting from a gradually decrease of ζ-potential with acidity process to pH 1.0. Besides, the capacity of biosynthesis silver nanoparticles (Ag NPs) by Se-car was studied and it made a comparison with κ-carrageenan. Results exhibited that Se-car could serve as an efficient reducing and capping agent for Ag NPs fabrication (remarked as Se-car@Ag). The kapp of Se-car@Ag NPs for catalyzing 4-NP degradation was 2.14 × 10-2 s-1. Antibacterial test revealed Se-car@Ag had an ability to inhibit the growth of Escherichia coli and Staphylococcus aureus. To combine the selenium health benefit and functional metal nanoparticles, Se-car@Ag might have potential applications in multiple areas like medicine, disease diagnostic, and drug delivery.

Alterations of the Gut Microbiome Associated With the Treatment of Hyperuricaemia in Male Rats.

Hyperuricaemia is an important risk factor for many diseases including gout, hypertension, and type II diabetes. The gut microbiota is associated with hyperuricaemia and has also been demonstrated to play significant roles in the effects of drug therapy. This study used Illumina MiSeq sequencing to explore alterations of the gut microbiome associated with allopurinol and benzbromarone treatment in the male rat with hyperuricaemia. After drug treatment, both allopurinol and benzbromarone caused an increase of the genera Bifidobacterium and Collinsella and a decrease of the genera Adlercreutzia and Anaerostipes. In addition, allopurinol and benzbromarone caused respective unique changes in genera. The genera Bilophila, Morganella, and Desulfovibrio specifically decreased due to allopurinol treatment. Decreased Butyricimonas and Ruminococcus and increased Proteus were caused by benzbromarone treatment. The PICRUST analysis indicated that allopurinol renovated the disorder of nucleotide metabolism and benzbromarone renovated the disorder of lipid metabolism in the gut microbiota of male rats with hyperuricaemia. These findings demonstrated that the gut microbiota may be altered by the treatment of hyperuricaemia with allopurinol and benzbromarone in male rats. Such alterations of the gut microbiota could be considered as indicators of the effectiveness of drug therapy.

TCMID 2.0: a comprehensive resource for TCM.

As a traditional medical intervention in Asia and a complementary and alternative medicine in western countries, Traditional Chinese Medicine (TCM) is capturing worldwide attention in life science field. Traditional Chinese Medicine Integrated Database (TCMID), which was originally launched in 2013, was a comprehensive database aiming at TCM's modernization and standardization. It has been highly recognized among pharmacologists and scholars in TCM researches. The latest release, TCMID 2.0 (http://www.megabionet.org/tcmid/), replenished the preceding database with 18 203 herbal ingredients, 15 prescriptions, 82 related targets, 1356 drugs, 842 diseases and numerous new connections between them. Considering that chemical changes might take place in decocting process of prescriptions, which may result in new ingredients, new data containing the prescription ingredients was collected in current version. In addition, 778 herbal mass spectrometry (MS) spectra related to 170 herbs were appended to show the variation of herbal quality in different origin and distinguish genuine medicinal materials from common ones while 3895 MS spectra of 729 ingredients were added as the supplementary materials of component identification. With the significant increase of data, TCMID 2.0 will further facilitate TCM's modernization and enhance the exploration of underlying biological processes that are response to the diverse pharmacologic actions of TCM.

Dissecting the Underlying Pharmaceutical Mechanism of Chinese Traditional Medicine Yun-Pi-Yi-Shen-Tong-Du-Tang Acting on Ankylosing Spondylitis through Systems Biology Approaches.

Traditional Chinese Medicine (TCM) has been served as complementary medicine for Ankylosing Spondylitis (AS) treatment for a long time. Yun-Pi-Yi-Shen-Tong-Du-Tang (Y-Y-T) is a novel empirical formula designed by Prof. Chengping Wen. In this study, a retrospective investigation supported efficacy of Y-Y-T and then we deciphered the underlying molecular mechanism of the efficacy. Herbal ingredients and targeting proteins were collected from TCMID. PPI networks were constructed to further infer the relationship among Y-Y-T, drugs used for treating AS, differentially expressed genes of AS patients and AS disease proteins. Finally, it was suggested that TLR signaling pathway and T cell receptor signaling pathway may involve in the biological processes of AS progression and contribute to the curative effect and proteins such as JAK2, STAT3, HSP90AA1, TNF and PTEN were the key targets. Our systemic investigation to infer therapeutic mechanism of Y-Y-T for AS treatment provides a new insight in understanding TCM pharmacology.