NMT2 alleviates depression-like behavior in a rat model of chronic unpredictable stress: An integrated proteomic and phosphoproteomic analysis.

Proteomics has been widely used to investigate multiple diseases. Combining the analyses of proteomics with phosphoproteomics can be used to further explain the pathological mechanisms of depression. In this study, depression-like behavior was induced in a rat model of chronic unpredictable mild stress (CUMS). We subsequently conducted the sucrose preference test, open field experiment, and forced swimming test to assess depressive-like behavior. Proteomic and phosphoproteomic sequencing of the hippocampal tissues from depressive-like behavior and normal rats were analyzed to identify differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs). Differentially expressed phosphorylated proteins (DEPPs) were obtained by intersecting the DEPs and DPPs, and functional enrichment analysis, as well as ingenuity pathway analysis (IPA), were subsequently performed. The study also investigated correlations among the DEPPs and used qRT-PCR to quantify the expression levels of key genes. Five DEPPs were identified, Gys1, Nmt2, Lrp1, Bin1, and Atp1a1, which were found to activate the synaptogenesis signaling pathway, induce mitochondrial dysfunction, and activate the phosphoinositide biosynthesis and degradation pathways. The qRT-PCR results confirmed the proteomic findings for Gys1, Nmt2, Lrp1, and Atp1a1. Importantly, inhibiting Nmt2 was found to alleviate depression-like behavior and alleviate neuronal apoptosis in the hippocampus of CUMS rats. In conclusion, we identified five DEPPs associated with the synaptogenesis signaling pathway, mitochondrial dysfunction, and phosphoinositide biosynthesis and degradation in depression. Furthermore, NMT2 may be a potential target for the treatment or diagnosis of depression. Our findings provide novel insights into the molecular mechanisms of depression.

Risk factors for irinotecan-induced liver injury: a retrospective multicentre cross-sectional study in China.

OBJECTIVES: The hepatotoxicity of irinotecan has been widely implicated in the treatment of multiple solid tumours. However, there are few studies on the influencing factors of irinotecan-induced hepatotoxicity. Herein, we investigated the risk factors for irinotecan-induced liver injury among 421 patients receiving irinotecan-based regimens (IBRs). DESIGN: Retrospective multi-centre cross-sectional study. SETTING: This study surveyed four hospitals in China. PARTICIPANTS: After excluding participants with missing variables, we retrospectively collected the demographic, clinical and therapeutic data of 421 patients who received IBRs in four hospitals between January 2020 and December 2021 and divided the patients into two groups: those without liver injury and those with liver injury. RESULTS: The 421 enrolled patients were grouped (liver injury group: n=92; control group: n=329) according to their hepatic biochemical monitoring parameters. In our study, the multivariate logistic regression results showed that three to four cycles of chemotherapy (OR (95% CI): 2.179 (1.272 to 3.733); p=0.005) and liver metastasis (OR (95% CI): 1.748 (1.079 to 2.833); p=0.023) were independent risk factors for irinotecan-induced liver injury. The Cox proportional hazards model demonstrated that alcohol consumption history (OR (95% CI): 2.032 (1.183 to 3.491); p=0.010) and a cumulative dose of irinotecan ≥1000 mg (OR (95% CI): 0.362 (0.165 to 0.792); p=0.011) were significantly correlated with the onset time of irinotecan-induced liver injury. CONCLUSIONS: These findings suggest that patients with liver metastasis or who received three to four cycles of chemotherapy should undergo rigorous liver function monitoring to prevent or reduce the incidence of irinotecan-induced liver injury. Moreover, patients with a history of alcohol consumption should also be closely monitored.

Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves' disease in children.

