DDID: a comprehensive resource for visualization and analysis of diet-drug interactions.

Diet-drug interactions (DDIs) are pivotal in drug discovery and pharmacovigilance. DDIs can modify the systemic bioavailability/pharmacokinetics of drugs, posing a threat to public health and patient safety. Therefore, it is crucial to establish a platform to reveal the correlation between diets and drugs. Accordingly, we have established a publicly accessible online platform, known as Diet-Drug Interactions Database (DDID, https://bddg.hznu.edu.cn/ddid/), to systematically detail the correlation and corresponding mechanisms of DDIs. The platform comprises 1338 foods/herbs, encompassing flora and fauna, alongside 1516 widely used drugs and 23 950 interaction records. All interactions are meticulously scrutinized and segmented into five categories, thereby resulting in evaluations (positive, negative, no effect, harmful and possible). Besides, cross-linkages between foods/herbs, drugs and other databases are furnished. In conclusion, DDID is a useful resource for comprehending the correlation between foods, herbs and drugs and holds a promise to enhance drug utilization and research on drug combinations.

MoDAFold: a strategy for predicting the structure of missense mutant protein based on AlphaFold2 and molecular dynamics.

Protein structure prediction is a longstanding issue crucial for identifying new drug targets and providing a mechanistic understanding of protein functions. To enhance the progress in this field, a spectrum of computational methodologies has been cultivated. AlphaFold2 has exhibited exceptional precision in predicting wild-type protein structures, with performance exceeding that of other methods. However, predicting the structures of missense mutant proteins using AlphaFold2 remains challenging due to the intricate and substantial structural alterations caused by minor sequence variations in the mutant proteins. Molecular dynamics (MD) has been validated for precisely capturing changes in amino acid interactions attributed to protein mutations. Therefore, for the first time, a strategy entitled 'MoDAFold' was proposed to improve the accuracy and reliability of missense mutant protein structure prediction by combining AlphaFold2 with MD. Multiple case studies have confirmed the superior performance of MoDAFold compared to other methods, particularly AlphaFold2.

Research trends of exercise therapy of college students in depression from 2002 to 2022: a bibliometric analysis.

Background: Depression is a serious psychological disorder that college students are experiencing. College students' depression problems, which can be caused by various factors, have been easily ignored and untreated. In recent years, exercise, as a low-cost and easily accessible method for treating depression, has attracted widespread attention. The purpose of this study is to use bibliometrics to explore the hotspots and trends in the field of exercise therapy of college students in depression from 2002 to 2022. Methods: We retrieved relevant literature from the Web of Science (WoS), PubMed, and Scopus databases, and generated a ranking table to describe the core productivity in the field. We used VOSViewer software to generate network maps of authors, countries, co-cited journals, and co-occurring keywords to help us better understand the scientific collaboration patterns, potential disciplinary foundations, as well as research hotspots and trends in this field. Results: From 2002 to 2022, a total of 1,397 articles related to exercise therapy of college students in depression were selected. The key findings of this study are as follows: (1) the number of publications has gradually increased, especially after 2019; (2) United States and its affiliated higher education institutions have made significant contributions to the development of this field; (3) there are multiple research groups in this field, but their connections are relatively limited; (4) the field is relatively interdisciplinary, primarily a convergence of behavioral science, public health, and psychology; (5) based on co-occurring keyword analysis, six main themes were summarized: health-promoting factors, body image, negative behaviors, increased stress, depression coping strategies, and diet. Conclusion: Our study illustrates the research hotspots and trends for the research of exercise therapy of college students in depression, presents some challenges and new insights, and provides valuable information for further research.

Single-dose rAAV5-based vaccine provides long-term protective immunity against SARS-CoV-2 and its variants.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.

Anti-inflammatory constituents from the stems and leaves of Glycosmis ovoidea Pierre.

Seven undescribed compounds, including four acridones, two coumarins, and a phenylpropanoid, together with 13 known acridone analogues were isolated from the ethanolic extract of the stems and leaves of Glycosmis ovoidea Pierre. Their structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR and HRESIMS spectroscopic data, and the absolute configurations were assigned by comparison of the experimental and calculated ECD data. Five compounds showed moderate inhibitory effects on nitric oxide production stimulated by lipopolysaccharide in BV-2 microglial cells with IC50 values in the range of 18.30-30.84 µM, and three compounds showed potent inhibition on 5-lipoxygenase (5-LOX) with IC50 values in the range of 2.08-10.26 µM. The possible binding sites of the active compounds with 5-LOX were further performed by molecular docking.

Anti-Neuroinflammatory Components from Clausena lenis Drake.

