Influence of earthquake on radon exhalation law at the beach of the uranium tailing reservoir under high temperature environment.

In this paper, the influence of an earthquake on radon exhalation rate of uranium tailings reservoir beach under high temperature environment is studied by using a self-made integrated simulation test device for natural disasters, and a scale model test based on similarity and dimensional laws. The results show that, (1)When the peak acceleration reaches 0.6g, the radon exhalation rate increases sharply with the increase of peak acceleration, and tends to be gentle after 1.0g. (2)Under the action of high temperature, the radon exhalation rate increases rapidly with the increase of high temperature time, and gradually becomes flat after the 4th hour. (3)Compared with loading the earthquake condition only, the coupling effect of high temperatures and earthquakes causes a greater degree of damage to the beach surface of a uranium tailings reservoir under the same acceleration conditions, and the fissure rate and radon exhalation rate of the beach surface are substantially increased.

Deep learning and targeted metabolomics-based monitoring of chewing insects in tea plants and screening defense compounds.

Tea is an important cash crop that is often consumed by chewing pests, resulting in reduced yields and economic losses. It is important to establish a method to quickly identify the degree of damage to tea plants caused by leaf-eating insects and screen green control compounds. This study was performed through the combination of deep learning and targeted metabolomics, in vitro feeding experiment, enzymic analysis and transient genetic transformation. A small target damage detection model based on YOLOv5 with Transformer Prediction Head (TPH-YOLOv5) algorithm for the tea canopy level was established. Orthogonal partial least squares (OPLS) was used to analyze the correlation between the degree of damage and the phenolic metabolites. A potential defensive compound, (-)-epicatechin-3-O-caffeoate (EC-CA), was screened. In vitro feeding experiments showed that compared with EC and epicatechin gallate, Ectropis grisescens exhibited more significant antifeeding against EC-CA. In vitro enzymatic experiments showed that the hydroxycinnamoyl transferase (CsHCTs) recombinant protein has substrate promiscuity and can catalyze the synthesis of EC-CA. Transient overexpression of CsHCTs in tea leaves effectively reduced the degree of damage to tea leaves. This study provides important reference values and application prospects for the effective monitoring of pests in tea gardens and screening of green chemical control substances.

SGAE-MDA: Exploring the MiRNA-disease associations in herbal medicines based on semi-supervised graph autoencoder.

Research indicates that miRNAs present in herbal medicines are crucial for identifying disease markers, advancing gene therapy, facilitating drug delivery, and so on. These miRNAs maintain stability in the extracellular environment, making them viable tools for disease diagnosis. They can withstand the digestive processes in the gastrointestinal tract, positioning them as potential carriers for specific oral drug delivery. By engineering plants to generate effective, non-toxic miRNA interference sequences, it's possible to broaden their applicability, including the treatment of diseases such as hepatitis C. Consequently, delving into the miRNA-disease associations (MDAs) within herbal medicines holds immense promise for diagnosing and addressing miRNA-related diseases. In our research, we propose the SGAE-MDA model, which harnesses the strengths of a graph autoencoder (GAE) combined with a semi-supervised approach to uncover potential MDAs in herbal medicines more effectively. Leveraging the GAE framework, the SGAE-MDA model exactly integrates the inherent feature vectors of miRNAs and disease nodes with the regulatory data in the miRNA-disease network. Additionally, the proposed semi-supervised learning approach randomly hides the partial structure of the miRNA-disease network, subsequently reconstructing them within the GAE framework. This technique effectively minimizes network noise interference. Through comparison against other leading deep learning models, the results consistently highlighted the superior performance of the proposed SGAE-MDA model. Our code and dataset can be available at: https://github.com/22n9n23/SGAE-MDA.

Effectiveness of zinc supplementation on the incidence of oral mucositis during chemotherapy and radiation: A meta­analysis.

