The effect and mechanism of inulin on atherosclerosis is mediated by the characteristic intestinal flora and metabolites.

BACKGROUND: Inflammation and hyperlipidemia can cause atherosclerosis. Prebiotic inulin has been proven to effectively reduce inflammation and blood lipid levels. Utilizing a mouse model induced by a high-fat diet, this study aimed to explore whether the characteristic intestinal flora and its metabolites mediate the effects of inulin intervention on atherosclerosis and to clarify the specific mechanism. METHODS: Thirty apolipoprotein E-deficient (ApoE-/-) mice were randomly divided into three groups. They were fed with a normal diet, a high-fat diet or an inulin+high-fat diet for 16 weeks. The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the three groups were compared. The gross aorta and aortic sinus of mice were stained with oil red O, and the area of atherosclerotic plaque was observed and compared. The diversity and structure of the mouse fecal flora were detected by sequencing the V3-V4 region of the 16S rRNA gene, and the levels of metabolites in mouse feces were assessed by gas chromatography-mass spectrometry. The plasma lipopolysaccharide (LPS) levels and aortic inflammatory factors were measured by multi-index flow cytometry (CBA). RESULTS: ApoE-/- mice fed with the high-fat diet exhibited an increase of approximately 46% in the area of atherosclerotic lesions, and the levels of TC, TG and LDL-C were significantly increased (P < 0.05) compared with levels in the normal diet group. After inulin was added to the high-fat group, the area of atherosclerotic lesions, the level of serum LPS and aortic inflammation were reduced, and the levels of TC, TG and LDL-C were decreased (P < 0.05). Based on 16S rRNA gene detection, we found that the composition of the intestinal microbiota, such as Prevotella, and metabolites, such as L-arginine, changed significantly due to hyperlipidemia, and the dietary inulin intervention partially reversed the relevant changes. CONCLUSION: Inulin can inhibit the formation of atherosclerotic plaques, which may be related to the changes in lipid metabolism, the composition of the intestinal microbial community and its metabolites, and the inhibition of the expression of related inflammatory factors. Our study identified the relationships among the characteristic intestinal microbiota, metabolites and atherosclerosis, aiming to provide a new direction for future research to delay or treat atherosclerosis by changing the composition and function of the host intestinal microbiota and metabolites.

Dual effects of serum urate on stroke risk and prognosis: insights from Mendelian randomization.

Background: To investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways. Methods: We used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA (n = 437,354) with any stroke (AS, FinnGen: n = 311,635; MEGASTROKE: n = 446,696), ischemic stroke (IS, FinnGen: n = 212,774; MEGASTROKE: n = 440,328), intracranial hemorrhage (ICH, FinnGen: n = 343,663; ISGC: n = 3,026), functional outcome after ischemic stroke at 90d (n = 4,363), and motor recovery within 24 months after stroke (n = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders. Finally, we further conducted a two-step MR to investigate the potential mediating role of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in the identified causal pathways. Results: Genetically predicted elevated SUA levels were significantly associated with increased risk of AS (meta-analysis: OR = 1.09, 95% CI [1.04-1.13], p = 3.69e-05) and IS (meta-analysis: OR = 1.10, 95% CI [1.01-1.19], p = 0.021) and with improved poor functional outcome after ischemic stroke at 90d (OR = 0.81, 95% CI [0.72-0.90], p = 1.79e-04) and motor recovery within 24 months after stroke (OR = 1.42, 95% CI [1.23-1.64], p = 2.15e-06). In MVMR, SBP and DBP significantly attenuated the causal effects of SUA on AS, IS, and functional outcome after ischemic stroke at 90d and motor recovery within 24 months after stroke. Further mediation analyses showed that SBP mediated 52.4 and 34.5% of the effects of SUA on AS and IS, while DBP mediated 28.5 and 23.4% of the causal effects, respectively. Conclusion: This study supports the dual role of genetically predicted SUA in increasing stroke risk, especially ischemic stroke risk, and in improving functional outcome and motor recovery. SBP and DBP are key mediators lying on the causal pathways of SUA with AS and IS.

