Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3/IKK/NF-κB signaling via gut microbial tryptophan metabolites.

With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aß and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aß and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.

Biotic regulation of phoD-encoding gene bacteria on organic phosphorus mineralization in lacustrine sediments with distinct trophic levels.

Organic phosphorus (Po) mineralization hydrolyzed by alkaline phosphatase (APase) can replenish bioavailable P load in the sediment water ecosystem of lakes. However, the understanding about the interaction between P load and bacteria community encoding APase generation in the sediment are still limited. Different P pools in the sediments from Taihu Lake, China were measured using sequential extraction procedure. The APAase activity (APA) were obtained accompanying with enzymatic dynamical parameters Vmax and Km. The abundances and diversity of gene phoD-harboring bacterial communities were assessed using high throughput sequencing. The analysis results showed the decrease of potentially bioavailable P fractions including MgCl2-P and Fe-P along sampling gradient southwards together with active P concentrations in the water. Conversely, increasing APA and absolute abundance of phoD gene were found with the decreasing of P loads southwards. Positive correlation (p < 0.05) between absolute abundance and APA indicated that phoD-encoding bacteria manipulated the APA and Po mineralization. Negative correlation (p < 0.01) suggested that the APA was restrained by high P load and was promoted under low P condition. However, higher Vmax and Km values suggested that high mineralization potential of Po maintained the high concentrations of potentially bioavailable P even the APA was restricted. The abundance increase of predominant genus Cobetia (from 15.51 to 24.34 %) mirrored by the reduced Calothrix abundance (from 24.65 to 1036 %) was speculated to be responsible for the APA promotion under low P condition. Higher diversity indices in the high P scenario suggested that high P load stimulated the ecological diversity of gene phoD-encoding bacteria community. Generally, rare taxa such as Burkholderia having high connected degrees in bacterial communities together with abundant genera synergistically manipulated the phoD gene abundance and APase generation. Interaction between P fractions and bacteria encoding phoD gene determined the eutrophication status in the lacustrine ecosystem.

Qualitative and quantitative analysis of chemical constituents in goupi plaster prepared by various extraction methods using UPLC-Q-Exactive-MS and UPLC-MS/MS.

Goupi plaster, a representative preparation of black plaster, has demonstrated promising effects in treating knee osteoarthritis. However, high temperature used in traditional frying extraction may cause decomposition of its effective components, thus limiting the efficacy. This study aimed to explore the scientific nature of the traditional preparation technology of Goupi plaster, and to compare the effects of different extraction methods on the types of chemical components and the content of index components. The UPLC-Q-Exactive-MS and UPLC-MS/MS technologies which have high efficiency, sensitivity and accuracy, were used to qualitatively and quantitatively analyze the chemical components of Goupi plaster under different preparation processes. The results show that the extraction solvent approach is different from the traditional frying extraction method, and has a positive effect. However, the mechanism of action of Goupi plaster is complex and its pharmacological effects are diverse. Future studies should explore whether it necessary to change the frying extraction method. This experiment provides a theoretical basis that will guide further scientific discussion and research into the frying extraction of Goupi plaster.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a "mucosal mask". The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.

Fabrication of diosmin loaded food-grade bilayer nanoparticles with modified chitosan and soy peptides and antioxidant properties examination.

Diosmin is a flavonoid derived from plants, possessing anti-inflammatory, antioxidant, antidiabetic, neuroprotective and cardiovascular protective properties. However, diosmin has low solubility in water, leading to low bioavailability. In this study, we constructed bilayer nanoparticles with trimethyl chitosan and soy peptides to improve the oral bioaccessibility and bioavailability of diosmin, and determined the characteristics and antioxidant properties of the diosmin-loaded nanoparticles. The results showed that the size of the nanoparticles was around 250 nm with the encapsulation efficiency higher than 97 %, and the nanoparticles were stable under regular conditions. In vitro digestion suggested the nanoparticles could protect diosmin from releasing in gastric digestion but promote the bioaccessibility of diosmin in intestine. Furthermore, the diosmin-loaded nanoparticles presented excellent antioxidant activities in vitro and significantly decreased the Lipopolysaccharides-induced brain Malondialdehyde (MDA) level by oral administration. Therefore, the reported nanoparticles may be an effective platform for improving the oral bioavailability of diosmin.