Oral mucositis (OM) is a commonly observed and debilitating side effect of chemotherapy and radiation therapy in patients with cancer, especially head and neck cancer. Although there is no proven therapy for the prevention and treatment of OM, zinc supplementation effectively decreases the incidence of OM. This paper provides a current and comprehensive meta-analysis of the efficacy of zinc compared with placebo/control in OM. A systematic literature review was conducted using MEDLINE and Central databases for randomized control trials (RCTs) comparing zinc supplementation (oral or rinse) with placebo/control in patients with various types of cancer undergoing chemotherapy, radiation therapy or combined chemo-radiation. The outcome was OM incidence, independent of the severity. A random-effects model was used to calculate the pooled risk ratio and subgroup analyses were performed. A total of 12 RCTs were included, containing information from 783 patients. A decrease in OM incidence was observed overall when all cancer therapies were considered. However, subgroup analyses showed that zinc did not significantly decrease the incidence of OM when studies were stratified by cancer therapy or scale/criteria used to assess OM. The results of the meta-analysis support the use of zinc supplementation in decreasing OM incidence in patients with cancer receiving chemotherapy or radiation therapy. However, the high heterogeneity between studies and the small number of studies are limitations of the meta-analysis.

Ginkgolide B facilitates muscle regeneration via rejuvenating osteocalcin-mediated bone-to-muscle modulation in aged mice.

BACKGROUND: The progressive deterioration of tissue-tissue crosstalk with aging causes a striking impairment of tissue homeostasis and functionality, particularly in the musculoskeletal system. Rejuvenation of the systemic and local milieu via interventions such as heterochronic parabiosis and exercise has been reported to improve musculoskeletal homeostasis in aged organisms. We have shown that Ginkgolide B (GB), a small molecule from Ginkgo biloba, improves bone homeostasis in aged mice by restoring local and systemic communication, implying a potential for maintaining skeletal muscle homeostasis and enhancing regeneration. In this study, we investigated the therapeutic efficacy of GB on skeletal muscle regeneration in aged mice. METHODS: Muscle injury models were established by barium chloride induction into the hind limb of 20-month-old mice (aged mice) and into C2C12-derived myotubes. Therapeutic efficacy of daily administrated GB (12 mg/kg body weight) and osteocalcin (50 µg/kg body weight) on muscle regeneration was assessed by histochemical staining, gene expression, flow cytometry, ex vivo muscle function test and rotarod test. RNA sequencing was used to explore the mechanism of GB on muscle regeneration, with subsequent in vitro and in vivo experiments validating these findings. RESULTS: GB administration in aged mice improved muscle regeneration (muscle mass, P = 0.0374; myofiber number/field, P = 0.0001; centre nucleus, embryonic myosin heavy chain-positive myofiber area, P = 0.0144), facilitated the recovery of muscle contractile properties (tetanic force, P = 0.0002; twitch force, P = 0.0005) and exercise performance (rotarod performance, P = 0.002), and reduced muscular fibrosis (collagen deposition, P < 0.0001) and inflammation (macrophage infiltration, P = 0.03). GB reversed the aging-related decrease in the expression of osteocalcin (P < 0.0001), an osteoblast-specific hormone, to promote muscle regeneration. Exogenous osteocalcin supplementation was sufficient to improve muscle regeneration (muscle mass, P = 0.0029; myofiber number/field, P < 0.0001), functional recovery (tetanic force, P = 0.0059; twitch force, P = 0.07; rotarod performance, P < 0.0001) and fibrosis (collagen deposition, P = 0.0316) in aged mice, without an increased risk of heterotopic ossification. CONCLUSIONS: GB treatment restored the bone-to-muscle endocrine axis to reverse aging-related declines in muscle regeneration and thus represents an innovative and practicable approach to managing muscle injuries. Our results revealed the critical and novel role of osteocalcin-GPRC6A-mediated bone-to-muscle communication in muscle regeneration, which provides a promising therapeutic avenue in functional muscle regeneration.

Research on safety early warning of uranium tailings dam based on abnormal radioactive indexes of water leachate.