The aim of this study was to systematically evaluate the correlation between the rs231775 locus polymorphism in the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene and genetic susceptibility to Graves' disease (GD) in children. Some studies found that the CTLA-4 gene polymorphism was associated with GD in children. The data up to February 2022 were retrieved from the databases. Stata 15.0 software was used for meta-analysis. A total of seven studies were included in our research. The results of the meta-analysis showed that the rs231775 locus polymorphism in the CTLA-4 gene in general and Asian populations was correlated with children's susceptibility to GD (A vs G: OR = 0.75, 95% CI (0.660-0.86); GG vs AA: OR = 1.34, 95% CI (1.04-1.73); AG vs AA: OR = 1.32, 95% CI (1.02-1.10); AG + GG vs AA: OR = 3.81, 95% CI (2.17-6.70); GG vs AA + AG: OR = 1.23, 95% CI (1.05-1.45)). In summary, the rs231775 locus polymorphism in the CLTA-4 gene may be a risk factor for GD in Asian children. The G allele may be a susceptibility factor, while the allele A may be a protective factor against GD in Asian children. In the future, more large-scale studies may be needed to verify our results.

Near-Infrared-I to III Absorption and Emission via Core Engineering of Open-Shelled Organic Mixed-Valence Systems.

A novel class of agents is developed based on the core engineering of open-shelled organic mixed-valence (MV) systems, which enable tunable absorption and emission across the near infrared (NIR)-I to III biowindow (700-1850 nm) by adjusting the number of central nitrogen oxidation sites and the length of the conjugated bridge. Organic mixed-valence (MV) systems are synthesized through a one-step partial chemical oxidation of starburst oligoarylamines, with varying nitrogen oxidation sites and conjugated bridge lengths, including tris(4-[diethylamino]phenyl)aminen+ (T4EPAn + ), N,N,N',N'-tetrakis(4-[diisobutylamino]phenyl)-1,4-phenylenediaminen+ (TPDAn + ), and N,N,N',N'-tetrakis(4-methoxyphenyl)benzidinen+ (TMPBn + ). The absorption wavelength of the MV systems redshifted clearly as the number of central nitrogen oxidation sites increased or the conjugated bridge length is prolonged. T4EPAn + with one central nitrogen oxidation site exhibits fluorescence emission in the range of 900-1400 nm, while TPDAn + with two central nitrogen oxidation sites demonstrate strong heat generation capabilities. Additionally, the absorption peak of TMPBn + with a biphenyl conjugated bridge reaches up to 1610 nm. Especially, these MV systems are highly stable for biological applications due to their high steric hindrance and hyperconjugation effect. These characteristics make MV systems promising candidates for constructing NIR-I/II/III emitters and photothermal agents, representing a significant advance toward developing the next generation of NIR-I to III agents.

Crude Extracts and Secondary Metabolites of Epichloë bromicola against Phytophthora infestans.

Potato late blight caused by Phytophthora infestans is still one of the main factors limiting potato production. Epichloë spp. can provide host plants with various resistances, which makes them show great potential in the biological control of diseases. In this study, we explored the potential biological activity of crude extracts of 20 strains of Epichloë bromicola to control P. infestans. The crude extracts of strains 1 and 8 showed significant antifungal activity with an inhibition rate of 88 % and 81 %, respectively, and showed different effects on the mycelium morphology of P. infestans observed by scanning electron microscopy. Moreover, the two crude extracts demonstrated an interesting therapeutic and protective effect on potato late blight, and none of the extracts had an adverse effect against zebrafish embryos. A total of 13 metabolites were isolated from the crude extract of strain 8, and these tested compounds showed a weak antifungal effect and the inhibition rate was less than 80 %. These findings suggested that strains 1 and 8 have potential for biocontrol of late potato blight.

Antifungal, Repellency, and Insecticidal Activities of Cymbopogon distans and Ruta graveolens Essential Oils and Their Main Chemical Constituents.