Clausena lenis Drake (C. lenis) is a folk medicinal herb to treat influenza, colds, bronchitis, and malaria. The 95% and 50% ethanol extract of C. lenis showed significant nitric oxide (NO) inhibition activity in BV-2 microglial cells stimulated by lipopolysaccharide (LPS). Bio-guided isolation of the active extract afforded five new compounds, including a chlorine-containing furoquinoline racemate, (±)-claulenine A (1), an amide alkaloid, claulenine B (2), a prenylated coumarin, claulenin A (3), a furocoumarin glucoside, clauleside A (4), and a multi-prenylated p-hydroxybenzaldehyde, claulenin B (5), along with 33 known ones. Their structures were determined via spectroscopic methods, and the absolute configurations of new compounds were assigned via the electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analysis. Compounds 2, 23, 27, 28, 33, and 34 showed potent anti-neuroinflammatory effects on LPS-induced NO production in BV-2 microglial cells, with IC50 values in the range of 17.6-40.9 µM. The possible mechanism was deduced to interact with iNOS through molecular docking.

Trimeric and Dimeric Carbazole Alkaloids from Murraya microphylla.

Seventeen new carbazole alkaloid derivatives, including a trimeric carbazole racemate, (±)-microphyltrine A (1), 15 dimeric carbazole racemates, (±)-microphyldines A-O (2-16), and a C-6-C-3″-methyl-linked dimeric carbazole, microphyldine P (17), were isolated from the leaves and stems of Murraya microphylla (Merr. et Chun) Swingle. The structures of the new compounds were elucidated on the basis of HRESIMS and NMR data analysis. The optically pure isomers of these isolated carbazole alkaloids were obtained by chiral HPLC separation and their absolute configurations were determined by electronic circular dichroism (ECD) data analysis.

Three new coumarins and a new coumarin glycoside from Micromelum integerrimum.

Three new coumarins, integmarins A-C (1-3), and a new coumarin glycoside, integmaside A (4) were isolated from the leaves and stems of Micromelum integerrimum. Their structures were elucidated on the basis of 1D and 2D NMR and MS data, and their absolute configurations were assigned according to the ECD data of the in situ formed transition metal complexes and comparison of experimental and calculated ECD data. Compounds 1 and 2 are two rare coumarins with butyl and propyl moieties at the C-6 position; compound 3 is a novel coumarin with a highly oxidized prenyl group, and compound 4 is a rare bisdihydrofuranocoumarin glycoside.

Carbazole alkaloids with potential cytotoxic activities targeted on PCK2 protein from Murraya microphylla.

From the 95% aqueous ethanol extract of Murraya microphylla, five pairs of new carbazole alkaloid enantiomers, (+/-)-microphylines N-R (1a/1b-5a/5b), were isolated, together with 20 known carbazole alkaloids. The structures of the new compounds were determined by the HRMS and NMR spectroscopic data, along with the calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. The known compound (+)-mahanine (21) showed significant cytotoxicities against Du145, HepG2, HeLa, and HCT-116 cell lines, and its possible mechanism was deduced to target on phosphoenolpyruvate carboxykinase 2 (PCK2) protein via surface plasmon resonance (SPR) and molecular docking.

A new prenylated coumarin diglycoside with insulin-release promoting activity from Clausena dunniana.

A new prenylated coumarin diglycoside, 6-prenylcoumarin-7-O-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (1) and five known flavonoid glycosides (2-6) were isolated from the leaves and stems of Clausena dunniana. The structures of these isolates were elucidated based on comprehensive MS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. Compounds 2-6 are obtained from the title plant for the first time. All these isolates were evaluated for their insulin-release promoting effects, and compounds 1, 2, and 4 exhibited significant activities (2.0 to 3.3-fold higher in comparison with the control, p < 0.01) at 40 µM.[Formula: see text].

Isolation and structure characterization of cytotoxic alkaloids from Micromelum integerrimum.

Ten undescribed alkaloids, named integerrines A-J, including one racemic heterodimer of carbazole and indole, two racemic, two scalemic, and one enantiomerically enriched biscarbazoles, two aldoximes, and one racemic pyrrolone, were isolated from the dried leaves and stems of Micromelum integerrimum. The racemic or scalemic compounds were resolved using chiral-phase HPLC and their configurations were determined by comparison of experimental and calculated ECD data. Four compounds exhibited moderate to weak cytotoxicities against HepG2, HTC-116, HeLa, and PANC-1 cell lines, with IC50 values of 14.1-67.5 µM.

Terpenoids from Resina Commiphora Regulating Lipid Metabolism via Activating PPARα and CPT1 Expression.

Commiphoranoids A-E (1-5), five novel sesquiterpenoids, dinorditerpenoids, and heterodimers with unprecedented carbon skeletons, were isolated from Resina Commiphora. The structure of 1 was secured by X-ray crystallography. Compound 4 represents the first example of C38 terpenoids, whereas 5 is a C30 terpenoid formed by two types of sesquiterpenoids. These metabolites possess lipid regulatory activities via activating PPARα and CPT1.

Phe-125 and Phe-226 of pig cytochrome P450 1A2 stabilize the binding of aflatoxin B1 and 7-ethoxyresorufin through the key CH/π interactions.