[Effect of Water Components on Aggregation and Sedimentation of Polystyrene Nanoplastics].

The aggregation and sedimentation of micro/nano-plastics significantly affect their migration and distribution in the environment. This study investigated the effects of Na+ and natural organic matter （NOM） on the aggregation and sedimentation of polystyrene nano-plastics （PS-NPs） in the aqueous phase. Six types of water， such as seawater， lake water， and domestic sewage， were used to evaluate the above effects and other potential influencing factors. The results indicated that Na+ could facilitate the sedimentation of PS-NPs when it was less than 80 mmol·L-1， whereas it could promote the aggregation and suspension of PS-NPs when the concentration was greater than 80 mmol·L-1. NOM molecules affected the aggregation and sedimentation of PS-NPs by changing the ζ potential and relative density of particles via forming a multilayer adsorption structure with Na+ on the particle surface. It was observed that NOM greater than 10 mg·L-1 enhanced the dispersion and suspension of PS-NPs， which might have been attributed to the decrease in relative density of the particles as a large amount of NOM was absorbed onto the surface. Compared with synthetic waters， environmental waters enhanced the aggregation of PS-NPs， which may have been related to the amino acid， protein， and other organic macro-molecules in the water.

Highly Sensitive Pressure Sensor Based on Elastic Conductive Microspheres.

Elastic pressure sensors play a crucial role in the digital economy, such as in health care systems and human-machine interfacing. However, the low sensitivity of these sensors restricts their further development and wider application prospects. This issue can be resolved by introducing microstructures in flexible pressure-sensitive materials as a common method to improve their sensitivity. However, complex processes limit such strategies. Herein, a cost-effective and simple process was developed for manufacturing surface microstructures of flexible pressure-sensitive films. The strategy involved the combination of MXene-single-walled carbon nanotubes (SWCNT) with mass-produced Polydimethylsiloxane (PDMS) microspheres to form advanced microstructures. Next, the conductive silica gel films with pitted microstructures were obtained through a 3D-printed mold as flexible electrodes, and assembled into flexible resistive pressure sensors. The sensor exhibited a sensitivity reaching 2.6 kPa-1 with a short response time of 56 ms and a detection limit of 5.1 Pa. The sensor also displayed good cyclic stability and time stability, offering promising features for human health monitoring applications.

Multi-omics for COVID-19: driving development of therapeutics and vaccines.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has raised global concern for public health and economy. The development of therapeutics and vaccines to combat this virus is continuously progressing. Multi-omics approaches, including genomics, transcriptomics, proteomics, metabolomics, epigenomics and metallomics, have helped understand the structural and molecular features of the virus, thereby assisting in the design of potential therapeutics and accelerating vaccine development for COVID-19. Here, we provide an up-to-date overview of the latest applications of multi-omics technologies in strategies addressing COVID-19, in order to provide suggestions towards the development of highly effective knowledge-based therapeutics and vaccines.

Multiscale Simulations on Synaptic Signal Transduction of Energy-Harvesting P(VDF-TrFE)-Based Artificial Retina.

Ferroelectric polymers have drawn a lot of research concerns recently due to their lightness, mechanical flexibility, conformability, and facile processability. Remarkably, these polymers can be used to fabricate biomimetic devices, such as artificial retina or electronic skin, to realize artificial intelligence. The artificial visual system behaves as a photoreceptor, converting incoming light into electric signals. The most widely studied ferroelectric polymer, poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)], can be used as the building block in this visual system to implement synaptic signal generation. There is a void in computational investigations on the complicated working picture of P(VDF-TrFE)-based artificial retina from a microscopic mechanism to a macroscopic mechanism. Therefore, a multiscale simulation method combining quantum chemistry calculations, first-principles calculations, Monte Carlo simulations, and the Benav model was established to illustrate the whole working principle, involving synaptic signal transduction and consequent communication with neuron cells, of the P(VDF-TrFE)-based artificial retina. This newly developed multiscale method not only can be further applied to other energy-harvesting systems involving synaptic signals but also would be helpful to build microscopic/macroscopic pictures within these energy-harvesting devices.