Essential oils produced by Cymbopogon distans and Ruta graveolens with a similar Chinese name could be explained as book fragrance in the Chinese idiom 'shu xiang men di', namely, a wealthy intellectual family according to ancient Chinese. Therefore, volatile oils from these two plants and their main compounds were tested to explore their antifungal, repellent, and insecticide actions. In this study, the essential olis (EO) of C. distans exhibited significant antifungal activity against Rhizopus stolonifera (97 %), Mucor racemosus (97 %), and Trichoderma viride (84 %); its main compounds exhibit interesting activity, such as methyleugenol (87 %) and elemicine (85 %) against T. viride and butyl hydroxytoluene against M. racemosus (90 %) and R. stolonifera (95 %). The EO of R. graveolens and other major chemical constituents showed weak inhibitory effects against other fungi (Aspergillus flavus and Fusarium oxysporum). Then, EO (C. distans and R. graveolens) and its main compounds exhibited obvious repellent activity (more than 85 %) at a concentration of 16 nL/cm2 , which was consistent with the repellency of the positive control (DEET). In terms of insecticidal activity, the mortality of C. distans volatile oil against R. padi (56.4 %) was lower than that of R. graveolens volatile oil (92.4 %), and all compounds showed weak lethal effects. These results provide a natural substance for controlling fungi and insects when storing books and that can be used as a biological pesticide for industrial production. Through our study, the book fragrance in the Chinese idiom 'shu xiang men di' was speculated to be the EO odor of C. distans.

Risk factors for oxaliplatin-induced hypersensitivity reaction in patients with colorectal cancer.

OBJECTIVE: Hypersensitivity reactions with oxaliplatin (OXA) have attracted much attention. This study aimed to analyze the risk factors for OXA-induced hypersensitivity reaction in Chinese colorectal cancer patients through a single-center retrospective investigation. METHODS: The information from 459 colorectal cancer patients treated with OXA in a hospital was collected retrospectively to explore the risk factors for OXA-induced hypersensitivity reaction. RESULTS: Among the 459 patients, 47 (10.24% incidence) cases developed hypersensitivity reactions, with a 3.70% incidence of grade III/IV reaction. The main symptoms included itching, flushing, dyspnea, and rash, which mainly involved skin and adnexa, respiratory system, and nervous system. Dexamethasone pretreatment presented no significant effects on the hypersensitivity reaction (P = 0.282). Multivariate analysis indicated that the previous allergic history (odds ratio (OR) 2.553, 95% confidence interval (CI) 1.139-5.721, P = 0.023) and OXA-free interval (OR 3.605, 95% CI 1.909-6.809, P = 0.000) were independent risk factors for OXA-induced hypersensitivity reaction. CONCLUSIONS: The incidence of OXA-induced hypersensitivity reaction in colorectal cancer patients was similar to those reported in other countries. Clinical medical staff should pay close attention to high-risk factors, such as allergic history and patients having OXA-free intervals in order to avoid or alleviate hypersensitivity reactions.

Clinical Features of Oxaliplatin-induced Hypersensitivity Reactions in Chinese Patients: A Retrospective Multicenter Analysis.

OBJECTIVE: The characteristics of oxaliplatin-induced hypersensitivity reactions (HSRs) in Chinese patients were investigated to provide a reference for patients treated with oxaliplatin. METHODS: The study reviewed the records of patients who developed oxaliplatin-induced HSRs in 17 hospitals from May 2016 to May 2017. We collected and analyzed the basic information, history of oxaliplatin administration and premedication treatments, chemotherapy cycles, HSR symptoms, and the management and outcomes of these patients. RESULTS: Oxaliplatin-induced HSRs were recorded in 137 patients who had been treated with oxaliplatin-containing regimens. Five different chemotherapy regimens were applied. The median infusion cycle when oxaliplatin-induced HSRs occurred was 7, and HSRs occurred during or shortly after oxaliplatin infusion. Most of the patients experienced grade 1 or grade 2 HSRs with mild symptoms of pruritis (49.64%), flushing (46.72%), chest discomfort (26.28%), and urticaria (25.55%). The majority of the patients completely recovered from HSRs following treatment with antihistamines and dexamethasone. Seven patients completed chemotherapy with oxaliplatin after the symptoms resolved with proper management. CONCLUSION: The results indicate that oxaliplatin-induced HSRs remain an important issue in safely and successfully fulfilling oxaliplatin-containing chemotherapy. Further studies are needed to analyze the risk factors and establish prophylaxis for such reactions.