Cytochrome P450 1A2 (CYP1A2) plays important roles in the metabolism of many planar and aromatic drugs and also contributes to the bioactivation of aflatoxin B1 (AFB1) in vivo. To date, the structural basis for CYP1A2's preference to the planar substrates remains unclear. Herein, we investigated the structure-activity relationships for pig CYP1A2 catalyzing AFB1 and 7-ethoxyresorufin (7-ER). A molecular docking study was performed based on a constructed model of pig CYP1A2, which predicted the contributions of Thr-118, Thr-124, Phe-125, Phe-226, Leu-260, and Asp-313 to the substrate catalysis. Site-directed mutagenesis and kinetic analyses exhibited the common grounds: Phe-125, Phe-226 and Asp-313 were vital to AFB1 oxidation (including exo-epoxidation and 9A-hydroxylation) and ethoxyresorufin O-deethylation. Meanwhile, Phe-125 and Phe-226 formed CH/π interactions with AFB1/7-ER, and Asp-313 formed hydrogen bonds with them. Based on other published reports, this study further emphasizes the critical roles of Phe-125 and Phe-226 in recognizing the planar substrates. Our findings highlight the structural basis of pig CYP1A2 specifically catalyzing AFB1 and 7-ER, and may help to elucidate the underlying mechanism of CYP1A2's metabolic preference to the planar and aromatic substrates.

Commipholactam A, a cytotoxic sesquiterpenoidal lactam from Resina Commiphora.

Diverse terpenoids including a novel sesquiterpenoidal lactam, commipholactam A (1), and a structurally related new cadinane sesquiterpenoid, commiphorane H (2), a new eudesmane sesquiterpenoid, commiphorane I (4), a new guaiane sesquiterpenoid, commiphorane J (5), and two new nor-abietane diterpenoids, commiphoranes K1 and K2 (6 and 7) along with two known terpenoids (3 and 8), were isolated from Resina Commiphora. Their structures with absolute configurations were characterized by spectroscopic methods and calculated electronic circular dichroism (ECD). Notably, commipholactam A represents the first example of cadinane sesquiterpene alkaloids isolated from Resina Commiphora. Biological assessment toward human cancer cells showed that the IC50 values of 1 against HepG2 and A549 cells were 21.73 µM and 128.50 µM, respectively.

Multiple CH/π Interactions Maintain the Binding of Aflatoxin B1 in the Active Cavity of Human Cytochrome P450 1A2.

Human cytochrome P450 1A2 (CYP1A2) is one of the key CYPs that activate aflatoxin B1 (AFB1), a notorious mycotoxin, into carcinogenic exo-8,9-epoxides (AFBO) in the liver. Although the structure of CYP1A2 is available, the mechanism of CYP1A2-specific binding to AFB1 has not been fully clarified. In this study, we used calculation biology to predict a model of CYP1A2 with AFB1, where Thr-124, Phe-125, Phe-226, and Phe-260 possibly participate in the specific binding. Site-directed mutagenesis was performed to construct mutants T124A, F125A, F226A, and F260A. Escherichia coli-expressed recombinant proteins T124A, F226A, and F260A had active structures, while F125A did not. This was evidenced by Fe2+∙Carbon monoxide (CO)-reduced difference spectra and circular dichroism spectroscopy. Mutant F125A was expressed in HEK293T cells. Steady kinetic assays showed that T124A had enhanced activity towards AFB1, while F125A, F226A, and F260A were significantly reduced in their ability to activate AFB1, implying that hydrogen bonds between Thr-124 and AFB1 were not important for substrate-specific binding, whereas Phe-125, Phe-226, and Phe-260 were essential for the process. The computation simulation and experimental results showed that the three key CH/π interactions between Phe-125, Phe-226, or Phe-260 and AFB1 collectively maintained the stable binding of AFB1 in the active cavity of CYP1A2.

Preparation and characterization of egg yolk immunoglobulin Y specific to influenza B virus.

The aim of this study was to prepare egg yolk immunoglobulin (IgY) for use in the prevention and treatment of influenza B viral infections. Laying hens were immunized with inactivated influenza B virus (IBV), and IgY was isolated from the egg yolk by multiple polyethylene glycol (PEG) 6000 extraction and ammonium sulfate purification steps. The titers and specificity of the purified antibodies were assessed. The specific IgY titer increased beginning the second week after the first immunization, with the titer peaking at the fifth week. The yield of IgY was 76.5mg per yolk, and the purity was 98.2%. The use of western blotting and the hemagglutination inhibition (HI) test demonstrated that IBV-specific IgY binds specifically to influenza B virus proteins, and a plaque reduction assay revealed the neutralization efficacy of IBV-specific IgY at reducing influenza infection in MDCK cells. Furthermore, when mice were treated intranasally prior to or after influenza B virus infection, IBV-specific IgY protected the mice from influenza infection or reduced viral replication in their lungs, respectively. These findings indicate that IgY is an easily prepared and rich source of antibodies that offers a potential alternative strategy for preventing and treating influenza B infections.