Peroxydisulfate-Driven Reductive Dechlorination as Affected by Soil Constituents: Free Radical Formation and Conversion.

We report a previously unrecognized but efficient reductive degradation pathway in peroxydisulfate (PDS)-driven soil remediation. With supplements of naturally occurring low-molecular-weight organic acids (LMWOAs) in anaerobic biochar-activated PDS systems, degradation rates of 12 γ-hexachlorocyclohexanes (HCH)-spiked soils boosted from 40% without LMWOAs to a maximum of 99% with 1 mM malic acid. Structural analysis revealed that an increase in α-hydroxyl groups and a diminution in pKa1 values of LMWOAs facilitated the formation of reductive carboxyl anion radicals (COO•-) via electrophilic attack by SO4•-/•OH. Furthermore, degradation kinetics were strongly correlated with soil organic matter (SOM) contents than iron minerals. Combining a newly developed in situ fluorescence detector of reductive radicals with quenching experiments, we showed that for soils with high, medium, and low SOM contents, dominant reactive species switched from singlet oxygen/semiquinone radicals to SO4•-/•OH and then to COO•- (contribution increased from 30.8 to 66.7%), yielding superior HCH degradation. Validation experiments using SOM model compounds highlighted critical roles of redox-active moieties, such as phenolic - OH and quinones, in radical formation and conversion. Our study provides insights into environmental behaviors related to radical activation of persulfate in a broader soil horizon and inspiration for more advanced reduction technologies.

[Effects of maltodextrin on water adsorption and thermodynamic properties of Codonopsis Radix spray-dried powder].

This study aims to reveal the effects of maltodextrin(MD) on the water adsorption and thermodynamic properties of Codonopsis Radix(DS) spray-dried powder by determining the moisture and energy changes of the powder in the process of moisture absorption. The static weighing method was used to obtain the isothermal water adsorption data of the spray-dried powder in 6 saturated salt solutions(KAc, MgCl_2·6H_2O, K_2CO_3, NaBr, NaCl, and KCl) at 3 temperatures(25, 35, and 45 ℃). Six models were used for fitting of the water adsorption process, and the most suitable model was selected based on the model performance. Furthermore, the corresponding net equivalent adsorption heat and differential entropy were calculated, and the adsorption entropy change was integrated. The linear relationship between net equivalent adsorption heat and differential entropy was drawn based on the entropy-enthalpy complementarity theory. The results showed that the water adsorption properties of DS and DS-MD spray-dried powder followed the type Ⅲ isotherm and was well fitted by the GAB model. The monolayer water content M_0 decreased with the increase in temperature. At the same temperature, the M_0 of DS spray-dried powder decreased after the addition of MD. The net equivalent adsorption heat and differential entropy of DS and DS-MD spray-dried powder decreased with the increase in water content, which presented a linear relationship. The addition of MD decreased the water activity corresponding to the lowest integral adsorption entropy of the powder, and the system became more stable. The results indicated that the spray-dried powder became more stable after the addition of MD.

Search for Snail Repellents: Antimollusc Activities from Stemona parviflora and Six Other Chinese Stemona Species.

Snails are important agricultural pests difficult to control, but data regarding molluscicidal assays are scant. Stemona alkaloids are typical secondary metabolites for the taxa and have been broadly investigated for their pharmacological and toxicological effects. This makes it possible for us to further develop the toxicities of these compounds to snails. In this work, we tested the antifeedant properties of leaves from seven Chinese Stemona species against the land snail species Bradybaena ravida in choice and non-choice feeding assays. The tested leaves Stemona parviflora exhibited the most deterrent effects, and a further phytochemical investigation of aerial parts led to the identification of 16 alkaloids. Among them, three novel alkaloids could be identified. The alkaloidal fraction and single alkaloids were further assayed against this snail species, and the results suggest a cocktail effect because the impact of the alkaloidal fraction was higher than the effects caused by single alkaloids. The study can promote the search process of natural antimollusc products from plants to control snails.