Macrocyclic Photoinitiator Based on Prism[5]arene Matching LEDs Light with Low Migration.

In this work, a naphthalene-based macrocycle prism[5]arene (NP5 OCH3 ) is developed as a novel kind of photoinitiator. When NP5 OCH3 is irradiated under light, the bond between methylene and naphthalene can be quickly broken owning to the existence of ring tension. The macrocycle is cleaved to linear oligomer biradicals, which can effectively initiate the free radical photopolymerization of acrylate monomers. Compared with conventional photoinitiators, NP5 OCH3 has strong light absorption in the wavelength range of 365-405 nm, so it can well match the environment-friendly light-emitting diodes (LEDs) light source to realize highly efficient initiation. In addition, there is no small molecule fragment generated during NP5 OCH3 fracture, and the resulted linear oligomer biradicals can be immobilized in the polymer after initiating polymerization, so NP5 OCH3 photoinitiators show much lower migration rate and cytotoxicity. Cleavable macrocycle prismarene may provide a new idea for the design of safe and efficient photoinitiators matching long wavelength light.

Pillar[6]arene: Light Cleaves Macrocycle to Linear Oligomer Biradical to Initiate Photopolymerization.

A novel kind of photoinitiator based on the macrocyclic molecule pillar[6]arene (P6OC2H5) is reported. Under light irradiation, P6OC2H5 was cleaved to a linear oligomer biradical, which could efficiently initiate free-radical photopolymerization. Owing to the absence of small molecular fragment generation, the macrocyclic photoinitiator exhibited a much lower migration rate and cytotoxicity than commercial photoinitiators. This is the first time that a macrocyclic molecule has been developed as a photoinitiator based on the macrocycle fracture mechanism.

Do Epichloë Endophytes and Their Grass Symbiosis Only Produce Toxic Alkaloids to Insects and Livestock?

Epichloë endophytes in forage grasses have attracted widespread attention and interest of chemistry researchers as a result of the various unique chemical structures and interesting biological activities of their secondary metabolites. This review describes the diversity of unique chemical structures of taxa from Epichloë endophytes and grass infected with Epichloë endophytes and demonstrates their reported biological activities. Until now, nearly 160 secondary metabolites (alkaloids, peptides, indole derivatives, pyrimidines, sesquiterpenoids, flavonoids, phenol and phenolic acid derivatives, aliphatic metabolites, sterols, amines and amides, and others) have been reported from Epichloë endophytes and grass infected with Epichloë endophytes. Among these, non-alkaloids account for half of the population of total metabolites, indicating that they also play an important role in Epichloë endophytes and grass infected with Epichloë endophytes. Also, a diverse array of secondary metabolites isolated from Epichloë endophytes and symbionts is a rich source for developing new pesticides and drugs. Bioassays disclose that, in addition to toxic alkaloids, the other metabolites isolated from Epichloë endophytes and symbionts have notable biological activities, such as antifungal, anti-insect, and phytotoxic activities. Accordingly, the biological functions of non-alkaloids should not be neglected in the future investigation of Epichloë endophytes and symbionts.

Highly Oxygenated Triterpenoids and Rare Tetraterpenoids from Abies chensiensis and Their Antibacterial Activity.