Association between serum 25-hydroxyvitamin D level and inflammatory markers in hemodialysis-treated patients.

OBJECTIVE: To investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level with novel inflammatory markers in hemodialysis-treated patients. METHODS: A total of 167 maintenance hemodialysis-treated patients were enrolled in this cross-sectional study. The patients were divided into vitamin D deficiency (a serum 25(OH)D level <20 ng/mL) and nondeficiency (a serum 25(OH)D level ≥20 ng/mL) groups. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) were calculated by the complete blood cell count. The relationship between 25(OH)D level with other parameters was assessed by bivariate correlation analysis and linear regression analysis. RESULTS: There were significant differences between the two groups in terms of age, diabetes, levels of albumin, creatinine, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as NLR and MLR (p = .004, p = .031, p < .001, p = .043, p = .008, p = .006, p = .002, and p < .001, respectively). There exist negative correlations between serum 25(OH)D level with age, diabetes, alkaline phosphatase level, NLR, PLR, and MLR (p = .002, p = .002, p = .037, p = .001, p = .041, and p < .001, respectively) and positive correlations between serum 25(OH)D level with albumin level, creatinine level, phosphorus level, HDL-C, and LDL-C (p < .001, p < .001, p = .013, p = .02, p = .002, respectively). Multiple analysis results showed that sex, diabetes, albumin level and NLR were independently associated with serum 25(OH)D level (p = .021, p = .015, p = .033, and p = .041, respectively). High values of NLR and MLR were associated with patients with serum 25(OH)D deficiency. There were negative interplays between serum 25(OH) D level with NLR, PLR, and MLR and also an independent association between serum 25(OH) D level with NLR. CONCLUSION: Collectively, serum 25(OH)D level has a negative correlation with inflammatory markers.

Chitosan oligosaccharide-functionalized nano-prodrug for cascade chemotherapy through oxidative stress amplification.

Redox nanoparticles have been extensively developed for chemotherapy. However, the intracellular oxidative stress induced by constant aberrant glutathione (GSH), reactive oxygen species (ROS) and gamma-glutamyl transpeptidase (GGT) homeostasis remains the primary cause of evading tumor apoptosis. Herein, an oxidative stress-amplification strategy was designed using a pH-GSH-H2O2-GGT sensitive nano-prodrug for precise synergistic chemotherapy. The disulfide bond- conjugated doxorubicin prodrug (DOX-ss) was constructed as a GSH-scavenger. Then, phenylboronic acid (PBA), DOX-ss and poly (γ-glutamic acid) (γ-PGA) were successively conjugated using chitosan oligosaccharide (COS) to obtain the nano-prodrug PBA-COS-ss-DOX/γ-PGA. The PBA-COS-ss-DOX/γ-PGA prodrug could tightly attach to the polymer chain segment by atom transfer radical polymerization. Simultaneously, the drug interacted relatively weakly with the polymer by encapsulating ionic crosslinkers in DOX@PBA-COS/γ-PGA. The disulfide bond of the DOX-ss prodrug as a GSH-scavenger could be activated using overexpressed GSH to release DOX. Particularly, PBA-COS-ss-DOX/γ-PGA could prevent premature drug leakage and facilitate DOX delivery by GGT-targeting and intracellular H2O2-cleavable linker in human hepatocellular carcinoma (HepG2) cells. Concurrently, the nano-prodrug induced strong oxidative stress and tumor cell apoptosis. Collectively, the pH-GSH-H2O2-GGT responsive nano-prodrug shows potential for synergistic tumor therapy.