Ginkgo biloba L. exocarp petroleum ether extract inhibits methicillin-resistant Staphylococcus aureus by modulating ion transport, virulence, and biofilm formation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As reported in the Ancient Chinese Medicinal Books, Ginkgo biloba L. fruit has been used as a traditional Chinese medicine for the treatment asthma and cough or as a disinfectant. Our previous study demonstrated that G. biloba exocarp extract (GBEE), an extract of a traditional Chinese herb, inhibits the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. However, GBEE is a crude extract that contains many components, and the underlying mechanisms of purified GBEE fractions extracted with solvents of different polarities are unknown. AIM OF THE STUDY: This study aimed to investigate the different components in GBEE fractions extracted with solvents of different polarities and their antibacterial effects and mechanisms against MRSA and Staphylococcus haemolyticus biofilms both in vitro and in vivo. METHODS: The components in different fractions were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Microbroth dilution assays and time growth curves were used to determine the antibacterial effects of the fractions on 15 clinical bacterial isolates. Crystal violet staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to identify the fractions that affected bacterial biofilm formation. The potential MRSA targets of the GBEE fraction obtained with petroleum ether (PE), denoted GBEE-PE, were screened by transcriptome sequencing, and the gene expression profile was verified by quantitative polymerase chain reaction (qPCR). RESULTS: HPLC-HRMS analysis revealed that the four GBEE fractions (extracted with petroleum ether, ethyl acetate, n-butanol, and water) contained different ginkgo components, and the antibacterial effects decreased as the polarity of the extraction solvent increased. The antibacterial activity of GBEE-PE was greater than that of the GBEE fraction extracted with ethyl acetate (EA). GBEE-PE improved H. illucens survival and reduced MRSA colonization in model mouse organs. Crystal violet staining and SEM and TEM analyses revealed that GBEE-PE inhibited MRSA and S. haemolyticus biofilm formation. Transcriptional analysis revealed that GBEE-PE inhibits MRSA biofilms by altering ion transport, cell wall metabolism and virulence-related gene expression. In addition, the LO2 cell viability and H. illucens toxicity assay data showed that GBEE-PE at 20 mg/kg was nontoxic. CONCLUSION: The GBEE fractions contained different components, and their antibacterial effects decreased with increases in the polarity of the extraction solvent. GBEE-PE limited MRSA growth and biofilm formation by affecting ion transport, cell wall synthesis, and virulence-related pathways. This research provides a more detailed overview of the mechanism by which GBEE-PE inhibits MRSA both in vitro and in vivo and suggests that GBEE-PE is a new prospective antimicrobial with the potential to be used in MRSA therapeutics in the future.

Rotor-based image-guided therapy of glioblastoma.

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.

MSH7 confers quantitative variation in pollen fertility and boosts grain yield in maize.

Fertile pollen is critical for the survival, fitness, and dispersal of flowering plants, and directly contributes to crop productivity. Extensive mutational screening studies have been carried out to dissect the genetic regulatory network determining pollen fertility, but we still lack fundamental knowledge about whether and how pollen fertility is controlled in natural populations. We used a genome-wide association study (GWAS) to show that ZmGEN1A and ZmMSH7, two DNA repair-related genes, confer natural variation in maize pollen fertility. Mutants defective in these genes exhibited abnormalities in meiotic or post-meiotic DNA repair, leading to reduced pollen fertility. More importantly, ZmMSH7 showed evidence of selection during maize domestication, and its disruption resulted in a substantial increase in grain yield for both inbred and hybrid. Overall, our study describes the first systematic examination of natural genetic effects on pollen fertility in plants, providing valuable genetic resources for optimizing male fertility. In addition, we find that ZmMSH7 represents a candidate for improvement of grain yield.

Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice.

OBJECTIVE: To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice. METHODS: Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aß pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micropositron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3ß (PI3K/Akt/GSK3ß) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively. RESULTS: BXD ameliorated cognitive deficits and Aß pathological features (P<0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P<0.01). Brain glucose uptake in the BG was higher than that in the MG (P<0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P<0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P<0.01), while the levels of GSK3ß were reduced (P<0.01). CONCLUSION: BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3ß insulin signaling pathway, and improving brain glucose metabolism.

Protective effects of Radix Stellariae extract against Alzheimer's disease via autophagy activation in Caenorhabditis elegans and cellular models.

Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aß and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aß fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a ß-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.