The radioactive index value of the leachate of the uranium tailings dam is affected by the internal damage of the dam. Therefore, a way of using the deviation of the radioactive index concentration in the leachate to warn the instability of the dam is innovatively proposed in this paper. Firstly, the SSA-BP algorithm is used to predict and analyze the five groups of parameters U, Ra, ∑ α, ∑ ß and Rn. Then, the deviation between the actual value and the predicted value is computed. Finally, an early warning is given based on the entropy weight extension decision-making model. The model is verified by the leachate environment monitoring data of a uranium tailings dam in southern China from 2016 to 2020, which shows that the model can effectively caution of the instability of the uranium tailings dam and provides a reference for the subsequent decommissioning management.

Protective effect of pinocembrin from Penthorum chinense Pursh on hepatic ischemia reperfusion injury via regulating HMGB1/TLR4 signal pathway.

Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and transplantation. Pinocembrin (PIN) is a kind of flavonoid monomer extracted from the local traditional Chinese medicine Penthorum chinense Pursh (P. chinense). However, the effect of PIN on HIRI has not determined. We investigated the protective effect and potential mechanism of PIN against HIRI. Model mice were subjected to partial liver ischemia for 60 min, experimental mice were pretreated with PIN orally for 7 days, and H2 O2 -induced oxidative damage model in AML12 hepatic cells was established in vitro. Histopathologic analysis and serum biochemical levels revealed that PIN had hepatoprotective activities against HIRI. The variation of GSH, SOD, MDA, and ROS levels indicated that PIN treatments attenuated oxidative stress in tissue. PIN pretreatment obviously ameliorated apoptosis, and restrained the expression of HMGB1 and TLR4 in vivo. In vitro, compared with H2 O2 group, the contents of ROS, mitochondrial membrane potential, apoptotic cells, and Bcl-2 protein were decreased, while the Bax protein expression was increased. Moreover, HMGB-1 small interfering RNA test and western blotting showed that PIN pretreatment reduced HMGB1 and TLR4 protein levels. In conclusion, PIN pretreatment effectively protected hepatocytes from HIRI and inhibited the HMGB1/TLR4 signaling pathway.

New insights into the function of plant tannase with promiscuous acyltransferase activity.

Plant tannases (TAs) or tannin acyl hydrolases, a class of recently reported carboxylesterases in tannin-rich plants, are involved in the degalloylation of two important groups of secondary metabolites: flavan-3-ol gallates and hydrolyzable tannins. In this paper, we have made new progress in studying the function of tea (Camellia sinensis) (Cs) TA-it is a hydrolase with promiscuous acyltransferase activity in vitro and in vivo and promotes the synthesis of simple galloyl glucoses and flavan-3-ol gallates in plants. We studied the functions of CsTA through enzyme analysis, protein mass spectrometry, and metabolic analysis of genetically modified plants. Firstly, CsTA was found to be not only a hydrolase but also an acyltransferase. In the two-step catalytic reaction where CsTA hydrolyzes the galloylated compounds epigallocatechin-3-gallate or 1,2,3,4,6-penta-O-galloyl-ß-d-glucose into their degalloylated forms, a long-lived covalently bound Ser159-linked galloyl-enzyme intermediate is also formed. Under nucleophilic attack, the galloyl group on the intermediate is transferred to the nucleophilic acyl acceptor (such as water, methanol, flavan-3-ols, and simple galloyl glucoses). Then, metabolic analysis suggested that transient overexpression of TAs in young strawberry (Fragaria × ananassa) fruits, young leaves of tea plants, and young leaves of Chinese bayberry (Myrica rubra) actually increased the total contents of simple galloyl glucoses and flavan-3-ol gallates. Overall, these findings provide new insights into the promiscuous acyltransferase activity of plant TA.

Acute heat stress-indued apoptosis in mouse skeletal muscle is not associated with alteration of glutamine homeostasis.