Tianma-Gouteng pair ameliorates the cognitive deficits on two transgenic mouse models of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Tianma-Gouteng Pair (TGP), commonly prescribed as a pair-herbs, can be found in many Chinese medicine formulae to treat brain diseases. However, the neuroprotective effects and molecular mechanisms of TGP remained unexplored. AIM OF THE STUDY: This study investigated the difference between the TgCRND8 and 5 × FAD transgenic mice, the anti-AD effects of TGP, and underlying molecular mechanisms of TGP against AD through the two mouse models. METHODS: Briefly, three-month-old TgCRND8 and 5 × FAD mice were orally administered with TGP for 4 and 6 months, respectively. Behavioral tests were carried out to determine the neuropsychological functions. Moreover, immunofluorescence and western blotting assays were undertaken to reveal the molecular mechanisms of TGP. RESULTS: Although TgCRND8 and 5 × FAD mice had different beta-amyloid (Aß) burdens, neuroinflammation status, and cognition impairments, TGP exerted neuroprotective effects against AD in the two models. In detail, behavioral tests revealed that TGP treatment markedly ameliorated the anxiety-like behavior, attenuated the recognition memory deficits, and increased the spatial learning ability as well as the reference memory of TgCRND8 and 5 × FAD mice. Moreover, TGP treatment could regulate the beta-amyloid precursor protein (APP) processing by inhibiting the Aß production enzymes such as ß- and γ-secretases and activating Aß degrading enzyme to reduce Aß accumulation. In addition, TGP reduced the Aß42 level, the ratio of Aß42/Αß40, Aß accumulation, and tau hyperphosphorylation in both the 5 × FAD and TgCRND8 mouse models. Furthermore, TGP ameliorated neuroinflammation by decreasing the densities of activated microglia and astrocytes, and inhibiting the production of inflammatory cytokines. TGP upregulated the SIRT1 and AMPK, and downregulated sterol response element binding protein 2 (SREBP2) in the brain of TgCRND8 mice and deactivation of the EPhA4 and c-Abl in the brain tissues of 5 × FAD mice. CONCLUSION: Our experiments for the first time revealed the neuroprotective effects and molecular mechanism of TGP on 5 × FAD and TgCRND8 transgenic mouse models of different AD stages. TGP decreased the level of Aß aggregates, improved the tauopathy, and reduced the neuroinflammation by regulation of the SIRT1/AMPK/SREBP2 axis and deactivation of EPhA4/c-Abl signaling pathway in the brains of TgCRND8 and 5 × FAD mice, respectively. All these findings unequivocally confirmed that the TGP would be promising in developing into an anti-AD therapeutic pharmaceutical.

Tumor microenvironment sensitization via dual-catalysis of carbon-based nanoenzyme for enhanced photodynamic therapy.

Photodynamic therapy (PDT) is limited in tumor therapy due to the mature antioxidant barrier of tumor microenvironment (TME) and phototoxicity/easy-degradation characteristics of photosensitizers. Therefore, we prepared Cu2+-doped hollow carbon nanoparticles (CHC) to protect the loaded photosensitizers and sensitize TME by glutathione-depletion and peroxidase (POD)-like activity for enhanced PDT. CHC significantly increased the maximum speed of POD-like reaction (Vm) of 8.4 times. By coating with hyaluronic acid (HA), the active sites on CHC were temporarily masked with low catalytic property, and restored in response to the overexpressed hyaluronidase in TME. Meanwhile, due to the excellent photothermal conversion efficiency (32.5 %) and hollow structure of CHC, the loaded photosensitizers were well protected from sunlight activation-induced unwanted phototoxicity and rapid degradation under the near-infrared light irradiation. In-vivo anti-tumor experiments demonstrated that the combination of photothermal-photodynamic effect achieved the best anti-tumor effect (tumor inhibition rate at 87.8 %) compared with any monotherapy. In addition, the combination of photothermal and photodynamic effect could efficiently suppress the cell migration, manifesting the reduced number of lung metastasized nodules by 74 %. This work provides an integrated platform for photosensitizers protection and TME sensitization for enhanced PDT.

Prognostic factors of fungal infection in anti-melanoma differentiation-associated gene 5 antibody-positive associated interstitial lung disease.