Meta-analysis of effectiveness and safety of glucocorticoid combined with hydroxychloroquine in the treatment of systemic lupus erythematosus rash.

BACKGROUND: Many studies have found that glucocorticoid (GC) combined with hydroxychloroquine (HCQ) has a good clinical effect in the treatment of systemic lupus erythematosus (SLE) rash, but there is no relevant systematic evaluation at present. The purpose of this study was to systematically evaluate and analyze the effectiveness and safety of GC combined with HCQ in the treatment of SLE rash. METHODS: Randomized controlled trials of GC combined with HCQ in the treatment of SLE rash were collected through computer retrieval of Cochrane Library, PubMed, Embase, CNKI, China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform (Wanfang), and China Biology Medicine disc (CBM) since the establishment of the database. The main outcome indicators included clinical total effective rate, adverse reactions, SLE disease activity index (SLEDAI) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement 3 (C3). A meta-analysis was conducted using Review Manager 5.3 software. RESULTS: A total of 11 studies involving 809 patients (406 in the test group and 403 in the control group) were included in this article. The meta-analysis results showed that compared with the single use of GC, GC combined with HCQ could improve the clinical total effective rate in the treatment of SLE rash (odds ratio [OR] = 4.27, 95% confidence interval [CI] 2.50-7.30, p < .00001), and reduce the occurrence of adverse reactions (OR = 0.26, 95% CI 0.15-0.44, p < .00001); effectively reduce SLEDAI score (mean difference [MD] = 1.88, 95% CI 1.66-2.10, p < .00001) and ESR level (MD = 7.92, 95% CI 5.66-10.19, p < .00001); increase C3 level after treatment (MD = 0.36, 95% CI 0.32-0.41, p < .00001); and reduce CRP level (MD = 3.22, 95% CI 2.87-3.58, p < .00001), with statistically significant differences. CONCLUSION: Compared with the use of GC alone, GC combined with HCQ can improve the clinical effectiveness of SLE rash treatment, with a low incidence of adverse reactions and good clinical safety. However, the number and quality of studies included in this article were not high, so the findings need to be further verified by high-quality, multicenter randomized controlled trials.

Cellular differentiation into hyphae and spores in halophilic archaea.

Several groups of bacteria have complex life cycles involving cellular differentiation and multicellular structures. For example, actinobacteria of the genus Streptomyces form multicellular vegetative hyphae, aerial hyphae, and spores. However, similar life cycles have not yet been described for archaea. Here, we show that several haloarchaea of the family Halobacteriaceae display a life cycle resembling that of Streptomyces bacteria. Strain YIM 93972 (isolated from a salt marsh) undergoes cellular differentiation into mycelia and spores. Other closely related strains are also able to form mycelia, and comparative genomic analyses point to gene signatures (apparent gain or loss of certain genes) that are shared by members of this clade within the Halobacteriaceae. Genomic, transcriptomic and proteomic analyses of non-differentiating mutants suggest that a Cdc48-family ATPase might be involved in cellular differentiation in strain YIM 93972. Additionally, a gene encoding a putative oligopeptide transporter from YIM 93972 can restore the ability to form hyphae in a Streptomyces coelicolor mutant that carries a deletion in a homologous gene cluster (bldKA-bldKE), suggesting functional equivalence. We propose strain YIM 93972 as representative of a new species in a new genus within the family Halobacteriaceae, for which the name Actinoarchaeum halophilum gen. nov., sp. nov. is herewith proposed. Our demonstration of a complex life cycle in a group of haloarchaea adds a new dimension to our understanding of the biological diversity and environmental adaptation of archaea.

The association of trace elements with arthritis in US adults: NHANES 2013-2016.