We previously demonstrated that exposing mice to heat causes functional and ultrastructural mitochondrial alterations and apoptosis in skeletal muscle. Emerging evidence indicates that glutamine (Gln) deprivation may increase cell susceptibility to apoptosis whereas Gln supplementation may protect cells against heat stress. In this study, we investigated the effect of short-term Gln treatment on heat-induced changes in mouse skeletal muscle. Male mice received vehicle, low-dose Gln (100 mg/kg/d) or high-dose Gln (300 mg/kg/d) through daily gavage for 10 days before a heat exposure test. During heat exposure, mice displayed a hyperthermic response and no significant differences in peak core body temperature were noted across the three groups. Neither heat exposure nor pretreatment with low-dose or high-dose Gln significantly affected Gln concentrations in plasma and gastrocnemius muscles. Heat-exposed mice had significantly higher caspase 3/7 levels in gastrocnemius muscle compared to unexposed controls. Heat exposure significantly increased ROS production and mitochondrial fragmentation and decreased mitochondrial membrane potential in flexor digitorum brevis muscle. These changes were not affected by low- or high-dose Gln pretreatment. Together, acute heat stress did not disrupt Gln homeostasis in mouse skeletal muscle and Gln supplementation did not protect mouse skeletal muscle against heat-induced injury. The results of this study do not support a role of Gln in heat-induced skeletal muscle apoptosis.

Positive effects of Mulberry leaf extract on egg quality, lipid metabolism, serum biochemistry, and antioxidant indices of laying hens.

Plant extracts are becoming a hot topic of research by animal husbandry practitioners following the implementation of a global policy to restrict antibiotic use in animal production. Mulberry leaf extract has received considerable attention as a new plant extract. Mulberry leaf polysaccharides and flavonoids are its main constituents, and these substances possess immunoregulatory, hypoglycemic, antioxidant, and anticoagulant properties. It is however less common to use them in poultry production. Therefore, we investigated the effects of adding MLE to the diet of laying hens on egg quality, lipid metabolism, serum biochemistry, and antioxidant indices in this study. A total of 288 Lohmann Silber layers, aged 38 weeks, were randomly assigned to four groups (six replicates of 12 hens each). Hens were fed a basal diet supplemented with 0 (control diet), 0.4, 0.8, or 1.2% MLE for 56 d. Results showed that the addition of 0.4-1.2% MLE to the diet improved aspartate transaminase (AST) activity in the serum of laying hens, reduced low-density lipoprotein (LDL-C) content in the serum, and significantly decreased yolk triglyceride (TG) and total cholesterol (TC) contents (P < 0.05). No adverse effects were observed on production performance (P > 0.10). MLE (0.4 and 1.2%) significantly reduced the TG and TC levels in the liver (P < 0.05). MLE (0.8 and 1.2%) significantly increased glutathione peroxidase (GSH-Px) activity in the serum, decreased alanine transaminase (ALT) activity, TG and TC content in the serum, and improved egg yolk color (P < 0.05). MLE (1.2%) significantly increased high-density lipoprotein (HDL-C) content and superoxide dismutase (SOD) activity in the serum and enhanced eggshell strength (P < 0.05). The liver-related lipid metabolism gene assay revealed that the relative mRNA expression of PPARα and SIRT1 in the liver was significantly upregulated and that of FASN and PPARγ was significantly decreased after the addition of MLE. In contrast, the relative mRNA expression of SREBP-1c in the liver dramatically decreased after the addition of 0.8 and 1.2% MLE (P < 0.05). The addition of MLE to the diet improved egg quality and the economic value of hens by increasing antioxidant capacity and lipid metabolism. The most appropriate amount of MLE to be added to the diet of laying hens was 0.8%. Our study provides a theoretical reference for the application of MLE in egg production and to promote the healthy and sustainable development of the livestock and poultry industry under the background of antibiotic prohibition.

Detection system of the lobster eye telescope with large field of view.

The lobster eye telescope is promising for large-field x ray imaging in astronomy. The special structure of the lobster eye system makes the focal plane a sphere, resulting in detector defocus when the field is large. In this study, we established a model based on the principle of lobster eye imaging and simulated the imaging at different image distances. The results reveal the relationship between the defocus and position accuracy and angular resolution. To ensure the optical performance of the large field lobster eye telescope, we propose a detection system design method using multiple detectors stitched together to form a spherical-like surface and apply it to the development of the Einstein Probe/wide-field x ray telescope (EP/WXT) submodule. About 70% of the detection area is out of focus within 0.5 mm. The scanning image of the integrated WXT submodule shows good uniformity of the point spread function (PSF) for various incident angles, and the effect of defocus on imaging is acceptable.