OBJECTIVE: To investigate the potential risk factors for mortality in fungal infection in anti-melanoma differentiation-associated gene 5 antibody-positive associated interstitial lung disease (MDA5-ILD). METHODS: Patients diagnosed with MDA5-ILD from April 2017 to November 2022 were included. The demographic data, laboratory examinations, therapeutic and follow-up information were recorded. Fungal infection diagnosis was established based on a combinations of host factors, clinical features and mycologic evidences. High-dose corticosteroid therapy was defined as the initial corticosteroid doses > 240mg/d. The primary endpoint was mortality. Potential factors for fungal infection occurrence and prognostic factors were analyzed using logistic regression analysis and Cox proportional hazards regression. RESULTS: In total, 121 patients with MDA5-ILD were included. During follow-up, 41 (33.9%) patients had suffered fungal infection and 39.0% (16/41) of whom had ever received high-dose corticosteroid therapy. The median interval from corticosteroid use to the occurrence of fungal infection was 29 (10-48) days. The mean survival time of patients with fungal infection was 234.32 ± 464.76 days. The mortality in MDA5-ILD with fungal infection was 85.4% (35/41), which was significantly higher than those without (85.4% VS 56.3%, P < 0.001). High-dose corticosteroid therapy (P = 0.049) was independent risk factor for fungal infection occurrence. Decreased serum albumin level (P = 0.024) and high-dose corticosteroid therapy (P = 0.008) were both associated with increased mortality in MDA5-ILD patients with fungal infection. CONCLUSION: Fungal infection is associated with an increased mortality in MDA5-ILD. The serum albumin level and corticosteroid dose should be taken into consideration when treating MDA5-ILD. Key Points • This study showed fungal infection is associated with an increased mortality in MDA5-ILD. In MDA5-ILD patients with fungal infection, the presence of decreased serum albumin level and high-dose corticosteroid therapy were identified as predictors for mortality.

G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis.

G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.

Streamlined enzymatic synthesis of human milk fat substitutes.

The positional distribution of palmitic acid (PA) in human milk fat substitutes (HMFSs) plays a pivotal role in mimicking the nutritional profile of human milk fat for nourishing non-breastfed infants. This study innovatively introduced a streamlined enzymatic process for preparing HMFSs rich in sn-2 PA using palm stearin, a PA-rich source without the necessity for positional distribution of PA. The initial step involved enhancing the sn-2 PA concentration through enzymatic interesterification using Lipase UM1, which exhibited superior catalytic efficiency than Novozym 435. This process increased the sn-2 PA level from 40.98 % to 64.51 %. Subsequently, acidolysis was employed to reduce PA levels by replacing PA at sn-1,3 positions using sn-1,3-regioselective lipases. The PA content decreased from 60.64 % to 26.73 %, simultaneously raising the relative sn-2 PA concentration to 71.57 %, meeting the benchmarks for HMFSs. This study establishes a robust conceptual framework for the prospective industrial synthesis of HMFSs.

Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways.

BACKGROUND: Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms. METHODS: BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days. RESULTS: MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats. CONCLUSIONS: MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways.

Effect of high-dose intravenous methylprednisolone pulse (IVMP) therapy in the survival of patients with anti-melanoma differentiation-associated gene 5-related rapidly progressive interstitial lung disease: a retrospective analysis.

OBJECTIVES: To assess the impacts of high-dose intravenous methylprednisolone pulse (IVMP) therapy in survival and the occurrences of treatment-related infection of patients with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease (MDA5-RPILD). METHODS: Patients with MDA5-RPILD from June 2017 to August 2022 in our hospital were retrospectively reviewed. IVMP therapy was defined as intravenous methylprednisolone (mPSL) 0.5g/day for 3 consecutive days during hospitalization or 7 days prior to admission and patients were divided into IVMP group and non-IVMP group based on who had ever received IVMP therapy. All-cause mortality and the incidence of adverse events during treatment were compared between the two groups. RESULTS: Sixty-four patients with MDA5-RPILD were enrolled. Among them, twenty-three (35.9%) patients had ever received IVMP therapy. The overall mortality was comparable between IVMP and non-IVMP group (IVMP group: 22/23, 95.7% vs. non-IVMP group: 38/41, 92.7%, p=0.11). And the incidence of treatment-related infections was also close (IVMP group: 21/23, 91.3% vs. non-IVMP group: 32/41, 78.0%, p=0.30). After adjustment for gender, age, smoking history, duration from symptom onset to diagnosis, and combination with steroid-sparing agent treatment, the Cox proportional hazards model showed that IVMP therapy was not associated with an improved survival (adjusted HR 1.10; 95% CI 0.57-2.13; p=0.77). CONCLUSION: Our study showed that the survival benefits and adverse events were comparable between IVMP-treated and untreated MDA5-RPILD patients. Future prospective trials are needed to investigate the optimal treatment regimen in MDA5-RPILD. Key Points • This observational study found that IVMP therapy may be not associated with an improved outcome in patients with MDA5-RPILD. • Treatment-related infections are common; however, the incidence of treatment-related infections had no difference between IVMP and non-IVMP group.