Ameliorative effect of Luffa cylindrica fruits on Caenorhabditis elegans and cellular models of Alzheimer's disease-related pathology via autophagy induction.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored. AIMS: This study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action. MATERIALS & METHODS: Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aß- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed. RESULTS: The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aß- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aß and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine). DISCUSSION: LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE. CONCLUSION: Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Organic-inorganic covalent-ionic molecules for elastic ceramic plastic.

Although organic-inorganic hybrid materials have played indispensable roles as mechanical1-4, optical5,6, electronic7,8 and biomedical materials9-11, isolated organic-inorganic hybrid molecules (at present limited to covalent compounds12,13) are seldom used to prepare hybrid materials, owing to the distinct behaviours of organic covalent bonds14 and inorganic ionic bonds15 in molecular construction. Here we integrate typical covalent and ionic bonds within one molecule to create an organic-inorganic hybrid molecule, which can be used for bottom-up syntheses of hybrid materials. A combination of the organic covalent thioctic acid (TA) and the inorganic ionic calcium carbonate oligomer (CCO) through an acid-base reaction provides a TA-CCO hybrid molecule with the representative molecular formula TA2Ca(CaCO3)2. Its dual reactivity involving copolymerization of the organic TA segment and inorganic CCO segment generates the respective covalent and ionic networks. The two networks are interconnected through TA-CCO complexes to form a covalent-ionic bicontinuous structure within the resulting hybrid material, poly(TA-CCO), which unifies paradoxical mechanical properties. The reversible binding of Ca2+-CO32- bonds in the ionic network and S-S bonds in the covalent network ensures material reprocessability with plastic-like mouldability while preserving thermal stability. The coexistence of ceramic-like, rubber-like and plastic-like behaviours within poly(TA-CCO) goes beyond current classifications of materials to generate an 'elastic ceramic plastic'. The bottom-up creation of organic-inorganic hybrid molecules provides a feasible pathway for the molecular engineering of hybrid materials, thereby supplementing the classical methodology used for the manufacture of organic-inorganic hybrid materials.

Influence of geographic origin and tissue type on the medicinal chemical compounds of Semiliquidambar cathayensis.

Semiliquidambar cathayensis is widely used in traditional Chinese medicine owing its high concentrations of polyphenol, triterpenoidic acid, and flavonoids. This study aimed to explore the impact of geographical origin and tissue type on the contents of chemical compounds of S. cathayensis, as determined by colorimetric and chromatographic methods. Therefore, we quantitively evaluated chemical compounds found in the tissues of various organs of plants collected in six different regions. Overall, we found that geographical origin affected the content of medicinal compounds in S. cathayensis leaves, with plants from Jingzhou county showing the best therapeutic potential. However, no specific correlation was observed with latitude. It is noteworthy that the amount of paeoniflorin and other compounds can be used as biomarkers of geographical origin and tissue type. Most medicinal compounds accumulated mainly in the leaves, whereas ursolic and oleanolic acids accumulated in the roots. These results show that the comprehensive medicinal value of the leaves of S. cathayensis in Jingzhou county is the highest, but the root should be selected first to collect oleanolic acid and ursolic acid.

ZmRPN1 confers quantitative variation in pollen number and boosts hybrid seed production in maize.

The number of pollen grains is a critical determinant of reproductive success in seed plants and varies among species and individuals. However, in contrast with many mutant-screening studies relevant to anther and pollen development, the natural genetic basis for variations in pollen number remains largely unexplored. To address this issue, we carried out a genome-wide association study in maize, ultimately revealing that a large presence/absence variation in the promoter region of ZmRPN1 alters its expression level and thereby contributes to pollen number variation. Molecular analyses showed that ZmRPN1 interacts with ZmMSP1, which is known as a germline cell number regulator, and facilitates ZmMSP1 localization to the plasma membrane. Importantly, ZmRPN1 dysfunction resulted in a substantial increase in pollen number, consequently boosting seed production by increasing female-male planting ratio. Together, our findings uncover a key gene controlling pollen number, and therefore, modulation of ZmRPN1 expression could be efficiently used to develop elite pollinators for modern hybrid maize breeding.

Comparative transcriptomics provides insights into the pathogenic immune response of brown leaf spots in weeping forsythia.