Nine new cycloartane triterpenoids (1, 2, 4, 7, 8, 12, 15, 17, and 18) and two new rare tetraterpenoids (24 and 25) formed via a [4 + 2] Diels-Alder cycloaddition between a lanostane triterpenoid and a monoterpenoid, along with 14 previously known triterpenoids, were isolated from the bark of the branches of Abies chensiensis. The structures and absolute configurations of new compounds were elucidated based on spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism. Some of the isolates were evaluated for their antibacterial activity by determining their minimum inhibitory concentrations and growth inhibition curves and examining for morphological alterations. Among the compounds tested, the new cycloartane triterpenoid 8 was the most active against Bacillus subtilis. Thus, morphological alterations of B. subtilis on treatment with 8 were observed by scanning electron microscopy, showing that the cells were irregular, wrinkled, and disrupted.

Phytotoxic ent-Isopimarane-Type Diterpenoids from Euphorbia hylonoma.

Thirteen new ent-isopimarane-type diterpenoids, 1-10 and 14-16, and seven known diterpenoids, 11-13 and 17-20, were isolated from the roots of Euphorbia hylonoma. Among these compounds, four pairs of C-12 epimers (1 vs 2, 4 vs 5, 12 vs 13, and 14 vs 15) were identified. The structures of the new diterpenoids were elucidated using spectroscopic data analyses, electronic circular dichroism, and single-crystal X-ray diffraction data. The phytotoxic effects of compounds 1-20 on the growth of the roots and shoots of Poa annua and Festuca arundinacea seedlings were evaluated. Among the tested diterpenoids, 18 was the most active for inhibiting the growth of P. annua seedlings, and this compound was as active as glyphosate.

Comprehensive Analysis of Codon Usage Bias in Seven Epichloë Species and Their Peramine-Coding Genes.

Codon usage bias plays an important role in shaping genomes and genes in unicellular species and multicellular species. Here, we first analyzed codon usage bias in seven Epichloë species and their peramine-coding genes. Our results showed that both natural selection and mutation pressure played a role in forming codon usage bias in seven Epichloë species. All seven Epichloë species contained a peramine-coding gene cluster. Interestingly, codon usage bias of peramine-coding genes were not affected by natural selection or mutation pressure. There were 13 codons more frequently found in Epichloë genome sequences, peramine-coding gene clusters and orthologous peramine-coding genes, all of which had a bias to end with a C nucleotide. In the seven genomes analyzed, codon usage was biased in highly expressed coding sequences (CDSs) with shorter length and higher GC content. Genes in the peramine-coding gene cluster had higher GC content at the third nucleotide position of the codon, and highly expressed genes had higher GC content at the second position. In orthologous peramine-coding CDSs, high expression level was not significantly correlated with CDS length and GC content. Analysis of selection pressure identified that the genes orthologous to peramine genes were under purifying selection. There were no differences in codon usage bias and selection pressure between peramine product genes and non-functional peramine product genes. Our results provide insights into understanding codon evolution in Epichloë species.

Dahurelmusin A, a Hybrid Peptide-Polyketide from Elymus dahuricus Infected by the Epichloë bromicola Endophyte.

One novel hybrid peptide-polyketide, dahurelmusin A (1), was isolated from Elymus dahuricus infected by the Epichloë bromicola endophyte. Comprehensive spectroscopic analysis revealed that 1 is the first example of hybrid peptide-polyketide possessing an unprecedented 5-hydroxy-2,2,4,6-tetramethyl-3-oxooctanoic acid moiety. The single-crystal X-ray diffraction analyses allowed the absolute configuration assignment of this compound. Compound 1 also exhibited significant insecticidal activities against Rhopalosiphum padi and Brevicoryne brassicae with LC50 values of 0.092 and 0.251 mM, respectively.

Advances in Research on Epichloë endophytes in Chinese Native Grasses.