Lipidomics Reveals the Effects of Detergents on Skin Surface Lipids in Young Adults.

BACKGROUND: Detergent is a chemical product commonly used in people's daily life. Contact with detergent solutions can damage the human skin barrier and cause skin diseases. Skin surface lipids (SSLs) play a decisive role in skin barrier function. This study aimed to observe the changes of SSLs in young adults after exposure to detergent solutions to explore the underlying mechanism of skin barrier function damage. METHODS: A self-controlled study on youth adults was conducted in Zhengzhou, China, in November 2020. The study lasted for a total of 1 week, and skin barrier function was assessed by trans-epidermal water loss (TEWL) values. The changes of SSLs before and after exposure to the detergent with subjects were measured using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry. RESULTS: The skin barrier function of subjects' hands was impaired after exposure to detergent (TEWL value increased, p < 0.001). A total of 520 SSLs were detected, divided into 6 main categories. The average relative abundance of these 6 major lipids decreased after exposure. Sphingolipids (mainly ceramides), free fatty acids (mainly long-chain fatty acids), cholesterol lipids, and glycerophospholipids are the most severely damaged lipids. CONCLUSION: Detergent solutions can damage the skin barrier function and SSLs of young hands; interventions targeting SSLs to eliminate detergent damage to human skin may be of value.

Hydrophobic Mn-Doped Solid-State Red-Emitting Carbon Nanodots with AIE Effect and Their Hydrogel Composites for Color-Changing Anticounterfeiting.

The aggregation-caused quenching has always limited the high concentration and solid-state applications of carbon nanodots. While the aggregation-induced emission effect, dominated by intramolecular motion, may be an effective means to solve this problem. Here, hydrophobic solid-state red-light carbon nanodots (M-CDs) with 95% yield are synthesized by a one-step hydrothermal method using 2,2'-dithiodibenzoic acid as the carbon source and manganese acetate as the dopant source. The disulfide bond of 2,2'-dithiodibenzoic acid serves as the symmetry center of molecular rotation and Mn catalyzes the synthesis of M-CDs, which promotes the formation of the central graphitic carbon structure. The M-CDs/agar hydrogel composites can achieve fluorescence transition behavior because of the special fluorescence transition properties of M-CDs. When this composite hydrogel is placed in water, water molecules contact with M-CDs through the network structure of the hydrogels, making the aggregated hydrogels of M-CDs fluorescence orange-red under 365 nm excitation. While in dimethyl sulfoxide, water molecules in the hydrogels network are replaced and the M-CDs fluoresce blue when dispersed, providing a potential application in information encryption. In addition, high-performance monochromatic light-emitting diode (LED) devices are prepared by compounding M-CDs with epoxy resin and coating them on 365 nm LED chips.

Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population.

BACKGROUND: Few studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association between testosterone and obesity. This study intended to examine the mediation effect of inflammatory markers on the association of testosterone with obesity and the moderation effect of androstenedione on the association of testosterone with inflammation and obesity in Chinese rural men. MATERIALS AND METHODS: This cross-sectional research enrolled 2536 male rural inhabitants from the Henan Rural Cohort study. The serum concentrations of testosterone and androstenedione were determined by liquid chromatography-tandem mass spectrometry. Linear and logistic regression were used to examine the relationships between testosterone, inflammatory markers, and obesity. Mediation and moderation analyses were carried out to evaluate the potential effects of inflammatory markers on the relationship between testosterone and obesity, as well as androstenedione on the relationships of testosterone with inflammation and obesity. RESULTS: After adjusting for confounding factors, the results showed that testosterone and androstenedione were negatively related to obesity, and inflammatory markers were positively associated with obesity. Besides, testosterone and androstenedione were negatively associated with inflammatory markers. Mediation analysis showed that white blood cell, neutrophil, monocyte, and high-sensitivity C-reactive protein had mediating effects on the association between testosterone and obesity. The most vital mediator was high-sensitivity C-reactive protein, and its proportion of the effect was 11.02% (defined by waist circumference), 11.15% (defined by waist-to-hip ratio), 12.92% (defined by waist-to-height ratio), and full mediating effect (defined by body mass index). Moreover, androstenedione played negative moderation effects on the associations of testosterone with inflammation and obesity. CONCLUSION: Inflammatory markers and androstenedione were first found to have modifying effects on the association of testosterone with obesity. Higher levels of testosterone and androstenedione could reduce the inflammation level and risk of obesity, indicating their potential roles in the prevention and treatment of chronic diseases.