Flavonol-Aluminum Complex Formation: Enhancing Aluminum Accumulation in Tea Plants.

Polyphenol-rich tea plants are aluminum (Al) accumulators. Whether an association exists between polyphenols and Al accumulation in tea plants remains unclear. This study revealed that the accumulation of the total Al and bound Al contents were both higher in tea samples with high flavonol content than in low, and Al accumulation in tea plants was significantly and positively correlated with their flavonol content. Furthermore, the capability of flavonols combined with Al was higher than that of epigallocatechin gallate (EGCG) and root proanthocyanidins (PAs) under identical conditions. Flavonol-Al complexes signals (94 ppm) were detected in the tender roots and old leaves of tea plants through solid-state 27Al nuclear magnetic resonance (NMR) imaging, and the strength of the signals in the high flavonol content tea samples was considerably stronger than that in the low flavonol content tea samples. This study provides a new perspective for studying Al accumulation in different tea varieties.

Effect of simulated earthquake loading on radon exhalation from uranium tailings dam.

Uranium tailings sand will continuously release radon-222. When the external condition changes, the exhalation of radon will also change. Thus, radon is being recommended as a tracer for dam damage assessment. When an earthquake is simulated on the uranium tailings dam with a shaking table test and the change in radon concentration is measured, it is observed that the earthquake causes micro-fissures in the uranium tailings dam, which aggregate to form fractures. During the process, the radon concentration will climb dramatically, as will the radon exhalation rate. To verify that the radon monitoring date is accurate, the acceleration response, surface displacement, and interior displacement are all monitored. The results show that radon can be utilized as a tracer to evaluate uranium tailings dam damage.

A systematic review and meta-analysis for the primary prevention of high risk of stroke by Nao-an capsules.

BACKGROUND: To date, Nao-an capsules are the only Chinese patent medicine primarily prescribed for the primary prevention of stroke. PURPOSE: To evaluate the efficacy and safety of Nao-an capsules in the primary prevention of stroke in high-risk patients. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials. METHODS: We searched 7 electronic databases and 2 registries from inception to January 13, 2022 for relevant randomized controlled trials. Two independent investigators selected trials, collected data, and judged the risk of bias. We performed a meta-analysis using the Review Manager software. RESULTS: Nine randomized controlled trials involving 14 744 patients at high risk of stroke were included. Nao-an capsules reduced the risk of first stroke compared with no intervention (risk ratio [RR] = 0.49, 95 % confidence interval [CI] 0.29 to 0.82, p = 0.006) or aspirin (RR50 mg qd = 0.47, 95 % CI 0.25 to 0.91, p = 0.03; RR100 mg qd = 0.46, 95 % CI 0.22 to 0.99, p = 0.05), without increased bleeding risks. The certainty of evidence was evaluated as moderate to very low. CONCLUSION: In addition to controlling specific risk factors, Nao-an capsules might provide additional preventive effects on first stroke with an acceptable safety profile for populations at high risk of stroke. However, as current evidence is too weak, a firm recommendation depends on further confirmation from more studies with more rigorous methodology.

Kaempferol From Penthorum chinense Pursh Attenuates Hepatic Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Inflammation Through Activation of the Nrf2/HO-1 Signaling Pathway.