Weeping forsythia is an important ornamental, ecological and medicinal plant. Brown leaf spots limit the large-scale production of weeping forsythia as a medicinal crop. Alternaria alternata is a pathogen causing brown leaf spots in weeping forsythia; however, its pathogenesis and the immune response mechanisms of weeping forsythia remain unclear. In this study, we identified two mechanisms based on morphological anatomy, physiological indexes and gene expression analyses. Our results showed that A. alternata induced leaf stomata to open, invaded the mesophyll, dissolved the cell wall, destroyed the cell membrane and decreased the number of chloroplasts by up-regulating the expression of auxin-activated signaling pathway genes. Alternaria alternata also down-regulated iron-ion homeostasis and binding-related genes, which caused an increase in the levels of iron ions and reactive oxygen species in leaves. These processes eventually led to programmed cell death, destroying palisade and spongy tissues and causing the formation of iron rust spots. Alternaria alternata also caused defense and hypersensitive responses in weeping forsythia through signaling pathways mediated by flg22-like and elf18-like polypeptides, ethylene, H2O2 and bacterial secretion systems. Our study provides a theoretical basis for the control of brown leaf spots in weeping forsythia.

Trifolirhizin inhibits proliferation, migration and invasion in nasopharyngeal carcinoma cells via PI3K/Akt signaling pathway suppression.

Nasopharyngeal carcinoma (NPC) is a highly recurrent and metastatic malignant tumor affecting a large number of individuals in southern China. Traditional Chinese herbal medicine has been found to be a rich source of natural compounds with mild therapeutic effects and minimal side effects, making them increasingly popular for treating various diseases. Trifolirhizin, a natural flavonoid derived from leguminous plants, has gained significant attention for its therapeutic potential. In this study, we confirmed that trifolirhizin could effectively inhibit the proliferation, migration and invasion of nasopharyngeal carcinoma 6-10B and HK1 cells. Furthermore, our findings demonstrated that trifolirhizin achieves this by suppressing the PI3K/Akt signaling pathway. The findings of the present study provides a valuable perspective on the potential therapeutic applications of trifolirhizin for the treatment of nasopharyngeal carcinoma.

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula.

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.

Acupuncture ameliorates Mobile Phone Addiction with sleep disorders and restores salivary metabolites rhythm.

Objectives: Mobile Phone Addiction (MPA) is a novel behavioral addiction resulting in circadian rhythm disorders that severely affect mental and physical health. The purpose of this study is to detect rhythmic salivary metabolites in MPA with sleep disorder (MPASD) subjects and investigate the effects of acupuncture. Methods: Six MPASD patients and six healthy controls among the volunteers were enrolled by MPA Tendency Scale (MPATS) and Pittsburgh Sleep Quality Index (PSQI), then the salivary samples of MPASD and healthy controls were collected every 4-h for three consecutive days. Acupuncture was administered for 7 days to MPASD subjects, then saliva samples were collected again. Salivary metabolomes were analyzed with the method of LC-MS. Result: According to our investigation, 70 (57.85%) MPA patients and 56 (46.28%) MPASD patients were identified among 121 volunteers. The symptoms of the 6 MPASD subjects were significantly alleviated after acupuncture intervention. The number of rhythmic saliva metabolites dropped sharply in MPASD subjects and restored after acupuncture. Representative rhythmic saliva metabolites including melatonin, 2'-deoxyuridine, thymidine, thymidine 3',5'-cyclic monophosphate lost rhythm and restored after acupuncture, which may attribute to promising MPASD treatment and diagnosis biomarkers. The rhythmic saliva metabolites of healthy controls were mainly enriched in neuroactive ligand-receptor interaction, whereas polyketide sugar unit biosynthesis was mainly enriched in MPASD patients. Conclusion: This study revealed circadian rhythm characteristics of salivary metabolites in MPASD and that acupuncture could ameliorate MPASD by restoring part of the dysrhythmia salivary metabolites.

Diagnostic validation and development of an algorithm for identification of intussusception in children using electronic health records of Ningbo city in China.