Atomic Insights into the Relationship between Molecular Structure and Dispersion Performance of Phenyl Polymer on Graphene Oxide.

The adsorption of organic polymers onto the surface of graphene oxide is known to improve its dispersibility in cement-based materials. However, the mechanism of this improvement at the atomic level is not yet fully understood. In this study, we employ a combination of DFT static calculation and umbrella sampling to explore the reactivity of polymers and investigate the effects of varying amounts of phenyl groups on their adsorption capacity on the surface of graphene oxide. Quantitative analysis is utilized to study the structural reconstruction and charge transfer caused by polymers from multiple perspectives. The interfacial reaction between the polymer and graphene oxide surface is further clarified, indicating that the adsorption process is promoted by hydrogen bond interactions and π-π stacking effects. This study sheds light on the adsorption mechanism of polymer-graphene oxide systems and has important implications for the design of more effective graphene oxide dispersants at the atomic level.

Active-site stabilized Bi metal-organic framework-based catalyst for highly active and selective electroreduction of CO2 to formate over a wide potential window.

Bismuth-based materials have been validated to be a kind of effective electrocatalyst for electrocatalytic CO2 reduction (ECR) to formate (HCOO-). However, the established studies still encounter the problems of low current density, low selectivity, narrow potential window, and poor catalyst stability. Herein, a bismuth-terephthalate framework (Bi-BDC MOF) material was successfully synthesized. The optimized Bi-BDC-120 °C exhibited excellent activity, selectivity, and durability for formate production. At an operating potential of -1.1 V vs. RHE in 0.1 mol L-1 KHCO3 electrolyte, the ECR catalyzed by Bi-BDC-120 °C achieved a Faraday efficiency (FE) of 97.2% towards formate generation, and the total current density reached about 30 mA cm-2. The operating potential window with FEformate values > 95% ranged in -0.9 to -1.5 V vs. RHE. The density-functional theory (DFT) calculation demonstrated that the (001) crystalline planes of Bi-BDC are preferable for the adsorption of CO2 and the conversion of *OCHO intermediates, thus ultimately promoting the electrocatalytic production of formate. Although the MOF structure of Bi-BDC-120 °C was insufficiently stabilized, the FEformate could be maintained at around 90% after 36 h of ECR operation. The long-term durability for formate production was attributed to the fact that the in situ reconstructed Bi2O2CO3 could retain the Bi-O active sites in the structure. These results offer an opportunity to design CO2 reduction electrocatalysts with high activity and selectivity for potential applications.

OpenNAU: An open-source platform for normalizing, analyzing, and visualizing cancer untargeted metabolomics data.

Objective: As an important part of metabolomics analysis, untargeted metabolomics has become a powerful tool in the study of tumor mechanisms and the discovery of metabolic markers with high-throughput spectrometric data which also poses great challenges to data analysis, from the extraction of raw data to the identification of differential metabolites. To date, a large number of analytical tools and processes have been developed and constructed to serve untargeted metabolomics research. The different selection of analytical tools and parameter settings lead to varied results of untargeted metabolomics data. Our goal is to establish an easily operated platform and obtain a repeatable analysis result. Methods: We used the R language basic environment to construct the preprocessing system of the original data and the LAMP (Linux+Apache+MySQL+PHP) architecture to build a cloud mass spectrum data analysis system. Results: An open-source analysis software for untargeted metabolomics data (openNAU) was constructed. It includes the extraction of raw mass data and quality control for the identification of differential metabolic ion peaks. A reference metabolomics database based on public databases was also constructed. Conclusions: A complete analysis system platform for untargeted metabolomics was established. This platform provides a complete template interface for the addition and updating of the analysis process, so we can finish complex analyses of untargeted metabolomics with simple human-computer interactions. The source code can be downloaded from https://github.com/zjuRong/openNAU.