The purpose of this study is to investigate the protective effect of kaempferol (KAE), the main active monomer from Penthorum chinense Pursh, on hepatic ischemia/reperfusion injury (HI/RI) and its specific mechanism. HI/RI is a common complication closely related to the prognosis of liver surgery, and effective prevention and treatment methods are still unavailable. Ischemia/reperfusion (I/R) injury is caused by tissue damage during ischemia and sustained oxidative stress and inflammation during reperfusion. Penthorum chinense Pursh is a traditional Chinese medicine widely used to treat liver disease since ancient times. Kaempferol (KAE), a highly purified flavonoid active monomer isolated and extracted from Penthorum chinense Pursh, was investigated for its protective effect on HI/RI. Our study indicates that KAE pretreatment alleviated I/R-induced transaminase elevation and pathological changes. Further analysis revealed that KAE pretreatment attenuates I/R-induced oxidative stress (as measured by the content of MDA, SOD and GSH) in vivo and reduces hypoxia/reoxygenation (H/R) -induced reactive oxygen species (ROS) generation in vitro. Meanwhile, KAE inhibits activation of NF-κB/p65 and reduces the release of pro-inflammatory factors (TNF-α and IL-6) to protect the liver from I/R-induced inflammation. Nuclear erythroid 2-related factor 2 (Nrf2) is a crucial cytoprotection regulator because it induces anti-inflammatory, antioxidant, and cytoprotective genes. Therefore, we analyzed the protein levels of Nrf2 and its downstream heme oxygenase-1 (HO-1) in the liver of mice and hepatocytes of humankind, respectively, and discovered that KAE pretreatment activates the Nrf2/HO-1 signaling pathway. In summary, this study confirmed the hepatoprotective effect of KAE on HI/RI, which inhibits oxidative stress and inflammation by activating the Nrf2/HO-1 signaling pathway.

A Probe into the Intervention Mechanism of Yiqi Huayu Jiedu Decoction on TLR4/NLRP3 Signal Pathway in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome (ARDS) Rats.

BACKGROUND: This study discusses the anti-inflammatory mechanism of Yiqi Huayu Jiedu decoction (YQHYJD) and studies the intervening effect of YQHYJD on the inflammatory cytokines in acute respiratory distress syndrome (ARDS) rats by inhibiting the TLR4/NLRP3 signal pathway. The aim of the probe is to provide evidence to support the identification of therapeutic targets in Chinese medicine treatment, which broadens the alternatives for the treatment of ARDS. METHOD: A lipopolysaccharide (LPS)-induced ARDS model group is established on rats by tail vein injection. A medicine group is established on ARDS rats by prophylactic administration using YQHYJD. Materials are collected, and tests are conducted according to experimental processes. RESULT: The rats in the medicine group gained weight compared with those in the ARDS model group. Pathological sections from the medicine group indicated improved condition in terms of pulmonary and interstitial edema in the lung tissues of rats compared with that from the ARDS model group. The percentage of neutrophil of the medicine group was significantly brought down compared with that of the ARDS model group (P < 0.001). Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in the level of inflammatory cytokines. It was observed that the levels of IL-1ß and IL-18 in serum of the medicine group significantly decreased (P < 0.001 and P < 0.01), the contents of TLR4 and NLRP3 in bronchoalveolar lavage fluid (BALF) of the medicine group decreased, and the contents of TLR4 and NLRP3 in lung tissue homogenate of the medicine group significantly decreased (P < 0.05, P < 0.001, P < 0.01, and P < 0.05). In further mass spectrum identification of the proteins from the same animal groups, it was observed that the expressions of inflammatory proteins TNFRSF1, LBP, and NOS2 of the medicine group were reduced. The differences were statistically significant. CONCLUSIONS: The pharmacological action of YQHYJD's anti-inflammatory mechanism is closely associated with the regulation of inflammatory cytokines TLR4, NLRP3, IL-1ß, IL-18, TNFRSF1, LBP, and NOS2 on the TLR4/NLRP3 signal pathway.

Analysis of equivalent thickness of geological media for lab-scale study of radon exhalation.

Geological media are omnipresent in nature. Lab-scale tests are frequently employed in radon exhalation measurements for these media. Thus, it is critical to find the thickness of the medium at an experimental scale that is equivalent to the medium thickness in a real geological system. Based on the diffusion-advection transport of radon, theoretical models of the surface radon exhalation rate for homogeneous semi-infinite and finite-thickness systems were derived (denoted as Jse and Jfi, respectively). Analysis of the equivalency of Jse and Jfi was subsequently carried out by introducing several dimensionless parameters, including the ratio of the exhalation rates for the semi-infinite and finite-thickness models, ε, and the number of diffusion lengths required to achieve a desired ε value, n. The results showed that when radon transport in geological media is dominantly driven by diffusion effect, if n > 3.6626, then ε > 95%; if n > 5.9790, then ε > 99.5%. When radon migration is dominantly driven by advection effect, if n > 2.5002, then ε > 95%; if n > 4.0152, then ε > 99.5%. Therefore, if the thickness of the geological media (x0) is greater than a certain n times the radon diffusion length of the media (L), the media can be modeled as semi-infinite. To validate the model, a pure radon diffusion experiment (no advection) was developed using uranium mill tailings, laterite, and radium-bearing rocklike material with different thicknesses (x0). The theoretical model was demonstrated to be reliable and valid. This study provides a basis for determining the appropriate thickness of geological media in lab-scale radon exhalation measurement experiments with open bottom.

Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling.

OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS: The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.

Poor Clinical Outcomes and Immunoevasive Contexture in Intratumoral IL-10-Producing Macrophages Enriched Gastric Cancer Patients.

OBJECTIVE: To investigate the clinical significance of IL-10+ tumor-associated macrophages (TAMs) in gastric cancer. BACKGROUND: Due to the plasticity and diversity of TAMs, it is necessary to phenotypically and functionally classify subsets of TAMs to better understand the critical role of TAMs in cancer progression. TAMs expressing interleukin-10 (IL-10) have been found to facilitate immune evasion in many malignancies, but the role of IL-10+ TAMs in gastric cancer remains obscure. METHODS: Four hundred and sixty-eight tumor tissue microarray specimens, 52 fresh tumor tissue samples of gastric cancer patients from Zhongshan Hospital, and data of 298 gastric cancer patients from the Cancer Genome Atlas (TCGA) were analyzed. IL-10+ TAM level and immune contexture were examined by CIBERSORT, immunohistochemistry, and flow cytometry. Clinical outcomes were analyzed by Kaplan-Meier curves and Cox model. RESULTS: Gastric cancer patients with high IL-10+ TAM infiltration exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. IL-10+ TAM infiltration yielded an immunoevasive tumor microenvironment featured by regulatory T cell infiltration and CD8+ T cell dysfunction. The combinational analysis of IL-10+ TAM and CD8+ T cell infiltration stratified patients into distinct risk groups with different clinical outcomes. Moreover, IL-10+ TAM infiltration was correlated with tumor-intrinsic characteristics including EBV status, PD-L1 expression, and genome stability in gastric cancer. CONCLUSIONS: This study revealed that IL-10+ TAMs might drive an immunoevasive microenvironment and determine poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy, indicating IL-10+ TAMs could be applied as a potential target for immunotherapeutic approach in gastric cancer.

Protective effects of dietary curcumin and astaxanthin against heat-induced ROS production and skeletal muscle injury in male and female C57BL/6J mice.

AIMS: This study aimed to: 1) investigate sex differences in heat-induced mitochondrial dysfunction, ROS production, and skeletal muscle injury in mice; 2) evaluate whether curcumin and astaxanthin, alone or together, would prevent those heat-induced changes. MAIN METHODS: Male and female C57BL/6J mice were treated with curcumin and astaxanthin for 10 days, then exposed to 39.5 °C heat for up to 3 h. Heat-induced hyperthermia, changes in mitochondrial morphology and function, and oxidative damage to skeletal muscle were evaluated. KEY FINDINGS: Although female mice had a slightly higher basal core body temperature (Tc) than male mice, peak Tc during heat exposure was significantly lower in females than in males. Heat increased ROS levels in skeletal muscle in both sexes; interestingly, the increases in ROS were greater in females than in males. Despite the above-mentioned differences, heat induced similar levels of mitochondrial fragmentation and membrane potential depolarization, caspase 3/7 activation, and injury in male and female skeletal muscle. Individual treatment of curcumin or astaxanthin did not affect basal and peak Tc but prevented heat-induced mitochondrial dysfunction, ROS increases, and apoptosis in a dose-dependent manner. Moreover, a low-dose combination of curcumin and astaxanthin, which individually showed no effect, reduced the heat-induced oxidative damage to skeletal muscle. SIGNIFICANCE: Both male and female mice can develop mitochondrial dysfunction and oxidative stress in skeletal muscle when exposed to heat stress. High doses of either curcumin or astaxanthin limit heat-induced skeletal muscle injury, but a low-dose combination of these ingredients may increase their efficacy.