BACKGROUND: Monitoring the risk of intussusception after the introduction of rotavirus vaccines is recommended by the World Health Organization (WHO). Although the validity of intussusception monitoring using electronic health records (EHRs) has been confirmed previously, no similar studies have been conducted in China. We aimed to verify the diagnosis and determine an algorithm with the best performance for identification of intussusception using Chinese EHR databases. RESEARCH DESIGN AND METHODS: Using the Regional Health Information Platform in Ningbo, patients aged 0-72 months from 2015 to 2021 with any related visits for intussusception were included. The algorithms were based on diagnostic codes or keywords in different clinical scenarios, and their performance was evaluated with positive predictive value (PPV) and sensitivity in line with the Brighton guidelines. RESULTS: Brighton level 1 intussusception was confirmed in 2958 patients with 3246 episodes. Fine-tuned algorithms combining the appearance of the relevant ICD-10 codes or the Chinese keyword 'Chang Tao' in any diagnostic reports with the results of enema treatments or related surgeries showed the highest sensitivity, while the highest PPV was obtained by further criteria based on typical radiographic appearances. CONCLUSION: Intussusception could be identified and validated internally using EHRs in Ningbo.

DNA damage and up-regulation of PARP-1 induced by columbin in vitro and in vivo.

Columbin (CLB) is the most abundant (>1.0%) furan-containing diterpenoid lactone in herbal medicine Tinospora sagittate (Oliv.) Gagnep. The furano-terpenoid was found to be hepatotoxic, but the exact mechanisms remain unknown. The present study demonstrated that administration of CLB at 50 mg/kg induced hepatotoxicity, DNA damage and up-regulation of PARP-1 in vivo. Exposure to CLB (10 µM) induced GSH depletion, over-production of ROS, DNA damage, up-regulation of PARP-1 and cell death in cultured mouse primary hepatocytes in vitro. Co-treatment of mouse primary hepatocytes with ketoconazole (10 µM) or glutathione ethyl ester (200 µM) attenuated the GSH depletion, over-production of ROS, DNA damage, up-regulation of PARP-1, and cell death induced by CLB, while co-exposure to L-buthionine sulfoximine (BSO, 1000 µM) intensified such adverse effects resulting from CLB exposure. These results suggest that the metabolic activation of CLB by CYP3A resulted in the depletion of GSH and increase of ROS formation. The resultant over-production of ROS subsequently disrupted the DNA integrity and up-regulated the expression of PARP-1 in response to DNA damage, and ROS-induced DNA damage was involved in the hepatotoxicity of CLB.

Atorvastatin attenuates allergic inflammation by blocking prostaglandin biosynthesis in rats with allergic rhinitis.

BACKGROUND: Prostaglandins (PGs) are bioactive lipid mediators derived from the nuclear and plasma membranes via the cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism. PGs bridge the interactions between various immunomodulatory cells in allergic rhinitis (AR) and are considered key players in regulating pro-inflammatory and anti-inflammatory responses. AA conversion to PGs involves rate-limiting enzymes that may be blocked by statins. The mechanisms by which statins regulate these enzymes in AR remain unclear. We investigated the effects of oral atorvastatin on PGs production in AR. METHODS: An ovalbumin-induced AR rat model was constructed and the changes in nasal symptom score and nasal mucosa histopathological characteristics of AR rats under different atorvastatin doses were assessed. qRT-PCR, western blotting, and immunofluorescence were used to detect the mRNA and protein expression levels of rate-limiting enzymes and downstream molecules of AA metabolism in the nasal mucosa and liver. RESULTS: Oral atorvastatin significantly alleviated symptoms and eosinophil infiltration in the nasal mucosa, inhibited goblet cell hyperplasia and mast cell recruitment, and decreased mucus secretion in AR rats. Increasing atorvastatin dose increased the anti-inflammatory effects. High-dose atorvastatin inhibited upregulation of the inflammatory mediator PGD2 in the nasal mucosa of AR rats. Compared to the control group, the mRNA and protein expression of the rate-limiting enzymes COX-2, PGDS, and PGES in AA metabolism in the AR group were upregulated but downregulated after the oral administration of high-dose atorvastatin. Atorvastatin also showed dose-dependent inhibition of ERK1/2 and downstream NF-κB phosphorylation in the nasal mucosa and liver of AR rats. CONCLUSIONS: Atorvastatin inhibited allergic inflammation and attenuated AR nasal symptoms by downregulating PGD2 and rate-limiting enzyme expression in PGD2 biosynthesis, possibly by blocking the RAS/ERK/NF-κB signaling pathway.