BACKGROUND: Arthritis is a common chronic disease, and is a major cause of disability and chronic pain in adults. Considering inflammatory responses is closely related with trace elements (TEs), the role of TEs in arthritis has attracted much attention. This study aimed to assess the association between TEs and arthritis. METHODS: Concentrations of TEs in whole blood [cadmium (Cd), lead (Pb), mercury (Hg), selenium (Se), and manganese (Mn)] and serum [copper (Cu) and zinc (Zn)] were measured in adults who participated in the US National Health and Nutrition Examination Survey. Logistic regression model and Bayesian kernel machine regression model were used to explore the association between TEs and arthritis. RESULTS: The levels of five TEs (Pb, Hg, Cd, Se, and Cu) in the arthritis group changed significantly. Three TEs were found to be associated with an increased risk of arthritis: Pb [OR (95% CI): 2.96 (2.18, 4.03), p-value for trend (P-t) < 0.001], Cd [OR (95% CI): 2.28 (1.68, 3.11), P-t < 0.001], Cu [OR (95% CI): 2.05 (1.53, 2.76), P-t < 0.001]. The Relative Excess Risk of Interaction was 0.35 (95% CI: 0.06-0.65) and 0.38 (95% CI: 0.11-0.64), respectively, suggesting that Hg ions and Se ions have positive additional interactions with alcohol consumption, which reduced the risk of arthritis. Subgroup analysis showed that Pb ions and Cd ions were significantly correlated with osteoarthritis and rheumatoid arthritis. CONCLUSION: Elevated concentrations of Pb, Cd, and Cu were associated with increased risk of arthritis. Drinking with high levels of Hg or Se may be a protective factor for arthritis. Future studies are warranted to validate these findings in prospective studies.

Exposure to multiple metals in adults and diabetes mellitus: a cross-sectional analysis.

Diabetes mellitus (DM) is the most widely recognized metabolic illness with expanding morbidity among ongoing years. Its high incapacity rate and death rate badly affect individuals' quality of life. Increasing proofs backed the relationship between metal exposures with the risk of DM, but the methodological boundedness cannot clarify the complexity of the internal relationship of metal mixtures. We fitted the logistic regression model, weighted quantile sum regression model, and Bayesian kernel machine regression model to assess the relationship between the metal exposures with DM in adults who participated in the National Health and Nutrition Examination Survey 2013-2016. The metals (lead, cadmium, and copper) levels were significantly higher among diabetic compared to the healthy controls. In the logistic regression model established for each single metal, lead and manganese were associated with DM in both unadjusted and mutually adjusted models (highest vs. lowest concentration quartile). When considering all metal as a mixed exposure, we found a generally positive correlation between metal mixtures with DM (binary outcome) and glycohemoglobin (HbA1c) levels (continuous outcome). Exposure to metal mixtures was associated with an increased risk of DM and elevated levels of HbA1c.

Artesunate inhibits development of esophageal squamous cell carcinoma via regulating expression of Skp2 and P21 / 中国药理学通报

Aim To clarify the regulatory effect of Artesunate(ART) on tumor cell function and cell cycle in the pathological process of esophageal squamous cell carcinoma(ESCC). Methods KYSE450 and TE14 cells were treated with different concentrations of ART. The cells treated with 0 mg •L

Artesunate inhibits development of breast cancer cells via affecting expression of Skp2 and CDKN1A / 中国药理学通报

Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-

Case report: Safety and efficacy of adalimumab in treating difficult-to-treat rheumatoid arthritis in a human immunodeficiency virus-positive patient, one year follow-up.