Mechanisms and Application of Gas-Based Anticancer Therapies.

Cancer is still one of the major factors threatening public health, with morbidity and mortality rates at the forefront of the world. Clinical drawbacks, such as high toxicity and side effects of drug therapy, and easy recurrence after surgery affect its therapeutic effect. Gas signaling molecules are essential in maintaining biological homeostasis and physiological functions as specific chemical substances for biological information transfer. In recent years, the physiological regulatory functions of gas molecules in the cancer process have been gradually revealed and have shown broad application prospects in tumor therapy. In this paper, standard gas therapies are classified and introduced. Taking H2, CO2, NO, CO, H2S, and SO2 gases as examples, the research progress and application of gas therapies in malignant tumors are mainly introduced in terms of biological characteristics, anticancer mechanisms, and treatment strategies. Finally, the problems and prospects for developing gases as anticancer drugs are outlined.

Comparison of efficacy between laparoscopic pectopexy and laparoscopic high uterosacral ligament suspension in the treatment of apical prolapse-short term results.

To compare the clinical efficacy of laparoscopic pectopexy and laparoscopic high uterosacral ligament suspension in women suffering from apical prolapse. The clinical data of 170 patients with apical prolapse (POP-Q score ≥ II) treated in the Third Affiliated Hospital of Zhengzhou University from January 2018 to July 2020 were retrospectively analyzed to assess the clinical efficacy of three surgical methods [laparoscopic pectopexy with uterine preservation, laparoscopic pectopexy with hysterectomy, laparoscopic high uterosacral ligament suspension (LHUSLS) with hysterectomy]. Patients were divided into three groups depending on Surgical methods: laparoscopic uterine pectopexy group (n = 23), laparoscopic pectopexy with hysterectomy group (n = 78) and LHUSLS with hysterectomy group (n = 69). The POP-Q points before and after operation were analyzed. The operation-related indices, perioperative periods and post-operative complications were compared. 1. The operation time of laparoscopic uterine pectopexy group was the shortest (p < 0.05). There was no significant difference in the incidence of apical prolapse and new stress urinary incontinence among the three groups during the follow-up period (p > 0.05). 2. The POP-Q points (Aa, Ba, C) in the three groups were better than those before operation (p < 0.05). Laparoscopic pectopexy with hysterectomy group had better Ap, Bp and C points and a longer TVL than LHUSLS with hysterectomy group (p < 0.05). 3. The postoperative PFDI-20, PFIQ-7 and PISQ-12 scores of the three groups were significantly improved than those before operation (p < 0.05). The PISQ-12 scores in laparoscopic uterine pectopexy group were significantly higher than that in the other two groups one year after operation (p < 0.05). The study concludes that laparoscopic pectopexy and LHUSLS can significantly improve the quality of life and sexual function for patients with apical prolapse. One year after operation, laparoscopic pectopexy has a more satisfactory anatomical reduction than LHUSLS with hysterectomy. The laparoscopic uterine pectopexy group had lower postoperative complications and better sexual function than that with hysterectomy group. Laparoscopic pectopexy should be used for the treatment of apical prolapse (POP-Q score ≥ II) patients who aim to better clinical efficacy and sexual function improvement.

Higher HDL-C levels attenuated the association of plasma polybrominated diphenyl ethers with prediabetes and type 2 diabetes mellitus in rural Chinese adults.

BACKGROUND: Plasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. METHODS: In this study, a total of 2607 subjects aged 18-79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. RESULTS: The geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high-density lipoprotein cholesterol (HDL-C) levels increased. CONCLUSIONS: Our findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.