Epichloë fungal endophytes are broadly found in cool-season grasses. The symbiosis between these grasses and Epichloë may improve the abiotic and biotic resistance of the grass plant, but some Epichloë species produce alkaloids that are toxic for livestock. Therefore, it is important to understand the characteristics of the grass-Epichloë s symbiosis so that the beneficial aspects can be preserved and the toxic effects to livestock can be avoided. Since the 1990s, Chinese researchers have conducted a series of studies on grass-Epichloë symbiosis. In this review, we describe the current state of Epichloë endophyte research in Chinese native grasses. We found that more than 77 species of native grasses in China are associated with Epichloë endophytes. In addition, we review the effects of various Epichloë species on native grass responses to abiotic and biotic stress, phylogeny, and alkaloid production. We provide an overview of the study of Epichloë species on native grasses in China and directions for future research.

Terpenoids with anti-inflammatory activity from Abies chensiensis.

The phytochemical investigation of Abies chensiensis led to the isolation and identification of nine new compounds including eight triterpenoids (1-8) and a new abietane-type diterpene (9), along with three known compounds (10-12). The absolute configuration of 9 was assigned by X-ray diffraction analysis. Compounds 1-11 were evaluated for the anti-inflammatory activity. Among the tested compounds, 1, 2, 5 and 6 exhibited potent inhibitory activity with IC50 values of 15.97, 18.73, 20.18 and 10.97µM, respectively.

Highly oxygenated triterpenoids from the roots of Schisandra chinensis and their anti-inflammatory activities.

A new highly oxygenated triterpenoid, schinchinenlactone D (1), and three known compounds (2-4) were isolated from the roots of Schisandra chinensis. Their structures were determined by combining the spectroscopic analysis with the theoretical computations. The anti-inflammatory activities of compounds 1-4 were evaluated, and compound 3 exhibits the most significant activity in the inhibition of NO production with an IC50 value of 10.6 µM.

Antifungal, Phytotoxic, and Cytotoxic Activities of Metabolites from Epichloë bromicola, a Fungus Obtained from Elymus tangutorum Grass.

The development of high-quality herbage is an important aspect of animal husbandry. Inoculating beneficial fungi onto inferior grass is a feasible strategy for producing new varieties of high-quality herbage. Epichloë bromicola is a candidate fungus that is isolated from Elymus tangutorum. A total of 17 metabolites, 1-17, were obtained from E. bromicola, and their biological activities were assayed. Metabolite 1 exhibited antifungal activities against Alternaria alternata, Fusarium avenaceum, Bipolaris sorokiniana, and Curvularia lunata. EC50 values ranged from 0.7 to 5.3 µM, which were better than the positive control, chlorothalonil. Metabolite 8 displayed obvious phytotoxic effects toward Lolium perenne and Poa crymophila seedlings, and it was as active as glyphosate. None of these isolated metabolites displayed cytotoxicity against Madin-Darby bovine kidney cells. The IC50 values were greater than 100 µM, and the metabolites increased the growth of the cells at a concentration of 12.5 µM. The bioassay indicated that E. bromicola may be a beneficial fungus for producing new varieties of herbage with various resistances. Additionally, metabolite 7, 3-(2'-(4″-hydroxyphenyl)acetoxy)-2S-methylpropanoic acid, is a new natural product, and its stereochemistry was determined by means of optical rotation computation and chemical reactions.

[Phylogeny of Neotyphodium endophyte from western Chinese Elymus species based on act sequences].

OBJECTIVE: We analyzed phylogenetic relationships between asexual endophytes isolated from western Chinese Elymus species. METHODS: Fifteen act sequences were cloned from asexual endophytes of the western Chinese Elymus species. The phylogenetic tree and network topology structure were constructed using act sequences obtained and Genbank. RESULTS: The act sequences from asexual endophyte were single-copy gene. The western Chinese asexual endophye (Neotyphodium spp.) has a different origination from the North American sexual endophyte ( Epichloë elymi) from Elymus species, but there is a closer relationship between Neotyphodium spp. and Neotyphodium chisosum from North American Achnatherum eminens. Further, endophyte gene-flow exists between sexual Neotyphodium chisosum from North American Achnatherum eminens ( Hap 8) and asexual Neotyphodium sp. from western Chinese Elymus species (Hap 3).