Rheumatoid arthritis (RA) is a joint-disabling inflammatory disease associated with the pathology of synovitis. Some patients with RA are difficult to treat, using disease-modifying anti-rheumatic drugs (DMARDs). Biology and targeted synthetic DMARDs (b/tsDMARDs) are options for patients with RA. Acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). Adalimumab is an anti-tumor necrosis factor therapy commonly used in patients with RA. However, there are no reports or related data on patients with RA-HIV/AIDS treated with adalimumab are available. In this report, we described the first successful case of a 60-year-old HIV-positive woman with difficult-to-treat RA treated with ADA after being screened for hepatitis virus, latent tuberculosis (LTBI), and other infections. She contracted HIV from sexual exposure while on adalimumab therapy. As the patient was resistant to first-line DMARDs, she continued adalimumab along with the initiation of highly active antiretroviral therapy (HAART). The patient was treated with adalimumab therapy for a year; her CD4+ lymphocyte count was normal, HIV-1 RNA decreased, and no new infections were triggered. The patient achieved clinical remission of RA. In conclusion, adalimumab is a safe option for patients with RA-HIV and may slow the progression of HIV infection. Furthermore, HAART has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA. Conclusions: Adalimumab is a safe option for patients with RA-HIV, and may slow down the progression of HIV infection. The HAART therapy has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.

Diuretic Resistance Prediction and Risk Factor Analysis of Patients with Heart Failure During Hospitalization.

Objectives: This study performed a prediction and risk factor analysis of diuretic resistance (DR) in patients with decompensated heart failure during hospitalization. Methods: The data of patients with decompensated heart failure treated in 2010-2018 with DR (n = 3,383) or without DR (n = 15,444) were retrospectively collected from Chinese PLA General Hospital medical records. Statistical analysis of baseline was performed on two groups of people, and the risk factor of DR was analyzed through logic regression. Six machine learning models were built accordingly, and the adjustment of model super parameters was performed by using Bayesian optimization method. Finally, the optimal algorithm was selected according to prediction efficiency. Results: The preliminary analysis of variance showed significant differences in the incidence of DR among patients with lung infection, hyperlipidemia, type 2 diabetes, and kidney disease. There were significant differences in estimated glomerular filtration rate (eGFR) (P < 0.001). In addition, some physical indicators like BMI were different, the laboratory results like mean red blood cell volume or C-reactive protein assay were also significantly different. The optimal classification model indicated that the best cutoff points for risk factors were vein carbon dioxide, 21 mmol/L and 29 mmol/L; total protein, 64 g/L; pro-brain natriuretic peptide (pro-BNP), 7,600 pg/mL; eGFR, 50 mL/(min ∙ 1.73 m2); serum albumin, 33 g/L; hematocrit, 0.32% and 0.56%; red blood cell volume distribution width, 13; and age, 59 years. The optimal area under the curve was 0.9512. The ranked features derived from the model were age, abnormal sodium level, pro-BNP level, serum albumin level, D-dimer level, direct bilirubin level, and eGFR. Conclusions: The DR risk prediction model based on a gradient boosting decision tree created here identified its important risk factors. The model made very accurate predictions using simple indicators and simultaneously calculated cutoff values to help doctors predict the occurrence of DR.

Amino acid-balanced diets improved DSS-induced colitis by alleviating inflammation and regulating gut microbiota.

PURPOSE: Inflammatory bowel disease (IBD) is a multifactorial chronic disease of the gastrointestinal tract. Dietary intervention in the treatment of IBD has gradually attracted more attention. In this study, amino acid-balanced diets (AABD) based on grains were developed and their influences on the regulation of IBD were investigated. METHODS: Dextran sodium sulfate (DSS)-induced acute colitis mice model was employed to evaluate the effects of AABD. Pathological symptoms, intestinal inflammation, gut barrier proteins and gut microbiota were determined after AABD intake. RESULTS: It was shown that AABD alleviated the symptoms of colitis by reducing the histological scores of mice colon, suppressing the expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and upregulating the expression of tight junction proteins. Analysis of gut microbiota revealed that AABD altered the structure of gut microbiota by decreasing the abundance and richness of harmful bacteria induced by DSS (Escherichia-Shigella, Parasutterella, etc.) and increasing that of beneficial bacteria (Akkermansia, etc.). Correlation analysis indicated that the alterations of pro-inflammatory factors were related with the change of microbiota, suggesting that the inhibitory effects of AABD on inflammation might be due to its regulation gut microbiota. CONCLUSION: The AABD could efficiently mitigate colitis, and this study indicated that AABD could be applied as a promising dietary regulation strategy of IBD.